key: cord-0034101-ttdtyoqc
authors: nan
title: Abstracts of the European Association of Nuclear Medicine Congress: 20–24 May, 1990 Amsterdam, The Netherlands
date: 1990
journal: Eur J Nucl Med
DOI: 10.1007/bf02266927
sha: 717c2af14852752abbbdef2bd39c00f0a6ef9e41
doc_id: 34101
cord_uid: ttdtyoqc

nan

To assess the diagnostic value of immediate postexercise left ventricular ejection fraction (LVEF-PEx) 176 patients were studied at rest, during maximal exercise and immediately post-exercise.

In addition, the correlation between LVEF-FEx and physical validity, defined as the level of exercise expressed as percentage of the estimated expected workload for the individual, was investigated. Sixty-one patients (35%) with a recent myocardial infarction (<4 wks), 86 patients (37%) with an old myocardial infarction (>4 wks) and 21 patients (12%) with valvular lesions were studied. Twenty-eight patients (162) with an abdominal aneurysm were considered as controls based on history and unchanged exercise ECG. LVEF and a cumulative regional wall motion score (RWHS) for 3 regions were obtained. LVEF-PEx improved significantly compared to maximal exercise (LVEF-Ex) in all 4 different diagnostic groups (p < 0.001), as applied to cumulative RWMS-PEx compared to RWHS-Ex in the recent and old myocardial infarction groups (p < 0.001). In the abdominal aneurysm group and the valvular group, however, no significant change was noted in cumulative RWMS-Ex to RWMS-PEx (p = 0.031 and p = 0.428 respectively). In each group a pattern consisting of a decrease of LVEF from rest to exercise and an increase from exercise to post-exercise, exceeding the resting value, was observed. Physical validity did not appear to influence this pattern. However, there was a good correlation between absolute LVEF values and achieved physical validity. LVEF-PEx response has no diaanostic value in the detection of patients with coronary artery disease, 

The seleation of patients for mechanical recanalisation post infarction is datermined by the extent of viable mycoardium at risk and by the amount of necrotic tissue within the occlusion/stenosis -dependent territory. The purpose of this study was to clarity the potential role of In-111 antimyosin antibodies (AMAB) in differentiating akinetic viable myocardium from irreversible tissue damage.

In 41 patients with evidence of myocardial infarction scintigraphy was carried out 48 h after i.v. injection of 2,5 mCi AMAB. In 27 patients this study was preceeded or folbwed by gated (25 frames/sect scintigraphy using 15 mCi Tc-ggm-Hexa-MIBI (MIBI) which provided the pattern of regional perfusion as well as that of wall motion. In 11 patients angiographical follow-up 3-6 months after the event was obtained.

An extended area of AMAB-accumulation was found together with a corresponding pedusion deficit and a corresponding akinesia in 13 patients (At. All of them had CK increase and none of them had angina within the period of the scintigraphic investigation, ST depression in the ECG or signs of a non-transmural infarction. 1/4 follow-up investigations in this subgroup resulted in an improvement of the ventricular function. Other 9 patients had large akinesia, but no or only faint AMAB-acoumulation and fairly normal MIBI uptake (B). Five of them had CK increase without infarct O and only two of these patients had angina or ST depression. In tour out of tire patients of this group an improvement of ventricular function was observed in the folbw-up investigations. Five patients had large akinesia with corresponding perfusion deficit, but no or only a slight AMAB-acoumulation. In two of these patients angioplasty was performed subsequently and an improvement of the ventricular function was observed in the follow-up investigations.

The three patterns suggest the following interpretations. A: extended irreversible myocardial damage. B: reperlused, akinatic (= 'stunned' myocardium) with good prognosis. C: rest ischemia with akinesia, if old scar is excluded (= 'hibernating myocardium').

In conclusion, a sufficient differentiation of viable akinetic myoeardium and irreversible myocardial damage following acute ischemia appears feasible with using AMAB and MIBI. 111In-Antimyosin (AM) myocardial uptake the first year after heart transplantation (HT) relates to the degree of rejection activity. To assess if persistence of AM uptake one year after HT could categorize patients at risk of subsequent rejection, AM studies were performed in 21 patients one year after HT. Patients were followed for a period of 18• months after the first year. Follow-up included endomyocardial biopsy every 4 months. A heart to lung ratio (HLR) was used for quantitative assessment of the AM scans. A HLR of >1.58 (mean value in normals + 3 SD) was used to define abnormal uptake.

Eight of 12 patients with HLR>1.58 one year after HT, presented with biopsy proven rejection (17 episodes) during follow-up. I of 9 patients with HLR SI.58 one year of HT, presented with I episode of biopsy proven rejection during follow-up (p=O.01). The number of rejection episodes per patient during followup correlated with HLR at one year of HT (r=0.64; p<O.01). The 9 patients with HLR~ 1.58 had 0.1 episodes of rejection per patient (I episode). 7 patients with HLR>1.58SI.T5 had 1.28 episodes of rejection per patient (9 episodes) . 5 patients with HLR>1.75 had 1.6 episodes of rejection per patient during follow-up (8 episodes) (p<O.05).

We conclude that AM scans are useful in risk stratification after HT. Persistance of AM uptake one year after HT indicates a higher risk of subsequent rejection episodes. Myocardial blood flow quantification by SPECT is an often used diagnostic tool for the evaluation of the therapeutic effects before and after interventions on the coronary arteries. This study was performed to test the reproducibility of a standard protocol for the relative quantification of myocardial blood flow in repeated stress studies in the same patient using SPECT and the new tracer Tc-99m Sestamibi. So far, 56 studies in 14 patients with known coronary artery disease were obtained prospectively within a coronary drug study. On day 1, a standard Tc-99m Sestamibi rest-exercise SPECT protocol was performed. On day 3, exercise was repeated twice at the same level before and after a dilatative agent, so that 2 stress perfusion sets were available for direct comparison. For blood flow quantification a semiquantitative polar coordinate program was used allowing the determination of significantly decreased blood flow in comparison to normal expressed in percent of total myocardium as well as in regard to standardized perfusion areas of the 3 coronary vessels. Decreased stress perfusion was found as follows: In addition, the extent of decreased perfusion within the singular areas was correlated between stress 1 and 2: Total: r = 0.96 y --0.72 x + 2.9 LAD: r = 0.97 0.84 x + 1.7 RCA:

r=0.83 v=0.78x+0.9 LCX: r = 0.62 )= 0.47 x + 1.7

Thus, the reproducibility of SPECT blood flow quantification of approximately only 4 % difference of total myocardium is fairly gbbd; but is has to be considered if effects of surgical or drug interventions on coronary flow during stress is to De measurea. 

To establish the role of different imaging techniques in quantification of myocardial scar size, gradient echo magnetic resonance Imaging (MRI) and myocardial MIBI-SPECT seintigraphy were compared.

To quantify myocardial scar systolic wall thickening and diastolic wall thickness were assessed by MRI and myocardial perfusion by MIBI SPECT scintigraphy. An equivalent method was developed to assess corresponding tomogramms. In each of 19 patients with chronic myocardial infarction 2 corresponding transversal MRI and S~ tomogramms were evaluated. Each slice was subdivided in 6 sections. In total 228 sections were assessed. In MRI scar was defined if systolic wall thickening and diastolic wall thickness were below 30% of normal values. For comparison 11 healthy volunteers were e=~_m!ned by Mill to set up the normal values. In scintigraphy a scar was defined if the MIBI uptake was 2.5 standard deviations below the values of a control group.

In 96% of the myocardial segments the results of MRI and scintigraphy agreed. Comparing the 2 scIntigraphic groups of segments (scar n=86, viable myocardium n=142 ) with the MRI parameters they were significantly different (p < 0.0004).

The results of this study showed a good agreement between the functional and morphological data obtained by gradient echo MRI and myocardial perfusion assessed by MIBI-SPECT in quantification of infarction size. Reduction of systolic wall thickening below normal appears to be a good indicator of impaired myocardial perfusion, which can be detected by MIBI-SPECT. The myocardial imaging by MIBI-SPECT appears to provide exact quantification of the extent of myocardial infarction, especially when compared with the morphological information of MRI. Both methods are complementary in the decision for coronary revascularizatlon. Antibodies are basic gamma globulins and cell surfaces contain acidic residues. Therefore, there is a potential-for non-specific ionic interaction which may increase non-target organ activities when antibodies are used in vivo. The purpose of this investigation is to modify monocional antimyosin FaD (AM) with highly negatively charged synthetic polymers carrying many chelating groups (for labeling with In-lll) and acidic residues (DTPA-Succinylated polylysine 3.3 and 17kD = PL3.3kD or 17kD) without affecting the affinity of AM, and to demonstrate lower in vivo non-target organ activities and better specific target organ localization relative to the conventional control lllIn DTPA-AM. Dogs were subjected to acute experimental LAD occlusion for 3 H, after which reperfusion was initiated. Fifteen min later 0.6 mCi of TI-201 was administered and after another 15 min, T1-201 distribution image was obtained. Then = 0.8 mCi in -8 ug of PL3.3k D-(n = 6) or PL17kD-AM (n = 6) or ~ 1 mCi in 250 ug of conventional In-lll DTPA-AM (n = 7) were injected intravenously. Gamma imaging was performed for the next 4 H. Serial blood samples were collected from 1 rain to 4 H. The animals were killed and standard biodistribution oerformed. Acute infarcts were visualized within 30 rain after administration of 111In-PL3.3kD-or lllIn-PL17kD-AM, whereas conventional AM required 1-2 H for visualization. Means of ratios of infarct (I) to normal (N) myocardial activities in 0-20% TI-201 distribution samples were higher for PL17kD-AM (32 _+ 10) than for PL3.3k D-or 19 .5 + 3 respectively) (P < 0.01). I/N for the latter two were not significantly different. The normal myocardial background activities were lower for PL3.3k D-and PL17~]2I-AM (0.5 + 0.01, and 0.4 + 0.01 respectively, MEAN + SD %ID/I00g) than

In-DTPA-AM (0.8 + 0.03) (P < 0.01). Similarly the liver activities were lower for the polymer modified AM-Fab. The most dramatic difference was observed in the kidney cortex activities (PL3. 3 kD-AM = 3.7 + 2.2, PL17kD-AM = 1.5 + 0.3, and In-DTPA-AM = 17.3 + 14.6 {P < 0.01}). Blood cleayance was very similar. Thus this study points to a potentially new approach to decrease non-target organ activities and enhance target visualization in radioimmunoscintigraphic application of monoclonal antibodies.

Recently it was demonstrated that rain labeled non-specific polyclonal human immunoglobulin is able to localize infections in humans and animals. The present study was undertaken to evaluate whether ~9"~Tc labeled modified polyclonal human immunoglobulin (HIG) could be used in this respect as well.

Mice with an infection of Staphylococcus aureus in the left thigh, were intravenously injected with HIG. At 1, 4, and 24 hr hereafter scintigraphs were made and after the last one the mice were killed and the amount of activity in several organs was determined.

HIG demonstrated a highly reproducible accumulation at the site of infection, ranging from a target to background ratio of 2.9 at 1 hr to 6.9 at 24 hr after the administration of HIG. Significant lower ratios were obtained at 24 hr using ~Tc labeled serum albumin or 99mTc labeled Fc fragments. The origin (human vs murine Ig), the amount of total protein (0.01-1.0 mg Ig per mouse) and the degree of polymerisation (mono-vs dimeric Ig) did not affect the level of localization. This level was also not altered in leukocytopenic animals. Furthermore there was a log linear relationship between the number of bacteria in the thigh and the target to background ratio. In this short-term infection the efficacy of antibiotic treatment with cloxacillin could only be followed by a sequential analysis of scintigraphs.

HIG does localize the thigh infection in mice: the higher the number of bacteria the higher the target to background ratio at the site of infection. Vascular permeability or Fc binding alone could not account for the mode of action of HIG. BiodisWibufions of biotinylated anti CEA antibody Mab 35 (Mab 35-BHZ) and 125I-labelled streptavidin (SV) were investigated in athymic mice bearing tumors of LoVo hu colon adenocarcinoma cells. Mab 35 was derivatized at carbohydrate sites with biotin hydrazide yielding fully immunoreactive and stable conjugates. Streptavidin was iodinated with the iodogen method to a specific activity of 5 mCi lzsI-SV/mg. Mice (2-3 animals per experiment) bearing LoVo tumors were injected i.v. with either 50 ItCi '25I-SV alone or after pretreatments for various times with 100 ;xg Mab 35-BHZ. I~I-SV alone showed rapid (maximal after 6 h), strong (14.7 + 2.2 % i.D./g) and prolonged (up to 7 days) kidney retention. Pretreatment for 24 h with 2 mg of unlabelled SV did not affect the massive kidney accumulation, whereas i.v. injection of unlabelled SV together with lz~I-SV reduced kidney uptake to 2.03 + 0.21% i.D./g. Simultaneous injections of 0.5 mg or 0.1 mg SV reduced kidney uptake to 6.54 + 0.42 % and 13.53 + 0.41% i.D./g respectively.

These results show that SV uptake into kidneys can be blocked by unlabelled SV but SV binding to sites in the kidneys cannot be displaced.

~2SI-Mab 35 biodistributions showed best tumor/organ ratios after 3 -5 days (5 -6 % i.D./g in tumors). When mice were pretreated for 3 days with Mab 35-BHZ, followed by 48 h of tzsI-SV, 1.4 +0.07 % i.D./g was found in tumors and the localization index (Mab 35-BHZ + I~I-SV/mSI-SV) was 3.5. Compared with unmodified Mab 35 the tumor/liver ratios were lower (1.6 vs 10.5) and the tumor/blood ratios were similar (2.6 vs 2.5). Simultaneous injection of 0.1 to 2.0rag unlabelled SV with nsI-SV for 48 h resulted in loss of specific tumor uptake. The results show that the strong kidney uptake of SV cannot be blocked by administration of unlabelled SV without comprising tumor uptake. The advantage of human over murine antibodies is the reduced immunogenic response, a prerequisite for radioimmunotherapy.

The IgM monoclonal antibody (MAR) 16.88 is of human origin and recognizes an intracellular antigen. The aim of the study was to investigate The sensitivity, toxicity, and whole body kinetics of 16.88 and the possibly beneficial effect of excess unlabeled MAR on sensitivity in advanced colon cancer patients (pts). Methods: 19 pts (strongly positive for 16.88) received 8 mg 16.88 iv labeled with 5 mCi 131I. After 2 weeks the infusion was repeated with addition of unlabeled HAg, either 200 (Spts), 500 (5pts), or 1000 mg (4pts). Whole body counts (uncollimated gamma camera) and planar images were obtained 2, 48, 120, and 168 hr pi. On the 7th day, 10 mCi 99mTc-HMPAO was administered iv and whole body images were acquired. Results:

in 74% of the pts images were pos. Of all sites (n=36), 64% could be detected. The size of the undetected lesions was ( 3cm. In 2 pts, immunoscintigraphy revealed lesions that were not known before. False positive images were obtained in pts with cysts, pleural fluid, and hydronephrosis. Excess of unlabeled MAB improved immunoscintigraphy in 2 pts. Best images were acquired from day 5 to 7. In some pts initially cold lesions in the liver were seen which corresponded with low perfusion of the metastases on HMPAO scintigraphy.

The biological whole body T 89 (mean• was 42.2• hr, not significantly influenced by addition of unlabeled MAB. Anti-human antibodies could not be detected. One pt developed a non-speclfic skin rash. Conclusion:

The human MAB 16.88 has tumor localizing properties in colon cancer patients; administration of repeated doses and upto 1 gram has not induced major side effects or anti-human antibodies. Addition of unlabeled MAR has no effect on whole body kinetics and does not substantially improve immunoscintigraphy.

of HMPAO-SPECT-Quantification is shown by the optimizing of the following parameters : -frequency-filters -spatial resolution -calibration of the SPECT-Camera -pixel bx pixel contour line analysis of the right and left hemisphere

The optimizing of the frequency filter and the spatial resolution was done by an iterative method using a special SPECT-Phantom. A calibration of the SPECT-Camera was done at different acquisition radii with a calibrated source to get an absolute value of the HMPAO-Uptake. To improve the standard quantification contour lines of 5,10,15 and 20 % reduced rCBF are calculated by a pixel-by-pixel analysis of the hemispheres additional to a common method using 4 ROls/hemisphere. The simultaneous use of this methods at more than 60 patient studies shows a much better spatial localisation of defects.

In some clinical studies the contour analysis shows up to 40 % reduced rCBF in close areas compared with the ROl-method at 15 -20 % .The spatial resolution was improved up to 12 mm. The total HMPAO-Uptake in the brain was in the range of 1.7 to 4 % of the applicated ggmTc- HMPAO. ceptors has been obtained in six closed-chest dogs with positron emission tomography and using MQNB as ligand, MQNB being a nonmetabolized hydrophilic antagonist of the muscarinic receptor. The protocol included four injections. The first injection of a trace amount of Cll labeled MQNB was followed 30 min later by the injection of an excess of unlabeled MQNB that competed with bound radioligand. Two additional injections of unlabeled MQNB with and without Cll labeled MQNB were administered at the 70 th and the 120 th rain respectively.

This protocol allows to evaluate separately, in each animal, the quantity of available receptors (B~z) and the association and dissociation rate constants (k+l and k-l). The parameters were calculated using a nonlinear mathematical model in regions of interest selected over the left ventricle and the interventricular septum. The average value of B~== was 41 4-12 pmol/ml tissue, the rate constants k+l, k-1 and Ka were 0.9 • 0.2 ml pmo1-1 min -1, 0.27 4-0.03 min -1 and 0.32 0.09 pmol/ml respectively, taking into account the MQNB reaction volume estimated to 0.23 ml/ml tissue.

Although Cll labeled MQNB binding could seem irreversible, our findings indicate that the association of the antagonist is very rapid, that the dissociation is far from negligible and that the dissociated ligand has a high probability of rebinding to a free receptor site instead of escaping in the microcirculation. We deduce that the PET images obtained after injection of a trace amount of Cll labeled MQNB reflect more blood flow than receptor density or affinity. After injection of Tc-99m DISIDA the radioactivity detected over the liver area reflects the netto balance of the extraction and excretion capacity of the liver. We report here a mathematical treatment allowing absolute quantification of these two hepatic functions. The distribution of the tracer was calculated using the tracer conservation equation including four unknown quantities: the liver, gut and bladder attenuation coefficients and a normalization factor for the vascular compartment. Abdominal scans being obtained every min over a period of 60 rain, the conservation law was written for every acquisition so that the number of equations obtained (60), largely exceeds the number of unknown quantities. The absolute radioactivity present in blood, liver, bladder and gut was obtained by solving these 60 equations using the Schmidt algorithm. Values of blood radioactivity calculated by this method were similar to those measured in blood samples. Knowing the activity of each compartment, the liver extraction rate was Calculated at each time by subtracting the blood and bladder activity from the total activity injected; the gut activity represents the hepatic excretion rate. By deconvolution we obtained an intrinsic extraction function independent of the quality of the bolus injection, and an intrinsic excretion function independent of the liver extraction capacity. Analysis of the intrinsic extraction function revealed the existence of two phases: a short initial phase characterized by a high extraction rate, followed by a phase of slow or even zero extraction. Preliminary results indicate that the rapid phase is mainly flow dependent whereas the second phase is flow independent. The ratio between blood and liver concentration ot the tracer remains stable during the second phase and is likely to represent the maximal hepatic extraction capacity. 

The need for prediction models in medicine currently overcomes the traditional available resources. Neural network provide effective tools for non-linear problems analysis, by emulating the behaviour of a network of parallel singlefunction computing devices modelled after a simplified simulation of a neuron. A neural network actually "learns" from a given experience rather than being programmed on a rule-based engine. We evaluated the pattern generalization capabilities of neural networks for predicting the distribution of coronary lesion starting from myocardial perfusion SPECT data. This program is a software simulation of a supervised three-layered network: connection strenghts follow the Hebbian rule and are adjusted after the output errors by a backpropagation algorhythm. The input layer handles myocardial left ventncular SPECT perfusion data while the output layer determines the probability of presence of coronary stenoses. A hidden layer provides interneural connect,ons. The network is handled as a matrix of values that give determined outputs while compared (dot product) with the input values arranged as an array of multidimensional vectors. After the training phase, network performance was evaluated with two datasets: single-vessel CAD and mixed single-and multi-vessel disease. The network was able of correctly predicting the stenosed/occluded vessel in all (16/16) cases when singlevessel CAD was present. When multiple vessel CAD was responsible for perfusion defects the overall success rate in correctly identify the most probable vessel(s) was 83% (20/24). Neural network perfomance is strictly dependent from design layout and the training dataset 

Gated SPECT during RNV is hampered by a high demand on statistics. The purpose of this study is to reduce the acquisition time below 8 min by a modified thick slice technique.

All projection profiles containing the ventricles are integrated to one profile for each RR-segment prior to backprojection. The resulting transversal thick slice shows sufficient data stability for subsequent phase analysis. The new, pseudoplanar, axial view corresponds to a imaginary cranial position of the camera with clear separation of the ventricles, good demarcation between ventricles and atria.

In 7 patients RNV and ISPECT was performed and in 5 compared with the results from the invasive eleetrophysiologie study. It was possible to exactly localize the onset of mechanic contraction in the two orthogonal views: during pacemaker stimulation at the apex of the right ventricle, at the lateral border of a large aneurysm during ventricular tachyeardia, and at the site of 3 out of 5 accessory pathways. In the remaining 2 bundles the onset contraction was located close to the area found during invasive mapping procedure.

Thus, ISPECT in addition to LA0 planar radionuelide imaging gives valuable information in non-invasively localizing the site of ectopic focus and thereby help to streamline the invaslve mapping procedure. No absorption correction was used with filtered backprojection in contrast to iterative reconstruction (RT-II version) . The purpose of the study was to determine the methodical influence on the clinical diagnosis. Two experienced observers analyzed the tomograms for redistribution and persistent defects. A fivepoint scoring system was assigned to 7 segments. (0: normal, i: probably normal, 2-4:mildly/ moderately/severely decreased thallium uptake). 23 tomograms were identically normal (0/i); 18 showed identical defects (deviation <i); 4 differed between the two observers and 2 showed a difference between the methods in both observers (deviation Z2). In these 2 patients filtered backprojection (fb) produced stronger defects in the inferior segments than iterative reconstruction(it) : Ischasmia 3(fb) versus l(it)(cardiac catheterization: occlusion of the right coronary artery) and persistent defect 4(fb) versus 2(it)(cardiac catheterization: severe stenosis of the right coronary artery and inferior hypokinesia). Our conclusion at the moment is that iterative reconstruction (RT-II version) does not have to be routinely recommended for 201-TI SPECT.

The aim of the study was to test the frequency and the effect on image quality of poststress upward creep of the heart during myocardial SPECT acquisition. Furthermore an interactive correction algorithm was designed to compensate the related artificial image distortion. For recognizing the upward heart motion a straight line was fitted to the upper and lower border of consecutively displayed tomographic projection images. In this way vertical translation of at least 1 pixel in size could be detected easily. On the assumption of a slow, but continuous upward motion of the heart a fast interpolative correction method was developed. Out of I00 consecutive supine ergometric exercise patient studies I, 2, or 3 pixels upward creep was found in 16, 4, or 3 patients respectively. It was found that only an upward creep of 2 pixels or more (7/100 cases) led to evident, mostly anteroseptal defects on quantitative bullseyes, whereas only upward creeps of 3 pixels or more (3/100 cases) caused false positive diagnostic results. The simple correction method offered a sufficient compensation of image and/or bullseye artifacts. These clinical findings could be reproduced in a computer model. In conclusion it can be stated that clinically significant upward creep of the heart during stress SPECT acquisition is relatively rare and its artificial effects can be corrected by a fast and simple algorithm.

JJ Su I, DG Pavel I, E Olea 2 U. of Illinois Hospital, 1740 W. Taylor St., Chicago, Ill. 60612, U.S.A. I, C. U. of Chile, Santiago, Chile z

We have developed several types of classification synthetic images (CSI) that offer the diagnosis of the left ventricular (LV) regional wall motion abnormalities (RWMA) on image data obtained by equilibrium gated studies. The SCI classify RWMA into 8 classes, from normal to dyskinetie. They are based on multiparametric representations of pixel time activities (mainly Fourier features) and relative pixel locations, on image filtering, and on computerized pattern analysis. The analysis include the following classification approaches: the k-th nearest neighbor classifier, the least square error and median transform, and its more complex generalization, the neural network (back-propagation based) classifier. The computer "learns" from teaching images (TA) which were derived from functional images of gated studies, ultrasound and cardiac catheterization results. The SCI have been developed on a data base of more than 80 cases. Ideally, TA and SCI should be identical; the preliminary ones on the training set have been in agreement in more than 90% of pixels, with false normal/RWMA error in less than 1% of pixels. The obtained regional diagnosis offered by the SCI is very similar to that given by the TA which derived by a consensus of physicians. By pointing out ambiguities in the interpretation of overlapping 3D dynamic structures in the 2D TA, the SCI have initiated a two-way learning process between computer and physician. The SCI types will be compared from points of view of computational demands, trainability, and classification accuracy. The SCI are superior to current parametric images, including phase analysis, especially in the diagnosis of mild RWMA.

M J Carroll, K K Solanki, A Soricelli, K E Britton, G M Besser. St Bartholomew's Hospital, London EC1A 7BE, UK.

The problem with Thallium 201 parathyroid subtraction imaging is the low count yield. Tc-99m MIBI, methoxyisobutylisonitrile Dupont, is actively taken up by parathyroid adenoma (Coakley et al, Nucl Med Commun 1989; 10: 791) . 18 patients with a biochemical diagnosis of hyperparathyroidism were studied. Injected Tc-99m pertechnetate 200 ~q was imaged at 20 and 25 minutes and followed by 300 NBq Te-99m MIBI imaged at 5, i0, 15 minutes after. For tomography (64 angles, 30s per projection, 64 x 64 matrix) a further 150MBq Tc-99m MIBI was injected. Data collection was with 3 x zoom on one computer for intrathyroid analysis and a full image on the second computer for ectopic lesions. Analysis protocol included polynomial surface fitting for background subtraction, translation rotation contour superimposition (made easy by the same energies of the two agents with high count rates giving good edge detection); normalisation to total counts with repeat to the MIBI image, and thyroid subtraction by serial thresholding (subjective) and by a change detection algorithm with probability mapping (objective).

Results showed excellent quality of parathyroid detection including mediastinal uptake.

3 patients negative on Thallium 201 showed positive sites of uptake. Surgical confirmation was correct to date.

Tomography showed the posterior position of adenoma in relation to the thyroid.

Tc-99m MIBI is in our hands a great improvement over Thallium 201 for parathyroid imaging. The isonitrile Tc-99m sestamibi has been shown to be at least as sensitive as TI-201 in pre-operative localisation of parathyroid glands.

To determine whether the superiority of image quality with sestamibi is due to the better physical characteristics of its Tc-99m radiolabel or different uptake behaviour, dynamic scans have been re-evaluated in ii patients undergoing parathyroidectomy.

The thyroid was localised using 1-123. Four hours later dynamic acquisition was performed after an i.v. injection of TI-201 and then Tc-99m sestamibi. Appropriate corrections were made for scattered radiation.

With both Tc-99m sestamibi and TI-201 peak activity in the parathyroid was 6-8 minutes following injection, but thereafter slower washout of tracer was seen with sestamibi.

Nine patients (4 adenomas, 4 hyperplasiaa, 1 carcinoma) were given simultaneous tracer doses of TI-201 and Tc-99m aestamibi at times ranging from 5-60 minutes before the removal of the parathyroid glands, and uptake in these measured.

This biopsy data showed higher accumulation of seatamibi in all glands removed.

For adenomas the Tc-99m/Ti-201 ratio ranged from 1.4-2.4, for hyperplastic glands 1.2-2.4, and for carcinoma was i.i.

There is greater uptake of Tc-99m sestamibi than TI-20I in parathyroid glands. The different kinetics of sestamibi, superior imaging characteristics of the Tc-99m radiolabel, and lower radiation dose make Tc-99m sestamibi the agent of choice for imaging parathyroid glands.

MALIGNANT PHEOCHROMOCYTOMA: EXPERIENCE IN A RECENT SERIES OF 17 PATIENTS 13 male and 4 female (aged 14-76 years) patients (pts) with metastatic pheochromocytoma were treated in our institution between 1985 and 1989 . A neurofibrematosis was associated in 4 pts.

Fourteen pts had a unilateral adrenal tumour and 3 had an extra-adrenal retroperitoneal tumour. Metastases occurred in all pts, at presentation in ii pts, with a I0 to 30 months delay in 6 pts and after 28 years in one case. Catecholamines hyperproduction was present in all pts, predominantly norepinephrine. Neuron specific enolase level was elevated in 9 pts, neurepeptide Y level in 7 pts and procalcitonin level in 10/14 pts. High dopamine and homovanilic acid excretion levels seemed to correlate with large tumours or terminal stage. MIBG uptake was found in 13 pts after a diagnostic dose and only after a therapeutic doae in 1 pt Surgery was performed on primary tumour (15 pts) and on distant metastases (8 pts). Iodine-131MIBG therapy was performed in Ii pts., 8 of them are evaluable. The cumulative dose ranged from 7.25 to 26.3 GBq (196 to 711 mCi) in 2 to 7 courses. We observed symptomatic improvement (5 pts), 2 partial hormonal responses and 2 partial tumour responses which lasted for 28 and ii months, terminating with a rapidly progressing disease involving the bone marrow. Stabilisation was observed in 3 pts. Moderate myelosuppression occured in 3 pts. External radiotherapy allowed pain relief on bone metastases in 7 pts. Chemotherapy (5 pte) gave no response in 4 evaluable pts. Twelve pts died with a median survival of 16 months (range 3-60). Response to therapy was poor and warrants further cooperative trials. 

To compare 131I metaiodobenzylguanidine (MIBG) scintigraphy with computed tomography (CT) and magnetic resonance imaging (MRI) in the preoperative localization and follow-up of pheocromocytoma (Ph), 33 consecutive pts (16 men and 17 women, age 37• yrs (mean• were studied with 131I MIBG (0.5 mCi iv; images at 24, 48 and 72 hr), CT and MRI (SE, TR/TE 300/12 and 2000/80 msec), all done within 1 week. MIBG, CT and MRI were evaluated by two independent observers. Pts were divided into 2 groups: Group 1 (19 pts) was scanned before therapy with subsequent pathologic confirmation of Ph (15 pts); Group 2 (14 pts) was studied after surgery with subsequent surgical (9 pts) and clinical (5 pts) follow-up. Results:

Group 1  Group 2  TP  TN  FP  FN  TP  TN  FP  FN  MIBG  13  3  0  3  8  4  0  2  CT  15  2  1  1  8  3  1  2  MIgI  15  2  1  1  9 2 2 1 (TP=True positive (p); TN=True negative (N); FP=False P; FN=False N). CT and MRI were the most sensitive in group i, but MIBG was the most specific; the accuracy of CT and MRI (90% for both) was slightly greater than MIBG (84%). In group 2 MRI was the most sensitive, but MIBG was the most specific and the most accurate (86% vs 79% for both CT and M]{I) test. In conclusion, preoperatively CT and MRI have slightly more accuracy, postoperatively MIBG is the most accurate.

Prolactinomas are slow growing, prolactine secreting tumors. Consequently the elevated prolactine levels, by incapacitating their production, seriously impair the action of the sex hormones. The aim of this study is to evaluate dopamine agonist therapy on prolactinomas in terms of protein synthesis and glycolysis with PET. In 4 patients (2 female, 2 male) the uptake of L-[l-zzC]tyrosine and 18FDG in tumor (I micro-, 3 macroprolactinomas) and reference tissues was measured prior to and at 18 hours after an im injection of 50 mg bromocryp~ine. L-[l-ziC]Tyrosine was selected because this amino acid is closely related to protein synthesis. A double beaded rotating positron camera was used as imaging device. PET images were correlated with MRI to localize the prolactinoma. Plasma prolactine levels were measured before and after therapy. We measured for L-[l-11C]tyrosine, after administration of bromocryptine, a 28% decrease' (P<0.025) in the tumor/cortex ratio (range 17-45%) ~nd a 29% decrease (P<0.05) in the tumor~cerebellum ratio (range 8-50~). With ZSFDG the delineation of the prolactinomas was not achieved. Discrepancies in tumor extent between MRI and PET/L-[l-1~C]tyrosine were found. At 18h after therapy, residual prolactine levels amounted 16• to the levels in the untreated situation. In conclusion, bromocryptine reduces the uptake of L-[l-11C]tyrosine, which can be explained as suppression of protein sythesis. 0n account of a low demand for glucose which is associated with the low ~rowth rates, prolactinomas cannot be visualized with SFDG. Correlations between the measure of reduction of the prolaetine level and the percentage decrease in the L-[l-1~C]tyrosine ratios could not be established.

MOJIMINIYI~ OA~ SHEPSTONE BJ., SOPER NDW. DEPARTMENT OF KABIOLOGY, OXFORD.

The purpose of this study is to apply the novel technique of radiolabelled antibody imaging to the detection of islet amyloid which is a common and major pathological finding in type II diabetic patients. The formative peptide of the islet amyloid has been extracted, isolated, characterised and termed Islet amyloid polypeptide (IAPP). A rabbit anti-IAPP antiserum was raised and shown to react with islet amyloid. Pure rabbit IgG was prepared from this antise@)~n, made sterile and pyrogen free and labelled with • with preservation of immunoreactivity. 5 patients with type II diabetes and 1 patient with insulinoma were studied with 37 -55.5 MBQ of the labelled antibody. 2 patients with type I diabetes were studied as controls. Scintigr&ms were interpreted by an experienced blind observer. The initial results have shown successful immunoscintigraphic localisation of amyloid deposits in the pancreas of 3 type II diabetic patients and i elderly type I diabetic patient. There was a false-positive uptake in the patient with insulinoma and 2 results were considered equivocal. The technical problems in the study are discussed. Despite the associated problems these initial results provide the incentive for further studies and refinement of the technique. About 50% of all pts. with MEN-2 syndrome develop unior bilateral pheochromo~ytomas (pheo). Clinical symptoms are not very helpful in detecting a pheo, which is a mafor cause of morbidity in pts. with MEN-2 were examined regarding the value of clinical symptoms, biochemical parameters, ultrasound, CT or MRI, and MIBG-scintigraphy for detecting pheo. 7 pts. had undergone surgery for unilateral and 5 pts. for bilateral pheo. In further 2 pts. a bilateral and in 2 pts. an unilateral pheo is assumed. Only 3 of the 15 pts. with pheo have had clinical symptoms and the pheo was detected earlier than the medullary thyroid carcinoma. The other tumors were identified by screening. The smallest one verified by operation was 12mm in ~, the biggest one 70mm. Plasma an D urine catecholamines were almost always slightly e1~#ated for both positive and negative pts. In 15 pt#<. the other methods were congruent regarding evidence or exclusion of pheo but for 5 pt the results were different: normal plasma catecholamine levels with a 3cm pheo (I), elevated values without any evidence of tumor (2), and divergence between CT and MIBG (2). Our results suggest that scintigraphy with MIBGcarried out with 250 MBq J123-MIBG (and in SPECT technique if possible) -is the most sensitive method with high specificity and should be used in spite of radiation burden at least once. Demonstration of only small uptake might be not an indication for surgery but indicates careful follow-up. 

Enhanced18F-fluorodeoxyglucose (FDG) uptake in myocardial segments with impaired function and reduced blood flow is evidence of myocardial viability. Reinjection of 2~ (Th) at rest after stress-redistribution imaging may also provide evidence of myocardial viability.

To compare this two methods, we studied 16 patients with chronic artery disease and irreversible defects on standard Th-SPECT imaging. Th was reinjected immediately after the redistribution study and SPECT images were reacquired. PET imaging was performed with FDG and 150-water.

A total of 432 myocardial segments were analyzed from comparable transaxial tomograms, 166 had irreversible Th defects on redistribution images before reinjection.

In irreversible defects with severe reduction in Th activity (<50% of peak), FDG uptake was present in 51% segments and Th reinjection showed identical results: 51% demonstrated enhanced uptake of Th after reinjection. In these severe defects, there was a concordance of data regarding myocardial viability by the two techniques in 88% of segments, with 45% identified as viable and 43% as scar on both PET and Th reinjection studies. Among the discordant segments, 6% were viable only by PET and other 6% only by Th reinjection. In conclusion Th reinjection seems to be an accurate method to identify viable myocardium in patients with coronary artery disease and left ventricular dysfunction.

DJ Pennell, SR Underwood, PJ Ell, RH Swanton JM Walker, DB Longmore MR Unit, National Heart and Chest Hospitals, London and Institute of Nuclear Medicine, University College and Middlesex Schools of Medicine DIPYRIDAMOLE THALLIUM MYOCARDIAL PERFUSION IMAGING; DIFFERENTIAL FLOW OR MYOCARDIAL ISCHAEMIA? The mechanism of action of dipyridamole used in thallium myocardial perfusion imaging is complex. Subendocardial ischaemia may occur but perfusion defects without ischaemia are possible when the flow ratio between arteries exceeds 250%. This study examines the contribution of ischaemia to the production of thallium defects by comparing dipyridamole thallium tomography with dipyridamole magnetic resonance imaging (MR) of wall motion. Forty patients with angina and an abnormal exercise electrocardiogram underwent thallium tomography and cine magnetic resonance imaging with an intravenous infusion of 0.56mg/kg dipyridamole over 4 minutes. The myocardiam was divided into 9 segments. Thallium uptake was classed as normal, reduced or absent and wall motion as normal, hypokinetic or akinetic and the changes induced by dipyridamole were compared Reversible thallium defects were found in 36 (90)% patients but in only 24(67)% of these did magnetic resonance imaging show reversible wall motion abnormalities. The 12(33)% negative magnetic resonance scans were associated with reversible perfusion defects of ~2 segments which was significantly less than the positive magnetic resonance scans (pC0.001). The extent of wall motion abnormality was smaller than the associated perfusion defect. Reversible wall motion abnormalities were correlated with worse coronary artery disease (p<O.Ol) and chest pain during dipyridamole infusion (p<0.001). Thus in 33% of patients, thallium defects either resulted from flow changes alone or ischaemia was present but undetectable by magnetic resonance imaging. The occurence and significance of transient ischemic dilatation (TID) of the LV during dipyridamole(dipy) stress redistribution TI-201 scintigraphy was studied in 73 pts who had both dipy TI-201 and coronary angiography. TID ratio was calculated by dividing the computer derived left ventricle area on the initial planar anterior image by that of the 4 hr image. The extent of myocardial ischemia was evaluated by TI-201 reversibility score (initial-redistribution visual scores) and a score of >7was considered to represent extensive ischemia. In the ii pts with non-significant (450%) coronary stenosis the lID ratio was 0.98 + 0.046. An abnormal TID ratio was thus defined as >1.T2 representing~_3SD above the mean normal value. Comparing the 15 pts with an abnormal TID ratio to the 58 with a normal ratio, the former group had a significantly higher (p<.05) incidence of critical (>90%) coronary stenosis (93% vs 55%) often with collaterals (67% vs 24%) and an extensive myocardial ischemia (54%vs 12.5%). The incidence of dipy induced positive ECG, increased lung uptake and chest pain was not significantly different. An abnormal TID ratio of>l.12 was a sensitive (5/8=62.5%) and specific (55/65=85%T marker of triple vessel critical coronary disease. We conclude that transient ischemic dilatation of the LV may be observed during dipyridamole TI-201 scintigraphy and implies extensive myocardial ischemia caused by underlying critical coronary stenosis. We have analysed during PTCA in 20 patients (pts) presenting single vessel disease assessed by angiography, with MIBI tomography (SPECT) transient myocardial ischemia (MI) consecutive to coronary balloon inflation. The extent of myocardial ischemia during PTCA was compared to the extent of MI at stress before PTCA, and to regional ejection fraction (EF) and left ventricular volumes. MIBI was injected intravenously and 5 seconds after first occlusion, on the PTCA day. In addition, in 5 pts, a selective thallium intracoronary injection was performed to visualize perfusion area distal to the balloon.The malperfusion score obtained from segmental analysis of MIBI tomogram is significantly higher in 18 pts during PTCA, than on stress tomogram before PTCA (p(0,01) while in 2 pts with collaterals, the extent of MI is larger at stress, than during PTCA. In these pts, thallium distribution overlaps with MIBI distribution while no overlap is observed in pts without collateral. Ventriculography performed during PTCA demonstrates the extent of mechanical ventricular dysfunction with a good correlation between the score of myocardial ischemia during occlusion and the area of abnormal ventricular wall motion and the Left ventricuLar EF (r = 0.81;r = -0.80). Intravenous injection of MIBI just after coronary artery occlusion during PTCA aLLows to visuaLize transient ME induced by balloon infLation, that correlates fairly with the extent of ventricular dysfunction during an-giopLasty while dual tracers studies provide the opportunity to demonstrate coLLateraL flow. 

Thirty-two patients with Hodgkin's disease (HI)), verified in all cases by lymph node histology, were investigated by bone marrow biopsy (BMB, n = 34), bone marrow scintigraphy (BMS, n = 35), and bone marrow mnLmetic resonance imaging (BMMRI, n = 37), for further sts~Ing. Additionally, 23 patients underwent bone scintigraphy (BS) All examinations were performed within a period of three month.

In only 2/34 eases (6%) BMB proved infiltration of the bone marrow. BMMRI in these two patients was suggested as being highly pathological, whereas BMS showed no pathologic findings. Of the other 32 patients, 11 had pathologic changes in BMS and 8 in BMMRI, indicating bone marrow infiltration in spite of negative biopsy results. In 7/8 "false-positive" BMMRI results, circumscript pathological lesions were located in other regions than the posterior iliac crest, suggesting false-negative findings of biopsy. Focal lesions larger than 7 mm 2 in BMMR/ were found in 3/8 patients (38%) with nodular sclero6ing HI), in 2/14 patients(14%) with mixed cellularity HD. No case with focal lesion in BMMRI was found in HD with lymphocyte predominance or lymphocyte depletion.

These findings suggest, that there is, other than in non-Hodgkin-lymphoma, no correlation between negative BMB and bone marrow imaging in HD. Furthermore, BMMRI detection of highly pathological circumseript lesions in patients without pathological BMB indicate, that BMB is not rarely false-negative. Therefore, staging of HD should include not only BMB, but also BMS and BMMRI. Tc-99m labelled monoclonal antibodies (TcNCAA), directed against NCA-95 and CEA, have been recently proposed for irauno-scintigraphy of haematopoetic bone marrow (IBM) in man. This report co@ares performance of IBM to bone scanning (5S) in 141 patients (pts) with malignant disease (Tbl.). IBM's were obtained 3-4 hrs after i.v. injection of 300 + 20 TCNCAA. BS was performed within 2 weeks according to standard techniques wind identical LFOV gamma-cameras. The ratio of ~etastatic to normal regions detected with IBM or aS, expressed in percent, was regarded as measure of the extent of skeletal involvement. Results were compared to plane radiographs (pR) and CT of selected skeletal regions.

No % metastatic lesions Since bone marrow is the primary soil of bone metastases in patients with breast cancer, bone marrow scans (BMS) should detect bone metastases at an earlier stage than bone scans (BS). Tc-ggm-labeled-NCA (Antigranulocyte antibody BW250/183) allows excellent bone marrow visualization. We performed BMS with NCA and BS with Tc-99m MDP in 32 female patients (mean age 50 years) with breast cancer (Stage 1:4 patients, II:12 patients, III:B patients, IV:8 patients) and suspected bone metastases because of bone pain and/or elevated serum alkaline phosphatase. BS detected bone metastases in 17/32 (53%) patients. BMS performed within the same week showed bone marrow defects in 25/32 (TS~). Bone marrow invasion was later confirmed in 23 of these 25 patients (p<O.OOl). BMS detected more sites indicating metastatic bone disease than BS in 12/I? (71%) patients. All patients with bone metastases in the axial skeleton seen in the BS had bone marrow invasion seen in the BMS at least at the same sites. Of 15 patients with normal BS, 8 patients (53%) presented with bone marrow defects in the BMS. Bone marrow invasion was confirmed in 6 of the 8 patients. Fifteen of the 24 (63%) patients with stages I-III, and the 8 (100%) patients with stage IV showed bone marrow invasion. Bone marrow scans with NCA are a sensitive method for the early detection of bone invasion in patients with breast cancer and clinically suspected bone metastases. AN EXPERIMENTAL MODEL IN THE RAT. Total body irradiation prior to marrow transplantation in haematological malignancy currently offers the best prospect for cure but causes life threatening nonhaematopoietic toxicity in 15% of patients.

Internal beta radiotherapy with Samarium-153 could potentially be used to ablate marrow prior to transplantation, whilst minimizing radiation toxicity. Sm-153 ethylenediaminetetramethylene phosphonate (EDTMP) localizes on the surface of cortical and trabecular bone and causes transient myelosuppression in patients treated for disseminated bone metastases.

However, when Sm-153 EDTMP is used alone in dogs or rabbits marrow is not ablated and we have shown that rats all recover spontaneously from single dose of 5-95 mCi/kg IV or 2 doses of 30 mCi/kg given 1 week apart. Marrow in these animals became severely hypoplastic but the spleen showed evidence of extramedullary haematopoiesis.

A chemoradiotherapy regimen of 15 mCi/kg Sm-153 EDTMP and a single dose of 9.5 mg/kg melphalan 5 days later was fatal in 80% of rats whilst all control animals given 9.5 mg/kg melphalan alone survived. Marrow transplantation of rats following chemoradiotherapy with 15 mCi/kg Sm-153 EDTMP and 9.5 mg/kg melphalan on day 5 resulted in survival of 80% of animals.

Thus marrow ablation may be accomplished in rats by internal radiotherapy with Sm-153 EDTMP combined with melphalan chemotherapy and animals may be rescued by marrow transplantation.

Application of this chemoradiotherapy regimen to an animal model of multiple myeloma in our laboratory is being used to assess the potential for treatment of haematological malignancy. There were 1 false positive and 1 false negative studies. Of the 40 abnormal AGAb scans in patients with confirmed bone infection, 29 (72.5%) showed hot foci and 11 (27.5%) showed cold images at the sites of bone infection.

One case in which bone marrow fibrosis without infection was confirmed, was interpreted as indicative of infection. Sensitivity and specificity were 97% and 88% respectively.

We conclude that AGAb scans are very usefull in detecting bone infection.

In the AGAb scans, bone infection may show itself as hot foci at those sites where there is no bone marrow, or as either hot or cold foci at those sites wich normally present bone marrow. In the i0 patients studied, the detection of OM with MAK was more accurate and obvious than with HIG. Perhaps the lack of specifity of MAK in the vertebral column could be improved with HIG. These preliminary results show, that ~Tc-HIG may be a potential tool for the diagnosis of chronic OM.

W. Becker , G.Horneff, F.Emmrich , G.Burmester, F.Sefer, A. Schwarz, J.Kalden, F. Wolf, Department of Nuclear Medicine , and tnternal Medicine f1I, FRG Tc-99m-labelled anti-CD4-(T-help.er lyrnphocytes) antibody scans for imaging of rheumatoid arthritis CD4 expressing T-lymphocytes are involved in the pathogenesis of rheumatoid arthritis. So anti-CD4-antibodies should bJe able to tocalize specifically all actively diseased joints. Prospectively 3 patients with chronic polyarthritis were examined with three phase bone scans and with 2rag of 555MBq Tc-99m-]abelled antHCD4 (lymphocyte) antibodies, The tqG1 isotypes were labelled according to the Schwarz method. ' 1" patient was examined with in-vitro antibody labelled Ficol/-Hypaque isolated CD4expressing lymphocytes. Whole body scans and joint scans were performed lh, 4h, 24h p.i.(a.p.; p.a.) The whole body distribution of the inected activity was calculated .Dynamic scans(lframe/min) of the joints were performed in one patient over 60m n mmediately after antibody injection. There was no difference in the antibody distribution between invitro and in-rive labelled cells. Actively diseased joints could be clearly imaqed as early as 75rain p.i. but not earlier, The images were comparable with the blood pool bone scans but not with the late bone scans(2h). About 4% of the activity was renally excreted, From 4h to 24h the splenic uptake(7.5%) decreased (4%), the liver uptake(25%) increased(30%), the bone marrow uptake (50%) was equivocal. The joint uptake (2%) slightly increased(2.5%) According to these data the authors conclude, that Tc -99m-labelled CD4 antibodies reliably image actively diseased joints in rheumatoid arthritis, Presumably the antibody labelled cells and not the antibody itself migrate into the inflamed joints. In comparison to granutocytes no splenic pooling could be demonstrated. So the typhaFbehaviour of lymphocytes could be maintained after" antibody labelling, In cementless total hip arthroplasty (]'HA) the secondary fixation of the prosthesis through osseointegration is necessary to achieve long term stability. In postoperative management and evaluation of painful hip arthroplasty it would be vary helpful to know the normal course and duration of the bony ingrowth of the implant. The aim of our study was to quantify the osseointegration of the prosthesis.with 9SmTc-diphosphonats bone scintigraphy.

In a prospective study nearly 200 patients were investigated 1, 3 wks., 6 and 12 mths after total hip arthroplasty ( THA ), with 3 phase semTc-diphosphonate bone scintigraphy. Quantitative measurements of osteoblastic activity was performed using ROI-technique marking the complete hip joint, the acetabular and trochanteric region, the tip and the collar of the stem in comparison to the contralateral bone,

The scintigraphic activity 1 week after implantation showed a summation of bone trauma with hyperperfusion and reactive osteoblastic activity. Enlarged activity was found around the socket as well as around the proximal stem. After 3 weeks an increased activity could be seen in the proximal part of the stem and at the tip with relatively low increase in the distal portion of the prothesis. 6 mths after implantion the activity decreased around the socket, the proximal and distal part of the stem still showed increased activity.

1 week after THA scintigraphic activity largely depends on bone trauma and hyperperfusion, after 3 weeks the beginning osseointagration is mostly responsible for the osteoblastic activity. 6 months later the ostsoblastic activity decreased but is still enlarged due to ongoing bony ingrowth and adaption on biomechanical needs. After 12 months the decrease of ostsoblastic activity continues but is still enlarged compare to normal bone. A different scintigraphical bshaviour may be a sign of non-integration of the prosthesis or loosening processes especially if there were mat by clinical or radiological findings,

L Eckart*M.Gericke ,,C.Otto*,F.K~,stner" *Dept. of Orthopedics,'Dept. of Nuclear Medicine Berlin Free University, UK Rudolf Virchow, Augustenburger Platz 1, D-1000 Berlin 65, FR Germany

Ectopic ossifications after total hip arthroplasty (THA) are an often occuring complication. An effective prophylaxis is only possible during the first days after operation. Therefore it would be very helpful to detect paraarticular ossifications in a very early stage.

In a prospective randomised study 80 patients underwent a 99mTc-diphosphonate sequence scintigraphy 7 days, 3 weeks and 6 months after cemenUess THA. Radiographs were done 3 weeks and 6 months after operation together with a clinical examination. 7 days after THA there was no reactive osteoblastic activity in the paraarticular region. After 3 weeks the scintigraphic findings showed a high correlation with the radiological results after 6 months. Clinically important ossifications (grade II-IV in the Broker classification) all displayed an increased diphosphonate uptake in the paraarticular region 3 weeks after operation. All patients without actopic ossification after 6 months had no paraarticular osteoblastic activity after 3 weeks, no patient with negative scintigraphic findings developed severe ectopic ossification. In a therapeutic study evaluating different prophylactic concepts against ectopic ossifications the bone scintigraphy after 3 weeks was an highly effective indicator of the therapeutic effect.

Ectopic ossifications after THA cannot be detected as early as necessary to realize an individual prophylaxis. 3 weeks after operation the bone scintigraphy is able to determine the extent of the ectopic ossification. The effect of a prophylaxis against ectopic ossifications can therefore already be seen after 3 weeks and ineffective methods can be ruled out without waiting 6 months for the radiographic examination. PAP and PSA are specific markers of tissue, used in management of prostate cancer (PC) patients (pts). Bone scan (BS) is sensitive in detecting bone metastasis (BM) in PC pt s-Serially we performed in 125 PC pts 650 serum RIA mea surements of PAP and 521 of PSA and 282 BS, for a period of 28.1 (5-57) months.

In pts evaluated prior to therapy(55 PAP measurements 43 PSA measurements, 52 BS), PAP was elevated in 78.2% and PSA in 100.0% and BS documented BM in 40.4% of the pts.Mean value of PSA prior to therapy in pts in remissi on was statistically different (p< 0.05) from that of pts with metastasis in follow-up. In 17 pts in clinical remission (209 PAP measurements, 169 PSA measurements, 34 BS) PAP was normal in 95.2% and PSA in 95.3% and BS negative in 100.0% of the pts.In 180 pts with evidence of metastatic disease (386 PAP, 309 PSA, 196 BS) , PAP was elevated in 59.3% and PSA in 83.8% of the pts. BM were documented in 122 BS. Before clinical evidence of disease, PAP was elevated in 24 and PSA in 35 pts; BS demonstrated BM in 29 pts. PAP and PSA declined in 100.0% of 8 pts in regression. In 60 pts that experienced progression,PAP increased in 76.7% and PSA in 88.0% of the pts.

Main conclusions were: i) PSA has higher sensitivity than PAP for diagnosis of PC and for detection of metastasis in follow-up;2) Levels of PSA prior to therapy has a prognostic value; 3) BS is essential for diagnosis of BM and can be the only positive finding,even before clinical evidence of disease. Compton-scatter correction is of prime necessity to improve scintigraphic image quality and extracted parameter accuracy. The conventional window acquisition (+ or -10%) is not entirely satisfactory. The proposed CFASS method allows to determine the spatial and energy distribution of the scattered photons. From list mode acquisition including energy information (60-180 KeY for 99mTc), an energy image sequence is derived. Then, estimates of the underlying spectral components (factors) are extracted from the sequence using a photopeak model as a constraint : one concerns the acquisition photopeak, the others the Compton-scattered photons. These factors are associated with factor images, which are the estimates of their spatial distribution. Results obtained with phantoms and patients using various radioisotopes will be presented. They show an improvement of the contrast of the images compared to the conventional ones. For a given acquisition, CFASS technique has the advantages :

-to process all scintillation events, -to depend on the patient as the data are processed on an individual basis, -to extract separately photopeak and scatter information. The conditions for a clinical implementation of the method will be discussed. Such an algorithmn was developed by Schmidlin* in 1972. Whereas this procedure had the advantage of a relatively short computing time increasing image noise was found when many iterations were performed. The purpose of this work was to increase the signal to noise ratio without decreasing image resolution 9 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 the projection elements 9 Thus, effects of digitalisation are minimized. The procedure is realised for rapid computation and therefore able to process routine PET data.

The RMS noise of PET images of a uniformity phantom increases from 6% for 10 iteration steps to 15% for 50 steps, whereas it increased from 24% to 41% if the image pixels were not weighted.' For the filtered backprojection RMS noise is 33% for the same data set. The image resolution (FttWM) was found to be 4.8 mm for all recontruction algorithms considered 9

The procedure described here is appropriate for the reconstruction of noisy tomographic data. It avoids image noise when many iterations axe done 9 In contrast to filtered backprojection it combines a high signal to noise ratio with an optimal image resolution 9 * P.Schmidlin, "Iterative separation of sections in tomographic scinitgrams." Nuclear-Medicine vol 11, pp.1-16, [1972] 53 M. Ivanovis D.A. Weber. Brookhaven National Laboratory, Upton, New York

Monte Carlo simulations of a Tc-99m point source placed in circular and elliptical phantoms made of one, two or three types of scattering media were used to describe a scatter distribution function, SDF, and its dependence on source depth, media density, changes in media density and source distance to the the boundary between two different media. SDF was fit to a single or dual exponential function and slopes and amplitudes of SDF as a function of depth and medium density were evaluated. The slope of the SDF is almost independent of medium density, but shows a strong dependance on source depth. The slope of SDF is best described by a power function of depth, y=ax b, with coefficients a=0.29• and b=-0.79• The amplitude of the SDF showed dependence on both depth and medium density, and can be described by an exponential function of depth for each medium with coefficients:

As=4.3 & bs=-0.025 for lung; As=16.2 & bs--0.129 for water; As=29.5 & bs=-0.255 for bone. SDF for nonuniform media shows a second peak in the vicinity of the media interfacefor a source placed in lower density medium. Amplitude of the second peak decreases exponentially as source distance from the interface plane increases.

Although the slope of the SDF is almost independent of medium density for uniform phantoms, it shows dependance on changes in media densities in the radial direction. The slope is best described by a power function of depth with coefficients a=0.349 & b=-l.06 for lung/water media combination, and a-0.471 & b=-l.16 for lung/bone media. The amplitude is an exponential function of depth. The equations derived for the slopes and amplitudes of the SDFs provides the basis for developing an accurate scatter correction algorithm for SPECT. SPECT images are impaired by the absence of any correct and appropriate attenuation correction. A new and fast transmission technique has been designed to measure attenuation coefficients (~ C) to be used towards a true correction. This technique combines a point source (PS) of activity (1-2 mCi) with an uncollimated yC. The PS is obtained by a collimated lead shield syringe having a small aperture and fixed on a rod. The rod rotates with the head of they C (Sophy DSX rectangular). The cristal is protected by an obstructor limiting the field of view to a rectangular window and aligned with the PS both separated by 70-100cm. Each projection is acquired in one second. It has a cone beam geometry. Data are rearranged, slice by slice, in a set of parallel projections before reconstruction with the standard SPECT software. Due to the cone beam geometry, the total field of transverse reconstruction is i0 cm wide, 5 cm on each side of the plane described by the source, pC values are calculated with the equation E~i = Ln (N0/N) where NO is a blank acquisition. Results in cold phantoms using a Tc-99m PS show a good resolution (FWHM < 8 mm with 64 x (64x64) projections) in the transverse plane. Furthermore, pC values show less then 5 % error on a pixel basis and 1% error on an average basis. Conclusion : pC can be obtained rapidly with a point source of small activity of any given isotope and with an uncollimated rotating yC. SPECT images can then be corrected for attenuation, using pC mapping, and an appropriate algorithm.

Although most ECT systems provide 3-D data, quantitation is usually performed on single slices only. Obviously this strategy is inefficient when the object extends axially over more than one slice. Quantitation of activity concentration or size of art object from an image can be viewed as a parameter estimation task. The Cramer-Rao lower bound (CRB) on the precision with which these parameters can be estimated reflects the fundamental limits of quantitation.

We calculated the influence of the axial extent of the data on the CRB on the standard errors on estimates of activity concentration and size. We assumed a 3-D Gaussian object of unknown activity and size on a 3-D Gaussian background of known size and unknown activity, imaged by a system with a 3-D isotropie Gansslan point spread function (PSF) . The FWHM of the PSF was 2.4 pixels; background size was 10 times the FWHM, and we studied lesion sizes equal to and 5 times the FWHM.

The percent standard error was calculated for several values of axial data extent (expressed in terms of the object size ~osj) and normalized to the percent standard error for estimation from the central slice (see 25 Increasing the axial data length from a single slice to twice the object size (4 r led to an improvement in precision corresponding to a 2.5-3 fold increase in sensitivity even for the small object. Our remits imply that significant progress in quantitation can be achieved without hardware modifications simply by using morn of the data that is already being collected. Development of true 3-D quantitatiun algorithms for clinical application should proceed with high priority. 1-123 MIBG scJntJgraphy has been used to delineate abnormalities of adrenergJc innervation in human myoeardium but characterization of a normal pattern is lacking. In determine a normal MIBG distribution in myocardJum 15 normal volunteers, 35-52 years old, were injected 5 mCi of 1-123 MIBG and SPECT imaging was performed 1 and 2 hrs later. 1 vertical long axis and 4 short axis views were analysed and variation in MIBG distribution > 25% was characterized as nonhomogeneous uptake. 6/15 subjects showed homogeneous MIBG uptake in both 1 and 2hrs images, while 9/15 showed intraimage heterogeneity; All 9 subjects showed reduced uptake at the apex while 2 also had defects to the inferior wall and 1 to the lateral wall. MIBG washout from 1 to 2 hrs ranged from 0 to 50% and varied tlnpredictably between walls and subjects.

In conclusion: 1) apical defects during MIBG 5PECT imaging are common and should be interpreted as normal variant 2) washout rate cannot help in de]ineatJng a normal pattern. MIBG, a structural analog of norepinephrine, enters the myocardial nerve terminals by the uptake i pathway, an ATP dependent mechanism. Therefore, MIBG imaging may represent a tool for the evaluation of myocardial metabolism and viability. The extent of Thallium (TI) and MIBG cardiac defects was compared in 14 patients with CAD. Infarcted areas was defined from Xray findings (hypokinesia + occluded vessel), ischemic areas from Xray findings (stenosis > 70 %) and from the presence of a significant redistribution on the delayed TI scans. TI (3 mCi) tomographic acquisition was performed immediately after dipirydamole infusion (i mg/kg) ; half an hour later MIBG (4 mCi) was injected. Dual isotope imaging was performed 3 hours later. Tomographie imaging and reconstruction were performed in a standard manner.

Bull's eye plots of short axis slices were used to assess quantitatively TI and MIBG uptakes in % of their maximum myocardial value. Results (mean + SD) :

Infarcted area 58 + 20 76 + 14 Ischemic area 77 + 14 83 + i0 Normal area 92 ~ 6 94 ~ I0 ANOVA demonstrated that MIBG uptake values discriminated between the 3 areas (p < 0.0001) while TI uptake values only descriminated between normal and infarcted areas (p < 0.05). Thus, MIBG imaging appears more powerful than TI imaging to detect viable myocardium and may represent a guide for the indication to a mechanical revascularization.

J.Lekakis, P.Kostamis, D.fsinikas, N. Vass.i lopoulos, A.Antoniou and Sp.Noulopoulos Dpt of Nuclear Medicine and Clinical Therapeutics "Alexandra" University Hospital, Athens, Greece.

Experimental data show that acute myocardial infarction (MI) resu]t in regional depletio(~ of myocardial cathecholamJne stores which is more extensive than the associated myocardial necrosis. To investigate the extent of myocardial denervation following HI in humans we examined 8 patients (pts) with recent NI (7-12 days old). Resting TI-201 SPECT imaging was performed to assess regional myocardial perfusJon. 1-123 Meta~odobenzylguanidine (M.I.B.G) was used to evaluate adrenergJc innervation from SPECT 4 hours Following NIBG administration. T1-201 and 1-123 MIBG defects were evahated quantitatively using polar maps and differences Jn defects were expressed as percentage of the total left ventricular mass. In all pts 1-123 NIBG defect was larger than TI-201 defect and difference ranged from 23,5% to 61,4% of left ventricular mass (52,3_+21,3%). In inferior MI difference was lower than anterior HI (2%4_+7,7% vs 54,2_+5,6,~ p 0,01).

In conclusion: a) pts with recent NI present an area of adrenergic denervstion which is larger compared to T1-201 perfusion defect b) pts with anterior infarctJon have a larger area of catecholamine depletion. 

Iodine 123 radiolabelled meta-iodobenzylguanidi~ acts as an ar~logue of noradrenaliue and as such is concentrated in adrenergic nerve terminals. This concentration has been quantified using a SP~T gamin cmera system in 29 patients.

The control group cormisted of 12 patients suffering fxom supra-ventricular tachycankia with no sympathetic component as judged by electro-physiological inv~tigatioilm imdertake~ in our institution. The study group comisted of 15 patients with emercise ~10~ced ventricular tac~ with a prove~ s~n~tlmtic c~t.

Two cardiac tx~ ~tiet~ also st~ed to emm~d~e the ~ of the MIBG uptake. Following injection of the 1-123 MIBG, sca~ was Imdertaken at three hours to allow equilibrati~al in the admmergic neurones.

Comparison between the twogroups~a well defined 'notarial' pattern with broadly homogenoes uptake of activity in the prop~qB~ to ndd-Beptum and the bamo-lateral left-ventricularwall. In the vr gnm~ each patient bad superimposed on the nonnal pattern a focal aacea of increased ~ptake indicatiug abnormal sympatheHc activity.

This study establishes the feasibility and quality of 1-123 MIBG imaging in arrh~ patients and demmi~trates the potential clinical value of this investigation1 as 10elt of the evaluatio~ of any abnormal focus. Aim of this study is to establish the efficacy of 99mTc-DMSA (V) in detecting occult metastases in patients with out clinical appearance of disease with persistent eleva tion of serum calcitonine after radical thyroidectomy. 9 pts (i month -15 years after radical thyroidectomy) were studied by whole body and regional scans after i.v. inj. of 555-740 MBq of 99mTc-DMSA (V). The serum calcito nine ranged between i00 to 22218 pg/ml. 2 pts underwent respectively 2 and 3 scans at 2-4 months intervals. At the first study, a pathological uptake was observed in 6 eases (5 in mediastinum, i in mediastinum plus neck).The se findings were subsequently eonfirmed by CT or MRI (i-4 months later). In one patient with a positive result in mediastinum, a subsequent study performed 2 months la ter, after radical resection of recurrence, showed an aspecifie sternal uptake. The third examination (4 months later) was positive in the neck. As regards the 3 patients with negative findings, 2 showed a clinical recurrence 4-12 months later (in one case with a positive scan). The last one is still free of disease, ~ months later. In conclusion in our experience 99mTc-DMSA (V) is a successful imaging method in early diagnosis of occult metastasis. In case of negative findings the study must be repeated every 4 mos. or in case of clinical appearance of disease. [• aim of this study was to assess the role of ~mTc(V)]DMSA scintigraphy in the management of patients with MCT. i0 patients with suspected primary, recurrent or metastatic MCT were studied. 2 patients had primary disease, 7 patients were asymptomatic but had persistent and serial elevations in serum calcitonin following previous thyroid resections for MCT and 1 asymptomatic patient with normal serum calcitonin was studied because of suspected hilar node metastases. The serial calcitonin peak in the patients was 0.04-43ng/ml (normal <0.08ng/ml). Scintigraphy was considered positive in 7 of the asymptomatic patients, negative in I and equivocal in I. The 2 patients with primary disease had increased uptake before but not after thyreidect0my. Localised recurrence and distant metastases in soft tissue (4 patients) and bone (I patient) were detected in these patients ~ and this resulted in surgical resection (3 patients) and early r~iotherapy (i patient). We conclude that [~nTc(V)]DMSA is a useful imaging agent in the evaluation of asympt0matic MCT patients with or without hyperealcitonemia, Aim of this study was to compare three different scintigraphic techniques for the localization of local recurrences and metastases in patients with medullary thyroid carcinoma.

Overall, 30 investigations were performed on 7 patients (3 men, 4 women, aged 22 to 65 years) one month to 8 years after the first surgical intervention ~ Three successive scintigraphic studies were performed in 5 patients ( 6 x 3 studies) within 2 weeks using TI-201 chloride, Iniii labeled F(ab' )z fragments of the anti-CEA monoclonal antibody BW 431/31 (MoAb), and 1-131 meta-iodobenzylguanidine (MIBG) . Additionally, ii studies were performed with the In-ill labeled MoAb fragment BW 431/31 (7 studies) or the Tc-99m labeled anti-CEA MoAb BW 431/26 (5 studies) . CT scans and ult rasonography demonstrated partly normal partly equivocal findings. Serum CEA levels were elevated in 4 patients. Golden standard for classifying s cintigraphic results were biopsy /histology /surgery /cytology.

Six regions were classified positive or negative in each study: thyroid region, 4 quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, TI-2GI was true positive (TP) in 7, false positive (FP) in i, true negative (TN) in 22, and false negative (FN) in 6, resulting in a sensitivity of 54 % and a specificity of 96 %. f-131 MIBG was TP in 4, FP in 0, TN in 23, and FN in 9 sites with a sensitivity of 31% and a specificity of I00 %.

Immunoscintigraphy (108 sites overall) was TP in 16, FP in 5, TN in 83, and FN in 4 sites resulting in a sensitivity of 80 % and a specificity of 94 %.

In conclusion, immunos cint igraphy with Inlll/Tc-99m anti-CEA F(ab' )2 fragment/antibody is superior to scintigraphy with TI-201 and 1-131 MIBG. Curative treatment of MTC requires surgical excision. Recurrences can be detected early because of elevated serum CEA and/or thyrocalcitonin (TCT) levels but must be localized (neck, mediastinum or obdomen) to facilitate surgery. IS using anti-CEA MAb offerts a useful alternative to morphological investigations (US, CT, MRI) for such localization.

the study involved 8 patients (2 women, 6 men) 30 to 61 years of age who had previously undergone surgery for MTC and were considered in complete remission. Recurrence was suspected because of high serum CEA and/or TCT levels. IS was performed to localize the recurrence site. Three days after injection of 1 mg (lllMBq) of In lll-labeled anti-CEA MAb F(ab')2.(Indimacis-ACE| ; CIS Bioindustries, France),

tomography and planar scintigraphy were performed at the cervicothoracic level. Anatomical landmarks were provided by previous Tc99m-MDP and Tc99m-albumin injection. Results : Anti-CEA IS was true-positive 5 times (i cervical and 3 mediastinal sites confirmed by surgery; 1 case with 4 bone localization, one of which was not imaged by radiography and conventional bone scintigraphy) ; true negative 1 time (because of secondary markers normalization without symptoms of recurrence); probably false-negative 1 time (no site detected, but CEA level continually increased); and doubful 1 time (recurrence site remains unknown).

Anti CEA IS is usefull in MCT for postoperative management and early detection and localization of recurrences. 131I scintigraphy is a recognized technique for the diagnosis of DTC metastases, but it does not always allow their accurate localization.

Since sometimes the lesions are not visible on Xray images and since they may be treated by local therapy (surgery, radiotherapy), we try to improve the localization of the 131I uptake by bone anatomic landmarking.

: After a diagnostic or therapeutic dose of 131I (185 or 3700 MBq) and 3 hours after an injection of 550 MBq 99mTc-MDP, 2 images are recorded simultaneously using a double tracer technique.

22 examinations were carried out on 16 patients treated with total thyroidectomy and 131I for DTC.

: The 131I scan was positive for 10/16 patients. Our procedure was contributive for 6 of these i0. In 4 cases, there were no CT scan abnormalities : in 2 cases, 1311 uptake was related to bone metastases (BM) (i costal and 1 clavicular) and in the other 2 cases, 131I uptake was not localized in a bone structure. In 1 case, 131I uptake was just above the sternal notch and the MDP scan guided the surgeon. In 1 case, a BM was already known but MDP scan showed other localizations, which didn't accumulate 131I. In 4 cases with known lung metastases or BM, the bone anatomic landmarking was net contributive. After a total thyroidectc~y and before 1-131 ablation, it is customary to obtain a diagnostic survey scan. We have used 5-10 nCi doses and encountered several cases who had functioning tissues with avid uptake on diagnostic scan, yet showed ~ch less uptake of subsequent therapeutic 1-131. This finding suggested the possibility that the "diagnostic" dose of 1-131 was suppressing the cellular function of the target tissue.

We reviewed a total of 22 patients (17 papillary, 3 follicular, 3 mixed) who had a total thyroidectomy, 5-i0 mCi diagnostic scan, 100-200 mCi 1-131 Rx and a scan using the therapy dose. All were off T4 for 6 weeks and off T3 for at least 2 weeks. Eighteen of 19 who had TSH assays done showed elevated levels (>50uIU in 13, 16 to 49uIU in 5). One without an elevated level received TSH injections. The scans using the therapy dose were co~pared with the diagnostic scans, and the relative uptake by the target tissues were visually assessed.

The result showed that the uptake of the therapy dose of 1-131 was less than expected in the target tissues in 16 of 22, more in 3, and the same in 3 patients. The lesions which took up more 1-131 on the diagnostic scan tended to show less uptake of the therapy dose.

We conclude that a 5-10 mCi "diagnostic" dose can impair the uptake-function of the thyroid remnant or metastasis, and prevent delivery of the maximal dose of 1-131 at the time of therapy. Diagnostic doses of this range may best be reserved for follow-up of cases whose initial low-dose (less than 5 mCi) survey is negative. The Hurthle-cell, eosinophilic or oncocytic carcinoma of the thyroid does not have any 1-131 uptake, therefore, the usual strategy of 1-131 scintigraphy cannot be used for follow-up. We investigated the role of TI-201 scintigraphy in patients with eosinophilic forms of thyroid cancer. We evaluated'182 TI-201 scans performed in patients with thyroidcancer between 2/87 and 12/89. All patients had clinical examinations, serum thyroglobulin levels, ultrasound examinations of the neck, and chest X-rays. In 167 cases 1-131 scans were performed within 3 months of the TI-201 scintigraphy. There were 118 studies of papillary (PC) or follicular (FC) carcinoma, 35 studies of mixed oncocytic-papillary (OP) or oncocytic-follicular (OF) and 29 studies of pure oncocytic cancer (OC). TI-201 scintigraphy was performed with 75 MBq, planar scans were obtained 30 minutes p.i., followed by a SPECT study of the chest. 

1-123 (S) -(-)-2-hTdroxv-3-iodo-6-methoxy-N [ ( 1ethyl -2 -pyrrol idinyl ] m@th~l ] -benzamide ( z2mIBZM, spec: act. 1380-6400 Ci/m~ol) ha@. recently been synv.neslzeQ Dy some or us in a sliqhtly modified method along w-ith its precursor, S[-)BZM, as %~ii as vine stergoisomer R(+)BZ~ The present study vailda~es .th/s newproduct for D2-receptor binding my an zn vzv_ro stu~.y in rat brairL

In vitro saturatlon binding curves with I=3IBZM for rat striatal membranes uszng i0 ~M S(-)W%~piride to determine aspe.ciflc binding yielded a ~no~ 0. 28 nM (SEM 0. 08; n=4). Displacement curves Eor_n with .~=3IBZM ~ 3H Spiperone as liqands revealeQ the same oraer orincreasing po~gncy for ,v~r.ious drugs: R(+)BZM (Ki 2. 7 and 2. 4 ~S), S(-)~piriae (Ki 0. 15 and 0. 15 ~M), S(-)BZM (Ki 0. 033 and D. 32 ~M) and S(-)IBZM (Ki 2.6 and 1.2 nM, respectively ).

In vivo ~/ptake of 50 ~Ci za3IBZM in rat brain was st .ud/ed at various time, points after injection in the tail veill Various br~in regions were di'ssected and counted for radioactivity. The striatum/cerebellum (S/C) ratio increased from I. 5 at 5 minp. i. to 6.9 at 2 h D.i. The olfactory tubercle/cerebellum (O/C) ra%io increased from I. 6 to 3. 3. Coinjection of 40 nmol S(-)IBZM or 200 nmol H@lope.ridol cli'sl~aced z23IBZM as estimated at 90 mln p.z. on v_ne nasis of the S/C and O/C ratios. 'Ine S/C ratio aecreased from 6. 2 at 90 m/n p.i. to • ? .my coinjection of 4 ~/~oi S(-)BZM and to 4. 1 by cozn3ecv~on or 4 ~mol R(+)BZ~ Also the ~. C ratio a ecreased from 2. 6 to I. I and i. 8 bY coinjection of 4~mol S(-)BZM and R(+)BZu respeotigely. Thus~ the suereoisomerity of the displacement by the active S(-)BZM and th~ inactive R~+)BZM could be confirmed in vivo. Displacement was also observed in s ubstant.ia nlgra, and pons-medulla oblonqata but not zn nlppo~ or ~rontal and occipi~31 cortez~ respec~zve• . _ Th.e_data provide u@ the r~uired background to llnitiate in vivo minding stud/es zor D2-receDtors in basal ganglia of h~ patients using 1-123 IBZM in SPECT analyses. Investigations into the use of antibody-streptavidin (AB-ST) and labeled biotin to improve radioimmunotargeting have shown background levels drastically reduced over the conventional approach. Nevertheless, accumulation of lll-ln-Biotin in normal tissue as well as AB-ST independent accumulation in tumor, was observed. Altering the biotin molecule to reduce this nonspeeific uptake without decreasing specific localization has been investigated. Three EDTA and DTPA derivatives of biotin have been synthesized. In addition to the DTPA-biocytin dimer (i.e. 2 biotins per molecule) the monoderivatized EDTA biotins have been synthesized. The labeled biotin derivatives were administered IP to normal mice implanted with avidin beads in one thigh. At 24 hrs post administration, a wide variation in biodistribution was observed among the biotin derivatives. The most favorable results were obtained with monoderivatized EDTA-biotin which showed the lowest accumulation in normal tissues but equivalent uptake in the target with respect to DTPAbiocytin. Averaged over 7 tissues sampled, the target/ nontarget ratio was 70 vs 8 for monoderivatized EDTAbiotin vs. DTP~-biogytin (n=6) and 140 vs 9 in an identical repeat experiment (n=6). Equivalent observations have been made in tumored mice and in culture with tumor cell lines. Positive accumulation of DTPAbiocytin was measured in tumor cells independent of AB-ST, however, a 16-20 fold reduction is demonstrated with EDTA-biotin monomer. These studies show that modification of the biotin species can not only alter accumulation in normal tissues but also reduce the AB-ST independent accumulation in tumor tissue.

J.Kropp*,F.F.Knapp,Jr.**, T.Assmann*,S.Urmetz*, H.P.Nissen***, K.R.Ambrose**, H.J.Biersack* *Nuclear Medicine, *** Dermatology University Bonn/FRG ** ORNL Laboratories Oak Ridge/USA

We administered 1-131-(p-iodophenyl)-(IPPA), I-125-(p-iodophenyl)-3-R,S-methyl-(BMIPP), and I-125-(p-iodophenyl)-3,3-dimethyl-pentadecanoic acid (DMIPP) to working and non-working rat hearts. After a 15 min perfusion period the hearts were lyophilized and weighed. The labeled lipids were extracted by an acidified Folch technique. Lipids were analyzed by high performance liquid chromatography (HPLC). Endogenous phospholipids (pl) were detected by UV at 203 nm and non-polar lipids (npl) at 214 nm. The first column (sio2) removed the npl as an early peak and the pl were separated. The npl were then separated into components with a RP 18 column. Effluent samples were collected and counted. The principal radioactive peaks ( en usea in single photon emission computea t o_.~phy (SPECT) to measure the benzoaiazepine (BZ) receptor aensity in several cortical hrrain r~iors (00) and the cerebellum (CB) in 6 healthy male numan volunteers ~age 25-50 years). SPECT scans were made 0. 5 and 3. 5 h after in3ection of 5 mCi ~=3I Iomazenil (SPECTI and 2, respectively). In 3 subjects,. 1 mg cold flu~enil was injected 2 h zoilc6ring r_ne zlrst injection (u~up A). In ~ owner subjects, no cold flumazenil was in3ected (C~3m~p " B). Ratios of wne aensity of radioactivity of 4 different cortical regions to wne cerebellum were calcuzater parieto-occipital (PO), p@rietal (P), zrontal (F), occipital (0) The correlation between evolution of rCBF defects in time as measured with SPECT and clinical condition was examined in 26 patients with brain infarction. Thallium-201-diethyldithiocarbamate rCBF SPECT imaging was performed within 24 hrs after stroke onset and repeated at 2 weeks and 6 months. Clinical assessment took place at the same intervals. The size of the flow deficit, both initially and after 6 months, on a visual semiquantitative scale, correlated with the clinical condition. Six out of 15 available SPECT scans showed some hyperfixation at 2 weeks. These patients had no better prognosis in terms of motor or overall function than patients without hyperfixation. At 2 weeks the SPECT disturbance had significantly decreased, without clinical correlate. The flow defect 6 months after the infarct had decreased in size in 9 from 15 available scans, this was parallelled with a more favourable motor improvement than the 6 patients whose deficit grew. The flow deficit at 6 months was somewhat smaller than at admission, this difference was not significant. In conclusion it can be said that the size and intensity of the flow deficit, either in the acute or in a more stable phase, do correlate with the clinical condition of the patient. Scans taken 2 weeks after brain infarction yield unreliable clinical information. The specific property of Tc-99m HMPAO is that its distribution pattern in the brain tissue is determined in a short period and kept for a long time. This property was applied to the evaluation of haloperidol (H) effects on brain function in schizophrenia using a high resolution SPECT system (Toshiha, GCA9a00A). In three schizophrenic patients one control subject, 555 MBq of HMPA0 was injected. Then I0 mE of H was intramuscularly injected at 3 min p.i. of HMPAO. Immediately after the Ist SPECT study (baseline) 925 MBq of HMPA0 from the same vial was additionally injected. Three minute later the 2nd SPECT study was performed. After reconstruction the Ist SPECT images were subtracted from the 2nd images to obtain images during H. EEG was simultaneously monitored throughout the study. and parietal count ratios were 0.92-+0.05, 0.93-+0.04, and 0.94-+0.03 at baseline, and 1.09+0.08, I.]5+0.13, and 1.08-+0.05 at H, respectively, for both hemispheres. These ratios were 1.01-+0.03 at baseline and 1.01 -+ 0.04 at H in the control subject. These r'esults suggest that the antipsychotic drug has substantial effects on regional brain function in schizophrenia. The drug may improve frontal lobe hypofunction and suppress temporo-parieto-oceipital hyper'function especially in the dominant hemisphere. 

(P) who have suffered from generalised hypoxemia due to cardiovascular arrest may have severe memory deficits such as global amnesia (GA) without pathological findings on NMR scans. The aim of this study was look for changes of the regional cerebral metabolic rate of glucose consumption (rCMRGIc) in such P. rCMRGlc was measured in 7 P (P1-P?) with GA and normal NMR scans using the high-resolution PET PC-4096 and the standard 18F-fluoro-deoxyglucose method, rCMRGIc was measured in various cerebellar, subcortieal, and cortical structures, and ratios (MCR) were calculated between rCMRGIc in each structure and the mean cortical rCMRGIc. The data obtained in the P were compared to the normal range (average • 2*s.d.) of 20 age-matched normal subjects. Significant regional decreases of either rCMRGIc or the MCR were observed in 6 of 7 P. These involved the thalamus in 4 of 7 P, the cerebellum in 2 of 7 P, the medial temporal cortex in 2 of 7 P, and the striatum in 1 of 7 P. P1 had an involvement of thalamus and medial temporal cortex, P2 an involvement of cerebellum and medial temporal cortex, and P3 an involvement of thalamus and striatum. P4-P6 had involvement of one structure only (thalamus or cerebellum). These data indicate that regional metabolic disturbances (RMD) detectable by PET occur in P with GA despite normal NMR scans. The localisation of these metabolic disturbances in brain structures relevant to memory suggest a possible causative role of these RMD in GA. CEA-BLOOD-LEVEL:INDICATION   FOR  IMMUNOSCINTIGRAPHY? There is the demand for sensible and sure techniques for detecting early tumor recurrences and metastases in patients with colorectal cancer. Ultrasound and CT often fail in the early stages because tissue-morphology alone presents no strong criteria at this time. We have tested the clinical value of the 99mTclabeled monoclonal anti-CEA antibody BW 431/26 (Behring/Hoechst) in 24 patients with increasing blood-levels of CEA (9 colon-,7 rectum-,2 hepatocellular-,l breast-cancer). Ultrasound and CT findings were doubtful (7) or negative. Pathologic antibody-uptake we got in 24 localizations,18 due to metastases in the liver (ii) and lymphnodes (7),3 due to local tumor recurrences. False positive uptake was caused by atypical vessel-formations

(3). Cold lesions caused by metastases occured in 7 tumors of the liver, two of them due to hepatocellular carcinoma. In sum we had 21 true positive findings (hot and cold spots together), 3 false positive findings (correct diagnosed uptake in a kinking aorta or in bowel structures after 24 h were not judged as false positive),2 false negative, and 4 true negative findings. We can conclude that doubtful or negative findings in CT,ultrasound,and MRI) are an indication for immunoscintigraphy in patients with increasing CEA-levels in the blood, as there is a high probability of tumorgrowth. anti-CEA/19-9 (IMACIS-1) = monoclonal antibodies. In 28 pts. with known primaries (group A) IS was performed to exclude metastatic disease, in 32 (group B) because of suspected recurrencies, and in 8 (group C) as routine follow-up. Surgery revealed a total of 69 lesions: 28 local recurrencies, 28 liver metastases, and 18 lymphnode metastases. Detection rates of IS were 21/28 (75%), 18/28 (64%), and 8/18 (23%) respectively. 5/6 unknown lesions were found in group B (2 local recurrencies, 3 liver metastases), 1 in group A (liver metastasis). In group C, 6 studies were found true negative, 2 false positive (specificity 75%). Only 2 IS studies led to therapeutic consequences: 1 local recurrency/1 liver metastasis were resected. So, clinical impact was observed in pts. with suspected tumor relapse and inconclusive outcome of conventional diagnostic procedures (16% of group B). Profit of routine IS, however, was low (8% of group A and C). These findings do not support general employment of IS. We have performed radioimmunoscintigraphy (RIS) in 30 patients (68 +/-9 years) with eolorectal carcinoma 48 hours before surgery. In 23 patients the primary lesion was studied, in 6 the recurrences and in 26 we looked for the posibi!ity of metastases (MI) in liver, with a total of 55 lesion sites. The antibody used was the BW 431/28 (BeLting) labelled with 99mTe (851 MBq), which was proved to be the most selective antibody for CEA out df three different antibodies studied by immunochemistry. The scans were performed al a and 24 hours after the injection. After surgery and histologycal study we have found :  'n  TP  TN  FP  FN  Primary lesion  23  13  0  I  9  Recurrences  8  4  1  0  1  M1 in liver  26  6  18  1  1  Total  55  23  19  2 ii The ~31/26 seems to be aseful ,in the localization and extension of eolorectal carcinoma. There was no relationship between the CEA levels and the RI8 findings The FN were tumors poorly diferenciated. The sensibility (S) in recurrences was 80% with an accuracy (A) of 83.3%. The S was lower in primary lesions (S=59.1%, A=56.5%} due to 5 FN in rectum, 2 FN by peritoneal careinomatosis and 1 FN by necrosis. The M1 in liver showed as hot or cold lesions (S=85.7%, A=92.3%). We recommend to be careful with cold lesions, as they could represent also non meoplasie lesions. In order to compare IS and PET for the detection of primary (n=3), or recurrent (n=10) colorectal adenocarcinoma, we studied 12 patients, 4 females and 8 males, aged 48 to 79, with CEA values ranging from 2.5 to 1755ng/ml. All patients were submitted to IS (2mg of monoclonal antibody BW431-26 labeled with 30.6+2.9mCi of 99mTc -98% efficiency), and to a PET study (2-10mCi of tSF-FDG). Eight healthy volunteers underwent PET as a control group.

Patients were studied by IS at 7+2 hours post-injection (pi) by both static anterior and posterior views of the whole body and SPECT imaging of pelvis and upper abdomen on a GE400AC camera with a high resolution collimator. Repeat static images were acquired at 25+6 hours pi.

PET emission scans of pelvis and/or upper abdomen were later performed, after bladder catheterization when indicated, on a whole body tomograph (Siemens ECAT 933) at 50+._20 minutes pi.

IS and PET data were evaluated by 3 independent observers, and their results were compared to surgical histology (n=10) and to classical radiological and endoscopic procedures.

Preliminary results show a good sensitivity for the two methods. Both seem particularly helpful in postoperative differential diagnosis between pelvic benign fibrosis and cancer recurrence. The tumor visualization contrast in PET is higher than with IS, but PET suffers from two drawbacks: a single PET acquisition covers only 10cm of abdomen, while IS covers 50cm at once, and PET requires bladder catheterization and washing to reduce disturbing urinary activity. IIIInL~B~'LL~ 0V-TL 3 F(ab')2:   IMPROVED DETECTION OF PERITONEAL METASTASES IN OVARIAN  CANCER PATIENTS COMPARED TO CT, MRI, AND ULTRASOUND. OV-TL 3 is a mouse monoclonal antibody of the IgGl subclass with a high specificity for ovarian cancer cells. In 24 patients (pts) the diagnostic accuracy of immunoscintigraphy (IS) with 150 MBq lllIn -OV-TL 3 F(ab')2 was compared to ultrasound (US), computer tomography (CT), magnetic resonance imaging (MRI), physical examination (PE), and serum levels of CA 125. Nine pts were suspected of having primary ovarian cancer (OC) and 15 pts of having recurrent or residual disease. Whole ibody counts (uncollimated gamma pamera) and planar images were obtained 3 hours and 1,2, and 3 days post injection (pi). SPECT images were acquired 2 days pi. Surgery followed in 17 pts and the exact localization of tumor deposits was compared to the results of the other diagnostic methods.

Results: The correct diagnosis (benign or malignant) was made in 92% (22/24) with IS, ~(17/24) with CT, 60% (12/20) with MR!, 75% (18/24) with US and PE, and 88% (21/24) with CA 125 levels. For omental and peritoneal localizations (n=21) in 13 operated pts with OC sensitivity with IS was 57Z, with US 19%, with CT and PE 10%, and with MRI (n=14) 7%. With regard to all OC localizations (n=34) 2 false positive localizations were found with IS, 1 with CT, and 3 with US. The mean (+ SD) biological whole body T% was 283 + 157 hours~ue to retention of lllIn in liver and b~ne marrow.

Conclusion: Immunoscintigraphy with lllIn -OV-TL 3 F(ab')2 is an accurate diagnostic method for the detection of @~ar~an cancer. For omental and peritoneal localizations immunoscintigraphy was substantially more sensitive than CT, MRI, ultrasound and physical examination. 

Purpose: Evaluation of Indium-111-1iposomes as s tumour imaging agent in patients with proven malignant tumours. Patients: 10 patients (9 males,1 female; mean age: 59.2 yrs.) with proven pharyngeal carcinomas (5cases), malignant melanomas (3 cases), a bronchial carcinoma (I case) and a Non-Hodgkin-lymphoma in I case were investigated using Indi~m-111-1abeled liposomes. 4 patients were treated by chemotherapy at the time of scintigraphic investigation.

Methods: Liposomes (100 mg VS 102; Vestar,USA) were labeled with In-| 11-chloride. Labeling efficiency was calculated by paper chromatography in all cases (75%-92%). Scintigraphic images were obtained 30min.,6h,24h and 48h p.i. (in addition 72h p.i. in I pat.). Results: 14 different tumour localizations were found in 10 patients (US,CT,surgery). 10 localizations of tumour disease were confirmed by liposome scanning (true positive: 10). 6 of these lesions were found to be positive only-on the late scans ( Breast cancer is the most common malignancy in female. To evaluate lymph node status biopsy of axillary lymph nodes was performed routinely. But in 20-30% retrosternal lymph nodes are infiltrated by mammary carcinoma. Internal mammary lymphoscintigraphy offers the possibility to evaluate true TNM staging, but is limitated by various anatomical details as single lymph chain and asymmetric lymph nodes. To improve this diagnostic tool, we investigated 21 patients by MRI additionally to lymphoscintigraphy (including SPECT in 5 patients). In 6/21 patients lymphoscintigraphy and MRI was normal. 8/15 pathological scintigraphic findings showed decreased uptake ipsilateral to breast tumor, 1/15 contralateral and 6/15 markedly asymmetrical lymph node status. In 6/15 patients with pathological findings by scintigraphy MR showed no lymph nodes in the suspect area. In 5/15 patients lymph nodes of normal size (lcm) were found by MRI and in 4/15 patients MRI showed enlarged lymph nodes without radionuclide uptake in scintigraphy indicating local infiltration. In conclusion MR investigation of internal mammary lymph nodes additionally to lymphoscintigraphy offers the possibility to improve TNM staging in breast cancer. Overall, 234 scintigraphic studies were performed. 181 studies were true negative without evidence of disease. 80 sites of disease had true positive Ga-67 uptake (in 21 pts/37 studies). 19 sites (in 12 pts/15 studies) were false positive. Among these, 7 were sites of persisiting colonic activity and 3 were in normal parotid glands. In addition, 31 benign lesions were detected and interpreted correctly in terms of malignancy. I0 lymphoma sites(in 6 pts/10 studies) were missed by scintigraphy. In all but two cases, scintigraphy detected at least one true positive site.

Sensitivity of Ga-67 scintigraphy was 89% calculated by sites and 79% calculated by studies. Corresponding specificities were 91% and 92%, respectively. Positive predictive values were 81% (sites) and 71% (studies), negative predictive values 95% (sites and studies).

In conclusion, scintigraphy with Ga-67 is a sensitive and specific method for follow-up in patients with Non-African Burkitt's Lymphcma. These results suggest that the added radiation safety provided and the consistent quality of the bolus injection obtained, will encourage the addition of a "ist Pass" phase to many of our clinical radionuclide investigations. The purpose of this investigation was to measure the count rate performance of a multiwire gamma camera (MWGC). The MWGC is a gas proportional device designed to operate at high count rates.

Data were acquired dynamically in one minute frames from a Ta-178 source in the NEMA Standards scatter phantom. The data base included high count rates typical of first-pass cardiac studies.

If the deadtime losses were zero, a plot of the logarithms of cps versus elapsed time would form a straight line with a slope corresponding to the 9.3 minute half life of the source. With a FORTRAN program, count rates were corrected for deadtime loss by a trial paralyzing deadtime and converted to their natural logarithms. Although not mathematically related, the data were shown to coincide with a 2nd order polynomial equation. The trial deadtime Twas adjusted iteratively after curve fittings until the coefficient of the squared term approached zero, indicating a straight line and the correct value of T.

The paralyzing deadtime determined by this method was 0.41 us. The validity of the method was further confirmed by the measured half life of 9.17 minutes, only 1.4% low. The camera therefore loses only 30% of the data whenoperated at 600,000 cps with Ta-178. Bar pattern images acquired up to 600,000 cps demonstrated no significant loss of spatial resolution or uniformity. This performance is unmatched by any NaI imaging device and is particularly useful in firstpass cardiac studies. 

A COMPARATIVE ASSESSMENT OF 3 COMMERCIAL PET SCANNERS Three whole body PET imaging systems were assessed as part of a pre-purchase evaluation procedure. The assessment was achieved by devising simple tests carried out with the aid of a SPECT phantom purposely modified for PET performance measurements. The PET scanners assessed were: (i) the Siemens 951, (ii) the Positron Corporatiom Posicam and (iii) the Scanditronix PC 4096-15WB. FOllowing a pre defined standardised test protocol ~ measurements of transaxial and axial resolution, uniformity, sensitivity, and cold lesion contrast were obtained. Flourine-18 was used throughout and cross calibration of isotope calibrators was also performed. The three scanners had radial resolution values varying from 5.0 to 5.gnm (on axis) and 6.7 to 8.1n~n (off axis). Tangential Resolution varied from 5.4 to 5.8ram (on axis) and 6.7 to 8.6ram (off axis). Axial resolution varied from 4.6 to ll.5n~n (on axis) and 6.6 to 13.6ram (axis). Sensitivity ranged from 77to 138 Kcps/pCi/cm3. Cold lesion contrast values for five different rods were measured and for the smallest, values from 22 to 37% were obtained. Systems differed most in their sensitivity and axial resolution. The method of measuring axial resolution to obtain a clinically realistic comparison is very important. Most of the differences between systems can be explained in terms of their design;crystal size, septa design and crystal/photomultiplier configuration being vitally important. A rare opportunity was seized to make a consistent comparison of state of the art PET scanner performance. F. Zito. A. Savi, M.C. Gilardi, V. Bettinardi, C. Messa, F. Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy.

