001

002

ELECTROCARDIOGRAPHIC AND BLOOD PRESSURE EFFECTS OF INTRAVENOUS INFUSION OF ADENOSINE IN NINETY SUBJECTS.

ANALYSIS OF REGIONAL THALLIUM-201 DISTRIBUTION FOLLOWING EXERCISE AND ADENOSINE INFUSION FOR DETECTION OF CORONARY ARTERY DISEASE.

F. Weiland, D. Belvedere, E. Coyne, P. Vande Streek, L. Spaccavento, R. Evans, and R. Borchert, Wilford Hall USAF Medical Center, San Antonio, Texas, [LS.A.

P. Vande Streek, F. Weiland, E. Coyne, D. Belvedere, L. ~paccavento, R. Evans, and R. Borehert. Wilford Hall USAF Medical Center, San Antonio, Texas, U.S.A.

Adenosine is an endogenous compound with a short halflife on intravenous infusion whose vasodilating properties have been recognized as potentially useful for diagnostic and therapeutic applications. To assess its effect on blood pressure and 12-1ead, ECG variables, we infused Adenosine into 50 normal volunteers and 40 stable pts with coronary artery disease. A 6minute infusion of Adenosine at a rate of 140 mcg/kg/min while ECG and blood pressure monitoring was done. Systolic blood pressure fell in 38 pts by 14.5+/-9 mmHg and in 40 controls by 13+/-8 mmHg. The lowest systolic blood pressure was 88 mmHg in pts and 78 mmHg in controls. Pulse fell transiently in 13 pts and 16 controls but ultimately rose in all pts by 17+/-11 bpm and in all controls by 30+/-13 bpm. The highest and lowest heart rates were 120 and 43 bpm in pts and 137 and 44 bpm in controls. PR intervals increased in 30 patients by up to 0.08 seconds. Two pts, 1 on calcium blockers and the other on calcium and beta blockers, developed third degree heart block lasting up to 4 seconds and resolved spontaneously. A third patient on calcium blockers developed Wenckebach phenomenon lasting 5 minutes. PR intervals increased in 22 controls by up to 0.16 seconds but no advanced heart block occurred. There was no clinically significant change in QRS or QTc duration in either group. We conclude that adenosine causes transient blood pressure and ECG alterations but no adverse clinical effect.

Exercise is a well known cause of alterations in biodistribution of Thallium-201 in patients with isehemic heart disease. However, not all patients are amenable to exercise Thallium-201 testing. Adenosine, a coronary vasodilating agent, has been suggested as a potential alternative to exercise treadmill testing in this patient population. The mechanism of Thallium-201 biodistribution is felt to be different in these modalities. This prospective study was designed to evaluate concordance of regional Thallium distribution with exercise and adenosine infusion. The 90 subjects received a standard exercise treadmill and on separate days a 6-minute infusion of adenosine at 140 mcg/kg/mln with Thalllum-201 injected at 3 minutes. Single photon emission computed tomography was performed. Total Segments: 450 Location Segments Concordance Anterlor 74 82% Septal 73 81% Inferior 71 79% Lateral 84 93% Apex 76 84% Total 378 84% This data suggests that adenosine will be a useful adjunct to the imaging of patients with ischemie heart disease.

003

004

THE NEGATIVE VALUE OF ELECTROCARDIOGRAPHIC CHANGES AND CHEST PAIN DURING ADENOSINE INFUSION AS A PREDICTOR OF CCRONARY ARTERY DISEASE.

DIPYRIDAMOLE-THALLIUM TESTING: SHOULD A STANDARD WEIGHT INDEPENDANT DOSE OF DIPYRIDAMOLE BE ADMINISTERED ? C.Labontg, J.Lette, D.Waters, M.Cerino, P.Ren~, MC.Eybalin, A.Levasseur, Maisonneuve Hospital and the Montreal Heart Institute~ Montreal, Canada.

D. Belvedere, E. Coyne, P. Vande Streek, F. Weiland, L. Spaceavento, R. Evans, and R. Borehert. Wilford Hall USAF Medical Center, San Antonio, Texas. The diagnosis of coronary artery disease in standard exercise tolerance tests is indicated by the production of typical 12-1ead EGG changes and/or characteristic anginal cbest pain. We evaluated the ability of adenosine infusion to produce ECG changes and chest pain in patients with CAD and in normal volunteers participating in a study of adenosine thallium imaging. Adenc.sine was administered to 40 patients with angfographically documented CAD and 50 controls (etls) by intravenous infusion of 140 mcg/kg/min for 6 minutes with continuous ECG monitoring. All subjects also underwent standard symptom-limited exercise tolerence tests. ECG results: Normal Nonspecific Abnormal Pts,Adenosine 27 12 1 Pts,Exercise i0 20 i0 * Ctls =,Adenosine 48 i I ** Ctls :,Exercise 47 I 2 (*p less than .001) (**p not significant) 2~ pts and 28 ctls reported chest discomfort ranging from mild in 8 pts and 16 ctls to severe in 7 pts and 4 ctls. There was no (significant) difference in the occurrence of chest pain between the two groups. We conclude that chest pain and ECG changes during adenosine infusion can not support or deny the presence of coronary artery disease. The diagnostic utility of adenosine infusion for CAD detection will rest with the Thallium-201 imaging.

Sunday, August26,1990

To determine if the probability of having a positive dipyridamole-thallium (dip-tl) study (reversible perfusion defect) is influenced by the total dose of dip administered, we studied 372 consecutive patients, including 210 men and 162 women with a mean age of 61.6 +/- 10.7 years old. Dipyridamole was administered as 0.56 mg/kg over 4 mn. The occurence of non cardiac side effects (98/372 =26.3%) (flushing, nausea, dizzyness, headache), chest pain, and variations in heart rate (5.5 +/- 8 bpm) and blood pressure (12.6 +/- 13 mm Hg) did not correlate with dip dose. The patients were divided into subgroups according to sex and dose range of dip administered: 153/210 (73%) men had positive scans: 6/14 (42.8%) for a dose < 31 ms, 28/39 (71.8%) for a dose of 31-35 mg, 49/61 (80.3%) for a dose of 36-40 mg, 35/45 (78%) for a dose of 4145 mg, 17/20 (85%) for a dose of 49-49.9 mg (p= 0.001). There was no statistical correlation in women, possibly because of a lower average weight and lower prevalence of coronary artery disease. Conclusion: since non cardiac effects and hemodynamic changes during dip-tl testing are not dose dependant, whereas the probability of having a positive study increases with the dose, further studies (consisting of repeat testing with larger doses in thin patients with normal studies) are warranted to determine if a standard weight independant dose is preferable.

Sl

005

006

TRANSIENT LEFT VENTRICULAR CAVITARY DILATION DURING DIPYRIDAMOLE-THALLIUM IMAGING: A SIGN OF SEVERE CORONARY ARTERY DISEASE AND A PREDICTOR OF POOR OUTCOME. J. Lette, J. Lapointe, D. Waters, M. Cerino, A. Gagnon, M. Picard, M.C. Eybalin, and A. Levasseur. Maisonneuve Hospital, the Montr@al Heart Institute and St. Luc Hospital, Montrfal, Quebec, Canada.

DIPYRIDAMOLE COMBINED WITH SYMPTOM-LIMITED EXERCISE FOR MYOCARDIAL PERFUSION ASSESSMENT: IMAGE CHARACTERISTICS. G.A. H u r w i t z , J.E. Powe, A.A. D r i e d g e r , A.C. MacDonald, N.R. Laurin and K.J.C. Finnie. University of Western Ontario, Victoria Hospital, London, Ontario, Canada

Transient left ventricular cavitary dilation (it car dil) during dipyridamole-thallium (dip-hi) imaging was reported in 45 (9%) of 510 consecutive patients (pts) referred for dip-hi imaging. Thirty-two pts underwent coronary angiography: 75% had either left main, 3 vessel or "high risk" 2 vessel coronary artery disease. Although 56% of pts with tr car d~l were either asymptomatic (49%) or had grade 1/4 angina (none had grade 3 or 4 angina), 78% had an ejection fraction above 40%, and only 7% had clinical signs of heart failure, nevertheless 64% of these pts sustained a cardiac event (myocardial infarction or cardiac death) during a mean follow-up of 12.2 months. Most events were cardiac deaths (69%); 87% of events occurred within 4 months of the test. Non-cardiac surgery was performed in 187/510 pts (125 vascular and 62 general surgery): the post-operatlve cardiac event rate was 2% in I01 pts with normal scans or fixed defects, 19% in 15 pts with reversible defects and 58% in 12 pts with tr car dil (p=0.0001). Thus, transient left ventricular cavitary dilation during dipyridamole-thallium imaging is a marker of severe underlying coronary artery disease, denotes a poor prognosis and predicts a high risk of post-operative cardiac complications in pts who undergo non-cardiac surgery.

C o m b i n i n g s y m p t o m - l i m i t e d e x e r c i s e (X) w i t h i n t r a v e n o u s d i p y r i d a m o l e (D) c o u l d i m p r o v e t h e qtuality of myocardial scintigrams. We h e r e f o r e a s s e s s e d o n i m m e d i a t e (4 min) p o s t stress images splanchnic/myocardial (S/M) a n d pulmonary/myocardial (P/M) r a t i o s of T I - 2 0 1 , as w e l l as t h e i n c i d e n c e of p e r f u s i o n d e f e c t s in p a t i e n t s a s s i g n e d to a c o m b i n e d t e s t - m o d e . In s o m e c a s e s (D+XI), o r t h o p e d i c d i s a b i l i t y o r early symptoms limited the exercise phase to <3 min; o t h e r s (D+XII) p e r f o r m e d a p r o g r e s s i v e supine bicycle protocol for >3 m i n to a symptomatic end-point. A concurrent control group had no pharmacologic or physical limitations, a n d w e r e t e s t e d w i t h X alone. C o r r e l a t i o n w i t h c o r o n a r y a n g i o g r a p h y (CA) a n d contrast ventriculography (CVG) w a s a v a i l a b l e in 375 p a t i e n t s (60 n o r m a l s , 315 a b n o r m a l s ) . S/M was higher after D+XI than after either D + X I I o r X (p<0.01) b u t w a s n o t d e p e n d e n t o n d i s e a s e s t a t u s as d e t e r m i n e d b y C A or CVG. For each test-mode P/M had similar normal values and increased concomitantly as C A o r CVG became abnormal. The safety and sensitivity of the test-modes appeared comparable; specifity was higher for D + X I I t h a n f o r D+XI. T h u s (i) P / M a p p e a r s v a l u a b l e as an i n d i c a t o r of s e v e r e d i s e a s e a f t e r D+X, (it) adding X to D decreases interfering background activity during myocardial scintigraphy.

007

OO8

IMPORTANCE OF THALLIUM-DIPYRIDAMOLE SCINTIGRA?HY IN PATIENTS WITH CONGESTIVE HEART FAILURE (CHF) OF ISCMEMIC ETIOLOGY.

COMPARISON OF CLINICAL SCORING SYSTEMS AND DIPYRIDAMOLE-THALLIUM TESTING FOR CARDIAC RISK ASSESSMENT BEFORE NON-CARDIAC SURGERY. J. Lette, P. Rene, D. Waters, M. Cerino, M. Picard, A. Gagnon, M. Kerouac, M.C. Eybalin, and A. Levasseur. Maisonneuve Hospital, St. Luc Hospital and the Montrfal Heart Institute, Montr@al, Qufbec, Canada.

F.H.Hironaka; T.Watanabe; S.F.Oliveira; J.Soares Jr.; J.A.F.Ramirez; J.C.Meneguetti; M.C.P.Giorgi; E.E.Camargo; F.Pileggi. The Heart Institute, Sao Paulo University, Brazil. 14 patients with (CHF) associated with coronary artery disease (CAD) were studied before and after suscessful revascularization surgery. Their age varied from 37 to 66 years, mean 56.8 and IS were male. All patients showed improvement of CHF after surgery. Of 26 vascular regions with patent grafts; 13 were at anterior descending coronary artery (ADCA). The seintigraphic findings before and after surgery (within 1 month) were as follows: persistent hypoperfusion pre1 post-l, transient hypoperfusion pre-4 post-l, persistent+transient hypoperfusion pre-8 post-l, normal prenone post-10. We conclude that clinical improvement of CHF with CAD patients is related to: a) possibility of revaseularizat~on of ADCA. b) presence of transient defect, isolated or associated with persistent hypoperfusion. c) normalization of Thallium uptake, even at regions with persistent defect.

S2

Clinical scoring systems are sti]l widely used by surgeons for cardiac risk assessment before non-cardiac surgery. Routine dipyridamole-thallium (dip-tl) testing in known and suspected coronary pts unable to exercise is underused because arranging for the test can delay surgery. We prospectively studied 178 pts (76 women and 102 men, aged 32 to 85 (mean 62.2) to determine the predictive value of individual clinical parameters, of 6 popular clinical scoring systems (Dripps-Amerioan Surgical Association score, Goldman Cardiac Risk Index score, Detsky Modified Cardiac Risk Index score, Eagle's clinical markers of low surgical risk, the Eagle equation and the Cooperman equation) and of dip-tl imaging before major general (58) and vascular (125) surgery. There were 20 post-operative cardiac events (13 cardiac deaths and 7 non-fatal infarctions). Results: Chi-square and Anova analysis showed no statistical correlation betwen pre-operative clinical descriptors and post-operative outcome. The presence of reversible perfusion defect(s) correlated with post-operative outcome (p<0.0001). The sensitivity and specificity of dlp-tI testing were 95% and 38% respectively. Conclusion: In pts unable to complete a standard exercise test, post-operative outcome cannot be predicted clinically, whereas dip-tl imaging successfully identified 95% of pts who sustained a post-operative cardiac event.

Sunday, August 26, 1990

009

010

UNUSUAL CLINICAL OBSERVATIONS DURING DIPYRIDAMOLETHALLIUM TESTING: SCINTIGRAPHIC AND ANGIOGRAPHIC CORRELATION. J. Lette, C. Labont&, D. Waters, M. Cerino, M.C. Eybalin, and A. Levasseur. Maisonneuve Hospital and the Montreal Heart Institute, Montreal, Quebec, Canada.

SIGNIFICANCE OF DIASTOLIC FUNCTION IN DETECTING CORONARY ARTERY DISEASE DURING DIPYRIDAMOLE-RADIONUCLIDE VENTRICULOGRAPHY. J,LekakJs, N.Vass~lopoulas, S.Rokas, Ch. Pala~stides, D.IsJnikas, N.Kokkolskis, P.Kostamisend Sp.Moulopeulos Dpt of Nuclear Medicine and Clinical Therapeutics, "Alexandrs" University Hospital, Athens, Greece.

C] inical observation, including serial pulmonary and cardiac auscultation was perfo[~ed during dipyridamo le~thal lium (dip-tl) imaging in 372 consecutive pts (210 men and 162 women, aged 62• Clinical findings included: I) dyspnea with transient exacerbation of a mitral regurgitation murmur, a reversible infero-posterior defect on thallium images and stenoses of the coronary arteries which supply the papillary muscles in 2 pts ; 2) severe dyspnea with ischemic pulmonary congestion in 4 pts; 3) dipyridamole-induced myocardial stunning (defined as prolonged but reversible post-infusion regional dysfunction) with acute pulmonary edema requiring intubatlon in I pt; 4) a transient third heart sound with multiple severe reversible perfusion defects in a p t with 3 vessel coronary artery disease; 5) of 50 pts with either asthma or chronic obstructive pulmonary disease (COPD) (mild in 45, moderate in 5 and severe in 2), bronehospasm occurred in 2 pts. The bronchospasm responded to aminophylline in I pt with mild COPD, but led to respiratory arrest ~n I pt with severe emphysema, no reversible component on pre- testing respiratory function tests ; he had tolerated well withdrawal from bronchodilators for 48 hours. Conclusion: clinical observation including pulmonary and cardiac auscultation during dip-tl testing can yield useful diagnostic inforn~ation.

01 '1 Tr~ AMRIN3h~ STIMULATION TEST: ON THE WAY TO DISTINJJISHNECROTIC F R ~ H I B E R N A ~ MYOCABDIUM. Dres, : P~rez Bali~o N~; Masoli 0"; Sporn V*; Ojeda G*; Perrone S* ; Oi Carli M*; ~4orleyM*; M. Sampere JJ**; Weilchenba~ E% * F~ideci6n Prsy/s - Sanatorio ~de~es. Buenos Aires. Argentina. ** Lhiversidad de Gr~r~3da. E ~ . ~he purpose of this study is the validatienof a diegnosticmethod for the asees~nent of myocardial viability in patients (P)with cenenary artery deseaee (CAD) ~ d left ventriculsrdisfunction. We ineluided 12 P with no contredrdication for c o r o ~ artery by pass ~ery (CABS), Of these P 7% were asymptomatic, 9~$ bad previous myocardialinfarction, ~.5% had evidence of heart failure, 31.~ ~lgina end 2 ~ had both angina and heart failure. The ar~inone stimulation test (i~r) consistedof a sin~itsneous left ventricular function (LVF)ar~ myocardial perfusiontest with Teggm-MIBIperformed at :rest(R) end 20 minutes after the adninistrationof a intravencus bolus of Img/Kg weight of anrirone (AT). The 12 P t~nderwentCABS without kncwnng the results of the AST. A new test was perfonred twenty ene c ~ later. Results: The mean eyection fraction (XEF) at R before sur~ery was 29.5 +/- 6 wich increasedto XEF 39.3 +/6.8 after AST (P ~ 0.005). Postoperativelythe XEF at R (37.8 +/8.5) was significantly hi~ner thsq the preoperative XEF at R. On lile other hand there were no significantdeferences between the XEF AST before CABS end the XEF at R after surgery. Conclusions: i- The preoperative AST EF w~s a good predictc~ of the LVF improv~ent obtained after CABS. 2- The imp~vement of ~he LVF with AST was able to distinguish necrotic fr~n hybe~rmted myocardi~n in P with CAD and depressed LVF.

Sunday, August 26, 1990

Changes of ejectJon fraction (EF) are helpful in detecting patients (pts) with coronary artery disesse (CAD) during dJpyr~damele-rad~onuelide ventriculography (D-RVG). To eveiuate the significance of diastolic function during D-RVG in the detection of CAD we e• 15 pts w~th CAD proved by coronary angJography end 8 normal centrols. EF, peak f~lling rate (PFR), t~me to pesk f~lling rate (TPF) snd rmp~d f~lling t~me (RFT) were measured before and immediately after infusion of 0.56 mg/Kg dipyridsmole. 9/15 CAD pts had abnormal response of EF (sensitivity 60%); all normal controls presented normel rise (>5%) of EF (specificity I00%). A rise of PFR < I was present in I/8 normal controls and 13/15 pts (sensitivity 87%, specificity 87%). Rise of PFR< I correeEly reclassified all pts w~th CAD and false negative response of EF. TPF and RFT changes were not helpful in JndentJlying CAD pts. In conclusion changes of PFR can increase ~he dis-

gnostic value of D-RVG Jn i d e n t i f y i n g pts with CAD.

012 EXERCISE 2 0 1 - T L UPTAKE IN HCM Gennady E__~. S e n d l i n , Gennady I . S t o r o z h a k o v , A n a t o l y I . S e l i v a n o v . 2nd Medical Institute, Moscow, USSR. To e v a l u a t e t h e total myocardial 201-TI up~ake and its washout 14 h y p e r t r o p h i c c a r d i o m y o p a t h y (HCM~ p t s and 12 sUbjEcts s u f f e r i n g from cardiac arrhythmias without evident heart disorders underwent 201-TI s c i n t i g r a p h y d u r i n g e x e r c i s e t e s t . 8 HCM p t s were i n v e s t i g a t e d a t r e s t as w e l l . The 1eft v e n t r i c u l a r m y o c a r d i a l mass i n d e x (LVMMI) i n HCM was s i g n i f i c a n t l y greater in comparison to analogous p a r a m e t e r in control group ( 1 1 6 . 6 + 8 . 3 vs 6 5 . 9 + 5 . 0 gm/sq.m, p <0.001). P r e c a r d i a l c o u n t ( P C } measured as a p e r c e n t of given 201 T1 dose was e s s e n t i a l l y g r e e t e r than i n c o n t r o l group (9.5+1.1 vs 6 . 4 + 0 . 3 %, p < 0 . 0 2 ) . T h e r e were n o v marked d i f f e r e n c e s in r e l a t i v e myocardial activity c ~ l c u l a t e d as PC/LVMM r a t i o i n b o t h grottos. We f i n d s i g n i + i c a n t decrease i n 201 - TI 3 h washout e s t i m a t e d as a p e r c e n t o f i n i t i a l PC ( 3 4 . 6 + 2 . 6 v s 47.0+--3.3, p < O . 0 2 ) . LVMMI and PC c o r r e l a t e d s t r o n g l y i n HCM p t s a t r e s ~ ( r = 0 . 8 5 , p < O . O l ) , b u t t h i s c o r r e l a t i o n was p o o r i n e x e r c i s e study i n c o n t r a s t with control group. C o n s e c u t i v e e x c l u s i o n o f maximal LVMMI values out of s t a t i s t i c s resulted in cerr e i l a + i o n c o e f f i c i e n t i n c r e a s i n g up t o 0.68 (p < 0 . 0 5 ) , when t h e LVMMImax d i d n o t a c h i e v e 156 gm/sq.m ( " c r i t i c a l v a l u e " f o r our pts). P r o b a b l y , p o o r 201-TI uptake i n c r e a s e d u r i n g e x e t c i c e i n HCM p t s w i t h LVMMI more t h a n 150 gm/sq.m r e f l e c t s t h e i r l o w c o r o n a r y r e s e r v e .

S3

014

013 CHARACTERISTICS OF 1-123 MIBG SPECT IN HYPERTROPHIC CARDIOMYOPATHY. H.Bunko, K.Nakajima, J.Taki, I.Matsunari, A.Muramori, M.Taniguchi, N.Tonami, K.Hisada. Dept. Nucl.Med., Kanazawa University Hospital, Kanazawa, Japan

REGIONAL ABNORMALITY OF MYOCARDIAL SYMPATHETIC NERVOUS ACTIVITY IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY. A. Kubo, Y. Tsukatani, H. Fujii, F. Kinoshita, S. Hash imoto, K. Nagami, S. Iwanaqa and S. Handa. Keio Univ School of Medicine, Tokyo, JAPAN.

Myocardial uptake and efflux of 1-123 metaiodobenzylguanidine (MIBG) is expected to be the indicator of myocardial adrenergic neuronal integrity. Aim of this study was to characterize the findings of MIBG SPECT with relation to TI-201 (TI) in hypertrophic cardiomyopathy (HCM) qualitatively. Sequential change of myocardial MIBG relative to lung (Lg) and liver (Lv) was also evaluated. Thirty nine patients (pts) (29 HCMs and i0 ischemic heart diseases (IHDs)) were included in this study. HCMs were classified into 3 groups according to septal thickness (ST) by echocardiography. Both SPECT and anterior view planar image were obtained at 15 min. (E) and at 4 hour (D) after injection of iii MBq (3mCi) of MIHG. T1 SPECT and PL were also obtained within 2 days after MIEG imaging. MIBG showed significantly greater Lv and Lg uptake than TI (p<0.05). Sequential increase of relative Lv uptake was more frequent in HCMs than IHDs (59% v.s. 14%, p<0.05). Relative Lg activity remained unchanged or decreased in 90% of HCMS and 58% of IHDs (p<0.05). Defect of MIBG in apicoinferior or at hypertrophied septum was frequently seen in HCMs (p<0.05). MIBG showed larger defect than T1 in both HCMs and IHDs. Sequential increase in defect size of MIBG was frequently seen in HCMs (E:52% and D:90%) suggesting increased efflux of MIBG in HCMs. This finding was common in ST>IS mm (86%) than ST{15mm (43%) which was comparable with quantitative efflux (13.4-3.8 and 1.5% /hr.,respectively). In conclusion, qualitative evaluation could characterize MIBG SPECT findings in HCMs.

To clarify the regional sympathetic nervous activity of the myocardium in patients with hypertrophic cardiomyopatby (HCM) , thallium-201 (TI) and 1-123 metaiodobenzylguanidine (MIBG) myocardial SPECT were performed in 18 p t s w i t h H C M ( l0 w i t h a s y m m e t r i c a l septal hypertrophy, g with apical hypertrophy and A with ether forms ), 4 pts with hypertensive LV hypertrophy and 7 pts with non-hypertrophic heart disease. Planar and SPECT images w e r e o b t a i n e d 15 min and a g a i n 4 hr a f t e r simultaneous injection of MIBG 111 MBq ( 3 mgi ) and T1 iii MBq ( 3 mCi ). In all cases, MIBG uptake in the whole heart was less than T1 uptake. According to the severity of LV dysfunction, MIBG uptake of the whole heart was decreased and that of mediastinum was increased. In pts with HCM, MIHG uptake in hypertrophied region was greater than that in non-hypertrophied region. T1 uptake in hypertrophied region was alse greater than that in non-hypertrophied region, however, MIBG/TI uptake ratio was greater in hypertrophied region than that in nonhypertrophied region. In pts with hypertensive LV hypertrophy, distributions of MIBG and TI were relatively homogeneous, and MIBG/TI uptake ratio was smaller than that in hypertrophied region of HCM. In conclusion, hypertrophied myocardium in HCM had higher sympathetic nervous activity than non-hypertrophied region. The activity of hypertrophied myocardium in HCM was high c o m p a r e d w i t h that of h y p e r t e n s i v e h y p e r t r o p h i e d myocardium. Regional higher sympathetic nervous activity may contribute to the myocardial hypertrophy in HCH.

015

016

ASSESSMENT OF ISCHEMIC DAMAGE OF THE CARDIAC SYMPATHETIC NERVE BY QUANTITATIVE ANALYSIS OF ~231 - M I B G ( M E T A I O D O - B E N Z Y L G U A N I D I N E ) - S P E C T .

COMBINATION OF HISTOMORPHOMETRIC AND SCINTIGRAPHIC PARAMETERS IN DILATED CARDIOMYOPATHY(DCM). D. L. Munz, H. R. F i g u t l a , A. Merguet, A. Bardosi, A.

K.Satoh, Toranomon

Holt-Grieb, and D. Emrich. Depts. of Nuclear Medicine, Cardiology, and Neuropathology, University of GSttingen, Uest Germany.

H.Murata, Hospital,

S.Nishimura, Tokyo, Japan

K.Katoh,

Recently, '2~I - M I B G s c i n t i g r a p h y has been developed for evaluating the function of

cardiac sympathetic nerve. ischemie damage, dual SPECT and 2~T I-C1 were performed

To assess its with ~nl -MIBG in 24 patients

with ischemic heart disease and 8 normal subjects. In o r d e r to e v a l u a t e extent and severity of ischemic damage, T1 and MIBG abnormal scores were calculated by Bull's e y e map. In p a t i e n t s with Non-Q wave myocardial infaretion(NQMI), MIBG abnormal scores were significantly h i g h e r t h a n T1 s c o r e s ( P < 0 . 0 1 ) . In t h e r e g i o n s where regional wall motion showed hypokinesis, MIBG abnormalities e x i s t e d o n l y in 42%. C o m p a r e d w i t h N Q M I w i t h improved wave and wall motion asynergy, NQMI with improved T wave and wall motion had lower MIBG abnormal score(P<0.Ol). Ischemic damage of c a r d i a c sympathetic nerve seemed to c o n t r i b u t e to n e g a t i v e T w a v e a n d s t u n n e d myocardium. ' ~2~I - M I B G s e i n t i g r a p h y w a s t h o u g h t to be a sensitive and useful method for clinical evaluation of i s c h e m i c h e a r t d i s e a s e .

S4

This study was performed to find out whether a combination ef 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 CD sternum

(jNM 30: 779, 1989) was determined from planar scans recorded 48 hr a f t e r i . v. i n j e c t i o n of 2 mCi In-111 antimyosin Fab. Scans were graded p o s i t i v e i f CDI exceeded 1.2 and no blood pool a c t i v i t y 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 o f these pts. In 11 cases, complete histomorphometric anal y s i s of the samples was possible. Percent myofibrils (MF) and percent interstitial fibrosis (IF) per area as well as diameter of myofibers (DF) was determined. These parameters were combined with CDI and EF to e cardiac status index CSI = CDI x EF x MF / IF x DF. In 6 pts with positive antimyosin scan, CSI was 6.78 + 2.58 (mean + SD). CSI determined in 5 pts with negaTive antimyo~in scan was significantly lower (2.15 + 0.74; p = 0.01). In both groups, CSI was markedly belo~ 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. 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.

Sunday, August 26, 1990

017 ~LI~-67 ~ G I N O IN THE DIAGNOSIS AND F 0 ~ W - ~ RHEUMATIC CARDITIS (RC).

018 0F

J.Soares Jr.; R.Snitcowsky; J.C.Meneguetti; F.H.Hironaka; R.V.C.Assis; M.C.P.Giorgi; M.Ebaid; M.Izaki; F.Pileggi; E.E.Camargo. The Heart Institute, Sao Paulo University, Brazil. To evaluate the importance of Galliun-67 imaging in the diagnosis of RC, 30 patients (pts) (15 male; 4-20 yrs) with active rheunatic disease were studied. All pts had acute phase positive serology. Cardiac imaging with Gallium-67 was performed 48 hrs after tracer injection and the scintigrams compared to endomyocardial biopsy (EB). Seintigrmns were positive in 25 pts and negative in 5. EB were positive in 15 pts and negative in 15. Disagreement between the results of the seintigraphy and the EB was obtained in i0 pts('~false positive"). We didn't have false negative results. Among 25 pts with positive seintigrams in the acute phase of the rheumatic disease we re-studied 16 pts in an interval between 3 to i0 months (mean 4.6m) and the following results were obtained: i0 pts presented negative scintigrmns (62.5%), 4 pts presented positive seintigrams though less intensive compared to the first study (25%) and 2 pts maintained the same patt e m of the first study (12.5%). In conclusion we can suggest that cardiac Gallium67 imaging in p t s w i t h rheumatic disease can be helpful: i) to determine the presence or absence of cardiac involvement and 2) as a criteria of regression of the cardiac inflammatory activity.

SINGLE CRYSTAL GAMMA CAMERA FIRST PASS LEFT VENTRICULAR REGIONAL WALL MOTION (RWM); COMPARISON WITH CONTRAST VENTRICULOGRAPHY (CV). H. Bishop, R. Perdoncin, J. Crossen. West Virginia University, Morgantown, West Virginia, United States. The reliability of RWM measured by a simple 15 sec non-ECG gated first pass radionuclide angiogram (FPRNA) was assessed in 29 consecutive clinically stable patients who had CV within 48 hrs. A medium sensitivity collimator was shielded to a 20cm circle to maximize counts/area. Following the peripheral i.v. bolus of 25 mCi 99mTc DTPA a representative cycle was derived from the list mode data of the 3 highest target to non-target count rate LV beats. Color-coded first harmonic phase mapping was used first to delineate the LV and then applied to the isolated LV ROI to show synchrony. Three blinded observers used both cyclic sequential count isocontours and the LV phase map to judge RWM. The same 25~ RAO view was used for both the FPRNA and CV. The RAO LV wall was divided into 5 segments, each of which was graded as normal, hypokinetic, akinetic, or dyskinetic. Intra-observer disagreements were resolved by consensus before objective comparisons were made. The results showed exact agreement in 118/145 segments (81%) and agreement within i grade of 143/145 (98%). The exact segmental agreements were: anterior basal: 26/29 (90%); anterior lateral: 23/29 (79%); apical: 22/29 (76%); inferior basal: 23/29 (79%); and posterior basal: 24/29 (83%). An ordinary gamma camera can be used with any 99mTc radiopharmaceutical to measure LV RWM with a simple 15 see first pass acquisition.

019

020

SIMPLIFIED FIRST-PASS TECHNIQUE FOR LEFT VENTRICULAR EJECTION FRACTION WITH REST/STRESS MYOCARDIAL PERFUSION IMAGING G.A. H u r w i t z , S.E. B a b e n s e e , T.D. C r a d d u c k , J.E. P o w e a n d A . A . D r i e d g e r . University of Western Ontario, Victoria Hospital, London, Ontario, Canada

CARDIAC FUNCTIONAL IMAGES DERIVED FROM RADIONUCLIDE VENTRICULOGRAPHY STUDIES. K. Kouris, K. AI-AIi, I.M. Hassan, H.M. Abdel-Dayem, C. Constantinides, G. Fettich, R. Bahar, S. A1-Mohanadi. Faculty of Medicine and Ministry of Health, Kuwait.

Myocardial perfusion agents labelled with Tc-99m provide the potential to use firstpass techniques to determine left ventricular ejection fraction (LVEF). We have developed a simplified first-pass f r a m e - m o d e (FPFM) E C G - g a t e d t e c h n i q u e t h a t c a p t u r e s u p t o 20 s e c o n d s of l a e v o - p h a s e of the injection. FPFM studies were acquired d u r i n g r e s t ( 3 2 0 - 4 0 0 MBq) or s u p i n e s t r e s s (1-1.3 GBq) i n j e c t i o n s of T c - 9 9 m h e x a M I B I in the left anterior oblique projection with c a u d a l tilt. F P F M s t u d i e s w e r e f o u n d t o be adequate for quantitation when ventricular counts were greater than 500/frame (more t h a n 90% of c a s e s ) . FPFM studies compared f a v o r a b l y w i t h l i s t - m o d e c o l l e c t i o n s in 20 cases. To v a l i d a t e L V E F d e t e r m i n e d b y t h i s method, FPFM and equilibrium acquisitions w e r e o b t a i n e d d u r i n g r e s t i n j e c t i o n of T c 99m labelled erythrocytes in 20 p a t i e n t s ; the 2 techniques for LVEF showed good a g r e e m e n t (r=0.96) w i t h s i m i l a r r e s u l t s f o r operator-dependent and automatic analysis methods; FPFM had somewhat greater interand intra-observer variability. For the hexaMIBI rest studies, good correlation was found between LVEF and scoring by contrast ventriculography (n=25, p<0.Ol). FPFM d e t e r m i n a t i o n of L V E F is a p r a c t i c a l a d j u n c t to m y o c a r d i a l s c i n t i g r a p h y w i t h t e c h n e t i u m based perfusion agents.

Sunday, August 26, 1990

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 4/5th 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 f~om 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.

$5

021

022

NONINVASIVE MEASUREMENT 0F LEFT VENT~ICULAR MAX dP/dt USING RADIONUCLIDEMULTIGATEDCARDIAC POOl. IMAGE

PHYSIOPATHOLOGIC AND PROGNOSTIC MEANING OF RIGHT LEFT VENTRICULAR EJECTION FRACTION COMPARISON CURRENT CARDIODIAGNOSTICS. A.Abbati, F.Capuano, A.Rossi, G.Guidarelli I.Adversi. Ospedale Maggiore, Bologna, Italy.

?.Miyakawa,N.Moriai,M.Kato, K. Nakai,S.gatsuragawa, T.Takahashi,and T.Yanagisawa. [mate Medical University, School of Medicine, Morioka, S.Motoaki. Tokyo Women's Medical College, Shiejuku, Japan. Max dP/dt is a useful parameter for assessing cardiac performance. Noninvasive measurement of l e f t ventricular max dP/dt was carried out using radionuclide mnltigated cardiac pool image(R~PI). The max dP/dt was derived from the following equation; max dP/dt = p 9 C-max(du/dt), where p is the density of blood, C is the pulse wave velosity of the aorta, and u is the velocity of the blood stream. RMPI images were acquired with Tc-99m by summing 300 heart heats, then l e f t ventricular volume curves were constructed using the third harmonics of Fourier analysis. The du/dt is the acceleration of the blood stream, therefore, value of du/dt was equivarent to dZV/dt z obtained from the RMPI volume curve. Pulse wave velocity was caluclated by means of simultaneoas recording of ECG, PCG, carotid pulse and femoral pulse. The l e f t v e n t r i c u l a r dP/dt was dtermined with a t r a n s d u c e r - t i p p e d c a t h e t e r and p r e s s u r e p r o c e s s e r in cardiac catheterization. Result was as f o l l o w s ; There was a s i g n i f i c a n t c o r r e l a t i o n (r=0.57, Y=l.18X +146, p < 0 . 0 5 ) between max dP/dt (X) measured from 16 s u b j e c t s by c a r d i a c c a t h e t e r i z a t i o n and c a l c u l a t e d max dP/dt(RI) (Y). It was concluded t h a t max dP/dt could be e s t i m a t e d noninvasively by RMPI method.

023

and

Recent studies (S.Hamada and eoll.,Jap.J.Nuc.Med., 1989, 26/4, 585-5S7) have pointed out the significance of RVEF in atrial septal defects. However, right ventricle overload is a condition which frequently oceours also in many non congenital r and non invasive assessment of RVEF and its comparison with values of LVEF are parameters which can identify the importance of rigth ventrieular strain. The authors have systematically studied RVEF and LVEF in all the patients submitted to TI-201 perfusion and Tc-99m albumin haemodynamio studies, to evaluate the clinical importance of these two parameters and their correlation. RVEF has been calculated in steady state studies following method of double area (J.Naddahy and coll., Circulation, 1979, 80, 581-589) utilising phase and amplitude images to delineate ventrieular profile. 20 patients (8 post infarction eardiomyopathies, 7 myocardial isehemias, 2 left BBB, 1 right BBB, 1 WPW, 1 congestive hearth failure in a patient with longstanding pace maker) were selected. As main observation it has been shown that low values of RVEF (<40%) associated with LVEF low (< 80%) or normal values (>50%) have a bad prognostic meaning also in patients with an otherwise acceptable cardiac compensation status.

024 OF'

ISOI'OPIC~

~

~

i4J:'i~ IAM. (]]MP~gISON W I ~ ( X ~ f Z i ~ L ~A/~ C~ I S ~ SCINI~f(~gAPHY

DOBJIXM]]~ ENG(~

AND

M.J. Argiieso, J.L. C ~ r r o , J. de Haro, M.J. Tabuenca, I. Castejon, A. Alonso, J. Ortiz Berrocal. Clinics Puerta de Hierro, Madrid, Spain

We have p e r f o r ~ conventional ergometry and studled the left ventricular function using isotopic ventriculography at basal levels and after dobutamine (DB) infusion (5,10,15, 20 ~g/Kg/ntin) in 30 patients, 7-10 days after acute myocardial infarct. Basal and postexercise scintigraphy (PES) were performed with thallium or RP-30 in 18 cases. Seventeen patients presented ventriculography with DB (descent in the ejection fraction of 5% ever basal or r~ximal level), resulting in: Of the 18 patients in whom ~i~(-) i 7 PES was p e r f o r m , only 2 showed periinfarct ischemia, and another presented another ~] ~(+) l 9 i0 isshemic iccalization (all in D B patients). Seven cases (-) (+) of (-) PES were positive for ventriculography DB. with dobutamine In conclusion, isotopic ventriculography with DB is a sireple and well tolerated test after acute ~ryocardial infarct. Its sensitivity with respect to conventional ergometry and PES may be greater owing to the difficulties in interpreting electrocardiographic changes and discerning areas of hypoperfusion or established necrotic ischemia.

S6

AND IN

THE EVALUATION OF LV CONTRACTILITY OF PACE-MAKER IMPLANTED PATIENTS BY LV EJECTION FRACTION (LVEF) RESPONSE TO THE ISOTONIC EXERCISE. H. Matsuo, M. Ishiguro, E. Shiroshita, A. Gotoh, M. Kondou, K. Itch, Y. Koto-o, N. Sugishita, H. Ouhashi, H. Oda, K. Ueno, T. matsubara, M. Arai, T. Hirano and S. Watanabe. Gifu Prefectural Hospital and Hirano General Hospital, Gifu, Japan. To evaluate the contractility of the patients (Pts) with permanent pace-maker implantation, who are supposed to have no organic myocardial and coronary artery disease by echo cardiography and oath study, we examined LVEF response to the hand-grip test (HGT) of 9 pts (Age:61-+ 9 , Sick sinus syndrome n=6, complete AV block n=3) with their pacing rate fixed to lO0/min. LVEF is serially monitored by Tc-99m blood pool activity with dual nuclear cardiac probe system which enable us to calculate the serial beat to beat basis time activity curve of LV by the substraction of background count located in the middle of right lung (one detecter targetting for LV chamber, another for background.) HGT was performed with their 50% of maximum strength as long as they can. We could find 2 ways of response of LVEF, Group i (GI) with elevated EF more than 5% at 3 min after the innitiation of HGT, Group 2 (G2) without elevation. There is no statistially significant difference between 2 groups in age, sex, rest EF, CTR, maxBP. But some tendency exist as follows, i) G2 is older than GI. 2) G2 have bigger CTR than GI. The difference of HGT durations is staistically significant (GI>G2, p
Sunday, August26,1990

025

026

MONITORING OF LV FUNCTION IN CORONARY CARE UNIT -EVALUATION OF THE EFFECT OF A VASODILATOR BY THE NUCLEAR CARDIAC PROBE-. S. Watanabe ~'~,M. Ishiguro~-, N. Sugishita~,~',H. Ohashi ~'-~', N. Morita ~,-~, T. Yasue ~''~, A. Goto ~ , T. Mizutani ~,-~,'-~and H. Miyake ~ - . ~Division of Cardiology, ~'~ Department of First Internal Medicine, ~ D e p a r t m e n t of Radiology, Prefectural Gifu Hospital.

THE E F F E C T O F A O R T O - C O R O N A R Y A R T E R Y B Y P A S S SURG E R Y ON THE F U N C T I O N A L S T A T U S OF THE HEART. S e r g i e n k o V . B . , A k c h u r i n R.S., K h a k i m j a n o v A.B. o s t r o u m o v Ye.N., A g a p o v A.A. All-Union Cardiology Research Centre, Moscow, USSR

We evaluated left ventricular (LV) function in congestive heart failure (CHF) under the treatment of a vasodilator, "Bucladesine Sodium" (BS) in Coronary Care Unit (CCU), where is specially protected for radioisotopes, ii patients with CHF were examined before and during BS infusion using the nuclear probe, and LV ejection fraction, relative cardiac output (RCO) and max dV/dt were evaluated. 4 patients without cardiac failure were also measured by the nuclear probe as a normal control group. As results, LV ejection fraction, RCO and max dV/dt of CHF group were increased during BS infusion with decreasing blood pressure and pulmonary capillary wedge pressure. We conclude that BS is a useful vasodilator drung for the treatment of CHF, and also the nonimaging nuclear cardiac probe is helpful in assessing global ventricular function in CCU, where rapid estimations of the ventricular function is needed.

The s t u d y o f the h e m o d y n a m i c f u n c t i o n of the h e a r t in a s a m p l e of 27 p a t i e n t s (pts) (males) s u f f e r i n g f r o m i s c h a e m i c h e a r t d i s e a s e (with an a v e r a g e age of 51) w i t h / w i t h o u t diff e r e n t d e g r e e of c i r c u l a t o r y f a i l u r e has b e e n performed by radionuclide equilibrium ventric u l o g r a p h y (REV) at r e s t b e f o r e a n d on the 1214 day a f t e r surgery. B e f o r e the s u r g e r y all the p t s h a d i n i t i a l l y the i m p a i r m e n t of the (global or segmental) m y o c a r d i a l c o n t r a c t i n g function. The r a d i o p h a r m a c e u t i c a l T c - 9 9 m a l b u m i n at the d o s a g e of 740 m B k w a s c h o s e for testing. T h e i m p r o v e m e n t of the L V f u n c t i o n of the h e a r t in the p o s t o p e r a t i v e p e r i o d (n=27) w a s n o t e d to be due to the p o s i t i v e s h i f t of the f o l l o w i n g indices: the i n c r e a s e d LV e j e c t i o n f r a c t u r e - f r o m 50% to 58% (p=0,05), the s p e e d of e j e c t i o n - f r o m 3,4 to 4,2 (p&0,05), the s p e e d of f i l l i n g - f r o m 2,8 to 3,6 (p~0,05), a n d a l s o the d e c r e a s e d L V e n d - d i a s t o l i c v o l u m e f r o m 90 to 75 (p~0,05), a n d e n d - s y s t o l i c v o l u m e f r o m 47 to 32 (pL0,05). The r e s u l t s of the e q u i l i b r i u m r a d i o n u c l i d e v e n t r i c u l o g r a p h y m a k e it p o s s i b l e to r e c e i v e the p o w e r f u l p r o g n o s t i c e v i d e n c e of the functi o n a l s t a t e of the heart, h e l p i n g , to a g r e a t e x t e n t , to d e t e r m i n e the p o t e n t i a l b e n e f i t s a n d r i s k s of o p e r a t i v e i n t e r v e n t i o n and the cons a n d p r o s of the s u r g i c a l t r e a t m e n t .

