key: cord-0006824-get431bj
authors: nan
title: Abstracts of the European Association of Nuclear Medicine Congress 23–26 August 1992 Lisboa, Portugal
date: 1992
journal: Eur J Nucl Med
DOI: 10.1007/bf00596386
sha: f4fc782ef8a078578b61f40cd4ac66e3909d33f5
doc_id: 6824
cord_uid: get431bj

nan

The possibility of identifing hibernating myocardial tissue with rest/stress SPET perfusion studies using [99mTc]MIBI and with PET metabolic studies using [18F] FDG under fasting condidion was tested in patients with CAD. Regional wall motion, assessed prior to and after CABG by first-pass and ECG gated peffusion imaging with [99mTc]MIBI, stress/rest [99mTc]MIBI and [18F]FDG uptake were scored in 5 segments in each of 14 subjects for a total number of 70 segments. By using as a reference the pre and postoperative wall motion function, the probability of regional wall motion recovery was estimated in relation to the preoperative regional perfusion and metabolic scores by a stepwise multiple logistic analysis. The segments with the highest probability (96%) of recovery from preoperative asynergy after CABG were those with marked [18F]FDG uptake prior to surgery. High probabilities of recovery were also estimated for the asynergic segments presenting with moderate and low [18F]FDG uptake (92% and 79%, respectively). A very low probability of functional recovery (13%) was estimated in the segments with no [18F]FDG uptake. The preoperative [99mTc]MIBI pattern of distribution was, per se, insufficient to estimate the outcome of the CABG in asynergic tissue. The results of the study confirm the paramount importance of the identification of asynergic, yet viable myocardium in the diagnosis of patients undergoing CABG and the suitability of [18F] FDG studies under fasting conditions for this purpose.

Group n FDG/~IBIpre FDG/~IBIpost A 20 1.07 ± 0,04 1.12 ± 0.05* B 12 1.38 ± 0.02 1.33 ± 0.06* C 29 1.94 ± 0.11 1.17 ± 0.05 § * NS, §: p <.0001 (pre versus post RV) A decrease of the FDG/~IBI r a t i o a f t e r RV as a r e s u l t of an i n c r e a s e d MIBI-UPT was only seen in segments with a "mismatch" pre RV (group C) in c o n t r a s t to segments with a concordant reduction of P and M (A). Also in Group B the r a t i o did not change due to a marginally (not s i g n i f i c a n t ) concordant increase of P and M. No s i g n i f i c a n t change of M was noted in e i t h e r group. From these data we conclude, t h a t FDG/~IBI r a t i o s ~ 1.5 ("mismatch" score) before revascularlzation predict recovery of perfusion a f t e r RV. In order to assess the presence and the extent of viable myocardium in patients with chronic myocardial infarction, up to now 11 patients with electrocardiographically and angiographically proven chronic myocardial infarction underwent positron-emission-tomography (PET) with 18F-2-deoxy-2-fluoro-D-glucose and 99mTc-methoxyisobutyl-isonitril single photon emission tomograhy/MIBI-SPECT) at rest. Myocardial FDG and MIBI uptake were plotted as bull's eye display (32 segments each) and normalized as percentage of the segment with maximum MIBI uptake. Scar was defined as regional. MIBI uptake 2.5 SD below the regional uptake in a healthy control group (n=l 1), regional FDG uptake was analyzed accordingly.

108 of 352 segments were scored as scar by MtBI-SPECT but only 42/352 segments by . 37/352 segments were concordantly scored as scar by 71 segments were disconcordantly scored as viable by FDG-PET but as scar by 5 segments were disconcordantly scored as viable by MIBI-SPECT but scar by segments were scored as viable by . In those 71 segments showing viability by PET but scar by MIBI-SPECT (FDG-MIBI mismatch) average FDG uptake was significantly lower than the uptake in the segments scored as viable by both methods (83°/o+19% vs. 95°/,~+17%, p<0.05).

Although of all segments concordantly with FDG-PET, FDG-PET identified significantly more viable regions than MIBI-SPECT. The significantly lower FDG-uptake in regions with FDG-MIBI mismatch may indicate tissue mixture of viable and necrotic parts in regions with non-transmural infarction.

There is controversy whether 201-Thallium (TI) uptake can be used to assess the presence of viable myocardium. We hypothesized that the change in uptake between exercise and 24 hours delayed images is a reliable marker of viable myocardium. We studied 32 consecutive patients aged 58±9 (mean±sd), who survived to a first myocardial infarction and were candidates for coronary artery bypass surgery (REV). They were submitted to pre and post operative exercise, 4 and 24 hours redistribution T1 SPECT imaging , rest 2D echo before and every four weeks for four months after REV. From matched 2D and T1 images 144 infarcted segments (IS) were analyzed; we measured regional systolic wall thickening (WT) from 2D echo and the amount of relative T1 uptake in each serial image. 144 IS had abnormal WT pre REV, respectively 75 (52%) and 104 of them (72%) improved WT (>2mm) by month one and three post REV, 40 (28%) remained unchanged. The changes in relative uptake between stress and 24 hours pre REV T1 images (ST1) and in post REV WT (~WT) were determined in all IS. There was a significant relationship (r=0.89, p<0.01) between 6TI and time to improvement of WT, and between the degree of WT improvement and ST1 (r=0.92, p<0.00). Time to WT improvement was " shorter and its degree was significantly superior in IS with greater ST1. In conclusion this study demonstrates the possibility of myocardial stunning after a REV procedure. Its occurrence and time to recovery is inversely related to the degree of pre REV ~TI. D. Agostini*, A. Takahashi, H. Iida, Y. Tamura, Y. Ono. Research Institute for Brain and Blood Vessels, Akita, Japan.*Department of Nuclear Medecine, Cyceron, Cash, France.

The myocardial tissue fraction (MTF) is a fraction of perfusable (viable) mass per volume of given region of interest (ROD and myocardial blood flow (MBF) is the regional flow per mass of the residual tissue, not per the total volume which includes necrotic and/or fibrotic tissues. To detect the ischernic but viable tissue in myocardial infarcted regions with dysfunction of wall motion, we studied 12 patients (mean age 59.6+6.3 years) by 2D-echocardiography and H 2 150 dynamic PET imaging 8.7_+9 months after an anterior infarction. MBF (ml/min/g of water peffusable tissue (PT)) and MTF (g of PT/ml of ROD have been measured according to a previously reported method. The PET study consisted of a transmission scan, a static C150 inhalation scan to measure the blood volume, and a H 2 150 infusion (2-min) dynamic scan to measure MTF and MBF. From the 12 pts, ROI's were selected on the infarcted zones based on 2D-echoeardiography to obtain 45 segments. Myocardial wall motion was divided into 3 groups: lateral control segments (Cn=21), anterior: hypeldnetic (H=12) and akinetic segments (A=12). (Mean+sd, *p<0.05, **p<0.01, ***p<0.0001).

Cn H A MBF 0.95_+0.25 '~* 0.59_+0.15 ~ 0.38_+0.18 *** MTF 0.61_+0.08 ** 0.49_+0.10 * 0. 41_-+0 .136 *** MBF and MTF decreased significantly and gradually from the Cn regions to the A regions. MTF reduced according to the severity of impairment in the wall motion suggesting that MTF is a direct indicator for assessing the wall function in the old myocardial infarction. MBF was decreased in regions around the infarcted center corresponding to residual wall function, i.e may be detecting the existence of hibernating myocardium. These data indicate tha,t the possibility to detect tissue viability by measuring both the size (MTF) and perfusion (MBF) of the residual tissue. A second T1-201 injection under resting conditions is able to improve differentiation between myocardial scar and ischemia compared to simple redistribution imaging. The aim of this study was to evaluate the dependence of this fill in effect on the degree of stenosis and the presence of collaterals. SPECT studies under exercise, redistribution (RD, 4h p.i.) and reinjection (RI, 24h p.i.) conditions were performed on 62 patients with 132 stenotic vessels (50 LAD, 35 LCX, 47 RCA). The left ventricle was divided into 17 segments and for each segment the results of the angiography and scintigraphiy were independently classified by two pairs of observers. From the angiography the degree of narrowing, the segments dependent on this vessel and the degree of collateralization were classified. Further wall motion abnormalities and the myocardinm supplied by each of the main coronary arteries were determined. Based on the scintigraphy all segments were scored according to their perfusion in the stress, RD and RI study. The perfusion score (PS) ranged from 0 to 3. To quantify the fill in effect for each area dependent on a stenotic vessel a fill in index was calculated according to the formula: (~PSRI -ZPSRD)/ZSegm. 41 of the 76 >90% narrowed vessels were collateralized (61%), but only 2 of the 56 <90% narrowed vessels was collateraiized (3.5%) . 39 of the 43 collateralized stenoses showed a fill in effect (91%), but only 3 of the 89 not collateralized (3%). The dependence of fill in effect, collateralization and > 90% stenosis was highly sigrdficant ( XZtest <0.0001). In our patient group only in vessels with a > 90% narrowing there was a benefit from the reinjection study. The fill in effect was closely correlated to the presence of collaterals. In these cases the fill in may be an indication for hibernating myocardium. A multicanter study (SIRT) on relnJsctlon Imaging (RJ-I) after conventional stress-redistribution Imaging (SR-I) is ongoing In Italy to test the Inddenca of discordant results for regional myocardial viability. Nine medical centers, equipped with the same gamma camera and computer software, partecipatad t 9 the protocol. These are preliminary results In 156 pts with Ischemlo heart disease (123 with previous M.I.) and perfuslon defects (PD) alter stress myocardial sclntlgraphy (planar method, visual reading, 15 segments, 5 point scale). Just after the 93 pts were ralnJoctad at rest and RJ-I was performed alter 30 rain (group A). Other 63 pts were ralnjected at rest in a separate day and RJ-I was performed 30 min and 4 h later. There were no significant clinical differences between group A and B with respect to age, sex, M.l., history of angina and ECG stress test results. In group B a more extensive impalremant of regional wall motion was detected by ECHO, performed within 15 days. At least one point difference In segmental score identified reversible (REV) and worsening (WOR) PD at SR-I. Segmental PD with unchanged abnormalities were considered llxed 0RR). Improved (RJ+), unchanged (RJ=) and worsened (R J-) PD were identified alter segmental comparison of RJ-I When comparing the incidence of R J+ versus RJ= plus R J-segments no significant difference was found between the two groups (p = 0A1). A good agreement of segmental scoring was found between 30 rain and 4 h RJ-I In group B (k-statistic = .725). Our results point out to a lesser incidence ol R J+ than previously reported and show that these findings are similar for both RJ procedures adopted.

Serial planar scintigraphy with tracer reinjection after redistribution imaging was performed in 37 patients with >_75% stenoses of the left anterior descending coronary artery and stable angina pectoris 1 to 8 weeks prior to aortocoronary bypass grafting. Anteroseptal T1-201 uptake was operator independently quantified in stress, redistribution and reinjection scintigrams. Intraoperatively, two transmural biopsy specimens were taken from the left ventricular anterior wall and the volume fraction of interstitial fibrous tissue (VvlNT) -as indicator of irreversibly damaged myocardium -was calculated by light microscopic morphometry.

VvlNT significantly differed between patients without prior anterior myocardial infarction (AMI; 26+7 Vol%) and patients with previous non-Q wave AMI (33+12 ¥o1%) or Q wave AMI (38_+9 Vol%; p=.020). On the other hand, no significant differences were obtained between patients with normal regional T1-201 uptake, redistribution or persistent defects on stress-red{stribution images; VvINT only tended to be higher (40+14 Vol%) in patients with severe persistent T1-201 defects (<65% of maximum tracer uptake) as compared to patients with redistribution or moderate persistent defects (30+9 Vol%, p=.073). Enhanced anteroseptal T1-201 uptake after tracer reinjection in segments with persistent defects on stress-redistribution images, however, was significantly associated with lower VvlNT as compared to segments without enhanced tracer uptake after reinjection (28+8 vs. 41+12 Vol%, p=,031). T1-201 reinjection also improved the correlation between the relative poststenotic tracer deposition and VvlNT (r=-.851, p<.001) as compared to the redistribution images (r=-.622, p=.034) .

The data suggest that the myocardial T1-201 distribution after tracer reinjection more precisely reflects irreversible structural damage as compared to (4 h delayed) redistribution imaging.

J. Lipiecki, J. M a u b l a n t , B. Citron, B. K a r s e n t y , D. M e s t a s , A. V e y r e , J. P o n s o n n a i l l e . U n i v e r s i t y H o s p i t a l and Centre Jean Perrin, Clermont-Ferrand, France 

The r e v e r s i b i l i t y of exercise SPECT d e f e c t s was c o m p a r e d b e t w e e n 3 m e t h o d s : 4-hour r e d i s t r i b u t i o n (redistr.), r e i n j e ct i o n (reinj.) a n d a s e p a r a t e d a y rest injection. 37 patients with d o c u m e n t e d coronary artery disease underwent a SPECT study at rest followed, one week later, by 3 other SPECT studies:

(a) i m m e d i a t e l y after injection of at peak exercise, (b) 4 hours later at redistr., and (c) following a h a l f -d o s e reinj, of . Each SPECT was b l i n d l y s c o r e d t w i c e u s i n g a s e m i -q u a ntitative analysis. Sensitivity for d e t e c t i n g c o r o n a r y a r t e r y s t e n o s i s was 70% w i t h redistr., 84% with reinj.

(p<0.05) and 83% w i t h rest (p<0.05) . A m o n g the ii p a t i e n t s w i t h o u t a p p a r e n t r e d i s t r i b u t i o n , 7 (64%) became positive at reinj, and/or rest. 86% of them had a >90% stenosis and a wall motion a b n o r m a l i t y , vs o n l y 43% in the o t h e r patients.

In conclusion, the 4-hour p o s texercise reinj, is a better alternative than the classical 4-hour p o s t -e x e r c i s e redistr., a n d is not s i g n i f i c a n t l y [3] [4] h post-exercise. Reinjection of a second dose of thallium-201 reduces the underestimation of myocardial viability although the optimal moment of thallium-201 reinjection is still in dispute. We investigated the possibility for detection of viable myocardium after early reinjection according a new protocol. Eighty-one consecutive patients suspected for coronary artery disease were studied after exercise, early reinjection and redistribution. The first dose, 75 MBq thallium-201, was administered at maximal exercise followed by planar imaging in the 3 standard views. A second dose of thallium-201135 MBq) was given immediately after completing the exercise-images. Image-acquisition was repeated after 1 h (early reinjection) and 4 h (redistribution). Each set of thallium-201 images was visually and quantitatively analysed. Sixty-nine patients showed diminished or absent activity in one or more segments (total 233 segments). After early reinjection 34 patients showed fixed defects in 74 segments; in these 34 patients 66 segments persisted at 4 h redistribution, and 8 segments showed filling-in. In 35 patients all defects (83 segments) improved or normalised after early reinjection. Further filling-in at 4 h redistribution of already improved defects was seen in 17 patients (21 segments). However in 16 patients (32 segments) the exercise-defects showed reverse redistribution at 4 h. Although 4 h redistribution imaging may show further filling-in of early reinjection-image defects, it did not improve the detection of myocardial viability in the individual patient. Therefore early reinjection circumvents the need for 4 h redistribution imaging and may become the standard procedure in assessing myocardial viability, being an effective, time-saving and patient-comfortable approach. Several studies have demonstrated that certain labelled free fatty acids might be more accurate markers of viability than T1201 after myocardial infarction (MI) . The aim of this study was to compare myocardial uptake of T1201 after redistribution and restreinjection to that of rest-injected Iodine-123 Methyl-Hexadecanoic acid (IMHA) after MI. A mean of 32 days after MI, 60 patients (53 + 8 years) underwent exercise SPECT T1201 with 4-hour redistribution and 37 MBq rest-reinjecfion, followed by rest SPECT with IMHA (100 to 200 MBq). Results were scored using a 20 segments division of the left ventricle. -Segment analysis : Of a total number of 373 segments with T1201 stress defects, 103 (28%) could be considered viable as evidenced by normal or near-normal uptake on either T1201 redistribution, rest-reinjection or rest IMHA scans. This residual viability was identified after T1201 redistribution in 49 cases (48%), T1201 redistribution or rest-reinjection in 79 (77%) and on IMHA rest scans in 102 (99%). -Patient analysis : When considering the only 16 pts (27%) with mild to important residual ischemia (> 3 segments) on IMHA scans, viability was underestimated on T1201 scans in 8 cases (50%), andextent of underestimation was > 2 segments (range 2 to 4) in 4 of them (25%).

-Conclusion : After MI, redistribution and rest-reinjection T1201 SPECT underestimate, with regard to IMHA rest imaging, the amount of ischemic but presumably viable myocardium, but the clinical relevance of these findings remains to be assessed. To determine the amount of exercise supplementation required to improve image quality, 120 patients referred for Dipyridamole (DP) imaging were randomized to five groups: DP alone (A), DP + 3 min. walking in place (B)~ DP + 3 min. at Bruce level 0 (C), DP + 3 min. at Bruce level ½ (D), and DP + 3 min. at Bruce level 1 (E).

Following completion of the protocol, anterior images of the chest were obtained. Regions of interest drawn over peak myocardial and liver areas, and immediately adjacent to the inferior wall of the left ventricle were used to generate ratios of heart to liver (H/LIV) and heart to adjacent infradiaphragmatic (H/ADJ) activity.

Images were also graded semi-quantitatively (S.Q.) on a scale of 1 to 3 (l=poor, 2=average, 3=excellent) .05 compared with control Group A. We conclude that walking in place and treadmill exercise at Bruce levels 0 and ½ produce an equivalent improvement in image quality.

A trend towards further improvement is seen with a higher level exercise. The clinical performances of dobutamine (DOB) and dipyridamole (DIP) stress SESTAMIBI MPS, using SPECT, were compared in 35 patients (4 females, 31 males, mean age 55.9 yrs, range 32-76 yrs) . The time between scintigraphic investigations was at most one week. A one-day stress-rest protocol (150 MBq SESTAMIBI at maximal stress and 750 MBq SESTAMIBI 4 hr later at res0 was used. The dose of DIP was 0.84 mg/kg over 10 rain, while those of DOB were 10, 20, 30, 40 and 40 ug/kg/min over 3 min in each step. Cardiac catheterization was performed in each patient within 2 weeks. 13 patients had single-vessel coronary disease, among them 3 patients with single-vessel coronary occlusion, 1 patient had 2-vessel disease, and 21 patients had normal coronary arteries or insignificant coronary lesions.

The sensitivities of DIP and DOB MPS were each 13/14; the specificity for DIP was 18/21, and that for DOB was 14/21. The positive predictive values for DIP and DOB were 13/16 and 13/20; the negative predictive values were 18/19 and 14/15, respectively. A false-negative result was found with both methods in the same patient with 95 % LAD narrowing. All 3 false-positive results with DIP and 4 of the 7 with DOB were found in patients with 20-50 % coronary narrowings. The extent of the ischemic area was practically the same in 12/13 true-positive cases. In 1 patient, the extent of the transitorily ischemic myocardium was larger with DOB than with DIP. In 2 of the 3 patients with single-vessel coronary occlusion, only DIP indicated transitorily ischemic segments, DOB demonstrating only persistent myocardial ischemia.

It is concluded that DIP and DOB MPS with SPECT have the same sensitivity, while DIP seems to have a higher specificity in the detection of IHD. (1) atrial ventricular block (AVB), starting at a mean tie of 2.0¢ +/-1.14 ~ean, resolving within 2 min of interrupting the infusion. ~cond degree (2) AVB occurred in 29 P (4.1%), with similar frequency in P with and without acut~ myocardial infarction (2.4% and i.~N) . In 17 of these P {5E.0%), 2 AVB wan preceded by I AVE. 2 AVB hegan at • man ti~ of 2.09 +/-1.8 min, was transitory or disap~ared within two min of stopping infusion. 2 AVB were ~bitz I in ig P and 2:1 in IIP. The Wenckebach cycles were 3:2 in 7 P, ~,:3 in ~ P, 5:~, in 3 P and 8:~ in 2 P. It was necessary t~ reduce ~e infusion in only two cases of 2 AVB, L~cauee of systematic ~low ventricular ra~ {4E bpm) with pr~t resolution. 4 P (O.EO~) develo~d third degree (3) AVB, at 2.28 +/-1.38 min. 3 AVB was transitory and did not last emre than 3 sin. Regarding t~ rssult~ of thallium201 scintigr~hy, 14 P with 2 AVB (~8.2~) hed nornml perfueion ~csns and 15 P (~1.85) had ~rfueion defects (~ ischemie, 6 scar, 3 iechsmia and scar); 2 P with 3 AVB had normal scans and 2 P hacI ~rfusion defectu (l scar, I scar and ischems). There was no difference in the frequency of perfusion defects in P wiLh and without 2 or 3 AVB (p:ns). We conclude Mat, AVB is an infrequent c~licstion of adenosine infusion. It is t, ransitory and rarely requires in~rruption of the study. Also, it occurs independently of ~e existence of ~rfusion defects, i~lying thaL the eechanis~ for AVB production during ~no~ine infusion is not relaLed to i~che~ia. . It has been suggested that differential washout of Tc99m teboroxime (TEBO) may be useful in diagnosis of myocardial ischemia. Utility of rapid STRESS, "redistribution" (P~D) end REST imaging with TEBO and Adenosine (ADENO) was tested in 22 patients and ADENO was infused for 5 Pin up to 170 mcg/kg/m/n, at 4.5 Pin 24 mCi of TEBO were injected. Stress SPEC2 imaging was started i. 5 Pin later using a single headed camera for a 4 Pin continuous circular counter-clockwise acquisition. RED images were obtained immediately. REST imaging was started at 26 Pin, 1.5 ~ after a 26mCi TEBO dose. In each pt, 5 myocardial segments were evaluated for presence of reversible or fixed defects. STRESS-REST and STRESS-RED in~ges were cc~pared.

The imaging was cc~pleted wi.thin 30 Pin in al$ pts. Of ii0 segments, 3 were not visualized due to intense liver activity. Only 9% (10/107) were misclassified by STRESS-RED cc~npared to STRESS-REST images: STP~SS-RI~3  STRESS-REST  normal  reversible  fixed  normal  52  0  0  reversible  0  25  3  fixed  0  7  20 Rapid acquisition of diagnostic SPECT images is feasible using the protocol. Also, complete diagnostic info~rnation is available in most patients already from the STRESS-P~D images. Clinic Foundation, Cleveland, Ohio USA

In a previous c o m p a r i s o n of 202 c o n s e c u t i v e patients e v a l u a t e d for c o r o n a r y a r t e r y disease (CAD) with m y o c a r d i a l p e r f u s i o n imaging with both PET, 27 patients were identified as having t r u e -p o s i t i v e images, but f a l s e -n e g a t i v e images. The p u r p o s e of this report is to ascertain the clinical outcome of these d i s p a r a t e results and d e t e r m i n e the effect on patient care.

No f a l s e -n e g a t i v e cases d i a g n o s e d by PET were c o r r e c t l y d i a g n o s e d by SPECT. The 27 patients c o r r e c t l y d i a g n o s e d by and i n c o r r e c t l y d i a g n o s e d by formed the p o p u l a t i o n for followup analyses.

Six of ii patients with no previous i n t e r v e n t i o n or i n f a r c t i o n had subsequent interventional procedures, receiving either c o r o n a r y artery bypass grafts (CABG) or p e r c u t a n e o u s transluminal coronary a n g i o p l a s t y (PTCA). Seven of eight p a t i e n t s with previous CABG or PTCA i n t e r v e n t i o n received additional t h e r a p e u t i c i n t e r v e n t i o n s as did three of the eight p a t i e n t s with known m y o c a r d i a l infarcts.

In conclusion, the fact that 13 of the 19 (68%) p a t i e n t s with no m y o c a r d i a l infarction received either a CABG or PTCA procedure indicates that m y o c a r d i a l imaging was instrumental in p r o v i d i n g a p p r o p r i a t e medical care to these patients. These 13 patients were all d i a g n o s e d as normal by and no i n t e r v e n t i o n would have been indicated. In this study, we have attempted to evaluate in 44 patients (pts) the diagnostic performance of dobutamine stress tomographic imaging (DST) to detect residual ischaemia (IS.) in the infarcted area or at distance. Four pts presented myocardial infarction (M.I.) in two vessel territories and twenty pts had multiple vessel disease. Data were recorded in the subacute phase of M.I. and compared to dobutamine stress echocardiography (DSE) and to angiography. Fifteen mCi of 99mTc-MIBI were injected at peak infusion of dobutamine (up to 40 mcg.kg/mim) and DST performed 90 min later to allow decrease of background activity. 'M.I. was visualiazed in all pts by both techniques. Myocardial IS. around the infarcted area was detected in 17 cases by DSTand in 20 cases by DSE while absence of IS. was observed in 31 cases with DST and in 28 with DSE (complete agreement in 58% of cases). DST identified multiple vessel disease in 13 pts (sensitivity of 65%) and DSE in 10 pts (sensitivity of 50%). Slight discrepancies were present for 20 pts : IS. in the infarcted zone was detected only by DSE in 13 cases and only by DST in 7 cases. For twelve of them, the angiogram showed the presence of residual stenosis of the infarct related artery.

In conclusion, the agreement between DST and DSE for detecting myocardial IS. in the infarcted area is good but the pronostic significance of these results has to be determined. Multiple vessel disease and IS. at a distance is more often recognized by DST than by DSE. Therefore, DST appears to be a promising technique to evaluate the extent of coronary artery disease after M.I.

S. Lastoria E. Vergara, L. Castelli, C. Carac6, C. Bonino*, M. Mariani* M. Salvatore. Nuclear Medicine Departments, University Federico II and National Cancer Institute, Napoli, *Sorin Saluggia, Italy.

RADIOIMMUNOSCINTIGRAPHY WITH MAb IN PATIENTS WITH OVARIAN CANCER.

MAb recognizes folate-protein binding (FPB) which is largely expressed in human ovarian tumors, while is not expressed in normal ovaries. MAb has been labelled in this study with 1311,125I, and 99mTc and administered intravenously (iv) or intraperitoneally (ip) . Preliminary studies in 8 pts., with recurrent disease, after i.v. injection of )~ detected all 14 tumor sites demonstrated at second-look laparotomy. The percentage of injected dose (%ID), measured by gamma-counter, ranged from 0. .7%ID/gram of tumors (T) and from 0.002 to 0.005% ID/gram of normal tissues (NT) with T/NT ratios as high as 105 fold. In a second group of 5 pts. a double paired protocol was performed coinjecting [3] [4] [5] mCi of 2ip and 0.5-1mCi of F(ab')2 iv, in order to determine which one of the two routes allowed a better tumor localization with elevated % of ID. A total of 15 lesions was correctly identified and in all of them a significant higher concentration of 131I over was measured, ranging from 1.8 to 37 fold in tumors, being equal to 1 in normal biopsies. In a third group of 10 pts RIS was performed by iv administration of 15-21 mCi of 99mTc- to evaluate this kind of radiopharmaceutical could allow a satisfactory localization of tumor-nodules. Using both planar and tomographic images primary tumors (6), peritoneal and omental spreading (9), and pelvic meatastases (4) were correctly detected as early as 6 hours p.i. The T/NT ratios were similar to those measured for iodine labelted preparations. We conclude that Specifically binds to ovarian tumors with levels greater then other MAbs currently used, mainly after ip injection; (b) represents, on the basis of %1I) bound to tumor one of.the best candidate for radioimmunotherapy; and suggests to reevaluate the use of methotrexate in chemotherapy, because of the role of FBP in tumor growth. Imaging of non-Hodgkin's lymphoma (NHL) with a 99mTc-LL2 (Fab') kit and therapy of NHL with 131I-labeled LL2 (whole IgG and F(ab')2 ) are being investigated. In a series of 8 patients with NHL and 1 patient with chronic lymphocytic leukemia, the 1-mg LL2 Fab' labeled with 20-25 mCi 99mTc by a rapid kit resulted in a total of 29/34 (88%) tumor sites disclosed if a single patient with high tumor burden is excluded. Antibody imaging with confirmatory and complementary to gallium 'results, as well 13~ as to targeting with the I-LL2 preparation in these patients. Splenic uptake was confirmed as non-specific, since this was also found in patients with carcinomas. It is concluded that'the LL2 imaging kit is useful for detecting and staging NHL, and may preclude the use of a battery of imaging tests, especially since NHL of different histopathology showed antibody targeting.

Therapy studies with mI-LL2 at low doses (<50 mCi) showed, among 10 assessable patients, 3 partial responses (2.5-7 .0 months), 1 minor, 1 mixed response, 1 stable disease, and 4 progressors. Two of the PR's were achieved after a single cycle (30 + 20 mCi) of treatment. Hematologic toxicity was seen in 5/12 patients having a dose-limiting _> Grade 3 toxicity. HAMA was found after multiple treatments. It appears that a repeated low-dose radioimmunotherapy schedule for NHL produces antitumor effects in this initial series of patients with advanced disease. (Supported in part by NIH grant CA39841.) G250 (murine IgGl) is a MAB that reacts with clear-cell renal carcinoma and has no significant normal tissue reactivity.

Sixteen patients (pts.) with renal cell carcinoma (RCC) were studied in a Phase I trial.

Groups of 3 pts. were administered 1-131-G250 intravenously at doses from 0.2 to 50 mg. Whole body planar and SPECT images were obtained in all pts.

Relevant tumour and normal tissues were obtained at surgery one week after MAB infusion and tumour and normal tissue uptake of radioactivity and antigen ooncentration estimated.

Of the 16 .pts. entered, 13 were antigenpositive; all primary and metastatic tumours in these pts.were successfully imaged.

Tumour uptake at day 8 was as high as 0.1% injected dose/gram tumour, with tumour:serum ratios being as high as 60:1.

Hepatic uptake was saturable, with the amount of antibody required being 20-100ug.

Serum clearance followed a hi-exponential pattern, with terminal TI/2 being 47 hrs;

there was no dose-dependence.

In conclusion, this is the first clinical study to show consistent selective uptake of MAB in renal cell carcinoma. Radioimmunotherapy with this MAB is planned.

D.M. Goldenberg, C.M. Pinsky, H.J. Hansen, and L. Swayne. Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Newark, NJ, Immunomedics, Inc., Warren, NJ, and the Immunomedics Cli&J~'~l T_r/a[ Grou~ (USA~. COLORECTAL C~CER IMAGING WITH : RESULTS OF A MULTICENTER PHASE-III TRIAL. A multicenter trial at 19 U.S. institutions has been completed with an imaging kit consisting of 1 mg of anti-CEA Fab' ( labeled with 20-25 mCi 99mWc by a fast, direct method. Patients (pts) with colorectal cancer were stratified into a group with at least one known tumor of 0.5 cm or larger (120 pts, 114 evaluable), and a second group with no evident disease, but a strong suspicion of recurrence due to a rising CEA, or other clinical signs (57 pts, 54 evaluable). Mean incorporation of the label in the field was 97% by thin-layer chromatography. One pt had a boost in a pre-existing human anti-mouse antibody response to the fragment (ImmuSTRIP®- HAMA-fragment) . In pts with known disease, by patient, sensitivity was 85% and predictive value of a positive reading was 92%. By lesion, sensitivity was 71% (79% in the liver) and positive predictive value was 89% (95% in the liver). In patients with occult disease, accuracy of the antibody scan has been 60% compared with 51% for conventional techniques, such as X-rays, CT scans or MRI. The increased precision in estimating extent-of-disease contributed to potential improvements in patient management of 27%, 50% and 35%, in known disease, occult disease, and the two groups combi~n~ed, respectively. We conclude that ImmuRAID-CEA[~mTc] is safe, easy-to-use and may contribute to improvements in the management of patients with recurrent or metastatic cancer of the colon or rectum. (Supported in part by NIH grant CA3984L)

A. McEwan 1, G. MacLean 1, L. Golberg 1, D. Groshar 1, G. Boniface 2, T. Sykes 2, A. Noujaim 2, 1Cross Cancer Institute and 2Biomira Inc., Edmonton, Alberta, Canada : A MONOCLONAL ANTIBODY FOR THE EVALUATION OF PATIENTS WITH BREAST CANCER MAb 170H.82 is a novel monoclonal antibody derived using synthetic TF antigen. In-vitro studies have shown high affinity to adenocarcinomas of various origins. including that of the breast. We have radiolabelled this antibody with and are currently evaluating it in an extended Phase 2 trial of patients with breast cancer.

To date, fifteen patients with primary or metastatic breast cancer have been entered into the study. All patients had been fully evaluated by clinical examination and morphological imaging techniques prior to entry into the study. Doses of 2 mg (8 patients) and 4 mg (7 patients) labelled with between 1,100 and 1,800 MBq. of were administered by slow intravenous infusion. Images were obtained using a GE 400 AT camera interfaced to a Picker PCS 512 computer immediately after injection and at 4 and 20 hours. SPECT imaging was performed at 24 hours.

No adverse reactions to the antibody were noted. The monoclonal antibody images were compared with sites of known tumor as defined by morphological techniques. Thirty-two soft tissue metastatic sites were identified. On preliminary analysis, monoclonal antibody images were positive in 25 of these. In one patient, equivocal pulmonary metastases identified on chest x-ray were not seen. Five patients had bone metastases; in only 1 of these was uptake identified. Two intra-mammary lesions were identified.

We believed MAb 170H.82 has significant potential as a new radiopharmaceutical in the evaluation of patients with primary and metastatic breast cancer, particularly in soft tissue disease. Clinical efficacy data will be presented. One of the major problems in tumor patients is the accurate assessment of tumor infiltration and spread. While methods like CT and MRI provide morphologic information, functional studies of tumor metabolism with PET may help to achieve a more accurate diagnosis. We use a two ring PET system for patient examinations. and/or N-13-glutamate are injected for studies of the tqmor metabolism, while O-15 labeled water is administered to assess the tumor peffusion. Metabolic studies in patients with recurrent colorectal tumors demonstrated, that PET can be used to determine the increased FDG metabolism in the malignant lesions. We were able to differentiate tumor and scar in 28 of 29 tumor patients and 13 patients with his~ tologically proven scar tissue using FDG. The accumulation of N-13-giutamate exceeded the FDC~uptake in the tumor region as well in the normal bowel. The comparison of perfusion and FDG uptake demonstrates, that perfusion measurements in soft tissue lesions are not reliable for the differentiation between benign and malignant masses. Problems existed in patients with inflammation (n-2) due to the increased tracer uptake. PET studies in patients with lung turrets (n-20) showed increased metabolism in malignant tumor and involved lymph nodes. Tumor recurrence after surgery and/or radiation therapy could be differentiated from scar tissue. Furthermore, the measurement of tumor metabolism with FDG or N-13-glutamate proved to be a reliable method for therapy follow up in patients receiving chemotherapy. We were able to show, that changes in tumor metabolism preceeded changes in tumor volume during therapy. was used in patients with liver metastases from colorectal malignancies in order to evaluate the uptake of the cytostatic agent in the lesions and the correlation to therapy outcome. The distribution of the FU metabolite concentrations shows, that 76% of all metastases (34/44) have low tracer concentrations, while 24% have higher concentration values. This rate corresponds to the average response rate of colorectal metastases to chemotherapy, as reported in the literature. We were able to demonstrate a high correlation (r=0.8) between the FU uptake in metastases.prior to therapy and the lesion growth rate during chemotherapy. Furthermore, PET studies with FU were used to compare different treatment protocols (systemic vs. regional application, pretreatment with folinic acid). Our results demonstrate, that PET is a promising tool for both diagnostic evaluation and therapeutic follow up in tumor patients. FU has been used in clinical practice to treat colorectal carcinomas for more than two decades. The average response rate is lower than 20%. Since tumor response to FU chemotherapy necessitates the accumulation of the cytostatic agent in the metastases, PET with F-18 labeled FU can be used to assess the tracer concentration in the target area. We used a PET system to evaluate the FU and its metabolite concentrations in patients with liver metastases prior to FU chemotherapy. The target area corresponds to the largest tumor diameter and was determined by CT shortly before the PET study. F-18 labeled FU was administered together with 500 mg nonlabeled FU in order to obtain therapeutic concentrations. Sequential PET images were acquired for two hours beginning with the FU infusion. Standardized uptake values (SUV) were calculated from the PET cross sections two hours after tracer application. All patients received FU chemotherapy after the PET study. The tumor volume and growth rate were calculated from follow up CT studies and compared to the FU accumulation in the metastases prior to chemotherapy. The preliminary evaluation includes 17 examinations. A correlation coefficient of 0.8 was o1~ tained for thsr~= ~r" standardized FU.,0~ ~ concentrations and the growth rate of the This investigation was undertake to explore the potential utility of positron emission tomography (PET) scanning with 2d Each region of increased FDG accumulation was interpreted as positive for malignancy. A total of 46 breasts (23 patients) w e r e studied.

Of these 21 breast w e r e clinically normal and received no biopsy. Histological evaluation w a s later performed on all 28 breast masses (involving 25 breasts).

Axilla + + 19 1 7 0 0 8 1 7 0 21 0 25 We conclude that PET w a s successful in imaging both primary breast carcinomas and axillary lymph node involvement in our study sample. Further research is needed to determine if PET can be routinely used to discriminate between benign and malignant breast masses and axillary nodes, with PC (n=24) or b e n i g n p r o s t a t e h y p e r p l a s i a (BPH, n=5) were i n v e s t i g a t e d u s i n g a CTI 953/15 P E T -s c a n n e r . F D G -u p t a k e ( s t a n d a r d i z e d u p t a k e v a l u e s -S U V ) a n d glucose u t i l i z a t i o n (t~mol/g/min-GU) were c a l c u l a t e d by R O I -t e c h n i q u e I a n d P a t l a k ' s g r a p h i c a n a l y s i s . P E T -s c a n s were a c q u i r e d s e q u e n t i a l l y a f t e r iv injection of 1 5 0 -3 0 0 MBq FDG in f a s t i n g s t a t e . To avoid s u p e r p o s i t i o n of p r o s t a t e by u r i n a r y F D G -e x c r e t i o n c o n t i n u o u s b l a d d e r i r r i g a t i o n was performed. Tumor p r o l i f e r a t i o n was q u a n t i f i e d by i m m t~o s t a i n i n g of p r o l i f e r a t i n g cell n u c l e a r a n t i g e n which l a b e l s t h e S -p h a s e of the 'cell cycle. In BPH a n d 19/24 PC SUV-a n d G U -v a l u e s Were low a n d only s l i g h t l y h i g h e r t h a n pelvic b a c k g r o u n d (SUV: 0.8, r a n g e : 0 . 6 -1 . 1 ; GU: 0.11, r a n g e i 0 . 0 8 -0 . 1 4 ) . In m e t a s t a t i c PC, h o w e v e r , r e s u l t s were s i g n i f i c a n t l y h i g h e r : (SUV: 2 . 1 , range: 1 . 4 -4 . 4 ; GU: 0.32, range: 0 . 1 6 -0 . 6 6 ; p<.05) i n d i c a t i n g h i g h e r metabolic d e m a n d s : of more a g g r e s s i v e tumors. No c o r r e l a t i o n was f o u n d b e t w e e n tumor d i f f e r e n t i a t i o n or p r o l i f e r a t i o n a n d F D G -u p t a k e .

We conclude t h a t glucose metabolism m e a s u r e d by FDG-PET h a s p r o g n o s t i c r e l e v a n c e in P~ a n 4 m a y be u s e d to s e l e c t pts. with high risk of m e t a s t a t i c d i s e a s e for a g g r e s s i v e t h e r a p e u t i c regimens.

T. Vander Borght, S. De Maeght, D. Labar, P. Goethals, M. Van Eijckeren, S. Pauwels. University of Louvain, Brussels, and University of Ghent, Ghent, Belgium.

Animal studies with radiolabelled thymidine showed that the amount of radioactivity remaining in proliferative tissues was partially related to labelled metabolites and was significantly higher when the label was located on the methyl group (Me-Tdr) compared to the 2C-ring positio n ( . These data suggesting that [2-11C] Tdr could provide a more specific PET signal of DNA synthesis, we have now compared the ~tential advantages of both tracers in 5 patients (3 gliomas, 1 oesophageal tumour and 1 rhabdomyosarcoma). After injection of SA 6 .6+3.1GBq/pmol), blood activity curves showed a rapid exponential clearance over the initial 10 min followed by a slow and constant decrease 0factivity. Using SA 0.4+0.3GBq/bunol) , the initial bl~ activity clearance was faster (at lOmin, 0.1% vs 0.19%dose/di for p<0 .005), but was followed by a slow increase of activity, so that at 60 min blood activities were sirailar for both tracers (0.12 vs 0.1%dose/d1 for NS) . As soon as 10 rain after injection of 2C-Tdr, [1!~] C02 accounted for 70% of total blood activity whereas this metabolite appeared only 40 min after injection of reaching 11% at 60rain. In tumoral and normal brain the %dose/100g measured by PET was significantly higher for 2C-Tdr than for Me-Tdr (0.12_+0.01 vs. 0.08+0.03; p<0.001) although the tumour/normal tissue ratio was not significantly different (1.54_+0.34 vs 1.64_+0.30). Similar results were obtained for lung metastasis. In contrast, radioactivity was 3-fold higher in the kidneys and 7-fold higher in the liver for Me-Tdr compared to 2C-Tdr, suggesting a higher accumulation of Me-labelled metabolltes In these organs.

In conclusion, turnout-to-background contrast was not improved by the use of [2-nC] Tdr compared to [Me-nC] Tdr, except for abdominal imaging. In the future, [2-nC] Tdr could provide an easier kinetics .modelling approach since [nc]c02 constitutes its major labelled metabolites.

W. Burchert, E. Schmoll*, J. van den Hoff, G.-J. Meyer, H. Hundeshagen. Dep. Nuclear Medicine and *Hematology/Oncology, Medical School of Hannover, Germany

Intraarterial chemotherapy of liver metastases in patients with colorectal cancer demands for a sensitive method to control the therapy response. Usually this is provided by tom0graphic methods, especially contrast medium angio-CT. To get direct metabolic information we use 15- 7 GBq) and PETto measure blood flow and energy metabolism of liver metastases:in 12 patients with colorectal cancer undergoing chemotherapy. Dynamic acquisitions were performed with a Siemens ECAT 951 as a basis for absolute quantification of blood flow and glucose metabolism. The input functions for the water studies were determined noninvasively in the abdominal aorta using geometrical corrections. A nev~ linearized fit was used to compute absolute blood flow values. The glucose metabolism was derived from a patlak analysis using pseudoarterial blood samples as the input function. Qualitative comparison of FDG and water studies resulted in areas of different types of tracer distribution: The central necrosis with low flow and FDG metabolism, a margin with low flow but normal or increased FDG metabolism and the outer, viable part of the tumor with normal or increased blood flow and FDG metabolism. The use of water as a flow marker underestimated the extent of viable tumor tissue compared to the FDG-scan. In clinical practice FDG is a more reliable.tracer for testing tumor viability. The finding of low flow areas in viable tumor tissue may indicate some difficulties in using contrast medium X-rays for the determination of tumor viability. 

Conventional imaging techniques such as CT, Angiography, and MRI have shown a significant limitation in detecting residual or recurrent musculoskeletal tumors. We have examined 56 patients with confirn~d bone or soft tissue sarcomas using F-18-fluorodeoxyglucose (FDG) and positron emission tomography (PET) during the past year to:evaluate results in detection and follow-up compared toother imaging modalities; CT/MRI and or sestamibi SPECT. There were 15 osteosarcomas, 3 Ewing's sarcomas, 3 chond~osarcomas, i0 malignant fibrohistiocytomas and 25 miscellaneous soft tissue sarcomas. Each patient underwent 3 consecutive PET scans of a known or suspected lesion after the intraqenous injection of 8-10 mCi of Thirty-nine patients showed abnormally increased FDG uptake, 13 studies were negative, and 4 were equivocal or technically inadequate. Of 29 patients positive on CT, 6 were negative on PET (inactive tumors). Of 17 patients positive on MRI, 4 were negative on PET. All patients positive on SPECT (ii) were also positive on PET, although T/NT ratios averaged 10.5 with PET and only 2.5 with SPECT.

In 38 patients with PET positive tumor uptake there was 1 negative CT, 3 negative MRI and 1 negative SPECT. There was 1 false-positive PET in a postoperative infectious focus. Eleven FDG positive patients were studied in follow-up and 3 became normal, 4 improved, 2 did not change and 2 worsened.

PET results more accurately reflected the clinical course than did other imaging modalities.

In conclusion PET is useful in evaluation and follow-up of local bone and soft tissue sarcomas and appears to be superior to CT and MRI. 

P'31 -NMR -SPECTROSCOPY (P31-MRS) Routinely CT and MRI are widely used for monitoring tumor response to therapy in terms of tumor volume decrease and necrosis although they are often no sensitive indicators. Bone seindgraphy as well is widely accepted in therapy monitoring, but is not very specific due to possible fractures, inflammation or the secalled flare phenomenon. Due to its nearly complete extraction from arterial blood 201TI promises to be more specific. P31 -MRS, which non-invasively provides information on relative eoncentratioas of high energy phosphates and tumor cell membrane phospholipids in vivo is as well a very promising method to monitor early tmnor response to chemotherapy. Furthermore beth TS aml P31 -MRS refleet tumor perfusion which is important because ttunors with poor blood flow have reduced cytotoxic drug delivers, and are likely to have high numbers of hypoxic ceils. 5 patienls (2 males, 3 females) (mean age 25.5 + 7.0 yrs.) underwent TS and 1'31 -MRS prior to, during and after chemotherapy. Ewing sarcoma (2 cases), osteosarcoma (2 cases) and malign histioeytoma (1 case). Histological tumor regression was verified according to patients were classified responders (R) (grade I or II) and 3 non-responders (NR) (grade V). TS were quantified by ROI-technique (tumor to con~ralateral region) . P31 spectra were acquired using a 1,5 Tesla imaging-speclroseopy system and a double tuned 16 cm surface coil. 512 -1024 free induction decays were averaged with an interpalse delay of 3 s. For volume selection ISIS (image selective in vivo spectroscopy) was used. In responders TS -ratio showed a decrease from 3.15 and 3.62 prior to therapy to 1.18 and 2.1 after chemotherapy. P31 -MRS in one responder showed a dramatic change of the metabolic profile towards a spectrum of normal muscle tissue, in the other patieatphosphocreatine(PCr)/anorganic phosphate(Pa) and phosphodiester (PDE)/phoaphomonoester(PME) increased whereas PC'r/adenosine triphosphate (ATP) decreased. In NR TS-ratio did not decrease. In one non-responser P31 -MRS showed a decrese of PDE/PME, PCr/Pa and PCr/ATP during therapy, in the two other only an initial increase in PDE/PME was seen.

1. 201TI -seintigraphy and P31 -M~S are suitable monitor tumor response to chemotherapy 2. Tumor perfasion assessed by in terms of high energy phosphates, tamor cell membrane phospholipids as well as metabolites of glycolysis as assessed by P31 -MRS may be complementary in evaluating early tumor response 3. Predierapeutica1201T1 accumulation has no prognostic value with regard to tumor response in contrast to pretherapeutic PCr/ATP and PCr/Pa ratios Tumor hypoxia is a factor which limits the cure rate of r a d i o t h e r a p y which has also been implicated as a mechanism for the development of drug resistance in solid tumors.

We have developed a novel marker of tissue hypoxia radiolabelled with 1-123 1-(5-Iodo-5-deoxy-B-Da r a b i n o -f u r a n o s y l ) - 2 -n We have compared IAZA uptake in tumor sites in 28 patients. Images of the area of interest and of the thorax and abdomen were obtained immediately after injection and at approximately 24 hours. 10 mg of IAZA labelled with MBq 1-123 was given by slow intravenous infusion over 20 minutes. These data are then compared with patterns of tumor perfusion.

The patient population was comprised of patients with small cell lung cancer (SCLC) (12), glioblastoma muhiforme (7), sarcoma (5), squamous cell carcinoma of the head and neck (SCC) (3) and prostate cancer (1).

In thirteen patients there was positive tumor uptake of IAZA, and in 14 the tumor sites were non-avid. Positive uptake of IAZA by primary tumor type was SCLC (5), glioblastoma (3), SCC (2) , sarcoma (2) and prostate (0). These data appear concordant with those obtained from in vitro studies using tritiated Misonidazole and showed an inverse correlation between IAZA uptake and perfusion.

1-123 IAZA appears to have potential as a functional agent for i m a g i n g t u m o r h y p o x i a , and may have applications in predicting response to therapy. In t h e pre-Rx g r o u p t h e r e s u l t s r e v e a l t h a t the sites detected by CT c o r r e l a t e d well w i t h MIBI i m a g i n g . MIBI i m a g i n g was t r u e positive in 85% of these cases, false n e g a t i v e in 10% a n d e q u i v o c a l in 5% w h i l e CT w a s true positive in 100%. The disease w a s located in the pelvis in all false n e g a t i v e a n d e q u i v o c a l cases on MIBI i m a g i n g . Conventional bone marrow scintigraphy (BMS) using labeled nanocolloid has the disadvantage of high liver, spleen and background activity. In contrast, preliminary results of bone marrow visualization with the anti-granulocyte antibody BW 250/183 showed significantly better results. We therefore initiated a prospective study to evaluate the clinical value of this antibody compared to lilac crest biopsy. 44 patients (25 females, 19 males, age: 19-76 years) were thus far studied. The diagnoses comprised 26 patients with 8 with Hodgkin's disease, 6 with acute lymphatic leukemia and 4 with plasmocytoma. The scintigrams were conducted as whole body studies and planar regional scans [3] [4] hours p.L of 555 MBq of Tc-99m-labeled anti-granulocyte-antibody. The marrow biopsy from the posterior sacro-iliac joint was conducted within 3 weeks following scintigraphy. 18 patients showed normal findings in both the scintigraphy and the biopsy. In 26 patients bone marrow involvement was diagnosed by either scintigraphy or biopsy. The comparison of scintigraphy and biopsy revealed the following results: Scan and biopsy positive n=18; scan negative and biopsy positive n=5; scan positive and biopsy negative n=3. The last three patients were reclassified according to the BMS. We conclude from this study that BMS using the BW 250/183 antibody visualizes the entire bone marrow with excellent image quality with a low liver/spleen and background uptake, and is clearly superior to the nanocolloid, suggesting that this antibody should be used more frequently in the initial and fo~tow-up stagin.q of malignant systemic disorders. or 100 MBq of . When no abnormalities were found at CRS, renovascular hypertension were ruled out (n=10); otherwise patients underwent a conventional renal scan. Amelioration or normalization in the latter study as compared to CRS led to RVH diagnosis (n=33),

whereas it was excluded in case of no changes (n=8). Correlation with CRS diagnosis was possible in 51 pts (18 cured, 19 improved, 14 failed (by-pass, nephrectomy, PTA) and post-intervention data (technical success, blood pressure, serum creatinine). Methodologies:

choice among DTPA, MAG3 and Hippuran as renal tracers. Objectives: to test CRT as both a diagnostic test for renal artery stenosis and a prognostic test for the clinical success of intervention. Design and methods: CRT, evaluated by quantitative and inspective renographic analysis, was compared with angiographic degree of stenosis and blood pressure response to intervention. Results were analysed in cases with ~70% stenosis, without stenosis or with a lesser degree of stenosis. Renal function was also tested as a determinant of accuracy. Positive response to intervention was defined as a normalization of blood pressure without an increase of drug treatment.Renal function recovery was .also tested. DTPA results have been prelimiharly reported elsewhere and demonstrated predictive values of the test ranging around 80-90%. Positive CRT was also strongly associated with blood pressure response after intervention. Overall results, comprehending also those obtained with tubular tracers, will be presented.

Beatrix K6niq, H. K6hn, Evelyne Dvorak, A. Mostbeck Department and L. Boltzmann Institute of Nuclear Medicine Wilhelminenspital, Vienna, Austria QUANTITATIVE RENOGRAPHY: COMPARISON OF DIFFERENT METHODS In 51 pts. 3 different methods were compared with the slope clearance (Sapirstein) as reference method with blood sampling for three hours using 99m Tc MAG3: i. A modification of the whole body clearance (Oberhausen) using a "whole body ROI" in the full field of view above the kidneys excluding the liver. 2. According to Piepsz and Assailly the excretion rate (dm/dt) was calculated in the initial segment of the renogram after depth and background correction. The heart curve was rescaled to cps/ml using one blood sample i0' or 17" p. inj. 3. The early uptake method with the same curve as described in 2., but without blood sampling, expresses the kidney's function in percent of the applied dose (Mostbeck). The early uptake was calculated 160 sec. after tracer application and 120 sec. after the arrival of the tracer in the kidney. All methods have been performed simultaneously. Depth measurement of the kidneys was performed on lateral DMSA scans. Results: The correlation coefficients between the different methods and the reference method were in the range 0. 8~ -0 .92 and did not differ significantly. No difference could be found between the 120" and 160" uptake (r=0.99). The lowest work load and inconvenience to the patient causes the early uptake method, which requires the measurement of the kidney's depth and the applied dose.

The efect of a small (<5ml) drink of water on the shape of the curve was investigated in 177 patients (343 kidneys) undergoing renography for a variety of clinical indications. 102/174 renal units (50.7%) with a rising or plateau curve fell by more than 5% (>5 S.D.) within 30 seconds of swallowing. In 44 (25%) the drop was >25%.

114/169 (67.4%) with a falling curve also showed a prompt increase in the gradient of downslope.

30/56 not responding to a first stimulus (53. 6%) responded to a second, as did those given dry biscuit. Diuretic (frusemide or bumetanide) was administered IV to 61 with a rising curve which did not fall after swallowing, with a response in 32 (52%), but after a delay of more than 3 minutes.

Drinking is effective much more rapidly (<30 sec) than diuretic (>180 see).

The small volume of fluid and timescale exclude haemodilution, the response being observed before there could have been appreciable absorption in supine subjects, whilst the rapidity excludes a humoral mechanism.

It has not been observed in any transplanted (denervated) kidney nor in patients with upper or mid cord transections.

The evidence therefore indicates that this is a neural (possibly vagal) reflex.

The rising curve may be due filling of the renal pelvis secondary to failure of the pelvic pacemaker to initiate peristaltic waves autonomously.

This must be distinguished from obstruction.

Lluis Bern~i Gustavo Torres, Rosa Cabezas, Montserrat Estorch, David Duncker, Ignasi Carri6. Hospital de Sant Pau, Barcelona.

OF R E C U R R E N C E S F R O M MEDULLARY CARCINOMA OF THE THYROID: A COMPARATIVE STUDY.

To comparatively assess the ability of proposed nuclear medicine techniques to localize recurrences of medullary carcinoma of the thyroid, we studied 13 patients with medullary carcinoma and evidence of recurrence based on elevated basal calcitonin levels and after stimulation (calciumpentagastrin test) and elevated CEA serum levels. Eleven patients underwent I~I-MIBG whole body scans, 13 patients underwent ~Tc-AntiCEA scans, 9 patients underwent =°iT1 scans and 8 patients underwent 9~Tc-DMSA(V) scans'. Confirmation of findings was obtained by CAT scans, NMR and/or surgery. lZI-MIBG scans localized the recurrence in 1 of 11 patients (9%). ~°IT1 scans localized the recurrence in 3 of 9 patients (33%). ~=Tc-AntiCEA scans localized the recurrence in 5 of 13~ patients (38%). 9~Tc-DMSA(V) scans localized the recurrence in 4 of 8 patients (50%). The association of ~Tc-DMSA(V) and any other agent did not produce improved sens!tivity. We conclude that nuclear medicine ~techniques have low s~nsitivity to detect recurrence of medullary thyroid carcinoma. I~I-MIBG scans are not useful to detect such recurrences. ~°IT1, ~Tc-AntiCEA and ~Tc-DMSA(V) can be used, however, when conventional imaging techniques do not provide localization of the recurrence. 

The purpose of this study was to determine the utility of PET scanning with FDG for the localization of pheochromocytomas in patients with false negative MIBG scintigraphy.

Two patients subsequently proven to have pheochromocytomas that were not detected by MIBG scanning have been studied. PET scanning with FDG was performed as follows: subjects were placed in the PET scanner with the region of the adrenal glands in the center of the field of view. After the injection of 10 mCi 18F-FDG, images were acquired dynamically for 50 minutes. This was followed by a "whole body" scan encompassing 40 to 60 cm in the z axis, Data were forward projected into images every 10 degrees for viewing as a series of rotating images.

In both patients, PET FDG scanning correctly identified the site of the tumors. In patient 1, scintigraphy with 1311-MIBG and 11C-HED (hydroxyephedrine) gave both false negative and false positive resulls, suggesting a pheochromocytoma in the left adrenal gland. This was resected but no tumor was present. However, a mass in the mediastinum adjacent to the heart was identified by PET FDG scanning. A pheochromocytoma arising from the left atrium was subsequently resected. Patient 2 had a left adrenal pheochromocytoma removed 7 years earlier. Symptoms recurred but 1311-MIBG scintigraphy was negative. PET FDG scanning located the tumor in the right adrenal gland, which was then resected and proven to contain pheochromocytoma. In both patients, whole body PET scanning considerably improved the anatomic localization of the tumors and facilitated comparison with conventional imaging techniques.

We conclude that PET scanning with FDG is valuable for the localization of the rare pheochromocytomas which elude detection with MIBG. The "whole body" technique greatly expands the capacity to find tumors outside their common locations. Further studies with FDG as an imaging agent for pheochromocytoma are warranted.

G.Pa~anelli. P.Magnani, C.Bonato, G.L.Di Sacco*, F.Sudati, D. Ge-lli* and F.Fazio We have evaluated the feasibility of three-step tumor targeting in medullary thyroid carcinoma (MTC) patients, using the anti-CEA monoclonal antibody (Mab) FO23C5 and the avidinfoiotin system in order to improve the target/non target ratio. Ten patients with histologically proven diagnosis of MTC were injected i v. with l m g of biotinylated Mab. After three days, 5 mg of Cold avidin Were injected i.v.; a third i.v. injection of labelled biotin was made 48 hrs later. Planar and SPET immunoscintigraphy was performed 2 hrs after Indium-111 biotin injection. All patients had increased circulating levels of CEA but only in three of them could conventional methods such as US, X-Ray CT and Technetium-99m DMSA localize the tumor. All patients had abnormal hot spots in the immunoscintigraphic studies. SPET was crucial for detecting small lymph-nodes with a diameter of 4 -7 mm. These lesions, not recognized as neoplastic by US, were confirmed to be neoplastic by fine needle aspiration. One patient, with US suspected solid lesions of 2 cm in the liver, had a negative liver scan and a hot spot in the neck. Histology revealed a benign liver lesion (angioma) and a metastatic lymph-node in the neck. These data suggest that this "three-step" method can have an important role in MTC follow-up MIBG is a specific marker in neuroendocrine tumors, such as pheochromocytoma (Ph), neuroblastoma (N), medullary thyroid cancer (MTC) and paraganglioma (pg), but it suffers in some cases (especially in MTC) of a lack of sensitivity. Thallium (TI) is a well known marker of cellularity with a great sensitivity and a lack of specificity. The aim of our study was to determine whethe r the association of these two markers is able to improve the detection O f neuroendocrinelesions. Patients and methods From 1989 to 1991, 107 sci~tigraphic examinations (exam) wer e performed using 1- in 83 patients (pts) referred either for suspioion (59 exam) o r for follow-up (24 exam) of Ph (52 pts),. N (6 pts),' MTC (i0 pts), MTC+Ph (6 pts), pg (9 pts). chloride was first injected (i MBq/kg), images were acquired from 4 to 20 min ; (4 MBq/kg) was then injected and images acquired 5 h and 24 h later. R e s u l t s Full agreement between MIBG and T1 : 47 negative images (including 5 false negative images with both isotopes) and 12 positive images (3 P h / 3 N, 1MTC, 2 Pg, 3 MTC+Ph) . sensitivities are reported,partly due to the non ideal properties of the radionuclide. A Technetium chelate should overcome the physical drawbacks of 201T1 and w i t h this aim 99mTc-MIBI,a myocardial perfusion agent, has been proposed for parathyroid scintigraphy.We examined the ability of the new radiopbarmaceutical in parathyroid adenomas localization and compared to 201Tl,ultrasound and CT. Sixty-six patients referred for suspected hyperparathyroidism entered the study and among them in the 27 thue far surgically explored,parathyroid enlargements were detected in 23 cases (4 were mediastinal).A correct location of the leeion/s was made in 22 (95%) by in 19 (83%) by 201Tl,in 15 (65%) by ultrasound and in 16 (70%) by CT. In one patient, a tertiary hyperparathyroidism, no parathyroid enlargement was detected and even surgery failed. In 3 patients the lesions resected belonged to the thyrold:one was a papillary carcinoma which showed a high uptake of 201Tl,while the 99mTc-MIBI concentration was very mild. The new radiopharmaceutical proved not only the best sensitivity, but in every case confirmed superior imaging ability, so that in the large majority of patients,lesion detection could be made by visual comparison of 99mTc-MIBI and 99mTcO4scans.We believe 99mTc-MIBI to provide a useful tool in parathyroid adenomas location and guess it will be probably the radiophar~aceutical of choice.

A. SIGNORE M. CHIANELLI, E. FERRETTI, E. TOMEI, P. POZZILLI, G. RONGA, G. CANTARANO and D. ANDREANI. Servizio Speciale Medicina Nucleate and Endocrinologia (I), II Clinica Medica, University of Rome "La Sapienza", Italy. We previously published that IL-2 (a T-lymphocyte growth factor), labelted with 1231, retains its capacity to bind in vivo to activated T lymphocytes, thus allowing the imaging of insulitis in diabetes susceptible animals by using a gamma camera. Aim of the present work was to apply this technique in newly diagnosed Type 1 diabetic patients to in vivo image the insulitis process occurring in the endocrine pancreas. Human recombinant IL2 (50gg) was labelled with 1231 using the Lactoperoxidase/Glucoseoxidase method and purified by HPLC before injection into the patient. To date, 4 newly diagnosed Type 1 diabetic patients, 2 long standing diabetics and 4 normal volunteers (age matched) have been studied by i.v. injection of 1 mCi of 1231-1L2. Dynamic gamma camera images were acquired for 60 mins after injection and a static image of the abdominal region was also acquired 4 hours later. ROl's were drawn over pancreas and major organs and time-activity curves were generated. In the same subjects we also performed an NMR study before and after bolus of Gd-DTPA using a 1.5 Tesla permanent magnet. Images were analysed using a fat suppression software. Gamma camera images showed that IL2 is rapidly cleared from the blood being mainly up-taken by kidneys. After 20 mins liver and blood activity was undetectable. Only in newly diagnosed diabetic patients we observed a high accumulation of the tracer in the spleen and in the pancreatic region being the first time that insulitis is visualized in humans. In 2/4 cases we also observed a concordant positive NMR result with high pancreatic signal intensity enhancement after Gd-DTPA, a sign of inflammation. 1231-1L2 is highly specific and can be used in alternative to other techniques for in vivo detection of pathological lymphocytic infiltrations. 

Phosphorus (P-31) nuclear magnetic resonance spectroscopy (P- allows an in vivo examination of energy metabolism in human tissues. It is known, that thyroid disorders are associated with abnormalities of muscle energy metabolism. The recent study was designed to evaluate whether in patients with latent hyperthyroidism deviations of the energy metabolism could be found similar to those observed in patients with overt hyperthyroidism.

In 25 patients (9 with overt hyperthyroidism before therapy and 16 with latent hyperthyroidism (TSH <_ 0.1 p.lE/ml)) and 24 healthy volunteers P-31-MRS of the calf muscle was performed (volumeselective, 1.5-Tesla whole body magnet (Philips)). For quantification of the spectra ratios between the peak areas of the muscle spectrum and of the spectrum of a K2HPO4 solution as external refence were calculated.

The table below showes the ratios of the peak areas between phosphocreatine (PCr), anorganic phosphate (Pi), and Especially, in patients with latent hyperthyroidism a significant decrease of the PCr compared to healthy volunteers was found. However, no difference of the PCr/Ref ratio occured between patients with latent and manifest hyperthyroidism.

Conclusion: Up to now studies on patients with latent hyperthyroidism without therapy showed psychosomatic deviations and only few informations about abnormalities of energy metabolism. The recent study seems to indicate that in latent hyperthyroidism deviations of metabolism can be measured by P-31-MRS and that they are similar to those observed in patients with overt hyperthyroidism.

Nuklearmedizinische Klinik ut~d Poliklinik Technische Universit~t M0nchen, *Krankenhauszweckverband Augsburg Germany

The diagnostical management of focal and diffuse thyroid diseases includes a variety of established examinations as serological parameters, sonography, scintigraphy and biopsy. Which additional informations can be expected from MRI? Material and methods 1) Retrospec~ve study: 151 MRI investigations of the head and neck region were retrospectivly studied, to evaluate thyroid diseases.

2) Prospective study: MRI was prospectivly performed on 32 patients with cold nodules or cold areas of the thyroid. Patients with suspicious aspiration biopsy had pdodty. Results and discussion 1) Thyroid disease incidence in retrospective study: struma diffusa 21%, struma nedosa 19%, cyst 10%, and adenoma 6%.

2) Diagnosis of cold nodules in prospective study : cyst 28%, adenoma 25%, struma nodosa 6%, thyroiditis de Quervain 3%, malignancy 37%. The diagnosis of a cyst in MRI can only be done in about 8% of the cases having ~n homogeneous fluid with low Tl-signal. Since adenomas show similar high signal in T2-weighted images and are often hardly distinguishable from cysts the diagnosis can only be certified by a contrast enhanced MRI showing enhancement only in the wall. The characteristical signal intensity for adenoma is hyperintensity in T2-weighted images and strong, homogeneus contrast enhancement after i.v. Gd-DTPA. Scintigraphic hot and cold adenomas show similar behaviour in MRL But after radioiodinetherapy the perfusion and the enhancement of an adenoma diminished significantly. MRI reveals a high soft tissue contrast and is suitable for imaging malignomas. Regardless of histology malignomas do not show similar signal characteristics in MRI, and are therefore not distinguishable from benign intrathyroidal lesions. Malignomas infiltrating the thyroid capsule are well shown. The accuracy of lymph node detection in MRI ist higher than with CT. MRI and its multiplanar images provides more information to the surgeon.

Focal, intraparenchymal thyroid changes should be known and recognized in MRI. Suspicious diseases acquire a further investigation by means of nuclear medecine. Additional informations are only expected in the diagnosis of malignomas.

Wolzt M t, Meghdadi S 1, Kletter K t, Leitha T 1, Angelberger p2, Schernthaner G 3, Dudczak R t. tDepartment of Nuclear Medicine, Vienna University; ~0FZ Seibersdorf; SKH Rudolfsstiftung, Vienna, Austria COMPARATIVE EVALUATION OF I123-OCTREOTIDE (OCT) AND I123- IN APUD-TUMORS The diagnostic potential of OCT and MIBG was compared in 7 patients with histologically confirmed APUD-tumors (4 carcinoids, 1 paraganglioma, 2 pancreatic endocrine tumors). All 19 primary or secondary tumor locations were verified by other imaging techniques (CT and/or NMR, sonography) and/or surgery. For OCT, dynamic (0-30 mi n p.i.; 14 lesions in the field of view), planar static (ap. and pa. projection; 2h, 4h, 24h p.i.) and SPECT images (360 °, 60 steps, 40 sec; 2h p.i.) were obtained. MIBG planar and SPECT images were performed 24h p.i. Images were classified as positive, equivocal or negative by two observers. I123-Oct I123-MIBG dynamic/static/SPECT static/SPECT positive equivocal positive equivocal A) Carcinoid 3/7/10 2/2/1 8/11 3/2 B) Paraganglioma 0/0/0 1/1/0 1/1 0/0 C) Pancreatic tumor 0/0/0 1/0/1 0/2 1/0 Number of lesions: A: n=15, B: n=l, C: n=3 All patients had abnormal scintigrams. Tumor visualization with OCT was best 0-2h p.i. (data in table) , only in 1 patient the result became positive 4h p.i. For MIBG the overall sensitivity was better. SPECT improved tumor detection for both agents. In one patient with carcinoid two lesions were only outlined by MIBG; one tumor of another patient was only seen with OCT.

APUDomas as OCT. Image interpretation with OCT is hampered by activity in the biliary tree, gallbladder and gut.

*R.Pani,F.Scopinaro,**G. DEPAOLA,^R. VACCARO, *L. VALLETTA *Med. Phys.,Sect. of Nucl. Med., Dptoof Experim. Med.,^Inst. Anatomy,Univ."La Sapienza",Rome,Italy,**FAMAF Unlv.cordoba,Argentine VERY HIGH RESOLUTION GAMMA CAMERA PROTOTYPE Anger camera has been perfected over the years an~ more or less complicated systems have been developed but spatial resolution did not improve oyer the limit of few millimeters. In this work we present some results relative to a new gamma camera prototype completely realized on our research laboratory to localize biological structures sized less than 1 mm. It is based on the use of a new photomultiplier position sensitive recently developed by Hamamatsu (R2486) with a cross wired anode on 6 cm of diameter. It has an intrinsic spatial resolution of about 300 micron. BGO and CsI scintillation detectors with different thickness were tested obtaining about 1 mm FWHM as the best spatial resolution~value. The system consists o~ gamma camera with 5 cm CsI detector diameter, special electronic chain and a 0.5 mm pin hole collimator. 99mT~ HMPAO (370 MBq[ were injected in a rat. The Drain was excisea and fixed-with glutaraldeide and cut into 0.5 cm thick slices. Images of whole brain (sagittal and coronal slices) and cerebellum were acquired. The gray matter was clearly imaged by the system. For example the cerebellar gray and white matter were recognizable in the acquired image without any treatmen. The slice of whole cerebellum were less than 1 cm large. Two different gray matter structures 1 mm distanced were clearly shown. This work has been supported by U.I.L.D.M. section of Rome.

K.Kouris G.Clarke, P.H.Jarritt. C.E.Townsend, S.N.Thomas, D.C.Costa and P.J.Ell. Institute of Nuclear Medicine, UCMSM, London, U.K.

The aim of this study was to compare the tomographic physical performance of the GE/CGR Neurocam and Toshiba GCA-9300A three-headed SPET systems. The former is a brain-dedicated device with its cameras fixed at 123 mm radius of rotation, fitted with HR or GP parallel hole collimators. The latter is a head and body system with adjustable radii (132-307 mm), lead fanbeam collimators (SHR) for brain, and parallel hole HR collimators for body studies.

Using a water-filled cylinder containing 99mTc, the tomographic sensitivity (kcps/(MBq/ml)/cm) was 30.0 and 50.7 for the Neurocam with HR and GP collimators, respectively. For the GCA-9300A, they were 34.8 and 33.8 with SHR and HR collimators calculated by exclu~ng the time during which data are not acquired during a scan. Unlike the Neurocara, these times are s~gnificant for the GCA-9300A: the rotation time per step is 8-12 s in a step mode acquisition; the rotation time prior to and after completion of a continuous rotauon acquisition is 8, 13 and 22 s for 1, 2 and 5 rain scans, respectively. Tomographic spatial resolution was measured using 99raTe line sources. The FWHM at the minimum radius for each system, at the centre, in air, was 9.0 and 10.7 mm for the Neurocam with HR and GP collimators, respectively, and 7.8 and 10.2 mm tbr the GCA-9300A with SHR and HR collimators. In warer it was 9.7 mm for the Neurocam with HR. collimators. compared with 7.8 and 11.0 mm for the SHR and HR GCA-9300A collimators. The tomographic contrast resolution was evaluated using the 3-D Hoffman brain phantom which simulates normal brain anatomy and a 4:1 grey/white nmtter ratio. With similar acquisition and processing parameters and using 8x8 mm 2 ROIs, the average grey/white matter ratio was 2.6 for the Neurocam with HR and 2.4 for the In conclusion, both systcres yield excellent image quality; inspite of its ~mproved FWHM. the GCA-9300A yields a lower grey/white matter ratio.

Kugi A, Bergmann H Dept. of Biomedical Engineering and Physics, University of Vienna, and L. Boltzmann Institute of Nuclear Medicine, Vienna, Austria EXPERIENCES WITH USER ACCEPTANCE TESTING OF 10 CAMERA-COMPUTER SYSTEMS During the establishment of a new nuclear medicine depamnent acceptance testing of 10 new gamma cameras, amongst them 7 SPECT systems, from 5 different manufacturers was carded out using a comprehensive test protocol. All the systems had been received in perfect working conditions according to the manufacturer.

The tests followed the procedures of the NEMA standard wherever possible, or the IAEA recommendations. For SPECT a test schedule by S. Graham was followed, including the use of a Jaszczak phantom for total performance and tomographic uniformity and contrast evaluation. Only about one half of the cameras passed all tests with the results within acceptance limits while the other cameras required major readjustments until the results were satisfactory. Some problems found during testing were that some evaluations were difficult to cant out due to unsuitable processing software of the system and that special programs for quality control, which were available in several systems, could not be verified independently. We conclude that comprehensive acceptance testing by the user is indispensable in order to ensure optimal gamma camera performance. User acceptance testing is supported at least partly by most modem camera-computer systems. However, the basic image and curve handling facilities of some systems are not well suited for purposes of quality control. In view of the obvious importance of independent acceptance testing some standardisaton in the latter area would be highly desirable. Ascq-France. (in coil. with ADAC Laboratories)

Present digital processing systems linked with (devoted to) the acquisition chain of scint~graphic examinations allow to fix up corrections for some distorslons (spectrometric and geometric) of the cameras. Concerning the uniformity correction, the usual way of doing consists mostly of using a collimated point-source which is set as far asposslble from the detector's hea~l (namely 5 times the diameter of U.F.O.V.)' removing the collimator one makes an acquisition summing up'several m~llion events. Thereafter a "correcting matrix" is computed which, once loaded into memory, will be use~t for every new acquisition.

This procedure can be credited with a relative easiness and fairly satisfactory results. However it cannot supply any precise and quantitative assessment of the quality of the setup correction, specially because of the use of a collimator during tliepatien~'s acquisition and not during the correction's acquisition. Fn practice, without any callibrated flood sources at medium and high energy. band, it is difficult to decide when, in consequence of variea drifts, the state of the corrrection has to be refreshed.

Thispaper intends to set up a orocedure making use of the wides-preaffF'.F.T, algorithms applie~t upon acquisitions of common sea-Ied sources (Co 57 anatomac marEers ani~ flood sources) or easily custom-made sources (Ga 67 and I131 quasi-point sources). Firstly, acquisition of the point-source is made witl~out collimator to ex-0tess, by means o f the F.F.T. transform, the intrinsic Modulation Transfer Function (M.T.F.) of the camera. The correcting matrix is also computed. After which 2 acquisitions of the same source are made with the collimator, with and without applying the correction.

An estimate of the non-corrected image is obtained by the use of the corrected image and of the inverse transform of the correcting matrix. This computed image is compared (least-square method) with the measured non-corrected image, in order to estimate the quality of the established correction.

Such a procedure can be performed for various energy domains (Low Energy, Medium Energy, Hight Energy), using the appropriate sources and collimators. After having got first results (works are in progress), we shall check to what extent the results are low dependents from the quality of the sources aud from the "computation noise".

T. S6ra, J. Mester, L. Csernay Albert Medical University, I~partment of Nuclear Medicine, Szeged, Hungary OPTIMAL USE OF A DYNAMIC LINE PHANTOM FOR THE DETERMINATION OF CAMERA DETECTOR UNIFORMITY Several methods are known for measurement of the uniformity of a gammacamera. A commercially available device, the dynamic line phantom has recently been proposed for this purpose. It consists of a line source which moves with constant speed over the surface of the detector. The problem is that, for a circular field of view, the observed count rate is a function of the position of the line source; it is the highest in the mid-position. With high count rates, deadtime losses or a pile-up effect may influence the measured values of the uniformity, while for low count rates, the stastistical uncertainity may be intolerable. We performed serial measurements on an older (Picker dyna 4C/15) large field of view camera, without a collimator, using the dynamic line phantom f'flled with 1.5 MBq 99m-Tc until the activity was decreased to 0.005 MBq due to radioactive decay. The uniformity was determined according to the NEMA standard. The uniformity values were stable only in the small activity range 0. 2-0.5 MBq. Below and above this range, they decreased significantly. The uniformity values determined in the optimal activity range are compared with those determined with a 20 MBq 99m-Tc point source in the table, which contains the data of 10 consecutive measurements with the line phantom and 5 measurements with the point source: It is concluded that the dynamic line phantom is suitable for the determination of detector uniformity even on cameras with a circular field of view, but the activity range of the line source for stable uniformity values must to be determined carefully.

CASE TESTING OF GAMMA-CAMERA QUALITY CONTROL EXPERT SYSTEM. P Slomka I T.D. Cradduck.Victoria Hospital, and University of Western Ontario, London, Ontario, Canada.

Routine QC testing of scintillation cameras usually involves a complex analysis of test results such as uniformity flood images and spatial resolution tests. Based on this analysis the user follows a set of troubleshooting prrecedures when the parameters fail to meet specifications. An expert system for quality control has been developed using a general purpose expert system toolkit ~Nexpert*. Various parameters of quali~ control images were derived by a separate image processing program which forms the basic input to the reasoning module. The objective of the system is to aid human decision making during quality control procedures, interpretation of results and troubleshooting. The major task in creating an expert system was the definition of valid and complete rules. Many rules, examples of which have been provided, are unique to the given camera-computer configuration. The prototype system has been developed using primarily simulated data and the application of the apriori formulated rules has sometimes been insufficient to properly identify the faults. The failure of the expert system to derive a correct diagnosis in these cases indicates the need to expand the rule database. A large database of quali~y control images with various well documented faults from different types of cameras is being collected and data are used to measure the performance of the system. Such a database can be used to incrementally improve the expert systom knowledge base in a learning fashion. In order to assess scatter, scintigraphic images were obtained over the standard 20% width energy window, with a 1 KeV step, either by list mode or multi-windows acquisitions. A detailed energy spectrum can then be obtained and analyzed in each pixel. An evaluation of scatter fraction was performed in experiments with a hot (Tc-99m) Phelps phantom with cold rods placed parallel to the gamma camera face at different distances with interposition of scaterring medium (lucite) of different thicknesses (0 -11 cm). Series of 28 images were obtained from 126 to 154 KeV for each position of the phantom. The energy spectra of 3 categories of pixels with different amounts of scatter were studied: pixels outside of the phantom (P1), over the rods (P2) and the radioactive phantom ( P3). In the areas P1 and P2 with the largest rods, the absence of peak and the low count rate above 140 KeV signed predominant scattering.The best polynomial fits of these scatter spectra were obtained with 3rd order polynoms but integrals of spectra and of 1st order polynoms were not significantly different. In the other areas P2 and P3, a photopeak was observed and increased scattering due to lucite resulted in: 1-the downshifting of 1 to 2 KeV of the peak while its 14 KeV FWHM did not change, 2-a significant increase of the count rate Ct at 126 KeV and 3-no significant count rate C2 change at 154 KeV demonstrating the absence of scattered radiation at that energy. With the hypothesis of a gaussian photopeak, C2 represents the photopeak contribution of C1 and the scatter Value at 126 KeV is (Ct-C2). Consequently, the total scatter count rate of an energy spectrum can be estimated as the triangnlar area 14 (Ct-Cz). The method applied to the phantom images produced considerable gain in image sharpness and the similarity of the different scatter free images. Conclusion: Scatter can be assessed from spectral analysis over the standard acquisition energy window. However, the clinical application still requires the optimization of a filter adapted to low count rate series of images. SPECT quantitation is improved by extracting scatter contribution from the projections prior to reconstruction and attenuation correction. As scatter proportion and distribution depends on the incidence, its estimation requires an adaptive procedure, such as Factor Analysis of Spectral Image Sequence using a Target Apex Seeking (FASISTAS). It has been proven to successfully separate primary and scatter photons in planar imaging for various radioisotopes (Tc-99m, . FASISTAS is assessed for Tc-99m SPECT studies. For each projection, a spectral image sequence covering a wide energy window (60-180 keV), obtained from a list mode acquisition, is processed by FASISTAS. The single a priori knowledge used by FASISTAS is an estimation of the spectral range including no primary photons. From each image sequence, FASISTAS extracts the underlying scatter and pure photopeak spectra and the associated images. The shape and proportion of the two spectra can differ from one projection to another to account for the variations due to the change of incidence. Filtered backprojection and Chang's first order attenuation correction were performed on the resulting scatter free projections. Phantom studies using various object to background ratios (from 0.2 to 6.2) have shown contrast improvement of up to 20% for scatter free slices when compared with conventional slices (reconstructed from 20% energy window projections). Spatial resolution has also been improved without introduction of artefact in uniform regions. By performing an adaptive scatter extraction, FASISTAS is an appropriate tool to improve qualitative and quantitative SPECT, and could be applied to SPECT studies using less favourable radioisotopes.

G Germano, T Chua, H Kiat, DS Berman Division of Nuclear Medicine, Cedars-Sinai Medical Center, Los Angeles 90048, USA OPTIMAL DYNAMIC SPECT IMAGING USING 99mTc-TEBOROXIME AND A MULTI-DETECTOR CAMERA.

The optimal acquisition/processing protocol and the technical challenges of 99mTc-teboroxime fast cardiac SPECT imaging were investigated on a high sensitivity Picker) .

Image quality, resolution and uniformity as a function of collimation (GAP vs. LEHR), detector rotation (continuous vs. step and shoot), orbit type (circular vs. non-circular) and angular range (1800 vs. 360 °) were studied with a commei'cial heart phantom and standard line sources. Optimal uniformity and defect contrast were obtained with continuous, non-circuiar 180 ° acquisition with LEHR and prefiltering of the projection data (Butterworth, order=5, cutoff=.215). This combination was applied clinically in conjunction with a "back to back", stress/rest adenosine teboroxime protocol, with data acquired as a succession of twenty 1-min dynamic frames.

Motion correction of the dynamic frames is very important if time-activity curves are generated via region of interest analysis, We devised a technique which makes use of a point sottrce marker to detect translational patient motion in the axial and transaxial dimension. All frames are automatically realigned (projection by projection) to a fit of the frame with the least amount of motion. The accuracy of the motion detection algorithm was tested with a point source in air and proved to be better than .04 mm or. 1 pixel.

Image artifacts are especially likely when high hepatic uptake is present, and may lead to severe underestimation of activity in the inferior myocardial wall. This phenomenon wa s observed in 7% of the patients.

In conclusion, dynamic cardiac SPECT imaging using 99mTc-teboroxime requires great attention to preserve image quality while increasing temporal data sampling. Fast scanning protocols will see their ideal application in regional tracer washout analysis to determine myocardial viability. 

PET and more recently SPECT studies provide dynamic three-dimensional data sets (4D). It results in possibilities to improve patient's physiological investigation with a special emphasis on quantitation. However, the huge amount of acquired data is difficult to analyze. A global processing method, FAMIS, based on multivariate analysis is proposed to estimate the underlying physiological kinetics and their associated volumetric distributions (3D). FAMIS was initially developed to process dynamic image sequences in planar scintigraphy. The method is based on a statistical fixed-effect model and assumes that each timeactivity-curve (TAC) associated with one pixel is a linear combination of the physiological kinetics. The analysis was extended to simultaneously process the whole set of slices under the single hypothesis that the kinetics shape corresponding to one structure is identical in the different slices. FAMIS is then performed from the TAC related to each voxel, which are clustered and thresholded. They are then submitted to an orthogonal analysis and an oblique rotation under positivity constraints, which provides a reduced number of factors. Factors estimate the tracer kinetics in the different structures : tissues or target organs. Their related 3D distributions are finally computed using a linear regression. The global analysis (time and volume) was compared to the conventional FAMIS approach (time and 2D) repeated for each slice, on both numerical simulations and PET studies. The 4D approach of FAMIS performs an accurate segmentation of functional volumes, improves the extraction of their related kinetics, and avoids the manual definition of volumes of interest. PET images of brain structures such as amygdala, thalamus or basal ganglia, which are relatively small compared to the resolution of the scanner, are degraded by the partial volume effect.

Quantitation of biochemical or physiological processes in these structures m a y therefore be inaccurate.

A stationary 2D frequency-domain restoration filter was optimized in order to compensate for the partial volume effect.

A 3D MRI-based, computer-generated brain phantom was used as test object for the filter performance. The actual radiotracer concentration is assigned on a p i x e l basis and thus known a priori.

The qorresponding PET image was computer simulated by convolving the MRI images with the PET point-spread function, giving an in-plane resolution of 13. mm. The filter was applied to the simulated image and the optimal roll-off frequency (f, cycles/pixel; pixel size 2.77 n~) was determined.

The coefficient of variation between the actual and simulated image was taken as a criterion of goodness of the filter performance.

The filter reduced the coefficient of variation in amygdala from 59% to 28% (f=0.25), in neocortical gray matter from 23% to i~% (f=0.23) and in white matter from 26% to 19% (f=0.20) .

Noise added to the simulated PET images increased the coefficient of variation in the filtered image for amygdala to 35%, for neocortical gray matter to 17%, for white matter to 26%.

The study indicates a new way of optimizing a restoration filter in PET based on a priori knowledge of the object. Quantitation and signal-to-noise ratio in relatively small brain objects such as the amygdala can thus significantly be improved. Images acquired using a new cardiac SPECT camera with two detectors joined at ?0 degrees may have the edge o£ the patient truncated. The effect of truncation and the performance of an algorithm to correct for the truncation have been evaluated.

Patient SPECT data were taken with a large f i e l d of view camera and the f i e l d of view was truncated to simulate the fieZd of view of the new camera. Both the original data and the truncated data were reconstructed with a f i l t e r e d back-projection algorithm. The reconstruction with truncated data showed a hot rim a r t i f a c t at the edge of the f i e l d of view with increased counts in the cardiac region. The magnitude of the a r t i f a c t was proportional to the t o t a l a c t i v i t y truncated from the image, so worse a r t i f a c t s were observed in studies with high extra-cardiac a c t i v i t y .

A d~rect non-iterative projection extension scheme was implemented to reduce the effect of truncation and these extended projections were reconstructed using the f i l t e r e d back-projection algorithm. Comparison with the original untruncated data showed that this technique produced minimal a r t i f a c t s and preserved the quantitative information in the heart region. Implementation of the extension scheme on a array processor gave an ~nsignificant increase in transaxial reconstruction time. Iterative algorithms have been suggested for the reconstruction of tomographic data containing a high noise level. Computer simulations show that when the iterative reconstruction algorithm passes a certain point, images begin to deteriorate. The purpose of this work was to reduce this effect.

The method reported here takes into account the area of an image pixel which contributes to a single projection element, using this area as a weight for calculating the projection elements. Thus, effects of partial plxel contributions are minimized. The iterative correction step was given by the arithmetic mean calculated as a sum of all quotients of measured and approximated projections. The procedure is implemented for rapid computation and therefore able to process routine PET data.

The method was assessed by comparing reconstructed and simulated (true) counts in each image pixel. For each of two parameters of image quality (normalized root mean square distance = SD and normalized mean absolute distance = AD) the reconstructed images showed broad minima. For SD the value was nearly constant from 0.210 for 20 iteration steps to 0.212 for 100 steps. The same shape was obtained for AD which varied from 0.147 for 20 iteration steps to 0.142 for 100 steps. Therefore the stopping rule was not sensitive to the number of iteration steps.

The procedure described here i s appropriate for the reconstruction of noisy tomographic data. It avoids image noise when many iterations are performed. In contrast to filtered backprojection it combines a high signal to noise ratio with an optimM image resolution. These effects involve the use of low-pass SPECT filter providing blurred reconstructed slices.

We propose some processing methods which compensate for these degradations. After scatter correction on projections by the Spectral Iterative Deconvolution method, spatial resolution and attenuation effects have been restored iteratively by a multiplicative algorithm.

Consequently, at each iteration, the signal to noise ratio was improved on resulting reprojections. Thus, the filter cutoff frequency has to be adapted at each iteration in order to preserve on the slices the benefits of these processings. This cutoff frequency was defined as the intersection point of the signal and noise power spectra calculated on the reprojections.

Quantitation of activity concentration, lesion detectability and volumes were performed before and after all corrections. MONTE CARLO simulations and Jaszczak's phantom results demonstrated the improvement of these parameters for the corrected images when compared to the original phantoms. Moreover, the whole processing automatically converges.

A.R. Formiconi, A. Passori Department of Clinical Pathophysiology -Nuclear Medicine Section University of Florence, Italy.

The performances of the least squares (LS) algorithm applied to region-of-interest (ROI) evaluation were studied by means of simulations and phantom studies. The LS algorithm is a direct algorithm which does not require any iterative computation scheme and also provides estimates of statistical uncertainties of the ROI values (covariance matrix). A model of physical factors, such as system resolution, attenuation and scatter, can be specified in the algorithm. In this paper an accurate model of the nonstationary geometrical response and attenuation for SPECT studies was considered. The algorithm was compared with three others which are specialized for ROI evaluation, as well as with the conventional method of summing the reconstructed quantity over the ROI. For the latter method, two algorithms were used for image reconstruction: filtered backprojecflon and conjugate gradients with the model of nonstatlonary geometrical response. In these cases, attenuation correction was performed ~nploying the Chang method. For noise-free data and for ROI of accurate shape LS estimates were unbiased within roundoff errors. For noisy data, estimates were still unbiased and the precision worsened slightly for ROI smaller than resolution: with a typical statistics of brain perfnslon studies performed with a collimated camera, the estimated standard deviation for a I cm square ROI was 10% with an ultra high resolution collimator and 7 % with a low energy all purpose collimator. Using conventional ROI estimates with the conjugate gradient iterative algorithm and the model of nonstationary geometrical response, bias of estimates decreased on increasing the number of iterations, but precision worsened heavily thus achieving an estimated standard deviation of more than 25 % for the same I cm ROL These results show that the LS algorithm with accurate modelling of physical factors applied to ROI evaluation allows to recover resolution effects with limited amplification of statistical fluctuations in comparison with techniques where image reconstruction is involved.

C. Van In order to achieve a reproducible delineation of the heart cavities during the cycle, we developed a program for the semi-antomated segmentation of 4D SPECT images. The red blood cells of 10 patients were labeled with 925 Mbq of Tcpertechnetate and a zoomed tomography was performed with a 3 head camera using a 64x64 matrix, 16 iimes bins, 180 steps on 360 degrees and 20 cycles per step. A planar acquisition the same day and an echocardiography were also performed. The automated segmentation used a modified split-and-merge algorithm which takes into account edge information during the splitting. We extended this segmentation to 3D and 4D in order to obtain more coherent segmentation results over the whole data set. Moreover, we also took into account the informations resulting from a Fourier transform. The operator is allowed to correct a degree of oversegmentation as a postprocessing step. The volume-time and activity-time plots for the 4 cavities were consistent in time. The left to right ratio of the stroke volumes of the ventricles was 1.02_+0.07 in healthy patients (n= 7) but was significantly increased (2.02+0.64) in 3 cases of mitral regurgitation, estimated at stage 2 by echography. A left ejection fraction of 70% or more and a right ejection fraction of 60% or more were considered as normal. The mean auricle to ventricle stroke volume ratios in normal conditions (7 patients) were 36.5 *. 10.7% right and 33.1 *-3% left. These limited results are promising for the clinical use of this kind of approach in the near future.

Clas Tegenfeldt, Michael Randen and Rj6rn Gudmundsson Image Processing Group, Dept. of E.E, Link6ping University, Link6ping,Sweden A system for fast interactive visualization of volumes obtained from SPECT is presented. The system is implemented on a SUN Sparc work station under X-windows. Volumes of size 64x64x64 voxels can be viewed either by browsing through the stack of slices or by generating projections of the volume from different view-points. Projections are displayed as 256x256 pixel image and the surfaces of the objects in the volume can be shaded by means of an illumination model ( e.g. Phong-shading) in order to enhance the users perception of the three dimensional structure of the volume data. To achieve the impression of a rotating volume, sequences of projections are generated by an algoritm that yields a speed-up factor of about 10 over traditional ray-casting methods. In the current implementation, rotation-sequences are generated and simultaneously displayed at sustained rate of about 5 projections per second ( the angle increment between successive 9rojections is set by the user) on a standard SUN sparc IPC. Sequences can also be saved for later replay at even higher animation rates (up 25 frames per second). Other features of the system include variable tresholding and pseudo-colouring of intensity intervals interactively defined by the user. The objective of our study was to compare the hemodynamic changes, the frequency and duration of ischemic ST-segment depression and angina pectoris, the occurrence of side effects and the duration of both tests as a whole, in 31 patients with angiographically proven CAD who where examined with both agents. The interval between the tests was one week. Dipyridamole (DIPY) 0.14 mg/kg during 4 minutes and from t=8 to t = 10 in the absence of angina pectoris or ST-depression. Adenosine (ADE-NO) 0.14 mg/kg during 6 minutes. Both tests were combined with lowlevel exercise. 6 EXC During both tests blood pressure, heart rate and ECG were recorded every minute.

Results: There were no statistical significant differences in the peak heart rates, increase of systolic blood pressure, the frequency and duration of angina pectoris and ST-segment changes but aminophyllin was needed in 14 patients after DIPY and in 6 patients after ADENO. Symptomatic hypotension occurred twice and dyspnea four times after DIPY and dyspnea occurred twice after ADENO. No AV-block was found. The duration of the ADENO test was 12.7±4.3 minutes, DIPY 18.7±5.0 (p<0.0001).

We conc{uded that Adenosine might be preferable to dipyridamole because of less severe ischemia and the shorter duration of the test. Cumulative reported data indicate a sensitivity of 91% for TM I-MIBG in the detection, staging and follow-up of neuroblastoma. However, 12~I-MIBG has more favorable characteristics for this purpose, such as a shorter halt-life, a 159KeV gamma-peak, the greater photonflux (for SPECT) and a shorter overall examination-time. On the other hand with 1231-MIBG it is not poesible to perform delayed imaging which may be a disadvantage in detecting tumors which have a slower uptake-mechanism or in detecting tumors in or near normal structures that have a relatively high MIBG-uptake. To determine whether 12~I-MIBG has the same sensitivity as comparative studies were done with both radiopharmaceuticals in 32 patients with neuroblastoma. The methodology of both tests and clinical examples will be presented. Scintigrams were scored negative (-) , positive (+) or very pesltive (++), and were given a score for image quality on a 0-5 scale. Patients. We treated 24 pts (mean age 51 yrsj affected by poliarticular RA for more then 5 yrs, previously treated with drugs unsuccessfully. According to ARA classes, 16 pts were in the 2nd class, 8 in the 3d; according_ to Steinbrocker's (radiographic lesior~ of the knee), 18 pts were in the 2nd, 6 in the 3d. In 3 pts both knees were treated, with an interval of more then 6 months. Treatment. The knees were injected intraarticularly with 90Y (160M~q), followed by 40mg of prednisolone. In 18 knees this treatment followed partial synoviecto~y (in artro~copy), with excision of the more important villuses. Results. The effectiveness was evaluated on clinical (pain, swelling, functional impairment) and ir~trumental parameters (Rx, arthroscopies) . Excellent results were seen even after i yr in 21 pts, mediocre in 2, poor in i. Radiodermitis at the injection site complicated 2.

Conclusion. The 2 pts with complications and the 4 with recurrences had not undergone partial arthroscopic synoviectomy before radiation therapy. On the c~ntrary, when the reduction of the synovial surface preceded 90Y, we had good results and no complications. The association of the two techniques is important when there are synovial loculus in the cavum, and when the synovial fluid is frankly corpuscolar at the arthrocenthesis. In our h a n d the m e t h o d shows e a s y to perform, f a s t anf reliable. 99mTc-MAG3 (D is at the moment the radiopharmaceutical of choice for renal function studies. However, some of its properties deserve further improvement, such as the unpractical and time consuming boiling step for its preparation and the limited shelf-life and activity of the reconstituted kit. We have now developed methods to eliminate both inconveniences, which may facilitate the daily use of this radiopharmaceutical.

Experiments to prepare 99mTc-MAG3 in a microwave oven (MW) have resulted in a very practical and fast method for the reconstitution of I with high (> 95%) radiochemical purity. A heating period of 30 sec is sufficient for completion of the labelling reaction. Many parameters, however, determine the conditions for optimal labelling: position of the vial in the MW, volume in the vial, power of the MW. It appears necessary to determine the optimal labelling conditions for each type of MW.