The ASPECT is a ring-camera brain dedicated SPET system (JNM 30:796, 1989 ). Due to the 22cm transaxial xl0.5cm axial FOV, 3D brain images are acquired in a single scan. We have compared the performances of ASPECT, a rotating rectangular 7-camera (901A TOSHIBA) and a PET system (Siemens 931/04-12) in terms of spatial resolution, slice thickness, sensitivity and contrast 9 Tc-99m and Ga-68 were used for SPET and PET studies respectively.Spatial resolution (FWHM in mm) was measured in air at different distances (D) from the center. For the 7-camera acquisitions a 13cm radius of rotation was used to simulate clinical studies. Slice thickness (ST in mm) was measured in air with a point and a line source for the SPET and PET systems respectively. Slice sensitivity (SS in cps/uCi/ml) was calculated using a standard 20cm diameter x 10cm uniform phantom. Based on the first six months of experience, it appears that the integration of nuclear medicine and general radiology facilities is a unique opportunity to improve productivity and diagnostic accuracy 9 The incidence of non-accidental trauma, or at least public awareness of it has increased dramatically over the past several years. Child abuse is second only to sudden infant death syndrome and true accidents as a killer of children. This problem has not only medical but social and legal ramifications as well. Consequently, recognizing non-accidental trauma has become increasingly important for the Radiologist.

Nuclear Medicine Imaging plays a key role in the evaluation of skeletal trauma. Recent findings in our department show that diagnoses other than skeletal trauma are often identified by recognition of subtle and unusual scintigraphic findings. The subject material will place strong emphasis on the less mentioned but often more important visceral and intracranial injury.

Selected scintigrams from 15 cases of child abuse as well as appropriate correlative radiographs will be presented.

Specific scintigraphic abnormalities to be demonstrated include:

a. Visceral and soft tissue (e.g., duodenal hematoma, splenic laceration, renal contusion, hepatic hematoma, rhabdomyolysis and soft tissue hematoma). b. Cranial (e.g., intracranial bleed, edema, and infarct, cephalohematoma, skull fracture and widening of sutures While mIBG has become a standard diagnostic tool in neuroblastoma, other infantile tumors are lacking specific diagnostic techniques. Histological findings ere difficult to interprete and sometimes lead to wrong diagnoses. We have found antimyosin-antibodies useful for the 'histologic' in vivo classification of myosarcoma. 3 tumors showed uptake of myosin-antibodies, while histologically they were classified as neuroblastoma (mIBG was negative). In the diagnosis of ii primary tumors we had 7 true positive findings, 1 true negative result in a pseudotumor detected in CT, and 1 false positive result in a hemangiopericytoma. After therapy 4 of 12 children correctly were classified as tumor-free, 6 had proven tumor-rests, false positive findings in two children were due to necrotic tumorous tissue.Metastases were correctly found in 4 children, i0 children in the follow-up were classified as free of tumor, false positive findings were due to chordoma and osteorrhagia. We failed to diagnose small tumorous nodules on the pericardium end peritoneum in a boy with a tumor-conglomerate in the basal thorax.All rhabdoid-tumors (3) showed intense uptake of the antibody, although histologically they ere very different to myosarcomas. We conclude that immunoscintigraphy with entimyosin-antibodies represents a useful tool for diagnosing infantile tumors. DMSA renal studies are now accepted as the most sensitive method for the detection of chronic renal scarring in children with vesicoureteric reflux (VUR). In this paper, the interim results from a prospective study which examines the incidence of DMSA abnormalities in children at the time of acute UTI, the natural history of these abnormalities and their correlation with the presence of VUR is reported. 66 previously well children with acute UTI had DMSA scans performed within 72 hours of presentation; in 33 children (50%) 7 the studies were abnormal, with t~0 of 132 kidneys (30%) being abnormal. 27 kidneys have so far been rescanned at 3-6 months; the abnormal appearances have remained unaltered in 4, improved in 12 and become normal in 11. 10 have been rescanned at 12 months; of the 5 previously improving scans, 3 have now become normal and the other 2 continue to improve, while those 2 kidneys that were previously unchanged remain SO. 14/47 children who had mieturating cystourethrography were found to have significant VUR (grades 2-5); of these 14~ 12 had abnormal DMSA scans and the remaining 2 had dilated upper tracts on ultrasound examination.

The following provisional eonelusions can be drawn -1. The incidence of DMSA abnormalities at the time of acute UTI is high (50%). 2. There is a tendency for these abnormalities to resolve with time. It follows that DMSA scans performed in the first few months after UTI have to be interpreted with caution. 3. An abnormal DMSA scan at the time of UTI identifies most children with signfieant VUR and it would appear that a combination of ultrasound and DMSA scan identifies them all. These results may have major implications for the clinical investigation of children with UTI. In a prospective study the bone marrow scintigrams and MRI examinations of 21 children with Acute Lymfatic Leukaemia (ALL) were-compared with the bone marrow aspirates. The ages of the children ranged from 14 months to 17 years. Bone marrow scintigrams were made after i.v. injection of 99mTc-Nanocolloid (dose adjusted to age). MRI examinations (TR 550ms, TE 30ms) were performed on a 0.5T MR scanner (Philips Gyroscan). Bone marrow aspirates were taken from the posterior iliac crest. Abnormal scintigrams showed hot spots or defects, with or without expansion. Tumor infiltration presented as areas of low signal intensity on MR images. MRI had a sensitivity of 83.3% and a specificity of 73.1%. The scindgrams had a sensitivity of 57.1% and a specificity of 82.1%. Three false positive scintigrams showed one or more hot spots. Two false positive scintgrams showed local defects that were also seen with MRI. One patient with false positive hot spots on the scintigram developed a relapse after stopping the maintenance therapy.

Although the number of patients in this study is too small to allow definite conclusions, these findings justify fttrther investigation and follow-up of children with ALL. We suggest that localisation of bone marrow aspirates must be directed by MRI and bone marrow scintigraphy. In doubtful cases T2-weighted images should be performed. Urinary tract infections (UTI) in children are a well recognised cause of chronic renal scarring and renal failure in a small percentage of children. The need to detect the children at risk at initial presentation is therefore vital, At present ultrasound and plinar DMSA are the primary investigations of choice. Planar DMSA has been shown to be a sensitive method for detecting evidence of renal damage following UTI but its specificity is relatively low. We have used single photon emission computerised tomography (SPECT) in conjunction with planar 99mTe DMSA in an attempt to increase the specificity of this investigation. 22children with known UTI, age range 4-12y, have been studied with planar and SPECT 99mTe DMSA imaging using an IGe starcam system, 64 20 sec acquisition for 360 ~ and 3D reconstruction programme. The results of planar and SPECT imaging were compared with the results of IVU. 22 scars were detected by planar DMSA. Whilst SPECT DMSA detected 14 of the 15 scars on IVU. Sensitivity of planar and SPECT is 93% but SPECT shows a higher specificity (92%) than planar DMSA (79%). Duplex systems, foetal lobulation and splenic impressions are the cause of false positive DMSA studies. These normal variants were more readily evident on 3D SPECT images and distinguishable from true scarring. This study suggest that SPECT imaging with 3D reconstruction gives the sensitivity and specificity required to accurately detect the presence of renal scarring in children with a history of UTI. In order to determine the diagnostic reliability of IRMCU we evaluated retrospectively 49 consecutive children (31F, 18M), aged 1 mo to 13 yrs in whom renography followed by IRMCU was performed as part of the initial work up, together with X-ray micturition cysto-urethrography (MCU) and cystoscepy. On MCU, VUR were absent in 5, unilateral in 18 and bilateral in 26 patients. Stage III or more VUR were observed in 14 patients with unilateral and in 25 (42 units) with bilateral disease. IRMCU was performed when activity had cleared from the renal pelvis after routine renography with 1-123 OIH (14 -20 uCi/kg). 5 sec frames were acquired starting 2 min before and continuing for 2 min after micturition. 56/56 units with VUR III on MCU also showed VUR on IRMCU. Only 4/14 stage I-II VUR remained undetected by IP~MCU although low grade VUR is not expected to be seen by this method. With respect to MCU, overall sensitivity was high (94%) but specificity was low (50%), as 14/28 units with no VUR on MCU showed pathologic IP/4CU, i0 of which presented meatal latera!ization and/or dilatation of mild (4), moderate (5) or severe (i) degree, 2 granular cystitis and 2 vesioo-urethral dyssynergy. In 3 of them renal function was impaired as it was in 4/14 low and 20/56 high grade VUR kidneys. The association of morphological and/or functional anomalies with VUR demonstrated only by IRMCU may partly represent MCU false negatives. IRMCU as a non-invasive and sensitive test,is a valuable complement of renography performed during follow~up of VUR.

Aim of this study was to test the value of single kidney effective renal plasma flew (I~I~PF) measurement with ranalsequenttal scintigraphy (RSS) for the recognition of renal involvement in paediatric patients affected by urinary tract infection.

We studied a total of 321 renal units in 162 patients (age range 20 days -13 years, median 3.3 years), affected by urinary tract infection according to clinical, b~teriological and instrumental data. All patients underwent contrast urography for the recognition of renal involvement, which was demonstrated in 83 kidneys. RSS was performed and the single kidney ERPF was calculated from the 1-123 hippuran clearance with our method based on external measurements only. The cutoff value for classifying EP.PF as abnormally low was 270 ml/min, which was the mean minus 2 standard deviations of the ]~PF in a group of agematched healthy controls.

Of the 83 affected kidneys, 83 had an abnormally low ERPF (sensitivity 98%); of the 236 healthy kidneys 231 had a normal ERPF (specificity 98% ): 3 false positive and 2 false negative ERPF results were found. The predictive value of a positive test was 92% and the predictive value of a negative test was 97%.

According to these results, we conclude that the single kidney ERPF measurements using RSS with 1-123 hippuran is an accurate method for recognizing renal involvement in pediatric patients affected by urinary tract infection. This approach has the advantage over contrast urography of a lower radiation burden and over renal scintigntphy of giving also an assessment of renal function, which might be very useful for follow-up studies. It is intuitive that children with hydronephrosis, in whom obstruction cannot be excluded on diuretic renography, should be considered for pyeloplasty, particulalry if they have impaired renal function. In many such children, the hydronephrosis is detected antenatally. We studied the effects of surgery on renal function and drainage in 29 children with unilateral, antenatally diagnosed, hydronephrosis. Thirty-eight other patients with this diagnosis, who, for various reasons did not undergo surgery, were also studied. Patients were studied on 2-6 occasions at ages ranging from I month to 5 years using Tc-99m DTPA diuretic renography. Kidneyswith less than 43% of total function were considered to have impaired function. Obstruction was defined on the basis of the response to frusemide and bladder emptying. Although drainage improved in 9/29 following surgery, there was no significant improvement in function, even when only those patients with obstruction and impaired function were considered.

In the non-operated group neither function nor drainage changed significantly, even in those with obstruction.

Indeed within the same group function improved significantly in 6/38 presenting with impaired function. We conclude that DTPA diuretic renography is unreliable for diagnosing obstruction in this age group and that a randomised controlled trial to determine the benefits of surgery is needed.

Hospital, POBox 85500, 3508 GA Utrecht , The Netherlands   Tc-99m-MAG3 AND 1-123-HIPPURATE:  CONSTANT INFU-SION CLEARANCE TECHNIQUE (CI) Tc-99m-MAG3 has been proven to be suitable for renographic studies and in this respect MAG3 mimics 1-123-hippurate (OIH). Nevertheless, the renal clearance of MAG3 (MAG3(Rcl)) has found to be lower as compared to OIH (OIH(Rcl)) and wide variations in absolute values have been reported. When MAG3(Rcl) will be used as a measure for renal function, accurate measurement of its clearance is indispensable.

The CI permits precise determination of the clearance of an indicator and has been considered as the classical method. After informed consent both MAG3(Rcl) and Med; 30:1955 -1959 (1989 Gammacsmera renogcaphy was performed in the supine position after hydration of the patients. Background was eliminated by a two-step procedure, first subtraction of extrarenal background using a perirenal ROI followed by either division of the net curve with the blood background curve obtained from a ROI over the heart (relative function) or regression analysis according to the Rutland space method (absolute function) using the same heart ROI. The uptake slope values were taken as measures of the individual renal clearance of each indicator.

Mean difference between MAG3 and DTPA split renal function was -0.6%• (right kidney in per cent of total) or -0.9%• (diseased kidney in per cent of total). With MAG3 there was no difference in relative function with or without subtraction of extrarenal background. The 99mTc-DMSA (DMSA) and 99mTc DTPA (DTPA) or 99mTc MAG 3) were evaluated in acute pyelonephritis, to confirms the clinical diagnosis (by Jodal's criteria) and to est~ blish the early pyelonephritis damage. Two groups of chil dren were studied. The first (48 pts) with DMSA and DTPA the second (30 pts) with DMSA and MAG3. DMSA was performed 8 days after the onset of the first known event and the second examination 8-12 days later. Each child unde[ went ultrasonography and cystography to diagnose a malformative disease, particularly a reflux nephropathy. An escretory urography was performed only in few cases. Afo cal scar or a diffuse hypocaptation of one kidney with a L/R ratio greater then 5% were considered as a positive result. The total sensitivity (76 pts) of DMSA was 70% (respectively 67% in the first group and 73% in the second group); higher sensitivity in 33 pts with malforma~ ive disease was observed; 88% vs 56% in absence of malfor marion. The total sensitivity of DTPA was very low: 28% (38% in pts with malformations). The sensitivity of MAG3 was 47% and raised to 64% in case of malformative disease. No case negative to DMSA was positive to DTPA or MAG 3. An urinary tract obstruction was found by DTPA in 6 pts and by MAC~ in 9 pts (in 4 pts without other signs of parenchimal abnormalities). In conclusion DMBA showed the best sensitivity. The role of MAG3must be further de_ fined for its relative high sensitivity in diagnosis of renal damage combined with the diagnosis of obstruct, uropaty. Studies in mice and baboons have shown that Tc-99m L,L-ethylenedicysteine (Tc-g9m EC, I), the di-acid metabolite of Tc-99m ECD, is excreted rapidly in the urine by active tubular transport without uptake in other organs. I can be obtained by instant kit preparation at room temperature and may thus be a practical alternative to Tc-99m MAG3 (II).

We have compared I and II in 2 volunteers (A, B) with 1-131 OIH as internal biological standard. After I.V. injection I was extracted efficiently from the plasma by the kidneys and transported rapidly to the urine.

Renograms of I and II were comparable, but for I time to renal max. was longer in A whereas its renal wash-out was slower and its renal retention at 30 rain slightly higher in both A and B. Renal max. as % of I.D. was similar for I and If. Uptake or retention of I in other tissues was negligible. Liver activity at 40 min p.i. was < 0.3% for I versus 3-4% for II. Ratios I/II for urinary excretion (0-65 min) were 0.98 and 0.93 in respectively A and B. Protein binding was much lower for I than for II and OIH.

As a result distribution volume was significantly larger for I. In both A and B the 1 hr-plasma clearance of I was 120% of clearance of II and about 75% of OIH-clearance. It is concluded that Tc-99m EC merits further clinical evaluation as a potential renal function agent in view of its instant kit preparation, high stability, the absence of hepatobiliary clearance and its similar renal handling as Tc-99m MAG3. patients proved to have no RAS, unilateral disease was found in 5 and bilateral disease in 7. RS+C correctly identified 17/19 diseased arteries and was falsely positive in three cases. EDF missed RAS in one case and it was not possible to carry out in axxgt_her one, due to abdcmdrkll meteorism. An obstructed artery was not detected by EDF while RS+C showed a severily i~paired ipsilateral kidney. False positive results were found in three cases with EDF. Both examinations were falsely positive in two patients. In one angicgraphy showed a renal artery bifurcation and in the second small irregularities of the arterial wall. ~he use of both exams correctly identified RAS > 50% in all instanoes. In conclusion beth RS+C and EDF seem to be sensitive to renal blood flow impairment and their ccmbined use may improve noninvasive detection of RAS in hypertensive patients.

Kletter K., Leitha ~., Dudczak R. Hypertension caused by unilateral RAS corresponds to the experimental two kidney, one clip hypertension, which is believed to be renin angiotensin dependent.lfi contrary in experimental two kidney, two clip hypertension plasma renin values are nennal or low and hypertension is believed to be volame dependent lhe usefulness of CRG for the detection of he~odynamically significant RAS is therefore regarded doubtfully. 24 patients with bilateral RAS were examined in caTparison to 35 patients with unilateral RAS. Renography was performed using 1123 olH as well as Tc99m DTPA with and without captepril (25 mg) in all patients. The plasna renin concentration was determined before and I hour after captopril aclninistration. CRG was positive in 15 patients (63%) with bilateral RAS. CRG was also positive in 20 patients (57%) with unilateral R/kS. Only 3 patients with bilateral RAS sl~ed a positive CRG bilaterally; in the remaining 12 pts with bilateral RAS and pos CRG only the higher graded stenosis was indicated. Ccmpared to pts with unilateral RAS baseline renin values were lower and the increase of renin concentration after captopril was smaller in pats with bilateral RAS. Fbwever differences were not statistically significant. Out of these results and according to the blood pressure behaviour after percutaneous translu~inal angioplasty we conclude: I ) lhe sensitivity and specificity of CRG for the detection of renovascular hypertension (RVH) is ccmparable in pts with bilateral and unilateral RAS. 2. In general in pts with bilateral RAS only the higher graded ~sis is indicated by CRG. 3) As the CRG non responding side mightinfluenee the RVH in case of bilateral stenosis, a mutual PTA should be performed, irrespectively if CRG is positive uni-or bilaterally. 

The purpose of this prospective study was to assess the diagnostic efficacy of immunoscintigraphy in the identication of lymph node (LN) metastases of bladder carcinoma (BC) as localized invasive BC can benefit from radical cystectomy whereas patients (pts) with LN involvement are treated by inductive chemotherapy (chx) first.

Methods. 2 mg of the intact MAb BW 431/26 (Behringwerke, FRG) directed against CEA were labeled with 150-185 MBq In-lll CI~ at >90 % efficiency and slowly injected i.v. 3 anterior a~nd 3 posterior planar images were obtained 24-48 h and again 48-72 h p.i. SPECT of the abdomen and pelvis was performed 24-48 h p.i. Surgical specimens (specific tumor uptake), immunohistochemistry, and serum CEA levels were obtained.

Results. 85 prospective studies in 68 pts (repeated studies after chx) were performed within 44 months where 29 pts were treated by cystectomy and 39 by systemic chemotherapy/TUR. The diagnostic accuracy of Immuno-SPECT was 89 % for primary untouched BC; 87 % for local regional lymph node metastases; and 92 % for distant metastases. The sensitivity of planar imaging was about 15 % lower. The tumor-to-non-tumor ratios ranged between 3.8 and 51 (mean 10.6). 90 % of the tumors expressed the CEA immunohistochemically whereas only 20 % showed elevated CEA serum levels (low secretors).

ConcLusions. This prospective study demonstrates for the first time that SPECT usln~ In-lll labelled anti-CEA MAb has a much higher sensitivaty (> 80 2) for the detection of lymph node metastases compared to CT scan (<20 2) and therefore can contribute essential information for the decision making between chx and surgery. scanned after inse-A total of 50 fema~ rabbits minati0n of I .10 ~ or 100.10 radiolabeled rabbit spermatozoa (SP). For gentle and stable radiolabeling of SP Te-99m-HMPA0 has proven to be an ideal agent. The time development of the activity distribution in the living animal was determined by serial imaging with a gamma camera. Blood samples were taken to measure the activity lossed from the SP. To discriminate the active or passive transport, a mixture of In-111-oxine labeled avital and Tc-99m-HMPAO labeled motile SP was inseminated. A mixture of unlabeled and Tc-99m-HMPAO labeled SP allowed an evaluation of the influence of labeling on SP motility. Results: Thorough cross checks excluded a relevant quality degradation of the SP by the labeling procedure. SP located in the uterus, the fallopian tubes, on periovary regions or intraperitoneally were easily identified.

Relative time activity curves were generated and, since the label was found to be stable under in vivo conditions, absolute SP numbers were deduced. Values as low as 100 SP could be visualized. The influence of the timing of the insemination relative to ovulation on the migration was demonstrated. Conclusion: Following insemination, migration and transport of Tc-99m-HMPA0 labeled spermatozoa in the femal genital tract can be visualized and quantified non-invasively. Thus -for the first time -in one individual animal the SP ascension can be monitored. The technique can be easily transferred to humans to investigate infertile couples. Although the spermatozoan dose can be restricted to values well below O.1 Gy, conception with labeled SP must be excluded, however, when used in human infertility evaluation. TC-99m-MRP20 (N(-2(IH pyrolylmethyl))N'(-4-pentene-3one-2))ethylene 1,2 diamine) belongs to a new class of neutral, lipophilic Tc complexes under investigation as a brain perfusion agent.

After approval of the institutional ethical committee and written informed consent, we have evaluated the safety, biodistribution and SPECT imaging characteristics of MRP20 in eight male adult volunteers.

Dynamic planar brain imaging was performed during the first i0 minutes after injection of 15-25 mCi of TC-99m-MRP20.

Rotating gamma camera SPECT studies and whole body biodistribution studies were performed 15 min, 3h, 7h up to 24 hours after injection.

Brain uptake of Tc-99m-MRP20 reached a maximum before i min p.i. and the initial activity plateaued by about 5 minutes.

At 15 min p.i. the absolute amount of injected activity retained in the brain was 5.2% i.d. (s.d 1.6).

This level of uptake remained constant over the first 7h: 4.9% i.d. (s.d 1.5).

Brain images showed an uptake similar to the pattern seen with other perfusion agents with a good differentiation between gray and white matter.

No redistribution of regional activity within the brain was observed until 24h post injection.

24h whole body retention was 70% i.d., the tracer being excreted through both the urinary and hepatobiliary systems.

Vital signs, blood and urine chemistries remained normal, no adverse reactions were observed.

These results indicate that Tc-99m-MRP20 is rapidly extracted and is retained by the brain in favorable conditions for SPECT imaging. Eight right handed chronic aphasics underwent two SPECT/IMP examinations: NS (baseline) ; and while tested with the BNT, a standarized picture naming test.

Data were quantitated to determine whether the BNT for aphasies evokes differences in specific brain areas as compared to the NS state.

Nine normal right handed controls had two NS studies.

Aphasic NS studies were compared to NS studies of the controls.

Cortical ROIs were generated for nine contiguous transverse slices by the method of Hellman, et al. (J Nucl Med 1987; 28:592) . Forty-eight left to right ratios (96 ROIs) were subjected to a repeated measures three way ANOVA.

Significance was interpreted with respect to variability observed in controls. No significant differences between repeat studies were obtained for controls.

As predicted, left to right ratios are decreased (p < .001) for aphasics as compared to normals for most cortical ROIs.

Left to right ratios decreased between baseline and BNT in Wernicke's (1.13 -0.98, p<.05) and in visual cortex (1.07 -0.84, p<.01) areas.

We conclude, that in spite of aphasia, significant changes in classically defined language areas of brain can be obtained using BNT and NS left to right ratios. HIGH RESOLUTION SPECT AND STROKE OUTCOME Treatments that may alter the outcome of stoke are being developed e.g. tPA or NMDA receptor antagonists. Early functional scanning may help in the evaluation of these.

In order to assess t~s we have carried out serial SPECT scanning using Tc HMPAO and the high resolution NOVO 810 multidetector scanner. 55 suspected ischaemic strokes were studied at 1 day, 1 week and 3 months with full neurological examination on each occasion.

CT scanning (or MRI) was done at i week.

SPECT and CT correlated exactly in identifying lesions over 3 cm diameter on CT with the advantage of immediately positive SPECT scans but the disadvantages of cost, longer scanning times, and failure to reliably identify haemorrhagic infarction and haemorrhage.

SPECT identified 50% of smaller lesions and often showed areas of remote decreases in IIMPAO uptake consistent with diaschisis.

There was no correlation between the changes in these areas and the clinical evolution.

In all cases clinical examination was superior to both SPECT and CT in determining prognosis.

Reperfusion was seen in 1 case at 24 hours and 5 cases at 1 week.

In all those studied there was no significant IIMPAO washout on rescanning at 6 hours.

Washout did not correlate with tissue survival except in the case at 24 hours.

SPECT will detect most strokes but adds little to clinical examination and CT.

It may have a use in the assessment of thrombolytic therapy for stroke where it will non-invasively demonstrate the extent and degree of reperfusion. 

A cerebral SPECT with 99mTc-HMPAO was performed in 21 patients (pts) affected by Parkinson's disease (PD), with suspension of medical treatment for 24 hours, and 13 controls. 12 pts were affected by hemiParkinson (hP) and 9 by bilateral PD (bP). In 5 pts tremor was the prevalent symptom, in 9 pts rigidity-akinesia, in 7 pts there was no prevalent symptom. No fecal lesion was evident at EEG and CT.

We identified in every significant tomographic slice, ten cortical symmetrical areas end, when possible, two symmetrical areas on basal ganglia; moreover two symmetrical areas were identified on the cerebellum. A semiquantitative analisys was performed with two comparisons: 1. the uptake of each area (cortex and basal ganglia) was compared with the controlateral to calculate the uptake ratio, (normal value from 0.9 to 1.1); 2. the counts of all cortical and basal ganglia areas were compared with the mean value of counts in the two cerebellum areas.

basal ganglia: a. basal ganglia/cerebellum uptake ratio was reduced in all pts; b. asymmetric distribution, present in bP pts, was more frequent in hP pts and absent in controls; c. in hP pts reduced uptake was observed on the same side of symptoms when rigidity-akinesia was prevalent and controlateral to symptoms when tremor was prevalent. The uptake of the tracer was simmetdcally reduced in pts with no prevalent symptom. cortex:

a. cortex/cerebellum uptake ratio was reduced in parietal region in all pts; b. asimmetry in tracer distribution was more frequent in bP pts: there was a general correlation between presence of cortical asymmetries and gravity of PD, according to the Hoen-Yahr classification, and time from the onset of the disease.

H. Feistel, T. Treig, B. Neundorfer, F. Wolf. Friedrich-Alexander Universit~t Erlangen, Erlangen, West Germany.

Transient global amnesia (TGA) is a syndrome of acute memory loss lasting for several hours without neurologic deficit. The etiology is unknown, three theories have been favoured: ischemic attack of the posterior cerebral artery, epileptic discharge in hippocampus, spreading depression (SD) in hippocampus. We report on 21 Patients who had been referred with symptoms of TGA (12 male, age 48 +/-15 Y 9 fem., age 59 +/-12 Y). HMPAO brain SPECT was initiated in 17 patients in acute phase, in 4 patients later. In 13 patients one or more control SPECTs were performed to a total of 36. All patients were right handed. Semiquantitative evaluation with PODREKA's algorithm was carried out by defining regional perfusion indices (RPI). Brain SPECT revealed decreased RPI in left hippocampus 8, in right hippocampus 6, left parietal region 2, frontal i. No deficit was seen in 4. Delayed control PSECT showed intact perfusion in 7 patients, remaining impaired perfusion in 3. Conclusion: i. There is a vascular component in etiology of TGA -primarily as ischemic attack or following SD. No evidence of epileptic activity with ictal hyperperfusion. 2. The side of the attack is independent from handedness. 3. In acute phase the impairement can be localized in hippocampus region. Decreased perfusion in other regions may be caused by additional vascular disease (frontal) or delayed begin of investigation. 4. Decreased perfusion may persist beyond clinical improvement.

.U. Buell, W Reiche, C Weiller, R Weigmann, EB Ringelstein. Depts Nuclear Medicine and Neurology, Technical University of Aachen, FRGermany 81NSWANGER'S DISEASE (BD): RESULTS OF BRAIN-SPECT (FLOW (Tc-99m HMPAO) / VOLUME (Tc-99m RBC)) COMPARED TO HRI BD represents vascular (mieroangiopathic) white matter (WM) dementia, defined by periventricular hyperintensity (PVH) in MRI and lacunes.

Severity is graded from such findings (MRI/CT).

In 17 pts with BD, MRI was used to classify morphologically.

Flow/volume(F/V)-SPECT (double-head, 2x180 , 6 steps) was performed to access pathophysiology by F (370 MBq) and V (750 MBq) slices (2pix thick) and assessing by slice division (F/V) the regional vascular reserve (CVR). Ratios were gained from ROI, drawn in paraventricular WH, cortex and cerebellum.

MRI (1.5 T) produced (proton-,Tl-,T2weighted) orbito-meatal slices (7 mm We conclude that in BD (a) WM-rCBF decreases with the severity of the disease, (b) cerebral vascular reserve in the WM is potentially exhausted and (c) grey matter (cortex) is less involved. Moreover, venous bloodvolume in cortical areas was increased, mainly from veins, filling in spaces from atrophy. Since reduction of rCBF precedes the onset of dementia, F/V-SPECT may play an important role in early diagnosis of BD. The localization and clearance properties of 1231 labeled N-isopropyl iodoamphetamine (IMP) as an indicator of regional cerebral blood flow (rCBF) were investigated in crack users and in smoker and nonsmoker control subjects.

Measurements included serial dynamic gamma camera imaging of IMP uptake in the brain (0-25m), early (-30m) and delayed (4h) SPECT imaging of rCBF and whole body scans of the distribution of 1231 IMP (-75m). IMP localization and clearance reproducibility was tested by quantitatively comparing localization and clearance properties of the procedures repeated at one week intervals in all control and 2 crack user subjects.

Studies completed in I0 control subjects and 6 crack users show; i) perfusion deficit (decreased IMP) were observed in the frontal parietal region of 3/6 crack users, 2) the mean slope of cerebral uptake (O-25 m) in crack users was 11.3% less than in nonsmoker controls, 3) reproducible, symmetric uptake is seen in gray matter structures in control subjects (e.g. R/L cortex uptake ratio: day i~i.01• day 7~i.04• n=10), and 4) cortical activity normalized to dose in early SPECT images was reduced by 48.1• % in smoker control subjects.

The study shows IMP SPECT imaging provides a sensitive and reproducible assay of rCBF; crack users show a high incidence of rCBF deficits; and smokers show major reductions in cerebral uptake of IMP on SPECT images. This study was performed to assess renal transplant viability and to evaluate the effects of different preservation solutions on kidney transplant energy metabolism by 17-31 magnetic resonance spectroscopy. Twenty human cadaveric kidneys were studied prior to transplantation using a 4.7 Tesla/40 cm NMR spectroscopy system. P-31 MRS was performed at 81 MHz using a surface coil tuned to 81/200 MHz. Eight kidneys were preserved with Collins solution (COL) and measured 3.6+1.6 hrs after explantation, and 12 with University-of Wisconsinsolution (UW), measured 3.9+2.4 hrs after explantation. All 3 ATP peaks were clearly identified visually in 4/8 of COL and in 9/12 of UW kidneys (n.s.). Relative quantification of 13-ATP, monophosphates (MP) and inorganic phosphat (Pi), however, for direct group comparison proved to be less meaningful because of the different inorganic phosphate content of the two preservation solutions. Thus, the results of P-31 MRS showed expectediy different ratios of g-ATP/Pi and MP/Pi in the two groups studied as shown in the 

SCINTIGRAPHY AND CONVENTIONAL RADIOGRAPHY 23 children with Legg-Perthes disease (25 affected hips) were prospectively evaluated with MRI (Tl-weighted SEsequences in sagittal and coronal plane, gradient-echo-sequences in transverse plane), bone scintigraphy (tracer: 99m-Tc-HMDP) and conventional radiography both at first presentation and during follow-ups. For the early diagnosis of LCPD MRI was similiar as sensitive as isotope bone scan and more precise than conventional radiography. The extent of the necrotic area within the epiphysis could be better assessed by MRI than by conventional radiography or bone scan. Providing a more detailed depiction of bone marrow and soft tissues MRI showed exactly the position and contour of the femoral head including the femoral and acetabular cartilage. The loss of containment of the femoral head could be earlier diagnosed by MRI than with conventional radiography (p = 0,03). Staging of LCPD according to the histopathogenesis was possible with MRI in elder children at least by comparing the tomograms with previous images, The beginning revascularisation of the necrotic area can be reliably assessed only with isotope bone scan, whereas the onset of reossification can be determined most exactly by radiographs. To summarize, for the evaluation of LCPD MRI proved to be especially useful for excluding other hip diseases and in follow-ups (assessment of complicative changes of the femoral head). It is possible to reduce the amount of X-rays and to avoid invasive arthrography. with myocardial infarction, in particular following application of the contrast agent Gadolinium-DTPA. In an attempt to quantify the extent of infarcted myocardium, infarct size was estimated in 21 patients with proven acute myocardial infarction using serial MRI after i.v. injection of Gd-DTPA (0.2 mmol/kg bodyweight). Early reperfusion after thrombolytic therapy with 750.000 E streptokinase i.v. was documented by coronary arteriography in 9 patients (Group I). In 12 patients (Group II) no reperfusion was obtained (5 patients) or no thrormbolytic therapy was given (7 patients). All Group II patients were considered to have no reperfusion. MRI was performed with a 0.5 T Philips Gyroscan at an average of 8+4 days postinfarction; 16 patients underwent a second MRI study at 26-+i1 days post-infarction. Nine slices (i0 r~n thick, 2 mm gap) perpendicular to the long axis of the left ventricle were obtained and for every slice the area with enhanced signal intensity (>mean+2 SD) was considered to be infarcted. These areas were summed for all slices and infarct size was expressed as a percentage of the total left ventricular volume. Infarct size was smaller in Group I (8+5%) vs Group II (15-+4%) at early MRI (P<0. 001) . Follow-up MRI studies showed similar differences in infarct size between patients with and without reperfusion. We conclude that MRI using Gd-DTPA can measure infarct size and discern patients with reperfusion, both in the early and late phase after acute myocardial infarction.

DJ Pennell~ SR Underwood, PJ Ell, RH Swanton, JM Walker, DB Longmore MR Unit, National Heart and Chest Hospitals, London Univ. College and Middlesex Schools of Medicine DOBUTAMINE P~GNETIC RESONANCE IMAGING IN ISCHAEMIA HEART DISEASE; A NEW TECHNIQUE Magnetic resonance imaging is difficult during dynamic exercise and this has limited its value in patients with coronary artery disease. Using intravenous dipyridamole and cine magnetic resonance imaging, we have previously demonstrated wall motion a6normalities in two thirds of patients in whom thallium defects were seen. In order to increase this sensitivity we have now used intravenous dobutamine, which increases myocardial oxygen demand and has the advantages of administration by peripheral infusion, a short half life and low arrhythmogenicity. 22 Patients with stable angina underwent coronary angiography, thallium tomography and cine magnetic resonance imaging. Images were acquired in three perpendicular planes before and after dobutamine, allowing direct comparison of perfusion and wall motion, which were graded in nine segments as normal, reduced, or absent. 20 Patients had coronary artery disease, of whom 19 (95)% had reversible perfusion defects following dobutamine. All 19 also had reversible wall motion abnormalities. The perfusion and wall motion defects corresponded very closely in site and extent. The 2 patients with normal epicardial arteries also had corresponding wall motion and perfusion abnormalities. Chest pain oceured in 18 patients but was easily controlled by decreasing the infusion rate. Transitory dysrhythmias were seen in 8 patients but were insignificant. The average increase in double product with dobutamine was 34%, 57%, 87% and IO4% with 5,10,15 and 20~g/kg/minute respectively. We conclude that magnetic resonance imaging during dobutamine stress is safe, feasible and well tolerated and that it may be possible to extend the clinical role of magnetic resonance in patients with coronary artery disease. MRI of left ventricle (LV) has proved to be an excellent method to measure systolic wall thickening (SWT). The aim of this study was to find a correlation of SWT and regional myocardial perfusion determined with TI-201 SPECT. 65 patients -42 with and 23 without history of OMI -underwent SPECT and, within the next two weeks, MRI. Enddiastolic and endsystolic spin echo images were obtained by reduced permutation technique. For measurements, on}y long axis sections through LV near the equatorial Plane were used. Slice orientation was selected according to the findings of SPECT, imaging the infarcted wal] segment by single or double angulation. In 7 equidistant points of LV wall SWT were measured and compared to the corresponding regional pe~fusion va}ues of SPELT in terms of percent of maximal perfusion. In a prospective study 26 patients, age ranged from 33 to 75 years ( mean age 52,4 years ) with clinically and / or histologically proven spondylodiscitis underwent magnetic resonance ( MR ) -imaging and radionuclide studies. In 17 patients additional follow -up examinations were performed after initial diagnose. In all studies plain x-rays were available. MRI -teehnioue: 1.5 tesla superconducting magnetic system. TI( TR: 400 --600 msec; TE: 20 -30 msec) and T2 ( TR: 2500 msec; TE: 68 -80 msec )-weighted pulse sequences ( sagittal and transversal plane ), 1"2-weighted gradient-echo-sequences ( sagittal plane ); in 15 patients additional T1 weighted pulse sequences with Gadolinium -DTPA ( 0.2 mmol /kg ;i.v. ). Radionucllde teehniqug; 10 -20 mCi 99m Tc-HMDP; i.v. Re~lt~: Typical changes of spendylodiscitis in plain x-rays and MRI are blurred outlines of the superior and / or inferior end plate of lhe vertebral bodies. In addition mostly we found a decrease of height of the disc space. In acute pyogenic and tuberculous spondylodiscitis there is a low signal of the disc and the adjacent plates of the vertebral bodies in TI weighted plain images and a highly increased signal in T2-weighted images, as well as a significant contrast enhancement in TI-weighted images after administration ofGd-DTPA. In patients with pyogenic infection there is a high uptake of 99m-Tc-HMDP in acute spondylodiscitis In cases of tuberculous infections ( n=3 ) we found a minimal uptake in 2 patients; no uptake was observed in one patient. In patients of chronic spondylodiscitls bone scintigraphy was positive in all examinations, but generally we found a lower technetium -uptake in comparison to acute infections. Conclusion: 1) MRI in comparison to bone scintigraphy is more sensitive in chronic and tuberculous spondylodiscitls and shows the same sensitivity in acute pyogenie spondylodiscitis.

2) The important rank of bone seintigraphy in addition to MRI is the possibility to differentiate between pyogenic and tuberculous spondylodiscitis. In a preliminary PET study, we have shown that [methyl-11C]thymidine overestimates liver regeneration due to the hepatic accumulation of labeled metabolites.

We also obtained evidence that the use of 11C-labeled thymidine in C2-position would avoid such overestimation since the labeled metabolites would be rapidly eliminated in the form of CO2.

In the present study, the hepatic uptake of [2-11C]thymidine was evaluated with PET in 70% hepatectomized rats, lh (when DNA synthesis is not increased; n=13) or 24h after the surgical procedure (when DNA synthesis is maximal; n=t2). Serial tomographie scans were performed over a period of 120min after injection of ImCi [2-tIc] thymidine together with 50BCi 3H-labeled thymidine.

Already 10min after injecticn, PET imaging showed a significantly higher [2-11C]thymidine uptake in regeneratiug (RL) compared to nonregenerating livers (NRL), reaching after 120min a 4-fold difference between both groups.

Radioactivity measured on liver samples taken at 120min was significantly increased (p<0.001) in RL compared to NRL, and this for tiC-radioactivity measured in the whole tissue (RL: 4679Z1729 versus 759• dpm/dose/g for NRL) and for 3H-activity measured in the extracted DNA fraction (RL: 10807• 4937 versus 843• dpm/g for NRL).

Whole tissue 11C-radioactivity correlated with DNA 3H-activity (r=0.92, p<0.001).

The difference of sensitivity between in vivo PET counting and in vitro counting was related to a partial volume effect due to the small size of liver rat. In conclusion, these results indicate that [2-ttC]thymidine constitutes a sensitive tracer for noninvasive quantification of liver regeneration with PET. Measurement of the extraction of serotonin on a single pass through the lungs has been used a an early indicator of lung endothelial damage. The techniques used formerly required multiple arterial sampling in the dght heart. We have developed a non-invasive technique utilizing the double indicator dilution principle, a positron camera (Cycl. Corp. Model 4200), and 1 t C.semtonin and 11CO labelled red cells as substrate and intravascular marker respectively. This allowed the exact calculation of single pass extraction of 11C_serotonin in the lungs. In addition we have demonstrated a reduced extraction of 11C.serotoni n after pretreatment with imipramine, an inhibitor of serotonin transport.

With ROI techniques we obtained time activity curves in 0,5 sec. frames for 30 sec after i.v, bolus injection of 150-200 MBq 11CO labeled autologous red cells (0.5-1 ml) as a vascular marker. 10-15 rain later we injected 150-200 MBq ot 1 lC_serotoni n and extended the frame collection time to 5 min. Then 25-35 mg imipramine were infused slowly over a time period of 10 rain. and the injection of labeled red cells and serotonin were repeated after a further time period of 20 rain. In three normal volunteers t 1C_serotonin extraction was 64 +_ 3.6 % this decreased to 54 +_ 1.4 % (P<0.04) after the infusion bt imipramine. The rate of wash-out ot 11C from the lungs as a function of serotonin metabolism was 10 + 0.09 % without imipramine and 8.9 ___ 0.9 % after imipramine treatment (NS; P<0.1).

The single pass extraction of semtonine is quite high and therefore can serve as a sensitive indicator for the function ot the lungs endothelial wall. Although the effect of imipramine on lung serotonine extraction in man is less pronounced than in previously reported animal experiments, the decrease reached under the dose which could be administered to volunteers without serious pharmacological effects, has demonstrated the validity of the t 1C.serotonine approach to measure lung endothelial function. It has previously been shown that 11C-l-deprenyl is a tracer of monoamine oxidase type B (MAOB) activity.

In the present study a quantitative tracer procedure was developed for measurin9 the dose response curve of a reversible MAOB inhibitor (Re 19-6327).

Six normal volunteers received varyin9 single doses of this inhibitor and one subject received a single dose of 1-depreny] (20 mg) 12 hours before PETscanning.

One subject did not receive any pre-dose. Dynamic PET scanning was performed over a period of 90 min from time of bolus injection.

Arterial blood was continuously withdrawn and measured with an on-line BGO detection system.

Calibration samples collected at set times were used to estimate the plasma input function from the continuously measured arterial whole blood curve.

The so obtained plasma curve was further corrected for measured circulating levels of metabolites. Tissue time activity curves were fitted for K~, k2, k3, delay of the plasma curve and blood volume using a two tissue compartment model and standard non-linear regression analysis. Inclusion of k4 did not significantly improve the quality of the fits. With the fitted values of k3 it was possible to produce a well defined whole brain dose response curve of Ro 19-6327,

The values of k3 showed close correlation with independently measured platelet inhibition (r=0.948),

Since the dose response curve using Ki=K1k3/(k2+k3) contained more scatter and the correlation between K~ and platelet inhibition was worse full compartmental analysis seems to be required to assess MAOB activity.

A. Dimitrakopoulou, L.G. Strauss, U. Haberkorn, M. Knopp, P. Sehlag, E Hellas, G. van Kaiek.

Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg, FRG.

PET EVALUATION OF REGIONAL CHEMOTHERAPY USING F-18-URAC1L AND O-15 LABELED WATER.

Fluomuraeil (FU) has found use for both systemic and regional ehemotherapy in patients with liver metastases from eoloreetal tumors. We used PET and F-18-uracil in order to compare the accumulation of the cytostatie agent in metastases and normal liver parenehyma after intravenous and intraarterial tracer application. Furthermore, O-15 labeled water was injected to evaluate the perfusion pattern. The evaluation comprises 34 examinations (intravenous and intraarterial studies) in 17 patients with surgically implanted catheters in the gastroduodenal artery Standardized uptake values (SUV) were calculated using a ROI technique for the metastases, normal liver parenchyma and the aorta. The FU metabolite concentrations were higher in 13 of 24 metastases using the i.a. approach, while in 5 metastases the concentrations were lower following i.a. FU infusion. In one patient a five fold increase in FU uptake was noted after i.a. tracer application. We observed a higher systemic toxicity in 25 % of the patients. The accumulation of the perfusion tracer O-15 labeled water was up to 10 times higher in the metastases after intraarterial injection, while a <50 % increase of the FU uptake was noted after the regional application. Therefore, perfusion studies alone are not useful to estimate the FU accumulation in metastases. The results of the ongoing study demonstrate, that PET with F-18-uraeil should find preferential use to optimize the regional chemotherapy and to select those patients who do profit from the intraarterial approach. The purpose of this study was to examine the uptake of C-ll hydroxyephedrine (HED) in pheochromocytoma. HED is a recently developed false neurotransmitter which has been shown to accumulate in the storage vesicles of adrenergic nerve terminals. Five hypertensive patients, four with malignant pheochromomcytoma, were the subjects of this investigation.

Each underwent PET scanning after the intravenous administration of 20 mCi HED.

A 20 minute dynamic acquisition was followed by a rectilinear scan using the PET camera to screen the chest and abdomen for abnormal activity outside the areas imaged in the dynamic sequence.

Comparison was made to MI~G (I-131 or 1-123 labeled) soans.

In all five patients, HED PET scans and MIBG scintigraphy were in agreement: in three patients both studies were positive and in two both were negative. However, in the positive studies, HED PET scans showed deposits of pheochromocytoma earlier and more clearly than MIBG scintigraphy.

Abnormal foci were visualized as soon as 5 minutes after injection of HED, and target to background ratios were superior to those obtained with MIBG.

We conclude that PET scanning with HED may prove useful in the detection and localization of pheochromocytoma. The diagnostic work up of preoperative patients with thoracic tumors using conventional techniques and including CT and MRI remains limited compared to surgical staging with an overall sensitivity reported in the range of 50-80 %. Our study sought to use PET with a metabolically active compound, F-18-1abeled deoxyglucose (FDG), to detect increased uptake in neoplastic tissue to delineate active tumor from surrounding tissue, its lymphatic spread and to differentiate neoplastic from inflammatory tissue. We performed endpoint measurements 55 rain post i.v. injection of 440 MBq FDG and acquired 5 rain. transmission scans and 15 min. emission scans. Tracer uptake concentrations were calculated by a ROI-teehnique, standardized for injected dose and body volume and expressed as standardized uptake values (SUV). 30 patients with completed clinical staging for lung tumor were studied with PET prior to surgery. All malignant tumors were clearly delineated with high contrast to the surrounding structures. The preliminary evaluation includes 18 patients with 14 malignant tumors (5 squamous, 2 small cell, 1 adeno, 1 large cell, 2 mesothelioma, 1 metastase, 2 Pancoast) and 4 benign lesions (1 cyst, 2 gangrene, 1 castleman disease). Fourteen malignant and 3 benign tumors were correctly identified due to their different FDG-uptake values while the Castleman disease showed high FDG accumulation. In 5 out of the 14 malignant tumors, PET correctly changed the T-classification (3 lower, 2 higher) compared to the previous staging whereas 7 agreed. Our results show that FDG-PET can improve the preoperative staging and shows great potential for improving the sensitivity. When stable isotope labelled (15N2) urea was administered orally with a test meal, the high urease activity of Campylobacter-pylori-infected individuals yielded 15N-labelled ammonia. The 15N abundance of the urinary ammonia and urea could be detected easily 3 hours later using a simple microdiffusion technique and emission spectrometric 15N analysis. Individuals without gastric urease activity eliminated practically no (15N) ammonia over this period. This corresponds to an 15N(ammonia)/ 15N(urea) ratio less than 0.05. Infected individuals showed ratios above 0.08 and reached ratios more than 0.20.

Ten healthy subjects and fifteen patients with gastroscopically diagnosed C. pylori infection were involved in the study, which was approved by the departmental Ethical Committee. The new test has reliably identified all patients with positive cultures.

We conclude that the test is well suited for repeated application using the advantages of the non-distressing, non-radioactive, and simple method.

A.D.vanhetSchip, P.J.vanNoorden and P, Duif Dept.of Nuclear Medicine, University Hospital Utrecht, The Netherlands 99~Tc-MAG3: I~ADIOCHEMICAL PURITY AND STABILITY The aim of this study is to test how variation in labelling and use of mercaptoacetyltriglycine (MAG3) affects its radiochemical purity and its efficacy as a diagnostic agent in routine renal studies. According to the manufacturer's instructions MAG5 can be labelled with a maximum of 925 MBq 99mTc aflter which it must be used within 60 rain to retain 95% purity. For routine clinical use a more stable preparation is preferable. HPLC chromatography was used Lo monitor the radiochemica] purity of ~9~Tc-MAG3 as a function or "age" of the ~Tc-eluate used rap labelling, the amount of ~Tc (MBq) added to a kit and the time between preparation of the product and its administration to the patient. In 15 patients with varying degrees of renal function the radiochemical purity of HAG3 at the time or administration was correlated with the quality or diagnostic information obtained. All studies were scaled technically satisfactory or unsatisfactory from a viewpoint of persistent background or undesirable liver and gall-bladder uptake. Adequate labelling results of MAG5 (mean: 98.4%; SD: 05%) were obtained with eluates used up to 8 holms after collection. Using 15 hours decayed eluates, radiochemical purity became insufficient (85% ~Tc-MAG3, 15% free pertechnetate) for 1 orthe 2 batches tested. The amount of 99mTc added to a kit was varied between 500 and 2000 MBq in 1 ml eluate or less. No significant difference in radio-chemical purity was observed and maintenance of" over 98% purity was found for at least 8 hours. The observed in vitro stability was confirmed in vNo. Good quality images in accordance with clinical status were obtained with HAG3 administered up to 7 hours after labelling.

Conclusion: ]-he possibility to label MA63 with up to 2000 MBq ~9~Tc combined with its radiochemical stability allows an efficient use of this radiopharma 7 ceutical during a normal working day in a routine clinical environment. MRP20 (N (-2 ( 1H pyrolylmethyl) ) N ' ( (-4-pentene-3-one-2) )ethylene i ,2 diamine) has recently been shown to extract into the human brain and be retained over a long period. In the search for this ligand we have studied several closely related molecules and k~ ~ n /R the biodistribution of their techne-,~NH HN--~ tium-99m complexes. We present here R" our chemical and biological findings ~NH 0==~R ' for 8 of these complexes.

The sessed by reverse phase HPLC. These complexes decompose via one of two routes, giving either TcO~or a secondary, hydrophilic complex. This latter we believe to be the hydrolysis of the azomethine moiety since the same product has been identified in all ligands where n=2. MRP21 and MRP31 were the least stable withrapid to TcO~.Those complexes where n=3 were found to be unstable with insignificant brain uptake. Brain uptake is seen in all the complexes where n=2, ranging from 2.0% i.d. to 0.1% i.d. and MRP22, being considerably more lipophilie than the others showed the least brain activity. The hydrophilic complex was investigated and showed brain activity of < 0.1% i.d. In conclusion, this ligand structure generates a wide range of Tc-99m complexes which show promise as cerebral blood flow agents. 

N2Sz-chelates form uniform and stable 9~=Tc complexes. Therefore, we chose this type of ligand for conjugation with monoclonal antibodies, although we were aware that by using the active ester route the NzS2-1igand might react with itself. 7-(4'-bromobutyl)-3,3,11,11-tetramethyl-l,2-dithia~5, 9-diazacycloundecane (IIR-C4-Br), recently developed as a general purpose precursor for the synthesis of new N2Sz-ligands, was used for the formation of 7-(4'-(p-carboxylphenoxy)butyl)-3,3,11,11-tetramethyl-1,2-dithis-5,9-diazacycloundecane (IIR-C4-OPhCOOH). The reductive disulfide-bond cleavage was achieved with dithiotreitol (DTT).

The active esters were formed by treating IIR-C4-OPhCOOH with tetraflorophenol (TFP) and thiophenol (PhSH) in the presence of dicyclohsxyl carbodiimid (DCC). The active esters were isolated by reverse-phase chromatography. In protonated form the active esters were stable. Conjugation with IgG or other proteins was performed in aqueous solution at pH 8-8.5. Complexation of 99-Tc by the tin-reduction method afforded >95% protein-bound activity. We are currently testing this labeling method with a rat sarcoma affine monoclonal antibody (A2.6). Animal experiments including the investigations of tumor affinity, organ distribution studies and activity kinetics are in progress. We are seeking to understand the mechanism by which pentavalent 99Tcm-DMSA accumulates in medullary thyroid carcinoma (MTC) and other tumours. Our first objective was to characterise unambiguously the radiopharmaceutical. Despite common use of the term "pentavalent" the chemical identity of neither this complex nor the renal agent "trivalent" 99Tcm-DMSA has been experimentally established.

TLC, HPLC and eleotrophoresis under a variety of conditions show that carrier-free 99Tem-DMSA is chemically identical to the well characterised complex ggTc0(DMSA)2-in which the technetium is pentavalent and coordinated square-pyramidally by four thiolate donors and an oxo-group. NHR spectroscopy shows that the complex exists as three isomers with the carboxylate groups oriented 8y~-syn, ayn-anti, and antf-antf with respect to the oxo-group. It is not yet clear which (if not all) of the isomers are tumour specific. There is no spectroscopic suggestion of interaction between the metal and the carboxylie acid groups. Potentiometric titration shows that ca. 2 of the ~ earboxylie acid groups are ionised at pH 7. The proposed structure is supported by the similar biodistribution of the iS6Re analogue (shown spectroscopically to be the square-pyramidal complex Re0(DMSA)Z) in a patient with MTC.

We conclude that pentavalent 99Tc'-DMSA contains the well-known Tc(V) oxotetrathiolato-core, exists as three isomers which differ in orientation of the carboxylic acid groups, and has an overall charge of -~ at physiological pH. These data may have implications for turnout and kidney uptake mechanisms. containing an internal cleavable linking group between the antibody and chelated indium have demonstrated faster background clearance (JNM 30: 1693 (JNM 30: , 1989 . In this study linking groups have been added to one of the carboxylic acid groups of the semi-rigid chelate CDTA by either of two general synthetic routes. In the first, symmetrical linkers containing terminal amines were reacted with the monoanhydride of CDTA (CDTAMA). To avoid crosslink.ing, amines (ethylenediamine, 1,6-diaminohexane, 4,4'methylenedianiline, and 4-aminophenylether) were either reacted in excess with CDTAMA or converted to mono-t-Boc derivatives prior to reaction with CDTAMA. Hydrolysis of the t-Boc followed by treatment with thiophosgene produced the isothiocyanates of the CDTA-4,4'-methylenedianiline and -4-aminophenyl-ether. In the second route, symmetrical linkers containing terminal carboxylic acids such as 1, 10-decanedicarboxylic acid are ethyleneglycolbis-succinate were converted to their NHS esters and reacted in excess with CDTAethylene-diamine in DMSO. Concentration of the reaction mixture followed by CH2C12 addition precipitated the CDTAethylenediamine linker. These linker-chelates have been characterized by NMR, conjugated to antibodies, and stored under desiccant without loss of reactivity. Evaluation of these preparations in mice is currently underway. The above examples demonstrate the general synthetic utility of these routes to prepare a wide variety of CDTA-linkers. IESPI had a maximal effect on 3H-8OHDPAT (ICs0 = 6 10-9M) pointing out its specificity for 5HTzA receptors. These results showed that addition of an iodoethyl group on 3-N position of the spirodecanone part of spiperone or spiroxatrine does not prevent binding on specific receptors. We can assume that this method of iodoalkylation can be applied to spirodecanone parts of different compounds in order to give new iodinated ligands for monoaminergic receptors.

MaT. Allende, F.Vizoso*, MaC. Roiz, A. Fueyo**, L.Leanartz*** and A. Ruibal Nucl. Med. and Surgery* Services. Hospital General de Asturias. Oviedo. Spain. Physiology Dpt. University of Oviedo** and Abbott Laboratories (Germany)*** SERUM BCM BEHAVIOUR IN PATIENTS WITH NONMALIGNANT DI-SEASES AND WITHACTIVE NON BREAST TUMORS In order to study its behaviour, we have determined by an IRMA assay (M85/34 and A169 Mabs; Abbott )the serum levels'of BCM (breast cancer mucin) in 70 HBsAg-blood donors (control group), 155 patients with non tumoral pathologies and 161 with active non breast tumors. In control group, BCM values oscillated between 2.6 and 15.3 U/ml (8.3+2.9) and 15 U/ml was taken ~as upper normal level (97.~ percentile. In non tumoral group, BCM values higher thafil5 U/ml were observed in 29 patients (18.7%); in general, antigen increases were moderate and infrequent, except i~ cirrhosis (42.5%; r:5.1-42.7; median 16) and acute hepatitis (28.6% ; r:2-39.5 ; median 16).When cirrhotic patients were excluded, BCM va lues higher than 15 and 25 U/ml were observed in 12 any 1 cases (10.4% and 0.8% respectively). In active non breast tumors group, BCM values higher than 15 U.ml were noted in 73 cases (44.7%), cooresponding the most im portant percentages of positives to ovarian (54.5%), -lung (65.6%), colo-rect~l (44%) and prostatic (35.7%) tumors. When 25 U/ml was used as threshold those values were: 24.2% , 28.1%, 14.6% and 21% respectively. These results led us to consider the following: a)It is possible to observe high BCM lecels in patients with non tumoral diseases, especially with cirrhosis, but they are ussually moderate and lower than 25 U/ml; b) 25 U/ml can be used as threshold for tumoral activity (2% of positives) and c) BCM is not specific for breast cancers, being ovarian, lung and prostatic tumors the entities those can determine BCM serum levels higher than 25 U/ml. In non breast tumors there was a correlation between antigen increases and distant dissemination. The aim of this study was to evaluate the utility of tumor markers CA 549 (Hybritec) and SP2 (Sorin) determined by IRMA together with of other markers commonly used: CA 15.3, CEA and TPA. Serum levels of these markers were analyzed in 188 female subjects classified as follows: 54 blood donors (control group) and 135 patients with breast carcinoma of which 71 had active disease and 64 were in complete remission.

CA 549 results in the control group oscillated between <5 and 11.7 U/ml; mean=5.75 and SD=I.7. SP2 levels oscillated between<2.5 and IS.6 U/ml, mean=5.76 and SD=2.3. Cut off levels fer CA 549 and SP2 were situated at 12U/ml and ii U/ml respectively. These limits were obtained from the cancer group patients utilizing various upper normal limits. Cut off levels used for CEA, CA 15.3 and TPA were 5 ng/ml, 30 U/ml and ii0 U/I respectively.

Sensitivity (S), Specificity (Sp) and Accuracy (A) in the cancer group patients were: CA 549 S=84.5%, Sp=87.5% and A=86%; SP~2 S=40.8%, Sp=87.B% and A=64%; CA15.3 S=87.3 Sp=92.2 and A=89.6; CEA S=67.6%, Sp=93.V% and A=80%; TPA S=81.7%, Sp=81.2% and A=B1.5%. CA 15.3 showed the best global results although no significant differences were observed between CA 15.3 and CA 549. SPg showed poor S with high Sp. If 2 or 3 markers are used in combination (considering a positive result the elevation of i of 2 and 2 ef 3, respectively) the best results are obtained with the associations CA 15.3 and SP2 (S=94.4%; Sp=82.8% and A=B9%) and CA 15.3, CA B49 and TPA (S=86%, Sp=93.7% and A=89.6%) altheugh no significant differences were observed globally with the isolated use of CA 15.3 or CA5~9 Therefore combinations of 2 er 3 markers are net necessary to correctly evaluate patients with breast cancer. In order to evaluate the diagnostic and predictive value of SCC-Ag, serum levels were analysed in 43 patients with cervical carcinoma, 38 with squamous cell carcinoma and 5 with adenocarcinoma, before and during treatment. All patients were staged according to the FIGO classification; they were further subdivided into three groups; St 0 and la (carcinoma in situ and micro-invasire carcinoma), St Ib and II (early invasive carcinoma) and St III, IV and recurrent disease (advanced carcinoma).

Serum SCC-Ag determinations were performed by radioimmunoassay (Abbott-kit) using a cut-off value of 2,5 ~g/l, the positive rate of SCC-Ag was 48,8% (50% in squamous cell carcinoma and 40% in adenocarcinoma) with a median value of 2,23 ug/l and a range of 0,08 ug/l ---> 46,10 ug/l.

In the first group there was no elevation of serum SCC-Ag; in the second and third group however, a positive SCC-Ag value was demonstrated in 42,1% and 68,8% respectively. SCC-Ag seemed to reflect well the degree of advance of cancer, showing a good correlation between its positive rate and the clinical stage. Effective therapy was followed by a rapid decrease in SCC-Ag in the individual case.

In conclusion, SCC-Ag is not useful for diagnosis because of low sensitivity.

In more advanced cancer however, serum SCC-Ag levels increase proportional to the extent of the disease.

Furthermore SCC-Ag seems to be a reliable index of recurrence and a potential means for evaluation of treatment results. assessing whether a palpable nodule is benign or malignant and thus in selecting patients for surgery. This is why,following the study of Fossel and Cart (1986),we investigated the potential usefulness of water suppressed Proton Nuclear Magnetic Resonance spectroscopy for thyroid cancers. Our prospective study concern 71 patients (58 women with mean age 53 and 13 men with mean age 50 ),consulting for thyroid nodule or nodular goiter for I$ months. Each patient had a 123 I scintigraphy and most of them ultrasonography imaging and 201 Thallium scintigra~, Blood samples (5 ml ) were collected from all the patients,plasma were separed and stored at 4' C, then analysed by NMR spectroscopy with blinding of diagnosis. For each plasma, .a spectrum was obtained and the mean line width of the methyl and methylene resonances was measured The final anatomopathologic diagnosis were : 16 malignant tumors (6 medullar carcinoma and I0 vesicular or trabecular carcinoma), 23 benign tumors,14 goiters without cancer and 18 others pathologies. Statistical analysis of the mean values demonstrate that there is neither significant difference between the mean line widths for medullar carcinoma group (45,9 I-Iz +/-II.9,67.2 I-Iz +/-9) and other thyroid carcinoma group (40.8 l-lz */-4.9, 71,I Hz */-16,2) (P >0,05 ) nor between the whole thyroid carcinoma group This study was undertaken to determine the ro. le of TAG72 as tumor marker and its comparison with CEA,Ca 125,Ca 19-9,Ca 15-3 in pts with malignant diseases.

Total 901 blood samples were collected from 754 pts with malignant diseases(gastointest.c. Increased levels for TAG72 were found in43,3% of pts with ovarian cancer against 47,9% for Ca 125 and 38,5% for Ca 15-3.In pts with gastrointestinal cancer TAG 72 was elevated in 35,6% against 57,2% of Ca 19-9 and 44,3% of CEA.In advanced stages of breast cancer TAG 72 showed less sensitive(33,3%)against 82,2% for Ca 15-3, 73,3% of CEA and 57,1% for Ca 125.In lung cancer elevated levels of TAG 72 were found in 29,3% against 40,6% for Ca 125 and 25% for CEA. The sensitivity of all markers was very low in pts with head neck cancer and renal cancer also in pts with benign diseases. Conclusion.These results suggest that I)TAG 72 is more sensitive in ovarian cancer and comparable with Ca 125 2)In gastrointestinal,uterine and lung cancer TAG 72 was found sens• as the other markers but the sensitivity increased by the combination of all markers 3)In headneck and renal cancer the sensitivity was low while the specificity was very high. We have tested a newly developed sandwich assay for the determination of Tg (Dynotest Tg, Henning, Berlin), based on two monoclonal antibodies in the follow up of patients with thyroid carcinoma.

The technical performance of the assay was excellent. This enabled us to determine Tg with high precision down to values < 1 ng/ml.

The coefficient of variation (CV) for the intra-assay reproducibility was < 5 % at levels of 10, 40 and 150 ng/ml. For the inter assay reproducibility we found 10 + 9%,42+4.3%and 149+_5.1%.

Excellent correlation was found with the older Tg-RIA method for the values between 6.5 and 500 ng/ml. The correlation coefficient for the double logarithmic plot was R = 0.98. The values found with the new kit are 2 times higher than the former ones.

Of 70 thyroid ca patients (48 papillary, 22 follicular) 53 had values < 1 ng/ml, two of which were falsely negative, showing metastases in 1-131 whole body scintigraphy.

17 had Tg values varying from > 1 to > 500 ng/ml. 16 of those (including 3 patients with Tg = 1,2 resp. 3) had corroborative positive evidence for the presence of tumor tissue. For one patient with Tg = 1, more evidence is required.

The new IRMA Tg assay will obviously enable us to find evidence for the presence of thyroid ca tissue at an earlier stage in many cases. More evidence will have to be collected on patients with lower serum values, before a cut off value can be given. Tc 99m-labeled human poiyclonal immunoglobulin (HtG) has been shown to be able to localize inflammatory sites. Hypothetically the immunoglobulins bind directly to bacteria, directly to Fc-receptors on the surface membrane of leukocytes or simply permeates increased permeable vessels. To get turther informations the Following in-vitro experiments were performed with the blood of human volunteers. 0,5mq Tc-99m-HIG(Mallinckrodt Diagnostika), 2mg Tc-99m human atbumFn(Behring-Werke) and 0 5mqT&-99m-labeled routine monoc ional antigranulocyte antibodies (?~ehring-Werke were added to in-vitro isolated human 'pure' leukocyte pellets and to 40ml of tile whole blood of 6 healthy volunteers. The whole blood and the direc~ ly labeled leukocyte pellet were layered and separated on a discontinuous PERC 9 gradient. The activity distribution was measured within the gradient with a ROI -technique by the means of a gamma-camera and %n gn-line computer-syw

Th, e s,ame experiments were repeateo aTter preincuDation oT the Cell pellets with increasinr concentrations of unlabeled human polyclonal im-munoqlobulinsCSandoglobln, SANDOZ) ( 0, 5rag, 2rng, 5mg, lOmg) . The Tc-99m-HIG laiSeled gradients showed a significant, uptake of the activity within the monocyte layer(direct: monocytes(m):20%; ~ranulocytes(g): 2.7% red cells(r): 5.8%/whole blood: m: 17.1% g: 3.3%, r: 1.6% . The Tc-99m-albumin gradients showed no specific albumin uptake in any eetluiar band(direct: m: 4.1%; g: 2.4%; r: 2.1%; whole blood: m: 2.2%; g: 0,5%, r: 0.4%), The Tc-99m-antibody labeled gradients showed a significant increased uptake on granufocytes(direct: m: 12,2%; g: 26.,~%; r: 4.6%; whole blood: m: b.6% g: 26.4%; r: 7.9%)(x+/-2SD;n=10). The Tc-99m-HIG uptake in the rnonocyte layer could be competetively blocked with increasing amounts of unlabeled human polyglobulin. The authors conclude, that in humans a specific monocyte associated uptake and binding mechanism of Tc-99m-HIG plays an important role ;n Iocalisation of inflammatory sites. We studied 12 consecutive patients with infection sites confirmed by surgery or culture of exudates in whom both 99mTc-policlonal immunoglobuline (IG) and 99mTc-ant%granulocyte monoclonal antibody (AGAb) detected the infection sites, and compared the patterns of uptake. Planar and SPECT scans were acquired after 4 and 24 hrs of i.v. injection of I mg of IG, and 48 hrs later of I m9 of AGAb (each agent labeled with 15 mCi of 99mTc).

The infection sites were delineated by manually outlining the zone of uptake and counting the number of pixels in a 128x128 matrix. The resulting size was normalized to percentage. Target to background ratio (T/B) was assessed deviding average counts per pixel in the infection site by average counts per pixel in the adjacent normal zones in the 24 hrs scans. The size of infection zones delineated by IG was larger than that by AGAb in 10/12 patients, and similar in I. AGAb scans showed a higher T/B in 9/12 patients.

Size We conclude that IG delineates infection sites with a more extended pattern and less target to background ratio than AGAb. This can be due to a more extensive area of inflammation detected by IG as compared to the granulocyte infiltration zone seen in the AGAb scans. Immunoscintigraphy with 99mTcMab-NCA95 (Moab) has been performed in 8 normal volunteers (A) and in 19 patients (B) to study kinetics of Moab and its clinical relevance in different inflammatory processes. Each subject received 370MBq Moab (0.3mg). Blood samples were taken at 5 ',15',30',lh,4h,8h (A,B) and 24h (A) to obtain blodd clearance curve (A),recovery rate (RR) at lh .peripheral leucocyte count,and granulocyte specificity of Moab at 30' with Percoll-Saline gradients (PS). A dynamic study during the first 30' (A) and scans at lh,2h 5h and 24h were performed. In vitro stability was >93% at ]h and ~ 85% at 24h. The peripheral leucocyte count was stable at24h. Blood e!earence curve fitted correctly with a biexponencial model (TI~=41.8~4.B',T2~=II78~82.5'). The RR at lh in A (48.4~6.1%) and B(~1.3~9.6%) were not statiscally different. In vivo curves show a progressively increase over Done marrow (BM),a rapid increase and then a p]&teau over spleen and a perfusion pattern over liver. Peripherie granuloeyte bound activity with PS at 30 t was only 10%. We studied 19 patients with these results: Clinical diagnosis n TP TN FP FN ~Tibia fracture. Bone infection 9 5 2 1 ~ 1 ~ ~Septie prosthesis. Tc-99m by a kit procedure (efficiency > 95 % (HPLC), no purification, preserved immunoreactivity; Schwarz Method) and given i.v. to 7 kidney transplant recipients and 1 patient after heart transplantation. Imaging (whole body/regional scans) was performed 20 man, 2-7 h and 21-25 h post injection.

Intense transplant uptake was found in all patients with acute cell-mediated kidney rejection (confirmed by biopsy) whereas the heart transplant showed no uptake (normal biopsy and negative antimyosin scan). Normal kidneys showed no antibody accumulation. Cytomegaly virus pneumonia was detected by immunoscintigraphy which demonstrated increased lung uptake. Short-lasting (<24 h) peripheral lymphopenia (FACS analysis) was observed at doses > 0.2 mg of the injected MAb. No HAMA response was found.

These preliminary data are promising and demonstrate that immunoscintigraphy using a Tc-99m labeled anti-T-cell monoclonal antibody can be used for the rapid and specific non-invasive identification of transplant rejection. Arterial occlusion may be treated by intra-arterial thrombolysis thus avoiding major surgery.

From the clinical history it is often difficult to determine the age of the thrombus and arteriography does not reliably distinguish between acute and chronic occlusions. Since the success rate of thrombolytic therapy falls if the thrombus is not of recent origin we have used the monoolonal antibody P256 Fab' for both the localisation and assessment of the maturity of thrombi.

20 MBq In-lll-P256 Fab' (iO0 ~g) was administered i.v. to 20 patients presenting with lower limb ischaemia and images recorded at intervals between 80 minutes and 24 hours.

Positive loci of uptake were clearly visible in 9 patients due to active platelet deposition at sites of occlusive thrombosis, stenosis and proximal aneuryam. 6 of these patients were lysed successfully although 1 with a popliteal aneurysm immediately rethrombosed.

In some cases sites of thrombus formation not clinically apparent were detected and additional information to that provided by arteriography was obtained.

Chronic 'non-active' thrombi generally greater than 30 days old were not visualised.

The high resolution of the images and the ease of preparation of this antibody make this technique a significant advance over other currently available methods.

Assessment of the maturity of arterial thrombi would be a valuable investigative tool for all patients presenting with peripheral arterial occlusion. We studied 21 patients with the thrombocyte specific mouse monoclonal antibody BW4 (n=13) and its Fab'fragment (n:8). Methods: Planar scintigrams were acquired 4 to 6 hours after intravenous injeetion of the antibody or its fragment labelled with Tc-99m. Whole body scintigraphy and dynamic seinti~Taphy of the anterior chest and the upper abdomen during the first hour p.i. were performed to study organ distribution. Recovery and cell associated activity were determined in blood samples taken 5, 15,30, 60 and 120 min after injection. Results: The recovery of the whole antibody was 20 % that of the fragment 24 % ( 2h p.i.). Average cell associated activity was 91% for the whole antibody and 37 ~ for the fragment. The whole antibody showed a higher lung uptake (39% of whole body activity) compared to the fragment (119). Ph~ebothrombosis proven by phlebography or Doppler Ultrasound could be visualized in 6 patients with the whole antibody and in 5 patients with the fragment. One false negative result was found with the whole antibody and with its fragment, respectively.

Conclusions: According to this study the monoclonal antibody BW4 is suitable for imaging phlebothrombosis in the early stage. The high lung uptake of the whole antibody probably due to platelet aggregation has the advantage that lung perfusion imaging and thrombus imaging can be performed with one single injection. The efficacy of aerosolised pentamidine (AP) as prophylaxis against Pneumocystis carinii pneumonia will depend on the dose delivered to the lungs. In 8 patients with AIDS pulmonary deposition (PD) of AP 300mg (6 ml solution)

was measured when given via 3 ultrasonic (UN) and 4 jet (JN) nebulisers (driven by an AFP Medical air compressor). 99mTc HSA (37 MBq, 0.i mg) was used as an indirect marker for pentamidine. PD and nonpulmonary (gastric and pharangeal) deposition (NPD) were measured using a gamma camera during and after 40 min. nebulisation. Deposition was completed more rapidly for the UN (<15 min)than the JN (>25 min) . PD (total, both lungs) is shown in the Objective : To evaluate the comparative efficacy of three nebulizers for lung deposition of pentamidine.

Methods : Pentamidine isethionate (150 mg), mixed with technetium-99m-labeled human serum albumin was administered by means of one jet nebulizer (Respirgard, Marquest) and two ultrasonic uebulizers (DP 100, DP medical ; Portasonic, De Vilbiss) to 8 HIV patients under primary prophylaxis with aerosolized pentamidine. All patients inhaled pentamidine with each nebulizer (one inhalation every two weeks) and the lung edge was previously defined by 20% contour of the chest posterior view on a 99-m Tc-macro-aggregates perfusion scan. Side effects during inhalation were recorded. Four indexes were determined : lung uptake / lung+stomach+nasopharynx uptakes (PF), aerosol penetration index (API) calculated by PIV/PIP where PI : peripheral counts per pixel/inner counts per pixel with PIV measured after inhalation and PIP after perfusion, total pulmonary uptake (TPU), absolute alveolar deposition (AAD) defined by API x TPU.

Statistics : Data were processed by a threeway ANOVA procedure Results PF (%) API TPU AAD Respirgard 1-80.6+_2.8 f" 1.63_-t-0.42 1"3045+552 6234+_2888 DP 100 "174.4+5.8 *f2.35+0.50 "75225_+451 12843+3553 Portasonic ~68.9i-_2.8 t-2.60-!-0.43 J-3629!-_510 9516+_2473 Conclusions : 1) Respirgard was the best tolerated nebulizer with the lowest extrapulmonary deposition. 2) The highest relative peripheral deposition reflected by API was obtained with the Portasonic although the absolute alveolar amount (AAD) was not significantly different. 3) Ultrasonic nebulizers with high potency quartz can achieve high alveolar deposition but are associated with more frequent side effects. Inhalation scintigraphy with radioactive aerosol has some certain limitations. Radioaerosol deposition in the airways follows not only regional ventilation but is also influenced by the particle size, airway geometry and breathing manoevre. In this study it is shown for the first time that not only the particle deposition but independently from this also the particle flow itself is changed by the physical characteristics of radioaerosol.

This was shown in a fantom of communicating glas tubes with built-in stenoses( 1.7 -9 m m). The gas flow in all 7 stenoses was kept constant by varying its length. A wet standard aerosol ( AMD 0.45 um ) and a dry ultrafine aerosol ( AMD 50 A, evaporation of Tc-99m pertechnetate at 2500 ~ on graphite ) was used. The flow in the fantom was increasd step by step from 5 to 50 ml/min and the passing radioaerosol collected in bacterial filters. In general a linear correlation was found between the input gas flow and the activity in each filter and tube together as a measure of particle flow However, in stenoses below 3 mm in diameter the percentage of slope was different in an opposite way in laminar and eddy flow for the wet and dry radioaerosol. In conclusion, dry and ultrafine radioaerosol provides more precise results in inhalation scintigraphy. In order to ascertain the role of 99m-To DTPA lung clearance in the management of interstitial pneumonitis (IP) by identifying the abnormal alveolar membrane permeability, characteristic of this condition, 160 studies were undertaken in 2 different populations in which IP is a common problem; 79 patients with AIDS and 25 children undergoing bone marrow transplantation (BMT). In baseline studies of AIDS patients without evidence of opportunistic infection, the mean half clearance time (T 89 in 33 non-smokers was 52.0 min (SD 17.4 min) and in 11 smokers was 22.8 min (SD 4.2 min). In the baseline investigation of 19 children, similar values were encountered in 17 (mean T} 51.7 rain; SD 22.1 rain), shorter values in the other 2, following exclusion of alternative aetiology, being attributed to pre-eonditioning chemotherapy. Abnormal clearance rates were obtained in 44 AIDS patients (mean 9.3 min; SD 5.5 mln), ll of whom initially had had normal results. Pneumocystis infection was the most frequent aetiological factor, being identified in 50 patients, all but 2 having accelerated T 89

An abnormal chest X-ray was associated with a shortened T 89 in 15/28 (54%) while blood gas abnormalities and raised lactate dehydrogenase levels were obtained in 26/35 (74%) and 21/26 (81%) respectively. In a further 1O children, 4 initially normal, the T 89 was accelerated (9.2 min; SD 6.2 rain), being associated with a variety of causes, including graft versus host disease and cytomegalovirus.

In only 5 of the 12 children with an accelerated T 89 was the chest X-ray abnormal. Measurement of pulmonary aerosol clearance does therefore provide a sensitive and inexpensive method for the early detection of suspected IP and monitoring of therapy. Deterioration from a personal baseline clearance has been found to be the most reliable indicator. A COMPARATIVE STUDY OF XE-133 AND Tc-99m-GAS FOR ASSESSMENT OF REGIONAL VENTILATION.

A new Tc-99m based ventilation agent Tc-Gas was recently introduced. The aim of this investigation was to compare, qualitatively and quantitatively, regional ventilation (reg.V) obtained with this new agent to conventional Xe-133 methods, and to explore the potential for SPECT of V and perfusion (Q). Sixty pulmonary regions from 10 patients in stable respiratiory condition with normal or varying degrees of pulmonary function testing abnormalities were evaluated 3 ways: I. blinded qualitative reading, 2. computer quantified reg.V and 3. consensus qualitative comparison. SPECT V and Q studies were evaluated by a new method where corresponding V and Q slices are simultaneous analyzed, and V/Q ratios computed.

All Tc-Gas studies had diagnostic quality, no hot spots were seen. Agreement in reading of reg.V for Xe-133 and Tc-Gas studies by 2 observers was 58% and 62% respectively. Significant correlations between quantified reg.V for Xe-133 vs Tc-Gas were found (r=0.8~ p< 0.001). The agreement (Bland/Altman) between the agents, for computed reg.V, was limited (coefficient of agreement = 55.6%, 95% limits of agreement = -63% to 48.2%). Clinically significant differences in consensus qualitative comparison were detected in six subjects.

Tc-Gas was quickly and easily produced on location and yielded, in all cases, images with diagnostic quality. Reg.V with Tc-Gas showed a linear relation to reg. V with Xe-133. However, limited agreement between the 2 imaging agents, by all 3 evaluation methods, was seen. These differences were clinically significant. The potential for SPECT of V and Q was confirmed. 

Theregional counts detected by a gamma camera from a 81mKr ventilation study depend on many factors, notably the regional specific ventilation inspired 81mKr concentration, number of breaths per image and the geometry of the lung and thoracic wall. A computer model was used to calculate the distribution of 81mKr in the lungs of a seated patient as seen by a gamma camera. The distribution in three zones, upper, middle and lower, was assessed following steady state brathing of 81mKr. Predefined values of specific ventilation and varying breath rates and breathing patterns were examined. The change in inspired concentration during the course of the breath was taken into consideration. In a group of 88 patients the median number of breaths to acquire a posterior image was 27 (range 9-101). The counting geometry was determined from a thoracic CT scan, assuming lung tissue densities of 0.2, 0.3 and 0.4 g/ml for the upper, middle and lower zones respectively. The detected counts per unit volume were 5% and 12% greater in the middle and lower zones compared with the upper zones. For a normal subject the gamma camera would have estimated the ventilation in all zones to within 2% of the true value. Breath rate, breathing pattern and inspired concentration changes had little influence on this result. Having the specific ventilation to any zone caused the ventilation to that zone to be overestimated by 6% with a corresponding underestimation shared between the remaining regions. In conclusion the distribution of 81mKr provides an indication of ventilation adequate for most clinical purposes, but accurate quantification of ventilation cannot be determined from routine 81mKr images. 

D-and L-alanyltriglycine (DAG3 and LAG3) can be considered as derivatives of MAG3 in which the mercaptoacetyl group is substituted by a 2-aminopropionyl group. We have labelled these tetrapeptides in high yield with Tc-99m, either directly at room temperature by mixing the ligand, SnCl~ and generator eluate in alkaline medium or by exchange labelling in the presence of sodium tartrate at different pH values. RP-HPLC analysis of the reaction mixtures showed that, irrespective of the labelling method or pH, each mixture contained 2 peaks in a 50:50 proportion, probably the syn and anti diastereomers of the Tc-99m complexes. After isolation by HPLC and storage at neutral or alkaline pH, each peak converts gradually to the other one. After 1 hr equal amounts of both peaks are again present, but no TcO 4 or other impurities are formed. Biodistribution of a 50:50 mixture of the two peaks of respectively Tc-99m DAG3 (I) and Tc-99m LAG3 (II) was studied using 1-131 OIH as internal biological standard. Urinary excretion in mice at I0 min and 30 min p.i. for I and II was similar as for Tc-99m MAG3 (III), but liver uptake of I and II was somewhat higher. The 1 hr-plasma clearance values obtained in a baboon are respectively 60% (I), 54% (II) and 51% (III) of OIH clearance.

Activity accumulated rapidly in the kidneys and was excreted efficiently in the urine. The results show the comparable biological behaviour of I and II with respect to Tc-99m MAG3. The study of the metabolites of the brain perfusion agent Tc-99m ECD has shown that the di-acid derivative, Tc-99m L,L-ethylenedicysteine (Tc-99m EC,I) is excreted rapidly in the urine. We have now investigated I in different animal species in order to evaluate its potential use as a renal function agent. I man be prepared within a few minutes in high yield (> 98%) at room temperature by mixing L,L-EC (l mg), SnCl~ (1O-lO0 ~g) and generator eluate (0.37-3.7 GBq Tc-99m) at alkaline pH. Labelling is complete after a few minutes.

Neutralization of the reaction mixture after labelling does not affect the radiochemical purity. Biodistribution of HPLC-purified I and Tc-99m MAG3 (II) was compared in mice and baboons, using DIN as internal biological standard. In mice (n=lO) at 10 min p.i. I shows a higher urinary excretion (ratio I/II=l.ll), a lower activity in kidneys (I/II=O.54), liver (I/II=0.32), intestines (I/II=0.54) and blood (I/II=0.84).

The ratios are only slighly different at 30 min p.i. Urinary excretion of I is decreased by 30% in probenecid pretreated mice, which indicates active tubular transport. After I.V. injection of I in baboons, activity clears rapidly through the kidneys to the bladder without visualization of liver or intestines. Renograms of I and II are comparable but renal retention at 30 min is somewhat higher for I.

Protein binding of I is lower than of II whereas its distribution volume and l hr-plasma clearance are clearly higher. The animal results indicate that Tc-99m L,L-EC may be a useful alternative to Tc-99m MAG3 for renal function studies. I~.Barbarics, Gy.A. J~noki "FJC" Natl.Res.Ins%. for Radiobiology and Radiohygiene, Budapest, Hungary

Earlier we have reported the synthesis and examination of three new 99mTc-labelled isonitrile complexes. The 2-methoxy-2-isobutyl-isonitrile (HIBI) was produced in a new and simple synthetic way in our laboratory; and we published 2-methoxy-2-methylbutyl-isonitrile (HHBI) and 2-methoxy-2-ethylbutyl-isonitrile (HEBI) first. The aim of our work was to synthesize two further isonitriles: the 2-ethoxy-2-isobutyl-isonitrile (EIBI) and 2-propoxy-2-isobutyl-isonitrile (PIBI). The 99mTe-isonitrile complexes were formed via the tin(II)chloride reduction of 99mTc-pertechnetate. Complex formations over % % were observed and an excellent in vitro stability for 8 hours. The biodistribution, pharmacokinetics, the rate of urine excretion and the metabolism of the labelled isonitriles were determined and compared in rats. Radio-HPLC analysis of urine shows that the rate of metabolism in case of HIBI was 15 %, EIBI was 30 during 2 hours.

Organ ratios I.D.

Heart Lung Liver Kidney Z-11~-chloromethyl-17~-iodovinyl-estradiol (Z-CMIV) has been synthesized and described as a very high affinity ligand for estrogen receptor (t0 times higher than estradiol).

Selectivity and stability are two crucial parameters to choose a 9ood radiopharmaceutical agent for radioimaging of tumour tissues.

Selectivity index is calculated as the ratio of the RBA (Relative Binding Affinity) for estrogen receptor and the RBA for plasma sex steroid binding protein (SBP).

Binding assay to SBP was performed by competition of the binding of tritiated estradiol at 4~

The resulting selectivity index is 4016 for Z-CMIV, 689 for the E isomer, 73 for ll~-chloromethyl-estradiol and t for estradiol.

Stability of Z-CMIV labelled with iodine 125 and 123 and evaluated by HPLC in plasma diluted medium (37~ or in solution (as ready to inject) is better than 95% after 24h. From biodistribution experiments in mice and rats, target versus non target tissues ratios above 200 were obtained.

The Z isomer was labelled with 1-123 and excellent radioimaging of a human tumour,grafted onto nude mice, was obtained.

As evaluated by the ROI metho~ the specific tumour uptake was reduced to 5% and 6.5%, if excess cold estradiol and Z-CMIV respectively were coinjected with the 1-123 labelled Z-CMIV.

We can conclude that Z-CMIV is a promising agent for the imaging of tumour tissues containing estrogen receptors as we seen in a great percentage of breast cancers. This work is supported by an European EUREKA grant (EU/18t/18). We present results of 28 patients with breast cancer who received 1-123 E2 and underwent SPECT imaginguf breasts and axillae to detect estrogen receptor positive (ER + ) breast cancer in vivo. Following approval by institutional review board and obtaining informed consent from the patient, 50pCi/kg ofi-123 E2 was injected intravenously, SPECT imaging was performed two hours after injection. A Siemens Orbiter and Sophy G § computer was used. Median clinical follow-up was 24-months (range 46-2 months.) I-123 E2 SPECT imaging demonstrated 8 of 9 breast cancers proven histologically present at time of imaging. Four tumors were ER+, 3 were ER-and two were of undetermined ER status. There was one false negative of unknown ER status. Four of four metastases were seen, six of six axillary nodes were seen. Initially there were 12 "false-positive" axillary nodes and two "false positive" scans showing mediastinal involvement. With clinical follow-up, 2 of 12 axillae are found to contain tumor and 1 of 2 mediastinum demonstrated cancer of adequate volume to be detected by current radiographic techniques. Asymmetrical 1-123 E2 uptake in breasts with dense mammographic fibrocystic disease was associated with breast cancer while no increase of 1-123 E2 has been associated with a benign follow-up. Use of 1-123 E2 has clinical promise. 

We report the results of the first trial comparing the new directly injectable agent 99mTc Human immunoglobulin (HIG) with lnIndium oxine leucocytes in the identification and localisation of focal sepsis and active inflammatory bowel disease. 61 studies were performed on 59 patients (31 male, 28 female, mean age 58, range 15-78) referred for labelled leucocyte studies. Local ethical committee approval was sought and granted for this study. All patients had an infusion of 20MBq of 11tIndium oxine labelled autologous leucocytes followed by an infusion of 200MBq of 99mTc-HIG. Patients were imaged on an IGE 400AC Starcam system. Simultaneous dual acquisition was obtained 1,4 and 20 hours post injection. A medium energy collimator was used.

There were no major or minor side effects to the agent. Blood pool activity remained high for at least 6 hours post injection. There was persistent clearance of tracer via the renal tract for 24 post injection. 

Recently the macromolecular nature of human polyclonal nonspecific immunoglobulin G (IgG) and the increased vascular permeability in inflammation foci were proposed to explain the clinical findings with In-lgG as a localizing agent for inflammatory lesions.

To evaluate the influence of protein type and radiolabel on abscess uptake, groups of four Wistar rats with a Staph. Aureus infection of the left calf muscle were injected i.v. with 4 M Bq of either 1-131-human serum albumin (HSA), In-111-HSA, Tc-99m-lgG, or In-111-1gG.Rats were sacrificed at 2, 6, 24, and 48 hr p.i. (Tc-99m up to 24 hr). Percentages of dose per gram (%lD/g) were calculated for various tissues. In addition abscess to muscle and abscess to blood ratios were calculated.

Highest abscess uptake: 1.25 +_0.22 (%lD/g; In-lgG, 48 hr). Lowest abscess uptake: 0.098 _+ 0.014 (%lD/g; I-HSA, 48 hr). Highest abscess to muscle ratio: 6.1 _+ 1.7 (In-lgG, 48 hr). Lowest abscess to muscle ratio: 2.8 _+ 0.6 (I-HSA, 48 hr). Highest abscess to blood ratio: 2.2 _+ 0.7 (In-HSA, 48 hr). Lowest abscess to blood ratio: 0.38 +_ 0.05 (I-HSA, 48 hr). All preceding values are means offour _+ SD. ln-tgG had the slowest blood clearance. Although the abscess uptake of Tc-lgG was lower than of either In-HSA or In-lgG, the abscess to muscle (A/M) ratio for these agents was not significantly different (2-24 hr p.i.). In-HSA showed a significantly higher tissue uptake than I-HSA. However the A/M ratio for both agents was not significantly different. IgG had a much higher kidney uptake than HSA. In-HSA was taken up in abscesses to the same extent as In-lgG, though less specifically.

In conclusion: we prefer In-lgG over Tc-lgG because the best results were obtained at 48 hr. The choice of the radiolabel and the size of the macromolecule seem to influence the extent and specificity of the uptake of radio-proteins in inflammation foci. The purpose of the present study was develop a radiopharmaceutical stable enough to withstand the drastic pH changes and enzymatic action prevailing in the GI tract. Polymeric latexes containing monodisperse polymeric spheres with extremely unit sizes (i~-i0~) were prepared by a novel coaxial dispersion polymerization of styrene and dimethylaminoethylacrylete (DMAEA). Polystrene was the basic carrier matrix. Poly DMAEA was a positively charched coating. These particles (25 mg in 0.5 H20 solution) were labelled with 99mTc04 -(370 MBq) by the use of the tin reduction method. The labelling efficiency was >99% as determined by ITLC-SG strips in acetone. The stability of the label was tested up to 48h after storage at R.T, The amount of free 99mTc04-was 0.39 + 0.29% ( 15 determinations). The labelled particles (37 MBq in 1 ml) were given orally to 5 rabbits. Scintigrams were obtained at certain intervals up to 48h by a gamma camera (Toshiba GCA 601S). ROils were drawn over the GI tract and whole body. The feces were collected and counted against std. Almost all the radioactivity (>99%) remained in the GI tract. The colon was visualized very well. The rest of the body including the thyroid could not be imaged. Our results indicated that the radiopharmaceutical developed in this study was stable both in vitro and in vivo and demonstrated the GI morpholgy in detail and was thus ideal for the intended purpose. The prevalence of human active atherosclerotic lesions imaged by lllIn-oxine radiolabelled platelets varies (3-90%) in various segments in different clinical conditions in adults. Patients (n=80) with positive lesions after autologous radiolabelling (100~Ci lllIn-oxine) of platelets suffering from coronary heart disease and peripheral vascular disease as well were selected. We examined the time course of local lesion piatelet deposition and platelet survival under the single and combined treatment of prostaglandins (PGI2, PGEI) and organic nitrates (nitric oxide [NO] donors: isosorbide dinitrate, molsidolate). The platelet uptake ratio (PUR) (i.e. counts over the lesion area divided by the ones over unaffected contralateral side after background subtraction) was quantified daily for 5 days before therapy and after 5 weeks during treatment. Platelet survival was calculated using the multiple hit model. Both the NO-donors had no effect on PUR and platelet survival significantly. The PG's (PGI2 > PGEI) caused a significant improvement of both PUR and platelet survival. The combined therapy of PG and NO-donor induced a further significant improvement in local (PUR) and systemic (survival) haemostasis. These findings for the first time show a synergistic action of prostaglandins and NO in vivo in reducing vascular thrombogenicity. We have recently demonstrated significant differences between regional cerebral accumulation of radiolabel derived from fluorodeoxyglucose (FDG) and glucose (GLU) under conditions of local stimulation. In order to better define whether these changes are caused by transport or metabolic differences, we developed a double tracer method for direct measurement and comparison of FDG and GLU rate constants.

We applied the technique to a series of normal rats. Each rat was given an infusion containing a mixture of F-18 FDG and C-14 GLU while arterial blood samples were drawn. Different groups of rats were sacrificed at 1, 3, 6, and 12 minutes. Autoradiograms of brain sections were digitized and compared to determine the relative and absolute concentrations of F-18 and C-14.

Kinetic constants for FDG and GLU were then determined by fitting the standard two compartment (Sokoloff) model to the data. Mean values agreed with reported total brain values from single tracer studies [ KI(FDG) = 0.38, KI(GLU) = .27, k3(FDG) = .18, k3(GLU) = .23 ]. Regional variations in rate constants occurred, but variations in those of FDG paralleled those of GLU.

Initial results under stimulated conditions have demonstrated regional alterations of both transport and metabolic constants, suggesting regional changes in the lumped constant. Uptake and metabolism of amino acids in brain tissue is of increasing interest because of the diagnostic potential lor grading of brain tumors. In order to transfer some of the potential, identified by PET users, to conventional nuclear medicine with SPECT, we have analysed the biokinetics of labeled p-lodo-phenylalanine (IPA) in rat brain and rat brain tumors and compared them with the natural amino acids phenylalanine, methionine and leucine. The rat brain tumor model used in this investigation is based on i.p. injection of ethyl-nitroso-urea.