027

028

ESTIMATION OF CARDIAC FUNCTION BEFORE, DHRING, AETERPTMC (PERCUTANEOUS MITRAL COMMISSUROTOMY) IN NEUCLEAR MEDICINE. M. Ishiguro, T. Hirano ~, H. Matsuo ~ , Y. Matsuno ~ , A. Goto ~ , H. Ohashi ~ , N. Sugishita~ , S. Watanabe ~ , N. Morita ~ and K. Inoue ~ . ~Dept. of Nuclear Cardiology, Hirano General Hospital, ~Divi. of Cardiology, Prefectural Gifu Hospital, ~ M a t s u n a m i General Hospital, ~ D e p t . of Thoracic Surgery, Takeda General Hospital.

SIGNIFICANCE OF ST SEGMENT DEPRESSION IN ANTERIOR PRECORDIAL LEAD IN ACUTE INFERIOR MYOCARDIAL INFARCTION : ASSESSMENT BY EXERCISE THALLIUM-201 MYOCARDIAL SCINTIGRAPHY. S. Inoue, S. Usumoto, T. Kanai, T. Maruoka, ~ Ozawa, Y. Koga, and T. Katagiri. Tokyo Seamen's Insurance Hospital, Showa Univ. School of Med., Tokyo, Japan.

Acute and subacute effects of PTCM (percutaneous transvenous mitral commissurotomy) to cardiac function in MS pts. were estimated by LV P-V loop with single probe and cardiac blood pool scan. During the decrease of blood flow through mitral valve by balloon inflation, LV P-V loop shifted to left lower part in P-V plan and the area of loop decreased markedly. The area of that increased markedly by the reopening of mitral blood flow. Hemodynamic changes were as follows : n

MltralValve,'Lrea(,,')

II

Mean Mitral Gradienl (--.s) LA-Pressute (~IIS)

II

Caldlacllldez(~/~lm') LVEF (.';) Stroke V o l ~ l (.f) LV EDV (.t) LV ESV (-O

]1 [I 7 7 7 7

bofo, o

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1.44+-0.47 1.93+-0,55"" 8+-4 3• 13+-5 8• 4.81• 5.47• 50• 49• 58• 66+-15 tO0• 17 118r 52• 63•

n

5yztalicWark(J) Net Walk (I) DiaslolM Work {J) EjecllonThne(,n.c) Peak [jectLo. Ilale (c/.r ~ FJllhlz Fraction (,~;) Peak [Uii.g Title (
belore

7 0.8• 7 0.74• 7 0.07• II 297• I] 337• tl 43• I1 306• II 2O6• *p<005

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0.91• 082• 009• 313+-44 349• 39• 282• 143• **p<001

The result suggested that the LV dysfunction in mild ~moderate MS without rigid mitral complex attributes to the diastolic dysfunction mainly depending on the decreased preload, PTMC improves the LV dysfunction by increasing the preload to LV. The dynamic effect of PTMC to cardiac function and clinical course can be assessed well using neclear medicine technique.

Sunday, August 26, 1990

The purpose is to identify the significance of ST segment depression in precordial leads in evolving inferior acute myocardial infarction (AMI). 24 patients with inferior AMI were included in this study. Standard 12 lead electrocardiograms were~corded within 6 hours of the onset of chest pain, and according to presence or absense of ischemic ST depression greater than 0.2mmV, patients were devided into two groups. Group I consisted of 15 patients with ischemic ST depression and group 2 consisted of 9 patients without it. Before discharge, exercise thallium-201 myocardial scintigraphy and coronary angiography were performed in all 24 patients. Scintigraphic findings in anterior wall were classified as having no perfusion defect (ND), persistent defects (PD), or defects during stress not present at rest (redistribution). Significant left anterior descending coronary artery (LAD) disease (greater than 75% stenosis of luminal diameter) was observed in 9 cases of group I. In scintigraphic findings, 6 out of 15 cases of group I revealed redistribution and all these patients had significant LAD disease. In group I, out of 7 cases of ND, 3 showed significant stenosis of LAD. Thus precordial ischemic ST depression in inferior ~MI may be connected with LAD disease. So coronary angiography should be done in such cases.

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029

030A

A S S E S S M E N T OF P O S T - I N T E R V E N T I O N A L C H A N G E S IN R E G I O N A L C O R O N A R Y F L O W BY R E G I O N A L M Y O C A R D I A L U P T A K E OF T H A L L I U M - 2 0 1 . S. W a k a s u g i , Y. H a s e g a w a and S. N a k a n o . The C e n t e r for A d u l t D i s e a s e s , Osaka, Japan.

PERSISTENT THALLIUM-201 MYOCARDIAL DEFECTS WITH LITTLE OR NO EARLY REDISTRIBUTION: WHAT FACTORS INFLUENCE LATE REDISTRIBUTION? M.A. Chess, R.G. Schwartz, B.S. Greenspan. University of Rochester Medical Center, Rochester, NY.

The use of r e g i o n a l m y o c a r d i a l u p t a k e of thallium-201 (T1) as an index of c o r o n a r y f l o w was e v a l u a t e d . TI m y o c a r d i a l i m a g i n g was p e r f o r m e d u n d e r i d e n t i c a l s t r e s s loads b e f o r e and a f t e r s u c c e s s f u l a n g i o p l a s t y (PTCA, n=54) and m e d i c a t i o n w i t h p r o p r a n o l o l (PROP, n=26) in p a t i e n t s w i t h s t a b l e a n g i n a p e c t o r i s . I m p r o v e m e n t in p e r f u s i o n d e f e c t s was f o u n d in 81% (n=44) a f t e r P T C A and in 65% (n=17) a f t e r PROP. In i m p r o v e d P T C A p a t i e n t s , TI u p t a k e n o r m a l i z e d by i n j e c t i o n d o s e i n c r e a s e d 23% (mean) (P<0.01) in i s c h e m i e s e g m e n t s and o n l y 5% (NS) in n o r m a l l y p e r f u s e d s e g m e n t s . In i m p r o v e d PROP p a t i e n t s , TI u p t a k e d e c r e a s e d 4% (NS) in i s c h e m i c s e g m e n t s and 12% (P
To evaluate clinical data that may predict the presence or absence of late (24-72 hr) redistribution (LRd) of persistent thallium-201 myocardial defects (PMD) with little or no early (2-3 hr) redistribution (ERd) following exercise, we studied all consecutive patients (pts) (n=97) who had late thallium-201 myocardial imaging from 1988-1989. Of these, 35 pts had PMD and coronary arteriography within 6 months. ERd and LRd were scored on a scale of 0 to 3. Moderate ERd of P ~ was seen in 4 studies that were excluded. Of the remaining 31 pts with little or no ERd, 19 (61~) had moderate to complete (2-3) LRd (group I) and there was little or n o LRd (0-i) in 12 pts (group II). LRd of P ~ was prevalent (4/12) in the culprit vascular distribution in pts withQ-wave myocardial infarction (MI), and was more prevalent in pts without MI (15/19, P=0.03). No difference was found between groups I and If, respectively, in exercise time (473 + 168 sac vs. 507 • 183 sec), angina peetoris on exertion (13/19 vs. 8/12), rate-pressure product (20190 i 6380 v s . 20310 • 5360), i s c h e m i a b y ECG ( 8 / 1 9 v s . 4 / 1 2 ) , o r number o f c o r o n a r y v e s s e l s w i t h > 50~ s t e n o s i s ( 2 . 4 • 0 . 8 v s . 1 . 8 i 0 . 9 ; P=NS f o r e a c h ) . The degree of stenosis of the cnlprit artery did not correlate with LRd. We conclude that none of the clinical factors studied permit prediction of late redistribution of persistent post-exercise thallium-201 myocardial defects.

030B

031

DETECTION OF PATIENTS WITH HIBERNATING MYOCARDIUM BY EXERCISE ECG AND THALLIUM-201MYOCARDiAL SCINTICRAPHY Shigehide Suzuki, Tomoya lino, Nobuo Toyosaki, Taka'aki Katsuki, Makoto Furuse, and Toshio Yaginuma. Jichi Medical School, Tochigi~ Japan

EXERCISE/REINJECTION MYOCARDIAL SCINTIGRAPHY ACCURATE MARKER OF MYOCARDIAL VIABILITY

The improved left ventricular function has been reported in the patients (pts) with hibernating myocardium (HM) who received coronary angioplasty (PTCA). However~ this therapeutic indications in pts with old myocardial infarction (MI) has not been clarified. The aim of this study is to discriminate the pts with MI who have HM by evaluating the exercise ECG and Thallium-201 myocardial scintigraphy (Sc). Methods: 43 pts with old MI and responsible one-vessel disease who underwent submaximal exercise Sc with 12 lead ECG monitoring were analyzed. From the ECG ischemic ST segment depression (horizontal and>0.1 mV) in the opposite leads to the infarcted sites was or was not and from the Sc the redistribution area around the infarction (R) were evaluated. Redistribution area ratio (R%) was defined as the defecting area changes at the cut-off level of 40% between exercise and delayed Bull's eye images. Results: 5 of 26 pts with anterior MI (19%) had ischamic ST changes (A+), and 21 had not (A-). 8 of 17 pts with inferior MI (52%) had ST changes (I+) and 9 had not (I-). The average R% of A+ was 32.4• and significantly higher than the average of 13.0• in A- (p<0.02). The R% of I+ (9.1• was also significantly higher than that of I- (0.i!0.3%, p<0.01). Therefore, if the limits of R% more than 30% in anterior MI, and more than 10% in the inferior MI are adopted, at least 9 pts who had extensive R and significant ischemic ST depression were discriminated. Two of those discriminated pts who received PTCA showed improvement of diseased wall motion. Conclusions: This simple method, not using positron emission tomography might defect the pts with HM.

S8

AS

AN

H.Itagana, K.Akioka, A.Tahara, M.Yasuda, M.Teragaki, l.Toda, H.Oku, K.Takeuchi, T.Takeda, H.Ochi, Osaka City University Medical School, Osaka Japan. Exercise myocardial scintigraphy(ES) often underestimates the mass of viable myocardium in ischemic heart disease. We studied reinjection images(REINJ) obtained with 37 MBq of TI-201 reinjected after completion of ES and compared them with rest images(RS) obtained on separate day. In this study 32 patients(pts) with acute mycardial infarction (AMI), 12 with old myocardial infarction(OMI) with postinfarction angina pectoris and 9 pts with angina pectoris(AP) were involved. Scintigrams were interpreted visually (VI) and quantitatively based on Bull's Eye(BE). For VI, the myocardium was divided into 20 segments and each segment was scored with respect to initial ES image(EI), delayed ES image(ED), REINJ, initial RS image(RI) and delayed RS image(RD). For BE, the severity scora(SS) was calculated quantitatively from the data of normal subjects. In addition, %SS, as an indicator of the degree of improvement in ischemia, was determined by dividing SS of ED, REINJ, RI and RD by EI score.VI showed that REINJ and RS proved of diagnostic value in AMI more frequently than in OMI and AP(p<0.01). When estimated from BE, %SS in AMI was 59.3+22.7, 39.6+19.4, 28.5+20.2 and 33.7~20.6 for ED, REINJ, RI and RD, --respectively; hence, values were more favorable for REINJ, RI, and RD than for ED. No such significant differences were noted in OMI and AP, with %SS for ED being 19.3+14.9 in AP and 33.0+20.7 in OMI. In AMI, in which ES used alone is likely to underestimate the mass of viable myocardium, REINJ provides a simple and useful means that can be advantageously substituted for RS.

Sunday, August 26, 1990

032

033

E. N. Ostroumov, V. B. Sergienko, N. M. Ahmedzhanow, B. Wezhinska, A. A. Lyukishev.

THE. POSITIVE~ MYOCARDIAl, UPTAKE OF THALLIUM-201 RE-EVALUATION BY SPECT. Tomoya lino, Shigehide Suzuki, Hiromichi Sekiguchi, Ken-ichi Kawasaki~ Takashi Natsume, Makoto Furuse, and Toshio Yaginuma. Jichi Medical School, Tochigi, Japan

GLOBAL LEFT VENTRICULAR THALLIUM-201 UPTAKE REDUCTION IN PATIENTS WITH TRANSIENT ISCHEMIC DILATION OF THE LEFT VENTRICLE.

Abstract received in a form unsuitable for reproduction

In order to determine whether the evaluation of positive myocardial uptake of thallium-201 (TI) by SPECT can discriminate the normal or diseased myocardium, though this has failed to be useful in the planar studies, we evaluated the SPECT images of 14 patients (pts) with normal coronary and left cardiac function who exhibited insignificant ST segment changes with submaximal exercise (N). Forty-four pts with single coronary artery disease were titrated for the more extensive myocardial damage (LRG) as in anterior myocardial infarction (MI), or proximal left anterior descending artery (LAD) disease, and for the less damage (SML) as in the inferior MI or non ~ D lesion. Each pt's demographic data including weight (BW) and target heart rate (THR) were completely obtained with precise measurement of injected TI dose (ITL). The maximum count, the sum of counts more than 70% of the maximum, and their logarithms (LMx, L70) were calculated by the circumferential profile method. Results: The three univariates of ITL, THR. and BW correlated well with LMx (r=0.79, 0.56, -0.391 and with LT0 (r=0.80, 0.58, -0.39) in N. ITL/BW also correlated well with LMx and L70 (r=0.96, 0.98). When the 95% confidential limits of L70-1TL/BW in N were adopted, 83% of LRG, 90% of i0 inferior MI, and 40% of i0 non-LAD lesion angina were detected~ and the deviations from the limits in [ae LRG were greater than those in the SML. Conclusions: The evaluation of positive TI uptake by LMx and L70 can discriminate the diseased myocardium and amount of damage. This method may allow the estimation of diffusely damaged myocardium such as in cardiomyopathy.

034

035

CLINICAL SUPERIORITY OF TI-201 REST-REDISTRIBUTE AND EXERCISE-REDISTRIBUTE SPECT TO PREDICT THE PROGRESSION FOR ISCHEMIC CARDIOMYOPATHY H.Namura, H.Yamabe, Y.Hashimoto, Y.Yasaka, K.Itoh, K.Maeda, H.Fukuzaki. The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Hyogo, Japan.

RESTING TI-201 ~ O C A R D I A L SPECT AND REGIONAL WALL MOTION ABNORMALITY OF NON-INFARCTED AREA IN PATIENTS WITH CHRONIC CORONARY OCCLUSION Y.Yasaka, H.Yamabe, H.Nanura, Y.Hshimoto, K. Itoh, K.Maeda, H.Fukuzaki. The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Hyogo, Japan.

Total 20 patients (Pts.) who had significant coronary artery lesions (>75% diameter stenosis) and reduced LVEF (<--40%) were divided into two groups; one included 9 pts had diffuse LV wall motion abnormality even in non-infarct zone (Group A), to the contrary, ii Pts belong to the other group had oniy corresponding to infarct zone (Group B). Three graded perfusion defect score (DS) were visually determined for each LV segment in initial (Init) and delayed (Del) image from Restredistribute (RS) and Exercise-redistribute (ES) SPECT, respectively. Group A Pts had longer psst history (31+IOM vs 17+8M, p<0.05), larger defect area (5.0-+1.2 vs 3.9-+1.1 segments, p
To clarify the mechanism of regional wall motion abnormality in non-infarcted area supplied by collateral circulation, we performed resting TI-201 SPECT, both initial image and 3hr delayed image, and LV cineangiography in 19 patients. All patients have no prior myocardial infarction and have chronic total coronary obstruction with collateral flow (22 lesions). All lesions were divided into two groups: lesions with LV wall motion abnormality (group A, n:8) and those without it (group B,n:14). Good collateral flow was less frequent in group A than in group B (i/8 lesions(12%) vs 10/14(71%),p<0.05). At initial image of resting TI-201 SPECT, perfusion defects were found in 6/8 lesions(75%) in group A and in 7/14 lesions(50%) in group B, and there was no significant difference in grade of defect score in these area between the two groups (1.2+0.8 vs 1.0 +0.9,ns.). On the other hand,at 3hr delayed image, persistent defects were more frequent in group A than group B (6/8 lesions(75%) vs 3/14 lesions(21%), p<0.05). These results suggest that both chronic myocardial ischemia due to reduced collateral flow and occult partial myocardial necrosis are pathologic mechanisms of regional wall m o t i o n abnormality in patients with chronic coronary occlusion.

Sunday, August26,1990

S9

036

037

TL-201 SCINTIGRAPHY IN THE ASSESSMENT OF PATIENTS WITH MULTI-VESSEL CORONARY ARTERY DISEASE UNDERGOING ANGIOPLASTY WHO HAVE PRE~IOUSLY HAD CORONARY BYPASS GRAFT OPERATION (CABG). S. Aiad, D. Katritsis, S. Noukla, T. Nunan, M. Webb-Peploe and M. Buxton-Thomas Departments of Nuclear Medicine and Cardiology St Thomas' Hospital, London, UK.

OUANT1TATION OF ISCHEMIA EXTENT FROM THALLIUM MYOCARDIAL TOMOGRAMS EDelcourt..I-PBinon Departmentol'Nuclcar Medicine C.H.U. AVESALE MontlgnyleTillcuI. BELGIUM

Previous investigators have suggested the limitations of the use of TL-201 in uniform global myocardial ischaemia where initial perfusion defects on TL-201 images may be absent altogether. We have studied 12 symptomatic patients with multivessel coronary artery disease undergoing angioplasty who had previously undergone CABG. TL-201 imaging was carried out in 12 patients prior to, six weeks and six months to one year post PTCA. Prior to PTCA, TL-201 imaging correctly identified the site of the dominant lesion in all patients in correlation with the catheter results. Six weeks post PTCA, seven cases who had angiographically successful angioplasty showed persistent defects on TL-201 imaging. In five out of these 7 cases, follow up catheter showed that re-stenosis had occurred. Six months to one year post PTCA, TL-201 imaging was found to have good correlation, beth with catheter results and symptons. (>dr results suggest that TL-201 imaging has a role in the management of patients with multi-vessel disease undergoing angioplasty.

Quantitative evahlatiou of rcgitlnal myocardial hypoped'usion from thallium 201 SPECT images requires comparison with data from a reference population of liealthy individuals: which in turn implies standardizaUon of sampling, from myocardial segments, display, and quantltation. The "bullseye' is a multislice diagram representation (MSD)of the tomogram displayed in a single "/mage, with the apex of theheart appeamng in the central part and the base in the outer part of the image. A direct quantitation of the ivlSD image will however be inaccurate, due to an increasing contribution of the tomographic slices when going from the apex towards the base of the heart. Therefore, we ap ~ly to each pixel identified as corresponding to an ischemic area a coefficient inversely proportional to the area of the ring containing this pixel. A second normalization of each slice allows to ebtain a lesser contribution of the slicespresumably containin~ thinner (basal) or narrower (apical) myocardial sections. TNereby, each pixel in the MSD image willrepresent the same elemeniary myocardial volume. The processing includes the following steps: 1) Six short-axis slices are reconstructed extending from the apex to tfic base of the left ventricular myocardium. 2) A MSD representation is created from the angular profile of the maximum l~ixel value in each slice. 3) A mapping of the ischemic zones is then oblained by comparing this short axis MSD with a data base of normal sub ccts ~male or female). The zone of ischemia is represented by th~ pixeis with a value I';elow 3 standard deviations from its aveiage in normals. 4) The first and last slices are assumed to represent 10 percent of the left venlricular myocardium, and all other four slices to represent 20 percent each. The 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 renrientation of the heart and in definition of reconstruction limits. The crealion of the MSD image and all following slops require no further operator intervention.

038

039

DIAGNOSTIC SIGNIFICANCE OF INCREASED LUNG UPTAKE OF THALLIUM-201 ON HYPERVENTILATION STRESSED MYOCARDIAL SCINTIGRAPHY IN VASOSPASTIC ANGINA PECTORIS M.Shima, K.Matsuhara ~, K.Umamoto, K.Miyao, H.Sugihara*, M.lwamami, T.Shudo, H.Takakura, N.Tsuji, M.Kitamura, H.Katsume*, M.Nakagawa ~. Kyoto Second Red Cross Hospital, ~The Second Department of Internal Medicine, Kyoto Prefectual University of Medicine, Kyoto, Japan

Relationship between the occurrence of late potential and the location and size of myocardial infarction evaluated by Thallium-201 SPECT K.Nakai, C. Ire, N. Mortal, T. Miyakawa, M. Kato,T. Takahashi T. Yanagisawa. Iwate Medical University, Iwate, Japan. High-frequency, low amplitude signals, late potentials (LPs), in the terminal portion of the body surface QRS of the signal-averaged ECG were frequently observed in ventricular tachycardia (VT) following myocardial infarction (MI). In this study, we evaluated the correlation between the occurrence of LPs and the size and location of MI estimated by Thallium-201 myocardial SPECT in 35 MI patients. The positive LPs were identified by the value of %RMS40, the percent ratio of the root mean square voltage in the last 40 msec of the QRS complex to that of the total filtered QRS from the signal averaged ECG using bipolar X,Y,Z leads. The spatial distributions of LPs were evaluated by the LP30 area maps obtained by the body surface mapping using forty-five unipolar electrodes. Sixty projections were obtained over 180 degree b y rotating gamma camera after 5 minutes intravenous injection of 74 MBq of Thallium-201. After low-pass filtering, images were reconstructed into short-axis, horizontal long-axis and vertical longaxis tomograms. The maximum count circumferential profiles for each short-axis cuts were generated from the apical to basal cut and they were expressed into two-dimensional polar functional maps (apex to the center), Bull's eye map, to represent myocardial T1 distribution. Normal limits o f myocardial TI distribution were established as the mean minus 2 standard deviation from those of normal subjects. The MI size was estimated as defect volume ratio (DVR), the percent ratio of abnormal region to that of total volume of left ventricle. Significant differences in DVR were observed among MI with LPs and without LPs. The DVR was higher in MI with LPs (anterior MI : 47+10 %, inferior MI : 34-+5 %) compared to that of MI without LPs (anterior MI : 23-+10 %, inferior MI : 18-+8 % ). In all 9 cases with LPs, the spatial distribution of LPs were concordant with the MI locations in Bull's eye maps. In conclusion, the size and location of MI may play a role for the occurrence of LPs.

The purpose of this study is to clarify diagnostic significance of increased lung Thallium(Tl) uptake on hyperventilation stressed(HV) myocardial scintigraphy in vasospastie angina pectoris(VAP). Myocardial tomegrams were obtained both at immediately after HV and 3hour later in 38 subjects with complaint of chest pain at rest. Regions of interest over the heart and lung were selected on the computer-generated images, and lung/heart uptake ratio of TI(L/R) was calculated. The stressed and delayed L/H were compared with the ischemic severity score(summation of semiquantitative defect score in 13 regions on stressed SPECT), and number of vessels in which spasm was provoked with ergonovine in coronary angiography. In 20 patients (group P) trasient myocardial perfusion defects were demonstrated on SPECT, and no defects in 18(group N). On HV images L/H in group P(46.0 ~ 9.5~) was significantly higher(p
Sl0

Sunday, August 26, 1990

O40

041

TALLIUM-201 WITH LEFT

MYOCARDIAL SCINTIGRAPHY VENTRICULAR ANEURYSM.

IN PATIENTS

V.B.Sergienko, L.E.Samoylenko, R.S.Akchurin, A.A.Shirjaev, E.A.Rusinova, A.A.Agapov.All-Union C a r d i o l o g y Research Center, Moscow, USSR. The purpose of this study was to evaluate effect of surgery on myocardial pe~fusion in patients ( pts ) with left ventricular aneurysm. 26 pts ( mean age - 45 yrs ) were examined using rest or stress TL-201 myocardial scintigraphy . Defects of perfusion were in all pts. Quantitative assessment of initial and delayed scintigramms ( i0 min and 4 hour ) showed perfusion defects in 59% of segments (sgts) , and wash-out abnormalities in 63% of sgts: reversible defects were in 47% of sgts,normal perfnsion and wash-out abnormalities - in 16% of sgts, and fixed defects - in 12% of sgts. The uptake of T5-201 in the ].eft ventricular was normal in ii pts and abnormal in 14 pts . Normal heart-lung ratio was in 14 pts , and high lung uptake was in ii pts . Bypass surgery was performed in 8 pts , among them in 5 in combination with aneurysmectomy. Morphometric studies of the aneurysm showed presence of atrophic muscular fibers in the regions c o r r e s p o n d i n g to the sgts with wash-out abnormalities and perfusion defects _ In postoperative period ( up to 4 weeks ) during higher load of exercise the number of normal sgts increased in 3 pts, there was no significant difference in perfusion defects in 4 pts, deterioration of perfusion abnormalities were documented in 1 pts. Thus , myocardial TL-201 scintigraphy is valuable test for evaluation of pts before and after surgery .

042

Nuclear Medicine and Cardiology, Ospedale Molinette, Torino, Italy. To evaluate the clinical utility of 1-123 phenylpentadecanoic acid (IPPA) in the diagnosis of myocardial ischemia, we studied 84 patients with or without M.I.. SPECT scintigraphic studies were performed with TI-201 and 1-123-1PPA. Patients were divided in three groups: Group 1 (detection of viable myocardium): 32 patients with prior MI. and irreversible TI-20I defect. Group 2 (detection of ischemia): 28 patients with reversible TI-201 defect. Group 3 (detection of ischemia): 24 pts with non-Q M.I. or with less than 50% coronary stenosis and no TI-201 defects. Tomographic studies with 1-123-1PPA were performed 5 and 40 min after administration. In group 1, 47% of segments with irreversible TI-201 defects showed 1-123-1PPA uptake (metabolic activity). Only 15% of patients showed early positive 1-123-1PPA scans. After rivascularization TI-201 images were similar to pro-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 pts with coronary stenosis greater than 75%. No positive 1-123qPPA or TI201 scans were obtained in pts of group 3. In our preliminary experience, 1-123-1PPA appears to allow an improved detection of viable myocardium. However, perfusion scintigraphy appears to be superior to 1-123IPPA in the detection of myocardial ischemia.

043

~2~UA~:{ f ; P ! I'.:E L V A L L ; A r l O i ~

OF :d~C,CA,q:DIAL FEIq:FUS~ON b l T ~

~,,:-s-~.-dlBZ SPE:-T JN NORMAL SUBJETCS AND CAD F'~iJEN~S. M. - . o : , ' o . F . Carder, as, j . F . E;a~_sta ~nd L. Santa. NatloFi~] ] r , s t l t u t e eJf Oncc,~oL~y ~ Havana, Cuba= .*q.-oE~t.dlaJ pe!.Tt~Li.JFi wl~h

Tc-99r,~-P1:EI

SF'Etl

at rest.

-2,_!b~e:LtE ~[iL~ -. ;rib' Oa~ie;%i.~ ~D~_= ) rJocLh~ei-{teG o~ EOPoFiar iE>'.3~aph~ [ttg:=, ;.B~S~ ~§ ime~ed a~ reef ,J~l~ig 29~ M#;],~. e t ~ . = _ ~., , _ t . !. r c ; . a,,d . 4. h o .u r s . l a t .e r , . a f.t e r . a ~:'.S M~G. dCf=e ~c,! ~r;S .~= s-t.,d]~ ~, ~ ! , i r : ? - t w o pPoje,::t~oqa of the IlL.,Lt a t d i u l ~ ;~ePe a z q L i / f . e , ] ] ; h r o u l g h ~ COLar.tet'cioc~:wl~Ze 17/,.P~ i,,,L f~'~!~ LH'd t ' ] [~.~LJ D 9 {ine-pt~.el ci-,lc~: tbansa;ial Bilee~ were ~econpi.m_tctict,~ir:g a ,:on~.en~Ioeai ta~TIQ-flltet-ed algo! lUh~i. L,SAg a~iO s h o t ,~ 5;:I=- LV slices were obtai;]e,3. Sl}
:~i,g,;he T'jr- qL;~i;t; flC_~tiL);l. {'leaq vaJues of pePfualer, oePc.er r a g e s we.~e o e t e r m i , - ; e d for e a c h r e g i o n ai-!d n o r - ~19] i ZeC t;0 i.iie fri~;:liT!L!Pl. The W112o;(on signed-ran~: test

wae ~_~ed to compare each p8;r o~ h,:molo~ous ~.aiues re,brace'=cO ~ct !:he normal and pathological groups. A s!:_~ri]fis pet~liLlSlcir! inc, ement d,_iring E~: in e_~,:h ,~egiorl ( p : O . ( . ! S i Was f o u n d to,*" the n o r m a l G_'C,DUD. Later;_>l and ante:-ior LV wall showed supe-ior ~.a!ues ot pet t _~l!]r, than o~her Pe~ions. In CAD ptE the areas coit esou,r:d!n..:_, ~o ssenosed ai teries m-hewed sJgel fica!-!t 'p~,~.CiL; le=-s or" abaer, t increment of poPeeritual per~t-=~of, ~:s#~ test rE, E;; s~udies. Rsc!za::~l_~gP BLJi s Eye image ia a .valuable mean te ;]u_~,,t.j i ,

UTILITY OF 1-123-1PPA IN THE EVALUATION OF THE ISCHEMIC PATIENT: COMPARISON WITH TI-201. T. Varetto, M. Baccega, P.G. De Fili0#i. W. Martiny, A De Berardinis, M. Casaccia, P. Cesana, R. Ropolo. Dept. of

:e~ioea~

m-ocardial

Sunday, A u g u s t 2 6 , 1 9 9 0

pePfiisio0

with

tl]~.~.

REGIONAL ~;OCA,q'C,IAL F'ERFUBION IN NORMAL S U B J E C T S AND L:~D's F'~IENTS BY SFECI WITH M E T H O X Y - I S O B U T Y L - I B O NITRILE ~MIBi ~. .Ft. Cardenas. J. Batista, M. BorrOn, A. Toruncha, L. Serma and J. Oliva. National Institute of Ontology, Hev~n~, Cuba. Forty ~hree persor~s of both -se~s, from the Department of CarO~oJa, gy of "Hnos Ameijeiras" Hospital~ were s~udled and divided into three groups: a~ 25 patiente ~pti~ wlth anglc~gPaphically doo4mented CAD, b~ 9 pta with documente.a CAD and p r e v i o u s myocardial irlfaP,zt (Mi~, ~,~ c! i0 normal subjetcs. MyocaPdlal ~er§ SPECT by MIBI was performed in all cases. Protocol of acquisition was as follow." li 20~ Meg of Tc99m-MIBI was administered iv to rest and fasting pts, 2) One hour after MIBI injection 32 projections of the m y o c a r d i u m were acquired through a c o u n t e r c l o c k w i s e 180o_ arc from LF'O to RAO positions, S,i th~'ee static 64x64 frames at classical positions were a~quired, 4) 4-5 hours later 925 MBq of this c,~mpound were injected during subma• excercise and inmediately after a fat meal was offered to the pts, 51 Steps 2 and 3 were repeated again. Tomog.'~aphic slices were reconstructed uslng a conve,tier~al t'amp-filtered algorithm. Medial slice of each transversal, sagital and coronal sectiol~s were i,sed to e~,aluate LV per'fusion, and divided into 5 se~m, e n ~ s _ th_~t, were evaluated with a 0 to w~ points a,La! a. In the groug., ot pts with CAD SF'ECT showed 95% senslt]v]ty to Oatect artery lesions in any coronary btanch, in ~ne group with previous MI SPECT identified r,er "eels region and new ~erfusion defects, in i:,lanai selntlgraphies set,aCtivity to detect CAD was inre, ;o,' (o S[-ECi.

Sll

044

045

Early kinetics of ggmTcMIBI a f t e r IV injection l o r myocardial scintigraphy. Need for tomographic acquisition with that tracer. P. MARTIN*, B, PEPERSTRAETE*~, J. PATERNOT*and M. VERHAS* Departments of Nuclear Medicine ~ and Cardiology**, Brugmann University Hospital 4, place A Van Gehuchten, B 1020 Brussels, Belgium. We showed earlier (Strasbourg lgag) itWaS possible to calculatea LYEF by a 30" acquisition of ggmTcMIBI activity immediately after the IV injection of 550 MBq of the tracer for myocardial scan, In order to b e t t e r assess the early kinetics of ggmTcMIBI, we generated t i m e / a c t i v i t y curves of 4 selected ROI'S (Myocardial cavity: MC, myocardial wall: M~, lung: LU and liver: LI) and followed the evolution with time of MC/MW, LU/MW and MW/LI in 14 patients (62+_12 years old) referred to our department for ggmTcMIBI myocardial scan. The acquisition time was 5' in a LAO view. The evolution of MC/MW activity with time was best described by a negative power function: MC/MW=3,axtime'-0,3 (r=0,9; p<0.001). The a c t i v i t y of the wall became equal to that of the cavity 85 seconds after the injection of the tracer. The activity of the lung decreased rapidly with time: LUIMW=I,17xtime'-O,2(r=0,B; p(0,001).According to the curves, the activity found in the cavity was still,10R of that of the wall at 30' and 30% at 60'.The residual activity of the lung at 60' was 23~ of that of the wall. In patients who had records at one hour, the evolution of the ratios confirmed that predicted by the theoretical curves. The MWILI ratio showed a rapid increase of the liver activity:MWlLI=30xtime % 0,77 (r=0,8; p(0,00I ). However, the later evolution of the ratio did not correspond to that expected by the curve, because of the accumulation of ggmToMIBI in the gall-bladerand its excretion by the biliary ducts. At one hour, ~he average activity of the wall was 113 of that of the liver. TO conclude: in case of planar scintigraphy, in spite of a rapid decrease of activity in the cavity and lungs, an important background is still present st one hour, with as consequence an increased risk of false negative scans, especially for small lesions of the wall. Moreover, the activity of the l i v e r could be responsible f o r difficulties in the interpretation of left lateral views. In order to Ovoid those problems, when ggmTcMIBI is used as tracer, SPECT should always be prefered to planar scintigraphy.

M~OLAFLqAL ~ E S ~ : T c - 9 9 m - M I B I .-~, T i - 2 < : i l . J.F. Batis~a; R. CArde~as~ A. 7or-unch.~ M. BGrr.te, L. SenPa, Institute of 0neology, Navana. Cusa. Thi rty-one Datlee~]~= Q avu ;~om LFO t;o RAG poEitlon-g. Temographlc slices we, e Pecon_=tv/~cted sslng a conventional r~mptittered al,~u!'lthm, ario Isng an,.~ shcr~ a; ~hree =-e~sra~,ed obae:.,ePs, and me~iel alice of creGs~,ePe~i~ segitsl a',~Q coPor, al g r o u p s ~ere quantitat~veiy ev_~luated di,,:ding li~te 5 segment each ='ice _~ed aslgn~ng scope valde fro,], l_.' tO 3. 8eqsitivILy top the detection or ,~'egions of LV both CO,~pOL:[~ds iL~5%:, as well as especi~icity <~95%i, !he images ~iti~ MIBI were in general more uniform and ischemic areas more defined than were wi~:h ~i20! =

046

047

13 THERE W A S H O U T OR R E D I S T R I B U T I O N OF T c - 9 9 m MIBI IN TH~ M Y O C A R D I U M ? H.M. Abdel-Dayem, K. Kouris, M.M.J. Mohammed, IM Hassan,M. Awdeh, M. Nair, C. Constantinides. Kuwait U n i v e r s i t y and M i n i s t r y of Public Health, Kuwait.

CLINICAL USEFtKN~

We have investigated w h e t h e r the uptake of Tc99m MIBI in the m y o c a r d i u m undergoes washout and/or r e d i s t r i b u t i o n by comparing the early (E) and delayed (D) B u l l s e y e plots (BPs) from E and D SPECT studies ~6quired I h and 3 h after a single injection at stress or res[. The acquisition p a r a m e t e r s for the E and D studies were the same. A p r o g r a m was d e v e l o p e d which performs decay correction of t h e E B P to the time of the D study so that in the absence of w a s h o u t or r e d i s t r i b u t i o n the corrected EBP would be identical to the DBP. The two BPs are then displayed side by side with their corresponding h i s t o g r a m s u n d e r n e a t h in 10% steps. Each h i s t o g r a m p r e s e n t s the no. of BP 'pixels' Vs %counts where 100% denotes max (EBP, DBP). In the second display each BP is transformed to a 5-colour image and c o r r e s p o n d i n g h i s t o g r a m in 20% steps with respect to the same maximum. In the third display, all BP pixels with counts in a user specified range are b l a c k e n e d and their respective number in the BPs indicated. In another d i s p l a y the E-D and D-E images are d i s p l a y e d with negative values set to zero. Finally, the % ( E - D ) / E and %(D-E)/E p a r a m e t r i c images are p r e s e n t e d with histograms in 5% steps. The former reflects washout and the latter redistribution. This p r o g r a m was applied in 27 T c - 9 9 m MIBI p a i r e d (E and D) studies. All p a t i e n t s had IHD. Significant changes in MIBI m y o c a r d i a l u p t a k e w i t h i n the hime p e r i o d of 3 hrs were observed. There is variable w a s h o u t in the same p a t i e n t w i t h i n 5 - 20%.

S12

~#IT~ T ~

CF T ~ T c ~ I

BI~r~LTA~OUS TEST. COMPARISON

RADIONLLT/DE ANGIOGRAPHZ, THALLIUM 201 ASS C0RdNARY ANGLO-

~HY. Victor Sporn ?~3; N~stor P ~ e z Bali~o ND; Csvaldo YEsoli ND; Ricardo Mendez ~43; @ustavo 0jech ND; Msrcelo Di C2rli ~3; 5~9rio Lugones ND. Ssntorio Gdemes - Ftndaci6n Prexis ~t~lica. Buenos Aires. Ai~entina. The aims of this study

is to determine the sensibility (Se)and

specificity (Sp) of the Tc99n 2Netoxy Isobutil Isenitrilo 8i~ilteneses 'Test (MIni-ST): I) For 2)

the

identification of the vessel involved.

The detection of myoceedial ischemis hsving the blood pool ~ t e d

(BB3) end thallium 201 (TIIOI) as gold standard. Thicthy ognsecutive patients with

stable ~

ST consisted of a Perfusion

(~)

were

study at rest

TI2OI and CA were

ir~luided prospectively. MIBI-

first pass a n g i o g r ~ ,

followed by a Myocardial

8nd ducing excercise.

Stress BPG,

performed. ~:Inen analysing the Wall Motion (bM)

end ?ED 180 and 540 se~nents were c(~psred. A significant correlation was present between Eyection Fraction EF wich were 0.85

in stress. A h i ~ correlation was present between the fED score

(0.94 end 0.82 was

8nd WN of both studies,

of a 0.92 end 0.89 respectively in rest and of 0.90 and

of

in rest

end stress). The overall Se of a MIni-ST

9~/~. The Se end Sp of ~ I - S T

detection of each vessels lower than ~ t The ~IBI-ST

end BPG ~

siml]ac for the

involved. The Se of MIBI was slightly

of TII01 for the detection of myocardial isehemia.

is highly sensitive for the detection of ischemia end/c~

necrosis, as well useful in the sesessrent of the EF and ~ .

Sunday, August 26, 1990

048A

048B

THE PROGNOSTIC UTILITY OF DIPYRIDAMOLE Tc-99m METHOXY iSOBUTYL ISONITRILE (MIBI) SCAN IN PATIENTS WITH A FIRST TIME ACUTE NON Q WAVE MYOCARDIAL INFARCTION. T Jaradah, AH Elgazzar, SK Bhatnagar, Y Kiwan, AM Omar, A Ai-Boni, G Fettich, HM Abdel-Daeym, AR Yousef. Depts. of Medicine, Nuclear Medicine and Ministry of Public Health, Kuwait.

COMPARISON BETWEEN ONE DAY PROTOCOLS FOR MYOCARDIAL IMAGING USING Tc-99m MIBI. I.M. Hassan, MMJ Mohammed, C. Constantinides, M. Nair, N. Bellani, A.M. Yousef, H.M. Abdel-Dayem.

The reinfarction rate is high in patients with acute non Q wave MI. In this study the prognostic utility of early dipyridamole Tc-99m MIBI scan done within two weeks post MI is evaluated. We studied twenty patients who had an uncomplicated acute non Q wave MI confirmed by CKMB rise. Each patient was i.v. infused by 0.56 mg/kg dypridamole over 4 minute interval followed by i.v. injection of 10 mCi of Tc-99m MIBI. SPECT imaging 45 minutes later was performed. Resting study followed in the same day was done after i.v. injection of 15 mCi of Tc-99m MIBI and reimaging 45 minutes later using SPECT. Coronary angiogram was performed for 9 patients at 4 week interval after hospital discharge. During dipyridamole infusion 7 patients developed mild angina and 6 had ST-T changes. No significant hypotention or arrythmias were observed. Tc-99m MIBI scans showed scars in 7 patients (35%), scar and ischemia in i0 patients (50%) and only ischemia in 3 patients (15%). Coronary angiography showed complete blockage of the infarct related artery in patients with scar (3) and significant coronary artery disease in those with scar and/or ischemia (6). We conclude that dipyridamole Tc-99M MIBI scan helps separate patients with scar only from those with associated ischemia who have high risk of reinfarction.

049

Tc-99m MIBI has been proved as a TI-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 Tc-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 table. Sensitivity (%) Specificity (%) Accuracy (%) R.E.E.R. R.E. E.R. R.E. E.R. Anterior 75 91 100 83 89 88 Septal 90 100 i00 75 92 88 Lateral 93 73 90 83 92 76 Inferior 87 i00 89 83 88 94 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.

O5O DETECTION WITH Tc99m

[J~/, ~,~f ~ l,,.
85 % 80,~ 83;~

65;~ 93,~ 80,~

91 ~& 93,5 92,&

Of the 8 false positives, 4 were in hAD territory (3 had L6~b, I had myoc~-.rdial brid~ej;2 in .~LA ter~_'~,tory were <.a~'~, ~ to diapilra~atic attenu~:.tion confirmed by il. gin in erect ~,e~tlon;2 in Gx territory due to breust attenu,~'tion. Cf the 16 false nega5ives,3 could not achieve the target double product,9 had bra,ch lesionskdiagonal br~nch of L..D ,~, t[.-i had mainstem !~.~siona mor< than 70}&'diameter.The diaorepalc~' betwee~ nor::,l H:lfusion :t ~.eak szl'~ss and abnormal an~iotr]i:is iri IS L, tients reflects the a~ility of f:yocerd[a! : err cion iLojin: ~ he ~ter ~redict ~,e [,h/sJo!cgical i~,pcrt ~.ce of stei:~>tic lesions, fhe lb. it tioils of c,,rct ary ~rteric,~ra/h,/ 3's : o l d atand~{rd fez the assessment of c,,li.~ri~ lesions are I:O;; batter ~'.:}reciated.

Sunday, August 26, 1990

OF MIBI

DISEASED CORONARY VESSELS AND MYOCARDIAL SPECT.

M.Dondi F.Tartagni, M.Levorato, P.Antonioli, P.Limonetti, C.Corbelli~ S.Fanti, N.Monetti. Dept of Nuclear Medicine and Inst of Cardiology, S.Orsola-Malpighi Hospital, Bologna, Etaly We evaluated three study protocols for detecting diseased coronary vessels in three groups of coronaropathic patients, undergoing myocardial SPECT with Tc99m MIBI. Group I patients (n=24) underwent a first study after dipyridamole infusion (0.14 mg/kg/min over 4 min), followed bZ the rest study two hours later. Group 2 (n=24) was first submitted to the r e s t study and two hours later to an erEometric s t r e s s w i t h t r a c e r i n j e c t i o n at peak exercise. F o r b o t h g r o u p 1 a n d 2 the second tracer dose was threefold the f i r s t one. Group 3 (n=23) underwent an ergometric s t r e s s as p r o v o c a t i v e test. T h e rest study was performed in a separate day. Myocardial w a l l s w e r e r e l a t e d to the three coronary a r t e r i e s a n d the f o l l o w l n g result were obtained:

~ r o u pS P Z1 LAD RCA LCX

group 2 group 3 SZ SPZ SX SPX ............................. 63 93 60 78 75 100 89 64 64 60 67 73 80 47 69 81 55 85

Single-vessel disease was identified in 8/8, 6/7 and 8/8; m u l t i v e s s e l d i s e a s e in 9/15 , 1 3 / 1 8 , a n d 7/11 c a s e s , f o r g r o u p i, 2 a n d 3. In c o n c l u s i o n diagnostic accuracy for protocol 1 and 3 s e e m s to be in the same range w h i l e the r e s t / s t r e s s sequence in a "same day" study was slightly less sensitive.