To enhance the stability we have studied the effect of a post preparation purification through a Sep Pak C18 cartridge equipped with a 0.2/~m sterile filter (SPC). Therefore, the cartridge is first activated with 5 ml of ethanol p.a., 5 ml of HC1 lmM and 5 ml of air. Then the preparation is loaded on the mini-column. Polar impurities are removed with 5 ml of HC1 lmM and finally, highly pure 99=Tc-MAG3 is eluted with 4 ml of ethanol 10% through a sterile 0.22 #m filter and diluted with saline.

Radiochemical purity (RCP) of 99"Tc-MAG3 was determined by paper chromatography and RP-HPLC. Purification by SPC of a 100 mCi preparation boiled for 10 min at 100°C improved the RCP from 95.5% to 98.5 %. The stability of the filtered 99mTc-MAG3 was > 20 hours.

It may be concluded that the use of a MW combined with a purification step through SPC provides a fast and reliable method for the preparation of very stable and pure 99mTc MAG3. Lymph node imaging represents a sensitive indicator of disease, however current methods are limited by the need for regional injection technics. We have developed a new class of imaging agents which localize in lymph nodes following intravenous injection. These compounds consist of a polymeric core of poly-I-lysine-DTPA with an external coating of dextrans of varying molecular weight. Labeling with both radionuc des and magnetic resonance imaging contrast agents has been accomplished.

One of these compounds, with molecular weight of 200,000 daltons, was radiolabeled with In-111 by ligand exchange and tissue distribution studies were performed in rats at 1,6,12,24 (n=6) and 48 (n=2) hours following intravenous injection. The percent of injected radioactivity was determined for all major organs. Regional lymph nodes were harvested and pooled. Whole body and organ distribution and clearance were monitored by sequential gamma camera imaging of all animals. Blood and lymph node kinetics are shown in figure. DEXTRAN-POLY-L-LYSI NE-DTPA Blood activity cleared with a ~E~ENr roSE ~ER~t~ T1/2 = 2.5 + 0.2 hrs; at 12 hours !I 02~ ~ ~0.~0 following inaction a maximum ~ 7\ / ~ L¥~"N~; "°'2° ~ concentration of 10.8+_0.8%dose/ ~ 0.~0 f= g was seen in lymph nodes, 35.7 ~, 20 ~ 0.00 _+ 3.7% in spleen and 0.75 + 0.2 0 ~0 20 ~0 ~0 50 in liver. Minimal uptake was H0~S observed in all other organs. Preliminary results in an animal with a thigh abscess showed marked uptake in lymph nodes draining the inflamed region.

These studies suggest that lymph node imaging can be performed following intrmvenous administration of dextrangrafted polymers that may be useful for detecting inflammation. A typical case is 2-123I-4-F-Ketanserin i.: 4-Br-2-F-Ketanserin ~ is a typical impurity in ~, the required precursor for labelling. ~ shows the same lipophilicity as i and also comparable binding properties for 5HT2 receptors. If about 0,1% of ~ is ~nitially present in ~, after the labelling reaction using about 10 -6 mol of ~, 10 -9 mol of ~ is collected with NoC.A. If injected there is a i00 fold excess competition of ~ for 5HT 2 receptors present in small amounts in thin layers in the brain cortex, thus decreasing the uptake of 2-123I-Ketanserin and rendering the SPECT interpretation erroneous. This was also observed in vitro and in the brain of small rodents. A high performance purification and high sensitive quality control of ~ was required. The terminal carbonylglycine moiety is believed to play an essential role in the interaction of PAHA, OIH and 99mTc-MAG3 (I) with the renal tubular cartier proteins. We have now synthesized and evaluated the in vivo behaviour of two derivatives of 99mTc-MAG3 (II and Ill) with a drastic change in the elecron density distribution of this terminal moiety due to conversion of the amide bond to -CH2-NH-CO-COOH.

The S-protected ligands were labelled with 99mTc by exchang.e labelling at I00°C in the presence of starmous tartrate. Analyms ,and preparative purification was performed by RP-HPLC on a Hypersil ODS column. For each of the ligands mainly one radiochemical species was obtained with a surprisingly shorter retention time than I. Biodistribution was studied in mice (n=5) at 10 and 30 minutes p.i. The 99mTc-labelled ligands were cleared from the blood by the kidneys and efficiently excreted in the urine. Activity in the bladder at 10 and 30 rain p.i. for 89 .5%) and for 99mTC -l] ] (78.6%, 86.9%) was higher than for I (69.6%, 85.2%) whereas liver uptake was lower for 99mTC-II (1.28%, 0.30%) and 99roTe-Ill (2.35%, 0.48%) than for I (5.55%, 1.22%).

In the baboon no distinct liver uptake was observed but clearance from the blood was much slower than in mice, which underlines the inter-species variability.

The study of two additional terminal oxamide derivatives of I is in progress and will be reported.

MIXED LIGANDS 99mTc (V)-COMPLEXES WITH TRIPODAL ANU MUmU-DENTATE THIOL AS CO-LIDAND: PREPARATION AND BIOLOGICAL  STUDIES. Recently we have studied the synthesis and character i z a t i o n , at c a r r i e r l e v e l , o f oxotechnetium (V) t r i p odal NzSz and NS3 complexes containing p-methoxy-thiophenol as co-ligand. In the present study we r e p o r t the preparation at tracer l e v e l , of this new class o f oxotechnetium neutral complexes. Biological results are reported as w e l l . The complexes prepared were o f the f o llowing type:

TcO(MeOC~H,S)[ X(CH~)zN(CHzCH~S)~ ] where X=EtS ( I ) , Et~N ( I I ) . Labelling: To a 9~mTc-glucoheptonate s o l u t i o n , equimolar q u a n t i t i e s o f the tripodal ligands and p-MeOC~H,SH were added in acetone. The mixture was exctracted with CHiCle, the solvent evaporated and the residue was subjected to HPLC analysis. Peaks corresponding to authentic samples of (I) and ( I I ) , prepared at T c -c a r r i e r level, were biod i s t r i b u t e d in mice. The need for reliable production of Fluorodopa (A) has led during the last past year to reports of various syntheses for this compound. Recently, a regioselective and enantioselective preparation of (A) starting from [lSF]fluoride produced by the lSO(p,n) nuclear reaction on leO-enriched water was described by our laboratory. The present work, can be considered as an improvement of this method which requires the asymmetrical alkylation of Boc-BMI (B). The main parameters for the application of this technique are described below.

The synthesis involves the regioselective [lSF]fluorination of the 6trimethylammonium veratraldehyde triflate in DMSO at 90°C for 10 rain (45 % EOB). After purification by the traditional C-18 Sep Pak procedure, the ftuoroveratraldehyde is quickly converted into the [lSF]benzyl iodide derivative by treatment with diiodosilane (DIS) and easily purified by column chromatography (Silica gel: CH2CI2) (36 %). After evaporation of the solvent, the alkylating agent dissolved in THF is added to the lithium enolate of Boc-BMI. Asymmetric atkylation (-78°C, 10 min, 27 %) , hydrolysis with HI (20 rain, 200°C) and preparative afford the L-[lSF]fluoro-amino acid in an overall radiochemical yield of 23 % (EOB) with an overall synthesis time of 90 rain.

Through this procedure, starting frorn 250 mCi of fluoride lSF', multimillicurie amounts (32 mCi) of n.c.a. (A) are now available at E.O.S. with good radiochemical purity ( e.e. -> 98 %).

In addition, using the same nucleophilic approach several other aromatic amino acids in the n.c.a, state such as 2-fluorotyrosine can be made at a high level of activity.

J.L.MORETTI*,C.BLANCHOT*,J.J.KOENIG**,R.ZINI*, F.X.JARREAU**,R.GERMACK*,G.DEFER*,P.NICOLAS* Radiopharmacology Laboratory (CHU Bobigny,CHU H. Mondor)) **Delalande Research -France

OH 3Bromobenzyloxy Phenyloxy Hydroxymethyl Propanol was labelled with Iodine 125 by exchange using SnSo4, gentisic Acid and cuso4 by eating at 140°C for 45 min according to MERTENS method. Labeling yield was around 92%. using HPLC and RPI8 column, Iodo*MD (MW ~ 412) was obtained without carrier (specific activity 125Ci/mmole) Biochemical experiments were carried out in vitro showing Ki for MAOB of 5.4 nM and of 5000 for MAOA (HA/B=926). Using Ex vivo Kinetic inhibition on rats (dose: 5 mg/kg p.o), results demonstrated a stron~ similarity of action of Bromo MD and Iodo MD with a inhibition percentage lowering with time ( 9 1 % 1 h, 48 % 8 h, 2 % 24 h). Brain rat iodo MD concentration was maximal after the first pass and inhibition decreasing slowly with time (T 1/2 = 1.8 hours). Rats were dissected at differents time post IV injection (0-2 hours), principal organs and brain were obtained, brain was separated in 7 pieces. Radioactivity was concentrated in liver (58,2±1,4%), kidney (2±0,5%) and brain (3,6±0,3%) larger in subcortical structures and cortex than i~ cerebellum. MD 360194 I125 was prouved to be interesting for brain structures labeling, its relatively slow reversibility with time makes its application possible for brain SPECT in humans when labeled by 123 Iodine. 

99roTe-labelled red bloodMells (RBC) are superior to 99mTc-HSA for ventriculography, but their labelling is more complex, time consuming and risk-beating (in vitro labelling) or suffers from interference of some medications (in vivo labelling). We have now modified human serum albumin (HSA) by the introduction of mercapto groups with the purpose to prepare a stable with long retention in the vascular system. Such preparation would constitute a potential practical alternative to HSA was incubated with 20-100 mols CHa-CO-S- to introduce an acetylmercaptoacetyl chain on some of the lysine amino groups. After purification by size exclusion chromatography (SEC) on Sephadex 025 the mercapto groups were deprotected by different methods: incubation at pH 11, pH 9,5, pH 7 or treatment with NH2OH. The presence of free thiols and their number was determined by measurement at 412 nm after treatment with Ellman's reagent. The reaction products after deprotection were used after or without SEC-pufification for direct or exchange labelling experiments with 99roTe at neutral or acidic pH. SEC-I-IPLC on a 300x7,8 mm Biosil was used to determine labelling yields and to isolate pure 99mTc-MA.

After reaction of SATA with HSA in a 25:1 ratio and deprotection with NH2OH a very stable (> 6h) 99mTc-MA could be formed by direct or exchange labelling in > 95 % yield. Its stability and retention in vivo in plasma (mice) is clearly higher than that of 99mTc-HSA. Improvement of the in vivo stability and of a kit preparation is now under investigation.

The preliminary results indicate that the preparation of a stable 99~Tc-mercaptoalbumin is possible, it will be further compared with 99mTc-RBC tO determine its clinical usefulness. A specific binding site for cocaine has been identified in the human brain and related to drug self-administration and to cocaine dependence. The binding site appears to be localized to the dopamine transporter presynaptically on nerve terminals in the basal ganglia. ~-CIT (2 ~ ~ carbomethoxy-3~-(4-iodophenyl) tropane, Kd=0.11 nM) is a cocaine derivative. To examine cocaine binding in the living primate brain ~-CIT was labelled with IIc by Nmethylation of nor~ -CIT with (llC)methyl iodide. The total radiochemical yield of (IIc)~CIT was 40-50% with an overall synthesis time of 35-40 min (inel~ding HPLCpurification and sterile filtration). The specific radio~ activity at time of injection was about I000 Ci/~mmol. In PET-studies (IIc) ~CIT was injected into Cynomolgus monkeys. Specific binding to cocaine receptors was examined in a displacement experiment with unlabelled cocaine. PET-analysis demonstrated accumulation in the striatum with a striatum to cerebellum ratio of about 5 aft k er 87 minutes. In the displacement experimeni, radioactivity in the striatum but not in the cerebell~m was reduced after injection of 20 mg cocaine. This finding indicates that striatal radioactivity following injection of (IIc) ~-CIT is associated with cocaine binding sites and that the binding is reversible. (IIc) ~ -CIT has the potential of a suitable radiotracer for the imaging of cocaine binding sites in the human brain in vivo by PET. TcN-NOET, his (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium (Tc-99m) is a new neutral myocardial imaging agent now under preliminary clinical studies. In order to improve its imaging properties, we studied the effect of the modification of nitrogen side chains on the uptake of target and non target organs in dogs. The following neutral TeN bis dithioearbamato complexes TeN (R R' NCS2)2 were prepared : R=C2H5, R'=CH3OC2H4 (1) ; R=R'=CH3OC2H4 (2) (1) and (4) on the N side chain shifts the H/Lu maximum ratios toward earlier times than NOET, while two ~-methoxy groups (2) gives a too rapid heart clearance. /~-ethoxy derivative (3) has best H/Lu ratios than NOET but the latter displays the better H/Li ratios during the overall experience. The mRNA of nucleated cells in blood were targeted for developing a new technique of labeling neutrophils by in vivo hybridization with In-DTPAAHON with ttistone4-specific mRNA. The anti-sense oligonucleotide(25mer) specific for histone4 and sense (control) was synthesized with DNA synthesizer and coupled with aminolink (Applied Biosystems). AHON was coupled with DTPA-isothiocyanate and purified by gel-filtration. 200-300 ~Ci of I n -l l l chloride was added and unbound I n -l l l was separated by gel-filtration. Cauine, porcine and human blood was collected in ACD anticoagulant and neutrophils (NP) were separated by Volex-sedimentation. We optimized the conditions of the NP~ uptake e.g. concentration of DTPAAHON, pH, time and temp. Aliquots of human NP, platelets, red ceils were incubated with both probes in ACD-plasma for 30 rain at 37°C and washed with ACD-saline For a long time attemps have been made to evaluate 99roTe-based tubular secreted renal function imaging agents. In order to substitute iodo-hippuric acid, the development of 99mTc-MAG3 was a first success. Nevertheless, because of the relatively low clearance ( 50 % el. p-amino-hippuric acid) it is desirable to develop new To-based renal function imaging agents. The present study describes the synthesis of 99mTc-Diaminomereapto(thio)ethers as a new class of tubular excreted compounds. Therefore a first compound of this series, ,10-dithia-deeanoic acid (.D has been synthesized by the reaction of Suecinimidyl-Sbanzoyl-thioglycolate and S-Aminoethyl-L--cysteine. The 99roTe-complex of _1 can be obtained in radiochemical yields of > 90 %. HPLC results in a product with a radiochemical purity of more than 99 %, either by hydrolysis of the protecting group prior to the complexatiun ("cold kit') or during the labeling reaction ("hot kit"). The complex is stable at room temperature over 24 hours as well in aqueous as in organic solutions. Octanol-water partition coefficients indicate a very hydrophilie compound, but surprisingly, electrophoresis shows a neutral complex between PH = 2 -7. Organ distribution was determined in rots. Within 24 h 40 % of Tc-DAMTE are excreted to into the feces and 43 % into the urine, whereas 15 % were bound to blood cells and 10 % were retained in the kidneys. In contrast, first studies in humans showed a very fast renal elimination of Tc-DAMTE, a lower liver uptake (< 10%) and no retention in the kidneys. The protein binding of > 95 % and the renal clearance of ea 200 mllmin/1.73 m 2 suggest a high tubular axeretiun rate of the compound. These results show, that Diaminomercapto(thio)ethers are very promising as renal function imaging agents. The synthesis of other DAMTEderivatives will be reported.

R. Pasqualini, E. Bellande, V. Coma72i, A. Duatti, CIS bio international, Gif sur Yvette, France. Universi~ di Bologna, Italy.

NrrRIDO D1THIOCARBAMATE MYOCARDIAL IMAGING AGENTS.

Neutral bis(dithiocarbamata) nitrido teelmedum (V) complexes are new promising imaging agents, which showed high myocardial uptake in various animal species and in humans. Ws reported recsntly the preparation of these compounds, at no-carrier-added leve~, though simple substitution reactions of dithiocarbamate ligands onto a performed interm~iate containing the Tc=N group. This Tc-99m uitrido intermediate was obtained in high yield (>98%) by carrying out ths reaction of pertechnetate with S-methyl, Nmethyl dithiocarbazate, in the presence of HCI and tertiary phosphines, at 100°C.

We studied the preparation of bis(dithiocarbamato) ultrido techntium(V) complexes using dithioearbamate ligands bearing side chain modifications on the basic [NC(S)S] functional moiety. Since it was generally observed that side groups on these ligands were unstable in acidic conditions, we tried to form ths Tc=N bond at neutral pH. Stannous chloride was used as rednstant in the reaction becans~ of the dirainished reducing power of tertiary phesphines in neutral sofutiuns. It was also investigated the ability of various hydrazine-like derivatives to donate ultride nitrogen atoms.

The results showed that the highest yidds of formation of the Tc=N group were obtained at 100°C (97%), and at room temperature (88%) using Smethyl, N-methyl dithieearbazate, which appeared to be the most efficient dunnor of intride ions. Chromatography and ligands exchange reactions showed that the Tc-99m nitrido intermediate prepared through this alterastive routs is chemically differant from that obtained using the previous procedure. However, reaction of this species with dithioearbamate ligands led always to the same final bis(dithiocarbamato) nitrido technetium (V) complexes without altering ths uptake of these radiopharmaeautieals by myosardinm cells. 

A "crossed cerebellar diaschisis", i.e. reduction in metabolic activity has been demonstrated by Baron (1980) in unilateral lesions of one cerebral hemisphere. In the present study, we investigated if reverse effects do exist, i.e. a arop of the cerebral blood flow (.CBF) in the cerebral hemisphere contralateral to a cerebellar lesion.

We examined 12 patients with one unilateral lobar (S cases) or lobar and v e r m i a n ( 4 cases) cerebellar haemorrhage. CBF were analysed using the SPECT method, bE inhalation of 133 Xe. The measurements were obtained from 3 slices (OM plane +1, +5, +9, cm). The rCBF values were quantified in the cerelSellum (CER) and in 9 areas on the cerebraq hemispheres: frontal anterointernal (Fro/), anteroexternal (FRo2) and posterior (FRo3), temporal anterior ( T e m l ) a n d posterior (Tern2), parietal (Par), occipital (Oct), lenticular (Len) and thalamic (Tha). "The rCBF values and next the asymmetry'indexes (A.I.) of the patients were statistically compared (p = .01 ; Mann Whitney) to those of 24 control, age-matched, sub-~ cts.

The. comparison of rCBF values in the patients and control subiects showed that the median values were significantly inferior in t~e patients in the controtateral areas Fro2, Fro3~ Len and in the ipsi!ateral Cerebellar and Frol regions. The analysis of the AI revealed that the median cerebellar AI was significantly higher in the patients ; the same phenomenon was observed in the areas Fro2, Len and for the whole hemisphere. Furthermore~ the period that had elapsed since the stroke was not correlated wrth the rCBF values. Significant tendencies ~.01 < p < .03) were observed between the ¢limcal cerebellar score (0 to 8) and some of the rCBF values of the c0ntralataral: (Teml, Tern2, Par, Occ, Len and Tha) and of the i,~.siiater.al (Par, Occ, Tha) hemispheres. LqSCUSSIOU.

~ These results suggested that a reduction of rCBF is associated to the controlateraF curebellar lesions. This phenomenon predomifiates in the anterior part of the cerebral cortex and in the basal ganglia. It can be related to the essential and reciprocal anatomical conuections between the cerebellum,, the thalamus and the frontal structures. The tendency to correlation between the clinical score and the rCBF values also suggested a link between cortical deactivation and severity of ataxia. Nimodipine is a calcium antagonist that has a potential beneficial effect on the neurologic outcome of acute ischemic stroke. To investigate its effects on cerebral peffasion in acute stroke, we studied 9 patients who suffered a first acute ischemic stroke, and who took part in a randomized trial of nimodipine. The diagnosis was confirmed by clinical observation and CT. Six patients received nimodipine by continuous intravenous infusion, from the first day of their hospitalization to the 5th day onwards. Three patients received placebo. Brain perfusion SPECT with HMPAO was performed on the first and fifth day of treatment. After termination Of the trial, the control group was expanded further with 12 consecutive patients complying with the same diagnostic criteria and treated conventionally. SPECT data were reconstructed and two circumferential profiles consisting of 64 4*4*4 pixel samples were generated, one representative for the frontaparietal cortex, and the other for the lower frontal and the temporo-occipital areas. Data were normalised to the cerebellar activity. Patient data were compared to a database established in 11 healthy volunteers, and consisting of mean values and standard deviations for each data points in the 2 profiles. For each patient study, data in the profiles were recalculated as differences to the mean normal value, measured in standard deviations. An ischemia index, I, was defined as the area (measured in standard deviations) of the profiles extending below the lower confidence limit of the normal population. A hyperperfusion index, H, was defined as the area of the profiles extending above the upper confidence limit. On the first day, no statistically significant differences were found between the treatment and control groups for I (treatment group: 14 =113~106; control group: 11=72+70 ) nor H (treatment group: H~=10~_15; control group: H1=38-+41 ). On the 5th day, ischemia had decreased in both groups (treatment group: 15=93+91 , control group: 15=42+57). Hypedusion had slightly increased in the treatment group (H5=17+19), and had remained stable in the control group (Hs=38+43). However,the changes of I or H from the first to the second study were not statistically different between the groups. In conclusion, within the 5 day time frame studied, we found no significant effect of nimodipine on the extent and intensity of ischemia/infarction, nor on luxury hyperperfusion. Alterations in central nervous system function have been observed after expeditions on high altitudes. The underlying physiopathological mechanisms, though incompletely understood, are presumably in great part related to hypoxia and hypoxia-induced reduction of cerebral blood flow (CBF). Nine members (8 male and 1 female, mean age 32 years) of the "Belgian Tibet Expedition 1991", underwent a Tc-99m HMPAO brain SPECT study before and after their stay on high altitude. Two persons reached a maxi-mal altitude of 8043 m; seven individuals went to -+ 5800 m at least. Each scatter corrected, reconstructed and reoriented data set was submitted to a semi-quantitative analysis, consisting of a circumferential delineation of the cortical and cerebellar activity in 4 consecutive transverse slices: 64 cubic, partially overlapping, 43 pixels containing volume elements (VE) were automatically generated with a constant angular increment of 360°/64. This procedure was carried out for a lower, middle and upper cerebra! level. The count value of each VE was normalised to the maximal cerebeliar value. In order to compare individual regional CBF (rCBF) before and after the expedition, relative differences in rCBF were calculated for each VE as: relA (%) = 100.(value after expedition -value before expedition)/value before expedition. Results: A) in 4/9 cases regional relA values were negative in most cortical regions (with minima between -10 and -20% predominantly left temporofrontal); in 3/9 persons relA ranged between-5 and +5% and 2/9 climbers showed a positive relA value in most cortical regions; B) the mean relA (per cortical VE) ranged from -9.6 to +6.3%; C) for the group in its totality: 1) a mean decrease of 1.7 % in global cortical CBF and 2) significantly(p<.01) negative relA values (corresponding to a diminished rCBF) in a left temporal-temporofrontal cortex region were observed.

In conclusion, the applied semi-quantitative analysis of Tc-99m-HMPAO SPECT data enabled us to demonstrate rCBF changes after an expedition on high altitudes. In the 99mTc-HM-PAO SPECT study a semiquantitative assessment of regional cerebral blood flow was performed by means of a relative perfusion index between the two hemispheres. Squared regions of interest, 4x4 pixe], were placed in the anterior, medial and posterior cortical areas o£ the brain cortex in four consecutive txansaxial slices, excluding cerebellum. Three index values for each of the four slices were calculated by the ratio between symmetrical count values. Among 15 left brain damaged patients, 7 were aphasics, 6 of them had left cortical hypoperfusion and only one o£ the non aphasics showed a reduced cortical perfnsion (limit index = 0,8"/). On the 18 right hemispheric damaged subjects four had neglect, 3 of them had regional parietal hypoperfusion and one patient with transitory neglect had also parietal hypoperfusion. Moreover, 3 patients with localized frontal hypoperfusion failed to show neglect.

1. A good correlation is obvious between left cortical hypoperfnsion and subcertical aphasia. 2. In right hemispheric subcortical lesions a correlation between cortScal hypoperfusion and neglect seems to be present, but only if hypoperfnsion is localized at parietal cortex. Two essentially identical multi-center trials were conducted to determine the sensitivity and specificity of Neurolite® kit for the preparation of as an aid in the diagnosis and localization of stroke. In each trial, European (02) and North American (03), at least 100 evaluable stroke patients and 30 neurologically normal volunteers had a Neurolite® SPECT imaging study. All evaluable SPECT images were read institutior~ally by the principal investigator and three blinded readers who did not participate in the trial. The location of perfusion defects, which was noted independent of clinical assessment, was compared to the location of the functional defect determined from the overall clinical impression excluding the Neurolite® study. Neurolite® was safe and well tolerated in all subjects. Neurolite® sensitivity and specificity percentages for localizing stroke are listed below:

Institutional Blinded Read ~'~'~gy # 02 03 02 03 Sensitivity 87 86 74(78) 61 (73) Specificity 9 7 9 8 8 8 9 8 In general, the sensitivity and specificity of Neurolite® was the same in all phases of stroke. Inter-reader reliability was very consistent in both blinded reads. Lower sensitivity in the blinded reads is expected and was partly attributed to the blinded readers lack of familiarity with the multiple format of SPECT images. Sensitivity was similar for all types of strokes except for lacunar which showed decrease sensitivity both institutionally and in the blinded reads. The lower blinded read sensitivity of study 03 disappeared when lacunar strokes, which had a higher incidence in the 03 study, were excluded (value in parentheses). In conclusion, Neurolite® SPECT images are sensitive and act as a specific marker in localizing brain regions which are functionally impaired due to stroke.

E.Kreuzer. R.Wagner ~, J.Hasenberger ~, N.Schad* Herzchirurgische Klinik, Klinikum Gro6hadern, D-8000 Mfnchen 70 and ~St~dtisches Krankenhaus Passau, D-8390  Passau   METABOLIC-FUNCTIONAL  IMAGES OF HEARTS WITH CORONARY AR-TERY DIS EASE AND DECREASED VENTRICULAR FUNKTION: INVE-STIGATIONS USING 123 Metabolic-functional images ~rom hearts of patients (pts) with coronary artery disease {CAD) and reduced ejection fraction (EF) provide informations about regional metabolic processes in dyskinetic and akinetic wall areas. 23 pts [mean age:58.8 years) with a reduced EF (mean EF: 41.6%) underwent pre-and postoperatively (p.o.) metabolic imaging ~n a fatty acid study ac res~ and during exercise. There was a total of 27 infarctions in the pcgroup, resulting in 21 cases of akinesia and 7 cases of aneurysms of the anterior ventricular wall. Angiographic examinations revealed 17 times a three-vessel disease, 7 times a two-vessel disease. Parametrlc images of regional rates of IPPA clearing (5-oxidation) and IPPA increase { accumulation} for different time intervals after injection were generated by a multi-crystal gamma camera comparing coronary angiography and ventricular angiography. 1 mCi of IPPA was applied i.v.. In comparison of pre-and postoperative fatty acid images we see an increase of metabolic processes in the akinetic and dyskinetic areas after revascularisation in more than 90% of the cases. There was an increase of accumulation and clearing rate of 6.56% (S. ~.=ii.02), 1.23 (S, n 1 =7.8) resp. The subjective wei~:~ing was found us~n~ l questionary also improvement was defined in more than 90% of the pts. We conclude resting IPPA imaging identifies viable myocardium in patients with low EF and hypokinetic and akinetic ventricular wall area, providing a safe, cost effective technique for myocardial viability assessment. patients with systemic myopathies proven by muscular biopsy (mitochondrial (28), Curshmann-$teinert (7), congenital (3 I, muscular-dystrophy (7), etc.), were investigated with 15-(p-[I-123] iodophenyl)pentadecanoic acid (IPPA, 6 mCi) and sequential SPECTscintigraphy after subma×imal exercise, radionuclide ventricu[ography (MUGA) at rest and stress (99mTc-RBC, 20 mCi), ECG, 24 hour-ECG (LECG), and echocardiography (US). The quantitative comparison of the oblique slices of the SPECT-studies revealed turnover-rates as a qualitative measure of B-oxidation. Serum levels of lactate (L), pyruvate (P), glucose (G) and triglycerides (TG) were measured at rest and stress. Anamnestically 85% of the patients had cardiac chest pain. The clinical investigations (auscultation, RR,.etc.) revealed a pathologic result in 40%. In 55% and 75% of the cases the ECG and LECG were abnormal, respectively. US revealed a pathologic result in 47% whereas the MUGA was abnormal at rest in 28% of the patients and, in addition, 25% had a pathologic stress reaction. In 83% of the patients fatty acid metabolism was disturbed (disseminated in 45%; regionally in 38%). In 99% there was a coincidence of abnormal fatty acid results ~ with cardiac chest pain. The IPPA results were not due to raised serum levels of the competing substrates (L at rest: 1.2±0.8; at stress: 1.9±0.9 nmol/I p >0.5; P at rest: 62±21 ; at stress: 66±39 i~mol/I, p >0.5; G and T6 unchanged). In conclusion, IPPA-SPECT is a sensitive indicator o~ cardiac involvement in patients with systemic myopathies and is a pathognomonic imaging procedure in these diseases. Work supported by the U.S. DOE at ORNL (DE-AC05-84OR21400), NATO (CRG 900966), and the Alexander von Humboldt Foundation (FFK). Two normal, f a s t i n g v o l u n t e e r s were examined for 30 m i n u t e s on t h r e e d i f f e r e n t d a y s a t rest, d u r i n g s u b m a x i m a l e x e r c i s e and a f t e r i n t r a v e n o u s injection of 0.5mg/kg dipyridamole. Dipyridamole was used to i n c r e a s e t h e myocardial blood flow i n d e p e n d e n t l y of the metabolic demand. Pulse r a t e and blood p r e s s u r e were monitored c o n t i n u o u s l y during t h e s t u d y in order to e s t i m a t e t h e m y o c a r d i a l oxygen consumption by the r a t e -p r e s s u r e -p r o d u c t . In all studies, the myocardium was c l e a r l y d e l i n e a t e d . The time c u r v e s of m y o c a r d i a l a c t i v i t y were a n a l y s e d by the P a t l a k plot method, using p l a s m a a c t i v i t y c o r r e c t e d for m e t a b o l i t e s by HPLC a n a l y s i s . A l i n e a r P a t l a k plot was o b t a i n e d in all c a s e s i n d i c a t i n g i r r e v e r s i b l e u p t a k e . The slope i n c r e a s e d a b o u t 60% during exercise, but r e m a i n e d n e a r l y u n c h a n g e d a f t e r a d m i n i s t r a t i o n of dipyridamole. In a g r e e m e n t , the r a t e -p r e s s u r e -p r o d u c t was doubled during exercise. T h e s e p r e l i m i n a r y r e s u l t s i n d i c a t e t h a t the u p t a k e r a t e of FTHA into m y o c a r d i a l ceils is d e p e n d e n t on t h e i r metabolism and oxygen demand, and not on myocardial perfusion. 

The o b j e c t i v e of this study is to d e t e r m i n e if the s e v e r i t y of relative perfusion defect can d i s t i n g u i s h v i a b l e m y o c a r d i u m from scar. imaging were analyzed for p e r c e n t a g e uptake in i r r e v e r s i b l e defects. Ten patients had scar; ten had viable tissue confirmed by F-18 FDG scan. All 56 i r r e v e r s i b l e segments were q u a n t i f i e d by a 10% and 5% color scale.

Segment P e r c e n t a g e D e c r e a s e d To quantify noninvasively stable and unstable regions of myocardial oxidative metabolism and physiologic workload changes,"transfer characteristicn-PCr/Pi of ~ P-MRS variations were systematicaly analysed in vivo,in the canine heart,4 healthy volunteers and 11 patients with hypertrophic cardiomyopathy,using modified Michaelis--Menten approach.Siemens MRI/MRS system operating at 2T was used at 35.89 HHz.The canine's heart was stressed with persistent hypoxia(Fi02 12%,then 8%)causing two episodes of cardiac failure.Normal operating zone(OP) was observed at PC~/Pi at 4.9;first metabolic crisis with OP at PCr/Pi at 0.7 and 10 min later a second failure occured with OP off scale to the right at PCr/Pi of 0.2 which was irreversible.For healthy persons OP of PCr/P± of 2.1 was calculated;and for patients with hypertrophic cardiomyopathy and lowered Vmax for oxidative metabolism an OP of 0.9 for PCr/Pi wa~ calculated.Thus, the findings suggested that PCr/Pi values of less than 1.0 for cardiac tissue causes an unstable OP that leads to initial hypertrophy and e~entual heart failure and PCr/PI of 0.6 or less,suggest imminent heart failure. This simple rational of metabolic control based on the modified Michaelis-Menten theory of enzFme action identifies significant stable and unstable regions of myocardial oxidative metabolism and physiological workload. To assess the influence of vessel and/or graft patency of dectively revascu/arized coronary arteries on postoperative outcome of dysfunctioning but viable myocardium, 20 patients (pls) with preoperative regional wall motion (RWM) abnormalities underwent prospective serial quantitative coronary and left ventricular contrast angiography prior to (pre) and 5-~1 months after (post) PTCA (n=ll) or CABG (n=9). All pts preoperatively demonstrated evidence for preserved tissue viability by nuclear imaging using Tc-99m MIBI SPECT for evaluation of resting perfusion, and PET in combination with F-18 FDG for metabolism analysis in the region supplied by the vessel to be revascuiarized. SPECT/PET data were compared semiquantitativelyin a computed polar map format using customized software. RWM was analyzed independently by the centedine method (LAD and RCA regions only) and is expressed as difference in SD from normal RWM of a reference population. Negative values indicate hypokinesis. Results are given as mean of RWM for regions grouped as A (good angiographic result at follow-up), B (>50% diameter stenosis at follow-up) , and C (normal or i m ~aired RWM at baseline, but not revascularized), l~e~ions ( 2-bis(dihydro-2,2,5,5-tetramethyl3 (2H)-furanone-4methyleneamino) ethane) bis(tris (3 methoxy-lpropyl)phosphine)99mTc(11I)) has been demonstrated to have optimized properties for myocardial perfusion imaging. To promote the ready use of this agent, we have formulated a one step kit. Aim of this study is to confirm that the characteristics of purified Q12 and Q12 prepared from a kit are equivalent.

Biodistribution of kit formulated 99mTcQ12 was evaluated by conjugate view counting procedure in 3 fasted, resting, normal, male volunteers at 1, 3 and 5 hours post i.v. injection of 12 mCi. SPET images were acquired at 1.5 hour; blood and urine samples were obtained throughout the study up to 24 hours after injection. Kit formulated 99raTcQ12 shows to behave as the purified material; the heart uptake (2.3+0.1% i.d. at 1 hr) is rapid, without significant myocardial washout up to 5 hours p.i. In addition, kit formulated 99mTcQ12 is cleared rapidiy through the hepatobiliary system, allowing images acquisition within a few minutes after injection. Twenty patients with demonstrated coronaropathy were studied with SPET using a rest/stress protocol; in 5 patients, ejection fraction and wall motion were also evaluated during the rest session. Under fasting conditions, excellent image quality could be achieved 30 rain after administration of 20-25 mCi of kit formulated 99mTcQ12. These results confirm and extend the potential of 99mTcQ12 as a promising tracer for routine myocardial function studies. 

Validation of the Method in Isolated Rabbit Hearts Purpose: The use of Rubidium-81 allows quantification of absolute myocardial blood flow. Prinoiple of the measurement is the flow related change of the equilibrium between Rb-81 and its dif-i fusable daughter Krypton-81 m in the myocardium. Flow can be calculated by F=3.2P((Rb/Kr)-I). [F: Flow in ml/min/g; P: partition coefficient for Kr gas; Rb/Kr: activity ratio between Rb and Kr], We compared myocardial perfusion measured by m with coronary sinus effusion in an experimental model. Methods: Isolated rabbit hearts were prepared in a modified Langendorff technique which allows quantification of coronary sinus effusion. Hearts were labeled with pure Rb-81 by injecting the tracer into the aortic cannula. After a single injection spectroscopic measurement of and Kr-81m gamma radiation was performed repeatedly with a germanium detector. Perfusion was variated between 0 and 4 ml/min/g by changing the aortic pressure. Kr/Rb ratio was calculated in 325 measurements. 

The influx of the tetraphenyl phosphonium ion into myocardial cells is related to the resting myocardial potential. An analog, the [11C] Methyl triphenyl phosphonium ion ([11C]MTP) was synthesized and its cardiac kinetics and radiation dosimetry determined after i.v. injection into mice and dogs.

[11C] Methyl triphenyl phosphonium was prepared by reacting triphenylphosphine with C-11-methyliodide. The final product was of high specific activity (>1000 mCi/#mol). The biodistribution of [11C]MTP in mice was measured at different times after administration. In mice, uptake by the heart was rapid and the concentration of [11C]MTP in the myocardium was high and remained constant between 15 and 90 min (20.3 % -25.3 % of the injected dose per gram of tissue). The heart/blood ratio was 80:1 at this time point. Estimates of the radiation absorbed dose to major organs ranged from 0.61 to 126 mrad/mCi with the maximum radiation dose to the urinary bladder.

[11 C]MTP was also administered to three anesthetized dogs weighing ~ 20 kg and serial PET images were obtained. At 5 min after injection the heart/lung ratio was 8.6, that of heart/liver was 2.2.

These results indicate, that the uptake of [11C]MTP in myocardial cells is high and high heart/lung ratios provide excellent imaging properties for [11C]MTP.

lgnasi Carri6, Lluis Bern~i, Lurdes Prat, Manel Roca, Vicens Rlambau, Gustavo Tortes, David Duncker, Montserrat Estorch. Barcelona, Spain. IgG  A C C U M U L A T I O N  IN  EXPERIMENTAL ARTERIAL WALL INJURY. 111In-IgG has been used to delineate atheroma formation in animals. Proposed mechanism for IgG accumulation is binding .to Fc receptors on the foam cells present at the site of the plaque. We performed balloon deendothetialization of carotid arteries in 14 New Zealand male rabbits. After surgery, the animals were fed with normal diet and allowed to heal. Six weeks later 7 animals were injected with 200/zCi of I~I-LDL and 7 animals were injected with 100#Ci of l~qn-IgG. 48 hrs later the animals were sacrificed. Carotid arteries were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral arteries served as controls.

Significant IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting (% of the injected dose/g of 0.0438+0.06 verus 0.0058 +0.003 in the contralaterals, p < 0.05)), whereas no significant accumulation of LDL was seen (% of the injected dose/g of 0.0016+0.0009 versus 0.0013+0.0003 (p =NS)). Light microscopy of the specimens revealed injured endothelium without active atheroma formation. We conclude that IgG may accumulate in injured arteries without active atheroma formation. Inflammatory cells in the regrowing endothelium may be responsible for IgG accumulation independently of atheromatous plaque formation.

J , M a u b l a n t .

Z c e l l s of n e w b o r n rats w e r e incubated with 37 kBq of tracer and cellular uptake was m e a s u r e d after 2, 5, i0, 20, 30, 60 and 120 min of incubation.

W a s h o u t was m e a s u r e d at the same times after 20-60 min of p r e i n c u b a t i o n then r e n e w a l w i t h n o n r a d i oactive medium. Results represent the highest cellular concentration at uptake (max cc, in % of the total dose, m~+~sd) and the time to r e a c h h a l f of the m a x i m u m at u p t a k e and washout (Tl/2, in min It is concluded that NOET shows a much higher cellular uptake than the other tracers and a n e a r THROMBUS DETECTION USING TECHNETIUM-99m LABELLED TISSUE PLASMINOGEN ACTIVATOR. Inhibited rt-PA was radiolabelled with Tc-99m and has demonstrated promising results of in-vivo thrombus localization in a rabbit model. Commercially available rt-PA (Boehringer Ingleheim) was inactivated with PPACK to permanently inhibit the plasminogen catalytic site. The reducing agent 2-mercaptoethanol was used to cleave the disulphide bridges within the rt-PA molecule. Following purification labelling was performed via stannous reduction of pertechnetate in the presence of an excess of low affinity chelating ligand (Gluconate). Two studies were performed, low (100~g) and high (ling) dose injections, which had labelling yields of 45% and 75% respectively. In-vitro studies showed that both preparations were immunologically active, incapable of plasminogen activation and the Tc-99m was bound to intact rt-PA. Thrombi were created in the external jugular vein of New Zealand rabbits, followed by an injection of Tc-99m rt-PA into the femoral vein. A control group was injected with Tc-99m HSA. The initial blood half clearance time for Tc-99m rt-PA was 5 minutes. At 2 hours post injection, thrombus:blood ratio was 4.5 _ 0.96 (mean 4-SEM) and 3.7 __. 0.6 for the low dose and high dose studies respectively. For Tc-99m HSA control study, thrombus:blood ratio was 0.27 4-0.08. Planar scintigraphy visualized thrombus in 4 out of 6 low dose and 4 out of 4 high :dose Tc-99m rt-PA animals. The thrombi not visualized were significantly smaller than those visualized (mean: 30mg vs 164mg, p<0.01). These preliminary results suggests that this radiopharmaceutical may be useful in human thrombosis scintigraphy. OF SYSTEMIC-PULMONARY SHUNTS WITH ECG GATED ACQUISITION The present study aims at the validation of ECG gated acquisition of the pulmonary blood activity as a method to detect and quantitate systemicpulmonary shunts. The method is based upon the detection of the nearly sinusoidal local activity variations oecuring in the lung ROI, during the cardiac cycle, after blood pool labelling with 99mTc and ECG R-wave synchronized acquisition with a Gamma Camera-Computer System 1. The phase distribution of the variations detected in healthy controls shows two peaks for different phase angles, the former represents the pulmonary flow and the latter, small and oecttring at grater phase angles, corresponds to the systemic-pulmonary flow. The ratio of the sum of the amplitudes of the pixels in the 2rid peak m the summation of the amplitudes in all the pixels in the lung ROI gives the relative blood flow of the systemic-pulmonary shunts. This was proved by animal experimentation in the present study. Systemic-pulmonary shunts from the ascending aorta to the pulmonary trunk were implanted in ten mongrel dogs. After introduction of a Swan-Ganz catheter in the pulmonary trunk the flow of the shunt was evaluated using thermodilution by sublracting the cardiac output after and before the shunt's implantation. Linear regression between the values obtained by the proposed method (A values in the figure below) and those obtained by thermodilution (B values) shows r = 0.918 with p = 0.0002.

10 20 30 40

In conclusion, ECG gated acquisition may have a role as a method to the noninvasive assessment of systemic-pulmonary shunts. The studies of the alveolar-capillary membrane permeability (ACMP) are presently made In Nuclear Medicine using 99mTc-DTPA aerosols, in this work a new method to map the local ACMP to the 133Xe is proposed. The study of the ACMP with 133Xe is a more physiulogical approach to the study of permeability of 02 and CO 2 than the techniques using liquid aerosols. The study can be performed immediately before the ventilation study and using the same 133Xe activity for both. The technique is easy to carry out. The patients lying supine, and after a preparatory period, are asked to inspire a bolus of 15 mCi (555 MBq) of 133Xe to their total lung capacity and retain the breathing for as long as possible. During this time, activity is acquired to a Gamma Camera/Computer System in a sequence with a raaximum of 200 images (64x64) with individual duration of 0.6 s. The processing consists of calculating the mean 'times for the decreasing 133Xe activity on each pixel and building a parametric image. A colour scale is adopted to allow for the quantitative visualization of the local membrane permeability. Former studies of the pulmonary function (ventilation and pea'fusion) were performed (133Xo and 99raTe-HAM). The software developed allows the simultaneous display of the permeability, ventilation and perfusion parametric images, q~is information can also be displayed as four parameter histograms. A group of fourty three patients was studied, divided into 7 subgroups consisting of 5 healthy controls, 16 pulmonary embolisms, 8 interstitial pathologies, 9 POCDs, 3 pulmonary vascular pathologies, 1 pulmonary neoplasia and 1 pulmonary abeess. For the pathologies studied the proposed technique showed sensitivity and specificity. It can be useful in the detection of ACMP alterations and also in the ACMP study of the evolutive behaviour of pathologies eavolving ACMP. The average of the half-times of disappearance for the healthy controls is 28. see. ~Vhen comparing the average values of the half-times of disappearance of 133Xe in the POCD group with the healthy controis, statistically significant differences occur. The same situation prevails for the TEP and interstitial diseases groups, For the groups of pathologies quoted the half-times of disappearance are shorter than in the healthy groups. Advantages of the proposed method with respect to the aerosols tecnhique are: it uses a more physiological tracer; the images have no artifacts; better dosimetry; allows ventilation study with the sgme 133Xe activity; shorter in time and easier to execute. 

T Purpose: To summarize the' results of 111In-octreotide scintigraphy performed in Over 700 patients in our hospital. Methods: [1111n-DTPA-D-Phel]-octreotide (mean dose 281 MBq) was injected i.v., and static images were obtained after 24 and 48 h. Results: Nine of 12 gastrinomas, 11 of 20 insulinomas, ~ glucagonoma, 9 of 11 unclassified apudomas, but none of 18 pancreatic adenocarcinomas were visualized. Also, 58 of 60 carcinoids, 24 of 24 glomus tumors, 18 of 25 medullary thyroid carcinomas, 6 of 8 GH producing and 8 of 12 clinically nonfunctioning pituitary adenomas were visualized. 111In-octreotide scintigraphy revealed the primary tumor and its metastases in 23 of 24 patients with Small Cell Lung Cancer (SCLC), whereas the primary tumor could be visualized in 26 of 27 patients with non-SCLC. AS somatostatin-receptors are absent on most non-SCLC investigated thusfar, their in vivo visualization is probably due to uptake of radioactivity by the tissue surrounding the tumor. In 46 of 66 patients with breast carcinoma, 22 of 28 patients with Non Hodgkin lymphomas, 13 of 13 patients with Bodgkin's disease, and all of 17 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and 111 lymphomas, In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques. Conclusions: 111In-octreotide scintigraphy is a simple and sensitive technique to demonstrate tumor localizations in the majority of patients with tumors of neuro-endocrine origin, and also in patients with lymphomas or granulomas. Apart from its merit in tumor localization, 1111n-octreotide scint igraphy, in consequence of its ability to demonstrate somatostatin receptor positive tumors, could be used to select those patients with neuro-endocrine tumors who are likely to respond favorably to octreotide treatment. 

The aim of this study is to combine the convenience and quality of immunoscintigraphy using 99m-Tc labelled monoclonal antibodies immediately preoperatively with the demonstration using a probe at operation that suspicious areas on the images and at surgery in adhesions, lymphnodes, omentum, in the tumour bed and deep in the pelvis etc. are or are not due to tumour. The Oncoprobe, 99m-Tc sensitivity of 110cts/s/KBq, was shown to have an appropriate spectrum of response, linearity, collimation, size and weight for this purpose. 600MBq 99m-Tc labelled PRIA3 for colorectal cancer, SM3 for ovarian cancer and anti PLAP for granulosa cell cancer were given i/v for immunoscintigraphy at i0 min, 6 and 22h with surgery following and probe localisation at 24h. Using a criteria of over 1.5:1 "Tumour" to normal tissue for a positive finding. 24 sites in 6 patients with colorectal cancer showed correct localisation in 20 (83%), the liver being the main problem.

Average count ratio was 3.3 (range 1. 3-15.2) and average count ratio in excised tissue was 11.6 (2.0-21.1) 0.0077 % injected dose /g. 14/14 sites in patients with ovarian cancer (100%) were confirmed histologically.

Average count ratio was 3.1 (range 1.6-6.1) and average count ratio in excised tissue was 3.2 (2.4-5 .1), % injected dose/g 0.0052.

In granulosa cell tumour, the count ratio was 11.9 (7. .1). One true negative (colon cancer thought to be ovarian, SM3 negative) had a count ratio of 0.98 (0.79-1.1).

This preliminary and ongoing study shows that intraoperative localisation is practical with 99m-Tc labelled antibodies. In vitro studies with EGF receptor positive cell lines using anti-EGF receptor MAb 425 and its fragments could show the ability to displace the natural ligand EGF from its receptor. Therefore ~ 425 shows great potential as antitumor agent by blockage of the tumor cell growth stimulatory effect of EGF. The complete receptor blockage could be obtained with the intact MAb at the concentration of 3 nmol/l, the F(ab) ~2-fragment at 10 nmol/l and the Fab-fragment at 40 nmol/l. In vivo studies with 1- 125-1abelled MAb and the fragments showed a high and uniform distribution of the F(ab) ~2-fragment in human tumor xenografts with a high EGF-receptor density early after injection. Within 6 h p.i. the tumor uptake was found as 19% injected dose per gram of t u m o r tissue, increasing to 2 3 % / g at 24 h p.i., leading to tumor/blood ratios ( 

Conventional protocols for the postsurgical follow-up of pts with differentiated thyroid cancer (DTC) include serial whole body scans with 131I (WBS) and determinations of serum thyroglobniin (hTg). Given the 15-20% incidence of discordant results, we sought a new, sensitive monitoring procedure, assuming that specific i31I uptake, however low not to be detected at WBS, should ensue appearance in serum of thyroidal products (hTg, T3 and T4) endogenously labeled with 131I.

This study was conducted in 135 DTC patients routinely monitored for tumor recurrence. A plasma sample taken 72 hrs after a diagnostic 13~I (370 Mbq) was fractionated on Sephadex G25 Superfine using a new method developed to this purpose (saturation with ANS, preliminary elution of all the radioactive components except thyroid hormones with 0.05M phosphate pH 7.4 and 0.01M KI, followed by bulk elution of labeled T3 and T4 with normal human serum). The results of chromatography (TH-Seph) and those of WBS and hTg were compared with the final outcoume of patients evaluated by other independent techniques and by adequate follow-up. Sensitivity and specificity of TH-Seph were 88.5% and '100% (accuracy 97.8%), versus 83.3% and 97% for WBS (accuracy 92.7%) and 59% and 100% for hTg (accuracy 74.6%). Combining TH-Seph with hTg achieved the highest gains in sensitivity and accuracy (97.4% and 98.5%) versus TH-Seph plus WBS (93.6% and 96.4%) as also versus WBS plus hTg (91.5% and 95.6%).

These results indicate that the new chromatographic method set up for the chromatographic isolation of radioiodinated thyroid hormones neogenerated in vivo following a diagnostic dose of 13tI is able of identifying patients with recurrences from DTC with satisfactory sensitivity, specificity and accuracy, especiatty if combined with the conventional procedures. We m e a s u r e d the uptake of these agents in cultures of normal rabbit skin fibroblasts (RSF), neonatal rats fibroblasts from skin (NRSF) and h e a r t (NRHF) , n e o n a t a l rats myocytes (NRM), and of human melanoma cells with high or low melanine concentration (HMH and H M L , respectively). Monolayers of these cells wege incubated for one hour with 37 kBq of trace[. Uptake is expressed in percent of the total activity and per million cells. 17-28 23-26 23-28 20-26 22-29 21-22 Therefore teboroxime uptake remains nearly constant, irrespectively of the type of cells or of the species, w h i l e T I -2 0 1 a n d especially sestamibi uptake greatly increase in cells with high metabolic activity. The comparative uptake between these tracers has potential applications in the scintigraphic imaging of tumors. In the present study we examined the biodistribution of Tc-99m-HmPAO-LAK cells in well established pulmonary metastases (mets) bearing C57BL/6 mice to evaluate their possible diagnostic and clinical role. Experimental mets were produced in mice by I.V. injection of B16F10 murine melanoma cells (1 x 10 e cellstmous,e).

On day 27, experimen~:al mice (n =110) and controls (r)= 10) were each injected with 1 x l 0 s labelled LAK ceils (370-740kBq). Five mice from each group were ;sacrificed at 2 and 24 hrs. post injection respectively and blood, liver; spleen and lungs were removed, weigh4d and counted for radioactivity. The percent of the injected dose: per gram were calculated for the tissues, The results showed that there was 2-4 times higher retention of LAK cells in the )ung, liver and spleen of the tumor bearing mice as cbmpared with the controls at the 2 hr. time point. The radioactivity in the liver and spleen remained unchanged over the 2 4 hrs. period; howeber, the uptake in the lung declined from 6% to 2.4% at 24 hrs. in the tumor bearing mice. The results implies that LAK cells have a significant affinity for metastatic foci. The potential use of autologous radiolabelled LAK cells in scintigraphy and possibly in treatment is currently being investigated. concentrations by means of a double antibody-solid phase assay. The adopted cutoff level was 30 U/ml which in our laboratOry corresponds to the 95th cantile. Tho CV calculated on a panel of samples with different concentrations of CA 15.3 ranged from 6.2% to 12.3%. Recovery ranged from 95% to 118%. The sensitivity and specificity of the test were evaluated in a preliminary study on 277 patients. The overall sensitivity was 26.9%: 9,5% in patients with negative axillary lymph nodes, 11.3% in node-positive patients and 58% in patients with distant naetastases. The specificity for benign breast diseases was 96%. Single determinations of CA 15.3 were performed in the follow-up of 864 breast cancer 'patients. 731 patients had no evidence of disease, 24 had I ocoregional recurrences and 109 had distant metastases. Only 58 of 731 patients with no evideuce of disease had positive CA 15.3 levels (specificity 92.1%). In relapsed patients the sensitivity was 54% for locoregional recurrences and 74% in patients with distant metastases. In this series of patients the positive and negative predictive values of CA 15.3 were 62% and 95%, respectively. In a group of 150 node-negative breast cancer patients serial CA 15.3 determinations were perfonned during follow-up (range 4-48 months) . Eighteen patients relapsed, 9 with locoregional recurrences and 9 with distant metastases. CA 15.3 levels were increased in only 2 of the 9 patients with locoregional recurrences while of the 9 patients with distant metastases 8 showed a progressive increase in marker concentrations. In the CA 15.3-positive patients, cancer relapse was demonstrated by marker elevation 4-48 months before the metastases were detected clinically. In conclusion, CA 15.3 does not display any validity in the detection of primary tumors and its main clinical use will be in the monitoring of disease-free patients to anticipate the clinical diagnosis of distant metastases. The CA 15-3 is a monoclonal antibody produced against I15D8 and DF3. To estimate the utility of the tumor-associated CA 15-3 in the diagnosis and monitoring of patients with breast cancer,. 2224 patients (595 pts with metastasis) were investigated. Thereof metastasis was linulted to bone in 215 pts, to liver in 28 pts and to lung in 56 pts. Plasma levels of CA 15-3 and CEA were determined using IRMA method. The sensitivity and speci ficity of CA 15-3 in detecting a metastasis were compared with those of CEA using several cut-off values. The association of two markers improved the-diagnostic sensitivity of CA 15-3 determination alone. In detecting bone, liver and lung metastasis CA 15-3 had a higher sensitivity (73%,85%,73% vs 62%,67%,41%, respectively) than CEA. During therapy an increase higher than 25% of initial value of CA 15-3 was observed in 74.6% of pts with a new metastasis or recurrence, while CEA had an increase only in 49.3% of pts. During remission CA 15-3 was decreased>50% of the initial value in 55% of patients, but only in 30.6% of pts with CEA. Combination of both markers seems to be confirmatory to detect a metastasis of breast cancer, but CA 15-3 appears to be more suitable than CEA to assess the response to therapy. Application of systemic adjuvant therapy for primary Breast cancer requires the identification of patient at high risk for recurrence.

Expression of the Estrogen-regulated lysosomal protease Cathepsin D and the Estrogen-regulated pS2 protein was studied in a series of 138 Breast cancer patients.in the surgically resected primary tumors, Estrogen and Progesteron Receptors have been quantitatively assessed by dextrancoated charcoal method (Scatchard and saturation curves ), In the same cytosols using two-site solid phase sandwich immunoradiometric assays, we quantified the total Cathepsin D (precursor & processed forms) and the pS2 protein.

No correlation was found between the concentrations of Cathepsin D, steroid receptors and the pS2 concentrations. Using cut-off values previously described by many authors:(40 pmol/mg protein for Cathepsin D; 31 ng/mg protein for pS2 (11 ng/mg Foeken's equivalent (1); 10 fmol/mg protein for steroid receptors)we studied the qualitative relation between these cytosolic factors and others prognostic parameters ~s menopausal status, histological grade, axillary lymph node status, microscopic tumor size and patients age. According to the X 2 test : -no statistical correlation was found between the Cathepsin status and the other parameters even pS2 and lymph node status.

-low significant association was determinated between pS2 and steroid receptors, inversed and low relation with menopausal status, patient age, but not with node Status, tumor size or differenciation grade.

With 2 years mean follow-up (15 to 47 months) our prospective study is insufficiant to evaluate clinical survival. Anyway our preliminary results show that all the patients with earlier recurence or metastasis, independently of their node status are Cathepsin D positive ~ind/or pS2 negative. If the prognostic value of these two independent factors is confirmed by other and longer studies, Cathepsin D and pS2 measurement could be used as a tool for optimization of individual treatment. CA-549, a c i r c u l a t i n g breast cancer associated antigen was determined in 434 female patients presenting a h i st o l o g i c a l l y proven breast cancer by an immunoradiometric assay at the same time as 2 other markers (CA- .1263 determinations have been realized (I to I I / pat,) in d i f f e r e n t stades of the disease; among them 106 patients presented metastatic disease,15 a local relapse and 33 a remission a f t e r treated relapse or generalisat i o n . A l l cases had had at least ly of follow up a f t e r the l a s t CA-549 determination.The overall accuracy of the CA-549 test was 77,4% with a s p e c i f i c i t y of 90,9% and a s e n s i t i v i t y of 59%.The main group of the false negative cases provided from the patients before the i n it i a l treatment presenting stage I and II disease,independently from estrogen-receptor and the a x i l l a r y lymph node status.True positive results in case of generalisation corresponded mainly to soft tissue and bone l o c a l izations,ln 89,6% of the cases there was concordence between CA-549 and CA-15-3 results; the concordence was 62,7% between and CEA.81% of the concordent CA-549/CA-15-3 cases were true positive or true negative.CA-549 corrects 44,5% false positive and 7% false negative CA-15-3 results of the discordent cases.When compared to CEA,in case of discordence The recognition of TPS (tissue pol~eptide specific antigen) as a proliferation marker led to the question about its clinical role in contrast with that of tumour markers in the serum of patientswith~ynaecologic cance~. Fourty-one patients were studied; 28 of them had breast carcinoma (TINOM0 -T2NP/W2) and 13 ovarian carcinoma (pT2NOM0 -T3cN/MI). In 87 (5~+33) serum samples the concentration of TI~ (as proliferation marker) as well as of CEA, CA CA 125, and CA 72-h as tumoor markers were determined using monoclonal imm~]noradiometric assay (IRMA). A rise of serum TPS was found in 9 of ~i patients (21,9 %), among them 8 of 28 (28,6 %) with breast carcinema (2~ serum samples) and i of 13 (7,7 %) with ovarian carcinoma (~ serum samples); progredient tumour growhhwas noted in these women. An elevation of tumour markers in serum was observed frequently: CA 15-3 in 16 patients, CA 125 in iI, CA 72-~ in 10, CA 19-9 in 7 and CEA in 6 patients. One woman with breast carcinoma showed an increase of solely serum TPS as proliferation marker whereas only l tamourmarker (serum CA 125) followed several months later. According to results of other studies, a rise of serum TPS may be due to an increase of the proliferation of tumour cells. In contrast, an elevation of tumour markers in serum appears to be related rather to the mass of a tumour, possibly the number of tumour cells. A total of 40 patients with advanced prostate cancer (6 stage C, 4 stage D1 and 30 stage D2) treated by hormonal manipulation between July 88 and January 92 were studied to evaluate the use of serum PSA for predicting outcome. All patients had serum PSA determinations before treatment, every 3 months during the first year of followup and every 6 months thereafter, using commercially available radioimmuno-assay kit. Outcome variables were biological progression (BP) and clinical progression (CP). BP was defined as 2 increasing PSA levels within a minimum interval of 3 months. Initial PSA ranged from 1.1 to 212.8 ng/ml ( mean 59.1 -+ 36.2 ng/ml) and followup ranged from 6 to 37 months (mean 22 months). During this period 18 patients presented BP, 15 presented CP and 8 died. For all patients the biological response rate (BR) was computed and defined as the percent decrease of PSA at 3 months. Initial PSA levels and BR rates were correlated to BP and CP.

No correlation was observed between initial PSA level and disease progression. BR correlated significantly with BP (r=0.467, p=0.002) and CP (r=0.489, p=0.001). The 40 patients were divided in 2 groups according to BR and were examined in relation to the survival free of BP and CP. At the cutoff point of 80%, the median survival free of BP was 14 months for patients that presented a BR lower than 80% compared to 34 months for patients presenting a BR higher than 80% (p=0.0006). Similarly, the median survival free of CP was 17 and 34 months for patients presenting a BR lower and higher than 80%, respectively (p= 0,007).

In conclusion, initial serum PSA level is not useful for predicting outcome. BR correlates significantly with disease progression and survival free of progression. BR requires a single determination of PSA at followup to be computed, and provides accurate predicting information eady in the course of the disease. These observations suggest that patients with a BR rate lower than 80% are at increase risk for developing progression and are strong candidates for eady adjunctive non-endocrine therapy. In patients (pts) with advanced neuroblastoma (Nb), measurements of urine vanillylmandelic acid (VMA), serum ferritin (FER) and neuron-specific enolase (NSE) have been suggested as useful tumor markers in assessing the success of therapy. In this study, we evaluated 15 pts (7 M and 8 F, ranging in age from 2 to 68 months) with histologically proven advanced Nb pre-and post-5.7+2.7 months of chemotherapy (CRx) (Cisplatin, Vincristine, Cyclophosphamide, Achiamycin and Teniposide) using iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy (0.5 mCi iv; images at 24, 48 and 72 hrs) and urine VMA measurement. Serum FER and NSE serial measurements were also obtained in 10 and 8 pts, respectively. Abnormal M/BG uptake was qualitatively graded using a 5-point scale (from 0=absent-to 4=peak-activity) on both pre-and post-CRx 48 hrs images. Pre-CRx, a total of 37 Nb lesions with abnormal MIBG uptake were detected. Post-CRx, only 21 of the 37 pre-CRx lesions persisted and 5 new loci of increased MIBG uptake were additionally localized. With CRx, MIBG abnormal uptake was significantly reduced in the majority of Nb lesions (p<0.01). Although the overall reduction in MIBG uptake, there was variability in the change of MIBG uptake for each lesion (decrease, disappereance, increase, no change or new abnormal foci). Although. there was a trend to diminish of VMA, FER and NSE levels, these tests did not show significant differences between pre-and post-CRx values. In conclusion, these data show that: 1) MIBG scintigraphy allows to completely evaluate lesion by lesion the heterogeneity of CRx response in advanced Nb; 2) VMA, FER and NSE tests can only show the functional status of the total Nb masses and are not helpful in defining the response of individual lesions to the treatment. 25 children (18 males, 7 females, aged 10 days to 11 years at diagnosis) underwent 75 MIBG and 68 bone (Tc-99m-DPD) scans. According to the Pediatric Oncology Group classification 1 patient had stage A, 7 each stage B and C, 6 stage D and 4 stage Ds disease. Histology showed 10 neuroblastomas (N1), 10 differentiated neuroblastomas (N2) and 5 ganglioneuroblastomas (N3). 48/75 MIBG and 34/68 bone scans were abnormal. At diagnosis, both studies were performed in 11 children. Uptake of both compounds was shown in 9/11 primary tumors. With respect to histologic differentiation 8/8 N1, 9/9 N2 and 3/5 N3 showed tumor uptake of MIBG at staging and/or follow-up. 2/2 N1 and 1/1 N2 had normal MIBG scans during complete remission. 7 children with proven bone marrow involvement showed bone lesions on concomitant MIBG (7 scans) and DPD (6 scans). Metaiodobenzylguanidine(MIBG) and the monoclonal anti-NCAM-antibod¥ BW575/9 have been proven successful in imaging neuroblastoma(NB). As NBs tend to differentiate to minor malignant counterparts, the question arised, whether or not, and if so, to what extent this cellular change is paralleled by a change in uptake of the above two pharmaceuticals. The answer to this question may be essential for the ,assessment of their value in NB management. The ai~mof this study was to document quantitatively the potential change of both the MIBG-and BW575/9-uptake in an in vitro NB cell line model. We used the human NB cell line SK-N-SH, which is known to take up both MIBG and BW575/9, and RA which induces a variety of differentiated functions,including phenotypic differentiation. MIBG-and BW575/9-uptake assays were established to assess quantitatively the respective uptake in an in vitro cell line environnement. SK-N-SH was continuously exposed to 5 uM all-trans BA for 8 days. Results: Most of the SK-N-SH cells showed a marked increase in neurite extention. MIBG-uptake d~oped down to 57~ of the uptake of control cells without EApretreatment (as already published by our group), whereas BW575/9-uptake raised slightly for about 30~. Conclusions: These data show that (i) RAinduced differentiation is followed by a different uptake behaviour of the two NB-avide substances,i.e, a marked decrease for MIBG and a slight increase for BW575/9. (2) In clinical situations where differentiation of NB is likely, the use of MAbs such as the BW575/9 should be considered as a complement to MIBG for both scint~graphy and therapy.

A.FACELLO, J.HADDAD, B.BRUNOT, A.CONSTANTINESCO CHRU Hautepierre, STRASBOURG . FRANCE.

CEZEBRAL BLOOD fLOW (CBF} FOLLOWING PERINATAL ASPHYXIA ASSZSSEO BY BRAIN SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT).USING 99mTc HMPAO. 14 neonates (35-42 weeks G.A.) with perinatal asphyxia and in whom 99mTc HMPAO brain SPECT was performed, were studied prospectively during the f i r s t years of l i f e . 2 groups were individualized : G1 (n = 6) developped normally; G2 (n = 8) 6 died in the neonatal period and 2 severely delayed. HMPAO SPECT was performed following asphyxia either in the acute phase (A) (0-12 hours) G1 = O, G2 = 4; in the subacute phase (S) (12-96 hours) G1 = 6, G2 = 5 or in the chronic phase (C) ( > 96 hours) G1 = 4, G2 = 2. TcPC02, TcP02, and d i a s t o l i c v e l o c i t ies (DV) were recorded. SPECT analysis based on the counts in R.O.l./pixel/body/weight/dose of radiotracer was performed. Two perfusion indexes ( I ) , ICBF,I regional CBF (IrCBF) of cerebellum, f r o n t a l , p a r i e t a l , occipital and basal ganglia were derived.

Percentage of HMPAO brain uptake was also calculated. In G2, there is a difference (p~O,05) between A and S regarding TcPC02 (32 vs 18); DV (11.8 vs 28.8) and IrCBF of the cerebellum (13.2 vs 11.3). Comparing G1 and G2 in S s i g n i f i c a n t differences ( p~O , O l ) are noted regarding TcPC02 (39.5 vs 18.6) whereas ICBF are similar (48.1 vs 46.1). ICBF and HMPAO brain uptake in S were higher than those noted in C in both G1 ang G2 (12 % vs 6 %). We conclude that following birth asphyxia, increase in CBF (hyperemia) occurs mainly in S and is related to adaptive response to hypoxia hypercapnea. However in severe asphyxia, i t is predictive of bad outcome i f CBF/PC02 r e a c t i v i t y (increase in CBF despite low PC02) is lacking as in G2. Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure in neonatal refractory respiratory failure.

During ECMO, the infant's blood is shunted from the right atrium, via the right internal jugular vein (RIJV), oxygenating it through the membrane oxygenator, and returned to the systemic circulation via a cathetar in the right common carotid artery (RCCA) after the ligation of RCCA.

ECMO has been used since 1985 at Jefferson and since January 1992, 5 neonates treated with ECMO had measurement of regional cerebral blood flow (rCBF) using Tc-99mHMPAO and a triad (Trionix, Twinsburg, OH, USA).

Each neonate received 2 mCi of Tc-99m HMPAO IV and sedated with chloral hydrate (50mg/kg, oral).

One hour post injection, the patients were scanned after having the patients in the most comfortable position in either supine or prone aad turning the head to either side. One-hundred-twenty frames of 40 sec were acquired with 1.4 zoom mode. using 128x128 matrix and tomographic slices were reconstructed using 128x128 matrix after making the correction for patient's position and head tilting.

Two neonates had "normal pattern" of neonates with high rCBF in sensorimotor cortex, thalamus, brain stem and cerebellar vermis. Three neonates had significant decrease in rCBF within the right cerebral hemisphere.

In summary, brain SPECT was successful in neonates after ECMO and a potential clinical value of brain SPECT in long-term follow-up of neurodevelopmental outcome after ECMO is under investigation at our institution. O~A~~-~ ~0~ ~OL~T~ The aim of this study is the assessmen~ of ~he gallbladder (GB) motill%y in response %o meal stimulation in healthy volunteers and in patients after %oral gastrec%omy (Roux Y), in order %o evaluate the effect of vago%omy early and late after surgery.

The study was performed in ~ subjects: i~ controls Wlthou% (C), 8 With (CS) meal stimulation, and in 6 early (<~ months) (EPG) and 7 late (i-a years) (LPS) postgastrectomy patients, also after stimulation. Data were collected (Nora, MlcroDelta) during (~ h,10 ml/h) infusion of 150 MBq, 025 m~/ml 99m-Tc-EHIDA, preceeded by a loading dose, AccoPding ~o %he %~e when "pla%oo" in ~ was observed (97-i~5 mln), test meal was given in la0 mln,

In comparison ~o %he C (X=56,Smin +/-S6,0), emptying time (Te) was significantly decreased (p< 0.01), in all groups after s~imulation (CS, X: $7,Smin +/-li.@; EPS X:aa.Tmin +/-i~,~; LPG, X= ZT,Smin +/-la.6). However, Te didn't differ (p>0.05) between the later three groups. Least square ra%io (Le~) between ascendent and descenden~ slopes_of the ~B curve was signi~cantly higheP in EPG (X:R,5 +~-0,7) than in CS (X= 0,8 +/-0,5; p<0.01) LP~ (X:L0 +/-0,7; p<O.05) and C (i,~ +/-0,9; p<0.05), without the significant difference between the later three ~roups (p>0,05). Ejection f~ac%ion (EF) was much higNer_ (p<0.05) in the CS (X:76,~Z +/-.17.9) %hart in C (x:~a.lZ +/-7.a) and EPS (x:~i.TZ +/-i£,~), There was also significant difference (p<0.01) between the values in EP~ and LPG (X:7@,SZ +/-ILS), while those between CS and LP~ didn't differ (p>0.05) On the contPaPy, filling %i~e, "pla%oo" ~ra%ion, and integral ra%lo between the ascendent and descendent ~rt of the SB curve were not proved ~o De valuable parameters in the SB motility assessment between the ~roups of patients studied (p>0,05), ~, Let ~d ~ are important parameters in GB motility assessment In ~esponse to stimulation, in the controls and after total gas%rectomy. SB motility recoveres later after %o%aI gastrec%omy with v~o%omy that ~n be explained by establishment of some other mechanisams, predo~nantly hormonal (CCK). 

(In-111 -IgG) SCINTIGRAPHY Exacerbation of disease activity is a common event in the course of IBD. Endoscopy, radiographic contrast studies and labeled white blood cell (WBC) scintigraphy are frequently used in the diagnostic work-up of these episodes. Since In-ll 1-1gG scintigraphy has many logistic advantages over labeled WBC scintigraphy, we assessed the utility of In-111-1gG scintigraphy for evaluation of disease activity in patients with IBD. Four male and six female patients with clinical evidence of active disease were studied. Eight patients had Crohn's disease (CD). Three of these patients had CD of the small bowel, two had CD of the large bowel, and three had CD of both the small and the large bowel. Two patients had ulcerative colitis. Scintigraphic images were recorded 4, 24 and 48 hours after injection of 75 MBq . SPECT was performed 24 hours postinjection. The scintigraphic results were verified at surgery, with endoscopy and/or contrast radiography. In-111 -IgG scintigraphy correctly identified presence and extent of small bowel involvement in 5 patients, presence and extent of colon involvement in 4 patients, perianal involvement in 2 patients and abdominal abscesses in 2 patients. SPECT was absolutely essential for adequate interpretation of scintigraphy. Other diagnostic techniques did not reveal additional bowel lesions.

In conclusion, In-l11-lgG scintigraphy accurately detected presence and extent of disease activity in patients with IBD. Advantages over are the convenient preparation and the possibility to obtain high quality SPECT images. However, other current diagnostic techniques remain necessary for identification of structural abnormalities, such as stenosis and fistula.

Hovi I; Vorne M, Lantto T, TaavitsainenM: The separated autologous leukocytes were labelled with freshly prepared Tc-99m-HMPAO and reinjected. The mean dose of labelled leukocytes was 260 MBq. HIG was labelled with about 555MBq of pertechnetate according to the m a n u f a c t u r e r ' s instructions. Sequential i m~e s from 2 min to 6 h and even 24 h were obtained with both methods. For comparison the findings were classified in three categories: O: not detectable; I: detectable; 2= readily detectable.

Twenty patients had focal purulent disease as final diagnosis. The lesions were better seen with leukocytes in 14 cases, equally well with both methods in 2 cases, and not detectable with either in 2 cases. Two purulent spleen lesions were seen as focal defects in the active background. HIG was not better in any of the studies.

Conclusion: Tc-99m-HMPAO labelled leukocytes are superior to in the detection of focal purulent disease. 

T h e aim of t h i s w o r k was to e v a l u a t e t h e r o l e of t h e 99mTc-HMPAO g r a n u l o c y t e s c i n t i g r a p h y In conclusion, GS not only shows intensity and extent of active inflammation and complications of CD, but also demonstrates that active inflammation often persists during remission and in responders to treatment.

M. Pap6s, *F. Nagy, J. L&ng, L. C s e r n a y A l b e r t S z e n t -G y 6 r g y i M e d i c a l University, D e p a r t m e n t of N u c l e a r Medicine, *County H o s p i t a l Szeged, H u n g a r y A simple non-invasive test for the exocrine function of the pancreas would be attractive to diagnose various diseases of this organ. 1, 2-dipalmitoyl~3-[(15-p-[I-131 ] -iodophenyl)pentadecan-1 -oyl]rac-glycerol (1, has been evaluated for this purpose. After oral administration, IPPA is released from the triglyceride by the action of pancreatic lipases followed by intestinal absorption. Radioiodinated benzoic acid (IBA) is the metabolite of IPPA and is then conjugated and excreted in the urine. To establish the normal range of excretion, we investigated 6 normal volunteers and 5 patients without signs of pancreatic disease. About 30 izCi of 1, were administered orally with subsequent urine collection for two 24 h periods. Blood samples were withdrawn after 1,3, 4, and 6 hours in 3, 5, 1, and 2 patients, respectively. TLC analysis was performed on the serum lipid extracts with two different solvent systems. After 24 hours, 76 % of the administered activity was in the urine (SD: 13.8 %) and after 48 hours 98.6 % (SD: 14.9%). The TLC's showed two major peaks which corresponded to the IBA and tripalmitin standards, The proportion of IBA increased with time. No difference was obvious between the two solvent systems. In conclusion, urine analysis after 1, may masure pancreatic lipase activity by a simple non-invasive technique. The s.mall standard deviations of the normals suggest this agent may be useful to diagnose insufficient pancreatic activity. Feeding either CE or CDD induces fatty liver in rats. This project was undertaken to measure quantitatively the effect of fat accumulation on liver function; 10 rats were fed a 36% ethanol diet for 4 weeks and another 10 rats fed CDD for 25 weeks. QMS was performed at 2nd, 5th, and 25th week in the CDD group and at 4 tlnweek in the CE group. Data were acquired at 1 frame/20 sec for 20 min. using a gamma camera after the injection of 30(3 uCi of Tc-99m-Mebrofenin into the tail vein. Hepatic ex traction fraction (HEF) and excretion half time(T-i/27 were obtained. The rats were sacrificed and blood and liver samples were collected for bioc/nemiaal and histoli gical examination. Marked fatty infiltration on the liver was observed in both groups; this did not alter HEF but significantly prolonged T-i/2(mp<O.OS)suggesting a possible derangement in the excretion of bile. It is concluded that QMS may provide a sensitive and noninvasive method for detection and quantification of altered hepatic function due to fatty liver. A new approach to quantify the esophageal peristaltic function (segment pump mechanlsm) has been developed by our Group: DECONVOLUTION analysis. A good specificity and reproducibility was calculated for this method when patients withou~ stsnosis were studied. The aim of this study was to evaluate, with such an efficient methodolo~DL the altered esophageal function in patients with esophagitis and in those with peptic stenosis. PATIE1N~rs: Three Groups of patients were included in the study: Group "E", 40 patients ~dth reflux esophagitis, grade II\III; Group "S", 15 patients with a fixed peptic stsnosis; a control Group CC") of 27 volunteers. M]~2~:IOD: The esophageal transit of two kinds of food mixed with ll3mIn was studied: a) a 3ml water holus (supine); b) a spoon full of a baby flour pope (standing). Acquisition and processing algorithms were implemented for a computerized gammagraphic evaluation by DECONVOLUTION analysis. Two parameters were computed from the output function curves: mean wave transit time (1VfW) and maximal transit time (TMax = clearing time). RESULTS: 1) LIQUII)S: The MW was longer in Groups "E" (p<.01) and "S" (p<.001) than in "C"; in Group "S" was greater than in "E" (p<.01). The TMax was longer in Groups "E" (p<.01) and "S" (p<.01) than in "C". 2) SEMI. SOUDS: The ~ was elongated only in Group "S" (p<.0001); "E" mean valugs were not different from "C' and were smaller than "S" ones (p<.0001). No statistical significant difference was disclosed between TMax values in the semi-solid evaluation. 3) In Group "S" all but 2 patients have abnarrnal ~ values in both studies. CONCLUSION: Patients without stenosls CE") have MW and TMax disturbances mainly in liquids transit evaluation as the study was performed supine. In this Group of patients with a peptic stenosis CS") a ve~ important and statistically signiilcant delay in the liquids and in the semi-s~lid esophageal transit ~ quantitativeness Was disclosed -mean values were greater than those in Group "E". The non-elongatlon of the Tmax in Group "g" was due to the predicted effect of re-entry of activity in the proximal esophagus as a consequence of supra-stenotic retention. 

(HP) has been evoked as a possible cause of delayed gastric emptying (GE). To our knowledge no study has specifically addressed this problem yet.

The aim of our study was to evaluate GE in asy~ptomatic patients with evidence of HP. No patient had a history of gastric disease nor was taking any medication likely to interfere with gastric emptying.

We have studied 10 patients (8 males and 2 females; mean age 57 ± 18 year) with a TSH value measured by RIA > 20 ~U/ml (normal range 0.i -5 ~u/ml) and compared their results with a normal data base of 20 subjects.

After an overnight fast, all patients underwent the same test procedure. The standardized test meal consisted of 1 scrambled egg labeled with 1 mCi of Tc-99m-SC, 2 slices of bread and 125 ml of water. Anterior and posterior images of the stomach were recorded every i0 minutes for 2 hours. Gastric counts were determined at each time interval and corrected for Tc decay.

Geometric mean of the counts was calculated and the percentages of activity retained in the stomach after 60 and 120 minutes were then determined. T 1/2 was obtained using the modified power exponential function y = 1 - (l-e-kt) B and compared to the normal subjects values. GE was significantly delayed (p < 0.05) in patients with biological HP (mean T 1/2 = 116 ± 44 min.) compared to the control group ( mean T 1/2 = 53 ± 17 min.). Individually, 8 out of the ten patients were outside the upper normal limit, i.e. > 87 min. (mean ± 2 SD).

In conclusion, our study confirms that dysfunction of the thyroid gland may influence gastric motor function and demonstrates that, in asymptomatic patients with biological evidence of HP and who are not receiving a substitutive therapy yet, GE of solide is significantly delayed. Most of the hormone producing gastrointestinal tumours contain high density of binding sites for somatostatin. Octreotide, a synthetic, long-acting octapeptide, is a somatostatin analogue which has similar biologic characteristics as the native peptide and allows in-vivo labelling of somatostatin receptor positive mmours. Indium pentatreotide (DTPA coupled octreotide, Octreoscan R, Mallinckrodt Diagnostica, Netherlands) was used for scintigraphy in 8 patients with clinically and histologically proven GEP tumours (4 insulinomas, 3 carcinoids, 1 VIPOMA) The study was approved by the local ethical committee; written consent was obtained. Labelling was performed by the addition of In-111-chloride to the pentatreotide. Quality control, using SEP-PAK R cartridges and methanol as eluent revealed a radiochemical purity of about 95%. After injection of pentatreotide planar images in at least two views and SPECT of thorax, abdomen and pelvis were acquired 4, 24 and 48 h p.i. using routine gamma cameras. There were no false positive results. 3/4 insulinomas were true positive. One insulinoma did not visualize the ligand. The patients with carcinoid and VIPOMA had metastatic disease, which was detectable in all cases. In two of these patients metastatic tissue was identified, which was not detected before by other imaging modalities. SPECT was superior to planar images in visualization of thoracic and abdominal foci. In-111 pentatreotide scintigraphy is a potential tool for diagnosis of endocrine active GEP-tumours. In some cases detection of primary tumour tissue and metastatic disease is superior to X-ray, ultrasound, CT or MR/. High binding levels of pentatreotide in the tumourous tissue can help to consider therapy with octreotide and vice versa. 

18 patients with bulky recurrent glioblastomas (17 brain,l medullary) received intralesional radioimmunotherapy since both surgery and radiotherapy resulted ineffective. The BC-2 and/or BC-4 murine MAbs (SORIN-BIOMEDICA,Italy) were utilized. They strongly react against tenascin (TN),which is an extracellar antigen higly expressed by the stroma of glioblastoma. The MoAbs were labelled with 1-131 and were injected directly in the tumour mass by means of the stereotaxy to maximize the glioblastoma irradiation. The mean dose was 2.45 mg antibody and 647 MBq 1-131. In most cases the RIT applications were repeated.No systemic adverse reactions were recorded.The brain tolerance to direct antibodies injection was quite good.The MoAb concentration in the tumour was high (3.56%/gr/24hrs) and the antibody residence time in the glioblastoma was very prolonged (effective T/2 = 71.7 hrs) thus acheving a mean cumulative radation dose to the tumour more than 35.000 cGy. The diffusion of radiopharmaceutical through the neoplastic tissue was satisfactory homogeneous so irradiating uniformely the whole mass. In 15 evaluable patients we recorded 4 tumour stabilization (lasting, on mean, 9 months), 3 partial remission (I0 months), and 2 complete remission (14 months). The response rate was 33.3% and has to be considered very favourable since achieved in cases of very advanced disease. Clinical usefuhaess of immanoseintigraphy (IS) with anti-CA 125 monoclonal antibodies (Mab) in deteetinn of early ovarian cancer recurrences and for staging has already been proven. Anti-idintypic human anti-manse antibodies (HAMA) are frequently triggered by PC 125 Mab..am extremely well dbtieal course contrary to poor prognosis was obsereed in patients producing anti-idiotypie HA_MA following IS with routine anti-CA 125 Mab. Aim of this study was to relate these clinical findings with in vitro testing of HAMA. Patients and methods: 10 patients (pt) with ovarian cancer (n=9) or uterus cancer (n=l) received at least twice (up to five times) 1-2 mg of anti-CA 125 Mab (PC 125 or B 43.13 Portal vein thrombosis, a factor of poor pn3gnosis in patients (Pts) with HCC, is a contraindication for chemoembolization. Intra-arlerial injection of 131 Ilabeled iodized-oil (131I-IO) however, which does not modify arterial flow, is still conceivable in this condition. The aim of this prospective randomized controlled trial was to compare the efficacy of treatment by injections of to that obtained by medical support alone (Gr 2) in patients with stage l or II HCC (classification of Okuda) with portal thrombosis (trunk, left or right vein). Patients and Meth0d~ : 22 HCC patients (21 men, 1 woman), aged 66+/-7 years, with portal vein thrombosis (diagnosed by angiography, CT scan or duplex) were randomly assigned to Gr 1 (n = 11) or Gr 2 (n = 11). Additional injections of 131 I-IO were given 2, 5, 8 and 12 months' afXer initial therapy. Medical support treatment was composed of: tamoxifen (n = 5), 5 FU i-v (n= 1), NSAIDs or corticostemids (n = 3), Efficacy was judged according to survical rate (Kaplan-Meier method ; Logrank test), AFP serum values (measured at 2, 5, 8 and 12 months) and tumor size (CT) at 5 and 12 months. Results : The two groups were comparable with respect to: *Child's classification A/B Gr 1 : 6/5, Gr 2 : 5/6 ; *Okuda's classification I/II Gr 1 : 4/7, Gr 2 : 4/7 ; *Liver function tests, " location of the thrombus mink/right/left vein Gr 1 : 8f2/]. Gr 2 : 9/1/1 Tolerance was excellent in Gr 1. AFP serum values were > 50 ng/ml before treatment, and in 7 patients (Gr 1 : 5, Gr 2 : 2) reevaluated showing : Gr 1 : 2 partial responses (PR), 2 minor responses (MR) and one increase of this level ; in Gr 2 : 2 increases. On angingraphs the thrombosis disapeared (n = 1) or decreased in size (n = 2) in Gr 1. The actuarial survival curves were significantly different (Chi 2 = 19.8 ; p < 0.001) between the two groups, the survival rates at 3, 6, and 9 months being for Gr 1 : 71%, 57 %,57 % ; andGr 2 : 18 %,0 %,0 %. Conclusion : Intra-arterial hepatic injection of 1311-IO is a sa~e and effective treatment of HCC with portal vein thrombosis.

A. We have evaluated the efficacy of Strontium-89 as adjuvant therapy at the time of first requirement for local radiotherapy for painful bone metastases. 132 patients were randomized to receive either 400 MBq. of or placebo at the time of radiotherapy. 68 received active treatment and 58 placebo. Six patients were randomized but not treated. Data were then collected for llfe assessing survival, toxicity and efficacy at 3, 4, 5, 6, 9 and 12 months after treatment.

No significant survival difference was seen between the two arms. At three months post-treatment significant differences between the active and placebo arms were seen in analgesic requirements, painfree status, quality of life assessment and further radiotherapy requirements. Statistically significant differences between the two arms were seen to 6 months after follow-up in all parameters measured at 3 months.

A comparison of cost effectiveness based upon parameters such as medication requirements, radiotherapy requirements and days in hospital suggested that the active group required less medical intervention than the placebo, suggesting a possible cost benefit ratio in favour of We conclude that Strontium-89 as adjuvant therapy has a role in the treatment of patients with advanced metastatic prostate cancer. Benzodiazepines (BDZ) are used as therapeutic agents in several diseases. Since 1985 endogene BDZ and metabolites are known. The aim of the present study was tO show BDZ receptor distribution in patients with anxiety disorders. Patients: 9 Patients (4 male, 5 female, age 22 -52 y, me~th different forms of anxiety disorders gave informed consent. 3 subjects showed reactive depression and delusion of reference, 3 revealed anxious depression and 3 panic attacks. Grading was done with HAMILTON rating scale for anxiety (HRSA). 3 patients with the lowest anxiety score were considered a reference group. Urine benzodiazepine excretion was negative. Methods: Pat. were rested for 15 minutes and then injected with 150 MBq I-IZ3-Iom~zenil. i0 and iZ0 minutes p.i. two SPECT acquisitions were carried out (ORBITER with Neurofocal collimator, 64 increments, 30 sec/ view). Semiquentitative evaluation of first ("perfusion") and second ("receptor binding") phase was performed by means of modified regional perfuslon indices. Results: Compared to reference subjects 3 patients with mean HRSA score showed no alterations of perfusion and receptor binding. However, those with "panic attacks" revealed decreased receptor density in the right hippocampus(1), and left temporal lobe resp.(2) An additional hypoperfusion was found in this lobe. Conclusions: Decreased receptor distribution may be a reason for unsatisfactory binding of endogene BDZ ligands in panic attacks, a not object related form of anxiety, whereas ligand binding in neurotic forms of phobic disorders seems to be normal. The in vivo quantification of myocardial muscarinic receptors was performed after orthotopic cardiac transplantation in 6 patients (pts) u~ing PET data, MQNB (an antagonist of muscarinic receptors) as a ligand and a non linear model including 3 compartments and 7 parameters.

All were men, mean age 45 -5 years, and time from surgery was 4 7 _ 2 3 months. A three injections protocol, ,. The density of available receptors (Bmax) and the affinity constants were compared to those of 6 normal subjets. No pts presented either adverse reaction or change in heart rate (86 -4 bpm), while the heart rate increased from 70 -+ 10 to 101 + 13 bpm in normals. The receptor density d!d not differ significantly between pts and controls (respectively 26 _+ 6 and 27 __-7 pmol/ml). The equilibrium dissociation constant (Kd) was significantly increased (0.65 -0.28 vs 0.26 ___ 0.06 pmol/ml, p<0.02), mostly due to a dramatic decrease of the association constant (k+~) (0.44 + 0.13 vs 1. 3 -0 .3 ml/(pmol.min), p<0.001).

Conclusion : 1, This study confirms that PET allows the in vivo detection of changes in affinity constants of muscarinic receptors. 2. The lack of changes in receptor density and its decreased affinity for the antagonist seems consistent with the absence of supersensitivity to acetylcholine in the extrinsically denervated canine heart. Blood clearance was f a s t (Tl/2 = 40 min) with urinary excretion (192.6±99.8 %/g at lh) that was due to i n t a c t 99mTc-DMP (96.4 %) as determined by ITLC.

In conclusion, 99mTc-DMP is preferred to 67Ga c i t r a t e f o r the v i s u a l i s a t i o n of inflammatory lesions although s i m i l a r A/M and A/C r a t i o s were obtained, due to lower blood and i n t e s t i n a l a c t i v i t i e s allowing the detection of abdominal abscesses and t o b e t t e r physical character i s t i c s of 99mTc. The SPECT data presented confa'm current pathophymol, concepts supposing normal or upregulated postsynaptic D2 receptor density in IPS. L-Dopa, stored in praesynaptie vesicles, did not compromise postynaptie IBZM binding. Dopamine agonists, however, located postsynaptieally, tended to reduce the number of receptors available for IBZM. Thus, for correct interpretation of SPECT resuits treatment of ]PS-pts has to be known and taken into account.

G. Castellano*, V. Podio*, D. Giobbe °, T. Spandonari*, P. Morello*, P. Antonacci*, M. Bessone*, G.L, Turco* *Cattedra di Medicina Nuc/eare ~ Universit~ di Torino (/ta/y) °Divisione di Neuro/og!a -USSL TO-I V-Torino (/ta/y) 

In Parkinson's disease there is a primitive impairment of dopa release by presynaptic neurons of substantia nigra; PET studies in the ear!y stage of PD already demonstrated that the reduction of dopa release results in an increased number of "free" dopa receptors (D2 receptors) exposed by postsynaptic neuron on its surfaCe. It was already shown that/-dopa used in PD treatment, reducing the number of "free" receptors,, impairs uptake of D2 receptors markers; it is not yet clear how.long it takes to return to basal conditions after treatment suspension. We studied 22 PD patients patients after i.v. injection of 350 MBq of [~z31]IBZM, a new lygand of postsynaptic D2 receptors; according to Hoen-Yahr scale, all patients we~'e graded in the clinical stage I (10 pts), II (6 pts) or III (6 pts); among our patients, no one was graded IV or V. SPET images were obtained 30 minutes after injection (12 patients) or 2 hours after administration (10 patients). Our patients population was divided in two groups: treated subjects and patients with no treatment at all or, at least, for 24 hours; these two groups were homogeneous; als0 between patients who underwent the test 30 minutes after injection and those who underwent SPET 2 hours post injection it was not possible to find any difference. Our results and statistical analysis (unpaired Student t-test) show that there is a significant increment of the basal ganglia/cerebellum uptake ratio from 30 minutes to 2 hours post injection (p <10-9) . This uptake rati o is higher in unt(eated PD patients than treated ones; the difference between the two groups is already highly significant (p < 0.00"~) if test is performed 30 minutes after injection, but becomes much more significant (p < 2 • 10 "8) if SPET is acquired 2 hours post injection. Our experimer~tal data, obtained on slight or medium severity PD patients, Confirm that SPET should be performed 2 hours post injection. Moreover, our results support the hypothesis that in .early stage of PD there is an initial impairment of function of presynaptic dopaminergic neurons and an increase in the number of "free" D2 receptors on the surface of postsynaptic cells. In vivo imaging of dopamine receptors is conceived to deliver clinical informations related to etiology, drag response and therapy control in parkinson disease (PD). Aim of our study was to evaluate the new D2 receptor ligand Iodobenzamide 0BZM) in de novo parldnson patients and parkinson patients under treatment. The majority of the patients demonstrated latemlisation of their symptoms. Patients and methods: 15 patients (pt) were studied, 6 de novo pt without any previous anti-parkinson medication~ 11 pt had unilateral symptoms or side preference. Duration of disease in de novo pt was 0.75-4 years (mean 1.79) in the othe.r pt under L-DOPA medication (150-1000 rag/daily) 1-12 years (mean 6.1). L-DOPA was withheld at least 6 hours prior to imaging. After iv injection of 185 MBq 1-123 IBZM SPECT was performed (2 hours p.i., 40s/frsme, 64 frames, Sopha medical camera). Back projection was performed with Butterworth 6/16 filter. Uptake ratios of basal ganglia (BG) and frontal cortex (FC) were calculated. Results: Normal 2 hours BG/FC ratios (1.33+/-0.04 according to Tatsch) were seen in 8 pt (1. 29-1.40) , 7 pt had reduced BG/FC ratios (0. 93-1.25) . 5/6 de novo pt had normal BG/FC ratios. Regarding lateralization of PD, 7/11 pt with unilateral symptoms or side preference had an increased IBZM uptake in the affected BG (5-2!% , mean 12%, compared to comralateral BG) whereas only 3 pt showed increased IBZM uptake in the nonsffected BG (6-27%). 1 pt had no different uptake. Regarding lateralization of PD we found increased IBZM uptake predominantly in the affected BG, a finding also supported by PET studies using raelopride. This can be explained as an upregulation mechanism especially i n early disease. From these preliminary data of de novo and hemiparkluson patients we conclude that IBZM D2 receptor scintigraphy can provide valuable information on long term disease course. Poor data about side effects on pregnancy derived from high 131I doses have been reported. We evaluated a group of 68 female patients (pts), who had one or more pregnancies after 131I therapy (131I-TH) for DTC. All pts underwent total thyroidectomy and 131I-TH, in 5 cases to cure metastases to lung, in 16 to lymphnodes and in 47 to ablate remnants. 131I doses ranged 50-300 mCi, mean SD = 118.9 68.3. All pts were then treated with L-T4 at TSHsuppressive doses, thus giving a slight hyperthyroidism. This is known to represent an additional potential risk, other than 131I-TH. for the foetus. All pts were considered to be tumor-free at the time of pregnancy on the basis ot mdiological, scintigraphic and thyroglobulin findings. Mean age~D of pts at the time of 131I therapy was 24.3t5.0 yrs, mean agdSD at time of pregnancy was 29.~t4.2 yrs. During pregnancy, maternal serum T4, FT4, T3 and TSH levels were checked at least every two months and L-T4 doses were modulated accordingly. Foetal growth was also periodically checked. Moreover, in all infants after birth, thyroid function and clinical examination were performed. At present, 72 infants were followed-up and 8 pregnancies are in progress. Mean agr"SD of infants was 5.1r3.9, ranging 2 mths-15 yrs. Out ol these 72 infants, 1 was affected by Fallot trilogy, 3 had low birth-weight, but a successive regular growth, and the other 68 were considered to be healthy. Due to the mother's mild hyperthyroidism, breast-feeding was preferable no longer than 30-40 days to avoid infant's hyperthyroidism. On the basis ol these data it appears unrational to dissuade young female DTC-pts, previously treated with 131I, to consider pregnancy. However, it is recommended: 1. a time-interval from 131I-TH of at least 2-3 yrs, to evaluate complete remission of disease, and 2. frequent measurements of maternal thyroid hormones during pregnancy to avoid TSH fucreuse or hyperthyroidism.

H. L. Sharma. N.C. Jackson and H. Jackson Dept, of Medical Biophysics, University of Manchester, Oxford Road, Manchester, UK.