[1251]-IPA was prepared by exchange labelling.

[14C]-amino acids were obtained from Amersham. Rats were injected 0.9 mBq of either compound intravenously and sacrificed at lime intervalls ranging from 5 to 120 min. Brains were removed, dissected and homogenized. Protein bound activity was precipitated by trichloro acetic acid. The non-bound fraction was separated from the protein traction by centritugation.

In plasma the natural amino acids are cleared rapidly. Metabolites appear in plasma after 10 min. In contrast IPA remains at a constant level after its distribution for at least 120 min, indicating that it is not metabolized. The uptake of phenylalanine in brain tissue is fast and completed in a short time for as for other amino acids. The uptake of p-Iphenylalanine is characterized by a fast initial rise to nearly the same level as for phenylalanine, followed by a further but slower uptake phase which continues for 60 minutes. The protein incorporation of phenylalanine and leucine reaches 90 %, that of methionine 78% at 120 min. In contrast IPA is not incorporated into proteins at all. The celluar uptake consists at all times of free p-l-phenylalanine. The uptake of IPA can be blocked efficiently by saturation of the carrierenzyme in the BBB by methionine.

In conclusion we have found that p-l-phenylalanine is carried across the blood brain barrier by the same carder as phenylalanine, despite a total lack of further metabolism in brain tissue. The uptake in brain tumors is comparable to the uptake of methionine, which has established itself as a standard amino acid for brain tumor investigations with PET.

Allen S J+, Blake G M+, McKseney D B+, Lazarus C R+, Blower P*, Singh J*, Page C4+, Clarke S E M+ +Dept. of Nuclear Medicine, Guy's Hospital, London, UK q-~Dept, of Nuclear Medicine, St Thomas' Hosp, London, UK *Biological Laboratory, University of Kent, Canterbury A NEW RADIOPHARMACEUTICAL 186RE-V-DMSA FOR THERAPY OF MEDULLARY CARCINOMA OF THE THYROID 186Re is a beta emitting radionuclide (Emax = 1.07 MeV, T 1/2 = 3.8 days) with 10% of disintegrations leading to emission of 137 KeV gamma rays.

99mTc-v-DMSA is known to show high uptake into medullary carcinoma of the thyroid (MCT).

This suggests that substitution of 99mTc by 186Re might lead to a useful therapeutic agent in patients with MCT.

A tracer study was carried out in a patient with MCT to examine the kinetics and dosimetry of 186Re-v-DMSA and to evaluate its therapeutic potential. Following injection of a 700MBq tracer dose, gamma camera imaging, whole body counting, measurements of urinary excretion and whole blood and plasma concentrations were performed for 7 days.

The results were as follows. Total body retention was 21% at 24 hours, falling to 6% at 7 days. Whole body distribution on planar and SPECT imaging was identical with that of 99mTc-v-DMSA.

Excretion was through the kidneys, with a plasma clearance rate of 20mls/min. Whole body dosa was 0.05Gy/GBq, bladder dose IGy/GBq, kidney dose 8Gy/GBq and tumour dose 3Gy/GBq.

Our results suggest that, with pharmacological modification to eliminate the 186Re-III-DMSA renal uptake, 186Re-v-DMSA may prove a useful therapeutic agent for treating MCT. TC-99m-MRP20 (MRP20 is (N(-2(IH pyrolylmethyl))N'(-4pentene-3-one-2))ethylene 1,2 diamine) is a neutral technetium complex that show interesting possibilities as a brain perfusion agent. After obtaining the approval of the institutional ethical committee and written informed consent, we evaluated the safety and whole body biodistribution of TC-99m-MRP20 in four healthy male volunteers ~anging in age from 23-27 years. Blood samples were taken for biochemical analysis at i0 min before and 24h after injection. All vital signs were carefully monitored. Blood samples were also taken at 2,5,10,20,30, 60 mins and 2,4 and 24h p.i. Urine and faecal collections were made over 24h p.i.

Whole body images were acquired at lh,3h,5h and 24h p.i. and the absorbed dose measurements were determined from these by expressing specific organ uptake as a % of the injected dose. The calculations were made using standard MIRD tables. Brain uptake was 5.2% i.d. (s.d 1.6) after 15 mins, giving an absorbed dose of 6 mGy/GBq. The testes receive a dose of I mGy/GBq.

The bone marrow receives a dose of 3 mGy/GBq and the thyroid I mGy/GBq. The critical organs are the intestines (46 mGy/GBq) and the kidneys (31 mGy/GBq).

For an injected dose of 750 MBq, the effective dose equivalent was calculated to be 9.6 mSv.

No adverse signs or blood chemistries were detected and the data shows that Tc-99m-MRP20 is safe for human administration. The experimental problem in estimating the radiationdose resulting from the application of this human granulecyte selective antibody is the lack of cross reactivity with granulocytes of other species and therefore the lack of a direct animal model.

The kinetics using such an antibody reflects a superimposition of two conditions: i. direct intravasal labelling of granulocytes 2. extravasation of MAb and binding to cells in the tissue (e.g. already localised in the inflamed area) .

In a first step radiation dose resulting from these two extreme situations are calculated by adopting the kinetics of 1. in vitro labelled cells resp. 2. of tumor directed MAbs of the same isotype. The derived effective equivalent dose values are 4.6 resp. 2.8 mSv refering to an injected activity of 350 MBq. This estimation of a range of possible dose values allowed to start clinical trials in patients. These investigations finally delivered data to calculate the actual radiation dose. Evaluation of time-activity curves was possible in patients besides the whole body for liver, spleen and bone marrow.

Excretion of activity was negligible. Quantification of activity in the total bone marrow was done by upscaling the share of marrow seen in scintigraphs of ten patients without an inflammation in this area. About 1/3 of injected activity was found in the marrow and it was declining with an effective half live of 5.8 hours. The resulting effective equivalent dose -3.9 mSv/350 MBq -lies in the range of the preliminary calculation. DTPA-conjugated non-specific polyolonal human immunoglobulin G Sandoz labeled with Indium-lll (In-lll-IgG) is currently used for the detection of infection foci. Until now no data on the biodistribution and radiation burden of this radiopharmaceutical are available. After approval by the ethical committee 20 MBq In-lll-IgG was administered to healthy volunteers for dosimetric purposes.

Quantitative organ uptake and retention was calculated by planar gammacamera measurements on three consecutive days. Both photopeaks of Iniii were used. Bloodsamples and total urine and faeces excretion were collected for 72 hours. Total body retention was measured with a specially designed whole body counter. The radiation burden was calculated according to the MIRD concept. After 3 hours the uptake in the liver was 6% of the injected dose, kidneys 4%, spleen 1% and testes 0.2%. The following days no significant accumulation in or clearance from these organs was found. The 48 hours urine contained 10-20% of the administered dose. Approximately 80% of the urine activity was excreted in the first i0 hours. In the faeces only 1-2% was recovered.

In the first 20 hours the initial bloodactivity was reduced to 50%. After the first 8 hours the bloodactivity fitted well with a mono-exponential curve with a half-time of 50 hours. After 48 hours the whole body measurements showed a biological decay of 10%-20% in 6 days. The radiation burden to the liver was 0.4 mGy/MBq, kidneys 0.6 mGy/MBq, spleen 0.3 mGy/MBq and testes 0.3 mGy/MBq. The effective dose-equivalent was 0.2 mSv/MBq. Assuming a biodistribution of In-lll-lgG in patients similar to that in healthy volunteers, administration of 75 MBq In-lll-IgG (the standard dose administered to patients) will result in an effective dose-equivalent of 15 mSv and a dose to the testes of 25 mGy. Visual interpretation of the scintigraphie distribution in patients suggests that the uptake in the testes in elder men may be higher than in young volunteers. The relationship between chronic gastritis (CG), ulcer disease, and the importance of C.pylori (CP) infection measured by UBT, was evaluated in 211 patients : on basis of biopsy, 79 had a normal mucosa, 132 CG and 126 CP infection. Patients were given 185KBeq [14C]urea in 25mi water. The specific activity of breath 14C02 collected at 10min (%dose.kg; SA10min) was found to be reproducible and was not influenced by the rate of gastric emptying.

Using a SA10min value of 0.3% as the upper limit of normality, the sensitivity and specificity of UBT reached 98 and 95% for detection of CP, and 95 and 94% for detection of CG. Compared to a semiquantitative histological grading (0-3) for CP, and severity and activity of CG, mean SA10min values increased significantly between grades 0 and I, and between grades I and 2.

UBT (SA10min,%) Our data provide evidence of a quantitative relationship between the number of CP organisms, measured by UBT, and the activity and severity of gastritis. They also indicate that in CP+ patients, the presence of ulcer disease is not associated with a further increase of urease activity compared to values obtained in absence of ulcer disease. Hepatobiliary scintigraphy is necessary for the differential diagnosis of the cholestatic jaundiced infant.Sur gical correction of biliary atresia (BA) must be perfor I med within the first two months of life. In jaundiced pa tients (pts),hepatic uptake of Tc-99a-HIDA and its derivatives may fail to produce clinically useful images when the serum bilirubin is over lOmg%. The aim of this study was to evaluate the usefulness of Tc-99m-EHIDA,a recent Tc-99m-labelled hepatobiliary agent,in infants with high levels of conjugated hyperbilirubineaia.

We studied 9 infants(1.1-12.0 months of age)with choles tatic jaundice,5 for possible BA and 4 with previous sur gical correction of BA. Total serum bilirubin ranged 2.2 -18.0mg/dL. O.ImCi/Kg body weight (minimum of 2mCi) of To -99m-EHIDA were administered IV with the pts positioned on the gamma camera for an anterior image of the abdomen, Following injection,images were acquired in frame mode os to the computer for 60 minutes. If necessary delayed im~ gas were obtained until radioactivity was identified in the intestine or until 24 hr.

We could obtain in all pts liver visualisation despite high levels of bilirubinemia and time-activity curves and parameters,namely liver uptake index and hepatic excretion and biliary ducts(when patent) excretio ratios.Scintigraphy permited to eliminate the existence of biliarytract obstruction in 2/4 pts with previous surgery and 3/5 pts with suspicion of BA.Inconclus$Sn, hepatobiliary imaging with Tc-99m-EHIDA is useful in the differential diagnosis of the cholestatic jaundiced infant and in the evaluation of hepatocyte dysfunction, even in the presence of high Levels of hyperbilirubinemia. 7he ~urpose of this work is ccmparative study of blood flow in portal venous system. ~ith deppler-ultrasonography (D-L~) and hepatic radionuslide angicgraphy (Sarper's improved method, ~A), in 18 patients with various vascular disturbances of portal venous system.

In partial portal venows thrombosis (n:3), with slow blood flow velocities beside the thromb, participation of venous (~) component (controls, n=8, ~=67~-~/~) is decreased to 42.51%, 25.00~/ok~d 11.10%. Different res~Jlts were obtained in cc~lete portal vein thrombosis (n=2) where only collateral blood flow was found with D-US end exclusively hepatic arterial vascularization was proved with HRA. In reca~lised umbilical vein (n:4) in portal hypertension, portal blood flow was hyperkinetic or slow, but always hepatof~l. In two of these patients liver vascularization was arterial (V =0), in two 9 k. , patients V, was decreased (24.4% end 36.07%), like in patients after splenKectomy (n=2) : 22.26% and 19.36%. However, in accessory spleens (n=3) having their own visible blood vessels (D-US), V, was increased: 75.31%, 71.11% end 76.00~.

K . I~ patients ~Eth portal vein aneurys~m (n=2), 35x19m~ end 20x~m~ in diameters with turbulent portal blood flow (D-US), ~ was increased: 73.87% and 54.3~as in two patients with spleneme~y: 76.79~/~ and 69. I~/~. D-US and PIA are complementary methcds for detection and evaluation cf blood flow disturbaces in the portal venous system, for distinction between sbsent or decreased end nom~al or increased portal blsed flow, ard for differentiation of hepatofugal fY.em bepatopetal portal venous blocd flow. These hemodyna~c parameters are today ~ery inportamt in port~l hypertension diagnostics, for evaluation of liver/spleen blood perfusion and for selection (.f ccnservative cr surgica2 methods of treatment. mchronic active hepatitis D. Zenaqui, S. Pauwels, J. de Ville, E. Sokal.

University of Louvain Medical School, UCL 5430, av. Hippocrate 54, B-1200 Brussels, Belgium.

Segmental stenosis of the common bile duct is a major complication that may occur after OLT in children. Evidence of such complication may be obtained noninvasively when ultrasonography (US) demonstrates a bile duct dilatation. Preliminary data suggested however that biliary stenosis could not be ruled out by a negative US examination.

Therefore, we have now evaluated the usefulness of Tc-99m DISIDA scan in the early diagnosis of biliary stenosis in liver transplanted children with abnormal gammaGT values but normal US.

Stasis of the tracer in the biliary tree was evaluated visually and graded from GO to G3. The final diagnosis was obtained by percutaneous cholangiography (PLC), liver biopsy or surgery.

In 41 cases, the bowel was visualized without accumulation of the tracer in the biliary tree (GO).

In only I of these cases, the final diagnosis of biliary stenosis was retained. In I patient, neither the biliary tree nor the bowel were visualized and PLC demonstrated a common bile duct stenosis.

In 31 cases, stasis of tracer was observed in the bile ducts (GI to G3).

The final diagnosis of biliary stenosis was retained in 21 of these 31 cases, and rejected in 10 cases. These results indicated that the sensitivity and specificity of DISIDA scan reached 96% and 80%, respectively with negative and positive predictive values of 98% and 69%, respectively.

The present findings provide evidence that DISIDA imaging constitutes a reliable aid in the early detection of bile duct stenosis in post-OLT children with normal US examination. Methods to determine ileal dysfunction are often not very reliable. Se-75-HCAT seems promising to detect bile acid malabsorption (BAM) due to late radiation damage. C-14-Glycochol is sensitive for BAM and bile acid loss due to bacterial overgrowth (BO). Using daily uncollimated gamma camera SeHCAT retention measurements up till 7 days and scintigraphic images with a collimated camera, combined with subsequent C-14-Glycochol breath tests, 31 patients with a history of abdominal irradiation for pelvic malignances with (A) and without (B) ileal resection (IR), mostly with complaints, were investigated for BAM and BO. BAM was considered severe when SeHCAT retention reached <8% of the initial 2h-value (100%) within 72h and mild when it was between 96 and 168h. >15% after 7 days wasnormal. In group A (n=lB) BAM was severe in 9 (20-80cm IR) and mild in 2 (20am IR). In 1 with 13 cm IR not distal SeHCAT was normal. Breath test was negative in 5 severe and 1 mild BAM. In group B (n=19) BAM was severe in 2, mild in 4. Normal was seen in 12 and intermediate (12%) in I. In 3 normal SeHCAT breath test was positive (BO). SeHCAT T~ varied between 4 and 19h for severe, B5-40h for mild, 55-265h for normal. Additional imaging revealed cases of prolonged Se-75-HCAT colonic transit time causing spurious retention values.

Conclusions: i) Combined use of Se-75-HCAT and C-14-Glyoochol differentiated BAM from BO. 2)SeHCAT permitted to distinguish between severe and mild BAM with implications for therapy (e.g.cholestyramine). 3)Systematic Se-HCAT imaging improved accuracy of the test. 4)High inei~ dence of false negative C-14-Glycochol was noted in severe BAM possibly due to rapid bowel transit time.

MMC Tiel-van Buul~, CJJ Molder =, EA van Royen ~, EHH wil~ink 5 ~ .lln:gat ~. Academic Medical Cehter, depts of nuclear medicine ~, gastroenterology-hepatology ~ and pharmacy% Meibergd~ef 9, 1105 AZ-Ams~eroar~

(XgVERAGE OF 5-ASA C(~q/I~/NING ENEMA IN 30 PATI~VI~ WITH ULCERATIVE COI~S In order to investigate, the re tp0gr~e spread in the . co~on argl its ralat~onsnlp to r_ne ex~en~ of r~e ~iseasea area, w~ evaluated a i00 ml, 1 gl=am, '~ amlr~salicY 89 acl(l enema (Pentasa ~) in a consecutive series oz ~u ~atlents with idiopathic inflammatory bowel disease. 'l'i~ Pentasa ~ enema was leloeiled with I0 MBq 99~l~chnetlum-human serum albumin mlcrocol][oi~L After a~icatlon of the enema the Datlent@. were lying on a the first 5 minutes on their -ef~ side. Ga~macamera scintigraphy was performed after 5 minutes, I and 2 hs. Anterior ~ lateJral views were obtaine~ ~T~e results ~the f acintigra~0hy w~re c c~@ared with the extension of the semse as zouno ~y eolonnscopy..:If the enema reacneo entire affected area it was in~erpreue~eo as ".t.opically. edequg, te". ........ ~Ll pU ~lez~c8 ~ a ~lare or CL~Sr.~L u~cera.~ive .. colitis.

The mle/=ema~e ~o .w~ i. u, me~za~ age ~ ~, = 16-68 y). Zn 6 l~tien~ ~e~. ~. no p~z~s, SIOIi of the enema b@.yor~l thg^recuosi~oid while in 4 ~ne rnid-deacerKling co~on, in iu r.n 9 s~er~q . f-exurb, in 8 the tra~-v~rse colon an~ in z ~azier~ ~ne mid-esoendinq color~ 'ins Pentesa ~ enema was ~ound zo cover the tos m@croscx)pically involv@d area in 24 out of 30 patients arm was ~nerexore conslaered "topiom,ly __adequa%_e" We conclude that a I00 ml Pentasa ~ enema reaches the affected area in 80 % of the patients with left-sided colitis. ~his result is superior to the length of spread of the 40 ml home-made (van Buul et al, Gas@~oenter~lo~7 1988). Increasing ~ volume of the 5-ASA enema from 40to i00 ml i~@roves r.ne Ix~sibility of full topioaz uner~_py or une total diseesec~ segmen~ in cases or ,eft sided colitis. RESUI.,TS : In summary,though slightly less sensitive than '1111noxine, the BW 250/IB3 seems quite accurate and represents a valid option for quick and aseptic labelling without blood manipulation and may be used in the management of IBD patients. (IqG) has been proposed to localize infection disease.In 7 cases of Crohn's disease we have compared a new radiopharmaceutical,the Tec hnescan HIG(Mallinckredt Diagnostica),with 99m Tc-~MPAO labeled leucocytes,which we routinely use as the alterna tive test to radiologic and endoscopic study in the follow rio of patients with inflammatory bowel disease. 555 MBq of 99m Tc-IgG were injected intravenously immediately after labeling,4 days after the leucocyte scan,and images were collected at 1,2,6, and 24 hours.No side effects were seen.In all patients an endoscopic study was done within 1 week before or after the IgG scan.In one case with no disease,the 99m Tc-~MPAO scan and endoscopy were negative.Technescan was negative at 6 hours but positive at 24 h.In the other six cases the location and disease activity by leucocyte scan corresponded exactly to endoscopy.The disease was located in 1 case in the transverse,descending colon and sigma, in 1 case in the descending colon, in 1 case in the cec~a, in 1 case in the ileum, in 2 cases in the terminal ileum and ileo-cecal valve.With Technescan the uptake was faint and no all fo ci of infection ~re seen.Therefore,the extension of inflammatien and the ~gree of activity in the different bowel segments could not be exactly evaluated.

In conclusion,we consider Technescan HIG scan inferior to 99m Tc-~MPA/) and not suitable as an alternative method in the evaluation of Crohn's disease. Labeled leucocytes showed ten false negative (seven skeletal, two intestinal, and one renal) and three false positive lesions (one skeletal, one intestinal and one vascular). In these 17 cases IgG scintigraphy shows a significantly better diagnostic accuracy than labeled leucocyte scintigraphy (p<0.001, Chi-square test). We conclude that In-lll-IgG scintigraphy is a convenient diagnostic tool with higher diagnostic accuracy than In-lll labeled leucocyte scintigraphy in this group of patients. 

In patients with neutropenia and fever the localization of the infection is often unknown. Indium-ill labeled polyclonal non-specific human immunoglobulin G (IgG) may be of great value to delineate a focus in an early phase. We studied six male and four female febrile neutropenic patients (mean age 39.2 years). The mean white blood cell count was 1.3 • 0.2 x 109/1 (• S~).

The mean granulocyte count was 0.6 • 0.2 x 109/1 (• SEM). Ten IgG scintigraphies revealed ten lesions in seven patients. One thoracic wall infiltrate, one mandibular infiltrate due to a molar root infection and six pulmonary infections, were proven either by micro-organism cultures or other diagnostic techniques. In three patients the pulmonary infection was caused by Aspergil-1us fumigatus. A sterile femoral head necrosis also showed increased IgG uptake. One focus in the kidney region has not been validated yet. Three patients had negative IgG scintigraphies. In two patients no infection could be proven. The third patient, suffering from a thoracic wall infiltrate, showed no increased focal IgG uptake. This was the only false negative study. We have the impression that IgG scintigraphy in neutropenic patients performs as well as in patients with a normal or elevated leucocyte count. In-111-IgG scintigraphy appeared to localize foci in an earlier phase than current diagnostic techniques. Advantages of In-111-IgG over leucocyte scintigraphy -necessarily with donor leucocytes-are the quick and relatively easy preparation of the radiopharmaceutical and the absence of possible immune reactions. 

Erythromycin, a macrolides' group antibiotic, has been shown to mimic the effect of motilin on gastrointestinal smooth muscle and to dramatically accelerate gastric emptying in patients with gastroparee[s diabeticorum after acute IV administration. The purpose of this study was to assess the effect of short and long term oral intake of Erythromycin using the dual radionuclide technique. Twelve diabetics patients with gastroparesis symptoms were studied. A baseline study was first performed in each patient, followed by a second test after an 15 min. IV perfusion of 200 mgr. of Erythromycin starling at meal ingestion. Ten out of the 12 patients were restudied after a 3 week and after a 3 month oral administration of 500 mgr. t.i.d. Ten age and sex matched healthy subjects were used to define the control range, Gastric emptying of solids and liquids were determined using Tc-99m-Sc scrambled eggs and In 111-DTPA in water, respectively. Simultaneous anterior and posterior images were recorded for 2 hours using a dual-headed gamma camera and corrected for decay and downecatter, Regions of interest were manually drawn around the stomach for each anterior and posterior Tc-99m and [n-ll 1 image and solid and liquid geometric mean data were generated. Percentages of each isotope retained in the stomach after 60 and 120 min. are summarized below (mean + SD) :

204-14 ~ **p< 0.005 versus Controls ~ ~ p< 0.0005 IV and ~ p< 0.05versus Baseline IV Erythromycin overnormalized gastric emptying and abolished the so-called solid liquid discrimination phenomenon. Compared to baseline, gastric emptying of both solids and liquids remained accelerated after short and long term oral intake, but the effect was less striking than after the IV perfueion and the distinction between solid and liquid curves persisted. Erythromycin appear8 to be a promising oral gastrokinetic drug which could be useful in gastroparesis diabeticorum to better regulate the absorption of food and to improve the blood glucose control. 

Using the standard isotopic gastric emptying test combined with a new data acquisition and processing method, the contractions characteristics of the stomach were analyzed and correlated to gastric retention in 10 healthy subjects. After ingestion of a test meal consisting of scrambled egg labeled with 3 mCi of Tc-99m-Sc, bread and water, static and list mode images of the stomach were acquired sequentially for 2 hours using a computerized dual-headed gamma camera. All images were decay corrected. Percentage of activity remaining }n the stomach was determined on static images at each time interval. Each set of list mode frames was compiled in a 5 rain. static image to draw a ROI around the antrum end 250 millisen, frames were created. Antral time-activity curves were generated and analyzed using a curve-peak finding algorithm and a phase-amplitude Fourier analysis to determine the frequency (CF), amplitude (CA), peak contraction rate (PCR) and peak filling rate (PFR) of gastric contractions at 15, 30, 60, 90 and 120 min. after meal completion. The dynamic motion of the gastric walls and the phase progression images of gastric contractions were also generated. Results are summarized below for each parameter (mean+lSD .0+-25 9 p < 0.05 versus T 15' CF was inversely related with food retention in the stomachJn contrast CA decreased progressively during the gastric emptying course. PCR and PFR remained constant throughout the study. The patterns of phase distribution and sequential phase changes of the food in the stomach we observed indicate that the proximal stomach does not undergo phasic contractions while in the distal stomach, contractions originate in mid-corpus and propagate aberrelly to the pylorus. This is in agreement with results already obtained by other investigators with invesive techniques, In conclusion, the scintigraphic test can be used to noninvasively and quantitatively characterize gastric motility and to delineate the spatial sequence of gastric contractions. This technique can be applied to study the pathophysiology of gastric emptying in various motor disorders. The purpose of the present investigation was to introduce the clinical application of a newly developed radiopharmaceutical. 99mTc-latex particles, which passed through the entire GI tract unmetabolized. A group of 5 healthy volunteers (i F,4 M Age 29-52 y) and 6 pts (5 M,I F, Age 25-59 y) with GI pathologies including enterocatannues fistula (n=2), colon ca (n=3) and spastic colon(n=l) were studied after getting their informed consent. Following 12h fasting state, the patients were given orally 150ml of water containing 37 MBq of 99mTc-latex particles. Sequential frames (2 min/each) up to 3h was recorded to document temporal progression of radio-activity. The patients were allowed to eat standard meal at given times. Abdominal and whole body images at certain intervals up to 48h were recorded with anotomical markers. It was noted that only GI tract was visualized. The ratio of GI tract/whole body 99.2-+0.05 % (mean of 6 normals). In normals the tracer arrival time at caecum and sigmoid colon were 2.2-+ 0.6h and 9.2-+2.9h, respectively. In pts with enterocutaneous fistula, the site of fistulas could be localized accurately, by means of nine mode, using the 3h dynamic images that was confirmed by surgery.

In conclusion, 99mTc-latex particles allowed us to monitorize the passage of radioactivity through the GI tract, even soon after surgery, without any interference from background and other organs, thereby providing functional information. In addition, it was possible to evaluate GI tract morphology with excellent detail. Since 1984 we have treated 15 children with neuroblastoma stage Ill or IV. A total of 40 treatlmmts were carried out.The median follow-up time was 13 months and in 5 patients 4 years. Most of the children suffered from a recurrence. In 12 patients a stage IV was found. They were treated i -6 times. The median tumor dose was 25 Gy. The MIBG half life in the tumors of this group was 2.5 days. In 7 patients a tumor reduction was achieved proved by various parameters as radiological and sonographie examinations and tumor marker detecminatiens. 3 of these 12 patients are alive, 3 patients with a st~e Ill disease were treated 2 -5 times. The median tumor dose was 22 GL with a half life of 2.3 days. All 3 children are alive. In 2 cases the tumor was reduced in size. 2 cases could be operated successfully after MI~-treatment and they are still in remission. In one child who could not be oberated after MIBG, there was so progression. ~s MIBG-activity was 326 MBq/kg for both stages. The half life of the whole body was 1.8 days, the resulting whole body r~iation exposure was 0.5 Gy. Side eff~ts consisted of a reversible reduction of leukocytes and thrombocytes. Thrombocytes were more affected than leucocytes. In 3 cases a leucopenia and in 6 cases a thrombecytopenia was induced. No other severe side effects were registrated up to now. We ~mncl~e that most cases of nenroblastoma III and IV respond well to MIBG-treatmest. The therapeutic response does not differ in patients with stage III or IV. No patient became completely free of tumor by MI~ treatment only. Therefore it is necessary to continue therapy after MIgG treatment with other medalities. Patients ~ith ,a neuroblastoma Ill may be cured if a radical operation can be done after MI~ therapy. Side effect are moderate. Neuroblastoma is the most common extracranial solid tumor of childhood, in most cases showing specific enrichment of meta-iodo-benzylguanidine (MIBG). The aim of our study was to determine the reliability of MIBG in primary tumor diagnosis and evaluation of metastatic and recurrent disease. From 1982 to now, we performed 137 MIBG-scintigraphies in 97 children, either with iodine-123 (n=71) or iodine-131 (n=66). Indications for scintigraphy were the differential diagnosis of abdominal masses (n=ll), staging of neuroblastoma before and after surgery (n=68), monitoring of disease status after chemotherapy (n=51), or the evaluation of clinical symptoms (n=7). 79 patients had neuroblastomas, 56 of them suffering from stage III or IV disease. Specificity in primary tumor diagnosis was 98 %, sensitivity = 91%. For bone marrow involvement and recurrent disease, sensitivity was 75 % each. It decreases in cases of very large tumors or weak bone marrow involvement. In 30 cases, an additional bone scintigraphy was performed. 22 children had bone lesions with corresponding findings of both examinations in 20 cases. MIBG scintigraphy and bone marrow biopsies after chemotherapy showed correlating results. 43 MIBG scans were true negative, Ii scans showed false negative results, 6 of them being performed after chemotherapy. We conclude that MIBG scintigraphy is a sensitive and highly specific method in routine monitoring of neuroblastoma. We performed 63 studies in 41 patients(pts)with suspected or proved disease.19 pts were males and 22 females. The age of the pts ranged Im-16y(mean 4,7y).13pts had no therapy before the examination.In 28 pts the study was performed to evaluate the response to therapy and/or to detect recurrences.The studies were acquired 48,72 and 168h after i.v.injection of 18.5MBq of 131-I-MIBG in a gamma camera GE 40OT coupled to a StarII computer.Static images of 600s using a 128x128 matrix were acquired.When necessary bone,kidney and hepatosplenic area were imaged using 99mTc labeled products.SPECT was used as well. We found 25 studies normal corresponding to ]7 pts in remission and 8 pathologies other than neuroblastoma.38 studies were abnormal:f8 showed the initial lesion and 20 demonstrated the recurrences or residual lesion. 131-I-MIBG was able to confirm all the suspected lesions and gave additional lesions in lO:lymph node involvement in 3,bone metastases in 3 and bone marrow involvement in 4 studies. These results show the importance of 131-I-MIBG scintigraphy in initial and differencial diagnosis,staging and evaluation of the response to therapy. 131I-MIBG is an established radiopharmaceutical for the localization and radiotherapy of neuroblastoma. However, the therapeutic effect is hardly ever leading to complete regression and some neuroblastoma lesions have lost the capacity of accumulating MISC. Hence, it is interesting to search for other substances which may be used in combination with or as an alternative to MIBG. Monoclonal antibody BW575/9 (Behringworke, Marburg, FRG) is a promising candidate. It was found be show impressive localization in neuroblastoma patients, especially in lesions that are localized in or near to bone marrow, while soft tissue processes tended to accumulate less effectively. To compare the accumulation and the time-concentration integral of MIBG and BW575/9 under standardized conditions in the same individual~ ~Je have established nude mouse xenograft models using tumor lines SK-N-SH and SK-N-MC, which showed high and low uptake of MIBG as well as high and lo~, binding of BN575/9, respectively. Autoradiographic analysis of tumor uptake in vivo revealed a fairly homogenous accumulation of both radiopharmaceuticals in SK-N-SH, while aeeumulabion in SK-N-MC was .hardly above background. Paired label experiments with SK-N-SH-bearing animals using 1311-MIBG and 1251-BW575/9 revealed three major differences: i) The absolute amount of MIBG uptake was low, peak values being one order of magnitude below those of the antibody (2.9% iD/g versus 23.7% iD/g). 2) Peak values were ovserved i h after injection of MIBG but 48 h after injection of BW575/9. This was paralleled by a rapid blood clearance of MIBG and a slow blood clearance of the antibody. 5) Release of accumulated radioactivity from tumor bissue was rapid with MIBG but slow with BW575/9. These results suggest radioimmunotherapy of neuroblastoma with an appropriate monoclonal antibody to be a promising approach. The sensitivity of radiolabeled metaiodobenzylguanidine (mIBG) scintigraphy in the detection of neuroblastoma is >90~. On occasions, false negative planar scans are due to organs of physiological uptake of mIBG e.g. heart, liver, bladder obscuring areas of disease. This study was undertaken to determine whether SPECT enhances the contribution of mIBG scinigraphy in neuroblastoma.

Images were agg~ired 24-hours after the injection of 75-185 MBq -~ImIBG using a GE Starcam camera and on-line computer.

Planar images were acquired over 10 minutes, and SPECT views of the thorax, abdomen and pelvis created by back projection o 1 after 360 rotation of the single camera head. A total of 26 studies were performed on 16 patients with neuroblastoma.

In 4 studies, 5 lesions not noted on the planar views, were detected by tomography.

Three possible and one 'definite' abnormality seen on planar scans were shown not to be pathological by SPECT. Improved anatomical localisation of abnormalities was achieved by SPECT in 16/26 studies. Overall, in 61.5% of studies, tomography provided additional information. patients who had painful tumors, the pain disappeared or decreased markedly ; AFP serum levels (n -32) dropped > 50% in 14 and 25-50% in 2 ; tumor size (n -41) was reduced > 50% in 16 and 25-50% in I0 patients. In terms of AFP and/or tumor size, the response was complete in none, incomplete in 20 and partial in i0 . Survival time was 42.5 • 4.4 weeks. Actuarial survival was correlated to OKUDA's staging (p<O.02) and MAKI's staging of 1-131-Oil intratumoral retention (p<0.001). Conclusion : The trial :

confirms the good tolerance of this HCC treatment ; shows its feasibility by other centers add objective signs of tumoral response in 60% cases ; encourages the conduct of a phase Ill trial. AUGER electron emitting radionuclides like 1-123 release most of their energy within a few nanometers of the parent isotope.

If the decay occurs in the vicinity of the DNA, it will induce double strand breaks and less than I00 disintegrations are sufficient to kill a cancer cell. However, if it occurs at the cell surface or within the cytoplasm it has a negligible effect on cell survival. One way to bring these radioisotopes near the DNA is to attach them to steroids with high affinity to the nuclear associated estradiol receptor (ER). We synthesized an estradiol derivative, the Z isomer of the l l~-chloromethyl-17~-iodovinyl estradiol (Z-CMIV). This molecule has an affinity for the ER i0 times higher than estradiol and a affinity for the plasma sex steroid binding protein 400 times lower than estradiol.

In vitro cytotoxicity of the 1-123 Z isomer was assessed using a clonogenic assay and a modified MTT assay. The Z-CMIV was 1000 times more toxic for MCF7 human breast carcinoma cells than for human bone marrow cells. Our data suggest the estradiol receptor could be a sui- The  purpose  of  this  work  was  to  synthesise pentavalent IS6Re-DMSA, analogous to the tumour imaging agent pentavalent 99Tem-DMSA, for assessment as a radiotherapy agent for medullary thyroid carcinoma (MTC) and other tumours.

Having established the identity of the technetium agent as the square pyramidal complex 99Tc'O(DMSA)2-, solid [Bu4N][Re0(DMSA) 2] was prepared by aqueous stannous reduction of Re04-in the presence of mesodimercaptosuecinic acid, and characterised by spectroscopic methods.

A sterile tracer dose containing 20 mCi 186Re-DMSA was prepared by reconstituting 5 combined standard Amersham DMSA kits (for renal imaging) with 21 mCi 186Re04-in i0 ml saline and heating to 100~ for 50 minutes. The preparation was loaded onto a BondElut NH2 disposable sample preparation column, washed with acetate buffered saline (pH 5.5, to remove iS6Re04-) and eluted with 0.i M sodium carbonate. The product was terminally sterilised by filtration and adjusted to pH 8. 5 with 8.4% sodium bicarbonate. Radiochemical purity was at least 99%, radioactivity concentration 2.2 mCi/ml, yield 20 mCi. In a patient with MTC the biodistribution was similar to that of pentavalent 99Tc~-DMSA.

We conclude that pentavalent ISeRe-DMSA is readily prepared, is analogous in chemical structure and biodistribution to pentavalent 99Tcm-DMSA, and is worthy of further investigation as a radiotherapeutic agent. Catecholamine uptake and the storage capacity of normal sympathoadrenal tissue in adrenal medulla, salivary glands, heart and spleen as well as in neuronal tumors such as pheochromocytoma and neuroblastoma can be imaged by iodine labeled metalodobenzylguanidine (MIBG). In this study, the hypothesis was tested whether the sympathoadrenergic tissue of the lung may be evaluated selectively by aerosol administration of the tracer into the lungs and subsequent dynamic lung scanning. This approach was applied in 13 studies in normal subjects, after drug interventions and in patients. The clearance half time from the lungs was measured after aerosol application of 5 -10 MBq 1-123 MIBG by continuous gamma camera imaging at 30 sec intervals for 20 min and exponential curve fitting of the lung time activity curves. 1-123 MIBG lung clearance evaluated in 7 normal individuals was 129+_.32 min thus showing a wide range of normal. In patients with possible effects of an underlying disease on the lung sympathoadrenergic system no significant difference in MIBG lung clearance was found. It was 112.2 min in bronchial asthma, 139.4 in hypothyroidism and 105.1 in a patient with hyperthyroidism. However, if repeated in 2 normal volunteers after oral inderal the clearance half life decreased from 192.9 to 139.9 rain and from 101.1 to 92.1 min; and after oral reserpine from 190.0 to 113.1 rain. In conclusion, the results of this study give evidence that ventilation scintigraphy with 1-123 MIBG allows the selective evaluation of the sympathoadrenergic system of the lungs without overlap of other organs. The clinical impact needs certainly further studies. The procedure might become useful in evaluating the effect of known or new oral, intravenous or inhalation drugs on the sympathoadrenergic control system of human airways. Iodobenzyl propanediamine (HIPDM) can be easily labeled with radio-iodine and has been proposed as a suitable tracer for studying pulmonary metabolic functions by noninvasive gamma imaging techniques. Pistolesi et aL demonstrated that HIPDM is retained by the human and rabbit lung in a slowly effluxable pool and that lung persistence of HIPDM is prolonged in asymptomatie smokers and in patients with various lung disorders as compared to normal nonsmokers. We used the rabbit as a valuable experimental model to investigate the mechanism(si by which HIPDM is taken up and retained by the lungs.

From in vitro competition binding studies with the 8-antagonist 1251-iodocyanopindoloh we found that 8-adreno-raceptors may be involved in the binding process of HIPDM to lung tissue.

To ascertain whether HIPDM is associated with membranous structures In the lung, we evaluated HIPDM lung kinetics and distribution in rabbits receiving i.v. injection of 1251-HIPDM. Animals were sacrificed at various intervals from 2 rain up to 5 hrs after injection, and subcellular fractions and postmierosomal supernatant were obtained by differential centrifugation of lung homogenates. HIPDM content, protein concentration and dry weight were determined in each fraction. HIPDM time-activity curve derived from lung homogenates was similar to that observed in humans (mean time of lung clearance 7.6 vs 6.7 hrs). HIPDM was recovered only from the particulate fractions -the nuclear and mitochondrial fractions containing the bulk of the compound -and the highest HIPDM specific activity was found in the mitochondrial fraction. A negligible amount of inieoted dose was recovered from alveolar sudactant and macrophages. At any time, HIPDM radioactivity in each fraction (as % of total activity in lung) did not appreciably change, suggesting no redistribution of HIPDM among the fractions, In a rabbit model of lung injury (phorbol myristate acetate 40 p.g/Kg i.v.), the profile of HIPDM lung distribution was similar to that observed in normal rabbits. However, 2 rain after HIPDM injection, we found a significantly reduced amount of HIPDM (as % of injected dose) in lungs of treated animals as compared to normal rabbits (43% vs 89.5%). These findings suggest that the kinetics of HIPDM in the lung may reflect a dynamic interaction with subcellular membranous structures and that the longer persistence of HIPDM in the lungs of patients with lung injury cannot be accounted for by a different subcellular distribution of HIPDM. 'gas', produced by a commercial system has been evaluated from the practical, clinical and safety aspects. V/Q lung studies were performed in 89 subjects (age 59 + 17 yrs) referred with a clinical suspicion of pulmonary embolism [PE).

For 'V' scans, 3-4 consecutive deep inhalations of 'TcG' were taken until the count rate in the anterior view was greater than 1K/sec (~40 MBq).

The 'Q' scan was performed by injecting iv 160 MBq Tc-99mMAA. Images were acquired for 200K for 'V' (,w4 min/view) and 400K for 'Q' studies in six standard views.

Image quality of the 'V' study was assessed visually for diagnostic quality by 3 independent observers.

Of the 89 patients, 26 had chronic obstructive airways disease, COAD, 15 had COAD with PE, 17 had PE, and 31 had no evidence or a low probability of PE.

There was good clinical and radiological agreement with V/Q scans in 83 cases. In all 'V' studies, the images were satisfactory and clinically interpretable with good interobserver aggrement.

In eight patients with COAD, some bronchial and gastric deposition was observed on the 'V' study. Compared to Tc-99m DTPA aerosol a ten fold decrease in contamination was recorded with 'TcG', 500 KBq in the air-conditioning filters,.~ 1 KBq for personnel, and~,l I<Bq for couch and linen for each study. Contamination was more with severely dyspnoeic patients.

In conclusion 'TcG' is an excellent tool for V/Q studies, which is readily available, easy and safe to use, giving good quality images.

A, Zwijnenburg, E.v Royen, A.v Dongen, D. Zanin.

Academic Medical Centre, Amsterdam, The Netherlands.

~Tc-TEC~EGAS AS A VENTILATION ~RACER; COMPARISON WITH ~Kr-GAS ~mTq~Technegas (TG), an ultra-fine dispersion of ~=~Tc labelled carbon, has been proposed as an ideal ventilation tracer, suitable even for examining patients with severe chronic obstructive pulmonary disease. We examined ii consecutive patients referred to our department ~or ventilation-pe~fusion scintigraphy using ~mTc-TG as well as ~Kr-gas for ventilation scinti-~m graphy and Tc albumin mac~aggregates for perfusion scintigraphy. The ~mTc-TG was administred as described by Burch (1986) . Both ventilation tracers were administred in the sitting position. In 9 patients the question was pulmonary embolism. Two patients were admitted for quantification of regional pulmonary function. In 7 of the 9 ~tients the sam~ diagnosis was reached with ~Tc-TG as with mKrgas. In the other 2 patients no diagnosis could be made because of artefacts in the WmTc-TG images. In 1 patient quantitative analysis was unreliable because of severe artefacts. In the other patient the analysis (L:R distribution) was not significantly different from ~mKr gas despite some central depositions. Image quality was comparable in both ventilation tracers in 6 patients with homogeneous ventilation. In 5 patients with inhomogeneous ventilation artefacts were present due to centIal depositions of the ~mTc-TG. In 4 patients ~mTc-activity in the lower lung fields was higher than in the upper lung fields compared to ~mKr-activity. Although the number of patients was limited, we ~oncluded that, despite the promising name, mTc-TG has the properties of an aerosol rather than a gas like ~*mKr. The results obtained do not justify its greater technical and economical expense compared to that of aerosols.

PREDIC P., DRNOVSEK P., VOGA G., ~URAN I., KRIVEC B.

Hospital Celje, Celje, Yugoslavia ISOTOPE DIAGNOSTIC OF PULMONARY EMBOLISM AS CORRELATED WITH ISOTOPE PHLEBOGRAPHY It is known that over 95% of pulmonary embolism results from the vein thrombosis in lower extremities. The simultaneous detection and positive findings of vein thrombosis in lower extremities and positive findings of perfusion omission in lungs reliably confirm pulmonary embolism. 1960 phlebographies have been analysed, made in the last five years with Tc-99m-MAA, and compared to the perfusion lung scintigrams. The investigation is performed by means of gamma camera after injection of ca. 2 ml Tc-99m-MAA into the foot dorsum vein and with the surface veins squeezed with two Esmarchs so that the flow in deep veins is achieved. 50 images are obtained by computer in 200 seconds ( i img/4 sec). After the isotope phlebography has been performed, the perfusion lung scintigram. Out of 1960 cases of phlebography of lower extremities with simultaneously made perfusion lung scintigrams 1220 cases showed perfusion omission in lungs. 1160 (95.08%) cases out of these 1220 showed at the same time also a positive phlebography of lower extremities of whom 780 cases (63.93%) had blockade in deep veins of lower knee and 380 cases (31.15%) blockade in iliac veins. In only 60 cases (4.92%) the phlebography of lower extremities was negative, but with the existing lung perfusion omission. Due to large simultaneous correlation of positive phlebographies of deep veins in lower extremities and lung perfusion omission-data corresponding also to literature-it is reasonable also to make isotope phlebography of deep veins in lower extremities in all patients suspected of lung embolism. 

The present work shows an application of computer facilities to simultaneously an independently display the local information of ventilation and perfusion from functional lung studies in a single image instead of V/Q ratio images. This is achieved by setting on each pixel of the pulmonary area a thin prism with height proportional to the count rate in the same pixel of the perfusion image and modulating the colour of the prims by the local ventilation. Perspective views of these plots appear as three dimensional four parameter histograms (FPHs). To ease the analysis of the total pulmonary R0I the developed software allows display of views from the basis or from the vertices seen from right to left or the reverse. If an accurate activity/body weight is used in the perfusion studies and the heights of the prims are normalized to the average maximum value of normals and if the colour scale is conveniently chosen, comparison between different FPHs is possible, inasemiquantitative basis. A reference in each FPH indicates the average maximum normal value of perfusion. Data from a total of 150 patients including 13 normalshavebeen processed in order to have the FPHs. Comparison of FPHs with the corresponding V/Q ratio images by a gorup of 3 pneumologists, for 120 of the patients studied, indicates FPH as easier to interpret, with more information and more valuable as a complementary diagnostic tool. These results show that the FPHs may represent an improvement in the output of functional lung studies in Nuclear Medicine. Work supported by AIEA

MS Alexander, j Cleland, HL Henderson, AM Peters, JMB Hughes and JP Lavender, Hammersmith Hospital, London W12, England.

We have shown previously a relationship between cardiomegaly and reduced left lower lobe ventilation on routine V/Q scanning.

In a prosepctive study on 19 patients with large hearts a marked improvement in left lower lobe ventilation was seen in the prone compared with the suspine position. Although there was a similar change in normal volunteers this was less marked.

In order to elucidate the mechanism of this change, 11 patients with enlarged hearts were studied using inhaled Kr-81m and I.V. Xe-133.

The change in the difference in signal between the right and left bases was expressed as a ratio on passing from suspine to prone. In those showing a reduction in ventilation at the left base using inhaled Kr-81m the ratio on moving from supine to prone was 2.40 (+ 0.46) representing a real increase at the left base (no changes were seen at the right base). No change was seen with I.V. Tc-99m MAA acting as a marker of lung position (0.96 + 0.08), or in regional lung perfusion using Tc-99m M~and the peak of the I.V. Xe-133 curve (1.1 + 0.21). There was also no change in ventilatory turnover, and thus no evidence of air trapping, from the Xe-133 washout curve (1.35 + 71). An index of volume, derived from the Xe-133 and Kr-81m data, changed significantly at the left base (3.05 • 1.7). This suggests the mechanism of the phenomenon is lung compression and alveolar closure, and that a change in position reverses this closure, improving lung ventilation and gas exchange.

JAGERU., LOBOFF U., SCHOPKAB.-J.

To perform a standard quantitative quality control on a SPECT-Camera a special multifunctional

This Phantom includes 6 hot rods of diameters from 5 mm to 30 mm, hot and cold grids, two line sources and an homogeneous part. With this SPECT-Phantom the quantitative analysis of the parametgrs is performed : differential and integral uniformity, differential and absolute linearity, spatial resolution, resolution of two point sources and sensitivity 9 The acquisition, reconstruction and complete analysis of the data takes c. 2 h 9 That makes this procedure suitable for weekly checks of SPECT -Cameras. The influences of the acquisition radius, C.0.R.-deviations and different frequency filters on the results are discussed. The analysis of these parameters at four different SPECT-Cameras shows differences of up to 40 % :

Integral uniformity 20 -40 % Diff. uniformity i0 -30 % Abs. linearity 3 -7 mm Diff. Linearity 2 -6 mm Spatial resolution ( 1 Line ) 8 -17 mm Spatial resolution ( 2 Lines) 15 -20 mm Contrast for hot rods 30 -88 An iterative optimizition of frequence-filters is performed by predetermination of the optimum parameters. This method can solve the filter-problem in the daily routine of SPECT-reconstruction.

University College London THE GENERATION OF SYNTHETIC DATA FOR TESTING SPECT COMPUTER SYSTEMS.

As part of the COST B2 initiative, a software package has been written to create test data sets for tomographic reconstruction on different SPECT computer systems. The current software generates a set of projection images of a complete (3-D) Jaszczak phantom, with the possibility to modify a number of parameters such as matrix size, number of angles, zoom factor, resolution and signal to noise. While the present package generates unattenuated data without scatter, these are in the process of being incorporated.

The package runs on a conventional IBM type PC and generates output in a number of forms, including the new proposed standard, Interfile. The output has been used after reconstruction to test a variety of different commercial systems and has highlighted a number of problems, for example associated with centre of rotation and reconstructions for other than 360 ~ . It is possible to make quantitative measurements on the reconstructed data, and compare these to theoretical predictions to assess the influence of the reconstruction software and in particular, of the influence of any filters used. It is believed that this package provides a useful tool for testing SPECT system software. 

Many problems attributable to faulty A/D or D/A converters in the chain oz scintillatlon camera / computer circuits are easily recognise(i De.gradation in time can me su/Ycle and is difficult to evaluate without a special experimental set-up.

In some sclntillation camera systems A/D and D/A conversion processes are chained, for exa~01e inside a ,inearity correction circuit, which ma.y give rise to artifacts due to interaction between the cascaded converters.

By obtai[~ng a Fourier spectrum of the digitized data O~ a sui'~e uni~ormity~floodsource, aegradation may me l(len~izleQ ~ qu@ntiilect A short p rQgrmm and a few minutes of co~uter-time is all tha% is needed to qenerate the spe~ Exampl_e spectra for mathematical phantoms and actual acquired da~a obtained from various cameras are qiven. These spectra have an improved detection threshold for most A/D or D/A converter-related problems, when co~.

with other esr_anlished qu~ity-control techniques.

.We reco~nd t/~t a Fourier spectrum, under We here present a simple and clinically relevant procedure to quantify the image distortion caused by pile-up in scintillation cameras. Characterisation of the count rate performance should imply more than just correctable count losses. Pulse pile-up is the cause of unreconstructable image distortion due to miss-positioning of pile-up events.

The information in the images of an uniform 99-Tc-m-phantom at high and low count rate is used. The fraction of the total count rate with correct position is determined as the peripheral count density divided by the count density in the whole image. This ratio is corrected for the nonuniformity at low count rate.

Applying these calculations on the GE-camera used for development of this method gives the following result: 20 % count losses at 30.000 s-] measured count rate, of those are 91 % right positioned.

This method gives the fraction correct positioned events as a function of expected or measured count rate with high sensitivity and an accuracy, which varies with count rate. According to NEMA the "System count rate performance with scatter" (point 12} the measured count rate giving 20 % count loss should be reported. We suggest that this paragraph is complemented with a measure of fraction correct positioned events at this count rate. This fraction can be measured with an accuracy of a few percent using our method described in this paper.

F Mannting and MG Morgan. University Hospital, Uppsala, Sweden.

Increased pulmonary (P) TI-201 uptake is a marker of left ventricular failure. The aim of this investigation was to assess early temporal changes of pulmonary/myocardial ratios and wash-out (WO) rates of T1 uptake in the lungs and myocardium (myoc). P-T1 uptake, WO, and uptake ratios (mean cts in upper left lung (ull)/mean cts in brightest myoc segment (STP), mean cts right lung (rl)/BKG-corrected mean myoc. cts (PMI), and mean cts ull/BKG-correeted mean myoc. cts (PM2)), were assessed in 12 normals (NL)(mean age 48.5 yr +13.3, 6 men) and in 30 patients with CAD (mean age 54.8 yr +10.6, 20 men). Assessments were obtained i0, 25, 40 min and 3h after T1 injection (inj) by planar and SPECT data.

Pulmonary uptake ratios, by all 3 methods, were significantly higher at 10 vs 25 min (all p<0.Ol) in NL as well as in CAD, no differences between the uptake ratios at 25 and 40 min were seen. P-T1 content at i0 min was higher than at 25 min (p<0.001, for NL and CAD), no differences between 25 and 40 min were seen. The initial P-WO (10-25 min) for rl was 16.0% +2.7 for NL and 18.7% +5.7 for CAD (p=0.13 NS), and 16.1% +2.8 and 18.1% +6.8 ~p=0.33 NS) for ull. No WO between 25 and 40 min (p~0.05 for rl and ull) was seen. Mean cts in the brightest myoc segment decreased between 10-25 min (p<O.001) in NL and CAD, but not between 25-40 min. Mean BKG-eorrected myoc cts were similar at I0, 25 and 45 min (p>0.05) in CAD, but decreased in NL (p<0.01).

We conclude that a rapid pulmonary WO, similar in N1 and in CAD, occurs between 10-25 min post T1 inj. No significant pulmonary WO between 25-40 min was observed. This phenomenon influences P/myoc uptake ratio assessments, and may affect myoc SPECT images acquired during this "ehsnein~" period (10-25 min followin~ T1 inj). R Giubbini, M Galli, R Campini, E Bosimini, W Bencivelli, L Tavazzi. Fondazione Clinica del Lavoro, Institute of Care and Research, Medical Center of Rehabilitation -Veruno (Novara) Italy.

Purpose of this study is to ascertain the capability of mental arithmetic stress (MAS) to reproduce site and extent of perfusion defects induced by exercise (EX). In 24 patients with recent myocardial infarction (NYHA class I) and EX induced ischaemia documented by MIBI scintigraphy, a perfusion study following MAS test was performed within 2 days. Three views, basal, EX and MAS planar scintigrams were reviewed and scored, each in 15 segments, on a 4 grade scale by 2 blind observers, with the aid of circumferential profile analysis. EX test induced ECG abnormalities (ST > lmm) in 15/24 patients, and chest pain in 5; MAS induced neither ECG changes nor pain. Reversible perfusion defects were demonstrated by MAS in 20/24 patients. EX induced transient MIBI uptake defects in 99/360 segments. 48 of these developed a corresponding reversible abnormality during MA$. Of the remaining 51 segments 20 were contiguous to hypoperfused segments correctly detected, suggesting a lesser extent. On the contrary 10 segments showed a reversible defect only at MAS: 7 contiguous to an area of reversible hypoperfusion at EX, and 2 located in an area of fixed MIBI defect at EX. One of the segments with a reversible defect at MAS had a completely normal uptake pattern at EX. In 12 patients, injected with calibrated activities, an absolute stress/rest uptake ratio was calculated: all of these patients had a decreased uptake ratio below a defined range of normality in segments with reversible MIBI defects; moreover in 8/12 subjects a decrease of MIBI uptake below the rest values was observed. In conclusion MAS can reproduce EX perfusion abnormalities in a high percentage of patients (83%), but to a lesser extent. Irrespective of a possible pathogenetic mechanism, a decrease in absolute uptake of 99m-Tc-MIBI is observed after MAS in the majority of myocardial sites with reversible defects at visual inspection.

JF Verzijlbergen, MJ Cramer, NG Niemeyer, CAPL Ascoop, EE van der Wall, EKJ Pauwels.

Hospital Leiden, the Netherlands.

The aim of the study was to assess the diagnostic accuracy of Tc-99m-SESTAMIBI (MIBI) myocardial scintigraphy using an EKG synchronized planar imaging technique, thus diastolic and static images could be obtaine~ Also observer variabilities were studied.

Conseeutively 60 patients were studied, all underwent Thallium-201 (TI) imaging on the same day and to the same exercise level as with MIBI. All of them underwent coronary angiography within 3 months of the exercise protocol.

Segmental concordance between static MIBI and T1 was 77%, between diastolic images and TI 76% and between static and diastolic 92%. Nineteen percent of all 900 segments demonstrated ischemia with both static and diastolic MIBI, compared to 20% with TI. Overall sensitivity to detect coronary artery disease with static MIBI was 86%, specificity 78%, with diastolic MIBI 89% and 70% and with TI 89% and 78% (differences not significant). Vessel-specific comparative detection rates also revealed no statistical significant differences.

Intra-observer variability for the static images was 12%, for the diastolic 21% and TI 14%. Inter-observer variability was respectively 14%, 24% and 17%. We conclude that although the physical characteristics of MIBI enable to performe high-eount density imaging and EKG gating, no significant differences were found when planar static and diastolic MIBI images are compared with TI and are well within observer variabilities. 

Recently, a new short retention technetium (99m-Tc) myocardial perfusion agent has been made available for human investigation. 99m-Tc-Teboroxime, a boronic acid adduct of technetium dioxime complex, has been shown in laboratory animals to be extracted by myocardium at an equal or greater percentage than TI-201 and in proportion to coronary blood flow conditions. In an attempt to evaluate the safety and efficacy of this agent for routine human use, we performed exercise perfusion scintigraphy in 90 patients with or without coronary artery disease.

Standard planar imaging was utilized in 20 patients and SPECT imaging in 70 patients undergoing 99m-Tc-Teboroxime scintigraphy. Both planar and SPECT TI-201 images were comparable in all patients to 99m-Tc-Teboroxime images with regard to distribution of tracer and post-processing image quality. Liver excretion of 99m-Tc-Teboroxime and its short retention time in the myocardium (< 15 minutes) made interpretation of planar images more difficult. SPECT imaging allowed improvement of interpretation with regard to both liver uptake and short retention time. When 99m-Tc-Teboroxime images were compared to both TI-201 images and cardiac catheterization data sensitivity and specificity for detection of coronary artery disease was 66% and 96%. SPECT imaging sensitivity was 72% and specificity was 93%. All patients tolerated 99m-Tc-Teboroxime perfusion imaging well and there were no adverse reactions noted.

In summary, 99m-Tc-Teboroxime exercise scintigraphy is comparable to planar and SPECT TI-201 scintigraphy and has utility in the detection of coronary artery disease. SPECT imaging appears to be advantageous when using this agent.

Initial experience has shown a high degree of correlation between teboroxime (TEBO), a neutral Tc-99m complex and thallium (T1) for the detection of coronary artery disease. However, a comparison of scinfigraphic vascular territories (VT) utilizing planar imaging with TEBO and TI has not been done. Accordingly, using a rapid dynamic acquisition and upright positioning, 39 pts underwent TEBO imaging at rest and immediately after treadmill exercise.This was compared to standard T1 scintigraphy. TEBO and T1 (n=28) were given during separate exercise tests, and in 11 other pts both tracers were given simultaneously. Each TEBO scan was completed in < 5 min, compared with 25-30 rain for T1 imaging. Overall, diagnostic agreement was present (normal vs abnormal) in 34 of these 39 pts (87%; p<0.01), and ischemia and infarction were concordant with TEBO and TI scanning in 77% (p < 0.01) and 67% (p<0.05), respectively. No obvious difference in diagnostic accuracy was present between the separate and simultaneous TEBO/T1 injection protocols. Comparing results of both protocols, TEBO imaging demonstrated 68 segments with ischemia, which was more than present on serial T1 scans (segments=56). Additionally, concordance for VT between the studies was present in 82%, 85% and 82% for the LAD, RCA and LCX respectively (p<0.01 for each VT). Thus, TEBO and TI demonstrate similar diagnostic accuracy in general and for each VT. However, more ischemic segments are present with TEBO scanning and imaging time was substantially longer for T1.

Hospital Celje, Celje, Yugoslavia

Reperfusion of the heart muscle in the earliest stage of myocardial infarction diminishes the size of necrotic tissue of the myocardium. We studied 18 patients with acute anterior and inferior myocardial infarction.Eleven patients were treated with 750000 IU to i0000OO IU of streptokinase by rapid intravenous infusion. Immediately after, those patients were given 550 MBq Tc-99m-DPD; 90 minutes later myocardial scintigram was taken by computer and with the help of gamma camera in three projections. When the scintigram was negative, the procedure was repeated after 24 hours. In 7 patients where fibrinolytic therapy was contraindicant, myocardial scintigram was made during the first ten hours and then repeated after 24-36 hours. In 9 patients, out of ll, who were treated with streptokinase the reperfusion was successful. The interval between the outset of pain to the positive scintigram was 448~189 min. In the two patients with unsuccessful reperfusion the time interval between the outset of pain to the positive scintigram was more than 24 hours. In the control group of 7 patients, who had no fibrinolytic therapy, however repeated scintigraphy after 24-36 turned out positive in all seven patient. In conclusion we can say that early myocardial scintigraphy with Tc-99m-DPD represents one of the noninvasive methods by which we can prove early myocardial reperfusion; we can show the moment of reperfusion, the locat~n and the size of the necrotic heart muscle and thus guide further treatment.

W Martin, A C Tweddel and I Hutton. Department of Medical Cardiology, Royal Infirmary, Glasgow G31 2ER, Scotland.

Patients who have typical anginal chest pain but who have angiographieally normal coronary vessels present a major clinical problem.

Ten patients, 3 male and 7 female, with typical exertional angina and abnormal exercise thallium scans underwent angiography and were found to have entirely normal vessels, with no evidence of coronary artery spasm. Myocardial flow was assessed using Xenon washout.

Xenon was injedted intraeoronary under direct vision and scans obtained with a mobile gamma camera fitted with a biplane collimator, which allows simultaneous acquisition of 30 ~ and 70 ~ LAO projection.

Distribution within the myoeardium was assessed, and flow calculated from washout curves using peak to 30 seconds and applying the Kety formula.

At rest RCA and LCA distribution and flows were within normal limits; RCA flow 55.5 ~ 8.8, LAD 66.6 ~ 11.3, Cx 62.3 ~ 9.9 ml/1OOg/min.

With atrial pacing to a heart rate similar to that achieved during exercise, chest pain occurred in all patients.

Distribution volume fell in at least one coronary distribution in all patients and this was associated with reduced coronary flow by a mean of 28.6 ~ 9.8%, p <0.05.

By gating the scans to the electrocardiogram and re-constructing listmode data into a representative cardiac cycle, wall motion can be obtained from the same data that produced the washout curves.

Areas of reduced distribution and flow were associated with reduced wall motion in all 10 patients.

These results, a combination of reduced myocardial flow and associated wall motion abnormalities, suggest an ischaemic response, presumably at the microvascular level.

XJ Liu, D Jain, U Raval, EB Raftery, A Lahiri. Northwick Park Hospital, Harrow, HA1 3UJ, UK.

In-ill antimyosin antibody (In-AM) imaging has been shown to be a sensitive and specific method for detecting myocardial necrosis, but a quantitative method is lacking.

A prospective study was performed in 114 patients (pts) with suspected acute myocardial infarction (MI) using planar In-AM imaging.

A simple ratio of peak heart counts over adjacent lung background (H/L ratio) (2x2 pixel) was obtained from the 24hr left anterior oblique images.

This value was compared with LV ejection fraction (EF) and peak CK enzyme (CK). The pts were classified into groups (gr) based upon standard criteria for MI: Q-wave MI (QMI) (n-50), non Q-MI (n=21), unstable angina (UA) (n-15) and those with no evidence of MI or UA (n=28). The mean • ratio in the QMI gr was 2.28• and was > non QMI 1.98• (p<O.02).

In pts with UA 7 had positive In-AM scans (ratio:

1.75• and 8 were negative (ratio: 1.29• (p<0.001).

In the gr without MI or UA the H/L ratio 1.24• and this was significantly lower than QMl, non QMl and those with positive scan in the UA gr (p<O.001, respectively).

However, there was no significant difference between the negative UA gr and those with old AMI and also between those without MI or UA.

There was good correlation between the H:L ratio and CK (r=0.76, p<O.O001) and correlated moderately with EF (r=-0.44, p<0.0001).

Thus, this simple quantitative method may he useful for early detection of AMI and for quantification of the extent of necrosis and assessment of subsequent risk.

A Lahiri M Lomsky, T Ruddy, R Senior, SO Stromlad, V Kujaeece, P Manspeaker, HJ Berger.

Multicentre Study Group, Centocor, Malvern, PA, USA.

In-Ill ANTIMYOSIN FOR ASSESSMENT OF MYOCARDIAL NECROSIS AND LEFT VENTRICULAR FUNCTION.

In-Ill antimyosin (AM) imaging has been shown to be sensitive and specific for detecting acute myocardial necrosis.

In a prospective study of 60 patients (pts) with acute myocardial infarction (AMI) AM imaging was performed between 1-294 days after the acute episode. During the blood pool phase of AM a gated blood pool (GBP) study was performed using 74M~q of In-Ill and this was compared to a standard Tc-99m(Tc) GBP scan.

The mean • SD ejection fraction (EF) for Te was 50.7• and for AM" it was 48.3• (p-NS). There was excellent correlation: r=0.95, p<0.O001, mean difference • SD = 2.5• between the In and Tc GBP scans. In a subgroup of pts (n=17) wall motion abnormality (WMA) was evaluated in the LAO view. WM_A was concordant in 46/51 segments between AM and Tc furthermore, r=0.92 for EF and positive myocardial uptake of #LM was present in 15/17 patients. However, the count ratio between Tc and In GBP scans over the LV was 5.5:1. This data suggests that a single injection of In-lllAMmaybe utilised for the simultaneous evaluation of LV function in conjunction with deliniation of the extent and location of associated myocardial necrosis.

This method may improve prognostic risk stratification using a single dose of In-ill antimyosin. P. MARTIN*, B. PEPERSTRAETE**, d. PATERNOT* and M VERHAS* Departments of Nuclear Medicine* and Cardiology**. Brugmann Univ. Hospital, 4, pl. A.VAN GEHUCHTEN, 1020 Brussels, Belgium.

IIIIn ant]myosin Ab were described to be specific of myocardial necrosis. However, previously, we also found in some patients an uptake in case of ischemia. To further assess the ability of the Ab to be fixed in that situation, 46 patients with a coronary bypass and suspected recurrent ischemic disease received 74 MBq of the tracer. They underwent a 5 views (0,45, 90 ~ planar scintigraphy 48 H later. I patient had a global cardiac failure as assessed by echography. Results were compared to those of angiography. None of the patients underwent adverse reactions. Independently of angiographic lesions, the patient with cardiac failure showed a severe diffuse uptake. 5,t of the remaining 45 other patients had one or severa] thrombosis of their bypass. In 50 of them (88~), the scan was concordant with angiography. In 3 cases (g~), it involved larger territories ordid not correspond to angiographic lesions. In | case (3~), despite an abnormal angiegraphy, the scintigraphy was negative. 1 I patients had a normal angiography. In 7 of them (64~), the scan was also normal. In the 4 last patients (3B~) however, an abnorma] diffuse uptake was observed. If one excludes the patieDt with cardiac failure, the general agreement between scinti~graphy and angiography was 84~ (30 true + and 7 true -). In 16% (5 cases: overestimation on other territories than expected involved and ,t cases: diffuse uptake), the scan was falsely +. There was 2~ ( 1 case) of false -scans. To conclude: It appears obvious that the antimyosin MoAb are fixed by ischemic myocardial wall with possible interpretation problems in case of differentia] diagnosis with infarction. Moreover, it must be noted that the Ab is sometimes fixed by a larger than expected territory, possibly because of a more important injury than predicted by angiographic method. As expected, a severe diffuse uptake is found in global cardiac failure but intriguing is the diffuse uptake in patients without evidence of such a problem. Recently S12 monoclonal antibody (MAb) has been developed by McEver et al that is targeted against an alpha granule membrane glycoprotein (GMP-140) that becomes exposed during the process of platelet activation. In g rabbits, we studied the feasibility of in vivo imaging of activated platelets contained within occlusive arterial thrombi by Tc-99m (Te) labeled S12. Totally occlusive femoral arterial thrombi were induced by transcarotid insertion of copper coils into the femoral artery. One mCi of Tc-SI2 was infused 2 cm proximal to the thrombus followed by flushing. Sequential 2 min scintigrams and blood samples were obtained for 2 hours followed by sacrifice. The mean post sacrifice thrombus weight was 14.8 mg (range: 2.5-26mg). All thrombi were visualized scintigraphically immediately after Tc-SI2 injection with a mean in vivo thrombus to background count ratio of 2.5 (range: 1.6 to ii). The mean post sacrfice ex vivo thrombus to blood specific radioactivity ratio was 73 (range: 24.4-143.5). Tc-SI2 blood clearance rate was biexponential with T 1/2 of 40 and 99 min. In 2 experiments, i mCi In-Ill labeled isotype non specific MAb (control) was injected prior to Tc-SI2 which failed to visualize thrombi.

In conclusion, i) small, totally occlusive arterial thrombi may be imaged rapidly by using Tc-99m labeled S12 MAb, 2) in vivo interaction of S12 with thrombus is specific and 3) blood clearance of S12 MAb appears to be rapid. The results suggest that the process of platelet activation can be imaged in vivo. Accurate and reproducible determination of changes in bone mineral density (BMD) measurements can be of help in prevention and treatment of osteoporose. To improve the detection of these changes inter and intra observer variations should be avoided whenever possible. We propose an algorithm that performs an automatic comparison of two sequential studies F and G, which ensures a fixed size and shape of the ROI (L2-L4). The measurements were performed on a Novo BMC-LAB 22a. In order to find the best matching translation and rotation, the deterministic sign change criterion was applied [Venot et al., 1986] . The ROI of image F was superimposed on the transformed linage G. Then, the background levels were corrected by a determination over their common soft tissue area, subtracted, and the change in BMD was computed. In duplicate studies of 15 normals and 9 patients we obtained a coefficient of variation (CV) of the BMD measurements of 1.04% respectively 2.00%. The procedure worked satisfactorily in all studies and showed an improved CV compared to other studies on the same instrument (CV of 2-3% in normal subjects and of 3-5% in patients). The proposed method is as well applicable to dual energy X-ray absorptiometry images.

A Venot, J-C Liehn, J-F Lebruchec, J-C Roucayrol. Automated comparison of scintigraphic images, J Nud Med 27: 1337-1342 (1986 

In quantitative digital radiography using X-rays (QDR), photons from radionuclides can reach the non-collimated detector and can be counted as high or low energy X-ray photons, thus disturbing discrimination between soft tissue and bone. Therefore, we studied the influence of recently administered radionuclides on bone mineral density (BMD) measurements. Lumbar spine BMD was measured in 13 patients before and 1 to 3 hours after the administration of a radiopharmaceutical: TC-99m-MDP, Tc-99m labelled erythrocytes and TI-201 chloride. A Hologic QDR bone densitometer was used. Results are expressed as the ratio of the BMD value after to that before administration of radionuclides. The range of the ratios is tabulated. Reproducibility was estimated in normals, who did not receive radionuclides, by successive measurements of both LI-L2 and L3-L4 regions. The BMD ratio of the second BMD value to the first one ranged from 0.97 to 1.02. The outcome of BMD measurements after administration of radionuclides seems to be related to the administered dose and the distribution around the measured region. we conclude that, shortly after administration of radionuclides, serious errors in QDR measurements can occur. Probably, no correction is possible, since these errors are not consistent. 

Dual photon absorptiometry (DPA) is predominantly per-[ormed with dedicated scanners. DPA with a gamma camera (GCA) is a potential alternative for centres that are unable to invest in such specialized equipment. A gamma camera (Toshiba GCA 40a) was equipped for DPA measurements. It was fitted with a diverging collimator and a C-arm with a Gd-153 source in the focal point (Nuclear Fields Inc.). Four vials, containing 0, 0.5, 0.8 and 1.4 g/cm 2 of hydroxyapatite, were measured with the GCA and also with a rectilinear DPA scanner (NOVO BMC Lab 22a) and an X-ray bone densitometer (DEXA, Hologic QDR 1000). All three systems showed a linear response: GCA DPA: BMD = -0.0005 + 1.03 x trueBMD (R 2 = 0.999) rectilin. DPA: BMD = 0.0015 + 0.83 x trueBMD (R 2 = 1.000) DEXA: BMD = 0.02 + 0.90 x trueBMD (R 2 = 0.999) Repeat measurements with the GCA of a spine phantom yielded a precision of 1.6% to 2.8%, depending on the method of ROI selection. The projected area of the phantom was dependent on the position between source and detector, and it changed by 3.5% per cm. This effect precludes exact comparison of ROl's in follow-up scans. Measurements in healthy humans with rectilinear DPA and DPA with GCA correlated well, but identification of the intervertebral spaces was difficult with GCA. However, when taking the images with the photon beam directed from posterior to anterior, the separation of the vertebrae was easy. We conclude that BMD measurements can be made with GCA, comparable to other systems, to decide whether a patient needs treatment. For follow-up, the precision of GCA is inadequate compared to DEXA. 222 J. A. Negrin, R. P. Spencer. Department of Nuclear Medicine, University of Connecticut Health Center, Farmington, CT, USA.

While there is some correlation between bone density and the incidence of fractures, it is clear that additional parameters are required to identify those at risk (as well as individuals with low fracture probability).

We thus analyzed resuilts on 105 consecutive women who had both lumbar bone density (LBD) and proximal femoral (~F) estimates on a dual beam X-ray densitometer. Values for the PF density were subdivided into 3 regions (neck [N], Ward's triangle [W] , trochanter [T]). In each case, the highest and lowest values of the 3 PF regions were used to calculate a (highest/ lowest) ratio. Of the 105 cases, 90 fell in the range 1.15 to 1.70; the lowest value was 1.05 and the highest 1.96 (mode = 1.30). Thus there was great variation of bone density distribution within the PF; this will be followed for correlation with the incidence of fracture (and site) using a larger population.

The pattern of PF density distribution from highest to lowest, was NTW in 66%, NWT in 30%, and TNW in 4%. The prognostic significance of each of these patterns will also be estimated prospectively.

Relative independence of LBD and PF neck values was shown by variation of the LBD/PF ratio from 0.90 to 2.03 in these women. Further, analysis of the distribution of densities between the L2, L3, and L4 vertebrae showed all 6 combinatorial possibilities to exist. Most common (highest to lowest) was L3,L2,L4 (32%) and L2, L3,L4 equally common as L4,L3,L2 (each 22%).

These parameters, which await full prospective evaluation, suggest that additional factors can be analyzed in attempting to relate bone densitometry to the incidence of fractures. Myocardial sarcoidosis causes rest thallium defects which often improve after dipyridamole infusion. We compared MIBI vs TI SPECT in 19 pts (5 males, 14 females, age 43.5) with proven sarcoidosis and clinical or ECG features suggesting cardiac involvement. The procedure was : injection at rest of 3 mCi of T] I0 rain before SPECT, then g mCi of MIBI one hour before SPECT, and ~ hours later 20 mCi of MIBI after dipyridamole infusion (DIP MIBD and one hour before imaging. The table gives the number of pts (n) for each pattern (+ : abnormal ; -: normal scan ; + : partial or total improvement after dipyridamole) :

REST MIBI DIP MIBI n + -0

All pts with abnormal TI and 2 with normal TI scan had abnormal MIBI scan. Moreover, defects were better defined on MIBI than TI scan, except for the inferior wall. 12/13 pts showed improvement after dipyridamole. We concluded : I-MIBI SPECT is better than TI SPECT for the diagnosis of myocardial sarcoidosis. 2-Our results strongly support the hypothesis of micro vascular impairment, consistent with a low coronary flow but a normal or high coronary reserve (Am 3. Med, 19gg, g~ : lgg). In diabetes sympathetic nervous function is often decreased. In order to study spatial and temporal distribution of sympathetic inne~ation in heart of diabetic patients, we measured J23I-MIBG cardiac uptake in diabetic male patients with (ANP+; 6 cases) and without (ANP-; 6 cases) signs of autonomic neuropathy and in 6 age-matched healthy controls. Two SPECT-studies (I and 6 hours after injection of tracer) were carried out by detecting 32 frames (each 45 sec) from LPO to RAO. Transaxial slices were visually surveyed and myocardial ]231-accumulation was scored onto 4 groups: normal (3 points), slightly decreased (2), markedly decreased (I) and no uptake (0). There was no significant difference in J hour SPECTimages between patients and controls whereas 6 hour images revealed highly reduced 123I cardiac uptake in patients; image score being 0.7 +/-0.5 in ANP+, 1.7 +/-0.4 in ANP-and 2.6 +/-0.2 in controls, respectively. Correspondingly myocardium-to-liver ratio was lower in patients 0.32 +/-0.04, 0.49 +/-0.06 than in controls 0.69 +/-0.07, although liver uptake was same in all 3 groups. The results show that cardiac MIBG-uptake is decreased in diabetic patients both with and without signs of autonomic neuropathysuggesting a disorder in the cardiac sympathetic nervous function in diabetes. A desensitization of the myocardial 8 adrenergic pathway is observed after exposure to chronic hypoxia. This suggests an increased concentration of norepinephrine in the interstitial myocardial tissue. This local increase of norepinephrine could be due to a decrease in its neuronal uptake, which is the main way of inactivation.

Neuronal uptake function of norepinephrine in hypoxia was evaluated by MIBG uptake. Twelve adult male Wistar rats were IV injected with 25 W Ci in two conditions : 6 rats maintained in normoxia and 6 in hypoxia (3 weeks at a barometric pressure of 450 mmHg, Fi02 = 21%). Tissular MIBG activity (% kg dose/g) was determined (well counting) in the heart, 4 hours after injection. Tissular activity was also measured in lung and liver in which non specific uptake is known to be highly predominant.

Lung Liver fractions with RNA. All pts had normal LVEDD. RV end-systolic and end-diastolic volumes were evaluated as background corrected count ratios to LV at end-diastole. Those ratios could be analysed independantly of age variations.

A stepwise discriminant analysis of all 7 cardiac parameters, age at surgery and time from surgery was made to predict group I pts.: time from surgery (p<0,001), normalized RV systolic volume (p<O,OO2) and RV systolic pressure (p<O,Ol), which were higher in group I, permitted to class 90% of pts in group I and 88% in group II. Using only the two significant cardiac parameters, a new discriminant analysis permitted to class 1OO% of group I pts and 68% of group II pts. Though a longer time from surgery was an important predictor of the inducibility of SVT, the presence of RV systolic barometric and/or volumetric overload were always necessary to induce SVT. RNA is useful to appreciate this RV volumetric overload. An inverse relationship between left ventricular systolic pressure-volume variables and heart size has been documented in dogs, rising concern about the possible use of these indexes in the clinical evaluation of cardiac inotropic state. Aim of this study was to explore the relation in man between peak systolic pressure/end-systolic volume ratio (PSP/ESV) and end-diastolic volume (EDV) in different cardiac functional states. Twelve normal subjects (N), i0 pte with essential hypertension (EH) and 8 pta with dilated cardiomyopathy (DCM) underwent equilibrium radionucllde angiography and blood pressure monitoring in basal cor=litions, during maximal atrial pacing and isometric exercise (handgrip) . In each group of pts and in all conditions, PSP/KSV and EDV values showed an inverse relation, best fitted by a hyperbolic function ( Correlation of LBF in untreated "control" legs over 3 months, showed reasonable reproducibility (r=0.62,p=0.01).

LBF measurement was possible in all patients.

On the treadmill, 35% of patients were stopped by symptoms other than claudication; when this group was excluded, LBF showed better correlation with Mx.W.D than D.I (r=0.8,pf0.001 and r=0.65, p=0.003 respectively).

In conclusion, LBF is a reliable indicator of the result of Dynamic and Laser angioplasty and showed good correlation with functional improvement. Using a new very rapid (6 minutes) radioassay for total plasma thyroxine (T4)and a rapid ~ uptake (T3U), a free thyroxine index (FT4I) Js obtained Jn 6 minutes. The new total ~ assay uses Thyroxine Binding Globulin (TBG) (free of thyroxine) as speeJ.fJ.c protein and involves a) a 50 second denaturation procedure of plasma proteins b) a 2 minute incubati.on with TBG free of thyroxine e) a I minute vortexJng with charcoal incorporated into magnetJsable polymer particles and d) a 30 second isolation procedure of solid phase using an electromagnetic Field. This work evaluates this FT4I as a screening test for the assessment of thyroid function. Sera from 342 outpatients were examined by the two rapid methods and the FT4I was obtained. The patients were grouped according to the value of F~ 4I. Patients with FT4I values between 1.40-4.25 were considered normal according to previous findings, patients with FT41 values < 1.40 were considered hypothyroid and patients with FTal values > 4.25 were considered hyperthyroid. From the 298 patients with a normal FT~I, after Full clinical and laboratory i.nvestigation, 289 (96,9%) were confirmed as euthyroJd, whereas 5 were hypothyroid and 4 hyperthyroid. In the 16 patients with low FT4I, 14 (87.5%) were confirmed as hypothyroid whereas 2 were euthyroid. In the 28 patients with high FT4 I, 27(96.5%) were confirmed as hyperthyroid whereas 1 was euthyroid.

We conclude that this FT4I is quite useful for the assessment of thyroid function, especially since it can be obtained 12 minutes after the venipuncture and so only one visit to the hospital Js enough for a great number of patients to be examined and given instructions. The analytical performances of several commercial RIA kits for the assay of plasma atrial natriuretic peptide (ANP), which use different anfisera and tracers, have been evaluated in order to verify the levels of accuracy and practicability employing a special set of lyophilized reference materials. All the commrcial RIA kits evaluated in this study (supplied by Peninsula Laboratories INC, Belmont, CA, USA; INCSTAR Corporation, StiUwater, MI, USA; Amesherm International plc, Buckinghamshire, UK) showed a degree of sensitivity and precision which does not reach an acceptable precision (CV <15%) for the measurement of plasma ANP concentrations in normal subjects. An improvement of precision and sensitivity was obtained by using "fresh" (or purified) preparation of the tracer and standard solutions, and by adding PEG to B/F separation step. The direct assay (without preliminary purification) was not possible for the great overestimation of plasma levels due to the presence of interferences. Four different procedures for purification of plasma samples, which use the extraction of plasma samples with Sep-Pack C18 cartridges, were evaluated. In addition, an alternative purification of plasma samples which usees immunoextraction (C-terminal ANP-specific antibody bound to solid phase particles of Sepharose), was also evaluated. The extraction step increased the imprecision and the complexity of the assay. Moreover, the quantitative recovery of ANP added to plasma samples after the extraction procedure with Sep-Pak cartridges, with all the procedures tested, was poor (about 50-60%); while the recovery of immunoextraction was higher. Moreover, the comparison between the results obtained with the RIA systems indicated that the antisera employed have comparable sensitivity, but quite different specificity.

This interlaboratory survey employing lyophilized standards indicate that none of the RIA kits tested shows a good degree of sensitivity, precision and practicability. To significantly improve the assay performances, a new procedure should be set up with the use of the most speficic antiserum and the immunoextraction as purification step. During 1989 we promoted an external quality contPol (QC) collaborative study for the immunoaseays of the tumor markers CA I 9-9, CA125, CA I 5-3 in which participated about 100 laboratories ( 75 italian labs and 25 labs from other european countries) ; untill now 20 QC samples have been sent in two dispatches. Control materials were prepared adding the tumoral antigens (kindly supplied by dr.M.Boddin, Centooor Europe,Tongeren Belgium) to pooled normal sara , one QC sample (sent in both occasions) wee a pool from sara of patients affected by malignancies and another sample was prepared with Bioref control material (Bioref GmbH, Mombris, RFO supplied by Polymed, Florence, Italy). The QO samples were stored freezed and delivered at room temperature by mail. The kits more used by participants were : Abbott (5% of all results), Centooor (22%), CI$ (50%), Byk-$anotec (5%) and 6orin(12%). The batwecn-lab agreement (mean 61/observed in the results of all QC samples) was : CA 19-9 , concontration range 30-95 Ulml , CV= 17.6% ; CA 125 , concentration range 244-180 Ulml, OV= 18.3% ; CA 15-3, concentration range 32-120 Ulml , CY= 19. 1%. These preliminary data indicate that the between-lab agreement of the tumor markers included in the survey, is better or comparable with that observed for CEA assay (0V=23.6%) in the 1989 national interlaboratory survey for immunoassey organized by CNR. The satisfactory agreement found for the assays of CA 19-9, CA 125, CA 15-3 is probably explained by the fact that the kits used are relatively few and employ common reagents (antibodies and standards from Centocor). As far as the kit precision is concerned we observed that the within-kit variabilities ranged from 9 to I ,I CV% for CA 19-9, from 11 to 18 CV% for CAt 25 and from 17 to 18 CY% for CA 15-3. AFP,CEA;CA 19-9,CA-125 and CA 15-3 were studied by radioimmunoassay in 50 healthy controls (C) (16 M and 34 F, 46,5+2:2X+SEM yrs), in 23 uremics undergoing HD for 46~_7,2-MO (i3 M and iO F 48-+3,2 yrs) and in 30 transplanted individuals with a functioning renal graft for 42_+3,5 MO (24 M and 6 F, 42_+2,3 yrs).Nobody had any symptom or sing of neoplasia.

HD and TX groups presented the highest statistically significant serum levels of AFP,CEA and CA 15-3 when compared with C groups while CA 19-9 and CA 125 did not differ among all groups. In comparison with the HI) groups, transplanted patients has significantly lower levels of AFP and CEA while their CA 15-3 levels were higher.There was no correlation between the time on HD or TX and the levels of any tumor marker. Our results lead to the following conclusions : a. The elimination of AFP and CEA levels after TX suggests a possible active role of functioning renal tissue on them. b. The absence of changes in the levels of CA 125 and CA 19-9 among all groups,favors the reliability of these markers in patients undergoing HD or TX. c. Tne etiology or raised CA 15-3 levels in TX patients should be further evaluated.

L.Sal~ado,G.Ramos,T.Ferreira,M.Rosario Visira Nuclear Medicine Department,lnstituto Portugu~s Oncologia Lisboa,Portugal

Neuron-specific enolase is a glycolytic enzyme found in high concentration in the brain and neuro-endocrine tissue.It has been detected in neuro-endocrine tumors and is now currently used as a tumor marker in cases of neuroblastoma and small cell carcinoma of the lung.

The AA. evaluate the value of NSE in diagnosis,follow up and response to therapy of patients with neuroblastome.Using the double-antibody radioimmunoassay,65 determinations of serum NSE were made in 31 patients,21 with neuroblastoma and I0 with other tumors.

The median NSE values were higher in patients with neuroblastoma (79 ng/ml) when compared to the values in other tumors (17.3 ng/ml) (p<0.05).In 22 out of 31 determinations that were made simultaneosly with 13]I-MIBG scintigraphy,we observed agreement between NSE values and 131I-MIBG results (71%).Ten patients had simultaneous serial measurements of NSE and vanillylmandelic acid(VMA) In 7 of these patients,the variations observed in NSE and VMA values were in the same direction and accompanied clinical evolution in 6 out of 7 patients.NSE values returned to normal with chemotherapy.Nevertheless,serial measurements of NSE could not detect earlier relapse and/ or progression of disease. The ame of this study was the detection of irr~unization of patients diagnosed with the monoclonal antibody Bw 250/183 by help of the determination of h~man-anti-mouse-antibodies. Furthermore the results Of the investigations for the detection of inflammatory lesions were evaluated.

For the investigation 185-555 MBq Tc-99m of the labelled antibody were applied intraveineously. The protein amount lied in the range of 30-50 ug in children and 150-200 ug in adults. After the application scintigraphies of the suspected region or the whole body were performed in ventral and dorsal view after distribution,4-6 hours and if necessary after 20-24 hours.The HAMA determinations were done in a time period between 1 and 12 month after the application. Till now we have investigated more than 200 patients with the antibody.

For the evaluation of the diagnoses the results of I00 patients were available,The mean age of the male patients was 41 and of the female 49 years with a higher frequency in older subjects.The diagnoses were proofed by bacteriological or histological findings and by the clinical course of the disease.

The sensivity was 96% and the specivity 71%.The interpretation of the false positive results (ii of 16 of healthies) is still uncertain due to the fact that in these patiens the histological findings were doubtful. The HAMA's were negative in all of 65 controlled patients.

The detection of inflammatory lesions with MAB BW 250/183 is a high specific and sensitive method.According to the results available till now no immunisation can be exspected. For this reason multiple investigations can be done without risk for the patient. Specific labeling of amino acid residues in antibody proteins and peptides with positron emitting radionuclides of the halogen series (F-18, Br-76, and 1-124) should increase the potential of labeled monoclonal antibodies.

We have investigated two pentaflourophenyl (PFP) derivatives for use as reagents in the synthesis of F-t8 labeled proteins. These agents were tested for the rapid labeling of HSA in relatively high yield.

F-18 was incorporated into pentafluorobenzaldehyde, using the tetrabutylammonium (TBA) salt in DMSO, with a 60% decay-corrected yield within 30 minutes. Treatment of HSA with the aldehyde and NaBH4, using water/DMSO as solvent, provides a 15% yield (decay corrected). The total time for the synthesis is approximately 1.5 h. Similarly, 2,3,5,6-tetra fluorophenyl-pentafluorobenzoate readily incorporated F-18 under similar conditions, and reacted quickly with HSA, to give an absolute yield of 15% labeled HSA, in 72 mins., based on starting tetrabutylammonium fluoride (TBAF). This method appears to be better than existing methods in terms of overall yield and synthesis time.

Biodistribntion studies in rats (six rats at each time point) injected with a cocktail of F-18 and 1-125 labeled HSA, using the aldehyde method, showed similar distribution at 5 and 60 min. Clearance from the blood was minimal. At 60 min blood activity, in % dose per gram, was 5.04+/-.05 and 6.07+/-.06 for the F-18 and 1-125 labeled HSA respectively.

These studies suggest that both PFP derivatives are useful for labeling proteins. Galactose is metabolized in the liver in relation to the amount of healthy parenchyeQ. We have studied and analyzed the results of PET-('OF)FDGal studies on 5 healthy volunteers and ] patients with hepatic parenchyme disease. The local ethical committee approved of the study; all subjects gave written informed consent. The dose was 5-6 mCi and the imaging time 40-70 min. Blood samples were collected for analysis of plasma radioactivity throughout the study. Results: In addition to the liver, the kidney ~rtex and small intestine (i.e. biliary excretion of ( F)FDGal) were visualized. The radioactive uptake into the liver followed trapping kinetics as Patlak analyses were successful: the volunteers had a k. = 0.32+0.07, the patients 0.20+0.10. The kidney cortex followed similar kinetics as t-he liver. Comment:The small series shows that ('~ is a promisin----~ h--epatic imaging agent in conjunction with PET. Liver uptake follows metabolic trapping, at least in subjects with a functioning liver parenchyme. Thus, this radiopharmaceutical has potential as a tracer for following the state of the liver in patients with chronic liver disease. The biochemical mechanisms related to the trapping of the label need clarification to elucidate~hich specific metabolic step in the breakdown of ('~F)FDGal is disturbed in hepatic parenchyme disease. The kinetics of 18F-fluoride in normal and abnormal bone was investigated.

Dynamic imaging was performed to obtain time activity curves of blood pool, myocardial tissue, and bone.

Arterialized venous blood was sampled for the input function. Patlak graphical analysis and compartmental modelling were applied to estimate diffusion rates between plasma and bone, as well as for the state of incorporation. After 1 hr of dynamic imaging, whole body PET was performed.

Ten volunteers an~85 patients with bone disorders participated; 370 MBq F-was administered.

Analysis of the tissue curves revealed low uptake and rapid wash-out of F-from the myocardium. The uptake pattern in thoracic vertebrae and ribs was fitted with a 3 compartment model (3CM). Parameters kl and k2 (forward and reverse transport from plasma), k3 and k4 (uptake and release from bone) and K=kl.k3/ (k2+k3) were estimated with non-linear regression. Average results were : ki=.13+.05 k2=.19+.16 k3= .08+.83 k4 was very low, and k4:O-yielded si~lar results to those without this constraint. Patlak graphi-Call~nalysis suggests first order uptake and retention of F-, and estimates of K were in excellent agreement : K=0.038+0.016 vs K=O.040+ 0.0]4 (3CM). Bony metastases show-ed different patterns, with the expected higher incorporation rate andl~SOlute uptake.

These findings indicate that F" dynamics in bone can be adequately described with a 3 compartment model; permit Patlak graphical analysis, avoiding measurement of a complete input function. Absolute bone metabolic rates can be assessed to classify bone disorders. The utility of this method to evaluate osteoporosis and therapeutic responses is in progress. Various proteins were modified by attachment of l-imino-4-mercaptobutyl by reaction with 2-iminothiolane hydrochloride. 2-iminothiolane reacts with exposed primary amino groups of lysine and arginine residues of the protein with subsequent opening of the 2-iminothiolane ring. l-lmino-4-mercaptobntyl proved to be a suitable interchelator for binding of reduced 99m-Tc. The labelling with 99m-Tc proceeds rapidly with a yield up to 99%, so that there is no need for a final purification of the labelled product. Further, 99m-Tc attached to iff~unoglobulin was sufficiently stable to allow successful localization of infectious processes in animal and man, in~nunoglobulin being formulated in a dry kit: Technescan HIG. If stored at 4~ this lyophilized kit was stable for more than a year. Other proteins successfully labelled were: albumin, various monoclonal antibodies, Fc and F(ab)2 fragments and other polypeptides and peptides.

A method for producing teehnetium-99mlabelled antibodies of high specific activity and high immunoreactivity has been published by Schwartz (1988) and further developed by Matter (1989) . 0nly antibodies of the IgGl class have been studied to date and to broaden the range of availability of these potentially-useful diagnostic agents a study was conducted to investigate the application of the technique to antibodies belonging to other IgG classes and subclasses.

Efficiency and stability of labelling and the immunoreactivity of the radiolabelled product were studied.

Labelling efficieneies, determined by Sephadex G25 gel filtration analysis, were as high as 90% but detailed analysis of the antibody of the IgG2B class revealed the production of fragments and a significant reduction in cell binding and immunoprecipitation.

The proposed reaction mechanism for this labelling procedure involves reduction of some of the interchain disulphide bonds.

Immunoglobulin classes and subclasses differ in the number and distribution of these bonds and the significance of the results with respect to the proposed reaction mechanism will be discussed. 

A Tc-ggm agent able to localize inflammation (infl.) within 4-6 hrs of iv injection would be highly useful. HSA was labeled with Tc-99m by the ascorbic acid reduction technique developed in our laboratory. Following HPLC and ITLC analysis, 20 ug of HSA labeled with 40 or 160 uCi Tc-99m was injected to groups of five mice each bearing infl. lesion in the rt. thigh induced by i.m. injection of 50 ul turpentine (TP) or a i:I mixture of lOxE8 E. Coli and Entercocci (EC).

Agents admin, similarly were Ga-67 as control, Tc-99m polyclonal IgG, Tc-99m antinuclear antibody, TNT-I, and 1-125-TNT-1. Four or 24 hr later animals were imaged, sacrificed, and dissected. At 4 hr TP abscess/muscle ratio for Ga was 4.8+2.1. 1-125-TNT-I 4.3+1, Tc-99m-TNT-I 3.5 + 1.8, Tc-99m-lgG 3.9 + 0.6 andTc99m-HSA 4.3+i. Wi{h-EC these were 2.6+0]6-, 3.3+0.5, 3.4+0.08, ~.1 and 4.1+0.6 resply.