$13

051

052

Evaluation of exercise induced silent myocardial ischemia (SMI) by exercise Thallium-201 (TI-201) myocardial SPECT. N. Moriai, T. Miyakawa, M Kato, K. Nakai, K. Kato, S. Katsuragawa, T. Takahashi, T. Yanagisawa. Iwate Medical University, Morioka, Iwate, Japan.

In- 11 I-ANTIMYOCIN SCINTIGRAPHY ON ACUTE MYOCARDIAL INFARCTION. H.Naruse, M.Morita, M.Itano, J.Yamamoto, N.Fukutake, H.Kawamoto, M.Ohyanagi, T.Iwasaki and M.Fukuchi" The First Department of Internal Medicine, "Department of Nuclear Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. To evaluate myocardial damage, In-lll-Antimyocin seintigraphy (InAM) was performed in 17 patients with acute myocardial infarction. InAM planar imaging was obtained from 3 views ; anterior, left anterior oblique and left lateral. For comparative study, Tc-99mpyrophosphate scintigraphy (PYP) was obtained by same method and same equipment, and diagnostic coronary angiography (CAG) was performed in all cases. Then we judged visually the degree of myocardial uptake, the locations of infarction and the difference between InAM and PYP. As a result, the degree of myocardial uptake was ranged from low intensity as in bone marrow to high intensity as in liver. All of 17 cases showed positive myocardial uptake including low intensity. The locations of infarction judged by InAM were in agreement with those judged by electrocardiography, CAG and PYP. In 5 cases, the uptake of InAM showed a doughnuts-like pattern or a diffuse pattern which was occasionally observed on PYP. These cases showed myocardial uptake of Parkey's classification class IV with a doughnuts-like pattern on PYP, and showed involvement of left anterior descending artery on CAG. In some cases, the extent of myocardial uptake on InAM did not agree with those on PYP. In conclusion, InAM was sensitive and accurate method to evaluate acute myocardial infarction, although the uptake pattern and the extent of InAM were slightly different from PYP.

The purpose of this study was to evaluate exercise induced SMI by exercise TI-201 myocardial SPECT. TI201 myocardial SPECT was performed in 65 patients (38 ischemic heart disease: EA group, 27 ischemic heart disease with old myocardial infarction: EA+OMI group). Washout rates of the entire left ventricle were expressed via a two-dimensional polar coordinate map. The regions falling below the normal region (mean minus 2 standard deviation) were determined ischemic regions. The location of myocardial ischemia was represented on this polar coordinate map. The ischemic size was quantified by the defect volume ratio (DVR), and defect severity index (DSI). As for EA group, the values of DVR (15.7+12.1% in silent ) and DSI (1.4_+1.8 in silent ) in exercise induced SMI were respectively lower (p<0.05) than those of painful myocardial ischemia (DVR: 46.2+6.7%, DSI: 6.4+3.6 in painful). As for EA+OMI group, there was no significant difference between exercise induced SMI and painful myocardial isohemia for the values of DVR and DSI. In both groups, ischemic regions of exercise induced SMI were detected more often on inferior or lateral area of the Bull's eye polar map than on anterior area. In conclusion, the ischemic size , intensity ( and to a lesser extent, the location) may be important factor in exercise induced SMI.

053

054

~IX HOUR POST-INJECTION MYOCARDIAL INFARCTION VISUALIZATION WITH iii In ANTIMYOSIN AND BLOOD POOL SUBTRACTION.

1)IAGNOSIS AND QUANTITATIVE ASSESSMENT OF ACUTE MYOCARDIAl, I N F A R C T I O N U S I N G DUAL [SOTOPE METHOD. N. H o n d a , M. A b e , A. W a t a r i . T. A b e , and C. [ b u k i y a m a . Tokyo Medical College Kasumiganra Hospital, lbaraki, Japan.

LIEHN J.C. , GIBOLD C. , A M I C O S. , E L A E R T S J., B A J O L E T A., V A L E Y R E J. Institut Jean Godinot - Reims - France. iii in A n t i m y o s i n Monoclonal Antibody is now widely used for the visualization of infarcted myocardium. Due to high blood pool activity, only images obtained at 24h or, sometimes at 48 h post injection are used. In order to know if blood pool subtraction allows earlier visualization, we investigated 7 patients with proven recent myocardial infarction. The standard imaging protocol was used (2 m C i , planar anterior, LOA 45 ~ and LOA 70 ~ ), except that images were obtained at 15 m i n , 6 h a n d 24 h, f o r 5, i0 a n d 15 m i n r e s p e c t i v e l y . Using a software which automatically performs the geometric registration and the normalization of the images, we subtracted the image obtained at 15 m i n f r o m t h e i m a g e o b t a i n e d at 6 h. In all cases a well constrasted subtraction image was obtained which clearly showed the infarcted area, while the original 6 h images were not interpretable. In s o m e cases the blood pool subtracted 6 h image w a s e v e n b e t t e r t h a t t h e 24 h o r i g i n a l i m a g e . This technique, which requires no extra injection s e e m s to be a b l e to v i s u a l i z e the infarcted myocardium 6 h post injection. This may be a practical advantage when an early diagnosis is n e e d e d .

$14

Myocardial seintigraphies w e r e p e r f o r m e d on p a t i e n t s with a c u t e m y o c a r d i a l i n f a r c t i o n as: ~Tc planar method on 20 c a s e s ; a n d d u a l isotope SPECT m e t h o d ( 9 9 ~ T e a n d Z ~ on 12 eases. [n the dual isotope method, 99mTr a c c u m u l a t i o n rate was c a l c u l a t e d from C O R O N A L image o b t a i n e d and was e x a m i n e d c o m p a r a t i v e l y w i t h p e a k CPK, p e a k MB, t o t a l CPK, t o L a l MB and EF a f t e r one month. Sensitivities of d e t e c t i n g infarct in comparison w i t h the c a r d i a c c a t h e t e r m e t h o d were found as 71% u s i n g p l a n a r m e t h o d and 92% using dual isotope method. Infarcted site identification precision was 76% u s i n g p l a n a r m e t h o d a n d I80% u s i n g dual isotope method. 99mTc accumulation rate showed positive correlations wiL]l p e a k a n d t o t a l CPK a s r = 0.875 and 0.922, respectivel (p
Sunday, August 26, 1990

055

056

EVALUATION OF RIGHT VENTRICULAE INFARCTION AND REGIONAL RIGHT VENTRICULAR WALL MOTION USING Tc-99m PYROPHOSPHATE COMPUTED TOMOGRAPHY. A. Yamada, T. Fukuyama, T. Ashihara, I. Ogata, S. Higuchi, H. Tagawa, and H. Aoki. Cardiology, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan.

Tc-99m-MAA PERFUSION IMAGE OF BRONCHIAL ARTERY IN PATIENTS OF MITRAL STENOSIS [WITH THE ELEVATION OF PULMONARY VENOUS PRESSURE] COMPARING WITH CONTRAST BRONCHIAL ANGIOGRAM. Y. Uno ~ , S. Watanabe ~, M. Ishiguro ~, Y. Mort ~ and H. Oda ~. ~Division of Cardiology, The Prefectural Gifu Hospital, Gifu, 500, Japan and Division of Nuclear Medicine, ~-~Johns Hopkins University Hospital.

To evaluate right ventrieular(RV) infarction and regional wall motion of RV, Tc-99m PYP SPECT was performed in 27 patients with acute myocardial i n f a r c t i o n w i t h i n 7 days of i t s o n s e t . RV i n f a r c t i o n was diagnosed by abnormal radionuelide uptake localized to the RV free wall on Tc-99m PYP SPECT and RV wall motion was analyzed by first pass ventriculography at the r i g h t anterior oblique position. RV i n f a r c t i o n was found in 10 of 17 i n f e r i o r m y o c a r d i a l i n f a r c t i o n but none in 10 a n t e r i o r myocardial infarction. Global left and right ventricular e j e c t i o n f r a c t i o n ( E F ) and r e g i o n a l RVEF were compared w i t h i n t h e s e t h r e e g r o u p s : 10 c a s e s of inferior myocardial infarction with HV i n f a r c t i o n (groupl), 7 c a s e s of i n f e r i o r myocardial infarction without RV i n f a r c t i o n ( g r o u p 2 ) and 10 c a s e s of anterior myocardial infarction (group3). Left v e n t r i c u l a r EF was not s i g n i f i c a n t l y d i f f e r e n t within three groups (42, 51 and 45Z in g r o u p l , 2 and 3, respectively). However, RVEF in g r o u p l (37z) was significantly lower than t h o s e in group2 (46z) or group3 (51z)(p<0.05). On analyzing right ventriculography, we found s e v e r e l y r e d u c e d i n f e r i o r RV f r e e wall motion in g r o u p l . Thus, RV i n f a r c t i o n could be frequently complicated in inferior myocardial infarction and RV f u n c t i o n is s e v e r e l y d i s t u r b e d due to r e d u c e d RV wall m o t i o n .

We tested the hypothesis that abnormal bronchial circulation, such as the expantion and swelling bronchial submucosal vessels in mitral stenosis (MS), were related to the pulmonary venous (PV) pressure elevation. However, it remains to be not established whether the dilatation occurs in pre-capillarybeds or post-capillary beds. The aim of this study is to be designed to identify abnormality in the pre-capillary beds of bronchial artery in patients with MS, using by direct infusion of Tc-99m maeroaggr gated albumin (MAA) into the bronchial artery. 6 normal subjects and 12 patients with MS were done and compared with contrast bronchial angiogrom. [3 of these were done Degital snbraction angiography (DSA). ] As a result of this sutdy, contrast angiograms of bronchial artery and DSA showed that bronchial artery was not so much enlarged as slightly narrowed. MAA perfusion images showed various patterns because of their anatomical varieties, but no clear difference between normal subjects and MS group. However, MAA images shifted central side and it seemed to reflect the dilatation of post-capillary beds. These results suggest that high PV pressure could not enlarge bronchial artery and pre-capillary beds. And bronchial submucosal dilated vessles seemed to be from venous circulatory change.

057

058

PHLEBOTHROMBOSIS QUESTION !

OR

THROMBOPHLEBITIS:

C.CSt@, Pavillon St-Joseph, Canada.

THAT

IS

THE

CHRB Beauceville, Quebec,

Usually, we say that there is no valid distinction between phlebothrombosis and thrombophlebitis. The purpose of this study was to evaluate the usefulness of the flow study preceding the red blood cells venography, to distinguish between these two condiiions and to verify if there is any difference between these two groups of patients for the incidence of pulmonary embolism. 29 patients with a red blood cells phleboscintigraphy and lung scan were studied. Only two categories of lung scan were considered: normal and high probability. Results: with the flow study these 29 patients could be categorized in 2 groups. First: 15 with a normal flow and second: 14 with an increased flow. The first group of normal flow considered phlebothrombosis: 3 had no embolism and 12 had a high probability lung scan. The second group with an increased flow considered thrombophlebitis: 8 had no embolism and 6 had. This difference is statistically significative. (Chi square: 4.24, alpha: 0.05). We conclude: the flow study helps to distinguish 2 kinds of patients who had deep venous thrombi of the legs. These two groups of patients with a normal flow (phlebothrombosis) and with an increased flow (thrombophlebitis) have an expected different incidence of pulmonary embolism. Phlebothrombosis and thrombophlebitis may be are not a purely theeritical view.

Sunday, August26,1990

EFFECT OF COCAINE ON MYOCARDIAL PERFUSION: TL-201 IMAGING EXPERIMENTS IN DOGS. Z.H. Oster P. Som, and D.A. Weber. Brookhaven National Laboratory, Upton, NY and SUNY Stony Brook School of Medicine, Stony Brook, NY There is growing evidence that sudden death and acute M.I. after cocaine may be related to coronary vasospasm. Angiographic studies, show only moderate spasm of the subepicardial coronary arteries or are negative despite evidence of significant decrease of coronary flow and increased coronary resistance after cocaine. TI-201 studies were performed in dogs with and without cocaine to elucidate these inconsistencies. Baseline studies were performed in six dogs, at 5,20,120 and 180 min. after TI-201 (2mCi I.V.) injection. The studies were repeated one week later, with cocaine (2 mg/kg, I.V.) administered 5 min. prior to TI-201 and images were obtained similar to the baseline studies. The counts in the LV, 5 min. value was highest (100%). In the baseline control studies, there was gradual washout of tracer from the LV. In the post-cocaine studies, global LV counts were lowest 5 min. post-injection (- 40% of the 5 min. baseline value), with gradual "wash-in" of TI-201. Perfusion defects were seen in septal and apical areas. These studies indicate that cocaine induces severe temporary ischemia in the LV, corresponding to the decreased coronary flow and increased coronary resistance found in humans and experimental animals. LV ischemia detected by TI-201 after cocaine appears to be due to spasm of the smaller intramural arteries, rather than resulting from impaired flow in the subepicardial blood vessels.

S15

060

059 FATE OF RADIOLABELLED-DIGITOXIN IN THE R A T ' S BLOOD J. Rousseau, M. Dcveamt, P. Lecouffr X. Marchandisc Laboratoirc de Biophysiqua - Facult6 de M4decine

- Lille

- FRANCE

The rat is practically unscntitiw to massiw injection of digitoxin, but it is difficult to realize an accurate analysis of these cardiac glue~idns fate becaasr they are eliminated at a great speexl : about 10% of the injected quantity remains in blood f l w minutes after injection. With RIA methods, too many sample would be need which would have to bc collected at short intervals determined with unsatisfactory accuracy. The injection rate would also have to be taken into account,

in order not to take the experimenter's differences as individual

metabolic variations. In order to re..solvc that difficulties to study the rat's unsensitivity, wt ust: an home-made microcomputer-controlled gamma spectrometry device. On six anaasthnsized and intubated rats, a 1.5 ml r162 carotid-jugular shunt is dipped . . . . . 125 . . rite the counting well o f our apparatus. An rejection of 1/./elI-dlgltoxm and 0,5/JCiI31I-HSA is made downstream from the counter. Records are made over a period of 4 hours, each 106 in the first 10 rain, each 30* afterwards. Figure shows . . . . . . 131 activity curvns : mjectton and blood ddunon are not mstantaneoas ( I-Part A). --

A

+--.-.--

S

C -

,,.

The extremely fast

-

fL~a-

tion into the liver is shown (1251-Pa~ B). In~

of blood activity

(Part C) corresponds to the reluasr of a radioactive iodine from the

i

'

metabolite

l~vcr,

A cam-

partimenta[ analysis can be made, which take into account

injection

rate

l(,.nJ and activities in the rat's

PARAMETRIC IMAGES OF WASHOUT IN THE QUANTITATION OF THALI.IUM PERFUSION STUDIES. A NUMERICAl SIMULATION TEST. A. Gareia, J. Pavia, D. Ros*, I. Juvells + and J. Setoain Serv. Medicins Nuclear, Hospital Clinic. *Fisica M@diea, Fac. Medieina. +Lab. 0ptica, Fac. Fisica.Univ. Barcelona Spain A numerical simulation study was made to evaluate the possibility of using parametric images of washout in the quantitation of thallium perfusion imaging. Two aspects were analized: the elimination of non-cardiac background and the alignment of the stress and redistribution images. The study was carried out by numerical simulation of background and myocardium in LAO projection with a ischemic region. An artefact at different distances representing a high hepatic uptake was added. We studied three classic algorithms of background interpolation proposed by Watson, Goris and Nichols with a contour adapted to the myocardial shape. We also analyzed the ability of the correlation for making the a]ignment. The results in the interpolation showed, for 20 different positions of the artefact, a better performance of Watsonts method. Concerning the correlation, using for the alignment only those points the activity of which is equal to or greater than 50% the maximum activity in stress, we reached a maximum error of one pixe!. This error only appeared in 18% of the 150 tests made. The good results obtained in background subtraction and alignment allowed us to calculate a parametric image of washout. Without artefact, the mean washout error which could be assigned to the eomp!et process was 1% (maximum error 7%) in the normal area and 9% (max 26%) in the pathologic one. When an artefact was present these values were 2% (max 10%) and 10% (max 29%) respectively.

organs at the cad of. the i

10

ioo

experiments.

061

062

CLINICAL APPLICATION OF THREE-DIMENSIONAL SURFACE DISPLAY IN GATED CARDIAC BLOOD-POOL IMAGING IN PATIENTS WITH CARDIAC DISEASES. J. Ishimura, M. Fukuchi, M. Kawanaka, M. Suehiro, K. Tachibana, H. Naruse and T. Iwasaki. Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

THE DIAGNOSTIC VALUE OF POSTEXTRASYSTOLIC POTENTIATION ON LV FUNCTION USING LV PRESSURE-VOLUME COUNTS LOOP BY NON-IMAGING PROBE WITH SIMULTANEOUSLY AQUIRED PRESSURE DATA. S. Watanabe, M. Ishiguro, T. Yasue, H. Matsuo, Y. Uno, A. Goto and M. Kondo. Division of Cardiology, The Prefectural Gifu Hospital, Gifu, 500, Japan.

This study reports our initial experience of the clinical application of three-dimensional surface display (3DSD) in gated cardiac blood-pool (GCBP) imaging with Tc-99m DTPA-HSA. Twelve patients (I0 with myocardial infarction, 1 with dilated cardiomyepathy, 1 with constrictive pericarditis) were entered in this study. All patients had abnormal findings in two-dimensional echoeardiography and ventriculography. Twenty mCi (740 MBq) of Tc-99m DTPA-HSA was given intravenously, and i0 minutes later data were obtained at 32 projections in 360 degrees with 60 seconds per projection from 16 ECG-gated frames of 64• pixel. The SPECT images were reconstructed by the filtered backprojection method with attenuation correction. The GCBP surface image was made from the isocount outlines of the SPECT images. The threshold of the isoeount was 50% of the maximum count of the global pixels. The 3DSD was created from the surface image using the distance-shaded method. The 3DSD in GCBP imaging allowed excellent stereoscopic visualization of the structure and motion of the cardiac chambers, and clearly revealed abnormal findings in all 12 patients. Compared with the planar GCBP imaging, the abnormalities such as inferior hypokinesis and apical aneurysms were detected more accurately in 8 of 12 patients using 3DSD. These findings show that 3DSD in GCBP imaging is useful for visual evaluation of ventricular wall motion.

S16

The augumentation of myocardial contractility which occurs after an extrasystole (post-extrasystolic potentiation : PESP) has been suggested to assess the ventricle reserve. We developed a non-imaging probe for beat-to-beat monitoring ventrieular pressure-volume counts loop (P-VC loop) to permit continuous measuring relative ventricular works. PESP was induced by right ventricular pacing. Simultaneous acquistion of left ventricular (LV) volume counts with the probe and LV pressure data were made in pre-pacing, extrasystole and a first post-extrasystolic contraction to evaluate the LV functional reserve in patients with acute myocardial infarction (AMI) under treatment of direct percutaneous transluminal coronary angioplasty (PTCA) at onset of AMI and relative net works were calculated from LV P-VC loop. As results, increased net work by PESP in pts with successful PTCA (n=6) was 1.8 times larger than that in pts with unsuccessful PTCA (n=4) (p
Sunday, August 26, 1990

063

064

ASSESSMENT OF MULTIPLE CARDIAC FUNCTIONAL IMAGES DERIVED FROM MUGA STUDIES. K Kouris, K AI-AIi, IM Hassan, HM Abdel-Dayem, C Constantinides, G Fettich, R Bahar, S Ai-Mohannadi. Faculty of Medicine and Ministry of Public Health, Kuwait.

A. Tarkowska, F. Bitter, R. Wel]cr, E. Henze,

The % sensitivity SE, specificity SP and accuracy AC of the following functional images derived from Tc-99m multigated MUGA studies were assessed by consensus between six nuclear medicine physicians : amplitude AMP, phase PH, T4/5, peak emptying rate PER and peak filling rate PFR. The sample population comprised 14 normals and 26 IHD patients all with normal rest LVEF>50%. The IHD patients had been catheterized. These functional images were generated and displayed on a VAX-based Lexidata image processor. 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 4/5th 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. The results below indicate that the PFR image alone or in combination with amplitude as well as either PER or T4/5 are the most reliable. SE SP AC SE SP AC AMP 50 93 65 AMP+PMA 42 i00 63 PHA 27 i00 53 AMP+T4/5 54 86 65 T4/5 54 79 63 AMP+PFR+PER 62 93 73 PER 65 64 65 AMP+PFR+T4/5 58 100 73 PFR 58 86 68

W.-E. Adam. QUANTIFICATION OF FOURIER AMPLITUDES USING THE REFERENCE CIRCLE METHOD.

Abstract received in a form unsuitable for reproduction

065

066

CHANGES IN T/D RATIOS RETWEEN REST AND REDISTRIRUTION TL-201 IMAGES AS AN ADDITIONAL CRITERIA OF CAD. E . J . Gandsman- and+ E.W. Bough . Thomas Jefferso~ U n i v e r s i t y Hospital and Cardiovascular I n s t i t u t e , Mountain View, CA.

L D A : TI--Pr~I . . . . . . c P ~C C T a n d B u i l_, s - e y e rr,o ~7o-vasc u i ar o r e i u s i o m

The l e f t ventricular shell thickness ( t ) to cavity d i a m e t e r (d) r a t i o has been found t o be l i n e a r l y c o r r e l a t e d with the r e s t i n g l e f t v e n t r i c u lar ejection fraction. The apparent t / d r a t i o is a c t u a l l y a f u n c t i o n of the i n t r i n s i c wall thickness, wall excursion and r a t i o of time spent in systole compared to d i a s t o l e . In normal e x e r c i s i n g p a t i e n t s t w i l l increase and d w i l l decrease as a r e s u l t of t h e increased wall excursion but d w i l l decrease a l s o because the s y s t o l i c counts increase r e l a t i v e t o the d i a s t o l i c counts. Sensitivity, specificity and accuracy were c a l c u l a t e d f o r TI-20! stress imaging f o r 85 p a t i e n t s who had undergone cardiac catheterization and coronary arteriography (16 normal c o r o n a r i e s , 34 s i n g l e vessel disease, 18 two vessel disease and 28 three + more vessel disease. A l l 16 p a t i e n t s with normal coronaries e x h i b i t e d a positive ~(t/d) = t/d (rest) - t/d (exercise). Approximately h a l f of the p a t i e n t s with CAD e x h i b i ted n e g a t i v e values of ~ ( t / d ) . Use of the additional criteria that ~(t/d) < 0 represents a posit i v e t e s t resulted in improved accuracy. (See t a b l e I). Table I Sensitivity Specificity Accuracy visual inspection all 80 81 80 adequate exercise 88 81 86 visual inspection & A ( t / d ) all 89 81 87 adequate exercise 94 81 91

Previous studies demonstrated disagreement between several Authors about Spect with 201Thallium cloride in detection myocardial ischemia.Our a i m is to e v a l u a t e the utility of SPECT in s e l e c t e d patients with complete oct fusion of single vessel (es LDA) , demo~Tstr a t e d with X-Ray alTg i o g r a o h y . T1 ~ Spect has more accuracy f o r t h~R is vessel,fc, r this reason we have studied ~ patie-nta~ ( !7 m a l e , i female,mear~ age 54yy.range 41-65 ) and we in~ected 3 mCi " eOi-Tl after dipiridamoio stress. We have also utilized Spect images amd Bulls-eye analisis.We recorded site a~nd e x t e n s i o n c,f defects.We compared these results with clinical and ECG fi~,~imgs. The following table shows the resu its :

Sunday, August 26, 1990

a~,Taiysis

in

E=Brianzc, ni* ~ .Valentini*,S.Ancidei*, C =C i u c c l o v e * * , G. C o s t a n t i n i * * , * N u c l e a r e M e d ic ine, O s p - U S L - !5, M a c e r a t a **Cardiology Unit OspoLaTcisi,Ancoma

TL reversible persistent absent ............................................. angina + 6 (12-30%) 2 (3C)%) 1 ............................................. a~Tgina P_ ( < 1 2 % ) 7 (30-60%) ............................................. mote:(vaiue%)=% o f p i x e l <~~ sd The results suggest a good correlation between angiographic lesion and sites of SPECT defect if p r e s e n t . However we round a great variability c,~l t h e d i m e l n s i o n of the defects. In t h e o t h e r h a n d t h e r e is a good ec,r r e i a t i o ~ 7 between extension and clinical fi~dinqs, but not between extension and ECGsiqns.Pr6bablv these results suggest that in si{~g le vessel disease of LDA, the only angiographic and ECG pattern doesn't offer

sufficient notice for management of patients.Particularly the Spect w i t h Bullseye anal isis is important for better definitio~n visualization

of of

isehemia and viable myocardium.

correct

S17

067

068

ALTERNATIVE METHOD FOR QUANTITATIVE DESCRIPTION OF TI-201 RADIOTHALLIUM CARDIAC REDISTRIBUTION. Richard D. Baldwin, Richard P. Spencer. V.A. Medical Center, Togus, Maine and University of Connecticut Health Center, Farmington, Connecticut, USA.

A home-built miniature multidetector probe based on CdTe detectors for cardiac applications.

We sought a quantitative method for expressing TI201 cardiac redistribution data that would be easy to carry out and readily understandable. Let I be the initial counts in an area of myocardium and F the final counts. Then: D = F - I, where D is the difference. The F value has to be corrected for radiodecay. Thus: D = F.exp kT - I, where k is the decay constant of TI-201 and T is elapsed time. Further, in order to correct for differences in volume of tissue in each region, we divide through by the initial counts: D = (F/I)(exp kT) - i If D is positive, there has been a net "wash in," while a negative value for D means a net "wash out." To simplify the procedures, the term kT can be readily determined by imaging a fraction of the residual activity in the syringe used to inject the patient. Indeed, this marker can also have use in repositioning the individual. While the decay correction is minimal for studies at 3 hours, it is appreciable for both later images and 24 hour views. The most common comparison of initial and delayed radiothallium myocardial uptake is by means of a ratio: R = F/I. Thus the term R can be readily converted to the expression D, by: D = R(exp kT) - i. The method is being applied as a useful approach to the analysis of base to apex changes in normal hearts, and for quantifying redistribution abnormalities in myocardial disease.

C. SCHEIBER*, M.A. MOLINARI**, A. GALLMANN** and J. CHAMBRON* * Institut de Physique Biologique -Facult~ de M@decine4 rue Kirschleger 67085 STRASBOURG. ** Centre de Recherches Nucl@aires 6 rue du Loess 67200 STRASBOURG-CRONENBOURG.

Ambulatory monitoring of ventricular function parameters together with ECG data could be of some help in the management of patients with cardiac pathologies. Although a portable autonomous single INa detector system is commercially available (VEST Carpintech corp.), detector matrix using CdTe semi-conductors represent an alternative choice with several advantages : better spatial resolution, background selection, and quality control for detector motion during clinical investigation. We present the physical characteristics i.e. stability as a function of time, and temperature, isosensitivy curves in water, uniformity together with preliminary clinical experiments of a home-built system. The probe consist of 12 Cadmium-Telluride (CdTe) detectors i0 mm x i~ ram coupled to hybrid preamplication circuitry. The actual experimental system use conventionnal amplifiers and power supply. A dedicated hardware and software was developed to acquire and process the data as in conventionnal MUGA studies.

069

070

SERIAL iMAGING OF CEREBRAL VASCULAR RESERVES IN PATIENTS UNDERGOING CAROTID ENDARTERECTOMY. AR.Naylor, MV.Merrick, CV.Ruckley. Dept. of Vascular Surgery, Royal Infirmary, Edinburgh and Dept. of Nuclear Medicine, Western General Hospital, Edinburgh U.K.

INFLUENCE OF CAROTID ENDARTERECTOMY

Regional cerebral vascular reserves (rCVR, the ratio of regional cerebral blood flow to volume, and reciprocal of mean cerebral transit time - M C3"-[') have been measured serially in 53 consecutive patients undergoing carotid endarterectomy. The earliest study was not more than one week before operation, and all surviving patients have been followed up at least twice a year for up to three years (median 17 months). In 35 (66%) the preoperative studywas normal. Four developed asymmetry postoperatively, although in three this reverted to normal during follow-up. Fifteen patients had an unilateral (ipsilateral) impairment of rCVR pro-operatively. Ten ofthese became normal after operation; two of the four in whom asymmetry persisted immediately after operation became symmetrical on follow-up, one was unchanged and the other not retested. The three other patients had bilateral abnormalities. One reverted completelyto normal post-operatively whilst the other two remained abnormal on the non-operated side. No patient has developed significant asymmetry affecting the operated hemisphere on follow-up, but two have developed a significant asymmetry with unilaterally increased MCTT (reduced rCVR) on the non-operated side, associated with the development of significant carotid stenosis. We conclude that serial imaging of rCVR and MCTT shows considerable potential as a quick, inexpensive, quantitative, reproducible and sensitive test for the detection, assessment and follow up of patients with transient ischaemic attacks. Serial studies may identify those developing haemodynamically significant extracranial carotid stenosis during the course of follow-up.

S18

ON CEREBRAL BLOOD

FLOW : A LONG TERM FOLLOW-UP STUDY WITH SPECT AND TC - 99m HM - PAO G.Ferlin,

N.Borsato,

P.Zanco,

F.Chierichetti,

B.Saitta,

~G.Meneghetti, ~ F . D a l l a Costa Departements of Nuclear Medicine, Hospital Castelfranco Veneto, Italy, ~Neurology andS*Vascular Surgery, University of Padua,

Italy.

Cerebral blood flow (CBS) changes after carotid endarte_ rectomy may be evaluated by SPECT using Tc-99m Hexamethylpropylenesmine oxime (Tc-99m-HM-PAO). With this me thod CBF was measured in 25 cerebrovascular patients with mild or severe extracranial carotid stenosis before and after endarterectomy. Perfusion asymmetries between cerebral hemispheres were calculated on sixteen regions of interest (ROIs) that corresponded to the area of distribution of the anterior, middle and posterior cerebral arteries, respectively. Preoperative CT scan showed small hypodense lesions in 6 patients while the baseline CBF study revealed a significant perfusion asymmetries in 19 cases. A further CBF study performed one month after uncomplicated carotid surgery showed an improved perfusion on the operated side with a reduction of side-to-side asymmetries in 7 patients. On a later CBF control at a six month follow-up the improved perfusion was less evident while the decrease of side-to-side asymmetries still persisted. SPECT with Tc 99m HM-PAO allows to follow the CBF changes after endarterectomy and can be of help in identifying patients more suitable to carotid surgery.

Sunday, August26,1990

071

072

VALUE OF SERIAL PARAMETRIC IMAGING OF CEREBRAL VASCULAR RESERVE (CVR) IN SUB-ARACHNOID HAEMORRHAGE(SAH). A Netghi,MV Merrick,D Rawlock,I Robertson,C Ferrington, JD Miller. Departments of Nuclear Medicine & Clinical Neurc,sciences, Western General Hospital, Edinburgh.

CONTRIBUTION OF SPECT - 99mTc HMPAO TO THE HEMODYNAMIC EVALUATION PRE-PER AND POST-OPERATIVE OF MENINGEAL HAEMORRHAGEBY ANEURYSM RUPTURE. A STUDY OF 20 PATIENTS. Ph. Coubes*,***, F. Segnarbieux*, J. C h e v a l i e r * * , P.O. K o t s k i * * , Ph. Frerebeau, M. Rossi**. * Service de neurochirurgie B, Centre Gui de Chauliac, Montpel I i e r . ** Service de medecine n u c l e a i r e , Centre Gui de Chauliac, M o n t p e l l i e r . * * * Labor at oi r e d'automatique et de microelectronique, USTL-CNRS 371, M o n t p e l l i e r , France.

Sequential parametric imaging of CVR, CT and angiography were performed in 47 patients with SAH. 17 patients had neurological deficits contralateral to the affected vessel, associated with prolonged mean cerebral transit time (HCTT). In only one was there hemiparesis with ipsilateral prolonged MCTT, but CT and angiographic lesions were also confined to the same side. One patient had a prolonged MCTT and deficit on the side with severe vase-spasm, but a contralateral aneurysm. Two CT scans were normal, 6 showed haematomas and 5 ventricular dilatation; 16 had blood in the ventricles. In a second group of 17 patients with SAH and sneurysm but no neurological deficit only i0 (60%) showed MCTT prolongation, and in 2 this was opposite to the side of the aneurysm, probably indicating subclincal vasospasm, which was confirmed angiographically in one. 4 patients had no CT abnormality. A third group of 12 patients with SAH had neither aneurysm nor neurological deficit. Of these 4 had vase-spasm on angiogram, two sufficient to prolong MCTT. 30 patients underwent surgery for aneurysm or haematoma. 5 developed transient increase in MCTT post operatively, probably due to vasospasm on the side of operation. CVR is useful in assessing the cortical blood supply, correlates closely with clinical and angiographic findings and indicates compromised cortical blood supply in the absence of CT scan changes.

Twenty patients with meningeal haemorrhage secondary to an aneurysm rupture had a cerebral hemodynamic evaluation with Tc-99m HMPAO-PECT to evaluate the c o n t r i b u t i o n of t h i s technic in the choice of the timing o f the surgery (Spasm d i a g n o s t i c ) . The protocol was the same f o r each p a t i e n t : Daily c l i n i c examination and scoring - EEG pre, per and post-op t r a n s c r a n i a l doppler pre and post-op CT-SCAN pre and post-op SPECT pre, per, and post-op A s t r i c t s e m i - q u a n t i t a t i v e protocol is used, based on the semi-automatic determination of cerebral a r t e r i a l territory. P a r t i c u l a r l y , when the p a t i e n t is operated, a per-op i n j e c t i o n is r e a l i s e d under EEG monitoring. When a temporary occlusion of the monitoring vessel by a clamp is necessary (neuroanesthesia by ethomidate), t h i s procedure gives informations on the hemodynamic repercussion. With t h i s p r o t o c o l , we can do m u l t i f a c t o r i a l c o r r e l a t i o n s between c l i n i c a l data, EEG, doppler, catscan and SPECT. The f i r s t r e s u l t s confirm the growing i n t e r e s t in cerebral perfusion studies in Neurosurgery. In meningeal haemorrhage, SPECT is a r e l i a b l e and s e n s i t i v e tool f o r the periop hemodynamic evaluation c o n t r i b u t i n g to the choice of the best time to operate.

073

074

CEREBROVASCULAR CHANGES IN THE EVOLUTION OF CEREBRAL INFARCTION STUDIED BY Tc-99m HM-PAO AND MRI A. Ahonen, O. R a i t a k a r i , T. Kurki, A. Laihinen, H. Aronen, R. Raininko. Depts. of Nucl. Med., Neurol. and Radiol., Turku Univ. Hospital, Turku, Finland

REDISTRIBUTION MECHANISM IN CEREBRAL INFARCT: A SEMIQUANTITATIVE IMP SPECT STUDY Y. Maeda, K. Kuwabara, T. Asai, M. Kusunoki, and J. Shirai. Kobe Ekisaikai Hospital, Kobe, Japan.

Tc-99m HM-PAO was used to study hemodynamic changes in patients with i n f a r c t i o n and to evaluate MRI findings in connection with primary and secondary rCBF changes. 33 patients with brain i n f a r c t i o n were included. In 15 patients HM-PAO and MRI (a low magn. f i e l d , O.02T) were performed three times: during the acute phase, subacute phase and 4 weeks a f t e r ictus. Normal v a r i a b i l i t y was estimated f o r the rCBF in 15 cancer patients with no neurological symptoms or signs. SPECT was made on an ordinary r o t a t i n g gamma camera. Retrospective HM-PAO abnormalities consistent with the new i n f a r c t i o n area were seen in 17 out of 18 patients in single examinations. MRI indicated acute i n f ~ r c t i o n in 15 p a t i e n t s . Prospective study: 15 patients with minimal symptoms were studied. Abnormalities in HM-PAO scan in the acute phase were seen in 12 p a t i e n t s . Luxury perfusion was seen in 6 p a t i e n t s . Sometimes the defect in the acute phase was corrected in the subacute phase ( l u x u r y perfusion) and 4 weeks a f t e r ictus the defect was v i s i b l e again. In two patients in the acute phase MRI showed abnormal SE findings but in the subacute phase MRI was normal and l a t e r on again abnormal. i f great morphological r e s o l u t i o n is needed, MRI is superior, but since HM-PAO is a f u n c t i o n a l method, i t can give valuable additional information not obtained with MRI.

Sunday, August 26, 1990

Recently many SPECT studies for brain perfusion have been performed. However in 1-123 iodoamphetamine ( IMP ) SPECT study, the pathophysiological significance of redistribution is still controversial. In this report, the authors studied the significance of redistribution by the IMP SPECT imaging with semiquantitative method. The IMP SPECT study ( with 1-123 IMP 3mCi ) was performed in 7 patients with the chronic stage of cerebral infarct. Early and delayed images were obtained after 30 minutes and 3.5 hours. The relative blood flow value was represented by the radioactivity ( cpm ) in each ROI ( 4X4 matrices ). ROIs were set on the central area of infarcted lesion and the corresponding area of contralateral hemisphere, and also on the peri-infarcted area and several non-affected regions. The degree of redistribution was evaluated by the subtraction of such ROI's mean radioactivity ( early image from delayed one ). In 5 of 7 patients, redistribution of IMP was mainly observed in the affected lesion. On the other hand, no definite redistribution was observed in the non-affected hemisphere and also perifocal region, possibly including "ischemic penumbra". There is a possibility that the mechanism of IMP redistribution could be the passive diffusion of IMP into the infarcted ( necrotic ) tissues, rather than flow accumulation via collateral channels.

$19

075

076

RAPID QUANTITATIVE SERIAL EVALUATION OF REGIONAL CEREBRAL VASCULAR RESERVE FOLLOWING ACUTE STROKE. AR Naylor, MV Merrick, PAG Sandercock, TMJ Griffin, RJ Sellar, GP Wallow. Departments of Nuciear Medicine & Clinical Neurosciences, Western General Hospital, Edinburgh, U.K.

IMAGING OF CEREBRAL BLOOD-FLOW (rCBF) TO BLOOD-VOLUME (rCBM) RATIOS IN THE DIAGNOSIS AND FOLLOW UP OF CEREBRAL ARTERIO-VENOUS MALFORMATIONS (AVM). MV Merrick, A Notghi, I Robertson, JD Miller, IH Kunkler. Departments of Nuclear Medicine & Clinical Neurosciences, Western General Hospital, Edinburgh and Radiosurgery Unit, Weston Park Hospital, Sheffield.

We have studied sequentially 32 patients admitted with acute, first ever, non-haemorrhagic cerebral infarction using a new technique which takes less than one minute, is practical in very sick patients and produces parametric images of cerebral vascular reserve (CVR) - the regional ratio of cerebral blood fl0w (rCBF) to volume (rCBV). Transcranial Doppler ultrasound (TCD) measurement of blood velocity in the middle cerebral artery was not possible in 4; CVR was not evaluated in one patient who was unfit to move. There were no failures in the cVR studies attempted. Using Boniford's clasification, ten of the 14 having total anterior circulation infarction had unilateral impairment of CVR in the affected hemisphere; the others had bilateral abnormalities. Six died within 30 days. Twelve of 13 patients with partial anterior circulation infarction had normal CVR values although in five the interhemispheric asymmetry was abnormally large; there was evidence of luxury perfusion in the thirteenth. There was no abnormality of CVR in the three patients with lacunar infarcts but two had asymmetry on TCD. Aft 16 survived. Two patients could not be classified clinically. TCD and CVR findings were concordant in 25 ofthe 27 in whom both investigations were performed. In the remaining two, TCD was abnormal but failed to indicate the presence of a functionally significant collateral supply. We conclude that CVR and TCD are complementary. TCD identifies individual vessel patency, but is operator dependent, time-consuming and gives restricted information about collateral supply. Parametric imaging of CVR gives regional information, not obtainable by any other rapid technique, of the adequacy of the total local blood supply, including any collaterals, is easy to perform, reproducible, quick and operator independent.

The ratio of rCBF to rCBV, the cerebral perfusion reserve (CPR), can be calculated from the first pass of a non-diffusible tracer such as pertechnetate. Twelve patients who proved to have, or who were suspected of having, an AVM have been investigated, eight because they were thought to have an AVM, two fsllowing a single unwitnessed episode of loss of consciouness (UELC), not definitely proven to have been a fit, one with recurrent headache and one with recurrent suspected subarachnoid haemorrhage. Three patients were restudied after radiosurgery and one after therapeutic embolisation. The CPR study was the first evidence of an AVM in three, the two UELCs and the patient with headache. All were subsequently confirmed angiographically. An AVM was clearly identified in the CPR study in ten of the twelve patients. In the eleventh CPR was measured shortly after a large bleed, which destroyed much of the AVM. Angiography revealed only a small residual nidus. There was a substantial mass effect due to the haematoma. The remaining patient underwent cerebral angiography twice for a small dural lesion which could not be located at craniotomy despite a 4 cm haematoma in the left posterior parietal region. This was probably an angiomatous malformation rather than an AVM and may be considered a true negative. Following radiosurgery the CPR altered towards normal some months before changes were evident angiographically. We conclude that imaging of CPR is a useful low-cost and low risk investigation for screening patients with a low a priori probability of AVM, and for follow up after treatment.

077

078

EVALUATION CHANGES VENOUS

OF

AFTER

THE THE

CEREBRAL REMOVAL

MALFORMATIONS

BY

HEMODYNAMIC OF

1-123

THE IMP

ARTERIOSPECT.

G.Takeshita,H.Toyama,H.Maeda,K.Katada, K.Ejiri,A.Takeuchi, and University School of

S.Koga. Fujita Health Medicine,Toyoake,Japan.

To e v a l u a t e the c h a n g e s of the r e g i o n a l cerebral blood flow(rCBF) in the t i s s u e adjacent to t h e arteriovenous malfomations (AVMs) before and after removal, N-isoprorylp-[I-123] iodo-amphetamine(I-123 IMP) b r a i n s t u d y was p e r f o r m e d using ring typed SPECT. In s e v e n c a s e s of the A V M s , p o s t operative angiograms proved the total removal, s e r i a l r C B F i m a g e s w e r e o b t a i n e d at t h e t i m e b e f o r e the O p e r a t i o n , the next d a y of the r e m o v a l a n d a w e e k a f t e r the o p r a t i o n . On the preoperative i m a g e s the n i d u s of t h e A V M s s h o w e d the l o c a l i z e d d e f e c t s in a l l c a s e s . Perifocal low accumulation areas detected in f i v e c a s e s w e r e c o n s i d e r e d as low p e r f u s i o n a r e a s d u e to t h e s t e a l p h e n o m e n o n , a n d in t h r e e of f i v e c a s e s t h e y c h a n g e d i n t o m a r k e d h i g h a c c u m u l a t i o n on t h e next d a y of t h e operation and diminished a f t e r a week. It's c a u s e was c o n s i d e r e d as the p o s t o p e r a t i v e temporary hyperperfusion after the removal of the AVMs, according to the n o r m a l perfusion pressure breakthrough theory of Spetzler's. 1-123 IMP b r a i n S P E C T was q u i t e u s e f u l to d e t e c t t h e p o s t o p e r a t i v e hyperperfusion of t h e A r M s which sometimes caused fatal complications.