Although there is no definite correlation between low doses of radiation (internal or external) and mutagenic or other abnormalities, there is a need for re-examination of gonadal radiation doses from internally administered radionuclides.

In a series of experiments with In-ll4m labelled lymphocytes and labelled plasma, injected intravenously in laboratory rats, we have found 0,2 to 0.3% of the injected dose to be localized in the testes. The fraction remained relatively static over considerable long periods of time (upto 250 days). In a group of rats injected with 100 #Ci of In-ll4m via labelled cells or plasma, there was complete destruction of the spermatogenic epithelium, with the testicular weight reduced to around one third of age matched controls. Autoradiographs showed that, besides localization in the intertubular interstitial tissue, the Indium radionuclide became associated with morphologically mature sperm and their precursor cells -developing spermatids, apparently within the Sertoli cell cytoplasm. At a later time the In-ll4m could be seen in the epididymas sperm so that the label is seemingly retained during transport of these cells through the organ. It is of concern that In-111 will behave similarly when used in the form of labelled platelets or leukocytes in Nuclear Medicine because of the high mutagenic sensitivity of spermatids to radiation. Scans in patients are known to outline the testes.

These findings are both relevant and important regarding the possible entry of radionuclides into the germinal cells and the risk of mutagenic damage. -ethyl, N-ethoxy) dithiocarbamato] nitrido technetium(V) (TcN-NOET), is a new tracer currently under preliminary clinical evaluation as myocardial imaging agent. This compound is characterized by the presence of the Tc~N group and by a vanishing overall net charge. It is efficiently extracted by heart tissue in varinos animal models and in humans, and the clearance from the myocardium is generally slow (ca. 6 h). This tracer therefore constitutes the first example of a neutral technetiumradiopharmaceutical which remains localized in myocardium cells for a long time. Te-BATO compounds, which form the only other class of neutral myocardial imaging agents presently known, are rapidly eliminated from the heart within few minutes after injection. It would be therefore of importance to determine the subeellular distribution of TeN-NOET in order to increase the understanding of its mechanism of localization in heart tissue.

Subcellular localization of TcN-NOET was obtained by cell fractionation experiments. Following intravenous injection in male rats, cardiac specimens were removed, homogenized and subjected to differential centrifugation for the isolation of the subeellular organdies. Significant amounts of activity was found in all fractions, but not in the cytosol. These results suggest that TcN-NOET uptake probably involves nonspecific partitioning into the internal membranes of the heart cell, and that this process is regulated by the liphophilic properties of this neutral compound. They indicate also that the mechanism of localization TcN-NOET is basically different from that of observed with technetium monocationic compounds, which were found to bind selectively mitochondria. 

Accurate estimation of bone marrow uptake of radiopharmaceuticals is very important for accurate whole body dosimetry. In this study, a method to obtain normal bone marrow without inconvenience to the patient is described and compared to a commonly used region of interest (ROI) technique. In five volunteers (group 1, mean age 63.0 yr, range 49 -76 yr), 4 MBq indium-111 labeled human polyclonal IgG (In-111-1gG) was administered 48 hours before placement of a total hip prosthesis for degenerative osteoarthritis. After resection of the femoral head and neck, a bone chip was obtained and bone marrow was aspirated from the medullary space with a biopsy needle. In five patients without diseases affecting bone marrow (group 2, mean age 64.6 yr, range 56 -70 yr), bone marrow uptake was calculated from ROIs over the lumbar spine, 48 hours after injection of 75 MBq In-111 -IgG. Bone marrow uptake in group 1 (4.5 + 1.3 %D/kg) was significantly lower than that in group 2 (8.5 ± 2.1%D/kg), p < 0.01. Bone uptake in group 1 was 1.7 + 0.4 %D/kg. Blood and plasma activity did not differ significantly for both groups (5.5 _+ 1.1 vs. 6.3 + 0.9 %D/kg and 8.7 + 2.4 vs. 10.2 _+ 2.3 %D/kg, respectively). Intraoperative bone marrow and bone sampling provides a system for accurate, direct measurement of normal uptake in bone marrow and bone of all radiopharmaceuticals at various time points. It is a safe and simple procedure without any discomfort to the patient. Since small amounts of activity are sufficient, the radiation dose to the volunteer is low. Andersen et al. found that the lipophilic-hydrophilic transformation (LHT) of 99m-Tc-HM-PAO enantiomers differed considerably in the plasma and the blood, and proposed GSH as the rate-limiting reactant for LHT. However, the possible benefit of using isolated monomeric HM-PAO compounds for CBF studies or cell labeling is still unexplored. We found significant differences in the LHT rates (Kd) of the various chloroform-extracted 99m-Tc-I-IM-PAOs in the presence of 10 mg/ml GSH, with Ballinger's method (Kd. values: meso-:0.00221, d,1-:0.00687, d-:0.00498, 1-:0.01132 s=l). These results demonstrate that the LHT of 1-HM-PAO is about 1.7 times faster than that of the routinely used d,I-HM-PAO. Presuming that this difference would be in vivo too, we have developed a novel experimental leukocyte-labeling method to verify this supposition. Using 20 mg/ml GSH to stop the reaction, we could measure the cell-labeling efficacy with a resolution of about 10 sec. These experiments verified that 1-HM-PAO is "taken UP more rapidly .and in hig,her quantity by leuk.ocytes than are the d,1-and d-HM-PAO (2x10 ~ cells/ml 1.: 88.27 ~ 4.7% at 6 min, d,l-: 77.53 + 2.6% at 10 min, d-:80.65 _+ 2.77% at 12 min). The cell viability, the in vitro stability of labeling and the effects of volume and cell concentration for labeling efficiency were similar for all isomers of HM-PAO.

The results indicate that 1-HM-PAO is the best choice for celllabeling purposes, and probably for CBF investigations as well. 

Purpose: The aim of this study was to determine whether absorption of Egg-C057-vitamin(vit.)B12 differs from crystalline- .B12 in patients with low serum vit.B12 levels. Material and Methods: 250 kBq Co57wit.B12 was injected into the breast muscle of an egg-laying chicken on 3 consecutive days. Radioactivity in eggs became apparent 1 tO 2 days after the first injection, reaching a peak activity at day 6 to 8. Eggs nr. 4 -16 after injection contained a total activity of 300 kBq Co57. All activity was found in the eggyo~k. The yolk was separated from the white of the eggs, homogenized, and scrambled in a frying pan during constant stirring until a medium dry texture was obtained.

Twelve to 14 portions of about 12 gram each, containing 18 kBq Co57, were packaged in plastic containers and stored in a freezer at -20 ° C until served. At the day of administration one portion of Co57-scrambled egg was heated in a microwave oven for 30 seconds and served to the fasting patient. At 0 and 24 hr after administration of the egg-Co57wit.B12, 1 mg of nonradioactive cyanocobalaminum was injected intramuscularly to fill up vit.B12 depot in the body. Urine was collected for 48 hr and Co57 activity measured. A similar test was performed in all patients after oral administration of a capsule containing crystalline-vit.B12. Results: ITLC analysis revealed that more than 99 % of C057 was bound to eggprotein. In normals (serum vit.B12 150 -380 pmol/I) the 48 hr. urine conrained on average 10.5 % of the administered dose (I.D.) egg . After crystalline- .B12 this value was 20.5 %.The egg-Co57-vit.B12 / cristalline C057-vit.B12 ratio was 0.5. In patients with a poor assimalation of food vif.B12 this ratio was below 0.25. Conclusion!The use of egg-Co57-vit.B12 better reflects vit.B12 malabsorption compared to conventional crystalline- . With this technique it is possible to differentiate patients with poor assimilation of food vit.B12 from those with normal assimilation of food vit.B12.

The Isotope-Pharmacy 378 Frederikssundsvej DK 2700 Br~nsh~j, Denmark

A method for the preparation of a In-111 labelled recombinant tissue plasminogen activator (rt-PA}, with a radiochemical purity of more than 85 %, and an immunoreactivity of more than 80 %, is described.

The preparation is based on the commercially available drug 'Actilyse' (Boehringer Ingelhelm) . A preparation kit, which is stable for several months, is formed. The ready- for-use In-lll labelled compound is stable for several days without significant decreases neither in radiochemical purity nor in immunoreactivity.

The preparation has been used clinically to assess the biological half-life of rt-PA in conjunction with fibrinolysis treatments. Results from. the clinical application will be shown.

C..G~r~iq Department of Nuclear Medicine, Johannes Gutenberg-University Mainz, Germany FIRST EXPERZENCE WITH A NEW CAMERA AND COM-PUTER SYSTEM FOR MYOCARDIAL STUDIES COMBINED WITH FIRST BASS.

Since November 91 we are working with a new computer and camera system for heart studies in our department. The camera (Orbiter/Siemens) has special electronics and a crystal which can count more than 200000 cts/sec. That means we are able to do first pass an.d SPECT studies on one camera. After changing the collimator (LEHS/LEAP) the camera is ready for one of both examinations. For those special techniques.it is necessary to use a very fast and powerful computer system. In our department we use ICON (Siemens). ICON is able to acquire and to reconstruct data at the same time in an enormous speed. The computer is based on a Macintosh computer system (Apple) and is easy to handle. It offers the technologist and the physician new possibilities in processing and displaying the acquired data. This paper will present our first experiences with this camera and computer system and will show some examples.

S. Fischer Department of Nuclear Medicine, Johannes Gutenberg-University Mainz, Germany

During the last years computer systems in nuclear medicine changed extremely. New "Super Comphters" offer the technologist and the physician new possibilities in processing and displaying SPECT data. This paper will present our first experience with an "Odyssey" computer (Picker International). For processing there are new filter techniqves which allow either prefiltering of the raw data or postfiltering of the reconstructe d slices. For display "Odyssey" offers the possibility of a three dimensional (3D) image presentation. Within a very short time it is possible to see~a complete SPECT data set on the ~creen. We analysed 3D-SPECT data in many cases of bone scintigraphies, brain studies, lung ~tudies etc. in different ways to find an optimal way of presentation. 3D image presentation is not used routinely, but in some cases it seems to be helpful in understanding the spatial correlation between hot spots and organ surface. Cold lesions can only be seen if they reach the organ surface. If they are inside the organ only special processing allows their visibilty. To d~agnose the cause of pain in knee prostheses, it is necessary to identify the origin, which may be infection, mobilization of the prosthesis or aseptic inflammation. In an attempt to differ-en£iate among t_hem, a diagnostic protocol has been applied using 3 different explorations: 3-phase bone scintigraphy with DPD-Tc-99m, Ga-67 citrate a~d To-99n~labeled antigranulocyte antibodies (MoAb E~ 250/183), and the results cc~pared with those of 5 patients with asymptcmatic knee prostheses. In all, 25 patients with unilateral and 7 with bilateral krlee prostheses were studied. The patterns observed were: Normal: in the DPD-Tc-99m study, there may be an increase in phase-3 uptake, which is diffuse and nonfccalized, with normal distribution of vascularization, CA-67 citrate and antigranulocytes. Mobilization (9 pr~-theses): periprosthetic hyperuptake focalized in the mobilization sites with DR), and normal distribution in the other twD explorations. Acute infection (5 prostheses Conclusion: DBS is a sensitive method for a s s e s s i n g bone turnover rate according to the degree of skeletal uptake of radionuclide. In this manner it is possible to determine both the type of RO and its further d e v e l o p m e n t in repeated measurements. Patients with peripheral neuropathy or peripheral arterial insufficiency have more frequently various types of pathology and often require a bone scan to distinguish soft-tissue disease from osteomyelitis (OM). A three-phase bone scan was advocated as the method of choice for the diagnosis of OM, but specificity remains insufficient. We evaluated 99mTc-labeled nonspecific polyclonal human immunoglobulin scintigraphy (HIG) in 34 patients (21M:13F; mean age+/-sem: 60.6+/-2.0 yrs) with suspicion of OM of the extremities associated with diabetes or peripheral arterial insufficiency. Three-phase bone scans (BS) were done after iv injection of 20mCi/70kg body weight of . When necessary, a 24-hour image was also done. One day later, an iv injection of 18 to 20 mCi of HIG-99mTc was dor~e and images were acquired at 4 and 24 hours post-inj. The final diagnosis was recorded in the patient file at the time of release from hospital. BS was defined as positive for OM with the c.riteria: 3 phases positive (perfusion, blood pool and delayed image). Resutts: of the 34 BS, 69 focal hypercaptations (FH) were detected on delayed images. Among them, 48 FH were considered as compatible with OM whereas 21 were negative. The HIG scans of the 21 negative FH were also negative. HIG 0 f the 48 positive FH were positive in 31 cases and negative in 17. When the final diagnosis was considered, the 2"1 FH negative did not have OM. Among the 31 HIG& FH positive, 7 were false-positive. None of the !7 HIG negative & FH positive were falsely negative. Thus the sensitivity and specificity were 100% and 52.5% respectively for BS, and 100% and 82.5%, respectively for HIG& BS. Among the 7 false-positive HIG& FH 5 were present in 1 patient who hedimultifocal lesions of gout arthritis. Conclusions: These results indicate that HIG may add valuable information to bone scan, improve dramatically the specificity of diagnosis of OM and should be considered to be done in complicated sit~Jations in the presence of a positive bone scans to increase specificity of diagnosis of OM.

GP Schembri, LA Forstrc~n, BP Mullan, MF Hauser Nuclear Medicine, Department of Diagnostic Radiology Mayo Clinic, Rochester, Minnesota 55905 USA

The assessment of Indim,-lll oxine labelled leukocvtes studies (In-WBC) involves an appreciation of normal marrow pattern. In patients with trauma or prosthetic implants, this may be altered. Technetium Sulphur colloid (Tc-SC) bone marrow scans should be useful in these patients.

62 patients with 67 sites of possible infection were reviewed. All had In-WBC and Tc-SC scans and 61 had three phase bone scans (HDP). There were 40 males and 22 females (mean age 62). Sites included 9 GirdlestOne's procedures, 39 hip and 10 knee prostheses. The In-WBC scan was performed at 24 hours using 18 MBq of In-lll with i0 min/view. 370 MBq of Tc-SC was administered with 10 min/view. Final diagnosis was established by surgery (n=34) or clinical followup (n=28; m i n i m~ 6 months or until other diagnosis established). Infection was present in i0 sites.

The studies were retrospectively reviewed by 3 blinded observers using a 1 to 5 grading, l=definitely negative and 5=definitely positive. The In-WBC scan was read alone, then with the HDP scan and finally by adding the Tc-SC scan. Plain X-rays OR UNSPECIFIC

The uptake mechanism of Tc-99m-labelled immunoglobulins in inflammation is still unknown.Unspecific, specific or a combination of both aecumularion types is discussed.

Anti-rat CD4-mab(monoclonal antibody)(W3/25;IgG1)and antihuman CEA (BW341/26;IgG1)as isotype matched control mab were labelled with (37MBq )TC-99 of each mab were injeeted into normal and arthritic(AA;day 19) recipient rats.Joint uptake of radlolabelled mabs was monitored for 4h with a gammacamera(20min/frame) fitted with a pinhole collimator.Tissues were measured 16h p,i. in a gamma counter. Preferential accumulation of both anti,CD4 mab and control mab was detected in arthritic joints when compared to normal joints.In contrast the CD4-mab accumulated in lymphoid tissues,the anti-CEA mab remained of high levels in blood.

3 patients with human rheumatoid arthritis received 200-300ug of a 555MBq Tc-99m-anti-human CD4-specifie antibodies(MAX16H5//gG1).3 patients received lmg Tc-99m labelled human unspecific immunoglobulins (I-IIG; MALLINCKRODT). Gammacamera intages of the joints were performed lh,4h and 20h p.i..The uptake of both immunoglobulin(% of whole body activity)(CD4:2,4%;2,1%;2.0%; HIG: 2.0%;1.7%;2.6%)was comparable. In one female additional To-anti CEA joint uptake could be registrated (1.9%) in a reference joint(knee). In conclusion,the body distribution of anti-CD4-mabs is determined by their immunological specificity,the uptake in pathologic altered joints seems to be unspecific in an animal model and human arthritis.

J Ortiz Moulia~, J Panms Sanz, C Sanjuan Robles, M P4rez l~ramo, E Escribano, J Clabo, J Ortiz Berrocal Servicio de Medicina Nuclear, Clinica Puerta de Hierro, Madrid, Spain CLINICAL UTILITY OF ~ ANTIBODIES ~W 250/183 I~ THE DIAGNOSIS OF GOMPLICATIONS OF THIGH P~OS~?~SES Differential diagnosis between mobilization and infection in thigh prostheses is frequently necessary. Early detection of infection is of great clinical interest. To assess the p~ssible utility of Tc-99~-labeled antigranulocyte antibodies in these cases, 52 patients with total thigh prostheses (15 bilateral) were studied; 7 asy~o-t~matic prosthesis bearers (with over 6 mo of evolution) were used as controls. All were studied with 3-phase DPD-Tc-99m, Ga-67 citrate and Tc-99m-labeled antigranulocytes. The distribution patterns were: Normal (7 prostheses): no hyperuptake focuses in periprosthetic zor~s in any of the 3 studies. C~ronic infection (19 prosthe-~):

focal hyperuptake of DPD and Ga-67 and normal distribution of Tc-99m-labeled antigranulocytes. Acute infection (14 prostheses): hype~ of all 3 radi~harmaceuticals, which was focal; tb~t of antigranulocytes coincided with the infectious focus. In cases of extension to soft tissues, aocumulation of the antigranulocytes in the~ was greater than that of mobilization (27 prostheses) : focal or diffuse accumulation of DPD in the mobilization zone, and normal distribution of anti~ulocytes. Suspected macrophaqe activation (7 prostheses): in acute or chrcnic infection, we observed a very marked rise in uptake of antigranulocytes in the f~oral dial~hysis, which in one case, presented in contr~lateral f~s~r. antigranulocytes represent an easy and efficient tool for dete~ting acute infection focuses in periprosthetic zones of t/he thigh, surpassing the diagnostic aocuracy Of Ga-67 and DPD- . The l~hysiopathol~gic significance of the pattern we describe for suspected activation of micr~pheges, which play an i~0ort~nt role in the infla~tion/repair pro~ess, r~ains to be determined. Various radiopharmaceuticals and different methods have been used to image and quantify inflammation in peripheral joints. ~be aim of this study is to compare ~he response of STom-HMPAO labelled leucocytes and ~Tom-MDP to intraarticular steroid injection. The uptake of both radiopharmaceuticals in the synovium and bone of the knees of eleven patients with RA were measured using an interpolative background subtraction technique. The mean duration of RA was B.2 years. Significant neutrophil migration and MDP uptake occurred in the knees irrespective of disease duration. In the baseline study, neutrophil uptake was demonstrated in the knees of all patients at 22 hours and ranged between 0.014-0.512% of injected dose, while MDP uptake at S hours ranged between 0.357-S.66% of the injected dose. In all but one patient neutrophil mignation in the injected knee was reduced after intra-a~tieular steroid injection. The shanges in MDP uptake after steroid injection were variable. There was linear correlation between the changes in pain scores and those of neutrophil migration in the injected knee (r:O.87,p(O.O01) while a poor correlation occurred between changes in pain scores and quantitative bone scintigraphy [r=o.59,p~o.05). The MDP and white cell responses in the knee contralateral to that injected varied from negative to positive. Conclusion: The quantitation of the neutrophil componen~ of the inflammatory process is a sensitive index for monitoring RA activity and response to phammaoologisal interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA. Methods used formerly for the detectior~ of infectious osseous lesions (Tc-99m-HMPAO labeled leukocytes, Tc-99m-anti-granulocyte antibodies) did not always show a sufficiently high specificity (e.g. false positive findings in peripheral bones, false negatives in the spine). The.refore, in a prospective study the clinical significance of the new inflammation agent, Tc-99m-HIG, has been evaluated. 27 patients were thus far referred with the suspicion of: peripheral osteomyelitis (n=3), septic spondylitis (=5), septic prothesis infection (n=6), rheumatoid arthritis (n=10; 6 serum positive; 4 serum-negative), and fever of unknown origin (n=3). The scans were obtained as whole body studies and planar regional images 4 and 24 hours p.i., and were evaluated blindly by two experienced readers. In all patients a final diagnosis was established based on either surgery or long-standing clinical course.

Of the 27 sgans, 17 were true positive, 8 true negative, and 2 false negative. There were no false positive HIG scans. The true positive scan s comprised 4 patients with septic spondylitis, 6 with rheumatoid arthritis, 2 with peripheral osteomyelitis, 4 with infected protheses and one with fever of unknown origin. Of the true negative scans, 3 patients had the suspicion of rheumatoid arthritis, 2 of infected protheses, one of spondylitis and two of fever of unknown origin. Of the scans which were false negative, there was one battered child with traumatic septic osteomyelitis of the right forearm which had been clearly shown on the previous MDP study. The other false negative finding was a patient with monarthritis of the 2rid metacarpal joint.

The image quality of HIG scans is excellent since there is no interfering bone marrow accumulation. In this study HIG showed a greater sensitivity of detecting lesions in the central bones and a lower number of false positive findings in peripheral bones, 

Patients and methods Between february 1988 and november 1991, sixty patients (51 with hip arthroplasty and 9 with knee arthropl .ast.y) suspected of septic loosening were imaged four hours post-lnjecuon of autologous leukocytes labelled in RPMI medium with 200 MBq of 99mTc HMPAO (Ceretec Amersham). 99m Tc MDP scans were performed only in 27 cases. Scintigraphic diagnosis was confh'med by surgical control, results from bacterial cultures, histologic f'mdings or by clinical follow-up.

Label efficiency averaged 60 %. Fifty eight sites were studied in the hip arthroplasty group. Surgical control occured in 30/51 hip protheses (14 TN, 14 TP, 1 FN, 1 FP). Three false positive aseptic inflammation were found. The sensitivity and the specificity of sepsis detection were respectively 95 % a n d 9 1 % . Nine sites were analized in the knee arthroplasty group. Six positive scans were obtained, 3 of them proven by surgery. One patient with thigh hematoma post-arteriography was considered as false positive result. Two teeth abeesses, 1 sinusitis and 1 pulmonary abcess were also identified among 60 patients investigated.

A scintigraphic follow up occured in 6 patients. A second leukocyte scan made one to three months after the first remained positive.

Tc99m HMPAO labelled leukocyte scanning is a suitable method to manage suspected orthopedic prosthetic infection.

~t , M.Gericke#, U.Staboll#, L.Eckart* ,Praxis f. Nuklearmedizin, Dillenburger Str.1, 1000 Berlin 33, *Dept.of Orthopaedics, University Clinic Rudolf Virchow

Conventional Bone-SPEC'I: with 99mTc-diphosphonate was always limited due to the poorly spatial resolution. HR-SPECT with 3 head gamma-camera systems with UHR collimators and 128 X 128 aquisition matrices allowes superior image quality and topographical assignment. The most advantages of high resolution SPECT with 3D-reconstruction will oe expected in areas where complex anatomical structures have to be differentiated like the spine. Particular of interest was if higher image quality allowes a better Iocalisation and correlation with radiol0gical findings and leads to better differential diagnos~s.

45 patients with degenerative, inflammatory or metastatic changes were investigated with HR-Bone-SPECT. All patients had x-ray, CT or MRI-studies. 3 hrs. after 550-600 MBq 99mTc-MDP planar analog images were obtained (450,000 cts), followed by Bone-SPECT with 3 head gamma camera (Prism 3000,Picker), 40 (120) angles, 30 -45 sec.A'iew; step and shoot aquisition, total aquisition time approx. 20-25 minutes, FBP-ramp filter and post-reconstruction 3D-low pass filtering.

7.6 mm transaxial, coronal and sagittal slices were reconstructed. 3 dimensional surface rendering was done using optimized threshold and background correction.

The high-resolution bone-SPECT with 3-head-camera showed a superior image quality and allowed much better delineation of bony changes in the spine and an accurate topographical assignment. In cases with minor changes in the lumbal spine, HR-SPECT can visualise degenerative and inflammatory processes in the vertebral joints and and allowes exellent correlation with x-ray findings. Due to the high spatial resolution and better delineation, differentiation between dege-r~erative inflammatory or malignant cause of increased osteo-Dlastic activity seems to be more reliable. A Comperative study to Tc-99m MDP Introduction:The present study was undertaken in order to investigate the value of TI-201 scintigraphy in the evaluation of musculoskeletal (MS) lesions, in comparison with Tc-99m MDP scintigraphy. Method: A total of histologically confirmed 102 MS lesions (57 malignant, 45 benign) were included in the study. Static images were acquired 20 min. "after IV. injection of 3mCi . Within 4 days all patients (pts) were also underwent three phase bone imaging. Lesion MDP and TI-201 uptake ratios were obtained by means of ROIs assigned over lesion and contdateral sites. TI-201 uptakes of lesions were scored according to a four-point grading system taking heart activity as reference. Results:Tl-ii)l and Tc-99m MDP uptakes of benign lesions were 1.32 -+ 0.28 and 2.45-+0.91 (p<0.0005), of .malign lesions were 3.11-+1.52 and 3.16 + 1.27 (p > 0.4) respectively. It is noted that, there was no significant difference in MDP uptakes of benign and malign lesions. On the other hand, uptakes of benign lesions were significantly lower than malignancies, except for brown tumors (n:3) and giant cell tumors of bone(n:5). Seven malign soft tissue tumors showed TI-201 uptake but not MDP. In 5 cases, parenchymal metastases were detected by TI-201 scan. 2 of 7 pts, examined in order to differentiate postoperative fibrosis from recurrency, demonstrated positive scans which were consistent with pathological specimen, while CT and MRI were equivocal. Tumor therapy responses of 4 pts with primary bone sarcomas, monitored by TI-201 scintigraphy were well-correlated with pathological findings. Conclusion: scintigraphy is a valuable tool in differentiation of malignancy from benign MS lesions and local recurrences from post operative fibrosis especially when other methods are equivocal. This modaLity is also reliable in the evaluation of tumor viability in the posttherapy period. Tc-99m-HIG is generally considered as a promising agent for the detection of infectious conditions, It offers several logistic advantages over other agents already applied in this clinical context. The aim of the presented study was to assess the value of Tc-99m-HIG in orthopedic/trauma patients with suspicion of focal infection. 120 patients(82M:38F, mean age 57.6) underwent Tc-99m-HIG sclntlgraphy: All patients had an intravenous administration of 600MBq Tc-99m-HIG, acquisition of images was obtained 4-6 and 24 hours post infusion. Final diagnosis was established by open surgery (75/120) or clinical course (45/120) . Three pathological HIG accumulation patterns were identified: (F)ocal, (D)iffuse or (M)ixed and were judged indicative for infectious conditions. In all patients with proven infectlon(74 ) HIG was shown to be true positive with pattern F in 42/74, D in 26/74 and M in 6/74. In these HIGs, positivity was seen on the 4 hours p.i. images already. In the patients with final evidence of no infection(46) HIG was true negative in 3~/ 46. The 12/46 false positive HIGs were achieved in patients in whom surgery had only been performed <8 days before. In conclusion these rosults demonstrate the high sensitivity of Tc-99m-HIG in the assessment of infectious conditions of orthopedic/trauma patients. However, one should be aware of false positive HIG studies in patients with recently performed surgery. 79 patients with and without significant cognitive deficit were studied clinically and radiologicslly. 25 patients have died to date.

A ccmbirmtion of medial temporal lobe atrop~ revealed by X-ray cc~puted tomogrsp~f (or) and h~poperf~sion in the psrietotempoFal cortex revealed by single photon saission tc~ography (SPNT) was found in ~/51 with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT), in ~/i0 with other clinical t~pas of d~mentia, sed in 2/18 with no evidence of cognitive deficit (ref i). Of the 23 who have died, 18 had histopatholo~ical Alzheimer's disease, i had PSP, 1 had NPH, 1 had "pre-AD", end 2 were ccntrols with no signlficsnt CNS patholo~. 17/18 with AD showed a c~blnation of medial temporei lobe atrophy and pa~ietot~oral hypoperfusion. The ccr~bination was mot present in ar~f of the othem 5 cases. Tne~e were no false positives.

We st~gest that the ccmbination of medial te~DoPal lobe atrophy and pa~ietotempor'al hFpoparfhsion is a feature of Alzheimer's disease and that the functional chang~ in the parietote~noFal megion nmy be due to the loss of projection neumons in the parahippocsmpal gymls that innervate this region. Evidence for this fgom ou~ cohomt is that 10/12 patients (9 with SDAT) had greater than 3 nm moro medial tempor~l lobe atropkf on one side of the brs/n than the other, and equivalent 8synmetric pa~ietotempor-al l~fpoper4hsion g~eater on the s~ne side on SPET. 

H,Feistel z, D.Ebert 2, F.WolfZ Depts of~clear Medicine and 2Psychiatry Friedrich-Alexander-University , Erlangen, FRG   EFFECTS  OF  SLEEP  DEPRIVATION  ON  THE  LIMBIC  SYSTEM  AND  THE  FRONTAL  LOBES  IN AFFECTIVE  DISORDERS: A STUDY WITH TC-99M- HMPAO-SPECT Sleep deprivation has a nonpharmacological antidepressant effect in some ('RESPonder'), but not all patients ('NONRESPonder') with major depression, melancholic type. The aim of the study was to show if depressed responders can be differentiated from nonresponders by different patterns of cerebral blood flow. Patients and methods: We studied 10 depressed patients----~--~-IllhR~ 5 Women, 5 men, 38.9 +-9.1 years) before and after sleep deprivation with Tc-99m-HMPAO-SPECT between 8 and i0 a.m. All depressed Patients had a minimum score of 20 on the 21-item Hamilton Rating Scale for Depression (HRSD). RESP were defined to show a 50% decrease on HRSD after sleep deprivation. Semiquantitative evaluation of all brain SPECTs was performed and compared to normal subjects (n=8). Results: Five patients were identified as RESP (HRSD 29.1 +-5.7). In RESP. and NONRESP. the left frontolateral cortex was hypoperfused (p<0.01) before and after deprivation, RESP. were additionally hypoperfused in the upper left prefrontal cortex (p<0.01) before deprivation. Perfusion was found to be increased in RESY before deprivation in frontoorbital cortex, right hippocampus, and infratemporal lobes (p<0.01). After sleep deprivation there were no Significant differences compared with normals. Conclusion: The neural circuit connecting the structures with increased perfusion in depressed state is known aS "limbic loop" which subserves emotions and their behavloural consequences. Sleep deprivation normalizes the hyperperfusion. The aim of our ongoing study was to compare the results obtained by this technique in two diagnostic groups: major depression and schizophrenia. The other aim was to correlate the results with psychopathological symptoms. We have analyzed the results in 9 depressive and 16 schizophrenic in-patients. The mean HDRS (Hamilton depression rating scale) of depressed patients was ,~r4~0_+7.0. The PANSS (positive and negative symptom scale) ~rating of schizophrenics was 101.5+23.4 (total), 21.2_+8,3 for~positive symptoms, :~7,6+10.5 for negative symptoms, and 52.7+10.5 for general psychopathology. 6 of the depressive and 9 of the schizophrenic patients sho~ed a pathological blood fl~ pattern within the brain. I n 4 9f the depressive patie~,~/~ ~ild in'8 of the Schizophrenic patients we observed a hylJ~lSerfusion of the left temporal lobe. 3 bf the schizophrenic patients also had a hypoperfusion of the parietal lobe. -Schizophrenic"patients ~itl~ a ~ hyp0peffusion had a significant higher score of PANSS for positive symptoms (p < 0.01) and for general psychopathology (p < 0.05) compared to those wjt~ normal peffusion. Similar results were obtained for the I-IDRS Sc0fe in depressive patients showing a hypopeffusion (.p < 0.05) compared to those with normal HMPAO-SPECT findings. -In conclusion, the hypoperfusion of the left temporal lobe seems to be a common result in both schizophrenic and depressive patients, and psychopathology seems to correlate with pathological cerebral blood flow. More data are required in order to determine the role of specific symptom patterns associated with pathological blood flow results. Podosky.

To determine cerebral perfusion imaging's ability to differentiate multi infarct dementia (~ID) and Alzheimer's disease (SDAT) from other dementing disorders, we retrospectively evaluated the results of 1 or 3-headed Tc-99m H~PAO or 1-123 IMP brain SPECT scans in 26 demented, 18 non-demented, and 9 normal volunteers and correlated them with the patient's final clinical diagnosis.

Scans were interpreted blindly by consensus of 2 readers as either normal, single or multivessel cerebral vascular disease, SDAT, MID, or mbnormal non-specific pattern. Final clinical diagnosis was made without knowledge of scan findings using CT, MRI, EEG, Rashinski~s Score and neuro assessment and outcome. SPECT correctly categorized 8/10 SDAT and 6/6 MID. 3/4 Parkinson~s with dementia were classified as SDAT.

SPECT correctly excluded SDAT and MID as cause of dementia in 6/6 other pts. A SDAT or MID pattern was seen in 2/16 non-demented pts and in 1/9 normal volunteers.

The sensitivity of SPECT in detecting SDAT and MID was 80~ and i00~, respectively. Brain SPECT correctly differentiated all SDAT and MID from other causes of dementia except Parkinson~s disease.

Brain SpECT is a highly accurate method for detecting SDAT and MID and for differentiating SDAT and MID from other causes of dementia. Tc-99m-EC /N,N'-ethylen-L-dicysteine/ is a pr~ mising scint±graphic agent for dynaa±c renal studies /Verbruggen es, 199o/. Our first clinical results obtained by a new kit-form of TC-99m-EC /with labelling efficiency over 98 per cent/ are presented. 122 patients with hypertension and/or various renal disorders were studied. Biodistribution was evaluated by dynamic renal scintigraphy in patients with normal /n=32/ and impaired /n=9o/ renal function, Results: in patients with normal kidney function high renal uptake and rapid intrarenal transport of Tc-ggm-EC were found. Tmax values of the renal activlty-time curves were 4.2 + o.3 min, T 1/2 of elimination were 9.1 + 1.~ min, Plasm~ olearance values were 462 + ~5 ml/min/l.73 m ~ /by ~odified Oberhausen/ a'~d 451 + 32 ml/min/l,73 m /by Tauxe method/. PIas~a protein binding proved to be iow /28.3 + 2.5 per cent/, Good-quality images of the ~idney and urinary tract were obtained. No uptake in the liver was viauallzed even in patients with impaired renal function. In concluslon: our new commercially avaiIable kit of Tc-99m-EC proved to be a good agent for dynamic renal sclntigraphy. It seems to be a real Tc-99m-labeIIed substitute for Hippuran. 

As an alternative to the Tc-99m DMSA, we recently proposed a new renal imaging agent, for quantitative assessment of renal function: the bidentate-N,S chelate N-(mercaptoacetyl) glicyne (2GAM). After biodistdbution and toxicity studies in animals, Tc-99m 2G~M was evaluated in normal volunteers. 74 MBq of Tc-99m 2GAM (radiochemical purity = 98.5%) were injected intravenously. Blood and urine samples were collected for 24 hrs. Posterior activity was recorded at appropriate times for 24 hrs to evaluate kidneys time activity curves. Whole body biodistdbution was evaluated at 30 min, 1.5, 3.5 and 5 hrs p.i. by the conjugate counting technique. 2GAM rapidly cleared from the blood ( T 1/2 = 9 min.). Fifty percent of I.D. was excreted in the urine in the first two hours after injection. Dynamic data showed a rapid renal uptake that increases up to 45 min without significant washout over 8 hours, and a low, stable liver uptake as shown in the DMSA under the same experimental conditions. Tc-99m 2GAM is characterized by a faster rapid renal uptake (maximum uptake in 45 min vs. 8 hrs). We conclude that Tc-99m 2GAM has optimal properties for renal imaging in humans showing practical and dosimetrie advantages over DMSA. 

Planar static renal imaging with 99mTc-DMSA is of large interest for morphological studies. Specially in the paediatric field, it is useful to evaluate effect of infectious diseases on the renal parenchyma, and in that way to detect possible renal scarring, With the high spatial resolution collimators and detectors the limiting f~ctor of high quality renal 99mTc-DMSA imaging is now the renal motion artefacts.

Because of the poor kidney activity in 99mTc-DMSA imaging, it is not possible to correct motion artefact by simple kidney picture adjustment in a dynamic study, Because kidneys are moving essentially with respiratory cycles, we propose to synchronize the data acquisition with the respiratory cycles. Our method need a pinpoint 99mTc source fixed on the costal edge. We acquire a fast dynamic study of 800 0,5 sec imaging (128x128 with high resolution collimator). The motion correction is done by calculating the centre of gravity of the 99mTc pinpoint source and magnifing to 256x256 static imaging. The first results demonstrate significant enhancement of quality imaging, particularly in paediatric patients.

The localization of 99mTc-DMSA in kidneys was investigated in mice after induction of renal dysfunction symptoms resembling to the Fanconi syndrome in humans. Mice injected i.p.

with disodium maleate (MAL) (6 mM/kg BW) showed 90 min later, abnormal levels in urine of glucose,.

B~ oteins and aminoacids. In MAL mice and in controls ~mTc-DMSA pharmacokinetics was studied in the 5 min to 24 hr interval after i.v. injection and whole-body auto-~ diographies were performed i hr after injection of ~mTc-DMSA. The results show that blood clearance and urinary excretion of the radioactivity are delayed in MAL mice: 4 hr after injection of ~mTc-DMSA 10.34±0.98% of injected dose remained in blood compared to 5.28±1.87% in controls, and excreted activity in urine was 37.25±3.8% of injected dose in MAL mice compared to 48.41±0.60% in controls. By radioactivity measurements the kidneys did not show significant differences: 17.23±3.30% of injected dose in MAL mice compared to 15.55±3.92% in control.s. However, quite opposite intra-renal localizations of radioactivity were shown by autoradiography between the two groups of mice. In controls the highest cortex activity is located outside with a progressive decline towards medulla. This situation is inversed in MAL mice where the highest activity is cited very close to med-ull~ The results suggest that intra-renal perturbation of mTc-DMSA localization sites is an important diagnostic sign of renal dysfunction, which should be showed by a sensitive imaging technique in order to increase the clinical utility of the radiopharmaceutical. (sd 0.8), to the right 8.5%C0 (sd i.i) and to both 18.3 (sd 1.5).

Reduced RBF values were found in patients with renal failure (<5%C0). EF in the normal left kidney was 45% (sd 7.6) and in the right 49% (sd 9.5) whereas poorly functioning kidneys had EF as low as 19%. RBF determination in man is possible using 99Tcm-Mag 3 and its EF can be derived using dynamic scintigraphy. It therefore has the potential to investigate the effects of disease/treatments on RBF and EF. Extracorporeal shock wave lithotrlpsy (ESWL) is a new modality used for treating renal lithiasis. The aim of this s~udy was to determine whether there was any effect of ESWLon the renal function and in particular to demonstrate some possible evidence for the development of obstructive nephropathy. To this end, renal radionuclide studies were performed before and after (24-48 hr) ESWLand the following functions were measured. Relative renal function was assessed as the percentage uptake of the Tc99m DTPA by each kidney. Renal parenchymal transit times were calculated together with glomerular filtration rate values for each kidney. Theeffect of furosemide induced diuresis on the renal images and time/activity curves were also determined. A quantitative evaluation showed that the relative renal function and glomerular filtration rates in both kidneys showed no statistically significant change during post-ESWL period (p>O.05). The parenchymal transit times were prolonged significantly (p<0.05) on the treated side while no statistically significant change was observed on the treated side. We believe that parenchymal transit time is a more sensitive parameter for the evaluation of acute changes after ESWL, especially in the kidneys having relatively poor function. We recommend routine application of radionuclide techniques for the early assessment of obstructive uropathies after ESWL. AIM OF TI-IE STUDY: faced with an adult hip pain without imqammatory signs and a normal X-Ray RSDS and OTNH axe two possible diagnoses frequently involved (other etiologies: fissure, osteuld osteoma, ..). They demand a specific treatment and have a different prognosis. This retrospective study was performed to discuss present indications of BS and MRI for the eaxly diagnosis of OTNI-I and RSDS. PATIENTS: 300 MRI of patients with hip pain without accompanying inflammatory signs and with a normal Xxay include 50 OTNH and 25 RSDS. Among these 75 patients 43 patients with comparable MRI and BS were retained (25 OTNFI and 18 RSDS). MATERIAL AND METHODS: 1/MRI: A 0.28T (Bruker) was used. The standaxdLzed protocol was: T2 RARE/3000/22 (coronal.) and T1 MSSE/350/22 (sagittal). 2/NM: The gamma-camera (Elscint) was used in the planar mode for 3Phase BS 99mTc-MDP (740MBq) and qualitative analysis (films) was performed. RESULTS AND DISCUSSION: 1/MRI: sensitivity and specificity were close to 100%. 2/BS: a/OTNI-I a hot spot was found in 41/50, diagnosis of ONTH was suspected in 35/50. The raise negative (9/50) concern a controlateral pathology which was described (a hot spot in all cases) only when clinical symptoms were present b/RSDS all scans were positive but RSDS was suspected in 2/18 cases. Our data suggest that routine 3PBS has too low a specificity for the early diagnosis of OTNH/RSDS and is not sensitive enough for the diagnosis of a nonsymptomatic controlateral OTNFI. MRI was very efficient in both cases. The difference might be explained by the high resolution attainabIe rather than the specificity of the signal. These results might be reconsidered using, SPECT and seml-quantitative analysis which axe now being implemented. Nevertheless it seems to us that in these cases MRI is the procedure to chose when available. 

High resolution SPECT with 3 head gamma-camera systems with UHR collimators and 128 X 128 aquisition matrices allowes superior image quality and better topographical assignment. Higher sensitivity will be expected in areas of complex anatomical structures like the pelvis and hip region, where two accurate planar views cannot be achieved. A better differentiation and an earlier diagnosis of pathological processes like avascular necrosis of the femoral head, loosening of hip endoprosthesis or Perthes desease should be possible.

45 patients with suspicion of loosening of the acetabular cup after total hip arthoplasty (THA) or after revision of THA with implantation of bone grafts, or lesions of the femoral head have been investigated. 3 hrs. after 550-600 MBq 99mTc-MDP planar analog images were obtained (450.000 cts), followed by Bone-SPECT with 3 head gamma camera (Prism 3000,Picker), 40 (120) angles, 30 -45 secJview; step and shoot aquisition, total aquisition time approx. 20-25 minutes, FBP-filtering with ramp filter and postreconstruction 3D-low pass filtering. 7.6 mm transaxial, coronal and sagittal slices were reconstructed. 3 dimensional surface rendering was done using optimized threshold end background correction.

Results: In cases of loosening processes following total hip arthroplasty HR-SPECT with 3 dimensional reconstruction is helpful to visualise and assign the increased osteoblastic activity and allowes better visualisation and estimation of the loosening process particular of the acetabular cup. Especially in equivocal planar scans, HR-SPECT leads to higher sensitivity. In follow-up studies in patients with extended spongiosa plasty combined with total hip replacement the bony reaction inside and around the bone graft is better visualised. In avascular necrosis of the femoral head with normal planar bone scans, the increased activity could well be visualized with HR-bane-SPECT. HR-bone-SPECT should be routinely performed in equivocal cases of bone and joint diseases of the hip region 

Etiologically it is assumed that aseptic hip necrosis is caused due to lack of blood circulation in the area of femoral neck and head. The process is probably a progressive one affecting by stages different areas of head and neck in developing necrotic areas. Our work contained comparison of quantitative calculation of relative perfusion in the artery phase (3T) with the changes in SPECT scintigram of the femoral heads and necks. The examination was carried out by injecting as o bolus 550-740 MBq TC-99m-DPD. Then the symmetrical regular regions of interest were set over the femoral neck and head areas so that symmetrical curves of left and right side could be generated and quantitative calculation of 3T of the affected hip could be made in comparison with the normal hip. 3T was compared with SPECT images of hips in 3D view. 43 p~s with aseptic hip necrosis underwent our examination. 3T was analysed in all pts and compared with the stage of pathological changes on the SPECT scintigrams of hips. A lowered perfusion 3T was obtained ranging from 0.99 to 0.29. The values of lowered perfusion coincided with the stage of pathological accumulation in SPECT images of hips so that the lowest values 3T were obtained in pts in vhom the changes involved practically the entire head and neck of the affected hip. The reducedperfusion of affected hip correlates with the stage of changes on SPECT images which confirma that the aseptic hip necrosis primarily involves perfusion disturbances and subsequently development of necrosis in the affected areas. At the same time the results evidence that a gradually advancing process is in question.

T. Aras, M.T. Ercan, Z, Hasqelik, C.F. Bekdik and G. Erbengi Department of Nuclear Medicine, Hacettepe University, Ankara, Turkey.

Localization of experimental inflammatory lesion was evaluated by using Tc-99m labelled dexamethasone phosphate (DMP) and we obtained successful results. This study was undertaken to determine the usefulness of this agent f o r imaging inflammatory lesions of rheumatoid a r t h r i t i s and whether the results of this procedure could be correlated with the absence or presence of ongoing inflammatory process. In 21 patients Tc-99m-DMP gamma camera images of the j o i n t s were obtained with 20 mCi, at 3h postinjection. 500.000 cts/frame were collected (256x256). Tc-99m-MDP scintigraphy was performed under similar conditions to compare the results.

In addition to visual observation, joint-to-background ratios (J/B) f o r quantitative evaluation was also calculated f o r both studies.

Following these results i t was found that the Tc-99m-DMP uptake in 359 j o i n t s was well correlated with the c l i n i c a l symptoms of swelling and pain (r = 0.747; P<0.0005) whereas no c o r r e l a t i o n was found with Tc-99m-MDP. J/B ratios were : Our study has shown that Tc-99m-DMP was taken up by synovial structures in the active phase of rheumatoid a r t h r i t i s . In remission no uptake was noted. We concluded that this agent was proved to be useful f o r monitoring the a c t i v i t y of rheumatoid a r t h r i t i s . 

In a number of recent studies, the clearance rate of aerosolized 99mTc-DTPA deposited in the lung has been characterized as an index of epithelial integrity. In a group of 16 non-smoker patients with sercoidosis (3 male, 13 female, mean age 44.2 years' old, minimum 22 and maximum 66) we calculated and correlated this parameter with the radtological stage, the CO diffusion, the serum Angiotensin Converting Enzyme (ACE) and the grading of gallium-67 lung uptake. The patients had either normal (n=8), slight obstructive (n=l) or restrictive (n=7) lung function as determined by a complete set of pulmonary function tests. The inhalation studies were pert'armed after a 2-3 rain inhalation af 20 mCi of 99mTc-DTPA in a 2ml solUtion (CIS), in postert~anterior view, dynamic mode, during 30 rain, 30see]frame, in a 128x128 matrix, started immediately after the beginning of the inhalation. Lung epithelial permeability (IF.p) is calculated from clearance curves obtained from a total lung ROI and expressed as the half-time clearance of the lungs (normal >_ 80rain the LEP measure in these patients seems more sensible than CO diffusion (altered only in 3 patients); -it seems that active inflammatory process is a coadjuvant factor in the grading of LEP lesion; -LEP in these patients seems a good index of epithelial integrity and, being a quantitative parameter, may allow a more strict monitorization. Combined ventilation-perfusion (V-P) lung imaging using the ventilation first approach has the disadvantage of performing a significant number of unnecessary V studies since a normal P scan excludes pulmonary embolism (PE) with high certainty. However, post-perfusion aerosol V imaging requires a delivery system with high lung deposition efficiency. A new aerosol device (Mallinckrodt, Petten) using dry air (relative humidity 15-18%) for jet nebulisation of 99m Tc-DTPA generates a submicronic aerosol (MMAD 0.37#m, GSD 1.8), Lung deposition efficiency (percent activity of initial nebuliser load deposited in the lung) was 30-40%. Quantitative comparison with 81m Kr demonstrated excellent peripheral penetration (n=14, r=0,75, p<0,001) and comparable regional distribution (r=0,94, p < 0.001), A multicenter trial compared the immediate post-perfusion V approach (inhalation scan I) with a V scan performed on the next day (inhalation scan II) in 169 consecutive patients with clinically suspected PE. P imaging was perfo{med with 37 MBq 99m Tc-microspheres, initial nebuliser load for immediate post-perfusion V imaging was 370 MBq, for 24hr V imaging 185 MBq 99m Tc-DTPA. Agreement with respect to assessment of P defects matched or mismatched to ventilation was found in 166/169 (98%) patients. Image quality of inhalation scan I (underlying P) was equal to scan II in 72% of studies, image quality of scan I was superior in 11%, of scan II in 17%.

This aerosol system is well suited for same-day c0mbined perfusion-ventilati0n imaging in patients with clinical suspicion of pulmonary embolism. 

For the diagnosis of pulmonary embolism many cemres rely on a single posterior initial-breath I33Xe view followed by equilibrium and washout phases to evaluate ventilation, withom posterior-oblique or lateral images. We have assessed the ability of experienced observers to detect and locate defects of known anatomical location and size on the pesterer view lung scan by placing temporary occlusions at the openings of selected bronchi during fibreoptic bronchoscopy, with an inflatable balloon catheter. Ventilation studies were then performed in the standard projections using 'l=Kr. Occlusions of all lobes and segments were studied. Photographic images of the posterior views were presented to two independent, experienced Nuclear Medicine physicians who were asked to classify each scan as normal or abnormal. If abnormal they were asked to identify the lobe or segment involved. Results: A. Segments: 20% of the posterior view scans known to contain segmental defects were judged to be normal. 44 % of segmental defects were located to the correct lobe and only 25 % to the correct segment. B. Lobes: A scan known to have a lingular defect was judged to be normal by both observers. A right middle lobe defect resulted in a slightly abnormal scan but could not be identified as lobar. Conclusion: This study illustrates the limitations 6f the posterior view ventilation scan in identifying and locating defects to compare with multiple view perfusion scans. The results suggest that methods of ventilation scanning using the posterior view alone will tend to overdiagnose ventilation-perfusion mismatch, inappropriately displacing scans into higher probability groups for pulmonary embolism. Investigation of the lower limb venous system to d±~gnose DVT and/or the measurement of the serum D-Dimer levels have been advocated as alternate modes of investigation to pulmonary angiography in patients wi~h an intermediate V/Q scan. We have prospectively examined 21 consecutive patients without clinical evidence of DV~ who had an intermediate V/Q scan and who snbsequently had a pulmonary angiogram performed. All patients had the V/Q scan, pulmonary angiogram, bilateral lower limb venous doppler ultrasound and serum D-Dimer levels ~easurement by both the ELIZA and slide latex agglutination methods within a 24 hour period. 7 of the 21 patients (33%) had pulmonary embolism demonstrated on pulmonary angiography. Only one patient with PE (14%) and none of the patients without PE had DVT demonstrated on ultrasound.Thus, lower limb venous ultrasound had a sensitivity and specificity of 14% and 1Q0% respectively. D-Dimerwas measured using both the slide latex agglutnation and the ELIZA assay. There was no significant difference in the serum D-Dimer levels between the patients with PE and those without PE using either method of measurement, Levels above 2mg/l are generally considered to be significant for venons thromboembolism. There was only one patient with a D-Dimer of greater than 2mg/l and this patient had a negative angiogram and ultrasound. 

Budihna NV*, Mil~inski M*, Skralovnik-Stern A**, Peternel ~,~ M* Fidler V* Unversty Med ca Center, *Department of nuclear medicine */'Institute of pulmonary diseases and tuberculosis, ***Institute of gerontology, Ljubljana, SIovenia.

A m of th.e study was to see if measurement of right ventricular eiection traction (R.VEF) at the time of lung perfusion scintigra-pl~y can !mprove the diagnostic value of-standard lung ventilation pe, rru, sion scintigraphy (V/Q) for the diagnosis of pulmonary emoo~ism (PE). Methods F fty-f ve patients, 18-89 years old, were investigated for clinically suspected PE 1-7 days a.fter acute event. Ventilation p<0,001 23 #compared to the group with low probability or excluded PE S gnificapt n, egative co,rretation between the number of V/Q m smatci~ea segmentm or lar.cle subsegmental defects and RVEF was found (,r=-0.57, p<O.001). In ~16,, pts the follow-up investigation penormea aoout 10 days aner the acute event showeds gn ficant increase of RVEF (X-+SD=52+-12 before and 60- --8 ~n follow-up, p<0 .05). Concl,usio, n is that use,ful addit onal data. about,the right ventricu~ar tunction can oe obtained with the single injection of MAA at the time of lung perfusion scintigraphy. Significant negative correlation was found between the extent of PE and RVEF. Improvement of RVEF could be detected in some pts with lung embolism after successful treatment.

I .BAN2D,R .QUIRCE,J .SERRA~D ,J .J ,~CErlHA ,0 .TAI~J~CA , J . M .~ %~EDICINA ~%IIFAR.RADIO~DSIA Y ~I~ ~I~.~ ~ ~0 V~. S~ .~. ~ ~I~ ~ ~ D~ ~ ~ ~ ~ ~ (+) P A~ ~ ~t i v e l y ~t~ ~ c~t i~ of ~7 ~ ~ ~ ~ l~g c l~ (~) of ~A -T c~ a~l for ~l y ~ s~ of ~ ~l i~t i~ of ~ ~t i~. ~ ~udy ~u d~ ~ ~ (+) ~tien~ (p~) (27 iv d~ a~r s , 4 ~s , ~d i ~ ~t ) ~ f~er ~/or r~p~ato~ ~t~. F~ ~s ~ ~b l i~ ~ ~ ~ut~, b r~, ~, or ~ bio~. ~p~ p~ ~I~ ~A -T c~ ~I ~ by a n e~ d e~v~ ~st~ for 2-3 ~; ~t y ~ r~ord~ for ~ ~ ~ ~ ~e g~t~ fr~ ~ ~s of ~t~ ~ o~ i~ (ups, ~ddle, ~ i~) . ~ ~ ~r~ ~ ~/2 ~u~ ~ ~ (~ ! ~). ~ ~7 ~ ~i~ ~t ~d ~ ~ ~ ~s ~ter iv ~j~ti~ of 111-185 ~ of ~7 c i~. ~ ~i~ ~ ~I~ ~ i0 pts; ~i ~ ~ ~7 ~ ~d ~n~t~ c l~ ~ (~) ~ ~/2 v~u~ of 51.~ ! 21.~ ~ f~ ~ ~s ~ ~. 8 7 ! 4 .~ ~ for ~. ~ ~ ~ (~) ~ d~ ~ 15 ~, 14 of ~ (9~) ~ bip~ic c l~e ~ (~) ~ ~p~ ~/2 ~ (3.14 ! 1.21 ~) . ~ o~ pt ~ ~, ~7 ~ ~ ~ ~i~ (l~g up~e ~ ~ ~ver ~) ~ 9 ~ (~): 5 ~ u p S , 2 ~t~ u p S , ~d 2 api~ u~. ~ ~t~ to ~ ~ 4 ~ ~ ~t~ 3 ~ of ~p y . ~ c~ ~ ~t~ or b i~c ~ 6 p~ ~ ~ t u~c~; c l~ ~ ~ fr~ 5.1 ~ ~.2 ~; for ~, T1/2 ~ ~ 6.19 + 1.16 ~. ~7 ~ r~ l~g u p~ ~ 2 p~, ~ l~g ~l~h ~ ~ 2, ~ i~ ~ ~ ], ~d n~ ~ i. F~ u p~ of ~7 ~lat~ ~ X-ray ~ ~ ~e s~ ~ a ~y l~ ~. ~ of ~T c~ ~I ~ ~ to ~f o m , ~ g~ t o l~e ; ~i~- ~ty ~ ~tt~ ~ ~67 ~ ~, ~ ~ r~t s ~l~w for f~t ~. ~ ~ i~ ~t y , ~ a c~ ~ ~d ~ ~ ~t i~ for f~ ~c p~ (~, bio~). ~/2 ~ ~e ~ ~ ~ t u~ ~ ~ ~t i~.

Ugolotti G. 

The ability of current immunometric methods for TSH to distinguish between low-normal and subnormal hormone concentrations has been investigated using data collected in an external quality assessment (EQA) survey. To this aim the interassay precision profiles have been computed from results produced by 101 laboratories which used the 5 kits most popular in the survey; each laboratory assayed during the control period (one year) 4 EQA pools distributed (as hidden replicates) in 5 occasions.The interassay variability observed for the EQA pools was relatively low (9-13CV%) for three pools in the normal TSH range (> 0.8 mlU/L) but markedly higher (30-40 CV%, with the exception of one more precise kit) for the pool in the subnormal range (0.2 mlU/L). The effect of the between-run variability on the diagnostic accuracy (discrimination between normal and subnormal values) was calculated for three representative TSH concentrations (one -0.2 mlU/L -below the cutoff value, and two -0.4, 0.5 mlU/L -in the lower part of the normal interval) assuming a value of 0.3 mIU/L as the lower normal limit.

The results indicate that the three levels are reasonably discriminated (P < 5%) only with one kit showing a between-run precision lower than 18% at 0.2 mlU/L. For the other four less precise kits, only the higher TSH level (0.5 mUIfL) could be classified with an acceptable diagnostic reliability. Moreover, the effect of the between-run variability on the ability to discriminate among two low TSH concentrations (as needed in monitoring over time patients under T4 suppressive therapy) was evaluated. Using the most precise kit it is possible to distinguish two TSH concentrations -in the range 0. .5 mIU/L -differing 30% at least; with the other less precise kits, differences larger than 50-60% are needed to reach a reliable discrimination. These findings demonstrates that a large number of the laboratories fail to achieve the functional sensitivity of a "second generation" assay even if they use immunometric methods and emphasize the need for developing TSH assays with a better interassay precision in the low concentration range.

M.Giganti, D.Pelizzola, G.Marani, P.Colamussi, C.Cittanti, L. Uccelli, R.Barozzi, A.Piffanelli. Chair of Nuclear Medicine., Radiology Inst. University of Ferrara.

Since a direct IRMA for plasma active form of the renine has been available, the need of comparing clinical significance and laboratory. performances, with the P l a s m a Renine Activity ( P . R . A . ) determination, was evident. Eight laboratories, mainly in relation with Hypertension Study Groups, set up a collaborative study with the following alms: a) evaluation of intra and intedaboratory reproducibility of Renine assay and RR.A. b) correlation between plasma concentrations of active Renine and Plasma Renine Activity in normal subjects, pregnant women and in patients with essential hypertension, renovascular hypertension, hyperaldosteronism. This study has demonstrated: 1) high significant correlation between the two parameters in normal cases and subgroups of patients.

2) better interlaboratory precision coefficients for Renine

Clinical correlations confirm the reliability of active Renine assay for investigation of the renin-angiotensin system..

K. Mohari~ GY.A.J~noki, J.F~Ides~,L.KGr~si "FJC" t " " ~ N l.Res,lnst.for Rad~ob~ology and Radiohygiene, Semmelweis ~edical University, BUDAPEST, HUNGARY

Our research work aimed at to develope labelling method for the preparation of 125-I-TRH and set up RIA assay using magnetic separation for measurement of TRH hormone in serum. For the preparation 125-I-TRH we have used different labelling technioues (e.g.chloramine-T,Iodogen and lacto-peroxidase methods). We have found that the 125-I-TRH prepared by chloramine-T showed well preserved structure and immunological property. The labelling yield of TRH ranged . The labelled tripeptide was purified on Sephadex G-lO column, eluted with PBS of pH 7.4.The collected fractions were analyzed using 8IO-RAO HPLC system. B~O-Sil TSK 250 analytical column (350 mm x 7~5 mm)and 0.02 mol NaHgOPO~/O.05 mol NagSO~ buffer of pH 6.8 at flow rate of ~ mlFmin was us@d ~or separations. The analysis showed activity in the fractions No. [12] [13] [14] [15] [16] . A series of assay were examined simultaneously with the different active fractions. We have found that fractions No.l&,15 proved to be useful in RIA. In our experiment magnetic separation(size:lOum,4,Omg/tube, IOI)was used and compared to 2nd antibody method. The results of the assay were as follows:

~thods total binding non specific sensiti-recovery binding vity 2nd antibody 50-554 3-54 50 pg/ml 90-954 magnetic sep. 1-29 20 pg/ml We were able to measure the TRH in serum of healthy individuals in range of 50-900 pg/ml. RIA method developed in our laboratory based on magnetic separation showes significan±ly improved sensitivity. While TBIAb value as a prognostic marker in GD-patients (pts) treated with antithyroid drugs has been extensively investigated, poor studies with no univocal results have been reported on TBIAb role in GD-pts treated by surgery.

To better define this aspect, we evaluated a group of 40 consecutive GD-pts who underwent subtotal thyroidectomy after one or more unseccesful courses of antithyroid drugs. All pts were operated by the same surgeon with the same surgical technique. There were 37 females, 3 males; age ranged from 18 to 63 yrs, mean 43 yrs. T4, b-T4, T3, ultrasensitive TSH and antithyroid antibodies-ATA (antimicrosomal-TMAbs, antithyroglobulin-TgAbs, TBIAbs) were measured before surgery and then every 3-6 mths. L-thyroxine substitutive therapy (L-T4) was started when the patient was found to be overt hypothyroid (O. HYPOT) or whan"a condition of subclinical hypothyroidism (S. HYPOT), i.e. normal thyroid hormone and elevated TSH levels, was confirmed in two consecutive controlls. Before surgery, 63% of pts had TBIAbs, 52% TMAbs, 12% TgAbs. After a 3 yr mean follow-up (range 1-5 yrs) after surgery, 11 pts were euthyroid (EUT), 19 were O. HYPOT and 10 were S. ITYPOT. TBIAbs remained elevated in 7 pts: 4 were EUT, 2 were O. HYPOT and 1 S. HYPOT. Later, 2 out of these 7 pts developed a relapse of hyperthyroidism. No case of relapse was observed among pts who became TBIAb-negative after surgery. No relation was found between TMAb or FgAb variations and thyroid function after surgery. Our data indicate that the persistence of TBIAbs is more frequently associated with a condition of euthyroidism after surgery and that relapse of hyperthyroidism is possible in these cases. These pts should be considered at risk and strictly followed-up.

The Dysprosium (Y) is currently used in Australia as the standard radioA~harmaceutical for radiation synovectomy. An alternative agent, Dysprosium-165 hydroxide macro-aggregates (D) is produced by Australian Nuclear Science and Technology Organisation (ANSTO) and has a short half-life (2.3hrs) compared to Y (64hrs). We compared the two products in a double blind clinical trial in Sydney, Perth and Melbourne.

Patients were assessed by a rheumatologist as suitable for radiation synovectomy of the knee, were all aged >50 years, gave informed consent and had theirjoint symptoms-assessed-before-and for 12 months after injection wfth D (12GBq) or Y (185MBq). The limb involved was splinted for 3 days after injection, and the knees, groin and abdomen were scanned immediately, at 4, 24 and 72 hours to assess leakage of radioactivity. Blood and urine samples were also assessed.

Results in the 77 patients who entered the trial indicate that leakage of D from the joint was less than Y, both on imaging and from blood activity. No difference in clinical outcome was identified. Withdrawal from the trial before the 12 month follow-up was complete (knee surgery 15 patients, unrelated 2 patients) was not significantly different.

-• -The new radiopharmaceutical for radiation synovectomy has the advantage .of reduced leakage, and availablity from ANSTO improves flexibility. The short halflife allows a shorter hospital stay. Response to conventional chemotherapy in myeloma is 30-60% but is generally incomplete and of short duration. Total body irradiation (TBI) with bone marrow transplantation (BMT) greatly improves response rates but 15% of patients experience serious nonhaemopoietic radiation toxicity. We have used the inbred C57BL/KaLwRij mouse to develop a regimen of internal irradiation with the Sm-153 labelled bone-seeking chelate ethylenediaminetetramethylene phosphonate (EDTMP) with Melphalan chemotherapy to ablate bone marrow whilst preserving the capacity for haemopoietic recovery following syngeneic BMT. Treatment with 25 MBq/kg 153Sm-EDTMP and 18.5 mg/kg Melphalan prior to BMT in mice bearing 5T33 murine myeloma was initiated at 3 days and at i0 days following tumour inoculation of 8x105 myeloma cells in groups of 6-12 animals. Survival was compared with untreated controls and mice treated with 153Sm-EDTMP or Melphalan alone. Controls survived 23.1+0.3 days. Animals treated with 153Sm-EDTMP or Melphalan--alone survived 28.8+1.1 days. Combined chemoradiotherapy extended surviva~ to 37.2~1.7 days. Thus treated animals survived longer than controls (p< 0.01) and the combined chemoradiotherapy was significantly more effective than single agent t~eatment (p< 0.001). Monitoring of blood levels of the IgG2b paraprotein of treated 5T33 murine myeloma showed slower appearance time. The survival advantage conferred by the combined 153Sm-EDTMP/Melphalan chemoradiotherapy regimen for BMT in murine myeloma shows the potential for clinical application of internal radiotherapy for treatment of haematological malignancy. acid ( Sm-153-EDTMP ) may be beneficial for treatment of bone pain caused by metastatic lesions. isotope has favourable physical charscteristics with a half life of 46 h, suitable betaemissions and iQ3akeV gamma emission, making it suitable for therapy, and also for bone imaging and prospective estimation of radiation dose to metastases and bone marrow.

By this time we have treated 15 pts with numerous bone metastases. These patients with prostste or breast cancer had painful bone metastases, which did not response for analgetics. Only pts with bone metastases documented by recently performed bone scan and x-ray examinations with normal blood cell counts were included. Pts received Sm-153-EDTMP from 370 to 1480 MBq. Whole body gamma camera images were obtained at 3 and 24 h post. inj. Serial blood and urine samples were collected for up to 24 h after injection.

Complete relief from pain was experienced by 5 pts, substant, relief by 6 pts, slight relief by 2 pts and no response by 2 pts. Significant myelotoxity (WHO grade 3) was found only in 1 pt. Pain relief occured usually within i week after administration of tracer. Duration of pain relief lasted from 2 to 17 weeks. About 18-34% of the injected dose was cleared into the urine within 6 h, and, 23-39% by the first 21 h. Sm-153-EDTMP cleared very rapidly from the blood (TI/2 = 40 mAn) and less than 1% of the inj. dose remained in circul, at 4 h post injection.

These very preliminary results are encouraging, and suggest a further study with larger number of pts. 

Rhenium-186-hydroxyethylidene diphosphonate (186Re_HEDP ) can be used for palliative treatment of metastatic bone pain. As part of a dose escalation study we investigated the pharmacokinetic behaviour of 186Re-HEDP in 11 patients (17 studies). All patients suffered from metastatic breast or prostate cancer. The study was approved by the hospital review board and all patients gave witnessed informed consent. Following an intravenous bolus injection of 1295, 1850 or 2405 MBq 186Re-HEDP, blood samples were taken at timed intervals and total urine was collected during 72 hours post-injection. Half-life times of lg6Re in the three blood fractions (whole blood, plasma and plasma water) were 40.1 + 5.0, 41.0 + 6.0 and 29.5 + 6.4 hours respectively. Time dependent increase in plasma protein binding was observed, probably caused by in vivo decomposition of 186Re-HEDP. Total urinary 186Re excretion was 69 + 15% of which 71% + 6% was excreted within the first 24 hours after injection. The bone scan index (BSI : i.e. fraction of the skeleton showing scintigraphic evidence of metastatic disease) closely correlated with the fraction of dose non-renally cleared (R=0.98). This implies that the amount of radioactivity taken up by the skeleton and hence the bone marrow absorbed dose can be estimated from a diagnostic pre therapy technetium-99m-hydroxymethylene diphosphonate (99mTc-HDP) scintigram, according to the MIRD model. This has important clinical consequences, because the bone marrow absorbed dose will be the limiting factor in the application of 186Re-HEDP.

B a r b e r a F., G a r i b a l d i C., V i l l a G., S a n t a n i To define natural history, diagnostic and therapeutic approaches of PM, we evaluated a group of 134 patients (pts) with PM from DTC treated in oar Center from 1967 to 1989. Out of these, 78 were papillary (PC), 56 follicular (FC) cancers, 89 females (F), 45 males 0VI). All pts underwent total thyroidectomy, 131I therapy and then L-thyroxine therapy (L-T4). Follow-up was made by means of 131I 185 MBq total body scan (TBS), chest and bone xrays (XR), neck and liver echography, bone scan, CT scan, serum thyroglobulin assay. On the basis of TBS and XR results, pts were divided into 3 groups: Group I (G-l) = XR negative and TBS positive (42 cases, 31%), Group 2 (G-2) = positive both XR and TBS (54 cases, 41%), Group 3 (G-3) = XR positive and TBS negative (.3.8 cases, 28%). Differences among groups were calculated by means of Chi-square, log-rank and Student's t test, and survival curves by means of Kaplan-Meier method. PC:FC ratio was 1.5:1 for G-l, 1:1.2 for G-2, 1:2 for G-3 (p < .01). F:M ratio was similar in all groups (2:1). Means age~D of pts was 32.8~13.1, 56.~15.5 and 61.8~11.1 yrs, respectively (p < .01). Extracapsular tumor growth resulted 58% in G-3 whereas 36% in G-1 and G-2 (p < .01). Prevalence of cervical lymphnode invasion was similar in all groups (78%). Mediastinum involvement was shown in 14% of G-1 whereas in 29% of G-2 and G-3 (p < .01). Progression of disease to bones/liver/brain was documented in 34% of G-2 and G-3 whereas in 0% of G-1 (p < .01). 10-yr survival rate was 95% in G-I, 28% in G-2, 5% in G-3 (p < .01). Complete remission resulted 85% in G-I, 6% in G2, 0% in G-3 (p < .01).

In conclusion, PM detected only by TBS (31% of all PM) show a better prognosis in comparison with PM detected by XR, and are characteristic in young pts with PC and with contemporary lymphnode localizations. Thus total thyroidectomy seems to be the preferable surgical approach in these pts.

A. TOOD The ability to transfer image data between different systems is essential in nuclear medicine for both clinical and research requirements. The Interfile definition as originally published has been implemented by a number of manufacturers and has been developed under the auspices of the COST B2 Software Quality Assurance project of the EC. However, it has become apparent that a number of uncertainties exist in earlier definitions, in particular V3.2, which has therefore been revised. The new definition is expressed in a formal notation, and permits many important extensions. Formats for regions of interest and curves, the transport of data (additionally) in ASCII and floating point formats, and the definition of centre of rotation information are all now enabled. A mechanism for ensuring convertibility of Interfile data to other definitions such as ACR-NEMA V2.0 and V3.x (LEAPFROG) has been established. However, there remain many areas which are not currently covered, for example gated SPECT studies, and multidimensional studies in general cannot be transferred. Thus while V3.3 is conceived as a rectification of previous versions of Interfile, it is also intended as a stepping stone to a more general transfer format definition. For this reason, indexed variables and folders are being gradually introduced such that the current Interfile definition can be used with relatively little effort to enable the transfer of all types of nuclear medicine (and perhaps other types of) data. The current proposal is reported, future potential developments are presented, methods for implementation are reviewed and, in particular, the rationale is discussed to show why change is required and how such change is appropriate with respect to other potential standards for image transfer in medicine. A Muhi-Mddia MedicaI record (MMMR) dedicated to Nuclear Medicine has been created with two purposes : 1) to provide the Nuclear Medicine physicians all the data necessm2¢ for interpretation of Nuclear Medicine images and 2) to store those data within the Nuclear Medicine Department. The Multi-Media Medical record, applied to nuclear medicine includes text (medical report), structured database (medical data), images and oral messages (oral report, first interpretation for emergency exams). In order to implement such a MMMR, a workstation based on a PC 386 microcomputer equiped with DVI cards, software for image compression and decompression and OST cards for the NUMERIS access has been created. The capture of images is performed through digitization process using video JVC camera. Oral messages and sounds are also digitized and stored by means of microphones or audio stations. All images are displayed on high resolution SONY TV screen; their manipulations used DVI software facilities. The transfer of all complex data structures between hospital or physicians is realized by the ISDN (Integrated Services Digital Network) network NUMERIS throught wich images, records and phone call can be transmitted for a price less than twice a phone call. With the interactive tool "tele-cursor", which performed the real-time work on medical images between two distant physicians, the physician can point a local region, delineate a zone, draw on an image, and this draw appears in real-time on the TV screen of the distant physician. This tele-cursor tool, is the first step towards a real computer supported cooperative work (CSCW) in Medicine for the following years. The multi-media setup has been successfully tested in our institution with four Nuclear Medicine physicians. A collaborative programm of data exchange and interpretation of nuclear medicine images is in progress between Paris and Lille. 

A new approach for superimposing 3D images of different modaiities is presented and is applied to images of the brain.

The method proceeds in three steps: segmentation of the two 3D images into similar component, rigid reregistration of one component onto the other, and application of the obtained 3D transformation to the original data. Segmentation uses morphological operators to extract brain or skull volumes in each image according to a SPECT-CT or CT-CT superimposition. These two components are considered as rigid sets of ponctual masses. Each point of set 1 is attracted by its nearrest point of set 2 by a force proportionnal to the distance. The fondamental laws of Dynamics are then applied to that system. Motion is computed by an iterative time-dependant process providing translation and rotation parameters of set 1 at each time. Sets are superimposed when potential energy is minimum, that correspond to minimize all distances.

The algorithm has been tested on images of synthetic and CT objects in known positions. It works with images of different resolutions, even when parts of objects are considered. Its accuracy depends of the lowest resolution of the studied images.

Superimposition of CT or T1 SPECT onto HMPAO SPECT images of same patients were performed with good results.

The new method is fully automatic and does not require external references or manual determination of brain edge points used by other methods. It may be applied to different organs imaged by different modalities as soon as one can be included into the other. 

A S Houston, M A Macleod, P M Kemp, D C Barber* Royal Naval Hospital, Haslar, Gosport, U.K. *Royal Hallamshire Hospital, Sheffield, U.K.

An atlas of regional cerebral blood flow is computed generally by meaning a series of normal brain images following image registration. The significance of any deviation in an image obtained subsequently is then calculated using a mapping of standard deviation across the image. This procedure assumes that deviations in normal images are uncorrelated pixel by pixel. There is evidence to suggest that this is not the case for HMPAO SPECT images.

Following image registration, correlated normal variations may be isolated using principal components analysis. A mean image is extracted, followed by a few component images each corresponding to a correlated normal variant. For any image obtained subsequently, an optimal linear combination of these images may be said to represent the "nearest normal" to the new image.

The analysis has been successfully implemented using 53 images of normal controls. Ten component images were generated and their significance tested.

A demonstration of the potential of the method for subsequent studies has proved encouraging. In particular, deficit areas in new images are not apparent on the appropriate "nearest normal" image; while otherwise the appearance of corresponding images is remarkably similar. 

When biologically active peptides are labelled for in vivo diagnostic use, in order to inject as low as possible amount of the labelled protein with retained binding activity, labelling must be achieved with high specific activity (S. A.) and reaction should be carried out preserving as much as possible the labelled protein from physyco-chemical damages occurring during the reaction. Aim of the present study is the development of a new method for the 99mTc-labelling of biologically active peptides with high S.A. and retained binding activity. Labelling was performed via a two-step reaction using a bifunctional chelate with two active sites: one providing an N3S ring for coordination of 99mTc and the other, an activated ester, for protein binding via lysine residues. Ligand is first labelled with 99mTc and then conjugated to proteins. In order to preserve the immunoreactivity of proteins a low ligand:protein ratio must be used. To obtain a high specific activity, factors improving the incorporation of 99mTc into the ligand were studied such as boiling time, pH, stannous chloride, isopropyl alcohol (IPA) and gentisic acid concentrations. Optimal conditions were found as follow: the ligand (8 nmoles) was incubated in presence of stannous chloride (58.33 Ixg/ml), gluconate (1.45 mg/ml), IPA (20.83%) and gentisic acid (58.33 I.tg/ml) with 99mTc (800 MBq) for 8 minutes at 100°C at pH 2. After cooling at 4°C for 5 minutes, pH was raised up to 9 using borate buffer 0.5M, and the chelate was incubated for further 30 minutes with a test proiein, intedeukin-2 (60 ktg) at r.t.. Radiolabelled IL2 was then purified from unreacted chelate and 99mTc using a gel filtration Sephadex G50M column. In this condition labelling of the ligand was 78% and the labelling of the protein was 38% with a S. A. of about 4000 MBq/mg. Our data are a starting point for the use of 99mTc for labelling small biologically active peptides. 

The aim of the present study was to determine whether the method of 99mTc labeling polyclonal human immtmoglobuline (HIG) influenced the 99mTc-HIG stability in vitro as well as its binding capacity to bacteria in vivo. Optimization of experimental conditions of two simple and rapid methods to label HIG with 99mTc was performed: a) direct disulfide reduction technique using ; b) modified HIG by reaction of the protein with . The number of SH groups generated, determined by Ellman's method, was 3.5 and 5.5 per rHIG and m_HIG molecule, respectively. Lyophilized kits containing ling of either rHIG or mHIG and a small amount of MDP (Sn) kit corresponding to about 1.3 and 8.2 I~m of tin(II) were prepared: The 99mTc labeling of the HIG preparations was accomplished by adding the 99mTcO4" eluate. Radiochemical purity greater than 98% was achieved as determined by ITLC for both preparations. The stability of these radiolabeled preparations was evaluated by Cellogel etectrophoresis. Although the 99mTc-rHIG retained > 98% of the radiolabel when incubated at 37°C even in presence of human serum for 4 hours, the 99mWc-mI-IIG displayed some instability (< 80% as radiolabeled 99mTc-mHIG). Using electrophoretic tectmiques, similar instability was found for the commercial Technescan HIG, Mallinckrodt Diagnostica kit (ling 2-irainothiolans modified immunoglobulin and stannons tart~ate). Biodistribution studies of 99mTc-rHIG and 99mTc-HIG (Mallinckrodt) in mice bearing inflammation in right thigh induced by im. administration of a single clinical isolate of S. Aureus at 4 hours after injection indicate a ratio for the infected and non infected thighs of 4.6+1.3 (n=6) and 2.8+1.0 (n=5) respectively. Based on results obtained, we conclude that 99mTc-rHIG here developed has higher in vitro stability as well as higher ability to localize the infections. Eadlolabelled human iuunoglobulin (HIG) seintlgraphy has been ~reeagnized as a reliable medality for the localization and evaluation of pyo~enie infection in human. Four methods of labeling HIG wlth Tc-99~ as developed by the Institute of Nuclear Energy Research in Taivan were: (1) using ascorbic acid for direct labelin~ of HIG (Ase-HIG), (2) usin~ DTPA as a blfunctional chelate (DTPMHIG), (3) using 2-1mino-thiolane for modified protein (II~-HI6), and (4) using avldin-biotin system (avidln-biotin-HIG). Our study assessed these four preparations in the scintigraphic detection of infection.

Eight rabbi~s (two rabbi~ in each group) were included in this study. In each rabbit, lml of s~aphyloeoceus aureus suspension (about 10 viable bacteria) was injected into a thigh ~usele and at least 24 hr were needed for abscess formation. At 1, 4 and 18 hr after adminstration of 3 ~Ci 

in pseudo melt conditions yielding 80% of . Radiobromination is performed by Cu I+ assisted nucleophilic radiohalogenation. Using directly the IM NaHSO 4 Solution a labelling yield of 35% is obtained. Desalination of the 76Br-solution allows to obtain a yield of 85%. Pure N.C.A. is obtained with an overall yield of 55-60% after HPLC and mini-column purification. Although technetium labeled myocardial perfusion imaging agents have been approved by the FDA for over a year, there has been a reluctance for cormmunity practitioners of nuclear medicine to switch from thallium 201 to the new technetium labeled agents. We have performed 363 technetium 99m teboroxime (TEBO) myocardial perfusion studies in an outpatient office. Perfusion studies were performed on a single detector SPECT camera within 90 seconds of cessation of treadmill stress testing. Imaging was performed over 180 degrees, starting from LPO to RAO using 32 stops at approximately 8 seconds per stop. Total acquisition time was approximately 6 minutes and stress and rest studies could be completed within 90 minutes. Results of the perfusion imaging were compared with cardiac catheterization, treadmill stress testing, and/or subsequent clinical course. Analysis of the 363 studies showed 239 were normal and 124 were positive for ischemia, infarction, or both. Sensitivity and specificity were each greater than 95%, and accuracy compared with coronary angiography was 91%. Myocardial perfusion imaging with TEBO is an acceptable alternative to thallium imaging in an outpatient setting. The images obtained ere equal to or better than thallium, studies can be performed on a single detector SPECT system, and patient throughput can be significantly enhanced using TEBO. Two new methods of labelling ant±myosin with Tc-99m, direct (DIR) and RPI ligand (RPI) have been developed. These were compared with the standard In-Ill ant±myosin (In-AM) imaging technique in 29 pts with acute myocardial infarction within 72 hours of chest pain. 14 pts received DIR, and 15 were given RPI. imaging was performed at 5, i0 and 24 hrs, and In-AM at 24 and 48 hrs post injection. Plasma T~ (mear~+SD) of the Tc-99m and In-AMwere measured. The images were interpreted by 2 blinded observers.

Diagnostic Images ( 

Krause Th, Kasper W, Moser E. Department of Nuclear Medicine, University of Freiburg, Germany.

Stay of patients at the intensive care unit should be guided by clinical circumstances. Therefore, opportune evaluation of risks is desired. In 45 patients with AMI simultaneous PPi tomography was initiated. Two different PPi accumulation patterns were identified: 1. homogeneous (n = 33) and 2. inhomogeneous PPi uptake (n = 12) to the Infrequently, malignant ventricular tachyarrhytmias appear in patients (pts) with normal heart without apparent cause. To study possible alterations in adrenergic innervation of the myocardium in those pts we examined 5 pts (2 male, 3 female) 32±8 years old with sustained ventricular tachycardia (4 pts) and out of hospital ventricular f i b r i l l a t i o n (1 pt). In all pts LV function was normal, EKG did not reveal other abnormal i t i e s but arrhythmias and there was no history of heart disease. SPECT was used to assess perfusion and ±23I-MIBG SPECT (4 hrs after 5 mCi injection) was used to study adrenergic innervation.15 normal subjects were used as control group.All normal controls showed normal TI-201 study; 1231-MIBG showed homogeneous pattern in 6/15 and reduced uptake to apex in 9/15; 1 showed inferior and i lateral defect.Overall 2/15 normal controls showed reduced 1231-MIBG uptake elsewhere but apex. In 4/5 pts z231-MIBG pattern was abnormal, i pt showed lateral defect, i i n f e r i o r and lateral and 2 pts had defects to septum. perfusion was normal in all pts. z231-MIBG pattern was significantly different than the usual "normal pattern"

(homogeneous uptake or reduced apical uptake) (4/5 vs 2/15 p<O.01). In conclusion pts with malignant ventricular tachyarrhytmias of unknown etiology present nonhomogeneous adrenergic innervation of the myocardium evident by z~31--MIBG scanning. Technetium-99m T2GIs a n t i f i b r i n Fab' (Tc-AF) murine monoclonal antibody is directed against an epitope present in actively-forming venous thrombi. To prospectively evaluate the diagnostic performance of Tc-AF in patients with suspected acute deep venous thrombosis (DVT), 256 patients with signs and/or symptoms of acute DVT were injected with 0.5 mg Tc-AF labeled with 15-20 mCi Images of the legs were acquired immediately post-injection, at 90 minutes, and at 4-6 hours, and were evaluated by a blinded panel of readers. Acute DVT was confirmed by contrast venography. Diagnostic s e n s i t i v i t y and s p e c i f i c i t y for proximal DVT ( i . e . , DVT involving the knee and/or thigh) was 79% (77/97), and 91% (145/159), respectively. In the subset of patients with suspected acute recurrent DVT ( i . e . , patients with a prior history of DVT and new onset of symptoms), s e n s i t i v i t y was 100% (18/18), and s p e c i f i c i t y was 93% (26/28).

In all 13 patients with indeterminate contrast venograms and in all 22 patients who had indeterminate results by other noninvasive tests (plethysmographic-or ultrasound-based methods), Tc-AF provided d e f i n i t i v e diagnostic results. Injection of Tc-AF was well tolerated in all patients. Thus, Tc-AF is a safe and accurate non-invasive diagnostic test for acute DVT in symotmatic patients, differing from other diagnostic tests in its unique s p e c i f i c i t y for acute venous thrombi. The assessment of rapid myocardial washout (WO) of Tc-99m teboroxime (TEBO) has potential clinical significance in coronary artery disease detection. Teboroxime washout was studied in 46 pts (13 had a likelihood (LL) of CAD and 33 had angiography (CATH)). 20-25mCi teboroxime was injected at the 3rd rain of adenosine induced hyperemia and used .sequential 1 min SPECT imaging with a 3 detector camera. Washout of teboroxime was assessed as the average percent decrease in counts/rain from 1 to 4 n'fin post-TEBO injection in the summed short axis tomograms divided into 6 myocardial regions of interest (ANT=anterior, HL=high lateral, IL=inferolateral, IF=inferior, IS=inferoseptal , AS=anteroseptal). Regions were classified as normal (NL), ischemic (associated with >50% stenosis) or infarcted (MI) and assigned to the 3 major vascular territories.

Mean washout of ischemic(ISC), non-infarct regions were significantly lower than normal regions from CATH (p=0.001) and regions from low likelihood pts (p=0.003):

There was no differeffce in mean washout between NL, LL and MI regions. Using the lowest value in the LL regions as criteria for normal WO, 21/41(51%) ISC territories had abnormal WO vs 3/43(7%) territories with no stenosis >50% (p=0.001). Conclusion: Regional washout of teboroxime is detectably slowed in ischemic, non-infarcted telritories and may be clinically useful. HMPAO-SPECT In contrast to temporal lobe seizures the frontal lobe epilepsies (FLE) undergo a peculiar pattern of the ictal course, since after frontal onsetting epileptic discharges may propagate via a network of neuronal pathways, thus mimicking an extrafrontal focal seizure. Patients and methods: i0 patients with drug refractory FLE were included in preoperative monitoring. NMR imaging revealed structural lesions in 5 subjects (2 traumata, 1 atrophy, 2 white matter lesions). Focal localization was performed by means of implantable subdural electrodes and with the help of "ictal HMPAO- SPECT" (injection of 500-700 MBq Tc99m-HMPAO within one minute after ictal onset ). In 2 patients four ictal SPECTs were acquired. Results: 7 Patients with frontal loci could be localized and underwent surgical resection(n=6) or callosotomy (n=l, bothside loci) . In 3 of resected subjects no morphological alteration could be found, others had ganglioglioma (2) TO compare the usefulness of Tc-99m HMPAO SPECT and F-18 FDG PET in presurgical evaluation of patients with intractable focal epilepsy,12 patients (9 women~ 3 men) were consecutively studied with prolonged video EEG monitoring (EEG), MRI, PET, and SPECT. Seven patients had a unitemporal focus (Grou p I) and five patients bitemporal foc± (Group II). I~ the interictal phase, a PET scan was performed with 5-10 mCi 6f F-18 FDG and SPECT with 10-20 mCi of Tc-99m HMPAO respectively. We developed a semiquantltative 3-dimensional method (SQ-3D) for interpretation and comparison of PET and ~PECT using an anatomical temporal lobe compartment model to allow quantification of the extent of surgical resection. This allows a simple index based on the degree of asymmetry and the number of abnormal regions of interest.

In In 2 patients, both SP~CT and PET showed different bilateral abnormalities. SQ-3D evaluation based on surgical compartment model of the temporal lobe is simple and useful for objective assessment of epileptogenic zones. When compared to FDG PET, HMPAO SPECT provides similar information on the side of the epileptogenic zone but involves less abnormal ROI with iower index of temporal abnormality.

Asenbaum S=, Oder W., Egcker A., Lang W., Goldenberg G., Podmka I., Deanke L.

Neurological Clinic of Vienna, W~ringer Giirtel 18-20, A-1099 Vienna, Austria

Patients with closed head injury (CHI) in their history often show reduced concentradon and attandon, psychomotor slowing or mental fadgability, regardless of location or severity of cerebral damage demonstrated by computed tomography (CT). The aim of the present study was to describe HMPAO SPECT studies in patients with CHL to compare these results with corresponding CT-scans and to look, whether the HMPAO uptake changes showed any relation to event-feinted evoked potentials as a marker of information processing. Twenty patients {mean age: 32 a, mean duration of coma: 7 days and of postranmatic amnesia: 6 weeks) were investigated with HMPAO SPECT 3.5 years after the head trauma.

-CT scan showed abnormalities in 9 patients. -SPECT studies were evaluated visually andby calculating ratios of tracer distribution (regional index (R1)=(mean counts/voxal of ROI)/(mean cts/voxei of all ROD) in 32 ROIs covering predomiannte|y gray matter, which were drawn on 4 adjocent, 21.9 mm thick transversal slices. RI were compared to those obtained in an age matched control group. -Further evoked potentials were recorded over Cz during an acoustic task, where in an ignore condition standard (600 Hz, 80%) and deviant (720 Hz. 20070) tones were delivered in a randomised order, The Nl amplitudes for both tones were measured in the CHI group and compared to those of a control group. According to reduced RI (lower then 2-fold s.d.) patients were divided into those showing diminished HMPAO uptake only in frontal and or only in temporal ROIs. Correlations between N1 amplitudes and RI were calculated in these two groups. Nine patients revealed abnormalities on CT scans, whereas all patients showed one or more reduced RI in the SPECT study, always located in accordanco to the CT results. A lowered RI was found in fronto-basal regions in 12 patient, in the superior temporal region in I0 and in temporo-basal regions in 7 padenL The N1 amplitude of the CHI patients was significantly lower in both conditions than in normals (standard tone: t=-2.3g, p<0.02, deviant tone: t- --2.88, p<0.008) . Patients with no frontal abnormalities showed a significant correlation between N1 amplitude and fromo-basal HMPAO uptake (corr.coeff. varied between r--0.85 for left fronto-mesial ROI and I'=0.96 left fronto-basai ROD. and patients with no temporal alterations a correlation between NI and superior tempora| HMAPO uptake (r=0.813 left ROI, r=0.77 right ROD. Summarizing HMPAO SPECT demonstrated fronto-hasal and temporal abnormalities in a much higher percentage than CT scan. indicating cerebral micrdiesions or cortical deactivations due to diffuse axonal injury. The affection of the N1. a process, which is sensitive to stimulus change and therefore connected with arousal reactions and which is primarily generated in the superior temporal plane under influence of the reticular forrrlationbasal ganglia-frontal lobe loop, can be although explained by alteration due to diffuse axon~l injury; the correlations between NI amplitude and temporal HMPAO uptake are m accordance with the temporal site of the N1 generators, the frontal correlations confirm the aforementioned modulating influence of the f, mnto~basal cortex on the N1 generators. Patients with complex partial seizures can be treated by surgery and therefore the exact preoperative localize tion of the target is critical in the planning of neurosurgical treatment.

The aim of this study was to evaluate CBF-SPECT study during and 3-& days after pharmacological activation (Ketamine) of the epileptic discharges in the group of 10 patients with non-diagnostic interictal CBF examination. 9gmTc-HM-PA0 as a blood flow tracer and gamma camera Orbiter 75 connected with microDelta system (Siemens) were used.Several conventional EEG recordings and CT examinations were available in all cases. First study was performed ~ days before pharmacological test.During second study HM-PA0 was injected 5-8 min. after Ketamine application and SPECT was performed 2 hs. later. Third study was done 3-& days later. First CBF-SPECT study was non-diagnostic in all cases. Second examination showed a regional decrease of blood flow in the epileptic focus in 6 patients and third study in 8 patients. All three examinations were nondiagnostic only in one case.

In conclusion,CBF-BPECT study performed during and/or after pharmacological activation (Ketamine) can improve the sensitivity of the blood flow examination in patients with partial epilepsy. Epileptic fool showed diminished blood flow in comparison to the other brain regions after injection of Ketamine .

C. Schiepers*, P. Casaer**, E. Merckx*, M. Eyssen**, J. H-~gge*, M. De Roo* * Nuclear Medicine and **Pediatric Neurology, Univers i t y Hospitals, K.U.Leuven, Leuven, Belgium.

BRAIN PERFUSION PATTERN OF Tc-99m ECD IN "NORMAL" CHILDREN -EFFECT OF AGE. Brain SPET is a well accepted method f o r the diagnosis of epileptic foci or regional brain perfusion. For obvious ethical reasons i t is d i f f i c u l t to acquire a database of normal controls.

Retrospectively we evaluated all brain studies in children performed in 1989~1991 with Tc-99m ECD. There were 114 exams that were read as negative.

Of these, 12 children had a high quality scan and were f i n a l l y considered normal based on : normal EEG, normal CT and normal c l i n i c a l follow up f o r 1 year, no psycho-motor retardation; I0 boys and 2 g i r l s , age [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] . Studies were performed on a NOVO 810 neuroSPET system.

Reconstruction and 3D re-orientation along the AC-PC line was done with SME Neuro 900 software. Typical acquisition times were 4 min/slice with 10-12 mm spacing. Uptake was normalized to the cerebellum to permit i n t e r -p a t i e n t comparison. There were no L/R differences.

On average the gray matter perfusion index was 0.92 + 0.I0; highest value in the visual cortex I . I 0 + O;T3 and striatum 0.95 + 0.11. There were 3 age c1~sters : I four kids 2-3 y -o l d , I I f i v e of 4-9 y and I I I three of 12-14 y. Group I had overall higher indices than I I and I I I : fronto-medial 17%, f r b n t o -l a t e r a l 13%, sensori-motor 14%, parietal ]6%, occipital 14% and temporal 3%. Caudate nucleus was 13% higher, lentiform nucleus 18%, and thalamus 18%. Group I I and I I I were similar. These differences r e f l e c t matuPational changes of the developing brain. Conclusion : young "normal" children have a d i f f e r e n t perfusion pattern than older ones. These differences should be used in interpreting brain perfusion studies. Temporal lobectomy is an effective treatment for medically intractable temporal lobe epilepsy (TLE). The purpose of the study is to e v a l~t e F-18 FDG PET findings in patients who are surgical candidates with intractable temporal lobe epilepsy (TLE) but with normal MRI. Forty-two consecutive patients with TLE and normal M~RI: 22 males (ages 5 to 44 yr) and 20 females (ages 5 mo to 53 yr) were studied preoperatively. All patients underwent prolonged EEG/video monitoring with scalp-sphenoidal electrodes to localize the epileptogenic focus. In the interictal state, 4-10 mCi of F-18 FDG was given IV and scans were performed at 40 min. post injection. Reconstructed tomographic images in 3 planes were analyzed visually and semiquantitatively.

All patients had normal MRI. EEG showed positive lateralization in 32 patients (76%) and no lateralization or bilateral activity in 10 patients (24%). Interictal F-18 FDG metabolic PET scans were positive with focal hypometabolism in 35 patients (83%), negative in 4 patients (10%), and equivocal in 3 patients (7%). There was agreement between prolonged EEG/video and PET findings in 32 of 42 patients (76%). In 6 out of 10 patients who showed no lateralization or bilateral activity on EEG, PET showed positive focal hypometabolism.

The findings indicate interictal F-18 FDG PET scanning is clinically useful in preoperative evaluation of patients with temporal lobe epilepsy~ even in patients with normal M/~I, and in those with equivocal prolonged EEG/video findings.

E Stokland, M HellstrOm, U Jodal, P Lundgren, R Sixt Depts of Pediatric Radiology, Pediatrics and Pediatric Clinical Physiology. East Hospital, University of GOteborg, Sweden.