At 4 hr liver uptake was highest (257+8.9 and 16.5+10.6) for Tc99m-lgG and lowest (6+5.~ and 4.8+372-) for Tc-99mTNT-1, similar to those of 1-125-TNT-I. Results were also similar for 24 hr groups. Data suggest that a) the biological properties of protein, following Tc-99m labeling, remain unchanged (as indicated by the similarity of distribution between 1-125-TNT-1 and Tc99m-TNT-I), b) Tc-99m-HSA is a promising agent for imaging infl. foci giving as high abscess/tissue ratios as Tc-99m-lgG, Tc-99m-TNT-1 and Ga-67, and c) leakage into the interstitial space from increased capillary permeability of the labeled proteins is the most likely mechanism of uptake. 

Technetium labeled glucarie acid (Tc-99m-GLU), a 6 carbon sugar, localizes in areas of acute myocardial damage, but has minimal uptake in normal myocardium. The structure of this agent, particularly after coupling to technetium, while different than glucose, may still behave as a glucose analog. To determine if 99mTc-GLU respons to insulin, we determined the biodistribution of this compound in fed and fasted rats (n=6/group) with and with out insulin (2u s.c. 30 minutes prior to 99mTc-GLU).

One hour after IV administration of 10uCi of 99mTe-GLU, the concentration of radionuclide in blood, heart, liver, skeletal muscle and testes was measured: 1 These data suggest that insulin alters the biodistribution of 99mTc-GLU, as would be expected for a glucose analog. The increase in blood concentration following insulin was unexpected, and suggest that 99mTC-GLU is not a perfect glucose analog. 

The aim of this study was to test newly developed Tc-99m labelled glucosamine in order to obtain the specific tracer kinetics for the potential investigation of the carbohydrate metabolism. We recently succeeded in complexing 2-Aminodeoxy-D-glucose with Tc-99m pertechnetate and to get a complex stable under physiological conditions. 500 ~tCi/kg of Tc-99m-D-glucosaminehydrochlorid was administered i.v. in a single dose to 6 rabbits and 1 dog including metabolic interaction by drugs like insulin (ins) and glucoeorticoide (cort). Dynamic acquisition was carried out every 5 minutes up to 100 minutes of the whole body. The observed kinetics ofthe best visualized organs are given in the following table:

Radioactivity % after i.v. administration heart liver kidneys Time (sin) --ins cort --ins cort --ins cort 5 5,8 7,7 7,5 15,8 10,1 9,5 4,5 6,0 6,9 30 3,3 4,1 3,5 18,9 6,4 7,1 7,1 5,0 4,7 90 1,8 2,0 1,9 15,2 3,7 5,1 5,2 4,1 3,6

In conclusion this new tracer does not behave like glucose in myocardial metabolism. However, in liver there seems to be a substantial insuline effect suggesting that Tc-99m glucosamine is treated like a carbohydrate metabolite. While the stability of such a group is fundamental in de termining the robustness of a radiopharmaceuticals, its presence does not seem to affect the biodistribution of the imaging agent. In order to obtain robust Tc-99m radiopharmaceuticals we prepared new compounds having the more stable Tc---N group in place of a Te-oxo moiety, and evaluate their biodistributions in rats.

We recently reported a new efficient route for preparing Tc-99m radiopharmaceuticals containing the TeEN group (i), which is perfectly applicable to the nuclear medici ne practice, and is based on the reaction of pertechnet~ te with dithiocarbazic ester: 

Different forms of the monoclonal antibody (MAb) OV-TL 3, directed against an ovarian carcinoma-associated antigenic determinant, were tested as a vehicle for radioimmuno-localization of ovarian carcinomas in athymic mice bearing NIH:OVCAR-3 xenografts.

Intact OV-TL-3 and its F(ab')2 fragment were labeled with either In-111 or I-125. Radiolabeled intact OV-TL 3 (10 Fg/animal) or its F(ab')2 fragment (6.7 ~g/animal) was injected through the tail vein. Mice were sacrificed at 4, 24 and 48 hr after injection. Injection of the four OV-TL 3 preparations in tumor-bearing mice yielded a clear variation in tissue distribution. Highest tumor uptake was obtained with In-11 I-labeled intact OV-TL 3 (14.7 % I D/g, 48 hr p.i.). For both antibody forms uptake of In-111 in liver, spleen and kidneys was very high as compared to the uptake of the 1-125 label. Furthermore, In-111 cleared slower from most tissues than 1-125. As a result, tumor/tissue ratios with In-11 I-labeled OV-TL 3 were lower than with 1-125-1abeled OV-TL 3. F(ab')2 fragments cleared from the blood and tissues more rapidly than the intact antibodies. Highest tumor/tissue ratios were obtained with 1-125-1abeled OV-TL 3 F(ab')2 at 48 hr after injection. These ratios ranged from 6.9 to 53.

Although highest tumor uptake was obtained with intact OV-TL 3 these results suggest that the F(ab')2 fragment of OV-TL 3 will provide better tumor visualization than the intact antibody, due to its more rapid kinetics. The high persistent uptake of In-111 in liver, spleen and kidneys may hamper visualization of tumor lesions within or near these organs. The aim of this study was to determine inter-and intra-observer reproducibility evaluated by kappa concordance index, of immunoscintigraphy (IS) interpretation. Patients and methods: fourty six paired irm~unoscintigraphic examinations were performed on 43 patients with suspected ovarian carcinoma recurrence, using F(ab')2 fragments of OC125 antibody labeled first with In iii and then with I 131. All images (planar (SP) and tomoseintigraphy (ECT)) were interpreted blindly and separately by three observers. Reproducibility was considered as moderate when kappa value was >0.5 and substantial when kappa value was > 0.6. Results show superior values of kappa when In iii was used, despite significant difference was not found : we obtained for interobaerver reproductibility Ii kappa values < 0.5 and 8 > 0.6 with In iii, but 20 < 0.5 and 4 >0.6 with I 131. For intraobserver reproduetibility, we found 1 value < 0.5 and 13 > 0. 60 with In iii, whereas 5 were < 0.5 and 9 > 0.60 with I 131. According to the recording mode, superiority of reproductibility achieved by In lll-~labeled antibodies was more evident for ECT. Kappa values were also higher as observers had a longer is interpretation experience. We conclude that : 1 -IS reproductibility is satisfactory, 2 -better reproductibility can be obtained when In iii is used for labelling of antibodies ; 3 -observer training is required for good reliability of IS, and this more with I 131. .After extraction on octadecasilyl-silica (ODS) columns a RIA was performed with a pre-incubation procedure.Antiserum against purified AVP was raised in guinea pigs and Lys-vasopressin-125J served as tracer.The specimen required is 5 ml plasma,which enables a sensitivity of 0.3 pmol/l.Cross reactivity:oxytocin <0.001% and ACTH <0.001%.Recovery studies with tracer ranged between 92 and 96%.The intra assay coefficient of variation varied from 9.2-11.7 and the interassay CV between 10.4 and 12.3%.clotting in the column lowered the recovery,so special care to prevent this was taken.The assay was tes ted for physiological stimuli in 20 healthy male volunteers (20-26 yrs).They were tested with osmotic and baro receptor intervention.Blood samples were obtained after 1 hr of bedrest (B) and 5' upright position (U 

it is still discussed if normal pregnancy is an "ovedill" or "undertill" state. We used plasma levels ol atrial natriuretic factor (ANF) as a marker of intravascular volume and of body sodium and water balance in normal and hypertensive pregnancies.

Study was performed in pregnant women and only two groups were considered: 34 subjects with uneventful pregnancy, who delivered a normal baby at term, and 11 patients (pts) who were hypertensive (blood pressure > 140/90 mmHg) after 26 weeks of pregnancy. In seven of the hypertensive pts, pre-eclampsia was diagnosed on the basis of associated proteinuria > 0.5 g/24 hours and uric acid plasma tevels> 5 mg/dl. Every four weeks, beginning between the 8 th and the 12 th week of pregnancy, plasma levels of ANF, renin, aldosterone, uric acid, the clearance of urea, creatinine, free water and the fractional sodium extraction were measured.

During the first trimester ANF plasma levels in normal pregnancies are below normal values (p < 0.001); ANF levels become comparable to those of non-pregnant women after 17 weeks of pregnancy. There is a significant correlation (p < 0.05) between concentration of ANF and aldosterone, while none of the other correlation tested was significant. ANF values obtained after the 25 ~h week of pregnancy in hypertensive pts were lower (p < 0,05) than values obtained in normal pregnancies at the same gestational age.

In presence of low levels of ANF we confirmed the hypotesis of an "underfill" state at the beginning ol normal pregnancy. This "underfill" state does not disappear in pre-eclampsia. If our preliminary results will be further confirmed, the serial monitoring of serum ANF levels could be easily used to obtain informations about the true state of intravascular volumes, both in normal and pathological pregnancies, leading to better pathogenetic knowledge and specific therapeutic approaches. Several MRI-studies have shown that iv administered Gd-DTPA helps to delineate highly perfused body areas. Therefore we evaluated its relevance for thyroid imaging (T1, spin-echo (SE) mode), in particular for differentiation of cervical or thyroid nodules compared with conventional MRI techniques (T2/ proton weighted, SE-mode). 52 pts. were investigated in a 1.5T supraconducting unit (SIEMENS MAGNETOM) using a Helmholtz surface coil: 15 with benign, 6 with malignant disorders, and 31 following thyroidectomy and ablative 1-131 therapy (10d-2yr ago) because of differentiated thyroid cancer. MR-findings were validated by scintigraphy, ultrasonography, fine needle biopsies or surgery. 96% of the lesions or diseases (adenoma, malignoma, cyst, thyroiditis, Graves disease} were charcterized by increased signal intensities in T2, but normal ones in Tl-lmages (except hematoma). Enhancement by Gd-DTPA allowed to distinguish solid and cystic areas and corresponded with disease activity in thyroiditis and Graves disease. Remaining thyroid tissue after thyroidectomy could easily be recognized by typical enhancement of Gd-DTPA. In contrast, scar tissue remained unchanged. Typical features of tumor tissue (local recurrency, lymphnode metastasis} were high signal intensity in all sequences and intense enhancement by Gd-DTPA. Thus, GD-DTPA allowed to differentiate malignant from scar tissue. Accurate classification of intrathyrold lesions, however, could not be achieved. 

Several studies have confirmed the usefulness of the Tg measurement in the follow up of differentiated thyroid carcinoma. The major problem was the Tg sutoantibodies interference. The aim of this work was to evaluate a new Tg IRMA kit from Cis which associates to the Tg determination, an individual recovery test to exclude or to confirm an interference. Tg was determined in 51 healthy subjects and 53 treated differentiated thyroid carcinoma. The sensitivity of the assay was 0.58 ng/ml. The intraassay reproductibility was <gZ for concentration ranging from 1.25 to 470 ng/ml and 12Z for standard O. The inter assay reproductibility was 9Z. The dilution curves of sera paralleled the standard one. In the control sara, the Tg level range was 1.5 to 31.5 ng/ml (10.92 +-6.27). In sara from 40 patients in complete remission, Ig was <0.5 ng/ml. In 15 patients with metastases, Ig was > 260 ng/ml. The use of menoclonal antibodies allows a better sensitivity for the low values. The diagnostic efficiency of the recovery test was measured in 105 patients. Ig autoantibodies were determined in all sers using the RIA kit from Behring. They were positive in 54 and negative in 71 patients. The interference was confirmed when the recovery was ~75% There was not interference when recovery was>73Z. The test sensitivity was 0.76 and the specificity 1.00. The recovery test allows to valid the Tg measurement even in patients whith autoantibodies which did not cross react with monoelona] antibodies used in the kit. Recent imaging and neuropathological studies have reported minor structural abnormalities in the brains of schizophrenic patients. On clinical grounds, frontal lobe deficits have long been suspected. To test this, 25 young right handed male schizophrenic patients (DSM 3 diagnosis) and 25 matched volunteers underwent 99m-Tc HMPAO SPECT after ethical approval.The tracer was administered intravenously whilst the subject was engaged in a task known to demand frontal, particularly left frontal activity: the Chicago word fluency task. Tomograghy was then performed on a dedicated system, SME 810, acquiring multiple overlapping 15 ram thick slices parallel to orbitomeatal line. A relative measure of blood flow to eight cortical and two subcortieal regions was derived by comparing the Mean Information Density (MID) in each region to the eerebellar MID. The left anterior ratios were significantly higher (P<O.05) in controls compared to the patients. Results showed a predicted failure of frontal activation in patients compared to controls, with loss of cortico-subcortical correlation of activity.High negative correlations between test perfomance and right cauda<te reEF ( an inhibitory system) seen in controls were not seen in patients.The results suggest " Functional Hypofrotality" in schizophrenia. In infants who have suffered perinatal trauma, conventional investigations are not always indicative of site of cerebral injury. In this work, 10 neonates with severe impairment of limb, neck or trunk tone were investigated using Tc-99m HMPAO brain SPECT. Regional cerebral blood flow (rCBF) anomalies were demonstrated in all the i0 patients and ranged from unilateral focal hypoperfusion to extensive bilateral hypoactivity involving cortical, thalamic or cerebellar ar~as. In 2 patients with unilateral anomalies shown by cranial ultrasound scan, SPECT findings were congruent or more extensive. In I patient, bilateral thalamic injury was demonstrated both by cranial ultrasound scan and by brain SPECT. In 3 patients with cerebral oedema at the ultrasound suggesting severe cerebral injury, SPECT allowed to localize the site of lesion, in sensorimotor cortex and/or in thalamic area. Finally, unilateral or bilateral SPECT hypoperfusion were demonstated in 4 other patients, while ultrasound scan was normal. These results suggest that rCBF study using SPECT and Tc-99m HMPAO could have a contributing role in the determination of site of cerebral injury in neurologically impaired neonates. Tatsch I989) . The aim of this study was to determine, whether IFN treatment results in amelioration of cerebral perfusion. We examined 9 HIV-infected pts (8 males, i female) without neurological symptoms, ranging from Walter Reed stage I to V. They were treated with 5 Mio U IFN three times weekly. Before treatment and after three months several immunological parameters and a brain spect with 666 MBq Tc-99m-HMPAO were performed. Transversal slices were generated and a semiquantitative analysis including cortical and cerebellar regions was accomplished. Corresponding slices of both accquisitions were compared. Before treatment we found focal lesions in 7/9 pts, after three months 3 of them showed an increased perfusion of these lesions, in 2 pts there was a further deterioration and in 2 pts no change. The remaining 2/9 pts showed no focal uptake lesions before and during IFN treatment. Among the 2 pts with perfusion deterioration one developed neurological symptoms and in the other one immunological parameters worsened. In the 3 pts with increased perfusion these parameters were improved or unchanged as well as in the remaining patients. Conclusion: HMPAO-spect is a valuable tool for monitoring the treatment of HIV encephalopathy. Tc-99m HMPAO IMAGING: ASSESSMENT OF POST TRAUMATIC PSYCHIATRIC SEQUELAE Fifty patients who had developed neuropsychiatric changes post closed cerebral trauma were evaluated with SPECT using Tc-99m HMPAO to assess cerebral perfusion.

Because of technical problems in severely injured patients, SPECT imaging can be difficult in the acute phase post trauma due to difficulty in transporting severely traumatized patients.

Imaging was done in the patients between 1 month and 9 years post injury. All patients had developed changes in personality, affect or mood that were not symptomatic prior to trauma.

CT scanning in 55% of cases showed an abnormality that corresponded to the HMPAO abnormality on scanning.

However, in 45% of patients the CT scan did not show the complete extent of the abnormality that would be expected on neuropsychological testing that the patients had undergone as part of their post traumatic investigation.

Technetium-99m HMPAO imaging showed more extensive abnormality in these groups of individuals which corresponded to the area of suspected abnormality by neuropsychological testing in all but 4 cases. In these 4 cases the neuropsychological testing was borderline abnormal.

The predominant sites of injury are within the frontal lobes in the inferoorbital region, temporal lobes, the parietal lobes and occipital lobes are much less involved.

In situations were CT scans are normal, Tc-99m HMPAO brain imaging can give additional information and localize the sites of occult trauma. Contrecoup injuries were responsible for many symptoms. This study investigates gastric emptying for solid food in the patients with chronic gastritis with or without CP infection (CP+ or CP-). Material and method: The study included 17 patients with chronic gastritis of various degrees. All of them underwent gastroscoptc examination. Two bioptic samples were obtained from the antrum for the histological examination and CP detection. The urease test (UT) was used to diagnose the CP infection.

According to the intensity of the reaction UT becomes positive after 30 min-1 hr-2 hrs-24 hrs. Gastric emptying of solid food (standard meal) wa~ assessed using a scintigraphtc technique. The solid phase was marked with 99mTc. Emptying time is given by T 1/2. expressed in minutes. Results: The UT was positive in 11 pattents:-~tthln the first 30 minutes, and in 7 after 1 hr. Histological lesions were almost similar in the CP+ and CP-groups. In the CP+ patients T 1/2 was 164,3+98.4 mtn; in the CP-ones T 1/2 was 86.6+47.3--mln (p<O.O1). T 1/2 was 247.5 § ms in the pats with positive UT aft;r 30 min, and 119.7+65.9 min in those with positive UT after 1 h~ (p<0.03 Conclusion: In chronic gastritis with CP+ the gastric emptying of solid food is prolonged. Septic complications are the predominant cause of death in necrotizing pancreatitis. As surgical intervention is mandatory in the case of superinfection of necroses early diagnosis is essential for survival. The aim of this study was to prove the clinical relevance of monoclonal granulocytes antibody for this diagnostic question. The immunoscintigraphy (IS) was performed with i0 mCi (370 MBq) Tc-99m labeled antibodies (Abs; BW 250/183; Behringwerke, FRG). The images were done 4 hrs and mostly 24 hrs planar. 13 pts suffered from a severe acute pancreatitis under intensive care conditions (7 female, 6 male; age 50 • 15 yrs). In these pts we performed 27 investigations:

in 4 pts only once, in 5 pts twice, 3 pts three times and in one pat four times.

As all pts were operated the reliability of IS could be validated by bacteriological cultures. In Ii pts we found a true positive result and in 2 pts a negative result -these 2 pts showed just edema of the pancreas and no superinfection at the time of operation. Only in 1 pat with 2 investigations we found a borderline level of HAMA's. In conclusion: IS with granulocytes Abs seems to be a valuable imaging method to determine the correct moment of surgical intervention. patients had Crohn,s disease and 13 suffered from ulcerative colitis. Autologous leukocytes were labelled with 99mTc-d,l-HNPAO. The mean labelling efficiency was 48.26 + 11.57 %. The viability of the cells was checked by trTpan blue incorporation, and was found to be ?4.6 + 2.4 %. 50 minutes, 2.5 hours after the rein3ection of The labelled cells images were taken from the abdomen. The bowel was divided into ll segments, and the activity was scored by comparing it with the uptake of the liver and bone marrow. To charactecise the "inflamed bowel activity" the scores were summarised. Activity determined by leukocyte scan weakly correlated with the laboratory findings (with the leukocyte number r=0.526, with the alpha-2 globuline r=0.498 and with the fibrinogene c=0.519), but no correlation was found between the Best index. The segment localisatien (small bowel, ascending, transverse, descending colon, sigmeid and rectum) of the uptake was compared with the celonoscopic or irrigoscopic findings in 22 cases. The sensitivity, specificity and accuracy was 71.4 %, 80.8 % and 74.7 %. The most false negative results were found in the ative rectal processes. In conclusion, we suggest that the 99mTc-HMPAO-leukocyte scintigraphy is a suitable method for the localisation of the inflammatory bowel disease and the follow-up of the patients. in 18 studies.ECT was performed on day 2 only in the ca se of In.Twelve pts underwent second look surgery,in the others RID was confirmed by CT,US,endoscopy,barium enema or 6 mo follow-up. In 9 pts RID was the only non invasive technique able to detect local recurrences.The differences between the two groups may be explained by the higher prevalence and a more advanced disease in the iodine group,while the non specific uptake of In is probably responsible for FP results. However the In label,offering higher qua lity scans and the possibility of ECT,seems preferable. These results are more optimistic than considering dis rant metastases ~ too and,as CT and US are of limited value in the detection of pelvic recurrences,it seems worthwhile including RID in the follow-up of these pts. Repeated immunscintigraphy(IS)with 99m-TC-labelled monoclonal Anti-CEA antibodies(BW431/26) were performed in 9 patients(4m, Sw,42-77a;x=59~ with colorectal carcinoma for evaluation of recurrencies and metastasis and for control of chemo-or radiotherapy respectivly. IS was again repeated once in 6 patients,twice in two patients and three times in one patient.Time interval between studies ranged from 27-354 days (x=168 days).In a total of 24 immunscintigraphic studies 19 true positive,2 true negative and 2 false positive results could be observed. Imaging quality was excellent in nearly all studies.One study could not be evaluated because of intensive activity uptake in the liver and bone marrow,one further study showed a marked decrease of uptake in tumour recurrence in the 2nd study which was performed 27 days after the first study on request of the patient. HAMA'S were measured in all patients and were normal in all but one(w;57a) . In this patient IgG was 25,2 rel.U/ml and IgE 179 mU/ml 98 days after second application of the antibody and the patient showed minor side-effects 20' after the third antibody application. In our experience repeated IS with Anti-CEA antibodies(BW431/26)proved to be an important technique in management and therapy control of patients with colorectal carcinoma. Gastrin, a gastrointestinal hormone, is known to have cytoproliferative effects on tumors of the gastrointestinal tract. Since the biological effects of the hormone are mediated by binding to specific receptors, it was the aim of the present study to evaluate the gastrin receptor density in vivo by uptake studies of 1-125-gastrin into human tumor xenografts in nude mice and to correlate the obtained values with the in vitro determined receptor concentration. With a seven point Scatchard analysis a binding capacity of 14-88 fmol/mg and a Kd of 10 nmol/l was obtained in gastric tissue and in some gastric and colon carcinoma investigated. After injection of 2.5 u of 1-125-gastrin into nude mice bearing tumors that had shown an expression of the receptor by the in vitro studies, an activity concentration of 3.1%/g tumor tissue was obtained at 1 h p.i..The rapid blood clearance of gastrin resulted in tumor-to-blood ratios of 2.5 aleady within 3-6 h p.i.. No uptake of 1-131gastrin, however, was determined in receptor negative tumors. The results demonstrate the fast in vivo binding of gastrin to receptor positive human tumors and offers therefore the opportunity of visualization of the receptor status in vivo with short-lifed radionuclides. Blocking of the receptor and thus inhibition of the stimulating effects of gastrin may also be evaluated by scintigraphic imaging. Tc-99m-s galactosylated albumin (NGA) (Galactoscint | is a synthetic radiopharmaceutical specific for the hepatic binding protein receptor. After approval by our institutional ethical committee, the pharmacokineties of Tc-99m-NGA were evaluated in 5 healthy volunteers, 15 patients (pts) with liver cirrhosis (classified according to the Child-Turcotte score (CTs)) and 7 pts with a variety of non-cirrhotic liver disease. All subjects received a dose of 10 rag, 5 mCi,Tc-99m-NGA. By means of a LFOV gamma camera, anterior images were made in 1 min frames in order to generate time/activity curves for liver and precordium. A blood sample was taken 20 min after injection. Two parameters were systematically derived from the normalised blood disappearance curve, which, between 2 and 15 rain, could adequately be approached by a mono-exponential function: the fractional disappearance rate (k i in min d ), with a normal range of .089 • .006, and the initial distribution volume (VD i ), with a normal value of 8.3 + .5 1.

In all cirrhotic patients, a significant decrease of both parameters was observed. This decrease was highest in CTs C pts (for 1~ : .047 + .001 in CTs A, .062+ .016 in CTs B, .029• .011 in CTs Cand for VD i : 6.3 • .4 in CTs A, 6.0 • 1.7 in CTs B, 4.8 + 1.2 in CTsC). In non-cirrhotics k i was either within normal range or slightly diminished (range: .075 -.106), whereas VD i was always smaller (range: 4.2 -6.6).

In conclusion: Tc-99m-NGA scintigraphy discriminated completely cirrhotic CTs C pts from normals. 

Comparative studies in animals and patients by our own group and others have demonstrated the potentials of Tc-99m-mercapto-acetyltriglycine (MAG3) as a substitute of radio-iodinated hippurata for renal scintigraphy (RS). Since October 1986 more than 1200 RS studies with MAG3 have been performed in our clinic.

In 95 patients we evaluated the clinical utility of RS with MAG3 by comparing the outcome of RS (plus clearance determination in 76 patients according to a modification of Tauxe's method) with results of other imaging modalities and with clinical and biochemical data. 42 Patients were suspected of obstructive urinary tract disease, 10 had calculous disease, 9 infectious disease of the upper urinary tract, 5 a neurogenic bladder, 5 vesico-uretaric reflux, 4 an ileal loop conduit, 4 aplasia of one kidney, 2 a duplicated peivicalyceal system, and 16 had various other renal disorders.

In 41/42 patients suspected of obstructive disease RS with MAG3 correctly detected the presence or absence of dilation and obstruction. In 43/53 patients with non-obstructive urinary tract disease RS revealed a reduction of renal function (28 uni-, 15 bilateral). In 28/53 patients the MAG3 clearance was decreased, which was in agreement with biochemical data in 26 cases. In 7/53 patients a normal MAG3 clearance was found and confirmed by biochemical data in 6 patients. 39/53 Patients had morphological abnormalities (22 dilations of renal pelvis or ureter, 13 shrunken kidneys, 2 hypertrophic kidneys, 2 duplicated pelvicelyceal systems, and 1 polycystic kidney), which were correctly detected by RS in 38 patients. One duplicated peivi-calyceal system was not seen at RS. Reflux was correctly detected by RS in 4 and missed in 3 patients.

We conclude: by providing most reliable functional and morphological data on the status of the kidneys RS with MAG3 is of great clinical utility. RS without micturition at the end of the study is not suited for reliable detection of vesico-uretedc reflux. Radionuclide renography is a useful non-invasive technique in the postoperative assessment of renal transplants as an aid in the diagnosis of vascular insufficiency, acute tubular necrosis, and rejection. Many non-immunological complications such as haematoma, lymphoeele, outflow obstruction and urine leaks were reported. Our aim is to elaborate on the usefulness of the radionuclide renogram in detecting these non immunological complications during the routine follow up studies. Base-line radionuclide renography is usually performed at 24-48 hrs after transplantation, every other day whenever there is evidence of immunological complications, and in subsequent follow up.

Several types of photon deficient areas (n = 12) were seen at different times during the routine investigation of 107 renal transplanted patients done between April 1988 till December 1989. All were detected before causing any symptoms and were confirmed later by ultrasonography. There were two haematomos : one detected during the base-line study. Seven lymphoceles were detected between 18 days to nine months after transplantation, outflow obstruction secondary to lymphocele was seen in 6 out of 7 and three had urine leaks.

In sunmlary, the availability of radionuclide renography as a non-invasive tool for early detection of complications, dramatically lowers the incidence of hazardous consequences. PET showed that metabolic tracers seem to be the most suitable in identifying viable myocardium,when compared to perfusion tracers. Recently a new gamma-emitter metabolic tracer, II23-IPPA, has been available for SPECT studies, presenting potential larger clinical applications. Therefore we studied 12 pts with recent myocardial infarction (beyond the 3rd week) by SPECT, performing firstly a metabolic study (MS) at rest with II2S-IPPA (early and delayed imazing) followed by a rest/stress perfusion study (PB) with tc99m-MIBI. We compared the segmental extent (BE) and the grading of the uptake (UG), between the 2 rest studies. We also evaluated the presence of residual ischemia (RI) in the area of infarction (by r/s PS) and the segmental kinesis by ECO.The ES and UG were the same in 6 pts (50%) while the other 6 pts showed at MS (delayed imaging) less large defects than at PS. The presence of RI was just the same in these 2 groups (83% vs 83%). CONCLUSIONS:our data suggest that MS by SPECT can give interesting information on viability as regards PS,especially the delayed imaging of II23-IPPA. However fur ther studies on larger populations are necessary to confirm the better effectiveness of II23-IPPA in identifying viable myocardium. Early detection of small and bilateral, arduously detectable varicocele (BV) is important because if remain unrecognized improvement of spermatogenesis after surgical correction could fail. The purpose of this study was to determine the frequency of BV in infertile males and to ascertain diagnostic performances of two-phase scrotal blood pool scintigraphy (SBPS). SBPS using erythrocytes in vivo labeled with 175 MBq of 99mTc was performed in 251 infertile males. Dynamic phase of SBPS consist of 24 frames, 4 seconds per frame, was used for detection of retrograde blood flow in testicular veins. On delayed static image (500 KC) foca] zones of increased activity in dilated pampiniform plexus were searched.

In the first group of 121, non strictly selected patients, results of SBPS were compared with clinical examination, phlebography and surgery. BV was found in 18 patients (15%). Sensitivity of SBPS was 93% and specificity 83%. Rates of false negative and false posibive results were 7%and 17%, respectively. In second group of 130 patients with clinicaly overt varicocele BV was found in 50 subjects (38%). In 38 patients (26%) with clinicaly detectable left-sided varicocele, SBPS revailed also varicoceles in the oposite hemiacrotal areas. In conclusion: thorough clinical examination of scrotum is not su~cient for detection of small varicoceles or BV. SBPS is simple and reliable method in early detection of BV and could prevent varicocele effect in infertile males. L. E ck art *, MA~L~iC]~',~ ', B. G r,",n ert*, R. Reyes 9 *Dept.Orthopsdics,'PDept.Nuclear Medmine Berlin Free University, UK Rudolf Virchow Augustenburger D-1000 Berlin 65, FR Germany Platz 1,

99mTc-bene scintigraphy is acknowfed~led as a highly sensitive and specific method in detecting loosening processes in cemented hip adhroplasty, Since 1980 a growing number of hip arthroplasty has been performed without using bone cement. Scintigraphic follow-up studies showed an increased diphosphonate uptake at least for two years after the implantation without clinical or radiological signs of loosening due to the process of osseointegration and biomechanica] adaption. In the evaluation of a painful hip arthroplasty it is necessary to differentiate pathological diphosphonate accumulations in loosening from 'physiological" accumulations.

To determine the "normal" scintigraphic pattern 50 patients from a prospective study underwent a clinical radiolo@ical and scintigraphical investigation 6 years after cemsntless htp arthroplasly (titanium/ aluminium/ vanadium stem, polyethylen socket System ZweymSIler) In 40 % locally increased uptake was found mostly at the tip of the stem and in the trochanteric region. Those patients showed neither radiolocigal nor clinical signs of loosening. But the radiographs in correlation to the scintigraphies showed distensions of the cortical bone and areas of higher bone density according to the regions of higher diphosphonate uptake. In the acetabulum all patients without signs of loosening showed no increased osteoblastic activity. In patients with radiologically obvious loosening of the polyethylen socket in 50% higher diphosphonate uptake could be detected.

In about 40 % of the patients an increased reactive osteoblastic activily could still be detected in the femor 6 years after camentless hip arthroplasty without clinical or radiological signs of loosening due to bony ingrowth of the titanium alloy stem and also radiologically visible biomechanical adaption. The criterias used in scintigraphy of cemented hip arthroplasty can surely not be transferred to cementless hip arthroplasty. Because of different biomechanical concepts in various comentless hip prosthesis typical scintigraphic patterns have to be established and correlated to the radiographs to avoid misinterpretation of the images. The acatabular region with the polyethylen socket showed no increased osteoblastic activity after 6 years.

M. Gerickeu L. Eckart*, U. G6ke*, J. PannhorstV, Ro Felixu Dept. of. Nuclear Medicineu Odhopedicst, Radiology* Free University of Berlin, UC Rudolf Virchow, Augustenburger Platz 1, D-1(300 BERLIN 65, FR Germany

Early diagnosis of postoperative septic osteomyelitis in orthopedic sugery is quite important. Infection scintigraphy with 99mTc-labelied nanocolloids has been shown a reasonable method with high sensitivy ( 90 % ) and specifity ( 92 % ) in infections after total hip arlhroplasty ( THA ) and bone operations and fractures with no dependency of nanocoll uptake on perfusion and bloodpool.

In our study we comprehended the behaviour of Tc~em-labeled nanocolloids in about 150 patients with questionable postoperative infections and we prooved the potential of this method in differentiating postoperative changes vs. ostecmyelitis. In equivocal cases ( n = 25 ) additional anti granulocyte scintigrams were peformed. Comparision of perfusion, bloodpool and quantitative uptake 45min., 4 and 24 hrs. p.i. in both methods were done.

The sequence scintigraphy with Tc~m-labeled nanocolloids is an important method in detecting acute and chronic septic osteomyelitic processes.

Problematic were postoperative cases with large wound trauma, i.e. within the frist 2 months after total knee arthroplasty, where in all cases enlarged nanocolloid uptake was seen in the surrounding bone tissue due to the unspecific inflammation, so that septic infection could not be differentiated. The additional granulocyte scintigram showed the same scintigraphic pattemthan the nanocolloids. In equivocal chronical cases of osteomyetitis the granulocyte scintigram showed different results. Some cases had exactly the same pattern than the nanocolloids, some showed more Iocalised enrichment due to hig granulocyte accumulation.

For clinical routine, we prefer the scintigraphy with Tcgem-labeled nanocolloids because of faster results, lower cost and radiation dose and less allergic risk than mouse anti NCA-Granulocyte-AB. The goal of our investigation was to experimentally determine the influence of aortic sclerosis on the measurement of bone mineral content (BMC) of the lumbar spine performed by dual photon absorptiometry (DPA) in the a.p. projection.

A total of i00 dissected abdominal aortae (55 male, 45 fem., age 21-89) were scanned on the osteodensitometer OSTEOTECH 300 over a human spine cast in lucite (LS-Phantom). The values obtained were compared with the values measured for the LS-Phantom without aorta. The atherosclerotic lesions were grouped in five categories: No atherosclerotic lesions, fatty streaks, fibrous plaques, low-grade and high-grade complicated lesions. Results:

The average increase relative to the mean for the vertebrae L2 to L4, for aortae with high-grade complicated lesions, was 2.4% (maximum deviation 7.4%). Aortae with fatty streaks or fibrous plaques did not cause significant increases of the BMC. Aortae with low-grade complicated lesions showed a mean deviation within the range of instrument precision. Conclusion:

DPA measurement of the lumbar spine is only moderately influenced by the superimposition of a calcified aorta. Only in two out of 17 cases with high-grade complicated lesions the deviation of the BMC value was greater than 5%. Objective of the study was to compare Ga-67 citrate, In-lll leukocytes, Tc-99m HM-PAO and In-lll antimyosin (which has been shown to localize in skeletal muscle injury) in experimentaly induced inflarmnatory lesions. Inflan~natory regions were induced by intramuscular injection of 0.5 ml turpentine oil in left hind leg, the right leg was used as control. An abscess was allowed to develop for 7 days. Each radiopharmaceutical was injected intravenously into five rabbits. Using a gamma camera interfaced with a minicomputer and the rabbit lying in supine position, static images of 5 min. were obtained at 2, 6, 12, 24 hrs postinjection. Region of interest were assigned over the inflarmnation sites in the left leg and identical one on the right leg. The ratio of the amount of radioactivity of the left leg to that of the right leg was obtained. At all imaging times, the uptake at the inflammatory site was well visualized at 2, 6, 12, 24 hrs post injection. However, the ratio of the uptake to background radioactivity of In-ill antimyosin and Ga-67 citrate were statistically the same but higher than those of In-Ill leukocytes and Tc-99mHM-PAO leukocytes which were statistically equal. Images of the abdominal area using Ga-67 citrate and Tc-99mHM-PAO leukocytes showed activity in the small intestine. In sur~ary, the quality of the images were in the following order Ga-67 citrate ~ In-lll antimyosin > In-lll leukocytes ~ Tc-99mHM-PAO leukocytes. Whole body scans of ~23I Icmazenil have been made in 6 male volunteers (age 25-53 year@_) to visualize ki'netics of uptake and mer=nnolism and to determine r~e l~rcentage up~sae in the brain of tne uqs, e , admin/stert~/ At I and 3 h after im0e~ion ~p. i. j oz 5 mCi ~=31 Iomazenil both anterior ar~ posterior imaqes were made with a Tochnicare Whole Bode Scanner (ra~e 20 cm/min). Regions of interest were drawn over the whole body and over various orwars and the geQmetric mean was taken at 1 (WB I).and 3 h (WB 2) p.i. Blood sar~les w~re r~men ar~ urine was collected up to I and 3 h after injectior~ Date were corrected for radio-active decay. In 2 sv~ects, I mg cold flumazenil was inj ect~l 2 h p.i. (Grou~ A). The 4 other subj'ects did not receive a secorn injection (Group B).

Percentage of total dose administered (X -+ SD): Patients and methods: 20 patients (pts) with SCC of larynx and 7 control subjects were imaged at 1.5-2 hr after injection of I0 mCi 99mTc(V)DMSA. Anterior,left, and right lateral views of head and neck were obtained with 5QO Kcounts. The scan results were compared with histopatbologic results of neck surgery.

Results:~ The scans showed focal intense uptake in the anterior midline of the neck in pts with SCC of larynx and no focal intense uptake in control subjects. Two pts were imaged postoperatively and showed focal intense uptake as wello It was found a 100% sensitivity, a 77% specificity, and a 92% accuracy for primary lesion. Of 9 pts with cervical lymph ndde metastases, in 5, the scansshowed intense uptake in the region of palpable lymphadenopathy which were ~ 2 cm in diameter. The test revealed 55% sensitivity, 9Q% specificity, and 75 % accuracy in detecting the metastatic lymph nodes. Conclusion: ~e conclude that the uptake of 9gmTc(V)DMSA in primary SCC of larynx is highly sensitive, But the value of the scan in cervical metastatic lymph nodes still needs further evaluations, since they are very critical in making decision for the treatment plan. In a variety of neural crest tumors including neuroblastoma and medullary thyroid carcinoma. Recently. Tc-99m (V)-DMSA has proven to be a useful agent in detecting the primary and tile metastatic medullary cancer of thyroid. These findings encourage us to investigate whether TC-99m(V)-DMSA has a contribution in detecting primary and metastatic conditions of neuroblastoma.

The study was performed in 16 children (age canee:2.Smonths-7 years) with histologically proven neuroblastoma. 10 patients had operation before the study. All patients underwent TC-99m(V)-DMSA, Tc-99m MDP and 1-131 MIBG scintigraphic studles at one week intervals.

In addition, bone marrow biopsy, computed tomography and/or radiographic imases and various biochemical tumor marker levels including vanillylmandelic acid, neuron specific enolase. ferritin, alpha fetoprotein and carcinoembriogenic acid were carried out in all patients, 6 patients had primary tumor at the time of imaging. All Of these primary tumor showed intense uptake of 1-131 MIBG, whereas less intense uptake of Tc-99m(V)-DMSA and Tc-99m MDP were seen in 4 and 2 palients, respectively. 7 patients had metastatic deposits in bones and 2 had metastatic spread in bone marrow. The sites of metastasis were in cranium (3 cases), spine (2 cases), pelvis (3 cases), humerus (i case)~ femur (2 cases) and metaphyses of femur (3 cases). Neither Tc-99m MDP nor T-99m(V)-DMSA was able to demonstrate the metaphyseal and bone marrow deposites of neuroblastoma. The rest of the bone deposits were shown by both Of these procedures.

In contrast to this findings. 1-131 MIBG concentrated in all sites of bone and bone marrow deposits. Remaining 3 patients were found to be normal in all scintlgraphic studies. These results are better than those with In-ill or 1-123 as labels for these antibodies and confirm that Tc-99m is the label of choice for RIS.

BIANCO A., CARRI~UIRY G., LAGO G., GAUDIANO J., GONZALEZ M., TOUYA E.

The aim of the present study is to define the real usefulness in clinical application of immunoscintigraphy (IS) with radiolabeled monoclonal antibodies in the management of primary and recurrent colorectal cancer. A prospective study was carried out in 24 patients (13 women, 11 men) with a mean age of 58 yr (range 34 to 85). In 7 patients primary colo-rectal cancer was suspected on the basis of imaging and endoscopic methods but not confirmed by histopathology. In the other 17 patients who had already undergone surgery for colorectal adenocarcinoma, recurrent disease was indicated by tumor marker levels, clinical or imaging results. Subjects with preoperative histopathologic evidence of malignancy were intentionally excluded.

Patients received IV1 mg each of 1311 -labeled anti-CEA and 19-9 F(ab')2 fragments. Abdominal and pelvic planar scintigraphy images were recorded using a LFOV gammacamera (DYNA 4/15) interfaced with a DIGITAL PDP 11/34 data-processing system. Identical views were performed with 99m Tc to obtain anatomical landmarks. Images were recorded at 3 and 5 days after injection, and later if necessary.

Immunoscintigraphic results were correlated with pathologic studies in 17 patients. All results for primary tumors were accurate : 6 true positive (TP) and 1 true negative (TN). In patients wtih suspected recurrence during follow-up, iS results were TP for 6 patients, TN for 3 and false negative (FN) for only 1 who had diffuse abdominal carcinosis. Despite the use of 1311 for antibody labeling there was high sensitivity and specificity for diagnosis of primary and recurrent colorectal adenocarcinoma (including liver metastasis). The most conspicuous indication of IS is in the followup of patients previously operated on for colorectal carcinoma who have a suspected but inconfirmed recurrence. IS may also indicated in the management of primary colorectal cancer not diagnosed by conventional methods. The determination of the absolute uptake of radiolabeled monoclonal anttbodies (Mab) in metastases is essential for dosimetry. The aim of the study was to validate a special iterative SPECT reconstruction program for quantification based on the principle of maximum likelihood. The SPECT-images were acquired using a 360~tating gamma camera (I/2 inch crystal; medium energy collimator; 64x64 matrix). The measurements were performed in an anthropomorph phantom of the abdomen including spheric tumorphantoms (~ 3 cm) and in patients with solitary liver metastases (~ 3-4 cm). The contour of the tumor in the SPECT slices was determined by analysis of the countrate profile. A background region surrounded the tumor in a defined distance. The countrate in the tumorregion increased with increasing background radioactivity because of scatter. Based on these results a diagram was established showing the calibration factors for different tumor-to-background ratios. In 3 patients with solitary liver metastaseS 120 MBq of 131-I labeled Mab to CEA/CA 19-9 were injected. SPECT acquisition of the abdomen was performed before surgery. Immediately after surgery, the radioactivity in the metastases was measured in a well counter. 3 kBq +20% In conclusion, the described procedure is a reliable method to determine the uptake of 131-I labeled Mab even at low tumor-to-background ratios.and can provide information on tumor biokinetics of Mab in man.

Lecouffe 

The aim of the study was the scintigraphic evaluation of splenic function in patients who underwent splenectomy for trauma and its correlation with the haematological findings. Thirty two patients aged between 18 and 65 (Mean 33J were studied.ln 12 of these,at the time of the splenectomy pieces of spleen (SP) were transplanted to the omentum.ln all patients the number of Howell-Jolly bodies(HJB),from 2 blood smears of 5000 RBC each,were counted and serum levels of IgA,IgG,IgM,C3 and C4 were measured.All patients had liver/spleen scintigraphy with Tc-99m HSA microspheres (diam.<l.O~m) and the scans were examined for evidence of the existence of splenic tissue;their position,number and intensity of uptake in comparison with the liver were noted.

In 23 of the 32 patients(72%) splenic tissue was detected (12 with splenic implants).Thirty five SP were totally demonstrated.Their size on the scan ranged from 1-21.3cmZ.HJB were found in all patients.

There was a negative correlation between the number of the HJB and the size and activity of SP (r=0.51 p<0,05) but there was no correlation with immunoglobulins and C3 and C4 levels though the latter was in the lower limit of the normal value in all patients. COnCLUSIONS:In 12 patients with transplants, all SP were demonstrated.

Splenosis occurred in 40% of cases. The largest remnants were found in the left hypochondrium.HJB count was considered a sensitive indicator of splenic function and showed a negative correlation with the size of functioning SP which were however unable to remove them entirely from the blood. Aim of the study: Bone aointigrephy with whole body ar 8yateme 8re widely used. We have studied the performance differences between planar single view bone loans and whole body bone scans.

The instrumentation we tested were 9 large field scintillation camera {MB @200, GAMMA MOVEK) and a 8X @00 whole body eolntigraphy system (PICKER INT.) equipped with a general purpose low energy collimator. Sclntigrams were performed with 9 radioactive paper-stripo phantom. Metutues are simulated in ,= range from O.E up to 3.0 r diameter and with a target/nontarget activity contract varlatlbn from 1.3 up to $.7 (further conditions: patient bone scan related count rates, scatter condition E cm water). For e=,ch Mmulation set we produced scans In two ways; a) planer, single view mode b) whole body mode 8cane were exposed on x-ray film.

Result=P. The performance were determined from nine obeervere' ROC-datu and rank test numberl. Bued on individual ROOId-tu, averaged/pooled ROC-detu and rank teat numbers no elgnlfic4nt performance differences we have found. The known sensitivity dependence from aimuleted metastases oontraet and meteet~eee diameter were cleerly to see. But in both, the planar single view and the whole body scinttgrams, sensitivity under comporable oonditiono are in the same range. The inter-observer variation ere greather then the performance differences between the two scanning methods. In addition and following to ultrasound (US) the thyroid scan provides information of the functional state of nodes. While in US the link to the local clinical findings is easily given, this is not true for a scan taken by a gamma camera. We determined PAP and PSA by immunoradiometric assay (Hybritech Europe 5.A.) in 90 patients with previously untreated PA diagnosed by biopsy. For all these patients, PAP and PSA levels were simultaneously controlled after therapy for possible correlations between PAP and/or PSA serum activities and response to treatment (range of follow-up 2 to 28 months,mean : I8 months). The localized desease group (LD) corresponded to 50 patients treated by curative radiotherapy (RT) with or without TURP and extented disease group (ED) to 40 ones treated by hormonotherapy with or without palliative

PSA and PAP levels were high in 76 % and 32 % of cases in LD and in 95 % and 80 % of cases in ED respectively. The association of the two markers did not improve the diagnostic accuracy of PSA determination alone. PSA values were not closely correlated with the clinical stage of disease although the levels tended to correlate with its extent. A substantial decrease of PSA levels was observed when having o reponse to therapy after some weeks to 6 months in LD ans after a longer time in ED (mean time 6 months). A rise of PSA levels during the remission phase predicted several months before clinical recurrence. Besides a transient rise has been observed in I4 cases during RT. These connections were not so clearly evidenced with PAP. Similarly, clinical course and current state after therapy were more accurately predicted by PSA than by PAP. The PSA determination provides unequivocal advantage for diagnosis in tumor progress and control under therapy of PA. In order to studying t~e CA 195 behaviour,recent tumor-associated antigen defined by Mabs, we have determined by IRMA (Hybritech) the serum levels of this antige~ ih 315 subjects having non tumoral diseases. In control group (i01 HBsAg-blood donors) CA 195 levels oscillated between 1 and 14.7 U/ml, with a mean value of 3.07+3.3 (M (51):r:i-14; 3.4+_3.6 ; F (50): r:i-14.7; 3.07+3?3; smokers (28): r:I-9.9; 1.95+2.0 ; non-smokers (3-4"): r: 1-14.7 ;2.12+--2.7). We have~aken 12U/ml (97.5 percent_i le) as upper normal level. Values higher than 12 U/ml were observed in 69 cases of the study group (22%)()15 U/ml: 16.8% ;> 20 U/ml: 12.6% ;> 25 U/ml:10%), corresponding the most important percentages of positives to cirrhosis (46%; r:i-149), acute pancreatitis (39.2%; r: 1-53.4), cholelithiasis (33%; r:i-96.4), choledocolithi@ sis + OJ (67%; r:l-)120), chronic renal failure without-liver involvement (17.5%; r:i-33.5) and lung diseases (17%; r:i-39.2), preferently chronic obstructive bronchopneumopathies. We have observed a statistically significant difference in choledocolithiasis with (6/9 +; r:l->lg0) and without obstructive jaundice (0/6 +; r: 1-7).

Our results led us to the following: a) It is possible to observe high levels of CA195 in non malignant di seases, preferently cirrhosis, acute pancreatitis, cholelithiasis and choledocolithiasis with OJ ; b) In differential diagnosis between pancreatic cancer and acute pancreatitis, 55 U/ml can be used as threshold (4~ % v 0%);c) Excluding cirrhosis, chronic renal failure, chronic gastritis and lung diseases, a CA195 value~20 U/ml represents the following possibilities: 53.8% acute pancreatitis, 15.3% cholelithiasis and 30.6% of choledocolithiasis with obstructive jaundice. The hybridoma technology has produced monoclonal antibodies (MAbs) against antigens associated with a wide range of tumors, including epithelial ovarian cancer (EOC). A characteristic of antigens expressed by EOC is that they are often shared with other epithelial neoplasias, such as breast and gastrointestinal cancer. CA549 is a high molecular weight glycoprotein recognized by an immunoradiometric assay involving two monoclonal antibodies: BC4E549, developed against a breasttumor cell-line and BC4N154, developed against a milk-fat globule membrane. In order to test the reliability of CA549 assay in the diagnostic approach of EOC, we measured the levels of CA549 (reference value [RV]: 10 U/mL), CA125 (RV: 65 U/mL), CA19.9 (RV: 40 U/mL) and CA15.3 (RV: 32 U/mL) in blood samples collected preoperatively at diagnosis from 42 patients (pts) with EOC and 84 pts with benign ovarian pathology undergoing laparotomy. CA549 had a sensitivity (SE) (76.2%) near to that of CA125 (83.3%) and greater than the SE of CA19.9 (31.0%) or CA15.3 (61.9%). In particular, CA549 showed the same SE of CA125 for serous (78.6%) and undifferentiated (100.0%) histotypes, while it was less frequently expressed by mucinous tumours (20.0%). The incidence of elevated serum CA125 and CA15.3 levels was significantly greater (p=0.00004 and p=0.025, respectively) in advanced stages than in early ones, while CA549 and CA19.9 assays positivities did not correlate with the extent of neoplasia. However, it is worth noting that CA549 assay seemed to be more suitable than CA125 assay with 65U/mL for the detection of early tumors. CA549 was less specific than CA125 with 65U/mL as RV and CA15.3; in particular CA549 assay had a high percentage of false positive values among pts with serous cystoadenoma (18.6%) and endometriotic cyst (21.1%). Since these preliminary data showed that CA549 had a good SE for non mucinous EOC, we are now evaluating reliability of the serum measurement of this antigen in monitoring the disease course. and TPA were high in 50% of GC, Ca 19-9 in 25%. The ccmbined use of the markers increased sensitivity in grcup B both in RC (80%) end GC (7[~/o). All the pts were followed with serial meastmements of the markers for 8 -15 menths. Two RC and 1 GC of group A, who originally bed high Ca 195 levels, exibitod a further rise which preceded the appearance of metastases by 4 -6 mcnths. Ca 195 also rose in 5 pts (3 RC, 2 GC) with initial normal values end metastases bensme %cparent 5 -6 months later, while in one case of disease rel~cse,Ene marker remained within normal limits. TPA, Ca 19-9, (FA displayed an early rise er further inoreaes, if already abnormal, in 7 pts. In group 8, disease progreesien occurred in 19/30 RC and in all 4 CC despite chemotherspy. Ca 195 rose progressively in all of dqem and TPA In 16/S0 and 3/4, CEA in 17/30 and 2/4, Ca 19-9 in 14/30 end 3/4 respectively. In the ii pts with disease regression Ca 195 sigdificantly fell, if already high, or refm3ined no~. TPA, CEA and Ca 19-9 eilher fell slightly er were enchanged. Our data dem(z~strate that Ca 195 is useful in advanced GIC to confirm the presence of metastases; its sensitivity is higher than TPA, CEA and Ca 19-9. Moreover, serial measurements of the marker can detect early recurrences in ~oparent inactive disease and can evaluate tumor resDcnse to treatment. In cerebral palsied children, motor disabilities often hamper the evsluation of intellectual and somesthetic functions. In this work, we have investigated by means of Tc-99m HMPAO brain SPECT 13 children aged 13 months to 12 years suffering from spastic cerebral palsy. In 4 hemiplegie children with large sylvian porencephalic cysts, SPECT hypoperfusion was congruent with CTscan findings in 3 patients and demonstrated additionally a bilateral hypoactivity in the prefrontal areas in 1 patient with severe mental retardation . In 1 hemiplegie child with cerebral atrophy limited to the contralateral parietal cortex, the SPECT study showed a more extensive abnormality, including the superior motor area. In 1 hemiplegic child with normal CTscan, there was no demonstrable reduction of cerebral blood flow in the motor cortex but a left parietal hypoperfusion suggesting the existence of somesthetic disabilities. In di-and tetraplegic children, in which the CTscan of the head was normal or showed cerebral atrophy, SPECT study was normal in patients with mild diplegia, showed bilateral superior motor cortical hypoperfusion in children with moderate di-or tetraplegia and bilateral reduction of perfusion in the superior motor, inferior motor, prefrontal and parietal cortex in children with severe di-or tetraplegia. These results suggest that Tc-99m HMPAO brain SPECT could be valuable for a thorough neurological assessement in spastic cerebral palsy. We have started to treat children with neuroblastoma stage IV with Interleukin-2 (4 children) and a monoclonal ganglioside-antibody (Gd-2, 3 children) directed against epitopes on neuroblastoma-cells, when there is poor response to the usual therapeutic scheme with chemotherapy,surgery,irradiation,and bonemarrow-transplantation. While the disappearance of a single femoral metastasis in one child after IL-2 therapy could be due to the delayed effect of a 131-1-MIBG-therapy, a rapid tumor regression in another child already after the first course continued for four courses until the formation of lymphnodes in the pelvis indicated tumor progression. A girl with multiple bone-metastases and a diffuse bone-marrow infiltration showed a good response to one course of Gd-2, (four doses within one week) confirmed by the 123-I-MIBG immunoscan and the decrease of pain. The monoclonal antibody Gd-2 complements MIBG in the detection of neuroblastomas and allows to determine the binding-rate of the antibody given for therapy. IL-2 and Gd-2 have shown the capability of tumor regression in poor responders to the usual therapy and are integrated in our therapeutic scheme of children with neuroblastoma stage IV. A method to study the pulmonary arterial circulation based on the computer processing of the periodic variations of the lung activity, during the cardiac cycle, at pixel level, in patients with labelled blood pool and ECG gated acquisition is presented. This method is an application of work published on the visualization of the pulsatile lung blood circulation (de lima et al., 1986) . In vivo tagging of RBC with 740 MBq of 99mTc and posterior view acquisition was used. Fourier analysis was applied and first harmonic amplitude and phase images obtained. A normal histogram (number of pixels/phase angle) shows a large peak for the pulmonary circulation followed by a small peak, at a larger phase angle, which respects the bronchial circulation. An increase in the latter means increase in the pulmonary arterial flow which may be a shunt. The ratio of the sums of the amplitudes of the pixels in this peak and of the amplitudes of all the pixels in the histogram is, approximately, the ratio between the pulmonary arterial flow and the total blood flow in the lungs. In a study of 24 normals the estimated bronchial flow was 1.9• In a group of 9POCDpatients the value was 7.4-+3.0% which significantly differs from normal (P<0.0001). This method may have a role as a noninvasive easy technique for the study of pulmonary circulation. Uptake of radioactivity into some types of tumors and the skeleton have been registered after application of various radiolanthenide complexes by animal studies. Results of first clinical trial with the complex 1S9 Ybnitrilo-tri-acetate (NTA) in 21 pts. suffering from primary or secondary malignant pulmonery tumors can reported now. These neoplasms have been diagnosed reliabely by means of XCT end biopsy eg. and assumed histologically after surgery. The iv injection of 185 MRq 189 Yb NTA has been followed by the registraLion of time course of radioactivity. The regions of head, chest end abdomen were imaged 2, 5, 24 and 48 hrs. pi. Furthermore, the concentration of radioactivity in tumors and in the surrounding tissue could estimated postsurgically. High tumor/lung tissue ratios rangin 9 from 3.4 to 10.9 allowed the localization of both primary tumors and metastases in excellent manner except cases with completely necrotic processes. True positive results were found in 19 from 21 persons (93 ~). In 12 pts. the maximum of radioactivity uptake entered after 2 hrs. already. Inflamed tissue showed a lower uptake end a very quick elimination of radionuclide compared with the tumors. Hitherto existing results confirm IG9 Yb NTA as a valuable radiotrecer for both primary and secondary pulmonary tumors. It will be investigated if such a high affinity exists ?or other tumor species. In LAS/ARC patients 67-0A showed 20 l~g and 14 mediastinic positivities of chest X-Nay: 6 pati~ts with abnoroal scintigraI~hy and normal X-Nay developed PCP 2 months later. No positivities have been showed by 67-C~ and chest X-Nay in nor~ controls.

Conclusion: ~he 67-Ga chest scan in HIV correlated pathology has shown: i) a better accuracy and a more high sensitivity (89%) than X-Nay (8~) in AIDS patients; 2) optimal topographical definition of the l~g pathological area; 3) it reveals mediastinic invelv~rent; 4) early detection of lesion X~ay negative~ 5) necessity of che~oprophylaxis for PCP in 67-C~ positive IAS/ARC ~bjec~. were employed (AUA1,B72.3~BW494/32,FO23CS).They were selected on the basis of the in vitro imfnunohi stochemi str'y exarni nation and wer'e ] abel led with I131. The NAbs were injected intr'aper'itoneally. Nany patients were retreated up to 5 times. The systemic, hematol ogi c ~ hepat ic and r'enal toxicity was very mild.

The results recorded are:7 Progressive Disease (PD) lasting 6.~ months as median time),5 Stable Disease (SD) (8.2 months),5 Partial Remission (PR)(5 months),3 Complete Remission (CR)(9 months).

The factors which resulted more favour'ably affectCn,~ the response wer'e :1) a quite short t~me elapsed since fumour, dCagnos~s and RIT (<7) months);2)a str'on9 Cmmunohisiochemistr'y pos~tivity (> 2 plus);3) previous multiple chemotherapy eour'ses (>5);4) repeated RIT cycles(>2); 5) a cumulative r'ad{ation dose to the turnout > 5000 cGy;6) a quite limited extension of the disease which had to be confined in the per'Ctonea] cavity~with number of r'ecurrences tess than 5 and with their' diameter' <2 cm. However in 2 cases a PR r'esult in liver' metastases was observed. A variety of cancers result in widespread metastases to the skeleton.

Such metastases are often associated with significant skeletal pain despite conventional forms of treatment.

Strontium-89 (Sr-89), a pure beta emitter with a maximum energy of 1.5 MeV and a half life of 50.5 days, has been used in a general hospital setting for the palliation of skeletal metastases.

We have evaluated 83 courses of Sr-89 therapy in 60 patients over the past 18 months.

Patients were treated with 1.5 MBq/kg body weight in a single intravenous injection.

The patients were retreated at three month intervals as required using the same dosage. All patients kept a detailed pain diary, medication record and quality of life assessment during the course of their therapy. Total body bone scans were performed initially and then at three month intervals. Results showed that greater than 80% of the patients experienced at least some relief of pain and/or a decrease in the amount of pain medication required. No significant hematological depression was noted during the course of the therapy or after repeat treatment.

Sr-89 is effective in pain relief and improving the quality of life in patients with disseminated skeletal metastases. 

Diagnosis of right ventricular (RV) infarction, which is principally a complication of myocardial infarction involving inferior wall of the left ventricle (LV), is of importance, as it requires a specific therapeutic approach. Gated equilibrium radionuclide ventriculography was performed in 29 patients with enzymatic and ECG evidence of inferior transmural infarction in order to identify the eventual RV involvement.

In addition to reviewing a cine display, and fight and left ventricular ejection fractions (RVEF and LVEF) determination, phase and amplitude functional images were generated. In all 29 patients, phase and amplitude analysis confirmed LV inferior wall damage, and in ten of them, a normal LVEF was preserved, in 41%, (12 patients) phase and amplitude abnormalities indicated RV involvement. In 9 of these 12 patients, RVEF was significantly diminished (mean 29, +-6%), and in 5 of 12 patients LVEF was depressed (mean 40, + 8%). These 12 patients also have fulfilled one of the following criteria for diagnosis of RV infarction: clinical signs, ECG evidence, or hemodynamic impairment. In 17 patients with no indication of RV dysfunction, as well as in three patients with evidence of RV involvement, RVEF was normal or slightly reduced (mean 50 -+ 8%).

Our data suggest that phase and amplitude functional images represent a valuable approach in the detection of regional RV wall motion abr/ormalities and visualization of the extent of RV involvement in inferior myocardial infarction. Thus, functional imaging complements visual assessment of RV wall motion and quantification of RVEF in determination of RV dysfunction. Idiopathic VT is frequently due to focal arrhythmogenic dysplasia (ARVD) ; the assessment of RV wall motion abnormalities (WMA) is usually based upon X-ray anglo, and difficult because of the complex RV geometry. We tested the accuracy of Fourier analysis of GRA in 41 pts with reccurent idiopathic VT (LBBB pattern) : 26 with abnormal RV at X-ray anglo (Gr I) and 15 with normal X-ray anglo (Gr ll). GRA were acquired in LAO 30 ~ and RAO 20 ~ RV-WMA were assessed on time of systole (TS).images of the first (HI) and the sum of the 3 first harmonics (H3) as a delayed area ; mean RV and mean LV-TS were quantitatively compared (t-test Stimulated skeletal muscle flaps, contracting synchronously with the heart, have been proposed to reinforce or partially replace ventricular walls in the treatment of irreversible myocardial failure. Thus, the aim of our study was to evaluate the effect of latissimus dorsi cardiomyoplasty on ventricular function in the treatment of dilated cardiomyopathy by gated blood pool imag, ing (GBPI). We have studied 7 male patients (16-53 years) who were in NYHA class III or IV despite maximal medical therapy. GBPI was performed at rest after i.v. injection of 1111 MBq of RBC before surgery and 3 and 6 months after surgery. Images were analysed qualitatively (LV diastolic volume) and quantitatively (left ventricle ejection fraction-LVEF, right ventricle ejection fraction-RVEF Congestive heart failure (CHF) is typically associated with reduced left ventricular (LV) performance. We previously described 58 patients (pts) with CHF and normal LV systolic performance. The long term prognosis of these pts is presently undefined. We followed 52 pts (90%) for seven years. Mean age was 71 years (range 36-96),mean LV ejection fraction (EF) 61% • 11% (all pts LVEF>45%). CHF was scored by a clinico--radiographic index with a mean of 7.0 • 2.3 (13-~orst CHF). In 37% an S gallop was present and 33% had ~ 3 ' ~ acute pulmonary edema. Cardiovascular (CV) diagnoses included coronary disease (52%),hypertensive/hypertrophic cardiomyopathy (CM) (31%),and restrictive CM (13%). CV mortality (Mt) 

All-inclusive analysis of the high-risk group for CAD, specialy hypertensive patients, might reduce folse + and -results of T1 studies and increase it's post-test probability.

Non-uniform and diffuse slow T1-201 washout pattern without perfusion defects (PD) occurs in some conditions of balanced hypoperfusion so that PD analysis alone, without analysis of washout variations within normal range, could obscure prognostic implications. Therefore, we analysed the magnitude of isolated non--uniform washout (INUW) and it's connection with the presence of CAD in hypertensive patients. Circumferential count profiles analysis was utilased.

Of 166 Nonhomogenous distribution of cardiac adrenoceptors may be important in the genesis of ventricular arrhythmiae in patients with acute and subacute myocardial infarction (MI).I-123-MIBG scintigraphy is a reliable noninvasive technique to evaluate sympathetic innervstion of the heart.Aim of our work was to study possible relationship between distribution of cardiac adrenerg receptors and ventricular ectopic activity in patients with transmural MI. 1-123-MIBG and Tc-99m-Cardiolite planar camera scintigraphy were performed in 12 patients with acute /12 studies/ and subacute /4 studies/ MI. Semiquantitative measurements of discrepancy between results of perfusion and adrenoceptor imaging data were performed using conventional circumferential activity profils of different projections. Data of continous ECG(Holter) monitoring were also analyzed. Size of MIBGdefects was significantly larger than that of resting perfusion defects in ll out 12 patients with acute MI. Discrepancy was found to be smaller in 2 out of 4 patients on control study performed in subacute phase. Patients with discrepancy larger than 3o degrees on circumferential profils had more frequent ectopic ventricular activity. In conclusion: 1-123-MIBG cardiac sointigraphy may be useful in evaluating patients wi~n ventricular arrhythmias after aoute MI,thus may support rational adrenerg blocking therapy. 

To assess if In-111-Antimyosin (AM) scans were able to detect myocardial damage after chemotherapy including doxorubicin, AM scans were performed after 10 cycles of doxorubicin with a total cumulative dose of 500 mg/m 2 (treatment also included cyclophosphamide and 5-fluorouracil) in 20 women with advanced breast cancer. A heart to lung ratio (HLR) was used for quantitative assessment of the AM scans. Left ventricular ejection fraction (EF) was determined before and after treatment.

EF decreased ~5% after chemotherapy in 8/20 (40%) patients. ~7/20 (85%) patients presented with AM uptake in the myocardium (p<O.01 Abnormal wall motion was found in 98 segments (9.2%), of which 33/735 (4.5%) in the LV and 65/327 (19.9%) in the RV (p<0.001). Regional analysis of LV and RV showed abnormal wall motion in the following segments: for the LV, posterobasal 6 (5.9%), inferior 2 (2.0%), anterior 5 (4.9%), anteroseptal 11 (10.1%), apical 5 (4.6%), posterolaterat 4 (3.7%), and for the RV; septal 44 (40.4%), apex 15 (13.8%) and the free wall 6 (5.5%). LV ejection fraction and LV peak filling rates have already been extensively used in the follow-up of patients treated with doxorubicin. Present data show more wall motion abnormalities in the RV compared to LV, particularly in the RV septum. We conclude that clinical outcome of doxorubicin cardiotoxicity should not only reJy on LV function, but also on hemodynamical changes of the RV. These results suggest that 123I IPPA is more sensitive than 99mTc-MIBI radiopharmaceutical in order to detect ischemia in multivessel CAD and previous myocardial infarction.

Lack of uptake in the infero-posterior walls may mask a poor uptake of 99mTc-MIBI in the A and/or AS walls but does not mask focal lack of aerobic metabolism. It has been recently shown that oPPA is transported into the eardiomyocyte similar to pPPA. In contrast to its para isomer oPPA does not undergo B-oxidation (Kaiser et al. 1990 in press). Thus using the kinetics of oPPA and pPPA an estimate of the rate of B-oxidation corrected for hackdiffusion of the labelled fatty acid may Be determined. The present study was undertaken to evaluate fatty acid metabolism in dilated cardiomyopathy (DCM). Ten patients with DCM and three normals were investigated at rest after an overnight fast. oPPA (4 mCi) and 55 min later pPPA were intravenously injected and a dynamic planar study in LAO-45 projection was acquired. Time activity curves over the regions of superior vena cave and myoeardium were generated and pPPA activity was corrected for background of oPPA. The ratio between the half-lives of 9PPA to cPPA was greater in patients with DCM (0.73 +/-0.17; mean +/-SEM) than in controls (0.40 +/-0.20). There was a correlation hetween left ventrieular end-diastolic pressure and the half life of pPPA (r=0.66, p<0.05). Parametric images (pPPA -oPPA) taken at 2 -7 minutes after injection of tracers showed rather similar image patterns whereas images at25 -30 minutes revealed still remainder accumulation in patients with DCM and no uptake in controls. The results suggest that patients with DCM have reduced oxidation of free fatty acids as compared to controls. The pPPA elimination rate is related to the end-diastolic left ventricular pressure. Isonitrile were injected, respectively. One hour after injection planar images in three views (RPS) and a SPECT study (RPT) were performed. 200 MBq of IPPA were injected at the highest level of a submaximal exercise and two SPECT studies were performed within 45 min (IPT). The planar images were analyzed visually and the SECT's were compared quantitatively to detect "Redistribution" in the RPT or turnover rates in the IPT. 1,8, and 8 pts had 3-,2-and 1-vessel disease. One patient had a normal angiogram. Out of 14 infarctions all were detected by RPT and IPT. Only 50% were diagnosed in RPS. Additionally, 3 fixed defects were seen in the inferior wall in RPS related to severe artery stenoses. IPT showed viable myocardium in these regions. True positive diagnoses of ischemia related to the coronary arteriogram was detected by RPT, RPS, IPT in the LAD, RCX, RCA-territory in 85, 30, 90; 75, 40, 85; and 65, 38 , 92 %. Falls positive diagnoses occurred globally in 5,0,and 2 territories in RPT,RPS,IPT, respectively. We conclude that in our small patient group RPS is not able to detect CHD sufficiently. Sensitivity of RPT end IPT are in the same range. IPT detects viability more reliably than RPT and the Isonitriles may be less specific than IPPA. PET showed that metabolic tracers seem to be the most suitable in identifying viable myocardium,when compared to perfusion tracers. Recently a new gamma-emitter metabolic tracer, II23-IPPA, has been available for SPECT studies, presenting potential larger clinical applications. Therefore we studied 12 pts with recent myocardial infarction (beyond the 3rd week) by SPECT, performing firstly a metabolic study (MS) at rest with I123-IPPA (early and delayed imaging) followed by a rest/stress perfusion study (PS) with tc99m-MIBI. We compared the segmental extent (SE) and the grading of the uptake (UG), between the 2 rest studies. We also evaluated the presence of residual ischemia (RI) in the area of infarction (by r/s PS) and the segmental kinesis by ECO.The ES and UG were the same in 6 pts (50%) while the other 6 pts showed at MS (delayed imaging) less large defects than at PS. The presence of RI was just the same in these 2 groups (83% vs 83%). CONCLUSIONS:our data suggest that MS by SPECT can give interesting information on viability as regards PS,especially the delayed imaging of II23-IPPA. However fur ther studies on larger populations are necessary to confirm the better effectiveness of II23-IPPA in identifying viable myocardium. Aim of our study was to evaluate the clinical utility of 1-123 phenylpentadeeanoic acid (IPPA) in the evaluation of patients with coronary artery disease (myocardial ischemia or viable myocardium). SPECT seintigraphie studies were performed with TI-201 and 1-123-1PPA in 84 patients with or without M.I.. Tomographic studies with 1-123-1PPA were performed 5 and 40 min after administration.

Patients were divided in three groups:

Group 1 (detection of viable myoeardium): 32 patients with prior M.I. and irreversibile TI-201 defect. Group 2 (detection of ischemia):

28 patients with reversible TI-201 defect.

Group 3 (detection of ischemia): 24 patients with non-Q M.I. or with less than 50% coronary stenosis and no TI-201 defects.

In Group i, 47% of segments with irreversible TI-201 defects showed 1-123-1PPA uptake (metabolic activity). Only 15% of patients showed early positive 1-12$-IPPA scans.

After rivascularization TI-201 images were similar to pre-intervention metabolic images.

In Group 2, 1-123-1PPA

showed a good concordance with TI-201. However metabolic defects were always of smaller size than TI-201 defects.

Positive 1-123-1PPA studies were obtained in 82% of patients with coronary stenosis greater than 75%.

No positive 1-123-1PPA or TI-201 scans were obtained in patients of Group 3. IPPA appears to show an improved detection of viable myocardium while TI-201 seems to be superior in detection of ischemia.

TMarwick, WJ MacIntyre, RT Go, D Underwood, G Saha. Cleveland clinic Foundation, Cleveland, OH.

Positron emission tomography using Rb-82 (Rb-PET) identifies reversible ischemia (I) but not hibernating tissue (H). To find whether post-exercise imaging of myocardial F-18 deoxyglucose uptake (FDG-PET) could detect both I and H, we studied 35 non-diabetic pts with technically satisfactory scans by Rb-PET at rest (R) and after iv dipyridamole stress (S), and FDG-PET after recovery from fasting, symptom-limited exercise.

A FDG/RbR ratio, corrected for standard doses of 60 mCi Rb-82 and 10 mCi FDG, was conceived to correct for the influence of perfusion on FDG uptake. Angiographically defined zones of normal perfusion (N) had RbS activity within 20% of maximum, with identical areas of interest having a FDG/RbR ratio of 0.08~0.04. I by Rb-PET (~20% reduction of Rb-82 activity from RbR to RbS) was present in 15 pts. FDG-PET identified I (FDG/RbR ~twice N) in 14 of these sites, and also in another 2 sites subtended by significant coronary stenoses but without I diagnosed by Rb-PET. The FDG/Rb ratio of I zones was 2.5+0.9 times higher than N.

Fixed perfusion defects were split into 2 groups based on this FDG/RbR ratio. H was defined by FDG/Rb )twice N (n=18); regional wall motion index improved in these pts examined post revascularization. Non-H fixed defects (n=ll) were associated with no change of wall motion index at follow-up. Conclusion. Post-exercise FDG/RbR correlates well with dipyridamole Rb-PET for the diagnosis of ischemia, and can also identify hibernation. This technique may be useful to assess total ischemic burden. 

In patients with coronary artery disease and previous myocardial infarction (MI), pre-operative assessment of residual myocardial tissue viability by PET-FDG predicts the degree of post-CABG functional recovery, independently from the presence of contractile dysfunction. However, the relationship between the degree of impairment of regional wall motion (RWM) and the presence and extent of FDG uptake has not been investigated. We studied 41 patients with documented MI by 18F-FDG PET after overnight fasting.

FDG uptake and RWM (biplane angiography) were visually assessed by four independent observers in blind in 6 corresponding segments of the left ventricular (LV) myocardium. RWM was defined normal (N), hypokinetic (H), akinetic (A), dyskinetic (D); FDG uptake was scored as absent (AB), mild (MD) or important (IP 10 (17%) 15 (20%) 0 (0%) Although D was invariably associated with little or no FDG uptake, no differences were noted between H-and A segments as regards the presence and magnitude of FDG uptake. Therefore, assessment of post-MI residual tissue viability by FIX~-PET studies provides important information that cannot be derived from standard angiographic techniques and might prove useful for establishing indications for revascularization procedures. {MS) The mean maximal work 10ad was 126 Watt for the RNV-group and 127 Watt for the MS-group All patients proved to have patent vessels in angiography 2 to 4 months after dilatation The frequency of one-or multi-vessel diseases or previous infarctions was comparable in all groups.

In the RNV-group 26 patients (33 %) showed a significant increase of global EF at rest from 49 before PTCA to 58 % after PTCA This result paralleled a significant higher ischemic score in ECG under exercise of 25 in comparison with 12 in the RNV-gruup without an increase of global EF at rest In the MS-group 12 patients (38 %) improved their "*Tl-uptake after PTCA in sectors without or incomplete redistribution before PTCA (scar -like behavi0ur in still viable my0cardium)

In conclusion we assume that in this subgroup the lack of complete 2"*Tl-redistibution before PTCA in patients without a previous infarction indicates hibernating myocardium These MS findings are comparable with the improvement of the rest function of RNV in 33 ~ of the patients The functional reserve of hibernating myocardium may be considerably high proved by a mean therapeutic increase of rest EF of 9 ~ in this subgroup after successful PTCA. Thrombolytio therapy in the myocardial infarction patient may produce a patent epicardial vessel but whether the myocardium is viable is less clear. Fourteen patients with first myocardial infarcts were treated with APSAC and heparin within 3 hours of onset of symptoms.

All underwent coronary angiography within 24 hours and myocardial flow was assessed by the Xenon clearance technique.

Scans were obtained using a motile Gamma camera fitted with a biplane collimator that allows simultaneous acquisition of a 30 ~ and 70 ~ left anterior oblique projection.

Myocardial clearance was calculated from peak to 30 seconds using the Kety formula. Data was obtained at rest and following 0.1 mg of intracoronary nifedipine, which in normal vessels we have previously shown to increase flow by 95% ~ 21%. Ten patients had an angiographically patent vessel.

In the left ventricular myocardium subtended by the 'infarct artery, mean myocardlal flow was 65.7 -17. 

These results suggest that, although the infarct related vessel is angiographically patent, the subtended myocardium does not produce a normal vasodilatory response. 

In the phase image a tongue-like stripe in the interventricular region often can be observed, which is in phase with the atria. The computer simulation gives hints for a motion-artifact.

In the amplitude image a CD often can be observed even in patients without any regional wall motion abnormalities. We examine a theory9 in which the CD is due to the "too good" resolution of the gamma camera. We found the size of the CD to depend linearly on the endiastolic volume and inversely on the ejection fraction. We consider our model to be helpful for relating basic heart kinetics to results in RNV and for testing nuclear medicine software.

Do,an Bor, Hikmet Bayhan 1 Turkish Atomic ~ergy Authority I Gttlhane Military Medical Academy Nuclear Medicine Dept.

Artefacts related to the crystal structure are mentioned in the literature. Their inspection in the flood field images are possible if they can reach a detectable size. Observation of crystal ~th a naked eye under the strong day light ill~ination (after PM tubes removed) can net visualize these artefacts unless they ere strongly hydrated.

Since the NaI(TI) crystal is excited most efficiently in the 250-310 ~ range, we ill~ninate the crystal with ultraviolet light in total darkness and visualize the artefacts in sufficient detail. Observation of six different old crystals is accomplished ~rlth this method and these spots were detected in all of them. They were all located deep in the crystal, i.e., close to entrance surface.

On the,other hand, propagation of artefacts in time is followed wi~h the inspection of flood field images of t%~o c~m~-ras which are routinly obtained during a four-year-period. The rate of increase is two times in number and their size reach 1-2 cm in four years. As these crystals disassemble for the replacements with new ones, their photographs ar~ taken by using a UV light. When alumint~n cover is removed from one of the photographed crystal, some distorted spots on the crystal face and their trace are seen as yellow dots at the inner surface of the cover. This evidence is a definite correlation of artefacts with their flood field images and UV photographs.

We think that some loose points between the "er[stal and aluminum cover which are not in close contact with each other were affected by temperature changes in time. As a result of this, an increase in size and number of artefacts arised.

The UV light method is useful both for the acceptance test of just arrived crystals and for the solution of persistent nonuniformity related problems. In Nuclear Medicine, the quality of the images depends mainly on the uniformity and the spatial resolution of the imaging system.

In order to corr'ec, t simultaneously the degradations due to tlne lack of uniformity both in the activity and resolution as well as due to the poor spatial resolution., a new method of variant restoration has been developed. A variant method obliges us to have the imaging system characterized by as many Point Spread Functions (PSF) as possible. Due to this, a phantom was developed to obtain 1.51. PSF by means of 27 point sources. The conclusions drawn from this experimental phase showed that the hypothesis of invar'iance, which is the basis of the usual restoration methods, was not valid. This result reinfor(-ed the need for a variant method in which the invariance assumption was no longer used. The method consists in obtaining, on a pixel by pixel basis, an estimation of the object from the general expression for-images formation.

This method Inas the advantage that it can be applied both in variant or" invariant fore by ju~st varying or fixing the PSF for each pixelo

In this way the results can be easily compared. 

List mode acquisition and processing of gated cardiac examinations offers advantages over standard frame mode acquisition and processing. These include uniform data density in all frames, avoidance of smearing of end systolic data, and better definition of diastolic f'dling parameters. Despite these advantages, list mode processing is infrequently employed in routine clinical studies because of the usual need for time consuming postprocessing of stored data.

We developed hardware and software for use on a personal computer which supports list mode-type processing (including fixed duration framing, variable duration framing, and forward-backward framing) of data as it is being acquired. We evaluated the system in 50 patients referred for evaluation of cardiac function, comparing the results with standard frame mode acquisition and processing. Count rates exceeding 20,000 per second could be processed in real time without significant loss. Systolic ejection and diastolic filling parameters were better defmed than in corresponding frame mode studies, particularly in patients with varying heart rates.

The ease of use of this real time approach to list mode data processing supports its general application in gated examinations of cardiac function. A shorter than usual time of acquisition of GBF studies is desirable in situations where the stabiIity or reproducibility of ventricular contraction cannot be maintained. Stress testing or ventricular tachycardia are such common circumstances. Because the injected dose cannot be increased, the images would have a very low statistics (= 50 photons/pixel/image with 16 images in the RR interval). A low statistics implies the use of algorithms adapted to the construction of accurate GBP images. Because the count rate of each pixel of a cardiac study can be modelized as a heterogenous Poisson process, a discrete series of images is not exhaustive. This led us to the use of a maximum likelihood (ML) technique using the time of arrival of each photon. This additional information may not be sufficient to produce high quality images. Therefore a Bayesian (B) technique was combined to produce a spatial smoothing effect. The method was applied to a set of simulated curves (with different amplitudes and statistics) and to cardiac phantom acquisitions with low statistics. The Poisson parameter was approximated by a 2 harmonics Fourier series. The parameters of the cosine functions were calculated with ML, BML and also with least square (LS), BLS methods and Fourier analysis (FA) with or without a median filtering. References were obtained with a very high statistic acquisition. Amplitude (A) and time to minimum (Tmin) were calculated with the different methods and compared. Results : on a pixel basis, LS is the best method, ML is worse than LS and FA when the A Ere low. Overall, BLS is the best method for the A and BML the best for the Tmin. Conclusion : BML and BLS methods produced promising results with low statistics data. One can expect the same results on gated blood pool acquisitions in patients.

University Clinical center, NHR Center, Belgrade, Yugoslavia

To avoid some limitations of SPAM~ sequence and since random noise contrast (RNC) fluctuations of an NMR image depend on local contractile forces of myofibrilla, RNC and it's local vibratory eomponents generated over affected area of myocardium were analysed as a possible measure of cardiac transmural gradient of wall motion (CTGWM).

Affected areas documented by MUGA and echo were outlined and divided into arbitrary estimated subendocardial and subepicardial equal surfaces on the standard SE, gated ED/ES images. Overall signal intensities and RNC on a pixel-by-pixel basis and with vertical phase encoding for both regions were calculated. Subsequently, inverted phase encoding was used to enhance contractile noise component, and RNC was estimated over both regions and adjacent to both side of myocardium. All results were statlsticaly varied, systematicaly analysed and computerized for 2D polar ploting.

In eonculusien, lower RNC was present in affected area and next to it as compared to remote and normal regions and can be used as a measure of CTGWM. Prevalence of low subendocardial CTGWM was greater in regions with reg. ejection fraction less than 35%. Quantitation of CTGWM with 95~ confidence interval is possible in high grade stenosis, otherwise vibratory and thermal components of noise have poor statistics for practical measurements. It has long been noticed that MRI and PET provide complementary information about the structural and metabolic behavior of in-vivo live tissue. To be able to produce, mostly for brain studies, composite images and results facilitating evaluation and diagnosis, we implemented in our lab a multi-modality imaging and processing systemt able to match and display two, or more, sets of data from the same patient.

The matching methodt based on 3D contours, does not make any assumption on the relative positioning between modalities, allowing the use of different types of head holders, and also the matching of data from different time periods and/or labs, for comparison and/or combination (2D/3D). This method, which can be set up such as to enhance the matching of specific structures only, also permits inter-patient comparison through the alignment with a common "reference" template.

In our application, MRI not only helps in delineating the inner brain structures, allowing correct localization (limited by the resolution of the acquisition devices) of the most common regions of interest, but it also allows the identification of the different tissue types (e.g. fluid, gray and white matter), permitting the use of proper parameters when applying metabolic model calculations to the whole PET data set.

Besides further automatization of the whole process, future developments should include more efficient correction of metabolic data through the use of tree structural data (attenuation, partial volume effect, etc...), and also the introduction of other modalities (particularly spectroscopic magnetic resonance -a missing link for composite processing) into the list of modalities the system is now able to handle. Also, more automatized processing protocols (acquisition, matching, display, calculations) might be developed for studying and/or evaluating specific molecules and pathologies. were studied using SPECT. The results were also compared with 3 phase bone scintigraphy (BS) and computerized tomography (CT). Using a standart ROt, counts per pixel determined from coronary slices for both femoral heads and metaphysis, and left to right ratios were obtained in i0 normals and all patients, to identify the aid quantitative methods (QM) in the diagnosis. FHO were detected in 33 hips with core biopsies.When, the photopenic defect (Pd) cosidered as the sign of FHO, SPECT demonstrated 24 of the 33 involved hips (73%). The sensitivity of BS and CT were; 33%,27% respectively. The time interval between the onset of pain and the SPECT study was 0-6 months in the patients that PD was identified and 4-24 months in patients that only showed hyperactivity on SPECT. Femoral head and metaphiser left to right ratios determined by QM showed that increased metaphiser activity was present 64% of the involved hips. In conclusion, SPECT was more sensitive when compared with BS and CT in the early detection of FHO and metaphiser hyperactivity may be a useful quantitative parameter besides Pd, in the diagnosis of FHO. 

Quantification of regional findings in SPECT-studies of the brain is mainly done by comparing left and right side count rate differences of semiautomatically defined regions in operator-selected slices. As a consequence count rate differences up to 15 ~ are commonly taken for normal. To overcome these shortcomings an algorithm was developed, which transforms the individual shape and size of the tomographic slices into a standard circle form(1). This method allows the following options: i.

Creation of pattern of average and normal lower limits of HMPAO-uptake of a group of normals.

Quantification of findings in tomographic brain studies on a pixel-by-pixel base by comparison to the distribution of normals, including the calculated standard deviation levels.

Automatic delineation of blood flow distribution areas and evaluation of normal ranges. 4. comparing these region values in a given patient to normal limits. The evaluation of 15 normals in this study shows significantly lower SDs as expected; 6~ on pixel/pixel base and well below 4E in regions, respectively. In conclusion it can be stated, that quantitative evaluation of HHPAO-studies following CIRCLE-TRANS-FORMATION and standardized ROls is helpful in decreasing the standard deviation of the expected normal values, supporting objective medical decision making at brain-spect studies. 

We compared regional cerebral perfusion assessed with a brain dedicated SPET system (ASPECT by Digital Scint.

assessed with PET (ECAT 931/12 by CPS-Siemens) and We developed an automatic method based on a powerful detection of edges (1). Edges are obtained by a multidimensional operator designed for optimizing their detection and the localization of in a noisy. This operator is implemented with fast 2nd order recursive filters and uses all the space and time data according to the image dimension. We tested the method on MUGA and SPECT studies. As a result the accuracy of obtained edges and the reduction of artifacts allow to define reliable region of interest or to compute better surfaces than usual two dimensional methods.

In the future the method may help the extraction of quantitative or representative informations about from NMI.

(i) 3D edge detection using recursive filtering : Application to scanner images. CVGIP, 1990 in press. Many methods have been suggested in order to correct Compton scatter in Nuclear Medicine images. An innovative algorithm is proposed here named constrained Factor Analysis of Dynamic Structures (FADS). The procedure needs the whole energy information obtained either by list-mode or multiwindows acquisition. In the later case, FADS is performed on the.series of N energy images. Two oblique factors are extracted, one representing the scatter, and the other a combination of photopeak and residual Compton information. It is impossible to get a pure photopeak factor. A theoretical factor and the Compton factor extracted by FADS are then projected on the initial energy series in order to compute the corrected and the scattered images. This approach is tested on MONTE CARLO simulations and real phantoms, both on planar and SPECT studies. Some clinical images will be presented. The results were compared to those of the Jaszczak's weighted subtraction procedure. The recombination algorithm is more efficient than the two energy windows method, particularly improving the contrast and the signal-to-noise ratio.

This new recombination method shows greater quantitative accuracy in SPECT studies, as pointed out after attenuation compensation with the modified Chang's iterative method. We applied some processing methods which compensate for these effects in order to improve quantitation in SPECT. Scatter radiation is corrected by Factor Analysis of Dynamic Structures (FADS) using N energy acquisition as detailed in another communication. The accuracy of resolution and attenuation correction, essential for SPECT quantitation, will be improved by a new method based on the generalization of iterative MOROZUMI's algorithm. After total volume reconstruction, projection data were generated from slices, first with the effects of attenuation and detector response, and in a second time without any alteration. We used our automatic contour detection and some measured point spread function at different depth. The initial acquisition set is then multiplied by the ratio of these computed projections at each iteration. This algorithm converges automatically.

Numerical and experimental phantoms with a known radioactivity distribution are used and demonstrated the greater quantitative accuracy obtained with our technique correction. In order to avoid movement artifacts a stable patient positioning during SPECT acquisition is mandatory. A gamma-ray transparent device has been constructed, that will serve for this purpose.

A rectangular block with moulding for the head is the center piece and helps to avoid flat positioning, which our older patients can not comply with. A flat extension below the patients chest helps to stabilize the block by the patients own weight. On the opposite side a thick extension gives support to the left forearm at a level just above and anteriorly to the face. This comparatively high positioning puts less stress to the left shoulder joint. A slight slant of the forearm support tends to hold the arm in the position by its own weight, which is further assisted by a sling, which may be held by the patient.

This integrated head-arm-support is well accepted by both, the patient and the technicians, is believed to be an important means for quality control in SPECT, and shoud be implemented before sophisticated movement correction algorithms are applied. The phenomenon of geometric mispositioning was studied and characterized on Neuro-and whole body PET systems employing 2-D modular detectors (C~I-831/08 and 931/08) as well as an older system (CTI-911). Based on a simple model, a correction technique was developed which is accurate and remarkably independent of the system used.

Geometric mispositioning is caused by two factors, 1) the non uniform sampling normal in a circular detector array system and 2) the combination of finite stopping power and non-collinearity of adjacent BGO detectors at off-center positions (parallax effect). In a circular system, the spacing between lines of response (LORs) connecting directly opposing detectors grows smaller as one moves away from the center of the field of view (FOV): if sorting of coincidence events into the sinogram is done assuming equal spacing, events will be mispositioned. Conversely, when a photon passes through a detector and deposits its energy in an adjacent detector, the LOR is bent towards the center of the FOV. Measurements performed with precisely spaced line sources showed global mispositionings of -1.4, 1.5 and 14 mm (931 and 911), -0.5 and 10 mm (831) at 10, 20 and 30 cm (931 and 911) and 10, 20 cm (831) from the center of the FOV.

Fast, on-line geometric correction was performed by creadng new, uniformly spaced sinograms to be mapped to the original sinograms. The parallax error was estimated by linear fit of the data corrected for mispositioning due to sampling alone.

In conclusion, geometric mispositioning creates image distortion of structures close to the edge of the FOV. Such distortion is count rate independent and is a function of detector material, size and inter-detector separation. Our correction method can be easily tailored to any PET system available on the market. A new head holder for patient repositioning and fixation in PET has been designed and tested. The device was also used in different neuroimaging systems to obtain an accurate correlation between functional vs functional (e.g. PET vs PET) and functional vs anatomical (e.g. PET vs MRI ,PET vs CT) brain images. Head repositioning is obtained taking as anatomical reference the subject's dental morphology. Using a dentistic precision impression material a complete mould of the subject teeth is obtained in one minute. The moulding substance rests on a bracket that is fixed to the head holder. Every time when the subject undergoes to a new study his personal mould will be used for repositioning. Head fixation during the study is then obtained using a commercial foam or a special pillow connected to a vacum pump that moulds the subject head and hardens in few minutes. External markers made visible on midsagittal MRI, lateral CT and PET images, and successively on the reconstructed final images allow to record and recognize the orientation of the scan and are also used to correlate images from different image modalities as well as follow-up or activation studies using the same device. The head holder was tested on several subjects, a repositioning precision < of 2.5 mm was achieved in the axial, and in the transaxial reconstructed plane while orientation accuracy was 1 degree. This head holder results in a simple noninvasive and accurate method for repositioning, restrain and correlation of brain images. 

In infantile hypertrophic pyloric stenosis (IHPS) the circular muscle layer of Torgersen's muscle is thickened. Weber-Ramstedtpylorotomy is an operative procedure which demages this physiological unit playing an important role in gastric emptying. Several authors have reported disturbances of gastric motility in patients after operative treatment of IHPS although long-term results of operative versus conservative treatment have been discussed controversially. Methods: Gastric emptying rates for solids and I~qdl-ds--(2.2 MBq ~9~Tc-Sn-colloid in a standard meal and in 300 m! of apple juice, respectively) were determined by scintigraphy in 53 patients 17-27 years after operative (n=36) or conservative (n=17) treatment of IMPS. Results: Symptoms of delayed gastric emptying ~, vomiting) or of gastric and duodenal ulcer disease did not occur more frequently in patients having been treated by pylorotomy or conservatively compared to controls. Gastric emptying rates did not differ significantly from normal values in both treatment groups. Conclusion: Our data demonstrate that there are no disturbances of gastric motility after operative and conservative treatment of IHPS at long-term. Since the patient feels better sooner and complications are seldom, operative therapy is superior to conservative treatment.

M. Horowitz, A. Maddox, J. Wishart, P. Harding, B. Chatterton, D. Shearman. Departments of Medicine, Endocrinology and Nuclear Medicine, Royal Adelaide Hospital, Adelaide, Australia, 5000.

We have assessed the prevalence of disordered solid and liquid gastric emptying (GE) and oesophageal transit (OT) in 87 randomly selected diabetics (67 Type 1 and 20 Type 2). All diabetics were assessed for gastrointestinal symptoms (questionnaire), autonomic nerve function (cardiovascular reflexes), glyeaemic control (plasma glucose and glycosylated haemoglobin), GE of a solid and liquid meal (scintigraphic) and OT of a solid bolus (scintigraphic). GE and OT were classified as delayed when values were greater than a control range. 18(11-35) 29(5-120) <0.001 0T was delayed in 43% of the diabetics. 41% had delayed solid GE (% retention at 100min). Liquid GE (50% emptying time) was delayed in 36% and more rapid in 2%. Solid and liquid GE were both delayed in 25% of the patients. There were poor correlations (r>0.24, p<0.05) between OT and GE and between solid and liquid GE. Gastrointestinal symptoms (r>0.21, p<0.05) and the score for autonomic nerve dysfunction (r>0.35, p<0.01) correlated weakly with both GE and 0T. OT and liquid GE were slower (p<0.01) when the blood glucose concentration was >15mmol/L. We conclude that disordered GE and OT in diabetes mellitus are frequent, cannot be diagnosed with confidence on the basis of symptoms, and are related to both autonomic neuropathy and blood glucose concentrations. GE in diabetic patients should be assessed with both solid and liquid markers. 