S20

Remote cortical effects of deep lesions involving the pyramidal tract: a rCBF study using 99mTc-HMPAO and SPECT. M. Rubinstein. J. Braeckeveldt*, A, Collier-Geulette*and J. Abramovici. Departments of Radioisotopes and Neurology*, I.M.C. Ixelles, Brussels, Belgium. Homolateral cortical hypoperfnsion (CH) involving motor area has been described in patients with subcortical lesions (SCL) and hemiplegia. Most of these lesions involving the basal ganglia, CH is considered as "functional" and attributed to the interruption of the cortico-striato-thalamo-cortical circuit. On the other hand the disruption of the axona is known to have dramatic remote physiological consequences on the neuron body. Thus a lesion strictly limited to the pyramidal tract (PT) might be associated with a hypoperfnsion of the motor cortex. In order to test this hypothesis, we reviewed the 99mTcHMPAO tomoscans (25 mci; 60 frames of 20 s. on 360 ~ of 12 patients with recent hemiplegia (onset of the symptoms < 2 weeks) and SCL. CT showed evidence for basal gaglia (8) and capsular (4) involvement. Additionnally we studied 1 patient with a pyramidal syndrom due to a more distal lesion: a recent onset (<48 h) vascular injury of upper mid-brain (Weber syndrom). In all 12 patients with SCL there was a significant CH (difference of activity >15 % of the symmetrical area) even in those 4 with a lesion limited to internal capsule on CT. On the opposite, the patient with a pure PT lesion had normal sustenterial rCBF SPECT. In conclusion, a normal cortical perfnsion pattern in the only case where a pure acute PT could be demonstrated, which is indeed very rare, suggests the absence of remote cortical effect. Consequently, CH in patients with hemiplegia and SCL indicates cortico-striato-thalamo-cortical circuit involvement, even when CT shows strictly capsular lesions.

Sunday,

August26,1990

079

080

CEREBRAL B L O O D F L O W / C B F / I N P A T I E N T S W I T H BRAIN-STEM SYMPTOMS. LESZEK KROLICKI.

T1-201 3PECT FOR EVALUATIONOF BRAIN TUMORS AS C O ~ E D WITH 1-123-1MP SPECT AND F-18-FDG PET N. 0riuchi, T. Inoue, K.Tomiyoshi, T. Shibasaki, T. Imai and Y.Sasaki, Gunma Univeraity, Maebashi, Japan

Dep.

of N u c l e a r

~edicine,Medicsl

School

of

Warsaw, Warsaw, Poland. The aim o f t h i s s t u d y wss to i n v e s t i g a t e the CBF changes

in patients

with

symptoms

of brain-stem lesion.CBF was measured b y using Tc-99m-H~-PAO and SPECT method. Side to side ratios from different brein s t r u c t u r e s e n d g l o b a l u p t a k e o f t h e tracer i n t h e cerebral hemispheres / f r o m t h e p l a n a r A P scan/ was c a l c u l a t e d . G l o b a l u p t a k e index / B e k i e r et e l . / w a s c a l c u l a t e d a s e n u m b e r of counts/pixel/ImCi appliceted activity/ 1 . 7 3 m 2 . V e r t e b r a l a r t e r i o g r a p h y and CT were also performed. T h i s s t u d y i n v e s t i g a t e d C B F i n 12 n o r m a l c o n t r o l s a n d 20 p a t i e n t s w i t h c l i n i c a l l y d e f i n e d : a t a x i a , n u c l e a r nerve palsy/III, IV,VI/, dyssrthria, dyspnoe. R e s u l t s : CT was p a t h o l o g z c o n l y i n 3 c a s e s /hypodense area or a t r o p h y of t h e one c a r e bellar lobe/.Arteriography was normal in all c a s e s . C B F studies were p a t h o l o g i c i n 16 patients: An asymmetry in H~-PA0 uptake between both cerebeller hemispheres w a s observed i n 15 c a s e s . I n 8 c a s e s a d d i t i o n a l l y a decrease of global HN-PA0 uptake index was noted.In one p a t i e n t a n a s y m m e t r y i n t h e territory of the basal ganglia was observed. In conclusion: An asymmetry in the H~-PA0 uptake between both cerebeller hemispheres c a n b e o b s e r v e d , a s a n e f f e c t of b r a i n - s t e m d y s f u n c t ion.

Clinical usefullness of TI-201 SPECT(TI) for evaluation of brain tumors was studied in comparison with 1-123-1MP SPECT(IMP) and F-18-FDG PET(FDG). TI and IY~P were performed in 40 patients with central nervous system diseases. In 14 patients FDG were also performed. T h e SPECT was taken using a ring type machine (Shimazu Corp. Ltd. ) and PET with neuro PET (Hitachi Comp. ). Twenty one out of 32 patients with brain tumors showed increased accumulation of TI in tumor sites. Most of these cases were found to have malignant tumors including glioblastoma, grade3 astrosytoma, germinoma~ malignant shwannoma and metastatic brain tumor. Twenty seven of the 32 cases(84.h%) did not accumulate IMP in the tumors. Eight out of 12 tumor cases revieled increased regional metabolic rates of glucose (rCMRgl) in tumors by PET study. All of these 8 cases showed increased uptake of TI in the tumors. IMP shewed decreased radioactivity in the tumors in ii of the 12 cases. In 2 non-tumor cases TI and IMP did not accumulate in the lesions and no evidence of increased rDMRgl was seen. In the lesions surrounding tumors no accumulation of TI and IMP ~as observed. Combined images of TI with IMP resembled FDG images in patients with malignant brain tumors. Our results indicates that TI SPECT may prove useful for the detection of viable malignant tumor tissues in the brain and that combined images of TI and IMP may serve to substitute FDG PET for the evaluation of brain tumors.

081

082

CEREBRAL BLOOD FLOW IN MENINGIOMA BEFORE AND APTER SURGERY EVALUATED WITH A BRAIN DEDICATED SPECT, A. Soricelli, R. Spaziante, L.Mansi, C. Irace, A. Postiglione and M, Salvatore. Univ. of Naples, National Council of Research, National Cancer Institute G. Pascale, Naples, Italy.

CROSSED CENEBELLAR DIASCHISIS (CCD) AFTER CARBAMAZEPINE (CBZ) THERAPY IN PATIENTS WITH PARTIAL EPILEPSY.

Cerebral blood flow (CBF] by means of SPECT is a well established p a r a m e t e r f o r the d e t e r m i n a t i o n of b r a i n p e r f u s i o n . I n t h i s work we h a v e e v a l u a t e d CBF in 14 p a t i e n t s (8F,6M] w i t h meningioma b e f o r e and a f t e r s u r g e r y . CBF h a s been s t u d i e d w i t h a s i n g l e s l i c e B r a i n D e d i c a t e d SPECT (Tomomatic 32, Medirnatic Copenhagen) u s i n g t h e Xenon-133 i n h a l a t i o n t e c h n i q u e - 740 ~/Bq/lt air -. B e f o r e s u r g e r y , t h e flow s t u d y has been p e r f o r m e d a f t e r a s e l e c t i v e d i g i t a l a n g i o g r a p h y and a CT s c a n . The t o m o g r a p h i c l e v e l w h e r e to p e r f o r m e t h e CBF s t u d y was i d e n t i f i e d by the CT s c a n . CBF was i n c r e a s e d in t h e n e o p l a s t i c region in 7 p a t i e n t s , and r e d u c e d i n t h e r e m a i n i n g , as cmpared to the c o n t r a l a t e r a l area. All patients w i t h h i g h CBF v a l u e s i n t h e m e n i n g i o m a r e g i o n had e l e v a t e d t e n d e n c y to bleed during surgery, while those with low CBF had low bleeding. CBF and CT were performed approximatly 10 days and 6 months a f t e r s u r g e r y . In t h e e a r l y p o s t s u r g i c a l s t u d y CBF was r e d u c e d i n t h e o p e r a t e d a r e a , while in the l a t e s t the low flow showed a : ' p a r t i a l r e g r e s s i o n . C T r e t u r n e d a l m o s t to normal a f t e r 6 m o n t h s . I n our o p i n i o n , CBF s t u d i e s u s i n g t h e Xenon-133 t e c h n i q u e , i s u s e f u l b e f o r e the r e m o v a l of t h e tumor to i d e n t i f y t h e s u r g i c a l r i s k of b l e e d i n g , and f u r t h e r i n v e s t i g a t i o n s need to e v a l u a t e t h e s i g n i f i c a n c e of low CBF s i x m o n t h s a f t e r s u r g e r y in t h e l e s i o n a r e a .

Sunday, August 26, 1990

G'P'Sechi'F'Oore'G'R~ ! giu,A,Arru,A.R.Casu,G.Madeddu. Institutes of Neurology and Nuclear Medicine, University of Sassari - I t a l y We studled in, 3 epileptic patients with an electroencephalographlc (EEG) glndling of l e f t fronto-temoora! focus in i n t e r c r i t i c a l stage, r~ gional cerebral blood flow(rCBF)by SPECTafter J.v. lnjec~on ~ 25-30~i of Tc-ggm-HM PAO. lhe test was pe~Fopmed, in pesting cJnditlon, sixty mlnutes after cl{nical and EEG recordings as well before as after one month of CBZ therapy (600 to BOO mg q.d.). No patient was receiving other drugs. Brain CT and neurological examination were normal in all instances. Before treatment, SPECT sho~ed a decreased rCBF in the l e f t Pronto-temporal region in two cases and in the l e f t parleto-temporel region in one case. After one month on CBZ, at serum levels between 6.5 and 7.8 ~g/ml, SPECT study showed a l e f t fronto-parieto-temporal hypoperfusion in all cases; in one patient a Focal decrease of rCBF was also ascertained in the controlateral right parietal region. In addition, a marked hypoperfusion in the right cerebellar hemisphere was present in a l l instances. This phenomenon of CCD was previously described {n acute infarctions, hemorrhages and tumors and was associated with frontal, parietal and putamlnal lesions. I t was reported also in epilept{c patients after the Wada test with sodium amytal and occasionally on phenytoin and barbiturate treatment. Concerning our knowledge, CCO observed in our brain CT negative cases Following CBZ therapy was not previously described. These findings suggest that CBZ depress the cortico-ponto-dentatethalamo pathway ; such a depressing action may be a useful tool for better understanding the neuronal basis of CBZ antiepileptlc mechanlsm.

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083

084

Tc-99m HM-PAO SPECT IN THE EVALUATION OF PATIENTS WITH A REMOTE HISTORY OF TRAUMATIC HEAD INJURY: A COMPARISON WITH COMPUTED TOMOGRAPHY. B. Grav. M. Ichise, D. Chung, J.C. Kirsh, and W. Franks. University of Toronto, Toronto, ON, Canada.

PATHOPHYSIOLOGY

OF SPONTANEOUS

ORTHOSTATIC

HEADACHE:

CLUES FROM ISOTOPIC CISTERNOGRAPHY. J. Verreault, M.D., J. Reiher, M.D., E. Frenette, M.D., G. Bisson, M.D., P. Deslauriers, M.D. Dept. of Nuclear medeeine of radiobiology and service of Neurology, University of Sherbrooke, Canada.

Traumatic head injury is a major cause of morbidity and mortality. Sequelae are often subtle and difficult to document by stan dard imaging techniques. The present study chose a newer imaging modality (Tc-99 HM-PAO SPECT) to evaluate brain parenchyma. These results were compared to those from computed tomography (CT). SPECT imaging was performed 15 mln. ailer I.V. injection of 20 mCi (740 M Bq) of Tc-99m HM-PAO using a rotating gamma camera. Data were processed to reconstruct one pixel th ick (4 mm) slices in the coronal, saggltal and transaxial planes using a modified Harming back projection filter with attenuation correction and a zoom factor of 1.8. Semiquantificatlon analyses were performed on transaxial images using 4x4 pixel ROIs over multiple regions in each lobe: frontal-6, temporal-2, parietal-4, and occipital-2, and 1 region in each basal ganglia. These values were compared with those from the cerebellum to give cortical/cerebeUar perfusion ratios. Patients with no prior history of cranial surgery or multiple head trau ma (n=38, age range 15-45) were imaged with SPECT and CT at an interval greater t h a n 6 months aller their head injury. The majority of cases (24/38) had concordance of the results, i.e. findings were similar on both modalities, In 24% of the cases an abnormality was seen on the SPECT images only. However in 8% of the cases an abnormality seen on the CT was not apparent on the SPECT. The CT findings in these latter cases were of mild atrophy. The two modalities, SPECT and CT, look at anatomy and perfusion respectively, Thus, as shown in the present study, they complement each other in the detection of subtle abnormalities in the brain parenchyma. This might prove useful in the clinical management of such patients.

The pathophysiology of spontaneous orthostatic headache (SOH) is yet unclear. SOH is a rare syndrome characterized by recurrent bouts of headache over a period of 3 to 5 weeks. The cephalalgias are triggered by standing and relieved by recumbency. A markedly lowered eerebrospinal fluid (CSF) pressure is commonly observed. Treatment has consisted mainly of prolonged bed rest; epidural blood patch (EBP) has been proposed recently for more rapid control of the headache. Identification of distinctive eisternographie findings in our laboratory relevant for the understanding of SOH symptomatology and for the rational selection of EBP, as a preferred mode of treatment prompted this report. A radionaclide cisternography (RC) was carried out in 3 of 7 patients with SOH. In each one, but in none of the controls referred for investigation of low pressure hydrocephalus, a characteristic proeminent thoraeolumbo-saeral Christmas tree pattern was observed along with early urinary tract excretion of the tracer. Following treatment with EBP; durable relief from headache was immediate. An attenuated Christman tree pattern, more limited to lumbo-sacral segments was observed in the only one control RC performed. Those eisternographic and clinical data suggest that an accelerated CSF spinal reabsorption can readily explain the decreased CSF pressure and symptoms of untreated SOH. it a p p e a r s ithat initially increased spinal CSF clearance is sufficiently corrected by EBP to aeeount for headache subsiidence,

085

086

6-ENDORPHIN AND CORIISOL LEVELS IN PLASMA AND CEBEBBOSPINAL FLUIO(CSF) IN EXPERIMENTAL SPINAL CORD INJURY. p.L.Oeriu,V.Petruzzi,P.Melis,M.A.Caria,F.Dore,A.Arru,P.Vargiu,M.g. Azz~ na,A.R.Casu,G.Madeddu. I n s t i t u t e s os Neurological Rehabilitation,VeteL inary Surgery,Human Physiology,Nuclear Medicine. Universities os Turin and Sassari - Italy

CLINICAL APPLICATIONS OF BRAIN PERFUSION IMAGING WITH 99mTC-HM-PAO Lin Xiang-Tong, Song Wen-Zhong, Liu Yong-Chang, Zhu Tong, Liu Hong-Gong, Xi Zun-Qin, Xue Fang-Ping. Department of Nuclear Medicine, Huashan Hospital, Shanghai Medical University, Shanghai 200040, P.R. China.

To f u r t h e r investigate the pathophyslologic role of B-endorphin in spinal trauma,we measured the opiod by RIA both in plasma and CSE in 45 adult rabbits of both sexes:f5 had cervical laminectomy(C5-CN)and spinal trauma (according Allen method)with severe hypotenslon,shock and t e t r a p l e g i a (group i ) ; 1 5 had lumbar laminectomy(LB-L5)and spinal trauma with paraplegia (group 2)and the remaining 15 had only cervical laminectomy(C5-C8) and served as controls. Blood and CSF samples were drawn percutaneous]y in the anaesthetized rabbits from marginal ear vein and from clsterna magna respe~ t i v e l y , 39 i and 120Wollowing surgery and spinal trauma while samples taken seven days preceding the experiment served as basal O-endorphln values.ln Bl animals 7 from each group,we also measured c o r t l s o l which always inc~ases in stress condition. In plasma 8-endorphin s i g n i f i c a n t l y increased in a l l the rabbits but the variations were higher in group i when compared to the other groups slnce basal values (62.2 ! 15.5 pg/ml)markedly rose a f t e r sp! hal trauma and shook to a peak o? 135.4 • 41.3 pg/ml at 301 . Cortisol present ed the same trend but the maximum increase was at 120'. In the CSF a s i g n i f i cant (p
S22

200 patients with central nervors system diseases were studied using 99mTC-HM-PAO and SPECT, including: Parkinson's disease (PD) 47 cases; Vascular headache 69 cases; CVD 34 cases; Epilepsy 26 cases; Head truma i0 cases; Brain tumor 5 cases; Other 9 cases. Some of cases had compared with the results of MRI, X-CT and EEG. THe positive percentage of PD is 61.7 %. Showing decreased perfusion in local cerebral and basal ganglla. 4 cases had lower parfusion in cerebellum. The positive percentage of headache is 46.4 %, picture showed variable. The images of CVD showed decrease per fusion, luxury perfusion and the phenomenon of "diaschisis". The positive percentage is 79.4 %. The most foci of patients with epilepsy localized in temporal lobe and had closed relation to the results of EEG. Brain tumor showed decreased uptake of tracer. The blood perfusion pictures of brain showed vareable after head truma and widespread decrease ("watershed" sign) in patients sufering from Alzheimer' s dementia. In the conclusion, the clinical significance of brain perfusion imaging with 99mTC-H~l-PA0 was discussed.

Sunday, August 26, 1990

087

088

OBSERVING OF IMAGE OF BRAIN BLOOD PERFUSON IN PARKINSON 'S DISEASE Song Wen-Zhong, Lin Xiang-Tong. Department of Nuclear Medicine, HuaShan Hospital, Shanghai Medical University, Shanghai 200040, P.R. China.

CEREBRAL PERFUSION CHANGES IN SCHIZOPHRENIA PATIENTS USING Tc-99M HEXAMETHYLPROPYLENE AMINE OXIME (HM-PAO). A. Sehweil, S. Ei-Hilu, S. Jahan, E. Higazi, M. Salhat, S. Ai-Mohannadi and H.M. Abdel-Dayem. Dept. of Nuclear Medicine, Kuwait Cancer Control Center and Faculty of Medicine & Dept. of Psychiatry, Ministry of Public Health, Kuwait.

Forty patients with parkinson's disease were studied using 99m-TC-HM-PAO and SPECT. 62.5 % showed abnormal blood perfusion. 55 % showed local decreased blood perfusion of cerebral cortex. 22 % showed asynnnetric decreased blood perfusion in basal gaglia. 10 % shewed lower uptake of tracer in cerebellum. The abnormality of brain blood parfusion may be the changes of the multifactorial pathophysiology of the disease.

Schizophrenia is known te be associated with brain atrophy. We studied cerebral perfusion changes in 20 patients with clinically documented diagnosis of Schizophrenia. Mean age was 29.6+4.2 years. All patients were on medication. The aim of the study was to detect the extent of cerebral perfusion abnormalities in such group of patients. Single photon emission computerized tomography (SPECT) was performed 15 min after i.v. inj ef 555-740 MBq Tc-99m HM-PAO. The results showed a spectrum of abnormalities as follows: diffuse decreased perfusion involving the majority of one side or both sides of the brain in 6 pts. 37 focal areas of perfusion changes less than one lobe was seen in the remaining 14 pts : 28 foci (78%) were decreased perfusion and 9 foci (24%) foci of increased perfusion. The incidence of the fecal lesions were : parietal 12(32%), occipital 8(22%), temporal 7(19%), frontal 5(14%), basal ganglia 3(8%) and cerebellum 2(5%). This study confirms that Tc-99m HM-PAO SPECT study is a sensitive method for detecting the extent of cerebral perfusion abnormalities in Schizophrenia patients.

08s

090

Tc-99m H M P A O S P E C T ANALYSIS OF H A L O P E R I D O L E F F E C T S ON R E G I O N A L BRAIN FUNCTION IN SCHIZOPHRENIA. H. Matsuda, I. Jibiki, K. Kinuya, K. Hisada, N. Yamaguchi. K a n a z a w a University Hospital, Kanazawa, Japan.

CORRELATIONS

The specific p r o p e r t y of Tc-99m H M P A O 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 S P E C T system (Toshiba, GCA9300A). In three schizophrenic patients 555 MBq of H M P A O was injected. Then l O m ~ of H was intramuscularly injected at 3 mln p.i. of HMPAO. Immediately after the 1st S P E C T study (baseline) 925 MBq of H M P A O from the same vial w a s additionally injected. Three minute later the 2nd S P E C T study was performed. After reconstruction the 1st S P E C T images were subtracted from 2nd images to obtain images during the H treatment. E E G was simultaneously monitored throughout the study. Regional flow c h a n g e s by H were quantitatively estimated in frontal, temporal, occipital, and parietal cortices. These three schizophrenic patients showed quite consistent responses to H in spite of no E E G change. Right to left count ratios were 0.96• (mean • SD) at baseline and 1.12• at H for all regions. Frontal to temporal and occipital count ratios were 0.92 • and 0.93 • at baseline, and 1.09• and 1.15 • 0.13 at H, respectively, for both hemispheres. These results suggest that the antipsychotic d r u g has substantial effects on regional brain function in schizophrenia. The d r u g may improve frontal lobe hypofunction and suppress temporo-occipital hyperfunction especially in the dominant hemisphere.

This work was undertaken in o r d e r to d e t e r m i ne wether 1/2 q u a n t i t a t i v e HmPAO SPECT data were correlated with Neuropsycholegical Patterns (NPP) i n A l z h e i m e r ' s disease (A.D). We studied 27 patients with "probable A.D" (NINCDS ADRDA), S c o r e s w e r e u s e d te a s s e s s e d Apraxia (Ap~, Anosognosia (A), spatial and v i s u a l A, i d e o m o t o r , ideational and construetionai Ap, and language. HmPAO SPECT tomegramme were recorded with the "Tomomatic 64". V a l u e s w e r e q u a n t i f i e d u s i n g an i n t e r n a l standard according with Kuhl's method(I987) and indexes computed in left a n d r i g h t frontal and p a r i e t a i c o r t e x . A Right/Left (R/L) R a t i o was a l s o c a l c u l a t e d . Statistical assessments were performed using non parametrioal tests. The R / L r a t i o w a s lower in p a t i e n t s w i t h Ap ~p < O . O 2 ) , ideomotor, ideatory and constructionnal Ap ( p < O . O 1 ] , A a n d S p a t i a l A (p < 0 . 0 1 ) . C o n v e r s | y we f a i l e d to f i n d a n y correlation b e t w e e n the R / L r a d i o a n t the severity of the apriasia. So we f o u n d a s t r o n g correiation b e t w e e n a lower a c t i v i t y in the right hemisphere a n d NPP u s u a l l y a s s o c i a t e d with right hemisphere abnormalities. T h e lack of c o r r e l a t i o n with aphasia could be linked with the c h o i c e of a g l o b a l s c o r e of a p h a s i a w h i c h lead to a loss Of i n f o r m a t i o n s and the fairiy poor dispersion or the a p h a s i a s c o r e : 2 3 P / 2 7 rLad a s c o ~ e o t 1 or 2 .

Sunday, August 26, 1990

BETWEEN NEUROPSYCHOLOGICAL

PAT-

TERNS AND TC-HmPAO SPECT SEMI QUANTITATIVE DATA IN A L Z H E | M E R ' S DISEASE. LEYS D . . HUGLO D . , SOETART G., PETIT H., VERGNES R , . S T E I N L I N G M. C.H.R.U. ; Lille ; FRANCE,

S23

091

092

Tc-99m HM-PAO SPECT IN C H R O N I C FATIGUE SYNDROME. M, Ir162 I.C. Salit, S.E. Abbey, D. C h u n g , B. Gray, J . C . Kirsh, a n d M. F r e e d m a n . University of Toronto, Toronto, ON, C a n a d a .

DOPAMINE D-2 RECEPTOR IMAGING WITH 1-123 2'I O D O S P I P E R O N E AND S I N G L E P H O T O N E M I S S I O N C O M P U T E D TOMOGRAPHY. Y. Iwasaki, Y. Yonekura, H. Saji, Y. Iida, N. Matoba, T. Eujita, N. Tamaki, S. Yamaguchi, H. Fukuyama, J. Konishi, and A. Yokoyama. Kyoto University, Kyoto, Japan.

The C h r o n i c Fatigue S y n d r o m e (CFS) is a d i s a b l i n g illness o c c u r r i n g p r e d o m i n a n t l y in y o u n g e r w o m e n a f t e r a n a p p a r e n t a c u t e infection. The c a u s e of CFS is u n k n o w n , b u t t h e r e a r e b o t h cognitive a n d psychological a b n o r m a l i t i e s , We e v a l u a t e d 6 0 p a t i e n t s with CFS a n d 15 n o r m a l c o n t r o l s {NC) w i t h T c - 9 9 m HM-PAO SPECT. T h e p a t i e n t s i n c l u d e d 4 5 females a n d 15 m a l e s with a n average age of 3 6 y e a r s (18-49 years). T h e NC g r o u p c o n s i s t e d of 7 females a n d 7 m a l e s with a n average age of 32 y e a r s (25-48 years). SPECT i m a g i n g w a s p e r f o r m e d 15 m i n u t e s a f t e r i n t r a v e n o u s injection of 2 0 mCi (740 MBq) of T c - 9 9 m HM-PAO u s i n g a r o t a t i n g g a m m a c a m e r a . The d a t a were p r o c e s s e d to r e c o n s t r u c t o n e pixel t h i c k (4mm) slices in t h e c o r o n a l , saggital a n d t r a n s a x i a l p l a n e s u s i n g a modified H a n n i n g b a c k p r o j e c t i o n filter w i t h a t t e n u a t i o n c o r r e c t i o n a n d a z o o m factor of 1.8. S e m i q u a n t t f i c a t i o n a n a l y s e s were p e r f o r m e d o n t r a n s a x i a l i m a g e s u s i n g 4 x 4 pixel ( 1 6 x 1 6 m m ) ROI's over 6 r e g i o n s in e a c h f r o n t a l , 2 r e g i o n s in e a c h t e m p o r a l , 4 r e g i o n s in e a c h p a r i e t a l , a n d 2 r e g i o n s in e a c h occipital lobe, respectively, p l u s 1 region in e a c h b a s a l g a n g l i a a n d in e a c h c e r e b e l l u m to c a l c u l a t e r e g i o n a l c o r t i c a l / c e r e b e l l a r p e r f u s i o n ratios. While t h e r e w a s c o n s i d e r a b l e overlap b e t w e e n CFS a n d NC g r o u p s , t h e CFS g r o u p s h o w e d s i g n i f i c a n t l y lower a v e r a g e regional p e r f u s i o n ratios, p a r t i c u l a r l y in the s u p e r i o r frontal lobes (right 0 . 8 8 2 + 0.031 [NC] vs. 0 . 8 3 6 + 0 . 0 6 0 [CFS], p = 0.004; left 0 . 9 1 6 + 0 . 0 4 4 [NC] vs. 0 . 8 6 0 + 0 . 0 6 2 [CFS], p = 0.001) a n d left b a s a l g a n g l i a (0.840 + 0 . 0 3 9 [NC] vs. 0 . 7 9 3 + 0 . 0 6 2 [CFS], p = 0.005). T h e s e findings a r e similar to o t h e r studies examining patients which major depressive episodes (MDE), T h i s is c o n s i s t e n t w i t h o u r o t h e r s t u d i e s s h o w i n g t h a t t h e r e are clinical similarities between MDE a n d CFS.

A radioiodined butyrophenone derivative, 2'-iodospiperone (ISP), has been demonstrated to have high affinity to dopamine D-2 receptor. In this study, we extended our work to in vivo mapping of dopamine D-2 receptor with single photon emission computed tomography (SPECT). ISP was labeled with 1-123 by iodine exchange reaction, and purified by h i g h p r e s s u r e liquid c h r o m a t o g r a p h y for c l i n i c a l use. Labeling yield was 20-35%, and radiochemical purity was greater than 98%. The specific activity was 11-15 GBq/micro mol at the time of injection. Following an intravenous injection of 111-222 MBq of ISP, dynamic SPECT imaging was performed for 60 min followed by late SPECT i m a g i n g at 2 hr and 4 hr by m e a n s of a multi-detector SPECT scanner. The early SPECT images revealed homogeneous distribution of ISP in the brain in proportion to cerebral blood flow. However, the a c t i v i t i e s in the c e r e b r a l c o r t e x and c e r e b e l l u m decreased by time, while those in the basal ganglia were fairly constant f o r 2 hr a n d d e c r e a s e d thereafter. Maximum uptake ratio of b a s a l ganglia/cerebellum was obtained at 2 hr a f t e r injection. In conclusion, ISP is a promising radioiodinated ligand for mapping dopamine D-2 receptor with SPECT. ISP SPECT imaging may be a useful tool for diagnosis of neuropsychiatric diseases with altered dopamine receptor function.

093

094

CEREBRAL HEMODYNAMICEFFECTS OF THE ACUTE ADMINISTRATION OFC<-METHYLDOPATE IN PATIENTS WITH ESSENTIAL HYPERTENTION. Gregoire I . , Salomez J-L, Verguhlt, Steinberg M. Service central de medecine nucleaire et neurologie C; L i l l e , l a b o r a t o i r e MSD, France.

ASESSMENT OF CHANGES IN REGIONAL CEREBRAL BLOOD FLOW BY DOUBLE INJECTION OF Tc-99m HM-PAO AND SPECT. N. MATOBA, Y. IWASAKI, Y. YONEKURA, T. FUJITA, and J. KONISHI. Department of N u c l e a r Medicine, Kyoto University Faculty of Medicine, Kyoto, Japan.

Regional cerebral blood flow (RCBF) measurement coupled with vascular r e a c t i v i t y tests to 1 gr of Acetazolamid have been done with SPECT a f t e r the i n h a l a t } o n of Xe133 (tomomatic 64), 24 hours before and two hours a f t e r the perfusion o f 500 mg ofcK-methyldopate (AHD) in 15 patients with non treated essential hypertension. A r t e r i a l pressure and Pa C02 were measured continuously. ROl's local and global were studied f o r each exam. Results were analysed by variance analysis (Friedman). With ADF, the s y s t o l i c pressure is lowered ( P < . 0 5 ) but not the RCBF. However, the mean hemispheric r e a c t i v i t y was s i g n i f i c a n t l y higher (P<.OI at OM*5cm, p < 0.005 at OMt9cm). AD.q perfusion did not produce s i g n i f i c a n t m o d i f i c a t i o n of the reqional RCBF - I t suggests t h e absence of d i r e c t d i l a t a t i o n e f f e c t on the cerebral vessels. However, i t causes an increase in a l l t e r r i t o r i e s o f the cerebral r e a c t i v i t y index to acetazolamid, meaning an increase in the d i l a t o r y capacity of cerebral vessels.

S24

Regional cerebral blood flow (rCBF) and its changes by acetazolamide were measured with double injeeion of Tc-99m labeled d, l-hexamethyl-propyleneamine oxime (HM-PAO) and SPECT. Control rCBF was o b t a i n e d by intravenous i n j e c t i o n of 7 mCi of T c - 9 9 m H M - P A O followed by SPECT scan for 15 min. Second dose of Tc99m HM-PAO (20 mCi) was administered 20 min after the acetazolamide (10mg/kg) administration, and SPECT scan was p e r f o r m e d for I0 min. P o s t - l o a d i n g rCBF was o b t a i n e d by s u b t r a c t i o n of the control data with correction for the physical decay of Tc-99m. Control and post-loading rCBF SPECT images were calibrated for the i n j e c t e d activity as w e l l as for the d a t a acquisition time. In order to validate this approach, the stability of the Tc-99m activity in the brain was e x a m i n e d by a c e t a z o l a m i d e administration without second i n j e c t i o n of HM-PAO. Both d y n a m i c planar imaging and SPECT scan demonstrated no significant c h a n g e s in t h e b r a i n a c t i v i t y by a e e t a z o l a m i d e loading. Among 4 cases with "Moye-moya disease", only one case with unilateral occlusion of internal carotid artery showed more profound decrease in HM-PAO uptake in the diseased hemisphere by post-loading rCBF, and 3 other cases did not show any c h a n g e s in r e g i o n a l hypoperfusion pattern. These results may suggest an abnormal cerebrovascular reactivity in "Moya-moya" disease. Tc-99m HM-PAO SPECT with double injection technique is a valuable tool in evaluating the rCBP changes by acetazolamide loading as well as by various stimulation studies.

Sunday, August 26,1990

095

096

CEREBRAL OXYGEN CONSUMPTION MEASUREMENT BASED ON A SINGLE OXYGEN STUDY BY PET.

A NON-INVASIVE QUANTITATIVE MEASUREMENT OF CEREBRAL BLOOD FLOW USING N-ISOPROPYL-[I-123] p-IODOAMPHETAMINE (IMP) AND SPECT. Y. Araki, S. Imai, T. Uno, Y. Imao, T. Andeh, N. Sakai and H. Yamada. Department of Neurosurgery, Gifu University School of Medicine, Gifu, Japan.

S. Ohta, E. Meyer, A. Gjedde. Positron Imaging Laboratories, Montreal Neurological Institute, Montreal, Canada. A current model of blood-brain exchange of oxygen assumes that the initial clearance of labeled oxygen (/i"i) from blood to brain equals the net rate of oxygen clearance. CMRo2 may be directly calculated as the product of KI and the arterial concentration of oxygen by equation (I) because the clearance is independently estimated and the activity of recirculating water has little effect on the estimation of K~. C~(1) is the total radioactivity in blood and M ~ ( t ) the extravascular radioactivity of brain tissue. The table shows CMRo~ estimated directly by equation (1) with* and without** correction for recirculating water.

To compute CMRo2 image, we applied a 3-weighted integration method to equation (1) which was expanded to include a term for the blood activity ignored in the ordinary 2-weighted integration method in which there is no CBV correction (]70). CMRo#2 (see table) was calculated by this method. There is a significant correIation among the three CMRo2 values. Hence, CMRo~ images can be made from a single oxygen study by the 3-weighted integFation method.

A non-invasive quantitative method using N-isopropyl -[I-123]p-iodoamphetamine(IMP) was described for assessing regional cerebral blood flow(rCBF). Twenty four cases with cerebral lesions underwent the SPECT Xe-133 inhalation method(Xe-SPECT) and IMP-SPECT using a Tomomatic 564. In the IMP-SPECT cases, sequential imaging was performed 9.7!2.1(meaniSD) min, 21.4• min and 221.0• min after the IMP intravenous injection (El image, E2 image and D image). The IMP-uptake value (counts /pixel/sampling time) in the region of interest (ROI), which was chosen in the non-affected cortex in the middle cerebral artery territory(MCA cortex), was counted on each image(E1 value, E2 value and D value) and the EI/D ratios and E2/D ratios were consequently caliculated. There were significant correlations noted between both the EI/D ratios and the E2/D ratios, and the absolute values of rCBF in the non-affected MCA cortex: y=A• (y:rCBF, x:EI/D ratio(E2/D ratio), A=55.1(75.4), B=4.0(-21.7), r=0.772(0.793)) Using these equations, a 66 years old female with subarachnoid hemorrhage and ruptured anterior communicating aneurysm was studied by sequential Xeand IMP-SPECT. There were similar changes between the rCBF values obtained by Xe-SPECT and those deduced by IMP-SPECT. This simpler rCBF quantitative method was found to be clinically useful and non-invasfve.

097

098

REGIONAL CEREBRAL-BLOOD-FLOW MEASUREMENT BY MEANS OF N-ISOPROPYL-P IODOPHETAMINE AND SPECT USING A ROTATING GAMMA CAMERA: A CLINICAL EVALUATION OF A SLANT-HOLE COLLIMATOR. Hiroshi Kurokawa* and Kiyohiko Tamura. Department of Radiology, Senboku Kumiai Hospital*, Omagari, Department of Nuclear Medicine, Akita University, Japan.

C E R E B R A L H E M O D Y N A M I C S S T U D I E D BY F A C T O R A N A L Y SIS O N B R A I N R A D I O N U C L I D E A N G I O G R A P H Y . K . N a k a z a w a ~ k. Ishii, F . S a k a i ~ K . T a d o k c r o ~ K . Y o d a and T . M a t s u b a y a s h i . Kitasato University~ S c h o o l of M e d i c i n e ~ S a g a m i h a r a , K a n a g a w a , Japan .

dM~(t) _ K~C~(t) - k2M~(t) dt (#mol hg-' min-') I CMR~7 CMR~* Normocapnia (n=4) 1474- 8 148=I=8 Hypocapnia (n=4) 1564-11 153:Ell

(1)

CMRo# 142+ 8 149+11

N-isopropyl-p-I-123-iodoamphetamine (IMP) can be used to evaluate the regional cerebral blood flow (rCBF) using singlephoton-emission computed t0mography (SPECT). However, highquality images of conventional SPECT using rotating gamma camera have not necessarily been obtained because this system has a larger head-to-detector distance. Two hundred and seventy rCBF measurements were performed on 250 patients with ischemic cerebrovascular diseases using IMP and a rotating-gamma-camera SPECT equipped with a newly deve'~]oped slant-hole collimator (GCA-601E gamma camera, Toshiba Medl~eal Company). In the phantom study, the values of FWHM were 5.08 mm in the planar image and 20.07 mm at the phantom surface (center) in the SPECT image. A focal decrease of rCBF was observed in 90.0% of the cerebral infargtions. The rCBF decrease in a small infarction (10xl0 mm) in the caudate nucleus on X-ray CT could be detected on SPECT. The rCBF measurement using IMP and rotating-gamma-camera SPECF with a slant-hole collimator is not only noninvasive, with a superior inspatial resolution (1.7 mm/slice;total 64 slices), but also makes possible a three-dimensional evaluation of the entire brain. The SPECT using a digital rotating gamma camera with the newly developed high resolution slant hole collimator gives sufficiently high
Sunday, August 26, 1990

F a c t o r a n a l y s i s has b e e n w i d e l y u s e d to a n a l y z e the data of g a t e d c a r d i a c b l o o d p o o l and of K r - 8 1 m g a t e d p u l m o n a r y v e n t i l a t i o n . In this study~ f a c t o r a n a l y s i s w a s a p p l i e d to the b r a i n r a d i o n u c l i d e a n g i o g r a p h y to e v a l u a t e cerebral hemodynamics . A s c i n t i l l a t i o n c a m e r a ( M a x i 4OOT~ GE Co.) and m i n i c o m p u t e r ( S i m i s 3~ I n f o r m a t e k Co.) s y s t e m was used. The d e t e c t o r was p l a c e d over the h e a d of the p a t i e n t in a s u p i n e p o s i t i o n . The d a t a w e r e c o l l e c t e d by the c o m p u t e r for 90 sec in the f r a m e m o d e ( l sec i n t e r v a l ) f o l l o w i n g the i n t r a v e n o u s i n j e c t i o n of T c - 9 9 m RBC or T c - 9 9 m - H S A . The d a t a on f i r s t - p a s s t h r o u g h the b r a i n w e r e s m o o t h e d b y the s p a t i a l and t e m p o r a l filter. The s m o o t h e d d a t a w e r e t h e n p r o c e s s e d by f a c t o r a n a l y s i s . 11~ n o r m a l volu]~teers, the f a c t o r i m a g e w a s s i m i l a r ii~ r i g h t arld l e f t c e r e b r a l h e m i s p h e r e s . In p a t i e n t s w i t h c e r e b r a l i , f a r c t i o n ~ f a c t o r i m a g e was a b n o r m a l in the i s c h e m i c c e r e b r a l h e m i s p h e r e . In p a t i e n t s with Moyamoya disease(bilateral ICA o c c l u s i o n ) , f a c t o r image was abl~ormal in b i l a t e r a l f r o n t a l cerebral regions. The a p p l i c a t i o n of f a c t o r a n a l y s i s to the b r a i n r a d i o n u e l i d e allgiography p r o v i d e s a u s e f u l m e t h o d for e v a l u a t i n g c e r e b r a l h e m o d y n a m i c s in patieilts w i t h i s c h e m i c c e r e b r o vascular diseases.

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099

100

TRIDIMENSIONNAL STUDY OF CEREBRAL ACTIVATION INDUCED BY AUTOMATIC LANGUAGE. A. Mazingue; M. Rousseaux; D. Huglo; M. Steinberg. Service Central de medecine nucleaire; 59037, L i l l e , Cedex, France.

SUPERIMPOSITION OF TOMOGRAPHICIMAGES OF THE BRAIN: PRINCIPLES AND METHODOF A TECHNIQUE APPLIED TO 99m-TcHMPAO SPECT AND MAGNETIC RESONANCEIMAGING (MRI). Ph. Coubes*,***, PO Kotski**, M Rossi**, PH Frerebeau*, M Bal dy-Moul inier+. * Service de Neurochirurgie B, Centre Gui de Chauliac, Montpel I ier. ** Service de Medecine Nucleaire, Hospital Lapeyronie, Montpellier. ***Laboratoire d'Automatique et de Microelectronique, USTL-UA CNRS 371, MONTPELLIER. -~ Service de Neurologie, Centre Gui de Chauliac, Montpellier, France.

Cerebral blood flow (CBF) was measured a f t e r Xe-133 inhalation in 20 normal subjects during automatic language, without and a f t e r with oral expression. 3 types of d i f f e r e n t i a l mapping (flow v a r i a t i o n ) were obtained, showing the language elaboration, the oral language and his m o t r i c i t y . 25 Roi's were studied semi-quantitatively on each of them. The flow variations were analysed by the Wilcoxon test and the Principal Composent analysis (PCA). Our results show that the increase of the CBF is secondary to the superposition of the two a c t i v i t i e s : one peculiar to the structures involved in the language m o t r i c i t y , asymetrical, the other corresponding to the elaboration of the intern language implicating large zones of the cortex but also the striatum. I t shows also that the flow increase is i n s u f f i c i e n t to show the specific role of a cerebral region which appears c l e a r l y with the PCA analysis: so, the flow increase in the Broca's region for the language m o t r i c i t y is less q u a n t i t a t i v e l y than the frontal lobes but i t is completely isolated from the 24 others regions in PCA analysis.

Principles: In spite of i t s great c l i n i c a l i n t e r e s t SPECT imaging s t i l l suffers from the lack of spatial resolution. A rigorous method for the superimposition of anatomical images (MRI and CT) on the functional images resulting from SPECT and PET should improve their interpretation. Methodology: Spatial or geometric superimposition of 2 images is done through translation and rotation of the referential system of one image r e l a t i v e l y to the other. When the dimensions of the images are d i f f e r e n t , e l a s t i c superimposition can be achieved by the i n t r o duction of f i d u c i a r y points and/or appropriate computer processi nq. Application: We developed a headstall with an appropriate r e f e r e n t i a l system permittino and exact repositioning of the head under each imaging system. A common plane of reference could thus be i d e n t i f i e d , and the introduction of appropriate fiduciary points guided the reconstruction and the realignment of the images. This technique was used to properly l o c a l i z e the e p i l e p t i c foci ( i n t e r c r i t i c a l hypoperfusion) in 20 patients suffering from p a r t i a l epilepsy before neurosurgery for which such an anatomo-functional correlation is essential.

101

102

FILLING OUT PHeNOMenON WITH TC-99M D,L HEXAMETHYLPROP~INE OXIME (HM-PAO) BRAIN SPECT AT THE SITE OF MILD CEREBRAL ISCHI~4IA. K.Hayashida, T.Nishimura, S.Imakita, S.Kumita and T.Uehara. National Cardiovascular Center, Osaka, 565 Japan.

"HOT SPOT" LESIONS AS A SIGN OF POSTOPERATIVE INFLAMMATION? (TC-99m HMPAO BRAIN SPECT STUOIES AFTER EC-IG BYPASS SURGERY) L. P~vics~ L. Csernay, T. 06czi and M. Bodosi. Albert Szent-Gy~rgyi Medical University, Szeged, Hungary.

Although the distribution of Tc-99m HM-PAO in the brain said to be in flow-related manner without temporal change, we present the cases with leakage of Tc-99m ~M-PAO in the late image of brain SPECT (Filling out phenomenon) and clarify its clinical significance. SPECT data was obtained from by 64 projections for 15 sec into 64x64 matrix with STARCAM 400AC/T. The filling out phenomenon was observed in 7 out of 21 cases of cerebrovascular disease and 4 cases of arterio-venous malformation. The leakage of Tc-99m HM-PAOwas also confirmed by visual and semi-quantitative analysis. In the pharmacokinetics of Tc-99m HM-PAO in the blood, the percent dose of plasma fraction at 4 hours was reduced to 54% of activity at 30 min. The percent dose of brain blood could be predicted as 3.36%/1 at 30min. and 2.35%/1 at 4 hours after correction with hematocrit of the brain ~ The filling out phenomenon of Tc-99m HM-PAO was attributed to a significant reduction of blood activity of Tc-99m HM-PAO in the plasma. Since the initial image might mask reduced rCBF with an increase of rCBV, the late image would have an advantage in accurately evaluating rCBF from the clearance of Tc-99m }94-PAO bound to the plasma. Therefore, the filling out phenomenon of Tc-99m HMPAO with late image of brain SPECT could show the area of mild cerebral ischemia accompanying cerebral vascular reserve.