Purpose: To correlate the DMSA scan appearance with clinical and laboratory findings in children with first time acute pyelonephritis. Material and Methods : 187 children 0-6 years of age (median 5 months) with their first recognised UTI were studied, Inclusion criteria were significant bacteruria and temperature >38.5 °, For children below one year fever was not required. The study population comprised an estimated 90% of all chil4ren in GOteborg fulfilling the inclusion criteria. The study protocol included clinical history, laboratory findings, DMSA scintigraphy, IVP and VCUG. The DMSA scintigraphy was performed 1-66 days (median 13) after start of s y m p t o m s and classified as normal, equivocal or abnormal. Results: 43% of the children had abnormal DMSA scans and 18% had equivocal. The scan was performed within 14 days of start of symptoms in 105 children. In this group 53% had abnormal scan compared to 30% in those with later scan. The frequency of equivocal findings was 10% in the group with early and 27% in the group with late scans. 74% of the children had temperature ->38.5 and CRP >20 and were classified as pyelonephritic. Of these children 52% had abnormal scans. In those with early scan the frequency of abnormal findings was 64%. Conclusion: In children with clinical signs of first time pyelonephritis the frequency of abnormal DMSA scans was 52%. Even when the scan was performed shortly after initiation of treatment as m u c h as 36% of the scans were normal or equivocal. Various explanations can be offered: the kidneys were not involved or discrete changes were not detected or had disappeared due to early and effective treatment. The presence of focal renal damage gives a child a 10% chance of developing hypertension in the latter life. Tc 99m DMSA has a high sensitivity in the detection of a scar, and allows estimation of differential function. In children with a urinary infection indirect cystography is frequently carried out to assess differential function and exclude renal reflux. Analysis of the MAG3 study included differential function assessment and the evaluation of scars on a functiona'l image created on a pixel by pixel basis, representing renal clearance based on the Patlac plot. The functional MAG3 clearance image was created in a series of children with normal Tc 99m DMSA scans. Different levels of noise were added to the images to ascertain the minimum count rate required to produce a useful image. The results suggest that at count rates encountered in clinical practice using a dose schedule of 80 MBq/I.73 m ~ and normal renal function will provide a MAG3 clearance image with a sensitivity of 80% in the detection of a renal scar. Thirty four children with UTI underwent both Tc 99m DMSA and MAG3 within 4 weeks. Good correlation between the differential function on DMSA and MAG3 was found (CC = 0.97, R ~ = 93.9%), the sensitivity of Tc 99m MAG3 in the detection of a focal defect in the presence of normal differential function was 80%. Tc 99m MAG3 in the clinical setting of a chiId with urinary infection allows accurate assessment of differential function. A normal functional image suggests that there is a n 8 0 % chance of the kidney being normal.

S . C a m m i l l e r i * , J . C . D u b u s °, F . K h e l i f a * , S . S i l e s * , H . C o l t °°, D . U n a l °, G . K a p h a n * P e d i a t r i c ° a n d N u c l e a r M e d e c i n e * , C H U Timone, M a r s e i l l e , F r a n c e a n d P u l m o n a r y d i v i s i o n °°, UCSD, S a n _ D i e g o . CA. U S A 

~T E

Thirteen patients with suspected myocadltis were evaluated with Endomyocardial Biopsy (EB) and 1111nantimyosin antibody (AM) imaging (16 studies). There were 4 males and 9 females, average age 61.4 ± 48 months, with a congestive heart failure which average evolution time was 5.2 ± 5.6 months.

The ES was interpreted as diagnostic of myocarditis when it showed myocyte necrosis with white cell infiltration (Dallas criteria). 72 hours previously to EB, these patients received according to their weight 1 mCi/250 Bg or 2 mCi/500 ~g of 111In/Fab monoclonal antimyosin antibody and planar imaging was performed at 48 hours. AM scan was evaluated as positive when uptake in the region of the myocardium w a s e q u a l or higher than s t e r n u m a n d the heart/lung ratio was higher 1.6. AM STUDY ÷ E. BIOPSY -R E S U L T S Ten EB showed myocarditis: five active myocarditis, three borderline myocarditis a n d two resolving myocarditis. Five EB did not show significant findings a n d one endocardial fibroelastosis. The A M s c a n was positive in 15 patients and negative in o n e whose final diagnosis w a s i d i o phatic dilated cardiomyopathy.

Eleven over 15 had accordance between EB and AM scans. In four over 15 the results were discordant, one of these however had a positive EB 8 months before and died 4 months afther rheAS4 scan. T h a r e w a s n n n e negative AM scan with positive myocarditis by EB.

s c a n s shows to be a sensitive diagnostic method for acute myocarditis in children. Portasystemic shunting (PSS) is a major complication of portal hypertension in patients with chronic liver disease. We have shown in animal studies that transrectal portal scintigraphy (TPS) using Tc-ggm pertechnetate (Tc-ggm) was capable of detecting 'and quantitating the PSS. In order to evaluate the portal-systemlc shunting in children (5-15 yo) with chronic flyer disease [8] [9] [10] MBq/kg, Tc-ggm was instilled into the upper rectum using a thin polyethylene tube. 5 sec sequential images of the upper abdomen and chest were acquired for 5 min. Shunt indices ($I) were determined by the areas under tlme-activltly curves of heart (H) and liver (L) ROI's, expressed as % H area divided by the sum of H and L areas for a period of 25 sac. In the noncirrhotic group with diffuse l i v e r disease, SI ranged from 10.2 to 24 % (mean-17.7, . In cirrhosis verified by histopathology Sl ranged from 30 to 77.4% (mean 54.6, . SI was 63.8±17.2% in 5 of these children with endoscopically diagnosed esophageal varices. The results of this study suggest that TPS is a useful technique for the diagnosis and the management of the patients with portal hypertension, This method is ideally suited as a ~ rognostic indicator in children with portal ypertension due to its simple, safe and noninvasive nature. The purpose of this investigation was to determine the feasibility and explore the utility of performing PET FDG scans in children with known or suspected malignancies.

Fifteen children, ages 7 months to 17 years, have been studied. Final diagnoses included neureblastoma(9), Ewing's sarcoma(3), medullary carcinoma of the thyroid(I), hepatic sarcoma(I), and benign arterio-venous malformation (l) . Four of the patients with neuroblastoma and the patient with medullary carcinoma were studied during the course of therapy. The remaining patients were studied at the time of diagnosis, including two patients with Ewing's sarcoma and one with neuroblastoma also studied following chemotherapy. After a brief transmission scan for attenuation correction, images of the tumor were acquired dynamically for 40-50 minutes following the intravenous administration of 10 mCi F18-FDG/1.7 sq m. In later studies, this was followed by a "whole body" acquisition, covering 40-60 cm in the z axis. The data were forward projected into images every 10 degrees for viewing as a series of rotating images.

Tumors were detected in each of the 14 patients with known or subsequently proven malignant disease. The uptake of FDG was considerably higher in untreated than treated neoplasms. Standard uptake values ranged from 1.8 to 6.4 in untreated tumors and 1.2 to 1.7 in the treated tumors. In one subject with Ewing's sarcoma, PET FDG scanning detected 2 metastatic deposits not visible on MDP scanning. In 3 of the 14 patients with malignant neoplasms, PET scanning showed that large areas of the tumor did not take FDG, indicating necrosis. Whole body PET scanning provided significant improvement in anatomic localization of the tumors and facilitated comparison with conventional imaging, eg. MDP and MIBG scintigraphy and MR imaging.

We conclude that PET scanning with FDG is useful for the study of tumors in childhood. The "whole body" technique facilitates the scintigraphic detection of metastatic disease in children. The sensitivity of BW250/183, a monoclonal antigranulocyte antibody labeled with Tc-99m, to detect marrow lesions is well established. The aim of this study was to assess the usefulness and reliability of this antibody (Moab) in the qualitative and quantitative evaluation of the hemopoietic bone marrow.

Moab scintigraphy was compared to Fe52 scan, the reference method, in 13 patients with various hematological disorders. Moab scintigraphy was obtained 1 hr and 16-24 hr after injection of 555-740' MBq Tc-99m labeled antibody and Fe52 scintigraphy was performed 4-24 hr after injection of 18.5-37 MBq Fe52. The uptake in 9 marrow areas and the spleen was qualitatively compared using a 4-point visual score by comparison to the liver uptake. Relative quantitation (% total activity) was obtained using ROIs drawn on marrow segments, the liver and the spleen.

Agreement between the visual score was achieved in 82 % (96/117) of the marrow areas (p < 0.001). Fe52 spleen uptake was visible in 7 patients whereas the spleen was visualized in all patients with Moab. The visual score correlated well in 11/13 patients and was discordant in 2 patients with primary aplasia (overestimation of marrow activity by the Moab method). The correlation between the relative uptake of both tracers was globally excellent for the marrow segments (r=0.88; p<0.001) and the spleen (r--0.88; p<0.001) but not for the liver (r=0.55). The relative organ uptake of both tracers was well correlated in 10 individuals (p<0.05) whereas no correlation was found in 2 patients with primary aplasia and 1 patient with chronic myeloid leukemia with acceleratior~ of the leukemic process.

In conclusion, Moab scintigraphy can be proposed as an alternative method to Fe52 scan for assessing the distribution of hemopoietic marrow except in aplasia and for detecting extra-medullary hemopoiesis in the spleen. In the two latter situations, Fe52 scan remains the procedure of choice. DETERMINING THE SENSITIVITY AND SPECIFICITY OF Tc-99m LABELLED LEUCOCYTES USING DUAL ISOTOPE SCINTIGRAPHY. 111In-oxine labelled leucocytes is the test of choice in detecting occult infection and localising focal inflammation. The procedure for labelling leucocytes is technically complex, time consuming and expensive. Leucocyte labelling with 9~Tc tin colloid ldt has been considered an alternative method, however no studies have directly compared the two techniques.

Leucocytes from 38 patients referred for investigation of occult infection or localisation of inflammation were simultaneously labelled with rain and 99~Tc (Leucocyte Labelling Kit, Radpharm, Australia) with dual isotope acquistion (10 minutes per image, 256 x 256 word matrix, DIACAM gamma camera) performed at 1,3, and 24 hours. 24 hour 99~Tc scans were corrected for rain downscatter. Each case was independently interpreted by two experienced observers using the rain leucocyte scan as the gold m standard. 19 patients demonstrated positive In leucocyte scans.

In 35 of the patients studied, the two procedures demonstrated congruent behaviour. Clinical follow up verified that two patients had false negative 9'~Te leucocyte scan and one patient had a false itive scan. Using rain leucocyte scans as the gold standard, c leucocyte scanning has a sensitivity of 90% and a speciflcityl of 95%.

We conclude that 99~Tc leucocyte scanning is a reasonable alternative to raIn leucocyte scanning where !IlIn labelling facilities are unavailable, Immunoscintigraphy with Tc-99m-antigranulocyte antibodies ( NCA-95; IgG1)has proven to be useful in localization of infectious diseases. Smaller fragments promise a more rapid localization of infectious diseases.

For this reason 10 patients with suspected osteomyelitis, abdominal sepsis or sinusitis were prospectively examined wit 740-900MBq Tc-99m NCA-95-Fab'-fragments (IMMUNOMEDICS; IMMU-MN3).Gamma-camera images were performed in planar and SPECT technique 1, 2~ 3. 4, 6 and 20h p.i. 24h later'mixed" leukocyte preparations labelled with either 10MBq In-lll-oxin or 200MBq Tc-99mHMPAO were injected and seintigraphy was performed 3h and 24h p.i. Both methods demonstrated comparable results in all patients. The focus of infection could be demonstrated with Tc-99m-NCAfragments as early as lh p.i. Uptake ratios of immunoscintigraphy were 1.4(lh),l.7(4h), 1.2(20h), of leukocyte scintigraphy 1.6(4h) and 2.1 (20h). Late Tc-99m-NCA-seans revealed no additional information. The whole body distribution showed high renal uptake (18%+/-5%) and up to 11.2 +/-3% uptake in the liver. Bone marrow could clearly be demonstrated. The radiation exposure to the patients was calculated with 2.5-5.2 uGy /MBq whole body dose, 8. .5uGy/MBq spleen dose and 16 -20 uGy/MBq kidney dose.

In conclusion, immunoscintigraphy with Tc-99m-labelled NCA-95 Fab'-fragments shows comparable clinical results with leukocyte scintigraphy with In-lll-oxin or Tc-99m-HMPAO labelled granulocytes. Infectious lesions could be demonstrated as early as lh p.i. The radiation exposure is significantly lower than with In-lll-oxifi leucocytes. This study was undertaken to get insight into the labeling mechanisms and possible metabolism of the antigranulocyte antibody (AGAb) as well as into the migratory behavior of neutrophilic granulocytes labeled in vivo.

Twenty-eight consecutive patients (15 m, 13 f, age 20-83 yr) with osteomyelitis (n=I8), lymphoproliferative systemic disorders (n=6), and solid neoplasms (n=4) were i.v. injected with 555 MBq of the Tc-99m AGAb directed against non-specific cross-reacting antigen 95. Planar spot scans of the whole body were taken with a large field-of-view gamma camera i, 3, 6 and 24 hr p.i. HPLC was done on plasma and urine samples.

There was no fundamental difference of the activity distribution pattern and metabolism of the AGAb between the patient groups studied, in all patients, bone marrow and spleen demonstrated an activity increase followed by a decrease with a maximum [3] [4] [5] hr and 1-3 hr p.i., respectively. A "perfusion kinetic" was found in the liver. There was a continuous activity increase in the kidneys as well as in florid granulocytic inflammatory loci. In peripheral blood, a biexponential activity slope with a fast and a slow component was observed. Low molecular weight AGAb metabolites and free pertechnetate increased from 1 to 24 hr in plasma and urine.

In conclusion, the data obtained in this study support the hypothesis of a multi-compartment model with labeling of mature granulocytes primarily in the hematopoietically active bone marrow and, to a lesser degree, in the spleen. Labeled granulocytes then migrate via circulating blood into peripheral tissues and inflammatory loci. The AG~ is partially metabolized in vivo. in 12 patients. 9 out of the ii CV positive were positive with TcPLT. In fresh DVT TcPLT showed defect in filling in the dynamic image and very intensive uptake in thombi thereafter.

In 5 out of the DVTs TcPLT uptake was noticed already at i0 min. In 2 cases TcPLT showed false negative result. One of them was under heparin treatment.

All CV negative were also negative with TcPLT, Our results suggest that TcPLT venography is a useful alternative in diagnosing patients in whom CV is contraindicated or otherwise unsuccessful.

It is possible to obtain the diagnosis within two h. There is no doubt about importance of evaluation for residual splenic tissue after splenectomy.

14 splenectomized patients (range year old) were examined with technetium 99m-labeled heat-damaged autologous red blood cells. Imaging was accomplished with a ganunacamera, either in planar or SPECT mode. Abdominal echography never shown any splenic tissue. 7 times the examination was performed after traumatic splenic rupture a~d every time an heterotopic splenic autotransplantation was carried out. Sclntisoans were performed 3 to 8 months after spleen removal, then 2 to 4 years later (group 1).7 times the search for ectopic splenic tissue was performed, according to the relapse 4 to 37 months after splenectomy, of an idiopathic thrombocyt0penic purpura (group 2).

A functional heterotopic graft was found, in original implantation site, in all patients of group 1 and in 3/7 cases in other abdominal loci (post-traumatic splenosis). No patient in this group developped postsplenectomy infection. 6 times an ectopic spleen was found in the patients of group 2.

The ectopic spleen was succefully removed 3 times but in one patient it was not found after the laparotomy.

Imaging ~with heat-damaged labeled RBC appears as a sensitive and specific method to localize spleen tissue after splenectomy but in some cases it will need p~roperatory localization with intraoperative probe.

Montreal Heart Institute and University of Montreal, .Montreal, Quebec, CANADA

Multivariate Analysis (MVA) of data generated in nuclear medicine is now accepted and more widely used. Several tecl~fiques acquiring a series of frames in time or in energy in order to assess some multidimensional image properties have been proved useful to describe the elementary imaging processes such as the scatter contamination or the dynamics of physiological phenomena. Principal Component Analysis (PCA) is generally used to extract the image features. PCA explicitly assumes that an image in the multidimensional energy space can be decomposed in a series of orthogonal features. Oblique rotation can be used to further refine the multidimensional description of the data for nothing ensures that features are effectively orthogonal. But oblique rotations address only the description of the non-principal axes since the first will always be the direction that cumulates the highest possible variance. However, a simple inspection of the multidimensional data clearly shows that the main (first) axis is intrinsically curvilinear. The new model allows for a more complete variance compression and a reduction of the (effective) image dimensionality. The curvilinear model has been tested using both simulated images and clinical data. Proportion of the variance contained in the principal axis due to this curvilinear model is highly object dependent and ranges from almost nothing (adequacy of the linear model) to 5 to 8 % in the worst case. The curvilinear model explains the fine structure of the holospectral data leading to a higher accuracy in the image description and object estimation. 

A precise quantification of SPECT images requires an accurate correction for attenuation. When attenuation coefficient (It) maps are measured from transmission scan, cumbersome iterative methods are necessary. A significant attenuation compensation can be mathematically obtained by dividing each actual pi×el value of emission projections by the average of all the attenuation factors ( exp (-~ Ix ) ) of all voxels along the same projection ray. The efficacy of this simple method, compatible with filtered back projection algorithms, has been tested on simulations of cardiac and cerebral transaxial images on a Vax using the RECLBL library. In the cardiac model, myocardium, chest wall, lungs, mediastinum and spine received different activities and It values. In the cerebral model, striata, cortex, white matter and skull had also different activities and ~ values. Three types of emission projections were generated: the ideal projections obtained by summation of activities along each projection ray, the corresponding attenuated projections and the ones corrected for attenuation. Comparison of projections on a pixel by pixel basis showed differences of less than 10% between the corrected and ideal projections whereas the attenuated projections underestimated the true count rate by at least a factor of 3. Using filtered back projection, the above attenuation correction method greatly improved: 1-the quantification of the absolute activities of the different structures, 2-the striatum to cortex activity ratios and 3-the relative uniformity of the myocardial activity. In models, this simple method produces an efficient compensation of attenuation on the projections and does not require a systematic segmentation of the attenuation coefficient (It) maps. Cone beam transmission maps are currently obtained in patients with an uncollimated gammacamera for further validation of the method. The Johns Hopkins University School of Medicine, Baltimore, MD.

(ECT) .

The study describes a computer-generated, MRI-based three-dimensional phantom of the human brain developed for quantifying effects of finite resolution and testing the accuracy of restoration algorithms.

The model differentiates gray matter, white matter and cerebrosplnal fluid as determined by MRI. Voxels representing these compartments are assigned values to reflect in vivo conditions for a given radiotracer.

The simulated ECT image is generated by convolvlng the coded MRI images with the 3D pointspread function of the corresponding ECT device.

The accuracy of the model was tested by comparing acquired ECT images of a physical brain phantom with the corresponding simulated images.

The mean error between the uptake in the acquired and simulated ECT images (n=4) was less than 6%.

Based on the simulated ECT images, regional recovery coefficients were estimated for various brain structures.

Their application in relating in v i v o and in vitro measurements of muscarinic acetylcholine receptors in human brain resulted in a significant improvement of the correlation. A restoration filter was applied and its accuracy evaluated.

In the amygdala application of the filter resulted in a 50% improvement in quantitation of activity concentration.

In conclusion, the model is suitable to compute the regional radiotracer recovery in various brain structures for a given subject.

It permits testing the accuracy of image restoration techniques in ECT that involves anatomically complex brain structures. Time-activity (TA) curves for fixed regions are commonly used to evaluate the transport of food through the gastrointestinal tract. The input function describing the food entering the organ is highly variable and does not resemble a Dirac functiou. Deconvolution is impossible. Therefore TA-curves are difficult to analyze and prone to erroneus interpretations i.e. due to reflux. Pathology proximal to the region also modifies the i~lput function. Compressed images are of limited help i.e. reflux and the delayed swallowiug of part of the activity cannot always be distinguished. We describe an algorithm, to obtain a set of time-locatlon (TL) curves of the activity, that is unbiased in the statistical sense. The method remains valid even when part of the ingested activity is not in the field of view of the camera for some time. It is compatible with all classical corrections such as for motion, attenuation, scatter and decay. The TL-curves describe the position at any time that was passed by a certain percentage of the ingested activity. The time interval between the passage of two anatomical points for the 50th percentile TL-curve is a true transit-time, independent from the shape of the input function. The difference between the transit times for different percentile curves can be used as a measure of convolution ('m.ixing') when combined with the difference in arrival times at the input of the organ(segment). The method was successfully applied to compressed images obtained from oesophagal transit studies and gastric emptying studies. Conventional pharmacokinetic modeling does not satisfactorily define the early phases of tissue biodistribution of radiolabeled murine monoclonal antibodies (MoAb) in patients. In particular, nonspecific MoAb binding in the liver, spleen and bone marrow does not seem to follow a linear, first-order kinetics. To test this hypothesis, the experimental design was optimized to characterize early biodistribution immediately after injection of a radiolabeled MoAb, and a new pharmacokinetic model was developed to fit such experimental data.

131I-AR-3 (an anti-adenocarcinoma IgG1 MoAb) was injected i.v. as a single bolus into 5 patients with suspected pancreatic cancer. A computerized gamma-cameru (GE Starcam 400) was utilized to record dynamic scintigraphic maps over the chest/abdomen from 0-30 rain post injection. Static whole-body maps were then recorded at daily intervals from 0.5-144 hrs. Blood samples were also taken from 0.05-144 hrs, and the fractions of circulating undegraded 131I-AR-3 and free t31I-were measured by Sephadex G25 chromatography. Specific ROIs for the heart, liver and spleen helped to define the kinetics of activity over these organs both in the dynamic sequence (0-30 rain) and in the later phases (0.5-144 hrs).

Pharmacokinetic modeling based upon this set of experimental data identified a saturation-like, nonlinear zero-order process for activity accrual due to binding in liver and spleen, with doubling times of 1.83 + 0.17 hrs and 2.13 + 0.31 hrs, respectively, after subtracting radioactive contributions from blood circulating in these organs. This data compares with late removal from these sites having half-lives of [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] hrs. Integration of these kinetic parameters into a complex multicompartmental model helped to define the exchange and removal rates of ~3~I-AR-3 with greater accuracy and better identifiability (by chisquare analysis) than conventional pharmacokinetic modeling based solely on linem', first-order kinetics.

P. Wane?% M. Rubinstein, J. Abramovici, Department of radioisotopes, Ixelles hospital, Brussels, Belgium.

We have adapted to a gamma-camera a rotating collimator consisting of parallel 0.2 mm thick lead foils spaced by 0.8 mm thick slits. These slits have a 25 cm length and a 3 cm width. The system may be rotated around the center of the crystal. 60 projections are carried out for each 6 degrees step. The final picture is reconstructed by a back projection algorithm and a Metz filter. We have shown experimentally on a series of uniform discs of activity that the R.M.S. uncertainty is related to the number of counts in the image (n) and the number of pixels (N) containing the activity by the Budinger Equation : RMS = 120 N ~4 / nm. The geometrical efficiency of a parallel slit collimator is 100 to 200 higher than for classical holes collimator. For a 1000 pixels object, R.M.S. is reduced by 1.5 to 2. It follows a 3-fold increase in effective sensitivity We have used a phantom consisting of a series of cold spots (4 mm to 18 ram) surrounded by uniform Tc-99m activity to compare our rotating slit collimator with a hole collimator of the same resolution. We have observed that the effective sensitivity is multiplied by 3 for the slit collimator, without decreasing the resolution. Tomographic acquisition were performed on a brain phantom. 60 frames were acquired for each of the 60 steps of the tomography. We have compared the slit collimator with a high resolution parallel collimator and a fan beam collimator. The fan beam gives a better resolution than the parallel high resolution with the same count rate. The resolution of the slit collimator is better than the fan beam with a higher sensitivity. Non statistical differences were obtained in the indexes between groups, and high, medium and low uptake areas in each slice could be better resolved in the images of the B group.

We conclude: I. The astigmatic collimator has a point source sensitivity five times greater than the LEHR collimator.

2. High counting statistics images are not necessary to obtain better results with the astigmatic. 3. The time spent to acquire a better quality image with the astigmatic is lower than with t h e L E H R collimator.

K. S. Pentlow. Memorial S]oan-Kettering Cancer Center, New York, NY, USA.

Many procedures that use 1-131 labelled pharmaceuticals or monoclonal antibodies require an accurate in vivo determination of the activity distribution within the patient. This is usually carried out by imaging the 364 keV photopeak using a gamma camera with high energy collimator operated in either planar or tomographic (SPET) mode. Using such standard techniques, it was found that septal penetration and scattered radiation from the higher energy peaks of 1-131 resulted in a significant number of counts recorded in the 364 keV photopeak window which then significantly affected quantitation. In typical patient measurements the average contribution over the whole field of view was found to be 20 to 35% of the 364 keV photopeak counts. Within the image, however, the contribution varied widely, being lowest within small areas of high activity and highest within areas of low activity adjacent to high activity. Phantom measurements indicated that septal penetration of the higher energy photons was the major component of this effect and that improvements in accuracy of quantitation could be achieved by subtracting an image acquired simultaneously at an energy just above the photopeak. Since this secondary image involved mostly low spatial frequencies it could be smoothed to minimize added noise. The method was applied successfully to patients who had received 1-131 labelled antibodies. This study examined the cost-effectiveness of in-house service engineers, ccmpared to vendor service contracts, for the maintenance of nuclear medicine gamma cameras. The maintenance costs for 18 gan~a cameras (13 analog, 5 integrated syst~us) were tracked over a 3.0-year period. Equipment age was 5.9+2.7 years (mean+_s.d.) with an average cost of $196+_--67k per system.

In-house engineers repaired over 95% of all system faults, and vendor service engineers were only required for major equipment problems. Mean downtime for all systems was 20.4+ --16 .5 hours/year. Assuming a 2,340-hour working year, this represents less than 1% downtime. Integrated systems (gaurm~ camera + computer) had a significantly higher downtime than analog cameras ( 35.6+_17.6 hrs/yr versus 14.5+_12.2 hrs/yr, respectively, P < 0.01). There was no correlation between gamma camera age, downtime per year, and service costs.

.Annual maintenance costs per system averaged $5.5+4.8k, but ranged frc~ $0.01 -$17.1k. Two in-house engineers cost a total fo $128k per year. Total service costs averaged $12.5k per system per year, or 6.4% of purchase price. These costs are considerably less than costs of vendor service contracts which normally range frcm 9-11% of the purchase costs. In-house service has resulted in saving of approximately $128k per annt~n, and beccmes cost-effective for departments with mere than 5-6 gamma cs/~er as. A new whole body counter has recently been completed in the new universiv/hospital of Vienna. Its main features are high sensitivity, the use of NaI(Tl) and I-IP Ge detectors simultaneously, a proEde scanning attachment for localization, heavy use of digital control of the measurements and automated analysis of the spectra.

The detector system consists of four low-background NaI('rl) detectors (20era dia x 10 em thick each) and is located in a low background room (background index 0.2 epm/cm 3 of detector volume) with walls composed of layers of 15 cm steel, 2 em of lead and 0.fi can of copper. Each detector may be positioned and scan the patient independently of the others. The counter has been calibrated for scanning as well as for stationary geometries. Characteristic MDA values for the scanning genmetry are 84 Bq for mI and 98 Bq for rues. Focused slit collimators designed for energies of up to 1.5 MeV may be attached to the Nal-detectors. A high resolution HI' germanium detector (30%) is used for the identification of radionunludes. Energy spectra am evaluated automatically by a Microvax computer using special purpose software. An automated dead time correction based on a count rate conu'olled change of scanning speed indelxmdenfly for each detector has been implemented. Positions and scatming speeds are controlled by the computer to ensure reliability of the results.

The main applications a,% m~tabolic studies, in vivo dosimetry of radiotracers and the assessment of radioactivity in radiation workers and in the general population. In general, resolution of a gamma camera is measured by using a point or a line source, imitating a delta function as input to the system. But this technique may only be applied if the size of the source is very small compared to the resolution of the gamma camera. In practice the activity concentration will be the limiting factor, especially when gas filled sources (e.g. 81mKr) have to be used. However, if the theoretical projection of a source on the detector can be determined, then the system resolution can be computed from the measurements of the extended source by means of iterative deconvolution. (Due to the finite extend of the ideal projection of the source and the noisy acquisition data, the usual deconvolution methods -sequential deconvolution or via Fourier transformations-cannot be applied.) We have tested this technique for thick, tube shape sources filled with 99mTc and 81mKr, both in air and submerged in water. The measurements were compared with resolution measurements using very thin line sources filled with 99mTc. After acquisition of a projection image of the both phantoms, profiles were generated perpendicular to the direction of each phantom, followed by deconvolution of the tube response profile. The results obtained with both techniques closely matched. The tube filled with 81mKr revealed a slightly decreased resolution, probably due to the higher energy of the emitted photons. We conclude that extended sources may be used for resolution measurements as long as an appropriate deconvolution can be applied. 

A whole body counter is an useful tool for the quantification of very low radioactivity levels in-vivo. The present discussion about low dose effects increases the importance of those systems. Additionally to 4 NaI(TI) detectors a low efficiency Ge-detector (31%) was used for spectroscopy. Our investigations should evaluate, whether the low efficiency system is able to determine the body activity and allows a practical correction method for geomelry of this single detector model. Furthermore the influence of multiple nuclides on the minimal detectable activity (MDA) is discussed. Measurements with the detector are acquired by bottle-phantoms (4...90 kg) filled with Tc-99m, 1-131, T1-201 , and through scatterphantoms with point sources. After the determination of the calibration factors (CF) in single nuclide solutions, we calculated the changes of the MDA by various activity concentrations for different radionuclides. The graphs of the CF's as a function of body weight (m= 50...90 kg) show an energy constant (60 keV -400 keV) and a finear relation. After con'ection for the normalized emission rate a regular standardized equation was found: CF = -0.01om+2.4 [10-4 cts/soBq] r = -0.96 (I-131); -0.98 (Tc-99m); -0.99 ( T1-201) The calculation of body activity can be done with a simple measurement of the CF,by the described device. Additionally, the dependence of the CF and MDA from different activity concentrations in nuclide mixtures is demonstrated. Our results describe a correction function for geometry in a single detector system. The good correlation (r~0.98) gives a reliable value for energy and weight correction. The Ge-detector offers advantages in the simultanous detection of multiple nuclides compared to the great influence of compton effects in NaI-cristals. At least, low incorporation levels (ca. 100 Bq) of mainly used radionuclides in nuclear medicine can be ascertained. Accreditation and certification are a means of objectively recognizing compliance with quality standards. Before implementation of such a system, quality standards must be defined and accepted within the health care system. A 3-year project is in progress in the Netherlands to establish practical and feasible standards for 20 different hospital departments. This is coordinated by an external body (Centre for Medical Teehnology-TNO). The standards have been developed using formal methods based on the ISO 9000 series and modelled after the Guide to Accreditation of Canadian Health Care Facilities. Eight hospitals (4 teaching and 4 general spread throughout the country) were initially involved. Inter and intra-organizational relations and procedural processes within each department were described using flow charts that showed the links between processes, intermediate results, cheeks, decisions, and actions. These were then transcribed into draft standards. The flow charts were then examined and modified by the equivalent departments in the other 7 hospitals, and the standards amended. For nuclear medicine these standards apply to the organlzatlomd structure, staffing, faellltles, purchase and storage of materials, radiopharmaeeutical preparation, quality control and servicing of equipment, all sequences of activities eoneernlng a patient study, training, and quality assurance evaluation. In the final project stage to be completed in 1993, the draft standards will be nationally assessed and verified in the field to assure general couseusus. They will then assume official status for implementation into a nationwide accreditation system.. Where data is lacking, either an educated guess or a small scale experiment can be made, to fill the gaps. This results in global optimization, better insight in the factors that influence quality and optimal use of quality control resources. This technique was applied successfully for the 125-Ifibrlnogen uptake test, resulting in a threefold reduction in injected dose, better criteria for the reference point and for diagnosis, a better calibration procedure and formal criteria for equipment performance. It is concluded that system analysis is a powerfull method that can be a valuable Q.A tool. The s t u d y was p e r f o r m e d w i t h t h e P E T -s c a n n e r P C 4 0 9 6 -15WB ( S c a n d i t r o n i x ) , a n d i n c l u d e d two p a r t s : ]) p l m n t o m m e a s u r e m e n t s , 2) a n a l y s i s of p a t i e n t d a t a . 1) A c y l i n d r i c a l p h a n t o m filled with n o -a c t i v e w a t e r c o nt a i n e d 6 s p h e r e s (diam.: 10 -30 mm), w h i c h were filled with IBF-labelled s o l u t i o n ( c o n c e n t r a t i o n = 140 kBq/ml). In a d d i t i o n to a BI t r a n s m i s s i o n a n d a n emission s c a n , five AI t r a n s m i s s i o n s c a n s (T1-TS) were a c q u i r e d w i t h i n 6h. 

K~Reichmann, R.Kohley, R.Knopp, H.Schmidt and H.J.Biersack. Clinic for Nuclear Medicine, University of Bonn, Germany.

The uniformity of a gamma camera is of maior importance for clinical routine. This presentation shows the difference between the uniformity obtained by maps generated with Tc-99m and . A Genesys camera (ADAC) was used (15x20 in FOV). We used pointand flat sources of to generate uniformity maps. To simulate the influence of scattering (S) in the patient, we used a lucite block (38 mm thick). Maps were generated without and with S. Maps obtained with the Co-57 flat source never simulated S. QC was performed with the point sources (without and with S), a Co-57 flat source and a Tc-99m flat source (60 mm thick, zoomed FOV). To investigate the influence of the camera zoom for brain SPECT (resulting field of view: 25.4X25.4 cm), QC was performed for the total and zoomed FOV. Tomographic acquisitions (phantom=water) were obtained to see the effect of different maps on SPECT images. For QC we calculated the int. and diff. uniformity for the UFOV and CFOV and zoomed FOV. Measured uniformities for the point sources were (no S) 1.42%(Tc)/1.66%(Co) and 1.66%(Tc)/1.49%(Co) (with S); for the flat Co-source we obtained 1.72%. Camera zooming decreased uniformity to 2.69%(Tc)/2.53% (Co) (no S) and 2.42%(Tc)/2.52%(Co) (with S); for the flat field we obtained 2.87%. Use of point sources for maps (Tc and Co) decreased uniformity to 1.50% compared with flat source maps (0.85%). Applying the maps generated by point sources and the Co flat source to the Tc flat source the uniformity decreased to 4. [3] [4] [5] .9%. There were only small quant, and qual. differences between Tc-99m and the Co-57-generated maps in the modulation of the tomograms. (The authors thank DuPont, Germany, for supplying the C-57 sources required for these studies). 

Quality assurance in Nuclear Medicine does not only include quality control of the imaging systems, even though this item is heavily stressed in several publications. Internationally accepted test procedures have been defined (ACR/NEMA, I.A.E.A., etc.) to assess the quality --uniformity, spatial and energy resolution--of planar systems. Comparable and additional tests have been proposed and are cur[curly under discussion for SPECT imaging systems. However, quality control of whole body imaging systems, which are already in use for many years for the registration of the radionuclide distribution throughout the human body, received only minor attention. Since more and more systems have this imaging capability and the number of patient studies performed with these systems is increasing, definition of quality assurance procedures dedicated to the special aspects of these imaging systems is getting important. We defined a set of tests dedicated to the special problems which can appear in whole body imaging systems. The tests, for both acceptance testing and daily quality control, can be applied to analog and digital, and to small and large field of view imaging systems, as well as to whole body imaging systems based on moving imaging tables. Applications of these tests to several systems with various configurations wilt be presented. The tests witl be part of the quality control protocols of the Dutch Society of Nuclear Medicine. 

The Dynamic Line Phantom (DLP) is a multifunction phantom which consists of a thin line source on a movable source holder. The movement of the source,which is controlled by a microprocessor, allows the generation of a complete set of patterns to evaluate the characteristics of a gamma camera.

In the present paper the authors have analyzed the possibility to get, in a quantitative manner, the MTF of a gamma camera using the appropriate DLP pattern.

Moreover this result has been checked by getting the MTF also from the Fourier transformation of the Line Spread Function obtained in the same acquisition conditions.

The agreement between the two methods suggests that DLP is a useful system to control the resolution capability of a gamma camera and to perform the routinary quality checks in a simple and quick manner without using high performances computers. A data base of clinically validated cardiac software phantoms for quality assurance of applications programs is needed but as yet unavailable. To enable the categorisation of results according to normal and specific abnormal patterns, the selection of suitable patient studies must satisfy well defined clinical and non-radionuclide test criteria. The Cardiac Working Group of the European COST 132 project, in association with the Cardiac Task Group of the EANM and the Working Group on Nuclear Cardiology of the European Society of Cardiology, has developed selection protocols for the creation of a software phantom data base of normal studies and three typical patterns of cardiac disease: recent transmuml myocardial infarction, isolated myocardial ischaemia, and dilated cardiomyopathy. These include criteria for the interpretatiou of qualitative and quantitative nonradionuelide data. The radionuclidc studies encompass rest and exercise myocardial perfusion studies (planar, SPECT) using T1-201 and Tc-99m MIBI, and rest gated blood pool studies. The methods for data acquisition are defined. For each software phantom a unique portfolio is established. This contains all of the patient's data, anonymity being assured. For each software phantom, compliance of data with the selection criteria will pass review by an international team. The quantitative radionuelide parameters to be assessed have also been proposed. A preliminary study is underway to investigate the problems and logistics of distributing radionuelide studies in Interfile format between a range of computers and institutes, and to ascertain the statistical procedures necessary for analysis of the range of quantitative results to be expected.

Dirk Tombeur and Frank Deconinck, Vrije Universiteit Brussel, Brussels, Belgium:

A PROTOTYPE IMAC ENVIRONMENT WITH NETWORKWIDE DISTRIBUTED DATA ACCESS, DATA PROCESSING, DATA VISUALIZATION AND GRAPHICAL USER INTERFACES.

Classical IMACS or PACS use centralized data access, processing and visualization, associated with image transfer between stations using protocols such as ACR-NEMA. In this paper we describe a prototype environment developed around applications in nuclear medicine, using general purpose UNIX workstations, the X window system and the C++ language. Nuclear medicine imposes specific constraints on image processing systems: although the 2D image sizes are smaller (64*64 to 512"512) than typical radiological images, they often come in time series or as 3D volumes. Furthermore, sophisticated processing techniques such as 3D reconstructions or temporal Fourier analysis are routinely performed. Most image processing tasks require interaction, and are performed in real time, including 3D visualization. Decomposing tasks into relatively small cooperating, but independent programs is a software implementation of the way nuclear medicine specialists interact with their data: integrated facilities which support multiple views on images, curves, regions of interest and related data, simultaneously, combined with flexible tools to operate on the data. We have chosen to develop the prototype environment on UNIX workstations, as UNIX provides innovative tools such as the X window system, which are hardware independent. C++ allows object oriented programming without losing the efficiency and portability of C. The X window system was used to implement the graphical user interface because it is a network transparent graphical environment. The prototype environment is based on the use of NFS for the distributed data access, on the Allegro toolkit for distributed data processing and on the InterViews toolkit for building the user interface under X. The NIH class library has been used to implement high level data structures and support mechanisms. Using those tools, we have built a file manager, an input-output manager with format handling, image overview components, a color table manager, and an image calculator. The distributed IMAC environment as well as the different elements will be described. 

High compression rates are needed because of storage economy and also because of multimedia a n d d a t a t r a n s m i s s i o n r e a s o n s . Each pair (original, comp/decomp) was analysed as usual, using exactly the same ROIs. Both subjective (parametric images comparison) and objective (global and regional ejection fractionr left ventricle volume curve, etc) analysis showed that there were no clinical s i g n i f i c a n t a r t i f a c t s or d i f f e r e n c e s introduced (all correlation coefficients were at least better than 0.998 and the maximum relative error found on left volume curve was 0.8%),

O. Nickel, G. Haberern, P. Bayer, K. Hahn Department of Nuclear Medicine, Johannes Gutenberg-University Mainz, Germany

Since PACS installations were not available commercially in nuclear medicine in the past, we implemented an own low-cost system on basis of an ethernet network and MSDOS-PCs. Methods: The PACS includes centralized archiving of images on optical disks, image display and processing of studies on MSDOS-PC's. 5 Acquisition systems of 2 manufacturers are integrated into the department networ k , whose images can be processed by the PC's. CT and MR images can be loaded from a hospital-wide network by file transfer and displayed on the PC's. Results:. Despite of relatively low investment costs the system is working very well: Image archiving has become more comfortable, all workstations have simultaneous access to the data. The processing of dynamic studies is done on the PC as fast or even faster than on older dedicated computer systems. Images from gamma cameras of different manufacturers can be displayed on one PC-workstation.

The PC on the physicians desktop can show now nuclear images together with all other patient informations from a database, processing of nuclear studies can be done retrospectively on a large database. The exchange of programs is done easily because MSDOS-PCs are available in almost all institutions.

~, L.Pareschi Nuclear Medicine S.Anna Hospital, Ferrara, Italy

A very large PACS system has been installed in s. images.

A gateway system which operates in Ethernet network connect a Sun IPX graphic workstation, Two Quadra 900 and the PhiliDs-AT&T PACS system. Using C compiler and UNIX ~t's possible ~o transfer the da~a coming from digitizer, data acquisition module and other modalities to Sun and Quadra. T h e productivity and diagnostic implications of the introduction of the two different PACS are investiggted.

In our experlence appears that the integration of whole diagnostic devioes currently used in an Imaging Department of a General Hospital connected w i t h a PACS system is a unique opportunity for improving the productivity and the diagnostic potential, but several limitations are present and the results obtained with the dedicated PACS system for Nuclear Medicine are at this time better.

OF NUCLEAR MEDICINE STUDIES. .~_~lomka, T.D. Cradduck, Victoria Hespital~ University of . estarn Ontario, London, Ontario, Canada.

A mini-PACS system consisting of two Ethernet local area networks (LAN) using the TCP/IP protocol and bridged by a serial line has been built to serve a two campus department of nuclear medicine. Five acquisition computers, three Unix workstations, six PC's and two X-tanninals serve one campus; the second campus is served by two acquisition computers, one Unix workstation and one PC. SPECT reconstructions are performed on the Unix workstations and all nuclear medicine studies are archived on re-writable optical disks. An image database package has been written which allows access to any of the acquisition station discs or the presently mounted optical disc from a Unix workstation for study selection and analysis. The data are archived in a non-lossy compressed format using the Lempel-Ziv algorithm; the compression and decompression be!ng performed transparently "on the fly" with compression as great as 6:1 being achieved in some cases. The optical discs have a raw capacity of 600Mbytes which is sufficient to accommodate approximately 6000 computer studies in our department. A cumulative index of all patient studies on the optical discs is maintained. Images can be transferred between campuses using a TCP/IP protocol over a tied phone line and, although this takes several minutes depending on the size of the study, it is preferable to the physician making a special trip to review the study. Experience to date has been favourable with a good user interface being a major contributor to acceptance of the system.

Human-Computer Interface is an important aspect of a 'medical software appfication since it determines the efficiency of information transfer between machine and users, beyond a friendly usage possibility. In Nuclear Medicine a significant part of that computer information must be evaluated subjectively by physicians which increases the importance of the HCI technique. Although being important as a final product, its development is quRe time comsuming apart being repetitive from application to application. The idea of this work is to automate the development process using a friendly tool.

A Unix based system running X Windows was used to develop a software package that interactively generates graphical interfaces.An object oriented approach was used to create simple dynamic entitties having independent logic and graphic characteristics. Dialog boxes, pulldown menus and scroll bars are examples of objects that could be defined and mapped into the interface. Simultaneously with the graphical description of these endties are also defined the functional characteristics of the objects such as its behavior and interaction with the user in the final application interface. The output of this tool is a C code file that should be included with the user application program to obtain the f'mal expected result (both the interface management and the application solution itself).

The Graphical Interface Code Generator is a standard package that eliminates the needs to produce the code that creates and manages graphical interfaces. It permits a quick design of new interfaces without debbuging problems. An object database could be created enabling the development of user visual standards. The registration of images from different modalities (in particular SPECT, MR and CT), and at different times, is an important clinical tool to relate function, the evolution of functional change, with anatomy. A clinical area of considerable interest is that of the localization of regions of abnormal function in children with epilepsy where nuclear medicine techniques permit the observation of both ictal and inter-ictal information. Four methods have been investigated: the use of external markers, the use of internal markers, matching of surfaces using the 'cap-hat' algorithm and matching using principal axes. For children, the use of external markers has been found to be inconvenient, and the definition of internal markers manually is time consuming, or, if automatic, unreliable. The use of principal axes gives excellent results with normal function and anatomy but can fail when large defects are present. The 'cap-hat' method must be carefully tailored to avoid local minima, and a multi-resolution technique has been devised starting with a very coarse image progressing to pixel level (fine) information to local minima which is still reasonably efficient. It has been necessary to devise strategies to accommodate defects in the (normally functional) image to eliminate bias in the matching process. Symmetry provides a powerful tool for the detection of such defects. A 'belt and braces' method is proposed combining the use of internal markers, principal axes (to establish a good starting point) and the multi-resolution 'cap-hat' to refine the registration. The technique has been applied to brain images of epileptic children at various ages undergoing HMPAO SPECT, MRI (and MRS), and in many cases CT. While the clinical value of this technique remains to be proven, trials have been performed on phantoms (<2mm) and patients to assess accuracy of registration. ,MicroDELTA-M~xDELTA ''~ system, with the host computer "~LicroVAX iI ''~ (10 ~ CPU, 450 Mb Winchester disk, 95 Mb streamer magtape) supports the data processing from 6 gamma cameras, located at 6 nuclear medicine departments in our Institute. The disadvantage of the system is that storing the data from 6 "MicroDELTA" computer workstations rapidly occupies the memory spaee on the host computer's hard disk. Tne purpose of the developed program ("DEC") is to enable tne controlled periodical storage of the "raw" imaging data through the local workstations at particular departments. Tne program was written in DCL (Digital Command Language) under the "VMS v. 4.5 '#-~ operating system, enabling the software data storage to be controlled by interactive users at local workstations. The program assum_es that users will DOCument the "raw" imaging data, which means to prepare the images for their transfer to the subdirectories inaccessible by the "unauthorized" local user. The preparation includes in~brmatics data, which are stored in the textual library and accessible by the key words. Periodically (monthly) the data are semiautomatically ( 

A b s o l u t e q u a n - We have developed a semi-automated, dynamic polar map technique to analyze regional washout in dynamic 99m-Tcteboroxime SPECT data from myocardial perfusion studies.

The software determines the location and orientation of the left ventricle (LV) and the ray trace search limits from the reconstructed stacked transverse images, using an interactive 3-D procedure. As in another program (CEqual) previously developed by our group, LV dimensions are calculated using heuristic algorithms. Unlike in CEqual, re-orientation of the Wansverse images into short axis slices (reslicing) is not needed prior to circumferential profile generation, with inherent preservation of image resolution. Circumferential profiles are calculated by taking the average count density over the myocardial wall width, which is estimated by edge detection on motion corrected, summed sequential frames.

Our clinical protocol calls for data to be acquired in rapid sequential mode (20 frames, 1 min each) on a 3-head camera (Prism, Picker), with continuous detector rotation, LEHR collimation, and reconstruction from 180 ° projections without attenuation correction. Perfusion polar maps are calculated for every frame in volume weighted and distance weighted formats. The derivate (second generation) washout polar maps are calculated as the normalized decrease of perfusion over adjacent frames [(early frame-late frame)/early frame]. Thus, 19 washout polar maps are generated, as well as an average washout map (average of all washout maps) and a total washout maps [(first frame-last frame)/first frame. Normal database generation capability is built into the program.

The time-activity curves produced by region of interest analysis of the polar maps represent the regional, temporal variation of tracer clearance, and may prove useful in the assessment of regional myocardial viability. This study was carried out to reconstruct a quantitative SPECT image by eliminating the counts of scattered photons from a planar image and also by using accurate attenuation correction.-For the scatter correction, we have developed a new method considering the local scatter fraction of the planar image. With this method, the count data are acquired at each pixel by using three windows: a main window centered at photopeak energy and two subwindows on both sides of the main window. The scattered photons included in the main window are estimated as a trapezoidal region shaped by the counts of the subwindows and the width of the main window. By subtracting the count of those photons from that acquired with the main window, the count of the primary photon can be estimated for each pixel, and then quantitative SPECT image was recoustructed by filtered backproject±on, followed by Chan attenuation correction using a map of attenuation coefficinets obtained by X-CT. The method was evaluated by a Monte Carlo simulationusing numerical phantoms.

The simulation tests showed good agreement between the activity distribution recostructed from unscattered photons and those reconstructed from corrected data by the proposed methods. Then we made phantom studies and preliminary clinical studies using a commercially available gammacamera (Toshiba GCA-9300A) equipped with special hardware. For the clinica study, brain perfusion imaging with Tc-99m HM-PAO was first applied.

The results showed that accurate quantitative measurement of the activity on brain perfusion imaging is possible without adding any data acquisition/processing time. 

MTF's and other associated frequency descriptors are used to describe a system's high contrast resolution capability and for the design of digital imaging filters. These metrics depend on the quality of LSF measurements. Several experimental variables affect LSF measurements but have been neither experimentally nor theoretically analyzed. The effects of line source misalignment (LSM), LSF truncation (LSFT) and inadequate background noise (BN) subtraction have been evaluated through simulation studies and analysis of experimental LSF data obtained from a high-resolution and low-energy general purpose collimator for both scatter and nonscatter conditions. Experimental LSF data were fitted to a sum of two (without scatter) and three (with scatter) gaussian curves using a nonlinear least squares routine yielding contributions of the geometric, septal penetration and scatter components.

The area under the MTF curve (MTFA) and equivalent bandpass (Ke) were used as figures-of-merit. The effects of LSM depend on profile width and are neg-'ligible for reasonably aligned sources (i.e., 0-5 ° misalignment) .

LSFT shows spurious increases in the MTFA and K e with increased truncation.

The BN distorts the MTF by causing oscillations in the scatter and penetration components.

The artifacts caused by BN and LSFT are interrelated." Visual diagnostics of the MTF curves aid in the interpretation of the quantitative data. Recommendations are made regarding optimization of LSF measurements. A new method for idenfication and localization of taskspecific changes of regional cerebral blood flow (rCBF) in activation studies of individual subjects with positron emission tomography (PET) is presented. Identification and quantitative evaluation of the task-specific rCBF changes was based on an exponential ranking algorithm that uses automatically drawn regions of interest (ROIs) at a 30% isocontour of the maximal pixel value in the subtraction images. The threshold rank of 0.98 was validated on subtraction images of a cylindrical phantom containing a background compartment with low 18F activity and six spheres of different size filled with a ten times higher 18F activity. Localization of the task-specific rCBF changes was performed by retrospective spatial alignment and integrated display of PET and highresolution magnetic resonance (MR) images. In-plane PET/MR alignment was accurate with an average residual misfit of 2.3 mm as determined by a further phantom study. The specific rCBF increases measured with [150]-butanol in six subjects undergoing unilateral manual exploration were identified accurately in the contralateral motor, premotor, and sensory cortex and with high quantitative and anatomical precision. Several questions arise in clinical practice when using such a method even for small organs. This work concerns some of them, using Monte Carlo simulations and real phantoms.

Firstly, the effect of the attenuating cylinder size was evaluated on hot sources phantoms immersed in three cylinders (@ = i0, 12,16 cm) . The right locations and relative activities of the sources were obtained using VSF acquired in the 12 cm-cylinder. Right quantitative activities were recovered by using a correcting factor equal to the diameters rate.

Secondly, the behaviour of the method was studied when a source was outside D (8 mm). Using a very few number of SV, the sources were correctly located in D but the source outside D was folded into the sampled volume. Using more SV, artefacts were generated everywhere in D.

In conclusion, such a method is very sensitive to both attenuating medium size and correct location of the D-sampled volume. If the consequences of the first mismatch are easily corrected, that is not the case for the second one. Thus the D-sampled volume must fit the whole attenuating medium, leading to very large computer memory requirements.

St.Miiller 1, M.Wenzell,J.Farahati ~, Th.Philipp2, B.Guth-Tougelidis t , Chr.Reinersl-Nuclear Medicine 1,Nephrology2,University Essen, FRG.

Captopril scintigraphy has recently been introduced for the detection of renovascular hypertension. Various parameters have been suggested to characterize the time-activity curves for aiding diagnosis. We investigated the suitability of severai parameters using discriminant analysis. We studied 79 angiographically and clinically normal kidneys, 10 kidneys with stenoses of 60-70%, and 13 kidneys with higher grade stenoses. After hydration of the patient, a baseline study was acquired over 30 min. using 25 MBq 1-123 Hippuran. 60 min. after administration of 25 mg Captopril, the second study was performed. Background corrected time activity curves were generated for further analysis. We calculated time and amplitude of the maximum, rise and washout times to 30%, 50%, and 70% of the maximum, the integrals from 0 to the maximum and from the maximum to the end, and the parameters of a non-linear fit of a gamma variate plus a constant background including a normalization constant.

The lowest Wilks-1 of 0.76 and the best reclassification was achieved with the peak, rise, and washout times. A subset thereof or a combination of peak, 50% rise and washout time, and integrals normalized to a peak height of 1 were not significally inferior.

Our analysis suggests that the characterization of the renogram curves by simple time and area parameters is superior to more sophisticated quantities derived from the fit parameters. Three dimensional (3D) image presentation is a modality which became recently available in nuclear medicine. To achieve reasonable processing times, powerful computers need to be employed. However, the presentation of a complete SPECT data set in one image promises a couple of advantages. We employed an Odyssey computer system (Picker Int.) for constructing three dimensional images. 3D SPECT data were analyzed for MIBI myocardium studies, haemangioma studies, brain examinations (HMPAO, IOMAZENIL), kidney imaging, lung studies and in a variety of bone scans. This paper will discuss the optimization of 313 image presentation and image processing such as the overlay of two 3D images in order to achieve precise spatial correlation. The value of 3D images for the different diagnostic procedures will be discussed in respect to the suspected finding. Results: 3D image presentation provides directly the recognition of hot spots in correlation to organ surfaces. Cold lesions can be easily detected if they reach the organ surface. Cold lesions within organs can only be visualized with more refined data processing. The extend of a lesion is clearly recognized in 3D images and the same holds for its relation to anatomic structures. And finally, 3D images may be helpful for presenting the data to referring surgeons. The aim of this study is to validate a method useful in clinical routine to express brain uptake per cm 3 in percent of the injected dose. For patient studies, four point sources of 5p.Ci(185Bq) Tc-99m are made by pipetting 5 pl of a I mCi/ml (37MBq/ml) solution on a hardly absorbing paper and dried. The point sources with a diameter of 3 mm and prepared in 10 rain are fixed on the orbito-meatal axis of each patient before performing the HMPAO SPECT study using a three detector system (Trionix Triad) .

After reorientating the slices parallel to the orbito-meatal axis, ROle are drawn over the sources and the total counts calculated. Knowing the pixel size Z, mean total source counts CS, activity of sources AS, injected dose ID, delay between soume and injected dose measurements T, a factor K is calculated.

K =AS. e-0.00193. T. 105/CS. ID .Z3

Multiplying each pixel of the SPECT slices by K, the image values are expressed in 103% of the injected dose percm 3 brain tissue. The use of calibrated Tc-99m sources as standard was validated on a Jaszczak phantom, the hollow spheres filled with 111Bq/ml , and the ratio measured on real activity calculated in function of point source activity~(37 to 222Bq), acquisition array (64 and 128) and acquisition time ( 10 to 30 rain). Overestimation of the activity was observed at low source activity and short acquisition time using a HR fan-beam collimator. Excluding these acquisitions the ratio was 1.00 SD 0.06 for the HR fan-beam and 1. To validate a new method for the analysis of gastric emptying involving linearization of the stomach, followed by the generation of eompressed images and tlme-loeation eurves, a phantom was designed and constructed. The basic design included options for: variable motion (of the phantom), variable attenuation and scatter, peristaltic movements of the stomach with variable amplitude and speed. The underlying assumption of the time-location curves was that transit times obtained using time-location curves more truly reflected the passage of food than classical timeactivity curves. It was therefore required to design a phantom that would allow verification of this assumption. For this verification, the testmeal was replaced by a semifluid eonsisting of tiny spheres in which only one sphere was labeled. 

Nuclear image blurring is the consequence of scatter and statistical fluctuations. Contrast enhancement is obtained by removing the irrelevant out-of-source signals and keeping unchanged the source information. Linear filtering methods are inadequate for such a purpose, since all the pixels are processed in the same way. Thus, a non-linear approach is required. For discriminating the two different populations, i.e. source and out-of-source pixels, usual planar photopeak data is insufficient to perform non-linear filtering. A third dimension is at least required and no other one than the energy axis seems to be useful. Thus, acquisition of all the energy information can be performed either by list-mode or frame-mode. The ROI method is used to define an o u t -o f -s o u r c e vector using the p h o t o p e a k image. A theoretical normalized source vector is also defined under some very straightforward physical considerations. The energy series are then projected u s i n g these two vectors, leading to a non-linear filtered image. Planar physical phantoms and clinical data using 99mTc tracer are processed by this simple method. Resulting images and contrast measurements are presented. Guidelines are suggested for t h e choice of the theoretical source vector when using various tracers. Assuming energy acquisition facilities are available, the algorithm is very easy to implement, requires a few computer time processing and is effective whatever the tracer used. We propose computerized methods for quantifying the reversibility in myocardium with the perfusion state of stress/rest difference and for scoring persistent defects in terms of extent-weighted severity.

At first, the reconstruction of transverse slices with 0.4 Nyquist frequency and order 5 Butterworth filter and extraction of maximal count per pixel in circumferential profiles for each sector was done just as cedars-Sinai method. Normalization of stress/rest polar maps in comparison with normal polar maps of each gender was done. For reversibility, the stress polar map was subtracted from the rest map in areas with counts less than the normal range. Positive-valued pixels were categorized into three grades and summed. For severity of persistent(rest) defect, the extentweighted scores were calculated using the assigned grades for each pixel and their number of pixels on the rest polar maps. This procedure was to be done automatically with this program. The reversibility and severity scores were produced for each of the coronary artery territories or any combination of these. Clinical utility in postinfarct or angina patients before and after PTCA (pre-PTCA reversibility scores were related with the changes(r=0.8)) and utility in postinfarct patients with severity scores of persistent defects (regional wall motion abnormalities reflected severity score) was validated.

We conclude that our computerized scoring algorhithm for reversibility and severity on the subtraction map was useful in the assessment of the myocardial ischemia and infarct and for quantitative display of these two. Time-activity curves over fixed regions used in the analysis of gastric emptying studies show a high variability and a low reprodncebility because of motion artefacts and convolution effects. To overcome these problems, a new method was developed iu which the stomach is "linearised" in all frames after correction for scatter, attenuation and motion. From the lincarised frames compressed ima{ges are obtained. The compressed images for each phase are corrected for activity outside the field of view, counts lost during motion correction and decay. Time-location curves are obtained by calculating for each timeslot the heigth (y-axis) that was passed by a certain percentage of the activity ingested. The difference in time between arrival at the stomach and departure from it using the 50 % time-location curve is the transit time. This transit time is a true transit time without any need for curve fitting or other indirect parameter extraction. Results using both old and new methods are given for normals and patients.

G. Cerulus and J.P. L~onard Clinique Parc Leopold, Brussels, Belgium

E f f e c t s on s p a t i a l r e s o l u t i o n in SPECT studies and influence of angular sampling, pixel size in a c q u i s i t i o n matrix , reconstruction matrix size, and variable f i l t r a t i o n were assessed in two modified backprojection (BP) methods: a distance-weighted BP technique (DW) and adual-window scatter correction procedure (SO) . Conventional BP reconstruction with attenuation coefficient p = 0.12cm'lwas performed for comparison. A rotating GE A¢4000 camera f i t t e d with a high resolution collimator was used in experiments with a 22 cm diameter cylindric phantom containing six cold spheres (diam&ters from i2.7 to 38.0 mm ) in uniform solution ofnmTc. Transaxial slices were reconstructed from planar data (12,8x128 or 64x64 matrix, 64 or 128 views) prefiltered by a 2-0 Harming f i l t e r with cutoff at a fraction of the Nyquist frequency. Results were compared in terms of image contrast and signal to noise (S/N) r a t i o . Contrast showed a dramatic improvement when the DW and SC methods were used, approaching the expected contrast value of 1.0 f o r the largest spheres (diam. > 2.5 cm). Contrast was only slightly better with a smaller pixel size, showed no change with different angular sampling and was s l i g h t l y decreased with sharper cutoff..S/N ratios exhibited a marked f a l l with the two modified BP methods, but more f i l t r a t i o n increased the S/N ratio.

I t was concluded that, taking into account the count density in these experiments, SPECT image contrast was markedly more increased by the use of the D W and SC modified backprojection methods than by moderate changes in f i l t r a t i o n , angular sampling or pixel size. procedure~as as follows: I/ The optimal windo~J (WIND,~,t) was determined for the radioactive pbanto~ (D~TA SPECTRUM) of the le~t ventricle (optimal window: previ~des maximal contrast at acceptable uniformity in short-axis slices; 4 perGusion defects of different size and pesitien w~re generated, and 35 8÷~.,(f) were tested: fs=O.4~O.5,0.6~O.7,0.8fn and n=I~2~3,4,5,6,7).

2/ Averaged Fourier spectrum (AFS) .from 36 different projections of the phantc~ was created.

3/ Mathematical relation between AFS and WIND~=~ (in Fourier space) ~as determined on the basis of i/ and 2/. 4/ a/ ~FSs were created for i0 stress SPECT patient studies from 180 projections and~ separately~ for I0 rest studies from 180 prejections; having AFSs for clinical projections, WINDo,~ for patient studies wes cLorived (on the basis of 3/). b/ The windo~ was further validated in comparisons of the diagnostic quality of the myocardial sections reconstructed ~ith different windoms.

Using proposed data acquisition protocol (the same number oG counts -&O~O00 as measured in LLAT projectior in each stress and rest study, HiRes, 180°~ 64 views, matrix 64x64)~ B÷=..(f), f==O.4f~, n!6 and f~=0.59., n!4 were selected as the windows optimal for clinical studies ~ith Tc-99m-MIBI at stress and rest, ~hereas B÷=..(f), f~=O.6f,~, n!4 bad been optimal for p h a n t~ studies.

A Pamplona 31080~ Navarra, SPAIN.

A prospective study on SPECT of the thyroid was conducted to evaluate acquisition and processing protocols in different thyroid diseases (TD).

Both planar thyroid scans and SPECT images were obtained in 19 patients (6 multinodular goiter (MG), 8 solitary thyroid nodules (SN), and 5 diffuse goiter (DG)) using Tc-99m. SPECT acquisitions parameters included LEAP and LEHR collimators, 64x64 and 128x128 matrix, 5" to 25" per projection, and 360~ orbit.

The following reconstruction filters were tested: Ramp (R), Shepp-Logan (SL) The following protocol is suggested: LEHR collimator, 64 images of 10"-15" each, a 128x128 matrix, and a 360e orbit; reconstruction with a Ramp filter and a COF between 0.4 and 0.6 N depending on the TD. 

Accuracy in in vivo quantitation of brain function with PET is often limited by the partial volume effect.

An observed difference in the apparent radiotracer concentration may thus be solely due to a different degree of atrophy.

The study describes a correction method which permits estimation of the actual gray matter radiotracer concentration on a pixel-by-pixel base.

An algorithm was developed which relates the regional fraction of gray matter, as determined by MRI, to partial volume effects. In computer simulations and phantom studies on a high and low resolution PET scanner, the GM-PET-algorithm permitted a 100% recovery of the actual tracer concentration in neocortical gray matter and hippocampus.

Errors in the segmentation of gray matter and in registration of PET-and MRI-images encountered in routine image processing resulted in loss than 15% inaccuracy in the GM-PET image.

GM-PET was applied in a human subject with temporal lobe epilepsy revealing an increase in gray matter that was undetected in the PET images before Correction.

GM-PET permits accurate determination of the actual radiotracer concentration in human brain gray matter in vivo.

The method differentiates whether a change in the apparent radiotracer concentration reflects solely an alteration in gray matter volume or rather a change in radiotracer concentration per unit volume of gray matter.

Future applications include studies of aging and degenerative brain diseases when partial volume effects are prominent. 1sO-Butanol seems to be superior over H21~O for. the assessment of cerebral blood flow (CBF) because of its better extraction. This paper presents a method and and error analysis for the quantitation of CBF with ~O-Butanol. Using a PET camera PC4096-15WB and an automatic blood measuring system cerebral tissue and arterial blood data were recorded in 1 sec intervals for 3 min after intravenous injection of 1500 MBq 1nO-Butanol. From the dynamic PET data one single frame of 40 sec containing all 15 image planes and a time-activity curve related to a representative brain plane were derived. Based on these data CBF was quantified in two steps: Using the common single-compartment model, time-activity curves of tissue and blood were fitted to estimate the partition coefficent p, the time delay ~ t between these curves and a constant DC used for the dispersion correction of the blood curve. With these data a look-up table was calculated to relate the pixels of the 40 sec 1nO-Butanol-image to regional CBF values. Furthermore, the influence of different model parameters on the calculated CBF data was examined. Fitted global CBF and p ranged from 45 to 70 ml/(min 100g) and from 0.55 to 0.8, .respectively. Regional CBF ranged up to 250 ml/(min 100g), The quality of the curve fit was primarily sensitive to the dispersion correction. Variations in fitted CBF und p values were directly related to calibration errors between PET and blood measuring system. An underestimation of p (e.g. 0.5 instead of 0.77) resulted in considerably higher regional CBF data. The described method of quantifying CBF is time-efficient. The combination of a fitting procedure for global model parameters and a look- up- A previous investigation has shown that selectively labeled glucose, [l-llc] -D-glucose after correction for the loss of [IIc]c02, measures the average rate of glucose oxidation for the whole brain rather than the rate of total glucose consumption. To examine if this hypothesis is valid also for the regional glucose utilization, five healthy volunteers were investigated with [l-llc We found that global CMRglc falls 5-10 % below global CMRO2.In a scatter plot of rCMRglc versus rCMRO 2 the values are grouped around a straight line with slope less than i. Accordingly, the rCMRglcmmaps have somewhat less contrast than the rCMRO2-maps. This deviation may be explained by one or more of the following reasons. This study was designed to determine the optimal time frame and analytical procedure for the measurement of regional cerebral glucose utilization (rCMRglc) in human subjects with PET and [18F]FDG. We established a time interval during which effects of product loss remain insignificant and a lower time limit consistent with acceptable errors due to incomplete equilibration of tissue pool and errors due to inaccuracies in the kinetic model and rate constants. In recent years various models have been discussed for a quantitative description of amino acid uptake and metabolism in brain tissue. For natural amino acids protein incorporation is the dominant pathway.

Since this pathway represents a metabolic sink, this fraction can be described quantitatively by the "Gjedde-Patlack" analysis. This approach has been validated, even for pathological conditions, such as in brain tumors, and for several amino acigs. However, this approach does not allow a quantitative interpretation of individual metabolic pathways. It summarizes the kinetic behavior of the fraction, which, within the observed time window, enters a metabolic sink.

Difficulties arise upon more detailed analysis. Our calculation approaches of individual kinetic transfer constants have shown that a standard three compartment model as e.g. used for the modelling of fluoro-deoxyglucose utilization, can not sufficiently describe the behavior of amino acids. Simulation studies with the modelling tool "THINK" running on a Macintosh computer and models calculated by a program developed by ourselves on the basis of "MATLAB", on the SUN computer, have both shown that the influx component for amino acids is dominating the response function to such an extent that an additional comparmaent had to be introduced into the model for description of amino acid uptake. An unambiguous biochemical interpretation of this compartment is not offered up to now. It may either be called an activated state of the amino acid after the membrane passage, or may be a trigger function on the transport mechanism itself. Although our model fits the measured values excellently, more biochemical investigations on the uptake mechanism are necessary. 

With the development of dynamic quantitative clinical studies, particularly in PET, the practice of compartmental modelling is widely spreading. However the numerical identification of the parameters is still questionable. Estimation quality depends on the reliability of the optimization method, which is the critical part of the solving process. A simulation study was carried out to compare the practical performance of 5 currently available algorithms : Marquardt, Quasi-Newton, Powell (issued from Harwell library), Simplex, and the one used by the program SAAM. It was designed to study the hepatic receptor-binding of GalactosyI-Albumin. One linear and 3 saturation models were generated with respectively 3, 3, 4 and 5 compartments, and 2 experimental time-activity curves. Three signal-to-noise ratios were ~ considered, leading to a set of 180 noisy curves for each configuration. An adaptive Monte-Carlo method searched parameter initial values, satisfying successively narrow and large a priori defined bounds. These values were then provided to the 5 minimization algorithms. Simulation results obtained on SUN SPARC workstation enabled the comparison of the 5 algorithms in terms of : -quality of fitting (values of the parameters, correlation of the residuals, sensitivity and identifiability of the parameters), -execution time. For instance, using the first model, which is structurally identifiable, all the methods are efficient, except Powell whose accuracy decreases as soon as noise and initial values uncertainty increase. Therefore, an estimation strategy is suggested according to the chosen model and the related experimental conditions. 

The accurate determination of LGBF values utilizing the Kety-Schmidt one compartment model for freely diffusible tracers requires the knowledge of the true arterial input function in the tissue. Because measured input functions usually are significantly delayed with respect to the true influx a determination of the time shift is called for. Our aim was the derivation of an algorithm which allows for a fast, reliable and sensitive way of determining this delay. We present a transformation of the model equation which achieves this goal: In our representation the LCBF and the corresponding distribution volume are simply given as y-intercept and x-intercept of a straight line y(x)=a+bx. We demonstrate that one observes strong deviations from the expected linear behaviour when the measured input function is delayed with respect to the true one. This enables an unambiguos determination of the delay by means of a fast one-dimensional least squares minimization. The described procedure has been in use at our institute for some months and is well suited for clinical applications where a stable method and the option for a quick check of the correct performance of the system is needed.

Frank Deeoninck, Vrije Universiteit Bmssel, Brussels, Belgium.

A MODEL FOR DESCRIBING AND ANALYSING THE IMAGE UNDERSTANDING PROCESS. This paper will propose a model for describing and analysing the exploration process by which, given a particular task, an observer extracts all relevant information out of an image. It is based on the experimental finding that an image professional (such as a photographer, an art critic or a radiologist) extracts more and more rapidly objective information, out of an image than an untrained observer, and that one can therefore learn how to look at images with the aim of extracting information. Learning implies a possible methodology, which in turn implies a model of the elements which influence the understanding/learning process. In medical imaging, the training seems mostly based on experience, which is often equivalent to trial and error. This may be a proven method with good results, but in a specific medical area, one may try to avoid errors, as well as speed up the training period by means of an optimized methodology. This is what we hope to achieve in following this proposed model. The model is based on a sequential flow of information between conceptual modules, in which the flow induces information loss. Training should aim at reducing this information loss. The model is also based on the assumption that maximal information is extracted by looking to discover (exploration), rather than by looking to recognize (pattern matching). It consists of 6 modules and associated information flow: from transducer for pictorial presentation to perception/observation, with influences of technical and perceptual nature; from perception/observation to representation/classification with influences of conceptual nature; from representation/classification to integration of non-pictorial information with influences of a-priori knowledge; from integration of non-pictorial information to personal interpretation with cultural and psychological influences; and from personal interpretation to cognition with influences of the intellectual capacity of the observer. The different modules and the interactions between the modules will be illustrated by means of pictorial examples, and a possible methodology for training will be deduced. Material and methods: The biokinetics of Tc-99m-DMSA was studied in four infants, (between 2 weeks and 6.5 m o n t h s old), undergoing routine scintigraphy. Anterior and posterior gamma camera images were acquired at 20 rain, 1, 2, 4, 6, 9 and 24 h p.i. Urine was collected during 24 hours. The activity in various organs was quantified using conjugate counting. Results: The maximal kidney uptake (8-9 h p.i.), the initial uptake in the liver and the activity excreted via urine during 24 hours are shown below (all corrected for physical decay). % of inj. acfivityll 2 weeks I 1.5 month 3 months 16. was introduced as an appropriate PET-tracer for cerebral blood flow (CBF). Although it is used in various laboratories, no data about the radiation dose to the patient have been published. Therefore, we extended the diagnostic CBF-studies to determine the radiation dose to the patient. Studies of neuronal activation were performed as sequences of up to 6 PET-scans while applying various stimuli. For each scan about 1500 MBq 1sO-Butanol were intravenously injected. All measurements were done using a whole body PET-camera PC4096-15WB. For each cBFstudy PET data were recorded for 3 min. In each patient one cerebral scan was extended to 14 rain to monitor the tracer activity in the brain for 7 half-lives. Directly after the last scan the patient's bed was moved, and measurements over different organs, e.g. the liver, were performed for another 10rain. Based on the measurements in 8 patients time-activity curves were obtained, from which the accumulated activity and the radiation dose were calculated. The liver received the highest radiation dose of about 2.5 mGy per 1500 MBq of injected t50-Butanol.

The dose to the kidneys was 1.3 mGy, to the stomach 1 mGy, to the brain 0.16 mGy and to the total body 0.18 mGy. These data do differ from the dose caused by tnO-water, which is commonly applied for PET-CBF-studies. Whereas the latter tracer has similar doses to all organs of about 3 mGy for a whole study with 6 scans, a liver dose of about 15 mGy must be considered when using t~O-Butanol. The human T-cell acute lymphoblastic leukemia (ALL) cell line CEM was established as a subcutaneous growing tumor in the CD1 nude mice and served as tumor xenograft model for leukemia treatment with antibody-radioimmunoconjugates. The aim was to evaluate by immunoscintigraphy the in 'vivo binding of the cytotoxic CD7 T-cell antibody TH 69, which demonstrates already non radiolabeled significant tumor cytotoxity. The antibody was labeled with 1-131 via the Jodogen method using 74 MBq of 1-131. After labeling the 1-131 bound antibody was seperated from free iodine by submitting the antibody solution to a 10 ml sephadex G-10 column. Those fractions which contained the labeled antibody were then combined for latter application. Normally 6.5 MBq J-131 were injected i.v. into the tumor bearing mice. Scans were obtained until day 10 p.i. using a pinhole collimator. Organ preparation and activity measurement was performed on day 11. High specific activities in the lungs (9.30%/g) and the iliacal lymphnodes (10.97%/g) were found. Histological examination ruled out tumor metastasis in these organs. So this only could be caused from complement induced tumor lysis and accumulation of immunoconjugates in the local lymptmodes and in the lungs. Nevertheless the tumor could easily be localized by gamma camei'a imaging and although unspecific transport of immunoconjugates a specific activity of 7.5%/g could be detected in the tumor mass. In conclusion non radiolabeled TH-69 is very effective in the therapy of T-cell lymphomas and in refractory cases 1-131 labeled TH-69 will improve the success of tumor therapy. It has been shown !hat 1231-Granuloszint (ab47) is a useful tool to detect hidden infections with SPET. However, the unsatisfactory supply with this nuclide should be eliminated by developing the 99mTc labelled ab47 ~mTc-Granuloszint). The now developed prototype of a Tc-kit (single step labelling) consists of a derivative ab47, namely a tetraaza-ligand coupled with an amide bond to the free amines of ab47 and tin tartrate. After the addition of pertechnetate and a simple filtration process to eliminate colloidal Tc by-products, the 99mTc-Granuloszint is ready for injection. The comparison of scintigrams obtained with ab47 labelled with the two mentioned nuclides did not show significant differences, but a clear difference in the elimination from blood was observed. An interesting result was obtained by analysing the excreted urine. Paper chromatography showed about 70% of the excreted activity at the same P~ value as the 9emTc-tetraaza-complex, the rest being mainly pertechnetate and small amounts of unidentified by-products. In the case of 1231 the excreted activity was found at the Rf value of iodide. The radiation dose to all organs including the liver is reduced in the case of 99~Tc-Granuloszint, which is mainly due to the shorter half-life of 99rnTc. Successful imaging of neuroreceptors in vivo depends on the ability of the tracer to cross the blood-brain-barrier (BBB), to bind with high affinity to the receptor, and to exhibit low nonspecific binding. In vitro assays have shown doxepin (DOX) to have a higher affinity to the histamine H1 receptors than pyrilamine (PYR) (Kd DOX = 0.02 nM; Kd PYR = 1.0 nM). C-11 DOX and C-11 PYR were prepared from their normethyl precursors by N-rnethylation using C-11 iodomethane. Male CD-1 mice, weighing 20-30 g, were injected intravenously with 0.2 ml (200-300 ~Ci) of either C-11 DOX or C-11 PYR. At different times after injection, the regional radioactivity distribution in the brain, as well as the uptake in various other organs was determined.

C-11 DOX crossed the BBB to a considerably greater degree than C-11 PYR : mean % injected dose/total brain at 30 min = 1.8 vs. 0.6 for C-11 DOX and C-11 PYR, respectively. Whereas C-11 P~(R concentrations in different brain regions at 30 min after injection were proportional to the density of H1 receptors in these areas, the C-11 DOX distribution failed to reflect H1 receptor site densities. Highest C-11 DOX concentrations were found in cortical areas, whereas highest C-11 PYR concentrations occurred in the hypothalamus and hippocampus. Preinjection of unlabeled DOX (up to 10 mg/kg) did not inhibit C-11 DOX binding in any of the regions. Biodistribution of the two compounds showed higher retention of DOX than PYR in various organs, especially in the lungs. This was most likely due to the higher lipophilicity of DOX than PYRo

These data indicate that C-11 PYR, is likely to be a better tracer than C-11 DOX for in vivo imaging of histamine H.'I receptors.

Gustavo Torres, Luis Bem~i, Montserrat Estorch, C/mdido Juarez, David Duncker, Ignasi Carri6. Hospital de Sant Pau, Barcelona, Spain.

Immunoscintigraphy requires administration of radiolabelled monoclonal antibodies. However, HAMAs could produce immunological effects and alter the outcome of immunoscintigraphy. We performed 99mTc-labelled antigranulocyte antibody (BW 250/ 183, Behringwerke) immunoscintigraphic studies, to assess bone marrow invasion in four cancer patients (pts) who had been previously exposed to radiolabelled monoclonal antibodies (2 pts to BW 250/183 and 2 pts to 99mTc-antiCEA BW 431/26). HAMA levels were determined from sera samples obtained 6-24 hours after immunoscintigraphy. Sera samples of I0 pts who did not have immunization with mice antibodies served as control serum. HAMAs were determined by means of a double enzyme-linked immunosorbent assay in 3 dilutions. HAMAs were rated positive if the HAMA factor was twice as high as the mean of control serums at least in one dilution. HAMA occurrence was demonstrated in all pts. When immunoscintigraphy was performed, all pts showed abnormal biodistribution of the antibody with increased hepatic uptake.

Pt The feasibility of absolute estimates of rCBF with ECD was evaluated by measuring the regional brain net clearances (Ki, ml/min/g) of this tracer. Then the Ki values of ECD were compared with those of HMPAO. In this study a grotip of five neurological patients (2 affected by consolidated stroke and 3 by dementia) was studied with the two tracers injected 7 days apart. Arterial blood gas analysis was performed prior to the intravenous injection of the tracer. The brain activity concentrations were measured using SPECT at 40 rain after injection. The arterial input (AI, t~Ci*min/ml) of each tracer was measured with arterial sampling and rapid octanol extraction. During the first 3 min after injection, the ratio of diffusible to total circulating radioactivity resulted significantly higher (up to 25%) for ECD than HMPAO. The AI values were referred to the injected dose and resulted 0.029 __. 0.009 % and 0.024 -t-0.05 % (mean _ SD), respectively for HMPAO and ECD: these values were significantly different (P<0.001). These results taken together suggest that ECD may have a larger distribution space outside the brain than HMPAO. The Ki values of the two tracers were strongly correlated (r=0.78, DF=72). The difference per cent of Ki between HMPAO and ECD was calculated on a patient by patient basis and resulted 0.66 + 6.62 % (mean +__ sere).

In conclusion, circulating and brain kinetics of HMPAO and ECD have quantitatively similar effects in defining AI and brain retained fraction. However our data cannot be used to estimate the relative weights of extraction limitation, backflow and retention. Our results suggest that ECD has the same quantitative potential of HMPAO in measuring rCBF. The major advantage of ECD is its rapid clearance from vascular and extravascular spaces outside the brain which results in a better bain-background contrast and in a reduced dosimetry to the patients The Study was prospec%ively performed to evaluate.:l, the mechanism of TI-201 uptake in malignant tumors (MT.); 2. the utility of lesion to n o r~l ratios iL~N) for differentianting MT. vs. benign lesions (BL.).

Forty-two pts.with known or suspected MT. had 53 thallium scans (TS),each inmaediately followed by a three phase bone scan (TPBS).Lesions in areas of normally increased blood pool (BP) and in the brain were excluded from our study. The diagnosis was verified by biopsy (38) or follow up studies (15). The analysed lesion was malignant in 35 cases and benign in 18.

The TI-201 LIN ranged from 1.01 to 8.12 in MT. and from 0.73 to 3.77 in BLs.However, in 12153 cakes the TI-201 L/N was higher than LIN in BE and BP images and all lesions were malignant. In 6/53 cases with high TI-201 L/N the BF and BP L/N was higher than TI-201 L/N and all lesions were benign. The TI-201 L/N did not strongly correlate with BF and delayed LIN in MT. (r=0.50 and r=0.53 respectively, n=35) but a better correlation was found between n=35) .

The mechanism of TI-201 uptake in MT.is not dependent on BF alone and other factors (metabolic rate, cellularity, etc.) influence the magnitude of TI-201 uptake.The TS specificity for MT significantly increased when TI-201 LIN were Interpreted together with BF and BP L/N. Radiation protection on a radiotherapy ward with patients receiving large doses of radioiodine should consider all possible sources of contamination and incorporation. The risk has been minimized in our institution by ~i rigid scheme: Almost consequent protection by baryt enhanced wails, almost no contact to patients within the first 3 days, and for the rest of the hospitalisation period only short contact with as much distance as possible. The purpose of this study is to calculate and to measure the remaining risk of air contamination (1) and to determine the incorporation by staff (2).

(1) For the theoretical calculation the following assumption has to be made: On average 3.7 GBq iodine-131 are given to each patient. 33 patients are treated per year. 0.05 % of the activity is exhaled by each patient during the first three days. The patient room volume is 100 m**3, with an air circulation of 5 x/hour: The resulting average air contamination then is 15 Bq/m**3. By measurements of dust filters no iodine-131 activity above the detection limit is found. The activity measured in charcoal filters results in 2.9 Bq/m**3. During these days the total application of iodine-131 is 13.8 GBq.

(2) All measurements of the thyroid gamma detector are performed with an acquisition time of ten minutes. With small amounts of iodine-131 the lower limit of detection is found to be 0.6 Bq/1 ml thyroid tissue by using a thyroid phantom. In all measured members of our staff the values are below this limit.

In conclusion first the results of the measurements are similar to the calculated data. Second the standard air conditioning filters have no capacity to trap radioiodine. Specialized, expensive filters (charcoal, silver nitrate) should be chosen for this purpose. Third room air contamination on radiotherapy wards with patients treated with radioiodine is low and exposes nurses and doctors to little risk. The rigid scheme of handling radioiodine has proven to be worth the effort. 

In recent experiments in rats, our autoradiographic studies of frozen testes sections have demonstrated a considerable degree of concentration of radioactive In-ll4m in spermatids and their derived sperm which persisted through the cpididymal transport and maturation. Furthermore, Rao ct.al., J. Nucl. Med. (1983) have shown the Auger cmitting radionuclides (used in Nuclear Medicine) arc more radiotoxic to the spermatogenic system than beta emitters. Therefore it is important to examine radiopharmaceuticals in the context, of testicular localization and spermatogcnic cell radiation damage even for short-livc radionuclides.

Wc have measured the testicular and cpididymal uptake of 201Tl, in rats at 3h and 24h time points. The uptake in % of injected dose at 3h being 0.01, 0.6, 0.01 and 0.004 respectively in testes and 0.09, 0.29, 0.005 and Q.005 in the epididymis.

201T1 showed notable uptake (0.6%) of the injected dose at 3 hours increasing to 1.1% at 24 hours. If this data wcrc used for the radiation dose calculations to the testes in the human, 0.6% will give a self dose of 3.8 Rads from 2mCi injected 20IT1 and will be 7 Rads for 1.1% uptake.

Experiments on other radioactive tracers are in progress. These experiments are being extended to autoradiographic investigations of the radionuclide distribution within the interstitial and spermatogenic cells. Practical information on radiation protectiou measures for general personnel is lacking. Especially the risk for internal eontamination and the build up of background radiation levels are hard to predict. We devised practical suidelines, and tested them prospectively during two clinical trials where 125-I (1 -2.5 MBq per patient) was used. The guidelines were modelled after those for the nursing of patients contaminated with pathogens resistant to multiple antlbioties. Only the nurses were instructed. A quality control prosram was set up, resulting in data on the oeeurenee of contaminations and the recovery of the radioiiodine. Over a period of several months, involving 3 wards and more than 100 personnel and 60 patients, the measured recovery (excluding estimates of unmeasured, but known losses) never fell below 90%. Currently our cumulative experience totals 370 patients on 5 wards, 3 intensive eare units and more than 200 personnel. The highest concentrations found in waste never exceeded 750 kBq/l. No contamination exceeded 40 kBq and all contaminations above the detection treshold of 1 Bq/em2 were visible. No build-up of background levels occurred. No detectable thyroid uptake was found in the 20 persons most exposed. As we consider the waste routing of 125I in this ease representative for most isotopes, it is concluded that radioactive excreta and other waste can be safely handled by general nurses using our guidelines. The International Commission on Radiological Protection (ICRP) is the most important commission in radiation protection worldwide. It publishes recommendations, which have great influence on the national legislations. Therefore the revision of the famous publication No.26 was expected with great interest. In 1991 it now has been issued as publication No.60. This paper reports about the main changes, which in brief are the following: The risk coefficients have been magnified by a factor of 4 according to new findings in the biological effects of ionizing radiation. A new classification for the tissue weighting factors has been introduced and the radiation weighting factors have been altered. One of the most important changes is the reduction of the dose limits: The "public" limit is now 1 mSv per year and the "occupational" limit is 20 mSv per year, averaged over defined periods of 5 years. Unfortunately and this gives rise to criticism the dose limits have not been defined depending on age. The ICRP Publication No.60 will be of considerable effect on all future national and international regulations and therefore is of greatest interest for everyone who is involved in radiation protection. The investigation of bone-seeking 9gents is one of the firsts and constant works in Nuclear Medicine, with three stages: I, Experimental: studies about metabolism Ca-P. II, Scintlgraphy: studies of tumoral disease with nuclldes non adequate. III, Phosphate complexes: that has made bone scintigraphy in an excellent procedure to study skeletal pathology. Thank its contributions, the bone scan is necessary in daily clinic, and in addition, has helped to the development of radlopharmacological and instrumentation in Nuclear Medicine. MATERIAL AND METHODS. Based in our experience (2700 bone sc~]/year), we have analyzed the utility of bone scan, clinlcal demand, frequency, positivity and sensitivitv,in various pathol.ogical groups: Metastasis (300 pa%lents), primary mal±gnant tumours (80 pts.), osteomyelitis (50 pts.), ~ethological hip (i00 pts.) and Paget's disease (50 p%s.). In all groups, we have analyzed the differents techniques: bone scan, WBBS, vascular, quantification, and the indications. RESULTS: Metastasis: early diagnosis, 30-50% lesions detected before radiology. Primary malignant tumours, index positivity high (96-100%), the bone scan are useful to: local extension, detection of metastasis, and to assess the response to therapy. Osteomyelitis: early diagnosis before radiological visualization. Pathological hip: diagnosis of synovitis, and avascufar necrosis femoral head; detection of prostheses complications: loosening and infection. Paget's: the scintigraphic pattern is characterist, and of utility in diagnosis extension grade of act±vity and treatment evaluat{on.

' ' CONCLUSIONS: i. The bone scan is a exploration with high sensitivity, and high index of positivity (80-100%) in earlv dlagnosis of many pathological.process of bone, 2. The bone scan must be complement wlth the others scintiqraphics procedures, to increase the specificity. 3. The bone scan is a exploration with a high cllnical request, and one of the more frequents in Nuclear Mediclne Services. Viable hone graft is the key to stable fixation to acet~bulum ,:~hich is essential pre-requ~site for successful total hlp a,.throplasty(THA) in patients wlth acetabular d:KsplBsla(AD). The fate of bone graft used for acetehular augmentation ~n THA was assessed hy semiqu@ntitat~ve SPECT ai~d pinhole hone sein~igraphy.

Twenty AD patients ( The Harris hip score improved slgnificantly after THA(82.6 Vs. 91.3). Roentgenography sho~ed all with good bone Union except one with resorption > 50%. The ratios of BG/IC, BG~,~ and BG/CA were slgnlficant decrease beyond one year after T HA by the signed rank test(P< 0.003, < 0.0006 and < 0.0001 respectively). One recelved revised THA due to acetabular loosening and bone ~raft incorporated with good bony support was noted. The ratios vide supra revealed no de£iaite chanse hut slgnlficant increased in the one with resorption > 50%.

In concluslon, semlquantltatlve SPECT and pinhote bone sc[ntigraphy may offer dynamic physiologic monitorins of the incorporation process of the nonvacularized bone graft and provide biological viability ~nformation. The aim of the study was evaluation of scintigraphy with albumin nanocolloid labelled with Tc 99m in differential diagnosis of aseptic and inflammatory complications after total hip replacement surgery. From 1988 to 1991 sixty one hip joints were evaluated after arthroplasty in 46 patients aged 48-79 years. Examination wins performed on 40 "painful hips" and 21 hips without pain in patients operated bilaterally. Inflamatory process was confirmed bacteriologically in 17 cases, while the rest was diagnosed as a mechanical loosening or a periarticular ossification. Gammacamera pictures were made in 2 hours after intravenous injection of nanocofloid. Obtained pictures were estimated according to 4 steps picture intensity scale, established by comparison of tracer accumulation around the hip prosthesis and in an iliac ala. For precise analysis of isotope location in the area of interest "contourgraphic technique" was applied by X-ray picture overlaping on the nanocolloid gammagram. Scintigraphic results of 30 patients were verified by subsequent surgery and the rest of results -by clinical, radiological and bacteriological exami nation. Calculated on this basis quality control parameters were equal: sensitivity 85%, specificity -88%, accuracy -87%, positive result predictive value -77%

and negative result predictive value -92%. Above results reveal usefulness of presented method in the differential diagnosis of "the painful hip" after total replacement surgery. The aim of the work is to present our experience in scintigraph~c investigation of osseous hemangioma~ Hemangiomas are rare bone lesions,but sometimes they cause c l i n i c a l manifestations and diagnostic problems° Radiographic ~pearance may be c h a r a c t e r i s t i c , b u t in many cases the diagnosis shouldbe confirmed by computed tomography or invasive procedures,as angiography,biopsy or operative exploration, We applied 3-phase bone scintigraphy(BS)CTc-99m pyrephosphate) followed by dynamic and s t a t i c scanning of blood pools with Tc-99m labeled autologous red blood cells(RBC) in the investigation of suspect bone ].esions i n 3 patients(P).The lesions were located in:P 1-preximal femur(later approved by operative and histopathology f i n d i n g s ) ; P 2-in parietal bone(approved by computed tomography); P 3-in lumbar vertebra;BS showed increased perfusion only in the lesion of P I and higher a c t i v i t y in II phase ~n a l l others,including in another,previously unknown lesion in P 1.The late bone scans visualized intense uptake of a c t i v i t y in the femur lesion and 16ss intense uptake in a l l others.Scanning with Tc-RBC revealed the same findings as those of BS in i t s dynamic phase The scans obtained On 35-45min .after the i n j e c t i o n , v i s u alised increased blood pool in the hemangiomas.

We conclude that the application of 3-phase bone scintigraphy combined with Tc-RBC scintigraphy may contribute to a more accurate diagnosis of osseous hemangiomas. 

Radionuclide techniques are more sensitive than roentgenograms in detecting skeletal abnormalities, which may also be true for some soft-tissue diseases that produce extra-skeletal ossification. Serial three phase bone scans were applied to 25 paraplegics (22 men and 3 women, mean age: 34 ~ 12.5) under the risk of myositis ossificans (MO) once every three weeks for a period of 3 months, beginning with the onset of paraplegia. Simultaneous serum alkaline phosphatase (SALP), serum calcium (SC) and urine calcium (UC) levels were measured and radiographic correlations were made. If an evidence of MO was determined on any of the tests, the frequency of the tests were increased to once every two weeks. The patients were followed for a mean period of 14 weeks (range: 12-17 weeks) after the onset of paraplegia. Four patients were diagnosed by three-phase bone scans before any development of a radiographically detectable abnormality. The earliest radiographic detection of MO in these patients occurred after 3 weeks of radionuclide positivity. Three patients had both scintigraphic and radiographic evidence of MO at the time of detection and the rest did not develop MO within the follow-up period. SALP levels were found to be elevated in 3 of the 7 patients a week after the scintigraphic detection of MO . Four patients with high SALP levels did not show any evidence of MO either scintigraphically or radiographically. The SC and UC levels remained in the normal range regardless of high SALP levels or the presence of MO. We concluded that, three-phase Tc-99m MDP bone scintigraphy is a valuable diagnostic tool in the early diagnosis of MO which is important in terms of proflactic interventions. Stress fractures could happen on healthy bones in case of excessive mechanical stimulation, and particularly during sport practice. The purpose of this study was to evaluate the interest of bone scintigraphy in patients whose Physician's suspected a stress fracture and ask us to confn'm or to infirm their diagnosis. Spontaneous fractures occuring on fragilized bones (ost6oporosis,tumours) were excluded from this study.17 young adults(mean age=28 years, 11 male and 6 females) were explored. They received an injection of 15 mCi (555 MEq) of Tc99m-m6thyldne diphosphonate. The vascular phase was studied on anterior incidence, late images(3 hours post-injection) were performed in anterior and posterior incidences, and sometimes with profile when necessary for a better visualization. Twelve stress fractures were confirmed later by clinical evolution and delayed appearance of radiological signs, such as localised cortical thickening~ Mean age of these patients was 23 years. Localisations found were seven tibias, four fibulas and one metatarsis. Three patients had only a periostitis(evidenced on profile incidence). One case with an aggravation of clinical symptomas, was histologically identified as a bone metastasis of a lung cancer. The last case correspond to an osteonecrosis of the cuboid (higher signal on T2weighted MR image). This study did not involve any false negative, but five false positives of whom three were corrected by profile incidence(periostitis). It is one of the weaknesses of this exploration, related to its high sensitivity. The more difficult diagnosis to elimine remain ostdonecrosis or algoneurodystrophy. Tumours happen in different context and are more easy to eliminate. In conclusion, bone scintigraphy, because of its high sensitivity, may have an important contribution in early diagnosis of stress fracture and help for elimination of others diagnosis. 

The aim of this present study was to determine the value of Tc-labelled dexamethasone phosphate (Tc-99m DM~P) in the evaluation of osteomyelitis compared to Tc-99m MDP bone scintigraphy. 15 patients (age 11-58, mean 38) with a presumed diagnosis of osteomyelitis in the extremities were studied. Imagingwas done three hours following the injection of Tc-99m DMP. In addition to visual interpretation, quantitative analysis was carried out in order to establish ratios. Individual regions of Interest were drawn over the area suspected to have osteomyelitis. These areas were compared to the contralateral side, and lesion to nonlesion ratios were calculated. The mean ratio calculated in patients found to have osteomyelitis was 2.166 + 0.609 which was si2w/ficantly higher from patients free ofosteomyelitis [(1.299 + 0.222)(p < 0,05)]. Bone scintigraphy was performed at three h o u r s following the Injection of .m MDP. Although bone scintigraphy showed increased uptake in regions of osteomyelitis, it overestimated the total area, whereas Tc-99m DMP scIntigraphy more pre-. cisely showed the area Involved. Therefore we conclude that Tc-99m DMP scintigraphy is a sensitive indicator of osteomyelitis, and the results suggest that it shows the extent of infection more accurately in comparison to Tc-99m MDP bone scintigraphy.