The effects of cigarette smoking on gastric emptying (GE) are controversial; both delayed and accelerated GE of solids (S) and liquids (L) have been reported. The effect on small bowel transit time (SBTT) has not been studied. The aims of this study were to determine the acute effects of smoking 1) on S & L GE, with particular reference to the early phase of emptying, and 2) on SBTT. We studied 10 fasting, habitual smokers (5M:5F) on two separate occasions following 12 hrs abstinence from smoking. Subjects smoked either two cigarettes (1.2 mg nicotine), or sham smoked, immediately after ingestion of a test meal of scrambled egg labelled with 20MBcI of 99Tcm-sulphur colloid & 150 ml of water with 20MBq of II~Inm-DTPA& 10 g of lactulose. Anterior and posterior gastric counts were collected with frequent sampling (3-8 rain) for 2 hrs in the upright position and the geometric mean used to perform attenuation correction. Cavernous hemangioma (CH),is the most common benign liver neoplasm.They are usually asymptomatic but may cause symptoms when traumatized,may bleed spontaneously or may cause pain with its mass effect when enlarged. The differential diagnosis of CH is important in order to pursue an appropriate therapeutic course.Another important point is to provide a fearless life span without the doubt o2 being cancer.

To evaluate the value of Tc-99m RBC blood pool SPECT in CH detection;planar colloid liver scan,abdominal US,x-ray CT,angiography and Tc-99m RBC blood pool SPECT were applied to 30 patients (13 male,17 female) with the suspection of CH,within a week.Angiography is taken as a gold standart smeng the applied tests and the value of the other tests were appraised according to the angiographic findings.

While the Tc-99m RBC blood pool SPECT findings were 100% correlated with the angiographic findings, the correlation of the US,planar colloid liver scan and x-ray CT were 85%,66% and 65% respectively.

We concluded that US and planar Tc-99m RBC blood pool imaging could be used as screening tests and if needed Tc-99m RBC blood pool SPECT might be performed. Tc-99m RBC blood pool SPECT should be prefered against angiography or at least be done as a complementary test as being non-invasive,practical,non-allergic,cheap and reproducible. 

We studied 54 subjects (18 normal control and 36 patients with gastroesophagie reflux disease (GER)) to assess the predictive value of gastric emptying (GE) and 24h pH-measurement (pH-M) patterns in the severity and therapy response of patients with GER. GE studies were performed following ingesta of two identical meals on consecutive days. Meal composition was one-egg omelette, i00 g of chicken and 200 ml of orange juice.

Liquid phase was labeled with 99mTc-DTPA on the first day, on the second day the omelett was labeled with 99mTo-sulphur colloid (labelign efficiency: 85~-3%). Anterior and posterior images (2 min/image) were adquired during 180 min every 20 min, and the curve of GE was obtained (geometrical mean of each point). GE was considered normal, accelerated or slow when the curve was inside, above or under the normal pattern (mean*_iSD) respectively. GER patient were diagnosed by high endoscopy and ambulate ry pH-M. an anion-exchange resin proved to be effective in lowering serum cholesterol in hyperlipemic patients. Its main effect is blocking enterohepatic circulation of the bile acids. SeHCAT-test (a bile acid analogue) is a reliable noninvasive technique to evaluate bile acid absorption. Aim of our paper was to study bile-acid metabolism after Cholestyramine quantitatively in patients with familial hypercholesterolemia. 22 patients were studied before and after one-month Cholestyramine treatment. A seven-day SeHCAT-test was performed by daily measurements using scintillation camera technique. Serum concentration of bile acids,HDL-and LOL-cholesterols and lipoproteins were also determined. Highly significant decrease of bile acid retention in terms of half-time values was found after Chole~ styramine treatment /p<o.ool/. Decrease of SeHCAT-activi• seems to have a linear pattern. Significant relationship was found between half-time values of bile acid depletion and lowering of serum LOL-cholesterol level /p~o.o5/. However no correlation was found between total serum bile acid concentration and SeHCAT-absor~ tide suggesting altered bile acid-cholesterol metabolism. In conclusion:SeHCAT-absorption test seems to be useful in monitoring therapeutic effect of Cholestyramine in patients with familial hypercholesterolemia. A condensed imaging technique is introduced, which permits the evaluation of gastric motility patterns additionally to standard quantitative measurement of gastric emptying. Up to now 75 patients with normal gastric function and disorders of gastric emptying due to various diseases (peptic ulcer, pylorie obstruction, postoperative dumping syndrome, postvagotomy, diabetic gastroparesis etc.) were studied. Gastric emptying was measured after ingestion of a standard semisolid test meal labeled with 99mTc-DTPA. Dynamic acquisition was performed with a LFOV-gamma camera (160 frames, 15sec/frame, word mode). Quantitative data (e.g. T I/2) were calculated using the time activity curve derived from a gastric ROL For additional qualitative evaluation of gastric motility a condensed image of the gastric Re/ was created in each study. Condensed gastric imaging (CGI) provided well defined images of gastric motility. Characteristic CGI-patterns were not only obtained for normal, rapid and delayed gastric emptying but also for specific states of hypo-and hypermotility. Distribution and behaviour of the test meal within the stomach were excellently visualized by CGI as well. In 34/75 patients CGI provided more information than quantitative measurement of gastric emptying alone. Evaluation of gastric function by CGI permits to visualize normal gastric motility and its disorders. The characteristics of emptying, distribution and behaviour of the test meal within the stomach result in defined CGI-patterns, representing the predominant pathophysiological aspect of the underlying functional disorder. CGI provides valuable information not obtainable by standard quantitative measurements, thus indicating a new, successful approach for the evaluation of gastric motility and its disorders.

A. Chetanneau*. L. Aillet**, J.F. Chatal*, J.P. Galmiche**, P. Peltier*, A. Bardy***. * Medecine Nucleaire, CRLC, Nantes, France ** Hepato-Gastroenterologie, CHU, Nantes, France *** CIS Bioindustries, Gif-sur-Yvette, France

Sucralfate-Tc99m planar scintigraphy (PS) was performed on 8 adult women (mean age 30 years) with hemorrhagic colorectitis or Crohn's disease to assess detection sensitivity for gastrointestinal ulcerations. Methods: 1 g of sucralfate was labeled with 600 MBq (16 mCi) of MDP-Tc99m and administered per us in association with metoclopramide (1 tablet) and 500 ml of mannitol 10%. Abdominal PS in anterior and/or lateral views was performed from the 2nd to 6th hour on day 0 and from the 20th to the 24th hour on day 1. Scans were interpreted in ignorance of clinical data and of systematic colonoscopy performed in two cases 8 and 21 days before PS and in six others 1 to 7 days after PS. Results: Colonoscopy was normal for 3 patients. Ulcerations were noted in 5 patients: rectum and sigmoid (3 cases) or pancolitis (2 cases). Intestinal ulcerations showed uptake foci in the ascending (2/2 cases), transverse (1/2), descending (0/2) and rectosigmoid (2/4) colon. Overall results for rectocolic mucosa gave 4 false-positive (including 3 with normal colonoscopy). The 4 other patients were truepositive; however, compared to colonoscopy results, uptake foci were less extensive in 2 cases and more extensive in the other two. Conclusion: Sensitivity, which was 50% at best for the rectum and sigmoid, seems inadequate to consider clinical application of sucralfate-Tc99m scintigraphy. 

Is alcohol absorbed through the stomach wall? In order to answer this question we compared the GE kinetics of two alcoholic beverages, in addition to the evolution of the blood alcohol level(BAL). Material and method: Six men and six women (mean age 35,8_.9,1 years) after an 8 hrs fast consumed 660 ml of beer of 6,43%(A) or 3,02%(B) alcohol content over a period of 3min. The beer was labelled with Rhenium sulfur colloids. The procedure was repeated one week later. Scintigraphies of the stomach were executed every 10 rain over a 3 hr period with the subject in up-right LAO position. The alcohol content was measured in the expired air every 20 min, and BAL was measured after 60 min. Accessory spleens (AS), accidentally found during abdominal ultrasonography (US) n=25, are sometL~es hardly dlstiguished from tu~ors of the left kidney, adrenal ~land, lymph nodes or colon, despite their characteristic appearance. This work presents cur results of comparative US and planar spleen scintigeaphy (PSS) study of accessory spleens in 16 patients.

PSS was performed with radiocolloid or/and denaturated RBC, supplemented in 6 cases with SPECT. Splenectamy during surgery for associated abdominal tumors was done in 8 of these patients. AS (7-70 mm in size) were found in the lower splenic pole (14 patients), in splenic nilus (7), and in the upper pole (4). In 7 patients large (2 30 m~) ball-shaped lobes ca wide bases were observed and spleen was enlarged in 10 patients. AS and spleens had the same echo-pattern.

PSS proved US findings of AS in 11/16 patients, and SPECT in additional 4, while in a patient with splenectomy and splenerenal shunt, AS was not confirmed. Scintigeaphic imeges shc~ed atypical shapes of AS, splenic enlargement and /or different intensity of activity recorded (appearance of double contours due to partial or complete suporposition of splenic and AS tissue).

Spleneetomy was done in 8 patients with associated abdc~nal tumors (lymphcma in 5, pancreatic tutor in 2 and gastric neoplasm in I ) and US/PSS findings were confirmed on surgery. US as a very sensitive, and PSS and SPECT as more specific, are complementary and reliable methods for AS detection and differential diagnosis of various t~mors adjacent to the spleen.

Lecouffe P. Venel H, Meuriot S, Guillemot F, Triboulet J-P, Cortot A, Marchandise X Services de Medecine Nuci6aire, de Chirurgie G6n6rale et de Gastroent6rologie -CHU de Lille -59037 LILLE Cedex (F)

Stomach may be used for esophageal reconstruction after resection of esophageal cancers. In Akiyama procedure, anastomosis is cervical (residual esophagus, RE < 5 cm) ; in Lewis-Santi procedure, anastomosis is thoracic (RE > 8 em). Our aim was to assess gastric motility in these procedures. METHODS : 8 patients with Akiyama esophaguplasty and 7 patients with Lewis-Santi esophagoplasty were studied at least 2 months after surgery. Manometry of the gastric transplant was performed and its emptying was measured by gamma-camera imaging of a 474 kcal mixed meal, solid phase (egg) being labelled by 99mSTc (18.5 MBq) and liquid phase by mln-DTPA (3.7 MBq). Usual corrections were achieved. 10 healthy volunteers acted as controls. Evaluation of clinical interest of radioimmuuoguided resection needs further data. We describe clinical results obtained in 10 men and 20 women, age 39 -74, studied since April 1987, which were to benefit from a curative or a palliative treatment of colorectal carcinoma. Surgery was undergone 5 days after 125 iodine labelled monoclonal anti-CEA F(ab') 2 injection (500 microCi). We used a hand-held Cadmium telinride probe.

Dukes staging of 20 colon cancers and 10 rectal cancers was as following : A : 2, B : 7, C : 17, D : 3 and villous polyadenomatous lesion : 1. There was no second-look. Serum CEA levels were high in 7 cases (while CA 19-9 was raised in 3 other cases).

Detection was considered as positive when iesion /healthy tissue ratio was larger than 1.5. Over 38 tumoral locations, 32 were correctly identified. 6 false negative results in 5 patients were attributed to technical difficulties in approaching the probe close to the lesion ; other advocated reasons of failure were a second injection of monoclonal murine antibodies, a low Dukes staging, a high thyroidal activity in spite of thyroid Lugol blockade. Over 11 non tumoral lesions, 1 false positive result was registred (ovarian/healthy tissue ratio being 15).

In the conditions of our study, sensitivity was 84 % and specificity was 91%. There was no quantitative relation between antibodies anti-CEA uptake and tumoral staging or circulating serum CEA activity. In clinical practice, there was very little gain in primary surgery. Interest in recurrence management is currently under evaluation. 

Hitherto, increased faecal bile acid excretion and symptomatic improvement following treatment with bile acid binding agents have provided indirect evidence of bile acid malabsorption in patients with postvagotomy diarrhoea. The purpose of this study was to determine whether the SeHCAT test could be used to detect bile acid malabsorption in patients with post-vagotomy diarrhoea. 7 day SeHCAT retention ratios were measured in 5 patients with unequivocal post-vagotomy diarrhoea following truncal vagotomy and a drainage procedure. The results were compared with an age matched group of asymptomatie control patients (n=4) each of whom had previously undergone truncal vagotomy and drainage and a further group of normal volunteers (n=6).

The median SeHCAT retention ratio in patients with post-vagotomy diarrhoea was 2.0 per cent (range 0-9 per cent).

In contrast, the median SeHCAT retention rate in asymptomatic controls was 29.0 per cent (range 26-61 per cent) and 38.0 per cent (range 19-70 per cent) in normal volunteers (P> 0.05, Wilcoxon ).

These results demonstrate, for the first time, that there is significant bile salt malabsorption in patients with post-vagotomy diarrhoea and that SeHCAT scanning is an effective screening test in these patients. dela~ and .9 ,7.ontemporar'r weiqht loss due to a 500 ml intra,.qastric balloon.

Kaposi's sarkoma lesions scintigraphy with Te-99m-nanocolloid is very helpful, especially in the colon. 

Proglumide is a glutaramie acid derivative used for the treatment of gastric and duodenal ulcer in humans. In several mammalian specicies PG blocks the choleeystokinin (CCK) stimulated contractile response of the GB both invitro and invivo as previously reported from animal studies. The aim of this study is to assess the effect of PG on human GB contraction after stimulation by a standard oral milk. A total of 14 healthy male underwent two Tc-99m EHIDA studies one week apart. Each study was for 2 hrs acquisition. In the base-line studies (n=14) milk was given 1 hr after EHIDA injection and i0 min later 10 ml i.v. saline was given. In the second study, PG 400 mg (n=7), and 800 mg (n=7) was given i.v. instead of saline. Several parameters were assessed from the TAC generated over the GB. Lag-time (LT), ejection fraction (EF), ejection period (EP) and ejection rate (ER).

Our results have shown that although the 400 mg PG caused marginal drop in the EF (72.7 + 17.7% Vs 54.3 ! 16%) and ER (2.9 ~ 0.7%/min Vs 2 _ ~ 1.2%/min), yet there was significant delay in the LT. The 800 mg PG produced marginal improvement in EF (61 ~ 16% ~rs 69 Z 13%7, ER (2.9 Z 1.6%/min Vs 3.7 Z l.l%/min) and shorten the LT (5.9 + 4.5 min Vs 3.9 + 2.5 min).

We conclude that with the above pharmacological doses (400 & 800 mg), PG has no inhibitary action on the CCK induced by Qral milk drink. These results contradicts previously published data from animal studies.

Methods and Materials: We carried out 78 9~mTc-HMPAO-mi xed leukocyte scans in 63 patients having suspected inflammatory bowel disease(IBD). The final diagnosis was: 27 Crohn's disease, 9 ulcerative colitis, 2 indeterminated colitis, 8 functional bowel disorders, I acute gastroenteritis, I gastric edenocoroinoma, 1 ccalonic adenocarclnoma, I ischemi c colitis, I postradiation enteritis and I gyardiasis. Reference methods: -A) Activity of disease: Harveys Index (n= 78), C-reactive protein (n= 52), ESR (n= 66), leukocyte count level (n= 73) and Hcto (n= 72). B) Lecalitation: radiology (n= 33), colonoscopy (n= 29) and surgery (n= 5). We performed sequential AP images of thorax and abdomen, and caudal view of pelvis, at 30' and 3 h. Results : The scan sensibility in the detection of active IBD was 91.9 %, the specificity 93.7 % and the positive predictive value 97.6 %. If we evaluate only the 30' views we obtained a 86 % of sensibility and I O0 % of especificity. The scans failed to reveal three fibrotic stenosis in the termlnal Ileum. The FP scan in 3 h. views was a ischemlc colitis. The laboratory tests, Harvey Index and radiology were less sensitive and specific. The colonosoopy results were; $= 80% and E = 100%. In the 28 patients wlth colonoscopy, the gemmagraphic and endoscopic findings were concordant in 23 (84%-), in 4 (14%) the scan showed more diseased segments, and in I the calonoscopy showed more diseased segments. Olf we only evaluated those segments in which it was possible to make an effective colono~copy (n= 49), we can see a correlation in 48 (97.5 %) and no correlation in I (2.5 %). Conclusions: The 99mTc-HMPAO leukocyte scan: I. Is an ecourate technique in the detection of active IBD. 2. Has a good correlation with the colonoscopy In the assessment of bowel involvement. 3. A negative scan, in a clinical context of disease activity, must suggest a flbrotio stenosis. 4. The 30' views are less sensitive but more specific than the 3 h. views. The aim of the study is to compare the accuracy of emission scintiscan (SPECT) with that of computed transmiss{on tomography (CT) in a series of 23 normal patients and 49 patients with documented alcoholic liver disease. Normal patients are a group initially referred to exclude a metastatic involvement of the liver; aH of them had a normal liver biology and no evidence of liver involvement on initial CT scan or a negative clinical and biological follow-up on a 6 month period. Abnormal patients include 23 patients with histologically documented steatosis and 26 patients with cirrhosis proved by fiver biopsy or portal hypertension. SP'ECT diagnosis is based on the value of the pathological score derived from seven independent quantitative parameters: liver and spleen volumes spleen to liver and marrow uptake ratios spleen to hver volume ratio nonhomogeneous liver uptake 1J't to right hepatic lobe ratio. CT diagnosis is based on qualitative estimation of spleen and liver volumes,-heterogeneity, Hounsfield Unit number of the ver, and presence of ascites. Data were reviewed b3{ a radiologist and a nuclear l~hysician unawared of the final dm~nosis. Nonparametric statistical analysis used Mac Nemar's test for paired observations including Yates' correction for continuity, and binomial test for data not satigfying the requirement of ten discordantpairs. Including all criteria, the sensitivity of CT is significantly lower than SPECT m the whole alcoholic group, (SPECT 84%, CT 63%, p<.025) and in the cirrhosis subgroup (SPECT 92%. CT 69%, 0<.05). A similar difference concerns the steatosis subgroup ISPECT 74%, CT 57%) but results do not reach the significance level, owing to the little number of patients included. With a true negative ratio of 23/23, both techniques yield a specificity of 100% We conclude that SPECT liver scintiscan is a clearly more sensitive technique than CT in patients with diffuse alcoholic liver disease. 

Twenty patients with lower extremity ulceration or cellulitis and suspected osteomyelitis were studied. Iti In and 99mTc-HmPAO-leukocyte scintigraphy (LS) as well as 99mTc-HDP bone scan (Bs) were performed within the I st week of investigation. In all cases I11 In and 99mTc-HmPAO LS showed concordant results (14 positive and 6 negative). In 10 patients the diagnosis of osteomyelitis was scinti graphically excluded because of either negative BS and L5 or negative LS and positive Be (suggesting non-infected osteopathy like Charcot foot),or positive LS and negative es (suggesting soft tissue infection).These patients received local treatment +/-short-term antlbiotherapy and showed rapid clinical improvement. The 10 patients with positive L5 and BS were treated as osteomyelitis and had control 99mTc HmPAO L5 2 months later. LS interpretation turns out to be uneasy when local discharge is present because the resolution of the scan not always permits clear distinction between osseous and extra-osseous localization of the leukocytes. A portable detector equipped with a home-built focused collimator (3cm focal depth) is now under evaluation to overcome this problem. The aim of our study was to apply the principle of compartmental analysis to study the insulin kinetics using 1231-insulin. We studied 6 normal subjects, 6 Type 1 and 6 Type 2 diabetic patients. After i.v. administration of 37 MBq of 1231-[A14]-insulin (Medgenix), gamma camera images were acquired for 40 min at frame rate of 1 image/15 sec. Regions of interest (ROI) were defined over the heart and liver and time-activity curves (TAC) were generated. Heart TAC was then subtracled from liver TAC after normalization of curves. The resulting curve was fitted with a biesponential function. The constants kl and k2 and related T1/2 were calculated. Blood samples were also taken at 2, 3, 4, 5, 6, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 30, 35 and 40 min. after injection of tracer and plasma was precipitated with 20% perchloric acid (PCA) and radioactivity counted in pellet and supernatant. Plasma insulin disappearance curve was fitted with a bi-esponential curve and related parameters were calculated. A preliminary report has suggested that the isonitrile technetium-99m sestamibi could be used as an alternative to thallium-201 in preoperative localisation of parathyroid glands. To compare these agents we have investigated 42 patients with suspected hyperparathyroidism, to date 22 have undergone surgical exploration.

The thyroid was localised using 1-123. Dynamic acquisition was obtained for 20 minutes following i.v. administration of TI-201 and for a further 20 minutes for Tc-99m sestamibi.

After allowing for scatter, conventional subtraction procedures were performed. Of the 22 patients who had surgery, 14 had adenomas (13 positive with Tc-99m sestamibi, II positive with TI-201, I missed on both scans) 6 patients had hyperplastic glands (16 positive glands identified with sestamibi, 12 with TI-201) and 2 patients with metastatic parathyroid carcinoma had abnormal uptake with both agents.

The quality of the Tc-99m sestamibi images were generally superior to those using TI-201. The Tc-99m agent is at least as sensitive as thallium in localising abnormal parathyroid glands and gives a lower radiation dose. However it is more expensive than thallium and this may limit its routine adoption for parathyroid imaging. Of 26 patients treated by rsdioiodine 1-12 years ego, TRAb levels normalized in 21 (18 euthyroid, 3 hypothyroid), end remained elevated in 5 (~ hyperthyroid, 1 hypothyroid) during 1-2 years sfter treatment.

Of 22 surgicely trested patients TRAb serum levels normalized in 17 (16 euthyroid, 1 hypothyroid) and remained elevated in 5 (ell euthyroid) for 12-24 months.

These findings support observations on TRAb significsnce in psthogenesis end evolution of Graves" disease. POST-SURGICAL FOLLOW-UP OF PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA: IMPORTANCE OF 131-1 WHOLE BODY SCAN. Serum thyroglobulin (Tg) levels are often measured in the postsurgical follow-up of patients with differentiated thyroid carcinoma either alone or together with other parameters such as the uptake of 131-iodine by whole body scan (WBS). The aim of our study was to measure Tg levels in 61 patients receiving L-Thyroxine therapy after thyroidectomy for differentiated thyroid carcinoma and after suspension of therapy, before performing a WBS. The sensitivity, specificity and accuracy of Tg levels, during L-thyroxine therapy, for diagnosis of tumor residue or metastases were then calculated and compared with results obtained by diagnostic WBS. According to our data it was not possible to discriminate between patients with or without metastases based only on Tg levels either during or after suppressive therapy. Nineteen patients (31%) had normal levels of Tg during Lthyroxine therapy and 9 of them had metastases or local recurrences as evaluated by performing a WBS. Of particular interest, 2 of them, had a negative diagnostic WBS but were treated with 1311 therapy on the basis of clinical considerations and showed the presence of metastases in the lung after a second WBS performed after 1311 therapy. The sensitivity, specificity and accuracy of Tg levels determination were 83.3%, 58.1% and 70.5% respectively, whereas for the diagnostic WBS were 76.6%, 100% and 82.0% respectively. If results of WBS and Tg were taken into consideration, sensitivity reached 95.7%, specificity 100% and accuracy 96.7%. We conclude that in the management and follow-up of patients with differentiated thyroid carcinoma periodic 131-1 WBS are essentials since Tg measurement alone does not allow the identification of a significant percentage of patients with metastases. WBS can be integrated by measurement of Tg after suspention of suppressive therapy. Sequencing and cloning human thyreglobulin gene /Tg/ localized on chromosome 8 allows to study its structural changes. The aim of study was to analyze individual DNA sequence variation detected as restriction fragment length polymorphism /RFLP/ at the Tg gene in patients with congenital hypothyroidism. DNA samples were isolated from white blood cells of 20 con genital myxoedema patients and 30 controls. Samples of 10 ug DNA were digested with various restriction endonucleases /Pvu II, Msp I, Hind III, Taq I, BamH., Eco RV/. After electrophoresis and blottinglonto nitrocellulose filter the blots were hybridized. As hybridization probes were used four Psi I human Tg cDNA fragments of the length of 4.05kb pairs cloned in pBR 322. Probes were labelled with /alfa 32-~/ dAT~ /A~ersham/ with specific setivity of 0.5-2.0xi0 dpm/ug. RFI~ were observed for the following enzymes: Taq I, Pvu II, Msp I, Hind III. The respective allele frequencies were approximately: 4%, 8%, 26%, 12%. The use of Tg probes labelled by 32-P-dATP could be of help in the studies of pathogenesis and in prenatal diagnostic of hereditary defects in the synthesis or structure of thyroglobulin. The validity of the SimulTRAC FT4 (Co-57)/"sensitive"TSH IRMA MAb (I-125) kit (Becton Dickinson) kit, as regards cost effective thyroid functional profiling, was evaluated in a group of untreated patients (pts) (176 overt or subclinical hypothyroids, 285 overt or compensated hyperthyroids) in comparison with 401 euthyroid controls. Sensitivity (SE) and precision of the simultaneous methods were appropriate for clinical use (SE:0.11 pg/mL and 0.06 pJU/mL for FT4 and TSH respectiveIy;working range:l.8-100 pg/mL and 0.48-105 IzIU/mL for FT4 and TSH respectively).When FT4 and TSH data were evaluated according to the ROC analysis, the best discrimination between pathological and normal conditions was obtained at values of 7-17 pg/mL and 0.3-3.35 IU/mL for FT4 and TSH, respectively.As expected, TSH test, as regards SE, predictive value (+), diagnostic accuracy, proved to be definitely superior in recognizing all the considered pathological conditions. However, FT4frSH test provided a more accurate evaluation of the actual clinical status of subclinical hypothyroidism and of both overt and compensated hyperthyroidism. In the last group, 79.4% of cases with undetectable TSH serum concentration, showed normal FT4 value in agreement with the ascertained normal metabolic status. These results demonstrate the usefulness of this method as a screening procedure in an unselected population; moreover, FT4frSH simultaneous assay, when associated with FT3 assay, provide a definitive functional assessment of both treated and untreated thyroid disorders. 

In the differential diagnosis of euthyroid patients (pat) with goiter the spontaneous 99m-Tc thyroid uptake (TcTUo) alone often does not succeed in identifying pat with autonomy. The aim of the study was to evaluate the usefulness of the TcTU after exogeneous TSH suppression (TcTUs). Because of the scintigraphic and sonographic findings 104 euthyroid pat with goiter were suspected to have uni-or multifocal autonomy. Therefore an additional scintiscan with quantification (TcTUs) was performed after exogeneous TSH suppression. In 15 pat with subnormal TSH before suppression the TcTUs revealed no difference to the TcTUo. In the 89 pat with normal TSH a significant decrease of TcTUo and dTcTU (TeTUo-TcTUs) with increasing iodine excretion was observed, whereas no correlation was found between TcTUs and iodine excretion. A low TcTUo of !2.0% resulted in an TcTUs!l.l% in all 22 cases. These low TcTUs values exclude relevant mass of functional autonomous tissue. In the second scintiscan only 17 of the 89 pat (19%) had TcTUs values ,1.5%. Conclusions: l) In euthyroid pat with goiter and subnormal TSH a second scintiscan is not useful, because additional TSH suppression does not result in any change of TcTU. 2) In euthyroid goitreous pat with normal TSH and TcTUo!2.0% a scintiscan after TSH suppression is not necessary, because there is no relevant mass of functional autonomous tissue. 3) In all other cases only the TcTUs is relevant for identification of thyroid autonomy. 4) Autonomy with higher risk of hyperthyroidism after iodine contamination (TcTUs>l.5%) was suspected in only 19% of the goitreous pat with normal TSH. Three hundred and sixteen patients with solitary or dominant thyroid nodules and 20 controls were imaged both with 99mTc pertechnetate and 123I. Images were read indepen]dently by 5 experienced readers qualified in nuclear medicine image analysis. In the first trial each reader read one batch (201 films) in the first reading. In the second reading, the readers changed batches so that each film was seen by 2 different readers constituting one pair. Five batches were read by five different pairs of readers. The study w-as organized to follow a balanced incc~lete block design allcmring the 5 readers to read only 40% of the films to cc~lete the study.

A high percentage of disagreement (in more than 1/3 of cases) between two readers for all five pairs of readers w-as found. In a category of impression (normal, nmltinodular goiter, cold nodule, not nodule, diffuse goiter) sc~e readers found 2 to 3 times rsgre cases belonging to one category than their conterpart in the same batch.

The second trial consisted of direct (simultaneous) cc~ parison of 9~Tc and 123I scans of each patient. There was agreement about the type of discrepancy between two readers who saw the same cases in only 1/5 of these instances. In as many as 2/3 of the discrepant cases there was disagreement about the very existance of a discrepancy. Only 2 pairs of readers had statistically significant agreement in preference for one radionuclide while 3 did not. There seemed a greated variation among the observers than between the radionuclides.

The study showed a striking high disagreement among the readers. There is a general belief that thyroid malignancy in hyperthyroidism with thyroid autonomy is exceptionally rare. To appraise the risk of overlooking the malignancy in our patients designed for radioiodine therapy,we performed ultrasound guided (US) fine needle biopsy (FNB)of the hot and, in multinodular goiters in cold noduses as well, in log pts with hyperthyroidism caused by thyroid autonomy. The age span of pts was 30-90 years.8 were male. The average TSH value in pts was 0.i mU/l, TT4 165 55,TT3 3.58 J 1.02. 44 pts had a solitary hot nodule,26 pts had 2 hot noduses, 32 pts had 3 or more hot spots on 99m-To and iSi-J scintigrams. 132 noduses were punctured. In four pts cytological atypism was found. In one of three pts H~rthle cell tumor, in two follieularcell carcinoma was confirmed. It was not possihle to verify the suspected diagnosis of H~rthle cell adenoma in the fourth pt. One pt with uninodular goiter had follicular carcinoma. Three pts with detected atypism had multinodular goiters. Scintigraphicaly the follicular carcinomas were hot. The pts with HHrthle cell tumors had several hot spots shown by the scans, wherefore it was impossible to decide if the tumor tissue accumulated the tracer. Conclusions:In 2.9% of our hyperthyrotic pts with uninodular or multinodular thyroid autonomy thyroid malignancy was detected. We consider this incidence high enough to warrant US guided FNB in every pt with thyroid autonomy before definitive treatment with radioiodine. ]he diagnostic value of 99m Tc (V) dimercaptosueninlc acid (I~A) was investigated in 14 patients (4 females and i0 nmles),sged ii~7, with proved medullary thyroid carcinoma. 5 were ~N IIA and 9 sporadic MIC. They had all been previously treated with total thyroJdentomy and presented persistently elevated CT levels (12 sqhjsets beaally and 2 after stin~lus). Planar scan with 444 MBq of 99mTc~NCGA was made 180 minutes after tracer administration. In the first exa~fimation, seintigraphic inmgiags obtained with (V)I~A gave 9 negative responses out of 14. In a second study performed 8 to 18 months later, 3 patients out of 9, who had previously been negative, became positive at (V)I~A, probably in relation to the increasing size of the mass. If we consider only those patients who presented already proven recurrent disease (8 subjects), 6 were {~{SA positive: in this case (V)O~BA sensitivity was 75%. Such sensitivity is much lower (50%) when considering all the 14 subjects with high CT levels. Taking only those subjects with high CT levels and negative ins~tal investigations, (V)I~A sensitivity is about 17%. Recently, using SPgCT we found with (V)~V~A 2 positive cases which were doubtful at planar scan. Frcm our data it cornea out how the planar (V)I~BA aniatigraphy is able to identify with good sessiti~ity metastases that were ulresdy identified with other investigations. But the sensitivity is much lower when recurreneas are unknown, as we already reported at the 7bird International Workshop on MeaII in Heidelberg (Sept. 89). Probably better results can be obtained by 

Out of 272 pts with thyroid nodules operated on from 1987 to 1989, we studied 126 pts (27M, 99F; age range 16-73 years) with solitary nodules (SN): all pts underwent neck palpation, ultrasound study and routine thyroid function tests; 80 pts were submitted to Tc99m-pertechnetate thyroid scan (IS)(55 cold nodules, 25 hot nodules) and 79 pts underwent FNA as well. 36 oul of 126 pts (28,6%) showed neoplasm on himtologic specimen. Trying to assess the usefulness of various diagnostic procedures for selecting pts for surgery, we divided pts into four groups: G i) 40 pts with positive or suspicious findings for malignancy on FNA (28 pts were malignant on hystology). G 2) 55 pts with cold nodules (26 pts had positive findings for neoplasm on histology). G 3) 31 pts selected for surgery on the basis of other diagnostic procedures (5 pts showed neoplasm on histologic examination). G 4) 31 pts with positive or suspicious FNA and cold nodules (23 pts were histologically malignant). Our data emphasize that malignant or suspicious FNA seems to be the most reliable diagnostic procedure (70%)(G.I); IS (cold nodules) is reliable in 47.3% of cases (G.2); other diagnostic methods than IS and FNA are valuable in 16.1% of cases (G.3). At last, if we evaluate G.4 pts (submitted to both TS and FNA), diagnostic accuracy increases to 74.2%. Therefore our experience suggests that in the preoperative assessment of SN pts, criteria with exclude TS and/or FNA are less accurate in selecting pts for surgery than IS alone, and FNA provides adequate procedure for surgery in 70% of cases, but when TS is employed in addition to the preoperative assessment of SN, overall perc6niaQe of correct diaqnoses increases to 74.2%. IN~TCED BY A~IIODARO~N The thyroid dysfunctions,especially the hyperthyroidism observing during the long term therapy with Amiodsrone(A) can occur also a life-threatening advers reaction in cardiac patients. Since A inhibits the peripheral co~version of thyroxin(Ta) to triiodthyromin(T3),the measurement of the serum-levels of T4 and T3 don't reflects correctly the real thyroid condition.In most cases the basel TSH-level reflects correctly the exact thyroid state,however in subclinical conditions the THH-TSH-teet is more suitable for investigation of patients treated with ~. in 60 patients on long term therapy with A total T4, total T3, free T4, free T3, reverse T3, basal TSH measurements and TRH-TSH-test was performe~. In 38 patients(63%) the T4-1evels increased above the upper limit.In 42 patients(7@~) the T3-1evsls decreased below the normal range. The TSH-respomse to TRH was overshooting in lo patients(16%),partially suppressed in 5 pstiemts(8%),totslly suppressed in 4 patients (7%). Among the patients with totally suppressed TRH-TSH-test 3 were clinically hyperthyroids, while i patient remained euthyroid. Among the patients with pmrtially suppressed T~H-TSH-test 2 was euthyroid,2hsd features of subclinlcel hyperthyreodism, I of cZinical one.

The autors call attention to the fact, that in c~se of totally suppressed TRE-TSH-test the withdrawal of A is nece~eary. The patients with partially suppressed TRH-TSH-test require s closer fellow-up. In case of moderate increase of basel TSH and/or overshooting TI~H-TSH-test the withdrawal of the drug is not necessary, however follow-up is very important.

J.F~ldes 7 g.Tarj~n, Ce.B~nos, J.N~meth and P.Lakatos First Oepartmant of Medicine, Semmelweis University i083 Budapest, Hunoary.

Aim of the study was to detect thyroid hormone effect at peripheral tissue level in patients with functional thyroid adenoma with special regard to preclinieal hyperthyroidism.

Serum procollagen III (PIII)~ osteocalcin (00), sex-hormone binding globulin (SHBG) and plasma fibronectin (pFn) were determined. Patients with hot thyroid nodules were classified into 3 subgroups: i. nontoxic nod. goiter (n=15): Clin. euthyr., se. FT-3, FT-4 and TSH measured by a sensitive method within the normal range; 2. preclinical hyperthyroidism (n=2r Clin.euthyr., suppressed TSH despite nor-me1 FT-3, FT-4; 3. toxic nod. goiter (n=32) were significantly elevated.--All these parameters were normal in nontox.nod, goiter. Conversely, in some subjects with preclin, hyperthyr, elevated assay results were obtained which correlated negatively with se, TSH and in this respect PIII (0.91 + O.18), pFn (553.38 ~ 145.0) and OC (9.7~ 1.5) prove~to be more sensitive than SHBG (47.4 + 16.2). It is suggested that elevated PIII, pFn or-OC with simultaneously suppressed TSH may reflect excessive effect of thyroid hormones at peripheral tissue level in some patients with preclinicsl hyperthyroidism which may be detrimental in the long-term. The detection by gamma camera imaging of pathological lymphocytic infiltrations may have relevance for the diagnosis of inflammatory lesions, lymphoproliferative disorders and autoimmune diseases. Attempts using radiolabelled autologous lymphocytes or using radiolabelled, lymphocyte specific, monoclonal antibodies have practical and/or clinical disadvantages. Interleukin-2 (IL2) is a lymphocyte growth factor that binds only to activated lymphocytes and monocytes. We have labelled IL2 with 123Iodine. The Lactoperoxidase/Glucose oxidase technique was the labelling method of choice leading to immunoreactive IL2 with high specific activity (150-200 I~Ci/p.g). Labelled IL2 (50-100 p.Ci) was injected i.v. in 28 Non Obese Diabetic (NOD) mice. These mice spontaneously develop an autoimmune diabetes similar to human Type 1 diabetes characterized by lymphocytic infiltration of the endocrine pancreas. Eight NOD mice were injected with 1231-Lactalbumin a protein of the same molecular weight of IL2. Twenty NOD mice were sacrificed at different times for single organ studies and autoradiography; 8 were used for gamma camera images. Results showed that pancreas radioactivity was significantly higher in mice injected with IL2 as compared to those injected with Lactalbumin (3.87_+0.04 vs 0.75_+0.15, % of injected dose per gram of tissue 5 min after the injection, p<0.0001, and 2.57+0.15 vs 1.05+_0.22, 20 rain after the injection, p<0.003). Gamma camera images also showed uptake in the generated region of the pancreas. There was a positive correlation between counts in this region and the extent of infiltration histologically evaluated (CC=0.908; P<0.03). Autoradiography of pancreas sections confirmed the localization of radioactivity on lymphocytes infiltrating the islets. In conclusion, 1231-labelled IL2 retains its capacity to bind in vitro and in vivo to activated lymphocytes and this technique can be applied to humans for the in vivo detection o! patholngical Ly m p h ecyti~ jnf~tr a~Jons. 

We previously demonstrated in a preclinical model the feasibility of a 2 step strategy utilizing biotinylated monoclonal antibodies and radioactive streptavidin. Two mg of biotinylated Mabs MOV18, followed 3-5 days later by 100-150 p.g of In-111 streptavidin (specific activity 280 MBq/mg) in 500 ml of normal saline were injected i.p. in 8 patients with ovarian carcinomas. Of these, 5 had documented lesions and 3 had no evidence of disease (NED). No toxicity was observed. One patients developed a human anti-streptavidin immune response. Planar and SPECT imaging was performed for up to 48 hours post radioactivity injection. Four out of five patients with documented lesions had positive scans; out of three patients with no evidence of disease, two had negative scans and one had a hot spot in the pelvis. All patients underwent surgery after scanning (3-7 days later). One patient with primary cancer was a true negative (no antigen expression at immunohystochemistry). Two NED patients were true negative and one was a false positive (granuloma). Resected tumor and normal tissue were counted for dosimetry calculation. Tumor to normal tissue ratio was 20:1 (range 12:1 -28:1). Injected dose (i.d.) per gram of tumor was 0.2+0.1%. Over 24 hours 17% of the i.d. was found in the urine, 8% in the blood, 60% was still in the peritoneal cavity. These preliminary clinical data suggest that this 2 step strategy may be superior to the conventional approach (radiolabelled antibodies) for tumor localization and therapy. 

The major drawback of the intraoperative tumor detection with radiolabelled monoclonal antibody by means of a probe is the long time interval needed between injection of MoAb and surgery (at least 20 days). We describe a new method which entails injection of 1-125 labelled biotinylated monoclonal antibodies and cold avidin in order to obtain a rapid blood clearance of the radiotracer. One-three mg of cold avidin were injected i.v. in 10 patients bearing colorectal cancer three to five days after the injection of 1 mg of specific biotinylated anti-CEA (FO23C5) Mab, 1-125 labelled. No toxic effects were observed. Blood samples and external probe counts were taken, daily after the MoAb injection and 1, 5, 10, 30, 60, 120 and 180 minutes after the avidin injection. Blood clearance was determined. A single injection of avidin reduced the circulating activity by 37% in 10 minutes and by 42% in 180 minutes. These values were achieved in 6-8 days with the traditional method. Thus repeated injections of avidin allowed the surgeon to operate the patient with minimal blood-pool activity within 5-7 days instead of 20-25 days. 

Radioimmunodetectian af colo-rectal cancer wlth the ~023C5 anti-CEA monoclonal antibody (gabz and Fab fragments) labelled with 1311 and lllln has been widely employea in a large number of patients. A preliminary evaluation in 51 patients and an extensive multicenter study in cooperation with other Nuclear Medi cine Centers (2'/7 patients) were performed ta assess the efficacy of the method. The results obtained in detection of colorectal carcinomas were: sensitivity 77.5% accuracy 80%. Predictive value of positive results $8.9% A praspectlve trial in 50 patlents wlth suspected local relapses was performed with 1311-F(ab' ]2 fragments ta evaluate the clinical utility af RIS: a comparison with other diagnostic methods such as CT, US, MRI was made. Sensitivity (90%) and accuracy [90%) were comparable to those obtained with NMR (93%, 85%) whereas less favourable values were obtained with CT (69%, 67%) and with US (36%, 31%). An extention of this study using whole IgG and F[ab' )2 fragments af the same antibody labelled with 99mTc is in progress. The foreseeable advantage due to the use of tl]is radionucllde, as obtained in our previous studies on RIS of melanoma, includes the more favou rable measuring conditions, allowing also the routinary use of SPECT, end the reduction of the radiation burden to the patient. The preliminary data obtained seem to canfirm the expected results.

L6hde, E., Barzen, G.*, Schlicker, H., Abri, O., Kraas, E. l.Chirurgische Ahtl.,Krhs.Moabit, Turmstr. 21, Berlin *Nuklearmedizin Abd., Univ.Klinikum Charlottenburg, Berlin

Mmnoclonal antibodies (MAB) gain increasing importance for diagnosis,therapy and follow up control of gastro-intestinal carcinomas.For investigating the accumulation kinetic and distribution of different MAB's an ex vfvo perfusion system was established. Methods: After resection of the tumor hearing colon segment the main arteria was canulated and its vascular network angiographically controled.

The gut was interposed into an oxygenized circulation using erythrocyteenriched human serum albumin. Metabolic parameters, pH, pressure etc. were controlled.

Radioactive labeled MAB CIP83antiCEA(Kalthoff,H.et al.)and the AUAl(Epenetos,A. et al.)were applicated into the circulation. Its distribution were continuously analysed by scintigraphy. Activity-profiles were done and the accumulation of the MAB were measured in different tissues as counts/g.

Immunochemnisty proved all tumors highly positive for the used MAB(n=30).However,a different binding pattern turned out after intra-vascular MAB-application. The MAB CIP83 showed a high and rapid binding to highly differentiated carcinomas (tumor/non-tumor ratio: 4.7:1) but no enrichment in poorly differentiated carcinomas. The MAB AUAI reached the tumor/nan-tumor ratio 5 In 16 patients selected for a cytestetic perfusion therapy of the extremities due to a malignant melanoma we have performed an immunoscintigraphy with the Mab bw 575/931. All patients suffered from a malignant melanoma of one extremity only with local metastasis. Further metastasis were excluded by CT,NMR,X-ray or ultrasound investigations.

The Mab BW 575/931 used for this study is a murine immuno-globulin of the isotype IgG l.The Mab was produced as a double-component kit by the radiochemieal labaratories of the Farbwerke Hoechst.

For the investigation 185 555 MBq of the TC-99m labelled Mab were injected to the patient. Later on scintigraphies of the whole body in ventral and dorsal view were done with e dual-heed-gamma-camera (Rota II from Siemens)immediately after injection,4-6 and 20-24 hours later.

Till now 16 patients were investigated. From them 7 showed a positive and 9 a negative result. From the negative results two were false negative. The evaluation of the studies gives a sensivity of 78% and a specifity of 10O%.Mest of the true positive findings were histologically melanomas of the nodular type.The two false negative ones were a amelanotic and an ecrolentigeinous melanoma. Beside the lecalisation of the tumor we could detect in one Patient two other metastasis in the lung and in the leg unknown at the time of the immunoscintigrephy . The results ere promising that the Mab BW 575/931 could be a helpful diagnostic tool in the diagnosis of malignant melenoms. Lower immunogenicity of chF~b is expected to be an advantage in repeated immunoscintigraphy (IS). This study compared biokinetic data obtained after simultaneous injection of chMAb (human IgG4) and murine (m) anti-CEA Y~b 25/B7 (IgGl) from which the chMAb was derived, by paired labeling (I-125/I-131). 19 patients (P), 14 M 5 F, were studied. Detectability of tumor lesions with cb/MAb, labeled with 1-123, was evaluated in 17 P: 6 primary (ITu), 5 recurrent (RC) colorectal carcinomas, 1 suspected sigmoid carcinoma, metastases (M) of liver (6) and lung (2) and 1 ovarian cancer. 4/4 ITu, 4/5 RC, 6/6 liver and 2/2 lung M were shown on IS (planar & ECT) performed at 6 and 24 hrs. There was 1 true negative and 1 false positive (FP) ITu, IFP RC and 2 FP liver M. 4 sites (3RC, I liver M) were previously unknown. Mean tumor uptake (% of injected dose per gram), measured 24-48 hrs after injection, was comparable: 0.011 for chY~b versus 0.Ol0 for ~b.

Whole body TI/2 of c~MAb was 62.2 + 21.3 (x + ISD). Plasma disappearance (mean TI/2) was measured simultaneously in the same patients for c~4Ab and mMAb and showed no significant difference: 35.3 versus 33.8 hrs.

Binding on CEA/Sepharose of both M~b was measured after labeling and in the sera of patients after 1 (n=9) and 24 hrs (n=3). Mean binding (range) for chY~b and m~b was 69% (51-83) and 71% (49-80) after labeling. In the sera, it was 48% (21-85) and 48% (25-75), after I and 40% (15-67) and 45% (16-77) after 24 hrs for chMAb and mMAb respectively. This data show that chM~ may replace m/~b in IS. Repeat studies are necessary to further establish this point. 

The MAb DD 3B6/22 which recognises the D-dimer (DD) epitope of human cross-linked fibrin is currently being evaluated as a radioimmunoacintigraphic agent for detecting vascular thrombi. The MAb binds well in vitro to blood clots from human and baboon but not to rabbit clots. A rabbit model was established by seeding jugular vein clots with human DD conjugated Sepharose beads. The pharmacokinetic profiles of Tc-99m labelled Feb' fragments of the MAb were determined in rabbits and baboons.

The whole body clearance rates of the MAb conjugate were in the range i. 35-1.85 rml/min/kg. Assuming a two compartment model, the rapid phase contributed 56.5% to the plasma clearance in rabbits and 47.5% in baboons. Biodistribution studies in rabbits showed localisation of MAb conjugate only in the thrombi, kidneys and bladder which form the normal route of excretion. This pattern was confirmed in baboons where the kidneys were also the critical organ accumulating 19% of the injected dose-at-peak.

35-40% of the injected dose was recovered in urine at 3 hrs p.i.

No effect on binding of MAb conjugate to DD-Sepharoae or human pre-formed clots were demonstrated in vitro with heparin or venographic contrast media at clinically relevant concentrations. Localisation studies in the rabbit model indicated a level of 16 ~g/ml free circulating DD antigen was needed before the quality of the clot images" was adversely affected.

The TC-99m-DD-3B6/22 Feb' MAb conjugate appears to have properties suited for the rapid scintigraphic detection of vascular thrombi in humans. 

The purpose of this study is to compare the results of three FT4 assays in sick patients whith nonthyroidal illnesses (NTI) which can alter the concentration of FT4 measured by an analog method. Patients and methods : Sere are obtained from 54 euthyroid controls and 82 patients with NTI (18 renal fai-lures~ ii infectious diseases~ 21 medical intensive cares, 16 myelomes and 16 carcinomas). The methods are two one-step assays (Amerlex-M radiolabeled analog method and Amerlex-MAB method based upon a competition for a labeled antibody, both from AMERSHAM) and one two-stage method (RIA-gnost From BEHRING which uses coated tubes and 1251-T4 derivative as tracer). Results : Decreased mean FT4 values are found in patients with sepsis syndrome (P<5%) or in medical intensive care (p<O~O01) only with Amerlex-M. FT4 concentration measured by one-step assays are more affected by renal failure (p<O,O01) than those estimated with two-step RIA-gnost (P<5%)-Among patients with myelome, only results of Amerlex-M and RIA-ghost are lower than normal (P<5%). On the other hand, if the mean FT4 value of. each method appears higher than normal in the group of carcinoma, the difference is statistically significant only for Amerlex-MAB (P<5%). Conclusion : These Findings confirm that in the overall patients without neoplasic illness, FT4 measured with the Amerlex-M kit should be considered with caution, in these patients, especially in those with renal insufficiency, the RIA-gnost kit appears to be the most effective. On the other hand, among patients with myelome or carcinoma, the results of the Amerlex-FiAB and RIAghost kits appear not to be better than the estimations of the Amerlex-M kit. Although a close relationship has been reported in some papers beetween Human-alpha-Atrialnatri'uretic peptide(H-~ANP) values and the functional status of thyroid,generally there is a discordance about the existence of this relationship.

In order to enlighten this subject H-~ ANP p!asnm levels ~ere measured in I0 hypothyroid and i0 hyperthyroid cases before and after treatment.In I0 healthy subjects,H-~ANP values were also measured as control.

Before treatment, there was a significant difference (P<0.O05) between H-~ANP values in hypothyroid patients (41.99774.58 pg/ml) and in controls(102.117~0.05 i pg/ml) but not between in hyperthyroid patients(102.297 ~12.717 pg/ml)and in controls.Not only between before and after treatment values(Hypothyroid:65~9.36pg/ml~ Hyperthyroid:64.43756.08 pg/ml) of beth groups,but also control and after treatment values were significantly different (P(0.0Ob).While there was a significant difference (P<0.005) between H-~ANP values of both hypothyroid and hyperthyroid groups before treatment, after treatment this disappeared(P)0.10). This significant difference between before and after treatment values of H-~ ANP in hypothyroid and hyperthyroid patients has shown that there is a relationship between the levels of the thyroid hormones and 1{-ANP.It is also concluded that some of complications seen in the thyroid dysfunction might be related to changes of H-~ANP concentration in plasma. The circulating parathyroid hormone (PTH) is a mixture of native hormone and degradation fragments; change in renal clearance induces an increase of the fragments that reflects immunological but not biological activity; we compared in patients on dialysis the results obtained with 3 different radioimmunoassays at the beginning and at the end of the dialysis. Two groups of patients were studied: the first one included ii patients dialysed with a polysulfene membrane, and the second one i0 patients dialysed with a cuprophane membrane; radioimmunoassays kits recognize either the intact PTH (PTHi BAXTER), the C terminal fragments (PTHc ORIS) or the median fragments (PTBm BAXTER). At the beginning of the dialysis, whatever membrane is used, PTHc and PTHm levels were always increased; PTHi levels distinguished from the others because 8 values in 20 were within the normal range; at the end of the dialysis, every value of PTH decreased when polysulfone membrane was used; in the opposite the PTHi alone decreased when using cuprophane membrane; this particular behavior of PTHi cannot be explained by a crossing through the membrane because its molecular weight is too high; that may be explained by regulation mechanismes or adsorption phenomena; experimental data with radiolabelled PTH agree with the second hypothesis. Our study shows the singularity of PTHi assay. It proves the necessity in dialysed patients to take into account the time of blood collection during the dialysis, the nature of the membrane used and the type of parathyroid hormone measured. 

We report here a study on concentration of FT4 measured simultaneously by four radioimmuno-assays among euthyro[d patients through pharmacological situations. Patients and methods : Each test is evaluated in 5q controls, 36 patients on psychotropic treatment, 20 on amiodarone and 5 on oral contraceptive. FT4 concentration is measured by two one-step assays : Amerlex-M which is a radiolabeled analog method and Amerlex-MAB, based upon the competition for a labeled antibody (both from AMERSHAM) and two two-step immunoextraetion assays : GammaCoat FT4 from BAXTER and RIA-gnost FT4 from BEHRING which use an 1251-T4 derivative as tracer. Results : The results confirm the finding of significantly decreased values of FT4 among patients of psychotropic treatment (p<0.001, except for the RIA-gnost kit p < O.01) FT4 concentrations are more altered by diphenylhydanto[n or coneomlttant administration of these drugs than by lithium, carbamazepine or Phenobarbital treatment. Among patients on amiodarone, only two-stage assays give normal values in at least 95% of the cases, and FT4 concentrations determined with the use of the one-step assays are significantly higher than normal (p<O.001). In women on oral contraceptive, the mean of FT4 levels assay is lower than normal for each assay (P<5% for Amerlex-MAB and p<2% for Gammacoat). Conclusion : These findings suggest that the RIA-gnost kit is the most effective assay through these pharmacological situations. 

Type III collagen is a major component of most dense and loose connective tissues, derived from a procollagen, wich has propertide extensions at both ends of the molecule. Type Ill procollagen is suggested to be a new important index expres-.sing the pathophysiological dynamics in conditions of breakdowq and growth of connective tissue. In an attempt to assess the diagnostic effectiveness of type III procollagen (PIIINP)~ we measured its serum values by RIA in 69 subjects, classified as follow: 13 normal volontiers (control group),37 patients with hyperthyroidism and 19 patients ,with thyroditis Hashimoto. Results: In the control group PIIINP serum were found to be between 1.4 to 4.6pg/I while in the patients between 5.2 to 8,1 ~Jg/I. The serum levels were statistically higher in the hy L perthyroidics (p<0.01) compared with the Hashimoto's cases. Sensitivity and specificity have been studied, according to the site and the extent of the disease. PI]INP specificity washighef in the hyperthyroidism (87%), compared with thyroiditis (71%), while sensitivity appeared to be almost equal in both under study diseased groups (69% in hyperthyroidism, 67% in thyroiditi~, Conclusion:Determination of PHINP is an easy to perform assay. it shows to be an of high sensitivity index while it promises to be developed as an excellent criterion for the follow up in the thyroid disturbances. Testosterone is present in human serum in Free (unbound) solutlon end bound to transport protelne as albumin and sex hormone binding globulin. The free fraction is eoneidered as the main biologically active androgen. Recent studies suggest that the free testosterone (FT) may be s better discriminatory index between hlrsute and non hirsute women than total testosterone (TT). Therfore, the aim of this study is to determine the contribution of the FT in the evaluation of hirsutism. Serum samples from 76 hirsute momen (study group) and 21 normal women (control group) were analyzed for TT, DHEAS, FSH, LH, and FT using RIA kits from DPC/Behring. According to the clinical features and biological results the study group was divided into ) groups : -group I, n=16 (21~) : ovarian hirsuhism when LH/FSH ratio greater than 2 at the day 5 of the menstrual cycle (polycystic ovary syndrome, PCOS); -group II, n:8 (11~) : mixed hirsutism when DHEAS is also increased (adrenal congenital hyperplasia); -group Ill, n=52 (68%) : idiopathic hirsutism when ovulatory menstrual cycles are associated to normal or lightly increased androgen levels and to familial hirsutism. Our results chow that in secretory hirsutism TT is increased in 57% and FT in 60% oF patients and in idiopathic hirsutism TT is increased in 7% and FT in 48% of patients. From these data, we suggest that FT assay is useful in the investigation of hirsute women and may be considered aS a better parameter of androgen action than TT. We observed a hihg number of false positive values in patients with acute inflamatory or congestive prostatic pathologie.When we excluded this patients, especificity for PSA was 97% and 96% for PAP.

In monitoring PC,PSA discriminates the kind of response to treatment (NPCP criteria), while PAP does not differenciates patients whit partial or complete response. Progression of the disease was detected in 95% for PSA and 85% for PAP. This results confirms a superior clinical efficiency of PSA in diagnosis and staging prostate cancer, been and excellent index in monitoring this neoplasm.

Marko TARLE, Nuclear Medicine and Oncology Clinic, Universitg Hospital "Dr M Stojanovi~', Zaqreb, Croatia. Yugoslavia

In 227 patients with progressive prostate cancer serum PSA, PAP and EtA vere measured during treatment, regardless of the outcome. In 106 of those subjects (81.99[) normal CEA level was recorded (mean value l.l ng/ml) together with PeA (mean 42 log/roll and PAP (mean 1.9 ,g/roll concentratinns, yielding PeA/PAP ratio 22.2. CEA level was found to he elevated (mean 4.0 ng/ml) in 41/227 (18_1~) of these patients free of soft tissue metastases. The mean PeA (45.4 ng/ml) and normal mean PUP level (1.9 ay/ml) gave PSh/PAP ratio 22_8. Statistical distinctions among all these values, coming from too groups of patients, are not significant (P> 0_05). In patients vith CEA higher than 4,5 ngfml (8/227 patients), mean CEA is 6.9 ng/m], PeA 45.4 ng/ml, PAP 0.9 ny/mi, and PSA/PAP 48.2). Elevated CEA concentrations , and especially those accompanied vith the declining P/tP values, indicate in the majority of subjects the presence of aggressive cell snbpopolations. These results are in line with preu suggestions, both our and from others, that initial genetic changes in prostate cahcer cells teadiay ~award a more anapiaatic tumor (CEA>4_5 ng/ml) have little intlueace upon PSA production (per gram u| tumor), but relatively supress eutopic PeA praductian. The addition of serum CEA value to bath PeA and PAP markers, leading to a triple prostate cancer marker test. describes tumor clinical|u ~,ore closely than a single tumar marker assessment. In order to find the biological profil of response to hormonal therapy in metastatic prostatic cancer, we determined in 30 patients seric levels of prostatic specific antigen (PSA) and prostatic acid I~osphatase (PAP) every tree months. In the follow up of this patients ranged between 6 and 39 months dosified 197 determinations of PSA and PAP.

A double antibody RIA (DPC,USA) was used to determine both tumor markers with a lower sensitivity limit of O. 2 og/ml. At three months of the begining treatment, 20 pts responded partially and we observed a mean percent decrease of PSA, related with the level before treatment of 92% (82-99), while other 10 pts were stabilized, been a mean percent of decrease of 51% (22.8-81.9 ). PAP decreased 70% in patients with partial response (0-98.9) and 35% (0-81.8) in stabilizated patients. Follow-up made evident that 50~ progression Fate in patients with greater decrease of PSA than 82% take place between 21 and 24 months while it did between 12 and 15 months in patients with lower decrease than 82%. Moreover, serial determinations of PSA allows to do diagnosis of progression of the disease till nine months before than clinical methods with a mean of 4.1.

We conclude that PSA can provide a biological profil of response to treatment of diseiminated prostate cancer an a prognosis value in the stablisment of progression of this neoplasm. The sensitivity (73Z) of CA 15-3 antigen, considered as a tumor marker specific for breast cancer, is high for the group of patients with this malignant disease, while is very low for the group of the other malignant diseases and non malignant effusions.On the other side high effusion CA 125 levels were found, in this study, in all types of disorders and benign diseases not known to produce the antigen.

Our The quantitative radiolmmunoassay of CA 72-4 in serum has promoted its use as a tumour marker mainly in patients with gastric and colorectal cancer. The first results in women with malignant gynaecologlc tumours stimulated us to extend the assessment of the efficacy of this tumour marker in such patients. Sixty-five women were examined, among them 12 aged 50 -81 years with ovarian cancer (T2NOM0 -T3N1M1), 40 aged 29 -95 years with breast cancer (T1NOM0 -T2N2M0) and 13 aged 49-85 years with uterine cancer (T1 bNOM0-T2bNOM0). In blood samples taken prior to treatment and during follow-up, the serum level of CA 72-4, CA 125, CA 15-3, CA 19-9 and TPA was determined by radioimmunoassay using monoclona[ antibodies in the case of CA 72-4, CA 125, CA 15-3 and CA 19-9. Serum CA 72-4 was elevated in 5 patients with ovarian cancer, 10 with breast cancer and 2 with uterine cancer. Serum CA 125/CA 15-3/CA 19-9/TPA respectively, was raised in 6/8/3/6 women with ovarian cancer, in 13/21/10/12 with breast cancer and 3/4/4/3 women with uterine cancer. CA 724 had risen as the only tumour marker in one woman each suffering from uterine or breast carcinoma. The sensltlvlty of serum CA 72-4 was 5/12 (41,7 %) for ovarian cancer, 10/40 (25, 0 %) for breast cancer and 2/13 (15,4 %) For uterine carcinoma. The specificity of serum CA 72-4 amounted to 93,3 %. In conclusion, the use of serum CA 72-4 as tumour marker in patients with ovarian, breast or uterine carcinoma deserves further attention. The purpose of this study was to get insight into biodistribution of CA 72-4 by its simultaneous determination in effusions and serum, and assess its value in diagnosis of malignant effusions.Immunoradiometric essay of CA 72-.4 by CIS kit was made in effusions and in serum of 43 pts with nonmalignant dise~es and in 65 pts with cancer of various origin. TI~ normal vsJiues in effusions and in serum were up to 6 U/ml. False positive value was found only in one pt with nonmalignant lung disease and none with liver cirrhosis.The pathological levels in effusions were registered in: gastrointestinal ca 19/29(serum 14/29) ~ lung ca 7/ll(serum 4/11), ovary ca 13/18(serum 8/18), other ca 1/7( serum o/7). The incidence and levels of CA 72-/} ~mre higher in effusions than in serum. Significant correlation between the values of CA 72-4 in effusions and serum was found (r=-o,4425;p~olol) . Through the evaluation of results by sensitivity-specificity diagram it has been established that CA 72-4 in effusions has acceptable diagnostic characteristics. In conclusion~ the determination of CA 72-4 levels in effusions is useful aid in differentiating nonmalignant from malignant peritoneal and pleural effusions.

Koutsiouba P.~Go~ou L.,Trivizaki E.,Kolindou A, Patsis G.,Tsialta A. Department of Nuclear Medicine Metaxa Cancer Hospital of Piraeus-Greece.

CANCER. The use of tumor markers in diagnosis and monitoring of cancer diseases could be of decisive help. Five tumor markers(CEA,Ca 19-9,Ca 50 TATI,TAG 72)were analysed in serum from 151 pts with gastrointestinal cancer and 125 with non malignant diseases of digestive system. Seventy eight patients with cancer(colorect. 51,stomach 12,hepatobiliary 12,pancreas 5)were in advanced stages of the disease and the other 72 in early postoperative period and in followup without evidence of malignancy during at least 10 months of the follow-up.

CEA resulted elevated in 29,]% > 8ng/ml,Ca19~ in 50,7% > 35U/ml,Ca 50 in 52,3%) 20U/mI,TATI iu 62,8% > 25~g/I,TAG 72 in 43,5%~ 4U/ml in pts with gastrointestinal cancer. Correlation between marker's values in pts with malignant and benign diseases was found significant difference(p<0.01) . Elevated serum levels in pts with advanced stages were found for CEA in 55,8%,for Ca 19-9 in 77,9%,for Ca 50 in 70,3%,for TATI in 82,2% and for TAG 72 in 73,2%. A new correlation between marker's levels in pts without evi dance of tumor progression and in these in advanced stages was statistically significant.

Conclusion] These results confirm 1)The utility of these markers in detecting metastases or recidive of the disease.2)The new markers Ca 19-9,Ca 50,TATI and TAG 72 were more sensitive than CEA in gastrointestinal cancer. 

Neuropeptide Y (NPY) is a 36 amino acids peptide secreted by the adrenal medulla, the sympathetic nerves and the heart. NPY induces a prolonged arterial vasoconstriction and a still controversial natriuresis in human. The aim of this work was to develop a sensitive and specific radioimmunoassay for measurement of plasma NPY. Rabbit antibodies were raised against porcine NPY (pNPY) which differs from the human peptide (hNPY) in the substitution of methionine at position 17 by leucine. The assay includes a three steps procedure: preincubation of diluted antiserum with hNPY or extracted samples, incubation with 1251-Bolton Hunter labelled pNPY then precipitation using a goat anti-lgG second antibody. A solid phase radioimmunoassay for gastric parietal cell autoantibodies is described. Plastic tubes were coated with microsomal or membranous fraction obtained by ultracentrifugatlon of gastric mucosa taken from kidney donors with blood group 0 . The concentration of antigens in coating solutions were 4. ug/ml. Tile tubes were washed with PBS and incubated with 3Z skim milk in PBS for blocking the remaining active groups. Human sera diluted 1 : 600 in 0.5% skim milk in PBS were added to the tubes and incubated for 16 hrs in 20~

The retained autoantibodies were detected by subsequent incubation with 12S I-labelled Protein A. Non specific binding (NSB) was below 0.St. Sera from 30 healthy subjects gave a mean binding of 4.7~. • 1.7% (SD), The binding exceeded 2 SD of the mean for healthy subjects were considered as positive, The positive sera were examined over the range of dilutions of 1 : 1200 to 1 : 153000. The antiparietal cell autoantibodies were present in high tltre in the majority of patients with atrophic gastritis confirmed by gastroscopy and biopsy. The results obtained In this studies indicate that anti-microsomal autoantibodies coexist with anti-membranous autoantlbodles, The RIA was of much higher sensitivity than the tmmunofluorescence method. In 39 normal controls and in 51-patients with homozygous B/T,29 with splenectomy (13 M and 16 F aging between iO-29 yrs X 22,4 yrs) (group I),and 22 without splenectomy, (7 M and 15 F, aging from 3-30 yrs,X 15.7) (group 2)also in 17 patients with S/T,(7 M and i0 F aging from 17-65 yrs X 35,4) (group 3) BTG and B2-M was determined by radioimunoassay. All patients had normal renal function; also care was taken during blood collection in order to avoid B/TG release from platelets. The increased B-TG in all groups-as compared to the controls (P<O.OOl) is attributed to the plate!et st9 mulation as they pass the damaged endothelium of the vessels of these patients.The greater increase in the non-splenectomised and in the sickle-cell thalassaemic patients as compared to the splenectomised (P<O.O5) is moreover attributed to the presence of the spleen and the existing diaphragms of the reticuloendothelial system which make difficult the blood flow and results to platelet stimulation. No difference between the level of B2-M of normals and those of the three groups was observed.This correlates well.with the good renal function of all of these subjects, normals and patients. Msli~cy has been associated with abnormslities of blood cosg~aticm which can create a hypereosgulable state, often mild and clinically non apparent, but proceeding to lh~is c~ nmnnifesting as disseminate intravsscular casgulatic~ (DIC). To further investigate this problem we measured, by RIA, FPA (n.y.:l,08-5,8 ng/ml) in the seru~ of 9S fete patients previously masteetomized for breast cancer. None of ~ase had clinical symptons of venous thr~lism or infection and neither had ~they received snticasgulant drugs or ~ndergone chemoTherapy at the time of the first observation. Fifty-two cases were claasifled as stage I -II and presented an apparently inactive disease (group A), 41 cases had an advanced disease with metastases (grotp B). FPA was elevated in 7 (i3.Ff/o) patients of gro~o A and in 2g (70.7%) of group B. Average levels of FPA were significantly higher than in 20 normal controls (S.l + 2.8 ng/m), both in grotp A (15.2S + 8.4 ng/ml) and in group B (g3.63 + 28.13 ng/ml). When cancer groups were mutually cc~pared, FPA was si~aiflcantly elevated in group B. All patients were controlled with serial measurements of FPA. In i0 patients of grs~ A FPA was either high (4 eases)c~ rose (6 eases)6-7 ~nths prior the clinical detection of metastatic disease. The re~ining S patients with initial and persistent high values have not developed metastases tp to date. In the grot<o B, 18 patients t~derwent disease progreasic~l and FPA, initially elevated, further rose. In the g eases, with apparent disesse remission, FPA fell in the S with previously high levels, but not within normal range, and it remained normal in the others. No change of the disease Occurred in the remaining 14 patiente end FPA was imrmdified, if already high, or it increased. Our data suggest that persistent high FPA levels in patients masteetomized for breast cancer could reflect subclinical recurrences, preceding clinical appearenee by several months; however, normal values do not exclude this. In addition, FPA might prove important in follow-up of patients with advanced breast cancer, since it tended to increase in CUE cases with disease progression while decreased or was normal in patients with disease remission The aim of this study was to determine the urinary prostagiandin levels in cirrhotic patients with ascites before and after therapy.

Methods: Prostagiandin E2 concentration in 24 h urinary excretion was determined in I0 healthy subjects and in 15 cirrhotic patients with ascites, evaluated before and after treatment. Prostaglandin E2 (PGE2) was analyzed by equilibrium radioimmunoassay (RIA) using a highly specific antibody (Institut Pasteur Paris). PGE2 was extracted with ethyl acetate, isolated on silicic chromatographic column and eluted with toluene-ethylacetate-metanol (70:30:5). The bound to free fractions were separated by dextran-coated charcoal. Our affinity constant (Ka) for the antibody used was 5xiO moles -i. The coefficient of variation in 10 determinations in urine of three normal subjects was 4.6 within assay and < 7% between assays. The results were expressed as mean+ SD. Controls: 0.24 + O.13ng/ min, cirrhosis 14.2 # 13.3 ng/min and 6T45 + 4.7 ng/min before and after treatment, resDectively. Differences were significant (p <0.05). Conclusion: The results suggests that highly specific antibody used by RIA is a good method to measure the urinary PGE2 levels in cirrhotic patients, before and after treatment. 

Gross cystic breast disease is a common condition. A wide number of substances may be found in human breast cyst fluid in different amounts according to the cyst type. Women with Type I cysts may be associated with an increased risk of breast cancer. The aim of this work was to assay in breast cyst fluids the levels of two hormones: dehydroepiandrosterone-sulphate (DHAS) and estradiol (E), and of two tumor markers (CA 15.3 and MCA), and their possible correlations to investigate if local factors may predispose to malignant progression.

According to thelr Na /K ratio the cysts were divsded Fluor-18-Deoxyglueose (FDG) can be used to visualize regions with increased metabolism. The possibility to get accurate quantitative and reproducible data about the glucose uptake allows the application of the method for chemotherapy treatment planning. We evaluated the change in tumor metabolism as measured by FDG and the changes in tumor or lymph node volume in 12 patients with head and neck tumors. PET studies with FDG were performed prior and after the first chemotherapeutic cycle. The chemotherapeutic protocol included 5-FU (1000 mg/m 2) and Cisplatinum (150 mg/m2). Volumetric data were obtained from tumors and lymph nodes using computertomographic slices and the growth rate was calculated assuming an exponential function. After standardization of the PET-FDG images for the body weight and the injected dose a quantitative evaluation was done with a region of interest technique. The final evaluation includes data about the glucose uptake in 4 tu mors and 11 lymph nodes, while data about the growth rate were ob tained in 3 tumors and 8 lymph nodes. We noted an increase in FDG accumulation in one ease and a decrease in 7 lesions. No change in metabolism was found in 7 eases. In the same patient multiple lymph nodes may show a different metabolic activity prior to chemotherapy and also differing changes in metabolism during therapy. A 10% decrease in FDG uptake after therapy was followed by a 2.7-fold higher decrease in tumor volume as compared to lymph node volume. The changes in FDG uptake and the tumor growth rate showed a high correlation (r=0.9). Our results show that PET with FDG should find use for chemotherapy management. Recombinant interleukin-2 (rIL-2) has been employed for cancer immunotherapy but its use has been hampered by cardiac side effects. We studied I0 patients (pts) (mean age 49• years) with no evidence for cardiac disease, who u~derwe~t a 120 hrs i.v. infusion of rIL-2 {3x10 CU/m /day) for advanced cancer. Radionuclide ventriculography was performed before and 2 hours after rIL-2.

Ejection fraction (EF), peak emptying (PER) and filling rate (PFR) normalized for heart rate (HR), and left ventricular (LV) wall motion (WM) were analyzed. HR, systolic (SBP) and diastolic blood pressure (DBP), ECG and enzymes were also monitored throughout the study. Twenty patients with malignant melanoma were imaged with F(ab')2 fragments of ant• monoclonal antibody (MoAb)225.28S labelled with teehnetinm-99m(Tc99m).Patien ts were placed in two groups.The low suspicion group (8 patients) consisted of patients with no evidence of disease.In four patients (50%) the immunoscintigraphy(ISG) revealed disease that was not expected;in two patients, four imaged sites could not yet be confirmed by conventional studies.The high suspicion group consisted of patients with established evidence of metastatic disease; the ISG was performed to confirm those findings and to search for involvement of other organ systems.Of these scans II were true positive and one false negative.In this group a total of 45 sites demonstrated localization of radiolabelled antibody;40(88.8%) corresponded to known sites of the disease;5(11%) were "discovered" by ISG and subsequently confirmed by conventional studies. Routine clinical analyses to evaluate hematopoietic,hepatic,pancreatic and renal functions were performed before the administration of the radiopharmaceutical and were repeated two weeks later.No adverse reactions were ever observed. The aim of the study was to assess the value of the bone marrow scintigraphy in various hematological conditions. The test group comprised 56 adult patients /pts/, including malignant lymphoma /30 pts/, acute mylogenous leukemia /5 pts/, myelodysplastic syndrome /5 pts/, myeloproliferative syndrome /9 pts/, multiple myeloma /5 pts/ and aplastic anemia /2 pts/. The bone marrow scintigraphy was performed 90 min. after iv injection of 99mTc nanocoll. Fifty-five out of 56 patients showed following abnormalities in the bone marrow scintigraphy: focal areas of increased activity, focal cold lesions, peripheral bone marrow expansion with high uptake of the colloid in the central areas, peripheral bone marrow expansion with reduced uptake of the radiocolloid in the central areas, reduced uptake of the radiocolloid in the central areas without peripheral bone marrow expansion. It is concluded that the scintigraphy is a valuable method for detecting and describing bone marrow abnormalities in hematological diseases. The synovial and to some extent the spinal joints are common sites for OA and yet most patients will experience no symptoms. The aim of our study is to determine whether there is an inflammatory contribution to the disease process. Nine patients with OA of the knees diagnosed el%~ically and radiologically w~Ke "_mmaged using ~Tcm-HMPA0 labelled white ceils and ~Tcm-MDP. Three normal volunteers were imaged with ~^Tcm-~MPA0 labelled white cells only. Knee positioning, marker images, scanning at 22 hours and) quantitatiOn(l of uptake was previously described . At the time of scanning, pain in each knee was measured using a visual analogue scale. In the three D~rmal volunteers there was no apparent uptake of ~Tcm-~PPA0 labelled white cells in the knees. Uptake measurements in OA patients ranged between 0.001-0.05% of injected dose (ID), (mean 0.019+/-0^~12). In individual knees of three patients, ~Tcm-~g~PA0 labelled white cell uptake was nil; irrespective of whether such pa~ents experienced any pain in the knees. >>Tcm-MDP uptake in all 9 patients was 0.204-0.96% ID (mean 0.626+/-0.21). Conclusion. The uptake measurements and localization of the ~Tcm-HMPA0 labelled white cells at sites affected by OA may suggest a low-grade inflammatory process occurs at certain stages of the condition. -JANABI et al, Nucl Med Commun; 1988,9: MBq per extremity, 99mTc-sulfur eolloid).Ga-67 was always the first study and was abnormal in all pts: lung, 13/13, several degrees of uptake; liver, 3/13; spleen 1/13; bone, 3/13; ganglia 8/13; salivary glands, 3/13. BS was abnormal in the same pts and bone regions as Ga-67. RES was abnormal in 6/13 pts: "cold areas" were shown in liver (4 pts) and spleen (1 pt); peripheral bone marrow presented abnormal uptake in 6/13. In i case uptake was not continuous and this was interpreted as a focus of fungii. LS was interpreted in comparison to Ga-67 and was abnormal in 6/13 pts. All studies were performed again in 5/13 pts 3-6 months after the beginning of specific therapy. Ga-67 normalized in 4/5; one pt maintained lung and salivary gland uptake but in a less severe degree than previously noted. BS normalized in 2 pts and presented a reduction of severity in i. RES normalized in liver and spleen in all pts; peripheral bone marrow normalized in 4 and reduced the degree of uptake in 1. LS normalized in all pts.

Ga-67, BS, RES and LS can be of great help in the evaluation of the extent of this mycosis before therapy and in the follow-up of the pta after therapy started. 

Noninvasive rest-exercise testing after attempted intravenous fibrinolysis in evolving AMI was performed to assess left ventricular function and coronary functional reserve. Regional left ventricular ejection fractions (REF) were evaluated regarding the site of infarction and patency of infarct related coronary artery. 67 pts after acute myocardial infarction (36 anterior, 31 inferior,47 treated with iv streptokinase -SK, 20 controls-CTR), underwent rest-exercise radionuclide ventdculography (RNV) before hospital discharge and 31 SK pts coronary angiography between 5 and 10 th day. Quantitative analysis of RNV with cubic spline function interpolation for global (GEF) and 9 regions ( 

One hundred and fifty consecutive symptom-free patients (pts), underwent, two to twelve months after an uncomplicated acute myocardial infarctionmaximai, treadmill exercise testing (EST), rest and stress radionuclide angiography (RNA); 90 of these pts underwent coronary angiography (CA). Pts were followed for a mean of 32 months. Non invasive and invasive tests were assessed for their value in predicting hard (death and reinfarction) and soft (angina and coronary surgery) coronary events.

Exercise stress test was considered to be positive if the pt developed ischemia or angina during effort; for lhe RNA both ejection fraction (EF) criterion (failure to increase of at least 5 points percent during effort) and standard deviation (SD) of the LV phases criterion (failure to decrease during effort) were considered. Coronary angiography was considered to be positive if a significant lesion (>_ 70%) was detected in non infarct-related coronary artery (Mvx). Sensitivity (Se), specificity (Sp) and positive predictive value (PPV) 1or each lest were calculated, and results are reported in the following table. Z 2 was calculated for each test and no significant correlation was found.

Total (hard) coronary events.

It is concluded that exercise stress test, radionuclide angiography and coronary angiography are not helpful 2 to 12 months after an episode of uncomplicated myocardial infarction for identify pts who will suffer a new coronary event.

Ann C Tweddel, William Martln, Stuart Cobbe and Ian Hutton. Department of Medical Cardiology, Royal Infirmary, Glasgow G31 2ER, Scotland.

Left ventricular function is thought to improve following thrambolytio therapy in patients with myocardial infarction, but the mechanisms are not fully understood.

In 14 patients with first myocardial infarctions, treated within 3 hours of onset of symptoms with APSAC and heparin, angiography was performed at 24 hours and repeated at 5-7 days in 10. At the time of angiography myocardial flow was assessed by the Xenon clearance technique.

Following intracoronary injection of Xenon under direct vision, scans were obtained using a mobile Gamma camera fitted with a bi-plane collimator, which allows simultaneous acquisition of 30 ~ and 70 ~ LAO projections.

In 4 patients the infarct vessel was totally occluded at initial angiography, in one patient this was patent at 5-7 days and a further 2 patients developed totally occluded vessel. Ventricular function was unchanged (LVEF 24.5 ~ 5.5% at 24 hours, 25.7 ~ 5.1% at 5-7 days) An all patients, but in the 5 of 6 patients with occluded vessels, with angiographically demonstrated collaterals l@ft ventricular function tended to improve (23 3 3.9% to 27.3 ~ 4.5%). Xenon flow showed improved collateral flow from 43.1 ~ 10.2 to 65.9 ~ 11.4 ml/100 g and increased distribution to the left ventricle (14 ~ 3% to 21 3 4%) from the collaterals.

These results suggest that, in the post infarct patient, collateral flow tends to improve with time in those patients with occluded vessels. Diagnosis of constrictive pericarditis (CP) is usually based upon suggestive haemodynamic data. The aim of this study was to evaluate how a global and sectorial analysis of volumic changes during the early and late filling of the left ventricle (LV) by RNA might contribute to this diagnosis.

Population included 9 patients (28-64 years) with evidence of isolated CP, in sinus rythm and without noticeable systolic LV dysfunction (LV EF:56 + 8%), valvular disease, hypertension or LVH. Their results were compared to those of 15 normal age-matched subjects.

Methods: From LAO acquisition with 16 frames per cardiac cycle, one global LV and 10 sectorial time activity curves and their first derivatives were constructed with 64 pts/cycle by Fourier transform. The parameters studied were filling fractions at 1/3 (FFI/3) and 1/2 diastole (FF1/2) and during atrial contraction (AFF), peak emptying rate (PER), peak filling rate (PFR) and peak atrial rate (PAR), PFR/PER and PAR/PFR. ratios, time of PFR (TPFR) and TF1/3 as the delay between the endsystole and the occurence of one-third filling. Filling asynchrony was assessed as the average of the absolute differences between global and sectorial values of TF1/3 and TPFR.

Results: With reference to normal subjects, the patients with CP showed an increased early LV filling and a decrease of the atrial contribution as judged upon a higher FF1/3 (ns) and FF1/2 (p<0,05), a rise in the PFR (p<0,05) and PFR/PER ratio (p<0,02), a shortening in the TPFR (p<0,05) and TF1/3 (p<0,05). The filling asynchrony tended to decrease and a significant inverse relation was observed between the value of the global PFR and asynchrony (p<0,05). During the late diastole, the PAR, PAR/PFR ratio and the AFF trended towards a diminution (ns).

Conclusion : This LV filling profile agree with a predominant impairement of the LV compliance as seen in CP. It is quite different from those usually seen in the other cardiac diseases leading to a diastolic dysfunction. Thus, analysis of the global LV filling by RNA may be particularly useful for CP diagnosis. Besides, the sectorial analysis seems promising for diagnosis of localized CP but th!s point deserves further studies. 

Changes of ejection fraction (EF) are helpfuI Jn detecting patients (pts) with coronary artery disease (CAD) during dipyridamole-radionuclide ventrJeulography (D-RVG). To evaluate the significance of diastolic function during D-RVG in the detection of CAD we examined 15 pts with CAD proved by coronary angJography and 8 normal controls. EF, peak filling rate (PFR), t~me to peak filling rate (TPF) and rapid filling time (RFT) were measured before and immediately after infusion of 0,56 mg/Kg dipyridmmole. 9/15 CAD pts had abnormal response of EF (sensitivity 60%); all normal controls presented normal rise (%5%) of EF (specificity IOOZ). A rise of PFR < I was present in I/8 normal controls and I]/15 pts (sensitivity 87%, specificity 87%). Rise of PFR correctly reclassified all pts with CAD and false negative response of EF. TPF and RFT changes were not helpful in indentifying CAD pts.

In conclusion changes of PFR can increase the diagnostic value of D-RVG in identifying pts w]th CAD. Exercise induced radionuclide angiocardiographic (RNA) dysfunction has been shown to be more sensitive and more specitic than exercise ST-segment depression in detecting patients with myocardial ischemia and tend to occur before the onset of angina in the ischemic cascade, To identify variables related to clinical symptoms occuring during exercise myocardial ischemia, 83 consecutive patients (pts) with exercise induced wall motion (WM) abnormalities and exercise ejection fraction (EF) > 5% below that predicted by age were investigated: 68 pts were asymptomatic (silent ischemia: SI) and15 pts presented angina (A) during upright bicycle symptom limited exercise first pass RNA.

Exercise ECG test was positive in 32 pts: 27 in SI, 5 in A (p=NS). None of the following RNA variables was significantly different in the 2 groups. For A and SI, respectively: rest EF 56.4_+9.9 vs 54._+9.9; exercise EF 44.9-]:8.9 vs 44.0-!-9.3; EF changes -14.4+7.0 vs -12.8+_5.7; rest WM score 14.5+-3,9 vs 13.6-+3.7; exercise WM 9.1_+3.8 vs 9.2:[:4.1 and WM changes -5.4_+2.3 vs -4.4+2.6 (p>,05 for all variables).

Among 17 clinical, exercise and angiographic variables, only 5 were significantly (p<.05) different in the 2 groups: an history of angina pectoris and an history of myocardial inlarction were more frequent in A while taking betablo~ers and the presence of coronary collateral vessels were more frequent in SI. Exercise work load was significantly higher in SI as those pts were not limited by symptoms.

We conclude that clinical symptoms during upright bicycle symptom limited exercise are not related to the extent of exercise induced myocardial dysfunction. Admittedly, First-Pass (FPS) and Equilibrium (EQS) studies give the same evaluation of the left ventricle ejection fraction (LVEF). In some patients with cardiac dysfunetion, the LVEF values seem too low, given their good clinical status. This study compares these two techniques as a function of the homogeneity (or not) of the LV contraction: 36 consecutive patient records are analyzed: LVEF is computed both on FPS and EQS. Wall motion is scored from 0 to 3 as (normal, hypo-, a-, dys-kinesia), for the three segments seen on FPS (apex, inferior and anterior wall) and on EQS (apex, septum and lateral wall). The sum of these three values gives a total score (TS To evaluate left ventricular function of moderate to severe chronic aortic regurgitation (AR), we performed maximal exercise gated blood pool scintigrams in -Group A:39 asymptomatic or poorly symptomatic patients (29 male, 18-55ys.) with functional class I or II of NYHA and normal left ventricular ejection fraction (LVEF) at rest (>55%) and -Group B:22 normal controls (19 male, 24-48ys.).

We found in Group A, two different results according to exercise LVEF; -Group A1:24 patients, that showed LVEF elevation, had peak filling rate percentual variation (%PFR) and peak ejection rate percentual variation (%PER) lower than Group B (p<O.05) and -Group A2:15 patients, that showed impairment of LVEF, had ~PFR and %PER lower than Group A1 (p<O.05), as showed: ECG-gated radionuclide ventriculography was performed in 20 normal subjects /Nm/ and in 55 patients with chronic myocardial infarctio~ /Ni/. Distribution of amplitudes within the left ventricular /LV/ area was measured using the reference circle method, developed lately. In Nm an amplitude decrease equal to SDU-I was found in 13.72% of the LV area and equal to SDU-2 in 0.89~.~ None of those subjects showed abnormality greater than SDU-2. Defect measure D~vI amounted to 0.85%. In patients with ~I the SDU, LVa% and Dr~ values were significantly greater than in Nm. The highest values of those indices were found in patients with aneurysm. A less pronounced PA reduction was observed in anterior wall infarction and the lowest one in posterior wall infarction. The sensitivity of the reference circle method in detecting regional hypokinesis was 85.27~, specificity 100.O% and accuracy 85.4%. In patients with regional hypokinesis the visual evaluation of the statistically encoded image revealed a sharply outlined, easy to detect area. It is concluded that the reference circle method enables regional hypokinesis to be detected, localized and quantified accurately. It may be concluded that combined LV radiocardiography and pressure measurement can be carried out in the oath lab, and with this method ischemic changes of systolic and diastolic LV function can be measured reliably in pts with coronary artery disease. 

Aim of this study was to find out whether a combination of histomorphometric and scintigraphic data can improve assessment of the cardiac status in DCM.

In 38 patients (pts) with DCM, a count density (CD) index CDI = (CD myocardium) 2 / CD lung x CO sternum (d Nucl Med 30: 779, 1989) was determined from planar scans recorded 48 hr after i. v. injection of 74 MBq In-lll antimyosin Fab. Scans were graded positive if CDI exceeded 1.2 and no blood pool activity could be seen on 48 hr SPECT images. Left ventricular ejection fraction (EF) was determined by gated blood pool imaging. In addition, endomyocardial biopsy was obtained in 31 of these pts. In 11 cases, complete histomorphometric analysis of the samples was possible. Percent myofibrils (MF) and percent interstitial fibrosis (IF) per area as well as diameter of myofibers (OF) was determined. These parameters were combined with COI and EF to a cardiac status index CSI =COI x EF x MF / IF x OF.

In 8 pts with positive antimyosin scan, CSI was 6.78 + 2.58 (mean + SO). CSI determined in 5 pts with negative antimyos~n scan was significantly lower (2.15 0.74; p = 0.01). In both groups, CSI was markedly below the normal range of 20 -50 as estimated for normal subjects even in case of missing antimyosin uptake. This was primarily caused by the'histomorphometric data included in CSI. There was no histological or immunohistochemical evidence of myocarditis.

In conclusion, CSI seems to reflect the actual cardiac status of a patient with DCM more exactly than each individual of the parameters combined. Follow-up studies will elucidate its prognostic significance. P Rautio, P Vainio, J Kuikka, M Tenhunen, E L~nsimies. Department of Clinical Physiology and Nuclear Medicine, University Hospital, Kuopio, Finland.

Hew comparable are kinetics of Tc-MIBI between normals and patients? Does possible discrepancies affect imaging protocls? Methods: 5 patients with extensive 3-vessel disease and 3 normal controls were studied. Rest and maximal exercise studies were done within a week. Injection to right medial cubital vein was flushed with 20ml saline in both occasions. Exercise continued 1 89 after the injection. Blood was collected 3, 6, 10, 20, 35 and 60 min after the injection. Four 180 degrees SPECT acqnisitons were made with Siemens Orbiter cammacamera. Blood extraction was calculated with Sejrsen's extrapolation. Myocardial and blood effective half-lives were calculated for rest and exercise. Lateral and septal profiles were corrected for partial volume effect and spillover. RESULTS: Extraction in rest was in controls 33 +-3% and in patients 34 +-i% (+-SEM). Fast component Ex-T~ was in controls 1.6 +-0.1min and in patients 3.0 +-0.6min and Rest-T 89 respectively 1.3 +-0.2 / 1.6 +-0.1min. Slow component Ex-T 89 was 4.3 +-5.0 / 76 +-30 and Rest-T 89 49 +-6.0 / 40 +-4.0min. In septal myocardiumEx-T 89 was 3.6 +-0.6h / 4.8 +-0.9h and in lateral myocardium 3.1 +-0.6h /4.4 +-0.9h. Corresponding rest half-lives were 4.2 +-0.i / 5.2 +-1.0 and 3.7 +-0.6 / 5.3 +-1.0h. Conclusions: Blood clearance is faster in controls probably due to more strenuous exercise. Myocardial washout is faster in controls than in severe coronary disease. This should be taken in account when protocols are designed. Assessment of reperfusion following i.v. thrombolysis after myocardial infarction is routinely based on clinical, ECG and enzymatic criteria that do not allow quantitative evaluation of myocardial salvage.

We studied 8 patients (pts mean age 53+llyrs) undergoing thrombolytic therapy (TT) with either streptokinase (6 pts) or TPA (2 pts) within 4 hrs (mean 3.6+1.5) from the onset of symptons. TC-99m MIBI (740Mbq) was given inmediately before starting "IT and tomographic imaging was performed 2/3 hrs postinjection (S1). The perfusion study was then repeated 2 and 15 days after TT ($2-$3). Tomographic data were analyzed semiquantitatively by circumferential profile analysis (60 segments) performed on I cm thick slices. In each segment, activity was expressed as percent of maximal value. In comparing sequential studies from the same pts only absolute changes of more than 20% in at least 3 adjacent segments were considered significant. After TT ($2) only 3 pts exhibited a 39+1% increase in activity in the infarcted region and a further 33% increase was observed in 1 in $3. Of the 5 remainig pts who showed no immediate changes in regional perfusion after TT(S2), 4 increased activity in the infarcted region (22_+2%) on $3, We may conclude that ,in AMI, TC-99m MIBI SPECT allows semiquantitative objective evaluation of the initial area at risk and the assessment of early and late reperfusion after thrombolysis. To evaluate if Perfusion Study (PS), in the acute phase of myocardial infarction, can correctly identify the extent of the area of necrosis, we performed PSs with Tc99m-MIBI, in the follow-up in 38 pts,who,in the acute phase, underwent a rest PS with Tc99m-MIBI.AII the pts were at their ~' AMI.The stress PS was performed, on the average, after 118 days from AMI; during the follow-up period no important coronary events occurred (NewIMA-PTCA-CABG).We evaluated, by 2 different operators, both the segmental extent (SE) and the grading of the perfusion defect (OPD) of the 2 rest PSs. In 83 pts SE was the same, in 5 was reduced; while GDP was the same in 21 pts, and improved in ]7.Between these 2 groups, we found no significant differences about mean interval at the 1 ~* PZ (62vs50hours), at the 2 ~ PS (107vsI30 days) and residual ischemia. At the ~f Pg, 15 pts (39%) had transmural perfusion defects (TPDs) and 23 noTPDs; at the 2 ~ PS only 6 pts (16%) shewed TPDs and 32 pts noTPDs. CONCLUSIONS:I) PS of NI in the acute phase correctly identifies the area of necrosis. 2)the larger perfusion defect observed in the 1 ~ rest PS is probably related to the areas of "stunned myoeardium" in the acute phase of MI. 3)therefore we think that, to obtain a correct evaluation of the area of necrosis,it's preferable to postpone the rest PS about at the S'4 week from acute episode. 

Coronary vascular reserve is invasively determined from vascular resistance. However, during routine myocardial SPECT, a ratio (exercise E/rest R) may he derived from global left ventricular (GLV) uptake values of Tc-99m MIBI, elucidating a noninvasive correlate, the CPR. In the present study 28 pts with no CAD and 54 pts with documented CAD were exercised and Tc-99m MIBI was injected twice (150 MBg E, 800 MBq R) within a 4 hrs protocol. With $PECT (double-head, 2x180 ), GLV uptake (kcts) was determined by summing up six slices (2 pix thickness). After correction (dose, decay, loss), CPR was computed by division (E/R; extraction fraction not corrected).

For correlations, double-product at E (DP) from RRsyst-max x heart rate-max and pretest-probability were formed and CAD was suhgrouped from anglo for i-3 vessel disease (VD We studied the diagnostic value of the MIBI Exercise/ rest ratio in 50 patients before and after PTCA. Methods: Myocardial SPECT-studies were performed I hour after injection under exercise (185 MBq) and rest (555 MBq) conditions, respectively. In 29 sectorial regions projected on polar plots of the myocardium exercise (VIE) and rest (VIR) vitality index were calculated. Additionally we determined the exercise/rest ratio (CE/ CR) of myocardial Tc-99m-MIBI-uptake in each myocardial region. Results: In 71.6% of patients CE/CR increased consistent with an improvement of coronar circulation after suecess~ full PTCA. The average increase was 11.6~176 of values obtained before PTCA in those regions supported by the stenosed vessels. Increase of CE/CR was most significant in myocardial regions supported by coronary arteries with stenoses less than 90 % (15.2% of pretherapeutic value), whereas it was only 8.7~ after PTCA of subtotally stenosed vessels and 8.8% after recanalisation. Conclusions: Quantified Tc-99m-MIBI-SPECT is suitable for monitoring patients undergoing PTCA. The lower increase of CE/CR in regions supported by subtotal stenosed or occluded vessels may be due to rarefication of the poststenotic microvasculature. Thus CB/CR is a new approach to study coronary microcirculation. Tc-99m MIBI has been proved as a T1-201 substitute for myocardial imaging. Two imaging protocols have been proposed for a one day study. We compared the segmental sensitivity, specificity and accuracy of SPECT myocardial imaging for 44 ischaemic heart disease patients. 24 patients underwent the restexercise (R.E.) protocol and 20 patients performed the exercise-rest (E.R.) protocol.