Thirty-two EC-IC bypass-operated patients underwent follow-up Tc-99m HMPAO rCOF SPECT investigations. In 9 cases, a circumscribed area with increased activity was seen on the postoperative rCBF SPECT images. The pathological reasons for these "hot spot" regions are analysed in this work. Two patients had completed stroke, where the increased Tc-99m HMPAO uptake may be a result of local hyporaemia. Six patients had well-localized inflammation at the operated region of the head without other complications. Of these, one healed before the follow-up rC8F SPECT study and no abnormality was seen on the images at the operated area. In the remaining 5 cases, increased radioactivity was detected at the affected region. The reason for the "hot spot" area could not be explained in two cases. It was concluded that the regionally increased activity on the Tc-99m HMPAO rCBF SPECT images after neurosurgical intervention may be a result of the wound inflammation. Elucidation of the exact pathological mechanism of this phenomenon demands further investigations.

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103

104

SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY DURING & AFTER AN EPISODE OF TRANSIENT GLOBAL AMNESIA K.Kimura, B.Moriwaki ~ , K.Hashikawa ~, H.Tanabe ~ , T.Nishimura ~ , A.Uehara ~, T.Kozuka ~, M.Matsumoto ~ and T.Kamada ~ . Biomedical Research Center, ~Dept. of Nucl. Med., r of Psychiat and ~ i s t Dept. of Med., Osaka University Medical School, Osaka, Japan

CLINICAL USEFULNESS OF RADIONUCLIDE BONE IMAGING IN NORMAL ROENTGEN VARIANTS OF SKELETON.

T r a n s i e n t g l o b a l a m n e s i a (TGA) is a w e l l recognized clinical entity, but its pathophysiology has remained obscure. Even if most authors attribute the amnestic attack of TGA to transient ischemia, there have been no r e p o r t s w h i c h i n v e s t i g a t e d the 3dimensional perfusion image during the episode. We were fortunate to get an opportunity to perform SPECT scanning using N-isopropyl-(I-123)-p-iodoamphetamine (IMP) in a pure case of TGA both during and after an episode. The patient is a 63-year-old right-handed woman without vascular risk factors except for labile hypertension. She exhibited the typical features of TGA: a suddenly onset of complete and transient (8 hours) anterograde amnesia associated with retrograde amnesia without neurological or neuropsychological abnormalities other than a deficit in memory. EEG and CT scan were normal. IMP SPECT scans were performed both daring and after the TGA episode with a high performance 4-head rotating gamma camera SPECT (FWHM = 9.8 mm). Data acquisitions were started i0 min after the injection of about 222 MBq IMP. During the episode, there was a marked hypoperfusion confined to the territory of the bilateral posterior cerebral arteries including the hippoeampal formations. After the episode, the hypoperfusion disappeared and cerebral blood flow returned to normal. These results seem to support the view that TGA is due to temporary ischemia in the territory of the posterior cerebral arteries.

105

R.Saito, T.Ohishi, Y.Igarashi, Y.Yamagishi, and K.Ebata. Department of radiology, Nippon Medical Scool, Tokyo, Japan. Diagnosis is often difficult of normal roentgen photographic variants of skeleton distinguish from another organic lesions as examples fracture,tumor, inflammation and so on. Radionuclide bone imaging is more reliable method to prove that variable skeletal lesions are biologically active or not active than clinical labolatory data, other diagnostic imaging modalities. Clarify the clinical usefulness of radionuclide bone imaging which performed in five cases of skeletal roentgen normal variants.

106 SOFTTISSUECOMPOSITIONAND FEMORALNECKBONE MINERAL ABSORPTIOM~rRIC DETERMINATION ROUSSEAUJ., MALEZIEUXX., LECOUFFEP., MARCHANDISEX. ServiceAssoci6de M6dacineNuclgaim- CHU de Lille- FRANCE

Althoughfemoralneck fractures haw a largelyheaviereconomicalincidencethan vertebral crashes, absorptiometric determination of bone mineral content is fairly less reliable in femoralneck than in lumbarvertebrae. Troubles in femoralneckmeasurements are numerous, mainlydue : - failurein positioningpatients in a reproducibleway, - difficultiesin designingaccurate Re#ons Of Interest, - variations of thickness and of fat/water content composition of soft ti~ues surroundingfemoralneck. To appreciate the importanceo f the later, in 10 patients, wr used simultaneously two diflerentapproaches : dual photort Gadoliniumabsorptiometer software was modifiedto determine fat/water content when scanning over soft tissues while data necessary to bone mineral content measurement were acquired when scanningover bone, - magnetic r~sonance imaging(MRI) using gradient echo sequences provided visualizationand volumequantificationof the soft c o m p o n e n t s of the thigh. Soft tissue compositionsdetermined in 10 patients by both methods were in good agreement. Using models suggested by MRI data, baseline corrections of bone mineral content measurements were interpolated from fat/water DPA studies with an adequate software. In a givenpatient, variationsas largeas 30 % in fat/water compositionand as 10 % in thickness of soft tissue can be observed in DPA study according to the ~ g i o n where soft tisauewas appreciated. This may lead to uncertainties in femoral neck mineralcontent which are quite largerthan theoreticalreproducibility. As a conclusion, software for femoral neck absorptiometry must include a comprehensivetreatment o f soft tissue attenuation. Collectingdata for comparisonbetween soft fat content and bone mineral content is under current studies. -

Sunday, August 26, 1990

MEASUREMENT OF BONE MINERALIZATION ON HYPERPARATHYROIDISM WITH BONE SCAN AND DBD. T. Okamura, Y. K o i z u m i , K. K o b a s h i , T. F u k u d a , J . Oda, H. I k e d a , H. O c h i , Y. Onoyama, S. l t a g i w a r a , H. M o r i i . Osaka C i t y U n i v e r s i t y Medical S c h o o l , Osaka, J a p a n . The b o n e s c a n o f p a t i e n t s w i t h h y p e r p a r a - t h y o i d i s m shows t y p i c a l p a t t e r n s u c h a s h i g h a c c u m u l a t i o n i n t h e skull. T h i s p a t t e r n becomes n o r m a l a f t e r p a e a thyroidectomy. To q u a n t i f y t h e b o n e s c a n , w e d e v i s e d a new m e t h o d ; t h e r a d i o n u c l i d e activity ratio (RN ratJo:RN activity of the skull~that of the brain) with SPECT. We s t u d i e d t h e b o n e m i n e r a l i z a t i o n usin9 dual

photon bone densitometer (DBD) and RN ratio of the skull on bone scan. The subjects of this study were 53 patients;9 of them were primary hyperparathyroidismIPHP) and 44 were secondary hyperparathyroidism(2HP) w i t h c h r o n i c renal failure. Bone scan with Tc-99m-MDP and dual photon absorptiometry(DPA) using DBD(Ga-153,1Ci) were performed. N i n e t e e n o f 53 underwent PTX ( 6 : P H P , 13:2HP) w e r e p e r f o r m e d b o n e s c a n and DPA b e f o r e and a f t e r PTX. P a t i e n t s o f 2HP showed much h i g h e r RN r a t i o and low b o n e m i n e r a l c o n t e n t o f t h e s k u l l arid t o t a l body b u t t h a t o f t h e l u m b a r s p i n e was n o t s o low. P a t i e n t s o f PHP showed r e l a t i v e l y high or normal RN r a t i o and d e c r e a s e d b o n e m i n e r a l d e n s i t y . Nineteen u n d e r w e n t PTX r e v e a l e d d e c r e a s e d RN r a t i o and i n c r e a s e d b o n e m i n e r a l c o n t e n t a f t e r PTX. The m o s t i n c r e a s e d s i t e on DBD was t h e s k u l l i n 2HP p a t i e n t s . Bone m i n e r a l c o n t e n t o f PHP became i n n o r m a l r a n g e w i t h i n 3 m o n t h s a f t e r PTX, on t h e o t h e r h a n d t h a t o f 2HP i n c r e a s e d c o n t i n u o u s l y u n t i l 12 m o n t h s . The r e s u l t s showed t h a t m e a s u r e m e n t o f RN r a t i o on b o n e s c a n and t h e b o n e m i n e r a l c o n t e n t w i t h DPA s e e m e d t o be u s e f u l f o r t h e h y p e r p a r a t h y r o i d i s m to detect demineralization and i m p r o v e m e n t s a f t e r PTX.

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108A

MEASUREMENTOF MINERAL DENSITY WITH DUAL PHOTONABSORPTIOMETRY OF BONE GRAFTS USED TO RECONSTRUCTDYSPLASTIC ACETABULI C.Koutoulidis, N.Demakopoulos, and E.Michelinakis. Nuclear Medicine and Orthopedics depts. NIMTS Hospital, Athens, Greece.

QUANTITATIVE EVALUATION OF BONE FORMATION BY PLASMA RATIO OF Tc-99m MDP/Cr-51 EDTA. D.._, Picard, L.G. Ste-Marie, N. Dion, P. D'Amour, R. Lepage, Ctre rech cliu A.-Viallet, Depts. of Medicine, Nucl. Med. and Biochemistry, Hop. St-Luc, U. de Montr6al, Montreal, Canada.

The purpose of this study was to measure with the dual-photon absorptiometry method(DP~, the bone mineral density of femoral heads homografts used to reconstruct the acetabulum. Eighteen patients had d e f i c i e n t acetabulum, f i f t e e n of them had dysplastic shallow acetabuli and the other three had unreduced congenital dislocation of the hip. The average age was 57,3 years and the t o t a l hip arthroplasties were performed three to five years p r i o r to the present investigation. The plain radiography showed the grafts were incorporated into the host bone. The measurments were done with the Roi's method, expressed in gr/cm 2 and compared with similar ones taken simultaneously from the area lying i cm above the tear drop. The results showed that the bone mineral density of grafts was higher compared with the bone corresponding to tear drop in fourteen from the eighteen patients and the rest showed s l i g h t difference in values. This study shows another application of DPA.I t suggests that the homographs not only are incorporated but they do remodel in response to stress from the underlying cup. This cannot be seen q u a n t i t a t i v a l y with other methods.

We wished to evaluate a simple method which assess quantitatively bone metabolism during bone scan. A blood sample is taken 3h after the stimultaneous injection of 1 GBq of Tc-99m MDP and of 3,7 MBq of Cr-51 EDTA, the latter being given to correct for the renal excretion of Tc-99m MDP. The results are expressed as the ratio of the % activity of Cr51 dose/1 of plasma to % Tc-99m dose/1 of plasma (Cr-51/Tc99m). In 11 normal subjects, the mean Cr-51/Tc-99m was 1,2_+ 0,13 (_+SD). In a group of 69 patients (age: 58,1 _+11,7 yr) with metabolic bone disorders (postmenopausal osteoporosis, n =25; osteomalacia, n=4; secondary osteoporoses, primary and secondary hyperparathyroidism, n=40) there were significant linear correlations between Cr-51/Tc-99m and: serum PTH (r=0,531, p<0,0001, n=66), serum alkaline phosphatase (r=0,508, p<0,0001, n=64). The 20 patients with elevated serum PTH (>10 pmol/1) had a mean Cr-51/Tc-99m significantly higher than those with normal PTH (1,90_+0,73 vs 1,47_+0,31, p<0,002). Histomorphometric analysis of transiliae bone biopsies (n=58) showed that Cr-51/Tc-99m correlated with osteoid surfaces (OS/BS, r=0,602, p<0,0001) and osteoid volume (OV/BV, r=0,564, p<0,0001), but not with bone volume (BV/TV) nor with eroded surfaces (ES/BS). In the 25 patients with postmenopausal osteoporosis Cr-~l/Tc-99m did correlate with OS/BS (r=0,421, p<0,05, y=ax ). Thus, this simple method, which requires little additional manipulationsto the usual bone scan, might be a useful parameter to quantify bone metabolism, especially bone formation.

108B

109

P. P. van Rijk, P. M. van Roermund, C. Haaring, and W. Renooy.

WHOLE BODY R E T E N T I O N (WBR) OF A M I N O H Y D R O H Y P R O P Y L I D E N E B I S P H O S P H O N A T E (APD)-Tc-99m IN O S T E O P O R O S I S STUDY. EFFECT OF T R E A T M E N T WITH APD. A.B.Otero,Z.Man,0.J.Degrossi,M.A.Mendez,A.Fraga,M.Cabrejas,E.Montuori,N.Altschuler. Sanat. Guemes and Com. Nac. E n e r g . A t 6 m i c a , B u e n o s Aires,Argentina.

UPTAKE OF TC-99M MDP IN EPIPHYSEAL REGIONS OF RABBITS D U R I N G THE G R O W T H P L A T E CLOSURE INTERVAL.

Abstract received in a form unsuitable for reproduction

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WBR was m e a s u r e d at 4 and 24 hs after iv injection of 36 MBq of A P D - T e - 9 9 m u t i l i z i n g a s h a d o w - s h i e l d whole body counter. R e p r o d u c t i b i l i t y was 2.2% and statisti cal counting error was less than 0.5%.The WBR was calculated as a p e r c e n t of injected dose; also the biological half life 4-24 hs and the fractional turnover rate (k ;h -I ) was calculated. Three groups were studied: C,12 health control vol u n t e e r s , a g e d 46~Sy(x and s.d.); OS, 22 o s t e o p o r o t i c pae., aged 60~I0y; and TP, 10 Os p a t i e n t e s aged 63~11y treated during 6 months with APD, 3 m g / k g b.w./day. Results: 4hs WBR 24hs WBR k(10 -4) C 64 + 5 24 + 3 318 + 73 OS 61 + 11 37 + 9 256 + 64 TP 53 ~ 15 28 ~ 6 303 ~ 111 These results indicate that 4 hs W B R is not an ade quate index of bone turnover. The 24 hs WBR and the bio logical half life allow to d i f f e r e n t i a t e OS from C as weel as from TP and appear as adequate index of bone turnover

Sunday, August26,1990

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THE VALUE OF Tc-99m-GP H,,t THE ASSESSME!qT OF HETABOLIC BONE D!SEASES B. E Caners, M T Ercan, and E. Varodjlu Department of Nuciear Hedicine, Hacettepe University, Medical Faculty, Ankara, Turkey

METAPHYSER HYPERACTIVITY IN UNILATERAL FEMORAL HEAD OSTEOh~CROSIS. M.Unl~, M.T.Kitapgl, H. Durak, M. Kz~, G. Erbengi, C. F. Bekdik. Hacettepe University Faculty of Medicine, Department of Nuclear Medicine, Ankara, Turkey.

Tc-99m labelled ~-D-Glucose l-Phosphate (GP) was introduced for lung tumor imaging by our group previously, As demonstrated in clinical studies, it was not taken-up by normal bone In the present study we evaluated Tc-99m-GP in ten patients ( 8 F, 2 M, age range: 1 7 - 7 2 ) w i t h known metabolic bone disorders, in comparison to Tc-99m-MDP Each patient received an IV. dose of 20 mCi Tc99m-GP. Scintigrams were obtained at 3 h postinjecCion, Three-phase Tc-99m-MDP bone scans were obtained 4 days l a t e r Quantitatwe analyses were done by drawing ROI on pathological (P) and normal (N) areas On qualitative analysis, it was noted that Tc99m-GP was taken-up only by pathological areas, but not by norrna! bone The mean PIll ratios ~n i5 active sites were 2,35 -+ 0.94 and 3.50 _+273 for Tc-99m-GP and Tc-99rn-MDP, respectively. Although the mean P/N ratio of Tc-99m-GP was inferior to that of Tc-99m-MDP, its selective acumulation in pathological bone tissues is an advantage over Tc-99m-MDP, Thus, it f a c i l i t a t e s the demonstration of metobolically actwe sites, especially m eeuwoca] cases and m syrrlmetMca! uptake

Quantitative evaluation of unilateral femoral head osteonecrosis by Tc-99m MDP SPECT was performed in 10 normals and 10 patients who had confirmed diagnosis by core biopsies. Using a standard ROI, counts per pixel were determined from coronary slices for both femoral heads and metaphysis.Femoral head ratio (FHR) was calculated as; right femoral head /left femoral head in normals and involved femoral head/intact femoral head in patients. Metaphyser ratio (MR) was calculated as; right metaphysis/left metaphysis in normals and metaphysis of involved side/metaphysis of intact side in patients. Mean FHR and MR was 0.99+0.9, i. 10• in normals and 0.88+0 50, 0.99• in patients, respectively. FHR and MR were positively correlated (r=0.64) in patients.Although photopenic defects were identified by SPECT in all patients,this correlation may be a useful parameter when the surrounding hyperactivity obscures the defect. Increased metaphyser activity may indicate the presence of femoral head osteonecrosis.

n o

_o.oo 1

FHR

2

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113

THE ROLE OF HUMANCENTRIFUC~TION IN THE TREATMENTOF REFLEX SYMPATHETIC DYSTROPHYSYNDROME. M.E. I s a s i * ' " , E.S. I s a s i * ' " , R. Wolff~ E. Touya" ~Cardiovascular and Centrifugation Investigation Cent r e , "Cardiology Centre, Hospital Maciel, "Nuclear Medicine Centre, Hospital de Cl{nicas, ~ Surgery Centre, Montevideo, Uruguay.

DOES EARLYTRACERUPTAKEINFLUENCE PERFUSIONAND BLOODPOOLIMAGESOF THE THREE PHASEBONESCAN IN PATIENTSWITH REFLEXSYMPATHETICDYSTROPHYSYNDOME? J. Roland,P. Herregods,L. Williame, R. Chappel,J. Vandevivere. MiddelheimGeneralHospital, Antwerp,BELGIUM.

The r e f l e x sympathetic dystrophy syndrome (RSDS) is a d i f f i c u l t condition to t r e a t . I t is known that the etiopathogenic basis of this affection is a "neurovascular d i s t u r b " . A new modality of treament is presented in this paper using human centrifugation (HC) by i t s "vasodilators effects". Twenty s i x (5M, 21W) (average age 42 yr) suffering from RSDS were studied. RSDShad been triggered by trauma in 22 and by surgery in 4 cases. All1 patients were run in a couch in supine position placing the head in the adjacencies of the rotation shaft. They were exposed d a i l y to acceleration p r o f i l e s from head to feet in a human centrifuge. The duration of the treatment depended on the p a t i e n t ' s response (2 to 20 sessions). The evaluation of the RSDS treatment by HC was per~)rmed by the c l i n i c a l evolution, the d i g i t a l pho_ t o p l e t s ~ g r a p h i c (DPHG) response and s t a t i c madionuclide bone images (SRNBI). Delay SRNBI were obtained 3 or 4 hours a f t e r the inj e c t i o n of 20 mCi Tc-99m MDP. Vascular diathesis was put on evidence by DPHG. C~inical and DPHG improvements were observed in 25 patients (94%). The r e l i e f is often inmediate and dramatic. Four patients had l i t t l e or no return of pain once the f i r s t session was completed. Radionuclide bone images persisted p o s i t i v e in spite of c l i n i c a l and DPHG improvements.

S u n d a y , A u g u s t 26, 1990

Although the role of the three phase bone scintigraphyin the diagnosis of reflexsympatheticdystrophysyndrome(RSDS) is well known,it has been postulatedthat the regionalperfusionand especiallythe regional bloodpoolimagescould be influencedby an early uptakeof Tc-99m MDP resulting in a possibleoverestimationof the bloodpool.Tc-99m human serum albumin (HSA) and Tc-99m MDP pertusionand bloodpoolstudies, madewithin a 4 day intervalwere comparedin 15 consecutivepatients with RSDS. A 7 minutesduring dynamicacquisition(3 seconds/ frame) of the affected and contralateralextremities,startingfrom the onset of the injectionof Tc-99m MDP or Tc-99m HSA was made.The tracerwas injected in a foot when an upperextremitywas affected.The first 60 seconds, startingfrom the arrivalof tracerin the regionstudied,were consideredas regionalperfusionwhile the last 60 secondsof the study correspondedwith the regionalbloodpool.The amountof tracer in the affected areawas expressedas a percentageof the amount measuredin the contralateralarea.The results obtainedwith Tc-99m MDP and Tc-99m HSA were comparedusing a Wilcoxon matched-pairssigned-rankstest. A significantdifferencewas not observedbetweenthe resultsobtained with Tc-99m MDP or Tc-99m HSA, neitherfor the pertusionnor for the bloodpoolimages.The meanvalues (+ sd) obtainedwith both tracers are presentedbelow: Regionalpeffusion Regionalbloodpool

MDP 213 (+ 52) % 232 (_+ 98) %

HSA 259 (+ 137) % 205 (+ 62) %

We concludethat a possibleearly uptake of Tc-99m MDP does not signi:icantlyinfluence the amountof tracer measuredduringthe imaging c,t the pertusionor bloodpoolin patientswith RSDS.

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Abstract withdrawn

HUMAN CENTRIFUGATION: A MECHANICAL STIMULUS RELATED WITH PROSTAGLANDINSLIBERATION. LYMPHOSClNTIGRAPHIC EVALUATI ON. E. S. Isasi * ~ M. E. I s a s i * ' " and E. Touya". *Cardiovascular and Centrifuqation Investigation Centre,~ "Cardiology Centre, Hospital Maciel, " Nuclear Medicine Centre, Hospital de Cl~nieas, Montevideo, Uruguay. The purpose of this investigation was to analyze the aspirin (ASP) or indomethacin (IND) effect on the lymphatic drainage of normal volunteers (NV) and patients (Ps) with lymphedema submitted to human cent r i f u g a t i o n (HC). Ten NV (3M,7W, mean age 48 yr) and 20 Ps (3M,17W, mean age 50 yr) with primary or secondary lower or upper limbs lymphedema were studied. Two lymphoscintigraphies (LS) were performed in d i f ferent days and a l l NV and Ps were submitted to HC in both situations. In the f i r s t LS any medication was taken. The second LS was performed a f t e r the ingestion of ASP 500 mg or IND 25 mq each 8 hours during 48 hr previous the HC. NV and Ps were exposed to acceleration p r o f i l e s from head to feet in a human centrifuge during 20 min. LS was performed i n j e c t i n g 1.5 mCi of Tc-99m Sb2S3 c o l l o i d subcutaneously into the i n t e r d i g i t a l space of the limbs. Five minutes s t a t i c images from the i n j e c t i o n site (IS) and the abdomen (ABD)were repeated at 1-2-3-4 hr post i n j e c t i o n . After the f i r s t imaqes at the IS and ABD the NV and Ps were exposed to HC. The parameters analyzed were: I) clearance from the IS and 2) l i v e r uptake time(LU). The results showed in the f i r s t LS (without medication) that the LU appeared at the f i r s t hour in 28 cases. The second LS (under ASP or IND effect) showed a s i g n i f i c a n t (P< 0.005) delay in the LU. On the basis of these results could be deduced that human centrifugation constitutes a mechanical stimulus related with prostaglandins l i b e r a t i o n .

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HUMAN CENTRIFUGATION A NEW THERAPEUTIC METHOD IN LYMPHEDEMA. LYMPHOSCINTIGRAPHICEVALUATION. E.S. Isasi * ~ M.E. I s a s i * ' " and E. Touya". *Cardiovascular and Centrifugation Investigation Centre, "Cardiology Centre, Hospital Macie], " Nuclear Medicine Centre, Hospital de Cl~nicas, Montevideo, Uruguay.

BRIEF AND INTENSIVE CENTRIFUGATIONTREATMENTIN PERIPHERAL ISCHEMIA. EVALUATIONBY RADIONUCLIDE ANGIOGRAPHY AND PHOTOPLETYSMOGRAPHY. M.E. Isasi * ~ E.S. Isasi * ' ~ C. Carrera*', J.C. Martino*" and E. Touya ~ * Cardiovascular and Centrifugation Investigation Centre, " Cardiology Centre, Hospital Mac i e l , : Nuclear Medicine Centre, Hospital de Cl~nicas, Montevideo, Uruguay.

The authors have previously published the effect of the centrifuqal force over the lymphatic drainage. They became interested in human centrifugation (HC) as a therapeutic device in lymphedematous limbs. Twenty six women and 4 males (mean age 54 yr) with p r i mary or secondary lower or upper limbs lymphedema were studied. To evaluate the HC treatment, volume measurements and lymphoscintigraphic (LS) studies (quantitative and q u a l i t a t i v e ) with b i l a t e r a l subcutaneous i n t e r d i g i t a l i n j e c t i o n of Tc-99m labeled antimony-sulfur c o l l o i d were performed before and a f t e r centrifuqation and patterns of radionuclide d i s t r i b u t i o n and l i v e r uptake were compared. All patients were run in a couch in supine position placing the head in the adjacencies of the rotation shaft. They were exposed d a i l y to acceleration p r o f i l e s from head to feet during one hour for a month. The results of this study showed: a) a s i q n i f i c a n t volume reduction in lymphedematous limbs (P 0.001) with increase a b i l i t y to work and ambulate. b) LS studies revealed an e a r l i e r l i v e r uptake (aft e r centrifugation (P
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The aim of this investigation was to evaluate the vascular effects of a b r i e f and intensive (one month) human centrifugation (HC) treatment protocol in patients suffering from i n t e r m i t t e n t claudication due to peripheral vascular disease (Fontaine stage l l b ) . Confirmed obstructive peripheral a r t e r i o athy was present in the 10 male patients mean age 59 y r ) . HC evaluation by c l i n i c a l test (walking distance (WD) and sural triceps test (STT), s t a t i c radionuclide angiography (SRNA) images, with Tc-99m and d i g i t a l photopletysmography (DPHG) were performed before and a f t e r 4 weeks of treatment. All patients were exposed d a i l y to acceleration p r o f i l e s from head to feet in a human centrifuge during 30 minutes. This study showed a s i g n i f i c a n t increase in the pain-free and t o t a l WD-STT (P< 0.001) and non-invasive studies showed a d e f i n i t e pattern of restored perfusion of the lower limbs improving c o l l a t e r a l c i r c u l a t i o n .

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A) B)

SRNA pre-treatment SRNA post one month of human centrifuqation treatment

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CRITERIA FOR SJOGREN SYNDROME BY SALIVARY-FUNCTION SCINTIGRAPHY USING Tc-99m PERTECHNETATE. H.Fujii, Y.Tsukatani, K.Ogawa, K.Nakamura, A.Kubo, F.Kinoshita, and S.Hashimoto. School of Medicine, Keio University, Tokyo, Japan.

Techniques for Radionuclide Evaluation of Post-tratmmtic oral pharyngeal Disorders. E. K o t l y a r o ~ L. Weiner and R. Reba; George Washington University Medical Center, Washington, D.C., U.S.A.

Salivary gland scintigraphy is an useful method for diagnosis of Sj~gren syndrome as used in the Copenhagen criteria. However, the quantitative criteria which were proposed so far have not been widely accepted. The purpose of this investigation was to establish new quantitative criteria by dynamic studies in salivary-function scintigraphy. Approximately 500 patients suspected of Sjogren syndrome underwent salivary-function scintigraphy over the past 4 years. Tc-99m pertechnetate (185 MBq) was injected intravenously rapidly, and sequential scintigraphs of the face were taken every 15 sec for 30 min. Fifteen min after the injection, one ml of lemon juice was administered into the mouth to stimulate salivary excretion. Regions of Interest (ROIs) were setted onto the four major salivary glands as well as the background area, and then, timeactivity curves were obtained for each ROI of salivary gland by using the computer programs we developed. From these curves, accumulation rate (Ac), excretion rate (Ex), and their products (Ac*Ex) were calculated. On the basis of these parameters, new quantitative criteria were established with reference to the Japanese criteria, as shown below; Criteria for screening with high sensitivity(90%), where specificity was 57%, were defined as either Ac of parotids glands < 0.25%, Ac of submandibular glands < 0.15% or Ex < 50%. Criteria for definite cases with high specificity(90%), where the sensitivity was 70%, were defined as Ac*Ex < 0.30.

Understanding of biomechanics of oral pharyngeal, esophageal function is of paramount importance for correction of post-traumatic dysphagia with removable oral pharyngeal prosthesis. During 1989, we e~nployed a combination of modified radionuclide esophageal transit study and radionuclide gastroesophageal reflux study in evaluation of 18 patients (total 35 examinations) before and after application of oral pharyngeal prosthesis stage 1 and stage 2. Studies were performed in upright position using 500 Ci of RC-99M sulfur colloid in 15cc of water for each test. The test lasts two minutes (analog and digital acquisitions) while patient asked to have a dry swallow at 15 seconds intervals. Analog images were obtained at 1 second intervals for 60 seconds and then at 2 seconds interval for 60 seconds. Computer acquisition performed in frame mode (64x64) at 0.1 second intervals. Percent of residual radioactivity was calculated at 15, 30, 60 and 120 seconds along with estimation of emptying time (T i/I0) in six regions of interest; oral cavity; hypopharynx; proximal middle and distal esophagus and entire esophagus. When baseline study is completed, the patient swallows 100cc of tap water to rinse out residual radioactivity and then test was repeated with oral pharyngeal prosthesis. By termination of the esophageal transit time tests patient swallows 200cc of orange juice and placed supine under the camera for radionuclide gastroesophageal reflux study. No additional radiopharmaceutical was employed. Reflux study was performed with applying increasing and decreasing abdominal pressure from "0" to "I00" r~n of mercury. This study reveals that radionuclide evaluaoffers a v~luable addition to traditional radiographic vloeo swallow.

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RECEIVER OPERATING CHARAcs SURFACE FOR ESOPHAGEAL TRANSIT SCINTIGRAPHY IN SYSTEMIC SCLEROSIS H.A. Klein, T.O. Graham, A. Wald, W.L. Campbell, V.D. SteemL, and T.A. Medsger, Jr. University of Pittsburc~L School of Medicine, Pittsburc~, PA, USA.

EMPTYING OF STOMACH USED FOR ESOPHAGOPLASTY D. HUGLO, H. VENEL, P. LECOUFFE, F.GUILLEMOT, J.-P. TRIBOULET, A. CORTOT, X. MARCHANDISE Service Associ6 de Mddecine Nueldaire, Clinique des Maladies de rAppareil Digestif, Service de Chirurgie Gdndralr ct Endocrinienne - H6pital Huriez - C H U Lille - FRANCE

We evaluated discriminating ability of esophageal transit scintigra~y (ETS) in systemic sclerosis with attention to the effect of patient selection. In each of 17 patients, who also underwent esophageal mancmetry, we evaluated RFC(4), an age-corrected parameter of ETS. It was derived by measuring RF(4), the permentage of orally administered aqueous Tc-99m sulfur colloid that remaine~ in the esophagus aftex" 4 swallows, and ccmputing its deviation frc~ the positively sloped regression line of RF(4) against age obtaJ_ne~ from 15 healthy controls. For RFC(4), the area under a receiver operating characteristic (ROC) curve was 0.82, where areas above 0.50 indicate significant discriminating ability. This area increased to 0.91 when we restricted the disease group to the ii out of 17 with <70% peristaltic waves (IW~) by manc~etry, and to 1.00 (perfect discrimination), when we restricted to the 8 with <60% PW. We stacked R0C curves to form a surface that depicts the relationship of true positive fraction, false positive fraction, and varying threshold values of I~4. The ~ curves are cross sections that ~ in area with increasing esophageal impairment of the r e d e f ~ patient groups. Discrimination was highly dependent on patient selection. The ROC surface illustrates this dependence.

The stomach may be used for esophageal reconstruction after resection of esophageal cancers. In Akiyama procedure esophagngastroanastomosis is cervical (residual esophagus < 5 cm) ; in Lewis-Santi prccedurr anastomosis is thoracic (residual esophagus > 8 cm). The aim of this study was to assess motility of these two types of csophagoplasty. METHODS : Eight patients with Akiyama retrosternal esophagoplasty (59.2+]'-7.4 year)and 7 patients with Lewis-Senti esophagoplasty (55 + ]'-7.2 ),car) were studied at least 2 months after surgery. Gastric transplant emptying was measured using gamma-camera imaging of a 474 kcal mixed meal. Solid phase (egg) was labelled by 99roTe-colloidal sulphur (18.5 MBq) and liquid phase by 111In-DTPA (3.7 MBq). Corrections for movement, Compton scattering and isotope decay were achiewd. Activity/time curves were obtained from geometric mean of pa~tcrior and anterior data. Ten male healthy volunteers acted as controls. Manomctry of the transplant was concurrently performed,

Sunday, August 26, 1990

RESULTS : Percentages of initial activity retained in transplant were expressed as mean +]'s.e.m. : Solids 20 min Akiyama 23.6+/-5.9 ** Controls 82.3+/-23 **

40 min 11.2+/-35 ** 623+/-4.8 **

Liquids 20 min 39.3 +/-10.7 N.S. 575+/-2.8 **

40 min 16.4+/-6.8 37.4 +/-3.9

L~wis

17.9+ A9.7 17.8+]'-10.2 16.1+]'-7.9 15.1+/-8.2 * = p < 0.05 ** = p < 0.01 (Wilcoxon teat) There was no solid-liquid discrimination in patients. No significant difference between the two procedures of plasty was observed. No propagated activity was found in both types of gastric transplant during manometry. CONCLUSIONS : So rapid emptying of the meal through the plasty without any solid-liquid discrimination suggests that gastric transplant does not participate actively in digestion. The length of residual esophagus does not influence plasty motility,

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THE ~SOTOPIC ELECTROGASTROGRAM : A NEW SClNTIGRAPHIC TECHNIQUE TO VISUALIZE AND CHARACTERIZE GASTRIC CONTRACTIONS. J.L. URBAIN, J. A. SIEGEL, E. VANCUTSEM, J. JANSSENS, G. VANTRAPPEN & M. DE ROO. Gasthuieberg University Hospital.Befgium.

FOURIER TRANSFORMATION: AN ADVANCED METHOD OF STOMACH SCINTIGRAPHY M.Jauch, W.Mueller-Schauenburg, U.Feine N u k l e a r m e d i z i n i s c h e Abteilung (Aerztlicher D i r e k t o r : P r o f . D r . m e d . U . F e i n e ) Radiologische U n i v e r s i t a e t s k l i n i k Tuebingen

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-ggm-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. Percentageof activity remaining in 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 and 250 milliseo, frames were created. Antral time-activity curves were generated and analyzed using a curve-peak finding algorithm and a phaseamplitude Fourier analysis to determine the frequency (CF), amp[itude (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+_1SD). TIME 15' 30' 60' 90' 120' Retention (%) 98+5 88+8 73+17 53+19 41_+16 CF (cycle/rain.) 2,9_+0.3 2.9+0.1 3.1+-0.3" 3.2-+0.2" 3.4+0,3* CA (%) 57-+8.8 55+5.2" 48+9,6* 46.6+7" 38+8.9* PCR (%/eec) 13.9_+I 13.2+2 14+2 13.5'_+0.5 14.1_+1 PFR (%/sec) 18.2+34 16.7+-31 17.9_+13 16.9+22 19.0+25 * p< 0.05 versus T 15' CF was inversely related with feod retention in the stomach,In 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 aborrally to the pylorus. This is in agreement with results already obtained by other investigators with invasive 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 pathophysiolegy of gastric emptying in various motor disorders,

We wish to determine the presence of m o t i l i t y disorders of the stomach, superimposed upon m o t i l i t y disorder of the esophagus, in patients suffering from achalasia, by help of compressed images and a FOURIER approach. PATIENTS: i0 normal and 20 patiens with achalasia. METHOD: 150 MBq T c - 9 9 m tin-colloid combined with curds. Aquisition: Digital images with if/sec plus if/3sec over a period of 45 min. Evaluated were:a) Transit Time parameters, b) Compressed Images, c) "FOURIER Navigation". Compressed images show distinctively the point of peristaltic movement during the aquisition. Using FOURIER transformation we are able to d i f f e r e n c i a t e the individual waves of the stomach. FOURIER N a v i g a t i o n Program guides selection of ROI, time interval and frequency and generates amplitudes and phase p r o p a g a t i o n playback. R E S U L T S : A c h a l a s i e is a general disorder of the nervus vagus, including esophagus and stomach. D I S C U S S I O N : " F O U R I E R NAVIGATION" and Comp r e s s e d Imag%s are able to detect distinctively disorders of the stomach.

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GASTRIC EMPTYING OF TWO SOLIDS IN HEALTHY HUMANS AND IN PATIENTS WITH GASTROPARESIS. D. Picard, L. Carrier, P. Poitras, M. Boivin, Centre de recherche

SPECT VERSUS P L A N A R STUDIES IN D I F F U S E L I V E R DISEASE EDelcourt. J-PBinon MVanhaeverbeek. RCalay, MBaudonx C.H.U. A V E S A L E MontignyleTilleul, BELGIUM

clir~ique Andr6-Viallet and Dept. of Nuclear Medicine, Hopital Saint-Luc and Univ. de Montr6al, Montreal, Quebec, Canada.

The aim of the study was to compare conventional and tomographic scintiscan accuracy in a series of 43 normal patients and 70 patients with documented alcoholic liver disease. Normal patients arc a group initially referred to exclude a metastatic involvement of the liver all of them had a normal liver biology and a normal CT scan or a negative clinical and biological folh)w-up on a b months period. Abnormal patients includes28 patients with a histological diagnosis of steatosis and 42 patients with cirrhosis proved by liver biopsy (26) or portal hypertension 06). The processing of the tomogram is operator independent. Seven quantitative parameters are cbnsidered: liver and spleen volumes spleen to liver and marrow uptake ratios spleen to]iver volume ratio, nonhomogencous liver uptake, left-to-ri~;ht hepatic lobe ratio. All these fealur~es are integrated into a global ~core giving the SPECT final answer. Conventional scintiscan is based on the same criteria assessed by visual evaluation of planar images. Data were independently examined by two experienced observers unawared of the diagnos~is. Conflicting.resuhs were next reviewed in concert to get a common interpretauon and then compared with the SPECT ~ata for accuracy with regard to the t real dmgm sis. The two observers disagree on at least one sclntisean feature in 56% alcoholics and 26% normals. All normal patients are correctly recognized by SPECT while conventional scintiscan has a 3/43 false positive ratio.(p =ns). Accordin.~ to the final diagnosis SPECT provides the correct answer in .59/70 (84%) abnormal patients against 47/70 (67%) for conventional seinttscan (p< .005). 8PECT yields a significantly better sensitivity in steatosis patients (SPECT 68%, Planar 36%, p< .005) but not in cirrhosis paUents (SPECT 95% Planar 88% p=ns). We conclude that 1) SPECT technique offers a clear improvement over conventionalplanar scintiscan in patients with mild alcoholic fiver disease' 2) SPECT with quantification yields no interobserver variability while visual appraisal of individual scintiscan criteria appears largely unreliable with the planar technique.

The differences in chemical (vg: lipid content) or physical properties (vg: resistance to desintegration) of the various labelled solid materials used can probably influence the gastric emptying rate (GER). Our aim was to compare the GER of 2 solids (egg and liver) ingested together with a complete mixed meal in heatlhy subjects and in patients suspected of delayed GER. Methods: 14 healthy subjects and 72 patients (65 suspected 0f idiopathic and 7 of diabetic gastroparesis) ingested a 511 kcal meal~l~55% carbonhydrate, 22% lipid, 23% protein) containing 30 g ~mTcSc liver and one IHIn egg. For 3 hr after meal, mean anterior and posterior abdominal activity was at 20 min interval and half time (tV2) GER was estimated for both isotopes. Results: In healthy subjects, liver GER (mean tV2: 103 min, range: 70-155 min) and egg (mean tV2:105 min, range: 75-155 rain) were similar. In patients suspected of gastroparesis, delayed GER of egg or liver (defined as W2 >__160 min) was documented in 20 of the 72 patients (28%). Each of these 20 patients showed delayed liver GER (mean tV2:172 min, range: 160- >180 min). GER of egg was delayed in only 12 of 20 patients (mean tV2:172 min, range: 160- >180 min) and was normal in 8 patients (tV2:125 rain, range 90-150 rain). Conclusion: In healthy subjects, both egg and liver ingested together in a mixed meal empty simultaneously from the stomach. However, in patients clinically suspected of gastric motor dysfunction, radionuclide-labelled liver is more sensitive than egg to recognize the GER delay with isotopic studies.

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THE EFFECT OF COCAINE ON RADIONUCLIDE LIVER STUDIES. G-J. Wang, P. Som, Z.H. Oster, D,A. Weber, Brookhaven National Laboratory, Upton, NY and SUNY, Stony Brook, NY.

I N T E G R A T E D D Y N A M I C L I V E R I M A G I N G IN L I V E R CIRRHOSIS. S.Kobayashi and Y.Suzuki. Tokai University S c h h o l of M e d i c i n e , I s e h a r a - c i t y , K a n a g a w a , Japan.

The noxic effects of cocaine on the liver in experimental animals are well documented and reports in humans are being published. The effect of cocaine on two radionuclide liver studies in mice were correlated with liver function tests and histology. The acute (AC) effects of a single dose (i,p.) of cocaine (50 mg/Kg),; and chronic (CH) effects of nine daily doses of cocaine (20 mg/Kg), and controls given saline were studied. Sixteen hours after the cocaine injection 20 #ci Tc-99m-S-C or Tc-99m-HIDA was given I.V. Tissue distribution, liver function tests and histology was performed. The SGPT blood levels were twice the normal levels after a single cocaine dose and five times higher after repeated (CH) cocaine. (Controls: 200• AC; 413• CH:I061.3• In CH mice hepatomegaly (+36% increase over controls) occurred. Focal necrosis, fatty infiltration and inflammation was seen. Tc-HIDA distribution was not affected by AC or CH cocaine. Global Tc-S-C liver uptake (% dose/organ) was 8% higher in cocaine mice, but the concentration was 18% lower in CH mice. A decrease in Tc-S-C uptake and concentration in the spleen was seen. In conclusion Tc-HIDA was not affected by cocaine. The decrease in Tc-S-C liver concentration probably represents congestion and the decreased splenic uptake is probably caused by vasospasm. The effects of cocaine in clinical practice are worth further evaluation.

The s t a t i c r a d i o c o l l o i d l i v e r s c a n has b e e n u s e d for m a n y y e a r s in d e t e c t i o n of local a n d d i f f u s e h e p a t i c d i s e a s e . The a i m of t h i s s t u d y w a s to d e t e r m i n e the c l i n i c a l u s e f u l n e s s of a s i m p l e n e w m e t h o d " i n t e g r a t e d d y n a m i c l i v e r i m a g i n g " in l i v e r c i r r h o s i s . The r e s u l t s o b t a i n e d in 82 c o n t r o l s u b j e c t s w e r e c o m p a r e d w i t h 63 c i r r h o t i c p a t i e n t s ( c o m p e n s a t e d : 41, d e c o m p e n s a t e d : 22). T h e c o n t r o l s t u d i e s w e r e u n d e r t a k e n in 82 p t s u n d e r g o i n g a s s e s s m e n t for l i v e r m a l i g n a n c y . I m a g i n g w a s p e r f o r m e d w i t h the s u b j e c t s s u p i n e b e n e t h a l a r g e f i e l d of v i e w g a m m a c a m e r a to i n c l u d e the lung, heart, liver, s p l e e n and b o t h k i d n e y s . A r a p i d i n t r a v e n o u s b o l u s i n j e c t i o n of 222 M B q of T c - 9 9 m - p h y t a t e w a s g i v e n i n t o an a n t e c u b i t a l vein. T w o h u n d r e d s e r i a l 0.5s i m a g e s w e r e o b t a i n e d as the b o l u s p a s s e d t h r o u g h the t h o r a c o a b d o m i nal c i r c u l a t i o n , a n d t h e n i n t e g r a t e d as a s i n g l e image. L i v e r to l u n g c o u n t r a t i o ( L / P ) w a s e s t i m a t e d by the i n t e g r a t e d image. T h e L / P w a s s i g n i f i c a n t l y r e d u c e d in c i r r h o t i c patients(compensated:0.80,decompensated:0.69 P<0.01) c o m p a r e d w i t h c o n t r o l ( l . 4 1 ) , P<0.01. The m e t h o d w a s r e p r o d u c i b l e ( 0 . 9 8 ) . W e conc l u d e t h a t s i m p l e c o m p u t e r q u a n t i f i c a t i o n of L / P r a t i o in i n t e g r a t e d d y n a m i c l i v e r image m a y be of v a l u e in e v a l u a t i n g the s e v e r i t y of l i v e r c i r r h o s i s ,

Research supported by U.S.DOE contract# DE-AC02-76CHO0016)

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MEASUREMENTOF PORTAL SYSTEMIC CIRCULATION BY ORAL AND PER-RECTAL ADMINISTRATION OF 1-123 IODOAMPHETAMINE. S. Shiomi, T. Kuroki, T. Ueda, N. Ikeoka, K. Kobayashi, and H. Ochi. Third Dept. of Internal Medicine and Dept. of Radiology, Osaka City University Medical School, Osaka, Japan

PORTAL SYSTEMIC SHUNTS IN P O R T A L HYPERTENSIVE RATS: A CRITICAL EVALUATION OF 201-THALLIUM (TI) PER R E C T U M SCINTIGRAPHY. M...,. Picard, F. Sutto, L. Giroux, P.M. Huet. Ctre rech din A.-Viallet, H6p. St-Luc and Univ. de Montreal, Montreal, Quebec, Canada.