F.Giammarile, C.Masciocchi, A. Barile, F. Iorio ® and I.Baschieri University of L'Aquila -Italy ® University of Rome I -Italy

Twelve athletes presentig unexplained pain and normal radiological findings were studied. MRI was performed with two magnet systems: a 0.5 T superconductive and a 0.2 T permanent, recording Tl-and T2-weighted images (Spin-Echo sequences) for the anatomical localization of the fracture. TPB images, performed after i.v. injection of 555 MBq of technetium-99m methylene diphosphonate, permited a functional valutation of the fracture from the evidence of lesion intensities. When present (nine patients), the areas of high signal intensity on T2-weighted MRI images correspond to the increased uptake of radionuclide in angiography TPB images, tardive TPB images seemed to be more extensive. Both TPB and MRI were sensitive and specific in detecting clinically suspected fractures. With TPB, highly sensitive, it is possible to have early diagnostic informations and to compare lesion intensities, while MRI, highly specific, better defines anatomic lesion sites in the cortical bone and in the bone marrow. Further experiences are needed to determine diagnostical findings in the follow-up of the occult fracture. We wanted to evaluate if a high resolution SPECT of the spine is advocated in oncological patients, with a normal planar bone scintigraphy and without complaints. Our patient showed, one year after the initial treatment, a rise of CA 15.3. The patient had no complaints and the staging could not reveal clear evidence of metastasis. Although on the planar bone sointigraphy the thoracic and lumbar spine were considered normal, an additional evaluation of the spine, was performed by means of MRI, and SPECT images after the injection of Tc-99m MDP as well as after the injection of Tc-99m monoclonal antibodies (BW 250/183). The tomographic acquisitions of the spine were in both cases obtained on a three headed high resolution SPECT system (TRIAD 88, TRIONIX) equipped with high resolution collimators. Forthy views/head of 30 seconds each were taken, resulting in a total acquisition time of 23 minutes. The acquisition images (matrix of 128 x 64) were reconstructed into a 64 x 64 matrix using a filterred backprojection. On the bone marrow high resolution SPECT images multiple cold lesions were found in the the thoracic and lumbar spine. These cold lesions could be superimposed on the multiple small areas of increased bone metabolism, seen on the bone SPECT images and considered as occul| metastasis. MRI also confirmed these findings and a planar bone scintigraphy taken six weeks later, clearly showed these lesions. Although planar bone scintigraphy still remains the examination of choice in the detection of bone metastasis, small lesions may be overlooked due to the overlying and the underlying activity. However these occult metastasis can be identified on high resolution SPECT images. In practice when the planar bone images are doubtful, it seems to be advocated to perform high resolution tom0graphy rather than additional planar images.

G.Holl,S.Samel,K.Koppenhagen Dep.Nucl.Med.,Free University Berlin SCINTIGRAPHIC FOLLOW-UP OF UNCOMPLICATED FRACTURES WITH NANOCOLLOIDS The behavior of 99mTc nanocolloids (NNC),a widely used tracer for osseous infections, was evaluated in cases of fractures. 31 patients (18 females,13 males,average age 55 years,2 with 2 different fractures) were examined.7 had conservatively treated fractures of the femoral neck,8 fractures close to a joint,and 18 shaft fractures. The first study was performed 2-4 weeks after the accident,the second one either 6 months later (14 patients) or 12 months later (7 patients).Each patient had a NNC scan 1 hour after the i.v.injection of 550 MBq 99mTc-NNC and a three-phase bone scan with 550 MBq 99mTc-MDP.

At 2-4 weeks there was a difference in tracer uptake depending on the site of fracture. Close to joints there was the highest NNC uptake (mean 3.81),the highest perfusion ( m e a n 2.57),and the highest MDP accumulation (mean 4.02).Conserv. treated fractures revealed the lowest values (1.19/1.21/1.6), with shaft fractures lying inbetween (1.46/1.52/2.81). After 6 months the same tendencies could be found on a lower level: For joint fractures 1.39/1.34/1.78, for conserv, treated fractures 1.07/l.02/l.26,and for shaft fractures l.ll/l.15/l.42.After 12 months no differences could be found.

In conclusion there is a strong NNC uptake in uncomplicated fractures,that makes this tracer less useful in evaluating osteomyelitis in fractures.

J,Banzo, E. Prats, M.D. Ab6s, M,Delgado, T. Escalera, M,~ercia-Miralles and R. 6ast6,. Ser~cio de Medicine Nuclear. Hospital Clinico. Zaregoza, Espa~a.

The aim of the present study was te asses the usefulness of the 99mTc-HIG in a group of paLienLs with suspicion of an infecLious or inflamma~ry disorders, Material and methods.Thirty four poUenLs have been prospectively s~died with clinical suspicion of: inflammatory bowel disease (IBD) (n=6), vascular graft infection (VBI) (n=B), bone infectious or int'lammatery disorders (61) (n=20). A dose of" 185-370 HBq at" 99mTc-HI6 was in~avonously injected, and staUc images were performed at 5 minutes, ,4 and 8 hours from injection. Delayed images (24 hours) were occasionally done. All the patients underwent other radionuclide imaging (99mTc-L-HMPAO and/or 99mTc-MDP, and/or 67Ga). The final diagnosis was stablishad by endoscopy and/or biopsy and/or blood culture and/or clinical evolution, Results. I) IBD (5 ulcerative colitis, 2 Crohn's disease and I gestroenterocolitis complicated with e toxic magecolon). The 99mTc-HI6 imaging was positive in 4 cases being impossible te asses the extension of the disease in 3 of them. 2) Bone disorders (5 osteomyeliUs, 2 prosthesis infeclion,2 septic arthrilis, 2 pseodoerthrosis,2 discitis,! osteiUs,1 osteochondriUs, l chronic sinovyUs, l eplcondilyUs, ~ loosening prosthesis, and 2 Lumoars). 99mTc-HI6 imaging was negative in patients with disciUs, osLeochondriUs, pseudoarthrosis, osteitis and loosening prosthesis. 3) VEil (5 VBI, I ex~aprosthosic infection, I infected retroperitenesl hemaLoma and I non-infected graft). 99mTc-L-HMPAO imaging was positive in all the patients with V61, whereas 99mTc-HIG was positive just, in `4. ]'he extraprosthesic infection was detected by the 99mTc-HIG and was not using 99mTc-L-H~PAO. The patient with the infected retcaperiteneel hematema had a positive imaging with 99mTc-L-HMPAO and negative with 99mTc-HIB. Conclusions: I) 99mTc-HI6 imaging is not usefull in the assesmont of IBD. 2) In the diagnosis of the V61 the high vascular pool, makes difficult te int~'prstate the early images, being necessary to obtain delayed images (24 hours). 3) Although the 99mTc-HIG may be uptal~ed by bone ~mours, it can be usef'ult in the evaluation of the BI, perUculary in the extremities ones.

A.R.Cavallini, I. Bagni Dpt. Nuclear Medicine S. Anna Hospital, ~errara ,Italy

Type I collaqen is the predominant secretory product of os%eoblast, its precursor extension peptides which are removed as fibres from the matrix and released into the circulation would ~p ear to be good markers of bone formations. 

Infection scintigraphy with 99mTc-labelled nanocolloids has been shown a reasonable method with high sensitivity (90%) and specifity (92%) in the diagnosis of osteomyelitis and to rule out early infections after total hip arthroplasty (THA). In early studies after total knee arthroplasty (TKA), other operations of peripher joints and fractures nanocolloid uptake was seen, so that early infection cannot be differentiated. The aim of our study was to determine the potential of this method in differentiation of post-operative changes vs. osteomyelitis. 20 patients after total kneearthroplasty (TKA) as well as 50 patients with other operations of the peripher joints and bones underwent a clinical, radiological and scintigraphical investigation.

Results: Nanocoll-scans were not much helpful, because of the unspecfic nanocoll enrichment in eady postoperativ and posttraumatic alterations without clinical signs of infection. Later controls after 6 months showed a decreased uptake. 12 months studies p.o. will be repor~ed, The additional granulecyte scintigramm showed simular scintigraphic pattern than the nanecolloids but less false positive results and more Iocalised enrichment. Because of the different results of nanocoll scintigraphy between hip arthroplasty (high specifity and sensitivy) and other postoperative/ posftraumatic alterations with a lot of false positive cases new indications and limitations of this scintigraphical method have to be discussed. To e v a l u a t e bone abnormalities, 44 p a t i e n t s were studies 84.4 + -55.8 m o n t h s after k i d n e y t r a n s p l a n t a t i o n . All p a t i e n t s made a) d i g i t a l r a d i o g r a p h y of hands and spine, b) dual e n e r g y X r a y 

In uremic osteopathy bane morphometry shows distinct pattern which often cannot be differentiated by labor~tory parameters. In this study tracerkimetic investigations were applied to diagnose bone metabolism in pati L ents on regular dialysis treatment. Studies were performed on e4 dialysis patients (? male, i? female) with different extent of secondary hyperparathyreoidism (HPT). Parameters of calcium metabolism e.g. intestinal absorption, whole body retention, flux rates on the basis of a catenary compartmental model ~ere evaluated by means of a t~in isotope technique (~SCa p.o., 9?Ca i.v.). After tetracycline labelling bone biopsies ~ere taken from the ilian crest. Additionally, biochemical parameters were determined e.g. intact parathyroid hormone (iPTH), AP, Ca, and Vitamin D metabolites ~5 HCC and i.~5 DHCC. Data show elevated iPHT in ~/~4 patients. However~ bone histology showed low turnover osteopathy (LTO) in 7 patients and high turnover osteopathy (HTO) in 8 patients whereas 9 patients presented with mixed formes (MUO). HTO was always associated with an increased calcium efflu× and high normal Ca-retention. By contrast, patients with LTO had diminished Ca-eff]ux and evident low Ca retention and 7/9 patients with MUO normal values of Ca-efflux and only slightly decreased Ca-retention. Calciumkinetic investigations are a useful t0ol for the evaluation of bone turnover which is closely correlated with bone morphometric estimation. Therefore, underlying forms of osteopathy are well to be differentiated by changes in internal calcium fluxes. The aim of this study is to present the interest of "pin hole" scintigraphy of chronic post-traumatic wrist pain. "Twenty five patients,15-52 years old, were studied with normal (3rd hour) (SN) and pin-hole (SPH) bone scintigraphy. Results were compared with findings of X-rays (25 cases), MRI (17 cases), Computed -Tomography (2 cases) and Open Surgery (8 cases) which were considered as the gold standard. Thirteen patients had osseous or ligament lesions of the wrist, 2 had Kienb6ck's disease, 6 had non union of the scaphoid with 2 avascular necroses of proximal splinter. In four cases no lesion was detected. Of the 13 patients with osseous or ligament lesions, SN was positive in 7 cases, SPH in 12. In only one case, SN and SPH were normal and arthroscanography showed adhesive capsulitis. In KienNSck's disease, SN showed a diffuse hyperfixation of the wrist and SPH demonstrated the absence of fixation of the Lunatum. In the 2 cases of avascular necroses of the proximal splinter (established by surgery), there was a defect of fixation of this fragment on SPH and this was correlated with MRI. In the 4 cases without osteonecroses (established by surgery), SPH showed an equal or decreasing fixation of the proximal fragment, highlighting the vitality of proximal splinter. In these cases there were 2 false positive identifications with MRI. In the 4 cases without lesion of the wrist, SN and SPH were normal. Diagnostic contribution of pin-hole scintigraphy in chronic posttraumatic wrist pain is better than standard scintigaphy. Pin-hole scintigraphy is more specific than MRI in the diagnostic of avascular necroses of proximal splinter i'n non-union of the scaphoid. Despite advanced automation of bone edge detection and region of interest positioning in spine and femur measurements of bone mineral with modern instruments operator review, and at times manual override, is required to correct for errors in bone edge detection. The threshold to trigger manual intervention by the operator is subject to different interpretations. The purpose of this study was to create guidelines based on pattern recognition to standardize such operator interventions between laboratories. Results are based on experience of two multicenter studies with over 10,000 spine and hip measurenP_nts of BND performed with D~A*.Results: (i) 8-15% of all L-spine and 12-27% of all hip scans needed operator intervention depending on technologist training. (2) For L-spine eight patterns are shown demonstrating different levels of inhomogeneity in B~K) distribution, scoliosis, long axis rotation, degenerative disease and compression fractures. Other patterns show artifacts frcrn patient movement, garments, intestinal content and poorly absorbed medication. 

In diagnosing the instability of hip endoprothesis the problemappears of differential diagnosis between the inflammatory and aseptic loosening of endoprothesis. In 47 pts suspected of loosened hip endoprothesis the threephase scanning of skeleton with HDP was made, along with the calculation of relative perfusioin in the artery phase (3T). After 24 hours the skeleton scanning was repeated with HIG foloowing the same procedure. In 17 pts no changes were observed on the static images while 3T was within the range from 0.18 to 0.41. In 16 pts scintigraphy with HDP showed on static images increased accumulation in the skelet of affected hip adjoining to the endoprothesis; 3T was within 0.62 and 0.88 implying increased perfusion of the surrounding tissue. The images obtained with HIG showed no increased accumulation; In 14 pts, the static images obtaindwith HDP as well as HIG showed indreased accumulation. 3T ranged from 0.90 up to 1.55 which evidenced extraordinarily increased perfusion~;6f the sur~ound~ng~tissue. All these pts had inflammatory septic changes in the areas adjoining to the endoprothesis. The quantitative diagnosis, including the 3T calculation and simultaneous analysis of static images obtained with HDP and HIG, allows determinantion of the changes of hip endoprothesis in the sense of aseptic or s~ptie loosening, and consequently proper further treatment. 

The purpose of this study was to assess the ability of bone sclntigraphy to demonstrate viability of bone grafts and to predict complications. 20 patients who had received 21 autologous bone grafts for reconstruction of the mandible after partial resection were evaluated. 6 grafts had been transplanted free, 15 revascularizted microsurgically. Bone sclntigraphy was applied within 14 days and approximately 4 month after surgery. Planar imaging of the skull was performed in 4 projections at 3 h after i.v. injection of 740 MBq (Tc-99m) MDP. SPECT data was collected with a rotating gamma camera over 360 degrees in a 64 x 64 matrix and smoothed with a Metz prefilter before reconstruction. Traceruptake in the graft was subdivided into 5 classes: 1.) intense, homogeneous, 2.) slightly decreased, 3.) aver~je, inhomogeneous, 4.) clearly decreased, 5.) not recognizable.

Complications concerning the graft appeared in 3 patients (2 osteomyelitis, 1 partial resorption). In these patients uptake class in the first planar scintigrephy was 4 or 5 respectively. Out of 12 grafts which each showed uptake class 3 in the first planar scintigraphy no complication occured. In 9 of these 12 a second scintigrephy was performed and showed uptake class 1 or 2. SPECT within 14 days after surgery in 2 patients who received free transplants showed uptake classes 4 and 5. Tc-99m labeled human nonspecific immunoglobulin (HIG) scintigraphy has recently been proposed for imaging the acute synovial inflammation in rheumatoid arthritis. The aim of the study was to evaluate the efficacy of HIG in the assessment of response to therapy.

12 females and 6 males adult patients (pts) with exacerbation of chronic rheumatoid arthritis were studied before and 1 to 3 mo after the beginning or intensification of therapy. Treatment consisted in local infiltration (9 pts), pulse steroid therapy (8 pts), cytostatic drugs (3 pts), Y-90 synovectomy (2 pts), gold salts (2 pts) and surgery (1 pt). Scintigraphic images of the joints were obtained 1 and 6 hr after injection of 555 MBq Tc-99m HIG. A 4-point scoring system was used to evaluate the uptake in 27 joints and the scintigraphic index was compared to a clinical joint involvement index (Ritchie index).

The summed clinical and scintigraphic indexes were lower after therapy than before (mean __-SD: 17.5 + 8.9 vs 12.8 + 9.2 for the clinical and 27.3 ± 12.3 vs 21.1 + 11.8 for the scintigraphic index; p<0.001 and p<0.005 respectively). There was a good correlation between the decrease of both indexes after therapy (r=0.73, p<0.001). Before and after therapy, the concordance between the clinical-and scintigraphic index was excellent (p<0.0001). In 60 % of the 972 examined joints, both scores were identical while in about 31% of the joints, the scintigraphic index was higher than the clinical score. In 14 out of 15 infiltrated joints, the changes of the clinical and scintigraphic indexes were in agreement.

In conclusion, these data confirm the sensitivity of Tc-99m HIG scintigraphy for the detection of acute inflammation in chronic rheumatoid arthritis and suggest that the method is reliable and useful for assessing the response to therapy. Malignant external otitis is a potentially fatal otitis which occurs in diabetic and ir~nunosuppressed patients. Clinically suspicious patients of having malignant external otitis do not always have the classical triad i.e diabetes, granulc~na and pseudomonas, whereas conventional imaging modalities including CT are not of any particular help. Aim of this study was to investigate the presence of osteomyelitis of the temporal bone as the main element of tissue involvement. We studied 5 patients with clinical diagnosis of external otitis (pain and oedema of the external auditory meatus) and suspicious of having malignant external otitis. ~i the ~9m~tients underwent 3 SPECI' studies of the head with c-~DP, 99m~c-Nanocolloid and 67Ga-citrate each. Radioactive uptake was evaluated on slices of the basis of the skull which showed the greatest involvement, ~ith the help of ROIs and count profiles. In one patient the protocol was applied as the main follow up method.

Four out of five patients had positive results on all 3 scintigraphic studies and had a difficult course of the disease. The patient who was negative on all 3 studies, ~as dismissed free of symptoms after a short course of antibiotic treatment and was considered as not having malignant external otitis. We conclude that ~ith SPEC~ it is possible to diagnose early temporal bone involvement, the sine qua non finding cbaracterising malignant external otitis. Injestion of water containing excessive flouride leads to chronic metabolic bone disorder known as Endemic Fluorosis. The disease leads to cripling deformities resulting in significant morbidity.Many radiological and metabolic abnormalities have been described.However,skeletal scintigraphic changes have so far not been documented systematically.The study has been performed in patients belonging to a village where the water fluoride content has been found to be 1. 2-12. gppm.The inhabitants of this village had many bony deformities,restricted joint movement and bone tenderness. Coventional skeletal X-ray survey showed changes like osteosclerosls ,osteopenia with increased cortical thickness,course trabeculer pattern and some times osteopenia alone.Skeletal scintigraphy was carried out with intravenous application of 99mTc-MDP using a large field view Gamma Gamete with high resolution collimator.Qualitative evaluation of scintigrams showed increased uptake in axial skeleton,tie sternum sign, faint to absent visualisation of kidneys and increased uptake in the diaphysis of the long and small bones of the hand and feet.These findings were present in all patients.The quantitative studies showed singificantly increased turn over as compared to normal patients.The scinti~raphic findings appear to be rapid bone turn over which is associated with this disease. In some patients this was observed where the conventional x-ray did not show any significant pathology.

L . E c k a r t +, M.Gericke*, J . P a n h o r s t H . T h i e r f e l d e r * , R.Felix*

The diagnosis of infection after bone operation should be fast to avoid complications in esteomyelitis. Infection scintigraphy with 99mTc-labelled nanocolloids has been shown a reasonable method with high sensitivity (90%) and specifity (92%) in the diagnosis of esteomyelitis and to rule out early infections after total hip arthroplasty (THA). In early studies after total knee arthroplasty (TKA) nanocolloid uptake was seen, so th~ early infection cannot be differentiated. In our study we comprehended the behaviour of Tc99m-labelled nanocolloids in about 35 patients after total knee arthroplasty (TKA) and we prooved the potential of this method in differentiating postoperative changes vs. osteomyelitis. In equivocal cases (n=25) additional anti-granulocyte-scintigrams were performed. After bolus injection of 740 Mbq Tc99m-labelled nanocolloids comparision of perfusion, bloodpool and quantitative uptake 45 min., 4 and 24 hrs. p.i. in both methods were done. Results: Within the first 2 months after TKA in all cases nanocolloid uptake was seen in the surrounding bone tissue, so that septic infection could not be differentiated. The additional granulocyte scintigramm showed simular results than the nanocoll scans. Some cases had exactly the same pattern than the nanocolloids, some showed less and more Iocalised enrichment. Later controls after 6 showed a decreased uptake, 12 months studies p.o. will be reported. For clinical routine sctintigraphy with Tc99m-labeled nanocolloids and mouse anti NCA-Granulocyte-AB in the early phase after otal knee arthroplasty (TKA) is not helpful. 

Aim of this study was to assess the value Of triple phase ( [3] [4] [5] [6] [7] [8] [9] bone scintigraphy in 45 patients (pts) with non-traumatic hip pain and different stages of femoral head avascular necrosis. 52 scintigraphic studies (32 3-P bone scans and 20 stanic studies of both hips) were performed in 45 patients (6 women, 39 men, age 3 -56 years) using Tc-99m MDP. Final diagnosis (clinical followup and radiography) was transient synovitis in 7 and femoral head %vascular necrosis in 38 pts. The scans were analyzed retrospectively by 4 independent experienced observers scoring the degree of %racer accumulation in femoral heads from -i to .3 and compared with corresponding plain radiographs.

Overall, 55 of 104 femoral heads had signs of necrosis on radiographs. In 10 % of the juvenile pts, scintigraphy was positive earlier than x-ray. Overall sensitivity and specificity of scintigraphy for the detection of femoral head avasc~lar necrosis was 91 % and 90 %, respectively. The positive predictive value was 91 %, the negative predictive value 90 %. In adult patients with femoral head necrosis a scintigraphic type I (increased femoral head activity > +I in all three phases) was correlated with early stages of the disease on radiographs (10/10 hips) while a type II (normal perfusion~ but at least + 1 in static phase) was correlated with late stages (13/16 hips).

In conclusion, 3-P bone Snintigraphy is a highly sensitive and specific method for the detection and with different perfusion pattern also a valuable ~pproach for staging of femoral head avascular necrosis• . . • V a l u e s of 1 , 2 5 ( O H ) 2 D and 2 5 ( O H ) D were s i g n i f ic a n t l y l o w e r ( 2 6 + 5 , 8 p g / m l ; 1 6 , 3 + 7 , 5 n g / m l ) t h a n the same on~s i~ E u ( 4 o , 5 + 8 , 2 p~/ m l ; 2 2 , 3 ± 7 , 6 n g / I ) . I P T H h a d~a l u e 1 9 , 6 + 6~l p g / m l , C -P T H 8~+ 4 7 n g / 1 ) . M a r k e r s~f o s t e o b l~s t f u n c t i o n A P , p -U o l l -C , G L A -p were h i g h e r than those ones in E u ( 1 2 6 + 2 o i U / 1 ; 1 8 2 + 6 o u g / 1 ; 1 3 , 4 ÷ 6 , 1 n g / 1 v e r s u s 59+ II I U / 1 ; 1 2 o~2 7 u g / 1 ; 4 , 4 +~, 4 n g / 1 ) . W e f o u n d ~ig n i f i c a n t c o~r e l a (15) or knee (4) prosthesis were referred to scintigraphic inflammation imaging. In all cases, previous X-ray images and bone scans showed typical signs of loosening of the prosthesis. Seven 111-In-leukocyte studies, ten 99m-Tc-nanocolloid studies, and three scans with monoclonal anti-granulocyte antibodies (AGAB) were performed. The scan findings were considered to indicate inflammation when there was a specifically increased tracer uptake in the suspected area. Thereafter, all patients underwent surgery for explantation or change of the prosthesis. Intraoperative bacteriology was positive in nine cases. The false-negative AGAB scan was seen in a case of infected hip prosthesis, whereas the nanocolloid study performed in the same patient showed a right-positive outcome. The results suggest that 99m-Tc-nanocolloid scintigraphy is an appropriate alternative to leucocyte scanning for identification of septic loosening of hip or knee prosthesis. visiting the Department of Rhetunatology with RA, according to 1987 ARA criteria and 5 healthy controls were studied. Imaging was performed 4 hours after 350MBq ~mTc-IgG injection. The following joints were investigated: shoulder, elbow, wrist, 5 separate metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, hip, knee, ankle and forefoot. Thirty-four joints of each patient could be used for evaluation. All joints were scored for pain, swelling and for degree of uptake of ~mTc-IgG on a 4-point scale. Excellent images of inflamed synovium in the RA patients were obtained. Scores for mmTc-IgG joint scintigraphy correlated highly with scores for joint swelling and CRP levels, weakly with pain scores and not with radiographic scores of joint destruction. The 5 healthy controls showed no ~bnormalities on joint examination and no increased uptake of the radiopharmaceutical in the joints.

We conclude that mmTc-IgG joint scintigraphy may provide an objective test to detect synovitis and to measure the activity of rheumatoid arthritis, The present study was undertaken to assess the evolution of bone mass in 1 ° HPT, at the lumbar and the appendicular sites after removal of a parathyroid adenoma. 2 groups of patients were selected: 25 patients (15-84y), (preop. serum Ca: 11,8 + 0,8 mg/100ml) had a preop. BMC measurement of the radial epiphysis (E) and shaft (S) and of the lumbar spine (L2-L4) (Gr. 1). 15 out of them had a 2nd measurement ly after surgery. 41 previously operated patients (29-83 y) (preop. serum Ca: 11,1 + 0,7 mg/100ml) had a postop, measurement > than 2 y after surgery (Gr 2). BMC was measured by single photon absorptiometry at radial sites and by dual photon absorptiometry at lumbar site. Results were expressed as a % of those obtained in ageand sex-matched normal subjects. In group 1, preoperative BMC was significantly decreased at the 3 sites: E:84+17% (p<0,01), S:88+15% (p<0,01), L2-IA:78+15 (p<0,001). Spine BMC was significantly more decreased than that of radial sites. In the subgroup of patients with preand postop, measurements, the preop, values were respectively: 85+16% (E), 91+14% (S) and 82+--12% (L2-L4). After surgery, a significant increase existed for E and spine: 89+--15% (p<0,05), but not for S: 92+-15% (NS). In group 2, BMC remained significantly lower than normal : E:86.+_.1 4 %, S:89+11%, L2-L4: 87+17% (p<0,001). To conclude:before surgery, BMC is significantly decreased, the decrease being more pronounced at lumbar site. A recovery exists after surgery, the increase being more important in areas rich. in trabecular bone. However, it remains partial since a residual bone loss is observed at the 3 sites, even in the long term. in patients with active soft-tlssue inflammation, Chronic inflammatory changes are not easily differentiated from increased"blood-pool" due to increased osteoblaatic activity seen on threephase bone scan. In our study 12 patients wlt~ posttraumatic myositis ossificans were studied prospectively.

Planar scintlgraphic images were taken Imeedistely, I, 2, and 4 hours after i.v. injection of 25o-3oo MBq Tc-99m-HIG. Conventional three-phase bone scan was also perfqrmed. Clinical and X-ray findings were correlated to acintigraphic results. Progressive focal accumulation of Tc-99m-NIG was found in the affected areas In patlents with clinical slgns of Inflammation /n=6/, 4 hours images were of better quallty. In 3 out of 6 patients without cllqical signs of inflammation increased "blooa-pool" was found due to increased mlnerallzstlon, but normal Tc-99m--HZG sclntigrsphlc results were obtalned in this group of patients, In conclusion: TC-99m--HIG seems to be useful In evaluating patients with myositis oseificans glvlng more reliable information about inflammatory activity and appropriate timing of surgical intervention, Imaging was performed at 6 hours following i.v. injection of 740 MBq of HIG obtaining anterior and posterior views of axial body and extremities. 38 pts were also imaged at 24 h.

In the bone-joint group, HIG images were truely positive (TP) in 21 of 24 pts with proven bone-joint inflammation, and truely negative (TN) in 12 of 12 pts with traumatic or degenerative disease. The false negative studies were obtained in S pts treated with antibiotics for at least S weeks. In the group of nonskeletal disorders, HIG images correctly identified the inflammatory site (lymph nodes, cellulitis, pelvic mass, oroesophagel C.Albicans, myositis and septic lung embolism) in 9 pts, and failed to detest 5 sites (liver, brain and lung). Large lung and liver abscesses appeared cold with NIG. In ii pts the study was considred TN and a false positive study was seen in a p t with knee synovial sarcoma.

IN the assessment of skeletal inflammation NIG offers excellent results with a high yield of TP and TN, the latter representing a great advantage over bone and gallium scanning, but still the tracer that will separate septic from aseptic inflammation is not available. The role of HIG in the study of other inflammatory sites is not so clear and some questions arise regarding relative insensitivity in certain tissues (lung, liver) and cost-effectiveness in the work-up of fever of unknown origin: purpose of this study was to investigate the potential of an ultrafast scan technique for dynamic perfuson studies in Patients with coronary artery disease (CAD).

Methods: 20 patients with CAD and 10 healthy volunteers were studied using a single-slice Turbo Fast Field Echo sequence with a 128"100 matrix on a 0.5 Tesla superconducting magnet (Philips medical systems). Cardiac triggering was used and the time resolution between dynamic scans was 4.5 seconds. After bolus administration of Gd-DTPA first pass extracellular perfusion of the contrast agent in normally perfused and ischemic myocardium, scar and reference tissue was documented using myocardial mapping of up to 30 ROIs' and time intensity curves.

Results: Time-intensity curves demonstrated peak enhancement in the mapping ROIs'. Local, regional and global perfusion profiles were obtained that were consistend with the underlying pathology confirmed by other studies and clinical findings as well as physiological understanding of normal tissue. Single slice acquisition and the lack of specific contrast agents were considered a preliminary limitation for complex evaluation.

Conclusions: The results demonstrate that ultrafast MRI can provide adequate time and spatial resolution in cardiac perfusion imaging. It appears to be a promissing tool for noninvasive screening of CAD. 22 patients (5 females, 17 males, mean age 52+/-10 yrs, range 37-72 yrs) with single-vessel (LAD) coronary disease were investigated by means of dipyddamole (DIP) stress 201-T1 myocardial perfusion scintigraphy, using SPECT, 1 week before and 2-5 weeks after coronary by-pass surgery (CBS)..The dose of DIP was 0.56 mg/kg, and the injected activity of 201-T1 was 2 mCi. Before surgery, after completion of the stress -3-hr rest imaging, a further 1 mCi of 201-T1 was injected. 10 min and 1 hr later, repeated SPECT acquisitions were performed. SPECT images were evaluated both subjectively and semiquantitatively, using a 4-grade segmental defect score system, with higher scores for more severe perfusion defects.

Before CBS, the 3-hr redistribution images revealed permanent peffusion defects in 20 patients. On the images taken 10 min after re-injection, these defects were completely filled in 5 cases, and partially filled in 12 cases. Further positive change s were observed on the 1-hr post-reinjection images in 5 cases. 3 of the 1-hr post-reinjection images exhibited paradox redistribution. The stress images after CBS corresponded well to the 201-T1 distribution on the preoperative 1-hr post-reinjection images in 18 cases. The sum of the segmental defect severity scores was 493 after stress, 290 at rest, 204 10 min after re-injection and 187 1 hr after re-injection. After surgery, the sum of the post-stress scores was 78 and that of the 3-hr redistribution images was 96. Correlation coefficients between the segmental score values of the post-operative resting study and the pre-operative 3-hr late, and the 10-rain and 1-hr post-reinjection studies were 0.62, 0.63 and 0.88, respectively.

It is concluded that post-reinjection 201-T1 images before CBS are good predictors of the myocardial perfusion after revasculadzation. The best results are obtained if imaging is performed 1 hr after re-injection. 

A total of 360 pts with either normal perfusion (314) or fixed defects (46) and no transient left ventricular cavitary dilatation on dipyridamolc-thallium (D-T1) scans were followed over an average period of 16 months. Of the 360 pts, 194 subsequently underwent major noncardiac surgery. There was a total of 8 cardiac events including 2 postop complications (1 fatal and 1 non-fatal myocardial infarction) and 5 cardiac events during long-term follow-up (1 sudden death and 5 non-fatal infarctions). During the follow-up period, 3 pts underwent coronary bypass surgery. There were no events in pts with f~xed defects. The low cardiac event rate could not be explained by a low pretest likelihood of coronary disease: 77% of the 360 pts had either typical angina pectoris, a previous myocardial infarction, or peripheral vascular disease.

In conclusion: In pts with a high pretest likelihood of coronary artery disease, the absence of thallium redistribution on a D-T1 scan denotes a low (1%) risk for major noncardiac surgery as well as a low long-term cardiac mortality (0.3 %) and morbidity (1.1%) rate comparable to that of pts with minimal (<50%) coronary stenoses.

Vers~ri A, Manari A*, M~nicardi E**, Salvo D, Ferretti PP***, Iori I**, Guiducci U*, Serafini D I Radiology and Nuclear Medicine, *11 Cardiology,**ll Medicine, ***Physics Depts.-S. Maria Nuova Hosp.,Reggio Emilia-ITALY

Coronary artery disease (CAD) is the main cause of death in diabetics. The aim of our study is to evaluate EgG exemise test lET) and TI201 SPECT (-FL) in detecting silent myocardial ischaemia in 42 NIDDM males (aged 39-60 yrs) with no cardiac symptoms but with at least one major CAD risk factor (familial, hypertension, hypemholesterolaemia, smoke ). All pts underwent maximal ET, stress and delay TL (110 MBq, am of view 180 °, bullseye elaboration), 2D-echocardiography (2DE), ophthalmoscopy and proteinuria dosage. 2DE was executed to exclude other cardiac diseases. ET was positive in 15 (36%) pts and ~ in 23 (57%)~ both tests were positive in 13 (31%). Coronary angiography (CA) was performed in 17 pts (7 E-LTL+, 2 8 ET+TL+) and showed stenoses >= 50 % in 8 pts (4 ET-TL+, 4ET+TL+). There is no correlation between retinopathy and the other tests. Preteinuria > 100 rag/24 hrs, an index of renal microangiopathy, was present in 16 of 23 TL+ pts (70%) while in only 3 of 19 TL-pts (16%). Referring to CA as gold standard, in our study sensitivity was low for ET (50%) and very high for TL (100%). Both tests presented very low specificity lET, 33%; TL, 22%): this result may depend partially on our selected cases and partially on CA unadequacy to investigate small vessel disease. In fact if we consider increased proteinuria there is a significant difference (p < 0.005) between TL+ (70%) and TL-(16%) groups while there is no significant difference between CA+ (87%) and CA-(67%) groups. Perhaps TL "false" positives are actually myocardial micmangiopathy 'true" positives. The follow up of these pts will clarify this question. 

In order to evatuate~ocardiai perfusion changes in patients With sclerederma or Raynaud's phenomenon (RP), we prospectively studied 67 patients (mean age 50.8 y. 63 women) with sistmsic sclerosis (SG) (56 limited and 11 diffuse forms) according to the c r i t e r i a by the American Rheua~atism Association, ned 25 patients (mean age 46.6 y. 19 women) with RP. Also, we included 10 normal patients (mean age 38.4 y, 9 worsen) with Low prebabitity of coronary disease for comparison.

We performed planar myocardial perfusion scintisraphic images with 111MBq of Thallium-Z01 injected 30 to 60 seconds before the end of the stimulation peried (ice-cold water bath of both hands -4~ g -during 2-S minutes) (cold test). Three hours Later, staedard redistribution images were obtained. Semiquantitative image anatysis was done by two experienced readers blinded to the c(Inical diagnosis. Left ventricular function was assessed in a conventional way by msans of echo-Doppler lED) and radionuclide ventricuLography (RNV).

Two patients (one with SS a~ one with RP) developed chest pain during cold testing, but none displayed EgG changes suggesting myocardial ischemia. Altogether, 66% of patients with $$ and 56% of patients with RP showed reversible t a t l i u m u p t a k e defects in the c o l d -r e d i s t r i b u t i o n study, while only a 10 % of the Unormals" did (p<.0002). Reversible t h a l l i u m defects were more frequently seen in patients with difuse scteroderma(91%) than in patients with l i m i t e d sclerederma (60%)a although such difference was not s t a t i s t i c a l l y s i g n i f i c a n t . The mean score difference between cold aed r e d i t r i b u t i o n images in patients with S$ was not s i g n i f i c a n t l y different than that of patients with RP. Defects were localised at random in both groups. Also, the percentage of myocardial segments with partial or no redistribution was similar in both groups. No differences were seen in left ventricle function parameters between patients with and without reversible thallium defects. CONMENTS 66% of patients with SS and 56% of patients with RP present with reversible myocardial thallium uptake defects elicited by cold stimslation of the hands. Such defects appear predominantly in patients with diffuse sclerodermB (91%), and are seldom seen in the normal population (10%), Thus, probably a cardiac Raynaud~s phenonwnenon accounts for such patterns of transient myocardiaI ischemia.

ii 660

Antimyosin-ln lzz imaging may be useful in the detection of acute myocarditis.

To examine its diagnostic accuracy in relation to endomyocardial biopsy, as well as the natural history of a positive antimyosin scaning in myocarditis, 11 patients (pts) (36±13 years old,9 male, 2 female) with suspected acute myocarditis underwent endomyocardial biopsy and antimyosin-lnZll scanning.Heart to lung ratio (H/L)was used to quantify antimyosin scanning; a ratio >1,6 was characterized as positive for myocarditis.

All 11 pts presented positive scanning (H/L 1,7-2,9 mean 2,1±0,3); 7/11 had also endomyocardial biopsy oos~tive for myocarditis.ln 4 pts with Antimyosin (+) Biopsy (-) results, H/L ranged from 1,9 to 2,5. Ejection fraction (EF) ranged from 11% to 57% (36±14~); 2/11 pts had EF>50%. 1 pt died and 3 pts were lost to follow-up. Nine antimyosin studies were repeated in 7 pts within 2 months after the first study (1,3 stud~ per pt). In 4/7 pts antimyosin scanning returned to normal with H/L<I,6, while in 3/7 it was persistently abnormal. In 3 pts with initial Antimyosin (+) Biopsy (-) results antimyosin returned to normal in 2/3 while in 1 it was persistently abnormal. In conclusion: 1) Antimyosin scanning is more frequently positive in suspected myocarditis than endomyocardial International) is a lipophilic, cationic diphosphine (Tc-D) which has been developed for myocardial imaging. We have compared Tc-D with imaging for the detection of coronary heart disease(CHD) and assessed redistribution characteristics of Tc-D in 23 pts. Mean dose of 9.5mCi of Tc-D was injected during exercise (Ex) and 26.6mCi 4hrs later. TI-201 exercise and redistribution study was also performed. Multiple planar views were obtained at 5 min, 30 min, 2 hr and 4 hr post injection and all images were assessed by a blinded panel to score pts with myocardial ischaemia(ISG), infarction(Ml) or normal scan interpretation(N).

Quantitative defect to normal wall ratio(d/n) was generated to assess redistribution with Tc-D during Ex but not with Tc-D. Diagnostic quality images were noted at 5 min 4 hr, and there was no evidence of any redistribution with Tc-D.

Tc-D compares well with TI-201 for the diagnosis of CHD. These data suggest that Tc-D is an unique, new Tc-99m agent for evaluation of patients with CHD and further study is indicated. 

Rationale of this animal study was to establish a model for testing the efficacy of different anticoagulation regimens for the prevention of platelet/fibrin deposition on coronary stents.

19 minipigs (27-41 kg) were simultaneously i.v. ±njected with 3 b~q in-ill oxine labeled autologous platelets and 3 MBq 1-125 fibrinogen followed by coronary ±mplantation of tantal~ra stents 14-19 h p.i. Animals were sacrificed 12 h later, and perfusion fixed parts of coronary arteries with and without stents were counted in a gaalma well counter (In-ill and 1-125 windows with spill down correction). Additionally, blood samples up to 28 h were counted. Three anticoagulation regimens were tested: Group i (n = 5; 7 stents) received a bolus of heparin, group 2 (n = 6; ii stents) a bolus of heparin + continuous heparin infusion, and group 3 (n = 7; 13 stents) a bolus of hirudin + continuous hirudin infusion.

Platelet survival curves as well as fibrinogen activity

in peripheral blood showed a biexponential decrease (t/2 = 3 h within the first 4.5 h; after that t/2 = 36 h). Platelet deposition (in I06 platelets / stent) was i17.1 +/-68.8 in group i, 64.3 +/-15.7 in group Z, and 19.7 +/-2.4 in group 3 (p < 0.05 vs group 1 and 2, respectively). Fibrin deposition fin ~g / stent) was 439.0 4/-162.4 in group i, 315.4 ÷/-119.6 in group 2, and 138.4 +/-34.8 in group 3 (p < 0.05).

Conclus±ons: i) the animal model described allows to test the efficacy of anticoagulation regimens in coronary stents;

i±) in the reduction of platelet/fibrin deposition, hirudin was more efficient than heparin. 

We evaluated 52 studies of iS patients with Pe~ection of gPade SA or higher, to determine the evolution of hemodynamics and myocardial damage produced by a significant episode of re~ection. The study protocol co_m pPised: NUGA left ventriculography with 99m To-Albumin; iii In-Antimyosin Antibody myocardial uptake (AbAM), and endomyocardial biopsy with results expressed according to the ISNLT classification. The three procedures were performed in a maximum interval of three d8%rs. Each patient had four studies: a baseline study with a 0 score before any rejection episode, a study during rejection of grade SA or higher and two follow-up studies in the first SOdays Left vent~icular function shows the most seve _ re impairment on the first follow-up study after re~ection; Maximum AbAm uptake coincides with re~ection episode. In conclusion, histologic resolution of severe re~ection does not imply a simultaneoms improvement in ventrioular function; and evidence of myocardial damaze exists for some time after histologic normalization of biopsy. 

In patients free of rejection, thallium scan has been used to detect coronary arter~ disease, but the pattern of the thallium uptake in these patients without coronary artery disease is unknown. The aim of this study was to compare the thalliun scan of these patients with a group of control subjects.

Patients were submitted to echocardiography, coronarogranhy, • biopsy and gol thallium myocardial tomoscintigraphy ~20IT~) coupled with dipyridamole test. 24 patients were studied one year after, heart trmasplantation and 10 among 24 were. also studied 2 years after.

In all patients, coronar0graphy was normal and biopsy was not indicative of graft rejection. The left ventricle :mlT1 uptake was studied by quantitative segmentation of tomogaphic slices in 13 segments. The relative uptake was calculated as the percentage of th0 highest value and compared to a control cardiac group of patients with normal ~oronary 'arteries. The mean ventricular mass (125,8 -+ 12 g/m ) was,aiso found at the normal upper limit.

On stress thallium scan, the uptake of the lateral wail was significantly reduced compared to the control group (90 -+ 4 vs 96 +-3,5 % : p < 0.01) and no significant redistribution was noted. The same pattern was observed two years after transplantation.

The presence of a mild hypertrophy, .the modification of heart geometry, and chronic rejection could be suggested to explain this particular pattern in uncomplicated transplanted hearts. An important conclusion is that quantitative thallium: scans of transplanted hearts should not be compared with a standard control group, but with thallium scans in noncomplieated transplanted patients. l e c t e d at 4 a n d 24-hr. T1 u p t a k e in 15 p l a n a r s e g m e n t s was a n a l y s e d q u al i t a t i v e l y on a 0-4 v i s u a l scale a n d q u a n t i t at i v e l y w i t h circum, p r o f i l e s (<40% p e a k a c t i v it y = s e v e r e d e f e c t ; > 4 0 % a n d < 7 0 % = m o d e r a t e d e f e c t ; a 10% c h a n g e f r o m S to 4-hr a n d f r o m 4 to 2 4 -h r was c o n s i d e r e d s i g n i f i c a n t ) . N o r m a l (score ~3) T1 u p t a k e was f o u n d in 3 4 4 / 9 3 0 (37%) s e g m e n t s . At q u a n t i t a t i v e a n a l y s i s 

Ege University Medical Faculty, tZMtR, TURKEY.

Patients with low ejection fraction rates have unable to reach maximum exercise and inadequate exercise may decrease the sensitivity of TI 2°t myocardial perfusion tomography. The aim of the study was to evaluate the value of T120t SPECT following dobutamine (Db) stimulation (which increases myocardial oxygen demand in 5-20 Mih'o gr/kg/min doses) in coronary artery disease (CAD) patients with low ejection fraction rates. 23 pationts had Tc 99m RBC list mode gated blood pool scintigraphy (MUGA) and Tle °1 SPECT study following Db. stimulation and at 3 hours in rest, prior to coroimry angiog~aphy (CA). Db and rest TI ~°1 SPECT data evaluated by both qualitative segmental analysis and quantitative polar m~ps. • All patients had ejection fraction rates below 37 % both in MUGA and CA studies. Ejection fraction ratio calcolated by both method were well correlated (r= 0,87). Overall sensitivity and specificity of TI 2°1 SPECT were 85 % and 80 % when compared with CA results. No significant difference was observed between qualitative and quantitative evaluation methods. Individual assessment of coronary artery lesions showed following results:

LAD LCX RCA Sensitivity 90% 70% 94% Specificity 98% 83% 76%

As a result Db T1201 SPECT offers a safe, readily available alternative stress test for the detection of CAD especially in patients with low ejection , fraction rates who cannot exercise adequately.

M' Eisenhut, W.D. Lehmann*, A. S~tterle University of Heidelberg, Dep. Nucl. Medicine and *German Cancer Research Center (DKFZ), Heidelberg

For the noninvasive assessment of myocardial utilization of exogeneous long chain fatty acids radloiodinated 15-(4'-iodophenyl)pentadecanoic acid (IPPA) is a clinlcally accepted radiopharmaceutical. The metabolism of this compound in the heart muscle is believed to end mainly with 4-iodobenzoic acid as the final product of B-oxidation. By using IPPA as a reference for the investigation of the metabolic fate of chemically modified fatty acids with the Langendorff rat heart we could not confirm the formation of 4-iodobenzoic acid as a main product, It merely appeared as side product in minute concentrations. As proved by FAB-mass spectrometry (FAB-MS) the main heart catabolite of IPPA is 4-iodocinnamic acid, with 3-(4'-iodophenyl)propanoic acid, and 5-(4'-iodophenyl)-3-hydroxypentanoic acid as side products. Additionally a surprising metabolite was isolated from hydrolysed heart lipids. Besides IPPA 11-(4-iodophenyl)undecanoic acid was detected and proved by FAB-MS. The formation of a single metabolite is possibly due to the consumption of catabolites by fatty acid synthetase in the cytosol. This result points to an additional metabolic loop of IPPA, which may be important for the interpretation of sequential scintigraphy. In a prospective study of 26 patients (pts) with first Q wave acute myocardial infarction (AMI), infarct-avid imaging and radionuclide ventriculography (RNV) were performed after injection of Tc-99m (740 MBq) labelled antimyosin (Tc-AM) within 72 hrs of chest pain. The early blood pool phase of Tc-AM was utilised for equilibrium RNV in the 3 standard views. Planar images for the detection of myocardial necrosis were obtained earlier and at 24 hrs in the same 3 views. Images were evaluated blind by two experienced physicians. Myocardial antimyosin uptake was seen in 21 out of 26 pts (81%). RNV was evaluated in 19 out of 21 pts with positive uptake of antimyosin. Mean±+SD left ventricular ejection fraction was 42±9% (range 25%-59%). Wall motion abnormality (WMA) was present in all the 19 pts and this matched with the location of antimyosin uptake. However. 7 pts (47%) showed WMA extending beyond the area of antimyosin uptake which may represent stunned or hibernating myocardium. In a further 4 pts (21%), the extent of antimyosin uptake exceeded the area of WMA, which may suggest myocardial viability in the area of injury. This data suggests that using a single dose of Tc-99m antimyosin, simultaneous assessment of LV function and delineation of the extent and location of myocardial necrosis may be achieved, improving prognostic evaluation in patients withAMI.

Lette A 3-step algorithm was developed to simplify the interpretation of dipyridamole-thallium images for preoperative cardiac risk assessment. The algorithm based on only 3 myocardial segments, was developed in a pilot study of 60 pts and validated in 355 pts referred for vascular (n --234) and major general (n= 121) surgery. Study endpoints were myocardial infarction (n=ll) and cardiac death (n=19) during hospitalization.

Low risk subset: tbe postoperative cardiac event rate was 1.3% in 255 pts with normal anterior, inferior and posterolateral segment perfusion and without transient LV cavitary dilation. High risk subset of 29 pts with either reversible defects of all 3 segments, transient cavitary dilation, or at least one severe grade 3/3 reversible defect, 52% (15/29) sustained a postop event. Intermediate risk subset: the remaining 101 pts were stratified according to age >70 (p=0.01), diabetes (I 3 =0.0004) and number of segments displaying reversible defects (1 or 2) with event rates ranging from 5% to 36%.

In conclusion, using a simple 3-step algorithm with dipyridamole-thallium images, it is possible to quickly identify the large subgroup of pts at low risk (63 % of pts with a surgical risk of 1.3%) and the small (8% of totai pts) subset at high risk (50%), who account for 50% (15/30) of total cardiac events. For patients who have had an infarction the standard method of detecting residual myocardial ischemia, including silent ischemia, is the exercise stress test. The aim of this study was to determine diagnostic and prognostic value of exercise stress test (EST), 24-hour Holter monitoring (H) and quantitative scintigraphy. All the three tests were performed 2-4 months following the acute myocardial infarction (AMI). The study included 74 asymptomatic patients (pts) after the AMI. The patients were divided into two groups by results of scintigraphy: Group I -44 pts with silent ischemia, Group II -30 pts without ischemia. In Group I, out of 44 pts, 9 had a positive EST, 4 showed a painless ST depression on Holter and 7 had both tests positive, whereas 24 pts had only scintigraphy positive. In Group II one patient had positive EST and Holter. Coronary arteriography was performed in 33 pts. The diagnostic value of these methods was assessed by Bayes' Theorem. During the follow-up period lasting at least 12 months, in Group I 3 pts died, 1 developed a new myocardial infarction and 15 pts had painful ischemic occurrences. In Group II only 3 pts developed symptoms of angina pectoris. Thallium scintigraphy was the only non-invasive test showing significant correlation with the follow-up outcomes. The diagnostic and prognostic superiority of thallium scintigraphy may indicate its value as a potential screening method for asymptomatic patients after the AMI. Holter did not show any additional contribution in relation to EST. Resulter Fourteen out of 3b patients (39X) had TI strses defects. Ot tOO segments 25 (13~) had grade 0 or i Tl uptake. Fourteen had Ri~ed de~ects and in II redistribution was observed, 13 patients 13~D had rev~ree redistribution.

All but one coronary aogiographiee were normal, while 4 US were abnormal. There was no statistically significant correlation between other organ involvement, serologic markers and scintigraphi~ Findings, A tendency For negative correlation between reveres redistributlon and illnema duration was observed, but it was not statistically significant. In conclusion : i. Myocardial perFusion defects can be revealed with IL-20~ stressredistribution SPECT in patients with aclmroderma with no clinical evidenca of myocardial involvement and with normal coronary angioraph~.

2. Reverse r~diatrihutioo ~s present in patients with or without stress deFecta~ mostly in those with short disease duration. This investigation was undertaken to elucidate the clinical significances of myocardial imaging with BMIPP and MIBG in HCM by measuring the total myocardial uptake rate (tMUR) in the planar images and the regional washout rate (rWOR) in the SPECT ones, comparing to those of T1-201 chloride (TL). In 9 patients (pts) with HCM (BMIPP), and in 18 pts with HCM and 7 normals (MIBG), myocardial scintigraphy was perfumed at 15 min and 5 hr after iv injection of the tracers at rest. The tMUR of BMIPP in HCM was 4.04_+0.72%ID (n=9), which was significantly lower than that of MIBG (5.09+1.89(n=18)) and of TL (6.75+2.21(n=9))(p<0.01). In the SPECT images, the myocardium was divided to 9 segments on the Bull's-eye display and classified into 3 groups according to TL uptake (low (L), middle (M) and high (H)). The rWORs of BMIPP in HCM were 17.75+8.63% (n=14) (L), 21.13-+8.52 (n=52) (M) and 25.89_-_+6.91 (n=15) (H) (L<H, p<0.01), while those of MIBG were 36.69+11.95 (n=21) (L), 26.85+17.79 (n=128) (M) and 26.01+11.41 (n=22) (H) (L>M, L>H, p<0.01), and were significantly higher than of the normals in the all segments of myocardium. These results suggested that the fatty acid metabolism in HCM might be impaired only in the high TL uptake segments, although the sympathetic dysfunction would be spread over the all segments of myocardium. We concluded that myocardial imaging with BMIPP and MIBG was a promising tool for the assessment of pathophysiology in HCM. We investigate the prognostic importance of thallium perfusion defects in hypertensive patients without significant angiographic coronary disease. 16 consecutive patients (pts) with these findings were followed up for a mean of 49 months (range 32-64 months).

All patients, mean age 61 years, were referred to exercise stress with thallium 201 SPECT for evaluation of chest pain (ii pts) or rest ECG abnormalities (5 pts). Seven pts had ECG or echographic evidence of left ventricular hypertrophy. None had left bundle branch block. Coronorography was performed within 2 months before (7 pts) or within i0 months after (9 pts) the thallium scintigraphy.

Positive exercise ECG results were found in 3/16 pts. Ten pts developped exercise perfusion defects that completely or partially reversed 4 hours later, six had fixed defects. ~erfusion defects were located six times in the posterior wall, twice in the lateral wall, three times in the ventricular septum and three times in the apical segment. One patient with aortic valvular disease died from cardiac failure during the follow up period. No patient underwent coronary angioplasty or bypass surgery. In the absence of significant angiographic coronary artery disease, hypertensive patients with exercise thallium perfusion defects have a good prognosis during 4 year follow up.

M. Charron, W. Follansbee, G.M. Ziady, R.L. Karmas.

P r e s b y t e r i a n -U n i v e r s i t y Hospital, U n i v e r s i t y of Pittsburgh, Pittsburgh, PA. 

Myosin plasma levels (MPL) are useful for assessment of myocardial infarct size, and for detection of perioperative myocardial necrosis (PMN) after coconary bypass.Accurate means of PMN detection are needed for assessment of more effective techniques in myocardial protection. We have determined MPL by an immunoradiometric assay (MYOSIN IRMA, ERIA Pasteur, France) in 120 patients with coronmy bypass, in order to compare 2 techniques of myocardial protection currently used in our institution : "topical cooling" (Group A, n=70) vs "ice" (Group B, n=50). No difference was found between the 2 groups concerning age, sex, aortic clampage duration, number of coronary bypass grafts, technique of cardioplegia, and medical treatment. Furthermore, MPL were compared between groups of patients with or without changes in the ECG.MPL were also determi, ned in 39 patients with valve replacement (VR). Results were (Normal values<300 UI/ml): A=2002_+1424, B=1434+975 (p<0,05). MPL were higher when ECG was modified, for whole population (2400_+1189 vs 1440_+867, p<0,05) and in each group. In patients with VR, MPL (1296+1013) were similar with those of patients without change of ECG. Conclusions: 1) MPL are statistically different according to technique of myocardial protection and appear to be a useful cdteria to compare the effectiveness of these techniques ; 2) according to this criteria, ice protection seems to be preferable.

Ignasi Carri6, David Duncker, Ricardo Serra, Lluis Bermi, Montserrat Estorch, Gustavo Torres. Hospital de Sant Pau, Barcelona, Spain.

Pathologic cardiac hypertrophy is associated with myocardial cell damage. To assess cell damage in pathologic cardiac hypertrophy we performed 11~In-antimyosin studies in 13 athletes with maximal wall thickness at echocardiography compatible with hypertrophic cardiomyopathy (>13 ram). Twelve athletes with maximal wall thickness in the range of physiologic hypertrophy (11-12 ram) composed a control group. Antimyosin uptake in the myocardium was quantified by a heart to lung ratio (HLR).

In the group of 12 athletes with maximai ventricular wall thickness of 11-12 ram, antimyosin studies were normal in 10 athletes and showed minimal antimyosin uptake in 2. HLR was 1.47 +0.09. In the group of athletes with maximal ventricular wall thickness _> 13 ram, antimyosin studies were normal in 2 athletes and showed positive antimyosin uptake in 11 (p<0.01). HLR was 1.70+0.19 (p<0.001). A correlation was found between intensity of antimyosin uptake and ventricular mass index (r=0.604, p < 0.05).

We conclude that positive antimyosin uptake is highly prevalent in athletes with maximal left ventricular wall thickness >13 ram. This reinforces the concept of these athletes having pathologic hypertrophy. Antimyosin studies may be helpful in distinguishing between physiologic and pathologic forms of myocardial hypertrophy. 

This report deals with angioscintigraphic results obtained at stress in a group of normal volunteers. They were recruited for a clinical pharmacology study and had normal clinical examination, ECG and echocar-

They were studied independently 4 times, before and after administration of the medication or placebo. No difference was found between any group; hence, all studies were pooled to obtain reference values.

After injection of 740 MBq of Tc-99m HSA, equilibrium imaging was obtained in the LAO 40" projection and in the 30 ° LPO projection at each patients'visit, permitting volume calculations (*). Images were obtained with the patients sittinq on an ergometric bicycle. First, two successive groups of 24 images were acquired at rest, followed by 2 or 3 stress groups, depending on the patient's physical condition.

All groups had a fixed acquisition time of 2 minutes. Beside the mean value of each rest or stress parameter, normal limits are reported as the 5 and 95 percentiles in all acquisitions.

The reproducibility of any parameter is the average of its standard deviation (SD) calculated from the four patient's studies. These data suggest that the results of an e~uilibrium stress study should be interpreted with cautlon regarding the fairly wide range of expected stress changes in narwhal subjects, as well as of the apparent variability of changes induced at stress in the same subjects studied at different instances. dual emission tomography (DET) has proven to be useful to detect and qualify acute myocardial infarction (AMI). However, quantification of infarct size is not usually accurate, since energy scatter, mainly from Tc to T1 windows, may cause an underestimation of the size of T1 perfusion defect. The purpose of this study is to correct for the dual energy interaction and to estimate true infarct size using a simplified technique.

In 15 AMI patients, we took initial T1 SPECT images (T! I) and then Tc was injected. Four hours later, we took second T1 images (TI 2) and Tc images simultaneously using both T1 and Tc energy windows.

Twenty four hours later, third T1 images (TI 3) were obtained.

The infarct size was calculated as an extent score .(E) using Bull's eye display.

When E was compared as a percentage of T1 I, T1 2 was 71±26% (p<0.01) and T1 3 was 96±29% (NS). Thus ~ was underestimated in DET.

We obtained energy scatter from Tc window to T1 window in 10 other patients only given ~8

The nonlinear relationship, Y=4.87 X (r=0.98, p<0.01), was calculated, where Y=Tc counts in T1 window and X=Tc counts in Tc window.

We applied this formula for correcting energy scattering of T1 2 imaging and found almost equal infarct size among these three T1 imagings.

Thus this simple technique is useful to estimate infarct size in DET.

H. Valette, P. Merlet, M. Bourgui~non, B. Bendriem, A. Syrota. SItFJ-DRIPP-CEA, Orsay, France.

To study the effect of the eccentricity of the heart on the size of perfusion defects, a phantom experiment was performed. A cylindrical glass phantom containing two rectangular cold spots (width:15mm and 10ram, thickness:10mm) was filled with water + 350 gCi of Tc99m. Two tomographic acquisitions were performed: 1) the phantom being centered with laser beams, 2) the phantom in the same position, but the gantry was moved 5cm apart. The radius of rotation was the same for the 2 acquisitions. The acquisitions (high resolution parallel hole collimator = 6.5mm at 10cm in air, pixel size: 4.2ram) were performed as follows = centered phantom: 64 steps over 360 ° (matrix format 64*64); non-centered phantom: 32 steps over 1800 (same matrix format). A standard software (Hamming-Hann filter) was used for reconstruction. The data of the centered acquisition was reconstructed using both 64 and 32 projections. Defects size were measured (null value of the second derivative of a profile across the defect) on a 256*256 reconstructed matrix. Results (in mm): The results suggest that centering the patient's heart is determinant for the assessement of the size of small perfusion defects. Myocardial perftmion studies have been demonstrated to provide important prognostic information after PTCA. Sestamibi offers the opportunity to obtain simultaneously left ventricular (LV) function data by using the first-pass RNA technique.

In this study we evaluated the incremental value provided by the LV response to exercise in predicting further coronary events after PTCA. Tc-99mSestamibi (30 mCi) LV first-pass RNA and quantitative myocardial perfusion SPECT were obtained at rest and at maximal bicycle exercise (2 days protocol) in 95 patients (pts) 6+I weeks after successful PTCA (106 dilated vessels). An abnormal LV response to exercise (RNA +), defined as exercise induced wall motion abnormalities and -> 5% decrease in LVEF, was observed in 20/49 pts with normal rest-exercise myocardial perfusion studies, in 4/18 pts with fixed defects and in 20/28 pts with exercise induced perfusion defects. During the 6 months of fullow-up, 17 pts had coronary events: documented recurrent angina (6 pts), repeat PTCA (6 pts) or bypass surgery (5 pts Conclusion: Exercise LV first-pass RNA provides independent prognostic information and improves risk stratification after successful PTCA. The diagnostic value of exercise thallium-201 myocardial sciadgraphy (ETMS) for the evaluation of coronary artery disease (CAD) waS assessed in 79 consecutiv~ patients with suspected CAD. ETMS was conducted by cycloergometer (Bruce protocol), injecting 74 MBq of thalliam-201 at peak of exercise; both early and delayed scans were recorded. On the basis of coronary angiography patients were divided into three groups: 0= normal coronary vessels; 1= one-vessel disease; 2= two-and three-vessel disease. Logistic regression analysis (LR) considered both individual variables (age, sex, smoking, diabetes mellitus, arterial hypertension, family history of CAD, hypercholesterolaemia, previous myocardial infarction) and test variables (chest pain during effort, ST change positive for ischemia, perfusional score index in baSal and in stress conditions and their difference).

In a first stop, die logistic regression model considered only the results of the perfusional study (model 1); model 2 added the ECG variables (ST changes during exercise), and model 3 included the above mentioned variables plus the individual variables.

Model 1 The results obtained demonstrate that the logistic function of model 1 (ETM~t alone) achieved a good diagnostic value for the identification and severity stratification of CAD; a progressive improvement of the diagnostic value was observed in models 2 and 3, mostly for the correct patients' classification and for th(~ evaluation of the severity of disease. 

Anthracyclines are effective anticancer agents but their therapeutic value are limited by their myocardial toxicity, To determine whether impaired LV diastolic function may be an early sign of anthracyclme cardiotoxicity, a prospective study was performed using radionudide angiography before any treatment and four weeks after the end of chemotherapy. Ten patients (4 women, 6 men) with a mean age of 49,2 years (range 23 to 69 years) were studied. The primary malignancy was acute leukemia in 5 patients, lymphoma in the five others. The five patients with lymphoma received Doxorubicin (DXR) and the five others Zorubiein. They received a mean cumulative dose of 315 mg/m2 of body surface area expressed as equivalent of DXR. No patient had any cardiovascular disease at the time of treatment. We have measured R-R intervals, ejection fractions (E.F), peak filling rates (PFR), PFR expressed as fractional end diastolic volume per second, and time to peak filling rates (TPFR) before and after the end of chemotherapy. Infarct size (I.S.) was noninvasively quantitated by SPECT and planar Sestamibi imaging in a multicenter t r i a l aimed at evaluating whether the addition of Bblockade or a bradycardiac agent to thrombolysis in acute infarction further reduces infarct size. 300 patients underwent the following procedures I0 to 14 days after onset of symptoms : coronary angiography, contrast ventriculography and planar and SPECT MIBI perfusion scan. Tomographic I.S. in ml (TIS) was obtained by an automated delineation algorithm developed at our i n s t i t u t i o n .

The planar defect integral (Pint.) was determined at Yale University. Global ejection fraction (EF) and regional ventricular function (hypekin. area and length) was determined by the centerline method.

I.S. was estimated by the 72 hours cumulative release of alpha-OHbutyrate dehydrogenase (HBDH Q72). Enzymatic and scintigraphic I.S. were not significantly different with or without adjunctive therapy. SPECT and planar infarct size correlated well (r=0.80). Corr. coeff, with non-scintigraphic parameters were: HBDH Q72 Hypokin.area Hypokin.lenght EF Pint.

0.68 -0.53 0.31 -0.60 TIS 0,71 -0,59 0.43 -0.58 Thus : I) at 10-14 days after thrombolysis SPECT and planar I.S. correlate well with each other; 2) both SPECT and planar I.S. correlated well with enzymatic I.S. and global EF; 3) SPECT correlates s l i g h t l y better with measurements of regional dysfunction. 

Serial dual-isotope sointigraphy following simultaneous injection of T1-201 and 1-123 phenyl pentadecanoic acid (IPPA) was performed in 25 patients with multiple-vessel coronary artery disease before and within 6 weeks after coronary artery bypass grafting (CABG). Planar scintigrams were obtained in the anterior, LAO 30 ° and LAO 60 ° views 5 rain, 1 h (IPPA delayed images) and 4 h (T1-201 delayed images) after tracer injection during symptom limited exercise. Regional myocardial tracer uptake and clearance was operator independently quantified using a recently developed computer algorithm.

In poststenotic myocardial segments supplied by patent grafts as demonstrated by postoperative coronary angiography (n=38), uptake of both tracers in initial (post stress) scintigrams was significantly enhanced after CABG (T1-20h p=0.017; IPPA: p<0.001). Tracer deposition in delayed images remained virtually unchanged. Whereas regional T1-201 clearance signiflcantly increased after CABG (p<0.001), regional myocardial IPPA clearance was only enhanced in myocardial segments (n=10) with anglographically improved regional wall motion after revascularization (43% vs. 36% preoperatively).

The present data indicate improved myocardial fatty acid uptake after CABG which parallels the improvement in regional myocardial perfusion. The data additionally suggest increased fatty acid oxidation (as reflected by increased IPPA clearance) in myocardial segments with improved regional wall motion after successful coronary revascularization. Quantification of PET data requires exact measurements of myocardial wall thickness for partial volume effect correction. Previous studies have suggested that such determination could be made by subtracting left ventricular blood pool from transmission image. The aim of this study was to correlate these PET data with wall thickness determined by a high-resolution and independent method, i.eo magnetic resonance imaging (MRI).

The two techniques were compared in 5 male patients with anterior myocardial infarction, in the same midventricular transaxial plane. Myocardium was divided into 6 equal segments (septum, anteroseptum, anterior, anterolateral, lateral, posterolateral) and thus, 30 segments were directly compared. MRI was performed with a 1,5 Tesla device (16 frames/cycle) and gated acquisition. Wall thickness was averaged through the cardiac cycle. PET imaging was performed with a 8 mm FWHM resolution scanner. Blood volume image was determined using 8 mCi of inhalated O-15 CO. The reconstructed transmission was normalized on a pixel by pixel basis to the activity in the left ventricular chamber determined on the CO image. The blood activity was then subtracted from the transmission data.

Comparison of segment thickness measured by PET and MRI shows an overestimation of wall thickness by PET (mean 12.4~3.4 mm, range 8. 3-19.2, vs I0.7~3 .6 mm, range 4.8±18.3 for MEI, p=0.02). By regression analysis the correlation coefficient is 0.77, and a positive Y intercept (Y = 0.73 X + 4.5, p=0.03) is shown. These correlation data are worse in the thinnest segments (r=0.64 for segments>10~m,and r=0.53 for segments<10mm).

These results can be explained by the low PET resolution and partial volume effect. Thus, wall thickness is overestimated by PET imaging, and accurate measurement of thickness requires an independent method such as MRI. and 14 "controls" were included. 7 angiograms were considered either normal or with non significant stenosis. Echocardiograms were analyzed in basal state and during DOB infusion at increasing doses up to 40 ~g/kg/min, ECG and blood pressure being continuously monitored.

Patients were injected with 740 MBq MIBI-Tc-99m at the end of the In patients with CAD and without MI (N = 31), the sensitivity was 87% for MS and 81% for In controls and cases with normal CA, the specificity of MS and 2-DE was 81% and 90% respectively. Both methods, but particularly 2DE, showed lower s e n s i t i v i t y in i d e n t i f y i n g i n d i v i d u a l v e s s e l s involved: 77% and 59% for LAD, 60% and 40% for LCx and 68% and 47% for RCA, but higher specificity : 78% and 84% for LAD, 97% and 100% for LCx and 97% and 93% for RCA by MS and 2 DE respectively. In patients with MI without multivessel CAD, a residual ischemia was falsely evidenced by MS in 2/18 patients (specificity: 9 0 % ) and a false positive response was observed outside the infarct zone by .

The area of n e c r o s i s was i d e n t i c a l l y w e l l located by b o t h techniques in all cases. The identification of multivessel C~D was observed in 4/5 patients by MS and 1/5 patients by In conclusion, DOB stress testing at increasing doses is a feasible and well tolerated stress in any condition.

It has some potential advantages over currently u s e d n o n invasive stress testing methods, particularly in patients with MI.

Combining the informations of both 2-DE and MS tests, performed under the same pharmacological intervention, allows an improved efficiency in detection of ischemia. 

Necrosis size is an important f a c t o r in prognosis of pts with AMI. To estimate the extend of myocardial necrosis, we studied II pts ( 8 males ) aged 57+9 years ( range : with an i n i t i a l AMI ( 7 a n t e r i o r , 4 i n f e r i o r ). Daily levels of myosin heavy type-beta chains were determined from admission to the 12th day using an IRMA method, to look Thirty-five pts with DCM were given 2 mCi of In-lll AM. Planar and SPECT scans were taken 48 hr later. Myocardial AM Up w~s detern~ined as heart/lung ratio (uppe~ limit: 1.50) and as count density index (CDI) = heart~/lung x sternum (upper limit: 1.20).

Increased AM Up was found in 13 out of 35 pts (37 %). The clinical, hemodynamic, and histomorphometrio data were similar in pts with normal and increased AM Up. During a mean follow-up period of 20 mts (1 -34 mts), 9 pts died, 2 with increased and 7 with normal AM Up. AM Up was significantly (p<0.05) higher (CDI=I.36 0.13) in the group of pts who died as compared to those who survived (CDI=0.97 0.11) .

The survival rate was significantly different between both groups as determined by Cox-Mantel statistics. Furthermore, AM Up was not related to changes in clinical stage or ejection fraction (EF). The EF at baseline was 33.6 +/-9 . 1 % in survivors and 25.4 +/-8.6 % in pts who died during follow-up (p > 0.05 fluoro-6-thia-heptadecanoic acid has been proved to be a metabolically trapped fatty acid in mice. We succeeded in synthesizing a phenylene bridged LCFA (13-(p-[1231] iodophenyl)-3-(p-phenylene)-tridecanoic acid, PHIPA [3] [4] [5] [6] [7] [8] [9] [10] probably trapped in myocardium by an analoguous mechanism. 123I-labelling was performed carrier free by bromine-iodine exchange. The studies in 3 normal volunteers were performed after written consent and have been permitted by the local ethical committee. Under fasting and resting conditions 50 -100 MBq PHIPA 3-10 were injected intravenously. More than 95 % Of PHIPA 3-10 were bound to protein, activity was cleared rapidly from blood within 15 min. 1 -2% ID accumulated in myocardium yielding a heart to lung ratio on an average of 2.0 [range 1. 84 -2 .06 (20 rain p.i.); 1. 82 -2.15 (15 h p.i.) ]. The heart to liver ratio raised from 0.62 (20 rain p.i.) to 1.10 (15 h p.i.) indicating a very long retention in the heart muscle. SPECT Was performed 30 min p.i. Quality of SPECT images is at least comparable to [201T1] thallium perfusion imaging. First patient studies comparing imaging with [201TI] thallium and PHIPA 3-10 will be presented. 

Gated SPECT processing has been modified to generate a threedimensional set of phase data allowing short acquisition times. The earliest phases could be shown to reflect the sites of initial contraction of the ventricles, demasking Kent bundles and the focus of ventricular tachycardias (VT). The purpose of this study is to validate the procedure by experimental work in pigs.

Open chest surgel T has been performed in 10 pigs during general anesthesia. All experiments ended by cardiac arrest and were approved. Epicardial electrodes were placed to simulate the arrhythmogenic substrates of the WPW-syndrome and of VT. 700 MBq Tc99m-HSA was given. Data were acquired for 32 angles with 8 frames per cardiac cycle during 8 rain effective acquisition time. Following filtering (restoration of scatter equivalent to 10 cm water) the coefficients of the first harmonic are ~xtracted and reprojected. Following double-angulation thick slices are integrated (ISPECT), which contain all of the ventricle under investigation. Short axis, long axis, and a 4-chamber view are obtained. These functional images correspond to the planar technique, but with no background, aligned to the long axis of the heart and little superposition of the cardiac chambers.

Stimulations have been performed in 25 locations totally, resulting in a geometric precision of at least 20 rnm. For the Kent bundle simulation different degrees of preexcitation were chosen, in I0 msec intervalls. A temporal resolution of -10 msec, i.e. negative preexcitations ("hidden WPW"), showed up in this technique.

Thus, the clinical performance of ISPECT in detecting WPWsyndrome and VT is in good agreement with the experimental findings and might be used in addition to surface-ECG in order to streamline subsequentinvasive procedures in patients. 

The temporal Fourier analysis has been used to study conduction abnormalities. In the present work, it was evaluated its contribution to the detection and localization of accessory pathways (AP) present in patients (pts) with manifest Wolff-Parldnson White Syndrome (WPW). In 17 pts with WPW, aged from 16 to 65 years' old (<age>=37+16), gated blood pool angiography was performed with red blood cells labeled in rive with 1 mg of stannous pyrophosphate and 740 MBq (20 mCi) of sSmTcO~ ". One study with 24 frames per cycle, was acquired in left anterior oblique view, during 400 cardiac cycles, using a lowenergy-general-purpose collimator and a Gamma-Camera 400 AC linked to a computer Starcam 2000. It was caleulatsd the left ventricular ejection fraction (EF) and phase analysis (PH) was used to study the regional motility and to localize the site of earliest phase in the left ventricle (L), septum (S) or right ventricle (R). The time elapsed between the activation of the first two ventricular areas was also calculated. The 12-lead surface electrocardiogram (ECG) of these pts was analyzed in order to give the same information. All pts but one, with EF=45%, had a normal left ventricular systolic function (<EF>=62+9%). None had significant regional wall motion abnormalities. The following accessory pathways were identified by PH: 2 L, 8 S and 7 R. These results were concordant with the ECG study in all pts, although only partially in 10, meaning S versus contiguous free ventricular wall (L or R). The PH postulated the presence of multiple AP in 3 pts, not detected by ECG. The PH can thus have the advantage of permitting to identify multiple AP, not suspected by ECG in the absence of tachycardia. According to these results, both PH and ECG seem to be useful and complementary before invasive studies of pte with WPW. However, it was not possible to detect a valid parameter for identification of high risk pts due to short ref~'actory periods, established by clinical criteria.

A. Pradella, G. Guardigli, D. Barbieri,__~ Bauni. Dp~. of Cardiology, Nuclear Medicine Service S. Anna Hospital , Ferrara , Italy.

AND BACKGROUND. The reinjection technique improves the uptake of by the myocardium with apparently irreversible defects. We can presume that the emodynamic effect of nitrates on coronaric and periferal circulation may be a main point in the redistribution process. Aim of the study was to verify whether the contribution of nitrates to redistribution can reduce the need for reinjection, reducing costs and radiating dose. METHODS. 45 male patients with TI-201 stress myocardial scintigraphy defects were admitted to the protocol. Isosorbide-dinitrate (ISDN) was given sub-lingual 5 mg three times after the first acquisi-tion. After an interval of 3.5 hours a second acquisition was performed, followed by the injection of 1 mCi Rest-reinjection of T1201, after exercise-SPECT T1201, increases detection of ischemic but viable myocardium. The aim of this study was to assess the predictive value of residual ischemia, evidenced on exercise-SPECT-T1201 with rest-reinjectionin, in post-MI patients in whom only medical therapy was decided on.

We included 58 consecutive post-MI patients (2 F, 56 M ; age = 55+8 yrs) who had undergone both coronary angiography (29_+34 days from MI) and exercise-SPECT-T1201 with l m C i restreinjection and after which medical treatment alone was instituted. Over a 20-month follow-up period, 10 had recurrent ischemic events : I sudden death, I recurrent MI, and 8 hospitalizations for recurrent angina of w h o m 5 were subsequently referred to coronary angioplasty (n=3) or bypass grafting (n=2).

Patients with ischemic events had a higher number of cardiovascular risk factors (2.9+0.9 vs 2.1+0.9, p<0.05) but did not differ significantly when considering angiographic or exercise-ECG test data : n u m b e r of >50% coronary stenoses (1.8+0.6 vs 1.5+0.8), LV ejection fraction (51+11% vs 55+I0%), m a x i m u m ST-segment depression (0.8_+1.0 m m vs 0.5_+0.9 ram), chest pain during exercise (30% vs 10%). On a SPECT-scan analysis using a 20-segment division of LV, patients with events had a higher frequency (90% vs 54%, p<0.05) and moreover a higher extent (2.3_+1.4 vs 1.0_+1.3, p<0.01) of reversible stress ischemia.

In patients treated medically after MI, ischemic events recurrence is highly correlated to the previous presence and especially extent of residual ischemia on post-MI exercise-SPECT T1201 with rest-reinjection. Extrapolation to higher risk population need further studies.

S,Mahmo0d~ C.E.Townsend, K.Kouris, D.C.Costa, J.R.Buscombe, P.J.EII. Institute of Nuclear Medicine, UCMSM, London, U.K.

The purpose of this study was to assess the ability of a multidetector gamma camera system (Toshiba GCA 9300A) to record high resolution myocardial perfusion single photon emission tnmography (SPET) scans with an 8 minute data acquisition sequence.

"Ihallium-201 myocardial perfusion SPET was performed after i.v. injection of 74 MBq. of T1-201 at stress and redistribution (3 hours p.i.) , in ten patients using high resolution parallel hole collimators and continuous rotation acquisition mode. Projections were binned at 60 steps, with a 128x128 matrix. Three studies were extracted: 8, 16 and 32 minutes. Butterworth prefiltering and Shepp and Logan backprojection filter were applied during reconstruction, Vertical long, horizontal long and short axis images were displayed for qualitative analysis by two independent experienced observers. These were blind to clinical history, time and mode of acquisition. Nine segments (apex, apical anterior, basal anterior, apical inferior, basal inferior, apical septum, basal septum, apical lateral and basal lateral) were analysed and scored as perfusion deficit (0) or hypoperfusion (I).

Results are shown in the following Chi-square test showed no significant inter and intra observer variability. No significant difference between the number of defects in studies performed with 8, 16 and 32 minutes of acquisition was found.

Conclusion: Eight minute myocardial perfasion SPET studies is now possible using a multidetector gamma camera. With adequate filtering, not only good quality images can be obtained but increased patient throughput is an apparent advantage of this protocol. 

To assess the prevalence of myocarditis in AIDS, Indium-111-antimyosin (AM) scintigraphy was performed in 40 consecutive patients (35 men, 5 women) suffering from opportunistic infections. Mean age was 26 -5 ; one patient had a recent prolonged chest pain suggesting a myocardial infarction with normal coronary arteries at angiography ; 39 were asymptomatic; 5 had non specific repolarization abnormalities on ECG. 28 pts were treated with Azydothymidine (AZ3"). 48 hours after injection of 74 Mbq of Indium-111 -AM, planar scan of the heart was performed (3 views anterior LAO 30 °, LAO 70 °) on the two photopeaks of Indium-Ill. Presence of abnorma myocarda uptake was assessed visually and by a heart to lung ratio (HLR) > 1.8 (= mean + 2 SD value in 5 normalpatients). Six patients (15 %) had a positive scan, with HLR = 2.01 --0,14 including the symptomatic patient and two with abnormal ECG ; 4 patients were taking AZT. 34 patients had a normal scan, with HLR = 1,50 -+ 0,06. Positivity was not associated with any particular type of opportunistic infection or duration of illnass.

We conclude that Indium-111-AM scintigraphy may be usefull in the non invasive diagnosis of myocarditis in AIDS, although a chimiotoxicity of AZ] cannot be excluded. Myocarditis in AIDS may be completely asymptomatic. Prevalence of myocarditis in this serie is concordant with previous histologic studies. 4P6 Since the value of Tc-99m sestaMIBI is known and a~c~pted in the noninvasive diagnosis of coronary artery disease (CAD), the aim of this study was to define its value in identifying the different vascular territories on patients (pts) with angiographically d~cumeated CAD. A consecutive series of 55 pts was studied, all of them went through coronary angiography which showed at least one significant coronary lesion (> 50%) in a main vessel (1 vessel disease-18 prs; 2 vd-18 pts; 3 vd-19 pts). The history and ECG of 35 pts were compatible with previous infarction. Scimigraphic studies carried ont 0x rest and after myocardial stress (treadmill in 43 and after Dipiridamol in 12) were processed with SPECT mid a segmental amdysis was made by w/rich the different segments were assigned to the three main vascular territorins. In pts with previous infarction, the concordance between the necrosis area shown by the ECG and the respective scintigraphy was :analysed. The Sensitivity, Specificity-, Predictive value and Accuracy-estimate of the me~hod in idantifying the different vascular territories were ~ased on concordance or discordance between the result of sci~igraphy and aagiogt-aphy. RESULTS: Only one scnitigrapMc study was completely-normal In 94.2% of the pts with previous infarction, a concordance was found between the scintigraphy and the necrosis area revealed by the ECG. In 18 pts without history or ECG compar.ible with previous inferction, fixed perfusioa defects were detected, which corresponded in 1,¢ pts (77.8%) to a vascular territory depending o~ coronary-atzery with significant stenoses. CONCLUSION: 1. The Tc-99m MIBI with SPECT shows a high diagnostic accuracy to segmant~l identification of CAD and it is the highest concerning significant steanses in anterior descending artery. 2. The presence of fixed perfusion defects in the population studied is very ltigh. As the presence of myocardial necrosis was excluded by medical history and ECG, evidence of fixed perfusdon defect was related, in the present series, to significant coronary srenosis in more than 3~4 of the pts, which gives rise to the problem of myocardial viability-diagnosis with this kind of radiophermacearica[. When baseline eLVEF = 0 to +11%, the lower limit of 95% PI allowed for a fall at 6 months ranging from 13 to 15%. For baseline exercise LVEF of 50% and 35%, the respective lower limit of 95% PI was 39% and 26%; e.g. the exercise LVEF could be measured at 50% (just normal) at baseline and as low as 39% 6 months later without necessarily indicating true deterioration.

Thus, long-term serial measurements of LVEF at peak exercise and ~LVEF by first-pass RNV are sufficiently predictable to contribute to the followup of minimally symptomatic CAD patients. Further study is in progress to determine whether prediction intervals should be set at a probability less than 95% to predict adverse cardiac events. In patients with coronary artery disease (CAD), silent myocardial ischaemia is readily detected by exercise radionuclide ventriculography (RNV).Such easily inducible ischaemia may ~ be assumed to reflect Susceptibilty to repetitive silent ischaemia during daily activity. To see!if this affects left ventricular (LV) systolic function over time, 34 aslrmptomatic, event-free, medically treated patients (age 57, range 37 -69) with silent ischaemia were prospectively studied. Nine patients had 3-vessel [-1 ,+4] ~LVEF -6 (6) -4 (9) 0.ii [-1,+5] Thus, in asymptomatic event-free CAD patients, silent ischaemia which is easily inducible despite medical therapy does not lead per se to deteriorationof LV systolic function at rest or exercise over 12 months.

Nili Zafrir, Roni Bassevitch, Ernesto Lubi~. Massada Nuclear Cardiology Unit, Nuclear Medicine, Beilinson Medleal Center, Petah-Tikva.

Dipyridamole Thallium myocardial imaging is a well known method for predicting future cardiac events. In this study we examined the ability of Dipyridamole (Dip) with First Pass Radionuclide Ventriculography (FPRNV) method to predict cardiac events.

One hundred fifty six consecutive patients who underwent Dip FPRNV between dates 1.89-1.91 were followed up for cardiac events including cardiac mortality,non-fatal MI, CABG, PTCA (mean follow up 326+200 days). Positive criteria for ischemia were: decrease of LVEF~5%, wall motion abnormality, or both. 99 pts (69%) had negative criteria and 45 pts(31%) had positive criteria for ischemia. The incidence of cardiac events are summarized in the following A slight but significant (p<0.05) increase of activity ratio was seen in the first group. Heart/lung ratio was 1.37 ± 0.20 before grafting and increased to 1.55±0.22 at 15 days and 1.58±0.13 at 50 days post transplantation. Similar results were obtained in the second group. Activity ratio was 1.39 ± 0.18 before irradiation and I,.56±0.16 after it (p<0.05)-Conclusion:

The slight but significant labeled antibody incresase seen in both groups may be due to slight, subclinical myocardial damage, lllInantimiosyn myocardial scintigraphy may be usefull in evaluating radiation myocardial day,age. After mantle field radiotherapy for Hodgkin's disease, the incidence of myocardial abnormalities remains controversial. Twenty five asymptomatic patients (11 males, 14 females, mean age: 35 years) were studied 7 years (range: [3] [4] [5] [6] [7] [8] [9] [10] [11] after radiotherapy. Thallium SPECT data were obtained 5rain after exercise (at least 85% of the predicted maximal heart rate), 4hours later and at rest (1 week later). Images were analyzed visually and quantitatively (sectorial analysis of bull's eye images of short axis slices) compared to those of 35 subjects with a low likelihood of coronary artery disease. ECG exercise testing was normal in all the patients. Images were visually abnormal in 21 patients (84%) showing an heterogenons T1 uptake. In 60% of the patients, T1 uptake (in at least one sector) was lower than the mean T1 uptake value measured in subjects with a low likelihood of coronary artery disease. Redistribution was present in 9 patients. In 2 patients, the resting images demonstrated a "filling-in" of a 4hours defect. In most of the patients, the location and the shape of the defect(s) does not seem be related to an epicardial coronary vessel stenosis. Thus, after mediastinal radiotherapy, T1 myocardial uptake is frequently abnormal. The observed pattern suggest a disease of the small coronary vessels and/or the existence of a myocardial fibrosis rather than a disease of large epicardial coronary vessel. 

The identification of ischemic but viable myocardium by thallium exercise scintigraphy is often imprecise, since many exercise perfusion defects do not improve on images 4 hours after redistribution. Aim. The purpose of the study was to determine reliability of detection of viable myocardium by imaging early after injection at rest by comparing these results with 24 hours redistribution images. Methods. Scintigraphy was performed 20-40 minutes after T1-201 injection at rest and 24 hours after exercise, in 44 patients (29 after MI) with defects on exercise thallium imaging 4 hours after injection. Results. Thallium uptake was seen in 55% of defects , seen 4 h after exercise on 24 h redistribution images. Uptake early after injection at rest was present in 51%, in two patients 24 h redistribution was not present. Concordance between both methods was 87%~ Viable myocardium was demonstrated in S2% of segments supplied by coronary artery with 75-99% stenosis, and in 48% of segments with total occlusion. Conclusions. Injection of thallium at rest and imaging soon after injection can reliably demonstrate viable but ischemic myocardium. This was the case even in the subgroup of patients surviving myocardial infarction. Experimental data show that heterogeneous sympathetic innervation of the heart is expected to result in asynchronous myocardial contraction.To examine a possible relation between sympathetic denervation post myocardial infarction (MI) and l e f t ventricular asynchrony, 18 male pts post MI (55±13 years old)with one-vessel disease were examined. Tl-201 SPECT at rest was used to assess necrosis and 123I-MIBG to assess denervation. Polar maps of TI-201 and L231-MIBG were generated. In all pts z23I--MIBG defect was larger than  indicating denervation outside the infarcted area. Difference of 1231-MIBG and Tl-201 defects was estimated as % of total polar map and located.Gated blood pool scanning was performed within one week.Fourier phase images (color-coded phase display) were used for detection of phase disturbances in regions outside the infarction, related to the locations of denervated but perfused myocardium.9/18 pts presented abnormal phase display in areas outside MI and related to the location of MIBG/TI mismatch.ln these pts mismatch was 21±11% while in 9 pts with normal phase display outside MI mismatch was 11±9% (p<O.05). In 5/9 pts with abnormal phase mismatch was >20% while in 2/9 pts with normal phase mismatch was >20%. In conclusion:l) Pts pMI present denervation outside infarct area, frequently related to abnormal phase display in denervated but perfused area. 2) Larger MIBG/TI mismatches are frequently associated with abnormal phase display. Dobutamine TI-201 scintigraphy appears to bea useful method for evaluating coronary artery disease butits accuracy in detecting residual ischemia in post myocardial infarction (MI) patients (pts) receiving antianginal therapy is unknown. 16 pts (12 male, 4 female) 56±14 years old, with recent (<3 months) MI were examined by SPECT for detection of ischemia in infarct zone and at distance; extent of disease was known by coronary angiography. B-blockers were administered in 7/16 pts, nitrates in 10/16 and calcium antagonists in 5/16 pts. IV dobutamine was infused in graded doses to a maximum of 40 Ng/kg/min. Coronary angiography revealed 24 diseased vessels (diameter reduction >50%); 16/24 were infarct related vessels and 8/24 supplied segments at distance. Heart rate rose from 65±10 to 97±21/sec and blood pressure From 135±21 to 160±23 mmHg. Angina presented in 5/16 pts and ST depression >1 mm in 3/16 pts.lschemia in infarct zone was detected in 12/16 pts; in 8 of them ischemia was detected only after reinjection. [schemia at distance was disclosed in 4/8 segments. 4 diseased vessels at distance were not detected;3/4 were left circumflex coronary artery, In conclusion: i) Dobutamine Tl-201 SPECT can frequently detect ischemia in infarct zone and at distance in post MI pts receiving antianginal therapy.2) Reinjection frequently is necessary to detect ischemia in infarct zone. In addition to the amount of irreversibly damaged myocardium, the critical factor influencing long-term prognosis following acute myocardial infarction (MI) is the degree and extent of residual ischemia. In a series of 43 patients (pts) with a first Q wave MI (19 anterior; 24 inferior), left ventricular firstpass ejection fraction (LVEF) and myocardial perfusion tomoscintigraphy were obtained with . Patients were studied 13+4 days after the acute event at rest and at maximal symptom-limited bicycle exercise: 3 pts had chest pain, 10 pts had >-lmm ST segment change, 21 pts had exercise induced wall motion abnormalities and a > 5% decrease in LVEF, and 30 pts had exercise induced perfusion defects involving either the infarcted territory (15 pts) or a remote territory (15 pts).

The clinical history, the location of infarction and the anatomical severity of disease on coronary arteriography were not predictive of the amount of myocardium at risk as it had been quantitatively assessed by the changes in LVEF, myocardial perfusion score, and ST segment depression. Furthermore, whether residual ischemia was present in the infarcted territory or in a remote territory, both the extent of myocardial perfusion defects and the LVEF at maximal exercise were of the same magnitude as for patients with fixed defects.

We concluded that the extent and severity of residual ischemia cannot be predicted and should therefore be assessed for each patient after acute MI.

J Schroeder B van Vlies, M Tiel, EA van Royen and AJ Dunning. Academic Medical Center, Amsterdam, the Netherlands.

Introduction: Reinjection (RI) of Thallium-201 in a persistent perfusion defect (PPD) has become a common procedure in most centers, which inevitabIy leads to a sharp increase in costs.

Patients and methods: To assess the relation between delayed uptake (DU) after RI and signs of ischemia during exercise or history of previous infarction (MI) we studied 72 consecutive patients with a PPD in planar TL-201 stress-redistribution imaging following symptom limited exercise. RI with 80 MBq TL-201 was performed 1-4 days later under nonischemic conditions. Images were obtained in LAO, anterior and left lateral view and evaluated for the presence of complete or partial DU in regions with prior PPD by two observers.

Results: During exerdse 16 pts had both chest pain (CP) and ECG changes, 28 pts had only ECG changes and 6 pts only CP without ECG changes. In 21 pts no CP or ECG changes occurred, 40 pts had a previous MI. Complete or partial DU was present in 46 pts. The 4 pts with DU without ECG changes or CP had no history of previous MI in contrast to 3 of the 17 pts without DU.

Conclusion: DU is frequent in pts with PPD after stress-redistribution imaging and highly related to the presence of signs of ischemia during stress or the absence of previous MI. RI and late imaging is therefore not necessary in patients with PPD and old MI without CP or ECG changes during stress testing.

~ ~rbas. M Calg~ner, S Kes, T Erbas, Y Karaaslan, CF Bekdik. Hacettepe University, Medical School, Depts. of Nuclear Medicine and Internal Medicine. Ankara-Turkey.

Behcet's disease is a multisyste m disease. However, cardiac involvement has relatively less recognized. Noninvasive imaging methods may reveal a cardiac disorder which has not manifested itself clinically. Radionuclide ventriculography (RV) and Doppler echocardiography(DE) were performed in 24 patients with Behcet's disease.

Patients had neither known heart disease nor cardiac symptoms. Ejection fraction, peak filling (PFR) and ejection rates (PER), 1/3 ER, 1/3 FR, time to peak filling (TPF) and peak ejection The other parameters did not differ significantly.

Nine patients (37.5%) demonstrated impairment of diastolic function, and three (12.5%) of them had abnormal systolic function using radionuclide method. Twentyfive percent of patients had diastolic dysfunction without Systolic impairment. DE observed abnormal ventricular compliance only in 13.6% of patients. As a conclusion, noninvasive imaging methods such as RV and DE may be valuable to detect diastolic impairment as an early sign of cardiac involvement in Behcet's disease. However, RV seems to be more sensitive than DE to assess diastolic dysfunction. 

Thirty-two patients (27 men and 5 women) were prospectively studied to assess the value of dobutamine Tc-99m Sestamibi SPECT and planar gated imaging in the detection of coronary artery disease (CAD). All patients underwent echocardiography during step-wise dobutamine infusion (starting with 5 ug/kg/min up to a maximum dose of 30 ug/kg/min). Sestamibi injection was made intravenously one minute after reaching the peak infusion rate. Tomographic and gated imaging were performed i hour after the Tc-99m Sestamibi injection and repeated 24 hours later with the injection of a second dose. NO complications were experienced due to dobutamine infusion. All patients underwent coronary angiography. The overall sensitivity and specificity of dobutamine Sestamibi SPECT and planar gated study were 88% and 93%, respectively; for the detection of CAD when compared with angiography. Information provided by Dipyridamole Thallium. SPECT quality is limited by the important thallium uptake in the infradiaphragmatic area. The aim of this study was to assess the ability of a low level bicycle exercise to improve the contrast between myocardium and adjacent area. After myocardial SPECT imaging, a whole body anterior image was acquired: -Grou~p I (13 patients): dipyfidamole infusion alone (0,56 mg/kg in 4 nunutes).

-Gro.up II (10 patients): maximal or submaximal level bicycle exerose.

-Group III ( 10 patients): hffusion of dipyridamole combined with a low-level b~cycle exercise during 4 minutes (40 watts for males, 30 watts for females). The mean ,pixel activity was determined in heart, lung, liver, spleen, and infradiaphragmatic area. Ratios of heart to lung (H/L), heart to liver (H/LI), heart to an infradiaphragmatic area (H/ID), and heart to spleen (H/S) were calculated.

H Univers!ty Hospital Frankfurt/Main, G e r m a n y Rubidium-generator (Mallinckrodt) was in use for two weeks. A total of 41 patients were examined. The clinical question were mainly suspicion diagnosis of CAD (n=20), follow-up under conservative run (n=12) or after invasive intervention (n=9). Scans were performed with the PET ECAT 951 (Siemens).1.85 GBq S2Rb were administered before and 3 min after Dipyddamol-infusion (0.56 mg/kg over 4 rain). Usually static scans were acquired over 6 min, in special cases dynamic sequences were taken. Including a follow-up observation of 30 rain the total procedure lasted about 90 rain ( 60-150min) . No adverse reactions were seen. Because of claustrophobia, 3 patients had to be treated with Diazepam. The daily load was between 3 and 6 patients. Despite of scout scans sometimes parts of the antedor and inferior myocardium were not completely mapped. After an initial adaption phase the 82Rb-generator was running smoothly. System restarts were somewhat frequent (6 times), sometimes during acquisition, however, all exams could be completed. Reorientated slices of 1.2 cm thickness were computed. Without 3-Dsmoothing of the transmission scan severe image artefacts were observed, which, at times, strongly affected the evaluation. Image documentation was done with absolute and relative intensity scale on Xray film. Diagnosis was performed on the basis of these images. An increase of myocardial blood flow after Dipyridamol-infusion was observed in 24 of 39 analyzed studies, relative decreases after Dipy. (ischemia) were found in 4 patients, constant flow decreases (infarction) in 11 cases. In opposite of the easy and safe use of fhe Rb-generator, the available software used for the exam has to be optimized. Compared to the SPET (2O~TI-or ~9mTc-MIBI) no improvement of the clinical results were seen when using the 82Rb-PET equiped with the standard software. This study examined the results of dobutamine (DOB) stress testing with evaluation of cardiac and non cardiac side effects in ii0 consecutive patients suspected of having coronary aruery disease (CAD) and in 49 other ones with a history of recent or previous myocardial infarction (112 males and 47 females; mean age 57, range 41 -70 years) .