All patients received 6 mCi Te-99m MIBI for the first injection and 20 mCi for the second injection with a 3 hrs period in between. All patients had coronary angiography within a period of 3 weeks. A total of 176 segments were analysed for both studies. They were read by 2 trained observers and disagreement was resolved by a third observer. The results are shown in this There is no significant difference between both groups. We conclude, that both protocols for same day exercise and rest injection of Tc-99m MIBI are equally reliable. Different departments should choose according to which ever schedules suit their work load. 

IN IHE DIAGNOSIS OF ISCHEMIC MYOCARDIAL AREAS. The following paper tries to answer the question if the evaluation of rest/stress quotient images after Tc-s SPECT can be useful for the detection of ischemic n~jocardial areas. During the study 50 patients underwent stress-and rest myocardial scintigraphy using Tc~IBI.

After the acquisition of 180~ studies oblique, short axis, 12 m~-slices of the left ventricle were reconstructed. In each case further evaluation of the conventional slices was performed by maans of a recently developped soft ware programn that was provided by the SIRENS AG. After equal reconstruction and zocming of stress-and rest slices this progra~m alows normalization on studies hotpoint before creation of contour images of the left ventricle autcmatically or by manual ROl's. Then rest/stress quotient images are calculated frcm corresponding contour slices and normalized to a n~Jium level of intensity. These contour quotient slices were juged by two independent observers. In the cases of disagreement consensus was found by discussion. Conventional evaluation, i.e., visual comparison of stressand rest slices was perfon~ed by a third coworker unconscious of the other results. We found 27 ischemic myocardial areas in 22 patients by conventional evaluation and 24 ischemias in 20 patients by quotient images. Both methods show a correspondence of only 33 % (9/27), i.e., 18 ischemias weren't recognised by quotient slices, 15 other were found supplementary. Towards these results the usefulness of rest/stress quotient images in the diagnosis of ischemic myocardial areas is doubtful. A disadvantage might be the appearance of border artefacts in the quotient contour slices caused by incongruences. Further clinical investigations as a c~arison with coronary angiography have to be done in order to der~3nstrate potential advantages of this new method. In a previous study, we have shown it was possible to evaluate the LVEF by acquisition of the myocardial cavity activity for 30" after the IV injection of 550 MBq of 99mTc MIBI for myocardial scintigraphy. To furtherassess the early kinetics of the tracer, we generated time/activity curves of 4 ROI'S (myocardial cavity: MC, myocardial wall: MW, lung: LU and liver: LI) and followed the evolution with time of MC/MW, LU/MW and MW/LI ratios in i4 patients referred for myocardial scintigraphy, who received 550 MBq of 99mTc MIBI. The acquisition time was 5' in a LAO view. MC/MW activity ratio decreased rapidly with time according to a negative power function: MC/MW=3, 3 (r=0, 9; p<0, 001 ) . 85" after injection, the wall activity was equal to that of the cavity The evolution of LU/MW was also best described by a negative power function: LU/MW=I,]Yxt^-O,2 (r=0,8; p<O,00]). According to the curves, the activities found in the MC and LU at 60' were still 3OP~ and 23~ from that of the MW. Inpatients who were recorded at one hour, the% found in the 2 ROI'S confirmed those predicted by the theoretical curves. The LI activity increased very rapidly: MW/ 77 (r=0, 8; p<0, 001) , but the later evolution of the ratio did not correspond to that predicted by the curve, because of the excretion of 99mTc-MIBI by the gallbladder and biliary ducts: at 60', the average activity of the MW was 1/3 of that of the LI. To conclude: in case of planar scintigraphy, despite a rapid decrease of activity in MC and LU, the residual important background at, I H could lead to interpretation problems, especially for small lesions. Moreover, the activity of LI could produce artifactua; images in the left lateral views. To ovoid those problems, SPECT should always be preferred to planar scintigraphy when 9gmTc MIBI is used as myocardial tracer. To identify patients (pts) with increased likelihood of future cardiac events because of viable but jeopardized myocardium, TC-99m-MIBI SPECT myocardial scintigraphy associated to dipyridamole test (DMS) and 2D echocardiographic monitoring during dipyridamole infusion (up to 0.84 mg/Kg over i0' ) (DET) were evaluated in 67 asymptomatic pts (62 male, age 57+4) with uncomplicated acute myocardial infarction (AMI) who have undergone thrombolytic theraphy . DMS was performed in 26 ($9%) and DET in 68 (94%) respectively out of 67 pts within 8-12 days after AMI. All pts underwent coronary sngiography (single vessel 47, double vessel 24, triple vessel disease 6). Mean follow-up was 12 months (4-20) : 1 death, 7 angina and 2 AMI recurrences. 8 PTCA, 3 CABG were observed. DMS, DET and DMS+DET showed a sensitivity for events of 88%, 5~/o and 85% respectively; a specificity of 50~ 71% and 45%; a predictive accuracy for negative test of 92%, 83%, 89%. DMS and DET were observed to induce reversible perfusion defects and new wall motion abnormalities confined to the infarct-related area in 7/18 e 15/45 pts With single vessel disease respectively, suggesting the presence of jeopardized but viable myocardium. Conclusions: DMS is an useful tool in risk stratification after thrombolysis in AMI. It shows a higher sensitivity than DET for predicting events. DMS+DET do not permit to increase the sensitivity and predictive accuracy of each method. Previously described platelet labelling techniques (e.g. iLIIn-oxine), take more than 24 hrs. before definitive scintigraphic assessment of thrc~enicity can be made. Recently,t~e lipophylic substance 99n~c-}94PAO,originally developed for brain scintigraphy, has been successfully used for leukocyte labelling (Peters A.M.et ai. Lancet II, 1986; 946) . We applied this method to platelets. A mean labelling efficiency of 63% and a mean release of 33% label per 24 hrs. was found. In vitro quality control of platelet viability (membrane integrity, energy rsetabolism, morphology, activation) was found only slightly less than for fresh platelets. In order to study whether these platelets, despite the considerable release of label, can be used clinically, they were re-injected in patients undergoing intraltmlinal intervention, 89 hour before angioplasty. The results of the first 5 patients show that this technique is a sensitive method to assess the thrombogenicity of (damaged) endotheli~n and has practical advantage above currently used ~nethods, because a decissive scan can be made already I hour after angioplasty. Despite prophylactic use of ASA, 99n~c accnmnulation was found at all sites of angioplasty and at the sites of introduction. A second scintigraphy, 4 hours after the first, did not yield extra infoz~ation. It seems forthwile to investigate the suitability of this technique as a monitor for anti-platelet drugs. H. Sinzinqer, irene Virgolini, F. Raoecha, P. Chiba, M, 8anyaJ

Bonocytes have been implicated in the pathogenesis of atherosclerosis, boeever, there is a lack of specific knoeledge about the uonocyte kinetics and their in vivo distribution. Prior to invnlvemont of patients basical in vitro labelling studies were carried out (Fig. left -~nocyte viability) , kutolog~e eonocyte-scintigraphies using IOE § monocytee/nl labelled with 15 pCi of tltln-oxine were perforIed in 15 patients with angiographically proven peripheral vascular dieeaee. Sequential lunging was done during the first 20 ninnies (I frale/30 s) over the carotid or femoral arterie% and alternatively over heart, liver spleen and lungs. Static inagingvua perforeudat 2, E, 18, 24 and 48 hoers after reinjection of autologoue nonocyteu. Blood kinetics vaTied extreiuly exhibiting a tale peak maximum between G and 18 hours after reinjection of autologoue monocytes in some patients. The tracer uptake imoged with viable cells (viability degree over 95[) was predoiinontly concentrated to the spleen, a lover degree in viability led to a iaaeive trapping by the lungs (and liver). In S patients hot spots eere identified over either the carotid or feioral arteries as early as 24 hoers after reine~ectionpreeenting a positive vessel inage, The approach of imaging non,tyros, t~ether vith platelet and LOL-iiaging in one and the same patient may offer a nee way to deteriine the clinical stage of atheroscleronie complication of arterial reconstructive vascular surgery, having a high incidence both of mortality (25-78%) and morbidity (0-52%) as limb loss. Because of non specific onset and clinical course, it necessitates an early and accurate diagnosis. Standard techniques (echography, angiography, TAC) even if useful, have not yet provided a complete and satisfactory reliability concerning sensitivity and specificity. The aim of this work is to evaluate the clinical usefulness of 99mTc-HMPAO-Leukocytes scan in the assessment of prosthetic graft infections. 26 patients with suspicion of graft infections were studied with 99mTc-HMPAO labelled white cell scan: 18 aorto-femoral, 2 iliaco-femoral, 2 femoro-femoral, 2 axillo-femoral, 1 aortoiliac, 1 aorto-aortic grafts.

All patients with positive scans underwent surgical exploration, the removed grafts were then submitted to bacteriological and coltural examination. In patients with negative scan a clinical follow-up was carried out for at least i year. The study provided the following results: 13 true positive, 13 true negative. No false cases were observed. These results show a clinical usefulness of the procedure. Tc-HblPAO-leukoccte scan can be used in the determination of both the presence and extent of the raft infection. Methods and materials: We nave performed 24 9mfc-HMPAO-mixed leukocyte scans, in 22 patients with vascular grafts: 19 were bilateral aortofemorat grafts, 2 were bilateral axflofemoral and I was eortoiliec. Five patients were evaluated for clinical suspicion of graft infection, two for femoral pseudoaneurysm and 15 were control patients. The vascular grafts had been implanted from !0 days to up to 5 years previously, tn two patients with graft infection we per'formed a control study four weeks after antibiotic therapy. Mixed leukowtes were prepared and labelled according to Peters's method. The images were performed at 30', 3 hours and 24 hours, increased uptake along the expected area of the graft was considered to be evidence of graft infection on the leukocile scan. All diagnosis were confirmed by subsequent clinical course and/ or CT and/or sus Results: Alt patients with proven graft infection had positive ~UmTc-HMPAO-mixed leukocyte scans, while all patients without infection (control patients and pseudoaneurysm) had negative scans. In one patient w~th a bilateral aortofemoral graft refection, the scan also showed an extension of the infection into the retroperitoneum, The scans taken after antibiotic therapy allways remamed positive. 

The usefulness of monoclonal 111-In-antimyosin antibody scan (Myoscint, Centoeor Co.) in detecting heart transplant rejections was shown. Prior studies were based on 48 h scans because of the lower background and better contrast. But patients and surgeons ask for earlier results (biopsy result after 4-6 hrs). 40 heart-transplanted pts were investigated 24 and 48 hrs after intravenous application of 74 MBq 111-In-antimyosin. The heart/lung ratio (H/L) of the anterior view as an indicator of myocardial cell damage was compared after 24 and 48 hrs in relation to the biopsy: The group with a moderate or severe rejection and thegroup with mild or no rejection showed similar decrease in H/L ratios from 24 to 48 hrs (0.19-+0.15 versus 0.22+0.13). Using a threshold of 1.80 H/L ratio at 24 hrs and 1.60 at 48 hrs, quite equal false negative results (24/48 h-> 30%) and false positive results (24 h->24%, 48 h-> 18%)were found. In summary the 24 h-scan is a valid base in the early diagnosis of the heart transplant rejection, better accepted by surgeons and patients than the 48 h-scan. The early scintigraphy Is the appropriate tool for successful clinical application. The effectiveness of In-lll antimyosin (In-AM) imaging (Centoeor, Leiden) for detecting moderate and severe acute heart transplant rejection is well-known. In order to determine its reliability in mild transplant rejection, 14 pas (12 males, 2 females) were assessed by endomyoeardial biopsy on day of In-AM imaging. When possible, 2, 4, 6 and ig weeks after transplantation, planar imaging (anterior, LAO 45 ~ or LAO 60 ~ ) were performed 48 hours after injection of 92,5 MBq In-AM. Immediatelz thereafter patients were injected 30 MBq Thallium 201 to locate, in the same positions, accurate heart ROI. Quantification of antimyosine uptake was calculated from ROI analysis : heart to lung ratio (H/L) and heart to total body count, on day of imaging (H/B). Thirty-one scintigraphic studies were performed (2 patients ~ x, 2 patients 3 x, 7 patients 2 x, 3 patients 1 x). EME showed 6 mild rejections episodes (MR) and 25 without reject$on (NR). No statistical differences (Student test) were found regarding H/L (1.90 for MR versus 1.83 for NB) and H/B (24% for MR versus 23% for NR) in the 2 groups. In stable patients H/L ratio decreased significantly after the fourth week (p = 0.014). During the first 12 weeks, In-AM imaging could not differentiate mild rejection from no rejecting heart transplant although heart ROI outlines were precisely defined. One hundred twenty five examinations were performed on 25 patients who underwent heart transplantation, in a prospective protocol for noninvasive diagnosis and follow-up of acute cardiac rejection. The followup period ranged between 15 days and 40 months. The protocol comprises:

NUGA ventriculography with 99mTcalbumin (740NBq) acquired using forward-backward by thirds framing mode, 32 frames/R-R and i0 million total counts.

Parameters of left ventricular systolic and diastolic function were analyzed. Antimyosin antibody (AB) labeled with lllIn (74MEG) was injected i.v. and myocardium/lung uptake ratios were obtained at 48 hours in counts/pixel. Endomyocardial biopsy was performed on all patients in the same week.

The results were evaluated by comparison of the mean values of each parameter and global and individual correlation analysis in relation to the presence of rejection. The following parameters showed statistical significance at p ~ 0.01: let third ejection fraction (ITHEF) and peak emptying rate (PER). Significance at p < 0.001 was achieved for global EF (GEF), average emptying rate (AVER), peak filling rate (PFR), average filling rate (AFR), and AN ratio. The aim of our study was to assess on a routine base in a private cardiologic department the value of 1111ndium-antimyosin imaging for the detection of doubtfull AMI. 96patients were examined either in case there was no correlation between the clinic, the enzymatic and the ECG changes or when it was impossible to differentiate an old from a new lesion.Two to three mCi of lIIIndium-antimyosin were given intravenously and planar scans were performed after 24 and 48 hours.

Without the result of the scan the cardiologist presumed AMI occurred in 48: the scan was positive for 38, for 5 not convincing and 2 were considered a bad tag. For the 48 patients where AMI was not retained by the clinician the scan was positive in 14. In 12 the diagnosis of AMI was afterwards confirmed.In all cases count density index was highly correlated to the degree of wall motion impairment : 2.5 +/-0.52 for severe loss of function.

We actually consider antimyosin imaging a usefull examination in clinical practice,especislly for patients where AMI is a possibility but the routine diagnostic methods remain inconclusive. The result of the scan is defining further diagnostic examinations which can have more morbidity and which are not always easily available. 

To examine the incidence and the predictors of a positive In-111 antimyosJn scJnLigraphy in patients (pts) with unsLable angina (UA) we prospectively analysed 21 pts with UA and 8 pts with stable angina; pts were injected 2 mC] [n-111 on admission and scanning was performed 48hrs later. Symptoms and signs indicating the severity of JschemJa were monitored during the period between injection and scanning. No patient deve-.loped rise of cardiac enzymes suggesLing myocardial necrosis. 6 (28%) pts with UA had a positive antJmyosin scanning; no pt with stable angina had positive scan-nJng. All 6 pts with UA and positive scanning had signs .off severe JschemJa (4/6 pts multiple episodes > 2/day, ;3/6 pts prolonged > 10 mJn episodes, 2/6 pts ST r 3 EKG leads), while only 1/15 pts with UA and negative scan-nJng had signs off severe ischemia (p< 0.05).

In conclusion 1) a sJgnJfiicant number of pts with UA present positive antJmyosJn scanning without elevation of cardiac enzymes 2) these pts usually present multiple or severe episodes of JschemJa indicating that during these episodes minor myocardial necrosis, undetected by enzymes, may happen. Twenty-five type-i diabetic uremic patients (14 men~ ii women, mean age 40 +_ Ii years, range, 19 to 60) were prospectively analyzed for coronary artery disease (CAD] by thallium scan (TLS) before synchronus pancreas and kidney transplantation.

Duration of diabetes ranged from i0 to 32 years (mean 22.4 + 4.8). Fifteen patients (60Z) were in dialysis from 3 to 60 months (mean 20 + 22). Advanced diabetic degenerative complications were present in all patients. Twenty exercise and 5 pharmacologic TLS were performed.

Forty-four percent of patients (6 men, 5 women, mean age 42 +_ ii years, range, 26 to 60)' had a positive (reversible defects) TLS. In 2/11 cases, severe CAD required further cardiac investigations for therapeutic management decision. A statistical correlation with resting ECG non-specific ST-segment and T-wave abnormalities was observed (p < 0.05) despite the absence of angor in 8 out of the ii patients with positive TLS.

In this particular diabetic population (young age, male/female ratio = 1.2) with high incidence of silent ischemia, resting ECG repolarisation abnormalities, though predictive, were not specific or prognostic of CAD severity; in these cases, TLS, a non-invasive and sensitive cardiovascular test, may be of great interest in diagnosis of CAD, allowing adequate cardiac management before, during and after pancreas transplantation. Elevated serum TATI was found in 32 cases (45%) with positive predicted value of 85% for malignancy. TPA was elevated in 51 (73%), with positive predicted value of 82%.

We found that serum TATI corelates pleural effusion concentrations. Such corelation was not found concerning TPA concentracions. TPA was significantly higher in pleural effusion than in serum. The aim of this study was to evaluate the frequency of reverse redistribution (RR) after stress Thallium 201 SPECT (TI-SPECT) and to correlate it to coronary angiography (CA). RR, defined either as an early defect worsening { he~es later or as a new defect appearing on the delayed scan, was studied in 1030 consecutive patients (pts) . RR was {~<~<~d in 90pts (8.7%). 56 of these with correlative CA within 60 days of TI-SPECT

were inc]u3~d. 23 had a previous myocardial infarction (MI), 2 had CABG~ 24 were evaluated early after PTCA, i0 for diagnosis. 14 pts had treated hypertension.

79 RR segments were noted: 41 anterior wall, 28 inferior wail, i0 lateral wall. 28/79 were only delayed defects. These results were compared with CA: In the first analysis, the detection of presence of coronary disease (CD) was tested. Significant variables (var) were: i) history of angina pectoris (AP), 2) sex, 3) quantitative analysis (QA) of TL-S, 4) age, 5) ischemic ST-response (ST), 6) AP during the test and 7) the pressure-rate product. The sens., the spec. and accuracy of classification using the DFA were 91%, 87% and 90%. The sens. was significantly higher than using visual analysis (VA) (sens.=70%; p<-O.05) or QA of TL-S (sens.=66%; p<0.05) alone, without significant loss of spec. (p=0.55; p=0.69).

In the second analysis, a DFA was calculated to detect multivessel disease (MVD). Significant var were: i) number of vessels (NOV) predicted by QA, 2) NoV by VA, 3) ST, 4) sex, 5) AP during the test. DFA showed a significant increase of sens. when compared with VA (78% vs 55%; p<0.05) and QA (66%; p<=0.05), without loss of spec.

This study demonstrates that DFA of noninvasire test results in QA TL-S allows convenient use for clinical purpose with improved results. At the average the LH-ratio's in ANT-P and ANT-T were not significantly different; these ratio's increased significantly in cases of ischemia and in LVD as compared to nonischemic situations. No significantly difference with regard to the related coronary vessel was found. However, the LH-ratio's in CS did not show a relation with ischemia, nor LMD and differed significantly from LH-ratio's assessed from the anterior approaches. In all cases large ovedaps of LH-ratio's existed.

In conclusion, the LH-ratio should be determined in ANT-P or ANT-T, not in CS. However, because of large overlaps in the measurement data estimation of LH-ratio is not clinically useful for the detection of CAD or LVD in the iedivdual patient.

W Martin, A C Tweddel and I Nutton. Department of Medical Cardiology, Royal Infirmary, Glasgow G31 2ER, Scotland.

The use of myocardial perfusion agents to assess the effects of interventions, such as coronary angioplasty and thrombolysis, requires the comparison of sequential images. The aim of this study was to compare a simple method of visual analysis of defect size with a computer generated semi-quantitative regions of interest technique. Maximal exercise scans were obtained in 20 patfents with angiographically documented significant coronary disease using a mobile camera fitted with a high sensitivity collimator.

Images were gated to the electrocardiogram in the anterior, 40 ~ and 70 ~ left anterior oblique projections.

Visual analysis was performed by 2 observers, with each projection divided into 5 segments and each segment further divided into 3 and the image defect expressed as a percentage of the total left ventricle. The correlation coefficient for defect size between observers was 0.94, with a mean difference of 3.6 ~ 4.3%. This was then compared with a semi-quantitative technique, with a region of interest drawn around the image defect and expressed as a percentage of the left ventricular region of interest. The correlation coefficient between observers was 0.921 with a mean difference of 3.2 ~ 3.3%. The visual assessment of perfusion defect, expressed as a mean of 3 projections, and semi-quantitative values agreed well, with a correlation coefficient of 0.87 and a mean difference of 8.3 ~ 5.8%. The visual technique systematically overestimated defect size compared to the semiquantitative method. These results suggest that a simple visual assessment of perfusion defect size is both accurate and reproducible when compared to semi-quantitative computer assessments. 

Ti-Washout (WO) was thought useful primarily in diagnosing coronary 3-vessel-disease.

We suppose that washout values can also be helpful to exclude artifacts (e.g. breast tissue attenuation) and therefore to identify patients without significant coronary lesions. We analysed myocardial washout in 119 patients without evidence os CAD (no typical angina pectoris, at least inconclusive ECG, normal TI-SPECT) and 21 patients with significant redistribution in TI-SPECT. Methods: The washout bullseye display was divided into eight segments of equal size and washout values were registered regionally. Regions with maximal (W=ax) and minimal (Wmt.) washout were identified and arithmetric mean of all regions was calculated as well as the quotient Wml n/Wmax , Results: Mean washout in normals correlated well with peak heart rate (r=0,32; p<0,001) and slightly with blood pressure amplitude at maximum physical stress (r:0,19; 0.05~p)0,02). We found no correlation between mean washout in normals and age, duration of work, and workload. Mean washout ot patients with significant redistribution didn't correlate with any parameter. Compared to normals mean WO (28, 79t6, 35 vs. 35, 25) and Wmt,/Wmax (0,34• vs. 0,63+-0,17) was lower in patients with suspected CAD. Conclusion: A quotient Wmlu/W.ax>0,5 may be a further indicator to identify patients without significant coronary lesions. W=1,/W=ax<0,5 may be a suspicious fact for CAD. 

(RR) has been described as thallium perfusion defects in delayed (or rest) studies where stress images were normal. Several mechanisms for RR in coronary artery disease (CAD) have been proposed, among which: differences in wash-out speed, post-ischemic increased reperfusion or stress induced collateral vessels opening, but none is fully accepted.

Moreover Dipyridamole produces myocardial vasodilation and this pharmacological stress has been used as a substitute for exercise for thallium scanning. The aim of this study was to directly compare thallium scans obtained following both challenges.

We studied 22 patients, 20 of whom were male, with arteriographically documented coronary anatomy.

Symptom limited maximal exercise tests were performed, a mean of 50.7 F~Sq of thallium being injected during the last 15 to 30 seconds. Scans were obtained, gated to the electrocardiogram, using a mobile gamma camera fitted with a high sensitivity Inter-observer variation in reporting was higher for dipyridamole. Left ventricular thallium uptake was similar with dipyridamole 0.87 ~ 0.22% and 0.79 ~ 0.23% (nsd), but RV uptake was lower (0.09 i 0.06% vs 0.12 3 0.06%, p<0.05). Both lung to LV (1.78 i 0.48 vs 1.47 ~ 0.505 p<0.O02) and liver to LV ratios (2.60 3 0.79 vs 1.27 -0.39, p<O.O01) were higher with dipyridamole.

These results suggest that dipyridamole is a less effective myocardial stress than dynamic exercise. The degree of aortic stenosis (AS) can be assessed noninvasively by Doppler -echocardiography. However,the high frequency (20 -60%) of concomitant coronary artery disease (CAD) necessitates invasive preoperative evaluation. This study was performed to evaluate dipyridamole -201thallium SPECT (dip-SPECT) for diagnosis of CAD in patients with severe AS. Patients and methods: 60 adults with AS, mean valve area 0.7 cm2,mean age 68 years. A visually assessed angiographic area reduction of at least 75% was considered significant CAD. The protocol for dip-SPECT was: 0.56mg dipyridamole/kg iv during 4-9 min, 2 min thereafter 74MBq 201thallium, 4 min later ll5mg theophyllamine. ECG and blood pressure was monitored. SPECT directly and 3-4 h later. Slices were visually assessed for the presence of reversible defects (revdefs). The study was approved by the Local Ethics Committee. Results: 17 pats experienced chestpain, relieved by theophyllamine. No serious complications were seen. 24 of 27 patients with CAD had revdefs (sens 89%). Revdefs were present in 16 patients with absent or minor CAD (spec 52%). Conclusions: Visually assessed dip-SPECT is sensitive in assessing the presence of CAD in patients with severe AS. The low specificity may depend on the visual analysis,on imperfections in the reference method and on decreased coronary blood flow reserve in pats with AS. THALLIUM MYOCARDIAL PERFUSION IMAGING USING DOBUTAMINE; AN ALTERNATIVE FORM OF STRESS Dobutamine is an inotrope which raises myocardial oxygen demand and increases coronary blood flow. Its 90 second half life, low arrhythimic potential and peripheral administration make it ideal for cardiac stress studies without the need for dynamic exercise. This study evaluates its use for thallium myocardial perfusion imaging. Twenty four patients with stable angina underwent thallium tomography. Dobutamine was infused in increments from 5 to 20ug/kg/minute or until the occurence of symptoms. Nine segments of myocardium were each graded for thallium uptake as normal, reduced or absent Reversible ischaemia was defined as improvement by at least one grade after redistribution. Coronary angiography showed that 21(88%) patients had coronary artery disease (3VD-6, 2VD-II, IVD-4) and of these, 20 had reversible thallium defects. The mean number of segments showing reversible ischaemia was 1.7, 4.3 and 5 for 1,2 and 3 vessel disease respectivily. The mean increase in double product was 34%, 57% 87% and 104% for 5, 10, 15 and 20~g/kg/minute respectively. No symptoms were experienced in four patients but the infusion was limited by chest pain in 19 and by nausea in one. Arrhythmias were seen in eight patients, extrasystoles (ventricular 6, atrial i), sinus pauses (i) and accelerated nodal rhythm (I), but none of these was haemodynamically significant. Non-cardiac side effects affected 18 patients, most commonly skin tingling(ll). Dobutamine is an effective, safe and well to-lerated~stressor. Its actiqn:is easily controlled ~aking it attractive not only for thallium imaging but also f r more rol ned "ma i g techni ues such as. The aim of the study is to measure the quantitative lower limb blood flow in peripheral arterial occlusive disease in monitoring the effects of theraphy.

We measured the lower limb blood flow in 5 control subjects(lO limbs) and 6 patients(22 limbs totally) before and after Prostoglandine E~(PGEI) theraphy.According toFontaine's classification,the patients were in the third and fourth grade of peripheral arterial occluff sive disesses. All the patients hadalready been treate medically and had sempatectomy.The patients were positiq ned supine with legs over a large field of gamma camera, Pneumatic cuffs were wrapped around each leg below the knee and were inflated to 300 mmHg to isolate the blood from the rest of the circulation.lO MBq Tc g9m HSA(huma~ serum albumin)was used as a tracer.The cuffs were released 3 minutes to induce a hyperemic response.The data was acquired in every second for I00 seconds.THe mean flow per unit of volume was measured from the least square gradients of the time activity curves,and a sample from the venous blood.The results were compared with doppler and thermography.

For the control group the mean flow per unit of volume was 16• ml/lO0 ml/min.For the patient group ,it was 3.1tI.3 ml/lO0 ml/min in the affected leg before the theraphy.After the treatment it was measured 4.8~2.4 ml/lO0 ml/min.The mean flow of the normal legs were raised to 16• ml/lO0 ml/min, from 6.7+-15.I ml/lOO ml/ m~n.These results were comparable with the clinical signs,doppler and thermography.

In conclusion ,this method has advantages over other methods such as doppler or thermography in that this gives absolute measurements of flow per unit of volume.

Thigh and calf scintigraphies were performed in 6 patients (5 patients between the grades II and III and 1 patient in grade IV according to Fontaine's classification) affected by peripheral arterial occlusive disease in order to assess a possible vasodilator effect of the SCS. Study of perfusion distribution in the legs during stress and during the resting state were performed before and after three months of treatment with SCS. 2OLTI -2 mCi were administred i.v. during typical claudication inducted by time variable walk. Static posterior views were performed over thighs and calves each one of 10 minutes of duration, 2 minutes and 2 hours after injection. The distribution of perfusion between the two extremities was defined with thigh to thigh and calf to calf ratios (affected/unaffected leg), with background correction. Results. Before SCS the uptake in the affected leg was lesser than the unaffected one both during stress and redistribution, without significant variation. The means (SD) of the therapeutic effects of SCS were:

TOTAL MIDCALF After SCS we observed a significant uptake increase in affected leg for the mildcalf and the total calf (p<0.05). This improvement was evident only during exercise, in contrast to the redistribution findings in which the changes were not significant. Only the IV stage patient had no variation neither on signs and symptoms nor in perfusion ratios. 2OlTI muscle scintigraphy appears to be adapted to quantify the functional results of this treatment and to evaluate the microcirculatory state in patients. 201-TI SPECT of both stress and distribution was perfor med in 15 pts with PVD previously documented by clinical and instrumental examination(doppler,contrast peripheral arteriography)and i0 healthy subjects. Stress test was ta ken by applying a cuff to the thighs of each patient. After ischemia(raising the manometric pressure to 50 m~H~ above SBP for 3 min)3 mCi of 201-Ti was rapidly injected and after i0 min. SPECT imaging of legs was begun using a large field gamma camera GE with GP collimator rotating around the patient's legs in a 360~ took 64 views for 20 sec/view and stored using 64x64 matrix.After 3 hr,re distribution imaging was performed using the same method. The trasverse axial tomograms was reconstructed by filte red backprojection. For a quantitative evaluation of 201-TI legs SPECT were reconstructed 21 slices( 19 mm thick) from knee to ankle of both legs displayed as "profile curves".Our results show a good correlation between arteriographic findings,doppler velocimetry alteration and leg SPECT (12/15 pts;80%);3 pts instead showed a normal profile curves. In conclusion 201-TI leg SPECT analysis can provide quantitative information and permit an objec tire and reproducible test in detecting ischemia of leg muscle. The success of therapeutic embolization of systemic AVMs is usually evaluated clinically and angiographically, neither of which are quantitative. We describe a technique of assessment of blood flow through systemic AVMs pre-and post-embolization utilising the microsphere like properties of Xe-133. This inert gas, which is extracted by the lungs in a single pass, was injected as a bolus into the main artery supplying the territory of an AVM. Gas which bypassed peripheral tissues via the shunt was recorded as an early signal by a detector over the lung whilst the remaining gas appeared later due to normal slow transit through the peripheral tissues. Successful embolization was identifiable as a reduction of the amplitude of the early activity signal over the lung. The reduction was quantifiable by comparison of the signal with that produced by the same dose of intravenously injected Xe-133.

In 5 control injections, no significant early signal (i.e. before 15 seconds) was seen whilst 12 patients with AVMs there was a clear early signal.

Following embolization, the reduction in shunt flow was highly variable ranging from 10%-95% with a mean of 36% + / -SD 29%. This simple inexpensive technique could provide the interventional radiologist with continuous quantitative monitoring of the efficacy of embolization. MEASUREMENT OF BLOOD LEAKAGE TO THE SYSTEMIC CIRCUIT DURING REGIONAL CHEMOTHERAPY OF MALIGNANT MELANOMA. In order to avoid ccmplications during regional chemotherapy the measurement of blood leakage to the systemic circulation is very important. We tested two methods for intraoperative and postoperative measurement and three formulas for the calculation of such systemic leakage. In four patients participating in the present study the tumor was localised on the lower limb. Four divided dosages of melphalan were injected in time intervals of ten minutes into the extracorporal circuit. Ten minutes after in vivo labelling of red blood cells(RBC) with 150 MBq of Tc-99m and the administration of 300 KBq of 1-125 human serum albumin (HSA) the blood samples preceded every bolus and the last one was taken I0 minutes after the last administration of mel phal an. By the help of a mobile well counter w~ were able to measure the Tcactivity and to calculate the systemic leakage intraoperatively. So the operating team was able to regulate the blood flow in the perfusion circuit according to the actual test results. Several days after the perfusion an automatic gamma sample changer measured 1-125 activity. The systemic leakage was calculated for both Tc-and I-activities by three different fonTulas for each perfusion interval. During perfusion the total activity show a mean decrease of 29.3 + 16.4 %(Tc) and 19.0~.5 %(I) respectively. The fomula (CAs(t) -CAs(t-I))~-V s D L<t ......

was best suited for the calculation of the sysT.em,~ leakage. We found leakages from 0 to 19 % (6.5+6.1%) in Tc-99m RBC labelling and of 0-20 % (17.8~27.1%) by 1-125 HSA. The corresponding flow rates from the extracorporal to the systemic circuit are 0-28.5 ml/ rain (9.7+9.3 ml/min) for RBC labelling and 8.4-30.6 ml/min (17. _9!8.9 ml/min) for 1-125 HSA. In free flap surgery with microvascular anastomoses 12mph vessels are not reconnected. In animals lymphatic regeneration is observed two weeks after limb replantation. In humans only scarce evidence exists that lymphatic regeneration occurs on the long run.

We studied lymphatic drainage in eight patients after flap surgery. Tc-99m-nanocolloid was injected subcutaneously in the flap and in the contralateral normal site, avoiding intravenous administration, at 5 days and 2 and 6 weeks after operation. In four patients the study was once repeated after a year. Seintigraphy of the injection sites, the regional lymph nodes and the liver area was done immediately after injection SEnd 2, 4, 6 and 24 h later. Digital data was obtained simultaneously for calculation of the tracer disappearance rate at the injection sites and the accumulation in lymph nodes and liver.

At the flap side hardly any radioactivity was present in the regional lymph nodes at day 5, 2 and 6 weeks. However the disappearance rate from the flap did not differ f~om the disappearance rate at the control site. Soon after injection part of the tracer was present in the liver. In the four patients studied after 1 year the disappearance rate from the flap was similar, but now the regional lymph nodes were visualized intensively while the liver uptake was minimal. In conclusion: lymphatic drainage from a transplanted free flap is taken over by the venous system during the first 6 weeks, thereafter lymphatic regeneration occurs. Nisoldipine is a newly developed calcium channel blocker with outstanding vasodilatory properties especially with regard to the coronary arteries. Thus it may find widespread application as a therapeutic agent in various ischemic heart disease syndromes.

The purpose of this study was to evaluate the effect of nisoldipine on the diastolic function of the left ventricle (LV) in the clinical situation.

A patient group on nisoldipine treatment was compared to a control group. In the nisoldipine group a maximum decrease of 17mmHg in the mean systolic blood pressure with an increase in the mean peak ejection rate (0.78 EDV/s) and peak filling rate (0.52 EDV/s) were observed. Mean LV ejection fraction increased by 6.4% and the time to peak filling rate decreased by 36.5 ms. After eight weeks of treatment the acute effects of nisoldipine were similar to the previous study. Nisoldipine therefore tends to improve both the diastolic and systolic function of the left ventricle. To determine the differences in global myocardial 201-T1 uptake and redistribution in left ventricular hypertrophy (LVH) in comparison to normal myocardium 2 groups of pts were investigated by means of 201-TI scintigraphy during submaximal exercise test. llpts of ist group had LVH due to hypertrophic cardiomyopathy with left ventricular myocardial mass index (LVMMI) more than 90 gm/m 2. 2nd group consisted of ii sugjects without LVH (LVIfMI less than 80gm/mn). The mean values differed signifacantly in two groups (121.5 • 8.1 vs 59.4 • g/m Z, p<0.001). Precardial radioactivity (PRA) measured as a percent of injected isotope dose was significantly greater in LVH than in control group (9.5 • vs 6.2 + 1.3%, p<0.05). However the relative activity calculated as PRA/ myocardial mass ratio was lower in pts with LVH (0.045 • vs 0.0062 • 0.003%/gm, p=0.05). We consider this phenomenon is caused by decrease relative per• s• (latter is characterized by PRA/mass ratio) is supported by a significantly lower isotope washout during 3h after 201-TI injection (34.6• vs 46.0• In control group, p<0.05). All mentioned above explains a bad correlation between LVMMI and PRA In HCM patients during exercise, whereas those parameters at rest correlated strongly (r=0.85 p<0.01) In 8 of these pts who underwent 201-TI scintigraphy as well at rest. A challenge in the all digital approach to acquisition, display, and processing of nuclear medicine images is the ability to generate hardcopy images for distribution to referring clinicians. While video format devices exist which can print images to x-ray film, this process is expensive and conflicts with a main reason for utilizing a digital approach. Standard 300 x 300 dot per inch (DPI) laser printers have been proposed as hardcopy devices, since images can be included with text reports, but resulting images lack the spatial and gray scale resolution of traditional analog film output.

We have investigated the use of a prototype laser imaging device with resolution of 400 x 1000 DPI, 4 times the standard data density. Software drivers were written to convert digitally acquired nuclear medicine images into standard formats used by the laser printer. Images were printed on plain paper using various line screens and gray scale patterns and then compared to their video display and analog film counterparts.

While not equivalent to analog film or high resolution video images, laser images of 91 lines per inch and 48 gray levels were of diagnostic quality, even when used for high resolution whole body bone scans. We are presently using the system for approximately 50% of our clinical studies. The ability to routinely obtain images with reports has been enthusiastically received by referring physicians.

We developed a Macintosh II-based, charge-coupled device (CCD), image digitization and analysis system for high-speed, highresolution quantification of autoradiographic image data. A linear CCD array with 3500 elements was attached to a precision drive assembly and mounted behind a high uniformity lens. The drive assembly was used to sweep the array perpendicularly to its axis so that an entire 20 x 25 cm autoradiographic image-containing film could be digitized into 256 gray levels at 50 micron resolution in less than 30 seconds.

The scanner was interfaced to a Macintosh II computer through a specially constructed NuBus circuit board and software was developed for autoradiographic analysis. The system was evaluated by scanning individual films multiple times, then measuring the variability of the digital data between the different scans. Image data was found to be virtually noise free. The coefficient of variation averaged less than 1%, a value significantly exceeding the accuracy of both high-speed, low resolution, video camera (VC) systems as well as low-speed, high resolution, rotating drum densflometers (RDD). Thus, the CCD scanner-Macintosh computer image analysis system offers the advantage over VC systems of the ability to digitize entire films containing many autoradiograms, but with much greater speed and accuracy than those of RDD scanners.

Karin Kne~aurek, University of Rochester Medical Center Rochester, New York, 14642. U.S.A.

The purpose of this study is to combine SPECT and CT images of the same sections. SPECT images are usually 64x64 matrices while CT images are 256x256 or 512x512 matrices. There is not only a problem in the different size of the matrix representations, but the images of the same sections very often are slightly tilted respectively to each other. So in addition to normalization of the pixel values between the two studies, corrections for image orientation involving two-dimensional translation, rotation, scaling and stretching were also performed. To investigate the probl6~s connected with adjusting and alignment of the SPECT and CT images, a specially designed phantc~ RH-2 was used. It consists of right and left ventricle and body unit. Lungs were simulated with wood powder and thoratic vertebra with teflon. Remaining space was filled with water. An insert 3 cm in diameter and 1 em high was placed in posterolateral position. Standard CT and SPECT acquisitions were performed and corresponding sections reconstructed.

For SPECT acquisition activity of 37 MBq and 9 MBq were uniformly distributed in the "ventricle wall" and right ventricle, respectively. CT images gave nice boundaries and shape descriptions while SPECT images gave "active regions". The results of our phantc~ study show that composite SPECT-CT imaging permits close correlation of the functional information of SPECT with the anatc~lic images of CT. Ccmloosite images were also used to investigate geometrical distortion in 180 ~ and 360 ~ TI-201 SPECT studies. Tc-99m DMSA Scintigraphy is a useful tool for the evaluation of renal parenchymal pathology.But the interpretation of planar images has some problems because of the interferance of the extraparenchymal structures and position of the kidneys.SPECT images provide a lot of additional useful information for the better evaluation of renal functional parenchyma.In this study we have evaluated the usefulness of 3D reconstruction in addition to the SPECT images for the interpretation of renal parenchyma. 56 kidneys of 26 patients have been evaluated usi ~ fig Tc-99m DMSA planar and SPECT renal scanning including 3D reconstruction.The pathological appearances in all three image series have been compared with ea-cH other in term of renal parenchymal lesion and its location,size with correspondance to the whole kidney and easy interpretation.

In conclusion,coronal SPECT images were found to be valuable especially in the evaluation of lower and upper pole lesions of the kidney.On the other hand, the routine use of 3D images seem to be potentially valuable in adding third dimension to images and give more information about the position,size,shape of the kidney and size of the lesion compared to the whole kidney,but it shouldn't be used alone for interpretation.

H. Natsuda, S.D. Oskoie, S. Tsuji, K. Hisada, R. Futatsuya*, N.

Kanazawa University Hospital, Kanazawa, and *Toyama Medical Pharmaceutical University Hospital, Toyama, Japan.

THREE-HEAD ROTATING GAMMA CAMERA SYSTEM. Excellent SPECT images of brain perfusion with Tc-99m HMPAO were obtained in three normal volunteers using a newly developed three-head rotating gamma camera SPECT system (Toshiba, GCA9300A) with high resolution (FWHM 7mm) and high sensitivity (30cps/KBq/ml for Tc-99m) equipped with fan-beam collimators made of tungsten. One GBq of Tc-99m HMPAO was intravenously injected. Acquisition of projection data was started from 5 min postinJection and lasted for 25-30 mln. Projection data were accum~llated in 256X256 format for 30 angles (4 ~ step, 120 ~ ) with 50 sec -I rain per angle for each detector. Transverse, coronal, and sagittal sectional HMPAO-SPECT images are closely correlated with corresponding brain magnetic resonance images of the same normal volunteers. The basal ganglia and thalamus were clearly delineated in details. The activities of head of caudate nucleus, putamen, and insula, were separately visualized from one another. Moreover very fine details of functional brain anatomy was obtained in such as pituitary gland, pulvinar of thalamus, dentate nucleus of cerebellum, red nucleus, hypothalamus, hippocampus, and cortical Eyruses that have never seen before. These SPECT images should be clinically effective in the evaluation of anatomo-functional correlation in various neurologic disorders. In conclusion this new SPECT system should serve as high resolution brain perfusion imaging in addition to offering anatomic information for identification of perfusion abnormality. We used high spatial resolution PET in order to evaluate the cerebral metabolic aspects of Alzheimer's disease (AD) in early phase. Nine patients with probable AD (according to NINCDS-ADRDA criteria) of recent onset (less than two years) underwent a quantitative 18F-FDG study with ECAT 931/04-12 (CPS-Siemens, Knoxville, Tenn, USA) tomograph. All patients had also MRI and extensive neuropsychological examination. The following metabolic patterns where observed: a) "typical" bilateral temporoparietal reduction in 5 out 9 cases (F/P and F/T ratios = 1,32 + 0,09 and 1,19 + 0,12 respectively); b) hemispheric asymmetry in2 patients with lateralized cognitive deficits (R/L ranging from -12% to +27%); c) extensive cerebral impairment with also marked frontal involvement in two cases. A subcortical involvement was also showed in 3 patients with thalamic and basal ganglia asymmetry ranging from-13% to + 21%. A crossed cerebellar diaschisis was present in 4 cases ( R/L cerebellar hemispheric asymmetry range:-18% to +8,1%)and this was not associated with cerebellar symptoms. In conclusions "typical" and "atypical" cortical metabolic patterns are present in early AD as well as subcortical and cerebellar involvement. These PET findings can be related to different clinical subtypes of the disease. 

18F-FDG and high spatial resolution positron emission tomography (ECAT 931/04-12 CPS-SIEMENS, Knoxville, Tenn, USA) was used to measure cerebral metabolism in 15 patients with definite multiple sclerosis (age 40.1 + 10.2; duration of illness 8.7 +_ 5.9; Expanded Disability Status Scale (EDDS) 3.4 +_ 2). A bilateral reduction of metabolism in the frontal and temporal Iobes was a common finding (13/15 and 7/15 respectively), as well as sensorimotor (9/15), thalamic (5/1 5) and cerebellar (1 2/1 5) hypometabolism. The following clinical/metabolic correlations were found: a) patients with severe neurological impairment (EDDS>4) had the most extensive cerebral hypometabolism; b) in most patients neuropsychological tests showed cognitive impairment which could be functionally related to local hypometabolism; c) in 4 patients with lateralized neuropsychological deficits cortical and/or subcortical metabolic asymmetry with 32% + 11 reduction in the functional related hemisphere was demonstrated. In multiple sclerosis, these PET metabolic findings might reflect a deactivation of cortical, subcortical and cerebellar areas induced by widespread white matter lesions. These distant effects might also explain the cognitive impairment demonstrated in most of the patients. PET with F-18-deoxyglucose (FDG) enables the quantification of the metabolic activity of tumors prior and during chemo-or radiation the rapy. The goal of this study is to use PET for evaluation of the changes in tumor FDG-uptake as response to the given therapeutic protocol and compare the chaoges in uptake to tumor volume. Each patient is studied prior to therapy with subsequent follow up starting after the second chemotherapeutic cycle. We performed endpoint measurements 50 rain post intravenous injection of 440 MBq FDG iv. and acquired 5 min transmission scans and 15 min emission scans. FDG uptake was quantified by the standardized uptake value (SUV) as determined by ROI measurements and normalized for injected dose and body volume. We studied 30 patients prior to therapy. 18 patients finished the follow up period, 14 receiving chemotherapy, 1 radiotherapy and 3 a combined protocol. All histologies were confirmed by either medianoscopy or biopsy. 12 patients carried small cell, 3 adeno, l squamous, 1 pleuramesothelioma and l metastases of a breast carcinom~L On the follow up studies 4 patient showed increased, 2 unchanged aml 12 decreased FDG uptake. We found a direct relation between decreased FDG uptake and clinical response (12/12) and unchanged or increased uptake with no response to therapy (6/6). The tumor volume decreased in 4 and remained unchanged in 2 cases of the 6 patients showing no decrease in FDG-uptake after therapy. The tumor volume remained unchanged in 4 and decreased in 8 of the 12 patients showing response aud decreased FDG-uptake after therapy. Our results indicate that the change of FDG uptake to therapy is more reliable and timely available than the evaluation by change in tumor volume. A ready selection of patients not benefiting from the given therapy (6/18) facilitates optimized therapy management. Fluorouraeil (FU) had found use for chemotherapy in metastatic co-Ioreetal carcinomas for more than thirty years. Since response to FU chemotherapy necessitates the accumulation of the cytostatic agent in the metastases, measurements of the FU metabolite concentrations should be performed prior to chemotherapy. While MR spectroscopy had been used for FU concentration measurements in the liver parenchyma, PET studies with F-18 labeled FU can be performed to quantify the metabolism of the cytostatic agent in the metastases. We used PET to evaluate the FU metabolite concentrations in 18 metastases prior to FU chemotherapy. CT preceeded each PET study in order to determine the target area and to calculate the tumor volume. All patients received FU chemotherapy after the PET study. Follow-up CT examinations were performed and the tumor volume was measured from the CT images. The tumor growth rate was calculated from the volumetric data and compared to the PET measurements of the FU metabolite concentrations prior to therapy. A linear correlation (r=0.8) was obtained for the standardized FU metabolite concentrations (SUV) and the growth rate. Cluster analysis demonstrated three groups: SUV <2.0 was correlated with increasing tumor volume; SUV 2.0-3.5 was associated with stable disease; SUV >3.5 was observed in lesions with decreasing volume. Our data demonstrate, that PET can be used to estimate tumor growth prior to FU chemotherapy and should find use for chemotherapy planning. On-line detection has been described for continuous measurement of whole blood concentrations 9

However, for many tracer studies plasma rather than whole blood time activity curves are required 9

Although in theory plasma curves could be obtained using on-line plasma separators, this approach has not been successful yet due to instabilities of the small separators required, In the present study a semi-automatic method for the measurement of plasma input functions was developed,

The method involves monitoring arterial whole blood concentrations using continuously withdrawn whole blood and an on-line BGO detection system, At set times calibration blood samples are withdrawn.

Whole blood and plasma concentrations of these samples are measured in a cross-calibrated well counter and a number of them are assayed for metabolite levels.

The whole blood concentrations obtained from the calibration samples are used to perform a first order correction of the continuously measured arterial whole blood curve for dispersion within the detector tubing. Secondly, the plasma to whole blood ratios of the calibration samples are fitted to a multi-exponential function, Finally, the measured metabolite levels are also fitted to an exponential function.

The continuous whole blood curve is multiplied with these functions to obtain a continuous metabolite corrected plasma curve, This method was applied to tracer studies with I~C-1-deprenyl and 110-citalopram. Non-linear regression analysis of these tracer studies using suitable compartment models was independent of the fitting interval used, indicating that the performed corrections provide stable results. Different chemotherapeutic protocols had found use for the treatment of patients with metastatic melanomas 9 We used PET in these patients in order to quantify the metabolic activity in the metastases prior and after therapy. The evaluation includes 10 PET studies in 5 patients. CT examinations preeeeded PET in each patient to determine the target area. PET studies were performed with intravenously injected FOG (370-444 MBq), followed by sequential imaging for 60 minutes. Standardized uptake values (SUV) were calculated from the iteratively reeonstrueted cross sections using a ROItechnique. The FDG uptake in lymph node metastases was 2.1-13.1 SUV prior to therapy. Lower values were observed in bone metastases (1.3 SUV), while the FDG-uptake was 2.5-3.0 SUV in metastases of the adrenal gland. Comparable results were obtained m hver metastases (2.5-3.4 SUV). Follow-up studies after chemotherapy with fotemustin (200 mg, 30 min infusion ) showed a 3 % decrease in tumor metabolism 90 minutes after chemotherapy. The decrease in FOG uptake was 9 % and 26 % one and two days after therapy and remained constant for one week. The median decrease in FOG uptake following chemotherapy was 27.5 % Our results show, that PET with FDG can be used to quantify early chemotherapeutic effects on tumor metabolism. Furthermore, the duration of the eytostatic effect can be demonstrated by PET. Therefore, different chemotherapeutic protocols may be compared on the base of PET studies. M.C.Gilardi, G.Rizzo, V.Bettinardi, G.Lucignani, F.Fazio.

A QUANTITATIVE TECHNIQUE FOR BIODISTRIBUTION STUDIES OF POSITRON EMITTING RADIOTRACERS.

The rectilinear scan acquisition technique in the transmission and emission mode allows the study of density and radioactivity distribution respectively. In this work the rectilinear scan procedure has been modified on a current generation PET scanner (Siemens 931/04-12), in order to compensate for radiation attenuation in the body and to correct for the radioactive decay during the acquisition time. Attenuation compensation consists in the following steps: 1) blank scan, B; 2) transmission rectilinear scan, T, of the object under study, before radioactivity administration; 3) calculation of a map of attenuation correction factors, F=B/T=exp(ux), u and x being the attenuation coefficient and the thickness of the object along the projection line respectively; 4) emission rectilinear scan, E, of the radioactive object, after radioactivity administration: attenuation correction is performed on line, by simple pixel by pixel multiplication E*--ExF. Compensation for the radioactive decay is achieved on a row by row basis, by knowledge of the acquisition (matrix filling) technique. Calculation of a cross-calibration factor allows the calculation of absolute radioactivity distribution. Experimental measurements on cylindrical phantoms, under different attenuation conditions, have been performed. Quantitative accuracy of the technique in the estimation of the activity present in the phantoms has been found to be within 6%. This modified rectilinear scan acquisition mode allows in viva quantitative biodistribution studies of positron emitting radiotracers in animal and man. Magnetic Resonance Imaging and Ultra-sound in anatomical diagnosis of hypertrophic cardiomyopathy.

In 40 consecutive pts with hypertrophic cardiomyopathy, we try to localize the distribution of LV hypertrophy in order to distinguish pts with asymetrical septal (AS) from those with concentric hypertrophy (C).

Triggered, diastolic, TI weighted, long axis paratransversal MRI slices were compared with conventional M-Mode and wide angle 2D echocardiography (US). AS was diagnosed when diastolic septal thickness (ST) was 1.3 time free wall T (FWT).

Both methods showed a morphological agreement (2~ pts, AS + C) and s~milar ratio ST/FWT (US = 2.01 -0.59 ; MRI = 1.87 0.37) in 18 pts (with AS). In 6 pts MRI and US were discordant. In 9 pts either MRI or US provide non diagnostic imaging and so, were complementary. Better agreement was obtained between IRM and US measurements when long and short axis slices were performed.

Thus, when US failes to differenciate AS from C, MRI may supply it, provided that slices were recorded in parallel and/or perpendicular planes to LV major axis. In other cases MRI and US show good agreement. Since 1982 trensluminsl bellasn engioplasty has been performed in children suffering from ccarctation of the aorta. The most severe postinterventional complications -aortic aneurysm end restenosisrequire regular follow-up. Beside the routine use of echocardiography, engiagraphy, end CT, the value of MR imaging as a noninvasive method was to be investigated. 18 children ( 13 boys, 5 girls) underwent MRI within 4 months to 4 1/2 years after dilelation. ECO-triggered l'l-weighted SE sequences were used in transverse and paraxial segittal slice orientation parallel to the aortic arch.

3 children showed pathological changes of the aw',.ending aorta, 2 of them had a moderate ectesy, only one had a severe dilatation of >5 cm In diameter. The aertic arch was normal in 14 ceses, 4 children showed small diameters. The origin of the left subclavian artery was displaced distally in 7 patients. In all cases mild to moderate changes of the wall or the lumen were observed at the site of CoA. The descending aorta was moderate spindly dilated in 10 children. In two c~es s circumscribed aneurysm was found. All findings corresponded well with those of angiagrephy.

The comparison with clinical examinations end angiagraphic findings showed, that I'IRI as a noninvesive method can be applied preferably In the fallow-up Of patients after engioplasty of ccarctetion of the aorta, especially in children. 50 patients with Graves" ophthalmopathy and 9 controls were studied at 0.5 T. 21 patients underwent follow-up exams after 12-18 months. Tl-weighted and T2-weighted spin-echo images were obtained in axial and coronal orientation and T2-times of inferior rectus muscles were calculated. 28 patients had typical eye muscle enlargement on their initial exam. Areas of high signal intensity on T2-WI were found in 19 of them; these changes could be interpreted as eye muscle edema. In 5 patients signal of presumably fibrotic eye muscles was low and T2-times below the normal range. On TI-WI fatty enclosures were found in eye mucles of 3 patients. T2-times of involved eye muscles in stage III and IV patients were found to be significantly (p<0.05) higher than those of controls. During follow-up T2-times returned to normal in 12 out of 21 patients, reflecting clinical improvement. Differentiation of eye muscle changes in Graves" ophthalmopathy by MRI may have a strong impact on application of anti-iflammatory medication. The aim of this study was to evatuate the usefulness ofperfluorocarbon emulsion perfusion in energy restoration for transplant organs. This was investigated using an in vitro perfusion heart model with hearts from slaughterhouse pigs and a 4.7 Tesla/40 cm NMR spectroscopy system. Pig hearts were harvested in the slaughterhouse 10 min post mortem, reperfused with blood, preserved with 4~ Bretschneider solution and stored for 1 hr. Then the hearts were reperfused with oxygenated perfluorcarbon emulsion at 25~ (n=3) and 10~ (n=3). P-31 magnetic resonance spectroscopy was performed at 81 MHz with a 5 cm diameter surface coil before and during reperfusion. PCr and ATP regeneration was achieved in all six experiments, the results of the 6 hearts PCr/Pi ratios are summarized in the figure.

IPCr(Pi25r IPCr/P]2[r APCI/Pi25c3 0PCr/Pil0 9

HPCr/Pil0c2 /~PCr/Pil 0c3 I~ 1,5 9 10 ; 1'0 10 3; ;0"5'0 10 70 Time of reper fusion with PFC emulsion (rain)

In conclusion, reperfusion of the pig heart with a synthetic perfluorcarbon emulsion can restore the intracellular high energy phosphates PCr and ATP. PCr and ATP regeneration seems possible even at low temperatures as 10~ and 25~ respectively. These findings could be important for clinical organ preservation, in that restoration of metabelism, at least partially, by a simple preoperative perfusion procedure could allow partial resuscitation of organ function before implantation. In addition, using P-31 NMR spectroscopy for on line monitoring of high energy phosphates might attow pretransplant pro spective discrimination of well recovering organs and organs compromised during storage. The aim of this study was to develop a system for recording F-19 images, spectra, and relaxation times with a standard H-1-tomography-birdcage-resonator with applications to organ models perfused with PFC emulsions. The developed simple hardware modification allows changing the spectrometer frequency from H-1 to F-19 resonance and vice versa without removing the object under investigation. This hydrogen/fluorine retuning tomography (HYFY) technique, developed on a 4.7 Tesla/40cm MR system, permits studies of identical slices or volume elements with H-1 as well as with F-19 resonance. In particular, it is possible to localize volume elements on the basis of multislice proton images and to investigate these volume elements with fluorine magnetic resonance spectroscopy. The pulse sequences including localized and spectroscopically resolved determination of spin-lattice and transverse relaxation times have been developed. Application of these techniques to phantom samples, pig kidney and pig heart perfusion models which have been perfused with PFC emulsions allowedF-19 imaging with a 256 matrix, 1 cm slice thickness and good image quality in 40 min, comparable to proton imaging in 4 min. F-19 spinlattice (T0 and transverse (T2) relaxation measurements are possible within less than 10 minutes. This might allow indirect measurements of 02 concentrations and O2 consumption in tissue perfused with PFC-O2 solutions as blood substitutes, since different saturation of PFC with 02 causes different T1-and T2-relaxation times of fluorine. In conclusion, the HYFY technique with a standard proton resonator pemaits the simultaneous record of H-1 and F-19 images, F-19 spectra, and F-19 relaxation times in mammalian organs within reasonable time. The technique described is easily transferable to whole body magnet systems. In this study, a simple liver perfusion model is presented useful for a large variety of metabolic experiments applying a 4.7 Tesla/40 cm NMR spec~xoscopy system. 32 pig livers harvested 10 min post mortem in the slaughterhouse were studied with 5 different perfusion protocols to evaluate and define conditions for optimum liver preservation: (1) In conclusion, an easy, non-expensive liver perfusion model using livers from slaughterhouse pigs together with P-31 MRS is feasible, allowing successful liver preservation for up to 24 hrs. The proposed perfusion model meets the needs of large scale experimental protocols, and may thus decrease the need for animal sacrifice in medical liver research. We have investigated the possibility of quantifying in vivo from positron emission tomography data, the myocardial fl-adrenergic receptors concentration. A kinetic method appearing difficult to use because the presence of metabolites which led to an input function difficult to measure, a graphical method based on a particular protocol has been proposed. An injection of a trace amount of Cll labeled CGP 12177 (dose D~), an antagonist of the adrenergic receptor, was followed 40 rain later by a simultaneous injection of Cll-CGP (dose D~) and of CGP (dose D1). Shortly after the two injections, the myocardial PET curve presents two plateaux at the concentrations C~ and C~ respectively which can be graphically measured. A additional injection of an excess of unlabeled CGP was administred at the 90 th min in order to estimate the dissociation constant.

This protocol has allowed to evaluate, in each animal, the concentration of the available receptors (B~az) which is obtained by solving this nonlinear equation:

whose B~a z is the unknown and whose the injected doses and two graphical measures are known coefficients. This method has the main advantage of not using an input function which is substituted by the hypothesis on the proportionality between the injected dose and the free ligand concentration. The average value of B~,~ obtained from five dogs was 31 5= 4 pmol/g tissue. The dissociation constant estimated from the slope of the PET curve after the displacement time was 0.014 ~= 0.002 rain -t D.Sandrock and D L Munz Department of Nuclear Medicine, Georg August University, G6ttingen, West Germany.

Objectives of this study were to develop an optimized double tracer subtraction technique based on physical and physiological considerations for the localization and differentiation of inflammatory bone lesions. The rationale of the new procedure was to use a monoclonal anti-granulocyte antibody (AGAb), which accumulates in florid granulocyte infections but also cross-reacts with normal bone marrow, and nanocolloid (NC) as a bone marrow tracer to overcome this cross-reactivity by subtraction Phantom studies (water phantom with Tc-99m sources of various activities simulating inflammatory lesions~background~ bone marrow/blood vessels) revealed a minimal count rate of 1000 net counts (= remaining counts after subtraction) per lesion for reliable count statistics. In order to obtain these counts rates in patients, minimal activities of 740 MBq for AGAb and 370 MBq for NC are required.-In all patients, dynamic flow studies, early (2 min p i ) and late (4, 24 hr p.i.) static images were obtained following i.v. injection of 740 MBq Tc-99m monoclonal anti-NCA 95 AGAb. After the 24 hr image, 370 MBq Tc-gSm NC were injected without moving the patient and dynamic flow study as well as early (2 min p.i.) and late (30 min p.i.) static images were obtained Subtraction procedure was performed with the 24 hr AGAb image and the 30 min NC image Normalization of both images was done by using a region of interest over the sacroiliac area as reference for normal bone marrow and calculating a multiplication factor for each image in order to get equal count rates in the reference region. The normalized NC image was then subtracted from the normalized AGAb image Persisiting activity on the subtraction image is read "positive" for a florid granulocytic infection For the "reverse subtraction", normalization was done the same way, but AGAb image was subtracted from NC image Persisting activity on the "reverse subtraction" image was interpreted as sign of a local macrophage process or specific inflammation.

Up to now, the protocol has been tried in 25 patients with encouraging results (92 % accuracy in the first 13 patients with follow-up). Thus, it seems to be a promising technique which overcomes the problem of bone m~rr0w cross-reaction of anti-NCA AGAb for the localization ! of inflammatory bone lesions The influence of posture on GER and aspiration of the gastric contents was evaluated in critically ill patient with orotraqueal tuhes(OT) and receiving continuous naso gastric(NG) feeding.

METHODS:50 mecanically ventilated patients(MV) and 24 spontaneously breathing patients(SB) were ramdomly allocated in a supine position or in an upright position. Six healthy persons were controls.l.-The NG feeding was suspended and the tube was cleaned with 50ml of water. 2.-To avoid contamination of the esophagus a small rathe terwas introduced into the NG tube.3.-18,SBq of 99mTc Sulfur Colloid was administered into the stomach through the eatheter.4.-The catheter and the NG tube were cleaned with water and ausence of contamination was checked with the gammacamera.5.-Patients were placed under the gammacamera after remainig 2 hours in the same position. The evaluationof the radionuclide results was done without knowledge of the patients' position.RESULTS:GER was present in 37 out of 50 MV patients(74%).In the upright position GER was detected in 16 out of 24 patients(67~), and in the supine position 21 out of 26 patients(81%). GER up to oropharinx was presented in 16 out ~f 26 with MV(61%) and in 21 out of 24 with SB(87%).(chi~=4.37,and P=O.O4).GEF was not detected in healthy volunteers. CONCLUSIONS:The radioisotope technique shows the elevated incidence of GEF in patients with NG and OT tubes. The GEF is more demonstrative in patients in supine position and with spontaneously breathing and elevation of the head of the bed does not seem to prevent the GER and aspiration of gastric contents. Quautitative evaluation of regional myocardial hypoperfusion from thallium 201 SPECT images reqmres comparison with data obtainedTrom a reference population of healthy individuals; which in turn implies standardization of sampling from myocardial segments, display, and quantitation. The "bullseye" is a multislice diagram representation (MSD) of the tomogram displayed in a polar fashion, with the apex of the heart appearing in the central part and the base in the outer part of the image. It has.gained some pooularity because it is a very convenient way to visuahze the abnormal areas in a single image. However, a direct quantitation of this representation win be inaccurate, due to an increasing contribution of the tomographic slices when going from the apex towards the base of the heart. Therefore, some normalization is necessary. We apply to each pixel which is identified as corresponding to an ischem]c area a coefficient inverselyproportional to the area of the ring containing this pixel. A second normalization of each slice allows to obtain a lesser contribution of the slices presumably containing thinner (basal) or narrower (apical) myocardial sections. Thereby, each pixel in the MSD image will represent the same elementary myocardial volume. The processing includes the followin~ steps: -6 short-axis slices are reconstructed extending from the apex to the base of the left ventricular myocardium. -A MSD representation is created frqm the angular profile of the maximum ELxel value m each slice. -A mapping of the ischemic zones is then obtained by comparing this short axis MSD with a data base of normal subiects (male or female). The zone of ischemia is represented by the pixels with a value below 3 standard deviations from its average in normals. -The first and last slices are assumed to represent 10 percent of the left ventricular myocardium, and all other four slices to represent 20 rcen t each. e extent of ischemia is expressed as the percentage of the left ventricular myocardial volume. Results are nearly operator independent because variability in the processing resumes in reonentation of the heart and in definition of reconstruction limits. The creation of the MSD image and all following steps require no further operator intervention. Original PACS are still cost intensive and dedicated for imaging devices, leaving nuclear medicine laboratory problems aside. We therefore developed a low cost computersystem to unite the organization of all working facilities in the department. Hardware: INTEL 80386 32bit processor, 380 MB hard disk, 12 MB storage capacity, streamer tape, 2x0.8 GB optical disc, 10 intelligent terminals, 2 matrix and 3 laser printers. Software: Specially disigned multi-user-multi-task system, using UNIX and INFORMIX as the basic software. On-line connection of 4 gamma-cameras and 2 RIA-processors and 2 PC's (terminal emulation). Results: The essentials of our system philosophy are: i.) Central data administration but decentralized on-line data aquisition and processing. 2.) Optimal use of peripheral and central hard-and software to save dual investment. 3.) All informations irrespectively from which procedure (imaging or lab) and from which time (follow-up) are attached to the same patient data file. 4.) Patient data files are transfered to the computer of the imaging devices together with the investigation request to assure data identity. 5.) Longterm storage of all data (pictures, lab-results and interpretation) on optical discs as final answer to archiving problems. Conclusion:

The system is able to meet the growing demands in cost e~fective data administration, handling, scientific questions and reducing archiving problems. An original program for MS-PC/DOS compatible microcomputers was developed for storing and reporting myocardial SPECT examinations. The core of the system is a data-form, actually handled as a bidimensional relational table, capable of managing 2x10 = examinations. SPECT data are relationally linked to patients' demographic data and clinical history information. To mantain data consistency each field (except patient's name) is predefined as a multiple choice field whose possible values are displayed in a pop-up window. An up to three levels deep context-sensitive on-line help is available. The schematics of the data system allowed to overlay a voice recognition program whose input comes, through a digital conversion board, from a microphone. The system has been trained for the possible different commands and verbal expressions; moreover the system is speaker dependent, thus adding a further layer of data-security to the password oriented log-in procedure: up to 200 nested operator-dependent command menues can be programmed in the voice command file. The SPECT data system analyses the myocardial perfusion patterns for rest and stress scans in the different segments of left ventricle that are then defined according to SPECT criteria as normal, ischaemic and necrotic. Final comments are automatically generated and can be printed out togheter with a schematic high quality plot of segmental left ventricular features. Remote image transmission will facilitate numerous applications such as distant interpretation, multicentric studies, comparison of images from different modalities or archiving. This task in Nuclear Medicine must satisfy the transmission of an amount of data in the range of I to 20 millions of bits with full security in a time of a few minutes to be acceptable in routine use. Conventional solutions are either too slow with telephone based system (2 to 35 minutes by modem at the rate of 9600 bits per second (bps)) or too expensive with specialized links. We used the new French public Integrated Services Digital Network RNIS which offers a fully secure transmission of data at the rate of 64000 bps over normal telephone lines at approximatively twice the price of a phone call, and an easy acoes through personal computers. Our local Nuclear Medicine network (ADAC lab.) consisting in several dedicated systems, personal computers, and an image digitizing system was connected to a remote rewiew site over i000 km away. Several 512 X 512 pixels -256 gray levels images of whole body scans and digitized MRI were accurately transmitted in an average time of 35 seconds each. RNIS incorporate simultaneous and bidirectional transmission of voice, text and images. Its future developments will include fastest rate (2 millions of bps and international connexions to equivalent networks). The intrinsic uniformity test, must be, ideally, performed using a point source; such geometry is difficult to obtain in practice. Aim of our work is to evaluate the importance of the variation of the uniformity index due to the size, form and position of a true radioactive source. A FORTRAN program which tests the geometrical influence of 3 different types (point, cylinder, cone) of source, positioned at different distances from scintillation camera and from the detector axis was implemented. The first step is the random choice of the photon start point inside the source volume. Then the program draws the direction of the photon and a check is performed: if the photon is directed on the detector the corresponding element of a 64x64 matrix is incremented, if the photon goes out a new photon is considered until 10 Mcount are stored in the matrix, Using this output the UFOV and CFOV integral and differential uniformity (I.U.,D.U.) are computed according to the NEMA protocol. The results obtained in this way only depend on statistical fluctuations and geometry. The validity of the program has been tested using a point source geometry positioned on the detector axis at a distance of 5 UFOV. Theoretically the UFOV I.U.

is expected to be about 2% on the basis of statistical theory.and I/R^2 formula; such value is in good agreement with the program result. Several runs were performed with different geometries; the values of I.U. obtained with cilinder and cone were about 5% worse than the values obtained using a point source. A further, small, worsening of I.U. due to the source shift from the detector axis was found. has been proposed for PET-data analyses in studies of glucose transport with 3-FDG. The object of this study was to investigate in a wistar rat model the kinetic and metabolic behaviour of 3-FDG in normoglycemia (N) and under patholocigal conditions (i.e. hypoglycemia (H), hyperglycemia (HY), ischemia (I) and after application of the neurotoxic radiosensitizer misonidazole (i mg/g BW with (M+) or without (M) additional intraperitoneal injection of glucose). After i.v. bolus injection of 3-FDG brain activity was continuously monitored by coincidence counting, while blood activity and plasma glucose concentration were measured from serial arterial blood samples. After 60 min animals were sacrificed and brains were assayed chromatographically for 3-FDG and 3-FDG-6-phoshate (3-FDG-6-P). Brain activity data were fitted with a 3-compartment-model regarding possible phosphorylation (rate constant k 3 of 3-FDG).

Control In N, HY and after inhibition of hexokinase (M, M+) a 2-compartment-model might be applied to fit 3-FDG data, since phosphorylation is low. However, in general and especially in H and I, when the tracer is significantly metabolized, a 3-compartment-model should be used. Neurotoxicity of misonidazole might be caused by inhibition of hexokinase and of glucose transport (reduction of k3, K M and Vmax). Plasma glycoproteins, after removal of terminal sialic acid residues to expose penultimate galamtose residues, are endocytosed by a receptor radiated process into hepatocytes and, following microtubule-mediated delivery to the lysosomes, are proteolytically broken down to small M.Wt. products.

Galactosyl neoglycoalbumin (NGA) is a synthetic ligand to the asialoglycoprotein receptor (hepatic binding protein) and, when labelled with Tc-99m, has been proposed as a useful agent for assessing liver function in man.

We have assessed the hepatic processing of NGA in the isolated perfused rat liver using several hepatoxic agents and inhibitors.

Control livers took up 37% of a pulse of 1-125-NGA (150 pmol) first pass.

Of the radioactivity taken up, 82% was released at the sinusoidal pole in predominantly acid-soluble form (small M.Wt. metabolites).

A further 8% was excreted in bile in an acid-precipitable form (intact protein) whilst 7% remained in the liver i hour after the pulse.

Pretreatment of rats with galactosamine (which causes acute hepatocellular injury) decreased uptake by 50%.

Pre-perfusion of livers with leupeptin (a lysosomal protease inhibitor) decreased the sinusoidal output of 1-125 by 55% whilst colchicine (a microtubule inhibitor) decreased both sinusoidal output (by 25%) and biliary excretion (by 60%) of 1-125.

~-Naphthylisothiocyanate, which produces intrahepatic cholestasis, decreased biliary output of 1-125 by 90%.

These results clearly demonstrate that NGA is processed by the isolated perfused rat liver in a similar fashion to endogenous asialcglycoproteins. 

In the vast naiority of patieuts epiphora is due to a lacrimal drainage system (LOS1 obstruction (LDSO) and, dace the treatment is mainly surgical, n earefd assessment or the drainage is necessary to deterniue accurately hhe level of the obstruction, There is little doubt that dacryoscintigraphy (DO) in an atrannatic, simple nnd easy to perform procedure and note physiological than either syringing or dueryncysbgrnphy, The present study evaluates if BS provides valuable inforntioa in the management of patlents ( The method measures the cumulative activity both in blood and in the total body, and determines the radiation dose from the cumulative activity using a relation implicitly based on the geometric factors formalism.

Having chosen the calculation procedure of the integral of the activity, the number and the sequence of samples (blood and urine) to be taken was dealt with.

Moreover, more highly patient-specific dosimetry was tried.

This involved using the geometric Factors formalism to evaluate the influence of the patient's weight and height on dose absorption. Our series included 37 tested thyroidectomized patients whose dose to the blood was assessed; 9 were selected and evaluated with the procedure here presented.

In 8 patients the 2 Gy blood dose was related to activities ranging 8 § GBq.

On the other end in 1 patient 2 Gy corresponded to 5 GBq. CONCLUSIONS It is useful to evaluate a patient-specific blood dose, both for the radioprotection of the patient ~nd to take in specific clinical cases the opportunity to exceed the usual limit of 7.4 GBq; these goals justify the requested increase of work for appropriate tests; a standard sampling procedure allows valid Comparisons of patients;the geometric factors formalism allows accounting for differences of weight and height. Platelet transit times following injection of lllInlabelled platelets were determined in 18 patients with idiopathic thrombocytopenic purpura (ITP). The transit times were determined by two established methods from the splenic time-activity curves recorded with a gamma camera-computer system: deconvolution analysis (=I) and the method of area of residue/dose ratio detection (=II). The mean transit times in all cases were 5.7 -+ 1.5 min (method I) and 6.3 -+ 2.6 min (method II), respectively. The transit time was significantly (p=0.013, Student's t-test) shorter (4.9 -+ 0.5 min, n=9) in patients with a positive platelet antibody test (platelet suspension immunofluorescense test = PSIFT) than in those with a negative PSIFT (7.6 -+ 2.5 min, n=9) when method II was employed. No such difference was observed when method I was used.

These results confirm and extend our earlier finding that the splenic platelet pool in ITP is enhanced by platelet-associated antibodies. We also conclude that the platelet transit time as calculated by method II gives'more specific information of splenic function in ITP than the intrasplenic transit time as calculated by method I. Method II is simple and based strictly on the observed time-activity curve and does not require potentially erroneous curve fitting procedures as does method I. to +65.2%. 0nly in two instances HMPA0 uptake decreased during the second SPECT study, in 3 patients no change was observed, while in the remaining 24 cases the change in HMPAO brain uptake was 6.9% to 65,2%. HMPA0 uptake differences between the "clinical" and contralateral hemisphere increased during the second condition. Our results indlcate, that estimation of global ~nd regional HMPAO brain uptake may help us to evercome the dilemma of simple visual estimation of HMPA0-SPECT images, By a simple calculation quantitative information between two drug-or stimulation induced brain functiun changes in the same subject can be assessed. 

The results of rCBF scintlgraphy with Tc-99m HMPAO and SPECT frequently make the availablllty of further parameters desirable in order to augment diagnostic information. In this context we evaluated the diagnostic efficacy of rCPR in 58 patients (37 men and 21 women) aged 21 -87 years. In 51 of them a cerebrovascular disease had been diagnosed, in 6 a malignant cerebral tumour and in one a benign cerebellar haemangioma. Twenty minutes after intravenous injection of Te-99m HMPAO rCBF scintigraphy was performed. Following in-vivo labelling of red blood cells with pyrophosphate, Tc-99m pertechnetate was administered intravenously. Subsequently SPECT of (rCBF + regional cerebral blood volume rCBV) and subtraction of rCBF from (rCBF + rCBV) were carried out so that rCBV and finally rCPR were obtained. rCPR was reduced in 18 patients (31,6 %). In 31 of 57 patients (54,4 %) rCBV was raised, in 14 patients (24,6 %) lowered. The assessment of rCPR during rCBF scintlgraphy using Tc-99m HMPAO and SPECT offered information about the extent of areas with deteriorated brain perfusion as well as about the local or regional intensity of dimlnuflO~ of cerebral perfuslon. Three nuclear medicine physicians independently rated SPECT/IMP images of 28 normal and 23 demented subjects, which were randomly ordered.

Raters were given a schematic of a transaxial brain slice through the basal ganglia, which was divided into 12 regions. Regions were rated on a 0-4 (normal-absent) scale. For each subject, each rater's scores for all 12 regions were sunumed to yield a global impairment (G) score.

This study evaluated the degree to which raters could distinguish normal from demented subjects; agreement between raters on G; and agreement between raters for the 12 regions.

There is complete agreement between raters for normal subjects using G, with a regional difference between raters of 0.65 regions (S.E. =.25).

For demented subjects, raters show poor agreement for 5 demented subjects (average of 3.80 discrepant regions), and good agreement for the remaining 18 subjects.

Regionally there is less agreement in ratings for demented subjects with average discordance of 2.39 (S.E. = .39) regions. Two step discordances > 20% were found for six regions.

Discordances greater than one step regionally occurred with less than a 23% frequency.

These results show good specificity for distinguishing normals from demented subjects but weaker specificity for regional pathology. There are conflicting reports as to whether or not CyA is present in brain tissues and CSF.

The objective of this study was to use 1-125 HIPDM to study any brain perfusion abnormalities due to CyA and to correlate the result with histological findings.

Two groups of Sprague-Dawley rats were injected subcutaneously wlth 50 mg/kg CyA or equivalent volume of vehicle (control) for 7 days. A total of 40 rats were studied as follows : 30 were injected with 1-125 HIPDM, sacrificed 30 minutes later and the brain dissected out. Twenty (CyA and control i0 each) were used for regional brain distribution studies and I0 (CyA and control i0 each} were used for regional brain distribution studies and i0 (CyA and control 5 each) for film autoradiography.

The remaining I0 rats (CyA and control 5 each) were used for routine histological studies. The CyA treated rats lost I0 -15% of their initial weight; showed lack of muscle co-ordination and slow whipping motion of the tail. Towards the 7th day, the rats had difficulty walking and 4 of the CyA treated rats died. The regional brain uptake of 1-125 HIPDM, autoradiographic and histological findings showed no discernible difference between CyA treated and control rats. These results suggest that CyA does not cause any brain perfusion abnormality indicating that the blood brain barrier was not compromised. opposite to a supratentorial lesion is called Crossed Cerebellar Diaschisis (CCD). We evaluated the presence of CCD with SPECT in a series of acute ischemic stroke patients at admission, at 2 weeks and at 6 months. The presence of CCD was evaluated by 2 blinded observers (kappa=0. 38), in case of controversy CCD was evaluated by the 2 observers together. The hemiparesis was measured with the Motricity Index. The size of the flow deficit was scored with a visual semiquantitative method. ACT scan was performed in all patients.

CCD was present in 42 of 55 scans where the cerebellum could be evaluated.

Nine patients showed CCD in all 3 consecutive scans, only 3 patients never showed any CCD. In II patients CCD was present in any scan. In 5 cases CCD was initially absent, and appeared in subsequents scans. None of these subgroups showed any difference in severity of hemiparesis, neither was there a correlation between presence of CCD and infarct location posterior or anterior from the central sulcus. There was a remarkable positive correlation though between presence of CCD and size of flow deficit.

It can be concluded that CCD was present in the majority of cases with a supratentorial brain infarction, and that it's presence was not related to the severity of hemiparesis or the infarct location, but it's presence did show a strong positive correlation with the size of the cerebral blood flow deficit. Follow-up of patients with primary and metastatic brain tumors after primary treatment with surgery, irradiation, and chemotherapy is often complicated by the appearance of suspected tumor and/or necrosis on computed tomography (CT), or magnetic resonance imaging (MRI). We report experience with four such patients studied by positron emission tomography (PET), with pathologic correlation. Fluorine-18 fluorodeoxyglucose (FDG) PET was performed under a research protocol approved by our Institutional Review Board. Patients were referred by neuro-oncologists and signed an informed consent. Five to i0 mCi of FDG was given intravenously. PET was performed with three consecutive sets of trans-axial images, which were visually inspected and correlated with CT and/or MRI. One patient with suspected recurrence of glioblastoma multiforme (GM) had a focal area of increased uptake. Resection revealed gliosis and abnormal cells, but no recurrent tumor. Another GM, an anaplastic mixed glioma (AMG), and a chondroblastic osteogenic sarcoma (COS) suspected of tumor or necrosis all.showed decreased uptake. Re-operation of the GM and AMG revealed anaplastic residual or recurrent tumor and necrosis. the COS showed inflammatory tissue and no tumor or necrosis. In using PET-FDG in follow-up of brain tumor patients following irradiation and chemotherapy, the differentiation of residual or recurrent tumor from gliosis and necrosis may be difficult, as illustrated by three of these cases. The presence of inflammatory tissue in one case was associated with decreased EDG uptake. The aim of this prospective study was to examine the value of thallium SPECT of braintumors for differential diagnosis and followup. We examined 27 patients with histologicaly proven primary brain tumors (astrocytomas I-II:5; astrocytomas III-IV:I5; oligodendrogliomas: 5 meningeomas:

2) by SPECT. 6 patients (astrocytomas 1-2:3 and astrocytomas 3-4:3) were examined during and after therapy over 6-18 month 3-5 times. In 7/27 patients dynamic studies for TL-201-brain-kinetic were performed. The Tumor/Nontumor (T/N) ratio were calculated by the region of interest technique. 4/5 patients with astrocytoma I-II and 13/15 patients astrocyctoma III-IV had a homogeneous TL-201 accumulation of 3.1 and 4.9 (T/N). 2/5 patients with oligodendrogliomas (T/N 5.9) and 2/2 patients with meningeomas (T/N 11.6 and 5.1) showed TL-201 accumulation. Preliminary conclusions: i. The high of TL-201 accumulation in astrocytomas seems to depend on the degree of malignancy. 2. Ti-201 accumulats within seconds in brain tumors and there is no washout in the first 3 hours demonstrable. 3. TL-201-SPECT may be able to predict prognosis and response to therapy.

I. Bangerl~ P, Pohl, G. Riccabona Depts. of Neurology and Nuclear Medicine, University Medical School, Innsbruckj Austria ,DOUBLE TRACER BRAIN-SPECT FOR ASSESSMENT OF AIDS ENCEPHALOPATHY CAIDSE) Our group has reported previously (I) about significant alterations in 123 I-IMP bra• SPECT-patterns in patients with AIDSE in c~ose correlation with clinical manifestations of the disease. Occasionally observed discrepancies between SPECT-images obtained after 99mTc-HMPAO (555 MBq) and 123 I-IMP (185 MBq) started a series of double tracer stud• after application of tracer amounts as described above with a single head ZLC-Digitrac-3700-0rbiter-camera using a microdelta software version and using identical image reconstruction programs. Time interval between both studies was 7 days (median). Data showed in 12/22 patients intensive "cold" spots after HMPAO while only 8/22 patients showed intensive defects with IMP. In 5/22 patients defects after HMPAO and IMP were similar, in 10/22 patients the intensity of defects was different with both tracers and in 7/22 cases localization of defects was not is tical. Overall almost all patients showed abnormal uptake. Only I patient had an abnormal CT/ NMR, SPECT-patterns did not correlate with clinical staging of AIDSE. These data seem to confirm that the HIV primarily attacks endothelial cells in the brain, thereby primarily and initially reducing rCBF. Brain-SPECT with 99mTc-HMPAO seems therefore adequate to demonstrate AIDSE even in cases with normal CT/NMR. hiteratuqe: (I) Pohl ~ et al. J.Nucl.Med. 29:1382 -1386 (1988 Iomazenii, series ozpo@terior dynami'c brain images were made (30 sec/im@.ge): R@gior~ or interest were arawn around the entire brain and total coun~ were determine~ Tne total counts measured at 10 rain were considered 100 % as the activity uptak~ curyv., was almost at its maximum at that time. In 3 s u~ects, 1 mg cold flumazenil was injected 120 rain p.i. The influence of sensory stimulation on the redistribution of deposited 123I labeled N-isopropyl iodoamphetamine (IMP) in regional cerebral blood flow (rCBF), studies was investigated in normal control subjects without history of head trauma or other cerebral pathology. Rotating camera SPECT rCBF imaging was performed on 5 subjects at -30 min, 3 hr and 4 hr post tracer administration. Measurements were repeated at 7 days in each subject with exposure to strobe light stimulation (ll flashes/see, i x 106 candela) for i0 min, 15 min prior to the 3 hr SPECT procedure. Redistribution and clearance of IMP were examined using ROI techniques on two pixels thick (10.6 mm) slices from each set of SPECT images. ROIs were defined for the vascular territories of the anterior, middle and posterior cerebral arteries, prefrontal cortex, primary visual cortex (PVC), cerebellum, basal ganglia, and thalamus. The results showed that a i0 min strobe light stimulation at 165 min post IMP administration has no significant "effect on redistribution or clearance of IMP in major structures of the brain (e.g. 4 hr washout in PVC: n=5, eontrols -23%, strobe -20.6%). Major differences in activity distribution and clearance was seen among subjects, however, the delayed visual stimulation did not significantly influence IMP distribution or clearance compared with that obtained for subjects maintained in quiet and low light ambient room Today,ECT is a rarely used method of treatment in psychiatric disorders because it is found to be non-humane and the principle effective mechanism is still unknown.But in some cases where medical and rehabilitative treatment methods fail and especially in patients who has an inclination to commit suieide,ECT is tried as a last chance.

To evaluate the effect of ECT on brain perfusien,Te-99m BM PAO Brain SPECT was applied to five schizophrenic patients(4 male,l female)before and while undergoing ECT by using the same amount of activity,acquisition and ECT parameters.Both Tc-99m HM PAO injections were performed in the ECT room under same circumstances in order to provide the same psychic conditions that may effect the brain per fusion.

ROIs were drawn around frontal,temporo-parietal, occipital cortexes,hasal ganglias,cerebral and eerebellar hemispheres on 6th,16 Eh and 20th,one pixel thick(4.78 mm. for 1.33 zoom)transaxial slices parallel to the orbito-meatal line.Using the sane ROIs in both studies,counts were taken from each drawn ROI and the ratio of the each ROI to the total ipsilateral hemispheric count was calculated.In addition pre and post ECT values of each ROI was correlated, reflecting the effect of ECT on brain perfusion.

While the ratio of each ROI to the ipsilateral hemispheric count remained almost constant' Jm pre and post ECT studies;there was a significant increase in the post ECT values of basal ganglias,occipital eortexes and eerehellar hemispheres with a mean in creasin_g value. Of I./Q~Ij[ and .75~ respectively, Despite effective antibiotic therapy mortality from bacterial meningitis is still high because it is often complicated by brain edema, increase of intracranial pressure or vasculitis. As these mechanisms may influence brain perfusion, the present study was designed to investigate patients with acute bacterial meningitis by HMPAO-SPECT. Up to now 14 patients (age: 15-69 years, median: 31years) with meningitis were investigated by HMPAO-SPECT. For correlation neurological examination and CT was performed in all patients, cerebral angiography in 8. In addition to baseline SPECT in the acute stage of disease one or more follow-up studies were available from 8 patients. 13/14 patients had pathologic SPECT findings, showing focal or multilocular uptake defects. 7 patients had severe focal CNS-disorders (6x hemiparesis, Ix ataxia) with SPECT-results excellently correlating to the neurological findings. CT-scans and angiography detected corresponding findings only in one case each. Follow-up studies with HMPAO up to 10 months after the acute disease showed a significant improvement of regional cerebral blood flow (rCBF) in 5 and normalization in 3/8 patients investigated. Alterations in rCBF are a common finding in acute bacterial meningitis and may represent the functional effect of brain edema, increase of intracranial pressure and/or vasculitis. In contrast to morphological findings obtained by CT or angiography, SPECT-results could well explain focal CNS-disorders occuring in some of the cases. As indicated by follow-up studies changes in brain perfusion were reversible or improved in most cases. Thus, HMPAO-SPECT may be a promising approach to pathophysiological mechanisms participating in acute bacterial meningitis. The prognostic value, however, has to be further established yet. The contribution of Tc-99m HVIPAO to evaluating the regional distribution of CBF is established yet clinical decision making usually depends on the global CBF, eg less than 600 ml/min indicates danger in operating on subarachnoid haemorrhage, SAH (Mahmoud et al, Nucl Med Corrrnun 1987; 8: 239) . The global cerebral clearance in ml/min of I-lV~AO is given by the difference between total supplied and the CBF as measured by a non diffusible tracer Tc-99m albumin. Deconvolution analysis of the input function from a probe over the aortic input with the content curves from regions of interest from a camera over the vertex gives the impulse retention function, IRF, for each asent studied serially in the same patient.

The IRF upstroke of each agent is fitted and the cerebral clearance of HVlPAO is given by difference.

The extraction efficiency is also given by the ratio of maximum cerebral uptake to the maximum cerebral supply.

HVIPAO clearance showed a direct correlation with cerebral blood flow, r 0.95.

These methods have been applied to 18 patients with SAH and 19 patients with head injuries.

The Glasgow outcome scale of disability was found to have a direct relation to global CBF, r 0.74 P<0.05.

Those with 1 or 2 perfusion defects had global CBF 1058 + 51 ml/min and those with 3 or more 718 + 69, P40.05T A further 17 head injury patients are being evaluated. Measurement of global CBF is a clinically important adjunct to region HVIPAO SPECT. N. P. I= G. Verhoeff, J. van Kantei~ E. ~-van Royen, n. weins~ein, ~'.l,,L van der Zant. Department o~ Nuclear Med/cine, Academic Medical Centre, Amsterdam, The Netherlands.

In 8 patients with dementia, 3 with very probably Alzhelmez ~ s disease (AD), 4 with senile d~mentia type Alzheimer (SDAT)and I with AIDS dementia, a comparison was mane oz Thallium-201 Dier_ny-dithiocarbamate (m~ and Technetium-99m-d,lhexamethylpropyleneamine oxime (~"~IcHMPAQ~) SPECT. The intei-vAl ~tween the 2 SPECTs varies ~rom nne same day in 3 patients to 18 months • one patient. =o~TIDEC and ~I~HMPAO SPECTs were co~pargd ~ semi~titatively by taking ratios of several cortical ROI's (t~ro-parieto-occiDital =TPO, parietal=P, frontal=F;, ~ occipi,tal~-O] and the cei~bellum (--C~ all in c ounr@/pixelj. 'lne ratios were drawn independenr--y, by 2 investigators. The TPO/C ratio deserve~ special attention because in several SPECT and PET s~udies a ni• reduced ter@9orp-parieto-occipital activity ~ been the most prevaleht finding in AD and SDA~ [I] . Statistical significance of the difference between the ratios o~ned with ~~ and ~'~TcHMPAO was calculated using the 2-tailed paired T-test (* = P < 0.05; ** = P < 0.001).

Cortex/eerebellum ratios (N = 8; X -+ SD): Both for =~ and for s~"~cHMPAO SPECT the TPO/C ratio was significantly lower than the other F/C, and O/C) ratios ~P < 0. 004). ,

is concluded that in ~ementia a reduced TPO/C ratio may be of diagnostic value in =o:TI.DDC and ~"~fcHMPAO SPECT and that the sensitivity of the former may be greater than of the latter.

i. Hellman et al. Radiology 1989; 172: 183-188. To investigate th~ relation between severity of memory disoraer t expresseu as a total score o~-all sum~ests ) and abnormalities on EEG, CT, and SPECT, Yates' corrected chi-square test was performe~ In th/s te@t, for SPECT two separat_e groups were taKer~ annormal coldspots (SPECTI), and aSnor~ml hotspots (sP~).

No dependency was observed between SPECTI and SPECT2 o~ SPECTI or SPECT2 with any other of the variables. The same was the case f-or NPB and CT. The only dependency observed was between EEGI and EEG2 (P < 0. D2).

It can be concluded that in ~atients with partial epl'iep6y cormplainir~ of memory qysfunctior~ , o~eo~ive~z.me~.uraple memory disorders uo i n~eeu exast. ~o direc~ relation nas neen onserved between o~ severity of ~ry disorder and the probability (~e~ec~ing an epi-e~toqenic zocus with SPECT, EEl, or CT. The findings oT t~e EEG are reproducible.

i. Loiseau et al. Rev Neurol 1982; 138: 387-400. 2. Aldenkarmp. Acta Neurol Scand 1984; 70: 206-209. 

H Henninqsenl, S Knechtl, B Bubeck2, P Jackisch3, P ReutherS, P Georgi2 Depts of Neurology (Mannheim I and University3 Hospital) add Nuclear Medicine2, University of Heidelberg, FRG PATHOLOGICAL 111-IkDIUMPLATELET SCINTIGRAPHY IN LOW DEGREE SYMPTOMATIC CAROTIDARTERY DISEASE In the absence of well founded data, thrombendarterectomy (TEA) in carotid artery disease (CAD) is preferentially performed on high rather than on low degree carotid stenosis. Evidence has been provided that pathological platelet accunulation (PPA) seen on platelet scintigraphy (PSC) indicates unstable plaque formation and active CAD with an increased risk of cerebral embolism. We therefore cc~pared the functional scintigraphic results of Irdi~-111PSC with those of angiography in order to determine the need for TEA specific to the degree of stenosis. -83 patients (pts) with cerebrovascular disease of established carotid origin were examined. Intracranial angiography, carotid sonography, holterECG, chest X-ray and routine blood work had been smp!oyed to exclude pts with cardiac e~Ibolism or intracranial thrombotic lesions.

Of 83 pts subjected to angiography 51 had low (<50 % vessel diameter) and 32 high (~ 50 %) degree carotid stenosis. Positive results were obtained in 77 % of all symptc~atic (sympt) and in 23% of all asymptomatic carotids (p < 0.001). In cases of low degree stenosis evidence for PPA (i.e. positive PSC) was found in 37 out of 51 pts (73 %) while in high degree stenosis 14 out of 32 pts (44 %) had positive PSC results (p< 0.05).