The portal c i r c u l a t i o n can be measured r e l a t i v e l y noninvasively by Tc-99m pertechnetate per-rectal portal scintigraphy (Shiomi et a l . , J Nucl Med 1988;29:460465). This method makes i t possible to see the portal c i r c u l a t i o n and to diagnose portal hypertension from the images of the l i v e r and heart. However, the method mainly r e f l e c t s c i r c u l a t i o n from the i n f e r i o r mesenteric vein, the contribution of which to t h e portal c i r c u l a t i o n is less than that of the superior mesenteric vein. Here, we devised capsules of 1-123 iodoamphetamine (IMP) that dissolve when the pH changes to evaluate the portal c i r c u l a t i o n arising from the superior mesenteric vein. 1-123 IMP enclosed in an enteric-coated capsule was prepared and given o r a l l y j u s t before 1-123 IMP was injected into the rectum. The per-rectal portal shunt index (RSI) and oral portal shunt index (OSl) were calculated from the counts of r a d i o a c t i v i t y of the l i v e r and lungs. Ten patients with chronic hepatitis and 15 patients with cirrhosis were examined. The mean RSI and OSI of patients with cirrhosis were both higher than those of the patients with chronic h e p a t i t i s (p < 0.001). Almost a l l of the patients with chronic h e p a t i t i s , the RSI was lower than the OSI, but in patients with c i r r h o s i s , the reverse was ture. This noninvasive method seemed to be useful in evaluation of the portal systemic c i r c u l a t i o n in chronic l i v e r diseases.

Recently per rectum administration of TI has been proposed in the estimation of portal systemic shunts (PSS) by comparing heart/liver uptake ratio (H/L). We measured PSS in rats using external H/L counting for 30 minutes following per rectal administration of T1 (40 #Ci). 42 rats were studied: 6 normal, 6 with portocaval shunts (PCS) and 30 portal hypertensive rats 2 weeks after partial portal vein ligafion around needles of different gauges (18,20,21 and 23). In these rats prior to per rectal T1, an ileocolic vein was canulated in order to measure PSS using injection of Sr-85 labelled microspheres (MS). After sacrifice, radioactivity of the liver, lungs and heart were measured for TI and St-85. Internal H/L was calculated from total Sr-85 activity in lungs and liver and PSS was calculated from Sr-85 activity in lungs and liver. Using MS, PSS was 0% in normal and 100% in PCS rats and varied between 1 and 100% in portal hypertensive rats. External H/L was 4.8_+0.6% in normal (mean-+SE) and 54.8-+4.3% in PCS rats and varied between 8 and 87% in portal hypertensive rats. Similar correlations were found between PSS evaluated by MS and external H/L (r=.664, p<.001) or internal H/L (r=.729, p<.001) but there was a large scatter in data. A significant correlation was also found between internal and external H/L (r=.787, p<.001). These data show that TI per rectum scintigraphy provides a rough estimate of PSS. The use of radiotracers with better rectal absorption may improve the accuracy of this non invasive method.

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QUANTITATIVE EVALUATION OF PORTOSYSTEMIC SHUNTING IN LIVER DISEASES BY TRANSRECTAL PORTAL SCINTIGRAPHY WITH 1-123 IMP. T. Kashiwagi, H. Fukui, K. Kimura, T. Kozuka, N. Sato, T. Kamada, M. Azuma, N. Mitsutani, and T. Koizumi. Osaka University Hospital and Osaka Kosei-Nenkin Hospital, Osaka, Japan.

PREVALENCE OF MALIGNANT HEPATIC NEOPLASM BEFORE AND AFTER BLOOD POOL SPECT IN PATIENTS WITH/WITHOUT PRIOR NEOPLASM

Portosystemic shunting was evaluated with rectal administration of 1-123 iodoamphetamine(IMP) in patients without and with liver diseases. After IMP(I-3mCi) was administered to the rectum through a catheter, images of the chest and abdomen were obtained for up to 60 min with a gamma camera interfaced with a computer. Images of the liver and/or lungs were observed within 10 min and became clear with time. IMP appeared to behave like a microsphere in these organs. Therefore, the portosystemic shunt index was calculated by dividing counts of lungs by counts of liver and lungs. In patients without liver disease(n=7), only liver image was obtained(shunt index=0%). The shunt index(Mean• was 4.3• in acute hepatitis(n=10), 5.9• in chronic persistent hepatitis(n=10), 11.4•163 in chronic aggressive hepatitis(n=20), 56.6• in compensated liver cirrhosis (n=31) and 88.1• in decompensated liver cirrhosis (n=25). The shunt index was significantly higher in patients with liver cirrhosis, especially the decompensated stage. Significant relationship was observed between the shunt index and hepatic function tests such as ChE, albumin, -globulin and ICG, whereas there was no relationship between the shunt index and hepatic function tests such as biliruhin, AST, ALT and ALP. In 7 patients with acute hepatitis, the shunt index was 0%. These results suggest that the shunt index obtained by this method is independent of hepatic cell function, so it appears to be an excellent indicator showing the degree of portosystemic shunt flow in liver diseases.

Dr. M.H. Malik, Pasqua Hospital and the University of Saskatchewan, Regina, Saskatchewan, Canada Seventy consecutive patients, 48 without and 22 with prior neoplasm but no evidence of spread elsewhere, who were referred for the evaluation of one or more focal hepatic lesions discovered by ultrasound, sulfur colloid SPECT or CT, had 4 phase blood pool Tc-99m scintigraphy including delayed SPECT, which revealed a total of 74 hemangiomas: 54 in 40/48 (83%) of patients without, end 20 in 12/22 (55%) of patients with prior neoplasm respectively. Those with negative blood pool SPECT had liver biopsy which showed malignant hepatic neoplasm (two hepatomas and one hepatic metastasis from carcinoma of the pancreas) in 3/8 patients without prior neoplasm. The others had FNH in three patients and an abscess and a cyst in one each. In those with prior history of neoplasm, I0/I0 had hepatic metastasis. Exclusion of patients with hemangioma resulted in the change of prevalence of malignant hepatic neoplasm from 6 to 37.5% and from 45 to 100% in patients without and with prior neoplasm respectively, which not only increased the percentage yield of malignant hepatic neoplasm by liver biopsy, but by avoiding unnecessary biopsy in 52/70 (74%) of all patients resulted in considerable cost and time saving.

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HEPATIC PIINFUSION INDEX IN HEPATOMA. S.J. Wanq, 5.H. Yeh, C.H. Kao, and C.G. (~en. Veterans GeJ]eral Hospital, Taichung, Taiwan.

EFFECT OF PROGLUMIDE (PG) ON HUMAN GALL BLADDER (GB). I.M. Hassan, M. Ai-Hassani, K. Kouris, G. Jacob, T. Ei-Sharkawy and H.N. Abdel-Dayem. Depts. of Nuclear Medicine, Physiology and Pharmacology, Faculty of Medicine, Kuwait.

The early detection of hepatoma presents a challenge to imaging technique since the early detection of hepatoma has important prognostic and therapeutic consequence. The hepatic perfusion index (HPI) has already been shown to be a sensitive method for detecting liver metastasis. This investigation assessed HPI in hepatoma. Subjects were required to starve for 12 hours before the procedure to avoid the increase in portal flow after eating. The subjects were studied supine over a large field garmm camera linked to a miniconi0uter. A rapid intravenous bolus of 3 mCi 9 9 m T c sulphur colloid was given intravenously and data acquired in 1-second frame of 64x64 pixels for one minute. The HPI was expressed as the ratio of hepatic arterial inflow gradient to total flow (hepatic arterial inflow gradient plus portal venous gradient). A computer routine adopted from Parkin et al. (Nucl Med Co~n 1983; 4:395) was used to calculate HPI. The HPI was studied on 47 subjects: 32 normal controls and 15 patients with hepatoma. The HPI values in hepatoma group was significantly increased when compared to normal control group (Normal control = 0.278 ! 0.099; hepatoma = 1.049 • 0.232; P < 0.001). Our preliminary results suggest that the HPI significantly increases in patients with hepatoma. The HPI may be used as a useful method of detecting hepatoma, especially in the high prevalence area of hepatoma.

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~roglumide is a glutaramic acid derivative used for the treatment of gastric and duodenal ulcer in humans. In several mammalian specicies PG blocks the cholecystokinin (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 i hr after EHIDA injection and i0 min later i0 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 • O.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% Vs 69 ~ 13%), ER (2.9 • 1.6%/min Vs 3.7 ~ 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 inhihitary action on the CCK induced by oral milk drink. These results contradicts previously published data from animal studies.

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DIAGNOSTIC VALUE OF THE REFLUX SIGN IN CHOLESCINTIGRAPHY. H. Itoh, N. Takahashi, K. lwata, M. Kawamura, M. Kataoka, R. Shimono-Sugawara, K. Murase, and E. Hamamoto. Matsunami General Hospital, Gifu, and Ehime University School of Medicine, Ehime, Japan.

ASSESSMENT OF SCLEROSING CHOLANGITIS BY DYNAMIC STUDY AND FACTOR ANALYSIS OF Tc-99m EHIDA EXCRETION AND SPECT. J.Lisin[, P.J. Sullivan, W.gormick, M.Boyd, Nuclear Medicine, Woden Valley Hospital, Canberra, Australia

This study reviewed 27 patients with the reflux sign in eholescintigrapgy to assess its diagnostic value in detecting incomplete obstruction of the common bile duct (CBD). Cholescintigraphy was performed using Tc99m PMT or Tc-99m (p-butyl)IDA and serial images were recorded before and after administration of IO~g os ceruletide diethylamine (caerulein). The reflux sign was determined positive when increased radioactivities in the right or left hepatic duct (minor reflux; MIR) or more peripheral intrahepatic ducts (major reflux; MAR) were recognized after gallbladder stimulation. The reflux sign was found in 30 out of 266 consecutive studies. X-ray cholangiograms were available in 27 (MIR= 13, MAR= 14). They included juxtapapillary duodenal diverticulum, biliary dyskinesia, CBD stone, chronic pancreatitis, papillary adenoma of the CBD, papiilitis, etc. The caliber of the CBD was ranged 4 to 16mm. Dilated CBD of more than or equal to ]Omm was found in 30% of MIR and in 79% of MAR. Apparent stenosis of the CBD was found in 8% of MIR and in 36% of MAR. Duodenal appearance time of RI was found prolonged more than 6Omin in 54% oK MIR and in 79% of MAR. Persistent stasis of RI was found in 36% of MAR only. When MAR sign was interpreted as positive for incomplete obstruction of the CBD, the sensitivity, specificity, and accuracy were 89%, 67%, and 74%, respectively. We concluded that MAR sign was helpful in detecting incomplete obstruction of the CBD, especially in patients with equivocal to mildly dilated CBD.

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The measurement of biliary excretion can be used to assess the functioning status of the hepatobiliary system. Ts-99m EHIDA scanning, Factor Analysis and SPECT were used to assess patients with Sclerosing Cholangitis. An anterior view dynamic study of biliary excretion at 1 frame per minute per 60 minutes is first obtained then followed by a SFECT study (360 ~ , 5 ~ step, 30 sec). Tc-99m EHIDA clearance half time from 3 regions of interest (Viz Right Upper Lobe, Right Lower Lobe and Left Lobe) are measured. Tomographie images are reconstructed to reveal locations of biliary dilatation and stasis. Factor Analysis allows the creation of time activity curves and images thereby differentiating the various phases of uptake and excretion within the liver so as to improve the accuracy of the diagnostic assessment. A significant error in the half time measurement is a result of physiological gall bladder filling. However it is possible to reduce the error by proportionately estimating and subtracting the fraction of the count due to gall bladder scatter. Patients with gclerosing Cholangitis had excretion rates ranging from normal (20 minutes) to greater than i00 minutes. The rate of excretion often paralleled their clinical state. Excretory rates however are nonspecific and the diagnosis is aided by using SPECT to help visualise beading and loealised holdup. It appears that Tc-99m EHIDA scanning will have its best role as a means of assessing patients over a time course and show evidence of deteriorating liver function prior to clinical or biochemical change.

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INFLUENCE OF CALCIUM LOAD ON INTESTINAL 51Cr-EDTA it4 ;II~'+I ++I ;J III IIl ' i l I ~I I I ; I tI l l P+Ii l l ;/+I +111tI ++~ | IIIII

LECOUFFE P., VERRIEZ O., HUGLO D., DEVEAUX M., MARCBANDISEX. Service A~oci~ de M@(lecine Nucl@aire et Service d'Endocrinologie et Diab~tologie - CHU Lille - FRANCE T o assess the effect of luminal calcium content on the results of the evaluation of intestinal permeability by Cr-EDTA test, we studied patients with steatorrhea as their luminal calcium content would be strongly influenced by calcium diet. Seven healthy adults (aged 29-32) acted as controls. Seventeen patients (aged 34-59) with chronic pancreatitis but no associated disease and no NSAI treatment were investigated twice before therapy as they received in a random sequence either a 1200 mg or a 300 mg calcium diet ; 13 ppatients were studied again on a 300 mg calcium diet after s two month pancreatic enzyme therapy. According to Bjarnason's technique, 24 h urinary excretion of 51Cr-BDTA was expressed as a percentage of the total oral dose. Compared with controls (1.47 % + .62, in Bjarnason's range), 24 h urine recovery of 51Cr-EDTA before treatment was significantly higher (p<.001) in patients on a high calcium diet (2.78 % + 1.12) or on a low ca|cium diet (3.75 % + 2.00). Excretions on high calcium diet was lowered by 45 % on low celcium diet and difference was statistically significant (pt,0.nS). Excretion on a 399 mg diet was 15 % lowered after treatment (p~.05). Our results suggest an abnormal intestinal permeability in patient with chronic pancreatitis. Although no strong correlation was found between amount of stool fat and excretion of 51Cr-~DTA, intracellular fat overload could modify the intestinal permeability of tight-Junctions. Alcohol is not concerned since all patients were studied at least four days after withdrawal and since the sequence of two first t ~ t s was variable. Chelation of calcium appears to influence dramatically test result : so luminal calcium load must be taken in account to assess exactly intestinal permeability to 51Cr-EDTA.

Sunday, August 26, 1990

C-13 RREATH TESTS FOR EVALUATION OF FLAH~_BSORPTION H.Ohara, T.Suzuki, K.Someya and Y.Sasaki ~ M.Tateno ~ St.Marianna University and Gunma University~ Kawasaki, and Maebashi ~ Japan

Breath tests using stable isotope C-13 labeled compouds were evaluated in animal models and limited numbers of patients in order to detect malabsorption+ C-13-palmitate or glycine cholate was given orally. CO 2 in the exhaled breath was collected serially preand 0.5-6 hours post administration of the tracers. Isotope ratios of C-d3/C-12 carbon dioxide were measured using specially developed infrared breath analyzer. The tests were performed in normal rats, rats with jejuno-colostomy or ligation of pancreatic duct~ and in 3 patients with jejuao-colostomy or choledoco-eolostomy. In normal rats C-13-C02 curves with peaks and flat curves were obtained after C-13-tripalmitate or C-13glycine-cholate administration, respectively. Fat malabsorption in rats with ligation of pancreatic duct was detected by relatively flat curves after C-13-paimitate ingestion. Deconjugation of bile salts in rats with jejuno-colostomy was detected by the curves with early peakes after C-13-glycine-cholate intake. In patients with jejuno-colostomy or choledoco-colostomy increased excretion of C-13 in the breath indicated malabsorption due to bile salts deconjugation in C-13 glycine-cholate breath test. Normal flat curves were obtained after surgical repair of the anastomosis. The C-13 breath test may prove usefull for the diagnosis of malabsorption syndromes. The tests can be used in place of 1-131-trioleim test, which is difficult to perform because of non-availability of the tracers.

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DOCUMENTING LATE ILEAL DAMAGE WITH Se-75 NCAT AND C-14 GLYCOCHOL IN POST THERAPEUTIC IRRADIATION CONDITIONS. R.A. Vald@s Olmos, F.C.A. den Hartog Jager, B.G. Taal, C.A. Hoefnagel. The Netherlands Cancer Institute, Amsterdam, The Netherlands.

CARBON-11 UREA FOR DETECTION OF HELICOBACTER PYLORI INFECTION USING DYNAMIC IMAGING. N.G. Hartman, M. Jay, U.Y. Ryo, R.J. Bera, D. Hill and C.J. McClain. University of Kentucky Medical Center, Lexington, KY.

Methods to determine ileal dysfunction are often not very reliable. Se-75 HCAT seems promising to detec 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 malignanees with (A) and without (B) ileal resection (IR), mostly with complaints, were investigated for BAN and BO. BAM was considered severe when SeHCAT retention reached <8% of the initial 2h-value within 72h and mild when it was between 96 and 168h. > 15% after 7 days was normal. In group A (n=12) BAN was severe in 9 (20-80 cm IR) and mild in 2 (20em IR). In 1 with 13cm IR not distal SeHCAT was normal. In group B (n=19) BAM was severe in 2, mild in A. Normal was seen in 12 and intermediate (12%) in i. SeHCAT T~ varied between 4 and 19h for severe, 25-40 for mild, 55-265 for normal. Breath test was negative in 5 severe and i mild BAN; 3 normal SeHCAT with positive breath test were considered to have BO. Additional imaging revealed cases of prolonged SeHC AT colonic transit causing spurious retention values. Conclusions:l)Combined use of Se-75 HCAT and C-14 glycochol differentiated BAN from BO. 2)SeHCAT permitted to distinguish between severe and mild BAM with implications for therapy (e.g.eholestyramine). 3)Systematic Se HCAT imaging improved accuracy of the test. 4)High incidence of false negative C-14 glycochol has been noted in severe BAH possibly due to rapid bowel transit time.

Helicobacter pylori (formerly Campylobacter pylori) is a bacterium with high urease activity and is associated with chronic gastritis. Diagnosis is made by a number of procedures including noninvasive breath tests employing liquid scintillation counting or mass spectrometry following administration of C-14 or C-13 labeled urea respectively. The present study in which C-11 labeled urea was employed, was conducted in a small number of H. pylori positive patients and negative controls. The C-11 label has the potential to overcome some of the limitations of the breath tests by using dynamic imaging to measure metabolism of urea in the stomach of H. pylori patients. C-11 urea was synthesized from C-11 carbon dioxide produced at the Univ. of Kentucky Van de Graaff Accelerator. To patients with positive gastric biopsies were administered 200 ~tCi of C-11 urea, along with 150 t.tCi of Tc-99m DTPA which served as a control for loss of radioactivity from the stomach via gastric emptying. Images were obtained from a ?-camera at 1 rain. intervals for a period of 20-30 minutes. Concomitantly, the appearance of C-11 in the breath was continually monitored. The H. pylori positive patients exhibited a Tc-99m:C-11 ratio of 2:1 in the stomach 10-20 min. following administration, compared to a 1:1 ratio in controls. This was indicative of metabolism of urea to C-11 carbon dioxide with subsequent diffusion of C-11 activity out of the stomach. The C-11 activity in the breath was greater in patients than in controls.

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MEASUREMENT OF SMALL BOWEL TRANSIT TIME WITH A STANDARD GASTRIC EMPTYING MEAL. M.G. Velehik, LC. Reynolds, and A. Alavi. Hospital of the University of Pennsylvania, Philadelphia, PA.

M E A S U R E M E N T OF S M A L L B O W E L T R A N S I T T I M E WITH A STANDARD GASTRIC E M P T Y I N G MEAL. M.G. Velchik. J.C. Reynolds, and A. Alavi. University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Small bowel transit time (SBTT) is a clinically useful but relatively elusive parameter of gastrointestinal motility. It would be cost-effective and advantageous with respect to patient dosimetry if the SBTT could be measured after routine radionuclide gastric emptying (GE) studies, 'analogous to the barium UGI and small bowel follow-through study. In order to determine the efficacy of measuring the SB'FF in conjunction with routine GE scans, a total of 30 SBT studies were performed in 20 patients and 6 normal volunteers. The patients ingested a meal consisting of either 150 or 300 Kcal of Tc-99mSulfur Colloid labeled egg-sandwich with the following composition: CHO 40%, protein 40%, and fat 20%. After the completion of the routine GE study, anterior I minute images of the abdomen in the supine position were obtained @ 15 minute intervals until radioactivity was evident in the cecum. The study was terminated if activity had not reached the cecum by 5 hours. The examination was > 5 hours in duration for 22 of the 30 studies including 7 of the 9 control studies. Blood samples obtained in 2 control patients did not reveal any significant radioactivity to suggest dissociation of the tag from the meal. In summary, it is not practical to conduct clinical SBT studies at the conclusion of GE scans with the routine GE meal. Accelerators of gastrointestinal transit such as lactulose make such measurements much more feasible.

Small bowel transit time (SBTT) is a clinically useful but relatively elusive parameter of gastrointestinal motility. It would be cost-effective and advantageous with respect to patient dosimetry if the SBTT could be measured after routine radionuclide gastric emptying (GE) studies, analogous to the barium UGI and small bowel follow-through study. In order to determine the efficacy of measuring the SBTT in conjunction with routine GE scans, a total of 30 SBT studies were performed in 20 patients and 6 normal volunteers. The patients ingested a meal consisting of either 150 or 300 Kcal of Tc-99mSulfur Colloid labeled egg-sandwich with the following composition: CHO 40%, protein 40%, and fat 20%. After the completion of the routine GE study, anterior 1 minute images of the abdomen in the supine position were obtained @ 15 minute intervals until radioactivity was evident in the cecum. The study was terminated if activity had not reached the cecum by 5 hours. The examination was > 5 hours in duration for 22 of the 30 studies including 7 of the 9 control studies. Blood samples obtained in 2 control patients did not reveal any significant radioactivity to suggest dissociation of the tag from the meal. In summary, it is not practical to conduct clinical SBT studies at the conclusion of GE scans with the routine GE meal. Accelerators of gastrointestinal transit such as lactulose make such measurements much more feasible.

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Sunday, August 26, 1990

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DETECTION OF ECTOPIC GASTRIC MUCOSA IN ENTERIC DUPLICATION. C. Coosemans, K. Seybold and J.Th. Locher Kantonsspifal Aarau, Switzerland.

~

E SPREAD OF 5-ASA C(~TI~INING END~A I N PATIENTS WITH ULCERATIVE CCK/TIS

Enteric duplications are rare congenital malformations, which arise if the notochord and the foregut fail to separate during embrionic life. Quite commonly they are lined with ectopic gastric mucosa, which in part is responsible for the lifethreatening complications such as ileus, volvolus or invagination of the bowel. We present the case of a 4 month old male infant with two separate manifestations of the split notoehord syndrome: one situated in the mediastinum, the other one in the abdomen. The abdominal duplication was identified only by the Tc-99m pertechnetate scintigraphy demonstrating the presence of ectopic gastric mucosa and was missed by other clinical and radiological methods such as ultrasound and CT. The thoracical malformation was seen on radiographs but showed no tracer uptake. Histology demonstrated a neuroenteric cyst without cellular elements of the alimentary tract epithelium. The case allows a didactically impressive demonstration of an early phase of organogenesis in humans.

In order to investigate the retroqrade spread in the colon ~ its relationship to the extent of-the cLzseasea area, we evaluated a I00 ml, I gram 5 amznosaliovlic acid enema (Pentasa ~) in a consecutive serles of 30 Patients with idiopatb/c infla,mmtory ~ bowel disease. The Pentasa ~ enema was labelled with i0 MB~ ~chnetium-human serum albumin microcolloi~ After icatign of .the enema t h e patients were lying on a rme zlrs~ D mlnu~es on tme~r lefn sloe. G@xm~acamera scintigraphy ~ performed after 5 r~nuuas~ i arm z ns. Anterior and lateral vie%m were obtain~i %31e results of scintigraphy were compared with r_ne extension of the ulsease as found by oolonoscopy. If the enema reached the entire affected area I t w a s interpreteted @s "to~ically adequate". ~ l ~u Da~lenr~ nac~ a z.J.euce o'r o~stil ulcerative colitis. The male/female ratio was i. 0, median age 44 yrs, range 16~68 y). In 6 patients there ~ no. . .. loro~resalon or v~e enema reyon~ TJ~e r e c ~ i g m o 1 ~ wn1• In 4 the mld-aascending colon, in 10 the s~leni,o rlexure, in 8 the r-ransvense colon and in z Patients the mid-ascending colo~ The Pentasa ~ enema w a s found = o cove z the tot~l maqroscop,icall.y involved area in 24 out .or ~u Pa~len~s arm w a s ~ e r e z o r e . c o n s i d e r e d " " = o p l c a l l y . aqequate" we conoAune that a 100 ml Pentasa ~ enema reaches the affected area in 80 % of the patients with left-sided colitis. This result is sup@_rlor to the length of s p r e ~ o f the 40 ml home-made (van Buul et il, ~troenterolczjy 1988). Increasing the volume of the 5~ ~lenema zrom-~0 to I00 ml improves r-he Possibility o z ~o2~9al. therapy of the to~al disease~, segment in cases OZ fez= Sl(l~C~COll~iS.

T i e l - v a n Buul =, CJJ Mulder=, EA van Royen=, E~H

w%~t~n~=, u ~ ',y~.gat=. Acaaemlc ~edical uen~er, depts O.Z nucAear medi,olne z, K a s ~ n t e r o l Q g y - h e p a t o l o g y = and p r i m a c y ~, AmszerQam, The Ner~erla/K1s.

~

145

146

N~deelae nuel;aire et Seei;t~

MEASUREMENT OF TSAb ACTIVITY IN PATIENTS WITH GRAVES' DISEASE BY cAMP RELEASE TO THE MEDIUM IN CULTURED CLONAL RAT THYROID CELLS FRTL-5. Lu Chao, Kasagi Kanji, Hidaka Akinari, lida Yasuhiro, Hatabu Hiroto, Konishi Junji, & Lin Xiang-Tong. Department of Nuclear Medicine, Huashan Hospital of Shanghai Medical University, and Department of Nuclear Medicine, Kyoto University, S c h o o l o f Medicine, Japan.

Le g o i t r e ~ H~u g i a n g ( d e l t a du Mekoag-Sud Vietaan) Phan Val Duyet,Huynh ~uang Mau e t =o11. Au Vietlam ~ eet~ dee z~nee d ' e n d ; a i e g o i t r e u e e a z r~gleno montagneusee aveo oarenoe d'iode ii y a dee

=~.ea goitreusem a u x plaiaea dent la cause a'eat paus eaeore d~termla~e.Dame ee travail une ~%ude our le goltre eomeeraamt 7200 sujete do la provimee de

H~U gia~g a meatr~ l e a r ~ s u l t a t s s uivant : i / A l'exeeptioa

d'us dlstriet littoral o~ le goltre

eat tr~e rare,lea trois autres distrlet8 oat uae 4eldemee goitreu6e de ~-lOX de la populatioa daa8 ua milieu de vie aans d~fs 2/

Xl y a ale eorr~lats

d'iode(16-39

nee/l).

laverme eatre le teal de

fixation d'Xl31(ohez lee goitreux et non goitreux) et la teleur el lode dee eaux potableo (r= -0,87). 3 / S G N ' , l a duret~ del eaux ne mallfeotent aueun

r o l e d ~ f i m i t i f t a l d i e que l e a substance8 o r g u i q u e 8 e x i e t a a t dams l e e eaux du fleuve(?_lO mg/1) Jeueat prebableaent un r ~ l e g o i t r i g ~ n e important ( r . 0.85)

A sensitive and practical assay for thyroid stimulating antibody (TSAb) was introduced based on Kasagi's methods with minor modification, using clonal rat -thyroid cell line FRTL-5. The supernatant of crude Ig preparations precipitated by 15 % PEG was incubated with cells in hypotonic and sodium minus condition. The cAMP concentration in the medium released by cells was measured to calculate TASb activities. In this assay system, bTSH was able to produce a significant rincrease of cAMP release at I ~IU/ml, and 40 out of 42 (95.2 %) patients with untreated hyperthYroid Graves' disease had positive TSAb compared with that in normals. There was a significant correlation between TSAb and TBII activities (r=0.7268, P< O.O01). No any 9 was observed in serum T3, or T4 with TSAb activities.

4 / Le geltre pout ;ire eonsidgr~ euthyreidlea anx

r;sultate dee radloi~alodoeaKe8

de T4,T3 et TSH.

5 / P o u r r~duire lee subatalee8 orgallqueo ea echoer

van% l'iode dale l ' e a u potable l'auteur reeoueJade ueer l'eau d~ealt~e apr~e l'alvJaage.

Sunday, August 26, 1990

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147

148

CORRELATION OF N U ~ S C A N N I N G W I T H D I A G N O S T I C U L T R A SOUND IN THYROIDDISEASES. i. PRIMARY HYPOTHYROIDISM. F. Khamsi, F. Mohamed, D. Kozak, P. Wilson. Advanced Diagnostic Facilities, Toronto, Canada.

CORRELATION OF NUCLEAR SCANNING WITH DIAGNOSTIC ULTRASOUND IN THYIg0ID DISEASES. 2. END~ValC GOITER. F. Khamsi, F. Mohamed, D. Kozak, P. Wilson. Advanced Diagnostic Facilities, Toronto, Canada.

Ten years ago we started a prospective study of the above subject. The parameters noted were the clinical findings,T3, T4, T7, TSH, thyroid antibodies and radioactive uptake. The parameters noted on the radionuclide scan were the size (as small, normal or enlarged); general pattern of uptake (as normal, patchy or very patchy) and presence of distinct abnormalities such as a "hot spat". On ultrasound the parameters recorded were the size, the hcmogeneity and echogenecity. The results of our first 6 years were analysed in patients with primary hypothyroidism of total of 71 cases. The radionuclide scan showed the gland to be small in 27%, normal in size in 40%, and enlarged in 33%. The generalized uptake was noted to be normal in 48%, patchy in 50% and dzstinctly patchy in 2%. The ultrasound showed the gland to be normal in size in 32%, enlarged in 41% and small in 26%. The hc~ogeneitywas normal in 35%; abnormal in 26% and distinctly abnormal in 39%. The echogenecitywas noted to be normal in 16%, hypoechoic in 80%, and hyperechoi C in 3%. In conclusion, the size of the gland may be reduced, normal or enlarged. However on ultrasound the hc~nogeneitywas abnormal in 65%. The.most interesting finding was that in 80%, the gland was hypoechoic. Our experience is that, on ultrasound, a gland with primary hypothyroidism almost always, has a severely hypoechoic appearance. A severely hypoechoic appearance in ultrasound is an extremely reliable evidence of primary hypothyroidisra.

Ten years ago we started a prospective study of the above subject. The parameters noted were the clinical findings, and thyroid indices. The paraneters noted on the radionuclide scan were the size (as small, normal or enlarged); general pattern of uptake ( as normal, patchy or very patchy) and presence of distinct abnormalities such as a "hot spot". On ultrasound the parameters recorded were the size, the hcmogeneity and echogenecity. The results of our first 6 years were analysed in patients with endemic goiter of total of 35 cases. The radionuclide scan showed the gland to be small in 2%, normal in size in 57%, and enlarged in 41%. The generalized uptake was noted to be normal in 0%, patchy in 84% and distinctly patchy in 16%. The ultrasound showed the gland to be noz~nal in size in 10%, enlarged in 90%, and small in 0%. The homogeneity was normal in 0%; abnormal in 0%, and distinctly abnormal in 10U%. The echogenecity was noted to be normal in 0%, hypoechoic in 67%, and hyperechoic in 33%. In the ultrasound studies cystic structures were noted in 30% of cases, solid structures in 48%, and mixed solid and cystic in 22%. On the radionuclide scan distinct areas of increased or reduced uptake was noted in 6 out of 35 patients. In conclusion the most significant finding on imaging for endemic goiter is a severely non-homogenous appearance on ultrasound. The echogenecity was either increased or reduced but never normal. The majority of glands also show enlargement both on radionuclide scan and on ultrasound. Should a gland have normal homogeneity and echogenecity on ultrasound then endemic goiter is almost certainly excluded.

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HIGH SPATIAL RESOLUTION SPECT OF THYROID GRANDS USING PIN HOLE COLLIMATOR WITH A NEW METHOD. H. Kawai,* M. Kaneko,* and T. Kato**. *Hamamatsu University School of Medicine, Hamamatsu City, Shizuoka Prefecture, Japan, and **Shimadzu Corporation, Kyoto, Japan.

THYROID UPTAKE AND SCINTIGRAPHY USING A MODIFIED DUALPHOTON ABSORPTIOMETRY SCANNER. C.S. Ahn, and D.E. Tow. Veterans A f f a i r s Medical Center, Brockton/West Roxbury and Harvard Medical School, Boston, Massachusetts, USA.

In order to obtain high spatial resolution SPECT images of thyroid grands we have developed a new method of SPECT using pin hole collimator. In our new method we used the existing rotating gamma camera and its attached computer without any special hardware. Data was acquired with 32 views over 180 degrees in a 64x64 matrix size. Acquisition dta was reconstructed in a few minutes using the modified filtered back projection, which was the essential point of our method. Fundamental studies were performed with line sources and a specially designed cylindrical phantom. FWHM of our SPECT was 8.5 mm at i0 cm radius of rotation. As a matter of course the shorter rotating radius, the higher spatial resolution. A cold spot of 7 mm diameter in hot phantom was detected at i0 cm radius. In clinical studies, SPECT image with the new method revealed detailed anatomical structures of thyroid gradns, which were hardly obtainable with the conventional SPECT. And small space occupying lesions in the thyroid glands were far more clearly detected by SPECT with the new method than by planar images. There were some weak points such as obtaining only one slice, limited field of view and slightly decreased sensitivity. But these were not important for SPECT of thyroid grands. Our new method of SPECT was considered significant to diagnose the diseases of thyroid grands.

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A microcomputer based dual-photon absorptiometry scanner, modified to perform thyroid uptake and s c i n t i graphy, in addition to bone densitometry (PolyScan) was evaluated f o r thyroid studies. The detector head consisted of 9 cm wide, 6 cm thick sodium iodide c r y s t a l . A f l a t - f i e l d c o l l i m a t o r was used f o r thyroid uptake study. Both high and low energy focusing collimators with focal length o f 10.6 cm were used f o r thyroid r e c t i l i n e a r scanning. The thyroid uptake values using 1-123 or 1-131 were closely matched with those obtained with a conventional thyroid uptake device. The r e c t i l i n e a r scan images obtained u t i l i zing Tc-99m, 1-123, or I-!31 in patients were s a t i s f a c t o r y in determining physiology as well as morphology of the thyroid in 1:1 size without dist o r t i o n . The images can be demonstrated in both f i l m and color p r i n t o u t . We conclude that a bone absorptiometry scanner modified to add thyroid uptake and scan c a p a b i l i t y is a useful device that can perform three important nuclear medicine studies with one instrument.

Sunday, August 26, 1990

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'l'H~'l,;t;il~ I;~;,'~N~'~",:;~ ANb FINE NEEI~LE A'-;I~qRATJuNI FNAI IN ']'H}', }'NI~k)['EK& I'l '#E E~/ALLIA'L'h3N t~F THYRO]D NODULES[TN ). ~L(]. TQni,C ~e Gandio,L.Lueiani ]'.~'eragioli,L.G~uliani University oi Pisa, italy.

ACCURACY OF Tc-99m THYROID SCAN IN DIFFERENTIATION OF MALIGNANT FROM BENIGN COOL NODULES AS COMPARED WITH FINE NEEDLE ASPIRATION; TRUCUT BIOPSY AND SURGICAL HISTOPATHOLOGY. D.W.Yeun$, P.Cheung, and J.Boey. Queen Mary Hospital, University of Hong Kong, Hong Kong, and UCSD Medical School, San Diego, CA, U.S.A.

From ]!Jt~7 to 1.9~9 272 pts with TN (212F,60M; age ra~ige 12-~i[. yrs) were operated on. Prior to surgery all pts ~mderwent neck palpation,US study and routine thyroid fl.alctJon tests. 140 pts,79 with solitary nod~le (SN)and 61 with multinodular goiter.(MNG)were submitted to FNA as well. ]n 120 pts[67 SN, 58 MNG] preoperative iqqA was in agreement with histologic sLeeimen:44 p{s pos]tlve findin~'s (neoplasm) and 76 ~ere uegative Jn both examinations. In 20 pts there was no agreement be~qeen preozerative FNA and histo]og~y: 17 pts diagnosed by FNA as ~<,sit.ive or' suspicious for neoplasm,were benign on surgical sLeeimens !faLse positive)and 3 pts were false negatiw,.67 of 6~ pts wit,!] SN and preoperative FNA were submitted t,O Tc -~Jm q< ~,erte<:hnetate T$ that showed cold nodules in []2 pts. Jn 16 pts,with SN and no preoperative FNA, ']'S showed r nodules in 6 pie.Therefore aunlong pts w]t.h :
Aim: A 3 years prospective study was performed to evaluate the efficacy of thyroid scan, fine needle aspiration (FNA) and trucut biopsy (TCB) in the diagnosis (Dx) of thyroid cancer (CA), so as to improve management strategy in patients presented with thyroid nodules. Method: Dynamic and static pinhole images of the thyroid gland were performed with 2 mCi.Tc-99m pertechnetate IVI. Probability of malignancy was computed using the 5 Parameter Analysis Method (Bayesian Theorem ) as reported previously. O FNA and TCB were also obtained before surgery. Results: Out of 1257 patients in the study, 117 patients had final surgical pathological diagnosis after thyroid scan. Criteria Sews. Spec. Accur. P-value I.Cool/Cold nodule:CA 100% 7.4% 24.8% 0,223 2.Scan Report Dx CA 59.1% 89.5% 83.8% 3.8xi0-~ --/ 3.FNA Dx for CA 47.4% 100% 90.5% 0xl0 4.TCB Dx for CA 42.9% 98.5% 88.9% 5.9xi0-~ 5.Scan or FNA Dx CA 84.2% 89.5% 88.6% 0xl0 Conclusion: (1)The study confirms that we can differentiate malignant from benign cool nodules with 84% accuracy using Tc-99m thyroid scan. (2) In view of the low (<50%) sensitivity of FNA and TCB, thyroid scan should be performed first. If scan is diagnostic of CA , the patient can proceed directly to surgery. If the scan is of low probability,FNA should be performed. o D.W.Yeung et al. Nuklearmedizin:493-495,1986.

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APPLICATIOi~ OF T}E RADIOISOTO• Cs-131 IN EA_RLY D I A G V O S I S O F TT:~:O!D CA::CER. SEITSITIVITY A ! ~ S P E C I F I C I T Y OF TIiIS ~ E T O D ,

FOLLOW-UP STUDY OF POST-OPERATIVE PATIENTS WITH THYROID C A N C E R BY T H A L L I U M - 2 0 1 SCINTIGRAPHY AND S E R U M THYROGLOBULIN MEASUREMENT. Y. lids, A. H i d a k a , H. H a t a b u , K. K a s a g i , and J. Konishi. Kyoto U n i v e r s i t y School of Medicine, Kyoto, Japan.

B. H u s z n o a n d Z. S z y b i ~ s k i . ~ h e b u c l e a r ~[[[ne-~ivision DeDart~nent o f E n d o c r i n o l o g y [~edieal A c a d e m y ~ i n Cracow, Poland. S e a r c h f o r t h e s e n s i t i v e mar[cer o f t h y roid cancer constantly lasts. The examination of thyroglobuline level and T!-201 sciniigraphy in t h e e a r l y s t a g e s of t h e t h y r o i d n e o p l a s m is so:~eti~es d e c e p t i v e . F o r a l o n g t i m e it has b e e n o b s e r v e d t h a t 0 s - 1 3 1 c a n accu~:mlate in t h e c o l d n o d u l e s of t h e t h y r o i d g l a n d . T h e s t u d i e s c o m p r i s e d during five years 8398 patients with nodules o f t h y r o i d a n d t h e i s o t o p i c e x a m i n a t i o n r e v e a l e d in 5 6 8 7 c a s e s the c o l d n o d u l e s o f t h a t g l a n d . In t h i s g r o u p 1 1 0 3 n a t i e n t s w e r e t r e a t e d s u r g i e a l y , a n d a m o n g t h e m 139 p a t i e n t s w e r e d i a g n o s e d as t h y r o i d m a l i g nant neoplasm. Each operated patient underwent additional scintizraphy of radioeesium Results of selective scan with Cs-131 were t r u e p o s i t i v e im 113 c a s e s , t r u e n e g a t i v e in 886, f a l s e p o s i t i v e in 7 8 a n d f a l s e n e g a t i v e in 26 c a s e s . T h e n t h e s e n s i t i v i t y of examination was calculated, it w a s s h a ~ n tbst the sensitivity of the identification o f the p a t h o l o g i c a l focus by radiocesium is e q u a l to 0 , 8 1 2 . It m e a n s t h a t ad,~itiona! s c i n t i g r a p h y bs' u s e C s - 1 3 1 e n a b l e d the p r e s u r g i c a l d i a $ n o s i s o f t h y r o i d c a n c e r in 8 1 , 2 % c a s e s . T h e h i g h e s t s~>eeificity o • t[~e aecu~latJo~ o f C s - 1 3 1 w a s sho~vn in r e l a t i o n to ~ a p i l ! a r y csrcJ21ol]i~ $~!]d t]len to f o i l . c a .

Sunday, August26,1990

T h a l l i u m - 2 0 1 chloride (TI-201) s c i n t i g r a p h y and serum thyroglobulin (Tg) measurement have been used to evaluate thyroid tumor. We e v a l u a t e d TI-201 scan and serum Tg c o n c e n t r a t i o n to detect r e c u r r e n c e in postoperative patients with thyroid cancer. TI-201 scan was p e r f o r m e d in 150 p o s t - o p e r a t i v e patients with thyroid cancer. Serum Tg levels could be measured in 86 patients at the time of TI-201 scan. A m o n g 55 patients w i t h positive TI-201 scan, 51 patients (92.7%) were r e c u r r e n t but 4 patients (7.3%) had no recurrence for 3 to 9 years. A m o n g 95 patients with negative scan, 15 patients (15.8%) were recurrent and 80 patients (84.2%) had no recurrence. T w e n t y - f i v e (89.3%) of 28 patients w h o s e serum Tg levels were more than 30 n g / m l were r e c u r r e n t and 43 (74.1%) of 58 patients whose serum Tg were less than 30 ng/ml had no recurrence. In 30 patients with positive TI-201 scan, Tg levels were more than 30 ng/ml in 19 patients (63.3%). All of them were recurrent. Among 56 patients with negative TI-201 scan, Tg levels in i0 patients (17.9%) were more than 30 ng/ml. Seven of them (70%) were recurrent. Forty (87.0%) of 46 patients whose Tg levels were less than 30 ng/ml had no recurrence. A l t h o u g h TI-201 scan was more accurate (p
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CLINICAL EVALUATION OF T e - 9 9 m ( V ) - D ~ W O SU(EINqlC ACID (IlV~A)FOR FOLIf~JJP OF PATIENIS WITH ~EULIARY THYROID CARCIN(NA. M.Redrignes,M.R.Vieira,R.Santos and E.IAmbert. Instituto Portugn~s de Oncologia de Prencisan Gentil, Lisben, Portugal.