In all patients, MIBI-SPECT and two-dimensional echocardiography were simultaneously performed using a DOB infusion stress a~ increasing doses up to 40 ~g/kg/min. DOB was adminisuered intravenously beginning at a dose of i0 ~g/Kg/min with increasing by 10~g/kg/min increments every 3 minutes. The ECG was continuously monitored andblood pressure was recorded at each stage. In some patients, Atropine (0.25 to 1 mg) was added to increase maximal heart rate (especially in treated patients by beta blockers and/or calcium antagonists when treatment could not be s~opped).

Most patients had transient minor side effects and some of them (16%) had significant side effects with DOB consisting of chest pain in 6%, hypotension in 1%, ventricular arrythmias in 3% and tremulousness and/or headache or dyspnea in 6%.

[schemic ECG changes (significant ST segment depression) were observed in 26% of cases.

Among 64 patients also undergomng cardiac catheterization, side effects were unrelated ~o the number of vessels with CAD. In these patients, the overall sensitivities of DOB stress MIBI-SPECT (87%) and were both higher than that of DOB stress ECG (23%). There were no deaths, myocardial infarctions due to DOB administration.

Intravenous DOB, at increasing doses, is relatively safe, well tolerated, widely available and easily feasible as stress testing and has few serious side effects. The purpose of this study was: (1) to develop a set of profiles of normal distribution of planar Tc-SESTAMIBI obtained from 20 male healthy volunteers, and (2) to study the results of quantitative analysis (QA) with a modified background algorithm to estimate the risk of CAD in 14 pts with normal coronary a~leries and in 46 pts with CAD and to compare the results with visual analysis. Univariate analysis of variables used during visual (v) and mean and maximal (Q) circumferential profiles in terms of Odds ratios. Our data indicate that processing on the basis of the maximal count profile resulted in a better prediction of the presence of CAD and diagnostic accuracy is significantly increased with combined visual/quantitative analysis (stepwise likelihood-ratio statistic: p=0,014). Brewerton (1985) in patients with ankylosing spondylitis (AS). We used gated radionuclide ventriculography (GRNV) to assess abnormalities in diastolic function in a group of AS patients without valvular disease. Method: 30 AS patients were studied with GRNV at rest and during upright bicycle exercise. The control group consisted of 30 matched healthy subjects. Mathematical procedures developed by our team were used to measure the following parameters of the activity-time curve under both conditions: ejection fraction (EF), peak filling rate (PFR), time of PFR (TPFR) and time of isovol~metric relaxation (TIVR). Student's t test was used in the statistical analysis. Results: No significant differences between the two groups were found in heart rate at rest or during~ effort. PFR at rest and during exercise was lower in AS patients than in control (2.0 + _ 0.6 vs 1.6 + 0.5, p< 0.05 at rest; 2.7 + 0.6 _ _ vs 2.3 ~ 0.7, p < 0.05 during submaximal exercice). No significant differences between patients and control were found in TPFR or TIVR under either conditions Conclusion: Evidence of an alteration in rapid ventricular filling was found at rest and during effort in AS patients; this change was probably due to an increase in myocardial reticulin. The aim of this work was to assess the value of gated single photon emission tomography (Gated-SPECT). 12 patients (7 men, 5 women, age= 63 + 13.8 years) were studied by Gated-SPECT and biplane ventriculography (BV) . Red cells were labeled with 740 MBq of Tc99m by the in vivo technique. Sixteen gated frames were acquired at 32 angles over a 180 ° rotation (left posterior oblique to fight anterior oblique). After reconstruction and reorientation, quantitative analysis was performed. From five slices (3 short-axis sli~es, a vertical long-axis slice and a transversal long-axis slice at the mid-ventricular level), septal, anterior, lateral, and inferior walls were studied at apical, median and basal levels. An apical segment has been added leading to the examination of 13 segments. Regional ejection fraction with background correction (EF) or without background correction (NEF), phase difference between the regional phase and the mean phase calculated from the whole slice (Phdiff) were calculated for all segments. From the BV, 125 segments were classified as normal with E F -66.12 + 16.6 %; NEF= 44.28 + 13.72 %, Phdiff= 0.18 + 8.81 ° . When studying normal segment according to their anatomical location, EF, NEF and Phdiff were not found to be different from one segment to the other. 31 segments were considered as abnormal : EF=47.83 + 1 9 . 7 1 % ~<.001), NEF= 27.7 +13.97 % (p<.001), Phdiff= 3.87 +_ 11.03 (NS). Phase analysis does not seem to be a sensitive method to detect wall motion abnormalities. The differentiation between normal and abnormal segmems evaluated by regional ejection fraction is not dependent on background correction. Gated-SPECT seems a promising technique to assess the regional ventricular function. systolic and diastglic function after maximal exercise in R hypertensive (AH), coronary artery disease (CAD) patients (pts) and in a group of healthy individuals (H). 22 pts with AH (aged S4 ± 7 yrs), 24 with CAD (SS±S yrs) and 20 H (52±14 yrs) were studied. All patients underwent rest and stress radionuclide ventriculography, with additional imaging 5, I0, 20, 30 min after exercise. The changes of left ventricular ejection fraction (LVEF)~ peak ejection rate (PER), peak filling rate (FFR), time to peak filling r~te (TPFR) and heart rate (HR) during and after exercise were monitored, y CAD'

The rate of recovery after exercise of LV systolic and diastolic function parameters is different between three groups. It seems that additional monitoring ~fter exercise add to diagnostic information. All stress dependent changes in LV function occur within first IS minutes after exercise in ~ii groups. The values at 20 minute after exercise are not statisticaly different from rest values. The monitoring further than 15 min after exercise does not obtain any ~dditional diagnostic information. The concept of severity of coronary obstruction based on grading coronary stenosis has been challenged. In order to reevaluate this concept we studied 57 patients with previous myocardial infarctYon with mean age 54.34+7.05 years' old. All patients were submitted to coronary anglography and thallium 201 SPECT studies (2mCi, stress in cycloergometer and redistribution after 4 hour of rest), performed within 3 tp 5 months of the myocardial infarction. We selected 29 patients (50.8%) with minimal anatomical lesions ~50%).

A total of 43 arteries with minimal lesions was found on coronary angiographies: of the main stem 3 arteries, with ischaemic thallium pattern (IsT1) in 2; of the left anterior descending artery 13, with IsT1, 4, with necrosis thallium pattern (NTI), 4, and with normal perfusion thallium pattern (NormalT1), 6 arteries; of the left circumflex artery 10, all with NormalT1; of the right coronary artery 17, with IsTl, 12, witla NT1, 3 and with NormalT1, 2 arteries. In a total of 43 arteries with minimal angiographic stenosis we identified 25 (58%) functionally significant lesions, 18 with ischaemia and 7 with necrosis. We may conclude that the criteria of coronary artery disease severity must be redefined. Thus the maatomical quantification of the obstructive lesion should be complemented with physiological information in order to evaluate the real functional capacity of the obstructed vessel. Technelium-99m MIBI is a lipophilic complex %h~% ~ocumula%es in viable myocardial %issue proportional %o the regional myocardial blood flow.

Thirty-two p~%ien%s with suspected coronary disease were studied by Single Photon ~nission Computed Tpmograplkv (SPEGT) imagining ~i%h oblique reconstructions of %he myocardium follo~ing %he intravenous. injection of Techne%ium-99m MIBI substance. All pa%ien±s also underwent %hree-vesel coronary angiography and ~oh~-Doppler si~idies.

The 8PEOT-%eol3/tique produced very de%ailed images allo~ng easy delineation of loe~lizod myooamdial defects..qe~en%al myocardial uptake defects were compared ~ith diseased vessels ~s sho%~ a% angiography.

Defeo%s~ even% small ones~ stand out so clearly %ha% less experience will be required %0 interpret %he images compared with s%~dar% planar Thalit~m studies.

We believe %ha% good quality of %he %omographi¢ images with MIBI-subsT~a~toe will enable us %0 approach the limit of accuracy of any isotopic %eohniqt~e for de%el~ninit~g myooamdi~l, perfusion, Oblique angle reoo&struo%ion was used %0 enable %omographio slice %0 be obtained rely%ire %0 %he long axis of %he hear%, %he lie of wioh was de%e~miAed drom %ranseevre and coronal images.

The digi%~l images were displayed on TV-moni%or in 16 grades of oolot~T linearly related %0 %he ima~. intensity o.a.d, with MIni ~ooumula%ion in %issueso 4P8-7 V. Sergienko, A. S~etnev, L.Samoilenko, F. Esschanova, A. Gorgaslidze.

To assess relationship between microcirculatozlz changes and left ventricular contractility in alcoholic heart disease (AHD) with ventricular ectopy we studied 30 patients (pts) with chronic alcoholism, II stage (aging 38,5+5,0 years) using 201TI scintigraphy and e£9/_ ilibritwn radionuclide ventriculography.

Tl-imaging was performed at rest and 3-7 days after stress tests followed by registering scans 4 hours after Tl-administration in both studies. All pts showed decreased perfusion in different areas, but primarily in the septal area, as well as diffusion abnormalities in washout. Total Tl-uptake at rest was 2,6+0,3%.

Responding to stress tests, many of the pts showed more ho~ogenic distribution of T12DI , normal washout and an increased 6+_2, 8%) . 20 pts with persistent perfusion defects showed normal coronary arteries by coronary angiegraphy.

All pts had normal left ventricular systolic function at rest and during exercise in the absense of local abnormalities of contractility.

Thus, many of the pts with AHD showed perfusion defects on a microcirculatory level which resulted in a decreased functional perfusion reserve without local contraction abnormalities. The aim of the study was to evaluate small vessel disease in patients with Insulin Dependant Diabetes Mellitus (IDDM) using exercise whole-body TL-201 scintigraphy. Patients and Methnd: 25 patients with IDDM (mean age:23) were studied. In 11 patients the clinical course of IDDM was less than 10 years (DM-1), whereas in 14 patients it was ever this period ( . 10 normal volunteers (mean age 25) were studied as a control group (C). 4 mCi was injected at the peak exercise. Early and delayed posterior whole body images were obtained (20 cm/min). Simetric ROl's were drawn from early and delayed images around the gluteal regions, thighs and calves. Regional Percent Activity of 

BLF v. Eck-Smit, BM Goslings, RAJ v.Sorge-v TBS is still controversial. Eighty-seven patients were examined in their follow-up for DTC. All patients were treated by total thyroidectomie followed by an ablative dose of I-131 (1850-2800 MBq) 4-6 weeks later. In 70 patients routine control of serum Tg, and TBS was performed 4-6 month after ablation and 5 weeks off T4. Seventeen patients were evaluated similarly because of increased Tg or clinical suspicion of recurrent DTC at later follow-up Parathyroid substraction scanning is usually performed using . The sensitivity using T1-201 varies widely and results as high as 100% or as low as 42% are reported. Tc-Sestamibi might be advantageous because of its physical and biological properties including its high mitochondrial concentration. A dual isotope substraction technique using Sestamibi minus iodine might therefore improve the sensitivity for parathyroid adenoma detection. We compared scintigraphy in the preoperative localization of parathyroid adenoma in 7 patients presenting a biological pattern of hyperparathyroidism (group A). Seven patients without hyperparathyroidism were studied using Tc-99m Sestamibi/I-123 only as a control group (group B). Two patients with cold thyroid nodule were studied before surgery (group C). In group A, we obtained correct localization in 3/8 patients using T1-201/Tc-99m and in 6/7 patients using . We observed one false negative result with both methods in group A. All patients of group B have negative results. Positive results were found in patients of group C. The tissular concentration of Sestamibi in a fragment of the parathyroid adenoms measured in one patient represented 150% of the vslue of a thyroid fragment.

In conclusion, parathyroid substraction scanning using Tc-99m Sestamibi/I-123 seems more sensitive in the localization of parathyroid adenoma without affecting the specificity of the method but its value after parathyroid surgery needs further investigations.

~ van Dongen' : N.P. i~ G. Verhoeff', F. B~melman", and ~.'. ~ van ~oyen ' ----. De ,l~rt~e. nts .of ' Nuclear and "Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands

In total i0 l~_tients (5 mer~ 5 women, ag~ed 28-72 yrs) have been st~/died with 11 iIn_Pentatreotide ( m • ~In-SMS, Oc,treo~.ca~.~; .sp~c.,.act., [11] [12] [13] [14] [15] [16] [17] MBq/~g) for various enaoor~no, OqlCil c~soraers.

,.Whole body planar imaging was performed in 7 patients at 19-48 h after ihjection of 82-220 MBq of • ~mIn-SMS~ using the Siemens dual head Bodysca~ .careers_ '.lne res01ts we.r 9 c.o .~_ with ~I-MIBG scans in 6.pa.t~,ents..In 4 l~.t/ents (3.with a metastasized carclnomd, 1 wl.th an intrahepatlc APUDoma) I~In-SMS ShsO~ ~ more leslons ~ Im~I..-,MIBG. In 2 p~tients the res ,us were comDaraole (I wir_n a metastasized carcl.noid~ I with a metastasized medullary thyroid carcanc~a).

,B~.'n.SP..E~T took place in 61patients at 5-48 h after ln3ectlon of 89-24? MBq ~In-SMS. The SMEs~o camera was used (5 sin/slice, I0 mm spacinq). In all ~at.ientg,, ,the hypophysis was clearly v, isibIe co ,m~led uo ~ne mack ,g~oun~, .-Skull met.~.tases oz a carcinolm were. bq.tte,r loc.allze,d ~ wlth pl ~a~a~, imagi.ng.~ A TSH prc~ucln@ nypopny~, eai aaenoma revea-~em a mar~y l.r~. reasea up~a~..e both in SPECT with ~In-SMS and with the selectlve dopamine D2-recept_or antagonist ~I-I_odobe_nza~i, 'de. ~The hypoph~si~s, of~ the patient with • e '±~ pr~_uclng aaenoma was uezinea using a 70 % msOcontour line ~n the ~=~I-Iodobenzam/de SPECT. The hasYS.is/ce.re.be.llu~, ratio in this patient was 2, the stria~um/cerebellum ratio was I. 6. Tl/is suggested that ,the dbpam/ne D2-rec_epto.r We investigated the metabolism and binding characteristics of in rats with the transplantable pancreatic SR÷ carcinoma CA 20948 after i.v. injection with IRC alone or 45 min after s.c. administration of I mg . IRC was accumulated in SR+ organs and in tumors, followed by a rapid clearance from these tissues, with specific uptake (untreated vs treated, %dose/g), 0.5 and 4 hr p.i., but not 24 hr p.i. In this study we could not visualize tumors by y-camera scintigraphy despite specific uptake in the isolated tumor(0.23 ± 0.07 vs 0.11 ± 0.02; p<0.001), 0.5 hr p.i. and (0.20 ± 0.05 vs 0.08 ± 0.02; p(0.001), 4 hr p.i. This is in contrast with the positive visualization of the tumor by y-camera scintigraphy in similar experiments using T30 (Bakker et El, J Nucl Med 1990; 31:1501 -1509 . In another study with normal rats we compared T30 and IRC by isolating several SR+ organs 4 hr p.i. Uptake was similar (IRC vs T30) for the adrenal glands (0.23 ± 0.08 vs 0.23 ± 0.07), but significantly higher for T30 in the pancreas (1.03 ± 0.15 vs 0.21 ± 0.05; p<0.001) and in the pituitary gland (0.32 ± 0.09 vs 0.07 ± 0.01; p<0.001). The higher remaining radioactivity in all organs analyzed (i.e. blood, liver, spleen, kidneys, lungs) with IRC indicates a higher background radioactivity. Experiments in the isolated perfused rat liver showed a rapid uptake of IRC and T30 in the: liver. The radioactivity excreted in the bile in the IRC-experiments was mainly not peptide-bound, while the T30-experiments showed more and intact T30, this indicates a lysosomal pathway for IRC. Conclusions: IRC did not have the expected potentials as a radiopharma-ceutical like T30 although there are differences in relative uptake in different organs. The main reason is the low tumor/background ratio of IBC. The primary hyperparathyroidism is most often developed by the adenoma of this Bland.The determination of PTH level itself is not sufficient to issue the decision of surgical treatment. In order to indicate precisely the site of surgery it is necessary to visualize the parathyroid glands.

In the Department of Endocrinology, Medical Academy of KrakOw, 9 patients suffering from primary hyperparathyroidism have been examined. They revealed increased PTH level and alteration in osseous system. Comouter tomography of the neck were performe d in all patients in order to evaluate morphologic state of parathyroid glands. They also underwent scintigraphy with subtraction method using a ZLC Digitrac Siemens scinticamera connected to a Microdelta computer. The examinations were carried out in two stages: with the use of 201 thallium and then with Sestamibi (methoxyisobutylisonitrile) labelled with 99m technetium. All 9 patients underwent then surgeries. Histopathological exams confirmed in all the patients the existence of adenoma in two parathyroid glands. The precision of adenoma localization was then evaluated. It was found that in four patients the CT diagnosis was COrDect, while in 6 patients the correct diagnosis was obtained with scintigraphy using thallium, and in as many as in 8 of ? pa tients, the scintigraphy using Sestamibi gave positive results. Our results show, that parathyroid adenoma may be also visualized by use of Sestamibi -99m Tc. The Radiopharmaceutical,meta(I-131) iodobenzylguanidine (I-131-MIBG) was found to concentrate in many neural crest derived tumors such as pheochromocytoma,neuroblastoma,carcinoid tumor,paraganglioma and thyroid medullary cancer. Thyroid medullary cancer is the tumor derived from parafollicular cell(C cell) and is said to be pathologically neuroectodermal cell origin. We have evaluated I0 patients( 3 men and 7 women) age 48~9 (mean~SD) whose serum calcitonin and/or CEA levels are high after surgery of the primary lesion. 

Hysterosalpingoseintigraphy has been proven as a method for the diagnosis of functional Fallopian tube patency. The radiation exposure of this procedure is only 1/10 of the exposure of conventional hystero-salpingography.

We investigated prospectively 56 females with infertility between day 9 and 16 of their menstrual cycles. For this reason 10MBq of Tc-99m labelled human serum albumin macroaggregates (diameter 5 -40urn) were applicated into the posterior vaginal fornix. Gammacamera (GE MAXICAMERA 300) images were performed in anterior projection of the pelvis 10min, lh and 4h p.i.. Sonographically the dominant follicle during this menstrual cycle was located in one of the ovaries. The patients were clinically followed up for at least 6 months.

In 35 of 56 patients at least one of the tubes could scintigraphically be detected and its patency be documented. In 34 of 35 patients (97%) only the tube at the side of the dominant follicle could be visualized, the opposite tube showed no transport of the rnacroaggregates . 16 out of the 56 patients became pregnant during the follow-up. In all of them tube patency could scintigraphically be detected. In 21 of 56 patients none of the tubes showed fanctional patascy . None of these females got pregnant.

In conclusion, HSS reliably shows functional patency of the tube andduring day 9 and 16 of the menstrual cycle only the follicle sided tube was patent. An endocrine regulation of the tube patancy has to be discussed. Thalas-saan~a Intermed~a (TI) . Hgpogcnadotrop~c hypogenadSan has been fotmd in some cases; whether Leyding cell f~ctJon is also affected is still controverdi~l. To fanther investigats this problem we studied, over a period oflO yrs, ii Beta hermozygoue male pts,who had never recdived i~ansfusic~s, sged initially 21-36 yrs, affected by TI. Eight pts hed undergone splanectany many yre befc~e the study. ALl cases were in ~ stsge £-5. Avensge F~ level was 9.11 ~ -1.7 ng/dl snd ~ ferritin 3234J~2302 ng/ml. In all pts and in 15 n~rmel adult male subjects, sertm FSH, LH and t~stoshm~mm (T) were detarmined by RIA in besal conditions and after G~-P~ (i00 ~/i.v.) and hCG (zOO0 I.U.i.m.) resp~rgively. At the first observatJc~ ~ FSH and LH were nc~mal c~ sl~qtly low in all cases with no diffm~mce in somparison with normal subjects. F~cept c~e case with normal respense to FSH and LH maximu~ incresses (2~, ) were suppressed or blunted and si~ficantly (p ~ 0.005) lower compared to controls (i.12-~0.7 vs 4.23-+1.89 and 5.5-+3.6 v.s. ii.7±3.2 ng/nl, respso-t~ely). Coly in one patimqt, with norma~ /k FSH and /k LH, bsssl T was icw; in the others the bzmmns was within normal limits as was its reaponse to HCG snd the values w~e not significmn~ly different from o~r normals (4.98+_1.93 vs 5.85+2.15 ~nd 7.8~+-2.5~ vs 9.2± 1.39, respectively). During t!~ i0 yrs 4 pts died of disease ccmpl~ cations. In the 7 pts who sn~vived, ~ FSH ~md LH ~ confirmed normal or slightly low while their responses to (~-RH w~ce ~ pressed. Coly the case with an ir~t-ially normsl response presemted a slight increase; in this sase patiant T ~alues, basal and slier ~G, further dimirfished and Free T w~s also low. An impaired pit,ritzy may be the cauae of subc]~nicsl h~poganedo~opic ~ypogon~llan in our casas;in oely cne gu~adal t~ssue ~msge se~mmd to play a role.All pts presented cl~dical pubertal matonstinn and, except ane case, normal T ssoretdon, although some of than w~re infertile. Chronic iron overload seems the most likely cause of ~ andoc~ime abnormality.

Lj. Lukinac, Z. Kusid, M. Lacid, D. N0thig-Hus Department of Nuclear Medicine and Oncology, University Hospita 1 "Sestre Milosrdniee", Zagreb, Croatia.

Autoimmune thyroid disease (AITD) is associated with the presence of serum autoantibodies to thyroglobulin (TGA), thyroid peroxidase (TPO) and microsomal antigen (TMA). I our study we .wanted-to determine which of the thyroid related auto,antibodies prevail in serum of patients with Graves' disease (G), Hashimoto thyroiditis (H) and in euthyroid subjects (EU 

The role of NP59 scintigraphy in patients with an incidentally discovered adrenal mass on CT and without signs of other primary tumor, pheochromocytoma or functional cortical adenoma, is still discussed. We studied 12 patients with incidentally discovered adrenal tumor and no significant hormonal abnormalities.

After Lugol's administration, 74 MBq of NP59 were injected and adrenal planar imaging was obtained 5 and 7 days later.

Increased uptake of NP59 by the tumor was seen in 8 patients.

In $ of them, the contralateral gland was not visualized. All had an adenoma (> 18 mm), the diagnosis was made by surgery (4) 

A.Masala, S.A~, ~9.Ceilis~,P.P.Rovasio, *C.Burr~d, A.GA~r~/, A.Pinna, A.R.Casu, ASpanu . and G.Ysdeddu. Depts. of Internsl Medicine, *Pediatrics ~nd Nuclear Medicine, thiver~ty of Sassari, Italy.

Biosynthetic GH treatment is now an useful tool in the management of GH deficient patients. In this study we evaluated the effects of a 2-year course of treatment with GM in 20 thalassaemic patients with severely reduced GH secretion (peak values in response to GRH, clonidine and levodopa less than 8 ng/ml). Ten male and i0 female multitransfused prepubertal patients entered this study. All had low IGF-I levels (46.82 ~ 12.34 ng/ml), delayed bone age and an average growth v~locity of 2.31---~--0.23 (mean ~ D.S.) cm/year. All were treated w~th GH at the dose of 0.9 U/Kg b.w. per week administered s.c. ~n 3 divided doses. HeSght and plasma IGF-I levels were estimated at 4-month ~ntervals. During the first year of treatment we observed a progressive rise in IGF-I and growth velocity in all of the subjects. Growth velocity at 12 months was S.47 ~ 1.36 am/year (p< 0.O1 vs basal values) and .64 ~ 20.45 ng/ml (p< 0.01). Treatment had to be stopped in 3 patients after 14-16 months because of GH resistance (n=2) with low IGF-I levels and type II diabetes (n=l). GH treatment was continued in the other patients w~thout ~noidence of side effects. At the end of the second year growth velocity was 5.03±1.47 era/year and IGF-I was 164.33~28.32 ng/ml. Data of the present study show that GH treatment may be useful in patients w~th thalassasmia and reduced GH secretion with a low incidence of adverse effects, in spite of the preexisting organ damage due to iron overloading. Recently 99m-Tc MIBI imaging was introduced in the follow up of differentiated thyroid carcinomas.

Our present experimental study was undertaken to evaluate the effect of TSH, L-Thyroxine and TRH on 99m-Tc MIBI accumulation of thyroid gland. CFLP mice (25-30 grs) of both sexes were used, 4 -4 ~oups were folq~ed with 12 mice per group. Groups: i. Untreated controls. 2. TSH:ZIU Ambinon (Organon) daily i.p for 3 days. 3. L-Thyroxin (Henning) 20 ~c3 daily i.p. for 9 days. 4. Z]~H (Berlin -Chemie) 8 ~/g daily i.p. for 5 days. ~he f~rst four groups received 5 MBq of 99m-Tc pertechnetate i.p. and the second 4 g~x)ups 5 MBq of 99m-Tc MIBI ("FJC" Natl. Res. IDst. for Radiobiology, Budapest). Animals were killed 30 minutes after the injection of isotope, the thyroid was removed and its activity was measured in well counter.

The 99m-Tc MIBI uptake was corrected consideri[~ the free pertechnetate fraction (1%).

Uptake Control TSH L-Thyroxine TRH 99m-Tc pertechn.

100% 251% 42% 6486 99m-Tc MIBI 100% 135% 59% 151% The 99m-Tc MIBI uptake was stimulated by exogenous TSH as well as TRH. The rise of pertechnetate uptake was almost twofold higher than the inc~ase of MIBI one. The MIBI accumulation could be less supressed by L-Thyroxin than the pertechnetate uptake. The unexpected effect of 5 day coui~se of ~ treatment on pertechnetate uptake needs further clarification.

Results of our experiments suggest that the effectiveness of 99m-Tc MIBI thyroid cancer imaging could be enhanced by endogeneous or" exogeneous TSH stimulation.

Fett~ The aim of this work was to estimate the changes of some hormones of thyroid gland and gonades in wounded people during combat operation in Yugoslavia 1991.

The concentrations of hormones were determined in 65 wounded. Blood samples were taken at the day of i n j u r y and in several time intervals a f t e r injury. Control group consisted of 33 normal blood dohors.

Serum T3, T4, and TSH levels were determined by the radioimmunoassay, using a commercial RIA T3 k i t , INEP DIAGNOSTICA, Zemun, Yugoslavia; FT4 concentrations using SPECTRIA FT4 k i t Farmos diagnostica; testosterone level by the RIA-mat testosteron, commercial k i t suplied by Byk-Sangtek Diagnostica. Our results show that the concentrations of T3 was s i g n i f i c a n t l y decreased in injured compared to controls group, while the concentration of T4 was decreasea only at the f i r s t day a f t e r injury. Concentration of T4 was increased in following days a f t e r injury. The level of FT4 and TSH did not show s i g n i f i c a n t changes. The levels of testosterone was s i g n i f i c a n t l y decreased at the f i r s t 24-hours a f t e r i n j u r y but concentration was normalized with recovery.

We concluded that war injuries caused significant changes of thyroid and gonadal hormons in blood of wounded people. 

To evaluate the motor function of esophagus in hyperthyroid and hypothyroid patients, the quantitative esophageal transit and clearance scintigraphy were performed.

The study was conducted in normal volunteers(15), patients with Graves' disease (16) and hypothyroid patients ~I/). 15MBq of Tc-ggm sulfur colloid in 15 ml ot water was administered orally to the patients. During the f i r s t swallow serial esophageal images were obtained with one second intervals for 15 seconds ( f i r s t phase). Subsequently the patients w e r e instructed to swallow 15 second-intervals for up to ten minutes (second phase). First and the second phase curves were generated and transit times were determined from each group and displayed for the quantitative comparison. In the l l t h sec. of the f i r s t phase, the esophageal transit of hyperthyroid patients began to differ from the normals. The differentiation time of hypothyroid patients from normals was 12th sac. During the second phase of the study the transit time were found to be significantly reduced at 8th and 40th swallows in patients with hyperthyroid and hypothyroid diseases (p<0.00l). The transit time was reduced more in hyperthyroid patients than hypothyroid patients. Moreover, seven hyperthyroid patients who had higher thyroid hormones also had greater reduction of transit time.

In conclusion, the thyroid hormones may alter the esophageal transit time by affecting the motor function of the smooth and striated muscles of the esophagus.The excess of thyroid hormones has a grater effect on esophageal transit time than the lack of these hormones.

Chr.Reiners t, H.Peters 2, Chr. Fischer 2, H.Schleusener 2, Nuclear Medicine t , University Essen and Clinic for Internal Medicine ~, Free University Berlin, F.R.G. DECREASE OF THYROID VOLUME AFTER 1-131 THERAPY FOR GRAVES' DISEASE 1-131 ist effective for treatment of hyperthyroidism in patients with Graves' disease. Up to now, little is known about the effects of I-131 therapy with respect to thyroid volume.

Within the scope of a German randomized prospective multicenter study on the effectiveness of two different d o s e regimens for 1-131 treatment, it was possible to follow sonographically thyroid volumes 6 and 12 months after therapy. The volume reduction by organ doses of 100 Gy calculated individually with respect to initial thyroid volume, maximal uptake and effective half-life of a test dose of I-131 shall be presented here.

Thyroid volumes were determined using real time sonography and a rotational ellipsoid as a geometric model. Volumes measured in 107 patients before treatment ranged from 5 to 175 ml (median 32 ml). Thyroid volumes of 57 patients could be followed individually until 6 months after 1-131 therapy; the median reduction amounted to 48 %. 12 months after treatment, volumes could be determined in 42 patients. The median reduction was as high as 65 %. The study shows that 1-131 treatment reduces goiter, size effectively in patients with Graves' disease; if thyroid volume does not exceed 50 -60 ml, complete normalization of gland size may be achieved. 

We have assessed the importance of thyroglobulin(Tg) as a prognostic parameter in patients with metastases of differentiated thyroid carcinoma(DTC) which received 131-I for therapy. We have studied 44 patients with m~ tastases of DTC over a period of 2 to i0 years, by periodically measuring Tg du~ing opotherapy and after suspension of it, and by performing 131-I whole body scan (WBS). When metastases were identified, a therapeutical dose of 131-I was administered. Patients were divided into 2 groups: Group A had always concordant WBS and Tg results (36 cases) and Group B had discordant WBS and Tg at one or more time (8 cases).64% of patients of Group A had a positive response to 131-I therapy and showed persistent negative WBS ~d low Tg levels. In the remaining 36% of patients of Group A we observed persistence of metastases after one or more doses of 131-I and both WBS and Tg levels were found pathologic~ In Group B,5 cases had a persistent negative WBS and high TE levels, and remaining 3 cases a positive WBS but normal Tg levels. We conclude that WBS should be always perfol~aed in these patients since a relatively high percentage of them may have Tg levels within the normal range despite the presence of metastases.

A. Vattimo, P. Bertelli, L. Burroni, L. Massini, T.

Giannini, P. Cappelli. Nuclear Medicine Unit, University of Siena, Italy.

The diagnosis of AFTN depends on the visualization of suppressed parenchima on thyroid scintigraphy with radioiodine or Tc99m after exogenous TSH stimulation. Since TSH test could be potentially dangerous and it is not available in several countries, recently Tc99misonitriles have been proposed for the viasualization of extranodular thyroidal tissue. We observed fourteen pts. with clinical and biomedical evidence (suppressed TSH plasma levels) of hyperthyroidism due to AFTN diagnosed by Tc99m: all were submitted to Tc99m-MIB1 scintigraphy in separate session.

In 5 pts.

Tc99m thyroid scintigraphy was repeated after TSH stimulation. In all pts. Tc99m-MIBI scan showed a good visualization of extranodular tissue even better than Tc99m imaging after TSH stimulation (nodular t~extranodular tissue ratio was 2.4 +/-1.06 in Tc99m-MIBI and 3.3 +/-1.9 in Tc99m post TSH scan). Anyway, in 10/14 pts. Tc99m-MIBI uptake was higher in the nodule than i~ the extranodular tissue. Since both Tc99m and Tc99m-MIBI scan showed "cold" areas in the nodule, this suggests a possibte flow dependent mechanism of thyroidal uptake of Tc99m-

In conclusion Tc99m-MIBI thyroidal imaging

represents an effective and feasible alternative method to TSH stimulation test in visualize inhibited extranodular tissue in pts. with suspected AFTN. Preoperative correct location of pathologic PG represents an important step in the management of hyperparathyroidism (HPT); it makes the operation shorter, reduces surgical complications and the risk of relapse. In the present study, diagnostic accuracy of 5 different imaging diagnostic techniques were compared in 36 consecutive HPT-patients (pts) : 27 with primary HPT (I-HPT) and 9 with secondary HPT (II-HPT). Diagnostic techniques consisted of: double tracer scimigraphies both with T1201/Tc99m (VrS) and with MIBI-Tc99m/Tc99m (MTS), NE with a 10 MHh-probe, CT and MR. All pts were studied with MTS, "ITS, NE and CT whereas the last 16 pts also with MR. A total of 65 pathologic PG were surgically removed; 11 of them were found in ectopic sites (retropharingcal, retroesophageal or mediastinal PG). Surgical and histological findings were taken as gold standard. Sensitivity (SE) and false positive (FP) cases in pts with I-HPT are shown in the table below.  TECHNIQUE:  MTS  TTS  NE  TC  MR  SE 90.3% 80.8% 90.3% 61.3% 62.9% FP 6.4% 9.6% 12.8% 16.1% 18.6% NE and MTS showed the highest SE, however, FP cases were less frequently observed with MTS. Combination of MTS plus TI"S and NE showed the beat diagnostic accuracy (SE = 96.7%). In cases with ectopic PG, MTS showed a higher SE (85.7%) in comparison with NE or TC or MR (71.4%), and with TTS (42.8%). Less enthusiastic results were obtained in II-HPT: SE resulted 67.6% with NE, 50% with MTS or TTS, 47% with CT or MR. These data demonstrate a good diagnostic accuracy of MTS in I-HPT. Thus, this diagnostic technique should be widely introduced in the preoperative study of pathologic PG.

Ehrenheim Ch, Busch J, Oetting G, Lamesch P, Dralle H, Handeshagen H. Abt. Nuklearmedizin und Klinik fflr Abdominal-und Transplantationschirargie, Mediziaische Hochschafe Hannover, D-3000 Haanover 61

The volume reduction of diffuse or nodular enlarged thyroid after therapy with iodine 131 is usually rated and may reach one or two thirds of the initial volume. Sonographic measurements depend to a larger extent on the observer and the method (ellipsoid, slices) which may induce errors up to 30%, further, mediastinal extension is not registered. MRI as a sectional imaging method overcomes this drawback and additionally provides excellent soft tissue contrast.

In order to evaluate the accuracy of both methods as a volumetric means phantoms and 11 healthy volunteers were examined. Consecutively, I 1 patients with diffuse or nodular enlarged goiter (6 pts with mediastinal extension) underwent volumetry during and after radioiodine therapy. The results of volumetric MRI were highly accurate and did not depend on the volume or the shape of the object (mean error < 1%), whereas ultrasound showed deviations + 20% (mean) that increased with increasing volumes. Patients goiter volmne ranged between 92 and 473 ml (mean 232 ml) on MR images. Sonographic measurements seized 67-100% (mean 89%). Therapeutic volume reduction was about 37% (76 ml) measured with MRI (range 12-81%).

MILl is an exact volumetric tool covering even mediastinal extension of the goiter. Examination time of about 15 rain seams acceptable. Our results point to different therapeutic effects of radioiodine on diffuse and nodular enlarged goiter. The aim of our study was to evaluate the gastric emptying (GE) in diabetics without symptoms of gastroparesis (GP) and the effect of erythromycin (E) administration. We studied 10 pts (5 m -5 f; mean age: 57 yrs) with diabetes for at least 20 yrs and cardiovascular tests indicating an autonomic neuropathy but no GP symptoms. The GE of solids and liquids was determined using the dual radionuclide technique (Tc99mcolloidal HSA scrambled egg and In111-DTPA in water). Images were acquired at 1- 10-20-30-40-50-60-75-90-105-120 min. Each pt was evaluated in basal conditions then after 200 mg of iv E; 6 out of these 10 pts were restudied after 1-month 500 mg oral E and 2 out of these 6 pts after 6 months oral E. The resuits are shown on the table (pementage meal retention: mean-+lSD).

(*) Urbain JLC: JNM,1990;31:1490-1493 Conclusions: 1)-Diabetic pts with autonomic neumpathy, albeit with no GP symptoms, have a delayed solids and liquids GE. 2)-The radionuclide GE evaluation is useful to select diabetics who run the dsk of dangerous, apparently unexplained, hypoglycemic crises. In these cases, E is a possible therapeutic means because it accelerates GE significantly afler iv administration but keeps its effect, although to a lesser degree, after chronic oral administration. After pancreato-jejunostomy for CP, a blind loop is formed, in association with the disconnected jejunum loop. If this loop is pathologically colonized by bacteria, this might cause or intensify steatorrhea and cholic acid malabsorption. Antibiotic therapy should reverse malabsorption secundary to intestinal bacterial overgrowth.

We studied this problem by 1 4 C -0 0 2 e x h a l a t i o n measurements after oral application of cholesteryi-[1-14C]octanoate (CO) or [1-14C]-glycocholic acid (GC) before and after a ten day antibiotic therapy (Tiberal r and Clamoxyl r ) in normal controls and in patients with CP with and without pancreato-jeju nostomy.

The GC-test did not show differences between normals and patients. After antibiotic therapy the 140-CO2 exhalation was generally reduced by an order of magnitude 2 h after application and even more after 6 h. This is to be expected because of the general reduction of intestinal bacteria after antibiotics. After CO -ingestion 14C-CO2 exhalation was lower in all CP-patients without operation and in 40% of the patients with operation, indicative of their steatorrhea. No difference before and after antibiotics was seen in all groups.

Thus our results do not support the hypothesis of the involvement of the blind loop in the pathogenesis of steatorrhea and cholic acid malabsorption. The Evaluation of Gallbladder Function by Quantitative Radionuclide Cholescintigraphy Before and After ES~ for Gallstones ~e ass~sed char~es of gallbladder function including concentration and the contraction in patients with gallstones after extracorporeal shock-wave lithotripsy (E$1/L). The abilities of concentration and contraction were expressed as a filling fraction (FF) at 90 min and an ejection fraction (EF) at 30 min after a fatty diet by cho]escintlgraphy.

A total of 12 patients who had symptomic gallstone without cholecystltis were included in our study. The E$~ was failed in 3 cases, FF was decreased in 2/3 cases, increased in 1/3 cases; EF ~s decreased in 2/3 cases, increased in I/3 cases after ES~L. In another 9 cases, the ES~L was thought successful, the gallstones were finally fragmented by ESWL. One month after E$~L, in 3 cases among the 9 cases, the gallstones had disappeared totally. In the 3 cases, FF ~as decreased in 2/3 cases, increased in 1/3 cases; EF was decreased in I/3 cases, increased in 2/3 cases at I month after ES~. In another 6 cases, there were still some residual stone fragments in the gallbladder after ES~L. After half a year, no fragments were found in the gallbladders, the 6 cases accepted the third Tc-~m DISIDA cholescintigcaphy. In the 6 cases, the changes of FF and EF among before ES~, I month after ES~, and 6 months after ES~L, ~ere irregular and fluctuant. However, no significant improvement of gallbladder function is demonstrated even if the ES~ was successful.

In our preliminary results, we found that not only the residual stone fragments but also the procedure of ESWL may impair the gallbladder function by the evidence of a noninvasive and quantitative Tc-99m DISIDA cholescintlgraphy. Technetium labelled polyclonal human immunoglobulin (HIG) is a new agent for the detection of focal infection and inflammation, especially in the musculoskeletal system.

This data served as a good starting point for our study in the detection and localization of inflammatory bowel disease, especially ulcerative colitis. Twenty eight patients were studied with established or suspected intestinal inflammatory disease. I0 mCi (370 MBq) of Tc99m-HIG were administered IV and images were obtained after 4 and 24 hours. Increased activity accumulation was observed in inflammation sites. Our results were compared with those of colonoscopy. Of the 28 examined patients, we observed that in 25 of them there was correlation between positive HIG and colonoscopy findings. In the remaining 3 patients while HIG gave positive results, colonoscopy findings were doubtful in 2 of them and negative in the third one.

In conclusion, clinical data indicate that Tc99m-HIG scintigraphy is sensitive to detect and delineate inflammatory sites in the bowel. 

The purpose of this study is the comparison of the GE rate of liquids measured by Sc and EI (1, 2); in order to evaluate the feasibility and reproductibility of EI, we performed simultaneously in 24 healthy volunteers (after 12 previous hours of fasting) 84 measurements of GE by EI and Sc. In a randomized order, half of them (12) ingested 380, 500 and 660 ml of regular and/or sparkling water. The second half (12) ingested 500 ml of sweetened water (water + orange juice, 84 Kcal/l). All the preparations were labelled with Tc-99m Rhenium colloids. Setting the volunteers in a i/2-dorsal decubitus, we performed the gastric scintigraphies in LAO over a 30 mn period. We measured the EI by a 6-electrode epigastrograph (London Medical Electonics). The GE half-time is given in the following table related to the type and/or volume of liquid studied as well as the correlation ratio (r) resulting from the two measurement procedures: 0,62 0,54 0,78 0,84 0,78 0,78 0,90 NO matter of the nature or the volume of liquids ingested, the EI provided reproductible results well correlated to the Sc. However, we noticed that the times given by El have been the half of those given by Sc. These datas are logically due to the fact that the volume and the gastric morphology are modified during GE, and from this modification results the exit of the area explored by the electrodes. (i) MANGNALL YF, Clin Phys. Physiol.1988: 249-254. (2) SUTTON JA, Lancet 1985: 898-900.

Martin W. G.. Schneider-Eicke J., Adolf J., Heidecke C. D., Senekowitsch R., Siewert J. R., Pabst H. W.

Procollagene-III-Peptide (P-Ill-P) is a parameter of increased fibrosis in chronic liver disease. In this prospective study, P-III-P values were determinated in 1020 blood samples by radioimmuno assay from 32 consecutive patients with o~thotopic liver transplantation (OLT), (21 male, 11 female, average age 46 _+ 10,4 years). Monitoring period after OLT was 340 +_ 285 days (range 45 to 930 days). P-III-P values were compared to standard laboratory tests. Microsomal liver function was quantified by means of the C14-Aminopyrine breath test (ABT).

Results: A 2 to 5 fold increase of the upper normal limit of P-III-P (normal range 6 -16 p~g/ml) was found in the early postoperative period in all patients. Three weeks after OLT the P-III-P values were constantly elevated in most of the patients to 2,5 fold of the upper normal limit. Compared to microsomal enzyme function, the course of P-III-P values was opposed to that of liver function i.e. the ABT values. In long term follow-up P-III-P values remain raised in most of the patients. During episodes of peritonitis or sepsis P-III-P values were elevated more than 100 fold of the upper normal limit. During these periods ABT values were dramatically decredsed. 

Hepatocellular extraction fraction (HEF) using deconvolution analysis is considered reliable to quantify liver function and to discriminate between early obstruction and hepatocellular dysfunction. We retrospectively reviewed the HEF of 38 patients (pts) with biliary-enteric anastomosis, preoperatively and with postoperative follow-up within 1 year (n=19), then up to 2 years (n=9) and to 3 and 4 years (n=4 each), and to 5 years (n=2). Number of postoperative HIDA-scans: 1 (5 pts), 2 (19 pts), 3-11 (17 pts) . We wanted to assess the diagnostic value of HEF in the two most frequent complications: cholangitie and recurrent stenosis, and to quantify the liver function after operative relief of the obstruction. Method: After injection of 2-6 mCi of 99mTc-iodida (Solco) dynamic acquisition was performed during 1 hour (30-60 sac/frame, Matrix 64 x 64, word mode), data were analysed with NucLear software. The Impulse Response Function (IRF) was given by deconvolution of the time activity curves obtained from ROI over the heart (input function) and the right upper liver lobe. The HEF was calculated es the ratio of the back extrapolated Y-intercept of the IRF monoexponential fit to the IRF maximum data point. Results: HEF was normal or slightly diminished (> 80 _< 100%) in cholangitis as well as in obstruction, in 2 cases of obstruction the HEF was strongly diminished (20% and 60%). These cases normalized after relief of the stenosis. Except 2 patients, a preoperatively diminished HI:F improved or was normalized after operation, even in case of biliary fibrosis/cirrhosis and long standing obstruction. These findings were confirmed by liver function tests (aminopyrine breath test and galactose elimination capacity), Conclusions: HEF cannot safely differentiate between cholangitis and recurrent obstruction. HEF can be strongly reduced in hepatocellular as well as in obstructive disease. But HEF is a very sensitive parameter in the follow-up evaluation of liver function after relief of an obstruction.

T. Aras, M.T. Ercan, H. $imsek, C.F. Bekdik, H. Telatar ~n l~ Departments of Nuclear Medicine and Gastroenterology, Hacettepe University, Ankara, Turkey.

We had shown in ~n experimental study that Tc-99m dexamethasone phosphate (MDP) is an effective agent for demonstrating inflammations. Since Tc-99m-DMP had a rapid clearance rate and low intestinal a c t i v i t y , i t seemed to be a proper agent for the assessment of inflammatory process. Therefore, we evaluated the diagnostic value of Tc-99m-DMP scanning in active ulcerative c o l i t i s (UC) in the present study.

Ten patients (7 M, 3 F) with UC and 30 normal cases (20 M, lO F) were included in this study (mean age : 32 ± 17, 55 ± 12 respectively). All patients with UC also had invasive amebic colitis proven histologically at the time of study. Following I.V. administration of 20 mCi Tc-99m-DMP, images were taken at l , 3, 6 and 24 h (Siemens Scintiview I I , 256x256, 500.000 cts/frame). Colon/background (C/B) ratios were calculated. Although there was no colonic activity in normal subjects, all UC cases showed colonic accumulation at 6 and 24 h ( Fig.) . The mean C/B ratio was 3.09 ± 0.78 in UC cases. Scintigraphic findings were in agreement with the activity and extent of ~C.

In conclusion, our results suggest that Tc-99m-DMP imaging is an accurate, rapid, noninvasive alternative method for the study of disease activity in c o l i t i s . Early detection of PCA is often delayed by diagnosis of concomitant chronic p a n c r e a t i t i s (CPA). It was the aim of the p r e s e n t s t u d y to e v a l u a t e FDG-PET for detection and d i f f e r e n t i a t i o n of PCA from CPA. A t o t a l of 25 pts. with s u s p e c t e d PCA ( n = l g ) or known CPA (n=6) were i n v e s t i g a t e d . 19 pts. were studied a f t e r a 2 4 -h r s . f a s t i n g period (group 1), in 6 pts. FDG w~s injected t o g e t h e r with a 40% glucose infusion (group .2). Static P E T -s c a n s were obtained 4 5 -6 0 rain. after iv injection of 150-800 MBq FDG. Q u a n t i f i c a t i o n was a c h i e v e d by ROI-technique c a l c u l a t i n g s t a n d a r d i z e d u p t a k e v a l u e s (SUV). Results of PET were v a l i d a t e d by histology of s u r g i c a l specimens (n=21) or clinical course of >6 months (n=4). In group 1 PCA could be recognized in all pts. ( n = l l ) by high ; range: 2. 3-7.3) .

In group 2 false n e g a t i v e findings were obtained in 8/4 pts. with PCA because of low SUVv a l u e s (mean: 2.1; range: 1.8-2.7) similar to those of CPA (mean: 1.2; range: 0.8-1.5) or abdominal background (mean: 0.8; range: 0.5-1.2). PET was false p o s i t i v e in 1/10 pts. with proven CPA. Increased u p t a k e (SUV: 2.5) could be a t t r i b u t e d to neighbouring g r a n u l a t i o n t i s s u e a f t e r p r e v i o u s l y performed g a s t r i c surgery.

We conclude t h a t FDG-PET has p o t e n t i a l -to improve e a r l y diagnosis of PAC by a c c u r a t e d i f f e r e n t i a t i o n between PAC and CPA. However, s t r i c t f a s t i n g prior to PDG-injection has to be observed to obtain reliable diagnostic r e s u l t s .

A.I. Fetter Antu~ne__s, E.Xavier da Cunha, F.Castro e Sousa J. Rodrigues Branco. Nuclear Medicine and SurgeryIII Departements,University Hospital, 3049 Coimbra, PORTUGAL

Hepatic peffusion index(HPI), the relative hepatic arterial contribution to total liver blood flow, derived by dynamic hepatic suintigraphy (DHS) has been suggested as a promising method in the definition of a high risk group of patients (pts) Wone to develop overt liver metastases after an apparently curative ressection.Itt this prospective study we attempted to evaluate the utility ahd reproducibility of preOperative determination of HPI in 147 pts with a digestive cancer.A normal range has been obtained in a group of 17 no neoplastic pts, with an upper limit of 0,28. Overt liver metastases were found in 34 pts undergoing laparotomy, and 26 had elevated HPI values (76,4%). No apparent liver metastases were found in the remaining 113 pts submitted to a "curative" resection of the primary tumonr.These pts were followed up by periodic clinical examination,hepatic ultrasonography and CT scans. At one year of follow-up 64 pts were evaluated.Seven pts developed liver metastases, six had initial elevated HPI values and one had a norton[ initial value. Fifty-seven pts did not developed liver metastases, 36 had elevated initial HPI values and 28 had normal HPI values. RESULTS:These data result in a sensitivity of 76,9% and a specificity of 43,3% for DHS and a predictive value for a positive HPI of 16,7% at one year~ and a predictive value for a negative HPI of 96,4%.CONCLUSION:These results showed that although initial elevated HPI values did not identify high risk group of pts prone to develop liver metastases, pts with initial normal HPI values have a confirmed low risk of developing liver met,%stases. This study was undertaken to evaluate the effect of ACBDO on hepatocyte function in rats studied by quantitative Tc-99m-Mebrofenin scintigraphy (QMS). 18 of 23 Spraque Dawley male rats had laparotomy and ligation of the distal CBD and the ~emaining 5 rats underwent sham laparotomy. QMS was cbtained before (baseline) and at 2 and 48 hours after ligation. Data was a¢quired at I frame/20 sec. for 20 minutes using a gamma camera fi~tedwith a high resolution collimator after the injection of 300 uCi of Membrofenin into the tail vein. Hepatic extraction fraction (HEF) and excretion half-time (T-I/2) were obtained by deconvolutional analysis and a nonlinear least square method respectively. After scintigraphy rats were sacrificed and blood and liver samples were colected for biochemical and histological examination. The degree of HEF reduction and prolongation of T-I/2 excretion values correlated well with ~he dura£ion of obstruction severity of live~ ~un~tb~ a~normal~t%,, and thei~istological hepatocyte injury, it is cone uQeQ that QMS may.provide a~onin~@sive method for detection and quant1~itatlon o£ the effect of ACBDO. In this study ROC (receiver operator characteristic) methodology was applied to evaluate the diagnostic performance of a multiple swallow test for the assessment of esophageal motility disorders.

Esophageal scintigraphy (ES) and manometry were performed in 47 pts. In ES the passage of liquid (1) and solid (s) test boluses was investigated with 6 swallows each. T max., transit time, mean transit time, mean time and esophageal emptying (%) at 10 and 12 sec were derived from a particularly created sum swallow. Manometric findings were used to define normal (n=26) vs. path. (n=21) function. Referring to this classification ES-results were categorized for various confidence thresholds. The two best sensitivity/specificity (SN/SP) pahs obtained for each parameter are listed below. For several quantitative parameters of a multiple swallow test thresholds for decision making have been optimized with ROC- analyses. Best discrimination of normal from pathologic findings was provided by emptying 12sec, suggesting the use of this parameter to diagnose esophageal motility disorders most accurately. Results for mean time and empfying lOsec were still acceptable, those for the remaining parameters were less satisfactory. Generally, increase in sensitivity at comparable levels of specificity, suggests to prefer sover l-boluses for evaluating esophageal dysfunction more reliably. 

The aim of the study was to evaluate the s e n s i t i v i t y and s p e c i f i c i t y of 14C t r i o l e i n breath test as a marker of pancreatic insufficiency. Study group comprised 25 unselected assymptomatic alcoholic patients (pts), observed on a follow up c l i n i c , who had been previously admitted for an "acute pancreatitis"~ with a time lag longer than 3 yrs. Results of the ~4C test were blindly compared with other biochemical and imaging parameters. After an overnight fast, pts were kept at rest. After an oral ingestion of 5uCi (185 K Bq) of t r i o l e i n ~4C, the expired C02 was collected at hourly intervals (I~2 . . . . 6hrs) into 20 ml vials, co~taining as trapping agent~ equal volumes of hyamine hydroxide and methanol (1:1), with 2 drops of thymolphtalein as indicator. The specific a c t i v i t y of expired 14C02 was measured by the method of Hepner. Results are expressed in percentage of the ingested dose of r a d i o a c t i v i t y exhaled per hour corrected for 9 mmoles endogenous C02 per Kg body weight. 15 pts had abnormal values: 2.06±0.87% dose/hr~ ~2 were true and 3 false positive. 10 pts had values within the reference range: 4.25±0.70% dose/hr~ 9 were true and I false negative. The mean peak value in the pts without steatorrhoea was higher than in the steatorrhoeic pts, and this difference was highly significant (p<O.01). Thus, 14C t r i o l e i n breath test showed a 90% s e n s i t i v i t y and 80% specificity to detect fat malabsorption.

In conclusion: this method appears to be reliable for the early d~agnosis of pancreatic insufficiency.

V Ivan~evi~ t'=, ~ Ku#ter t, D Ivan~evi~ t, B Kora~-Kova~evi~ =, B Vucelid ~. ~Institute for Nuclear Medicine and CDepartment of Gastroenterology, University Hospital Rebro, Zagreb, Croatia and =Department of Nuclear Medicine, Georg-August-University, G6ttingen, Germany

There is no reliable method for the assessment of the total inflammatory activity in IBD. The aim of our study was to develop a pathophysiologically relevant activit~ index for IBD by semiquantitative analysis of labelledleukocyte ECT.A mixed leukocyte suspension was labelled with 555 MBq ~"Tc-HMPAO. ECT was done 2.5 h p.i. at the average. After an iterative reconstruction algorythm the spleen, liver and marrow activities on the transverse slices were eliminated using ROI-technique and the result was put in ratio with the total abdominal activity thus generating a numerical activity index (AI). Clinical assessment o£ inflammatory activity in Crohn's disease (CD) was performed using the "Crohn's Disease Activity Index" (CDAI), the "van Hees index" (HEE8), and the platelet count (P). Ulcerative colitis (UC) was assessed by the Powell-Tuck (POT) and the Truelove-Witts index (TW). AI was 0.01±1.05 in 39 patients without IBD. In 49 ECT studies with CD and 14 with UC, AI amounted to 4.26±3.83 and 8.38±11.29, respectively.

Both were significantly higher than AI in controls (p<0.0001). Spearman's rank correlation (p)between AI and clinical indl is listed below: The results reveal a clear separation between controls and active IBD. As expected, we found a weak correlation between AI and the cinica] indices, the latter not fulfilling the criteria for reference methods. In UC with proctitis, AI tends to underestimate inflammatory activity for methodological reasons. In conclusion, AI seems to allow a reliable and reproducible estimation of inflammatory activity in IBD. 46 patients with endocrine active tumors of the gastrointestinal tract and of the pancreas (GEP-tumors) have undergone scintigraphy using Mallinckrodt Medical H.V., Petten, Netherlands) . Planar whole body imaging and SPECT were performed 4 and 24 hrs. after injection of 122 or 244 MBq. In 16 out of 18 patients who had histologically proven carcinoids scintigraphy visualized the tumor sites. We were able to demonstrate the tumors in 9 out of 11 patients with gastrinomas. Scintigraphy failed to visualize the receptor negative tumor in I patient, and gave a correct negative result in another patient after surgical excision of the tumor. No tumor was detected in I patient after surgical excision of an insulinema. I insulinomawas missed scintigraphically. Scintigraphy visualized 3 non-functioning tumors and metastases in 9 patients, but missed 2 primary tumors. After surgical excision scintigraphy gave a correct negative result in 4 patients but failed to visualize metastases in 3 patients.

As there is a close relationship between the results of sclntigraphy and the presence of somatostatin receptors in the tumors scintigraphy means an in vivo-demonstration of the receptor-status. It has to be proven whether apart from the detection of the tumor, this t~chnique can be used to predict the effect of treatment with Octreotide. Duodeno-gastric Reflux is an often postoperatory complication in patients who had gastrectomy. The symptoms are various. We studied 20 patients (8 males and 12 females). All of them had undergone a surgical operation on stomach, 14 had symptoms and 6 were asymptomatic. All of them were assesed by endoscopy. Method The patient must be fasting for 3-~ hours before the examination. With the patient in supine position and the collimator over the abdominal area 5mCi 99m-Tc-HIDA injected i.v.. Sequentfal views of 120 sec are taken for 15 minutes. 100-150 ml of milk was administered orally 20 min. after the i.v. injection. Finally, a small quantity (200 uCi) of 99mTc pertechnetate in 100 ml of ware9 was administered orally to outline the stomach area. Results From the 14 symptomatic patients 9 had a typical Duodenogastric reflux radiopharmaceutical imaging in the stomach.The other five symptomatic patients with no imaging in the stomach had a long time imaging of common bile duct and delayed passage of radiopharmaceutical to the duodenum and probably this was the reason of their s21~ptomatology. Two of the asymptomatic patients had a low grade of duodeno-gastric reflux. Conclusions Hepatobilliary scanning with Tc-99m HIDA is a excellent low risk high diagnostic value examination of Duodenogastric Reflux in patients after gastrectomy. To ascertain ileal localization, 24 patients with proved active Crohn's disease (CDAI > 150) underwent In-III-WBC scintiqraphy, celon-ileoscopy and small bowel enema. Diagnosis was confirmed in all patients (7 with terminal ileitis, 7 with ileo-colitis and i0 with colitis only > 5trough biopsies carried out during ileoscopy and surgical specimens. In patients with active ileal disease,scin-~igraphy was positive in all cases (14 out of 14). Small bowel enema showed a pathological terminal ileum in 86% ~f cases with 14% ~ 2 out of 14 ) false negative. Endoscopy histologically confirmed disease in 50% of ca-~es only, as ileoscopy was unsuccessful in the order 50% due to inflammatory stenosis of ileo-cecal valve. ~cintigraphy showed no pathological granulocyte uptake in the ileum in any of the ten patients with Crohn's disease localized in colon. Ileoscopy confirmed normal ileal mucosa in all of them.Small ~owel enema gave a false positive pattern in 20% and normal in 60% of cases. The above shows the diagnostic usefulness of In-III-~BC bcintigraphy in ascertaining ileal active Crohn's disease and as an indispensable complement to endoscopy and radio-~ogy.

Irene Virgolini, J. H~bart, Susanne Granegger, P.Angelberger, H.Bergmann, and H.Sinzinger I ~ept. of Nuclear Medicine, University of Vienna and =Ludwig Boltzmann Institute for Nuclear Medicine, Vienna, Austria.

Twelf patients with recently diagnosed acute viral hepatitis underwent serial~h~Tc-galactosyl-neoglycoalbumin~GA) scanning of the liver (up to 8 months). Injection of 7~'TC-NGA (150 MBq) at a rate of 3.5 mg (50 nmol; i ml) reve~led that the liver is the exclusive site of tracer-uptake. Simulation of ~mTc-NGA-kinetics allowed quantification of NGA-binding to human hepatic binding protein (HBP). Return of liver function tests to normal values was associated in 2 patients with hepatitis A, 4 patients with hepatitis B and 2 patients with hepatitis nonA/nonB virus infection with increase in HBP-concentration (up to 3-fold of the initial concentration), binding rate constant k b and hepatic blood flow Q. In the other 4 patients (3 patients with hepatitis B, 1 patient with cytomegalovirus infection) a prolonged course of the disease was monitored. In the mean, HBP increased from 0.41±0.11 pmol/l after onset q~ acute hepatitis (n=12) to 0.78±0.21 pmol/l after the 6'" month of follow-up (n=lO) (p<O.O01). During this period also K b (72.4±12.6 vs 82±11.5 ~mol/i/s; p<O.05) and Q (0.027±0.0051 vs 0.031±0.0083 l/s; p<O.05) increased. HBPconcentration highly correlated with actual laboratory tests for liver function (r=-0.98; p=O.O001).

It is concluded that scintigraphic evaluation of ctional hepatic cell mass using the new receptor-tracer c-NGA could provide an in vivo diagnostic means allowing both quantification of liver function and assessment of liver morphology. In addition, our findings suggest that changes in HBP-receptor concentration are likely to occur in vivo. The aim of. this study was to prove the clinical relevance of. granulocyte antibodies (Ab; BW 250/183; Behringwerke, Germany) for detecting perioperative septic foci. IS was performed labeling the Ab in a simple procedure with l0 mCi (370 MBq) if only planar imaging was possible and 20 mCi (740 MBq) Tc-99m if SPECT imaging was planed. Imaging was done by a digital camera (Elscint; Apex 401) 3 and 14 -24 hrs p. appl. The investigations were performed in patients after pancreatitis op., cholecystectomie, gastrectomie, hemicolectomie, nephrectpmie, st.p. operation of brain tumor etc. Most of the 53 pts (31 f, 22 m, age 55 __. 20 yrs were under intensive care conditions. We performed 59 investigations: in 48 pts only once, in 4 pts twice and in 1 pt three times. In 46 pts the final diagnosis was established by open surgery: we found a true prositive result in 36 pts, a true negative result in 5 pts, a true negative result in 3 pts and in 1 pt a false positive result. This would mean a sensitivity of 92 % and a specificity of 86 %. IS with granulocyte Abs is easy to perform and gives a reliable information about granulocyte accumulation in patients with septic loci. NON-ULCER DYSPEPSIA (NUD) .

Comparison of intragastric distribution (ID) and gastric emptying of solids (S) and liquids L) in symptom subgroups of NUD has not previously been performed. We studied prospectively 75 NUD pts (25M:50F, 48 ± 15 yrs) and 34 healthy controls.

Pts were divided into reflux-like dyspepsia (RD) (n=39) and motilitylike dyspepsia (ND) (n=36) groups by standard criteria.

Gastric emptying (GE) of S and L were performed, with calculation of S lag time, solid & liquid B, TI/2 , and rates of emptying (ROE); fundal TI/2 (FTI/2) and antral maximal fraction (AMF) for S & L were also derived.

Liquid B was significantly smaller in RD gp compared to MD gp (0.7~0.2 vs 0.9±0.2, p=0.03), and to controls (0.7±0.2 vs 1.0~0. 2, p=0.003) . L RoE at 20, 45 & 70 min were also slower in RD gp compared to both MD gp, and controls (all p<0.01).

SGE and LTI/2, however, were no different between symptom gps or controls. Abnormal L ID (value > 95 percentile controls) was commoner in RD gp compared to MD gp (9(25%) vs 3(8%)).

Individual values of ID were no different between symptom gps or controls.

Conclusions: i) Liquid GE is prolonged in pts with RD; this effect appears confined to the latter phases of GE, and 2) is accompanied by measurable alterations in ID. 

Scintigraphic methods (HBSS, red blood cell scan) provide functional features that make them highly specific in the diagnosis of benign liver tumors (focal nodular hyperplasia FNH, hemangioma). However, sensitivity is reduced when lesions are small. On the ofl~er hand, MRI as a sectional imaging method delivers information about tumor morphology and -in combination with dynamic contrast-enhanced images -functional information of smaller lesions, too, that allows tumor characterization, as well.

A number of features concerning signal intensity, morphology and contrast behaviour on MR images was evaluated in 216 intrahepatic lesions (71 hemangiomas, 4Q FNH, 39 HCC, 37 metastases, 4 cycts, and others). Scintigraphic appearance was analyzed in 104 and 117 lesions, respectively. The results were used to prepare a base of objective dam in order to develop a computer-assisted system for the differentiation of focal liver lesions. Diagnostic features are determined and weighted based on the probability of each diagnosis with different morphologic and functional signs. Functional and certain morphological (e.g. central scar) characteristics are of higher diagnostic value than features concerning lesion shape or margin. Signal intensity characteristics and contrast behavior range in between, or may be superior in some cases depending on the diagnosis (6.g. cyst).

On the one hand, tim application of the system in the differentiaOon of liver tumors is to be tested in a larger number of patients. The program can be used to analyze images systematically (teaching) and archive cases of inWahepatic lesions, on the other hand. To estimate the extent of necrosis, plasmatic levels of ventricular myosin heavy beta-type chains were determined by an IRMA method using two monodonal antibodies in 22 patients (aged 53 +-10 years), with an initial acute myocardial infarction (13 ant, 9 inf). The curve of myosin daily levels from admission to day 12, was drawn to look for peak, total amount and kinetics of plasmatic release and confronted with a myocardial underperfusion score at T1-201 SPECT (in percentage of total myocardium fixation) and a radiommlide ejection fraction obtained, both, 12 and 21 days after the onset of myocardial infarction.

The myosin peak appeared od average at day 5 (range 4 -7) with levels ranging between 339 and 7300 #U/I (average 2658 +-2065 ~U/I), and correlated well with T1 score (22 -+ 15%) : r = 0.84 (p < 0.0001) and EF (41 -~ 12%) : r = -0.63 (p = 0.01). The total amount of myosin released (average 12244 +-9667 t~U/1, range : 1348 -37269 tzU/l) was also well correlated with TI score : r = 0.90 (p< 0.0001) and EF : r = -0.67 (p = 0.01). Normal kinetics of myosin liberation curve (defined as rise, peak and normalisation at day 10) was present in 17 patients (77 %). Persistent release, probably indicating more extended myocardial damage, was present in 5 patients (23%).

As a conclusion, ventricular myosin heavy beta-type chains levels provide a good non-imaging estimation of necrosis size in patients with acute myocardial infarction. Pronostic implications of kinetics release could be determined in the future. 

In order to obviate the national dependence on imported antisera for the R.I.A. of reproductive hormones, the I.C.M.R. has embarked on their indigenous production. Testing the different bleeds of various immunized animals includes interalia determination of cross reactivity using pure cross reactive analytes, at concentrations tenfold of the concentration of the desired antigen against which the antisera were raised. These pure cross reactants are extremely expensive and of very limited availability and many are obtained by pituitary fractionation in the case of glycoprotein hormones. An economic and rapid method of the cross reactivity testing is described for identification of bleeds with minimal cross reactivity. This is a modification of the antibody dilution curve used for determining the initial and final dilutions at which an antiserum is used in which progressively increasing dilutions of antiserum are incubated with a small amount of the tracer analyte. If instead of the radiolabelled analyte one substitutes the radiolabelled cross reactants one obtains similar dilution curves from which it is easy to predict the cross reactivity. These can be used in much smaller quantities than the conventional cold cross reactants. The power of the technique is illustrated by the testing of an LH antiserum developed at Agra which has proved very promising material for the National Immunodiagnostic Programme. "Sandwich"-immunoradiomeLric assay developed on the basi~ o£ the components merltioned includes a Lwu steps procedure.

AL the ~iFst slags an analyte is incubated with immobilized monoclonal anLibodies reactive to ~res iambda chains o~ly.

SubsequenL wash removes intact immunoglobulins unreactive to immunosorbent. AL the second stage radiolabelled monoclonal antibodies are added. Solid phase activity value is directly proportional to the concentraLio~ el the antigen in quesLion.

Prelimi-RaFy data based on our measurements of SeTUle samples ~rom healthy donors and patienLs suffering from myeloma and some gammopathies indicate that the designed "sandwich"-assay system revealed increased {Fee lambdachains levels in paLients with mentioned diseases accompanied by renal damage. The validity of a unique method for the measurement of free thyroxine (FT4) serum concentration based on the use of 1251 labeled anti-T4 moncolonal antibody was evaluated in 311 euthyroids, in 177 overt or subclinical hypothyroids, in 255 overt or compensated hyperthyroids, in 100 normal pregnancies and in 10 cases suffering from FDH, Sera from 110 patients on L-T4 replacement or suppressive therapy were also assayed. Between-laboratory precision obtained in 48 assays from 4 different centers was quite appropriate for clinical use with a CV ranging from 4.6% (at 1.35 ng/dL) to 8.6% (at 0,36 ng/dL); the working range showed a CV --_10% between 0.12 ng/dL and 10 ng/dL; analytical sensitivity (CV=50%) was 0.04+0.01 ng/dL ~SD). A good correlation of FT 4 estimates was observed when data were compared with those obtained with 4 other commercial kits (r_<0.95). Euthyroid reference limits were set at 0.91-1.75 ng/dL (according to both the Youden approach and the mean+~SD values). The sensitivity of the assay in dissdminating both overt hypothyroids and hyperthyroids from control subjects was 0,95 and 0.96, respectively, As expected a low diagnostic efficiency was found in both the subclinical hypothyroids and compensated.hyperthyroids. However in the latter group the normality of FT 4 concentration agreed with the normal metabolic status of these patients, while suppressed TSH values were undistinguishable from those of the hyperthyroids. In pregnancy serum FT 4 levels decreased from early to late months of gestation. This method resulted in slightly increased serum FT4 levels in FDH subjects. In patients on L-T4 suppressive therapy FT4 concentrations appeared to be a poor indicator of their actual metabolic status. In conclusion, this multicenter trial demonstrated that this peculiar methodology, based on the use of a 1251-labeled anti-T4 MoAb, is simple, rapid, quite precise, reliable and minimally dependent on abnormal T4carrier proteins. Antibiotics( infectious diseases) and steroids(chronic inflammatory bowel disease=GIRD) influence the chemotaetic behaviour of leukocytes as the central mechanism of In-llloxine leukocyte scintigraphy.

Retrospectively 136 patients (CIBD n=79;infectious diseases n= 57),who underwent leukocyte scintigraphy( pure granuloeyte preparations on PERCOLL/plasma or METRIZAMIDE/plasma gradients), were examined, All patients had fever or leukocytosis of unknown origin at the time of scintigraphy. The final diagnosis was performed histologically, by biopsy or after a 6 months follow-up period. The inflammatory activity was determined (ESR; leukocyte count, orosomucoid).The period of antibiotic and steroid treatment was documented. The circulation of labelling efficiency was routinely performed before reinjection. Sensitivity and specificity in the CIBD group was 96%/99% without steroid pretreatment and 90%/98% under treatment. In infectious diseases sensitivity and specificity without antibiotics was 92%/83%, under medication 75%/99%. The overall sensitivity after a 2 weeks pretreatment was 73%, after a 2 -4 weeks treatment 90% and after a longer pretreatmant 90%. The difference between the groups was not significant. The labelling efficiency was 66.2% without and 67,6% under treatment.

In conclusion, an antibiotic or steroid pretrcatment, independant from the time, does not influence the labelling efficiency or the diagnostic accuracy of In-lll-oxin labelled autologous "pure'granulocyres.

F. J a m~ N. Leners, D. Labar and A. Ferrant. Centre de M6decine Nucl6aire and Unit6 de Tomographie ~ Positrons, University of Louvain Medical School, Brussels and Louvain-la-Neuve, Belgium. The aim of the present study was to evaluate the feasibility and the usefulness of a PET scan using thymidine labeled with C-11 on the 2C-ring position in patients with primary or recurrent non-Hodgkin Lymphoma (NHL). 20 single-slice PET studies were performed in 18 patients (2 patients were studied twice) classified in 3 histological groups according the Working Formulation. 2 studies were performed in patients with high grade lymphoma (HG), 6 in patients with intermediate grade (IG) and 12 in patients with low grade lymphoma (LG). After injection of -thymidine, dynamic acquisitions were obtained for 19 min. Fourty tumors (t) were analyzed (HGt : 7; IGt : 11; LGt : 22). In 16 cases, arterial activity curves were obtained.

All tumors showed significant Uptake of [2-11C]-thymidine. The maximal activity was reached before 10 rain after injection in 91% of the tumors. The uptake at the end of the acquisition (expressed on the percentage of the injected dose per 100 g tissue, % ID/100g) ranged from 0.07 to 0.62 % ID/100 g and was significantly higher in HGt than in IGt and LGt (mean + SD : 0.53 + 0.10 vs 0.26 + 0.08 and 0.21 + 0.10 % ID/100 g; p<0.0001 for both). The tumor to blood ratio (T/B) ranged between 0.75 and 3.29 at 1050 sec and was superior to 1 in all IGt and in 70 % of the LGt. However, T/B was not significantly different in IGt and LGt (mean + SD : 1.70 + 0.29 vs 1.43 + 0.63).

These data indicate that [2-llC] -thymidine provides a suitable signal for the assessment of proliferation in NHL. The [2-11C]-thymidine uptake in HGt was clearly higher than in LGt and IGt but there was no discrimination between the IGt and LGt uptakes. The long-term prognostic significance, if any, of in vivo measurements of proliferation in NHL remains to be evaluated.

Iervasi G, Pil~ A, Clerico A, Berti S, Baratto MT, Cazzuola F, Turchi S, Tongiani R, Pugliese S, Biagiui A, Bianchi R*. CNR Institute of Clinical Physiology, and * Institute of Nuclear Medicine, University of Pisa, Italy.

Although many detailed studies have been performed on ANP synthesis, secretion and biological effects, little is known, however, about the metabolism and clearance of this hormone, particularly under controlled steady-state conditions.

We have developed a tracer method to measure the plasma disappearance of the biologically active [nSI]ANP. Three ~g of synthetic ANP were monoiodinated by means of lactoperoxidase technique and then purified by ion exchange chromatography and tlPLC. About 80 gCi of sterilized tracer was IV bolus injected in 6 normal male volunteers who were at rest in clynostatic position for at least 30 min. Thirtheen venous blood samples were collected from 0 to 50 min after injection into ice-chilled disposable polypropylene tubes containing aprotinin and EDTA. To calculate the recovery of [I~SI]ANP known amounts of [~3II]ANP were also added to plasma samples. Three ml of plasma samples were extracted with Bond Elut C18 cartridges and then purified on HPLC. In all cases, plasma decay curves of [125I]ANP were satisfactorily fitted by a biexponential function; kinetics parameters were estimated using both noncompartmental approach. The mean total plasma clearance rate was 1654+588 ml/min/m 2 b.s. and the mean residence time in the body was 24.1+24.9 rain. The mean apparen~ initial distribution volume was 11.1+_2.7 L/m2 b. s., thus similar to the sum of the plasma compartment and the interstitial space.

The present study demonstrates that ANP is rapidly cleared from circulation in humans according with previously reported data obtained in experimental animals. Moreover, the biexponential shape of the disappearance curve indicates that some hormone molecules, after escaping from the initial distribution space, are able to reentry from the peripheral compartment before being degraded. The selection of the method for handling standard curve data for routine use is a c r i t i c a l step in method evaluation. AIM~ of the study was the comparison between some widely _ _ used standard curves for data reduction. We used an AFP IRMA commercial k i t . A standard curve with standards of O, 3, 30, 100, 250, 500, and 800 ng/ml in t r i p l i c a t e ~as performed using the following mathematical models of data reduction. I:CRM v.CONC(linear interpolation) ( l . i ) . 2) The estimated value of the control serum was very close to lOng/ml in 2, 4,5 (10±0.1 ng/ml) in contrast in 1,3,6 was (10±2,4ng/ml) 3) In all tested curves the PP of the~coefficient of variation was <10% for the range of 3 t6 800ng/ml. 4) The MDC was found in the LIN-LOG /LOGIT (Regression weighted parabolic curve) (RWPC) O.044"ng/ml. In-contrast-in B/Bo v CONC-(Li) was found 8~34 ng/ml. CONCLUSION:Although most laboratories dispose computers giving selection of data reduction packages, containing some index of "goodness of f i t " , i n those where there aren't, i t is necessary to know the limits of the method they used. We recoamend for high concentration serum levels, the dilution of the samples and in low,the use of LIN-LOG (RWPC).

A Thirteen clinically euthyroid goitrous patients with a long term L-T4 therapy program received a single oral L-T4 (150~g) dose. Serum TSH,TT4, fT4 concentrations were measured before and 0.5, 1,2,3,4,5 hours after the oral L-T4 administration.Basal serum TSH concentration(2.6 ~ 1.93~UI /ml,mean ± SD)progressively fell to 1.33 ~ 1.24pUI /ml value(p=0.0004);basal serumTT4 concentration (9.2 ~ 2.14pg/dl)began increasing significantly at the first hour(10.05 ± 2.14~g/dl,p=0.02)and rea ched the highest value at the third hour(ll.ll ~ ~ ;g/dl,p=0.0007);subsequently TT4 values tended to decrease,being 10.8 ~ 2.76@g/dl at the fifth hour;basal serum fT4 concentration(8.79 ± 1.89pg /ml)began increasing significantly after half an hour(9.46 ~ 1.67pg/ml,p=0.001),and reached the hi ghestvalue at the thirdhour(12.15 ± $.01pg/ml, --p=0 .0001),subsequently fT4 values tended t o d e c r e asebeing 11.62 ± 2o6pg/ml at the fifth hour. --Our data indicates that a single oral "therape~ tical" L-T4 dose reduces serum TSH concentration significantly and increases serum T4 concentration as well. This last effect shows h o w i m p o~ tant is the time interval between the daily L-T4 assumption and the blood sampling for dete _ rmination of serum T4 concentration in L-T4 treated patients. cell-labeling in whole blood and non-invasive imaging of blood-pool and infection. We optimized the conditions of the chelation e.g. concentration of reactants, pH, time and temperature. The 25-mer nucleotide sequence for histone4-mRNA was modified by coupling with aminohexyl group (AHON) and conjugated with DTPAisothiocyanate (1/10); 50 ~g of DTPAAHON were chelated with 37-370 MBq (1-10 mCi) of I n q l l chloride with high specific activity (30-100 #Ci/~g) and labeling efficiency (60-80)%. Incubation of In-DTPAAHON with whole blood (dog, pig and human) for 5 min indicated (95~+2)% retention by cell-pellet and sequence of binding affinity per million cells was leukocytes > > platelets > red cells. In-DTPAAHON was stable in plasma and indicated high permeability, cellular extraction and retention; 0.1 ~g/ml of In-DPTAAHON was found optimal for cell-labeling. The blood-clearance (5X) of In-DTPAAHON in Beagle dogs resulted in clearance of (75+6)% with a T,~. of (420+30) hours; 5 Yorkshire pigs were sacrificed for biodistribution at 3 hours after injection; (78±8)% of injected dose was in blood, (11+__3)% in lung, (6__+1)% in liver, (1.1_+0.2)% in lddneys and (11+2)% in muscle. On the other hand, injection of In-111 labeled sense probe resulted in early urinary excretion (45%). Ceils in blood could be labeled by direct injection with a new probe of In-DTPAAHON and blood-pool could be imaged non-invasively for MUGA and gastric bleeding studies. Gamma-emitting probe of molecular biology may find new applications in the future practice of diagnostic nuclear medicine. The purpose of this work is to present the first results of labeled WBC orbital scintigraphy (n:6).

The study was performed using autologus le~kocytes labeled by 99m- Tc-~PAO (Amersham), with leukoc~tes + recovery at 5~/o-11 and labelig efficiency of 6~/o113. Orbital anterior and both lateral static images were obtained 4 and 24 h following the i.v. administration of labeled WBC (150 MBq), using dualhead scintillation camera (Siemens), computer connected (Microdelta). Unilateral orbital accumulation of labeled WBC i.e. true-positive results (confirmed by PH, n=4) were obtained in five patients: I orbital inflammatory pseudotumour, I necrotic uveal melanoma with severe orbital reaction, 2 orbital tumours accompanied inflammation and I orbital tumour moderately inflammed as well as I true-negative scintigraphy -control following succesful conservative treatment of the inflammatory pseudotumour. Other imaging methods RTG, US, CT or MR did not suggest the inflammatory nature of these tumours This small series of leukocyte imagings demonstrate I. unilateral gathering of WBC whenever orbital inflammation was present, 2. a negative scintigraphy following sucesful treatment of an inflammatory lesion and 3. WBC accumulation in malignant tissue if necrosis or inflammation was present. 99mTc-HMPAO WBC scintigraphy looks to become a new, useful and specific tool in the detection of inflammatory loci and in the differential diagnosis of orbital lesions. is a new ia~unoradic~etric analysis using two specific antibodies against the m~m~rane epitopes of a breast cancer cell line (BC4E 549) and the fatty membrane of . Tne aim of this study is to determlr~ their normal ranges and assess their usefulness in the follow-up of breast cancer.

A oontrol group was established with i00 healthy, nonpregnant w~ren. ~his group did not present a normal distribution, and the normal maximal value was set at 12.7 U/ml, corresponding to the 97.5 percentile.

The group of patients was divided into two subgroups. Group I was made up of 135 female patients with stable disease, who had undergone surgery for breast cancer, or had positive axillary nodes, inoperable breast canoer or nouprogressive metastatic disease. None of the patients had reoeived chemotherapy or radiotherapy in the tWD months preoeding marker determination. Group II cc~sisted of 29 f~ale patients with metastatic disease in confirmed progression.

In g-fD%~ I, the CA 459 values ranged between 2.6 and 22.5 U/ml, with the values bey~md noln~al range corresponding to patients with nonprogressive metastasis.

In ~ II, the range went from 6. The cbjectives of this study were to evalute the safety of repeat administration of to humans, and also to determine the efficacy and imaging performance and it's relatic~zship to ~ anti-mouse antib(x~y (h~MA) develoim~nt. Patients with previously resected colorectal cancer, and at hzgh risk for recurrence, were enrolled in this trial. Each patient received 1.0 mg CYT-103 intravenously, to be repeated every 4-6 months if clhnically ~arrented. Planar and t~graphic images were obtained twice, usually between 2-7 days. Serial bloed sanples were evaluated for CfI~I03 clearance and HAMA develq~m~nt. To date, a total of 174 infusiens (infs) were aOministered to the 69 patients who received [2] [3] [4] [5] infs. Persistently Ix~itive kmMA levels (~ 0.4 ug/ml) were detectable in 23% and 31% of patients follo~/~g 1 and 2 infs respectively. FAMA positive patients had markedly increased clearance rate of C91~I03. F~ur of 105 repeat infusions (3.8%) were associated with d~/g related adverse events, 2 of which occured in patients who were HAMA positive. Sixteen of 22 known lesions were detected by immunoscintigraphy mostly in HAMA neg patients (73% sensitivity). TWo pbotopenic liver lesicns were idef~ified in }~MA p~sitive patients.

In conclusien, repeated infs of CY~-I03 can be safely a6~inistered, and c2n be clinically useful in }I~MA neg patients. ~e effect of rapid clearance on imaging efficacy is not clear frc~ this study because of the low number of confirmed lesions in HAMA positive patients. This ~s currently under investigation.

D.Hernalsteen, J. Oewelde, J.P. L~onard Clinique Parc L~opold, Brussels, Belgium.

In the follow-up after primary surgery and during chemotherapy in breast cancer patients, we have studied serum levels of a variety of tumor markers: 3 markers, considered to measure tumor mass: CEA (Pharmacia), CA , CA 125 (Byk Sangtec), and 2 markers considered to measure tumor proliferation: TPA ( Byk Sangtec, polyclonal anti-TPA) and TPS (Beki, . Marker values were determined retrospectively in 175 serum samples of 10 breast cancer patients, that have been sampled from the time of the i n i t i a l diagnostic (stage I I I or IV); the patients were selected to include those who developed recurrence and were monitored for 8 months to 5 years (median time: 25 months; 6-25 samples per patient ). Low concentration of the .two groups of markers was associated with stable disease or remission; progressive disease was associated with increase of CEA: 5/10; ¢A-15-3: 9/10; CA~125 : 2/3; TPA: 9/10 and TPS: 9/10. In 7/10 cases, markers showed a evident increase several months prior the clinical diagnosis of relapse. In 4/7 cases, TPA and TPS increased more precociously than the tumor mass markers. During therapy monitoring, TPS and TPA levels followed the increase or decrease of CA 15-3 and/or CEA levels in 8/10 cases. Moreover, TPA or TPS reacted much faster than the tumor mass markers to indicate response to therapy. I t was concluded that trends in marker concentrations showed a good cgrrelation with the clinical status and that a combination of markers assaying both tumor mass and tumor proliferative a c t i v i t y provided the best method for a more effective monitoring of breast cancer patients. Besides the steroid receptor status, several new, potentially, independent, biological, prognostic factors have been proposed. One of these promising factors is Cathcpsin D, a lysosomal protein, which belongs to the family of proteascs. It has been shown to be a marker of tumor invasiveness, and its measurements in cytosolic extracts of primary human breast tumors may particularly be of prognostic use for breast cancer. The primary objectives of the present multicentrie study are to evaluate the clinical significance of Cathepsin D and laboratory performance of its determinations. According to the standardization and external quality control sebeme, under the anspiees of EORTC Receptor Steroid Group, the nine participating centres have achieved these results: a) between-assay = 13%; b) within-assay = 10%. Regarding the 1552 cases' data, the main preliminary results are summarized as follows: a) Cathepsin D levels have shown in all cases no correlation with lymphonodal and menopausal status; b) besides, it was not sigulficantly correlated with receptor status in premenopausal Neases; c) however, it showed a correlation in post menopausal patients (p = 0.002) with N+ (p = 0.52). In conclusion, assays of Catbepsin D in tumor eytosol provide valuable prognostic informations for breast cancer patients with nodal involvment at the time of diagnosis. Novakovi~ R., Josifovski J., Kosti~ N., Milinid N. and The RU ard ~A valQes a L~, q, 2q hour's incresed s~eadly in a l l gP~lps. However, RU and %~"values of HIG wer'e sigqifican~]~ higher' than U-~at of . ~aPeover,RLI and V~A values Mere considerably increased in ~he Sa than Ec gr"~p by HIG sc!nEigPaphy; M~ereas there was no s i~q i f i c a r~ d i f f e r e n c e betwe~ these groups by 0a-67 Hormonotherapy is commonly used in the treatment of ederly patients with non metastatic prostate cancer. Serial determinations of PSA and rectal examination are efficient methods to follow this patients, but when to indicate a bone scan ?.

We rewieved records of 78 patients with non metastatic prostate cancer (i0 A2, 18 B and 50 C) and a follow up of 62. 3 months (6-192) , treated with hormonal therapy. During this follow we performed 821 determinations of PSA and 268 bone scans. We detected clinical progression in 17 patients, local clinical progression (LCP) in ii patients (14.1%) and metastatic clinical progression (MCP) in 6 (7.7 %). Incidence of metastatic progression was 35.3 %. Levels of PSA in LCP ranged between 4.6 and 180 ng/ml (48.9 + /-49.4 ) and between 219 and 490 (370.1 +/-109.8) for MCP. Positivity rate for 286 bone ycans was 2.1% (6 patients with MCP). Level of i00 ng/ml of PSA provided in the diagnosis of MCP i00 % of sensibility, 90.9 % of specifity, positive predictive value of 85 % and negative of 100 %, and efficacy of 94.1 %. Using this level of PSA we should have been avoiding 97.6 % of bone scan, having a sensibility of i00 % and efficacy of 85.7 %.

We conclude that in the follow up of patients with non metastatic prostate cancer treated by hormonotherapy, bone scan scintigraphy can be only indicated when P S A level overcomes more than i00 ng/ml, reducing a high number of bone scan uselessly indicated. Radioimmunoscintigraphy (RIS) with Tc-99m labelled anti-melanoma monoclonal antibodies (MoAbs) 225.28S is currently used to detect uveal melanoma particularly in presence of opaque ocular media. However, a low tumoral uptake and a high non specific background activity in the nasopharyngeal region make it difficult to detect small size melanomas and tumors located in the nasal quadrant of the eye. To overcome this drawback we evalueted the RIS with 3-step IN BREAST  TUMORS  BY  IN  VITRO  QUANTITATIVE  AUTORADIOGRAPHY USING IODINE-125 BC-2 MONOCLONAL ANTIBODY. Tenascin (TN) is a stromal glycoprotein expressed in breast cancer, while it is not in normal breast. TN is recognized by a murine IgGl: To detect and measure TN in 20 breast tumor biopsies we have performed in vitro quantitative autoradiography technique (IV-QAR) using (I-125)-labeled- . 14 consecutive sections have been cut from frozen tumors (thickness 8urn); 2 sections have been used for immunoperoxidase (IP) and 1 for H&E stainings, 11 for the saturation study of IV-QAR. In seven sections has been measured the total binding by incubation with increasing concentrations of 1-125 BC-2 (0.8 to 56.2 nanomoles/1), in other 4 the non saturable binding by pre-treatment with unlabeled BC-2 (lmg/ml) and by incubation with labeled (6.4-56.2 nmoles/l) plus unlabeled, in excess BC-2. The sections were then exposed along with sections of 1-125 standards to sensitive films. The opical densities of the standards were plotted vs. their specific activity (uCi/g) and a standard curve obtained to have the levels of BC-2 bound to the tissues. The molar content of TN was measurable in 17 cases ranging from 35 up to 300 pmoleslg; the expression was quite heterogeneous, being associated to the stroma and not to the neoplastic component. TN levels in normal breast were not measurable as well as in benign nodules. A strong positive correlation was found between TN levels and estradiol (E2) receptorial status (r=0.95) as well as a perfect agreement in the distribution of the antigen depicted by IV-QAR and IP. In three negative tumors to IV-QAR, lack of TN was also demonstrated by IP. These results indicate: TN represents a marker in breast tumors; TN is widely and heterogeneously expressed and its expression is related to the E2 status; and elevated TN levels, in primary breast tumors, justify the use of labeled BC-2 for RIS. Preliminary trials with B72.3 antibody have previously been can:led out in the USA. lmg doses of antibody were labelled with between , resulting in effective dose equivalents of up to 57mSv. In Europe administered doses are generally lower. To investigate the compromise between dose and image quality we have performed planar and SPECT imaging in two groups, each of 10 patients who received lmg of B72.3 antibody (Oncoscint CR-103) radiolabelled with either 80 or 150 MBq . SPECT data were collected in a 64 x 64 matrix using 64 incremental views of 20 seconds each through a 3600 rotation. Processing parameters were assessed using data from a hot rod phantom with target to non-target (T:NT) ratios of In-111 between 2 and 4 to 1. Optimum detection resulted by prefiltering the phantom data with a wiener filter (0.25 cut off) followed by reconstruction using a ramp filter. The smallest lesion diameters detected were 15 and 10mm at T:NT ratios of 2:1 and 4:1 respectively. Counts in the patient views increased by 65% with the increased dose resulting in images of higher quality. Overall antibody imaging demonstrated tumour sites not seen by x-ray CT in 21% patients investigated. SPECT imaging increased the confidence of tnmour detection; the clarity of tumour visualisation varied between planar, transverse and coronal views, although coronal views were especially helpful in assessing non specific bowel uptake.

This study shows the clinical value of SPECT imaging in relation to the activity administered and the image reconstruction parameters. The aim of this study was to compare scintigraphy with MRI for the diagnosis of tumoral infiltration of the spinal bone marrow. Included in this study are 14 children, 7 girls and 7 boys with neuroblastoma proven through pathological biopsy evaluation. All the children presented one or more abnormalities: tumoral infiltration of the bone marrow on biopsies, hyposignal of the vertebral body on MRI, abnormal uptake of the spine on scintigraphy. In most of the cases, the amount of injected was 1 mCi ( 37 MBq ), the radiochemical purity was determined by thin layer chromatography. Using a large field gamma-camera, multiple views of the head, thorax and abdomen were obtained. The duration of each scan was 10 minutes. 11 MRI examinations were performed on a 0,5 Teela and 3 on a 1 Tesla. T1 weighted images were obtained with a repetition time ( TR ) of 250 ms and an echo time ( TE ) of 28 ms. The interval between MIBG and MRI varied from 1 to 13 days. In all cases, the primary tumor was enhanced by MIBG. In 3 cases with neuroblestoma cells found in biopsies, there was no spinal abnormality on MIBG scintigraphy and MRt. In 6 cases, diffuse spinal abnormality on MRI and MIBG scintigraphy was demonstrated. In 5 cases, a normal spinal uptake was observed using MIBG and a Iocalised abnormality using MRI was revealed " a tumoral bone marrow was confirmed by biopsy examinations in 3 cases and the proof of a tumoral bone marrow infiltration was never obtained in 2 cases Considering it is very important to detect and to confirm a bone marrow infiltration, it was decisively indicated to perform these two explorations simultaneously. It's known that interferon (IFN) may increase the antigen expression of tu~r cells when added to cellular cultures or injected in animals bearing tumor xenograft. Rosemblum e t a ] . demonstrated that IFN a]fa can significantly enhances the uptake of 96.5 MAb by p97 rae]an~a antigen and consequently increase the tumor uptake improving radioi~unoscintlgraphy (RIS) of malignant melanoma.

The aim of our study was to verify possible variations of biodistributlon and tumor uptake of 225.28S MAb after IFN alfa administration in patients with advanced malignant melanosa. This antibody, largely used by us to perfor~ RIS of melanoma, is directed against a high molecular weight melanoma associated antigen (BMW-MN~). This preliminary study involved two groups of patients (A,B) with metastatic malignant melanoma, examined with RIS before and 24 hours after IFN alfa therapy. The antibody was injected as 99m -Tc-F(ab')2 with a mean activity of 800 MBq. Following the therapeutical protocol in use in our Institute six patients (group A) received i.m. administration of 3"IOE6 UI of IEN aifa and five patients (group B) i.m. admonistration of 9"IOE6 UI of IFN alfa. Whole body scan, planar imaging of thorax and abdo~en and SPET of the region involved by the tumor localization were performed at time O, at 5 and 24 hours after MAb injection. ROT were choosen in order to evaluate the biodistributlon and the uptake in tumor localization and in different organs. Blood sample were collected in order to deten~ine the blood clearance of the antibody.

Even though a faster blood clearance of the antibody was demonstarted after IFN administration, expecially by the use of the higher dose ( T1/2 fror~ 43 to 26 minutes), no statistically significant variations of tomor uptake were evident. In particular nor variation of false positive results was demonstrated nor new lesions were disclosed, nor was i t possible to demonstrate enhanc(~nent of tumor uptake. PET with FDG allows the estimation of the glucose metabolism in malignant tumors during therapy. These data about metabolic changes induced by a single agent can be used to develop a metabolic designed combination therapy. This in vitro study was undertaken to measure the effects of Hexadecylph~sphocholine (HPC) on the FDG uptake in MCF7 cells and to develop an app#opriate combination therapy. The cells were treated with three different doses of HPC for 2 hours or 24 hours. The FDG Uptake was measured with '4C-FDG one and four hours after HPC therapy in glucose-free RPMI1640 medium. The radioactivity was determined using High Pressure Liquid Chromatography and the FDG uptake was expressed as nCi/well or standardized to the number of viable cells. One hour after HPC therapy a dose-dependent increase of the FDG uptakes was observed (more than 200% for the highest dose); four hours after therapy a decrease was seen. However the accumulation in treated cells in all cases was higher or similar to the control value~ Thereafter a therapy was developed using the time-and dose-dependent effects of HPC on the glu.cose metabolism. Three doses of HPC and two doses of deexyglucese (DOG: lmg/ml or 2rag/mR were given in different time schedules: HPC and DOG simultaneously (K1), HPC and one hour later DOG (K2.), HPC and four hours later DOG (K3). The cell number was determined on day 1,2 and 3 after combination therapy using a Coulter Counter. On day 1 we found an 100% improvement for all combination therapies, on day 2 and 3 only K2 and K3 showed a benefit. K2, the application of DOG during the period of strongly enhanced FDG uptake, proved to be the best combination. These data show that in vitro the development of a metabolic design of chemotherapy is possible. However the in vivo application and the benefit of this approach for patients have to be shown using PET and 'aFDG. A comparison was made with mice depleted of endogenous biotin by sequential ip injections of 500Mg of streptavidi n every 15 hours.

Assay of serum biotin levels indicated <0.5 ng/ml in treated vs 4 ng/ml in untreated animals at one day.