Thus, in our series of sympt CAD the majority of stenoses encountered was of less than 50 % vessel diameter. PPA as an indicator of 6m~0olic risk was more frequent in low than in high degree stenosis. We conclude that decision on TEA cannot be based on angiographic degree of carotid stenosis alone but should be supplemented by information on the functional status of CAD. The aim of this study was to evaluate the change of regional cerebral blood flow and to find the neuroanatomical localization in infantile autism using brain SPECT.

We have performed brain perfusion scan using Tc-99m-HMPAO and SPECT in 64 patients with infantile autism (57 male, 7 female, age 3.8 + 1.3 years SD) and reconstructed images were interpreted qualitatively by at least two specialists who were blind to the diagnosis. The diagnosis was based on the DSM-III-R criteria.

Of the 64 patients, the reduction of regional blood flow in cerebral cortex was found in 30 patients (46.9%) and involvement in left side was more frequent than in right side (2.6% and 15.6%) respectively. The usual areas with pattern of decreased activity were seen in the frontal lobe.

H. Terada, R. Matsuda; K. Mizuno, S. Murakami, S. Sate, M. Nagamoto, A. Kuwajima, u [tiramatsu, K. Hisada; S. Iwabuchi, H. Samejima, N. u S. Higashi" Toho Univ. Ilosp., Tokyo. and *Kanazawa Univ. Hosp., Kanazawa, Japan CEREBRAL PERFUSION RESERVE SPECT IMAGING BEFORE AND DURING ACETAZOLAMIDE TEST USING CONSECUTIVE Tc-99m HMPAO SPECT STUDIES.

A new method using Tc-99m HMPAO SPECT imaging was developed for evaluating cerebral perfusion reserve by the acetazolamide (DIAMOXR;D) test.

The 1st SPECT study was carried out for 13 mid to obtain baseline images after 3 miD p.i. of 555 MBq of HMPAO using a single head gamma camera system (Shimadzu, SNC 51OR) and a high resolusion system (Toshiba, GCA9300A). At the same time as the start of the 1st study, lg of O was intravenously injected.

Immediately after the stop of the 1st study, 925 MBq of HMPA0 from the same vial was additionally injected.

Three minute later the 2nd SPECT study was carried out for 10 miD. After reconstruction the tomographic images in the 1st study corrected for data acquisition time were subtracted from the images in the 2nd study to obtain those during the D test. This subtraction technique gives independent images before and during the test.

Besides, the regional flow changes were quantitatively estimated. This method was applied to 21 patients with cerebrovascular disorders. In conclusion this method seem to be practically useful for evaluating regional brain perfusion befor and during the D test as a consecutive study with a short period of approximately 30 miD.

F.Dore, C.P.Secbi, G.Rosati_ M.L.PL~as, V.Agnetti, M.D.Azzena, A.Ga~oa, P.Varziu , A.Axru, A.R.Casu and G.Madeddu. Institutes of Nuclear Medicine and Neurology, University of Sassari -Italy CARBCNAZEPINE (CBZ) AND REGIONAL CES~BRAL BLOOD FLOW (rCBF) IN PAR-TIAL EPILEPSY. ASPECT STUDY WITH Tc-99m -~ PAO Only a few date have been reported proving the action of antiepileptie drugs on rCBF in partial epilepsy and these refer to patients studied by an intravenous Xenon 183 technique. To further investigate this problem, we studied 7 adult epileptic patients with partial seizures, in interictal state. EEG focus was demonstrated in all cases while CT and neurological ex6minations were normal; r0BF was studied, with patients rest~, by SPEOT after i.v. injection of 25-30 mCi of Tc-99m-H M PAO, using a semiquantitative regional analysis (sequential ROI and eirom~erential profile) -SPECT was performed twice for basal data before any treatnent and it was repeated SO, 60 and 90 deys on CBZ (6/33 to 800 mg q.d.). None of the patients were receiving other drugs. Basal SPECT showed a focal decrease of rCBF in left fronto-te~ and parieto-temparal regions in all patients; moreover, in 3 instances a controlateral parieto-temporal hypoperfusion was also present. Thirty days after basal tests, while the patients were on CBZ, with drug sertm levels between 6.2 -7.9 ng/ml, SPECf showed non si~/ficant variation in rdgF within epileptic loci, when compared to basal data; in all the other epparently uninjured cortical areas, a significant increase in ~CBF was fotmd, with mean values of i0.0!_7.~/o (p~O.05). This increase was evident, with slight chan~es, ~4nen SPECT was repeated at 60 and 90 days. Moreover, in 3 patients with basal hypoperfusion only in the left fronto-te~oorel regions, a crossed cerebellar diaschisis (CCD) was observed after one month on CBZ and also in the following SPECT. Our data seem to demonstrate that CBZ has a negligible effect an in the site of epileptic focus, while it could determine rCBF increase in uninjured regions even a distance from the focus. Fmr~over, we observed for the first time, to our knewledge, CCD in 3 Cf brain negative patients on CBZ, su~zasting a depressive CBZ effect on cortico-fronto-dentats-thal~mo pathway. Farther studies are needed to confirm these interpretations. is partly due to cerebral atrophy. As SPECT has less resolution than PET, but is replacing PET in clinical routine, we asked in the present study, whether the characteristic temporo-parietal hypoperfusion on SPECT in AD can be explained by cerebral atrophy measured on CT, or whether it adds new, useful information.

In 38 patients with a clinical diagnosis of probable AD regional tracer uptake of Tc-99m HM-PAO was measured in right and left frontal, parietal, and temporoparietal regions and expressed as a ratio, with the activity of the cerebellum as the denominator.

CT atrophy was rated by two experienced observers, who were blind to the SPECT results. Cortical atrophy of the temporoparietal region was scored on an ordinal scale. Statistical analysis reveals no significant correlation between regional cerebral atrophy on CT and hypoperfusion in the corresponding regions of interest on SPECT. It can be concluded that SPECT adds new, useful information to the aspecific finding of atrophy on CT. with an intracochlear implant were examined. Each patient was scanned 6 times with time intervals of 15 miD. 150 MBq H2t~O were injected for each scan. Scans were made from 0.5 to 5 minutes after injection. The 1. and 4. scan were acquired under control conditions. During scan 2 and 5 white noise (WN) was used as input of the cochlea implant, whereas words (WO) were used for scan 3 and 6. Activity concentrations of H2t~O were regarded as estimates of CBF. In each patient regions of interest (ROD were defined according to a neuroanatomical atlas in the two primary auditory cortices in two adjacent slices and related to the cerebellum so that 16 ROI were evaluated in the 4 patients. During stimulation with both WN and WO increases of CBF were found in 14 of the 16 ROI. The maximum increase was 21%. The average increase was 3.4% for WN and 3.9% for WO.

The greatest effect with an average increase of 9% was measured in one patient who succeeded far better than the other patients in the rehabilition program. The results of this case report show that PET studies with H2t~O

can assess effects of electrical auditory stimulation by a cochlea implant and might yield objective data about the rehabiiition process. The aim of the study is to'find out the diagnostic value of 9SmTc-HM-PAO-SPECT investigation in comparison with EEG and CT. Twenty patients with epilepsy (ll male and 9 female between 16 and 46 years old) were examined by CTand EEG; inmost cases the EEG focus was registrated in the temporal region. These patients were also investigated with 99mTc-HM-PAO. A rotating gamma camera ZLC 7500 (Digitrac) fy Siemens with high sensitivity low energy collimator was used for imaging. During one 360 ~ rotation 64 frames were acquired by 20 sec. for one frame. 32 transversal slices were reconstructed. No attenuating correction was performed. A percentual comparison between contralateral hemispheres was done. The analysis of the interictal Tc-HMPAO investigation revealed in ]6 cases (80%) pathologhical results (decrease of activity uptake). Conclusion: According to the literature the comparison with EEG respectively CT examination shows closely correlation to KEG results and better diagnostic statement compared to CT. The results of the study shows, that this method is suitable for revealing of epileptic foci, localized in one side of the brain. Quantitative three-phase scintigraphy of the hands was carried out in 32 patients in different stages of algodystrophy and in a control-group of 20 normal subjects. Twelve patients were investigated before and after surgical treatment. Serial images were acquired over both hands every 4 sec for I min and static blood-pool images 5-10 m_in after venous injection of 370-555 MBq 99mTc-MDP. The late metabolic bone scintigraphy was carried out 3 hours later. The following indices were calculated : perfusion-index (Perln), bloodpool-index (BPIn), metabolic-index (MetIn) and perfusion/metabolic ratio (P~I). Characteristic for the algodystrophy were the perfusions and the blood-pool disturbances, combined with increased metabolism of the wristbones. The quantitative three-phase scintigraphy of the hands allows an earlier diagnosis of the disease, before the radiologica! signs were established.The quantitative scintigraphic investigation permits an objective follow-up study of the disease and a precise evaluation of the therapeutic results.

The clinical improvement after surgery, leads to appropriate changes in the Perln, 7~Pln,Tqetln and PNR. Diffuse skull activity(DS) in bone scintigraphy(BS)is a pattern seldom referred in literature. Retrospectively we analysed 648 BS in breast cancer patients(pts) and 50 BS in endometrial cancer pts,as a control group(gr). In the breast cancer gr, 179 (27.6%)pts demonstrated intense DS, while in the control gr only 3 pts (6%) had DS.

We conducted a prospective study in 56 breast cancer pts with DS as the only positive finding in BS. The aim of the study was to determine the value of DS as an early indicator of bone metastasis and to correlate this finding with radiological patterns and biochemical parsmeters of bone metabolism(measurements of serum calcium,phosph 2 rus and alkaline phosphatase and urinary excretion of calcium and hydroxiproline).

During the follow-up period(3-19 months) we performed a total of 122 BS. Bone metastasis were found in 20 pts (35.7%). Fourty-nine out of 74 radiographs of the skull were normal,10 had osteolytic lesions,10 osteoporosisand 5 hyperostosis cranii.Biochemical evaluation showed only minor alterations (elevated serum calcium in 3 pts and elevated urinary excretion of hydroxiproline in 5 pts).We found no correlation between scintigraphic,radiological and biochemical data,namely in the gr of pts that developed bone metastasis. We concluded that the incidence of DS is greater in breast cancer pts than in pts with other malignancies(p <O.05).Since in a follow-up of 9.2 months 35.7% of the pts developed bone metastasis,we can regard DS as an early indicator of secondary bone deposits. So far, we have not been able to find a physiopathological explanation for the appearance of diffuse skull activity in bone scintigraphy. 99mTc-cc-D-Glucose 1-phosphate (GP) was introduced by our group for the detection of lung carcinoma. It was shown that 99mTc-GP did not accumulate in normal bone. In the present study 99mTc-GP uptake of tumoral bone was investigated in 24 patients (10 F, 14 M, age range:8-74, mean:31) with known bone tumors (14 malign, 10 benign) after getting their informed consent. Each patient was intravenously administered with 20 mCi (740 MBq) 99mTc-GP. Images were taken at 3 h post-injection (Siemens ZLC-75, Scintiview II). Three-phase 99mTc-MDP bone scan was obtained 4 days later. The tumor/normal tissue ratios (T/N) were calculated for both agents. All bone tumors imaged with 99mTc-MDP were also visualized by 99mTc-GP. Normal bone did not accumulate 99mTc-GP in either of 24 patients studied. In 28 abnormal sites T/N ratios were 2.91+1.61 and 5.25+2.93 for 99mTc-$P and 99mTc-MDP, respectively. It was concluded that although mean T/N ratio of 99mTc-GP was lower than 99mTc-MDP, its selective accumulation in pathological bone was a superiority compared to 99mTc-MDP, highlighting the abnormalities, particularly in equivocal cases. GP labelled with a suitable radioisotope may also be used for treatment. Conventional and LauensteIn X-Rays of the Idp as well as 3phase BSC and MRI with T 1-and T2-weighted coronal images were acquired in all patients. Diminished radionuclide uptake in the lateral an cranial part of the femoral head epiphysls in BSC was considered as avascular hip necrosis. Zones of diminished signal intensity in the hip epiphysis on T I-and T2-weighted images with or without of deformation of the femoral head were indicating MP in MRI examination.

In 10 patients all 3 techniques, accordingly, showed negative findings. In 8 patients, however, pathological findings were observed by all imaging techniques. These 8 patients were considered to have an advanced stage of IMP. Out of 6 patients with clinically suspected MP but negative radiological findings 2 showed hip changes at BSC and MRI. Two patients showed pathological findings of the hip in either BSC or MRI. In S of these 6 patients the diagnos~ of MP was later confirmed by X-Ray.

In In contrast SPECT has been designed to provide images of a spatial distribution of the tracer in the body overcoming overlap problems and offering better image contrast. Recently the software for 3-D-reconstruction of the acquired data from an 360 ~ rotating camera has become available. Ten patients with hip head necrosis were examined pre-and postoperatively performing 99mTc-DPD-SPECT to evaluate the viability of the hip head before and after treatment with a pedicled pelvic bone graft. One week before, one week and twelve weeks after surgery clinical features were compared with the results of conventional X-ray-examinations, superselective angiography and scintillationstudies (as described below). After intmvenoils administration of 99mTc-DPD the following parameters were acquired : 1. Imaging of the soft-tissue-and boneperfusion, from anterior,0-120 sec.p.i.(1 frame4sec,matrix 1282 pixel). 2. Bloodpool-imaging, from anterior,10 min.pi.(500 kilocounts, matrix 2562 pixel). 3. Static planar views from anterior, 3h.p.i. (500 kilocounts, matrix 2562 pixel). 4. SPECT, 3.5h.p.i. (malrix 642 pixel,Hanning-filter [resolution recovery = 0, cut off frequency=l]). Data obtained from SPECT were then reconstructed in a 3-dimensional fashion. Subsequently a quantitative analysis by ROI's was done. On planar scans the highest accumulation of the tracer has been found in the affected hip head one week after surgery and lowest twelve weeks thereafter. In detecting the extend of osseous hypermetabolism SPECT clearly proved to be superior to planar views. The postoperative follow-up of patients with hip head necrosis treated with a pedicled pelvic bone graft can be accomplished by different scintigraphic and radiologic techniques. Only SPECT and planar scintigraphy allow quantitative analysis of the regional metabolism of the bone. By the ROItechnique changes of the viability of the revitalized hip head can be detected earlier than by conventional radiographs and less isvasively than by superselective angiography. 3-D-display simplifies image interpretation and renders better topographic information than does diplay of single slices or planar views. 

A combination of granular ceramic, fibril]at collagen and bone marrow is a highly effective synthetically prepared bone graft material.

It is not known wheter new bone can form within this artificial graft or if it is only a framework for bone ingrowth from the skeleton. This study attempted to quantitate the volume of new bone formation within the ceramic collagen/marrow matrix using histomorphometry and ggT-(~ De scintigraphy. Thirty-four rabbits were used each with twelve different implants of ceramic, collagen and marrow in intramuscular abdominal pouches.

An extra-skeletal site was chosen to separate the osteogenic response of the implant from that which might be due to the surgical injury to the skeIeton. To quantitate the new bone formation within mixtures 50 Mbq/ml of ggTc~DP was injected i.v. 36 hours later animals were sacrificed, specimens dissected and placed in a gamma counter (results available the next day). After screening, all 351 implants were prepared for histological examination. Three sections were cut from each implant (1050 sections in total). On each section manual counting of 1000 points was performed and quantitation of the volume of ceramic, soft tissue and new bone were made (results were available 7 months later). In conclusion the histdmorphometric results confirm the isotope assay findings that a reduction of ceramic volume from 100% to 25% with an increase of collagen volume from 0% to 75% and a constant volume of marrow 20% encourages new bone formation. The Spearman's rank correlation test between histpomorphometry and scintigraphy assay confirm (rho = 0.809) a highly statistically significant correlation between these two methods of new bone detection. 

can present a problem, especially when the loci are located in areas of active hematopoietic or reticuloendothelial bone marrow. Tc-ggm labeled AGAb and NC are known to accumulate both in florid inflammatory lesions and in active marrow. Due to the fact that labeled granulocytes are enriched in granulocytic infectious lesions to a higher degree as compared to NC, we applied a subtraction technique to visualize abnormal persisting AGAb uptake surrounded by normally active marrow.

30 patients (18 men, 12 women, aged 49.6 +/-18.7 years) with suspected infectious lesions (8 in spine, 8 in hips, 9 in lower limbs, 2 in upper limbs, and 3 in other locations) were studied. AGAb scintigraphy (740 MSq Tc-99m anti-NCA 95 AGAb i.v. ) was performed as a 4 phase study (flow, early static,2 -5 min p.i., and late static images, 4 and 24 hr p.i.) immediately followed by a 3 phase NC scan (370 MSq Tc-99m NC; flow, early static, 2 -5 min p.i., and late static images, 30 min p.i.) with the patient in the very same position. Image processing was performed by normalizing the 24 hr AGAb image and the 30 min NC image by using a normal bone marrow region as reference and subtracting NC from AGAb image ("SI") and AGAb from NC ("RSI").

Nine out of 30 lesions had an increased uptake with at least one tracer (5 with AGAb alone, 1 with NC alone, and 3 with both tracers) . Subtraction procedure revealed persisting uptake on SI in 5 and on RSI in 2 lesions. Three out of 8 lesions would have been read false positive on the AGAb scan due to accumulation in marrow, which was also seen on NC scan resulting in no persisting activity on SI. In 13 cases with final diagnosis, SI/RSI was true positive in 4, true negati~ve in 8, and false positive in 1 as confirmed by histology, cytology, bacteriology.

In conclusion, SI/RSI is superior to imaging of inflammatory disease with AGAb or NC alone, especially due to its higher specificity. The aim of this study was to examine cancer patients with a solitary hot spot in the bone scintigraphy with magnetic resonance imaging (MRI) to evaluate the occurence of bone or bone marrow changes.

Twenty-five cancer patients were examined by MRI. An indlcaUon for bone marrow metastasis was a focal signal loss in T1-and a focal increase in signal intensity in T2-weighted images.

In 15/25 patients the MRI result was typical for metastasis. The spread was much wider in 5 patients than as suggested by bone sclntigraphy. X-Ray or CT of the hot spot region was suspect for metastatic lesion in 6/25. A solitary hot spot in bone scintigraphy in cancer patients is suggestive of bone/bone marrow metastases. The MRI of the bone marrow enables the detection of bone marrow metastases earlier than X-Ray or CT.

We suggest that a MRI of the bone marrow should be performed in cancer patients if a solitary hot spot in bone scintigraphy is diagnosed, especially if X-Ray studies do not show any pathological changes. The aim of this study is to determine the place of planar and tomographic skeletal scintigraphy in the investigation of patients with chronic low back pain of unknown aetiology, the results of these scintigraphic studies were compared with the results obtained from planar and tomographic X-rays.

28 patients (10 male, 18 female, age range 27-77, mean age 48 years) were included in the study if they had suffered severe low back pain for more than six months. Those with nerve root compression symptoms or with a known malignancy were excluded from the study.

X-ray CT was performed on a Siemens Somaton DR8. Planar and SPET skeletal scintigraphy was performed on an IGE 400A gamma camera interfaced with a Star computer 3 hours post administration of 700MBq of 99mTc.MDP. Of the 22 patients with a positive result using CT 16 had a positive SPET study. SPET was positive in 4 patients when CT was negative. Of those patients with a positive result with both modalities 4 patients had additional lesions seen with SPET when compared to CT. In total 26/28 patients had either a positive CT or positive SPET studies compared with only 21/28 for a positive planar X-ray or planar skeletal scintigraphy.

We conclude that CT and SPET are superior to planar X-ray and skeletal scintigraphy in patients with chronic low back pain but should be viewed as being complimentary and not competitive investigations. In order to detect skeletal metastases from Ewing's sarcoma (ES) bone scanning is commonly used. However little information is available about the seintigraphic aspects of the primary ES during treatment and follow up. Therefore we studied retrospectively the Tc-99m MDP follow up bone scans (interval 6-12 months) from 32 pts (age 2-30 y) with non-surgically treated ES. All patients had multiple drug chemotherapy. Local treatment consisted of radiotherapy. The total follow up period ranged from 2-15 y.

The scintigraphic findings at the primary tumor site normalized in 16/32 pts during treatment and histologically or clinically tumor absence was proven. No recurrence developed during the follow up period. This was in contrast to: (A) 10/32 pts where the scan remained abnormal at the primary ES site; in 8 of them a ES residue was present (in the other 2 pts a fracture and eetopic bone formationwere the cause), and (B) 6/32 pts where after normalization of the scan 6-12 months later a hot spot returned: in one case due to ectopic bone formation, in the other 5 pts a ES recurfence was present.

In conclusion: (i) persisting increased uptake at the primary tumor site during treatment, or recurrence of the hot spot within 1 year is suggestive for the presence of malignancy. Radiography should exclude benign causes like fracture and ectopic bone formation.

(2) Follow up scans turning negative and remaining negative for more than a year suggest the absence of local ES recurrence.

MMC Tie.l-van Buul, EJR van Beek, A van Donqen, EA Nooltgemacn~, AJ Bakker, AH Broekhuizen, EA van PQ_yen, Acaaefidc Medical Center, Amsterdam, The Netherland~

The unreliability of radiological diagnosis of scapnoid fracture after c~rpal trauma is a well-rec~/s.ecl problem. ~herezore we examined the value of ~-pnase none scintigr@pny in a consecutive series or patients with olini@x~l slgns of fracture of the carpal scapnoid bone am negative or non-diagnostic initial ra~ogr@pns.

36 1)atzents were inel~ed in our study, 16 men and 20 women, mean age 41. 8 y, .ran.ge 24-65 y. The time of imaging after trauma 9hriea zrom 3 to 30 days wir_n a mean of I0. days. ' 88 ex~li'ners reviewea rl%e scintigra_phio zindings imepenaenr~y, without knowing v_ne results of the scaphoid X-series. Another 4 examiners reviewed the radi.ograpb@, independently without knowing the results OZ sointzg~-phy.

A normal bone scan was fouf~ in 9 patients. In these patients there were no a]3norm@l radiological findings. Abnormal zoca& inoreaseo u~r~uxe in both dynamic ana static phase, SUSl0ect for zracture, in one or more • was round in 27 patients [scaphoid 14, radius 9, ulna 2, other (meta)car/pal bones ~I). In 8 pai;ients mere r_nan one none was ihvolve(i Of these 14 scintigzg.phi'eally suspected fractures of the scaphoid none, only 7 (50 %) s~ sttosequent radioioqieeLL evidence of fracture after a penc~1 of up toB weeks. Of r/le 22 ov~ler scintig~qaphio a.D.norn~alities 19 cases (86 %) could be radi'o• conxizIAea " as a zracture. TO inter~rgte r_ne d~nam/c p~e, v_ne static image s were neeuea in 25 cases. In 22 cg.t of 23 pet ients .t/}ere was no difference in quality of v_ne static image wir_n or without the plastercast_ .

. . . COnclusions: 1. In a c-inicallysuspeoted sc@pnoia zracture, the bone scan seems to De more sersitive than the scap hoid X-series; 2. In case of a fracture in another localisation the result of the bone scan can be a guide to the referring~hys..ician; 3. The dynamic phase alone is only in 30. % suzzicient for correct interpretation of vlae none scar~ 4. 'zne presence or a plastercast does not influence the result of the nones car~ Temporomandibular joint (TMJ) dysfunctions are not detected at the beginning because of lacking an objective diagnostic test, although they are symptomatic. The early diagnosis of TMJ dysfunctions provide some preventive interventions before irreversible changes occur. Recent studies have showed that bone scintigraphy can detect the changes in TMJ while are not visible with x-ray yet. In this study, Tc-99m MDP planar (P) and SPECT studies were performed to 33 patients (66TMJ) with TMJ dysfunction symptoms. Planar.transaxial and coronal images were evaluated both visually and quantitatively. The results were compared with x-ray (R) findings.

Both R and P were negative in 12 TMJ and positive 31TMJs. But, R-negative 15 TMJs were postive in P and R-positive 8 TMJs were negative in P. On the other hand, in all P-positive cases, SPECT were also positive but additionally 3 out of 8 TMJs which were negative in P studies. In conclusion, for earlier detection of TMJ dysfunction planar bone scintigraphy seems to be a very usefull test having SPECT possibility if it is negative.

The aim of the study was the evaluation of clinical usefulness of Tc-ggm albumin nanocolloid (NANOCOLL-SOLCO) scintigraphy in the differentiation of causes of painful hip after replacement surgery.

Hips radioisotopic images were obtained in 20 patients (13 females and 7 males) aged 49-79 (mean 61). In this group 26 hips with total prostheses were examined, including 11 suppurative, 9 with mechanical loosening and 6 without pain in bilaterally operated patients. Scans were made 2 hours after nanocolloid intravenous injection.

The original interpretation technique, based on topographic analysis with hips X-ray pictures, was applied in all cases. Results of nanocolloid examinations were verified by microbiological investigations in all patients and in 15 cases sampling was done during surgery.

Compatibility of nanocolloid scintigraphic scan and clinical as well as microbiological examination was found in 18 patients (24 artificial joints). One false positive and one false negative result were found, Sensitivity was 91%, specificity -93% and accuracy -92%. In all true positive pictures it was possible to establish anatomical localisation of suppurative lesion in joint space, acetabular or femoral area.

Presented results indicate Tc-99m albumin nanocolloid scintigraphy is of great promise for differentiation between mechanical loosening and suppurative lesion in painful hip joint after total arthroplasty. They suggest that the described method is helpful in detection of low grade infection and prevention of suppurative complications after total hip replacement surgery. Malezieux X, Lecouffe P, Rousseau J, Marehandise X Service Associ~ de M4decine Nucl4aire CHU de LILLE -59037 LILLE Cedex -FRANCE SOI~ TISSUE COMPOSITION AND FEMORAL NECK BONE MINERAL DETERMINATION Although femoral neck fractures have a largely heavier economical incidence than vertebral crushes, absorptiometric determination of bone mineral content is fairly less reliable in femoral neck than in lumbar vertebrae. Troubles in femoral neck measurements are numerous : failure in positioning patients in a reproducible way, difficulties in designing ROI, variations of thickness and of fat/water content of soft tissues surrounding femoral neck. To appreciate the importance of the later, we used concurrently two different approaches 9 1. DPA was modified to determine fat/water content when scanning over soft tissues while data necessary to bone mineral content measurements were accluired when scanning over bone ; 2. MRI provided visualization and quantitative data about the soft components of the thigh.

Soft tissue compositions determined in 10 patients by both methods were in good agreement. Using models suggested by MRI data, baseline corrections in bone mineral content calculations were interpolated from fat/water DPA studies with an adequate software. In a given patient, variations as large as 30 % in fat/water composition and as 10 % in thickness of soft tissue can be observed in DPA study according to the region where soft tissue was appreciated. This leads to uncertainties in femoral neck mineral content which are quite larger than theoretical reproducibility. Software for femoral neck absorptiometry should include a comprehensive treatment of soft tissue effects.

Collecting data for correlation between soft fat content and bone mineral content is under current studies. In consequence to a previous double blind study (Buchali st ai.1988) we studied the influence of therapy with a new protocol using different amounts of 89-St adapted to mass of metastases (3 injections, 75 to 150 MBq each). In 56% of 42 pats. pain relief is achieved, with no differnece to former placebo group. Regredient or stable skeletal scintigrams were found in 82%. Survival with median value 8.5 months also is not different from placebo group (p~.05). Grading and duration of disease proved as influencing covariates of survival (p= .085 and .028 resp.). Compared to previous reported groups, an increased number of low or undifferentiated cancers is revealed. Survival of these patients shows a tendency to increase survival, but without statistical proof due to low numbers. Haematological complications were found in 41%. An increase of pain relief or survival due to increased amounts of 89-Sr cannot be demonstrated. We recently showed (S. K. Shukla, et el., 1989 ) that spontaneous mammary tumours, Balbcf/C3H and Balbcf/CRIII, in mice have high affinity for chromatographically and electrophoretically pure anionic Ga-67, with which a clean seintigraphic image of the tumour can be obtained within 4 h p.i. The radionuclide is firmly bound to the tumour to allow its follow-up studies for 9 days. Since yttrium-90, like Ga-67, is trivalent we obtained it in anionic form in presence of sodium citrate, which was chromatographically and electrophoretically identical to mammary tumour-specific Ga-67 in solution. With this Y-90 solution at the dose of 20 MBq/Kg we cured spontaneous mammary tumours in mice without any side effect (S.K.Shukla et al., 1989) . In the present work we have extended our studies on the mammary tumour therapy with Y-90 to spontnaeous mammary tumours in dogs. Pure anionic Y-90 was injected i.v. at the dose o~f 20 MBq/Kg three times at the interval of 3 days. Within 15 days the tumour disappeared. The dog is tumour-free for 3 months. No side effect of the therapy was observed. Other dogs treated similarly are under study. These results encourage the therapy of breast tumour with mammary tumour-specific Y-tO, when higher quantity of carrier-free u is available.

V~na S., N~mec J., Rezek P., Nov~k Z. Research Institute of Endocrinology, Praha Teaching Hospital Praha Motel, Czechoslovakia

To evaluate the effect of radioidine treatment on the course of Graves" orbitopathy, late results of different therapeutic schems were compared: Dynamics of Hertel's measurement (dH) and of Werner s index (dW) were evaluated. Patients were treated with nonablative doses of 131 I from 70 to 350 Gy without prednisone (N=72) and with. prednisone (N=24) and with ablative dose lOOO Gy or more without prednisone (N=lG) and with prednisone (N=30). Most pronounced amelioration of both dH and dW was found after ablative dose in combination with prednisome (dH = -2,75 + 2,25; dW = -3,37 + 2,50). Ammelioration after ablalive dose without p~ednisone was moderate (dH = -0,84 ~ 1,78; dW = -1,15 + 1,59) similar to the effect of prednisone without 13f I (dH = -0,87 + 2,36~ dW = -1,62 + 2~14). Nonablative dose with pred Z nisone had also similar effect (dH = -1,22 + 1,95; dW = -1,13 + 1,23). Noeablative dose without prednisone had no -significant effect (dH = -0,08 t 1,75; dW = -0,56 ~ 1,16). There was no consistent increase of effect with increasing nonablative dose 131 I from 70 to 350 Gy both with and without prednisone. The use of ablative radioidine in combination with prednisone is recommended for Graves" orbitopathy. Rad~(dodime therapy of AFTA is very often prefered both by the patients and physicians as it is more convenient and without the risks of the surgery,and mostly because AFTA Occur in elderly people,lt has been documented that radiotherapy of thyroid diseases increases the risk for development of malignancy,but few patients with radioiodine induced malignancy after treatment of AFTA have been reported.

J-131 therapy was applied in 441 patients out of a setie of 1140 with AFTA observed during the period of 1966 -1982.The average therapeutic dose was 17,1 MBq(436/uC) .per gram of adenoma.The time of follow up of the sefie Is 1-17 years.ln 3 patients(O,68% of the treated ones) developed malignant tumors in the previous adenoma,after 9.5,11 and 12 years of =the therapy.The age of the patients at the time of the carcinoma diagnosis was:57,59 and 48 years,resp.The applied doses of J-131:23 MBq(625 ,uC), 9, 7 MBq(262, uC) and 8 MBq(216.uC) ,resp.Histologic ~indings Of the ~alignancies are:a~plastic carcinoma (spindle and giant cell variant),anaplastic and follicular carcinoma and follicular carcinoma with distan~ bone metastases.

The findings indicate an occurrance of thyroid malignancy about 100 times higher in I-,1,3r~ i~reated AFTA than in the other populatiOn,as in the sam~ period of time and in the same region of the country(about 2 millions people),144 cases of thyroid carcinoma are found. Despite recent technical advances the mortality and morbidity of the surgical removal of cranJopharyngiomas r~nains h~gh. Since the majority of these histologically benk/n, slow growing tumors are either totally or in large part cyst/c, trea~nent of the cystic component is the major part of the therapeutic attitude. S~ple aspiration has not proven to be adequate treatment as the cysts tend to recur. In order to prevent such recurrence the intracystic inject/on of collo~dal ~ emitting radioisotopes is currently performed in several centers. The main risk of this procedure is the irradJat/on of vital neighbouring areas by the cyst, brain, liver, kidneys, and bone marrow in case of leakage of the cystic contents. We have used IB6Re collo~dal sulfur to treat 41 patients harbouring cystic craniopharyngJomas. This choice was based on a) ~ emission has a mean penetration of about imm, thus sparing vital neighbouring areas b) gamma emission (137K eV ) allow s perfect survey of the rad~oiactive distribution in a search for possible leakage, c) T 89 of 90~ hours enables the delivery of the total dose over a shorter perk>d and a sooner reaspirat/on of the cystic contents. The protocole is as follow: a)Inject/on of a test dose/n the cyst. b~Brain, liver, kidneys ~mages are made 0, 24, 48, 72, 96 hours p i. to verify cyst tightness, c)In absence of leakage injecT/on of a therapeutic dose (0,7-1~GBq) d) new follow up and in case of leakage (abnormal activity in sub arechnoid space(SAS), liver, kidneys aspiration and washing of cyst and SAS. We have found IB6Re collo~dal sulfur to be a satisfactory radioisotope preparatdon for use in the stereotactic treatment of cystic cran/opharyngiomas. 

The aim of this study was to evaluate the radiochemical and immunochemical properties of an antibody preparate. Anti-human-ferritin IgG has been raised in goat and highly purified by affinity chromatography. The IgG was radiolabelled with 131-I by Chloramin-T method. In vivo properties of 131-I antiferritin IgO was determined in biodistribution studies on phenotypically immunosuppressed CBA mice bearing ferritin producer HeLa xenografts. The ferritin production of HeLa cell line was verified by FITC-labelled antiferritin antibody.

For localization index (LI) calculations non-specific IgG (normal human IgG) labelled with 125-I was used. The yield of labelling determined by TLC was 50-80 %, specific activity ranged 0.5-2 mCi/mg(18.5-74 MBq/mg). The results of immunoelectrophoresis and affinity chromatography (CNBr activated Sepharose-4B) showed preserved antigen binding capacity. Iodine released from IgG was about lO % during 3 weeks storage at 4~

The biodistribution was as follows: It is well known that PET with Fluor-18-Deoxyglueose (FDG) can be used to study the glucose uptake of malignant tumors in vivo. Moreover several authors reported that the FDG accumulation and the grade of malignaney as estimated by histological examination are correlated. The aim of our study was to evaluate the relation between the FDG uptake and the proliferation rate in patients. We examined 8 patients with histologically proven head and neck cancer using 444 MBq FDG. Perfusion studies with O-15 labelled water (3000-3700 MBq) were performed in 6 patients. Immediately after the PET examination a biopsy was performed from the target region. The cell eyele fractions were determined by onedimensional flow cytometry (DAP1 staining). We found that the FDG accumulation was increased in all eases (250%-500% relative to normal soft tissue). Perfusion values were also raised. The flow eytometric analysis revealed an increased percentage of S-phase and G2/M-phase cells (15-27% S+G2/M cells). The proliferation rate and the FDG uptake were nonlinearly correlated. These results show that PET with FDG can be used to estimate the tumors tendency to grow. Furthermore, besides the proliferation rate other parameters (e.g. tumor cell fraction, G0/Gl-phase cells) determine the FDG uptake in tumors. 

Specially prepared Y-90 sempounds seem to be useful for the endoradionuclide tumour therapy. We learned from o~n experiments that hereby skeleton and liver wsold be 1~e critical orgsns, obe %o the Y-90 biekinelics (K.~skm et el. 1989 ). ~rres~i~ side effects may be reflected by changes of the blood coU]ositinn. ]berefore we investigated the o~ of different blood parameters in healthy AB mice up to 40 days after intraperitoneal (i.p.) injection of Y-g0 radio~etivities (as citrate) between 18.5 and 570 M3q/kg body ~eight. We determined the alanine-aminotcansferase content (ALAT), the red blood sell csont (RBO), the median corpuscular hemoglobin ccntent (MCH), the hemoglobin content (He), the leucocyte number (~hite blood cell count : ~C) and Ire differential bemogram in blood samples beth of injected and non-injected mice. ]he m0st sionificent radiationinduced changes could be proven by ALAT-and WBC-analysis. After i.p. injection of 370 NBq Y-98 we found the ALAT-minimam of 0.59 pmol/s.l (normal value: 1.2 0.5) at the 15th day p.i. and the WBC-minimum of 0.4 G~ (ca. 9% of the normal value) at the 9th day p.i.. Furtbermore, the granulecyte/lyn]:tocyte ratio is distingtly increased at 2 days p.i. and later, at 9 days p.i., clearly deeresed. In conclusion, an influense on bore-marrow, the ly~tie system, and,. if higher red~oactivities are applied, on tbe liver porenehym mist be e~ected after Y-go application. IVe consequences for the survival time will be discussed. 

Patients and methods : renal studies were performed in 15 normal volunteers (7 men and 8 women) aged from 20 to 43 (mean : 34 years) using a dose of 1.33 MBq/kg 99mTc-MAG3 after hydratation (250 ml). The Effective Renal Plasma Flow (ERPF) was determined both by Blaufox and Piepsz methods. Using Gates fermula~ Global Renal Uptake (GRJ) was calculated as the percentage ratio between second minute counts for both kidneys corrected for background and depth over injected dose. Background was estimated by two Outlined Region of Interest (ROI) and also by a dilatation algorithm without ROI outline.

Results : after correction by body surface, ERPF mesured by Blaufox method was 343.9+_72.1 ml/mn (m+S.D.) with a distribution volume of 9.2_+1.9 i, while Piepsz method yielded 316.2+68.9 ml/mn. Blaufox method gave 18.1+2.4 min for 99mTc-MAG3 T 89 Differential Renal Uptake (DRU) was 53.5+4.3 % for the right kidney and 46.5+4.3 % for the left kidney. Global Renal Uptake was 18.6+2.8 % with a range of 14.1 to 24.3 %. Excreted percentage of administered dose (prevoid counts) was 13,5+3,1 Z and residual percentage (postveid counts) was -4.5_+1.7 %. Voided percentage (well counter) was 69.3_+8.4 %. Although no significant difference was found between ORU interobserver reproducibility of the two background methods, DRU interobserver reproducibility was significantly better with the dilatation method (~<0.05). Highly significant correlation was found for ERPF (Blaufox) and GRU (r=O.93). Images were excellent in all cases. Parenehymous time activity curves were peaking at 189s (+2S.D. 129-281s). In conclusion : determinatTon of GBU (14 -24 %) can be a simple and reproducible valid index of renal functionnality. We have investigated the effects of the following on the computed transit times derived using the matrix inversion method in Tc-99m DTPA renography : input ROI (left ventricle LV Vs aorta), liver and spleen involvement in the kidney ROIs, kidney and parenchymal ROIs, extrarenal background and reproducibility.

In 20 normal kidneys, the mean kidney MI<TT and mean parenchianal MPTT transit times were significantly higher (p < 0.03) when the LV was used as the input ROI instead of the aorta. Differences were greater (p <0.005) when the total area under the retention function was used rather than the area up to the first zero crossing. Use of the LV ROI is recommended. There were no significant differences (p > 0.5) in the MPTT and MKTT if part of the liver or spleen was included in the kidney ROI. MPTTs derived from two small box ROIs drawn on the upper and lower poles of the kidneys were not signicantly different (p > 0.06). There was no significant difference (p > 0.06) between either of these values and the whole MPTT. Background subtraction results in decreased transit times. The difference is significant only for the MPTT (p < 0.05) when the area up to first zero crossing is used. If the total area is used, the differences are significant (p < 0.005) for both MPTT and MKTT.

Concerning intra-observer reproducibility, the coefficients of variation CVs for the kidney and parenchymal ROI sizes were 5% an d i0%, respectively, for both normal and poorly functioning kidneys. The CVs for MKTT and MPTT were about 1% for normal kidneys and 4% for poorly functioning kidneys. The aim of this study was to evaluate Tc-99m-Aprotinin (A) renal scintigraphy and to compare with Tc-99m-DMSA (DMSA). 23 patients (serum creatinine 0.8-11.0 mg/dl) were studied,14 with both tracers.Estimation of kidney uptake and other simple quantitative indices was obtained from the 6 h image, i) There was a significant correlation (p<O.O01) between DMSA and A renal uptakes (r=+0.78). Individual uptake values differed for the two tracers (SED =• showed a strong correlation between the two tracers (r=+0.81 p<O.O01), and was lower about 50% for A. 2) (A) and DMSA uptake showed a positive linear correlation with inverse of creatinine(Cr) levels and with inverse of urea (U) levels. The correlation was stronger for A than for DMSA (r=+0.93 VS+0.63 for Cr and r=+0.81 VS+0.43 for U). The Bkg/pixel both for A and DMSA showed a highly significant positive linear correlation with Cr levels (r=+0.94 and r=+0.77). 3) Two experienced observers were asked to compare the scintigrams for each kidney of the 14 patients,without previous knowledge of the tracer used. The quality was judged identical in 7 left and 8 right kidneys. 4 L and 3 R kidney scintigrams were judged definitely superior with (A) while i R kidney slightly better with DMSA. These differences were statistically significant (SIGN TEST:X2=5.1 p<O.03). Conclusions: Renal scintigraphy with A is comparable and occasionally superior (in patients with renal insufficiency) than that with DMSA.Quantitative indices of renal uptake show that this superiority is due to reduced background.These indices show higher correlation with serum Cr in the case of (A) than DMSA. While the feasibility of 99mTc-MAG3 as tracer for clearance measurement is under discussion, an agreement about the best clearance-technique and its standardization has not been reached yet. Therefore, with the established tracer J131-hippurane the influence of instrumentation, algorithm, and the time point of the blood sampling on whole body renal clearance was investigated. The study included simultaneous sampling with a partially shielded whole-body counter (WBC) and a gamma camera to assess effective renal plasma flow (ERPF). The results obtained using two different analysis algorithms for each modality are compared. Although ERPF as determined by the Oberhausentechnique was significantly higher (p<O.O01) than that obtained using an own algorithm based on the 2-compartment-model, for each algorithm there was no significant difference between the WBC and gamma camera derived values in the range of 100 to 800 ml/min. Furthermore, positioning of the ROI was not critical for gamma camera derived ERPF (SD<1% for multiple cresentic ROls and appr. 4% for multiple rectangular ROls). However, the time of blood sampling did appear more important since the average ERPF from the 10-and 20minute-samples differed significantly (p<O.O01) from the 15-and 25-minute-samples for both algorithms. The methodology which we have validated provides a more precise tool for further investigations of the influence of medication, posture, and exercise stress on kidney function and also the assessment of other tracers as clearance substances.

Landspitalinn, Reykjavik, Iceland.

In 20 pts (age 15-79, mean 39.5, clearance values 7.9-148, mean 71.9 ml/min/l.73 sq.m. BSA) simultaneous Cr-51-EDTA and Tc-99m-DTPA clearances were calculated from 5 external measurements (over the heart), and i0 subsets of these, + 1 blood sample at different times post single injection, and these clearance values compared to the standard Cr-51-EDTA method (5 blood samples at 30 min intervals 2-4 hrs p.inj.).

In all cases a very good correlation was found. A corr. coeff, r=.977 was found for 5 external measurements of EDTA with 1 blood sample 2 hrs p. inj. and a corresponding value for DTPA was r=.978. A slightly decreasing rvalue was found the later the blood sample was drawn. A good accuracy was found by using two external measurements 2.5 and 3.5 hrs p.inj. and I blood sample at 2.5 hrs ( GI studies were performed first with MAG3 and thus with DMSA and 02 studies with MAG3 only. The DMSA uptake was determinated from a background and attenuation corrected 6 hours delayed image. The results were expressed as RUdmsa, the ratio of one kidney uptake to the sum of two kidneys uptake and as AUdmsa, the percentage of injected dose present i~the kidney at 6 hour. For MAO3 studies normalized, background corrected time ac-~iyity curve were used to calculed relative and absoute uptake. The relative uptake (~) were given by slope (SM) and integral (IM) methods.

The absolute uptake (AUmag) were the percentage of injected dose present in the kidney between 60 and 170 second post injection. Results The Perfusion Index (PI) has been widely used as a quantitative measure of blood flow to renal transplants, but is prone to large inter-operator errors. Recently, Peters et al* have measured blood flow as a percentage of cardiac output (BF), while we have used the ratio of blood flow to the cross-sectional area of the iliac artery (BF/AI) in a technique similar to that suggested by Lear et al**.

This study measured the inter-operator errors in the three methods. 21 studies were carried out on 10 patients, within 24 hours of surgery and subsequently during rejection. In each study a bolus injection of 8 mCi of Tc-99m DTPA was administered and an anterior dynamic study of Is/frame for 36s acquired. Two independent operators measured the three parameters of blood flow from the first pass of the bolus, and the differences in the rseasurements were analysed to find the inter-operator errors.

Pl ranged from 69 to 445 with a mean of 174, an inter-operator error of 47, and a coefficient of variation (CoV) of 27%. BF ranged from 2.3% to 20.3% with a mean of I0.9%, an inter-operator error of 1.2% and a CoV of 11%. BF/AI was measured in units of ml/min per square mm and ranged from 3.1 to 19.7 with a mean of 7.7, an inter-operator error of 1.6 and a CoV of 21%.

in conclusion, BF had much less inter-operator error than the other two methods, and should be considered as a replacement for PI. The impact of CyA on renal haemodynamics remains controversial. We studied 18 children receiving CyA for dermatomyositis. Each had 2-4 Tc-99m DTPA renograms over a period of 5-20 months. Renal blood flow (RBF), glomeular filtration rate (GFR) and filtration fraction (FF) were measured (Peters et al Nephron 1989, 51: 470) .

In 9 who had pre-CyA studies, there was a significant fall in GFR (138 + 20 to 127 + 30; p< 0.01)at the first post CyA study b~t no change-in RBF. Following institution of CyA, only I child displayed significant (but reversible) nephrotoxicity with a marked fall in RBF and increase FF. He was on the highest CyA dose (11mg/Kg/day).

CyA blood trough levels(parent compound)correlated significantly and inversely with GFR (r : -0.56, p<0.002) and FF (r = -0.51, p<0.01) but not with RBF or with CyA dosage. There was also a significant correlation between changes in GFR and changes in FF (r =0.54, P< 0.01) RBF remained relatively stable, fluctuating less than FF and not correlating with changes in GFR. CyA in the dose range 2.5-7.5 mg/Kg/day causes mild dose-related renal tubular damage, resulting in DTPA back-flow across the tubule and an apparent fall in FF. 

Since the introduction of early cyclosporine treatment in kidneytransplanted patients (pts), renal perfusion index (Hilson, '78) becomes less useful to discriminate between acute graft rejection (R) and acute tubular necrosis of transplanted kidney (ATN): this because cyclosporine itself has two pharmacological actions: clinical improvement in pts with R, but vasoconstiction and thus reduction of perfusion in all the pts. Although there are great differences in farmacokinetic behavior of 1-123-ortho-iodo-hippurate (OIH) and Tc-99m-mercapto-acetyl triglycine (MAG3) with respect to renal clearance, plasma albumin binding and apparent distribution volume, the overall excretion pattern of both agents is well comparable within the first 30 minutes after intravenous injection. 1

In the present study we tried to establish wether the performance of these two agents are also comparable with regard to semi-quantitative renal function, viz. the Hippuran Uptake Capacity (HUCI0) and its analogon the MAG3 Uptake In order to correllate renal tubular dysfunction (DMSA uptake) with morphological evidence of vascular injury, a pig model of complete, acute and chronic ureteric obstruction was studied. The pig kidney is anatomically analagous to that of the human. 13 kidneys in 9 pigs were obstructed for periods of 0.5 hrs (n:2), 24 hrs (n=2), 96 hrs (n:1), 240hrs (n:3) and 480 hrs (n=5). 4 normal kidneys were also studied as controls.

Live, anaesthetised animals received a intravenous bolus of Tc 99 DMSA, 10 minutes prior to nephrectomy.

All kidneys underwent ln-situ perfusionfixation at mean arterial pressure for 15 minutes. Resected kidneys were scanned on a gamma camera and then underwent plastic casting of the arterial tree. Sections of the kidney were macerated in HCL and examined by scanning electron microscopy (SEM). Results: DMSA scans were normal up to 96. Thereafter there was a progressive, focal reduction in uptake of isotope. SEM of normal kidneys showed no apparent vascular abnormality.

SEM of chronically obstructed kidneys revealed a discrete preglomerular stenosis in areas of reduced DMSA uptake.

Conclusion: Reduction in DMSA uptake correllates with areas of vascular abnormality in the pig model of chronic ureteric obstruction.

The vascular stenosis may represent a physiological sphincter. Although Tc-99m MAG3 renography is less sensitive to background than Tc-99m DTPA renograptiy due to a higher target/noise ratio background and attenuation remain the two main problems in renal function determination with a scintillation camera. The aim of our study was to evaluate the effect of background subtraction on the accuracy of left and right fractional renal function (FRF) calculated from MAG3 renography. FRF calculated from SPECT with Tc-g9m DMSA was considered as the reference standard since after reconstruction background in the kidneys areas is negligible and attenuation maybe considered equal in both kidneys and-tHerefore does not affect FRF. Fourteen successive patients referred for evaluation of FRF underwent a DMSA planar and tomographic study and next a MAG3 renography 48 hours apart. Absolute creatinine clearances ranged from 35 to 196 ml per minute and left DMSA FRF ranged from 17% to 65%, average 49% Left FRF was calculated from 1) two-to-three minutes MAG3 built-up image 2) MAG3 renal distribution volumes curves 3) posterior DMSA planar image and 4) DMSA tomographic images. The first three methods were compared with method-4. The average background in each kidney area (methods 1-3) was assumed to equal that :n a ROt surrounding the kidney. Attenuation was calculated from renal depth based on the height and weight of the patient according to Tnnesen's formula andTrom the measured attenuation coefficient of Tc-99m in plexiglas medium. To keep the total chance of making a Iy.pe 1 error below 5 percent, statistical analysis used Bonferonni paired t test following repeated analysis of variance. Results show a significant overestimation of left FRF compared with the reference in method 1 (4.9%) and in method 2 (3.8%) while the difference is still positive (2.5%) yet not significantly in method 3. We conclude that the background subtraction procedure using a perirenal area leads to an overestimation of the left FRF. This effect might be caused by an average background in the right perirenal area in excess over its corresponding renal area. "The smaller difference in method 2 and 3 may be explained by the fact that method 2 is independent of the vascular component of the background, while in method 3 the total background is generally rather tow. Epithelial clearance of aerosolised 99m Tc-DTPA is commonly measured over the lungs by the ROI technique. The disappearance rate of the radioactivity is thought to give a measure of the rate at which small molecules leak from the lung into circulating blood. Factor analysis provides factor images and time-activity curves of principal components corresponding to underlying specific structures, even if they overlap. When applied to dynamic inhalation studies (n=16), factor analysis in all instances extracted two simultaneously operating factors with different temporal behavior, one with rapidly decreasing kinetics corresponding to epithelial transport and one with horizontal or slightly increasing kinetics corresponding to mucociliary transport. In nearly all cases, factor images demonstrated overlap of both factors, even in the lung periphery. Clearance rates measured by the ROI technique did not differ from those calculated from the sum of both fectors plus the factor background (median: 1.35 vs 1.25 %/min, n.s.), but clearance rates of the factor related to epithelial transport were significantly fester than those measured by the ROI technique (median: 2.2 vs 1.35 %/min, p~0.001), strongly indicating interference of other clearance mechanisms with the latter. 183 MBq of 133Xe was administered for both perfl~ion and ventilation. For ventilation, 13$Xe was given at fuU inspiration and rebreathing ~,~as continued Llntil eqt~ilibrium. Each lung was divided into thi'ee zones as upper, middle and lovcer. Regional ventilation(Vr) vtas determined using the area ~indef the first peak at the begining of the procedure. Regional perfusion(Pr) was 'determined using the area under the peak af'~ef iv administration. Pr and Vr ale expressed as the percentdge of total for each lung. Slopas "~'~re calculated l],ging the first compartment of the washout curve. The absolute slope values of the washout curves after perf'usion(P~) and ve.ntilation (Vd) were also expressed as the percentsge of total for each lung. In normals, a correlation coefficient of r= .695 w~ found betveen Vr and V~, r= .585 ~as found betv~een V r end Ps, I"= .882 rcas found between Pr and P~ and r=.610, r=.461 and r=.685 were found in patients, respectively. Dif'f~rence betxceen regional Pr and P~ values "~'as statistically insignificant in narmals and in patients.

In previo~ studies, slope -~'alues of 133Xe clearence after perf,• ~ sho'~m to correlate with alvealar ventilation. In our study. "w~ have shown that Ps reflects regional perf,• in normals but the correlation with regional perf'usian diminishes in cases of impaired ventilation. Diminished perfusion and prolonged emptying of lung regian~ can both lorce.r the slope values. So, Vs can be a parameter for alveolar ventilation, but Ps mainly reflects alveolar perfusion.

T. Simon, S. Pfeffer, E. Molina, R. Hubbard, R. Crystal. Clinical Center and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Nil).

AUTOMATIC QUANTIFICATION OF DIFFUSE GALLIUM UPTAKE IN THE LUNG Diffuse pulmonary inflammation can increase gallium-67 citrate uptake in the lung. Although qualitative and semi-quantitative methods of describing diffusely increased pulmonary activity are clinically avaliable, their imprecision causes confusion that limits their widespread use. A quantitative procedure could explicitly and clearly describe the overall uptake. This study applied a new automated quantitative method to determine whether it distinguished among diagnostic groups. Subjects with diffuse lung disease were expected to show higher diffuse pulmonary uptake than those with focal thoracic disease and normal controls.

The method was prospectively tested under an ethically approved protocol with 14 consecutive subjects having diagnoses suggesting diffuse lung disease[D](9 with interstitial lung disease) and focal thoracic disease [F](5 with lymphomas) and 2 normals [C] . 48 hrs after 6 mCi(222MBq) iv Ga-67 citrate, whole body images were acquired by a moving gamma camera interfaced to a digital computer. Automatic software found the mean pulmonary uptake [LUNG] by averaging the count densities in anterior and posterior regions of each lung. Osseous and cardiac uptake were calculated from mean counts respectively over the sternum [BONE] We conclude that this method for quantitatively describing the average pulmonary uptake of Ga-67 is easily implemented since it is automatic. Moreover, the statistically significant differences among distinct groups, suggests it has diagnostic potential.

Dodig D., Ivicevic E., Poropat M., Tezak S., Bracic I. Department of Nuclear Medicine, University Hospital Zagreb and Clinic for Lung disease Zagreb.

The methodes for detection of pulmonary sarcoidosis activity are clinical and x-ray examinations, functional lung tests, bronchoalveolar lavage/BAL/, determination of angiotenzin converting enzyme /ACE/ and Ga-67 citrate scintigraphy. The group of 35 patients with histologic evidence of lung sarcoidosis were examined with various msthodes in order to determine sensitivity of quantitative Ga-67 scan in comparison with other methodes. According to x-ray e~amination patients were divided in 4 groups: 0-wihout changes (5pts.), I-hilar node involvement (6pts.), II-hilar and parenchymal involvement (14pts.), IiI interstitial reduction (10pts.). In order to determine activity of lung sarcoidosis we performed quantitative Ga-67 scan, functional lung tests, determined ACE in all patients and in 7 patients BAL was performed. In our group 42% of patients had abnormal lung tests, 34% elevated ACE and 74% had positive Ga-67 scan. In 2 out of 7 patients BAL was positive and in 4 out of same patients Ga-67 scan was positive. Our results showed that quantitative Ga-67 scan is the most sensitive method in detection of lung sarcoidosis activity expecially in x-ray stage "0" and "I". This method is usefull in determination of lung sarcoidosis activity as well as in follow up of disease. Thirty patients with histologically verified sarcoidosis (S) were studied with Galliumscintigraphy (GAS), bronchoalveelar lavage (BAL) and angiotensin converting enzymes in plasma (ACE). Gallium uptake was assessed by a computer based modification of Lines method. These measures were compared with the radiological pulmonary involvement (Xray), the pulmonary function tests forced ventilatory capacity (FRC) and carbonmonoxide transfer factor (TICO), and a summed score of FRC and TICO (Score The contribution of many metabolites of arachidonic acid (AA) in pathogenesis of AROS is unquestionable. However,the role of lipoxygenase products of AA,12-and 15-HETE, generated by lungs is still not clear.

The aim of study was the estimation of plasma concentrations of these substances and investigation of the correlation between above values and LIS in patients with post-traumatic AROS.

Venous blood samples have been taken from 5 patients who died (I group) and from 3-who survived(II group),during 3-5 days from the beginning of the disease.The concentrations of studied substances were determined using RIA kits (DRG,USA).Normal values were obtained from ii healthy persons.The LIS,which takes into account the changes in chest rentgenograms,hypoxemia degree and values of positive end expiratory pressure and lung compliance, changed from 0,75 to 2,5.

The results showed an elevation of 15-HETE concentrations at the first day of ARDS and subsequently,in the next days,decrease of these values in the I group and increase in the II group.The comparison with LIS values demonstrated the negative correlation.The concentrations of 12-HETE in both groups were lower than in healthy persons and did not showed correlation with LIS.

The negative correlation between the concentrations of 15-HETE and LIS in post-traumatic ARDS may indicate the usefullness of this AA metabolite determinations in biochemical monitoring of syndrome's course. Increased vascular permeability accompanied with acute organ failure lead to a massive deterioration of vital functions in ARDS. The sequence of lung microvascular permeability (LMVP) changes in early direct posttraumatic (n:21) and late indirect (n:7) pancreatitis i~ duced ARDS was studied and compared to a control group (n:10). A LFOV-Oamma-camera with a DEC-PDP-II-Computer was used. The inflow of in vivo labelled 113m In-transferrin into the extravascular space was visualized by calculating an index between the regional 113m In-activity and the 99m Tc-bloodpool activity of in vivo labelled erythrocytes over both lungs. The LMVP-Index CLMVPI) was used to quantify LMVP in dynamic scintigraphic measurements. In the control group the LMVPI was 2,6J2,8 %Zh f~ both lungs. The initial evaluation of patients with direct early posttraumatic ARDS showed for the injured side a LMVPI I0,8~5,1 Z/h, but normal values for the non injured lung, whereas 4 days later on the healthy side the LMVPI increased to 8,0~5,0 t/h, In indirect late ARDS the LMVPI was elevated in both lungs (I0,5t4,4 Z/h). The LMVPl-distribution and values were different in both ARDS groups indicating a different sequence of mechanism causing the ARDS due to direct and indirect injury. The study proved to be valuable for clinical management of ARDS. Seventy-fou~ patients with intrathoracic lesions were studied prospectively with planar Thal]ium-2Ol(Tl)scintigraphy to determine optimal imaging time and study its merits to discriminate between benign and malignant lesions. Histological findings served as golden standard in all cases. Serial images were obtained immediately after injection of 3Mci T1 in the cubital vein contralateral to the side of the lesion~ Calculation of the uptake ratios of the lesion compaired to the contralateral normal lung by measuring the mean voxel counts for regions of interest, demonstrated an optimal imaging time of 1.5 hours post-injection. Our study population comprised 23 benign and 51 malignant lesions.

NUMBER TP  FP  TN  FN  HISTOLOGY  smallcell lung carcinoma  7  7  0  0  0  non smallcell lung carcinoma 37  33  0  0  4  malignant others  7  7  0  0  0  benign others  23  0  9 14 0 TP=true positive, FP=false positive, TN=true negative, FN=false negative. False positive results were due to thymoma and bacterial or tuberculous infection leading to an overall specificity of 0.60. False negative results were mainly due to their localization posterior to the heart o~ their size smaller than 1.5 cm. Overall sensitivity in this study population was 0.92.

Results of our study population indicate the necessity of early and delayed imaging to improve discrimination betwee~ malignant and benign lesions. This will give rise to a higher specificity , whereas SPECT will be able to enlarge sensitivity. Ten bronchiectatic patients confirmed by broncography (BG) and 7 healthy controls were examined by Xe-133 gas ventilation study and washout analysis (VS). lime patients were also examined by chest X-ray (XR) and" perfusion scintigraphy (PS). Both lung{ were divided into three zones and comparisons of the diagnostic test{ were made based on these zones. 18 of these 60 zones were found 5ronchiectatic in BG. XR examination showed changes suggesting bronchiectasis in lO (56%) and nonspecific changes in 4 (22%) of the zones. All of the bronchiectatic zones revealed defects in PS and all but two of them showed delayed washout in VS. In addition to these zones, 2 zones in PS and 9 zones in VS were found abnormal. PS and VS revealed the ventilation abnormality in 4/18 (22%) of the zones which were found normal on XR, suggesting that perfusion and ventilation scintigraphy sigficantly increases the sensitivity of X-ray in detecting bronchiectatic zones. It was also found that VS showed a higher proportion (50% more) of airflow disturbance than detected as bronchiectatic involvement in BG which may be important as regards to the state of the remaining lung after surgical resection~ In order to replace (iSF)6-Fluorodopa by the more rapidly metabolizing (lSF)5-Fluorodopa in PET investigations of the dopaminergic system, the latter compound has been synthetized. 5-(2',2'-Dicarb et hoxy-2'-acet amido-methyl)-2,3-dimethoxybenzyl-diazoniumtetrafluoroborate was labelled with (lSF)Fluoride directly in the irradiated target water (D~SO) at 60~ for 15 rain. in a closed vessel. The labelled diazonium salt was then pyrolyzed at 120~ and the protecting groups were hydrolyzed with 48% hydrobromic acid. After distillation, the residue is dissolved into 0.1 M sodium dihydrogenphosphate PH 4.5 and is enantiomerically separated by HPLC chromatography on Chiraipak wH column 250.10 mm (15 rain). The reaction time is 50 rain, the labelling yield of the D,L product is 54%, the yield of (lSF)5-Fluoro-L-dopa is 25%. The specific activity is > 6.5 Ci/mmoh An alternative method, the pyrolysis in xylol, gives less by-products in the reaction, but takes 100 min. with the corresponding loss of yield. In both procedures, the enriched target material is recovered by distillation. Since they are one-pot reactions, the operation is carried out remotely controlled, starting with 200 mCi of lSF. We have previously shown that the evaluation of liver proliferation with PET and radiolabeled thymidine necessitates the use of a thymidine tracer labeled in C2position.

Therefore, we have now developed a rapid three-step synthesis of [2-11C] IMPROVED SYNTHESIS OF 11C-LABELED 5-HYDROXYTRYPTAMINE 5-Hydroxytryptamine (5-HT), (Semtonine) is one of the most common biogenic amines. Besides its important function as a neurotransmitter in CNS tissue, it serves as a potent vasoconstrictor, the blood level of which is rigidly controlled by lung tissue. t t C-labeled Serotonine was prepared from 5-methoxy gramine by nucleophilic substitution of the quarternary methosultate salt of the cold precursor with [11C] .HCN. The gaseous H 11CN was trapped in a solution of 6 pMol cryptotix K222 and 0.5 p.Mol K2CO 3 in 5 ml acetonitdle. Substitution was carried out on 12.6 ~Mol of the quarternary ammonium salt at 110~ for5 rain. Subsequent cleavage of the methyl ester by boron tribromide and final reduction of the nitdle led to Serotonine within 78 rain with an over all yield of 13%. The absolute yield was 11 +4 mCi. The synthetic pathway is similar to previously reported methods, however, refinement of the first step by introduction of K 222 Io support nucleophilic substitution and a change in the sequence of the subsequent reaction steps led to an over 100% increase of the production yield when compared with previously reported pathways. Purification of the product mixture by reversed phase HPLC led to a product traction which could be injected into patients directly.

Although the reaction conditions have been optimized in a series of experiments, the handling of the synthetic steps in terms of minimizing the synthesis time, could be further improved by partial automation. For the small sedes of production runs for human applications all steps were carefully monitored. From our experience we conclude that the overall synthesis time could be reduced to less than 50 rain., leading to absolute yields of ca 20 mCi of 11C-Serotonine, if partial automation is included.

M. CHIANELLi, A. SIGNORE, G.F. TONNARINI, G. RONGA, P. POZZILLI and M. NEGRI. Endocrinologia (I) and Servizio Medicina Nucleare, Clinica Medica (11), University "La Sapienza", Roma, Italy.

EFFECTS OF 125-1 AND 123-1 ON PROTEIN LABELLING. In the past decade several techniques have been developed for protein radioiodination, each giving different results and having different indications. The labelling technique can damage the proteins but, an effect can also be attributed to the isotope. 125-Iodine is commonly used for iodination of proteins for in vitro studies, whereas, 123-Iodine is the isotope of choice for in vivo studies. The aim of our study was to evaluate the effects, on proteins, of different labelling procedures and different iodine isotopes. We labelled human Insulin (INS, molecular weight 5800), human Interleukin-2 (IL2, molecular weight 15500) and human Growth hormone (GH, molecular weight 21500) using the following methods: Chloramine T, Lactoperoxidase/H202, Lactoperoxidase/Glucose oxidase (LPO/GOD) and Iodogen. We tested either 125-1 (IMS-30, Amersham) and two different types of 123-1 (Medgenix): Lab-W in water solution at pH 7 and Lab-B in 0.01M NaOH at pH 12. Labelled proteins were purified by HPLC and immunoreactivity tested by either antibody precipitation curve (insulin and growth hormone) or by evaluation of binding to specific receptors using the fluorescence activated cell sorter, FACS (Interleukin-2). Our results showed that when using 125-1 the method of choice depends on the sensitivity of protein to iodination, in particular the molar ratio Protein/Iodine must be kept between 1:1 and 10:1. When using 123-1 the method that gave the highest labelling efficiency (50-70%), without altering the immunoreactivity, was the LPO/GOD technique. A difference was also observed between the Lab-W and Lab-B form of 123-1, the latter being more stable and reproducible. In the case of 123-1 the molar ratio Protein/Iodine was also extremely important and should be kept between 5:1 and 10:1 in order to reduce labelling damages. Our results outline the importance of the molar ratio between the protein and Iodine during iodination and indicates that enzimatic methods are preferable when applicable. They may require more complex purification procedures in order to remove labelled enzymes but lead to immunoreactive iodinated proteins. The reduced labelling efficiency observed with 123-1 respect to 125-1 can be due not only to its higher specific activity but also to the presence of chemical impurities. The search for quality control methods useful for preclinical evaluation of radielabelled antibody are of special importance. In this work the labelling efficiency, stability and biodistribution of anti-CEA F(ab')? fragment was studied. HPLG analysis of antibodies-was performed with a BIO-RAD HPLC system. Samples were eluated with 0.02 M N%HPOJO.05 Na~SO~ buffer at pH 6.8, and flow rate o~ 1 ~I/min. ABso~bance at 280nm was monitored and gamma-radiation were measured with a flow-through detector. Ouring polyacrylamide gel electrophoresis (PAGE) samples were applied to 7.5 % non reduced gel and 0.2 M phophate buffer of pH 7.6. Electrophoresis was carried out at 4 mA per tube at 4% for 24 hrs. The biodistributian of antibody was determined in immunsupressed mices bearing CEA positive human tumor. The labelling efficiency of antibody ranged between 95 -98 ~, extraneous protein was not detected. Stability of compounds duringl-48 hrs of storage, at 4~ was not changed also. lll-ln release was less than 3%. These results were confirmed by PAGE as well. The ~ of I.D. per g tumor rose to a maximum value of 5-8% after 48 hrs, than decreased from this value by about 3 % at 72 hrs. High accumulation of activity was observed in liver ( 

CARBONYL COMPLEXES A groupof new cationic carbonyl complexes in which the Tc atom is in a low oxidation state has been prepared and characterized to evaluate their potential as heart perfusion agent. The starting material for these syntheses was Tc2(CO)10 prepared from dry NH4TcO ~ under less drastic conditions than those hitherto reported (i). Treatment of the latter with NOPF 6 in acetonitrile affords the cationic technetium(I) complex [Tc(CE) 3CN)(CO)5]PF 6 which is an excellent starting material for new cationic species since it reacts with a variety of bi-and tridentate chelate ligands containing N, P or S atoms. The biodistribution studies were carried out in guinea pigs. A number of these complexes showed significant accumulation in heart with competitive uptake in liver. Compound [Tc(CO)2(N,M){P(OR)3}2]PF 6 , where N,N stands for 4,4'-dimethyl-2,2'bipyridine and R for isopropyl, is a promising leading precursor suitable for further structural modification and optimization. Results of other biodistribution studies carried out with complexes of general formula [Tc(L)(CO)3]PF6, where L represents a macrocyclic ligand such as 1,4,7triazacyclononane, 1,4,7-trimethyl-l,4,7-triazacyclononane, 1,4,7-trithiacyclononane, etc. will also be presented. We performed the synthesis of the radioiodinated derivatives labeled with 1-125 from the correspondent amines using the Sandmeyer reaction or the Wallach triazene method. The screening of 1-125 compounds was performed after i.v. injection to C57BL6 mice bearing murine melanoma, BI6. Qualitative studies by autoradiography of whole body sections and quantitative studies of tissular and tumoral radioactivity showed that only one compound presented a selective localization in pigmented tumors. N-(2-die t hylaminoet hyl)#-iodobenzamide (Y=CONH) was evaluated in athymic mice bearing MM heterotransplants and showed : high tumor uptake from 1 t0 24 hr postiniection, high ratios tumor-to blood~ muscle, brain, lung and liver from 6 to 2g hr, rapid blood and urinary clearances

The radiolabeling of the amide with high specific activity by isotopic exchange reaction allowed scintigraphic studies in mice. Specific concentration in melanoma either routine or human, primary or metastatic, resulted in tumor imaging of good quality.

These results prompted us to validate them in man and the clinical evalution of metastases of MM will begin in a very near future. 

The need for a boiling step in the preparation of Tc-99m MAG3 (1) can be considered as a practical inconvenience in routine clinical practice. We have now developed a labelling method that allows direct preparation of I at room temperature (RT), using deprotected HAG3 as the Tc-complexing agent. In a first approach S-benzyl MAG3 was treated with Na in liquid NH R and the deprotected ligand was isolated.

Labelling was performed at RT by addition of 1 ml buffer pH 12, 50 ~g Tc-99~n {-oSnCl~' )2H~O and 2 ml generator eluate (0.74-3.7 GBq 1 mg of the ligand.

The pH of the reaction mixture was found to be of major importance, as labelling was only successful at pH > I0.

However, neutralization after labelling did not affect the radiochemical purity. Analysis by TLC and RP-HPLC revealed the presence of mainly one radiochemical species (II) ( 90%, starting from the unpurified deprotected ligand) with an identical retention time as that of Tc-99m MAG3 obtained by exchange labelling (I). In a second approach 2 mg of S-benzoyl MAG3 was stored shortly in alkaline medium before the addition of SnCI~ and generator eluate. Depending on pH differen~ Tc-ggm complexes were obtained. A procedure was developed that resulted in the formation within 5 min of >98% of a radiochemical species (III) with identical ret. time on RP-HPLC as I and II. Evaluation in mice and a baboon showed that HPLC-purifled I, II and III have identical biological properties. Further developmental work is still required to convert this new experimental labelling method to a kit preparation and to confirm the identity of the Tc-99m complex obtained by direct labelling. Colloids used for bone marrow scintigraphy give rise to a liver and spleen uptake which hampers the evaluation, especially of the bone marrow in the vicinity of the liver. The introduction of small-sized ("nano-sized") colloids (< I00 nm) has reduced the liver/spleen uptake, but not completely solved the problem. In this study, 4 small-sized commercial colloids labelled by 99Tcm are compared as regards the bone marrow activity relative to the liver, spleen and background activity. Three human albumin colloids (MICROLITE, E.I. du Pont de Nemours & Co; SOLCO NANOCOLL, Solco Nuclear; TCK-9, International CIS) and one antimony sulfide colloid (TechneScan Sb2S 3, Mallincrodt Diagnostica) are examined. The study is performed in patients routinely referred for liver/spleen scintigraphy and exhibiting a negative investigation. This is performed as a SPECT-registration. 15 patients are examined by each colloid. From a pilot kinetic study, it was found adequate to perform the examination 30 minutes after injection of the radiocolloid. After correction for attenuation and scattering of photons, using techniques previously developed at our laboratory, the activity concentration of the bone marrow of the lumbar spine is related to the liver, spleen and background activity concentration. The bone marrow/liver activity quotient of SOLCO NANO-CaLL and TCK-9 is almost twice the value for MICROLITE and TechneScan Sb2S 3. The bone marrow/spleen quotient is almost 4 times higher and the ~ bone marrow/background quotient almost twice for SOLCO NANOCOLL than for the other 3 colloids tested, between which there is no significant difference regarding these quotients. 

One of the 4 diastereomers of Tc-99m mercaptoacetyl-ala-gly-gly (1) is excreted very rapidly in the urine whereas another isomer is retained almost completely in the kidneys.

On basis of the finding that also tetrapeptides can form stable complexes with Tc-99m we have now studied labelling and biodistribution of Tc-99m complexes of gly-ala-gly-gly (II). These ligands can be considered as derivatives of I in which the thiol group is substituted by an amino group. The L-and D-isomer of II were synthesized by methods of peptide chemistry. Labelling with Tc-99m was performed by two methods. In the direct method 80 ~g SnCl~ and 2 ml Tc-99m generator eluate were added to 2 m' g of the ligand in NaOH O.IN. Reaction mixtures were analyzed by TLC and RP-HPLC and were found to contain 95-98% of a single radiochemical species (Ill) that remained stable in function of time, also after HPLC-isolation and storage at pH 6. Labelling by the exchange method in the presence of tartrate afforded about 40% of a product with the same retention time on HPLC as Ill. Biodistribution of isomers L and D of Ill was studied in mice using OIH as biological standard. Only small differences with respect to organ uptake and clearance were observed between III-L and III-D. Unlike one of the isomers of II, neither II-L or III-D was retained significantly in the kidneys.

Both III-L and III-D approach Tc-99m MAG3 closely. It will be interesting to evaluate these new Tc-99m complexes in other animal species as they can be labelled in high yield st room temperature and potentially constitute useful renal function agents. ionooytes localise in a large number of infectious, granulomatoue and neoplastic diseases. Because they acount for only I-~% of the total leucocyte count and are also difficult to handle in-vitro there are special difficulties in harvesting and radiolabelling these cell types. This preliminary study aims to investigate the feasibility and practicality of working with monocyte s.

Leacocytes were separated from 500 mls of whole blood and were layered onto Nycedenz (an iodinated gradient medium according to the method of Boyum (1983). The monecyte layer appeared at the Nycodenz/plasma interface. The cells were removed and washed. Diffential cell analysis was performed on six samples. In three the average proportion of menocytes to other cells was 53% + 23% S.D. In the other three samples the propertion of monocytes was less than 10%. Lymphocyte contamination in the six samples was 56% _+ 287~. Radiolabelling of the monocyte fraction with indium tropolonate gave a labelling efficiency of 45% + IO%. Viability as sho-~n by fluoresceln acetate staining was always above 9~. The results show that we were partially sucessful in harvesting end radiolabelling monocytes. The problems of collecting large samples of blood will be discussed as will the problems associated with the handling of monocytes. Also to be discurred are the celinioal possibilities of radiolabelled monocytes. i.e. 40.108 MBq/ mmol,the brain uptake decreased considerably. Blood sampling 60 min. post inj. showed that the larger part of the tracer was bound to plasma proteins (>90%). In vitro binding experiments proved that the binding of 131I-2-I-Ketanserin to human serum albumin is not saturable:L=K~Lo(F: free;o:initial) [eq.l]. Partition between octanol and tris/HCl buffer of PH 7.4 was carried out on 13zI-2-I-Ketanserin, within a concentration range of 3.10-i~ -I~ M. The apparent log P increased linearly with the concentration. If the extraction into the organic layer is comparable to lipophilic BBB passage,than LBr=L~/l+10exp-K2LF(Br:brain) [eq.2]. Combination of [eq.l] and [eq.2] yields LB=KILo/I+I0exp-KIKzL 0. Depending on the exponent [eq.3] will be pseudolinear or more complex. As the specific activity is also limited at its lower values due to carrier competition for receptor sites, the specific activity to be used becomes critical. In case of 2-~23I-Ketanserin the optimal receptor to back ground ratio was estimated to be around 3.108 MBq/mmol corresponding to 5.10 -I~ mol injected. Neutrophil function tests are often unsatisfactory in patients with RA. We have compared in vitro che~notaxis and in vivo neutrophil migration in the knees of ii patients with RA. Out of the 21 data points, 7 were post steroid injection.

The residuom of the labelled white cells suspended in plasma was used to measure in vitro ch~notaxis across two i0 micron filters between the syringe containing the cells and a syringe containing standardized enterotoxin. Results are expressed as a ratio between the activity on the first and second filters at 30 minutes. There was a linear correlation between in vitro chemotaxis and in vivo n~rophil migration into the worse affected knee (r=0.9, p~<0.001) and poor correlation with the least affected knee (r-~.33, p=>0.1).Correlation between ehemotaxis and ESR (r--0.52) and CRP (r--0.49) did not reach significance. These results suggest that the neurophil from RA patients is activated prior to migration into joints (systomic activation). The poor correlation between in vitro chemotaxis and the joints with lesser uptake suggests there may be local inhibiting factors or the more active knees may produce factors which stimulate local neutrophil migration. That RA is a systemic or multifocal disease depend on the balance between these local and systemic factors. 

The purpose was the correlation of neutrophil kinetics with the pathogenic course of septic shock in the baboon model, using scintigrsphy.

In-111-tropolonate labelled autologous neutrophils were used in six ncrmal and in six E.coli infected baboons.

Three of these (A) had the labelled neutrophils reinjected two hours After the onset and the remaining three (B) At the onset of the E.ccli infusion. . Scintigrams of the lungs, liver and spleen were taken every fifth minute, and later hourly for four hours, and time-activity curves generated. Table I summarizes the results as percent (mean + SD) of neutrophil clearance (lung) and accumulation (liver and spleen) from zero hour values at various times for the controls and for A and B. We note an early retention of neutrophils in the lungs of the infected baboons and initially (first 40 min) an abnormal slow rate of accumulation in the liver and spleen.

A and B comparisons indicate that any lung injury from changes in neutrophil behaviour should be due to events during the early exposure of neutrophils to the bacterial infection. Distribution values demonstrate that complex III is retained in brain and heart and tissue, exhibiting brain/blood and heart/blood ratios 2.315 and 2.176 respectively 2 h p.i.

99mTc-v-DMSA now has an established role in imaging patients with medullary carcinoma of the thyroid (MTC). Therapeutic options in this disease remain limited, however, and we have therefore assessed the effects of substituting 186Re for 99mTc with a view to using this new agent in therapy.

A tracer study using 700MBq of 186Re-v-DMSA was performed in a 41 year old male with bone and soft tissue metastases from his MTC. Whole body planar gamma camera images were acquired at 2 and 4 hours post injection and subsequently at 1 to 8 days after injection. In addition, SPECT imaging was performed 48 hours after injection. The results of imaging were compared with a planar and SPECT 99mTc-v-DMSA study acquired 4 days before the 186Re-v-DMSA study.

Results of imaging were extremely encouraging with uptake of 186Re-v-DMSA by the tumour at the same sites and with a similar intensity to that seen with 99mTc-v-DMSA. Uptake within the tumonr persisted for the duration of the study. By the fourth day of imaging, however, signilicant renal uptake was observed which was less intense on the earlier images.

186Re-v-DMSA is a new radiepharmaeeutical. It is highly suited to therapy with high energy beta emissions and a gamma ray similar in energy to that of 99mTc. This first case report of its use has yielded encouraging results with good persisting tumour uptake seen on the images. Renal uptake of tracer is an undesirable and unexpected finding, however, that requires a solution before this agent can be used in therapy. Nonreducible 99m-Tc(lll) cations has been shown to have potential as myocardial perfusion imaging agents (JNM 28: 1870 (JNM 28: , 1987 . Animal studies indicated that trans-(N,N'ethylene-bis(acetylacetone iminato)) bis (tris(3-methoxy-1prcpyl) phosphine)technetium-99m(lll) (99mTc-Q3) is particularly promising. We have evaluated 99mTc-Q3 as a potential myocardial perfusion tracer in human volunteers and patients. The biodistribution of 99mTc-Q3 was evaluated in 6 fasting volunteers after i.v. injection of ca.

555MBq (15 mCi) of preparations shown to be of >92% radiochemical purity by HPLC analysis. Anterior myocardial images were continuously recorded for 30 rain post injection in the dynamic acquisition mode; whole body biodistributions were acquired at 1, 2 and 4 h post injection according to the conjugate view counting protocol; blood and urine samples were obtained at appropriate time intervals. These studies show that 99mTc-Q3 clears rapidly from the blood and about 3% of the injected dose is taken up by the heart within the first 5 min post injection; no significative wash out is shown up to 5h. The agent clears rapidly through the hepatobiliary system, giving a heart/liver ratio of 1.3 at about 2 h post injection. SPECT imaging studies, in 6 patients with angiographically established blood supply defects show that 99mTc-Q3 effectively visualizes infarcted and ischemic areas of the myocardium.

Thus, 99mTc-Q3 appears to be a promising new agent for evaluation of myocardial perfusion by SPECT. Tc-99m HPPA has been investigated for use as a skeletal imaging agent. HPPA was prepared by hydrolysis of phosphomycin (phos) at pH 2.5.

The common periodate oxidation method for determination of diols was used. T I/2 for the kinetics of the hydrolysis process at room temperature, was 670 !?in. Purity of the obtained product was evaluated by ~H-NMR spectroscopy.

HPPA was formulated a~ a lyophilized kit. The HPPA was labeled by adding 2 ml ~vmTco-4. Chromatography on paper Whatman no. i and MEK, as a solvent, was used to control the presence of free pertechnetate (Rf 0.7) whereas the Rf of the labeled product was 0.0. Biodistribution studies in animals showed that the complex Tc-99m HPPA pH 2.5 has similar properties to those of Tc-99m phos pH 2.5. In mice, the 3 h post-injection retention in skeleton, was ]4.07_+1.9% of injected dose for Tc-99m HPPA compared to 15.05_+2.67% of injected dose for Tc-99m phos. Kidney activity due to renal excretion of the radioactivity was lower for Tc-99m HPPA (1.07+0.14% of injected dose) than for Tc-g9m-phos (1.80+0.26% of injected dose). The ratio bone to muscle, as % dose/g tissue, was 57.3+0.9 for Tc-99m HPPA and 55.8_+0.8 for Tc-ggm phos. The cumulative urinary excretion of Tc-g9m HPPA, 3 h after injection, was 60.2_+16.6% and that of Tc-99m-phos was 76.5_+3.5%. Whole-body autoradiographies of Tc-99m HPPA and Tc-99m phos. showed excellent contrast between skeleton and other soft tissues. It is concluded that both Tc-99m HPPA and Tc-99m phos. show promise as skeletal imaging agents. The use of (99mTc)-d,l-HH-PAO(HM-PAO) for the investigation of cerebral blood flow and for blood cell labelling has become widespread. It is well known that the relatively fast in vitro decomposition of the labelled complex renders it difficult to use this radiopharmacon. We have clarified the influence of the labelling conditions and kit formulation on the stability of the lipophilic complex (LC) and developed a novel kit formulation providing high LC stability. Analytical grade chemicals and self-synthetized HM-PAO were used. The radiochemica] purity of Tc-labelled compounds was meassured with three analytical methods: the three-strip method of Neirinckx et al., RP-HPLC and the solvent extraction method of Ballinger et al. The novel kit contains d,I-HM-PAO 0.30 mg, tio(II)chloride dihydrate 3.80 #g, and tetrasodium pyrophosphate decahydrate 2.52 mg. The radiopharmacon was prepared by adding 0.6-1.1 GBq (99mTc)-pertechnetate in 5.0 ml saline. The freeze-dried kit had considerable in vitro LC stability. LC komplex yields: 96.57 + 1.8 (n:150) at 1 min, and 81.98 ~ 2.1 at 120 min (nTBO). The age of the eluate used for labelling had no effect on the LC yield. We have used the novel kit routinely for human SPECT rCBF investigations (150 patients) and for leukocyta labelling (iO0 patients) for one year. The image quality was excellent. The cell labelling efficacy was 65.11 ~ + 1.24 using 2xlO 8 cells/0.5 ml. W.Burchert, J. Fl6ge, P. Gietow, J. SchS.ffer, I~. M. Koch, H. Hundeshagen. Depts Nuclear Medicine and Nephrology, Medical School of Hannover, FRG.

Recently we introduced 131-Iodine-g2-Microglobulin as a new tracer for the in vivo imagir~g of amyloid deposits in patients with chronical hemodialysisC Now we report our experience of scintigraphy in 29 pts. 72-96 hrs after application of 74 MBq 131-Iodine-82-Microglobulin the scan of selected regions was done by a gamma camera (Siemens ZLC 370) equipped with a 360 KeV collimator. Iti 14 patients we saw an increased uptake at pelvis, shoulders, knees, Wrists and spine. A correlation between positive scan and duration of hemodialysis was found. 2 pts showed an increased uptake without a sign of amyloidosis, 12 pts had a positive result in agreement with the manifestation of the amyloidosis.

In 3 pts the specific accumulation of the new tracer was proven by histology/autopsy. The results confirmed the usefulness of the scintigraphy as apossibly early -procedure to identify amyloid deposits in long-term hemodialysis. The aim of this study was to develope a simplified method to synthesize 1-123 labelled ANF and to investigate the kinetics of this new tracer for organs with ANF-receptors. ANF was iodinated by the Chloramin T-method and for subsequent purification a modification of the conventional High Pressure Liquid Chromatography ( HPLC ) -method was used. A simple gradient elution-technique was established which will avoid the need for an expensive linear gradient HPLC equipment. In the used HPLC development conditions the labelled protein was purified in a cascaded way. Seven gradients with a ratio of acctunitrile : water of 5 : 95 up to 65 : 35 and a time range of 5 minutes were applied. The iodinated ANF eluted at about 25% -30 % of acetonitrile. Centrifugation with a speedvac under vacuum was followed by the administration of the monoiodinated ANF in a quantity of about 500 gCi/kg to the rabbit. The kinetic profile was investigated by a dynamic study with a gamma camera. Fifteen images were taken at 5 minute intervals each with a total time of 75 minutes. Some data of the observed kinetics of the best visualized organs after i.v. administration are given in the following It is known that the labelling efficiency of M!BG decreases rapidly if the specific activity is mequired to be so high that the compound w~uld be suitable also for therapeutic use. Using /NH / SO as catalystl~ [ the isotope exchange,Aide ~ield of the --I-MIBG were 98-26% depending on the specific activity in the range of 28-12S3 MBq/mg. Slightly better labelling data were obt~ed in presence of CuCI or using Br/-l halogen ex-2 change reaction. On the other hand all o,f these procedures should consist of two steps: i. labelling 2. separation of free iodine. Based on earlier results a one-step p~ocedure was elaborated. As catalyst a layered derivatized zirconium phosphate at elevated temperature. After cooling the MIBG is dissolved in the buffer and the insoluble catalyg~lis retained on the filter. By this method I-M!BG with specific activity up to 7~0 MBq/mg can be obtained, the rediochemical purity is much higher than 95% checked by TLC /on Polygram SIL-NH-R layer/. The solution is Zr-free. The one step procedure is already a routine for the production of the diagnostic MIBG in Hungary, and clinical trial for MIBG therapy may begin this year. 

New technetium complexes with high infarct image contrast due to better myocardiac necrosis uptake and less bone activity are of clinical significance. The ureido (El)-and urethano(E2)-phosphonic derivatives of the ethylenediamino N,N diacetic acid (EDDA) were synthesized and labelled with s

The biodistribution and pharmacokinetics in lung, liver and kidneys as well as urine excretion of these coumpounds ia mice were determined. The muscular necrosis uptake of 99mJc-E1, 99mJc-E2 and 99mJc-PPiin experimental muscular necrosis and bone and heart activity I h.p.i, were measured and compared. The toxicity of 99m-[c-El and 99m Jr-E2 was also studied. The low accumulation, and fast kinetics of 99m-Tc-E1 and 99mfc-E2 in lung,liver and kidneys and high urine excretion were observed.

In conclusion, 99m-Tc-E1 and 99mJc-E2 showed higher muscular necrosis and lower bone uptake than 99m-Tc-PPi, fast organ kinetics and low toxicity. These preliminary data suggest that 99mJc-E1 and 99mJc-E2 are promising myocardiac infarct imaging agents.

During the last four months 13 children (aged 7-14 years) who had just overcome an asthmatic attack were studied after ending of the intravenous therapy and before leaving the hospital (4 to 7 days after the first study). The patients were injected 5-10 mCi Xe-133 (in o,9% NaC1) intravenously followed by a dynamic computer acquisition (i00 frames, each 3 seconds). After smoothing in time and space a MTT-image was calculated -each colour representing a specific transit time.

Besides the diagnosis "Xenon-trapping" we could estimate extent, intensity (quantified by the MTT) and the location of the ventilation disorder (diffuse or mainly in the lung bases). There was high correlation between scintigraphic evaluation and pulmonary function tests concerning the severity of the disease aswell as the improval under therapy. In all cases with pathological function tests we found Xenon-trapping. In the control study 2 patients with normal pulmonary function had prolonged transit times (more than 50 seconds). In one incooperative patient only scintigraphic examination gave reliable results.

The Xe-scintigraphy of the lungs can be performed easily and quickly without much collaboration of the patient, which is highly important in children. It enables to detect ventilation disorders and to evaluate therapeutic response comparable to common pulmonary function tests in some cases showing even higher sensibility. Furthermore it gives information about the location of the affected parts of the lungs. The value of these findings fbr therapeutic management is still under discussion.

G. Grimon, L. Andre, 0. Bernard, D. Alagille, A. Desgrez. CIRRHOSIS Hypoxemia due to IPS is a rare but severe complication of cirrhosis and is considered an absolute contraindication to liver transplantation (LT). Early detection of IPS is necessary before it is too late. We investigated the value of isotope detection and quantification of IPS in 70 children with cirrhosis awaiting LT and compared it with measurement of Pa02 under 21% and 100% 02 breathing. An IV injection of human macroaggregated albumin labelled with 99mTc was carried out in the patients in the recumbent position and activities over brain ROI(B) and lungs ROI(L) were automatically measured. An index of shunt was defined as: B/L index : i00 * B / L , and considered abnormal when above 1 because we observed in 2 children progression of index from 1.4 and 2.5 to 0 and 15 respectively over 2 and 5 years.

Patients status (Pa02 at rest) B/L >i severe <80%* :

ii 8 C hypoxia: 23 moderate 80-90%*: 5 2 L minimal 90-100%* 7 1 normoxia: 47 1 * % of inferior limit of normal for age B/L index was well correlated with hypoxemia at rest (r=0.85) but not with the degree of increase of Pa02 under 100% 02.

These results indicate that -i ~ the increased B/L index, which can be only explained by a right-to-left IPS, is more specific than arterial blood gases to detect IPS in children with cirrhosis, and -2 ~ suggest that it could become useful for the follow up of theses children. Imaging for tumour may be required for purposes of diagnosis of the the primary tumour, determining the extent of the pri~ary tumour and the presence of metastases (staging), choosing the appropriate therapy or following the response to therapy. Non specific nuclear medicine investigations, such as bone scanning often have a useful role in many of these respects.

Gallium-67 remains a useful tumour imaging agent, in spite of its non specificity.

Recent studies suggest that high dose Ga-67 SPECT imaging may be of considerable value in mediastinal assessment of lymphoma and bronchial carcinoma. The role of the metabolic markers 1-131 and labelled mlBG in appropriate tumours is well known, both in diagnosis and therapy. The potassium analogue T1 2UI appears of value in imaging some tumours, notably CNS lesions, thyroid cancer metastases and hepatoma. Pentavalent Tc-99m DMSA is currently being evaluated in various tumours.

Radiolabelled monoclonal antibodies (MAb) have been extensively investigated for tumour imaging, but problems with antibody specificity have often limited its applicability.

Optimum results for NAb imaging may require delayed imaging, SPECT acquisition, blood pool subtraction and consideration of alternative routes of administration, for example intra-peritoneal.

Tumour therapy using labelled MAb has a limited role at present but may become more widely applicable if problems of Ab specificity and radionuclide loading can be overcome. 

Obstruction of the common bile duct maybe diagnosed with Tc-99m DISIDA or by endoscopic retrograde choleoangiography (ERC). ERC as the 'gold standard' technique fs invasive and unsuitable for serial measurements on young cystic fibrosis patients. The purpose of this study is to investigate the usefulness of quantitative DISIDA scanning in measuring the extent of sub-total hepatebillary obstruction.

With the permission of the hospital ethics committee 33 subjects were studied-27 patients and 6 normal volunteers(NV). Based on clinical, biochemical and ERC findings the cystic fibrous patients divided into normal(NCF) and abnormal (DCF) liver function. Imaging was performed for 50 mins using 15OMBq Tc-99m DISIDA. Time/ activity curves were generated for a blood pool area(BC),superolateral aspect of the live~(SC). and whole liver excluding the gallbladder(TLC).

The TLC was used to calculate the amount of tracer excreted at 45mins(E45),6Omins.(E60),and a mean transit time(MTT).Finally, uptake halflife(UH) and excretion halflife(EH) were derived from the SC.

The Wilcoxon rank test showed a significant difference (P~.001) between the E45,E60, and EH values of the NCF and DCF groups. None of the other parameters were significantly diff-~nt for the two groups and none were different for the N and NCF groups.The importance of these findings in relation to cystic fibrosis management will be discussed. 

Purnose: The aim of this study was to determine whether increased gastrointestinal protein loss originated from the stomach or from the intestine. Patient and method: A 46 years old female suffered from abdominal pain, nausea and weight loss. Albumin concentration was very low:f5 g/l (normal 37-47 g/l). Measurement of protein loss according to the standard procedure with 51crC13 revealed a total gastro-intestinal protein loss equivalent to the protein-content of 2300 ml plasma/day.(normal:<30).

During this study gastric juice was siphoned for 12 hours, revealing a protein loss equivalent to the protein content of 200 ml plasma. However The patient was highly suspected of having a much greater protein loss in the stomach. Measurement of protein loss was repeated. Two tubes were introduced orally and located in the stomach. One was used for siphoning, the other for administration of 99mTc-S-Sb-colloid in 5% glucose at a low but constant speed of i0 ml/hr for 24 hr.(10 ml/hr 4MBq/hr) Meanwhile the patient was lying in bed on the left side. Result: Only 7 to 76 % of the administered dose was recovered in the eight 3hr. samples. The best recovery was found at night. Correction of the siphoned 51Cr activity for recovery of 99mTc-colloid revealed a total protein loss in the stomach equivalent to ii00 ml plasma/day.