RE EVALUATION OF "SUBCLINICAL HYPOTIIYROIDISM" AFTER I- 131 THERAPY C. Chou and S. Liu. PUMC Hospital, Beijing, China

Medullary thyroid carcinc~a(MIC) has a high incidence of recurrence. In 1984, the group of Kyoto University reported sucesfnl imaging of MIE using Tc-99m(V) - []~A (I~A). We evaluate the role of III3A imaging in 30 patients (pts) (19 female and Ii male) with histologically proven MIC, namely in the diagnosis of recurrence and metastases. Age at diagnosis range 14-81(mesn 47.9) yesrs.Two pts were imaged prior and after total thyroidectomy (IT)(5 studies) and 28 pts (34 studies) only after IT.Teanty pts (26 studies) had biocher~ical end/or clinical evidence of recurrent disease. Pts were injected with 10mCi Te-99m(V)-IIvEA IV and images were acquired on a gamin camera at 2 and 4 h postinjectiea.Anterior and posterior head, neck, thorax and abdomen images were obtained. The 2 pts imaged prior and after IT showed positive uptake of EN3A in thyroid prior and no uptake after IT. Positive uptake of ~FF~Ain metastases and/or in residual thyroid were observed in 21 studies;at time of imaging only 20 pts had elevated calcitonin levels, 16 pts elevated CEA levels and 13 pts dinical evidence of disease. No abnormal uptake of IPBA ~as observed in 4 pts with elevated calcitonin levels, 3 pts with elevated CEA levels and 2 pts with clinical evidence of disease. Three pts with positive uptake of IICSA in metastases had negative CAT scans; two other pts had metastases visualised on CAT scans and no abnormal uptake of II~A. Eight pts without evidence of di sesse after IT showed no abnormal uptake of I~A. We concluded that llVflAis a useful imaging agent for follow - up of MIE,with a sensitivity of lesion detection of 76.9% in pts with proven recurrence and/or metastases; positive upta&e of INSA can be the only positive finding, even before elevated calcitonin and ( ~ levels.

Late hypothyroidism is the main problem in thyrozoxicosis t r e a t e d with 1-131. Toll has r e p o r t e d that for euthyroid patients with elevated plasma TSH (subclinical hypothyroidism, SH), there is a risk of developing hypothyroidism in future years. 7n this work 2 groups of patients were studied: (A) 25 cases of SH patients (clinically asymptomatic 7-19 yr after 1-131 therapy, but with elevated basal TSH or increased TRH response, ATSH) were re-examined for 35 times during a follow-up period of 5-7 yr. (B) 14 euthyroid patients (botb clinically and biochemically normal, 7-22 yr after 1-131 therapy) were studied in the same period as a control group. Our" r e s u l t s showed: (1) I n g r o u p A, 2 p a t i e n t s d e v e l o p e d o v e r t h y p o t h y r o i d i s m , 8 p a t i e n t s became b i o chemically euthyroid, 4 fluctuated between SH and euthyroid stage and it had no apparent change. (2) In group B, 2 patients became SH, 7 remained unchanged and 5 fluctuated between euthyroid and SH. Conclusion: (i) SH may indicate an unstable compensatory state of hypothalamic-pituitary-thyroid function in patients after 1-131 therapy. Although most SH patients will remain unchanged for' a long period, some may transform into euthyroidism or fluctuate between SH and euthyroid and only a few will change into overt hypothyroidism. (2) The classification of patients into euthyroid and SH after 1-131 therapy has little significance, since the biochemical finding depends on the examination time. (3) The autoimmune processess and the natural history of the disease may be an important cause of "late hypothyroidism" after 1-131 therapy rather than the radiation effect.

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EFFECT OF SURGICAL TREATMENT OF PITUITARY ADENOMA ON HYPOTI~IC-PITUITARY-THYROIDAL AXIS FUNCTION Lu Chao, Lin Xiang-Tong, Yang De-Tai. Department of Nuclear Medicine and Neurosurgery, Huashan Hospital, Shanghai Medical University, Shanghai 200040, P.R. China.

PARATHYROID ADENOMA LOCALIZATION BY SCINTIGRAPHY SUBTRACTION TECHNIQUE USING TC-99m AND TL-201: PITFALLS OF THE TECHNIQUE. G.W. Moskowitz, J.N. Attic, A. Khan and P.G. Herman. Long Island Jewish Medical Center, New Hyde Park, New York, U.S.A.

The hypothalamic-pituitary-thyroidal axis function was studied in ten patients with pituitary prolactinomas and seven with growth hormone tumours pre- and post-operatively. There were significant decreases in serum TT3 in both groups ten days after operation compared with that before treatmeat (PRL tumour: 93.37• v.s. 71.57• ng/dl, P " O.01; and GH tumour: 97.85• v.s. 71.46• ng/dl, P ~ 0.05). No marked changes were found in basal TSM, TT4 and FT4. The TSH responses to TRH were decreased in 7/10 patients with prolactinoma and 5/7 with GH tumour postoperatively. In both PRL and GH tumour patients, serum rT3 was higher in some end lower in others after operation. The results suggest after surgical treatment of pituitary adenoma lead to transient decreases in TSH reserve and serum TT3 levels may result from both physiological stress and destruction of thyrotrophs hy the operation.

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A retrospective analysis of 102 patients with surgically confirmed parathyroid adenoma (PTA) revealed a Tc99m T201 Scintigraphy (TTS) sensitivity of 76% and a specificity of 99%. This study resulted in improved protocol and examination interpretation. Nodular thyroid disease simulates focal accumulation of T1-201 by PTA. Thyroid adenomas which have a high affinity for Tc99m cause over subtraction and require modification of the computer technique. The use of dual isotope method with simultaneous acquisition avoids motion artefact of the patient in the final image subtraction. Patients with borderline activity of the PTA require proper background subtraction prior to image correction. Injection of the Tc-99m pertechnetate first provides an opportunity for positioning as well as an image of scatter of the Tc99m photon into the T1-201 window. Performing the study in the morning on fasting patients utilizes the T1-201 at it highest activity without competition from gastrointestinal activity. TFS is not appropriate when a PTA is suspected to be outside the thyroid bed such as in the superior mediastinum. Meticulous adherence to the prothcol results in a simple, safe and accurate technique for the localization of PTA.

Sunday, August 26, 1990

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LOCALIZATION OF PARATHYROID ADENOMA: WHICH ONE OF THESE DUAL ISOTOPE SUBSTRACTION TECHNIQUES (T1-201/Tc-99m TcO4 VS T1-201/I-123) IS MORE EFFICIENT.'? Q-T Ton-That, D. Picard, M. Picard, R. Chartrand, L. Carrier, Dept. of Nuclear Medicine, H6p. St-Luc, and Univ de Montreal, Montreal, Quebec, Canada.

ADRENAL IMAGING IN THE EVALUATION OF INCIDENTALLY DISCOVERED ADRENAL MASSES L. Troncone, V. Rufini, M.S. Daidone, A.L. Valenfini, F.N. Danza. Catholic University, Rome, Italy.

Localization of parathyroid adenoma is currently done by dual isotope substraction technics (T1-201/Tc-99m or I]-201/I123). This study aims to demonstrate which of Tc-99m TOO4" or 1-123 will permit optimal substraction results. For this purpose, these 2 technics were separately applied on 2 normal voluntary subjects within 2 weeks apart. Each time, Tc-99m TcO4" or 1-123 was injected first and its scattering effect (in 71201 80 keV energy window) was obtained. Cervical images by dual isotope recording were then started with the injection of 3]-20I. From a flood of 71-201, different foci of various magnitudes were created simulating parathyroid adenomas and superimposed on T1-201 cervical images mentioned above. Normalized Tc-99m TcO4 and 1-123 images were substracted from this manipulated T1-201 cervical image (corrected or not for crosstalk effect of Tc-99m TcO4 or 1-123) generating images which were compared quantitatively (R - signal / noise ratio) and quantitatively. ReSults obtained prove that use of Tc99m TOO4 requires scattering correction in order to improve ~he quality of substracted images. However, in spite of a better R (1.3 before and 2.8 after correction), this correction does not permit better images quantitatively when compared with 1-123 corrected (R=2.0) or not (R=1.7) for crosstalk effect. In summary, use of 1-123 as a radiopharmaceutical for thyroid imaging offers the same result as Tc-99m TcO4" while avoiding the need for correction of scattering effect, thus being well suited for the simultaneous dual isotope substraction technique.

The wider application of sensitive imaging techniques has led to t h e d e t e c t i o n of a larger number of incidentally discovered adrenal masses which require further investigation. In this study we re-evaluated the e x p e r ! enee made in this field in the last two years. Thirty-one patients were investigated by adrenal seintigraphy using Se-75-selenonorcholesterol (ii.i MBg i.v.) and/or I-I31-MIBG (18.5-37 MBq i.v.). Fourteen out of 16 patients examined on the basis of clinical and biochemical data were correctly diagnosed by adrenal scintigraphy (i small aldosteronoma and i pheo were missed). Fifteen patients had an adrenal mass incidentally discovered and no biochemical evidence of adrenal hyperfunction. In 5 cases there were no uptake in the site of the adrenal mass (one of these, subsequently positive at I-ISI-MIBG scan, resulted to be a ganz]ioneurofibroma). In i0 cases an uptake by the unilateral moss was observed, suggesting the presence of a "non hyperfunctioning adenoma" (surgical and histological confirmation in 5 cases). This preliminary survey indicates the complementary role played by seintigraphy , when compared to CT,in the assessment of incidentally discovered adrenal masses and stresses its potential in characterizing them, maybe also gaining further knowledge on their natural history.

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ADRENO-CORTICAL SCINTIGRAPHY TO EVALUATE ADRENAL MASS INCIDENTALLY DISCOVERED ON COMPUTED TOMOGRAPHY E.Tsukamoto, K. Itoh, K. Nakada and M. Furudate. Hokkaido University, Sapporo, Japan

A D V E R S E R E A C T I O N OF 1-131 M E T A I O D O B E N Z Y L G U A N I D I N E THERAPY IN A R E S P O N S I V E CASE WITH MALIGNANT PHEOCHROMOCYTOMA K.Endo, T.Saga, H.Okazawa, M.Hosono, T.Nakai, Y.Watanabe, H.Sakahara, J.Konishi. Nuclear Medicine, Kyoto University Hospital, Kyoto, Japan

To assess the nature of adrenal mass incidentally d i s c o v e r e d on c o m p u t e d t o m o g r a p h y (CT), a d r e n o cortical scintigraphy (Ad-Sc) in 27 patients (pts) was retrospectively reviewed. All pts (22 having no cancer, 5 an extra-adrenal cancer) had no clinical symptoms and biochemical e v i d e n c e of a d r e n a l hyperfunction. Posterior images of abdomen were o b t a i n e d 3, 5, a n d 8 d a y s a f t e r i n t r a v e n o u s i n j e c t i o n of 0.5 m C i ( 1 8 . 5 M B q ) of 1 - 1 3 1 - 6 B iodocholesterol( Adsterol in Japan, the same as NP59 in USA). I n c r e a s e d tracer uptake o n the side of a d r e n a l mass was o b s e r v e d in 13 pts - c o r t i c a l adenoma in 9 and no growing tumor in 4. (no cancer pts were included.) Symmetric uptake was seen in 9 pts - I cortical adenoma and I ganglioneuroma, I no growing tumor, and no further examination was done in the r e m a i n i n g 6 pts (including 2 m a l i g n a n t cases). Those adrenal masses except gangliomeuroma were significantly smaller in size index calculated from CT image than those in the concordant group. Ad-Sc showed d e c r e a s e in the uptake in 5 pts m e t a s t a s i s i n 3, a d r e n a l c y s t in o n e , a n d no confirmation in one. Adrenal mass size was larger in this group than in symmetric group. Ad-Se was helpful in distinguishing functioning a d r e n a l masses ( all of w h i c h were b e n i g n ) from a d r e n a l masses w h i c h i n c l u d e d m e t a s t a t i c tumor, cyst, and n o n - f u n c t i o n i n g m e d u l l a r y tumor, when adrenal mass was large in size.

Sunday, August 26, 1990

1-131 metaiodobenzylguanidine (MIBG) is c o n c e n t r a t e d in c h r e m a f f i n cells and used for the localization of tumor derived from neural crest orign. It has been also clinically employed for the therapy of malignant pheochromocytoma and neuroblastoma and is e x p e c t e d to d e l i v e x s u f f i c i e n t radation to tumor tissues. We have p e r f o r m e d d i a g n o s t i c 1-131 MIBG scans in f o r t y s i x patients with p h e o c h r o m o c y t o m a . Primary tumors of all patients were s u c c e s s f u l l y operated. H o w e v e r , six p a t i e n t s f u l f i l l e d the criteria for malignancy. Among them, three patients r e c e i v e d t h e r a p e u t i c doses of 1-131 MIBG, which l o c a l i z e d well in all m e t a s t a t i c tissues except hepatic metastases due to the h i g h b a c k g r o u d radioactivity in the liver. Two patients with lung, b o n e or l y m p h n o d e s m e t a s t a s e s s h o w e d f e w or no objective improvement afterward and no toxic effects were encountered. One patient exhibited subjective and objective benefits and lung and liver metastases almost disappeared at three months after infusion of 3.7 GyBq of 1-131 MIBG. However, severe exacerbation of p h e o c h r o m o c y t o m a o c c u r r e d at one w e e k a f t e r administration and continued for two months, which paralleled massive catecholamine discharge. Reflecting the h e t e r o g e n e i t y of p h e o c h r o m o c y t o m a , adverse reactions seemed to be due to the radiation-induced damage to tumor cells. These results suggest that therapeutic doses of 1-131 MIBG may cause major but temporary adverse reactions in a responsive case with malignant pheochromocytoma.

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THROMBOTIC ALTERATIONS IN ENDOCHRINE AND METABOLIC AILMENTS

HORMONAL CHANGES AFTER A LONG LASTING STRESS: THE MARATHON RACE. A. C o q u e r e l , A. L o e b , E. P o r t i e r , G. Hue, F. Matray, P. Pasquis. Centre Hospitalier Universitaire de Rouen. FRANCE.

Miguel G. Avila - Consultorio de Medicina Nuclear - Libertad 666 Santiago del Estero - C.P. 4200 - Argentina

It is possible to measure the Thromboxane A in serum by RIE through its metabolic, hydrolized, unactive and steady 11 DiHydro-Thromboxane B2. We can observe its part in balancing synthesis of prostaglandines and its alteration in some ailments. 115 people were chosen for examinations and tests. This table shows the results of 11 DiHydro-Thromboxane B2 (pgrs/ml) and its statistical study: Group

1. Control 2. Hipothyr. 3. Hiperthyr. 4. D. Mellitus. 5. BreastCancer.

Age

N -~

Aver.

S.D.

Range

X2

10-60 18-60 20-60 35-60 48-6-

18 23 27 30 17

2,43 186,21 169,74 257,33 248,23

1,51 100,71 t 02,67 73,29 77,49

0,8 - 7,3 62 - 400 64 - 400 160 - 390 120 - 390

G2-G~:0,91 G3-G4:0,57 G4-GS:0,94 GZ-GS:0,59 G2-G4:0,61 G
The physiopathogenic of prothrombotic alterations in thyroid pathology, such as hiper and hipofunctions differs in Diabetes Mellitus and breast cancer that affect post menopausic women. In the 1" casethere would be a distorsion in the synthesis of coagulation factors with an increasing susceptibility of the activation mechanisms, and the formation of the clot during the evolution of the disease is smaller in follow-ups of patients under treatment. The clot formation in D. Mellitus and breast cancer is due to more sensibility to the aggregate effect plateletes and in the synthesis of thromboxane which is increased in its final result. There is more incidence of thromboembolism in D. Mellitus and breast cancer, according to clinical follow-ups. We suggest concomitant treatment of the specific one, especially for the people of Groups 4 and 5.

C l a s s i c a l l y s t r a i n t o l e r a n c e is a t t r i b u t e d to endogenous opioids "endorphins", and e x h a u s t i o n t o p l a s m a t i c c h a n g e s i n G l u c o s e (G) or L a c t i c A c i d (LA) levels. We studied i0 a m a t e u r r u n n e r s ( a g e d 27-50) b e f o r e a n d after ( 5 , 1 0 , 1 5 a n d 30 m i n . ) a m a r a t h o n . We assayed usual biochemical parameters, including G and LA, a n d v a r i o u s hormones implicated in the stress response: ACTH, Cortisol {C), g-Endorphin (BE) o r 6 1 - 9 1 LPH, and Prolactin (PRL). R u n d u r a t i o n w a s T >3 h 30 a n d <4 h 15, and the ambiant temperature 25-28 ~ Although free rehydration and feeding only 8 of i0 r u n n e r s a r r i v e d (3 exhausted). RESULTS: all biological constants were normal at start a f t e r w a r m - u p . A t f i n i s h (T+5') increases in L A w e r e c o n s t a n t b u t m o d e r a t e : + 0,8 ~ + 2,6 m m o l / l (pC 0 . 0 0 1 ) ; it w a s m a x i m a l at T + I 5 mn. G remains normal and the LA/G ratio persisted <0,5 excepted in one exhausted (maximum 0,88 at T+I5'). THE HORMONAL RESPONSES WERE IMPORTANT AND LASTING : C increased from (Mean • S . E . M . ) 433 • 27 n m o l / l to 1928 • 246 at T+5' a n d k e p t u p 1 7 6 2 • 117 n m o l / l at T+30' Hypophysal responses were explosive : PRL went u p f r o m 7 . 5 0 i 0 . 6 5 n g / m l t ~ 38.5 • 6.5 ng/ml (T+5'). ACTH and BE responses were parallel w i t h d r a m a t i c i n c r e a s e s : ACT}{ : b a s a l = 2 8 . 4 • 4.4; T + 5 ' = 469 • 96; T+30'= 304 f 48 (p <0.001). CONCLUSIONS: the amplitudes of the hormonal responses reflect better the stress.

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DETERMINATION OF KIDNEY PERFUSION USING ULTRASHORT LIVED It- 19 lm AS A TRACER K.J.A. Kairemo M.S. Kestila, O.A. Korhola, J.V. Hiltunen, R.I. Svahn, F.F.Knapp, C.Bdhaye.Helsinki University Central Hospital, Helsinki, Finland;Technical Research Center of Finland, Espoo, Finland; Oak Ridge National Research Laboratory, Oak RidgeTN; Cyclotron Research Center, Liege,Belgium

RENAL FUNCTION MEASUREMENTS USING POSITRON ENISSION TOMOGRAPHY (PET). R.J.Ott, M.A.Flower and J.W.Babich. Royal Marsden Hospital, Sutton, Surrey. UK.

For renal hypertension or renal transplant rejection renal artery flow and perfusion are important to determine. This rapid phenomenon can be studied by dynamic gamma imaging. When using short lived radioisotopes the radiation exposure is smaller and the study can be repeated within a short interval. We studied kidney perfusion in a rabbit model using ultra-short lived Ir-191m (tl/2 = 4.96 s), obtained from a Os-19 l/Ir-191m activated carbon generator system (JNM 27: 380, 1986). Dynamic studies were performed using a Siemens Rota gamma camera equipped with a low energy collimator. 5 frames/second were collected utilizing main gamma energy peaks (65 keV and 129 keV; 20% window). The bolus was injected into the ear veins of anesthesized animals and the kidney regions were imaged. Mean transit times and perfusion indexes were calculated. Several consecutive studies were performed in the same animals and the results were reproducible and repeatable. We also studied 5 healthy volunteers in several sessions and the results were repeatable. The prospect ofusing this minimal-radiation-dose method for evaluation of renal transplant perfusion and renal hypertension seems promising.

Renal function measurements using conventional planar dynamic scintigraphy suffer from the effects of background produced by extra-renal radioactivity. These effects in patients with poor renal function make it difficult to estimate functional parameters such as GFR or ERPF accurately and may have implications for treatment. The dynamic tomographic capabilities of PET make it possible to measure renal function with the extrarenal radioactivity excluded from the data analysis. In addition the high spatial resolution and sensitivity of PET allows intra-renal functional variations to be measured. We have acquired multiframe (50s/frame) tomographic images of the distribution of Ga-68-EDTA in the kidneys and surrounding tissues of a normal volunteer using the MUP-PET positron camera (I). The analysis of these data show that there are significant variations (x2-3) in extra-renal background activity caused by vascular tissues and by low radioactivity in the stomach and spinal regions. These variations would significantly effect any results from non-tomographic studies. We conclude that dynamic tomographic renograms may be required for the accurate measurement of poor renal function where the effects of extra-renal radioactivity are important. (i)

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Cherry et al, EJNM (1989) 15:694-700.

Sunday,

August26,1990

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174

VALIDATION OF EFFECTIVE RENAL PLASMA FLOW (ERPF) MEASUREMENT USING Tc-99m MERCAPTO ACETYL TRIGLYCINE (MAG-3). B, Bgg~, Ospedale S. Anna, Ferrara, Italy.

C O M P A R I S O N OF R E N A L C L E A R A N C E S C A L C U L A T E D F R O M D I F F E R E N T N U M B E R S OF P L A S M A S A M P L E S OF Cr-51-EDTA AND Tc-99m-DTPA. E. P 6 t u r s s o n a n d D. Davidsson, L a n d s p i t a l i n n , R e y k javik, I c e l a n d

The combined use of MAG-3 and a computerized algorithm based on the formula of Tauxe appears to be advantageous for the routine determination of the ERPF not only for the obvious implications of an automated procedure, hut also for the inherent possibility of reducing the radioactive dose to the patient and for frendly use of this radiopharmaeeutical. The validation procedure includes 150 patients who underwent radionuclide renography with MAG-3. They were 70 females and 80 males (mean age 53 years, range 15-70 y.) random selected. Intravenous simultaneous injection of 74 MBq of Tc-99m MAG3 and 0.74 MBq of 1-131 OIR was administered. Using a serum sample taken 44 minutes after injection the distribution volumes were evaluated for the two different radiopharmaceuticals. The renal time-activity curves are corrected for the decay and background and utilized to compute the fractional ERPF. The linear regression fit between the values of ERPF obtained by the two radioisotopes demonstrated the existence of a highly significant lineal: trend. The mean ratio between the two values of ERI'F is 0.52. The equation is: ERPF(OIH)= 1.621 x ERPF(MAG3) +105.1 The correlation coefficient is 0.84 and P <0.001. In our experience the routine calculation of ERPF from MAG3 clearance proved to be consistent with the result obtained from OIH clearance.

C r - 5 1 - E D T A c l e a r a n c e was m e a s u r e d by the s t a n d a r d m e t h o d (5 b l o o d samples at 30 m i n i n t e r v a l s 2-4 hrs p o s t single inj.) in 67 pts (age 3-94, m e a n 37.4, c l e a r a n c e v a l u e s 7.9 173, m e a n 79.9 m l / m i n / l . 7 3 sq.m. B o d y S u r f a c e Area). The c a l c u l a t i o n s w e r e done on a m i n i c o m p u t e r a n d c l e a r a n c e s were a l s o c a l c u l a t e d from i0 s u b s e t s of 2-4 samples a n d the v a l u e s thus o b t a i n e d w e r e c o r r e l a t e d w i t h the s t a n d a r d method. In a s u b g r o u p of 32 pts (age 3-92, c l e a r a n c e v a l u e s 7.9-148, m e a n 65.1) s i m u l t a n e o u s C r - S I EDTA and Tc-99m-DTPA clearance measurements were done a n d d i f f e r e n t m e t h o d s of c a l c u l a t i n g T C - 9 9 m - D T P A c l e a r a n c e s (cf. above) c o m p a r e d to the s t a n d a r d C r - 5 1 - E D T A method. In all cases a v e r y g o o d c o r r e l a t i o n was found. A corr. coeff, r=.983 was f o u n d b e t w e e n 5 b l o o d sample D T P A c l e a r a n c e a n d the s t a n d a r d m e t h o d a n d the v a l u e s for b o t h m e t h o d s w e r e a l m o s t i d e n t i c a l t h r o u g h the range of c l e a r ances. B y u s i n g t h e Ist and the last sample o n l y (2 & 4 hrs) we f o u n d r=.997 for E D T A a n d r=.981 for DTPA. By u s i n g samples at 2.5 & 3.5 hrs r = . 9 8 6 was f o u n d for E D T A a n d r=.977 for DTPA. C o n c l u s i o n : T w o b l o o d samples at 2.5 & 3.5 hrs p o s t s i n g l e i n j e c t i o n of e i t h e r 5 1 - C r - E D T A or 9 9 m - T c - D T P A are s u f f i c i e n t to m e a s u r e GFR.

175

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E V A L U A T I O N OF R E N A L C L E A R A N C E S C A L C U L A T E D F R O M E X T E R N A L M E A S U R E M E N T S AND ONE P L A S M A SAMPLE. E. P @ t u r s s o n a n d D. Davidsson, L a n d s p i t a l i n n , Reykjavik, Iceland.

CORRELATION OF RENAL UPTAKE OF T1-201 AND Tc-99m DTPA ANGIORENOGRAPHY. G.A. Hurwitz, J.E. Powe, A.G. Mattar, C.A. Wesolowski and A.A. Driedger. University of Western Ontario and Victoria Hospital, London, Ontario, Canada.

In 20 pts (age 15-79, m e a n 39.5, c l e a r a n c e v a l u e s 7.9-148, m e a n 71.9 m l / m i n / l . 7 3 sq.m'.BSA) s i m u l t a n e o u s C r - 5 1 - E D T A and T c - 9 9 m - D T P A clearances w e r e c a l c u l a t e d f r o m 5 e x t e r n a l m e a s u r e ments (over the heart), and i0 s u b s e t s of these, + 1 b l o o d s a m p l e at d i f f e r e n t times post s i n g l e injection, a n d these c l e a r a n c e v a l u e s c o m p a r e d to the s t a n d a r d C r - 5 1 - E D T A m e t h o d (5 b l o o d samples at 30 mill i n t e r v a l s 2-4 hrs p.inj.) . In all cases a v e r y good c o r r e l a t i o n was found. A corr. coeff, r=.977 was found for 5 e x t e r n a l m e a s u r e m e n t s of E D T A w i t h 1 b l o o d s a m p l e 2 hrs p. inj. a n d a c o r r e s p o n d i n g v a l u e for D T P A was r=.978. A s l i g h t l y d e c r e a s i n g rvalue was f o u n d the later the b l o o d sample was drawn. A g o o d a c c u r a c y was found b y u s i n g two e x t e r n a l m e a s u r e m e n t s 2.5 a n d 3.5 hrs p.inj. and 1 b l o o d sample at 2.5 hrs (r=.964 for EDTA, r = . 9 6 6 for DTPA) a l t h o u g h at c l e a r a n c e v a l u e s < 20 there were quite s i g n i f i c a n t d e v i a t i o n s w i t h EDTA. Still b e t t e r c o r r e l a t i o n was found w i t h e x t e r n a l m e a s u r e m e n t s at 2 & 4 hrs (r=.980 for E D T A a n d r=.977 for DTPA) w i t h s m a l l e r d e v i a t i o n s at low c l e a r a n c e values. Conr A s a t i s f a c t o r y e v a l u a t i o n of G F R t h r o u g h a w i d e range of c l e a r a n c e va
Sunday, August26,1990

Renal uptake of TI-20t reflects cortical blood flow and may have a role in evaluating hypertensive patients referred for myocardial scintigraphy. To assess differential renal uptake (DRU) of T1-201, we compared 5-minute TI-201 renal images with the vascular and cortical uptake phases of standard Tc-99m DTPA renography in 30 hypertensive patients. Sixteen of these had DRU of T1-201 outside the normal range (44-62% for the left kidney, 99% confidence limits), established in 30 normotensive patients. For the cortical phase, DRU of Tc-99m DTPA was quantitated as backgroundsubtracted uptake (left/total %) at 1-3 mins after injection; for the vascular phase, the ratio (left/right) of rising slopes on 0.5 second frames was determined. TI-201 and cortical-phase DTPA images were qualitatively similar with respect to renal uptake, although gluteal muscle uptake was higher with TI-201. Renal/background ratios were similar for the two tracers when considering liver, spleen or inter-renal regions as background. DRU of TI-201 corresponded to cortical-phase DRU of DTPA amd showed good correlation whether or not background subtraction was used for TI-201 (r=0.98 in either case); the vascular phase of the DTPA study also showed good agreement with T120] (r=0.98). However, of 13 patients with a significant left/right discrepancy in renal uptake, 10 image pairs suggested a greater discrepancy with T1-201 than with DTPA. This subtle difference between the 2 imaging modalities could relate to effects of the stress procedure with TI-201 or to differing tracer kinetics in the setting of renal artery disease, and suggests an advantage for background subtraction with T1-201. Thus, DRU of T1-201 provides data which are similar but not identical to standard renography.

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177

i78

INTRAVENOUS INFUSION OF D I P Y R I D A M O L E REDUCES G L O M E R U L A R FILTRATION MEASURED WITH Tc-99m DTPA. T.B.Latham, L.Diesbourg, F.S.Prato, G.Wisenberg, L. Reese. Departments of Medicine and Nuclear Medicine, St. Joseph's Health Centre, Lawson Research Institute, University of Western Ontario, London, Ontario, Canada.

PRIOR TRIAGE OF ADULT PATI~hTfS AND ~ T I O N OF Ram~CE (IIRVES IOWER ~9ROR OF FF ESTIMATION. W.N. Tauxe, D. Kundu, H.A. Klein. University of Pittsburgh, Pittsburgh, PA and University of Texas at Dallas, Richardson, Texas.

Our observation that dipyridamole reduced glomerular filtration rate (GFR) in dogs led us to investigate if dipyridamole, infused intravenously at rates comparable to those used in thallium myocardial perfusion tests, would alter GFR in humans. GFR was measured using a bolus injection of 10mCi Tc-99 DTPA in five males (19-63 years old) with normal serum urea and creatinine. Twenty minutes following the bolus injection a ten minute intravenous infusion of either dipyridamole (0.14mg/kg/min) or saline sham was given. The two studies were 5 to 7 days apart and the sequence of sham/dipyridamole was randomized. For the 60 minutes following the bolus injection, posterior images including the heart and both kidneys were collected. Heart rate (HR) and left arm blood pressure were measured every 2 rain during infusion and every 5 rain for the remaining time. Four to ten minutes following the start of the dipyridamole infusion a paradoxical rise in counts in the kidney region of interest was observed arid persisted for 10 to 27 rain. During this time a 13% to 52% (mean+SD, 40%-+16%, p<0.007) reduction in the exponential slope defining the clearance of counts from the cardiac region of interest occurred, implying a reduction in GFR. The mean H R increased 27---5 beats/rain, p<0.002, and the mean diastolic pressure decreased 12.9_+6.4mmHg, p<0.028, in comparison to mean pre-infusion values. The changes in systolic pressures were not significant. The reduction of GFR is consistent with the known effect of dipyridamole on endogenous adenosine causing constriction of the afferent glomerular arterioles. The increased renal retention of Tc-99mTc DTPA is likely the result of decreased urine flow rate due to decreased GFR and increased water reabsorption resulting from decreased hydrostatic pressure in the vasculature distal to the glomerulus. This finding would have to be considered if one was examining renal data obtained during dipyridamole thallium stress tests.

Because the filtration fraction (FF) is a quotient of glcmerular filtration rate (GFR and effective renal p l ~ flow (~iqPF) it is especially error prone. Since cyclospsorin attacks the glc~ar sieve, the FF with the least possible error is crucicial in the assessment of its status. Prior triage of patients into three groups I: expected normal values e.g. in prospective kidney donors; II: expected clinical pr~lem without azotemia and III: patients with a z o t ~ a , results in the lowest reported errors of estimation of both GFR and ERPF. ~hese can be estimated s i ~ t a n e e u s l y after the injection of 1-131 orthoiodohippurate (OIH) and 1-125 iothalamate (IOT) with pla-~a s a i l e d in the groups at various times after injection. Lowest errors obtained by sampling in group I at 12 minutes after injection of OIH and at 113 minutes after IOT. For group II 38 and 152 minutes, and group III at 69 and 290 minutes respectively. [~gPF errors are 34.7, 23.4, 19.1 Tnl/min. and 4.2, 3.7, 4.2 ~tl/nJil. GFR respectively, qhese are the lowest reported errors we know of. ERPF and GFR have been achieved by dividing the total dose (cpm) injected by cpm of each nuclide in plasma (per L) at the various sanpling times. The quotients V are used in the general formulae, ERPF or GFR = Axl-exp[-B(V-C)] A,B, and C for groups I for ERPF are 1573, 0.0198, 4.64 and for GFR are I: 1418, 0.0022, -0.57, II: 285, 0.0109, 5.80, III: 1142, 0.0015, 11.21.

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180

~WO MEASURES OF PARENCHYMAL REq~NTION OF 1-131-

EXPERIMENTAL EVALUATION OF PARENCHYMAL TRANSIT TIMES (FTT) IN THE DIAGNOSIS OF OBSTRUCTIVE UROPATHY (OU). A.H. Elgazzar, R.H. Bahar, F. Abu-Zidan, M. Sabha, H.M. Abdel-Dayem. Depts. of Nucl. Med. & Surgery, Faculty of Medicine, Kuwait University, Kuwait.

IODOHIPPURATE (OIH) OR T C - 9 9 m - ~ G 8 IN q ~ P L A ~ KIDNEYS. C.D. Russell, J.L. Palmer-Lawrence, C.V. Church, E.V. Dubovsky, University of Alabama Hospital and V.A. Medical Center, Birmingham, AL USA. Parenchymal retention is a hallmark of acute rejection or A T N on transplant ren(xjrans using either OIH or MAG3. (The two diagnoses are separated b y time course on serial studies.) Since 1975 (J. Nuc]. Med. 16:1115-1120) we have routinely measured retention b y an excretory index (EI) calculated from blood and urine assays. However, rising costs and shrinking budgets make it increasingly difficult to justify the use of skilled n~mnual laboratory procedures. Here we cfmpare the EI with a simpler quantitative measure of pare~chymal retention that requires no blood or urine sanples. All measurer~.~nts of transplant El for a 3-month interval (186 cases) were cc~oared with backgroundsubtracted 25-min/3-min count rate ratios. Abnormal EZ values (<0.7) were found in 125, with abnormal 25:3 ratios (>0.7) in 109 of these. Of 61 patients with normsl EI, the 25:3 ratio was normal in 49. T ~ s 85% were classified identically b y both tests. Similar results were found with ~ G 3 in another 29 patients. The 25:3 ratio thus yields information similar to the EI. It is simpler and less expensive, but to detezmine which method is truly cost-effective will require further study with detailed clinical correlations.

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There is difficulty in interpretation of some patterns of time activity curves (TAC) with images of radionuelide diuretic renograph y (RDR) for evaluation of OU. PTTs are reported to be more helpful. We ran a prospective study on 30 sheep, 9 with induced complete unilat ureteric obstruction (ob) & 21 with graded narrowing (nar) using french catheters of diff. diameters. Sheep were studied by RDR using Tc-99m DTPA with lasix at 15 min. post inj. Each animal was studied before inducing ob. or nat. and weekly after for a variable period up to 6 weeks and up to 7 weeks after relieving ob. or nar. PTTs were calculated for the side with nar. or ob. and the other side as a control. At the end of studies kidneys were submitted for path. exam. In the group of complete oh. PTTs were prolonged but came down to normal when kidney function became poor. TAC showed patterns of ob. There was no disagreement between TAC & PTTs. In the group of nar. 15 sheep had no significant nar. producing no path. changes. In these TAC showed no ob. while in 3 cases PTTs were prolonged. In the remaining 6 animals nat. was significant producing path. changes. TAC showed ob. and PTTs were prolonged, with no disagreement except in one case showing normal PTT when kidney function became poor. We conclude that PTTs, although sensitive, do not have advantages over the routine TAC, additionally they may give false results and only work in cases with good renal function.

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THREE PHASE DIURETIC RENOGRAPHY IN DETECTING OBSTRUCTIVE UROPATHY. (obst. ur.) AH Elgazzar, RH Bahar, M Eldadah, M Tuli, G Fettich, HM Abdel-Dayem. Dept. of Nuclear Medicine, Faculty of Medicine, Kuwait University, Kuwait.

O V E R E S T I M A T I O N OF LEFT R E N A L C O N T R I B U T I O N IN MAG3 RENOGRAPFtY J-P Binon Department ef Nuclear Medicine C . H . U . A . VESALE Mnntigny le Tilleul, BELGIUM

Radionuclide diuretic renography (RDR) is a useful technique to evaluate obst. ur. Sometimes it meets difficulty in the interpretation of time activity curves (TAC) patterns. There is no consensus regarding timing of diuretic injection. We have undergone a prospective study on 22 patients referred to our depart, with suspected obst. ur. All patients were hydrated & studied by two techniques using 10 mCi of Tc-99m DTPA. The first technique was acquired in 2 dyn. studies the first every 1 sec for 60 sec followed by the second every 15 secs for 29 minutes with lasix injected at 15 minutes. The second technique was acquired in 3 phases first every 1 sec for 60 sec, the second every 15 ssc for 29 minutes and the third after voiding every 15 sec for 30 minutes with lasix injected after 5 minute baseline. Discrepancy was noticed in 5 patients. In 2 occasions the TAC was of obstructive pattern using the two phase technique but was clearly not obst. in the three phase technique. In 3 additional cases the TAC were equivocal in two phase technique but not obstructed with three phase technique. This discrepancy is explained by various parameters among them is the bladder pressure affecting clearance from kidney pelvis in the two phase technique. We recommend the use of three phase RDR with the diuretic injected post void to avoid some equivocal or false positive studies for obstructive uropathy.

183 VARI~LETHRESHOLDLEVELS FOR ESTIMATION OF RENAL UPTAKE OF T c - D M S A B A S E D O N SPECT. Y. Ohishi*, T. Machida*, H. Yoshigoe*, H. Yamada**, Y. Mashima**, H. Toyama** and H, Murata***. *Dept. of Urology, The Jikei University School of Medicine, Tokyo, Japan, **Dept. of Nuclear Medicine & Radiological Sciences, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan and ***Divi. of Nuclear Medicine, Toranomon Hospital, Tokyo, Japan. To calculate renal uptake of Tc-DMSA more accurately using SPECT, it is necessary to estimate values of threshold level, which corresponds to the ratio of kidney to background(BG ratio). Thus the phantom study was conducted. Six kinds of renal phantoms of 80 to 339 ml, contained different radioactivity of 37 to 485 MBq were prepared. These phantoms were placed in a larger body phantom filled with 1-50% of radioactivity representing background. Results were as follows: I) The correlation between ]3(3 ratio and threshold level acquired from actual activities in phantom(r=0.99) and from reconstructed images(r=0.98) were significant. 2) A significant correlation between phantom volumes and estimated volumes obtained using threshold level based on BG ratio calculated on temographic images was found(r=0.99). 3) A significant correlation between total counts and radioactivity in estimated volumes was recognized(r= 0.94). 4) Known radioactivity in phantoms and radioactivity in estimated volumes were highly related(r=0.98). Thus, this method can calculate more accurate renal uptake of Tc-DMSA. Clinical application of this method was performed and showed valuable results.

Sunday, August26,1990

Although Tc-99m MAG3 renosraphy is less sensitive to back~rnund tfian DTPA Tc-99m ren~raphy due to a higher target / ~:xoise ratio bacbzround and attenuation remain the two mare problems in renal funct on determ nat on w Ih the scnt ation camera. Theoretically, fractional renal funclinn (FRF) calculated from SPECT with D~SA Tc-99m is not affected by background and attenuation problems since after reconstrtlction background in the kidneys areas is negligible and attenuation may be considered equal in both kidneys. The aim of the study was to evaluate the effect of background subtraction in the accuracy of left and right FRF obtained from MAG3 renography. Fourteen successive patEents referred for evaluation of FRF underwent a DMSA planar and tomegraphic study and next a MAG3 renography 48 hours apart. Absolute creatinine renal clearances ranged from 35 to 1.96 ml per minute and left DMSA FRF ran~ed from t7% to 65%, average 49% Left F~F was calculated from 1/two-to-three minutes built-up images 2) renal distribution volumes curves 3) posterior planar DMSA image and 4) tomographic DMSA images. The last method was considered the reference standard. In all t~ree other methods, average background in each kidney area was assumed to equal that in a ROI surrounding the kldney, Attenuation was calculated from renal depth estimate~l from theqaeight and weight of the patient and from the measured attenuation coefficient of Tc-99m in plexiglas media. Statistical analysis of differences between planar methods and reference used Bonferonni t test following repeated analysis of var|ancc, Results show a significant overestimation of left FRF compared with the reference m method 1 (4.9%) and 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 pcrirenal area introduces a bias with a slight overestimation ofleft FRF. This effect is probably caused by an average background in the right perirena} area in excess over the 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 lower.

184 PREDICTIVE VALUE OF RADIONUCLIDE METHODS IN THE DIAGNOSIS OF RENOVASCULARHYPERTENSION. A COMPERATIVE STUDY WITH ANGIOGRAPHIC FINDINGS.

H. K. Deininger, D. Beil and Ch. Schmidt, Darmstadt Municipal & Teaching Hospital, Dep. Radiology & Nuclear Medicine, Darmstadt, F.R. Germany The r e s u l t s of the radiorenogram and clearance, the renal scintigram, the rapid sequence urography and the excretion urogram of 547 hypertensive patients have been analysed and compared with the f i ndi ngs of the aortography and renovasography. According to the cause of the hypertension which was diagnosed by means of c l i n i cal parameters the patients were subdivided in three groups: 94 with renal hypertension, in 368 patients a renal caused hypertension was possible resp. could not be excluded, and 85 without a renal cause (essential hypertension). In 64 patients a renal a r t e r y stenosis was detected: 17 in the f i r s t , 36 in the second and 11 in the t h i r d group. Posi t i ve renograms could be found in 23.4 %, 21.5 % and 24.7 %. The analysis of those patients s u f f e r i n g from a renal a r t e r y stenosis showed d i f f e r e n t values: Renogram 45.5 %, 8.9 % and 31.3 %. Scintigram 14.3 %, 6.6 % and 14.3 %. I t means that the renogram is more s p e c i f i c in the diagnosis of renovascular hypertension. But in a l l three groups there is a high percentage of f a l s e negative r e s u l t s . Especially, in both non-renal caused hypertension groups remarkable rates of f a l s e - p o s i t i v e renograms were observed. Only a minor part of them could be explained by other diseases of the kidney or manifest and v i s i b l e nephrological lesions caused by the hypertension. In detecting a renal a r t e r y stenosis the r e s u l t s of the excretion urography were s l i g h t l y superior to these radionuclide methods. But the rapid sequence urography could not improve the diagnostic information.

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EVALUATION DU NEPHROGRAsMME ISOTOPIQUE (MAG3) AVEC TEST AU CAPTOPRIL DANS L'HYPERTENSION ARTERIELLE R E N O V A S C U L A I R E (HTARV). A KELLER J.-E.RYSER. etA. DONATH. Div de M6decine Nucl~aire.H C U G - 1211 Gen6ve 4 - Switzerland L'administration d ' u n inhibiteur de l'erazyme de conversion tel le captopril (CAPT) induit une diminution du t a u x de filtration g l o m d r u l a i r e en cos de s t 6 n o s e d ' u n e art6re r6nale. Les r 6 p e r c u s s i o n s fonctionnelles de cette st6nose p e u v e n t ~tre objectivs p a r le n d p h r o g r a m m e isotopique. Le MAC3. nouveau t r a c e u r techn6ti6, a ~t~ employe pour investiguer la sp6cificit6 diagnostique du n ~ p h r o g r a m m e isotopique avec test an CAPT dans I'HTARV. Nous avons effectu6 deux n d p h r o g r a m m e s ~. 24 hrs d'intervalle: Ic p r e m i e r s a n s a d m i n i s t r a t i o n et le second une h e u r e apr~s a d m i n i s t r a t i o n p.o. de 12,5 m g de CAPT. Chaque n 6 p h r o g r a m m e consistait en une acquisition dynamique de 22' apr~s injection i / v en bolus de 3 mCi de Tc99m-MAG3. Durant l'ann~e 1989, 14 p a t i e n t s cons6cutifs (age: 53.8-+14.6 ansi pr6sentant une suspicion HTARV investigu6e p a r art6riographie r~nale ont 6t~ s61eetionn~. Nous avons utflis6 c o m m e pararn6tre objectif, la valour du t e m p s de pic de la courbe ndphrographique (Tmax). Une a u g m e n t a t i o n du T m a x entre les 2 n ~ p h r o g r a m m e s du test de plus de 20" ~tait consid~rde comme significative. Sur les 28 reins (14 patients investigu~s}. 7 prdsentaient une st~nose de plus de 50% (S+) du calibre de l'artere rdnale s u r l'art6riographie et 21 u n e st6nose infdrieure & 50% du calibre ou u n e artdriographie nqrmale (S-). Les diffdrences m o y e n n e s entre los T m a x des 2 n e p h r o g r a m m e s sont: 196+61 sec ( m o y e r m ~ S E , n=7) et -139_+76 sec (n=21, p<0,02), r e s p e c t i v e m e n t Six des 7 reins (S+) pr6sentaient u n e a u g m e n t a t i o n signfficative du T m a x alors que la totalits des 21 reins (S-) ne pr6sentaient pas de modification significative du T m a x ; soft u n e sensibilit6 et sp~cificit~ diagnostique de 86% et 100%, r e s p e c t i v e m e n t . Les rdsultats e n c o u r a g e a n t s de ce test avec le MAG3 dans le diagnostic des st~noses artdrielles fonctionelles r~nales p o u r r a i e n t en faire u n examen de d6pistage appliquable en routine clinique.