Approximately 4% of the STAV-AB conjugate was localized per gram of tumor as measured by radioactivity, equivalent to approx 6~g of streptavidin per gram of tumor. Analysis of single cell suspensions of the solid tumor was made using a fluorescent activated cell sorter (FACS) and two fluorescent probes: FITC-goat anti-mouse antibody (to verify the presence of anti-CEA antibody} and biotin-phycoerythrin (to verify available biotin sites on streptavidin}. Although the STAV-AB was present on the cell surface through 48 hours, in both untreated and biotin depleted mice, as verified through the FITC-goat anti-mouse antibody probe, only in the biotin depleted animals were sufficient biotin sites on streptavidin observed; i.e., a 30-fold increase in fluorescent intensity was detected in biotin depleted mice relative to untreated. These results suggest that the small percentage of streptavidin delivered to a patient tumor via a specific antibody may in fact become saturated with endogenous biotin and not able to bind labeled biotin.

However, this can be avoided by increasing the dose of streptavidin. 

This prospective study has been undertaken to evaluate the clinical significance of MRI and bone marrow scanning (BMS) in the detection of marrow metastases in the follow-up of breast cancer patients, 21 patients were thus far included into this study during their initial staging (age: 28 -76 years) . The primary tumor stage was: T1, N0_l, M x. For MRI, a 1.5 Tesla whole body magnet (Philips Gyroscan) was used, and continuous coronal T1 weighted spin echo (SE) scans (5ms slice thickness) of the pelvis region were recorded. Also, sagittal T1 SE scans with 3.5 mm slice thickness of the entire spine were performed. For BMS, the Tc-99m labeled anti-granulocyte antibody (BW 250/183, Behringwerke, Frankfurt, FRG) was used. Whole body scans and single planar scans were obtained 4 hours post injection (activities: . Conventional bone scans using Tc-99m MDP were also performed in each patient. All image modalities were conducted in each patient within 3 weeks (mean). The scans of the 3 sodalities were then evaluated by two experienced (blinded) readers. Of the 21 patients studied, 16 had normal findings in all 3 sodalities. 2 patients had multiple metastases which were detectable with all 3 methods. Of these, one patient showed spine metastases on MRI and BMS which were not detected in the bone scan where only rib lesions were visible. 3 patients had unequivocal findings in one respective method which could not be confirmed by the two other. Considering the patients with doubtful findings as not positive, only 10% metastases occurred during the initial staging. The bone marrow scintigraphy seems to have a comparable sensitivity to MRI and the bone scan and it could thus be employed at the beginning of staging since the entire marrow can be visualized. Z. Kusi~, Lj. Lukinac, S. Ron~evi6, ~. Labar, D. Franceschi. Department of Nuclear Medicine and Oncology University Hospital "Sestre Milosrdnice" Zagreb, Croatia. THYROGLOBULIN DETERMINATION, 

The purpose of the study is to evaluate serum thyroglobulin (Tg) measurements, in 359 patients (PTS) with differentiated thyroid carcinoma (DTC). All PTS had undergone surgical treatment and radioiodine ablation of the thyroid remnant. They were followed-up by 1-131 whole body scintigraphy 0NBS). The Tg levels were determined in all PTS after T4 withdrawal, and in 89 of them during replacement therapy as well. WBS was performed in 19 PTS. Twelve of them had increased Tg serum levels, and in 15 PTS I-131 WBS was negative. The neck USG was obtained in 67 PTS with real time sonography using 5 and 7,5 MHz transducers.

Undetectable or very low Tg levels were determined in 279 of 297 PTS with no signs of tumor tissue. Increased Tg levels were found in the remaining 18 PTS (ranging between 11 and 89 ng/ml). These PTS are being carefully monitored. Elevated Tg levels (> 20 ng/ml) were measured in 27 of 28 PTS with metastases accumulating I-131 and in 6 of 9 PTS with nonfunctional distant metastases (> 260 ng/ml). In 15 PTS Tg levels were found to correlate with the disease progression or the success of treatment. The neck USG was positive in 20 PTS. In 6 of 8 PTS with nonfunctional lymph node metastases Tg ranged between 12 and 300 ng/ml. Increased Tg concentrations were found in 6 of 12 PTS with benign nodules (between 14 and 31 ng/ml). WBS was positive in six PTS. Three of them had negative 1-131 WBS and one patient had negative I-131 WBS and undetectable Tg level, In two PTS TI-201 WBS detected more metastatic sites than I-131 WBS.

In conclusion, serum Tg determination is of considerable value in the management and follow-up of PTS with DTC, while TI-201 WBS and neck USG with biopsy are useful in PTS with increased Tg levels, but without other signs of tumor tissue. 8P3-2 R. Claessens, W. Oyen, E. Koenders, J. "libben, L. Massuger, and F. Corstens, University Hospital, Nijmegen, The Netherlands. De-iodination in vivo is a well known feature of iodinated compounds. Release of indium might be even more important for indium labeled preparations. We compared the tissue distribution of indium labeled and iodinated polyclonal human IgG in an infection model. We did the same for the MoAb OV-TI 3 in an ovarian carcinoma model. As infection model we used Wistar rats with a Staph. Aureus abscess of the calf muscle. As turnout model we used athymic Balb/c mice with a subcutaneously growing NIH:OVCAR-3 turnout. Indium labeling was performed via DTPA. Iodination was performed using either Iodogen (IO) or the Bolton-Hunter reagent (BH). Human polyclonal IgG was labeled with either . OV-TL 3 was used as the F(ab')2 fragment labeled with either In-111 or I-123. Plasma samples taken at 24 hr were analyzed by gel filtration on Sephadex G-75 . For IgG at 48 hr the abscess uptake is 1.0% I.D./g (In) and .5% I.D./g (I both IO and BH), being 95 and 55% resp. of the maximum uptake (at 6 hr. p.i.). For OV-TL 3 the turnout uptake at 48 hr is 6.0% I.DJg (In) and 4.6% I.D./g (I both IO and BH), being 85 and 81% resp. of the maximum uptake (at 6 hr). After injection of I-IgG the thyroid uptake at 48 hr is 3% I.D. (IO) and 1.5% I.D. (BH) (p<.01). After injection of I-OV-TL 3 the thyroid uptake at 48 hr is 1.8% I.D. (IO) and .05% I.D. (BH) (p<.01). Only for I-IgG (IO and BH) a good positive correlation is observed between abscess uptake and blood disappearance (r~=.99). Both labeled IgG and OV-TL 3 are stable in plasma for at least 24 hr. is well retained in the turnout. Only In-lgG is sufficiently retained in the abscess. De-iodination seems only of minor importance with respect to abscess and turnout uptake. Apparently indium conjugated to IgG and IgG behave differently. Release of indium in the interstitial fluid might explain this phenomenon and might also contribute to liver and turnout uptake of indium labeled MoAb's. Clinical staging of neuroblastoma (NB), a very con~non extracranial malignancy of childhood, is crucial prior to successful management. has been used for the detection of bone disease but more recently MIBG labelled with Iodine has been used for imaging ( 1-123 ) and treatment ( 1-131). The aim of this study was to assess the relative value of these radlopharmaceutlcals in detecting bone secondaries and to study their distribution and frequency. Retrospectively, 67 biopsy proven patients (males: 35, females:32, age range: 3 months to 16 years, mean: 4.5) referred for ~P and/or MIBG scans were analysed, with a total of 138 MIBG and 73 MDP scans (within 2 weeks on 63 occasions) . Results showed that MIBG detected more lesions (847) than MDP (118)o Apart from the ribs and pelvis, there was no significant difference in the distribution of the lesions detected by both agents (Chi squared test, X 2 = 84.079, p>0.88). Likewise there was no difference in the detection of lesions by the two agents in appendicular compared with axial skeleton (X2=0.063, p>0.05) o Results from the combined MDP-MIBG studies showed that although MIBG detected more lesions, it missed some (mainly in the ribs) which were detected by MDP, while those lesions detected by MIBG solely were in the spine, and pelvis. We conclude that both MDP and MIBG are complementary and both are indicated in patients with neuroblastoma. 

Purpose studied/Introductlon: Often is not possible to be certain whether an abnormal bone scan represents a metastasis or not, this problem being particularly difficult in sollta~y hot spots. The aim of this work was to report our experience and results in suspected or not metastases using 99Tcra-labelled nonspecific polyclona] Human Im-munoGlobulin (-HIG) and to evaluate and compare its applicabilit~with 99Tcm-MDP findings. Nouspecific polyclonai IgG labelled with ~Tc ra, binds according to in vitro results, to the Fc receptors of monocytes and granulocytes (17.1% and 3,3% respectively, of the total radioactivity applied). In caracter to that, radlolabelled IgG, when injected intravenously should be attracted by pathologies with increased mono-and granulocytes and thus selectively detected by scintigraphic methods. Since the pathology of osteosclerotic metastases is not characterized by an osseous inflammatory reaction (osteocellulitis) but rather by tumour emboli and tumour cell proliferation, the attempt to image bone metastases using 99Tc-HIG should not succeed, and scinfi~ra~nhi,'c findings should be negative in contrariety to the positive one of "Tc MDP. Only bone metastases associated with osseous reactive cellulitis could give a positive 99TcraHIG scan. Method/Results: 555 MBq (15mCi) 99TcraMDP and 555 MBq (15mCi) 99Tcra-HIG were both injected to each patient, within a time interval between the two investigations of [3] [4] days. All 99TcmHIG scans performed in 58 pts with known metastases (with 99Tcra-MDP scintigraphy confirmed) were negative. is presently the only isotope of iodine used in the follow-up of patients (pts) with differentiated thyroid cancer by means of whole-body scan (WBS). Nevertheless, poor image quality, relatively high dosimetry to pts (due to unfavorable physical characteristics) and long duration of the study are the most important drawbacks encountered using this radioisotope.

Therefore we stared an investigation on the use of in place of 1-131 in the follow-up of thyroid cancer pts, given the better physical characteristics of the former. The study involved 10 pts (7 women and 3 men, aged 28-80 years) previously submitted to total thyroidectomy because of papillary or follicular cancer; 7 of the pts had already been treated with radiometabolic therapy. After discontinuation of substitutive L-T4 therapy or ablative surgery for at least 6 weeks, the pts underwent the following protocol: 1) WBS at 1, 6, 24 and 48 hours after the i.v. administration of produced by activation of Xe-124 through the (p,2n) reaction (supplied by Sorin Biomedica, Saluggia, Italy); 2) WBS 72 hours after the administration of 1-131 in either a diagnostic (185 MBq in 7 patients) or an ablative dose (3.7 GBq in 3 patients), one week latenWBS images were acquired with a LFOV gamma-camera (600 XR/T GE-CGR, Milwaukee, USA) using a LEGP and a HE collimator in a total time of 30-45 minutes for each session.

The quality of the scans obtained with the two radioisotopes was comparatively evaluated by two independent and experienced observers and the temporal pattern of 1-123 uptake was also determined, considering WBS at 1 hour as the total dose. The 1-123 WBS images definitely showed an overall better quality than the 1-131 scans, also allowing a satisfactory definition of the uptake areas and the visualization of anatomical regions (like the esophagus) not visualized by I-131 . The peak percent uptake values in the thyroidal region were observed about 24 hours after the administration of 1-123.

The results obtained in this study indicate that: 1) WBS with 1-123 in the followup of differentiated thyroid cancer is feasible; 2) the scans obtained with I-123 show a better quality in comparison to 1-131; 3) despite the short half-life of 1-123, the high target-to-background ratios observed already 24 hours after administration allow one to record serial scans from which to carry out quantitative estimates of radioiodine uptake; the examination times and dosimetry both to the patient and to the genersl population are thus highly reduced.

Maffioli L, Castellani MR, Cusumano F, Gasparini M, Del Bo R, Pascali C, Bombardieri E, Buraggi GL. (1-5 rag) at 2 hrs, 24, 48, 72 hrs after injection. In selected patients (n=6) blood samples were taken at regular time-points and 24 hr urine was collected throughout the whole study. Chest X-ray and CT studies were used for localization of the primary tumor and metastases thereof. Tumor biopsy specimens from all patients were MOC-31 positive using immunoperoxidase staining techniques on frozen tissue sections. No adverse reactions were observed in any of these patients. Blood clearance is represented by a single compartment model with a half life of 17 hrs. The 24 hrs urine excretion varied from [2] [3] [4] [5] .5 % of the injected dose and was constant during 3 days after injection. In 8 out of 11 patients tumor or metastases Iocalizations were detected by immunoscintigraphy. Detection of metastatic tumor lesions seems better than the detection of primary tumor suggesting poor penetration into larger tumor masses of the latter. Although the group of patients used in these experiments was small, preliminary results indicate that MOC-31 may be a promising diagnostic tool for staging of small cell lung carcinoma. In order to study the "in vitro" behaviour and radiopharmacokinetics of the anti-c~A monoclonal antibodies BW 431/26 (MAb), w~ have studied 40 patients with prh~axy turnouts of colon. Each patient was injected with 2.0 mg of the MAb (851 -+ 148 MBq) in 50 ml of saline solution 0.9%, infused through an i.Vo line in 15 • d_n. Blood sanloles were taken periodically a~d during surgery w~re also studied.

i.-The yield of labelling was 98 + 2% (n=40). 2.-"In vitro" stability was adequate two hours after labelling, with a radioch~ical purity higher tha~ 97%. 3.-Iramz~oreactivity after labelling was 84 ± 7%. 4.-Blood ~ at 30 minutes, 5 hours and 24 hours was 77. 0 -+ 8.9, 64.4 -+ 8.7, 41.7 -+ 5.6% I.D. respectively (n=8) . Utility of IS with 99m-Tc labelled MABs for detection of colorectal cancer (CRC) has been documented in numerous clinical trials. However, little Is known about limitations, in particular technical or tissue-dependent factors influencing tumor detection by IS. It was the aim of the present study to provide such data by comparing outcome of preoperative in-vivo IS in 16 CRC-pts with ex-vivo IS of surgical specimens and correlate findings with tumor size, location, CEA-expression, and RC. Invivo IS (planar and SPECT) was performed 5 and 24 hrs. after iv injection of 2mg anti-CEA MAB (BW 431/26) labelled with 1100 MBq 99m-Tc, ex-vlvo IS (planar) immediately following surgery. Overall sensitivity of invivo IS was significantly lower compared to ex-vivo IS (21/38 vs 82/38; p<.05) due to poor results in lesions <2cm (6/22 vs 16/22; p<.05). >2cm: 12.2 E-08%ID/g) of tumors <2cm or >2cm revealed no significant differences. Sensitivity for extra-and intrahepatic disease was similar, too (16/29 vs 5/9; n.s.). Higher percentage of small lesions (<2cm) in extrahepatic disease (19/29 vs 8/9), however, indicated inferior results of IS in liver metastases.

We conclude that diagnostic performance of IS is mainly limited by tumor size. Detection of small lesions is possible, but most of them may not be visualized because of technical limitations (spatial resolution, lack of attenuation correction) of gamma camera systems available today. 

Fluorodeoxyglucose (FDG) is considered as an accurate marker of the metabolic tissue activity. Quantitative PET FDG imaging was suggested for the characterization of malignancy and the evaluation of efficacy of therapy. We tested in vitro the relationship existing between FDG cell uptake and therapy effects. Using the human premonocytic U937 cell line, we compared the measurements of the metabolic, cytotoxic and anti proliferative effects of bleomycin (BLM), an antibiotic that showed cell toxicity by means of DNA strand-scission and that is used in particular for the treatment of epidermoid cancer. Methods: Cells were exposed for 1 hour and 22 hours (overnight) to increasing concentration of BLM (0.05 I.tM to 1 raM/well). Cell metabolism was measured by the 45rain uptake of FDG simultaneously to propranolol uptake (PROP) that was used as a control of cell mass. DNA synthesis was measured by the 4 hours uptake of It was evaluated in 9 patients with No tumor in the head and neck region (mean age : 54±7.9, 4 M, 5 F). Following submental, subperiosteal and submucosal administration of 500 ~Ci images were taken at I, 2 and 3 h (Siemens Scintiview II, 256x256, 500.000 cts/frame). Using the LPR01 program the percent radioactivity in the lymphatic system for both right and left sides of the neck was calculated and the results were statistically compared.

The lymphatic nodes were clearly visualized in the normal side. There was decreased radioactivity accumulation and slow lymphatic flow in the tumor side (mean percentage : 5.86±4.14 at 2 h, p ~.005). In the normal side the mean value of lymphatic uptake was 26.25±I0~09%.

In conclusion, Tc-99m-nanocolloid is a valuable radiopharmaceutical for cervical lymphoscintigraphy. The image quality is improved with this new injection technique. This technical advantage might be used in radioimmunolymphoscintigraphy with radiolabelled monoclonal antibodies. Accurate staging of primary head and neck cancer and identification of recurrences is a prerequisite for the choice of optimal therapy. The aim of this prospective study was the detection of locoregional lymph node metastases which are difficult to identify by conventional imaging modalities; A novel murine monoclonal antibody (174H.64, Biomira, Edmonton) was labelled with Tc-99m by a direct method for preoperative immunoscintigraphy in patients with histologically confirmed squamous cell carcinoma (SCC) in addition to panendoseopy, sonography, NMR, and CAT scan. MAb 174H.64 (IgG 1 subclass) detects a cytokeratin-associated antigen expressed by over 90% of all SCC as proven by immunohistochemistry.

1 mg of the intact antibody was labelled with 1.1 GBq Tc-99m by a rapid one-vial kit (labelling efficiency 98% as controlled by TLC) and injected i.v. in 25 patients (pt) after having obtained informed consent. Anterior and posterior whole body imaging was performed 4-6h and, 18-24h p.i. (1000kcts per image, 256x256 matrix) . SPEC'F of the heaa and thorax was done 6h up to 18h (optimal time) p.i. using a HR collimator (360 ° rotation, 5-15 ,000 k, modified Shepp-Logan filter). The imaging results were controlled by histology and immunohistochemical staining.

All primary tumors and all clinically known metastases were detected as immunoscintigraphic hot spots (n= 25 pt). In 20% of the pt, immuno-SPECT identified additional lymph node metastases as small as 1 cm which were not revealed by other staging methods but confirmed at subsequent surgery/histology.

Conclusion. Immuno-SPECT is very promising in the staging of primary head and neck cancer, especially for the detection of lymph node metastases and could play an important role in the preoperative evaluation and treatment planning. The aim of this study is to assess the value of Tc-ggm methoxyisobutyl isonltrile ~ Tc-ggm MIBI) in detecting the recurrence of TC comparing its uptake with Tc-ggm(V) DMSA and in the metastatic deposits of MTC.

Eleven patients with a histologlc diagnosis of MTC and persistently elevated calcitonin levels were imaged at one week intervals using Tc-99m (V) DMSA, 15, 30, 60 and 120 min images were obtained. The average uptake ratios of each agent were calculated from the ROI over the metastases divided by background. The mean of the average count ratios are as follows:

15min 30min 60min 120min ~'c labeled thymidine often is seen as a proliferation marker for PET measurements. This study was undertaken to determine whether this compound is a reliable marker for tumor cell proliferation dudng treatment. Three cell lines derived from an osteosercoma lung metastasis were b'eated with cispletisum and two cisplatinum containing phosphonic acids (AMDP, DADP1 The incubation tirn~ in the drug containing medium was 24 hours. For the thymidine uptake experiments the cells were pulsed with "C-thymidine for two hours. After washing they were lysed with perchloric acid. The acidinsoluble fraction was washed again with perchbric acid. lysed in NaOH and the radioactivity in acid-seluble and acid-insoluble fractbn was determined by scintillation counting. For the acid-insoluble fraction the DNA content was determined after ethanol precipitation. The accumulation was expressed as uptake,%vell, uptake/lO0000 cell s, radk)activity in the acid-soluble fraction/lO0000 cells and radioactivity/Jg DNA. After cisplatisum and DADP the uptake/well showed an 8% increase and no change for AMDI~ The increase in uptake/lO0000 cells was more pronounced for all . However this increase was not due to thymidine lecorporatbn into DNA. since the uptake/Jg DNA decreased in all cases. Consequently the uptake in the acid-soluble fraction hcreased. This finding may be expla!ned by an increase of the thymidine kinase activity. The data were compared to the results of two-dimensional flow cytometry. A bbck in G2 phase was associated with a decrease in thymidine incorporation into DNA. In conclusion we found that the thymidine uptake in treated cells is not necessarily caused by thymidine incorporation. Therefore the valse of thymidine uptake as proliferation marker during treatment may be questionable. We performed PET studies in a rat mamary carcinoma to evaluate the effects of an experimental therapy on the glucose uptake and tumor perfusion. The drug is currently applied in a phase I clinical study. Twelve Sprague Dawley rats with a methyl-nitrose-urea (MNU) induced mammary carcinoma were studied prior to an experimental chemotherapy (100 mg/kg p,o. = group 1 with 9 animals; 200mg/kg p.o. = group 2 with 3 animals). Follow up studies were undertaken in 7 animals 24 hours and in 6 animals 7 days after therapy. The PET examination was performed after i.v. injection (jugular vein) of 1-2 mCi FDG and 10 mCi 0-15 labeled water. ]-he perfusion measurement was done during the first 5 minutes after bolus injection and the FDG uptake study was done for 60 minutes. The PET data were standardized for the injected dose and the body weight (SUV). Six animals of group 1 and one animal of group 2 could be evaluated in the follow up. The FDG uptake prior to therapy ranged from 0.9 to 1.3 SUM In group 1 a decrease in FDG and 0-15 uptake was observed in 30% of the anirnats 7 days after therapy. In group 2 two animals died due to side effects. The surviving animal showed a marked decrease in perfusion and FDG uptake 24 hours after therapy without a change in morphology. These preliminary results of our ongoing study show: 1. metabolic changes due to therapy can be measured with PET at a very early stage before morphologic changes take place, 2. the kinetics of metabolic alterations is different for different doses. Since 50% of these MNU induced tumors are ras oncogene positive, differences in response may be due to ras-induced changes in the tumor cell. This is now under research in our institute. Malignant melanoma is the most frequently encountered primary intraocular neoplasm and its early diagnosis is essential for the further treatment.0n the other hand misdiagnosis rates have been reported at between 2.5-15%. Therefore this study was done to evaluate the validity of anti-melanoma MoAb 225.285 labeled with 9SmTc as imaging agent in patients with unclear diagnosis and suspicion of the ocular melanoma. 50 patients (18 females,12 males) were studied. In all cases CT/NMR,ultrasound,fluorescein angiography and immunosclntigraphy (planar and in some cases SPECT) were performed. Gamma camera ZLC (Siemens) and mikroDelta system were used. All patients were investigated scintigraphically twice or third within g& ha.

The tumours measured 5-18 mm in maximum diameter on ultrasound.The best sclntigraphlc images for tumour date ction were obtained between 3-6h after injection of 8-13 mCi radiotracer.

In 22 patients the scintigraphy was strong positive and in all cases malignant melanoma was confirmed hlstopatho logically.There were no false positive results.

In 2 patients scintigraphy was doubtful.Further clinical obserwation was performed an~ choroidal naevl (in both cases) were suggested.

In 6 Datients immunosclntlgraphy was negative.In this group only one false negative result was noted.

Ocular melanoma is a small definite lesion,on the other hand spatial resolution of the gamma camera is restricted Despite this limitations a high sensitivity and (espscla fly) specificity obtained in the study suggested that MoAb fragments demonstrate the potential for diagnosis of ocular melanoma.

A p r i l e ~, V a n g e l i s t a R, S a p o n a r o R, P r a t i U, V i s e n t i n E . , The murine monoclonal antibody CT-M-01 raised against the antigens of milk fatt globule membrane,labelled by 123-I has been used for axillary ILSC in 77 patients with histologically proven breast-ca, who underwent mastectomy 24 or 48h following the examination.(The study was realized with the approval by the Institute's ethical committee).In 29 patients the whole AB was used, 15 patients (A) receiving 1-i s.c. injections in the f i r s t web of both hands whereas 14 patients (B) underwent 2 interdigital injections as well as 2 thoracolateral deposits.The standard dose was 28MBq corresponding to 0,32-0,35 mg of the AB.For 48 patients (C) we used the 123-I-labelled F(ab)2 fragments of the same AB,injecting 14MBq (0,12-0,14 mg of the fragments) in the 2 f i r s t intradigital spaces only.All but 1 patients presented I to I l l stage disease;there was clinically 28 N1-cases. Gamma-camera images were realized 3,6 and ~4 hours postinjection.Lymph node uptake was determined by the ROI technique.Using the whole AB the proven involved axillary lymph node groups showed after 6h a significantly higher uptake,when compared to the contralateral, normale ones.ln the group A the sensitivity was 70%,the spec i f i c i t y 80%,whereas in group B we obtained respectively 40% and 55% for the same parameters.The sensitivity was 75% and the specificity 60% in the group C.There was concordence between morphological and quantitative evaluation in 71% of the cases.The final diagnosis was true positive in 5 out of 7 cases where only i LND was involved as well as in 5 out of 8 patients with only 2-4 positive lymph nodes.Axillary ILSC can thus be usefull in the preoperative evaluation of breast-ca, patients. Based on the tumor targeting potentials of the thymidine analogue 5- [I-125] iododeoxyuridine (IUdR) in experimental animal models, we evaluated the tumor incorporation of IUdR in patients (pts) with gastrointestinal or breast cancers following direct intratumor injection.

Ten pts with colon (C), 5 with gastric (G) and 7 with breast (B) cancers scheduled for ablative surgery were injected intratumorally with IUdR (4-8 MBq, ID) during endoscopy (C/G pts) or percutaneously (B pts) 24 hrs before surgery. Blood and urine samples were collected up to 72 hrs and analyzed by HPLC. Following resection, the radioactivity of the tumor samples was measured in a gamma-counter and microautoradiography was performed on semi-thin tissue sections.

After a peak (4-6% ID/L) reached at 1 hr after injection, plasma activity decreased with mean half-lives of 8.0 + 1.9 hrs, 7.5 +_ 2.9 hrs and 11.2 + 2.8 hrs, respectively, in the C, G and B pts. At HPLC, 95. 98% of plasma activity was free 1-125 in the C and G pts, with a higher fraction (25-65%) of undegraded IUdR in the B pts; in addition, the plasma of B pts contained about 10% of radioiodouracil. In all three groups 70-90% of urinary activity (65-90% ID recovered at 72 hrs) was free 1-125, 10-20% undegraded IUdR, and the remainder was iodouracil. The mean tumor/blood ratios at surgery were 1300 (C pts), 74 (G pts) and 33 (B pts). The mean tumor/nontumor ratios were also high.er in the C pts (2900) than in the G (29) or B (150) pts. An average 0.5% ID/g of tumor was found in the C pts, 0.0046% ID/g in the G pts and 0.025% ID/g in the B pts. Microautoradiography confurned the high tumor/nontumor ratios and demonstrated that IUdR was localized mainly in the tumor cell nuclei.

These results suggest the potential of IUdR for tumor targeting i n humans following direct locoregional administration, and also point out some important differences in the metabolic fate of this tracer in the C, G and B cancer pts, likely due to differences in biological and histological features. Since anti~CEA-scintigraphy is not yet a widespread part of routine follow-up in pts, with colorectal carcinoma it was therefore the aim of this study to evaluate the efficacy of this method in comparison to routine investigations. 28 anti-CEA-sc~ns were performed in 14 pts. 6-24 months after removement of colorectal cancer (DuKes A n=4, B n=6, C n:4) and compared to the results of 24 sonographical findings (including transrectal and vaginal sonography), 19 CT~scans, 16 combined CEA and CA 19-9 tumormarker findings and 12 barium enemas. I~m~noscintigraphy was performed with 740 MBq Tc99m labelled NAB BW 431/26 and planar images 5 min. and 6 hrs. p.i. as well as SPECT-images 6 hrs. p.i. were acquired. Results: ~nti-CEA-scintigraphy was able to detect all cases of tumor recurrences or remnants already 6 hrs. p.±. If2/ 28, sensitivity = I00%), However there was a high number of false positive (5/28) and inconclusive (~/2~) findings due to bladder diverticula and fecal retention of activity in colon and afferent loops of colestomy r~ucing specificity down to 50%. In 2 cases immunoscin~igraphy could detect tumor recurrence 4 and 6 months earlier than transmission CT, Elevated HAF~-titers with reduced image quality appeared in B repeated investigations. Sensitivity of CT~scan was 75% of sonography 50% of tumor markers 100% and of barium enema B3%. Specificity of CT scan was 7B%, of sonography 9B% of tumor markers 75% and of barium enema 100%. Conclusions: Because of it's high sensitivity anti-CE~-sc±nt±graphy should play a definite part in follow-up of colorectal carcinoma. Positive findings 6 hrs. p.i. should be checked by 24 hrs. i~ages to increase specific±ty. We performed this investigation to compare the utility of T1 201 chloride, already proved to be helpful for tumor localization, and Tc 99m 2-methoxy Isobutyl Isonitrile (MIBI) for sarcoma diagnosis.

Thirteen studies were performed in ii patients (pts.) with newly diagnosed or treated sarcomas, verified by biopsy (i0 pts.) or progression on MRI (i pt.). Each study consisted o£ a TI-201 scan(TS) followed by a MIBI scan. In addition a three phase bone scan (TPBS) was performed for each study. There was concordance between Tl201, MIBI and blood flow (BF)/blood pool (BP) images in i0 studies (9 pts.);9 were true positive and on~ £alse negative. In 3 studies (2 pts) there was discrepancy:

in one pt. with recurrent rhabdemyosareoma MIBI demonstrated increased uptake but there was no accumulation of TI201 in the tumor.There was minimally increased uptake on BF and BP in the tumor. In one patient with high grade sarcoma the TS was positive but the MIBI images did not demonstrate abnormal uptake in tumor.The lesion demonstrated increased blood flow.

MIBI and thallium 201 demonstrate increased uptake in sarcomas and both proved helpful in distinguishing residual tumor from post therapeutic changes.However,there are some discrepancies which require further investigation.

J.FarahatiX, St.Miiller 1, W.Sauerwein 2, Chr. Reiners 1. Nuclear Medicinel and Radiation Therapie 2, University Essen, FRG.

The adjuvant postoperative external radiotherapy of tumor bed and regional lymphatic system in high-risk patients with differentiated thyroid carcinoma is controversial. In a retrospective study we investigated its influence on the risk of recurrences and metastases.

We included 111 patients with papillary or follicular thyroid cancer in the stadium pT4 N0-1 M0. 45 patients underwent only thyroidectomy and ablation of the thyroid remnant With 1-131; 66 also received adjuvant external radiotherapy. There were no statistically significant differences with respect to risk factors or mean follow-up between both treatment groups.

We found 7 bone and 6 pulmonary metastases and 1 local recurrence in the 45 patients without external radiotherapy, whereas in the second group only 1 bone and 3 pulmonary-metastases and 3 local recurrences were observed in 66 patients; the risk for developing metastases is significantly lower with adjuvant external radiotherapy (p<0.01).

In addition to thyroidectomy and ablation of the thyroid remnant with 1-131, adjuvant percutaneous radiotherapy should be performed in all high-risk patients with differentiated thyroid cancer of stage pT4 N0-1 M0.

J.Farahad l, St.Mffiler 1 , R.Romanowski 2, G.Stiiben 3, W.Klaes4,Chr. Reiners 1. Nuclear Medicine x, Pediatrics 2, Radiation Therapie 3, and General Surgery 4, University Essen, FRG.

FOR THE DETECTION OF RHABDOMYOSARCOMA AND LEIOMYOSARCOMA Rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS) are tumors of myogenic origin, which often contain myosin. We therefore studied tumor imaging with an In-lll labeled Fab fragment of a monoclonal antimyosin antibody (Centocor). 11 children and 9 adults with histologically confirmed RMS and LMS were included in this study. Whole-body scans were performed 24 and 48 h after injection of 100 MBq True positive uptake of the tracer was observed in known tumor sites of 8 RMS and 2 LMS patients. The scans were true negative in 3 RMS patients and 1 LMS patient who were in complete remission. In 2 RMS and 1 LMS patients in complete remission, the scans were false positive; 1 at the primary tumor and 2 at other distant sites. One false positive was located in an area of recent radiation therapy, and another at the site of an intramuscular injection. In 1 RMS patient the antimyosin scan was false negative. We studied one patient before and after radiotherapy; before treatment, there was intense uptake in the primary tumor, and after complete remission was achieved, the scan turned negative.

Radiolabeled antimyosin monoclonal antibodies may provide a sensitive and specific non-invasive tool for the detection and followup of RMS and LMS. 

B72.3 is a murine monoclonal antibody that reacts with a tumorassociated glycoprotein ( which is expressed by most adeno-carcinomas. The purpose of this study is to evaluate the tracer kinetics and to obtain initial clinical results of this new radiopharmacon in patients with colorectal carcinomas.

Human biodistribufion of B72.3 has been studied in 9 patients with either high suspicior/ of or proven colorectal tumors, recurrences or metastases. The antibody was radiolabeled with In-111 over a linker-chelator complex (GYK-DTPA +B72.3 to the constant region. [4] [5] of MAb were given intravenously. There were no side effects observed. Whole body imaging was performed with a double-headed gamma camera and a digital interface. Organ uptake was estimated by calculating the geometric mean of opposing views and is given in % of whole body activity of the same day (standard deviation in brackets). Tumor delineation was not possible at 10 rain. Over time there is a drop in blood pool activity, while the liver uptake increases steadily. Tree positives were 5/6 and a true negatives were 2/3. A high unspecific uptake in the faeces interferes with detecting rectal lesions. So far, immunoscintigraphy with has shown maximal tumor uptake on the 48 hour scan with promising clinical utility. The high unspecific uptake in the testes might influence further use of this antibody. 

Intraperitoneal (i.p.) administration of radiolabeled monoclonal antibodies (MAb) has been proposed as therapy for ovarian carcinoma. I.p. administration is expected to result in lower radiation burden for organs at risk in combination with a higher uptake in small mucosal tumour lesions. In mice bearing a subcutaneous tumour we evaluated the effect of i.v. and i.p. administration on the biodistribution of the ovarian carcinomaassociated MAb OV-TL 3. The effect on bone marrow uptake was evaluated in normal Wistar rats. Radioiodinated (Iodogen) F(ab')2 fragments of OV-TL 3 were simultaneously administered i.v. (1311) and i.p. (1251) to (Balb/c nu/nu) ovarian carcinoma-bearing nude mice (tumour diameter: 0.5 -1.5 cm) and normal Wistar rats. Animals were sacrificed at 1, 4, 8, 24 and 48 hr post injection (p.i.). In tumour bearing mice in blood and normal tissues at 1 hr p.i. significantly higher uptake was found for the i.v. route (paired Student t test; p = 0.05). However, from 4 hr onwards for both routes of administration tissue uptake was similar. Throughout the study -as expected -uptake in the subcutaneous tumour was significantly higher after i.v. injection than after i.p. injection. For all times tumour/normal tissue ratios were better for i.v. administration. In the rat model at 1 and 4 hr p.i. significantly higher bone marrow uptake was found for the i.v. route (paired Student t test; p = 0.05), However, from 24 hr onwards uptake was at the same level for both routes of administration.

In conclusion, in the subcutaneous tumour model the higher uptake in normal tissues after i.v. administration is more than compensated for by the higher uptake in tumour. The perfusion of the target area is a main parameter for the chemotherapy of liver metastases. We used PET and O-15 labeled water for perfusion studies in patients with liver metastases from colorectal carcinoma and melanoma. All patients were scheduled for chemotherapy using surgically implanted catheters and subcutaneous port systems. Fifteen patients (18 metastases) had a catheter in the gastroduodenal artery, while three patients had a second catheter in the portal vein. In two patients a triple catheter system was implanted including the lienal artery. Repeated flow studies with O-15 labeled water were carried out after intravenous, intraarterial (hepatic artery), intraportal, and intralienal tracer injection (30-100 mCi). Five one-minute images were acquired. The quantitative evaluation was performed with ROIs in the metastases and the liver parenchyma. Higher tracer concentrations in the lesions were noted after intraarterial injection in 15 of 18 metastases. In one patient vascular anormalities resulted in lower tracer uptake using the catheter approach. We found in one patient with small metastases (<2cm) a high tracer accumulation only after intraportal injection, indicating that the intraarterial approach is insufficient for the regional therapy. In two other cases a mixed perfusion pattern (intraarterial and intraportal blood supply of the metastases) was ob-seCved. As our results demonstrate, PET can be used for repeated perfusion studies. The quantitative evaluation is useful for therapy planning]. Results: Plasma CEA was < 2.5 in 13% patients. TPS was < 70 in 39 % cases and TAG was < 3 in 52 % patients. Tumor CEA concentration was > 1500 in all cases but 6 (81.2%). On the other hand it was < 1500 in all samples of normal mucosa but 3 (90.6%). Distribution of TPS and TAG did not differentiate between tumor and normal tissue, tumor m a r k e r values in both groups overlapped widely, especially in the case of TAG. No significant differences were seen between diploid and aneuploid patients, neither in the case of CEA, nor with TAG or TPS. Summary: Tumor concentrations of TPS and TAG are not different from normal tissue concentrations. A CEA value in tissue > 1500 probably corresponds to tumor ( 81.2% of patients showed a CEA over 1500 in tumor).

Xenia Trapali, A.Zissimopoulos, N.Bazi~tis~ Ch. Papadogeorgopoulos, Ch. Kouracos, N. Demertzis, E. Yakoumakis and A. Papadimitriou Greek Anticancer Institute. Saint Savas Hospital~ NuclearMedicine Dept. Athens. THE APPLICATION OF Tc99m-V-~Mg~ ~N OSTEOS~RCOMAIO~LI-ZATION.

The technetium complex of dimercaptocuccinic acid has been applicated in the detection of medullary carcinoma. This data served as a good starting point for our study in theaccumulation of this complex in osteosarcomas. We studied Ig patients. 8 patients had a diagnosis of suspected osteosarcoma. 3 patients were referred with known bone inflammation and 3 had no malignancy. In each patient the results of the new agent Tc99m-V-DMSA was compared with the results obtained with Tc99m-MDP bone scanning mud biopsy. 10 mCi of Tc99m-V-DMSA were injected I.V. and gamma camer a images were obtained 2 ho~rs post injection. (Images are demonstrated). In o~ study we found in 8 patients strict correlation between increased accumulation of Tc99m-V-DMSA and histologically proved osteosarcoma. No radioactivity was observed in 3 patients with non-malignant tumour or in the remaining 3 patients with inflammation. These clinical data indicate that Tc99m-V-DMSA is an ongophillic agent proper to detect osteosarcoma and in comparison with Tc99m-MDP we found that it delineates better the tumour sites.

Castellani MR, Di Bartolomeo M, Maffioli L. Zilembo N, Seregni E, Buraggi GL. Istituto Nazionale per io Studio e la Cure dei Tumori - Milano -Italy Divisions of ~,clear Medicine and Medical Oncology "B"

Despite the relatively low diagnostic sensitivity, I-131-mlBG can be utilized for treatment in patients affected by carcinoid tumours with an intense uptake consistent with the extent of disease. From Apt "87 to Feb "92, 21 pts with carcinoid tumours were studied with 1-131-1-123~mlBG scan. The injected activity was respectively 41.4 MBq and 370 MBq. Whole body, planers and, in some pt s, SPECT studies were acquired at 24-48 and 72 hrs. Four pts were studied after resection of primitive tumour, apparently free of disease, mlBG scan resulted in every pt negative. 17. pts showed clinical or radiological evidence of disease. The images resulted positive in 8 pts (47%), negative in 8 pts (47%), doubtful in i pt (6%). In the eight positive pts mlBG uptake was intense and in line with the extent of disease only in 3 pts with bone (i pt), LA lymph nodes (i pt), liver (2 pts) and ileum localizations (I pt). Other sites of positivities were lung (3 pts), soft tissues (I pt), pancreas (I pt), liver (2 pts Radioiodine treatment (RIT) is the best adjunct to total thyroidectomy (TTX) in the treatment of differentiated thyroid carcinoma (TC). To obtain a sufficient uptake in tumor and metastases, a depletion of cold iodine (CI) by interruption of substitutive thyroxin is achieved, in order to evaluate the possible interference of the total body CI charge on the efficiency of RIT, a prospective study on 4 groups of patients (p) was conducted. The assumption was that the mean alimentary iodine intake in Switzerland (mainly by iodinized salt) is increased to 200 _+ 124 p.g per day (Mordasini, 1984) with an urinary excretion of + 96 % (1111 + 508 nmol). Patient groups: Group A: 17 healthy volunteers (29 -73 years, 16 female (f), 1 male (m)). Group B: 17 hypothyroid (hypo) p after TTX, before RIT (18 -84 years, 12 f, 5 m). Group C: 13 hypo p after TTX and RIT, deprived of T4 and T3 substitution (subst) for 6 and 2 weeks respectively (25 -77 years, 22 f, 8 m). Group D: 55 euthyroid p, after TTX and RIT, on full T4 subst, in all groups, the 24 hour total urinary CI excretion (TUI, in nmol/24h) and the total plasma value of CI (TPI, inorganic fraction (IPI) calculated in nmol/ml) were determined (Technicon-Autoanalyzer) and cor[elated to the mean TSH value (mEq/i). It turned out by this calculation that favorable, anatomically defined, geometric conditions do exist for C-cell sterilization: (i) the remaining nommal thyroidal tissue must not be too small to allow for sufficient 1-151 uptake. This may formally seem con-tradicto~y to the current concept of completely radical thyroidectomy and (2) the remaining C-cell nests have to 5e smaller than the mean range of the betaparticles of 1-151. Quantitative aspects of these limitations will be given and the conclusion be drawn that only in cases where the above conditions are fulfilled, I-l~l will be of some benefit in MTC. The initial activity (Ao) and effective half-time (Te) were derived from sequential quantitative scans using either a rectilinear scanner or gamma camera.

Mass estimates were obtained usin~ positron emission tomo~aphy following t~acer 1-124 together with CT or MRI for soft tissue deposiZs in lung and pelvis.

Dose-response data have been obtained for 54 patients.

Following total thyroidectomy and 3GBq 1-131, a mean absorbed dose of 4OOGy achieved complete ablation of small thyroid remnants in 73% of patients (78% of sites).

Absorbed doses in excess of 460Gy were requi~ed to eradicate cervical nodal disease.

Complete remission of solitary bone metastases was achieved with absorbed doses exceeding 200Gy although doses in the region of 30Gy achieved worthwhile palliation in patients with multiple sites of involvement.

In future, dose response data will allow precise dose prescription of radioiodine and avoid the morbidity, expense and staff hazards of ineffectual therapy. In order to reduce the dose limittng side effects and to improve the clinical response of CDDP, supra-additive effect of low-doserate continous P-32 irradiation on CDDP was studied using a cultured human ovarian carcinoma cell line. Cells were incubated For ]4 days with CDDP and P-32 in three different experiments. P-32 was added 2 days before, same day and 2 days after CDOP. When P-32 was added 2 days after CDOP, cell ktl]ing was 25-30 times greaLer than when P-32 was added 2 days before CDDP. 5 uCt of P-32 was sufficient to induce supra-additive effect. Higher doses of P-32 did not add significant gatn. Cell survival data was in good agreement with the improved clinical response in patients treated with intraperitoneal P-32 (SmCi) combined with CDDP chemotherapy. In conclusion, continuous low-dose-rate radiation by multiple intraperitoneal P-32 following each cyle of CDDP chemotherapy provides improved cell killing with acceptable toxicity for ovarian carcinoma patients. Groups of [3] [4] [5] [6] pts. were treated at doses from 15-90 mCi/m 2 in 15 mCi/m 2 increments.

A total of 24 pts.

(12F,12M), age 57+/-16 yrs yrs completed therapy.

The dose-limiting toxicity was haematologic, with thrombocytopaenia the predominate finding.

A differsntial effect on white cells, with predominate suppression of lymphocyte counts, was seen. E v a l u a t i o n of tumour response to therapy showed three pts. to have stable disease and two pts. had mixed responses.

Six pt~. were retreated at the same dose level 4-6 weeks after the first dose of radiolabelled MAB; in all there was significant increase in whole body and serum clearance of radioactivity with an associated decrease in tumour uptake. Calculated bone m a r r o w dose from whole body clearance data (Tell = 27 to 72 hrs) was closely correlated with platelet counts, and ranged from a mean of 45 fads at the 30mCi/m2 level to a mean of 120 rads at the 90mCi/m2 level.

The maximum tolerated dose (MTD) was 75 mCi/m 2.

In The prognostic value of lymphnode (LN) metastases in dif _ ferentiated thyroid ca. is still under debate. This has been the subject of a special survey carried out on 257 cases treated from 1967 to 1982. 76 of these patients with LN metastases at surgery(N+Mo) were selected (66 papillary and 10 follicular ca. ) and were divided into two groups: -Group I: 26 pts. with LN involvement still persisting after surgery. They underwent external radiotherapy(ERT) + 131-I (20 pts.), or 131-I alone (6 pts.). -Group II: 50 pts. with no evidence of 13nnphnode involvement after surgery. They underwent either ERT alone (10 pts.), ERT + 131-I (33 pts.), or 131-I alone (7 pts). The average follow-up was 10 yrs, with a maximum of 23 yrs. Among the 76 pts., 24 % relapsed (20% with complete ablation), 9 had loco-regional and 9 distant metastases. This series, when compared with a series of pts. NoMo, matched for age and tumor size (I), showed a slight higher incidence of local or distant metastases (24 % , median 72 years} with hormone resistant prostatic eancer with metastatic bone involvement and at least ~ hot spots on 99mTc-MDP bone scan were given 150 MBq --Sr-chloride (Metastron, Amersham) 

Urinary excretion of the radioactivity was 4.5 to 6.6 % of injected dose after 24 hours and 6.2 to 10.6 % after 48 hours. In 6 pts a transient increase in pain occurred the day after injection and subsided within 2 days, 1 pt needed hospitalization for 2 days. Assessment of pain relief was based on a combination of the oncologists evaluation of type and doses of analgesics needed, and the pts' description of pain as scored in EORTC's Quality of Life Questionnaire. Pain relief was reported in 14 of 29 evaluable pts after 2 months and in 11 of 23 after 3 months. Progression was observed in 6 pts after 2 months and in 7 after 3. Serum concentrations of prostate specific antigen (PSA) increased 36 and i00 % (median) compared to the pretreatment values, whereas alkaline phosphatase (APhos} decreased 23 and 19 % (median} after 2 and 3 months respectively, of 23 pts examined by bone scintigraphy after 3 months, 16 showed increased number and intensity of hot spots, most often combined with increased APhos. Reduced intensity of pre-treatment hot spots were seen in 3

pts. None of these showed decreased APhos concentrations. Leucocyte and trombocyte counts decreased by a median of 20 to 35 % after 2 and 3 months without reaching WHO toxicity graze . > 2 in any case. It is concluded that Sr represents an effective therapeutic modality in the Palliative treatment of bone metastases in pts with hormone resistant prostatic cancer. The biological significance of the frequent increase of PSA and decrease of APhos is discussed. 10 children with advanced NBL received MIBG as therapy. They were either refractary to conventional therapy or experienced relapse after initially successful treatment, in one patient the MIBG was given as consolidation therapy. 9 children revealed stage IV and 1 stage III. Choosing criteria has been: positive 123-I-MIBG in all tumoral lesions and no bone marrow infiltration. Since many of the patients have received previous intensive therapy, depression of pre-treatment blood counts may be limiting a factor for treatment. A total of 38 MIBG courses were administered. MIBG was administered by infusion. In most children the dose was split into two portions each infused over a period of 4 hrs. with a 24 hrs interval in between. Courses were repeated up to 4 times and the maximum activity given to one patient was 22.200 MBq. Main toxic effect was thrombocytopenia. Antitumor effects were evaluated: there were 1 complete remission; 4 minor orsubjective response and 5 no response (stable or progressive disease). Children suffering ~from bone pain became free of complaints during ~ the ; first three days after treatment. These data suggest that greater effort should be placed to identify the conditions in which NBL may have a real benefit from MIBG therapy in comparison with more standardized treatmen~ modalities.

M.T. Ercan, N. Ulutuncel, T. Aras, S. Nald~ken and ~. Arlnsoy Department of Nuclear Medicine, Hacettepe University, Ankara, Turkey.

The purpose of the present study was to investigate the potential of 99mTc glucose phosphate aerosols for SPECT ventilation lung imaging in comparison to 99mTc-DTPA aerosols. c-D-Glucose l-phosphate (GP) was labelled with 99mTc by Sn ++ reduction method with an efficiency of >99 %. Ten normal nonsmoking male volunteers (Age: 20-30) were studied with both radioaerosols 1 month apart after obtaining their informed consent. 30-40 mCi in 3 ml of each agent was placed in the nebulizer (Venticis II) and inhalation was performed for 5 min of normal breathing with oxygen flowing through. Dynamic imaging was performed by the use of a SPECT camera (Toshiba GCA 601E) connected to a computer (55 U) from the posterior view for 90 min with 45 frames on a 64x64 matrix. Rectangular ROl's over each lung was drawn and the decay corrected clearance curves and kep values were obtained by pulmonary epithelial permeability program. TI/2 of each clearance curve was calculated from kep values. % remaining r a d i o a c t i v i t y after 30 min, required for a SPECT study, was calculated for each agent.

Clearance curves were mono-exponential. The diffrence in TI/2 values between the right and l e f t lungs was s t a t i s t i c a l l y insignificant (P>O.IO). The mean TI/2 values were 316.5±44.7 and 80.8±13.4 min for 99mTc-GP and 99mTc-DTPA, respectively. % remaining radioactivities after 30 min were 89.3±3.7 and 74.2±5.0 for 99mTc-GP and 99mTc-DTPA, respectively. The difference for both parameters was significant (P~0.0005).

In conclusion, 99mTc-GP is a better radiopharmaceutical for SPECT ventilation studies of the lung due to its slower clearance. Tc-99m-labeled MAA were administered intravenously at a dose of 74 MBq (children) and iii MBq (adults) in supine patients. Four standard PLS of 1 million counts each and SLP were performed with a GE (400a) digital gamma camera connected to a $3000 computer (GE $3000). 64 projections of the lung were registered in 64 x 64 matrices. Data were reconstructed by filtered back projection. TBB were performed 48 hours after scintiscans. During 1991, 23 episodes of acute rejection were diagnosed by biopsy in ii transplant patients (7 double lung, 2 heart-lung and 2 single lung). In 22 cases SLP cohfirmed rejection. The most abnormal findings were noted in 4 subjects with both rejection and obliterans bronchiolitis. One false-negative SLP was obtained in a patient with a minimal grade 1 rejection which subsequently resolved without treatment. These results suggest that SLP may be helpful in detecting perfusion abnormalities associated with lung transplant rejection. Although further study will be needed, defects detected by SLP may guide the endoscopist in choosing his biopsy site thus reducing the number of biopsies necessary to diagnose rejection.

E. Obriel, K.Ingels2, K.Osmanagaoglul, M.Lippensl, V. Vanhoorn2, K.Schelstraetel Dept. of (1) Radiotherapy and Nuclear Medicine and (2) Otorhinolaryngology, University Hospital, Ghent,Belgium.

In unexplained infectious airway diseases a primary cil i a r y dyskinesia can only be excluded by evaluating the a c t i v i t y of the c i l i a e on a bioptic specimen. To avoid a biopsy a non invasive technique is needed to select those patients in whom the mucociliary (MC) transport is impaired. To evaluate the MC clearance several non-imaging, roentgenographic or radio-isotopic techniques are used. The non-imaging saccharine test is too subjective and radio-isotope investigations which are already in use need sophisticated equipment and the help of an ORL spec i a l i s t and explore only one mucus trace. In our study we tried to explore the whole nasal MC apparatus using a simple nebulizing dispenser in 15 healthy volunteers, non smokers and free from r h i n i t i s . A 99mTc-labeled colloidal albumine solution (Albures, Solco Nuclear) is used. The patient is positioned with the cheek against the parallel hole LEHR collimator of a gamma camera. 99mTc markers are placed at the top of the nose and the mastoid. Following one nebulization (0,6 ml containing 2,2 MBq 99mTc-Albures) in one nostril a continuous registration is started, 40 frames of 30 sec. in a 128x128 matrix. Every minute the distance between the top of the nose and the progressing a c t i v i t y is measured. Using least square linear regression analysis a slope is obtained, which correlates with the MC clearance rate. The weighted mean of all slopes is 6,25 mm/min (~ 0,66 S.D.). These values correspond with data reported using other techniques. CONCLUSION : This 99mTc-colloid nebulizing technique can be used as a simple screening test in the evaluation of nasal c i l i a r y a c t i v i t y . IN ACTIVE SARCOIDOSIS Altered permeability of the gut is a well-described feature in Crohn's disease. Because of pathological similarities between Crohn's disease and sarcnidosis, we Lnitiated a prospective study to evaluate the intestinal permeability in patients with pulmonary sarcoidosis.

METHODS. 18 patients with biopsy-proven sarcoidosis were studied. Active (n=8) and non-active (n=10) disease were compared with 22 patients with Crohn's disease (active n= 12, quiescent n= 10), 9 untreated patients with recent pulmonary tuberculosis, 6 patients with coal-worker's pneumoconiosis, 8 patients with idiopathic pulmonary fibrosis and 16 healthy volunteers. None of the subjects was a smoker or had pulmonary symptoms or did intake alcohol before test.

Intestinal Technically accurate examinations requirinq some patient collaboration are sometimes difficult to obtain in the elderly population.

The purpose of the study was to compare the applicability of Technegas and Rb-Kr generators for lung ventilation studies in a population of geriatric patients with various disease conditions and suspicion of pulmonary embolism.

Nineteen unselected patients (age 62 -96, mean 74) referred for a ventilation / perfusion study underwent a combined Kr-81m ventilation and Tc-99m perfusion study according to our usual protocol. After injection of 74 Mbq Tc-99m MAA, patients breathed in an open mouth mask delivering the Kr gas from a 740 Mbq Rubidium generator. Perfusion (P) and ventilation (v) images were acquired at the same time separately recording the photopeaks of both isotopes. A Ventilation study was subsequently obtained on the following day with the Technegas generator, using an eluate of 370 Mbq Tc-99m in the graphite cupule. All V and P studies included four images (anterior, posterior, and two postero-lateral views) acquired in matrix size 128 X 128. Images were acquired with a fixed preset count of 600 Kcounts for the MAA p and Kr-81m V images and with a preset count of 200 to 300 Kcounts for the Technegas V images, depending of the count rate.

The average frame acquisition time was 155 sec ~ 58 for the V/P studies and 331 sec Z 164 for the Technegas V studies. In 8/19 cases, the quality of the Technegas study was judged equal or even superior to that of Kr. In the remaining cases the quality of the Technegas study was significantly less than with Kr, with central hot spots deposition in 2 patients and no interpretable images in 2 other cases.

We conclude that Technegas offers the possibility of performing Ventilation studies in a majority of elderly patients with the obvious advantage of easier availability and lower cost than with Krypton. However, this can only be achieved at a price of a much higher examination time and generally with lower imaging quality. Furthermore, a significant number of patients remain unexplorable with Technegas due to critical illness or mental disability. 

A previous study comparing S~mKr and Technegas in, patients with suspected pulmonary embolism found disparities between the ventilation images in 3.2%, Hot spots(HS) on the Technegas images in 14% and Preferential basal deposition(PBD) on the Technegas images in 16%. The aims of this study in a group of patients with established respiratory disease were to assess the incidence and significance of Technegas/~l~Kr disparities and to evaluate the diagnostic potential of HS and PBD on Technegas images. 42 patient~ in 8 diagnostic groups were recruited. Patients underwent pulmonary function testing and afterwards ventilation imaging using the two agents was performed.

Technegas/SlmKr disparities were seen in 6 patients in 5 disease categories.

HS were seen in 50% overall but were most common in COAD, emphysema and asthma.

They were significantly associated with indices of lung function indicating airways obstruction.

PBD was noted in 33% overall but in 73% of patients with idiopathic pulmonary fibrosis and was significantly associated with abnormalities of lung function found in restrictive lung disease.

In the majority of instances Technegas and SlmKr images are comparable.

In the usual patient population studied because of suspected pulmonary embolism 30% have coexistent respiratory disease: extrapolating from the results of this series disparities could be expected in only 4% of the pulmonary embolism population.

Neither HS or PBD detract from the overall image quality and both may have diagnostic significance in lung disease other than PE. Unilateral and total hyperlucent lung is due to decreased intmpulmonar blood flow, among other factors. The diagnosis and haemodynamic evaluation of these situations are usually made with invasive methods. In this context, the AA propose a new noninvasive methodology for the diagnosis and study of this pathology. In order to achieve this purpose, 8 patients were studied. They performed clinical and laboratorial evaluations, chest X ray, ECG, functional respiratory studies, angiopneumography, aortography, qualitative and quantitative CT lung densities and radioisotopic studies. These include ventilation/perfusion studies with 133Xe and 99mTc-HAM leading to FPH (Four Parameter Histograms)1, WQ ratio images and pulmonary equilibrium images 2. The radiologically confirmed hypoplasic arterial network of the hyperlucent lung is corroborated by: a.the low perfusion in the FPH; b. a significant decrease on the CT density (p<0.001) when compared to the opposite lung (-832 Technegas is relatively cheap, non-toxic, readily available and provides good qu~it~ lung images. It combines the ready availability of --Tc-and its optimal imaging properties with an easily administered radiopharmaceutical of particle .size small enough to deposit ~n the alveolar walls. We have compared techne-Im gas and Kr as ventilating agents in 80 patients with suspected PE.

Of 72 patients, 49 had no evidence or low probability of PE, 18 had moderate/high probability of PE, and 5 had COAD. The probability of PE in the 49 and 18 patients was similar when °±Krm and technegas were used. In the remaining 8 patients, the d~agnostic probability altered significantly using °±Krm or technsgas. Centmal deposition was seen in S patients during technegas study, while stomach and thyroid uptake were visible ia i0 patients. The difference in diagnostic probability and the presence of extrapulmonary deposition could be related to physical, pathological and/or technical difficulties in the preparation and delivery of technegas. Quantitatively there is regional difference in the relative vezZilation of both agents.

~± m In normal and abnormal scans Kr permeates more in the apices of the lungs compared to technegas which appears to preferentially disZribute in the mid and lower lung zones. Conclusion: Technegas is easy to prepare and administer. Good quality ventilation imases are produce~ which are of equivalent or even superior quality to krypton. Unlike 81Krm, technegas is readily available ~hich improves the diagnostic service. were chest pain (62%), sudden onset of breathlessness (58%) and haemoptysis (16%). Chest X-ray abnormalities suggestive of PE were present in only 40 patients (pleural effusion 17, infiltrates 23, atelectasis i0). Perfusion (using Tc-99m MAA) and corresponding ventilation images (using "Technegas') images were obtained in six standard views. Clinical follow-up time period of the cases ranged from 4-18 months after the lung scan.

Lung scan reports showed that 22% of the patients had a high, 14% intermediate, 18% low and 9% very low probability for PE and 37% had normal lung scans. Based on the clinical outcome analysis the apparent sensitivity for the lung scan was 96% and specificity 93%. Conclusion: High quality ventilation images were obtained with "Technegas' which improved the diagnostic utility of lung scans. Based on clinical criteria a strategy for lung scanning in pulmonary embolism is outlined. 

In former studies Technegas has been shown to be an agent for ventilation- SPECT-studies. To get an impression of how the activity is distributed in SPECT-slices of normal adults,Technegas-SPECT-ventilationstudies were performed in 5 normal volunteers (the authors conducted the examination on each other, "normality" was verified by body plethysmography). The images were acquired with the SPECT-camera after deep inhalation of 1 mCi (37 MBq) of Technegas in supine and in prone position. Activity distribution in the images is analysed using a ROI-technique and calculating the anterior posterior activity relationindex (API) API should be 1,0 in homogeneous distributions.

Results: The calculated API shows deep inhomogenities:after inhalation in supine position, the activity is mainly concentrated in the dorsal regions. The API was calculated to be 0,48±0,05 for the right and 0,67±0,07 for the left lung. After inhalation in prone position, the activity is concentrated in the ventral regions (API = 1,3 ± 0,i r.lung) Conclusion: Technegas vent-SPECT images of normal adults show deep inhomogeneous activity distribution in the SPECT-slices, especially in the right lung. The inhomogenity is position dependend and correlates with the gravitation. The delivery of drugs by nebulisation way needs a reliable measurement of the pulmonary and non pulmonary deposition .

14 studies were performed in healthy volunteers 28.2~6.4 years dld with a jet nebuliser (Respigard II) and an ultrasonic one (Ultraneb 99) with various volumes of a solution labelled with 750~-23 MEq of technetium 99m-human serum albumin .

A dynamic posterior scan (68 images) in sitted position was performed during the inhalation using a Gammatome II gammacamera linked to a Sophy computer .

The semi automatic method, using a rectangular contour fitted to the lung edge obtained via an equilibrium image of xenon 133 at tidal respiration gives : one mediastinum ROI, one alveolar and one bronchotracheal ROI for each lung. After background substraction, correction of alveolar activity in case of superimposition of gastric area by use of the controlateral alveolar activity ; tracheal and bronchic, alveolar depositions and their ratio are computed on I~-16 min images of the aerosol deposition . Gastric and oropharyngeal deposits are assessed on static images in anterior and left profile views .

Comparison of tracheobronchic/alveolar ration shows an intraobserver correlation, (r=0,97,p<OoOO1,slope:0.86% 0.065, intercept:O.063) and an interobserver correlation~ senior vs junior (r:0.98, p<O.OO1, slope=0,95±O.O53, intercept:O.035) giving evidence of the reproductibility of the method. Similar results are obtained with extrapulmomary deposition assessment. The method allows the critical assessment of the nebulisers a quantitative and objective approach of trials of nebulised drugs .

Shigeru Tomi~ga,l)Takao Shimada,2)Kenj i Kawakami3)and Etsuo Moriya." i) Dept. of Internal Medicine, Juntendo Univercity Urayasu Hospital, Chiba, Japan. 2) 3rd Dept. of Internal Medicine and 3) Dept. Radiology, The Jikei University School of Medicine, Tokyo, Japan. REGIONAL PULMONARY FUNCTIONS IN LYMPHANGIOMYOMATOSIS OF THE LUNG. We investigated regional pulmonary ventilation and perfusion in seven cases with lymphangiomyomatosis of the lung and compared the results to these in fifteen cases with pulmonary emphysema. Ventilation study by gas and perfusion study by Tc-99m-MAAwere evaluated in each case.

In twelve cases of fifteen emphysema, washout of Xe-133 gas was dominantly delayed in lower lung field. Results of washout study in middle and upper lung field were variant in each case. Almost all of emphysema patients showed symmetrical ventilatory distribution in right and left lung. Whereas, in three cases of seven lymphangiomyomatosis, Xe-133 washout was dominantly delayed in middle lung field, in two cases, it was delayed in lower lung field~ and in other two cases, it was diffusely delayed in whole lung field. Uneveness of ventilatory distribution was more severe in lymphangiomyomatosis than i.n emphysema. These results shows variant distribution of ventilatory disturbance in lymphangiomyomatosis. Perfusion image was consistent with an image in the initial phase of Xe-133 inhalation study. Perfusion showed matched defects with ventilation in lymphangiomyomatosis. We followed three cases of lymphangiomyomatosis by Xe-133 for a few years. Washout of Xe-133 was progressively delayed in every lung field. This suggests that lymphangiomyomatosis of the lung is rapidly progressive disease. 

Purpose: The early detection of opportunistic in-fections in AIDS patients is most important for starting successful therapy. This investigation was undertaken to compare the diagnostic usefulness of 99mTc-albumin to 67Ga-citrate in the diagnosis of opportunistic lung infections.

In 19 consecutive patients (18 males, 1 female mean age 41 years (range 21 -64 years)) with positive HIV antibody titres and suffering from fever, dyspnea and cough we performed 67Ga-citrate and 99mTc-albumin scintigraphies. Images were fabricated 40 min. (99mTc-) and 3 days (67Ga-) after intravenous injection. Results: In 7 patients with PeP both scans were positive (I; PEP); in 4 patients without lung infection both scans were negative (II); in 5 patients without PcP but other lung problems neither the 67Ga-nor the 99mTc scans were positive (III). In 1 patient with a diffuse malignant lymphoma of the lungs the 99mTc scan was positive (67Ga scan negative!; IV); an-other 2 patients (1 vadcelta pneumonia, 1 mycobac-teriosis) showed positive 99mTc images (67Ga scans not done; V). Conclusion: in AIDS patients proves to be a very good effective new tool for non-invasive detection of opportunistic lung diseases. Further more it seems to be a usefull method for shortening the time between injection and acquisition from 3 days to 40 minutes.

C. Alberts, H. Balink*, A. Zwijnenburg*, C. Roos, H. Jansen. Dept. of Pulmonology, Academic Medical Centre, Amsterdam and Dept. of Nuclear Medicine, Spaarne Hospital,. Haarlem*, The Netherlands.

SARCO1DOSIS. Distribution of regional ventilation (Xf) and perfusion ((~) can be visualized and quantified by single photon emission computed tomography (SPECT), using Kr-81m gas as a ventilation tracer and Tc-99m microspheres as a perfusion tracer.

To determine the existence and impact of an abnormal 9/Q distribution on gas exchange in pulmonary sarcoidosis, SPECT of the lungs was performed in 34 patients (13 females, 21 males, aged 21-75, mean 40 yrs); 19 patients had chronic disease, of which 7 had maintenance therapy with corticosteroids.

In 15 patients (44%) normal 9/Q distributions were found with a reduced diffusion capacity (TLCO < 77% pred.) in nine of them; the decrease in TLCO may be caused by abnormalities in the alveolar-capillary membranes of the lung. Nineteen patients (56%) had an abnormal V/Q distribution. Twelve of these patients also had a decrease in TLCO at the time of investigation. Seven patients had abnormal 9/Q distributions without a decrease in TLCO. Of these patients, four had hypoxaemia, possibly solely due to 9/Q inequality.;

There was no relationship between chest radiographic stage of pulmonary sarcoidosis and 9/Q distributions.

We conclude, that ventilation-perfusion SPECT may give additional information about the pathophysiology of gas exchange in the individual patient with pulmonary sarcoidosis. Disturbance of gas exchange may partly be due to the existence of ? / Q inequality. Increased uptake in the salivary and lacrimal glands on Ga scintigraphy (GS) has been consistently .noted in patients with active sarcoidosis. Tissue involvement has been documented in 64.7% in one published series. Our study assesses the salivary function in 14 patients with sarcoidosis and correlates the degree of SGU to the extent of any salivary dysfunction based on clearance rate.

In 14 consecutive patients with sarcoidosis (12 women and 2 men, mean age 25.8 years), salivary gland sclntigraphy (SS) is performed using 3mCi of Tc99m04 i~m~ediately after GS. Five second dynamic images and two minute static images before and after the patients orally sucked a slice of lemon are obtained using both analog and computer acquisition modes. Two minute background images are also obtained and later used for background subtraction process.

SGU is graded from 0 to 4+, 2+ being comparable to liver activity.

In our laboratory, normal salivary clearance on SS ranges from 40 to 55%. Of 14 patients, ii had clinically active sarcoidosis while 3 had inactive disease.

Of II with active disease, 9 who had greater than 2+ SGU showed diminished clearance (2-25%) . The three with inactive disease and two with active disease but with less than 2+ SGU had normal clearance ( 37-5o~) .

Although this is a small group of patients, it appears that high SGU may indicate salivary dysfunction as well. The dysfunction may be secondary to actual tissue involvement and/or associated reactive process within the glands. GLOBALABDREGIONAL99m-Tc.DTPA EPIT~ELIALTRANSIT. A lot of pulmonary pathologies such as interstitial diseases, sarco~dosis, fibrosis, non cardiogenic oedema ... have the property to modify the integrity of the alveolo-capillar membrane.

Induced modifications are always in the way of an increased permeability of this membrane for solutes.

The measurement of this permeability's increase may be appreciated by the study of the speed with which a 99m Tc-DTPA aerosol transits from alveolar spaces to vascular compartement. This aerosol is obtained by means of a nebulizer specially designed for ventilation studies and called SEDI II.

The data acquisition is made by a 20 minutes dynamic study in a 128 x 128 pixels matrix/lO secondes/frames.

The transfer speed called clearance is estimated by the residual value at 20 minutes in % of the started value and by the period of the exponential curve (min).

Our results on a reference group are very similar to those obtained in the literature (65.5 +/-16 min to 63.3 +/-12 min).

In pathologies like fibrose, ws found a diminished residual value at 65.16 +/-8.3 % for 83.02 +/-5.68 % for the reference group. In pigeon'fancier, the residual value is also decreased to 6 5 . 7 1 % +/-11.66 %).

We study also other situations but each time a patient presents an altered membrane, this value is always under the normal average -1 S.D. which means an increased clearance. We think that this technique is very useful for the diagnosis and also i n the follow-up of pathologies which are incriminated in the structural modifications of the pulmonary epithelium. 

The 

The role of pulmonary thrombocmbolism in acute COPD is well known. Its detection is, however, frequently difficult owing to insufficiencies of the methods used to confirm its existence and localization. In this context 20 patitents with acute COPD were studied; all of them performed a ventilation study with t33Xe (local and global mean wash-out times after an equilibrrium period) and a perfusion study with 99mTc-HAM. An original software 1 was used to display and interpret data. This consists of building into the computer three dimentional histograms (Four Parameter Histograms-FPH) which allow simultaneous and independent information of localization, intensity and limits of normality for both ventilation and perfusion. The local and global values of ~'/~ ratio were also available.The Nuclear Medicine data were correlated with clinical, radiologieal and functional respiratory data of the patitents. The detection and localization of thromboembolic areas was possible in most of the cases studied. These results suggest the interest of this method, which is a noninvasive and well tolerated technique, in the study of thromboembolism in acute COPD. The aim of our study was investigation of the behaviour of plasma concentrations Of tumor necrosis factor alpha ( T N F -& ) , i n t e r l e u k i n -l p ( I i -l p ) , i n t e r l e u k i n -6 (I1-6) and endothelin-1 (ET-1)in ~ patients with post-burn ARBS (group I) and in 8 with post-traumatic ARDS (group I I ) . Venous blood samples were taken in 12 hour intervals from the f i r s t to the last day of hospitalisation or to the death of patients (5-of I and 4-of I I group),The control consisted of 8 healthy persons.

The concentrations of TNF-~ and I i -l~ were determined by means of IRHA k i t s (Hedgenix Diag.,Belgium),I1-6 and ET-1 using RIA k i t s (Amersham,England).

The obtained results showed continuous increase of TNF-~concentrations from the f i r s t day to the death of patients of both groups,reaching the values 150-(groupI) and 15 fold (group I I ) higher,comparing to controls.In the survivors of both groups the levels of TNF-~moderarely increased in the beginning of disease and were normal before recovery.The concentrations of I i -l~ changed from normal values in the f i r s t day through 2-3 fold augmented in the next days,to the lower than controls, before the death of patients in both groups.In the survivors the levels of Ii-l~ did not differ from control.

The behaviour of concentrations of I1-G was similar to that of Il-l~ .The plasma concentrations of ET-1 were considerably enhanced only in the non survivors of both group,particularly in the patients suffered from postburn AROS.

The results of our study showed that determination of plasma cytokine concentrations may be useful in monitoring and prognosis of ARDS of differen± types.

AK Padhy, KK Solanki, KE Britton, J Bomanji, T Chaiwatanratan, CC Nimmon Department of Nuclear Medicine, St. Bartholomew's Hospital, LONDON, UK Renograms, functional ratios and urinary excretion patterns of all three agents were similar in the same patients.

In conclusion, Tc-99m-EC has excellent imaging characteristics and very similar excretion properties with 1-131 Hippuran. It may be a practical diagnostic method in renal functional diseases due to its prompt availability and simplicity. Accuracy of the det~..r~nination of Fractional Clearances (FCs) calculated from MAG3 renal studies depends on an adequatu background referenea area (BKGROI) and depth attenuation correct*on. Our pur/~se was to t~st the effect of different BKGROIs s~lection of FCs ealen]at*on, either with the slope method or with a modified Gates' technique, and to evaluat~ the im/~qrtanea of using measured instead of estimated renal depth. irty-six unsolected patients were studied with MAG3 and DMSA in the same instance. DMSA was injected just after completion of the MAG3 study and a SP.ECT study was performed 6 hours later. Static DMSA images were also obtained wi~ radioactive markers on the table, permitting renal" depth mesu[ement. Pat*ents with evidence of obstructive dissase or with poor renal function were excluded due to possible residual MAG3 activity or a low uptake and pogr quality of the DMSA images.

Five pairs of BKGROIs were tested for FCs calculations: two supra-renal, sub-renal, peri-renal, or external ROIs, and one inter-renal ROI. The renal depth was calculated from the T6uneson formula and also measured from the DMSA.tran.saxial images. Since the kidney counts in the SPECT reconstruction images are proportional to kidney clearances while baing una~ ffected .b2 renaldepth and baekgruund, the DMSA study was taken as the relerence F~s calculat*on method. Based on histology, the Guy's Index was normal in 93% of cellular rejection and abnormal in 87% of vascular rejection (86% sensitivity and 94% specificity for detecting vascular rejection). In the total series also including patients with ATN the specificity was 77%. Ultrasound PI was 80% sensitive and 69% specific in detecting vascular rejection. Including the patients with ATN the specificity was 59%. Combining the Ouv's and Ultrasound Pulsatility Indices increased the sensitivity and specificity in patients with vascular and cellular rejection to 80% and 96% respectively. We conclude that the ~uy's Index is a sensitive method for differentiating between cellular and vascular rejection thereby reducing the number of patients requiring aggressive int~unotherapy. Ultrasound PI is less sensitive but can increase specificity if combined with the Guy's PI.

ATALAY lvl t., AKALIN E 2, KABALAK T z., DIRLIK A t., ALPER A. t., DUMAN yl. ()tonomic neuropathy is one of the major complications in diabetes mcllitus; because related symptoms of otonomic system involvement arc undcfinitc, stealthy and slowly progrcsing. They are very hard to diagnose in this group of patients. In this study we almd to show the bladder functions with nuninvasive radionuclid evaluation in diabetic patients without any significant symptoms related with bladder functions.

24 diabetic patients and 10 normal volunteers (control group) were used in this study. Mean age of them were 4,8± 13.4 year. After half as hour 15 mCi Tc 99m DTPA I.V, injections, patients voided in containers standing in frunt o[ the digital gamma camera ;md every other seconds 60 I'ramcs were taken to obtain the time-activity curve. By substracting background from time activity curve the parameters obtained from every patients, avaragc urine flow rate (AFR), bladder ejection fraction (E.F) and residual urine (R.U) were calculated. There were no significance in diabcllc duration, periphcric ncuropath and H baC levels in patients groubs (P > 0.05).

In lhis study wc showed that bladder dysfunctions ~e obse~ed in early periods in diabetic patients and this noninvasive radionuclid~ studi¢s arc useful in early diagnusis of diabctlc otonomic ncuropathy, h is su~cstcd thai it mus~ be used as a rautine test in ev~uat~g dialytic autonomic ncuropa~hy in diabcllc patients. The RUPV method is a GFR calculation based on the renal uptake and volume of distribution of 99m Te DTPA. The RUPV method was cc~pared to ~ 45 and 180 minutes blood sample determination of GFR in 96 pati6nts undergoing renal scintigraphy with 99m Tc DTPA ~(520 MBq i.v.).

During the first 3 minutes after injection, the volume of distribution of the tracer is assumed equal to plasma volt, he (PV), and the product of PV and renal uptake (RU) an expression of GFR:RUPV GFR = RU * PVn/t; RU was obtained frc~ net curm~lative kidney counts during t = 3 minutes using ROI over kidneys corrected by background and kidney depth and divided by total injected dose. PVn (ml) was obtained frcm 3 independent methods: PVI = (95.7 weight -274) * (I -Hct); PV2 = (0.37 height 3 + 0.03 weight + 0.6) * (I -Hct); PV3 = 84. MBq 99m Tc-DTPA. Transplant perfusion was classified using a time-activity-curve, which was generated over the first minute from the transplant and the contralateral iliac artery. For the initial phase were calculated the Hilson index from iliac and transplant curve and the time difference from the curve maxima (TDIFF). Additional a quantitative perfusion score (grade 1-6) was used. Analogous Scans were performed until 30 min. pi. in 5 min. periods to classify urinary excretion function. 90 studies were analyzed with a computer program, which was written in MEDICL computer language. For aqulsition a Siemens BASICAM and a MAX DELTA computer system were used with a 64*64 matrix and a temporal resolution of 0.5 sec for the first minute, respectively 15 sec. for the following 29 min. (altogether 236 frames). We could demonstrate a very good correlation between the perfusionscore and the TDiff (r=0.9). Altogether 10 renal transplants were severe affected. All 10 renal transplants had no significant perfusion (perfusionscore 6). 4 renal transplants ,which could scintigraphically not be detected, required an explantafion, because of a vascular graft versus host reaction. 5 renal transplants, which could scintigraphically detected, recovered in the clinical follow up. Only one renal transplant, which could scintigraphically detected, required an explantation. We conclude, that the analogous scan is of extraordinary importance for estimating of the transplant prognos~s in the severe affected renal transplant. For the diagnosis of transplant perfusion we consider both the qualitative perfusionscore and the quantitative TDIFF as suitable. Radionuclide phallography was performed using ~T c mlabelled autologous red blood cells in conjunction with papaverine-induced penile erections (Siraj et el. 1990). Serial blood samples were taken from the penile cavernosun to study the changes in vascular concentration of the penile corpus cavernostueduring pharmacologically-induced erections. A marked fall in the cavernosal haematocrit was observed after papaverine injection. The fall in the cavernosal haematocrit was found to be volume-dependent resulting from dilution of the cavernosal blood pool by the injected volume of the drug. This was not observed in erections produced by visual sexual stimulation. It appears that a restriction of the cavernosal venous outflow in response to papaverine injection causes sequestration of the diluted blood in the cavernosel compartment. Thus, an estimation of the penile blood volume based on the activity of a systemic venous blood sample following intracawernosal injection will introduce an error in calculation compromising the results. The degree of cavernosal haemodilution was found to aid in the differential diagnosis and was especially found to be valuable in differentiating patients of arteriogenic impotence from those with venous leakage. 

Intracavernous Technetithm Penogram (ITP) is a diagnostic technlq~le able to measure penil e outflow rate by the analysis of corporeal 99m-To clearance.

i0 patients wi~h venogenic impotence previously diagnosed by pharmacocavernometry, and a cantrol group of 30 patients affected by psycogenic impotence, underwent ITP with papaverine in order to quantitate penile outflow rates. Time activity curve and venous i~dexes were calculated a~d compared with maintenance flow rates, obtained in the same patients after pharmacocavernometry.

The average outflow rate per minute was 2.4% in venogenic impotence patients and 0.6% in psychogenic patie~ts~ while average maintemance flow rates were 95 ml/min, in venogenic patients and 30 ml/min, in psychogenic patients. Very interesting findings were also obtained from comparison of data regarding every single case.

In our experience ITP with papaverine was a simple, minimally invasive and reproducible screening test. A good correlation beteen 99mTc-outflow rates and maintenance rates confirms its reliability in venous incompetence diagnosis. 

ASSESSMENT OF TESTIS BLOOD FLOW CHANGES IN RATS WITH EXPERIMENTAL VARICOCELE, BY USING L~ ISOTOPE CLEARANCE TECHNIOUE The exact contribution of varicocele to infertility is still unknown. Some authors bare suggested that some pathophysiolo-gic consequences of varicocele might cause infertility. One of these consequences is the alterations in the blood flow of the contralatotal testis, but it has not been proven e x a c t l y y e t . I n this study, we investigated the changes in the contralatera~ testis blood flow in rat with experimental vari-cocele,using the Xe-133 local clearance technique We used 30 Wistar Albino rats,weighing 150-200 gr.

We separated them into 3 groups.Following anesthesia ,we produced left varicocele in the first group,by microsurgical techniques.The 2nd was the control group ~_ndt he 3rd was sham On the 30th day following the operation we did the local clearance study. Using 27 gauge needle we in, coted 0.I mCi liquid Xe-133 in a O.l ml saline percutaneous intratesticularly to the right side and acquired 40 images at 30see intervals by a gamma camera interfaced to a computer computer.Time-activity curves were generated.

Testicular blood flow was calculated according to F-- Inflammation around the abdominal catheter and its diffusion to peritoneum is the main complication of peritoneal dialysis. We performed Ii studies, in a double blind fashion, either by leucocytes scintigraphy (LS) and ultrasonography (US) in a group of 10 peritoneal dialysis patients of various age of dialysis. LS found 5 positive cases of catheter inflammation and a visceral diffuse uptake of leucocytes into abdomen in all cases by one. The uptake was graded as low or high. In three cases LS was repeated after dialysis and the diffuse uptake was unchanged.

The radioactivity of peritoneal fluid was found very low and floating radiolabelled cells were not showed. US agreed with LS in 3 positive cases and in 6 negative cases of tunnel inflammation but disagreed in 2. A peritoneal thickness of 1-3 mm was showed and the highest values were found either in patients with previous peritoneal infections and after the longest period of dialysis. The rank correlation coefficient of Spearman between the scores of abdominal LS uptake and peritoneum thickness was highly significant (R = 0.694, P = 0.021). Our results, obtained in a little but homogeneous group of patients, allow us to hypothesize that the abdominal uptake of leucocytes in peritoneal dialysis is a consequence of cellular proliferation of peritoneal mesothelium and that the radiolabelled cells are closely bond to mesothelium. Forty-six renal scans and sonograms of patients with acute pyelonephritis (AP) were reviewed to determine the sensitivity of renal scintigraphy (RS) and sonography (US) in detecting AP.

Each patient (pt) received a fractionated dose of either i0 mCi of Tc-99m glucoheptonate (GHA) or 5 mGi of Tc-99m DMSA.

Thirteen two-hour GHA and 33 threehour DMSA RS were then obtained in posterior, left and right oblique positions.

US was performed using a real time scanner in sagittal, transverse, and coronal sections. RS and US were performed within 96 hours of each other.

Isotopic and contrast cystogram, WBC count, urine culture, and U/A results were also reviewed.

Of the 46 pts with AP, RS detected 39, US 5. Twenty-one (46%) demonstrated reflux.

In the subset in which AP was due to E. Coli (31/46) RS detected 26/31, US 3/31. Thirteen (43%) demonstrated reflux, one was not evaluated.

RS is superior to US in detecting acute pyelonephritis.

RS's sensitivity was 85% and US iI%. Relative sensitivities were identical in AP due to E. Coli (RS 84%, US 10%). RS's sensitivity in detecting AP is also superior to previously reported contrast enhanced CT's sensitivity of 64% and IV pyelographies sensitivity of 24-28%.

The imaging technique of choice for diagnosing AP is renal scintigraphy. Direct radionuclide cystography (DRC) allows to detect vesico-ureteral reflux (VUR) by visual inspection of a dynamic image sequence. The aim of our study was to improve VUR diagnosis using a scatter correction methodology. 10 children (mean age 5.6 years) with recurrent urinary tract infections were investigated by DRC. It was observed in posterior view by direct bladder instillation of normal saline containing 37 MBq of pertechnetate in 500 ml. The acquisition was performed with a large field gamma camera equipped with a h!gh resolution parallel hole collimator and dedicated computer. A double word list mode was acquired using a 60 keV to 180 keV window to record spatial, time and energy photon information during bladder filling and compression. A time and energy sequence of 250 images was generated and then processed by Factor Analysis of Medical Image Sequences using a Target Apex Seeking procedure (FAMISTAS). In all patients, 3 spectra were extracted with their associated images : 2 scatter components associated with bladder and a pure Tc-99m photopeak. In the corresponding free scatter image the VUR was clearly identified in 2 patients. In the 8 others the VUR did not appear. The same results were obtained with X-ray cystography. As this methodology separates the photopeak from the scatter radiation, it could detect the small VUR in scatter free images. The renogram with furosemide has been proposed for the differential diagnosis between mechanical obstruction (Obs) and dilatation of the urinary tract without an obstacle. In the present work, 22 children were evaluated between 15 days and 10 months of life, corresponding to 48 renal unites (RU), with pre-natal echograplfic diagnosis of renal cavities' dilatation, confirmed posnatally. None had evidence ofyasico-ureteral reflux. A dynamic study was performed with 37 MBq (1 mCi) of 99~mTc-DTPA, 20 secYframe during 20 minutes, in a matrix of resolution of 128x128. In 9 children, furosemide (1 r a g / k g of weight) was administered e.v. simultaneous with the beginnihg of the acquisition (group 3) and in 13 other, at the end, if there w~s retention of the radiophaunaceu/dcal , continuing then the study for more 10 minutes (group II). Differentia] renal function was calculated using Gates' method. The Tenographic diagnosis of Obs was post~dated if there was a continuous accumulation of the radiopharmaceutical without definition of excretory phase (group I) or if at 30 minutes, there was an excretlon of less than 25% of the maximum activity retained (group II): This result was correlated with Obs confirmed by surgery. In group I, 5 out of 6 (83%) Obs were colrectiy diagnosed by furosemide study and in group I!, 3 out of 3 (100%). In group II, 4 RU defined as Obs were not yet submitted to surgery and are on functional follow-up; 6 RU are non Obs but with lower renal function (asymmetry>10%).

In conclusion, according to our results, it seems that both methods were efficient to screen children for surgery.

Gordon I, Toth-Abonyi M, Anderson PJ, Lythgoe M. Hospital for Sick Children, Great Ormond Street, London WCIN 3JH England.

WITHOUT A BLOOD SAMPLE.

The introduction of Tc 99m resulted in a Tc 99m labelled tracer with a high renal extraction. There is a need to provide absolute quantification of the clearance of Tc 99m MAG3 in children where renal maturation is continuing. Multiple plasma samples are not feasible in children, two techniques were reported where only a single plasma sample was required, this work reports the results without a blood sample. Thirty children underwent Tc 99m MAG3 renal scintigraphy, the dose was based on 80 MBq/1.73m 2. There were 14 children with evidence of impaired renal function. !Multiple plasma samples allowed clearance estimation. Simultaneous gamma camera scans were acquired for 40 minutes with the child supine.

iAn assumption was made that the volume of distribuation !is proportional to the bodyweight. Clearance was icalculated either using the kidney uptake method based on the Patlac plot or on the cardiac disappearance curve. The cardiac curve was converted to cts/ml by back-extrapolation using either a single or biexponential fit.

Best correlation (R z : 0.81) was obtained using the iterative biexponential cardiac curve for estimation of clearance. Using a direct blexponential fit on a heavily smoothed cardiac curve gave similar correlation (R ~ = 0.80). The SE was similar 32.3ml/min. vs. 35.46mi/ min. These results are promising and require further validation in order to avoid blood sampling when calculating absolute Tc 99m MAG3 clearance in children. We evaluated the usefulness of kidney tomography compared to planar scintigraphy in acute pyelonephritis. 55 children with a suspected first acute pyelonephritis had a planar and tomographic 99mTc DMSA scan of the kidneys. Scans were analyzed without knowledge of the result of the other acquisition by 2 independent observers.The kidneys were categorized as normal (no lesion), mild or severe abnormal (1, 2 lesions, > 2 lesions) . Tomographic diagnosis was compared to final diagnosis based on clinical complaints, inflammatory biology (VS > 10, + CRP, WBC counts >10000), urinary culture and planar scintigraphy. In 39 cases, the scan was compared to echography. The agreement between observers was 87%. The % of true+/-and false+/-are given in the table.

% true+ %true-%false+ %false-Tomo 58,2(32/55) 29,1(16/55) 7,3(4/55) 5,4(3/55) Planar 54,5(30/55) 29,1(16/55) 7,3(4/55) 9,1 (5/55) Echo 33,3(13/39) 23,1(9/39) 7,7(3/39) 35,9(14/39) The sensitivity was 91,4% for tomography, 85,7% for planar scan but only 48,1% for echo. Specificity was 80% for tomo and planar scan and 75% for echo. Predictive value was 88,9%, 88,2% and 81,2%.Tomography significantly better described the damage: planar scan was normal in 61 kidneys (55,4%), mild abnormal in 39 (35,4%), severely abnormal in 10 (9,1%). Inversely, with tomography, the % were respectively: 53,6% (59 kidneys), 13,6% (15) and 32,7% (36).

It also showed abnormalities (thinning o f cortex, dilated cavities) never demonstrated by planar scan. We conclude that tomoscintigraphy should be preferred to planar scan since , using it, the extend of renal damage is better demonstrated. Moreover, it allows the description of renal damages not directly related to acute pyelonephritis.

J.J.Fettich, R.Kenda. U n i v e r s i t y Medical Centre,

Aim. The purpose of the study was to determine the incidence of vesicoureteral reflux (VUR), renal scars and hypertension in asymptomatic siblings of children with VUR~ Methods. 10S siblings of patients with VUR were stud-~ed. Their age ranged from 4 months to 6,3 years. Direct radionuclide voiding cystography (DRVC) was p~rformed in all cases. Tc-S9m DMSA renal scintigraphy w~s carried out in 43 out of 47 siblings, where VUR was found and parental agreement'could be obtained.

Results. VUR was detected in 45% (47/105) of siblings. Most high grade VUR were seen within the first year of age, their incidence being 50% compared with a 9% incidence in siblings older than 2 years. Renal scars were found in 23% (10/43) of siblings with VUR and 10% of all siblings studied. One child h~d hypertension. Conclusions. Identifying VUR among asymptomatic sibling s could possibly prevent renal damage and its consequences. The predictive value of positive family history alone in identifying VUR was 45% and 23% of siblings with VUR were found to have renal scars. This appears high enough to justify routine screening of asymptomatic siblings, by using DRVC at an early age.

A.FACELLO, J~HADDAD, B.BRUNOT, A.CONSTANTINESCO CHRU Hautepierre F-67098 STRASBOURG-FRANCE 99mTc-HMPAO BRAIN SPECT NORMAL PATTERNS OF REGIONAL PERFUSION IN NEONATES.

To determine normal patterns of cerebral perfusion in neonates using 99mTc-HMPAO SPECT, after obtaining parental consent, we studied 13 neonates at risk of developing cerebral palsy, they range from 32 to 44 weeks of post-conceptual age~ At 12 months of follow-up, all children had a normal n~urobehavioral outcome. SPECT studies were interpreted by two physicians unaware of the clinical history of the neonates, qualitatively using a visual estimation based on a colour scale and semi-quantitatively by counts in ROl/dose/body/weight.

In prematures (32 weeks), cerebral perfusion was present in basal ganglia and brain stem. With progression of gestational age, cerebral perfusion increases respectively in the cerebellum, the striatum, the parietal whit~ matter and reach the sensori-motor cortex at 42-43 weeks. At term (40 weeks), low activity is seen in occipital, temporal and especially frontal lobes. Semi-quantitative analysis showed a good correlation of global cerebral perfusion with post-conceptual age : r = 0,88 (p~O,O01). Regional perfusions were also correlated with post-conceptual age : brain stem (r = 0,64), cerebellum (r = 0,58), parieto-occipital (r = 0,63), parietal (r = 0,70) and frontal lobe (r = 0,74) (all p~O,05). These normal SPECT patterns in neonatal period are congruous with progression of myelination (cephalad) and neonatal neuro behavioral.

In conclusion, 99mTc-HMPAO SPECT constitute an indicator of brain maturation. Normal patterns knowledge is important to evaluate abnormal cerebral perfusion in critically ill neonates. We lhink i~a~ ~e b_i~er sensibility of ~he iso~o~ic m~d ca be due ~o ~he m~tabolic nalnre of ~nis ~¢]~nique. We slso s~udied ~he iccation and n~r of lesion~ de~c~ed by each explo~atioa me~cd.

We fo~Id lhat differential dia~qosis between bone marrow infilira-~ion re, sin as an ~z~solved problem. We concluded lha~. scin~igra-p~y wilh ~N]BG is ~n useful m~lhod for early dis~r~sis of bone me-tas~sses in neuroblss?~a pa~ieni~. Bone marrow (BM) invasion is a most important criterion for staging, treatment and prognosis of neuroblastoma.

To evaluate the ability of the 1231-MIBG scan to detect BM invasion, 103 whole body scans performed in 17 children at the time of diagnosis and at follow-up were compared with the results of the concomitant BM smears obtained from the iliac crest. At the skeletal level 4 different types of tracer uptake could be distinguished : (1) no visualisation (the normal pattern), (2) diffuse MIBG uptake, (3) focal tracer accumulation, (4) diffuse tracer uptake in combination with focal hypercaptation. In only I of the 69 normal scans the BM cytology showed a slight tumoural invasion.

In 11 of the 15 scans showing a diffuse skeletal MIBG uptake (with or without foci), the BM smear was positive. Amongst 19 cases in which an extension to the BM was evidenced by a focal tracer uptake in one or several bones, a positive cytology was obtained in only 6; this is not surprising in view of the limited BM sample obtained at the iliac crest punction. In most cases the smears became positive whitin the next two months. Since only 11 of 16 MIBG skeletal foci correlated with a hot spot on the concomitant 99mTc-MDP bone scan, MIBG appears to be able to detect early tumoural deposits in the BM before osseous invasion occurs. These data suggest that for the assessment of BM infiltration by neuroblastoma,1231-MIBG scintigraphy is more sensitive than the cytological examination of BM smears obtained from the iliac crest.

I.P.Kor~l~uk, S.A.Plyasunov, T.I.Kaganova

I~edical Institute, Sama~ra, Russia

The work deals with the analysis of findings of s~intigraphic study of the lungs in 32 newborns with respiratory distress syndrome.. All the infants examined were divided into 2 groups: Group I included patients with unilateral and bilateral atelectasis of a pulmonary lobe /I9 cases/. Group 2 consisted of infants with an edematous-atelectatic form of pneumopa~hy /7 cases/ and those ~ithhyaline membrane disease /6 cases/. Perfusion scintigraph~ with ~Tc-NAA s~ud inhalation scintigraphy with ~J~Xe were performed. The studies carried out have shown that the perfusion scintigraphy findings a~sist in revealing predominaat involvement of pulmonary circulation and combination of this technique with inhalation scintigraphy permits determining the extent and n~ture of ventilatory disturbances in dependence on the form of pneumopathy. It has been found that interpretation of scintigraphic findings should be done with taking into account of clinical findings, results of X-ray examination and values of acid-base balance. Pulmonary first pass scintigraphy (PFPS), injecting an isotopic bolus, allows the quantification (in seconds) of right ventricle, pulmonary and left ventricle transit times. In children with cystic fibrosis (CF), a prolonged perfusion time to the lungs should be a first index of pulmonary hypertension (PH). AIM OF THE STUDY : to detect an increasing in pulmonary transit time, in various stages of the disease, as a first detection of PH in CF.

: 51 children (2 to 18 years) in different stages of their disease, have been submitted to a PFPS, lung perfusion scintigraphy and a Shwachman clinical score, Chrispin and Norman radiological score and functional evaluation. In the PFPS, computer constructs a phase image i{time of bolus arrival parametric image).

: In normal children (PFPS performed for other pathologies), as in children with low and moderate stages of CF, we have found an early and homogeneous lung perfusion. In front of that, in children with severe CF, the lung perfusion was retarded and asymetrical. In 4 children with very severe stage of CF, the lung perfusion was very heterogeneous, indicating a great perfusion asychronism between lobes or both lungs.

The graphics comparing pulmonary transit times with clinical, radiological and functional scores do not suggest a progressive apparition of PH in these children. In severe diseases, the lung perfusion is clearly asynchronic between lobes or between both lungs. What is it happening at the pathophyslological level, in severe CF: successive regional failures or diffuse, progressive pulmonary hypertension as in adults?