Total gastro-intestinal protein loss was 1650 ml plasma/day. Total gastrectomy was performed. One year later total gastro-intestinal protein loss was within limits of normal. The still existing 33% difference between the calculated protein loss in the siphoned gastric juice and the total gastrointestinal protein loss can be explained by leakage of gastric juice directly into the duodenum. Conclusion:

Measurement of protein loss from the stomach whithout correction of gastric siphon recovery largely underscores total gastric protein loss.

V. Van In thi8 study we have developed and validated a new scintigraphic acquisition and processing method to visualize the contractions of the stomach. Ten healthy subjebts were investigated. After an overnight fast, each subject was given a standardized test meal consisting of scrambled egg labeled with 3 mCi of Tc-99m-Sc, bread and water. Immediately after ingestion of the meal, each volunteer sat between the two heads of a dual-headed gamma camera interfaced to a computer. Sixty four by 64 matrix with a 2.6 acquisition zoom list mode images of the stomach were acquired for 5 mfflutes at 15, 3I, 61, 91 and 121 minutes after meal oomp[etion Each set of anterior and posterior list mode images was refrained in 250 msec. decay-corrected geometric mean images. A ROI was drawn around the antrum and antrel time-activity curves were generated. A curve-peak finding algorithm was then applied to each time-activity curve to indicate the start of every gastric cycle. List mode images were refrained in 20 images per cycle and for each 5 minutes set of dynamic acquisition 20 pseudo-gated images consisting of the sum of the same numbered frame interval in every cycle were generated. Fourier analysis of the time. activity curve in each gastric pixel location of the 20 pseudo-gated images allowed to generate phases images of the stomach in a color scale. The closed loop cinematic display of the phase images during a gastric cycle enables to visualize the progression of the wave of gastric contraction i.e. the gastric mechanical systole. Correlations between the antral time-activity curves cycle and gastric contractions were established in 5 dogs using the eerosal electrogastrographic technique. Three weeks after surgical implantation of 4 bipolar silver chloride electrodes distributed from the terminal antrum to the proximal fundus, each dog underwent the isotopic procedure described above. Simultaneous isotopic and serosal eleotrogastrograpphic recordings were performed to correlate the contractions electrical activity with the antral time-activity cui'ves. The patterns of phase distribution and sequential phase changes of food in the stomach we observed indicate that the proximal stomach does not undergo phasic contractions while in the distal stomach, contrac. tions originate in mid-corpus and propagate to the pylorus. This is in agreement with results obtained by other investigators with invasive techniques. In conclusion, the scintigraphic test can be used to noninvasively visualize gastric contractions and to delineate the spatial progression of the gastric electromechanical wave of contraction. This technique can be used to study patients with gastric disorders.

A. PieDsz. H. Pintelon, Akademisch Ziekenhuis, Vrije Universiteit, Laarbeeklaan 101, Brussels.

Nuclear medicine is particularly well suited for children, because the procedure is safe, non invasive and delivers generally a low radiation dose to the patient. Despite these favourable characteristics, many nuclear medicine departments are still reluctant to investigate children and particularly the very young ones, because of several difficulties. The first problem is that the child is a growing person and that the maturation patterns strongly influence the interpretation of a scintigraphic image as well as the quantitative estimation of a function. The second problem is that the indications of the pediatdc examinations dilter considerably from the adult ones. For instance, lung emboly is the main indication of lung perfusion/ventilation scintigraphy in adults, while tnis indication is seldom encountered in pediauius, 5i~, !i,d.lJ'l iiidicaiion being the evaluation of the remaining lung function in various acute and chronic lung diseases. The third problem is the radiation dose. The fourth problem, and may be the most important one, is the fact that special care should be taken when performing a nuclear procedure in children and this needs a well trained technical and medical staff. Having the collaboration of a smiling child will considerably contribute to the quality of an examination. This can be obtained only i1 the psychological atmosphere surrounding the child is favourable : adapted examination room, participation of the parents, sufficient explanation given to the child,... Drug sedation is exceptionally necessary and the immobilization of the child by means of vacuum cushions is very helpful : nevertheless, this will be successful only if the child has received sufficient attention and feels happy. Other problems are related to the choice of collimators, the position of the patient in front of the gamma camera, and the intravenous injection of the tracer. Finally, it is obvious that much more time should be devoted to a nuclear procedure performed on a small child. In the dept of Ped Clin Physiol, G6teborg, we have investigated children during the last 25 years. Our goal is to obtain the best possible examination with a minimum of discomfort for the child. When we two years ago got a gamma camera, we found our previous experience valuable. There are a number of problems specific to pediatric nuclear medicine that, however, may be alleviated. Anxiety of the sick child and its parents. Well informed patients/parents feel secure. Obtain confidance and trust. Never lie to a child! Take your time to inform about the procedure. Let the parents in! Make the camera room look Iess frightening. Fear of venous puncture.

Never say it does not hurt. Pain relief (topical anesthetic for intact skin (lidocaine/prilocaine 1:1; EMLA | Astra). Always use a helping hand. Low activity dosage at the expense of prolonged studies.

Take advantage of natural sleeping periods. Use deflatable cushions to minimize motion. Distract the child -e.g. video cartoons, music. Plain refusal to cooperate. Imagination, patience. With rather simple means it is possible to bring down study failures to a minimum. The use of general anesthesia decreased substantially when the camera investigations of children were transfered from an adult to the pediatric unit.

H. Pintelon, A. Piepsz, Akademisch Ziekenhuis, Vrije Universiteit Laarbeeklaan 101, Brussels.

GER scan represents about 25% of the daily pediatric work in our department of radioisotopes. The main indications are the detection and quantification of reflux in children with abdominal complaints suggesting reflux, in recurrent lung disease of unknown origin, and in near miss SIDS. A good psychological surrounding facilitates the different steps of the procedure. The tracer is mixed with a small amount of the usual milk preparation or pudding, and is administered to the child in comfortable conditions. Special care should be taken to prevent any clothes or skin contamination. The mouth and esophagus are rinced by adding a supplementary amount of the non-radioactive meal. This is checked on the screen before starting the recording period.The child is immobilized in a vacuum maitres and placed on the gamma camera in supine position, which allows the highest GER detection rate. The child is constantly observed in order to correlate later on the reflux episodes with manifestations like crying, coughing or pallor.The data are stored in the computer at the rate of 1 frame per 20 sec during 1Hr. The contrast of the images is enhanced, in order to visualize esophageal activity as low as 1% of the maximal gastric activity. The 180 images are visualized one by one, and all the episodes of reflux are noted. A time activity curve over the esophageal area is then produced and the reflux peaks are carefully compared to the corresponding images, in order to detect any artefactual peak due to an accidental displacement of the stomach into the esophageal area. A delayed high intensity image of the chest is obtained 4Hr later, in order to pick up any abnormal area of radioactivity which could suggest lung aspiration.The GER scan is non invasive, physiological and particularly well adapted to the child. The amount of information provided by this technique is essentially depending on the quality of the procedure. M. De Roo. Department of Nuclear Medicine, University Hospital Gasthuisberg, B-3000 Leuven, Belgium.

Only high quality SPECT imaging is able to visualize the complex gray matter structures of the brain. With regard to tracer substances for visualization of cerebral flow there are no major developments to signalize. Cerebrovascular disease is no longer the most important indication for blood flow SPECT. The principal drawbacks, in comparison to X-ray CT, are the false negative results in cases with lacunar infarcts in the basal ganglia and the white matter.

Diffuse diminution of brain blood flow without tissue necrosis is frequently only demonstrated using isotopic techniques.

Concomittant phenomena such as borderzone hyperaemia, luxury perfusion and effects at distance (diaschisis) are only visible on SPECT images, but the clinical relevance of this information is questionable. In dementia cases, brain blood flow is able to recognize different clinical categories in absence of typical CT images, the latter showing only atypical cortical atrophy.

In Alzheimers dementia, frontal lobe dementia and Pick's disease cases, typical patterns of abnormal tracer distribution can be demonstrated, providing neuropsychiatrists with valuable diagnostic information. Finally, cerebral blood flow imaging is able to localize the epileptogenic foci in a appreciable percentage of epilepsy patients during the interictal period. Cerebral blood flow SPECT evolved to a multiple indication technique and will therefore retain an important place in nuclear medicine.

Nederland. Voor bet aantonen van een eenzijdige FunctJonele nierarteriestenose kan het renogram met eaptopril van waarde zijn. Onder invloed van captopril ontstaat er een systemisehe tensiedaling en is in de zieke nier de secretie van hat radiofarmaeon geringer, de passagetijd langer en is de exeretie verminderd tot opgeheven, in tegenstelling tot de gezonde nier. Her verschil in functioneren van beide nieren wordt op hat renogram zichtbaar. De voorbereiding en uitvoering van het onderzoek moet volgens een standaard protocol gesehieden wil het onderzoek reprodueeerbaar zijn. Voorbereiding: de patient wordt voorgeschreven 2 dagen vooraFgaand aan hat onderzoek diurese medieatie te staken en 4 uur voor hat onderzoek geen vast voedsel te nuttigen, i uur voor hat onderzoek krijgt de patient 25mg eapLopri! oraal toegediend en wordt elke 15 minuten de bloeddruk gemeten. 50 minuten later moat hij/zij een 0.5 liter water drinken en alvorens met het onderzoek wordt begonnen gevraagd de blaas te ontledigen. Uitvoering en data analyse van hat onderzoek zijn gelijk pan die van het standaard renogram.

Conclusie: hat eaptopril renogram is een methode van onderzoek ~elke volgens standaard protocol kan warden uitgevoerd. The development of nuclear medicine is strongly dependent of the availability of new radiopharmaceuticals. As procedures become more sophisticated, the radiopharmeceuticals become more physiologically oriented and complex. Their handUg requires advanced knowledge at various stages. Three classes o! compounds will be considered in this review course.

First: the most routine PET-radiopharmaceuticals, like FDG, Oxygen labelled gases and water, as well as the generator PET-nuclides 68Ga and 82Rb. Most of them are non-commercial procucts which are prepared in house by radiopharmaceutical chemists. Their handling in routine applications requires special knowledge in safety and quality control, not only at the production level but also at the administration and application level.

Second: in house produced radiopharmaceuticals or commercially available reseach products for SPECT investigations which require purification steps and advanced quality control procedures. Iodinated receptor ligands, and amino acids as well as some fatty acids belong to this class of compounds. Their handling and application should be restricted to specially trained personell.

Third: not yet generally licensed radiopharmaceuticals which are, however, commercially available. Some new 99mTc -labeled compounds like ECD, HMPAO, RP-30, MAG-3, and most of the labeled anitbodies labelled with 99mTc or 111 In, are generally available under EEC-laws, although they are not jet officially licenced. Their handling is usually simplified to such a degree that their preparation and application does not require special knowledge in radiopharmaceutical chemistry. Nevertheless some precautions in their handling and knowledge about the legislative limitations of their application should be known by the persons who use these compounds. 

Louwes H., Dept. Nuclear Medicine R.K. Ziekenhuis Groningen, the Netherlands.

One hundred and seventy persons were investigated with 1111n-Tropolonate labelled platelets, 14 normalo and 156 patients: 70 with idiopathic thrombocytopenia (IrP), 76 with thrombocytopenia due to a variety of disorders and 10 with recurrent thrombocytopenio after spJenectomie. The following parameters were investigated: Mean Piatelet Life (HPL), Initial Platelet Recovery(IPR), Total Platelet Production Rote (TPPR) and the absolute uptake in liver and spleen after I hr and 5 days consecutively. In concurrence with a recommendation of the ICSH, the mean platelet life was calculated according to five different mathematieai models: linear, exponential or gammafunction, the average and the weighted average of the linear and exponential values. By means off a 2-compartmental model, the following parameters were calculated: the transport constant (k) from blood to spleen, splenic transittime and splenic blood flow. These parameters were calculated in order to gain a better insight into the platelet kinetics in patients with various kinds of thrombocytopenia. In our hands the labelling of platelets with 1111n-tropolonate was standard procedure. Parameters like mean platelet life, initial recovery, total platelet production rate and uptake curves in time over iiver and spleen proved to be clinically useful. The value of the calculations for the platelet kinetics as obtained by the 2-compartmental model still remained to be established, with regard to clinical management. Standard methods for Tc-99m leucocyte labelling with stannous fluoride colloid require freshly prepared reagents and result in a mixture of labelled monocytes and platelets. The colloid reagents are unstable even if stored frozen, and two thirds of the activity may be lost by adherence to reaction vials.

To overcome these problems we have produced a pyrogenfree sterile lyophilised kit. The kit was stable for at least 3 months and yielded smaller, more uniform colloid particles which label leucocytes more efficiently. Transmission electron microscopy studies demonstrated phagocytic uptake of labelled colloid by granulocytes, monocytes, eosinophils and platelets.

Interference by platelet labelling was reduced by differential centrifugation and removal of platelets from whole blood prior to labelling the leucocytes.

Blood from 5 healthy volunteers was labelled by both the fresh reagent method and by the lyophilised kit method, and the percentage of activity in leucocytes was determined by quantitative gamma imaging of labelled cells separated on a gradient density medium. The activity in phagocytes labelled by the fresh reagent method was 70.4 • 5.4% (Range 62-77%) and by the lyophilised kit method was 79.2 • 4.8% (Range 70-89%).

Preliminary clinical imaging studies in 15 patients demonstrated clear definition of focal inflammation and infection.

The lyophilised kit is sterile, stable and convenient to use. The method Of Te-99m leucocyte labelling using the kit is efficient, reproducible, validated by electron microscopy and demonstrated to be clinically effective for diagnostic imaging of focal sepsis. Although technological developments of other diagnostic modalities have changed the role of nuclear medicine in oncology, the field of nuclear oncology continues to expand. There is an increase of quantitative analyses of organ function to monitor possible side effects of oncological treatment; in tumor imaging there is a shift from organ-specific towards tumor-specific radiopharmaceuticals and single photon emission tomography is used in addition to planar scintigraphy. Moreover there is a renewed interest in the therapeutic applications of unsealed sources. Specific metabolic characteristics and biological properties of tumors are being exploited to target radiopharmaceuticals at tumors for diagnostic imaging and radionuclide therapy. After a survey of the various routes or mechanisms of tumor targeting and clinically available tracers, the methodological aspects of the following applications will be discussed in greater detail and clinical examples will be presented:

i) the use of 1311 and 201Tl-chloride in the follow up and treatment of differentiated thyroid carcinoma;

2) new tracers for the detection and therapy of medullary thyroid carcinoma;

3) diagnostic scintigraphy of neural crest tumors using 131I-MIBG; 4) 1311-MIBG therapy: conditions, procedure and response. Nuclear medicine techniques can be useful to document organ toxicity due to oncological treatment. E.g. during chemotherapy with Doxorubicine or Cis-Platin nuclear medicine methods have been demonstrated to be effective for early detection of cardiotoxicity and renal damage. With the introduction of new technical possibilities (linear accelerators, 3-D treatment planning) there is s tendency in radiation therapy to irradiate malignancies taking larger volumes in order to improve survival rates. This approach may cause injury of normal organs irradiated together with the tumor with the onset of complaints. after a short or longer interval. Establishment of dysfunction of these dose-limiting organs is important for the clinical management. Furthermore the accurate determination of clinical dose-effect relations is essential to optimize radiation -or chemotherapeutical regimens. In the Netherlands Cancer Institute we are using various nuclear medicine techniques to document organ dysfunction. After an overview of these applications and their clinical setting the methodological aspects of some of these modalities and clinical examples will be presented: i. Combined use of 75Se-HCAT retention measurements and 14C-Glycochol breath test to determine post irradiation late small bowel dysfunction. 2. Quantitative ventilation-perfusion SPECT in the assessment of lung radiation injury. 3. 99mTc-DTPA renography and quantitative 99mTc-DMSA scintigraphy for monitoring kidney function after radiation therapy or during chemotherapy. Monoclonal antibodies (Moab) have been prepared against a variety of tumour-associated antigens. After labeling with radio-isotopes, only a limited number appears useful for in vlvo immunosclntlgraphy. These Moab are candidates for therapeutical applications. There are several options for Moab-based antl-tumour therapy. One of these is the targeting of cytotoxic immune cells towards tumour cells. Our findings in this respect with a Moab directed against a pancarcinoma cell antigen (MOC31) are discussed. MOC31 was conjugated with DTPA and labeled with 111Indium. When this radioimmunoconjugate was injected into nude rats carrying a human lungcarcinoma xenograft, the radiolabel localized specifically intothe tumour. This indicated the usefulness of MOC31 for tumourimaging. To assess If, simllarlly, MOC31 may guide immune cells towards tumourcells, a bispecific monoclonal antibody (Biab) was made from MOC31. This Blab (BIS2) had one specificity against the MOC31-antigen and the other against the CD3-antigen on T-cells. BIS2 may not only link T-cells to tumourcells, but at the same time may trigger the former to become cytotoxic towards the latter, It was shown, in vitro, that BIS2-incubated T-cells induced the specific lysis of MOC31-positive, but not MOC31-negative, tumourcell-lines. Subsequently, BIS2-incubated T-cells were assessed in vivo by injecting the cells into the peritoneal or pleural cavity of patients suffering from carcinoma-induced ascites or pleural effusion. At various time points after injection samples were drawn and evaluated. The results show that BIS2-incubated T-cells form multi-cellular conjugates around tumour cells, already one hour after injection. Significant tumourcell-lysis was apparent after 24-48 hours. Also a large Influx of granulocytes was apparent at that time, Indicating local imflammation. The first 40 hours(5 days) were carried out in September 1989 , the second part in November. Finishing the course and pass of the examination gives an official permission for work in nuclear medicine departments. 2 months after the second part of the course a questionnaire was send to all participants. The evaluation of this post-graduate training will be presented with special interest of the usefullness for daily ~prk. Last year a description of the professional tasks of Nuclear Medicine Technologists in the Netherlands was formulated. This profile was initiated and commissioned by the Dutch authorities. A short description of procedures and results shall be presented.

BK Pounds Society of Nuclear Medicine, 136 Madison Ave. , New York, New York, 10016 THE STATE OF NUCLEAR MEDICINE TECHNOLOGY, 1990 .

The current state of nuclear medicine technology is one of excitement and anxiety. Technologists are encouraged by the recent development of new diagnostic radiopharmaceuticals, imaging devices, and procedures to assist with the diagnosis and management of patient care. Conversely, technologists are confronted daily with problems of providing the necessary patient services.

These problems include a drastic shortage of qualifiednuclear medicine technologists, increasing governmental regulatory requirements, and a lack of competitive salaries necessary to attract prospective candidates into training programs.

The Technologist Section, Society of Nuclear Medicine, was organized in 1970, "to encourage Nuclear Medicine technologists to join together in an association...for the purpose of maintaining the identity and quality of nuclear medicine technologists." The Technologist Section is composed of many committees concerned with special interest topics such as continuing education, government relations, and socioeconomic affairs. The Technologist Section has assisted with the development of a national certification examination which assesses the knowledge of the entry level skills necessary to be employed as a nuclear medicine technologist.

The Technologist Section also provides and coordinates continuing education activities, on both the national and community levels, and assists with the development and maintenance of nuclear medicine technology training programs.

The Technologist Section, Society of Nuclear Medicine, is an integral component to the continued success of the practice of nuclear medicine worldwide. It is known that planar non-uniformities cause ring artifacts in emission computer tomograpby (ECT) reconstructions. We studied the ring artifacts in tomograms of an uniform disc with a diameter of 33 pixels, by simulating 64 parabolic projections in 64x64 matrices with a known noise level and a known non-uniformity. The latter was definied conform the NEMA standards.

The purpose was to relate this NEMA non-uniformity to the intensity and the extent of the ring artifact, and to establish the maximum planar non-uniformity to guarantee an artifact level lower than a given value.

Our study showed that both artifact intensity and extent depended on the reconstruction filter. A planar non-uniformity of 5% in one pixel resulted with a Ramp filter in a 5 voxels thick ring artifact and an intensity of 11.2% above the mean intensity of the disc. With the Banning filter these numbers were 7 voxels and 5.9%, respectively. Furthermore, the coefficient of variation (CV=SD/mean) of the noise in the disc was 6.5% with the Ramp, and 3.2% with the Hanning filter. To obtain an artifact intensity comparable to the noise level (CV) of the disc, the planar non-uniformity had to be less than 2.5%.

It is concluded that as part of the instrumentation performance tests, the propagation of the planar nonuniformities and the noise should be evaluated for several routinely used filters and acquisition parameters. In addition, knowledge of the noise threshold, obtained with these evaluations, will improve the interpretation of the tomograms.

Technetium 99m HM-PAO SPECT is a widely used technique for the determination of the regional cerebral perfusion in normal and Alzheimer disease patients. 0ptimalisation of both the data acquisition and the introduction of a new method for semiquantification of the rCBF has been a topic at the Nuclear Medicine department of the KCL. Phantom studies and the application of information theory to SPECT acquisition modalities have showed that concerning image quality the system resolution is a much more important factor than system sensitivity (ref.). The system resolution of our longbore collimator in a nominal SPECT acquisition geometry (FW}{M = ii mm) is superior to the resolution achieved with the LEAP (FWHM = 17 mm). or FIR (FWHM = 13 mm) collimator. The striking resolution improvement is mainly due to the 40 percent decreased rotation radius which can be achieved with the longbore collimator. Several data analysis procedures for the semi-quantification of the rCBF have been published. Most of these methods are based on the determination of the activity ratio between cortical ROI's and a cerebellar ROI, assuming that the cerebellum is insensitive to pathological changes. This assumption is however a limiting factor for the accuracy of the quantification method because among other things biological variations are not taken into account. At our institute a rCBF-quantification phantom has been developed. This phantom can be positioned as an additional transversal slice while acquisition is performed simultaneously for both the brain and the phantom at 360 degrees and 64 views of 20 seconds each. The reconstructed transversal activity distribution is correlated to the corresponding areas in the phantom. The quantification analysis is implemented in a slightly modified version of the BULB program (Koskinen, Tampere). For this purpose the transversal slices as well as the phantom slice are divided in twelve pieshaped segments each representing a part of the brain. A simple outline of the data acquisition procedure and some preliminary results will be presented.

Reliable interpretation of myocardial perfusion images is directly related to the quality of the images. Many false positive and negative readings are due to technical errors incurred during the acquisition of the images.

The technologist plays a key role in recognizing and controlling these potential sources of error.

The sources of error resulting in poor quality images for both planar and SPECT myocardial perfusion imaging are: low counts in the images, poor positioning and repositioning, attenuation artifacts and poor uniformity and linearity of the gamma camera.

In addition, the quality of SPECT images is greatly affected by motion, upward creep and orbit selection.

Poor count statistics in the heart is the most common cause for poor quality planar and SPECT images. This can be improved by imaging for preset time on all patients, using an all-purpose col e limator and dual energy peaking when using TI-201. Strict adherence to positioning guidelines can elimi~ nate false-positive readings due to differences in positioning between exercise and delayed imaging. Attenuation by breast tissue and the diaphragm often results in false positive defects.

A line source marker outlining the breast on the perfusion images identifies the location of the breast in relation to the left ventricle.

Diaphragm attenuation artifacts can be eliminated by imaging the patient on the right side or prone.

Examples demonstrating these technical problems will be presented. The amplitude AMP and phase PH images are routinely employed in the interpretation of radionuclide ventriculography studies. We report on the derivation and assessment of the following additional functional images: T4/5, peak emptying rate PER and peak filling rate PFR.

The T4/5 image (introduced by us) is computed using the time activity curves TACs of all pixels within the 25% thresholded LV boundary at ES. The pixel T4/5 time interval is the time interval between late systole and early diastole of the pixel's TAC at the 4/Sth fraction of its stroke counts. The PER and PFR images are computed using all pixels within the 25% thresholded LV at ED.

Individual pixel PER and PFR are derived from the first derivative of the pixel's TAC fitted with the first two Fourier terms. These functional images were generated and displayed on a VAX-based Lexidata image processor. The software is also available on GE Starcam systems.

The usefulness of these images has been assessed utilizing a sample population of 14 normals and 26 IHD patients all with normal rest LVEF>_50%. The IHD patients had been catheterized. The PFR image alone or in combination with AMP as well as either PER or T4/5 have been shown to have better sensitivity, specificity and accuracy than the pair AMP and PH. Their use is therefore recommended. 

Tc-99m MIBI. The preparation of Tc-99m MIBI (1) requires a time consuming boiling and refrigeration step (~30 min), a practical inconvenience in routine clinical practice.

We have now studied the influence of heating time and temperature on the labelling yield and studied several methods for rapid quality control. Different PC and TLC methods were evaluated : (a) paper, eluted with acetone, (b) ITLC-SG, eluted with acetone, (c) ITLC-SG, eluted with saline, (d) aluminium oxide, eluted with EtOH (method recommended by manufacturer). More detailed analysis was performed by HPLC on PRP-I, eluted with acetone-NH4OAc buffer pH 4 gradient mixtures. Labelling at lOO ~ yielded over 96% Tc-99m MIBI after a heating time of l min. Prolonged heating did improve the yield only slightly.

Heating at 80 ~ for 5 min yielded also >95% of I. Labelling at room temperature resulted in 60% of I after l h, 75% after 2 h and 85% after 5 h.

After addition of (Tc-99m)-NaTcO 4 to a labelling kit and heating for 30 sec in a microwave oven a labelling yield >96% was obtained, but this method requires special precautions with respect to safety and potential contaminations. Analytical method (d) was found to be rather unpractical and could be substituted by a combination of methods (b) and (c).

Results obtained in this way are comparable with the results of HPLC-analysis. It is concluded that the preparation time of Tc-ggm MIBI can drastically be reduced to <5 min and a practical, rapid and reliable method for analysis is available. Scintillation proximity assay (SPA) is based on the activation of a fluorophor integrated in antibody coated beads. Only the antibody-bound radiolabelled ligand which is in close proximity of the bead activates the fluorophor. The light produced by activated microspheres is counted in a scintillation counter. Thus, immunoassay can be performed without the need to separate bound and free ligand. Therefore a positive effect on intra-assay variation as well as greater suitability with regard to automation may be expected. We set out to develop SPAs for cortisol and aldosterone in human plasma as well as a SPA for rat plasma corticosterone using commercially available SPA reagent. The level of plasma cortisol in a series of samples was measured by RIA and SPA. The results obtained with either assay were in excellent agreement (SPA = 0.002 ~mol/I + 1.007*RIA, r = 0.996, p < 0.01, n = 45). SPA technology can excellently be applied for the determination of steroid hormones provided that interference from plasma binding proteins, a general problem encountered in steroid hormone assay, is circumvented.

M. Gerits, P. Devos, M. De Roo. Department of Nuclear Medicine Universitaire Ziekenhuizen, K.U.L., Gasthuisberg, B-3000 Leuven, Belgium.

A clinically euthyroid patient had a huge and solitary elevation of serum T3, at variance with the other parameters of thyroid function.

T3 was 605 ng/dl (T3RIA bead Abbott; nl : 90-180 ng/dl); T4 was 6.8 ~g/dl (Tetrabead Abbott; nl : 5.5-12.0 pg/ dl); TSH was 0.4 mIU/l (TSH Abbott If; nl : 0.15-3.8 mIE/l). This could be explained by auto-T3-antibodies interfering in this competitive radio-immunoassay with a specific separation step. The presence of an endogenous binder was proved by measuring the non specific binding in the serum of a radioactive T3 tracer (T3*).

After precipitation with 20% PEG, 67% of T3* was bound by the patient's serum and only 7.4% by a control serum. The affinity and capacity of this binder was then evaluated by Scatchard-analysis.

A constant amount of T3 free patient serum (1O !~l) was incubated with six increasing quantities of cold T3 (0-800 ng/dl) and traced with T3* of known specific activity (2056965 dpm/pmole). According to the law of mass action, the following equation holds :

(AgAb) = (Bmax) -I/K (B/F) where (AgAb) is the bound concentration of ]igand, and (B/F) the corresponding bound to free tracer ratio.

To the six measured points, a linear Scatchard-plot could be fitted, from which K, the affinity constant, and Bmax, the maximal binding capacity of the antiserum for the antigen, could be computed. K = 7 E 10 I/mo] Bmax = 9.61 E -10 mol/l This high affinity, characteristic for antibodies, verifies the presence in this particular patient's serum of high affinity, Iow capacity anti-T3-auto antibodies interfering in the immuno-assay. In the last few years a number of changes have been made to improve the spatial resolution of Anger scintillation cameras.

This has come at the expense of field uniformity~ All stateof-the-art cameras contain special circuits which correct for the fundamental causes of nonuniformities although there is some variation in the technical implementation. Energy and distortion correction maps are prepared when the cameras are assembled and can be periodically updated in the field as needed because of the aging of electrical components and/or when photomultiplier tubes are replaced.

Regional variations in the energy response of the detector are eliminated by shifting the analyzer window or photopeak on an event-by-event basis as images are acquired.

Distortion, the primary cause of nonuniformity, is eliminated by repositioning individual events during acquisition.

In some cameras, a retrospective correction is applied to correct for collimator nonuniformities. Many cameras also use automatic, "continuous" balancing of the photomultiplier tubes to maintain the integrity of the energy and distortion correction maps.

Proper operation of these circuits is essential for maintaining the uniformity that is necessary for high quality artifact free SPECT images. Techniques for checking proper operation of these circuits will be described. Technologists should have a basic understanding of the radiation absorbed doses from nuclear medicine procedures. In addition to the doses to patients as a result of the administered radioactive material, persons who prepare or handle the radiopharmaceuticals, nurses, and others who care for the patients may receive doses from radioactive material taken into their bodies. This presentation will address the basic principles of calculating radiation dose, including the information that is needed so that doses can be calculated. Some practical suggestions will be given for keeping the doses to technologists from internally deposited radioactive material as low as reasonably achievable.

The families of patients and others are often concerned about the hazards to the patient and to family members from the nuclear medicine procedure. This presentation will also discuss these issues and give some guidance about the risks associated with low levels of radiation. Over welke bepalingen in de schildklierfunctiediagnostiek moeten worden gebruikt, is al veel geschreven. Hierbij speelt de keuze tussen de FT4 en de sensitieve TSH een belangr ijke rol. Het routinematig bepalen van de FT4 ~n de TSH heeft in veel gevallen financie~le conseguenties.Tevens zijn er discrepanties waar te nemen. In het isetopenlaboratorium van bet Lukas ziekenhuis is enige tijd ervaring opgedaan met het simultaan bepalen van FT4 en TSH ( FT4/TSH Simultrac van Becton Dickinson).

In kort bestek zullen de praktische en kwalitatieve bevindingen worden gepresenteerd. Een pati~ntenpopulatie (n=3504) werd nader bekeken ivm het voorkomen van discrepanties. Deze groep bestond uit diagnosepati~nten en onder behandeling zijnde pati~nten. Van 

Hot meten van de Linker Veotrikel Zjectie Fractie (LVEF) bij proeldieren is men bekende methode om de pompfunctie van her hart te beQa]en, ~ij kleine proefdieren, zealn ratten met een ventrikelgrnotte in de orde van i0 mm en kleiner, in doze methode minder gebruikelijk omdat de resolutin onvoidoende is. We hebben getra[ht nm de LVEF bij ratten te bepalen door gebruik te maken van men gemodificeerd plnhole systeem. Dit nysteem, uitgerust met men pinhole van h5 mm diameter, had een resolutie van 2 mm. Bij normn-en hypmrtensieve Wimtar-ratten I~50 -350 g) word in de lemoral~ vene men catheter ingebra[ht tot in de vena maya. Na anesthesia met pentabarbital i.v. en in rive labeIin~ van de rode bloedEellen met 74 tIBq 99nTc werd de LVEF bepaald met een pinhole collimator in din rizhting, waarbij de baste scheidiog tussah renhter-en linkerventrikeI word bereikt, De geBevenn wnrden npgenomen in histngrammode en vantgelegd in sen 64x64 matrix.

Om de LVEF te bernkenen ~erd gebruik gemaakt van men nemi-~tomatisch analyseprngranma. De LVEF bij dn normQtenmieve rattan wan 56 +/-8 % in=7). Bij de hypertensieve rattan was de LVEF 38 +1-8 7. (n=7}.

Hot verschi] in LVEF bij hl, pertenoievm en normotensieve fatten wan statistis~h sign.,~kant (p ( 0.01), Alhoewe} hot gebruik van de pinhole collimator de oensitivitelt vnrlaagt, laat nnn dn verkregen resoIotie van 2 mm toe, de LVEF bij ratten op betrnuwbare wijze te bepalen.

Ber~ett 

Bone Scanning agents are known to accumulate in certain nonosseous structures. Indeed, urinary excretion is expected and kidneys and bladder are commonly visualized. In certain cases for various reasons, diphosphonates will be bound or concentrated in other tissues.

We present a collection of interesting cases in which extraskeletal lesions show increased activity on bone scan. Correlative images are presented where relevant.

Cases include hepatic metastases from colon cs~,cinoma, malignant ascites from ovarian carcinoma, cardiac activity due to myocardial infarction, massive cerebral infarction, malignant pleural effusion due to breast carcinoma and vesico-colonic fistula complicating bladder carcinoma.

Capsule clinical histories and a description of findings will be included with each case.

~T,~, Pakbiera, ~ 1 ~ 1 ~ 1 Rijndern, T,L, HhO, M.J,P,G, van Kroonenbuvgb~ G.~,K, Heideadai, Academianh Ziekenbuia Hanatricht. RENOVASUULAIRE HYPHRTHH~IE EN H~NO~RAFIE VOOR HN NA CAPTOPRIL, Steeoae van een nierarterie leidt iu eee aantal gevmllee tot hypertensie. Capt0pril is sen amti-hypertensivum ~elk v00reamelljk via remmieg van de v0rming yam amgi0tensine2 leidt tot verJagieg van de perifere vaat~eeretand, In sen nier diataal van sen arteria renalis siennas kan captopriJ door aysteminche bJoeddrukdaling en ver~ijding van de effereete arteriolen sen afeame van de glomeruJaire filtratie veroorsakeu. Bii pati~nten met hypertensie ~erden t~ee renografieehe studies verricbt, ~n ala uitgnngs~aarde alameda eee t~eede een uur na orals toediening van bO mg, captoprih Alu radiofarmacon werd Tn-99m-~AG3 gebruikt, Bij vier pati~nten harden op groad van renografiache veranderinge~ ten gevol~e va~ captopril contrast angiografie van de aierargeri~u verricht+ In dese gevallen kon sen ntenose van de nierarterie van meer dan ~Og morden aangetoond aan denslfde nijde ale beg af~ijkemde renogram. Translumiua]e amgJophetiek gelukte bij drie van de vJer patihgen, l~ee van deae drie pagJ~nten harden post-operatief normotensief, De vierde patient ia mnmgebnden ann de vamtchirurg, Bij daze vier pngi~n{eu bleek eaptopril reuografie een bsgrou~bare metbode roor hat anntonen ran een functiomeel belangrijke removaanulaire s~enose,

[Jld.Hnppejan+ Q 9 ~,dlPlG,rmn Hroomenhurgh and Q 9

Department of Nuclear Medicine, Academic Hospital Maaatricht, the Netherlands, QUALITY ASSURANCE OF SPECT SYSTHM ALIGNMEHT, ~isalignment of the detector head of aapeot system relative to the axis of rotation or incorrect coiJimator hole angulation can produce loss nf spatial resolution and contrast in clinical studiesl In this study tmo types of measurements have been performed to assess %he qualJw of our SPHCT-sya%em {Gemini 700 camera with a Gemeral Electrfc/CGR Starll computer). FirnL~ precise mensursmeets of the augulatioa of the hoJee in our parallel hole colli=ator (LEHR) mere obtained at different positions on the surface of the collimator, ~eoond, several tomographJc acquisitions of a point source hare been performed ~Jth different radii of the detector orbit and at five translate poaJtionn of the detector ansembly, lhe first set of measurements indicated that coiiimator hale ssgulation uan leas than 0,5 degree, lomograpbic data demonstrated that backJash cauned differences in detector alignment equivalent to 4 millimeters error in the center of rotation. Apart from the effects due to the backlash the deviation in the center of rog~tion over the nhoJe translate range ~ae less than I millimeter.

In coccJunien these findings Judicate that qualiW cnntro] of SPECT ayntem alignment are of outmost importance. In this simulation study we have investigated the effects of relative kidney function, statistical noise and extrarenal background on the impulse retention function of the kidney derived from Tc-99m DTPA renography using the matrix inversion method. The effects on the calculation of the split renal function have also been studied.

We have found that statistical noise causes an underestimation of the mean transit time (MTT) which is more severe for poorly functioning kidneys. Curve data smoothing reduces the error in normal kidneys but not in poorly functioning kidneys where the signal/noise ratio is low. In contrast, extrarenal background causes an overestimation of the MTT which increases as the relative kidney function decreases and decreases as the MTT increases.

Background oversubtraction results in underestimation of the MTT. Statistical noise produces minimal error in the calculation of the split renal function from the relative amplitudes of the renograms in the time intervals I-2, 2-3 and 3-4 min. When split renal function is calculated from the ratio of the plateaus of the retention functions, statistical noise tends to overestimate the split renal function. Overestimation is more severe for poorly functioning kidneys. Extrarenal background causes overestimation of the split renal function if the true value is less than 50% and underestimation otherwise. The IMx CEA is based upon an automated microperticte enzyme irmu~assay. The anti-CEA coated microparticles and the CEA molecule in the specimen are forming an "antibody-antigen" complex. The anti-CEA conjugate (Alkaline Phosphatase) binds to this sub6trate, 4" MethytumbettiferyI Phosphate is added to the matrix and the fluorescent product is measured. The test states a linear range of 0 to 500 ng/mt, a mean reproductibiLity of 3.0% CV at s Level of 47 ng/mt. It employs monoclonal antibodies of the mouse too.

Although the same epimopes are present and a reasonable correlation : Y (R]A)= 1.08X (INx) + 8.50 (n: 119, r= 0.982) exists, we found in 7.OX of the cases depressed CEA IMx values (n= 8, mean RIA = 48.5, moan IMX 3.1 ng/ml out of 119 samples). This was found in a selected population of pathological results: moan RIA= 99.1, mean IMx= 84.0 ng/ml. Another way of illustrating the same point is through the evaluation the distribution of 203 randomly selected patient s~Iples. About 3.0X sho~ed up to be zero in the ]Nx assay disturbing the smooth shape of mhe distribution at the lol~er end.

Q/e conclude that the lowered CEA values of the IMx are falsely depressed and therefore recoenent me reassay low IMx CEA values with another assay, e.g. CEA-RtA. 

In radiology detailed protocols are available for the investigation of the different joints. A survey of 7 depts of Nucl Med in the Netherlands revealed no uniformity in positioning of the joints and imaging techniques. To develop a standard protocol for the scintigraphy of the knee joint we imaged 20 patients with complaints of the knee in multiple directions. In each patient anterior, posterior, lateral, and medial planar analogous (4 min) and digital (2 and 4 min; 128X128 matrix) images were obtained. Moreover, a condyl view was acquired in every patient.

Two experienced physicians in nucl med and two technicians separately interpreted the images. They were asked to select the most efficient approach and, if possible, to define a standard protocol. After evaluation of the first 5 patients, they agreed that the 2 min images were of sufficient quality. A single anterior image was insufficient to detect all lesions but a combination of an anterior and a posterior image revealed all localisations. In the majority of these 5 pts additional images of the painful and cent,alateral knee were necessary for optimal Iocalisation of the lesions. The condyl view gave confusion in 2 patients. The preliminary conclusion is that routinely an anterior and posterior image must be obtained. If lesions are detected, an additional medial or lateral image of the diseased part of the knee and the corresponding view of the cent,alateral knee should be obtained. Quality control (QC) is a major concern in nuclear medicin and nuclear medicin technicians become increasingly involved. In order to assess which activities of QC are taken by the average Dutch technician, we performed a survey in 31 Dutch departments of nuclear medicin. In most departments measures for QC were acquired by self-study, and were organised and effectuated by the technicians themselves.Only in the academic hospitals was this supervised by a physicist. We conclude that in all hospita]s at least some measures of QC are taken, but that uniformity is lacking. We suggest that in future training of technicians more emphasis be put on matters of Qc. It is proposed that a manual with a number of general guidelines be compiled.

Nuclear Medecine Department,lnstitut J.Bordet,Universit~ Libre de Bruxelles,lOOO-Bruxelles,Belgium. A.Verbist,A.Delcorde,D.Balikdjian and J.FrUhling.

IN A SINGLE REPORT. Most computer programs based on the use of the second derivative method for the automatic localization of the BG-ROI give often a far optimistic result of the left ventricular ejection fraction and merely does not allow any intervention of the operator in the selection and correction of the ROl's.Moreover,Fourier Analysis and the determination of the regional ejection fraction are often separate program modules in which a lot of data is recalculated without need.Our program combines operator decision,whenever wanted,for the calculation of the total and regional ejection fractions,based on a fixed BG-ROI for the LV with complete Fourier Analysis and puts the results into a single report.After zooming and smoothing,the operator draws roughly the LV-ROI on the ED-image(cine mode allowed).Final adjustment of the ROI is achieved by trimming the treshold value in the isocontour ROI function.A second ROI is drawed inside the first one serving as a reference for the BG-ROl.After selection of the center of "gravity",regional ejection fractions are calculated in 8 sectors.On demand,another image report is generated combining the results of the calculation of the right ventricle ejection fraction with the already obtained LV ejection fraction value. In order to give the maximum of information about the right ventricle,both,the amplitude image created by Fourier Analysis as the classical images can be used for the determination of the ROl's. Both programs can work independently,or can be linked together.These programs are for us pratically usefull in the follow-up of patients receiving cardiotoxic drugs during several chemotherapy cures. There has net been so far a standard method to differentiate between bone metast asis and degenerative bone lesions in skeletal scintigraphy.

In the present study sixty eight patients with solitary bone lesions were subjected to 4 & 24 hours Tc Tc-99m-MgP uptake.

The ratio of these lesions were compared to a normal vertebra (TF) in different groups including pure degenerative lesions, suspected degenerative lesions in cancer patients & suspected malignant lesions (both osteoblastic and o steolytic types).

The results showed that there was a h~gher TF ratio with significant difference in both'osteoblastie & osteolytic malignant lesions as compared to primary degenerative lesions or suspected degenerative lesions ( P<0.001 }.

In case of malignancy, TF ratio was of nearly equal value in the spine or other flat bones.

Also TF ratio had no significant relation to the primary site of malign ancy.

We concluded that TF ratio is a reliable method of analysis for separating solitary metastatic and degenerative lesions in bone scint igr aphy.

In our institute,a 4.7 Tesla/40 cmdiameter nuclear magnetic resonance spectroscopy (MRS) system was installed to evaluate its use for detecting high energy phosphate compounds, like phosphocreatine or ATP, in experimental organ perfusion systems as Phosphorus-31NMRspectroscopy (P-31-MRS) provides an ideal tool in non-invasively measuring high energy phosphate compounds. In order to avoid ethically sensitive and expensive in vivo animal experiments and sacrifice of higher developed animals such as dogs,pigs or monkeys, we used organs harvested from slaughterhouse pigs, i0 -15m in postmortem, for the development of simple organ perfusion models of heart, kidney and liver. These organs were studied with different perfusion protocols to evaluate and define conditions for optimum metabolic preservation. Reperfusion of plegic swine hearts, livers and kidneys with arterialized blood inside the magnet showed regeneration of ATP, documenting the viability of the organs. In conclusion, pig kidneys, hearts and livers from slaughterhouse lend themselves to easy, non expensive organ perfusionmodels. Together with P-31-MRS these organ perfusion models are used in our institute for a large variety of experimental protocols, such as metabolic studies of preservation solutions used for human organ transplants, effects of various pharmaceuticals on energy metabolism or testing of perfluorocarbon emulsions as blood substitutes.

,~eader .:;bker~biis ~aas~dc,~t.

HET NUT VAN 201-THGLIUM BIJ 8CHILDKLI~RGARCINOMEN.

,~e,~ten van schi]dk;ier~,eefael, locale uitbretdir:g e~ netastaa~'n ap af scirEti~r~fi~ch ~cJ~ b~ ~ ~et !:ill, Br zijr ~r%t~. ~evai!<~ ~at.ient is iiervan eel; ~y~iseh " 'e '~ V. 0r0.eiu Bet betreh ee;! 7?-jarige man ~elb nich i~] i97) meid~e met een err, tar ,arder~de selV_ldkiier, dik~lach<en e~ iichte heezLeid De ~iaggo[e r ,)fiuiair st, rata ~er~ ~esteld, ~,elke beh~rJei,~ ~'er,i ~et eer n,~t:t.:~tale h, ' " b,.i~*ecnr,'4e Her .~::bbginch c,~,der~oek reef:de feen ~ai:.:~nit, eit in i~*!i !987 krijgt patient opaJeu~ kl,:<.?,te ~',.~,is t.r ':a:~ z~eiiir}~ in de hab e,~: heea],eld Er vol:t eea nieu~e i~s ;~ar~,i! ~et, ?~, verda~ na ldat : f0lltcu!alr schiidkliereareinor P?4Hl,% 8evble ',an de e:;tr air .9"9 geeft oak aln resultant ee~ foilie, bir aabi'_:~kllercareiaoca, P.,,~toperatief krijgt de pader~t ee~ ablatiedoeie '/ar~ 1 88 F~B~ 13ii en aei~ suppre.~siednsi,~ ;'aa 8x25 t~g eyb~e! 8a enke!e maa~tdea bevindt patient dch ia een ;%~,po~hyreei~ie faee, Een diagaeatiseh anderzeek ~et 185 MBq 1311, hat geea reataktiviteit aien in bet schildklier~ebied, maar tle patient kri~t toch een therapeutisei~e dosis van 5.58 fiBq 151I, gezien de atagerin~. Veer g~ger: na de therapeutisci, e =ir is er ^~ ...... ~ ~ d, ide]ijke aecu~ui',tie in ~'~ ae~i!dkliergebie~ t,e den In febr~!ari i~88 ~;rijg~ de patient een Weede ti~erapeutiaetle d'~ai=:. aeintigraflsch zien ~e aleehts aen ~r vag~ reataktivitei~ in ~:et se~d Idk! iergebied. I," aagu~tu~ 1999 zien we ;~a adntigrafie se~. 1311 geen sehildkl:.erreeten RADIOMETRIC ASSAY OF FHOSFHOUPASE A 2 Phospholipase A2(PA2) catalyzes the cleavage of a fatty acid from the 2-position of phospholipids. PA 2 has a physiological role as a regulator of prostaglandine biosynthesis and as a digestive enzyme secreted by the pancreas. Autodigestion through PA2 probably is the main pathogenic factor in acute pancreatitis and serum levels of PA2 activity have been reported to correlate with the severity of the disease. A sensitive and straightforward assay of serum PA 2 activity thus would be a valuable tool in diagnosis and prognosis of patients with acute pancreatitis. The amount of 14C-labelled palmitic acid (PA) released from the substrate L-c~-dipalmitoyl-(2-[ 1-14C] palmitoyl)phosphatidy 1-choline (PC) after incubation with the enzyme source was used to measure PA2 activity, which was expressed as nmol of (14C)-patmitic acid per men per ml serum. After incubation the 14C-palmitic acid was separated from excess of 14C-PC prior to measurement of radioactivity. Using purified PA 2 from porcine pancreas various reagents and reaction conditions were tested to optimize enzymatic activity. Increasing the substrate concentration in the incubation mix resulted in maximal activity at 0.64 mM PC. The presence of calcium ions in the assay buffer was indispensable for PA 2 activity, the maximum occurring at 20 mM CaC12. The importance of detergents was shown by a twenty fold increase in activity when SDS (2.5 mM) was added to the assay buffer. The optimum pH of the Tris-HC1 buffer was found to be 8.0. Enzyme activity was constant in time for at least 2 hours. Within-run precision analysis with one serum source showed a coefficient of variation of 7% in the lower range of PA2 activity (mean: 0.44 nmol/min/ml; SD:0.03; n=9). The sensitivity of the assay allowed determinations of PA2 activity as low as 0.1 nmo] palmitic acid/min/ml seruro. Studies are presently i 9 progress to investigate in more detail the postulated prognostic potency of PA2 activity in serum. This study was undertaken to acquire objective data on blood loss in women complaining of heavy menorrhagia.

Fifteen patients aged 16-49 year(median:39 year) were injected with 300 kBq 59Fe, as ferricitrate c a few days after the last day of menstruatlon. Patients were instructed to collect during the following periods of menstruation all sanitary pads as well as urine in separate containers. After the last day of the menstruation the content of the sanitary padscontainer and the urine was measured for 59Feactivity and compared to that in 5 ml blood samples, using appropriate geometric conditions. One week after injection of the dose, a blood sample was taken to assess the amount of 59Fe-incorporation in peripheral blood.

In all patients the incorporation of 59Fe in peripheral red cells was above 85%. The total blood loss in 23 periods ranged from 12 to 310 ml (mean: ii0 +/-81 ml) In the urine 1-69% (mean:24% +/-18%) of the blood loss was found.

In eight patients bloodless was measured during two consecutive periods of menstruation.

The reproducibility, expressed as duple standard devlation for the percentage bloodless found in the urine was 6%. All patients used external sanitary pads. There was no correlation of the bloodless found in the urine between patients who had at least one delivery and those who had no delivery.

In conclusion: measurement of sanitary wear alone in women using external pads unuerestimates menstrual blood loss with about 25%. The amount of bloodless via or occuring during voiding is not to be neglected. ACG van Hooren, EGM D'haene, Merwedeziekenhuis~ Dordreeht, The Netherlands.

Onderstaande studie ~erd uitgevoerd als onderdeel van een acceptatie-test en om de stabi]iteit van sen Siemens 57 ZLC Orbiter met Paragoncomputer (Medasys) te testen. Oak werd onderzoek gedaan naar he& effect van versehillends collimatoren en matrices. De meetperiode #as 8 maanden. Gemeten ~erden: i. De unifermiteit (U) zo~el integraal (U-INT) als dif-Ferentiaal (U-DIF) met een C0-57 flood source. 2. De X-en Y-pixel size en center of rotation (COR) met 4 punten fantoom en Medasys-software. 5. Systeemtest met een Jaczczak-fantoom op lesiecontrsst~ U, en %RMS-ruis met LEAP en HRES~ verschillende matrices en countrates. Over de gehele periode ~aren de resukaten:

U-DIF 4,64% ~ 0,28~ en U-INT 5,91% + 0,42% (x ~ 2 sd); X-pixel 6,02 • 0,01 mm en Y-pixel 6,09 • 0,01 mm (x• COR-waarde: range 52,0-52,2. Deze resultaten golden veer een LEAP en 64x64 matrix. 0nze resultaten duiden op een dusdanig grote mechanische en electronische stabiliteit van het systeem dat controle van deze parameters slechts sporadisch nodig zal zijn. 0ns systeem voldeed ruim san de in de literatuur vermelde performance-eisen. Nagegaan werd ook bet effect van homgeniteitscorrectie (30 Mc bij 64x64 en 120 Me bij 128x128). Doze correctie gaf geen enkele visuele of rekenkundige verbetering te zion. Een collimatortest op hole angulation is wel aante bevelen. Ondanks sen lagsre eountrate verdient de HRES veelal de voorkeur boron de LEAP-collimator. Een elegante dag-tot-dag k#aliteitscontrole bestaat uit hot bij elke pati~ntstudie meetomograFeren van een eapillair van beken~grootte gevuld met aktiviteit.

Hepatobiliary scintigraphy is apromisingmethod to evalaate the degree if liver disease and common bile ste-n0sis in children with cystic fibrosis (CF). 20 Children (mean age 13 yrs) with liver disease due te CF were studied with 99mTc-trimethyl-3R-IDA scan (Ill MBq). After the baseline examination, in 9 pea the scan was repeated ~0 months later, to evluate the effects of ursodeoxicholic acid (UDCA) on the scintigrephlc finding. Morphological pattern as well as some functional parameters (T 89 of hepatic wash-out, time of visualization of intestine) were evaluated. At baseline~ a biliary stasis of various de~ree, was observed in ]9 cases: severe hillary obstruction in 2 cases, visualization of secondary and tertiary bile ducts in I0 eases~ dilatation of common bile in 7 cases. An enlarged ~allbladder with delayed emptying was observed in g pts and in 8 ~t could not been visualized. After UDCA therapy the scintigraphic pattern and the fnet~oaal parameter improved remarkably in all patients. In particular none showed evidence of biliary obstruction, ~he gallb!adder was seen in all case and the dilatation of imtra and extra hepatic ducts was reduced. In this group of pts. the T~ of hepatic wash-oat decreased from A0 to 29.2 mfn. and the time of visualization of intestine from 22.2 to 17 min. The se~ntigraphic findings at baseline may be related to the ispissated secretions due to CF and the improvement after LDCA therapy may be due to its choloretie effect. 

In 8 patients with a cerebrovascular accident (CVA) (5 wi%/% a middle meningeal artery infarction, 2 wir_n a lacunar inrarctzor~ and i with both types of inzarcti.'on) a co.ni0arison was made of the ear l~ inza~m:ion-aetecr_%ng ability twithin 24 h after onset oz inzarction} of CT, Thallil~a-201 Diethyldithiocarbamate (=oITIDDC), and Technetium-99m-d, l-hexamethylpropyleneamine oxime ( In this paper, the presence of unexplained large focal peripheral cortical abnormalities detected by isotope studies performed on renal allografts is reported.

Nineteen children who had undergone renal transplantation we~ studied ) hours followino the intravenous injection of99mTc D.M.S.A. in 17 and of 99mTc gluconate in 2. The studies were correlated with clinical information relating to both the donor and the recipient, technical perioperative details and the course of the graft from the time of transplantation to the scan. There were 10 normal studies and 9 abnormal studies, usually demonstrating multiple cortical abnormalities. Normal studies were seen much more often in grafts from living related donors (5 of 6 living related donors had normal scans vs. 5 of 15 cadaver grafts had normal scans) and more often relatively early post transplant (mean time from transplant to scan was 14 months in normals and 28 months in abnormals).

Analysis of donor information, ischaemia time, use of perioperative machine perfusion~ recipient data and subsequent clinical course revealed no other correlation with the scan appearance. One possible explanation for the focal abnormalities detected on these studies is graft infarction secondary to progressive obJiterative vascular disease.

The finding of frequent renal cortical abnormalities demonstrated bY isotope studies performed on renal transplant recipients is previously undescribed. In this initial study, we have looked for possible aetiologica] and pathophysiologica[ correlates. This phenomenon is clearly worthy of a further more intensive and detailed prospective study.

Y. Manntinq, M.G. MORGAN, E. MARIPUU. Nucl. Med. Section, Dept. Clin. Phys, University Hospital, Uppsala, Sweden

SPECT imaging of pulmonary perfusion (Q) has long been possible. Recent introduction of Tc-GAS for ventilation (V) opens possibilities even for V SPECT imaging. The aim of this project was, to establish I) a method for simultaneous display of corresponding V and Q SPECT images, and 2) a method for quantification of regional V and Q, and V/Q ratios in SPECT studies.

Guided by anterior reference images, corresponding transversal, coronal, or sagittal V and Q slices are selected and displayed simultaneously. Visual evaluation of V and Q studies is done by simultaneous stepping through the V and Q studies, level by level. For quantification of selected slices, the body outline is defined by a semiautomatic algorithm, as is the central lung demarcation vs mediastinum. The center of thorax is determined and from this point the lung tissue between the borders is divided into sectors. Mean cts in each sector is computed and displayed in relative values for V and Q. In each sector, the V/Q ratios are computed and displayed graphically.

This method allows alignment and fast, controlled simultaneous evaluation of single or multiple added V and Q slices. Semiautomatic quantification of regional V and Q, and V/Q ratios is easily performed. Accurate center of rotation (COR) correctidn is very importam for high quality SPECT imaging. A number of possible errom, including head tilt, collimator hole angnlation and zoom factor, may be of influence on the determination of the COR. h some systems the detector shows sag due to ils weight This willintroduce a shift of the projection imagesin the Y-di.rectiun. The magnitude of the shift will vary during rotation and is dependant on the radius of rotation. To prevent introduction of a head tilt, the detector has to be positioned to the amount of sag (0. 8 ~ in our system). After calibration a m-nan spirit level was attached to the detector, enabling to position tl~ detector to 0.8~163 ~ The influence of the radius of rotation on the COR correction was meamaedby acquiring SPECT studies of point sources.The paths that were described by a point source that was placed off axis, using COR corrections obtained with different radii, were ploUed. These ~owed that ~ag a different radius for correction as for acquisition, resulted in less accurate corrections. Resolution of point sources, measured as FWHM in axial, radial and tangential direction, was not significantly decreosvd when different radii (200 vs 350 nun) were used. Reconstruction of SPECT studies of a Jaszczak phantom, did not show differences in resolution and contrast when different COR corrections were used. This means that although the COR correction derived with a different radius is not able to fully correct the shift of the projection images, the influence is not noticeable in the recenstmcted slices. A new three-headed gamma camera, the 1GE NEUROCAM, has been recently installed in our Institute for evaluation in an everyday clinical environment. This new instrument is dedicated to single photon emission tomography (SPET) of the head and consists of: 1) a comfortable couch (of variable height) with a fixed height head rest; 2) three cuboid (40.5x40.5x25.3 cm) detector heads with a field of view (FOV) of 22x19 cm (central FOV = 20x17 cm); 3) an acquisition terminal, PC compatible. Each detector head has 27 photomultiplier tubes (PMT). Two types of low energy (LE) parallel hole collimators, a general purpose (GP) and a high resolution (HR) are available and interchangeable by a single operator. The reconstructed pixei size is 4 mm in a 64x64 and 2 mm in a 128x128 matrix. Data processing is carried out in the IGE STAR3000 computer linked to the PC terminal.

We have performed more than 80 SPET studies in 25 patients. 14 patients were injected with 99Tcm-HMPAO, 7 with 123I-IBZM and 4 with 99Tcm-MDP. DYNAMIC SPET (64x64x64x15 sec. views, total acquisition time of 5 minutes) was performed at 1, 10, 20, 30, 60 and 90 rain p.i. in 5 patients. 6 High Resolution SPET (HR-SPET) were carried out in 3 patients injected with 99Tcm-HMPAO. The acquisition parameters included LEHR collimator, 128x128x64x60 sec. views (total acquisition time of 20 minutes) or 128x128x64xg0 sec. views (total acquisition time of 30 minutes). Data processing was that of a routine protocol defined by our Institute, with attenuation correction always performed (u = 0.12 per cm).

The results show that patient positioning is extremely easy and time saving (less than 1 minute). High quality images are obtained in a relatively short total acquisition time (20 minutes). Shorter acquisition times (5 and 10 minutes per study) allow for higher than average spatial and contrast resolution. DYNAMIC SPET with some radiotraeers (i.e. 123I-IBZM ) is possible which permits the study of their kinetics. Finally IGE/NEUROCAM is a small compact system which fits into relatively small spaces. It seems to be ideal for Departments with a busy neurological clinical routine. The purpose of the present study is, to visualize and quantify dopamine D2 receptors in the living human brain using an [1251] labeled ligand and the SPECT technique, ledobenzamide (S(-)IBZM) has been shown to be a highly selective ligand with high affinity For D2 receptors in experimental studies. 5mCi (185 MBq) of [1251] labeled S(-)IBZM were administered i.v. to: 9 control subjects, 18 parkinsonian patienLs under L-DOPA therapy,7 parkinsonian patients without L-DOPA and 8 unmedicated patients with Huntington's disease. Data collection with e rotating double head scintillation camera started 1 hour after injection and lasted For SO minutes. In a semiquantitative approach a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral Frontal cortex, which was t.77 + O.11 in the control group. A marked reduction of this ratio was Found in patients with Huntington's disease (1.57 • 0.15. p = 0.0001), no changes in untreated parkinsonian patients (1.72 • 0.12), but a reduction in L-DOPA treated cases (1.60 • 0.15, p = 0.003). A curvilinear relationship was Found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under Full neuroleptic treatment was 75 to 80~. Preliminary results in acutely psychotic patients, who had never received neuroleptics did not show differences to the control group. S(-)IBZM binding is reduced with increasing age (p < 0.05). Specific binding was reduced markedly, when the racemic mixture of IBZM was used, and no specific binding was seen with the R(+)iaomere, demonstrating the stereoselectivity of IBZM binding. The results show, that dopamine D2 receptors can be clearly visualized with high resolution using the SPECT technique and S(-)IBZM as a ligand. A semiquantitative approach can give estimates for receptor blockade or receptor density. This method is of clinical value For the early diagnosis of degenerative neurological disorders, such as Huntington'a disease, and For the monitoring of neureleptic treatment.

EXPERIENCE IN IMAGING

1-123/I-151 MIBG FOR IHE DIAGNOSIS AND FOLLOW UP OF NEUROBLASIOMA

Delm, tmeut of Nucle~ Medicine

In one of the AIDS patients the D2-recepters were blockexl by administmSng 2 mg haloperidol 30 rain before the investigation. The 4 other patients did not use neuroleptlcs. At'tea" injection of 185 MBq 1-123 IBZM the.SME. 810brain .tom ograph w.~ ~ to perform single slice dynamic SPET at 0-60 mm p.t. at me lever of the basra ganglm, OlvlI~25-3Omm. This was followed by multislice SPET at 75-120 rain pa. from OML-5 ram to OML+ 60 mm in the volunteer and in one AIDS-putiem without neurolepties, as well as in the AiDS-patiant on hainperido!. Regions of interest we~ drawn for the basal ganglia (BG), fron~ .eo[tex (FC), pan.etal arttex (.PC), t~nparo-p~ieto~eipi~ eer~x O'POO, and oce~r~t~.cer~ex (.oc) .~ ~t~ynan?'e .~ multlslice SPET, and of the cerebellum (CB) m the muktshce ~r~ using L~:entuur lines of radioactivity (counts/pixel). During dynamic SPET the coefficient of . steepness of the uprising slope of the basal gangliafaental cortex (BG/FC) r~..o (Slope BG/FC') was determined ilsing linear regression

Dynamic SPET 60 rain p.i

Multislice SPET 105 rain pJ

mloperidol no statistically significant differences were observed between the ratios of the basal ganglia to the different oordcal reg!ons. No censistent difference was present between the ratios in the AIDS patients ,mthout neuroleptics and the healthy volanteer, although at 60 rain aft~ injection the ratios WP 13 [ Manntinq, & MG Morgan

Basal and post-stimulative 99mTc HMPAO (555MBq x2) SPECT's were performed in 7 controls and 9 profoundly deaf patients. After approval of the local ethical committee, HMPAO was injected through a catheter, in lying subjects with covered ears and eyes. The stimulation was a 40dB, 1000Hz sound in controls, or an electrical stimulation of the promontory (150 ~A) in deaf patients, for i0 mn. SPECT was obtained from 64x20 seconds acqu&sitions over a 360 ~ rotation.The activity was calculated in ROI's corresponding to temporal cortex including auditory areas, and referred to the background activity in a reference ROI outside the brain.The post stimulative activities were expressed in percent of change of the basal activities.In controls, a bilateral increase of temporal activity (+7 to +23 percent) was observed. In 8 deaf patients, the activity also increased (+7.5 to +22 percent) and was unchanged in 1 (less than 5 percent).These results indicate that HMPAO SPECT is able to detect the cortex and cochlear nerve response to an auditory stimulation, which is an important feature for auditory rehabilitation by cochlear implantation. 

Recently it has been suggested that single photon emission computeriz6~ tomography (SPECT) studies with a dopai~ne receptor lig=dI~ may be a useful diagnostic tool for differens I-DOPA ~ponsive patients with multiple system ar_ropny (MaA) from I-DOPA responsive pat lents wiv/% idiopath/c Parkinson's disease [1] . 1-123 (S)-(-)-2 -hycqro. xy-3-iodo-6 -me thoxy-N [ ( 1 -ethyl -2-Dyrro• (~231BZM, spec. act. 3~00-6400 Ci/nm~Dl], a prom/sing D2-receptor imaging agent for SPECT, ~ recently ~een syElr_nesize~ my some or us. Data oz in vitro and in vivo experiments in rat brain and of in vitro experiments in human brain provided us the requ/_red backqround to perform in vivo ~SIBZM SPECT stbdies for D2-receptor imaging in human basal gangli~ SPECT was performed with a rotati_n~[_ga~ma-ca~era after injection (p. i. ) of 5 mCi ~2~IBZ~ ,Striatum/cerebellum (S/C) ratios of radioactivity [counts/pixel) were calculatec~ In one healthy volunteer (man, 52 years), S/C ratios were 1.80 and I. 9.7 i. 5h and 3. 5h p. i., respectively. In a patient wiun progressive supranuclear palsy (PSP) (man~ 74 years] , S/C ratios were i. 36 and I. 74 I. 5h and 3,. 5h p. i., respectively. Another patient with PSP [man, 60 years~ had a B/C ratio o~ i. 39 i. 5h p. i. In a patient with striatonigr~, degeneration [~man, 40 years) , the S/C batio was i. 37 i. 5h p. i. Arm in a patient with. the Shy-Drager s ln?q]zqome_ [woman, be years), une S/C ratio was 1.45 1.5 h after inj ec%iork Our pi~liminary data suggest that ~mSIBZM SPECT can visb~lize a striatal D2-receptor defect in patients with MSA I. Qu/nn N. J Neurol Neurosurg Psychiatry Special Supplement 1989; 78-89.PURPOSE: MIBG scintJgraphy has earned a sJgnifiicant role in the diagnostic procedure of adrenergJc tumors. We present our experience using 1-123/1-131 MIBG for the diagnosis and fellow-up of pediatric patients with neuroblastoma. MATERIAL AND METHODS: The study included 36 children, aged from 3 months to 13 years oid, which were refered to our department for confirmation of the diagnosis of neuroblastoma and assessment of the clinical stage of the disease. Twenty ene of them were reexamined at various intervals after surgical treatment-chemotherapy. 

100%. We think that the higher sensibility of the isotopic method ca be due to the metabolic nature of this technique. We also studied the location and number of lesions detected byeach exploration method. We found that differential diagnosis between bone metastasis and bone marrow infiltration remain as an unresolved problem. We concluded that ecintigraphy with MIBG is an useful method for early diagnosis of bone metastases in neuroblastoma patients.

K.M el i___~e I ,J.Vandevlvere 2 IChildren's Hospital, 2AZ Middelhelm, Antwerp,

Over a 3,5 year period 147 children (59 boys and 88 girls; 99 under 5-years of age)underwent Tc-99m DMSA scan (DMSA). The images were acquired with an all purpose-or pinhole collimator, in the posterior and both posterior oblique projections. We compared the DMSA findings with the clinical history, intravenous pyelography (IVP), micturating cystourethrography (MO and ultrasound scan (US). Sixty patients presented with acute pyelonephritis (P-group), 62 with a lower urinary tract infection (UTI) (U-group) and 25 underwent urological investigation for other reasons. All 147 had DMSA and US; 93 had IVP and 81 MC. In the P-group DMSA was + in 69/120 kidneys whereas 27 were § on US. In the U-group DMSA was + in 27/124 kidneys with only 6 + on US. In the P-group DMSA was + in 49184 whereas 17 were + on IVP. In the U-group DMSA was + in 12/54 whereas 3 were + on IVP. In the P-group 33 kidneys showed vesicoureteral reflux (VUR) on MC with 8125 IVP +, 8133 US +, and 24133 DMSA +. 23133 showed a grade Ill or higher VUR. In the P-group 63 kidneys showed no VUR with 13/51 IVP +, 21/63 US +, and 34/63 DMSA +. In the U-group 13 kidneys showed VUR on MC with 114 IVP +, none US +, and 5113 DMSA +.Those 5/13 DMSA + showed a grade Ill or higher VUR. In the U-group 57 kidneys showed no VUR with 6140 IVP +, 11/57 US + and 1 I157 DMSA +. These results suggest that I ~ ) DMSA is more sensitive than IVP and US in the early detection of renal scarring, even without clinical signs of acutepyelonephritis 2 = ) scarring seems to occur in the abscence of VUR more often than generally estimated 3 ~ ) DMSA is a useful first line investigation of UTI in children and can be helpful in selecting patients who require a MC. At the end of this lengthy procedure pictures were of poor quality and from 33 patients we showed only 9 positive.

In 1988 we decided to change to I "~. The radiopharmaceutical itself is more expensive (a difference of approximately s Amersham 1990), which is a deterrent to many departments. However, due to ~ shorter T 89 and lower energy a la~g@r amount of I (200 MBq), as opposed to I " (20 MBq), can be administered to the patient. This results in the same estimated dose equivalent (ede) of 4mSv for both radio-nuclides. We used the protocol which enabled us to image the kidneys on injection, thus dispensing with a separate injection for the renal outlines. The total test involved 110 minutes imaging, only two visits to the hospital and one venepuncture. Images are of a higher quality and we have so far had 3 positives from 11 patients.We conclude that despite the higher cost, 1123 MIBG has many advantages, and provides happier patients and technicians.

Roll Lewander, Department of Diagnostic Radiology, Huddinge University Hospital, S-IQI g6 Huddinge, Sweden

The most requested investigation in a nuclear medicine department today is the technetium-99m-diphosphonate bone scan and in our department there is still a continuously increasing demand for this examination. The main reason for this is the enhanced interest shown by the orthopaedic surgeons, who have found the bone scan extremely helpful in a lot of different insults, be it traumatic, inflammatory, neoplastic or just bone pain of unknown origin.The bone scan is more sensitive than radiography but there is no contradiction between the methods which are assessing different parameters. The radiography is a static image of the mineral distribution and the bone scan is a functional image of the osteobiastic activity. Thus the bone scan shows: l) pathological changes earlier than the radiography, 2) if a lesion is active and has to be treated, or passive and can be negiected, 3) the whole skeleton, perfect for screening of malignant diseases. The diagnosis is usually based on both examinations and in some cases even supplemented by a bone marrow scan.The lecture will give a short survey of bone physiology, bone-scanning agents, the normal bone scan, imaging technique including 3-phase bone scan and examples of clinical application in different diseases. The pathophysiology of extraskeletal uptake of bone agents will also be explained. Finally a list of practical advices for technicians in order to avoid misleading results and misinterpretations will be presented. 

Most commercially available labelling kits for the preparation of Tc-99m MDP contain an antoxidant such as 4-aminobenzoic acid (PABA), gentisic acid (GA) or ascorbic acid (AA) in order to prevent reoxidation of reduced Tc-99m to pertechnetate.We have now compared the efficacy of different amounts of these agents in MDP-kits.We have also studied the potential usefulness of sodium metabisulphite (Na-MBS) and of sodium hypophosphite (Na-HP) for the same purpose. Kits were formulated containing 15 mg MDP and 0.5 mg SnCl 2 together with 0.5 mg to 2 mg PABA, GA or AA or l mg to lO mg Na-MBS or Na-HP. They were reconstituted with 0.74 GBq-ll.l GBq Tc-99m from a fresh or old Tc-g9m generator. The percentage of pertechnetate was determined up to 24 h after reconstitution by chromatography on paper, eluted with acetone. Na-MBS and Na-HP appeared to be completely inefficacious as antoxidant in Tc-99m MDP, as important amounts of TcO 4-were formed rather soonly. On the other hand, the 3 organic stabilizing agents were found to prevent reoxidation of Tc-99m very efficiently, even in the lowest tested amount (0.5 mg). Up to 8 h after reconstitution with high activities of Tc-99m the amount of TcO Z did not exceed a few percents. After 24 h the radlochemical purity of the preparations contai~ing'PABA or AA was still >99% but 7% to 10% of TcO 4 was present in the vials containing GA. It is concluded that for routine use all MDP-kits containing PABA, GA or AA will yield a Tc-99m MDP preparation that is stable for at least 8 h. 

The clinical roles of radioimmunoscintigraphy, RIS, in the management of cancer patients include the detection of subclinical subradiological recurrences after completion of therapy, the distinction between post surgical fibrosis from viable tumour, the identification of recurrent disease before the elevation of serum markers and the localisation of disease when serum markers are elevated.These apply particularly to the management of ovarian and colorectal cancer.RIS hes no role in screening well persons for cancer but is having an increasing part to play in post primary case finding, For example, in a recent study a positive pelvic ultrasound led to operation in 326 of 5000 well women screened in whom only 9 ovarian cancers were confirmed, RIS after ultrasound usin 8 the newer antibodies SM3, OVTL3 may reduce the number of inappropriate operations, In ocular tumours, the distinction between ~melanotic melanoma and haemangfoma, or melanotic melanoma and benign melanocytoma may be made using Tc-99m labelled anti melanoma antibody with 95% accuracy.The technical improvements in RIB include the move from 1-131 as the radio label through 1-123 and In-lll to Tc-99m. Now Tc-99m labelled menoclonal antibodies such as anti CEA or PR1A3 for colorectal cancer and tlVIFG1 or SM3 for ovarian cancer are bringing RIS out of the specialist department into routine use, so that a request received in the morning leads to a completed and reported study within 24 hours. 

Adverse reactions to radiopharmaceuticals continue to be a small but by no means negligible problem in Nuclear Medicine.Since the last reports to the European meetings in 1985 and '86, there have been further changes in the pattern of reports received by the U.K. scheme.Other Tc-99m materials and non Tc-99m radiopharmaceuticals have increased in both absolute and relative terms. True incidence figures are difficult to ascertain as it is certain that only a small proportion of cases reach the reporting scheme. However, the i1 reports of reactions to MIBG in the period 1985-1989 must represent a significant incidence; most appear to be of Type A -(undue sensitivity) -other materials such as red cell sedimentation agents have been implicated and TSH, Captroprii and sedatives are all associated with a small incidence of problems.The majority of radiopharmaceutical reactions are due to (Type B) hypersensitivity and difficult to avoid but preparedness and appropriate treatment can greatly alleviate the problems for both patient and staff. 

Tc-99m MAG3 has become the tracer agent of choice for renal function studies and can be prepared from a commercial (Mallinckrodt) kit by exchange labelling at lO0 ~ We have now compared radiochemical purity, stability and biodistribution in mice of kit-prepared (1) and of HPLC-purified Tc-99m MAG3 (II). Purification was performed by RP-HPLC on Hypersil ODS, eluted with an EtOH-phosphate buffer mixture. Radiochemical purity (RCP) was determined up to 8 h after preparation by a combination of TLC on ITLC-SG, eluted with acetone (determination of coll. Tc-ggm) and RP-HPLC eluted with EtOH-phosph. buffer gradient mixtures for detection of soluble impurities. Six commercial kits were labelled with 30 mCi of Tc-99m on consecutive days. The amount of colloidal Tc-99m was each time negligible.RCP varied from 89.5% to 96% immediately after preparation and was not significantly lower (< 2%) after 8 h. Radiochemical purity of II remained > 98% up to 8 h after isolation and was about 95% after 24 h. Biodistribution of I and II at 3 h after preparation was studied in mice (n=8) at lO min p.i., using 1-131 OIH as internal biological standard. The activity in the renal system (kidneys + urine) was slightly lower for I (ratio I/II = 0.95), whereas uptake of I in liver and intestines and its retention in blood was somewhat higher (ratio I/II~2). It is concluded that HPLC-purified Tc-99m MAG3 is superior to kit-formulated Tc-99m MAG3 and constitutes the most ideal preparation for renal function studies.However, the quality of kit-formulated Tc-ggm MAG3 is sufficient for clinical practice, even up to 8 h after reconstitution. 

Tetraglycine (G4) can be considered as an analogue of MAG3 in which the thiol group is substituted by an amino group. We have labelled G4 in high yield with Tc-99m in two ways, i.e. by direct labelling in alkaline medium (pH >lO) and by exchange labelling in the presence of tartrate at different pH values. RP-HPLC analysis of the reaction mixtures showed that direct labelling afforded over 95% of a Tc-99m compound (I) that remained stable in function of time.Its retention time (Rt) on HPLC was slightly shorter than that of Tc-99m MAG3 in the same conditions.Exchange labelling yielded a radiochemical species with identical Rt as I on HPLC, together with small amounts of side-products. Labelling of a I:I mixture of G4 and MAG3 with Tc-99m resulted in the formation of mainly Tc-99m MAG3, which indicates that the thiol containing ligand MAG3 (SN3 compound) forms Tc-complexes with higher stability than the tetrapeptide (N4 ligand). Biodistribution study of HPLC-purified Tc-99m G4 in mice showed that its urinary excretion is significantly lower and its hepatic uptake substantially higher as compared to Tc-99m MAG3. At 30 min p.i. stomach uptake was about 5% of I.D., probably due to the presence of TcO,-which is possibly formed by in vivo degradation of~he less stable Tc-G4 complex. It appears that tetrapeptides can easily be labelled with Tc-99m in high yield at room temperature. However, Tc-99m G4 has clearly less favourable renal characteristics than Tc-99m MAG3 and it is not suitable for renal function studies. Low radiation dose of 56 and 112 c~S given to mature female albino rats 1~d to diminution of the total estrogen(TE) and estradiol (EST) up to 24 hours,but a second peak of rise occured at 13 days with a second drop of a lesser magmitude on the 20-32 days following irradiation . Quantitative 99mTc -pertechentate sailography with citric acid s~imulation was performed in 48 patients with head and neck ~umors for studing early and delayed effects of~.irradiation on salivary glands. The shape of the time activity curves were classified into 3 grades according to the degree of radiation induced dysfunction. A ratio of pre-and post stimulation count (Rc) was applied in the major glands in relation to the radiation dose received and the volume of the glands included in the treatment. A slight rise of Re's is seen at 20 Gy and it was more evident in the group with partial glands irradiation.The radiation changes were more evident in parotids than submandibulars at 0-3 months and in dose range below 40 Gy. However ,a dose higher than 50 Gy after a peroid of 6-12 months lead to the maximum impairment of salivary function ,specially if all the glands involved in the radiation fields. On the contrary ,partial irradiation of the glands will lead to some degree of recovery in both glands at interval ranging from 30-60 months following irradiation. At our institution, a 4.7 Tesla/40 cm diameter nuclear magnetic resonance spectroscopy (MRS) system was installed to evaluate its usefulness for detecting high energy phosphate compounds, like phosphocreatine or ATP in human organ transplants. This 4.7 Tesla NMR system is used for evaluating the viability of human organ transplants by P-31-MRS. For this reason, first, a special cooling system was developed based on an original transplant cooling box to allow for sterile continuous cooling and, at the same time, optimum technical conditions for NMR spectroscopy (MRS) with a 5 cm diameter double tuned 81/200MHz surface coil. P-31 spectra were obtained at 81MHz pulse frequency after optimum shimming at the frequency of protons at 200 MHz for each individual organ. It could be demonstrated that plegic human pancreas and liver transplants contain enough ATP as viability indicator to be measured by MRS.Twenty human cadaveric kidneys were studied prior to transplantation. In 65% ATP peaks were clearly identified. In conclusion, P-31-MRS in the set-up described offers great potential for estimating non-traumatically the preservation state of human transplant organs.The value of P-31-MRS in predicting transplant function for the recipient patient is examined in prospective studies. might be higher in the AIDS patients.This may be due to decreased cortical p~usion.

The ratios in the AIDS patient on haldol were consistently lower than in the subjects without haldol, demonstrating the D2-reeeptur s p~lci .ty ~ IBZM.. . It is concluded that the dopamine D2-receptor density m the basal ganglta of panems with AIDS is normal or slightly increased. multislice SPET in one normal volunteer (male; age 25 years) and in 4 patients with schizophrenia (3 male, 1 female; age 28-52 years). Two patiunts used sulpiride (200 mg b.d. and 2000 rag/die), and one patient used trifluoroperazine (1 rag/die), whereas another patient was on ehloropromazine (100 rag i.d.s.). The patients were studied both on medication (SPET 1) and after a variable withdrawal interval flora raedieation (2-26 days; SPET 2).After injection of 185 MEq 1-123 IBZM the SME 810 brain toraograph was used to perform single slice dynamic SPET at 0-60 rain p.i. at the level of the basal ganglia, OML+25-30 n,n. This was followed by multislice SPET at 75-120 rain p.i. from OML-5 mm to OML+60 ram. Regions of interest were drawn for the basal ganglia, frontal cortex, and cerebellum using isocontour lines of radioactivity (eoums/pixel). During dynamic SPET the coeffieiem of steepness of the uprising slope of the basal gangiia/fi'ontat cortex (BG/FC) ratio (Slope BG/FC) was determined using linenr regression. During ranitisliee SPET both basal ganglia/cerebellum (BG/CB) and BG/FC ratios were determined, Significance P of the difference of these porameters in SPET 1 and SPET 2 in the 4 patients was determined using Student's 2-tuiled paired t-test The difference between the BG/CB and BGNC ratio in the patients both on (SPET 1) and off (SPET 2) neurolepties was not significant (P = 0.2 and P = 0.4, respectively). It is concluded that 1-123 IBZM SPET discriminates between patients on and off neuroleptios. Furthermore, the Slope BG/FC and the BG/CB and BG/FC ratios may be important parametem to monitor tiopamine D2-receptor oecupancy by these nemolepties. The higher BG/CB and BG/FC ratios in the patients after medication withdrawal as eorapared to the volunteer may be caused by dopamine D2-receptor upregdiation. To investigate r_ne relation between severity of memory disorder (expr~sed as a total score ol-all subtests ) and abnor~alities on EEG, CT, and SPECT, Yates' corrected chi-square test was parfozmecl In this test, for SPECT two sgparate groups were rm~er~ abnormal coldspots (SPECT1), and abnormal hotspots (~--~)" nde SPECT2de1:~s~enCVoE Pt~' rl~J-was observed between SPECTI and or SPECT2 with any other of the variables. The same was the case ~-or NPB and CT. The only dependency observed was between EEGI and EEG2 (P < 0. D2).It can be concluded that in ~atients with partial epi• ?~ainin9. oz memory .~yszunction, . . . o~ecr_~velymeasuranle memory u~sor~ers eo irK1eeu exist. No direct relation ha~ been observed between the severity of me.mory disorder and the probability of detectin~ an epileptogenlc zOCUS with SPECT, EEl, or CT. The findings o~ t[~ EEG are reproducible. The stability of d,I-HM-PAO in aqueous media is of particular interest because if d,I-HM-PAO is stable it is possible to divide the HM-PAO kit before labeling by technetium and thus to get the benefit of reduced costs. Using proton NMR spectroscopy we have shown that d,I-HM-PAO is stable in water solution. It is known that (99mTc)d,I-HM-PAO is not stable in vitro and its forms hydrophilic decomposition products, We have applied first time NMR technique for observing the formation of the unknown decomposition product of (99Tc)d,I-HM-PAO in aqueous environment at pH i0. The conclusions are that NMR technique is an efficient tool for examining these kinds of reactions and d,I-HM-PAO can dissolved in water and it is stable for a very long time and can be labeled just before use. Successful radioimmunotherapy (RIT) of human cancer is currently restricted by a number of contributing factors. Clearly, an important component is the isotope selected for use and in the past a high reliance has been placed on the use of 131I due to its availability and simple chemistry of linkage. 11 lAg would be a superior therapeutic isotope because of its low gamma component (6%) and high beta yield. The objective of this study is to develop the methodology required to link lllAg to an anti-tumour antibody and then compare this and a conventional 1311 labelled preparation as RIT agents. The well characterised Mab 35 antibody has been chosen as a model system, l/lAg was generated by neutron irradiation of palladium at the PSI. Labelling of Mab 35 antibody was by insertion into free sulphydryl groups which were introduced into the antibody (2.6 groups per molecule) using the SPDP reagent. This approach resulted in rapid 1 r 111 1 "ncorpo ation of Ag "nto Mab 35 and a proportion of the incorporated l 1 lAg (80%) appeared to be bound in a stable fashion. Spontaneous incorporation of 11 lAg into intra-chain -SH groups in a non-substituted Mab 35 was observed but occurred more slowly and was not stable (only 25% of incorporated material remaining at 2 days). Present studies are directed at the in vitro and in vivo characterisation of 11 lAg labelled Mab 35.

LaManna M, Mohama R, Slavich L, Lumia FJ, Lauderman R, Rambaran N, Maranhao V. Deborah Heart and Lung Center, Browns Mills, NJ CLINICAL INVESTIGATION OF 99mTc TEBOROXIME (CARDIOTEC): TECHNICAL CONSIDERATIONS Twenty-five patients mean age 58, underwent Thallium studies within 2 weeks of a 99mTe Teboroxime (Cardiotec) exercise stress and rest procedure.Optimal Cardiotec imaging requires a bolus administration of high specific technetium -.26ec mean volume at stress and a .45cc mean volume at rest.The mean stress dosage (MeaniSEM) was 20.9• and the moan rest dosage was 31.6• Patients were imaged using a LEAP collimator, 64 x 64 matrix, 180 ~ rotation, 13 seconds per frame, Butterworth filter 0.4 order 5, total imaging time 6.9 minutes with redistribution imaging performed at 1.5 hours.The mean interval from treadmill to scanning table was less than 120 seconds.Patients achieved comparable exercise stages for Thallium -%maximal predicted heart rate for Thallium was 86• %maximal predicted heart rate for Cardiotec was 86•The correlation coefficient between Cardiotec and Thallium was 0.92 with a p value of less than 0.001.The total study time for Cardiotec was approximately ii0 minutes.Attention to technical considerations is vital for optimal Cardiotee imaging.Cardiotec compares favorably with maximal stress Thallium imaging and provides considerable time savings.

A limitation of the newly introduced Tc-99m based myocardial perfusion imaging agents has been that they do not permit calculation of pulmonary uptake previously obtained from thallium 201 (Tl) imaging. Pulmonary Tl uptake is a recognized marker of stress induced LV dysfunction in patients with CAD. The purpose of this study was to determine whether pulmonary/myocardial (P/M) uptake ratios could be obtained with Tc-ggm MIBI, and if so, do they correlate to Tl P/M ratios and myocardial perfusion abnormalities.40 patients were investigated with Tc-9g MIBI. All patients performed maximal upright exercise and were imaged with SPECT. 22 were studied with MIBI and Tl imaging. P/M ratios were calculated in Tc-99 MIBI and Tl SPECT studies by published methods. The number of segments with abnormal perfusion (permanent & reversible) were totaled.There was no difference (p>O.05) in achieved rate~ pressure product and Watt between the 2 stress tests. Correlation between pulmonary uptake of Tl and MIBI was r=O.81, p<O.OOl for upper left lung uptake and r=0.87, p<O.O01 for lower right lung uptake. A highly significant correlation to number of myocardial segments with abnormal perfusion was seen (n:40, r=0.73, p<O.OO]).A pulmonary/myocardial ratio can indeed be obtained from Tc-ggm MIBI studies -analogous to Tl ratios. MIBI P/M ratios correlate to myocardial perfusion abnormalities. These findings dispel the original theory that P/M ratios can not be obtained from Tc-99m MIBI studies.

JT Nielsen, J Poulsen, C FIe, J Marquerse~, BV Niel-sen~ M Rehling. Dept. of Clinical Physiology and Nuclear Medicine, Aarhus Municipal Hospital, Aarhus, Denmark.

The present study was carried out to deteFmine the efficiency and the farmakokinetics of (F'fab>~) antibody-fragments (FC3001, Farmos Group'Ltd.~ Finland) for detection of metastatic prostatic cancer. Four patients were subject to intraprostatic injection of 1 mg FC3001 labelled with 85-100 MBq [In-ill] . The farmakokinetios were studied by sequential who!e-body counting, gamma-camera scintigraphy of pelvis and abdomen in AP and PA projections. Blood and urine samples were equally collected sequentially up to 72 hours after injection. The prostatic activity decreased with a half-life between 50.8 arid 197 hours.The blood concentration peaked shortly after injection and the antibody-fragments were cleared from the blood with a half-life of 21-24 hours. Only the liver accumulated antibody-fragments in significant amounts without reaching a peak value during the period of investigation. The normalized ac~tivity in the spleen and kidney varied and mostly paralleled background activity in the whole period of investigation. The urinary excretion varied between 30-35X of the injected dose in 78 hours. The antibody-fragments were not able to visualize known metastases with certainty in the four patients. However, in two patients small accumulations of activity close to the prostate were observed. Whether this activity represented specific binding to local metastases or unspecific accumulation in lymphnodes is not clear. That the known metastases were not seen may be caused by the slow release of antibody-fragments from the prostate. One of the drawbacks of classical 99Tc rn bone marrow scintigraphy (BMS) is its relatively low sensitivity, particularly in the detection of lesions in the lower thoracic (T9-T12) and higher lumbar (L1, L2) spirie. This is due to the high liver and spleen uptake of the nanocolloids (average size 60nm; 95% < 80 nm).In this work we describe the initial results of a novel approach to the imaging of the BM with a 99Tcm-label.The white blood ceils (WBC) of 5 patients were labelled with 99Tcm-HMPAO and reinjected intravenously in an antecubital vein. Whole body images were performed in an IGE gamma camera 3-4 hours post-injection. 2 patients referred with PUO and no evidence of bone infection were used as control. 1 patient had bilateral avascular necrosis of the head of the femur, l patient metastasis of Ca breast. 1 patient with Hodgkin's disease and Muhiple Myeloma has been referred for assessment of functional bone marrow after Mantle radiotherapy.The results show that BMS with HMPAO/WBC produces images of high quality (high spatial and contrast resolution, and high signal intensity) of the entire bone marrow, including the lower thoracic (T9-T12) and higher lumbar (L1, L2) spine. There is low uptake in the liver and higher uptake in the spleen. Femur/liver ratio is 0.06 for HMPAO/WBC and O.01 for nanocolloids. The spleen/liver ratio is 2.00 for HMPAO/WBC and 0.42 for nanocolloids.Bilateral avascular necrosis of the head of the femur was clearly seen as photopenic areas, as well as metastases, radiotherapy effects and relevant hyperplastic bone marrow was identified.Conclusion: HMPAO/WBC imaging of the bone marrow produces images of higher quality than those obtained with nanocolloids. In addition it has two major advantages: 1) lower liver uptake which interferes less with images of the spine; 2) lower effective dose equivalent (HMPAO/WBC 3.4 mSv; nanocolloids 6mSv). The aim of this study was to elucidate the value of IS in comparison to colloid scanning in the detection of BM-infiltration. Method: We studied a total of 23 pts, 10 with solid tumors and 13 pts with Hodgkin-or non-Hodgkin lymphema (stage I-IV). Sceletal scintigraphy, plane radiographs CT, MR and bone marrow biopsies were performed to confirm the skeletal lesions. The MAb BW 250/183 is directed against CEA and non-specific cross reacting antigen, exposed at the cellular membrane of peripheral granulocytes and myeZocytes in BM. Labeling procedure with Tc 99m was described by Schwarz and coworkers. Colloid scanning was done using a commercially available microcolloid kit (particle size<5g nm). 3 h after injection of 400 MBq of the Tc 99m labeled MAb and 1,5 h after application of the Tc 99m labeled colloid (400 MBq) planar scanning of the skeletal system with a gamma camera was performed. Results: IS showed s homogenous BM -and a moderate liverYspleen uptake with excellent visualization of a11 parts of the vertebral column. All 40 BM lesions detected by colloid scan were also seen by IS. However IS showed 17 additional BM lesions which were all confirmed by the diagnostic methods mentioned above. In 3 pts with recurrences of Hodgkin lymphoma and with case histories of radiation therapy, 12 BM lesions seen by IS and colloid scan were identified as fatty BM degeneration. In conclusion BM-IS with the MAb used is superior to colloid scanning. It is an excellent non-ivasive but unspecific method of excluding BM infiltrstion. Continuing the work with brain imaging tracers the iodo analog of SCH-23390 was labelled with 1-123. The substance is known to bind specifically to dopamine D1 receptors. Two different methods of labelling were investigated, namely electrophilic and nucleophilic substitution. Using the fn'st, the influence of different oxidants, reaction solutions and pH values on the labelling of deschloro SCH-23390, R(+) enantiomer, was investigated in detail. With IODO-GEN and PBS (pH 7.4) the best labelling yield was obtained. The reaction mixture was purified by RP-18 HPLC. The product fraction was worked up to give after sterile filtration a ready for use radiopharmaceutical. The second method used was halogen exchange with a Cu(I) catalyst in acidic and reducing conditions and the Br analog of SCH-23390 as precursor. The enantiomers of the precursor had to be separated on a Chiracell OD column. The advantages of the second method are the def'med labelling position, no byproducts and the virtually quantitative labelling yield. The pharmacokinetics of the 1-123 analog of SCH-23390 were tested in female spf Wistar rats 10, 30, 60 and 180 min p.i. The ratio of the whole brain/blood decreased in this time from 1.23 to 0.5. The main excretion path was through liver and intestine. The stomach showed an increasing uptake. The lungs and kidneys had in contrast to the other organs a high original uptake followed by a fast wash out. Binding and displacement studies with rat striatum proved the specific binding to this tissue. Clinical trials will begin shortly.

M. Hall, D.C. Costa, J. Shields, J. Heavens, M. Robertson and P.J. Ell. Institute of Nuclear Medicine, UCMSM, London, UK.BRAIN PERFUSION PATTERNS WITH Tc-99m-HMPAO/SPET IN PATIENTS WITH GILLES de la TOURETFE SYNDROME.Gilles de la Tourette Syndrome (GTS) has an estimated prevalence of 0.5 per thousand giving figures of 110,000 patients in the USA and 27,500 in the UK. The biochemical aetiology is unknown but it has been suggested that the basal ganglia are implicated in the pathophysiology of GTS. CT scanning shows no consistent structural abnormality.We studied 25 GTS patients with high resolution gamma camera HMPAO/SPET, paying particular attention to the perfnsion of the basal ganglia. All patients had a wide range of motor and vocal "tics", and ages from 7 to 48 years. 6 were female. A bank of 10 normal HMPAO/SPET studies were used as control.HMPAO/SPET was carried out with the IGE 400AC/STARCAM system using routine protocols for acquisition, reconstruction and analysis of the data. 10 MBq/kg (patient weight) of HMPAO was injected (i.v.) after a full explanation of the procedure and written consent signed. This study was approved by the local ethical committee.Qualitative analyisis of transverse.0nd coronal slices revealed, for all patients, a significant decrease in the tracer concentration in the basal ganglia nd thalami. There were perfusion deficits identifiable in the cortex of the frontal and particularly the temporal lobes. Semi-quantitative analysis with normalisation for the cerebellum confn'med these findings.Conclusion: for the first time perfusion deficits are shown with high resolution gamma camera HMPAO/SPET in the basal gaglia of patients with GTS, which may help to explain the extrapyramidal motor and vocal abnormalities found in these patients.