A S~I e Melo, MFR Botelho, L Gon~alves, A Marinho, C Santos, JJ Pedroso de Lima, LA Provid~ncia Cardiologia Pedi~ttfica -H. U. C. e H. Ped., Coimbm Servi~o de Biofisica -Facaldade de Medicina de Coimbra 3049 COIMBRA Codex -PORTUGAL

A method to detect and quantitate systemie-pulmouary flows using ECG gated acquisition of 99roTe blood activity was recently presented 1'2. This is based upon the detection of the nearly sinusoidal local activity variations occuring in the pulmonary ROI, during the cardiac cycle, after blood pool labelling and ECG R-wave synchronized acquisition with a Gamma Camera-Computer System. The phase distribution of the variations detected in healthy controls shows two peaks for different phase angles, the former corresponds to the pulmonary flow and the latter, small and at greater phase angles, represents the systemic-pulmonary flow. The amplitude of the pulsatility may inform about the magnitude and type of circulation, either poriferic or pulmonary. The phase may inform about the timing of the different flows in the ROI. The ratio of the sum of the amplitudes of the pixels in the 2ud peak to the summation of the anaplitudes in all the pixels iu the pulmonary ROI gives the relative blood flow of the systemicpulmonary shunts. Twenty five healthy controls and 26 childrea with cardiac congenital diseases have been studied with the method described. The detection and semi-quantification of pulmonary collateral flows and the assessment of irreversible changes in pulmonary vaseulature have been possible in a number of the eases studied. The simultaneous evaluation of both the phase and amplitude through mulfiparametrie histograms was used. The information obtained is an useful aid when more invasive methods may be avoided and it is complementary to pre-eardiac surgery assessment. The aim of this study was to assess the contribution of Tc-99m HMPAO brain SPECT in Barr~-Liou syndrome (BLS) . This disorder is characterized by cervicarthrosis, with episodes of headache and vertigo. The latter may be provoked by certain movements of the head.

Seven patients with posttraumatic BLS, aged 35 till 53 years, undenNent repeated SPECT with 2 days interval, at random before and after cervical manipulation. All had normal CT-scan findings and vestibular tests. The patients were asked to describe the movement of the head provoking symptoms. This position was applied to the patient and held for 5 minutes, dudng which time 25 mCi Tc-99m HMPAO was injected intravenously. SPECT was performed using a single head rotating gamma camera (Orbiter 75, Siemens). Images were interpreted qualitatively and only regional asymmetries >13 % were considered abnormal.

Only in 2 patients cervical manipulation induced symptomatology. The basal SPECT showed hypoperfusion in the territoP/of the posterior circulation (PCT) in 6 out of 7 patients and additional unilateral frontoparietal hypopedusion in 4 of these 6 patients. The 7th patient showed only unilateral frontoparietal hypoperfusion. In the 6 aforementionned patients cervical manipulation did not alter the distribution pattern, except in 2. These 2, one of which with induced symptoms, showed hypopedusion of the contralateral temporal lobe when compared with the basal SPECT findings. In the 7th patient SPECT now also showed PCT hypoperfusion after cervical manipulation which did not provoke symptoms.

In Barrd-Liou syndrome perfusion SPECT shows clinically relevant hypoperfusion in the territory of the posterior circulation. The meaning of the reversal of SPECT lesions after cervical manipulation in 2 patients, remains speculative since symptomatology allows no lateralisation. According to Albert (1974) , behavioral and intellectual changes observed-in PSP are characteristic of "subcortical dementia". ]n fact the neuropathologic changes are confined to the subcortical structures, the cerebral cortex appeared to be spared ( Steele', 1975) . However the cognitive impairment of PSP has been attributed to a frontal lobe dysfunction (Cambier 1985) that could be explained by desactivation. Frontal cortex hy~'ometabolism detected by PET scan seems to confirm this hypotliesis (d'Antona, 1985 ; Blin, 1990) .

The purpose of this study was : 1) to compare frontal cortex metabolism ~n PSP and IPD 2) to determine the value of SPECT as a diagnostic criteria for PSP 3) to establish correlations between neuropsychologicalperformances and regional metabolic changes determined wi~h SPECT.

We have studied 18 patients with PSP (group 1) (clinical criteria of Lees and Golbe). For each patient neuroosvchological performances were determined (Cambier protocal,'f985), and SPECT with Tc99m HmPAO. For comparison of metaSolic patterns, SPECT was also measured at once in eight patients with IPD (~roup 2) (clinical criteria of Gibb) and eight control subjects (group'5).

Our results showed a significant difference of left frontal cortical index studied by SPECT between PSP and control groups ; the difference wasn't significant between PSP and IPD groups ~lepending ant the evolution duration of PSP and IPD. Any correlation was discovered between psychological performances and fronr tal metabolic changes.

This frontal hypometabolism in PSP could result from a disconnection phenomenon secondary to subcortical lesions (d' Antona, 1985) , then the asymmetry of hypometabolism in the frontal cortex suggests that subcortical structures may also be asymmetrically invalved, at least in earlier stages of the illness. In our SPECT study non difference was discovered between PSP and IPD grouos. However the mean of disease's duration was statisca~lly different (p<0,01), then it would appear that frontal hypometabolism could exist more later in IPD's evolution, in the same proportion than in PSP.

Cort~s J.,LIorens V.,RodrIgusz M.,Rios G.,Genotte J.0Prets J.M~* and Fon~elltda J.C. Nuclear Medicine Service .~europediatrics Service *, Hospital de Cruces. Bilbao. Spain.

9c~I'NMPAO-SPECT has already been employed for seizure focus local|on in infant epilepsy.

The purpnee of this studymae to verify the utiilty of 99m-NRPAO-SPECT in the location of ep|leptogenic loci.

We have studied 40 epileptic children, aged betuee~ 5 ir~ths and 13 years (20 boys end 20 girls), in 31, focal epilepsy was suspected, 4 had West syndrome, 2 poiymorphic epilepsy in breastfed children, 2 Lennox-Gascaut Syndr~, 10tahera Syndro~, and 1 Celiosai sgenesis. In atl patients r~urologicst evaluation, EEG and 99R-NHPAO*SPECT were performed: In 24 cases magnetic resonance (HR) was also carried OUt, and in 28 computed tomography (CT).

SPECT Images were obtained with s GE gammecamera equipped with an sitpurpose co[imator. 64 images of 30 seconds were acquired over ]60eo The rediotrecer was injected by e.v rOUte, dosage ranging betueen 55-353 MBq. I#nen sedation was needed, clorpromazine was administred by i.m. route always fo[towlng HMPAO. T~mographic reconstruction was carried OUt with Hsnning(cut off frequency 0.7) filter. 2 pixei thick trensaxiai, coronal and eegitai slices were obtained. Reorientated slices parallel to orbitomaatai line uere also performed. SPECT images were analysed by two observers ~ho evaluated increased and decreased porfusion.

Lesion location correlated well with that expected by ctinicat means in 32 cases(80%). The most frequent location was temporal 19/34(55%). Only 50%(12/24) of the patients having had MR, showed abnermai images. In 11 (90%) the MR matched clinical findings. In 9 of 12, with normal MR, the NHPAO-SPECT was sb~ormai,andet[ these cases correlated well with clinical findings. Of the 28 cases with CT, abeormai findings were observed ~n 8. In all of these, the alterations were difuse end did r~t assist in the location seizures locality. In 30 Intracranial meningioma of grade I WHO with immunocytochemical markers as the proliferating cell nuclear antigen (cycline) revealed a proliferation rate PR (positive nuclei in o/oo of counted nuclei) varying by a factor of 20. PR, however, may govern the fate of such patients. TO find out whether F-18 DOG PET noninvasively yields a correlate to PR, it was employed in 32 pts with typical CT/MR-findings of IM and compared to PR, histopathologic findings and to Tc-99m DTPA SPECT, the latter used to assess passive tumor uptake. Following cranial transmission (CTI 953/15), emission was recorded for 80 min after 300 MBq . R~gional evaluation yielded standardized uptake value (SUV), tumor-to-grey matter ratio (TGMR) and Sokoloff analysis (~41mol/miu/gm) and from 8PECT/ the tumor-to-cerebellar ratio (TCR) for DTPA (40 min pi). All TCR were >1.3 (mean:3.4). TGMR, however, was > 0.9 in 8/32(25%) IM only. Further results (mean + SD) were: n SUV Sokoloff PR(o/oo) TGMR >0.9 8 6.6±2.0 0.48±.18 13.0±2.9" Grey matter 32 7.1±2.0" 0.46±.17" --TGHR <0.9 24 3.9±i.i* 0.20±.08" 6.9±5.9* (* vs *: p~.01, vertical reading). Histologic patterns revealed nO correlation to SUV or Sokoloff values. We conclude that F-18 DOG uptake in IM is not a passive process. IM may be classified for proliferation by F-18 DOG PET, even from TGMR. For absolute quantification, the Sokoloff analysis proved to be sufficient. IM with a glucose consumption of >0.3 ~mol/min/g showed significant higher proliferation and thus may be staged to be more agressive than grade I WHO. Affective disorders iu Alzheimer's disease (AD~ raises diagnostic and etiological questions. Elated mood (according to AS-BERG's criteria~ seemed to be an interesting feature to progress with the comprehension of affective disorders in AD as tSe other symptoms belonging to manic episode are not present in normal el-6erly. In order to ~o further in the etiology o f elation we searched arguments for maniac episode (with semi structured psy.chiatric interview and questionnaire to the care-giver) psychological impairments ( life events evaluation) and frontal Iobe dysfunction zn its neuropsychological aspects and regional Cerebral BIood Flow .

We have studied 11 elated patients with probable AD (according to the NINCDS-ADRDA criteria) and ~1 non elated patients with AD, matched for age, mean education, severity of ~tementia. All subjects were rlght-handed, rCBF was assessed by SPECT. Subjects were scanned on a Tomomatic 64 15 rain after intravenous znjection of HmPaO 99m Tc. Regions of ~ Interest were drawn according with a NMR Atlas ( C a b a n i s et al; 1986 ) in 2 paired regions : frontal antero external and temporo-occlpital. Uptake Indexes were calculated using cerebellum as reference. Furthermore, an anterior-posterior l~atio was computed. Data were analysed using non parametrical tests ( Mann and Whitney' s U Test. )

We did not find any argument for manic episode or psychological imparment but fronta'i lobe dysfunction assessement was more impaired in elated patients than in AD controls. SPECT stu= dies showed a lower Anterior-Posterior Ratio in elated patients compared with control AD and the difference was significant (Mann & Whitney, U=20, p<0,01).

Neuropsy~chological assessement and cerebral blood flow data suggested a fronta[lobe dysfuntion linked with elated mood. It could 5e an individualized frontal clinlcal-neuropsychological-CBF pattern within the heterogenity of AD. 3-iodo-6-methoxy-N-[(l-ethyl-2pyrrodinyl ) methyl] benzamide} is a highly selective central dopamine-2 receptor ligand for SPECT imaging. It has been suggested that the optimal D2receptor imaging time should be 60 min p.i. The aim of the present study was to investigate the change of tracer binding dependent on imaging time. 185 MBq of [123i]-IBZM was administrated i.v and SPECT was performed 60 mln and 180 mln p.i. The study group consisted of 33 pts(mean age:62±14 yrs,20 m, 13 f) with various extrapyramidal~disorders(15 idiopathic parkinsonism, 4 parkinsonism, 6 hemiparkinsonism, 4 progressive supranuclear palsy, 3 dystonia, one Shy-drager syndrom) and 3 volunteers. Volunteers were examined 60, 120, 180 and 240 min. p.i. to study the time course of receptor binding. Primary perfusion of substance was seen 60 min p.i. Specific binding of the radiotracer was observed mainly in the striatum 120 and 180 min p.i. The washout of [123I]-IBZM was noted 240 min after injection. Therefore the best time for the performance of [123I]-IBZM-SPECT seems to be between 120 to 180 min. after application. Semiquantitative analysis of tracer binding was performed on transaxial slices using ROI method. Basal ganglia/lateral frontal cortex (BG/LF) and basal ganglia/cerebellum(BG/C) ratios were calculated using the mean counts/pixel value of ROIs drawn on transaxial slices. Data from the first and third hour were compared to each other.

First hour(L/Ri Third hour(L/R) *<0.05 BG/LE * ~.17 ±0.06/1.17 ±0.06 1.21 ±0.07/1.19 ±0.07 BG/C* 1.32 ±0.11/1.32 ±0.12 1.47 ±0.11/1.46 ±0.14 According to our results, imaging time of [123I]-IBZM appears to be important in the semiquantitative assessment of D2-receptor binding. The results of patients should be compared to normals only performed with same post injection interval. introduction: There are few reports about the diagnostic relevance of in cerebral gti~nas as welt as in tumor recurrence or residual glioma tissue, Recently 201 Ti imaging in necrotic ttaaor areas is unknotm, Nethod: 201 Ti-ECT was porformed 20 min. p.c. (74-85 NSq) using tranversat CT anatoge sections. Regions of interest (ROI) were determined for calculation of the tumor/tissue r a t i o .

After surgry autoradiography (Phosphoimager v i t h d i g i t a l quantification) uas performed and co~parad with the immediate sections for microscopic exaalinetion of the lesions. Results: This report describes the resuls in 15 patients.We found no 201 Ti uptake in vivo and in v i t r o in necrotic areas, glioses and in 2 epidermoid cyts of the i f ! ventricle. One pituitary ader~l~a and one astrocytoma grading ]! showed a 201 Ti uptake in vivo but not in v i t r o . In contrast to these findings ue found a high uptake in vivo and in v i t r o in meningecmas, metastases, astrocytomas grading i i | and IV and in oligodendrogtiomas grading i l l . In two patients residual tumor tissue was detected after surgery Only with 201 Ti ECT and not in NR! or CT. In these cases the 201 Ti uptake cemaind very high.

In conclusion the 201 Ti-ECT is able to differentiate cerebral lesions. In contrast to other methods 201 Ti is enriched in residual tissue areas after surgery so that we can differentiate between brain s~elling and tumor tissue. This is an important finding for the postoperative procedure and the therapy planning. We also c o m p a r e d t h e MIBI SPECT i m a g e s with c o n t r a s t e n h a n c e d MRI or CT. 7 p a t i e n t s were imaged p r e s e n t i n g w i t h r e c u r r i n g h i g h g r a d e gliomas. They were c o m p a r e d to 5 p a t i e n t s with low (I a n d II) g r a d e gliomas who had been p r e v i o u s l y t r e a t e d b y r a d i a t i o n a n d / o r c h e m o t h e r a p y a n d whose clinical c o n d i t i o n was stable. SPECT was p e r f o r m e d a f t e r IV i n j e c t i o n of 740 MBq 99mTc MIBI. A l t h o u g h t h e r e was s i g n i f i c a n t u p t a k e in the scalp, all l e s i o n s could be i d e n t i f i e d . T r a n s v e r s e slices were summed up a n d a r a t i o of tumor over contralateral counts was computed. There was a significant difference between high grade lesion uptake ratio (2.47 + 0.91) and low grade (1.28 + 0o18), p<0.01. Furthermore, there were some discrepancies between the MIBI uptake and contrast uptake on CT and MRI images. In conclusions MIBI shows increased uptake in a g g r e s s i v e gliomas. The d i s c r e p a n c y b e t w e e n c o n t r a s t a n d MIBI u p t a k e d e s e r v e s f u r t h e r e v a l u a t i o n . We validated a method of semi-quantitative analysis of Tc-99m HMPAO brain SPECT based on circumferential profiles. For each SPECT study, 3 profiles, representing the top, middle and bottom section of the brain, were obtained. To generate these, the data cube was reoriented in the orbitomeatgl plane and 3 slices, each 4 pixels thick, were positioned by the operator on a sagittal display at the upper, middle and lower levels. The outline of the cerebral/cerebellar activity in the slices was fitted with an ellips. A second ellips with the same centre was then drawn automatically, the length of its axes being 60% of those of the first ellips. Radii were drawn through the centre of the ellipses, with 64 angular increments. The midpoint of the interception of these radii with the ellipses served as center points for 4*4*4 pixels containing volume elements, in which the cortical/cerebellar activity was sampled. The values were normalised to the maximal value in the cerebellar region.

In 12 normal subjects, who underwent brain SPECT after IV injection of 25 mCi (925 MBq) Tc 99m HMPAO, the intra-and interobserver reproducibility of the method proved to be excellent. Correlation coefficients of .98 (p < .001) were obtained for paired values determined by one observer on different days as well as for paired values measured by two independent operators. In this healthy population, the cerebellar maximum used for normalisalion was highly correlated to the mean cerebral activity (r= .99, p <.001). Profiles consisting of the mean ~2 SD obtained in this normal population provide a reference for evaluation of clinical brain SPECT studies. Use of this data bank allows more corffident interpretation of individual rCBF disturbances and their evolution. 

Sumatriptan --a selective 5-hydroxytryptamine l-like receptor agonist--is a highly effective novel drug in the acute treatment of migraine attacks. Its selective pharmacological profile may be helpful in studies of the pathophysiology of migraine. We studied regionat cerebral blood flow (rCBF) in 13 patients suffering from migraine without aura. 500 MBq 99mTc-HMPAO was injected shortly after the onset of a migraine attack. Then the patient was treated with sumatriptan, and when the patient was (almost) free of migraine related complaints imaging was started. Immediately after the first study a second dose 99mTc-HMPAO was injected and again a study of regional activity distribution was acquired. After few days without any migraine related complaints a third study was performed. Cortical (6) and white matter (4) brain regions (ROIs) were drawn on the attack free study and applied to all studies of the patient. In half of the patients the regions were drawn on the right side and then mirrored to the left side, in the other half drawing was started on the left side. After normalization of the count data for decay and region size rCBF was computed.

Overall we found no significant asymmetries or changes in rCBF, but individual analysis of the patients revealed two patterns of rCBF changes during attacks: 5 patients showed an increased rCBF in the temporal and parietal region at the attack-free side, while 8 patients showed a decreasing rCBF in that area. In both groups sumatriptan reversed the change of rCBF. Tc-99m HMPAO and SPECT has been used to study test-retest patterns of rCBF in one session using a 'split-dose' technique or on separate occasions (>24h). This study used visual stimuli to examine error sources separating effects of 1) in vitro degradation of tracer; 2) in vivo change of distribution; 3) the importance of statistics and movement/position errors. 24 volunteers participated in 4 groups of 6 (A,B,C,D). All had two xenon-inhalation scans (rest and activated). Groups A and B had 3 HMPAO injections (200 MBq each) on 3 diff. days. On day 1, (A=B), two recordings showed reproducibility and background for 'split-dose' examinations. On day 2 =rest, day 3 = activation injection of group B was delayed 50 min relative to kit reconstitution to simulate the second injection of a split-dose study. Groups C and D had split-dose injections (200+400 MBq). The 1. injection in rest; during the 2. injection, group D was activated, while group C was not. Total effective dose for both procedures was less than 10 mSv and the study was approved by the local ethical committee.

Images were analyzed in predefined ROI's transformed to standard sizes and positions, relative to 'global means'. In visual cortex responses of (18+5)% (n=24) was found with xenon. With HMPAO the values were (11 +2)% (n=6) in split-dose and (9+4)% (n= 12) in the two-session mode. Resting state reproducibility was excellent (SD__.3%). The in vivo stability under routine conditions (lipophilic fraction decreasing from 88% to 82% over 1 h) allows the use of a single vial in the split-dose application. Average tracer washout in excess of decay was 1.5% in 50 min. Counting statistics was dominated in any region by patient movement.

We conclude that HMPAO can be used for 'activation' studies in both split-dose and two-session mode. Positioning is the dominant problem. The loss in statistics by subtraction in split-dose mode is outweighed by a higher reliability of repositioning. Values obtained are only relative and measured activations underestimate real values considerably. The split-dose approach may be of interest in studies of seizure activity, control ofthrombolyric treatment, and pharmacological activation studies as with diamox. Local cerebral glucose utilization (LCGU) was measured in 51 structures of the rat brain after acute and/or chronic oral administration of ethanol using the quantitative autoradiographic method. In the acute experiments ethanol was given via a gastric tube 110 minutes before the 2-DG. The chronic pretreatment was performed using increasing concentrations of ethanol in the drinking water. Plasma concentrations of ethanol during the measurement of LCGU were 1.67 to 1.80 g/I (acute administration), 0.10 to 0.14 g/I (chronic administration) and 2.52 to 2.65 g/I (combined acute and chronic administration). The most striking effects on LCGU were seen in the inferior colliculus, where acute and acute plus chronic treatment with ethanol resulted in a significant decrease in LCGU by 33 and 37%, respectively, whereas chronic treatment significantly increased LCGU by 25%. In general, acute administration of ethanol decreased LCGU in 16 brain structures, particularly of the auditory system. Chronic treatment, besides its effect on the inferior colliculus, only decreased LCGU in the internal capsule. Chronic plus acute administration of ethanol decreased LCGU significantly in 22 structures. These structures were mainly identical with those influenced by the acute administration. It is concluded that an acute oral administration of ethanol has distinct and mainly depressive effects on the functional activity of several brain areas.

Tc-99m hexamethylpropylene amineoxime (HMPAO) brain SPECT imaging was performed in 12 patients 2 years after acute head trauma with consecutive prolonged apallic syndrom for more than one month. The most frequent cause for the injury was a vehicle accident. The coma following the primary lesion lasted between 1 and 4 months. The results of brain SPECT imaging were compared with MRI scan, neurological examination and neuropsychological testing. HMPAO SPECT revealed pathological results in all cases. In the most patients defects in the HMPAO SPECT agreed with the lesions in the MRI scan. In some cases HMPAO SPECT imaging showed additional lesions indicating hypoperfusions of morphologically unchanged brain structures. One patient was still comatose during the SPECT study. He showed no significant cerebral tracer uptake. In conclusion, HMPAO SPECT is a useful tool to demonstrate pathological blood flow patterns in all patients, who experienced severe acute head trauma and transitional apallic syndrom, whereas MRI scan could not show all lesions.

J.T. Kuikka, U. Iepola, K. Bergstr~m, E. I/Snsimies, P. Riekkinen, Departments of Clinical Physiology and Neurology, Kuopio University Hospital, SF-70210 Kuopio, Finland REGIONAL CEREBRAL BLOOD FLOW AND BENZODIAZEPINE RECEP-TOR DENSITY IN PATIENTS WITH PANIC DISORDER Seven patients suffering from panic disorder were investigated using dynsmic SPET and I-I 23 Iomazenil. The mean age of the patients was 37 yrs (range:31-45 yrs). They had no medical therapy for their sickness before the SPET study. A dose of 185 MBq of 1-123 Iomazenil was intravenously injected and the first SPET ([~rfusion imaging) was started 10 minutes later. The second SPET (receptor density imaging) was repeated 90 minutes after the injection of tracer. Six nm thick transaxial slices oriented in OM-line were reconstructed and visuallu survayed. The slice 40 nm above the OM-line was chosen for the placement of 6 symaetrical regions of interest: frontal, frontotersporal and temporal (sin and dex). A seventh ROI over the white matter was drawn and it served as an internal standard. The cortex-towhite matter ratios were calculated. Two control subjects were also studied. The perfusion images revealed in 4/7 cases "luxurious" perfusion in the fright frontal cortex. The results of cortex-to-white matter ratios are ~i z e d in the table as a mean ± one standard deviation.

F~ntal Frontotemporal T e~r a l Sin 6 . 4 ± I , 4 5 . 6 ± 1 . 2 6 . 7 ± 1 . 7 Dex 6.6 ± 1.4 6.0 ± 1. 

K Rootwelt, IA Grimstad, H Hirschberg Section of Nuclear Medicine and Department of Neurosurgery, Rikshospitalet National Hospital, N--0027 Oslo

Background. The demonstration and accurate localization of intracerebral mass lesions are commonly performed with computerized tomography (CT), which olden cannot determine the nature of the lesion. The purpose of the present study was to evaluate the usefulness of ~'~Fchexamethylpropyleneamiue oxime (~Tc-HMPAO) leukocyte seintigraphy and the serum C-reactive protein (CRP) level in the differential diagnosis between brain abscess and neoplasm, when they both have ring-like contrast enhancement on CT. Methods. 23 patients were studied. 22 of them showed ring-like contrast enhancement on CT, the exception being a negative CT despite clinical suspicion of intra-or extraeranial abscess in a patient operated for a menlngeoma. Autologous leukocytes were labeled according to the recommendations of the manufacturer (Amersham Int., Buckinghamshire, GB). The patients had all been off systemic steroid treatment for at least 48 hours before leukocyte labeling end reinjection. CRP was measured by a standard laboratory t~hnique. The final diagnosis was invariably established by microscopy of tissue specimens.

Results. In 10 of the patients the final diagnosis was brain abscess, and 13 patients had a brain neoplasm (nine with glioma and four with metastasis). The ~Tc-HMPAO leukocyte scintigraphy detected all cases of abscess. There were no false positives. Elevated CRP level (> 13 mg/l) was found in all but one abscess patients and In three cases with neoplasm; two of these three patients had dental root infectious which could account for the CRP elevations. The better sensitivity, specificity, predictive value and diagnostic efficiency of ~mTe-HMPAO compared to CIL! a was not statistically significant (p > 0.11, Fishar's exact test, two-tailed).

Conclusions. ~Tc-HMPAO leukocyte scintigraphy and Clap determination should be performed when there is a possibility that a brain abscess may exist. 99~Tc-HMPAO leukocyte scintigraphy compares favourably with the results reported by others with raIn-labeled leukocyte scint~raphy. Methods. Twelve subjects, (6 normal controls ~ 60C patients), were investigated using a split-dose activation paz-ddigm. All subjects reze/ved 2 doses of 99MTc-}~4P~/) (controls; mean doses 248 a~d 261 MBq, patients; mean doses 256 and 264 MB~. D~ta were acquired using a triple-headed, IGE Neurocam. Subjects were scanned in 2 conditions; a controlled resting state, and then during the performance of a visiospatial attentional task. Images were corrected for injected dose and for radio-active decay to allow comparison within and between subjects. Results. Comparison of controlled rest-state scans between normal and OC subjects revealed a global fall J J3 activity in the patient group of 21%, significant at the 1% level. Subsequent investigation of frontal lobe to cerebellar ratios demonstrated that the patient group had relatively decreased frontal lobe activity, significant at 1%. Performance of the activation task, itself involving increased activity in several brain regions in which the OC group had decreased activity at rest, failed to distinguish between the patient and the control group. CQnclusions. OC patients suffer frc~ a psychiatric condition affecting m~ny aspects of their lives. The evidence frcm this study indicates widespread disturbance of resting brain activity. Nevertheless, they appear to be able generate task-related ~ in cerebral activity in a cognitively demanding task in a manner s~m~]ar to normal volunteers. The aim of this study was to realize a quantitative comparison between two "microsphere like" tracers of the cerebral peffusion, 99mTc-ECD (ECD) and 99mTc-HmPAO (HmPAO).

14 patients (mean age : 50 y ; range 33-65 y) with chronic stroke were studied using a ~edicated SPErCT system (Tomomatic 64) : 6 with cerebral ischemia and 8 with intracerebral hematoma.

In 7 of 14 patients, 7 MBq/kg of ECD was injected intravenously 20 min before study and 4~8 flours later a similar study was reahzed with the same activity of HmPAO. ~n other patients, HmPAO was the first tracer. Order was randomly chosen.

For each study, 7 paired ROIs were drawn : cerebellar, anterior frontal, sylvlan, occipital, thalamic, superior frontal and parietal areas.

Regional Standardized Values (rSV : counts/mCi of injected activity x acquisition time), Uptake Indexes (UI : %) using cerebellar values as reference and Asymmetry Indexes (AI) of ECD were compared with respectively rSV, UI~ and AI of HmPAO, using no parametric methods (Wilcoxon's test and Spearman rank correlation coefficient).

ECD occipital rSV was significantly higher (p < 0.05) than HmPAO occipital rSV. There were no significant difference in other areas.

ECD UI were significantly higher than HmPAO UI in occipital, superior frontal and parietal areas but lower in thalamic areas. Spearman rank correlation coefficients between ECD and HmPAO UI were significant for the six areas.

AI were also highly correlated except for occipital areas. If simple linear regression analysis is realized, relationship will be : IAEC D = 1.25-IAHmPA O + 1.32

These results show the difference in occipital uptake of ECD and HmPAO.

Uptake and Asymmetry Indexes in other areas are significantly correlated. ECD AI which are higher than HmPAO AI, particularly in pathologic cases, result in a better contrast.

Pipit Lass Laboratory of Isotope Diagnostic~. Medical School, Gda~sk, Poland Brain blood pool changes assessed ~y gated brain scintigraphy.

Brain volume changes caused by the pulse ~ava are dependent on brain vessels distensibility and volume of vascular bed. These changes are expected to decrease in patients with diffuse cerebrovascular diseases.

We tried to assess the brain blood pool changes with the use of gated brain scintigraphy with Tc99m in vivo labelled erythrocytes. The investigations were performed in ]6 bat£ents at the occasion of standard gated cardiac studies, performed with planar Picker Dyna Camera 4. We aimed to determine the normal values, changes in different groups of patho-Iogy and the correlations with cardiac ejection fraction. For analysis we used a standard cardiac ejection fraction programme with minor ROI modifications.

We found normal v~lues of brain blood pool changes to be 16.8 ~ ).i ~ (ii pts.). In 14 pts. with mean-term diabetes type I we ~ound it + decreased to 6.5 2,8 ~. We also found the negative correlation between brain blood pool amplitude and cardI&e~ e3ection fraction in patients with congestive heart failure. Studies of depressive and demented patients are in progress. We believe, that this technique might be helpful in diagnosis of patients with di~use cerebrovascular pathology.

H. Matsuda, H. Sumiya, S. Tsuji, N. Shuke, N. Tonami, K. Hisada Department of Nuclear lVledicine, Kanazawa University Hospital, Kanazawa, Japan

A noninvasive simple method for quantitative evaluation of brain perfusion is developed using inl~avenous radionuclide angiography with Tc-99m HMPAO. The passage through the heart to the brain was monitored after bolus injection of HMPAO into the right brachial vein using a rectangular large-field gamma camera. Following injection, a sequence of 110 frames at 1 see intervals was started in a 128X128 format with the patients positioned in the supine position. Regions of interest were drawn over the aortic arch (ROIao~) and bilateral brain hemispheres (ROI,.~). Graphical analysis was employed for the evaluation of the unidirectional influx constant (1%) of the tracer from the blood to the brain. The 1% values were standardized to provide objective and comparable values, brain perfusion indices (BPI), among studied subjects by setting the ratio of R O I , m size to ROI~ora size to 10. The whole brain BPI values for the normal conlrols showed a significant negative correlation with advancing age (r= -0.632). The mean of the whole brain BPI of 7.0 with s.d. of 1.4 in 20 patients with cerebrovascular disorders was significantly lower than that of 10.6 with s.d. of 1.5 in 13 normal controls. BPI measurements showed only minimal intra-and interobsever variability. Changes of the ratio of ROI,o m size and R O I~ size did not significantly influence BPI values (C.V.= 4%). Hemispheric BPI values in 19 subjects showed highly significant correlations with hemispheric mean cerebral blood flow values obtained from 133Xe SPECT (r=-0.926). This technique is easy to apply as an adjunct to SPECT and may be helpful in the quantitative evaluation of brain perfusion in routine clinical studies. 99mTc-HMPAO accumulates rapidly in the brain and remains intracellulag thus presenting a pattern of cerebral blood flow (CBF) under conditions prevailing during its injection. This study investigates the influences of different anaesthetics on CBF patterns Ctz ~o in e baboon model using SPECT and ~mTc-HMPAO. The standard procedure for anaesthesia in the baboon requires a combination of darting with ketamine and subsequent maintenance on long or short acting general anaesthesia. This procedure determined the following ccmbinatiens of anaesthetics studied in six norms1 baboons:

A, thiopentone -thiopentons; B, ketamine -thiopentone;

C, ketaminepentobarbitone; and D, ketaminehalothane. The first thiopentone scan (in A)~ and the ketamine scans {in B~ C, and D} are "baseline" SPECT studies obtained after the coinciding i.v. administration of I~8 MBq of 99mTc-HMPAO. Thiopentona (2nd in A and B)~ pentebarbitone (in C), and halothane (in D) scans are SPECT "intervention" studies obtained after s second coincident double dosage H~PAO-injection, representing also contributions from "baseline" radioactivity. The transaxial, sagittal and coronal slices contained CBF information obtained during the two consscutively applied anaesthetics of each procedure. The respective ROI's yielded countrate data of these slices and B ratio R followed:

Intervention count (2rid anaesth) -baseline count (qst anaesth) R = baseline count (1st anaesth) N indicates the change of CBF during the second anaesthesia and equals 2 for no change. The results indicate different influences from first and second anaesthesia as seen from R-values deviating fro~ the value 2. This confirms that brain SPECT with HMPAO is sensitive to effects of anaesthesia on CBF and that animal experimentation needs standardising investigations under the chosen anaesthetic.

DS Lee, MC Lee, BW Yoon, J-K Chung, C-S Koh. Seoul National University Uospital, Seoul, Korea

With In-Ill-leukocyte planar scan, the activity not less than skull marrow was suggested to reveal brain abscess. Brain tumor with infiltration of leukocytes frequently causes confusion. We tried to find out whether 4 hour SPECT with leukocyte labelled with Tc-ggm by HMPAO could replace sequential/24 hour planar images in differentiating brain abscess from tumor.

Labelling efficiency of leukocytes with . 125 to 470 MBq was injected. After 4 hour pl~nar scan, SPECT was performed and attenuationcorrected three volume views were reviewed. Intense activity was found in brain parenchyme in 4 hour SPECT in 9(of 18) cases with abscess. One(of 18) was positive but was cerebral infarction associated with subarachnoid hemorrhage (specificity-90%). Planar scan of sequential/24B gave the right information in 4 cases of the above 9(44%):Two(of 9) were not found in planar scan because abscess was localized along the midline, and we could not discriminate the other 3(of g) due to less activity or deep localization. These abscess were proved histologically after operation. Four(of 18) cases of tumor was properly excluded with faint or no uptake. Remaining 4(of 18) were normal without anatomic lesion on MR. One(of 18) was new granuloma due to tuberculosis and had mild uptake. Flare-up of cysticereosis and recurrence of cerebral aspergillosis were not missed with leukocyte brain SPECT.

We concluded that attenuation-corrected brain SPECT of 4 hour with Te-99m-leukoeytes could differentiate brain abscess from brain tumor or normal. On the other hand, early phase of cerebral infarction might pose problem for differentiation. Gamma-amino-butyric-acid (GABA) ks the major central inhibitory neurotransmitter controlling up to 40 % of synapses. We attempted to determine the metabolic response to gabaergic stimulation, using the specific GABA-A agonist, THIP, in humans by [18F]FDG-PET.

Three normal volunteers and nine patients, refering for presurgical evaluation of temporal lobe epilepsy, underwent EEG monitoring coupled with [18F]FDG PET scans, under placebo condition and gabaergic stimulation with LV. 0.2 mg/kg THIP, within 48 hours. We compared cerebral glucose consumption (CMRGlu) and its extent of variation within brain regions between the two conditions.

The clinical and EEG findings under THIP showed sleepiness and decrease of alpha rhythms. We observed a widespread increase of global CMRGlu under THIP (2 to 46 %) in cortical regions, cerebellum, putamen and caudate. Grey matter had an average increase of 17.1% (p<0.015); white matter CMRGlu remained unchanged.

As expected, regions with low gabaergic receptors density, like in white matter, remained unchanged under stimulation. In gray matter, gabaergic stimulation would have suggested cerebral hypometabolism. The paradoxical increase in glucose consumption detected in grey matter could be explained, besides involvment of glial cells, by the fact that gabaergic activation uses, at least for a phase of its action, energy to produce an inhibitory action.

21 Leinsinqer, P. schmiedek, K. Einh~upl, A. Piepgras, Kreisig, C.M. Kitsch Depts. of Nuclear Medicine, Neurosurgery and Neurology, Kliniktu~ Grosshadern, University of Mtulich, Germany

The determination of cerebrovascular reserve capacity (CVRC = rCBF(stim.) -rCBF(rest); ml/100g/min) using the acetazolamide stimulation test was established in order to detect patients at risk of hemodynamic failure from ~nternal carotid artery occlusion. In previous studies especially those patients with severe reduction of CVRC seemed to have a benefit from bypass surgery. Therefore, 36 patients with a symptomatic occlusion of the internal carotid artery and severely compromised CVRC were selected for bypass surgery. The aim of this prospective study was to evaluate the longterm follow-up of rCBF[rest) and CVRC. RCBF of the middle cerebral artery territory was measured at resting conditions and after stimulation with Ig of acetazolamide using the 133-xenon inhalation technique (Tomomatic 64). Postoperative studies were performed six days (n=29), two months (n=29), one year (n=19) and three years (n=11) after bypass surgery. Mean preoperative resting flow of the operated hemisphere was 55Z9 ml/100g/min. There was no significant change of resting flow in the follow-up after surgery. Mean preoperative CVRC was 0.5±5 ml/100g/min. CVRC increased to 4±8 ml/100g/min (six days), 8±6 ml/100g/min (two months and I year) and 7±7 ml/100g/min (three years) after surgery. An improvement of CVRC was observed in 14/21 patients (67%) with a follow-up of more than one year. Severe perioperative complications were observed in 3 patients resulting in an operative risk of 8%.

In conclusion, the determination of CVRC is an essential parameter to select patients with hemodynamic risk who may have a benefit from extra-intracranial arterial bypass surgery.

An increased binding of the g-opiate receptor ligand 11C_carfentanll, but not of the nonspecific opiate receptor ligand llC-diprenorphine (DPN) has been demonstrated in lateral temporal lobe in patients with temporal lobe epilepsy fILE) (Mayberg et al.1991) We measured interictal regional glucose metabolism (rCMRglu) with 18F-FDG and binding potential (BP) of llC-DPN in 2 patients with well defined TLE of mesiobasal origin, rCMRglu was calculated using a 3-compartment model (lumped constant 0,42). The ratio ROl/primary visual cortex 40-90 min p.i. was used as an index for BP. In both patients there was a decreas~ of rCMRglu in the epileptogenic medial temporal lobe compared to the homologous contralateral region (asymmetry index (AI) of 9.1% and 9.0%), and a more marked decrease of rCMRglu in lateral temporal neocortex (AI=32% and 18.9%). Binding potential of DPN was lower in medial temporal lobe on the side of the focus in both patient s (AI=9.3% and 16.7%) and in lateral temporal cortex (AI =8.5% and 3.4%). These asymmetries of BP were within 2 sd of the mean AI for a group of normal subjects of similar age (n=8).

To date 1 patient has had selective amygdalo-hippocampectomy and was seizure free 5 month after surgery, when FDG and DPN scans were repeated, rCMRglu decreased further in the remaining lateral temporal lobe and BP of DPN in lateral temporal cortex was reduced on the side of surgery as well (AI= 18%, preop 3.4%). The data suggest a dowuregulation of opiate receptors following successful removal of the epileptic focus.

Mayberg HS et al. (1991) Ann Neuro130: [3] [4] [5] [6] [7] [8] [9] [10] [11] . The purpose of this study was to determine if the brain scans contributed to the management of neurologically devastated patients when it was employed to establish medico-legal precedence prior to withdrawal of life support systems.

From February 1991 to March 1992, 33 cerebral perfusion studies were performed on a total of 31 patients to diagnose brain death. The two major causes of injury were traumatic brain edema and spontaneous subarachnoid hemorrhage. All studies were performed using 15 mCi of technetium-99m Cerotec with static images obtained at one, five and fifteen minute intervals. Dynamic flow study preceded static images. Twenty-seven studies out of 33 were consistent with brain death. In two of six studies where the patient was considered alive, five and fifteen minute static images revealed diffuse, markedly diminished uptake of the Cerotec. Dynamic flow study was normal in both cases. In five of six cases where the brain flow study was normal, the patients were declared clinically brain dead within six hours and support systems were removed. In the remaining case, the patient lost cranial nerve functions and cardiopulmonary drive over the course of the next six days and was declared brain dead by clinicai criteria.

All patients evaluated by nuclear medicine for support of brain death were ultimately declared clinically brain dead within six hours to six days of the imaging study. The utility of such imaging studies must be questioned in view of the facts that patient management and, ultimately, outcome were net affected by the imaging results. Using positron emission tomography {PET) and %150, the orientation discrimination of visual stimulf was studied in 9 normal volunteers. Approval was given by the Ethics Committee of U.Z. GHB, Leuven. The data were collected with a CTI-931/8/12 PET scanner. The analysis was done with the SPM (statistical parametric mapping) software (Hammersmith Hospital). We compared activation in 6 tasks : two fixation tasks (with and without appearance of a grating stimulus), two detection tasks (detection of a grating and a noise pattern) and two orientation discrimination tasks (orientation discrimination of a single grating and of two successive gratings). During each task the stimulus appeared during 300ms and the frequency was 16 trials/min (9 tasks/min for the orientation discrimination of two successive gratings). The scan duration was 40s. Using a Bonferroni correction for statistical analysis of the activity distribution, the following results were found. Comparing the orientation discrimination tasks with the fixation tasks, foci of activation were found in the cerebellum, the gyrus lingualis and the cuneus.

The task with two successive stimuli showed greater activity than the orientation discrimination task with a single stimulus. Comparing the detection tasks with the fixations tasks only the foci in the cerebellum were found. This is probably due to motor activation (pushing buttons) which is the common part in the detection and orientation discrimination tasks. In conclusion : the orientation discrimination tasks the activity in the visual cortex is stronger than the activity during the passive viewing of the stimulus. The major interest of HMPAO-SPECT in temporal epilepsy Js to give one more criterion for decision when surgery is anticipated. Previously reported studies have initially confirmed the possibility for SPECT to locate the epileptogenic zone, but they do not really consider the surgical practice. A semi-quantitative method for interpretation of NMPAO-SPECT based on a surgical compartment model of the temporal lobe is proposed. The first step is the definition of a reference reorientation plane parallel to the insular-axis. It provides a global and continuous visualization of the mesio-temporal structures. During the second step, fifty ROI for each temporal lobe are automatically selected corresponding to five coronal slices. For each ROI, the L/R ratio is calculated.

Refering to 12 healthy volunters, the threshold of significant asymmetry is evaluated at ± 7%. In attempt to standardize the interpretation, the following graduation is defined : G0<7% (normal), 8%<Gt<15%, 15%<G2<22%, • G~>22%. A Tem~oyaZ Z~dex (TI) is calculated taking into account the exten6 and the grade : TI=~iGiN i with Ni the number of ROI with grade G i. In a first time, this model is experimentaly valided on HMPAO-SPECT and FDG-PET in a first group of ten patients with epilepsy. ~hen a clearly ictal or interictal EEC spiking is recorded, PET and SPECT provides correlated informations and the TI is cc~s tantly higher in PET. In a second time, the model is used in a second group of 35 patients with drug resistant focal epilepsy to analyse HMPAO-SPECT only. The preliminary results achieved are presented, analysed and confronted to clinical, EEG and MRI or CT data.

In conclusion, this surgical model provides a semiquantitative assessment of the grade and the extent of the focus directly analysable by the surgeon itself. 

A series of 3~-aryltropane-2~-carboxylic ester analogs and their N-substituted derivatives displayed high binding affinity to the cocaine recognition sites. Here we report the potential utility of this series of compounds for imaging presynaptic dopamine terminals with positron tomography. The in vivo pharmacnkinetics of these probes in monkeys showed that several minutes after I.V. administration, the brain activity increased in the candate-pumman region while decreasing in other brain regions. The binding became prominent in the caudate-putaman area and remained stable for the 90 minutes of the imaging study. The striatal:cerebellar ratio was increased to over 4: i for art compounds. The dopamine uptake blockers mazindol, cocaine and GBR reduced the caudate-putamen activity following their administration. The serotonin specific ligand citalopram did not change the striatal activity. The order of selectivity and affinity for the presynaptic sites was found to be [C The presence of Somatostatin Receptors (SR) on tumors in ZES may have diagnostic and therapeutic implications. Non invasive assesment of tumoral extension with a labelled somatostatin analogue was compared with CT, MR and endoscopic data. 13 patients (pts) with proven ZES were studied after injection of 120 MBq Octreotide. 4, 24 and 48H planar images were analyzed visually by 2 observers, blinded from radiological results. SPECT was performed in case of abnormal scans. CT, MR and echo-endoscopy allowed the detection of 21 tumors in 12/13 pts: liver (n=5), pancreas (n=9), colon (n=l), bone (n=l), duodenum (n=l), stomach (n=l), adrenals (n=l), chest (n=2). Scintigraphy was abnormal in 10/13 pts, one of whom was free of tumors by other techniques. Scintigraphy allowed the detection of 22 tumoral locations. 3 tumors were missed by scintigraphy (a 4mm-diameter duodenal gastrinoma a pancreatic gastrinoma and a lung metastase). In contrast, scintigraphy showed 4 previously unknown tumors: mediastinum (n=2), pelvis (n=l), neck (n=l). 24H images demonstrated both optimal signal to noise ratio and tracer uptake. SPECT contribution to hot spots localization was poor.

Conclusions: 1/Somatostatin receptor imaging provides sensitive additional informations concerning tumoral extension in ZES 2/Scintigraphy may be negative (14% in our short serie) 3/A simplified procedure is possible with a single 24H planar imaging.

Irene Virqolini 1,2 Q.Yang I, S.R.Li I, E.Koller I, P.Valent 3, N.Neuhold% P.Angelberger 5, and H.Sinzinger 1,2

Dept. of INuclear Medicine, University of Vienna and 2Ludwig Boltzmann Institute for Nuclear Medicine, Vienna, Austria.

Epidermal growth factor (EGF) is a polypeptide that is involved in normal cell growth, but acts also as a mltogen for human breast cancer cells. The mature cell membrane receptor (R) for EGF has been identified in breast cancer cell lines and in primary breast cancer. EGF-R expression has been proposed to be a highly significant marker of poor prognosis (early recurrence and death), useful as an indicator of how a patient will respond to endocrine therapy after relapse. We have evaluated the binding of a • 123 synthetzc I-labeled monoclonal antibody (Mab) directed against the extracellular domain of the human EGF-R to primary human breast cancer (n=lS) and to the human epidermoid carcinoma cell line A431. EGF-R-Mab was purified from ascites fluid by affinity chromatography on protein A sepharose and showed thereafter on SDS-PAGE a single band resolving at 12~ molecular weight of 155 kD. On gradient gel PAGE I-EGF-R-Mab, labeled to a specific activity of 250 pg protein (i.e.l.6 nmol)/mci, displayed identical bands (silver staining) as compared to unlabeled EGF-R-Mab. Both primary human breast t~o r membrane f~naC tions as well as A431 cells bound I-EGF-R-Mab ~ specific manner suggesting high affinity ligand binding. The respective binding data were a binding capacity of 14.3±6.9 gg protein/mg protein (Kd=7.2±3.3 gg protein/ml) for the cell line and of 0-500 pg protein/mg protein (K~= i0-i00 gg protein/ml) for primary breast cancer. 123I-EG~-R-Mab inhibited binding of 1231-EGF to A431 cells in a competitive manner, whereas EG~2~s well as the synthetic EGF-peptide showed no effect on I-EGF-R-Mab binding. The binding of 123I-EGF-R-Mab to normal human b~east cancer membrane fractions as well as to various other t~s u e s was only minimal or negative suggesting that this I-EGF-R-Mab preparation is worth to be tested in human in vivo for detection of human breast tumors and/or metastasis.

G. Berdin,q, K.F. Gratz, H. Kolbe, H. Hundeshagen Abteilungen f~ir Nuklearmedizin und Neurologie; Medizinische Hochschule Hannover; Germany

In this study of dopamine D-2 receptor imaging with (I-123) IBZM (iodobenzamide) SPECT the influence of attenuation and scatter correction on semiquantification and results in patients with movement disorders were investigated.

SPECT was performed in 3 patients with idiopathic Parkinson's disease (IP), 6 with Parkinson's syndrom of other aetiology (PS) and 5 patients with dystonia (DY). Data acquisition was started one hour after i.v. injection of 185 MBq (I-123) IBZM, collecting 64 frames of 50 sac each during a 360 degree rotation. Projections were smoothed with a Metz prefilter and reconstructed with a ramp filter into a 64 x 64 matrix. ROl's were drawn over striatum (ST) and frontal cortex (FC) and ratios ST/FC calculated. Each SPECT study was evaluated with and without correction for Compton scatter (dual-energy window technique) as well as attenuation.

Compared to studies without attenuation and scatter correction ST/FC ratios were significantly higer if scatter correction was applied (1,36 vs. 1,27; p<0,0005) and increased significantly if attenuation correction was performed additionally (1,50 vs. 1,36; p<0,0005). Using both corrections mean ST/FC ratios were 1,48 in DY, 1,48 in PS and 1,58 in PD. In two patients ST/FC ratios were more than 20% lower on one side as compared to the other and clinical symptoms appeared predominantly centralateral. In one patient who developed PS during treatment with methyl dopa ST/FC ratio increased more than 20% after withdrawal of methyl dopa.

It is concluded that: 1 .) correction for scatter and attenuation improves semiquantification of (t-123) IBZM SPECT significantly; 2.) probably (I-123) IBZM SPECT can demonstrate postsynaptic disturbance of dopaminergic transmission in the striatum of patients with movement disorders.

K. Scheidhauer 1 , (3. Hildebrand 2, C.Luyken 2, K. Schom~cker 1 , B. AIIolio 3, P.Theissen I , E. Voth 1 , H.Schicha 1 Depts. of Nuclear Medicine (1), Neumsurgery (2) and Endocrinology (3), University of Cologne, FR (3ermany

Pituitary tumors as well as meningiomas are known to have somatostatin receptors. Although both tumor entities are benign and non-metastasizing, surgical therapy is often difficult and relapses may occur. A second surgery at the base of the skull, however, is risky due to the narrow relationship of brain-structures. Knowledge of the somatostatin receptor status could offer a new perspective in diagnostics and pharmacological therapy with somatostatin-analogues.

We report the use of In-111 -Pentatreotide, a somatostatin analogue, as a scintigraphic imaging agent in 11 patients with recurrent tumors; tumor size ranged from 2 cm to 4 cm in diameter. (ongoing study): 3 -6 hrs and 24 hrs after iv-injection of 111 MBq, resp. 10 ug In-111 -Pentatreotide, scintigraphic images were acquired including planar images of the head in 4 views, and tomographic images (SPECT). Tumor localization was not known before image interpretation. All tumors were surgically and histologically proven and studied by conventional imaging techniques (CT and MR).

Six patients had recurrent meningioma of the base of the skull and showed positive scintigraphy with high activity uptake. Five patients had recurrent pituitary adenomas. Two of these tumors had a high uptake, one a moderate uptake and two showed no uptake.

All positive tumors could be seen already by planar scintigraphy, SPECT did not improve sensitivity, but did provide better information about anatomical localization and tumor extension and showed a higher tumodbackground-ratio.

These results indicate, that In-111 -Pentatreotide may provide a suitable in rive imaging test for receptor presence and therefore may facilitate new therapeutic approaches by therapy with somatostatinanalogues in non-operable meningiomas and pituitary adenomas. 1-123-IBZM is a highly selective ligand for the D2-dopamine receptor, to which most of the typical neuroleptics are known to bind. According to in vitro studies, atypical neuroleptics occupy D2-receptors to a lesser extent. By means of the IBZM-SPECT technique it is possible to obtain in vivo data about the amount of non-bound D2-receptors (predominantly in the striatum) in schizophrenic patients. In order to understand whether the antipsychotic effect of the neuroleptics is correlated with the affinity to the D2-receptor, we compared the D2-binding results of typical with those of atypical neuroleptics. In patients on typical neuroleptics (n = 11) such as haloperidol, the D2receptors could not be visualized as clearly as in drug-flee patients, presumably because they were already occupied by the typical neuroleptic. In patients receiving an atypical neuroleptic such as clozapine, the D2-receptors could be better demonstrated by the IBZM-SPECT. In conclusion, our data suggest that the antipsychotic effect of typical and atypical neuroleptics may not be closely related to the binding to the D2-dopamine receptor. A variety of linear and macrocyclic N-containing ligzinds and derivatives of ethylene diamine have been described the last ten years as potential 99mTc-complexing agents with the view to develop new radiopharmaceuticals. At this time, only 99mTc-l, has been evaluated in humans. However, it was not reported which isomer of CYC was used. Therefore we have investigated the labelling characteristics and biological behaviour in mice of the 3 isomers of CYC: the cisisomer, which is the meso compound (D and both trans-isomers 1R, 2R(+) or I] and 1S, 2S (-) or lIl. The isomers were commercially available.

An optimal labelling efficiency was achieved for all isomers in a 0.05M phosphate buffer pH 10 using 1 mg ligand and 100#g SnC12.2H20. The radiochemical purity, checked by paper chromatography with acetone and saline, was usually higher than 95%. An HPLC-system was developed consisting of a PRP-1 stationary phase eluted with gradient mixtures of acetone or ethanol and a 0.0125M NaOH/KC1 sointton pH 12.4. The electrophoretograms indicated a positive charge on all the complexes. In mice, the amount excreted in the urine, expressed as % of 13tI-OIH excretion, was at 10 rain p.i. 44% for !, 45% for I] and 53.9% for Ill whereas at 30 rain p.i. these values were respectively 61%, 65% and 71%. Plasma protein binding, determined by ultrafiltration, was very low (20% for I; < 6% for --a n d S . The results reveal that the biological behaviour of the 3 99mTclabelled isomers is different. However, their renal handling in mice is rather poor. Further investigation in the baboon will be necessary to elucidate their potential clinical usefulness. The kit should be prepared quickly in order to protect staff from radiation. But the addition of In-Ill is strictly limited by the producer ( . The purpose of this study is (1) to determine the radiochemical yield/purity by addition of different In-lll activities, (2) to examine possible losses on filter and (3) to test the in vitro stability of this linker-chelator complex. The in buffer pH 6 is added to the antibody. After a reaction time of 30 min at room temperature the mixture is steril filtrated with a 0.22 p.m filter. Quality control is done by thin layer chromatography and high pressure liquid chromatography (using a gel filtration column).

(1) The following table shows the radiochemical purity by different amounts of the In-111 solution: radiochem, purityIMBq] 222 99.5 259 98.7 296 92.1

(2) The filter loss is 6.9 -10.0 %. The aim of this study is the synthesis of a Tc-99m cation complex called Q-12, [99mTcllI (MP -1549 ) (TMPP)2] + where MP-1549 is a tetradentate Schiff base N,N 2, 4, ethylenediamine and TMPP is tfis (3-methoxypropylphosphine) . These kinds of [99mTclII(L)(X)2]+ complexes are usually prepared in a two step procedure. Pertechnetate is fast reduced at high temperature by stannous chloride in alkaline medium in the presence of Schiff-base ligand L. The intermediate formed incorporates a TcVO core and a doubly deprotonated L ligand anion. In the second step, the intermediate reacts with the excess phosphine X, acting as both reductant and ligand to give the desired Q product. The reaction course is monitored by HPLC with g ray flow detector. The product cannot be administered into humans at this stage. First, all reagents in excess, particularly phosphine must be removed, and the radiopharmaceutical prepared in physiological saline, should contain less than 10% ethanol. To achieve this, a purification procedure, involving C-18 Sep-pak cartridge, has been developed. The pure radiopharmaceutical is finally eluted with 80% ethanol-normal saline; the eluent must be diluted with normal saline to an ethanol content of below 10%, and filtered trough a sterile 0.21.tm filter The Q-12 agent showed both a very rapid liver and renal clearance (estimated 25% of the injected dose cleared through the kidneys). This is a very advantageous feature for a potential heart perfusion agent. As the myocardial uptake of Q-12 is more than 2% of the injected dose, lung uptake negligible, and blood clearance very fast, good images can be obtained as soon as 30 min. after injection.

The ligands were labelled by direct labelling at pH 12 (room temperature) and analyzed by RP-HPLC. Labelling of lrl with Tc-99m yields a single peak while the complexes of Tc-99m with IV and V appear on HPLC as two peaks, probably the two dlastereomers. After isolation they convert rapidly to each other. Retention time rises with increasing lipophilicity.

In mice all complexes show rapid clearance from the blood by the renal and the hepatobiliary system. Hepatobiliary uptake and transit to the intestines is more pronounced as lipophilicity increases.

In the baboon, III is cleared from the blood without important liver uptake. The 1-hr plasma clearance of III (39% of OIHclearance) is comparable with that of G4 (42% of OIH clearance) but lower than the clearance of the 99~q~c-complexes with (L)-I, (D)q, and II (respectively 54%, 60% and 74% of the OIH clearance). The results yield valuable information to elucidate the way of interaction of 99~q"c MAG3 and its derivatives with the tubular receptor proteins.

S. Mastrostamatis, M. Papadopoulos, A. Varvarigou and Eo Chiotellis. Radiopharmaceuticals Lab., NCSR "Demokritos" ~5310, Aghia Paraskevi Attikis, GREECE.

We have reported previously the synthesis and characterization, at Tc-carrier level, of new neutral technitium(V) complexes of the general structure TcO(Lz)CI where Lz: tripodal ligand. In the present study mixed ligand complexes of NS~ or N~S~ tripodal and a monodentate thiol ligand with TcO ~+ core were synthesized. The following ligands were used for the synthesis of the complexes: L~=X(CH~)~N(CH~CH~SH)~ and L~=p-MeOC~H,SH, where X=EtS(a), Et~B(b). 99 Sodium gluconate and TcO~reacted with SnCI~ to form Tc(V)gluconate complex in solution. Equimolar quantities of ligands Lz (a or b) and L~ was added in acetone. The complexes formed, were exctracted with CH~CI~ and isolated as brown crystalls. Elemental analysis showed that structure corresponds to the general formula TcO(Lz)L~. Elemental analysis, IR and UV-Vis data are given below. HPLC analysis performed on C-18 column resulted single peak elution patterns.

TcO ( To investigate the structural requirements, for an optimal handling of Tc-99m MAG3 (I: A_=D=CO) and related compounds by the tubular transport proteins, we have now synthesized and studied 3 derivatives of I with modifications in one or two of the amide bonds: (II: ~=D=CO; llI: _A=_E=CO; IV: _B=_E=CO).

A, _B_, D, _E = CH 2 unless otherwise specified Reaction products after exchange labeling of the S-benzyl protected precursors contained mainly 1 radioactive species that was isolated by RP-HPLC and studied in mice (table, % of I.D.). Compared to I, renal excretion characteristics of 1 , are superior as shown by higher activity in urine and lower uptake and retention in kidneys, liver and intestines. H shows higher hepatobiliary excretion and IV is cleared less efficiently from the blood. The first results of studies in the baboon indicate large inter-species differences with regard to renal handling of I to IV. rain p. Previously it was shown that mouse moncclonal antibody (MoAb) to anglotensln-convertlng enzyme (ACE), named 9B9, radiolabeled 5y 1-125, accumulates specifically in the lung of rat, hamster, cat, monkey and human. It is allows to obtain the images of lthng by gam/na-scintigraphy. Furthermore, we have demonstrated that MoAb 9B9 lung accumulation is a very sensitive marker of lung vessel l~njury.

The aim of this' study was to investigate the phenomena of specific lung accumulation of MoAb 9B9 in different species.

We estimated the specificity and efficiency of lung accumulation of radiolabeled MoAb 9B9 in rat, hamster, cat and guinea pig after intravenous injections and compared these parameters with a) carefully estimated ACE concentrations in the blood and lung of above-mentioned animals and also monkeys (Macaca and marmoset) and human, b) binding affinity of MoAb 9B9 with ACE from blood and lung of all studied species, c) lung and blood weight/body weight ratios.

This approach allows to evaluate the specificity and effeciency of radiolabeled MoAb 9B9 lung accumulation in vivo in monkey and human from the data obtained in vitro.

We conclude that the values of the specificity and efficiency of MoAb 9B9 lung accumulation in different species determined mainl~ by lung ACE concentrations and binding affinities of MoAb 9B9 to ACE from these species.

optimal hydration and fu~osemide during renography, it remains difficult to differentiate the patient with urinary tract obstruction from the patient with only a dilated pyelum without obstruction.

pyelum may give additional information.

Eight patients suspect fo~ urinary tract obstruction underwent renography with W~Tc-MAG3. Acquisition was performed posteriorly during 20 min with the patient in the supine position (matrix 64x64, 15 sec frames). For background correction a region was drawn between the kidneys. A region including the whole kidney, a small region over the cortex and one within the pyelum were used for analysis.

Of these 8 patients, retrospectively, 5 patients had whole kidney renographic findings concordant to obstruction or to only a dilated pyelum. In these patients the cortical region curve did not change the conclusion as obtained with routine renography. However, in 3 of these 8 patients routine whole kidney renography could not exclude a partial obstruction, despite furosemide i.v. The pyelum curve did not give additional information. The cortical curve, however, showed a normal peak, indicating only a dilated pyelum without obstruction.

Follow-up of these 3 patients confirmed these observations.

A separate region over the cortex may differentiate patients with urinary tract obstruction from patients with only a dilated pyelum.

Further prospective studies are warranted. Personnel radiation doses in nuclear medicine laboratory is caused by radioactive material and patients who have received radioactive substances.

A minor dose is caused by handling of radioactive waste.

We have studied radiation level in different places (hot lab, gamma-camera rooms etc.) and in different working conditions (preparing radiopharmaceuticals, during scan etc.) in order to minimize the personnel external radiation dose.

Measurements were done with a small portable radiation monitor (RM-60, Aware Electronics, USA) calibrated with a standard reference source. Data from radiation monitor were stored into a personal computer and were evaluated afterwards.

Our results indicate that there are only a few places and conditions which caused the extra personnel external radiation dose. We have also determined the "standard radiation level" in every room of our department in order to follow possible changes in the radiation level.

In conclusion the personnel external radiation dose can be minimized after finding out the places and conditions where the radiation level is significantly above the average.

The computerized portable radiation monitor helps out to control the variation of radiation level.

Microbiology* and Patholog~ 4" Departments, School of Medicine

Captopril Double-Isotopes Renography (CDIR) in Renal Artery Stenosis (RAS): The Influence of Exclusion Criteria on the Detectability of RAS

Not included are petients with obstruction in the udnary flow or patients with hypertensitive crisis after the stop of medication. The patients were referred to the clinic to clarify their hypertension: onset of hypertension or persisting hypertension under antihypertensive drug treatment. 11/26 patients had unilateral RAS > 50% (9 RAS >75% and <95%), proven by renal artedography ($eldingar's technique) within 1 weak after the CDIR. 18 MBq 1-131-hippurate arid 74 MBq Tc-99m-DTPA simultaneously, native scan and 1 hour after 25 mg Captopril orally, without hydration before the scan, stop of anti-hypertensitive drugs for 1

Exclusion criteria: renal insufficience with creatinine > 0.2 mMol/I, double renal arteries, renal duplication, relative renal uptake < 21%, pelvic kidney. RESULT: 4/26 fulfilled exclusion criteria, these 4 pats. had RAS (3/4 age >60 years). From the remaining 22 pats., 5 of 7 RAS-pats. were detected by CDIR: Sn=71%, 14 of 15 pats. without RAS had normal scans: Sp=93%. The inclusion of the excluded patients results in a diminution of

The Captopril ranography in our institution has the same Sensitiv~ and specifity like others [1]. The Captopril renography is in 36% of our pats. undecidable by reason of renal insufficiency, shrinkage or anomaly of the vascular supply

Gia~usso chair of Gerontology and Geriatrics * Chair of Urology ** Chair of Medical Physiopathology University of Catania -Italy INTP~kCAVERNOUS TECHNETI

Departments of Radiotherapy and Nuclear Medicine, *Pediatrics, -Semeiotica Medica, General Hospitul of

High prevalence of thyroid abnormalities in DP has been reported in literature. Little is known on oethiologie faetom involved. To this purpose, a prospective study on 300 DP is in progress. There were 166 males

88 subclinical hypothyroid (S. HYPOT), i.e. with normal thyroid hormones but elevated TSH levels. ATA were positive in 18% of cases and, in particular, in all DP with HYPERT or O. HYPOT,whereas in 17% of EUT and 16% of S.HYPOT patients. During the follow-up (6-24 mths) a w/de range of thyroid function variation was observed. R~garding DP initially EUT: 79% remained EUT, 13% became S. HYPOT, 8% became HYPERT. Regarding DP initially S. HYPOT: 50% remained S. HYPOT, 6% became O. HYPOT, 2% became HYPERT, 42% he.came EUT (TSH spontaneously decreased to normal range)

E~ndh~ver~ The ~etherlands LC~G-TERM UPREGULATION OF DOPAMINE D2-RECEPTORS IN A

The Johns Hopkins Medical Instutions Baltimore

COMPLEXES OF Tc-99m WITH AMINOISOBUTYRYL-, VALYL-AND LEUCYLTRIGLYCINE In view of the interesting biological properties of some Cmethyl derivatives of 99mTc-tetraglycine (e.g. R=Me, I, 'L or D) and of gem-dimethyl derivatives of 99mTc MAG3 (e.g. R=R' =Me, H) we have now studied the complexes of ~mTc with the tetrapeptides aminoisobutyryltriglycine

Plesmanlaan 121, 1066 CX Amsterdam. The Netherlands T}~ USE OI ~ t3PE COMPAI£ED TO [.PLC Pi]R .[~ DEI]Ib'MIN~IDJN OF [I-ISI]IODIDE IN I)dEUSION FLUIDS OF [I-i31]MI~ minicolumn method. The method, based on solid phase extraction (SPE), has been compared to HPLC with online rad~odetection. Procedure: i) A sample of the [I-ISI]MIBG infusion fluid, diluted with a solution of 5 mM hexanesulfonic acid pH 2.5 (called }{EX), is counted in a Nal solid scintillation well c~/stal, ll]is is 100% (called A). 2) A Sep~-Pak C18 cartridge is activated with methanol

HEX 2x ar~ water] are soul,ted. The sum of these four countings -related to A -is the percentage of free [I-i31]iodide. 4) Another th~-ee eluates feluent: acetonitrile) and the cartridge itself ea-e counted. The sum of the acetonitr~le + cartridge cot~tir_~s -related to A -con-esponds to unaltered

Linear regression of the percentage of free [I-131] iodide by SPE (dependent variable) and I-~LC (independent) resulted in the following equation

The long time interval needed between MoAb injection and surgery (at least 20 days) is one of the limits of intraoperative tumor detection with radiolabeled monoclonal antibody (MoAb) by means of a probe. It has been recently reported that avidin ~fficiently removes biotinylated MoAbs from the blood in animal model systems. We report our experience with 20 colon cancer patients operated on approximately of 7 days after i.v. injection of 1 mg of 125-I labeled biotinylated MoAbs (B72.3 or anti CEA FO23C5) followed by an equimolar amount of cold avidin 2 days later. Blood samples and external probe counts were taken to evaluate blood clearance of the radiotracer. A decrease of 94% (range 76-99%) of the circulating radioactivity was achieved in 3 to 5 days.Tumors were localized by probe in 13/20 patients (65%), with an average T/nT ratio of 2.8 (range. 1. .0).Immunohistochemical analysis showed that antigen was expressed in 15/20 patients. Five patients (25%) were true negatives and two (10%) false negatives; none was false positive. With the use of 125I-biotinylated MoAbs followed by avidin the surgeon was able to operate these patients with minimal bloodpool activity within 7 days, (range [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] rather than 20-25 days,identifying subclinical deposits of tumor in 2 cases of primary cancer and in 1 case of local recurrences. (pts) with advanced stage at diagnosis show a poorer prognosis. Fortunately, this is not a frequent condition and, as a consequence, poor data have been reported on prognostic factors in these pts. To better define these aspects, we evaluated a group of 214 pts with distant metastases from TC. There were 141 females, 73 males; 100 had papillary (PC) and 114 follicular (FC) cancer. Mean age was 44 yrs for PC-and 53 yrs for pts had metastases to lung, 76 to bones, 46 to medistinum. All pts underwent total thyroidectomy, 131I therapy and then were treated with L-thyroxine. In some cases with low 131I uptake (RIU) by metastatic tissue (less than .01% of administered dose) or with disease progression despite 131I, external radiotherapy (48 cases) and/or chemotherapy (34 cases) ff~re performed. Follow-up ranged from 5 to 25 yrs, mean 7.3 yrs. During the follow-up~ clinical, echographic, radiological, scintigraphic and thyroglobulin survey was made. Prognostic factors were studied by univariate analysis (log-rank test) and multivariate analysis ( Cox-model) . Chi-square test was used to compare frequencies and Kaplan-Meier method to calculate survival curves. Univarfate analysis showed that survival was influenced by age, histology, RIU and site of metastases (p < .0001). However, a closed inter-relationship was found among these factors. Multivariate analysis defined as significant and independent prognostic factors age (p < .0001), R1U (p = .001) and site of metastases (p ~-.002), but not histology. The worst prognosis was found in pts older than 60 yrs, with bone metastases or metastases with low RIU (10-yr survival rate < 10%). The best prognosis was found in young people with lung or mediastinal metastases and with high RIU (10-yr survival rate = 100%). Sex was not.proven to represent an important prognostic factor in our series.

L. Sd --gldv Twelve patients with MTC after thyroidectomy underwent 2~Kj/kg/min calciumgluconate (Spts) or O.Sug/kg/min pentagastrin (7 pts)infuslons tests.370 MBq of Tc-ggm (V) DMSA was injected at the 6th mln of calciumgluconate and pentagastrin infusion. Serum calcitonin and calcium levels were determined before and I, 2, 3, 5 and 10 min after each infusion. Anterior images of the neck and upper chest were obtained one week before and at 15, 30, 60 and 120 min after the infusions. Prior to and after the infusions the regions of interest were generated over the thyroldal region, metastatic sites of MTC and blood pool of the heart. The average count ratio of these ROI's to the background before and after the infusion were compared,The result of this study suggests that the uptake of Tc-ggm(V) DMSA is reduced in the metastatic sites of MTC and confined to the blood pool after the infusion of Ca-gluconate. On the other hand, no effect of pentagastrin was detected on the uptake of Tc-ggm(V) DMSA. Although both infusions increase the serum calcitonin and calcium levels, the level of calcium is higher in calcium infusions than pentagastrin infusion. We belleve that the uptake of Tc-99m(V) DMSA in the metastatic MIC is marked]y influenced by serum calcium levels.

H__. Si~zinger, W. Stackl, Irene Virgolini, J.. H6bart, S u s a n n e G r a n e g g e r Dept. N u c l e a r Medicine, U n i v e r s i t y of Vienna, A u s t r i aR a d i o l i g a n d studies reveal that the a m o u n t of high a f f i n i t y b i n d i n g sites for p r o s t a g l a n d i n e r e c t i l e response. The u n d e r l y i n g mechanism, however, remains to be established.

A.FRANCOIS-JOUBERT*, L. TASSI***,A. GASZNER**, A. JOANNAPdg* *, P. KAHANE* **, C. M~JNARI *** • Service de M~decine Nucl~aire -** Service de P~diatrie -F o c a l i n c r e a s e d s i g n a l h a s b e e n r e p o r t e d in 2 a d u l t p a t i e n t s w i t h e p i l e p s i a p a r t i a l i s c o n t i n u a (EPC) by i c t a l S P E C T w h i l e E E G f a i l e s to s h o w e p i l e p t i c c h a n g e s . H o w e v e r , t h e y w e r e w i t h o u t a n y a n t i e p i l e p t i c a l t r e a t m e n t . In t h i s w o r k we p r e s e n t a n e w c a s e ( a r t e r i o g r a p h y ) , r i g h t a n t e r i o r f r o n t a l a n d t e m p o r a l e n h a n c i n g l e s i o n (MRI), r i g h t a n t e r i o r f r o n t a l h y p o p e r f u s i o n a n d 

The nigrostriatal dopamine ne..urotoxin l-methy_l-4-. pheny~-l~2, 3, 6-tetr~ y~. yr.id/ne IMPTP) has been. use(1 in primate models oz ~_emi~rkinsonlsr~ Ex vivo au~o-.radiogr@p.hy with .the~ dol~_'ne.D2~receptor ~ag..t..a.gonis~t [ • =sI ]-(~) -(-) - 2 -hydrox~-3 -i ooo-~ -methoxy-N [ ( 1-ethyl-2-pyr~o_ lidinyl ) .methyl ] -I~.nzamide (~asI-IBZM) sh .o~e~ I-2 months after r_ne i.v. injection of MPTP in a rnesus monkev(Macaca mulatta) a 10-50 % increase of the density of dop~mi_ 'he D2-receptors 

We submitted 30 mechanically ventilated pts in state of coma (GCS <7) ~o 133Xenon dynamic SPET (DSPET) using in We conclude that the quantitation of CBF by 133Xe DSPET using and expecially the derived determination of CMR02 are capable to accurately predict the severe or favourable prognosis of comatose patients;the procedure employed using CERTO-96 resulted easy and cost effective. Wilson's disease is a rare familial disorder, inherited as an autosomal trait and characterized by excessive deposition of copper, especially in the liver and brain. Early treatment is essential for removal of copper before it can produce neurologic and hepatic damage. We applied Tc-99m HMPAO brain perfusion SPECT to 9 individuals of 3 families (8 men and I woman) having at least an individual with proven Wilson's disease in the family, for the early diagnosis of central nervous system involvement. We compared the SPECT findings with computerized tomography (CT). In two male individuals of a family, (one symptomatic and the other asymptomatic) we detected a hypoperfused region in the left frontoparietal cerebral cortex. CT of the neurologically symptomatic individual was abnormal and supported the scintigraphic findings, however; asymptomatic individual's CT was normal. SPECT and CT findings of the remaining 7 individuals were interpreted as normal. We believe that Tc-99m HMPAO brain perfusion SPECT is a useful tool for the early determination of brain involvement in patients with wilson's disease before the copper accumulation becomes sufficient to destroy the nerve cells. Since the disease is potentially reversible, appropriate therapy will prevent brain damage. This is a preliminary report and we think that a greater population having Wilson's disease should be investigated.

Dabasi HHRAO SPECT studies were carried ou± in 50 patients with Rarkinson's disease/PD/,comparing with MRI in all of the cases. The distribution of the patients according to the stages of Hoehn and Yahr was the following I:7, II:12, III:21, IV: i0. 18 patients showed clinical signs of dementia /PDD/ confirmed by psychological examinations. In early phase of RD/StI-II/ hypoperfusion of the bas~ganglia was observed in 6/19 of the cases, while HRI showed no morphological changes. In the late phase of PD/StIII-IV! hypoperfusion of the basal ganglia was found in 7/51 of the cases. Using HRI the presence o3 iron deposit was a common feature in these patients. Decreased bi-or unilateral temporo-parieto-occipital activity was observed in 16 patients, l& of them belonged to the PDD type. Summarizing our ~indings: -The hypoperfusion of ~he basal ganglia shows no correlation with the severity and duration of the disease -The posterior type of cortical hypoperfusion is nearly always present in ROD pa¢ien±s.

DC COSTA, J BROSTOFF, V DOULI and PJ ELL. Institute of Nuclear Medicine and Department of Immunology, UCMSM, London, UK.This study was designed to investigate possible changes in the brain perfusion (rCBF) of patients with Myalgic Encephalomyelitis -Chronic Fatigue Syndrome (ME-CFS), often related to depression.14 ME-CFS patients (age range 17 -51; 6 males and 8 females) had rCBF/SPECT with Tc-99m-HMPAO (550 MBq) and the GE/CGR Neurocam. Quantitative analysis (cerebrum over visual cortex ratios) was carried out comparing data from ME-CFS patients with 24 young, age matched normal volunteers (CONTROL). In addition, 9 old age normal volunteers (age range 71 -79) and 9 old age chronic depression patients (age range 69 -89) were studied, ME-CFS patients showed generalised lower brain perfusion than age matched controls. The most striking and statistically significant abnormalities were found in the following structures: Structure CF$-ME CONTROL p brain stem 0.75+0.05 0. p=0.006 Brain stem perfusion in the old age depressed group (0.85_+0.07) was higher (p=0.001) than ME-CFS patients.In conclusion these data support the evidence that patients with ME-CFS have lower rCBF than normals. They demonstrate, for the first time, hypoperfusion of the brain stem. This finding was not encountered in our cohort of patients with depression. The mesial temporal lobe is involved in the generation and propagation of complex partial seizures in humans.

The neurochemical mechanisms are poorly understood.We have evaluated whether m-AChR and blood flow are altered in the hippocampus and the amygdala in complex partial seizures.Four patients and two normal controls were investigated.The epileptic focus was left-sided as identified by 24 hour-a-day video-scalp-EEG monitoring.SPECT data were recorded interictally (NeuroSPECT, Bitatchi). m-AChR were assessed using 1-123 iododexetimide , and blood flow with Tc-99m HMPAO.Anatomical information was provided by MRI.Regions of interest were drawn on MRI images and transferred onto the co-registered sPBCT images.Data are given as left-to-right ratio of the mean count rate (R). In all four patients, 1-123 IDex to m-AChR was decreased in the anterior hippocampus on the side of the electric abnormality. The hippocampal left-to-right ratio for 1-123 IDex binding was 0.82 + 0.06 (mean ~ SD).There was no asymraetry in 1-123 IDNx binding in amygdala (R=1.02 ~ 0.06).Hippocampal perfusion in patients was syrametric (R=0.97 ~ 0.07).The controls showed no asymmetry in hippocampal 1-123 IDex binding (R=0.99 and 1.00).The results suggest specific changes of hippocampal m-AChR in partial complex epilepsy.The changes may be due to hippocampal cell loss or downregulation of m-AChR secondary to an increase in concentration of e n d o g e n o u s a c e t y l c h o l i n e , a c o n v u l s a n t neurotransmitter. The aim of our study was to investigate the influence of benzodiazepine medication on 1-123-iomazenil (8-defluoro-7-iodo-flumazenil) binding, which has been shown to be a very potent antagonist of central benzodiazepine receptors. 28 studies were performed on 12 benzodiazepine Ireated psychiatric patients, 9 patients after withdrawn of benzodiazepine medication and as control 7 patients without any benzodiazepine treatment. SPECT (double head camera) imaging was performed 10 min and 100 min after application of 200 MBq 1-123 iomazenil. For semiquantitative evaluation of the SPECT images regions of interest which follow anatomical structures of the brain were used. According to PET experiences the specific binding was defined as average counts/pixel in a cortical region minus average counts per pixel in the pons (100 rain p.i.). Results: The specific binding in benzodiazepine treated patients was reduced between 20-80% compared to benzodiazepine free patients. Moreover, benzodiazepine treated patients showed a more rapid wash out. After benzodiazepine withdrawal the activity distribution was found normalized. In conclusion, 1-123 iomazenil can be used to image and to quantify benzodiazepine receptor occupancy by SPECT in humans in relation to different benzodiazepines.

V Ivan~evi~, C Nauck t, D Sandrock, A K6gler, DL Munz, W Creutzfeldt t, D Emrich Department of Nuclear Medicine and tDepartment of Medicine, Georg-August-University, G6ttingen, Germany

mIn-pentatreotide has been reported to detect somatostatin receptor positive GEP. We examined 24 patients suffering from GEP (predominantly carcinoids, N=15) in whom active disease was established by imaging/invasive procedures (N=6), hormone levels (N=2), or both (N=I6). Single and multiple liver metastases were counted as one. A total of 50 loci was thus verified. Scintigraphy (planar and SPECT) was performed N verified loci 19 18 3 9 focus in the skull firstly detected by pentatreotide scintiqraphy proved to be a meningeoma. Critical analysis of the raise positive and false negative ratios turned out in tavoar of pentatreotide. There is little difference between the results after 4 and 24 h but sensitivity for bone metastases seems to be improved by 24 h-images. in conclusion, mln-pentatreotide is useful in detecting somatostatin receptor positive GEP/metastases. It could have an impact on therapy planning. In this study we concentrate on 2 of them that can be directly tested by muscarinic receptor imaging. One hypothesis is based on the observation that THA at clinical concentrations blocks a substantial amount of muscarinic receptors in animals. A second hypothesis is derived from animal studies that demonstrated significant down-regulation of muscarinic receptors after continued administration of cholinesterase inhibitors. The purpose of this study was to investigate these effects in human subjects after administration of THA. For this purpose quantitative muscarinic receptor imaging was performed in 7 Alzheimer's patients with positron emission tomography (PET) and [11C]tropanyl benzilate (TRB). The subjects were scanned before and 1 week after administration of THA (n=4) or placebo (n=3). The resuhs show an unchanged free muscarinic receptor density in all examined regions (thalamus, striatum and caudate). It is likely that down-regulation would have occured in regions with a high density of cholinergic neurons and receptors (striatum, caudate). Down-regulation was looked for in the thalamus which has many receptors but few cholinergic neurons. We conclude that the disappointing results of THA treatment in Alzheimer patients are not explained by receptor blockage or down-reguIation. Since 1982, the long-acting somatostatin analogue octreotide is available as a therapeutic agent for neuroendocrine somatostatinreceptor positive tumors. For diagnostic purposes, the [123-I-TyrOloctreotide has recently been developed. In preliminary studies with this agent, various tumors with somatostatin receptors were detectable. Due to some limitations of 1-123, the Indium-111 labeled agent [In-111 -DTPA-Phe~]-octreotide has also been developed (Mallinckrodt Inc., Petten, The Netherlands). The in vitro and in vivo binding properties of this new agent have been established and it is currently being investigated in a phase III clinical trial. We report the first results with this agent obtained in two children (2.5 and 8 years old) with stage IV neuroblastoma. Both patients were on chemotherapy during the study. Each child was injected with 30 MBq octreotide. The pre-tested labeling efficiencies were 97.5% and 99.5%. Whole body scans were conducted at 4 and 24 hours p.i. and the results were compared with other imaging modalities and with 1-123-MIBG scans which were performed within 1 week in both patients. In one pat. the IN-OCT showed neuroblastoma lesions (skull, liver, bone) with better image quality than 1-123-MIBG, and showed additionally two bone lesions. The other patient showed an overall weak IN-OCT uptake in a mediastinal lesion which was clearly visualized by 1-123-MIBG, and an MIBG-positive abdominal lesion was completely missed with IN-OCT. Since a close relationship between scan results and presence of receptors can be assumed from in vitro studies, these discrepant preiiminar~ in vivo findings may indicate that the investigated neuroblastomas may have different numbers of receptors or a different status of binding capacity even in the same patient. Large numbers of binding sites for somatoslatin h~ve been detected in-vitro in many tumours arising from central nervous system and endocrine organs. The scintigraphic localization of these receptors offers the possibility to detect metastases or to consider oetreotide therapy.We examined 35 patients with suspected somatostafin receptor bearing tumours(carcinoids n=16; brain and pituitary n=10, pancreatic n=3; gastrinomas n=3; small cell lung cancer n=l; medullary thyroid carcinomas n=2) .Tyr-3-Octreotide as somatostatin receptor analogue was labelled with a chloramin-T-method according to a previous published procedure.Gammacamera images (SIEMENS-ROTA; MICRO-DELTA) were performed 10rain, lh and 4h p.i.;SPECT-images 2h p.i. In 2 patients with islet celt carcinomas somatostatin receptors have been proven in-vitro by autoradiography.In 5 patients a positive therapeutic effect of octreofide was known,in 3 patients octreotide therapy failed.In all 7 patients with evident receptors I2123-TYR-3 -OCTREOTIDE localized the tumours . When treatment failed, no accumulation could be demonstrated. In 4 patients with metastases of careinoids receptors eunld be demonstrated, 12 patients demonstrated no uptake.2 of 3 gastrinomas could be localized. One small cell lung carcinoma had intensive uptake of the tracer. Oliomas demonstrated different uptake in dependence from their histological differentiation.In conclusion ,I-123-TYR-3-OCTREOTIDE is able to localize somatostatin receptors in turnouts. Positive scans are predicitve of a therapeutic effect of octreotide treatment.; negative scans of a negative octreotide effect. For irre~/lar ROI definltion a threshold of 60 % was taker~ The ROIs were drawn on the riqht and m~.'rro.red to th 9 left, and subsequently ad_a_ pted to the surucuures on ±eft-hand side. Care was taken that the surfa.ce of the right~ ~ qorrespo~nd~'ng .left regions ~was ~ same. ROIs ~ezine~ were wno±e s~ice (SLICE), .zron~.cor~ex (FC), pa.ri. 'eta± cortex (PC), po@terior ~emporal..i!.nze~rior~parle.tal c_o_r~.ex .(TPOC), occipital cortex t~), ~asaA _9-~ng-la (BGI, r/~alamus (TH)~ and white matter (WM). Als6 24 fixed ROIs were used, derived from a stereotactie brain atlas. The count rate..density was no.tin@l, ised for injected do~e ~ .body weign~.ar~ e.xpresse~ in SMU/(MBq/k~). The s~ecizic/ aspe_cizi.c r~t~os w~..re Cgrt.e.x/TH,, af~ CortexTBG.'±he aoso±u~e ra~oacuiviuy mensiSy corrected for the inje~cted dose and .k~.dy weig.h.t (in .S~U/_GBq/kg) remaine~ constant over time in rne cerebral cortex, bu~t degreased in th.e subg.ortical regions. The highest a.ctivi~y was presenu in ~ne occiDit~l and medial zrontal c.ortem The ratios of 0Q~/TH .and OC/~_ increasee over time..~ne injection or cold flumazenil rg. su~. t.e~_ in a .dgcrease " i~ r~di.oactivity.der~ity of smouu Du ~ i.n rm 9 cerebral cor~e~ '.he displacement characteristics ~n the various brain rewions as well as handedness of ~the Su~. 'ects (estimated with the Annett. Hamdedness QuestiSnnaire) will be discussed regarding the CBZ-receptor distribution in the brair~ 

The presence of somatostatin receptors on most GEP tumours offers the possibility for in vivo visualization of such turnours using a radiolabelled somatostatin analogue (OctreoScanRlll, Mallinckmdt Medical, Holland). In order to evaluate the diagnostic value of OctreoScanRll I scintigraphy, we investigated 28 patients with histology proven GEP tumours: 13 caminoids, 2 gasttinomas, 2 MEN-l, 2 nonsecreting tumours, 1 motilinoma. Planar acquisitions were obtained 4 and 24 h after injection of -200MBq OctreoScanR111 and SPECT was performed at 24 h. Scintigraphic resulis were compared with those obtained by morphological imaging methods (CT-scan in all cases, US and MRI).OctreoScanRlll showed lesions in 25 of 28 patients whereas morphological imaging was positive in 22-patients. Among the 3 negative scintiscans, 2 patients (1 gastrinoma, 1 MEN-l) had also negative morphological imaging studies and 1 insulinoma was positive at US only. In 4 of the 25 positive scintiscans no lesions were detected by the other imaging modalities. The primary tumour was visualized in 12 patients by scintigraphy and in 7 patients by morphological imaging. Local turnout recurrence was scintigraphically detected in 6 cases among which only 3 were found with the other techniques. Twenty-seven metastatic sites (13 hepatic) were shown by scintigraphy compared to 21 (12 hepatic) with the morphological imaging methods.In conclusion, Octreoscan~l 11 scintigraphy is a sensitive method for GEP tumour detection providing additional information compared to the morphological imaging methods. It allows to image primary and recurrent tumours as well as metastatic spread during a single diagnostic procedure.

Histamine is known to be effective in some cardiac functions including contractibility and electrical conduction in the heart. These effect may be via to the histamine H-I receptors located in cardiac tissues.The In vivo mouse experiment with C-f1PYR showed that tissue accumulations 30 min. after the injection were 2.2 ~ 0.4, 2.1 ~ 0.4, 5.6 ! 1.4 and 1.6 ~ 0.3 % injected dose/g tissue for atrium,left ventricle, lung, and blood respectively. Blocker injected 5 min before C-II PYR caused a mean 30 % decrease in percentage uptakes of atrium and left ventricle but none in the lung and blood.PET studies done in monreal dog using C-II PYP without blocker and after blocker (diphenhydramine 5 mg/kg) injection showed that cardiac HI receptors can be imaged easily in I0 min and uptake in the heart can be blocked in a maximum ratio.of more than 50 % These results show the possible potential of PET to understand the distribution and the effect of histamine H-I receptors in many cardiac disease in human. 

In order to localize tumor tissue with photosensitizing agents we have labelled hematoporphyrin and its derivative Photofrin lil with indium-Ill and technetium-99m. Using indium-III-oxine the starting activity was about 400-600 uCi and the concentration of porphyrin 1,5-2 mg/ml bicarbonate buffer pH 7.4. The vial was incubated at 110-140 C for 20 min and allowed to cool before the next step. Using the same incubation conditions with indium-Ill-chloride the initial activity was 500-600 uCi and pH was adjusted with 5% NaHC03 to 7.0 pH. After labelling the products were purified using reversed phase C18-cartridge$ activated with 5 ml of methanol and I ~ mol/I NH4-acetate buffer, pH 5.2. The reaction mixture was diluted with the same buffer before passing through the C18-cartridge. After washing with buffer and 20% methanol, the labelled product was eluted with acetonitrile: methanol (60:40, v/v). About 10 mCi of 99m-pertechnetate was reduced with stannous chloride (0.25 ml, 0.2 mg/ml) before labelling porphyrins. After 10 min the pH of the solution was adjusted to 7.4 with citrate solution and immediately after that 2.5 mg of porphyrin was slowly added to the vial. Labelling was performed within 30 min at room temperature. The labelling efficiency was good using both indium chloride and pertechnetate, 85-90%. Both reactions were affected by pH. When the pH diverged from the optimum of 7.4, labelling either did not occur or the efficiency was only 10-20%. With indium oxine solution the labelling efficiency was about 70%. 

Availability of Tc-99m sestamibi (MIBI) is limited especially in emergency cases due to the time-constmdng labeling procedure requiring a 10-min boiling water bath and a 30-rain radiochemical purity (RCP) analysis. These two restrictions have been surmounted by the combined use of a microwave oven (Me) heating method and a mini-paper chrcmatography (MPC) system. However, use of the Me presents sc~e potential problems: I) technical error in setting Me heating time and power setting; 2) ejection of the rubber septiml if vial is not evacuated; 3) breakage o~ vial during MO heating process; 4) inconsistent and inhe~Dgeneous M0 heating. Although a l-rain boiling water bath time is sufficient to provide an acceptable labeling efficiency of MIBI, an additional tin~ of 20-25 rain is required to heat the water to a boiling state. This study was undertaken to evaluate the use of an instant hot water machine to prepare MIBI. This device is commonly used to supply hot water (86.2+1.9°C, n=45) for preparing instant food (e.g., coffee, ~ea, etc.). Three milliliters of 5,500 MBq Tc-99m were added to a MIBI kit and then placed in a 150-mi insulated beaker filled with water frc~ an instant hot water machine. MPC was used to determine RCP of samples after i, 1.5, 2, 3, 4, and 5 rain incubation periods. Our results indicate that 2 rain was the shortest incubation time which yielded an acceptable RCP of 94.7+0.4% (n=60) over the 24-hr evaluation time. The use of an instant hot water m~chine not only avoids those probl(~s associated with the MO heating method but also provides a rapid, efficient, and relatively simple option for preparation of MIBI. Pl~telets seem to have great importance in the diagnosis of different thrombotic diseases. 9?mTc-HH-PAO has bee~ evaluated as an aBent ~o radiolabel h~man olatelets in vitro. In these experiments we controlled the affects of cadiolabelling and isolation orocedure on the viability, functionality and m~cromorphology of platelets obtained from healthy volunteers.9?mTc-HH-PAO was prepa~ec in our laboratory. To have labelled olatelets 2-~xlO cells were incubated with 0.180 mg/30 MBo 99mTc- HM-PAO in one ml at room temperature for 30-&O minutes. The labelling efficiency ranged between 50-60% ano the radioactivity release from the platelets amounted to aoou~ 8-10% in 60 minutes.Platelet micromorohology was studies by scanning ( 

OF 5- IODO-NICOTINAMIDE FOR BRAIN STUDIES Nicotinamide (NAM) is a potential marker for studying brain metabolism.It may be useful in the study of nervous disorders caused by vitamin deficiencies. In our study we developed a convenient labelling method of producing iodine (I-123, 1-131) -NAM for biodistribution studies which we have done in rats.Incorporation of iodine in NAM may have a significant effect on its biological properties.Also the lipophilicity of NAM is increased and the cerebral uptake may be increased when iodine is incorporated in NAM. NAM was labelled with iodine in the 5position by halogen exchange reaction. was synthesized from 5bromo-nicotinic acid (Aldrich).Br-nicotinic acid was acylated with thionyl chloride and the product was reacted with ammonia to produce Br-NAM. Proton-NMR spectra was obtained from the Br-nicotinic acid and from the purified Br-NAM. Iodine NAM was made by heating in the presence of catalyst and glacial acid.Iodine NAM was purified by RP-HPLC. Labelling percentage after exchange reaction was >90 %.After purification the radiochemical purity of the product determined by HPLC was >98 % and the specific activity of 1-123-NAM was >655 GBq/mg.In conclusion a method of producing iodine labelled NAM was developed. 

Our investigations on the development of new myocardial perfusion imaging agents have been extended to cationic phenanthroline complexes of Tc(II). The complexes were synthesized by reduction of pertechnetate with sodium borohydride in the presence of 1, 10-phenanthroline (phen), 4-methyl-or 5-methyl-l,10phenanthroline. After purification by HPLC the complexes were characterized by IR/VIS-UV spectrophotometry and magnetic susceptibility measurements demonstrating the d J configuration of Tc(II).. For biodistribution evaluation in mice, [99mTc(phen)]2+ was obtained with a reaction yield of 12% and radiochemical purity of 92.5%. The rather hydrophilic complex was predominantly excreted by the kidneys. Its low blood retention resulted in a heart/blood ratio of 4.2 at 100 min post-injection which may be improved by synthesizing the analogous complex of Tc(I) and/or by using suitable phenanthroline derivatives as ligands. In 1989 the successful use of gadolinium phthaleincemplexone as a hepatobillary NMR contrast agent in rabbits has been described (KAWAMURA et al.) . As this complex was applied obviously without preceding isolation and characterization, we wanted to improve the chemical aspects of that work. Trials to reproduce the poor production data failed, but we succeeded in synthesizing a new gadolinium phthaleincomplexone compound (Gd-PC) which could be isolated, purified and characterized by normal methods of analytical chemistry. Additionally the same complex labelled with the short lived gamma emitter 6 h) was produced with regard to biodistribufion studies In animals.Our synthesis is carried out by adding a solution of gadolinium nitrate to a diluted solution of phthalein complexone in the heat. The resulting crude product can be purified by gel chromatography. For labelling with , produced in a nuclear reactor, the synthesis procedure was scaled down by a factor of 103 . In contrast to the results of KAWAMURA our Gd-PC is sparingly soluble in water, but it can be sohited easily in isotonic sodium hydrogencarbonate solution. Whereas the ultraviolett spectrum of the compound differs only unessentially from that of the free phthalein complexone, the infrared spectrum shows some significant differences. Like the broad peaks in the NMR spectrum this points out to complexation. As a result of FAB mass spectrometry and activation analysis the molar ratio of gadolinium to phthalein complexune in the purified substance seems to be 1 : 1. The labelled product was shown to be identical with the inactive compound. 67-70 (1989) . 

Recently, 1-123 MIBG heart scintigraphy, to study m y o c a r d i a l a d r e n e r g i c i n n e r v a t i o n , a n d I n -l l l a n t i m y o s i n c a r d i a c s c a n , to Here described are techniques used for R~A tests with dobuta~ine dur/ng acute post-infarction(16_+4 days). The myocarcial perfusion study was carried out with TL201 SPECT,first with dobuta~ine stress,foll~wed by the hasa/ study 4 hours later.RNA was done t%~ days thereafter. 32 20" images were obtained at the initial -45 ° position,with a 180Q clockwise rotation.After filtering the u~ages, 3 oblique axes were reconstructed:l)short 2 ) sagit tal 3 ) coronal. In scroe cases,quantification was dome using the Cedars Sinai Method. RNA: done by labeling red blood cells,rich in ;under basal conditions and then with dobutamine stress at OAI -45Q.Dobu-t~ine is administered with an infusion pu~p, the do6e increasing to 5,10,15,20 ~nd 25(ug/kg/min),each one for 5 ~in. The dose increase is stopped, when the patient reaches suhn~xlmu~ heartrate or has precordial pain.The patient is ~onitorized, and ECG is done and blood pressure is taken under basal conditions and after each do~e increase.Maximu~ d~e is maintained throughout the study time and ECG is repeated at 5' and 10' after perfusion stopped. Patients were fasting and informed of the study and possible side effects. RESUL2~:of 33 patients,9(27%) had suns alteration,6(18%) had chest pain, 3(9%)bad reaction to pyrogens.Residua ! ischem/a occurred in 24(72%).An increase in ejection fractio n following dobut~nine occurred in 24(72%).f]~x~$1~I(l~S: Both techniques are most useful,cc~plementing each other in the study of post-infarction resich/al ische]lia. Secondary effects responded well to treatment.These techniques require utmost collaboration on the part of the specialist and the nursing tea~.