EFFECT OF ACUTE DIURESIS ON RENAL FUNCTION AFTER CAPTOPRIL (ACEI) H.B. Lee and M.D, Blaufox, Albert Einstein College of Medicine, Bronx, New York The physiologic effects of ACEI on renal function In patients with RVH have been used as the basis for differential diagnosis from essential hypertension. The effects in unilaterally nephrectomized animals are complex and differ from those observed in animals with 2 kidneys and I clamped. Volume expansion has been suggested as a reason for the differences observed. 46 male rats with 1K1C were studied. Group 1 received furosemide by IV 0,15 mg 15 rain prior to clearances, Gp 2 hydrochlorothiazide 1.5 mg 15 rain prior to clearances and Gp 3 chlorothiazide 1.0 mg/10 ml in drinking water overnight. The control group of the rats did not receive any diuretics prior to captopril clearance. Control clearances were performed in all animals prior to diuretic or ACEI except the chlorothiazide group. GFR was significantly lower after ACEI than after diuretic in all groups. Diuretic did not appear to affect ERPF, GFR did not appear to be significantly lower after Diuretic than without it compared to control: 1K1C GFR ERPF (ml/min/100g) (ml/min/100g) group cont diuretic capt cont diuretic capt n cont 0.363 0.265* 1.170 1.047" 19 gp 1 0.339 0.300+ 0.229* 1,249 1.060 1.122 10 gp 2 0.379 0.381+ 0.272* 1.165 1.151 1.090 9 gp 3 0.387+ 0.248 1.216 0.974 8 *=vs cont. p<0.00t, + =vs capt p<0.001 The effects of diuretic In animals with I KIc on renal function are variable. However the consequences of ACEI are similar with or without diuretic. These data suggest that diuretic therapy does not invalidate the results of ACEI in animals with RVH.

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DIAGNOSTIC USE OF RENAL SCINTIGRAPHY AFTER CONVERTING-ENZYME INHIBITION AND ECHO-DOPPLER F L O W M E T R u IN H Y P E R T E N S I V E P A T I E N T S .

THE EVALUATION OF EARLY POSTOPERATIVE CHANGES IN DONOR REMNANT KIDNEY FUNCTIONS BY Tc-99m DTPA SCINTIGRAPEY.

M.Dondl. N.Honettl. C.Corbelll, L.Barozzl, M.Levorato, F.Loslnno, A.Zuccala', P.Pavllca. Nuclear Medicine, Radiology and Nephrology. S . O r s o l a - M a l p l g h i H o s p i t a l , Bologna, I t a l y

B.KARAYALCIN,F.GUNGOR,M.ERKILIC,S.ASLAN,A.YILDIZ. DEPARTMENT OF NUCLEAR HEDICINE,AKDENIZ UNIVERSITY, FACULTY OF MEDICINE,ANTALYA,TURKEY.

The purpose of thls study was to a s s e s s diagnostic capabilities of both captoprll enhanced renal sclntigraphy (CERS) and echo-doppler flowmetry for d e t e c t i n g renal artery stenosls (RAS). A group of 21 p a t i e n t s , r e f e r r e d for e i t h e r h y p e r t e n s i o n or f o l l o w - u p of renal artery revascularizatlon procedures, were submitted to both examinations and subsequently to renal arterlography. RAS was detected in 10 p a t i e n t s w h i l e Ii p r o v e d to h a v e p a t e n t renal arteries. Of the 10 p a t i e n t s w i t h RAS, 3 had unilateral and 7 bilateral stenoses for a total of 17 i n v o l v e d a r t e r i e s . In two c a s e s of u n i l a t e r a l s t e n o s t s RAS w a s not d e t e c t e d with CERS and a f a l s e positive r e s u l t was found in another two. EDF w a s falsely n e g a t i v e in one p a t i e n t , f a l s e l y p o s i t i v e in two a n d g a v e no information in a case of c o m p l e t e t h r o m b o s i s w h e r e the renal s c a n was able to detect a s e v e r e l y i m p a i r e d kidney. A n g i o g r a p h y s h o w e d a renal a r t e r y b i f u r c a t i n g c l o s e to its o r i g i n in a p a t i e n t w h e r e b o t h CERS and EDF proved unilaterally falsely positive from the same side. RAS<50% was detected In one c a s e w i t h EDF but not w l t h CERS. The combined use of both procedures I d e n t i f i e d R A S > 5 0 t In all instances.

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The function of the remnant kidney in patients undergoing uninephrectomy shows various early adaptive changes.These functional and structural adaptive changes can start in the first hour of postoperative period.The aim of this study is to show these early adaptive changes at 24 hours postoperatively by quantitative Tc-99m DTPA renal scintigraphy. Renal sointigraphies were performed in 20 kidney donors ( mean age=38.2;7.7 ) in the preoperative (two weeks) and postoperative(24 hours) period.The ARTT,GFR, Tmax,serum creatlnine, BUN values and the length of kidney as parameters were calculated in pre and postoperatively and compared statistically by using ~ilcoxon test.We have observed the statistically significant changes in early postoperative perlod(24 h.).Table I. Parameter preoperative postoperative .............................................. ARTT(seo.) 4.7;0.2 3.530.2 GFR(ml/min) 57.7;2.7 48.6~3.3 Tmax(min) 4.8;0.2 3.1;0.9 Kld.Length(cm.) 10.470.2 11.0;0.2 Creatinine(mg/dl) 1.0;0.04 1.6ZO. I BUN(mg/dl) 14.2~i.0 18.9~1.8 ..................................................... Table l.p<0.05 for all parameters. We concluded that To-99m DTPA renal solntlgraphy can be used as a sensitive method to show early adaptive changes in donor remnant kidney.

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A SPECULATION OF THE RENAL GRAFT SURVIVAL FROM RENAL S C I N T I G R A P H Y IN ACUTE R E J E C T I O N . K.Yoshid~Le K.Kadowaki. Kitasato Inst. Hospital, Tokyo, Japan. M.Irie, K.Kumano, T.Endo, T.Sakai, S.Ikeda, A.Ishibashi. Kitasato Univ. Hospital, Sagamihara, Japan.

TEMPOR/kL OCCURANCE OF RENAL TPJkNSPIAXNT NON-IMHUNOLOGIC~L COMPLICATIONS DETECTED BY PJkDIONUCLIDE RENOGRAPHY. I.M. Hassan, N. Bellani, N. Kumar, H. Samhan, G. 8aeob, B. Jarada, G. /kbouna and H.M. /kbdel-Dayem. uepns, of Nuclear Medicine and Organ Transplant, Fac. of Med. and Ministry of Public Health, Kuwait.

Detection of severity of acute rejection is prognostic a i d in r e n a l transplantation. Scin~igraphy of renal graft is useful tool to evaluate graft condition. Twenty-two rensscintigraphy with 99m Tc-DTPA of the graft with acute rejection were retrospectively studied. We c l a s s i f i e d them into three groups. G r o u p 1; enlarged graft image and increased accumulation in the vascuJar phase. Group 2; decrease accumulation in v a s c u l a r phase w i t h smaller graft image c o m p a r e d w i t h that in functional phase. Group 3; markedly decreased accumulation especially in vascular phase. Eleven grafts o u t o f 13 c l a s s i f i e d in g r o u p 1 recovered good o r f a i r renal function at 6 months after the rejection episode, and only two cases resulted in g r a f t loss. In group 2, however, three grafts o u t o f 6 , and only one o u t o f 4 in g r o u p 3 c o u l d be survived. The major pathological findings were inter'stitial edema and minimal vascular change in G r o u p 1, b u t v a s c u l a r changes of renal cortex were stronger in g r o u p 2 and especially in g r o u p 3. These indicate that graf~s may have severer damages, namely poorer graft prognosis in g r o u p 2 and 3 than in g l ' o u p ] .

Radionuelide 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, lymphocele, outflow obstruction and urine leaks were reported. Our aim is to elaborate on the usefulness of the radionuelide renogram in detectin9 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 panients 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 summary, the availability of radionuclide renography as a non-invasive tool for early detection of complications, dramatically lowers the incidence of hazardous consequences.

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Abstract withdrawn

TURNOVER OF VLDL APOLIPOPROTEIN B !N CHRONIC RENAL FAILURE S.C. Wang and P. Hu PUMC H o s p i t a l , B e i j i n g , China C h r o n i c r e n a l f a i l u r e (CRF) h a s b e e n known t o be a s s o c i a t e d w i t h a p o l i p o p v o t e i n (Apo) and l i p i d a b normalities, leading to accelerated atherosclerosis (AS). T h i s work i s aimed a t s t u d y i n g t h e l i p o p r o t e i n (LP) m e t a b o l i s m o f CRF p a t i e n t s i n o r d e r t o e l u c i d a t e how t h i s m e t a b o l i s m i s l i n k e d w i t h AS. The f r a c t i o n a l s y n t h e t i c r a t e (FSR) o f Apo B i n v e r y low d e n s i t y l i p o p r o t e i n (VLDL) was d e t e r m i n e d by u s i n g endogenous N - 1 5 - g l y c i n e l a b e l i n g and g a s c h r o m a t o g r a p h y - mass s p e c t r o m e t r y a n a l y s i s i n 5 patients with CRF. Plasma lipid profiles of CRF patients were also studied. The results were compared with those from 5 normal controls. The N-15 glycine used was synthesized in our laboratory. The FSR of VLDL-Apo B obtained by this method was 5.6• in the normal subjects, while that for CleF patients ($.19eO.43%/day) was significantly lower (p <0.01). The CRY patients also had reduced levels of HDL-cholesterol (34.6• mg/dl) Jn comparison with the control (63.2• mg/dl). We find that total triglyceride and Apo B in plasma are closely corelated~ whereas a negative correlation exists between triglyceride and FSR of VLDL-Apo B in the subjects studied. We conclude that Apo B may play an important role in the LP metabolism of the CRF patients. Lowered turnover of VLDL-Apo B~ which is the major carrier of endogenous triglycerides~ tends to result in impaired triglyeeride removal from the plasma and may at least partly account for the high incidence of hypertriglyceridemia in CRY patients.

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DIAGNOSIS OF HYDROTHORAX COMPLICATING CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD) AND DEMONSTRATION OF SUCCESSFUL THERAPY

~Ea~CH O N E F F E C T O F TR~dDITIONAL C H I N E S E M E D I C I N E ( TCM ) O F T O N I F Y I N G T H E K I D N E Y A N D Tu~N-IFYING Tti~ D~/FINCINT ESJ~2~CE O N N h ~ R O T R A N SMITTER R~EPTuR OF SENILE HATS WITH RADIO ~ I G ~ q D D I N D I N G ASSAY.

BY SCINTIGRAPHY. D Mestas, 3P Wauquier, G Escande, 3C Baguet and A Veyre Centre 3ean Perrin and CHRU Clermont-Ferrand, France

We report our experience in the diagnosis and treatment of a d i a p h r a g m a t i c peritoneal leak (DPL) c o m p l i c a t i n g CAPD. A g l - y r - o l d man with end s t a g e renal disease t r e a t e d by CAPD was a d m i t t e d in our unit with a right pleural effusion. Peritoneal scintigraphy was performed using a 370 MBq (i0 mCi) dose of Tc-99m albumin colloid instilled i n t r a p e r i t o n e a l l y through the dialysis c a t h e t e r and flushed with the usual 2 { volume dia[ysate. Sequential scintJgraphic views obtained during the first eight min showed a norma] progressive diffuse pattern a c t i v i t y in the abdominal cavity, A t 9 rain appeared a high abnormal concentration of a c t i v i t y just above the left side of the right diaphragm, Repeat imaging at 6 h showed evidence of progressive leakage o~ dialysis fluid from the peritoneal c a v i t y to the right hemitborax. One day later, the p a t i e n t underwent a surgical c o r r e c t i o n by pleural talc. CAPD was suspended for the next l0 days and hemodialysis was r e p e a t e d three t i m e s during this period. Another scintigraphy study was r e p e a t e d i I days l a t e r and confirmed the absence of t h o r a c i c a c t i v i t y . CAPD was r e i n s t i t u t e d on day 12 with small volumes. P e r i t o n e a l scintigraphy is a simple and safe method already used for the diagnosis of hydrothorax c o m p l i c a ting CAPD ; it can also be very useful in showing the success of pleura] t a l c symphis, t h e r e f o r e allowing a more rapid return to CAPD.

Mo Qi-zhong, G o n g Bin, F a n g Jun, W a n g J u - m e i K a n g X i n g - w e i , C h e n R o n g . S h a n g h a i College of Traditional Chinese Medicine,

China.

We c h o s e 3 H - s p i p e r o n e , 3 H - D H A , 3 H - p r a z o s i n as r a d i o l a b e l e d ligand. I t was d e t e r m i n e d to the c o n c e t r a t i o n of l i g a n d - r e c e p t o r c o m p l e x (Rt) o f D A , ~ a n d ~, a n d its e q u i l i b r i u m d i s s o c i a t i o n c o n s t a n t s ( K d ) in s e n i l e r a t s c e r e b r u m a c c o d i n g to J . Z . F i e l d s , J . E . L e y s e n , A . L e v i t z k i and B a o J i n g - j i ' s m e t h o r d w i t h a l i t t l e modi-" f i c a t i o n r e s p e c t i v e l y . It Was a l s o d e t e r m i n e d to e f f e c t of a p r e s c r i p t i o n for t o n i f y i n g kid n e y Y i n ( B a o Z h e n g recipes) a n d p r e s c r i p t i o n for t o n i f y i n g d e f i c i e n c ~ o f k i d n e y Y a n g ( G u Zh= e n recipes) o n n e u r o t r a n s m i t t e r r e c e p t o r in b r a i n o f s e n i l e rats. The r e s u l t s s h o w e d t h a t it w a s m a r k e d l y d e c r e a s e d to levels of Rt o r K d o f ~ f , ~ , D A r e c e p t o r i n a g e d male: o r f e m a l e r a t ' s b r a i n t h a n t h a t of y o u n g one. H o w e v e r t h e l e v e l s o f ~, ~, D A r e c e p t o r R t or K d o b v i o u s l y inc r e a s e a t n the b r a i n o f m a l e o r f e m a l e rats b y fed o n r e s p e c t i v e l y Gu Z h e n and Bao Z h e n g recipes. The Gu s r e c i o e s is f a r b e t t e r t h a n the Bao Z h e n g r e c i p e s i n the b r a i n o f m a l e rats. B u t the Bao Z h e n g r e c i p e s is f a r b e t t e r t h a n the G u Z h e n r e c i p e s i n the b r a i n o f fem a l e rats.

195

196

ERROR ANALYSIS OF MEAN TRANSIT TIMES AND SPLIT RENAL FUNCTION IN DTPA RENOGRAPHY : A SIMULATION STUDY. M. Awdeh, K. Kouris, H.M. Abdel-Dayem, Dept. of Nuclear Medicine, Faculty of Medicine, Kuwait University, Kuwait.

L a b e l i n g hlood components in v i v o . E v a l u a t i o n of Tc-9qm Ascorhic a c i d . M,L, Thakur, J. DeFulvio, S. Kim and C.H. Park, Thomas J e f f e r s o n Univ. P h i l a . , Pa.

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 bauses 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.

S48

L a b e l i n g red blood c e l l s (RBC) or serum albumin (SAI with Tc-9qm in v i v o by s i n g l e iv i n j . of an a g e n t would g r e a t l y add to the s i m p l i f i c a t i o n of procedures to determine cardiac e j e c t i o n f r a c t i o n or localize G.I. bleeding. A common f e a t u r e between RBC p r o t e i n s and p o l y p e t i d e s , and the SA molecule is an abundance of s u l f h y d r y l (SH) and d i s u l f i d e (S-S) groups. Ascorbic acid (AA) has been used in our lab. t o reduce p r o t e i n S-S t o SH which p r o v i d e s t r o n g binding s i t e s f o r Tc-99m. Reduced w i t h 0.8 u g / u l Na~S~O,, Tc-99m was incubated w i t h 2.5 mg AA f o r 5 mianf- ~22~ a t pH 6 . 0 . Following HPLC and ITLC a n a l y s i s , agent was given iv e i t h e r d i r e c t l y or a f t e r o n l i n e i n c u b a t i o n (2 m i n . l w i t h 2 ml autologous blood. Serial 2 ml blood samples were drawn and Tc-g9m associated w i t h RBC and SA, p r e c i p i t a t e d by TCA was determined. A known q u a n t i t y of whole blood was counted along w i t h a standard and % radioactivity in c i r c u l a t i o n was c a l c u l a t e d . Of Tc-99m admin, f o l l o w i n g on l i n e i n c u b a t i o n , 84.4 + 4Z was bound to RBC and SA w i t h 72.4 + 7% to SA and 12 + 3.7Z to R B C . With d i r e c t admfn. 69.9 + 7.6% ad~ dose was bound to the two components, 33.5 + 5.6% to RBC and 36.2 + 4.2% to SA. At 5 min. pos-t admin. 99.6 + 0.5% of-Tc-99m was in c i r c u l a t i o n which then c l e a r e d w i t h a h a l f time of 30 rain, Part of the activity was taken up by the l i v e r and remainder c l e a r e d by the k i d n e y s . Results suggest the possibility of developing Tc-99m AA as a s i n g l e i n j . k i t f o r l a b l e i n g blood components in v i v o to determine cardiac e j e c t i o n f r a c t i o n or l o c a l i z e G . I . b l e e d i n g .

Sunday, August26,1990

197

198

Cr-51 LABELING OF RBC: DEMONSTRATION OF SPECIES DIFFERENCES IN ANIMAL RESEARCH G.J. Morrissey, D. Gravelle, J. Lo and A. A. Driedger. University of Western Ontario, Victoria Hospital, London, Ontario, Canada

EFFECT OF FLUID SHEAR ON THE LOSS OF Te-99m F R O M L A B E L E D P L A T E L E T S . M.K.Dewanjee,

The use of Cr-51 as a red blood cell (RBC) label has been well documented in humans. Application of established human protocols to animal research dictates caution in that species variation (SV) could influence interpretation of the data. An overestimation of Cr-51 activity, in sheep tissue samples to correct for RBC volume, lead our laboratory to assess applicability of established human Cr-51 RBC labeling protocols in sheep. RBCs were labeled with Cr-51, washed to remove unbound activity and labeling efficiencies (LE) recorded. Electrophoresis was performed by a standard cellulose acetate technique. Identification, quantification and Cr-51 LE of hemoglobin (Hb) species was performed. Average LE was 67.5% (n=13). Five sheep showed multiple types (A and B) of Hb. Ratio of Hb A/B = 1.16; Cr-51 LE ratio of Hb A/B = 0.23(n=4)(Day 0), 0.2 (Day i), 0.2 (Day 2). AXE SV was demonstrated of a lower LE in sheep. Washing of labeled RBC to remove uncomplexed Cr-51 is preferable to an ascorbic acid technique, especially if tissue sampling is part of the study. As wellj, various types of Hb of approximately equal proportions demonstrated different LE. Elution of Cr-51 appeared uniform from Hb types A and B. Thus, SV can be important when applying established human protocols to animals.

The major problem of Tc-99m labeled cells is the loss of Tc-99m from labeled cells and excretion via the kidneys and bladder obscuring the views in the abdomen. This loss is much higher in vivo than in vitro. We studied the effect of shear on the loss of Tc-99m from labeled platelets (TCPLT) with an in vitro flow chamber (Grabowsky); the platelets were separated from 43 ml of canine blood and were labeled with 10 mCi of Tc-99m HMPAO. They were resuspended in plasma and blood and allowed to flow at a rate of 2, 4 and 5 ml/min (shear of 740, 1550 and 1937 sec-l) at 37~ The loss of Tc-99m was measured by the centrifugation of aliquots of flowing TCPLT and the radioactivity in the supernatant and pellet was determined with a gamma counter. The results (mean + SD) of Tc-99m loss from TCPLT in the resting and flowing (5 ml/min) platelet suspension at 5, i0, 20 and 30 minutes of flow are shown below: TCPLT 0' i0' 15' 20' 30' Blood 97+_1 95+_1 95+_1 95+1 94_+1 Plasma 97+-1 93+1 91+--1 90+-1 87+1 The shear-induced loss of Tc-99m is significantly higher than resting cells, suggesting that physiologic shear results in the continuous loss of Tc-99m from labeled platelets. (Supported by DOE and FHTIC).

199

200

THE DYNAMICS OF PLATELET-THROMBUS FORMATION RATE (TFR], T H R O M B U S R E T E N T I O N T I M E (TRT) A N D R A T E O F EMBOLIZATION (ROE) O N C O N T R O L (CPC) A N D H E P A R I N BONDED POLYURETHANE ANGIO-CATHETER (HBPC) W I T H IN-111LABELED P L A T E L E T S (IN-PLT) I N A D O G M O D E L .

INCREASE OF INTRA-PLATELET FREE CALCIUM (IPFC) ION DURING THE EXTRACORPOREAL CIRCULATION (ECC) WITH HOLLOW-FIBER OXYGENATOR (HFO)-ARTERIAL F I L T E R (AF) A N D D Y N A M I C S O F P L A T E L E T - T H R O M B O S I S ON OXYGENATOR IN A PIG MODEL. M.K. Dewanjee,

M.Dewanjee, S.Rowland, M.Kapadvanjwala, M. Georgiou, G.Palatianos,D.MacGregor,G.Sfakianakis. Univ.of Miami, Sch of Med, Miami, FL., U.S.A.

G. Palatianos,M.Kapadvanjwala, L.Hsu, M.Yanis, Y. Ahn, G.Sfakianakis. University of Miami School of Medicine, Miami, FL, U.S.A.

The dynamics of platelet deposition on CPC and HBPC was evaluated with IN-PLT with a computerized gamma camera (CGC). Ten nonheparinized dogs (18-25 kg) were catheter-ized in both femoral arteries with i0 cm of CPC and HBPC (5 Fr., Cordis, Inc.) 24 hours postinjection of 300-420 microcuries of In-PLT and imaged for 3 hours with CPG. The regional platelet deposition curves (RPDC) indicated multiple peaks and valleys; the RPDC were analyzed for the early rate of thrombus buildup (RBP: upswing), thrombus retention time (TRT: full-width at half-maxima) of the peak of RPDC and rate of embolization (ROE: downswing) on three segments of catheters. The three parameters (mean/S.D.) of thrombosis on catheters were tabulated: TFR(Ct/Sec) TRT(min) ROE(-Ct/Sec) Cath(CPC) 2.5/2.1 60/20 1.0/0.8 Cath(HBPC) 0.7/0.6 75/5 0.3/0.2 The RBP and ROE are higher for the CPC than HBPC suggesting that heparin-bonding decreases early rate of thrombosis and embolization. Both in vivo (dynamic) and in vitro studies were necessary for evaluation of CPC thrombogenicity. (Supported by DOE and FHTIC).

The intra-platelet free calcium ions provide a common pathway for the platelet activation leading to thrombosis and embolization. The IPFC levels were determined by chlorotetracycline fluorometry (CTF) during ECC with systemic heparin in 8 Yorkshire pigs (30-40 kg, 3 control and 5 ECC); the ratio of slow phase of organelle Ca-sequestration to fast phase of plateletmembrane binding (CCTCR) is an index of free Ca. During the 3 hours of ECC with HFO (Bentley CM50) and AF (Bentley 1025), seven blood samples were collected at 5 min before and during E C C . The platelet-deposition (CPM/uCi) on HFO (PDHFO) was simultaneously measured with In-ill labeled autologous platelets (300-400 uCi) and a probe detector; the CCTCR and PDHFO values (Mean/ Std. Dev.) of free Ca during ECC are as follows: Time,min 0 5 30 45 60 120 CCTCR .6/.2 .7/.2 1.3/1.1 1.7/1.3 1.3/1 1/.2 PDHFO 0 6/1 10/3 13/11 9/2 7/1 During ECC, IPFC and HFO-thrombus increase significantly (P<0.05) at 45 min with respect to control values of 0.4/0.1, suggesting the direct participation of Ca-activated platelets in thrombosis on HFO. (Supported by DOE and FHTIC).

Sunday, August 26, 1990

M.Kapadvanjwala, S.Dewanjee, G.N.Sfakianakis Univ.of Miami Shool of Medicine, Miami, FL, U.S.A.

S49

201

202

ISOTOPIC EVALUATION OF RELATIVE THROMBOGENECITY OF 5 TYPES OF VASCULAR PROSTHESIS ON DOGS, J. Verreault, M.D. I, J. Teijeira, M.D. I, J. Branco, M.D. l, R. Guidoin M.D. 2, M. Normandin, T.N.M. i, G. Lamoureux, M.D. l i) Dept. of Nuclear medicine and radiobiology and service of Cardio-vascular surgery, University of Sherbrooke. 2) Laboratory of experimental surgery, Laval University

BONE MARROW SCINTIGRAPHY IN HEMATOLOGIUAL DISORDERS. A.Tarkowska, D.Wawrzoszek, A.Gawlik, J.Zaorska-RaJca, M.Hus. Department of Nuclear Medicine, Medical Academy, Lublin, Poland.

In search for the best vascular prosthesis (VP), we studied the thrombogenecity of 5 biomaterials: gamma rays sterilized polyurethane (GPU), ethylene oxide sterilized polyurethane (EOPU), human ombilical vein (HOV), bovine mammary artery (BMA), and polytetrafluoroethylene (PTFE). 40 dogs were divided into 8 groups of 5. In each group, a different type of VP was grafted in aortic position in each dog. All group of dogs were sacrified respectively 4, 24, 48 hrs, i, 2 weeks, i, 3, 6 months after surgery. Before the sacrifice each dog was injected with 4.6 MBq of 125 I-fibrinogen and autologous platelets labeled with 18.5 MBq of Iii Inoxinate. After sacrifice, each VP was remove and counted for iii In- and 125-I along with 1 ce of blood. Re lative index of platelet deposition (RIPD) and of fibrinogen deposition (RIFD) were obtained by dividing the ratio of graft activity over blood activity by the mean ratio value of the group. Mean RIPD were in order for the type of VP: 1.25 + 1.12, 1.19 + 0.60, 1.12 +_ 1.O7, 0.59 + O.17 and 0.93 + 0.85. Mean RIFD were in the same order: 0.89 + 0.57, 1.O3 + 0.47, 1.13 + 0.59, 0.73 • 0.25 and 1.12 + 0.50. Data analysis showed that BMA was significantly less thrombogenie than the others.

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/, myelodysplastie syndrome /5 pts/, myeloproliferative syndrome /9 pts/, multiple myelema /5 pts/ and aplastic anemia /2 pts/. The bone marrow scintigraphy was performed 90 mln. 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 scintlgraphy is a valuable method for detecting and describing bone marrow abnormalities in hematological diseases.

203

204

DIAGNOSIS OF LOWER-LIMB DEEP VEIN THROMBOSIS WITH DUPLEX ULTRASOUND AND RADIONUCLIDE VENOGRAPHY BY SUBCUTANEOUS INJECTION OF Tc-99m PERTECHNETATE. chung-Chieng Wu, Shiang-Bin Jong. Department of Nuclear Medicine, Kaohsiung Medical College, Kaohsiung, Taiwan, R.O.C.

GALLIUM 67 SCINTIGRAPHY

Lower-limb deep vein thrombosis (DVT) is not uncommon in Southern Taiwan. It usually occurs in chronic ill persons after long-term lying, e.g. C V A patients, and in patients with chronic vasculopathy, e.g. DM patients. Clinically the diagnostic methods of DVT are contrast venography, dupplex US, radionuclide venography (RNV), impedance plethysmography, etc. We report 2 cases of DVT diagnosed by duplex US and SC-RNV; the latter was a recently developed technique in our laboratory. C a s e I was a 58 year-old male, having chronic calf varicoses bilaterally, suffered from soft tissue swelling of left lower limb for > 2 wks. The SC-RNV revealed bil. varicose veins in calves and severe deep venous stenosis involving it. common femoral (CFV), superficial femoral (SFV) and popliteal veins. The duplex US disclosed a thrombus in the It. CFV. Case 2 was a 58 year-old male, being diabetic for > 2 years, developed soft tissue swelling of it. lower limb suddenly. The SC-RNV revealed severe deep venous stenosis involving the SFV, popliteal and calf deep veins. The duplex US disclosed thrombi in the it. SFV where no flow was visualized. Combination of SC-RNV and duplex US could be very valuable in diagnosis of lower limb DVT, we concluded.

neoplastic processes, scintigraphy wlth Gall~um--67 citrate has been widely used to find out pyrogenic lesions in cases of fever of nnknown origin (FUO). To examine if this modality is sti]l of practical value after the emergence of X-CT and ultrasound, 60 scans for FUO in the last 8 years were reviewed retrospectively. Gallium images of $5 patients were

S50

FOR FEVER OF UNKNOWN ORIGIN:

REEVALUATION WITH RECENT CASES. T. Misakl, S.Dokoh, K. Yagi, and S. Shimbo. City Hospital, Kyoto, Kyoto, JAPAN With its abi]~ty

interpreted

to detect

as positive.

Kyoto

both inflammatory

Besides

and

local inflammatory

l e s i o n s i n 25 c a s e s , seven c a s e s of g e n e r a l i z e d

disocdezs were found. There were 3 patients with reticule- or lympho-proliferatlve disorders, 3 with systemic autoimmune dxseases, and I wi~h severe EB virus infection. Three false positive readings were due to intestinal gallium retention in 2 cases and physiological pulmonary hilar accumulation in I . Of 25 cases with negative gallium scan, no definite cause of fever were found in 21, and most of them were cases with mild fever. False negative cases were; two with urinary tract infection on antibiotics, one with bacterlal meningitis~ aad one with po]yarteritls nodosa. Our resu]ts reconfirmed the excellent sensitivity and accuracy of gallium scan to diagnose focal inflammations, and also showed that it sometimes contribute to early detection of grave systemic illnesses.

Sunday, August26,1990

205

206

67-C~ Sq*JDY IN RHI~I~ATIC FEVER J.U. Caleqaro, A. C. Macedo de Carvalho, M. Medeiros, E. F. Games, et E.R.S. Campos. Hospital de ~ s e , FFH]F, Bras{lia - Brasil.

VALUE OF SKELETAL SCINTIGRAPHY IN D I A G N O S T I C S OF TUBERCULOSIS IN B O N E O R J O I N T .

In order to evaluate the validity of 67-Ga in the diagnosis of active carditis in Rheumatic Fever (RF) and the response to treatment, 55 67-Ga studies were reviewed retrospectively in 30 hospitalised patients -15 male, mean age 16,16 y.o., with a diagnosis of RF: 28 carditis; 20 with active carditis, 8 inactive; 1 RF without carditis, 1 Sydenham's chorea-, stsblisbed by clinical, laboratorial, X ray, EKG and ultrasound evaluation. From the 28 patients with carditis, 7 were in the first episode of RF, 13 with recurrent disease and 8 with inactive disease. The patients were divided in two groups: group A, 20 patients who received clinical treatment and group B, ll patients (one from group A) submited to surgical treatment. In the first group (~), the 67-Ga images correlated well with clinical findings, EKG and US results although 7 cases with positive 67-Ga images had rheumatic laboratorJal data negative. One patiente with negative 67-Ga image had clinical and FKG evidence of active disease an@ was considered as false negative. For this group sensibility was 0.94 and specificity 1.0. The second group (B), with biopsy, the clinJcal-scintigraphic-histologlc correlation matched in I0 cases and mismatched in one,showing sensibility 0,5 and specifity 1.0. The semi-quantitative analysis of the 67-ga images with ROI'S pixels over the heart x rigth lung in 22 normal patients showed index of i]4,5-+17% (2 s d); the patients with active carditis showed an index between 140 and 200%. The analysis os the images and this index showed good correlation in the follow -up of I~ clinically treated patients. Our conclusion is that 67-Ga studies is as important too] to caracterize the ~ c t i v ~ t y q f rheumatic c~rdi~i~, to evaluate . . the resulzs o medical zreatmenv an us ~eflne inactlvlty.

S. F. G r e b e , H. S c h a l e r m a n n , G.-L. F~ngewisch, H. M[iller, S. K. G r e b e , H. J u n g b l u t . Kerckhoff Clinic from Max Planck Sac., Bad Nauheim, West-Germany. 134 p a t i e n t s w i t h t u b e r c u l o s i s in b o n e o r joint were examined in t h e y e a r s f r o m 1 9 7 8 to 1985. The diagnosis was secured histologically or histologically and culturally (in c o m b i n a tion) o r c u l t u r a l l y or clinically. In 97,3 % of the cases the tuberculin test was positive. Conventional and CT X-rays and scans were t a k e n in a l l c a s e s . F o r 13 p a t i e n t s 3-phase scintigraphy was carried out. The X-ray findings showed typical morphological changes. Scintigraphy combined with uptake measurements offers information about activity of the specific inflammation process. Using this method repeatedly during therapy, verification o f s u c c e s s is p o s s i b l e . No significant additional information was presented by 3-phase scintigraphy.

208A

208B

LABELED WHITE BLOOD CELL SCINTIGRAPHY FOR THE DETECTION OF OCCULT INFECTION FOLLOWING TOTAL JOINT ARTHROPLASTY

~UBTRACTION SCINTIGRAPHY FOR I D ~ T I F I C A T I O N OF ACUTE I~TORY DISEASES OF THE VEHTEBEAL COLUMN. A. Bockisch, A. Hotze, W. R~ther*, F. M~ller*, B. Briele, H.-J. Biersack, Dept. Nucl. Med., Dept. 0rthop. (*), Universit~t Bonn, W. Germany

H.H.LAURENS,H.COUDANE,j.SOMMELET,J.ROBERT Service H~decine N u c l 4 a i r e , 1 8 , r u e Lionnois et C l i n i q u e de Traumatologie - F - 54000 - NANCY The value of white blood cell (WBC) s c i n t i g r a p h y to determine the presence of i n f e c t i o n was assessed in 40 p a i n f u l prosthet i c j o i n t s (31 hip and 9 knee prostheses) in 36 p a t i e n t s : 28 scans with indium l l l - o x i n a t e labeled pure granulocytes and 12 scans with g9m-Tc-HMPAO labeled WBC. II p a t i e n t s had i n f e c t i o n s , as determined by means of c u l t u r e or h i s t o l o g i e r e s u l t s : 13 scans, 8 hip prostheses and 5 knee p r o s t h e s i s ; twelve scans were p o s i t i v e ; only one I n - I l l s c i n t i g r a p h y was negative in a hip a r t h r o p l a s t y . Twenty-seven prostheses were non i n f e c t e d with a Tc-99m-HMPAO f a l s e p o s i t i v e scan in a p a t i e n t with knee p r o s t h e s i s . This represents a s p e c i f i c i t y of 96.3 %, a s e n s i t i v i t y of 92.3 %. I n - l l l - g r a n u l o c y t e s imaging has a b e t t e r s p e c i f i c i t y (I00 %) and is more s u i t a b l e f o r the d e t e c t i o n of hip a r t h r o p l a s t y i n f e c t i o n ; 99m-Tc-HMPAO WBC imaging has a b e t t e r s e n s i t i vity (lO0 %) and is m o r e a p p r o p r i a t e f o r p e r i p h e r i c j o i n t a r t h r o p l a s t y study. This study demonstrates t h a t leukocytes imaging is e s s e n t i a l to confirm or exclude periprosthetic infection and should prove useful f o r c o r r e c t s u r g i c a l management.

Sunday, August 26, 1990

Differentiation between acute inflammation of the spine and residual state is still a diagnostic problem. Radiolabeled leukocytes accumulating in the RES result in a marked visualization of liver, spleen and bone marrow. In leukocyte scans spondylitis, therefore, usually displays a cold lesion since the bone marrow is destroyed by the inflammation. The differentiation between active inflammatory disease and residual state is in many cases thus not possible. The findings are independent from the kind of label (in vitro: Tc-99m-HMPAO or in vivo: Tc-99m-nnti-granulocyte-antibody). On the other hand, the RES seeking nanocolloid is known to accumulate also in inflammatory areas. Assuming the leukocytes to be the specific inflammation and the nanocolloids the specific bone marrow marker, we performed subtraction studies using both agents. First the leukocyte study (Tc-99m-antigranulocyte-antibody) was performed 24h after administration of 550 MBq i.v., and then the nanocolloid scan was added 30 min after the leucocyte scan. For both studies the patient was in the very same position. The normalized nanocolloid scan was subtracted fro~ the leukocyte scan by means of a computer program. Scintigraphic images on which at the site of the cold lesion on the original leukocyte scan an increased count rate was found on the computer assisted "difference image" were considered to be positive. Of 14 patients with questionable active spondylitis, 6 cases were true positive, 6 true negative, and 2 case false negative. As reference for scintigraphic estimation served the results from surgery, biopsy with microbiol., and clinical course. Conclusion: These preliminary data are convincing that this new technique might help to overcome known problems in the diagnosis of infections of the vertebra column.

S51

209

210

uOMPAR• OF IN-Ill LEUKOCYTES, Tc-99m HM-PAO LEUKOCYTE, GA-67 CITRATE AND IN-Ill ANTIMYOSIN IN DETECTION OF EXPERIMENTAL ABSCESS. S. Sadek, A. Owunwanne, A.H. Elgazzar, T. Yacoub and H.M. Abdel-Dayem. Dept. of Nuclear Medicine, Kuwait Oniverslty, Kuwait.

DIAGNOSIS OF PYREXIA OF UNKNOWN ORIGIN WITH IN-111

Oojective of the study was to compare Ga-67 citrate, In-lll leukocytes, Tc-99m HM-PAO and In-]ll antimyosin (which has been shown to localize in skeletal muscle injury) in experimentaly induced inflammatory lesions. Inflammatory 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 gar~ma 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 infl~nmation 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-lll antimyosin and Ga-67 citrate were statistically the same but higher than those of In-ill leukocytes and Tc-99m HM-PAO leukocytes which were statistically equal. Images of the abdominal area using Ga-67 citrate and Tc-99m HM-PAO leukocytes showed activity in the small intestine. In suatmary, the quality of the images were in the following order Ga-67 citrate ~ In-lll antimyosin > In-lll leukocytes Z Tc-99m HM-PAO leukocytes.

LEUCOCYTES IE M a c S w e e n e y , Hammersmith

AM Peters and JP Lavender. H o s p i t a l L o n d o n , W12 0HS, E n g l a n d .

P y r e x i a of unknown o r i g i n (PUO), the commonest cause of is o c c u l t i n f e c t i o n , r e p r e s e n t s a d i f f i c u l t d i a g n o s t i c problem. R a d i o l a b e l l e d w h i t e c e l l s c a n n i n g p r o v i d e s a noninvasive and p o t e n t i a l l y useful diagnostic tool i n t h i s c o n d i t i o n b u t i t s efficacy remains c o n t r o v e r s i a l . In a r e t r o s p e c t i v e study, we analysed 30 I n - l l 1 w h i t e c e l l scans, performed between 1983 a n d 1988, on 25 p a t i e n t s w i t h PUO, s t r i c t l y defined as fever of at l e a s t 3 weeks d u r a t i o n r e a c h i n g 58.3 degrees C on more than 3 occasions and investigated in h o s p i t a l for a minimum of 7 days. Eleven s t u d i e s were on p o s t o p e r a t i v e p a t i e n t s , who, a l t h o u g h e v e lo p in g fever w i t h i n I week of s u r g e r y , s a t i s f i e d the above c r i t e r i a . O v e r a l l d i a g n o s t i c s e e s i t i v i t i y and s p e c i f i c i t y were 557` and 74Z. r e s p e c t i v e l y , w i t h an o v e r a l l a c c u r a c y of 6 7 ~ . This improved to 917` in p o s t o p e r a t i v e p a t i e n t s compared to an accuracy of 527, in spontaneous PUO. Accuracy d i d n o t c o r r e l a t e w i t h d u r a t i o n of symptoms, l e u c o c y t o s i s or i n d e x of c l i n i c a l s u s p i c i o n . In conclusion, although I n - I l l w h ite cell s c a n n i n g is not p a r t i c u l a r l y useful for t h e i n v e s t i g a t i o n of spontaneous PUO, it does have a role in postoperative PUO. which

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99mTc-HM-PAOLABELLEDLEUCOCYTESSCANNING IN BURNT PATIENTS

INFEC2ION: IMAGING WI~I TC-99M LI~JKOCYTES V.E.Soroa,A.H.Fraga de Suarez.Hospital Jos~ de San ~ . A . ~C.N.E.A. ,Buenos Aires,Argentina.

D. HUGLO, S. MEURIOT, D. HOCHART, J.P. GALIZ1A,M. DEVEAUX, X. MARCHANDISE ServiceAssoci4 de M4decine Nuclfaire,Centre des Bn%lGs- CHU de Lille- FRANCE When infectious syndrome occurs in burnt patients, cultures from apparently homogeneous bum may be falsely sterile. So the aim of this study was to assess if labelled

leucocytes scan could detect a patchy lesion with various bacterialovergrowthlevels. METHODS : Nine patients (17-62year) were studied : burnt area surface was t0 to 80 % and depth spreaded from superficial 2 nd degaee to 3rd degree. Studies were performed on the 3 4 day after the accident in 2 cases and over the tst week in 7 cases. According to cultures results, burns were called sterile (<105 germs/g), septic (>105 germs/g), and doubtful ( 105 germs/g) White cells HM-PAO-Tc labelling (Ceretec*, .~v~ERSHAM) was performed according to Peters'method (Lancet 1986, ii, 946-949). Whole body scan was aehleved using a large rectangular head camera (SOPHY CAMERA DSX) 3 hours after leucocyte injection (200 MBq). Simultaneously, a comparative 67Ga scan was obtained 6 hours after injection (92.5MBq). Scan was called positivewhen inhomogeneous activitywas observed in front of cutaneous l~ions.

RESULTS : sterile septic doubtful sterile

J8 (n =4) >Jg (1=2) >J8 (n = 2)

99roTe-leucocytes 6 7 G a + +/+ + +

Evolution non avalaible

Infection may still be a difficult diagnosis.The aim of this study was to contribute in the detection and localization of infectious conditions. We used the quick labelling Tc-99m a l b u m i n m i c r o coloid leukocytes methodology of Markus and Kuperus. The technology was chosen because of its low cost and easy availability in Latin America. Twenty four patients were studied with known or suspected diagnosis of intraabdominal or pelvic sepsis osteomyelitis, infected vascular surgery, arthritis, external malignant otitis or fever of unknown origin. Two patients had second scans in the follow up.Planar images were obtained not further than 4 hs. postinjection.Tomographic scans were performed when activity allowed and better localization was required. Labelling efficiency was about 76-80%.The false negative scan was due to a chronic inflanmatory disease.The false positive scintigraphy was obtained in a patient with lymphatic pelvic turnout.The Specificity was 93% and the Sensitivity 92% .The result proved the study to be a reliable tool in suspected infectious disease.

bad

good good

In one case, initially doubtful burn was studied again as it was sterile. DISCUSSION : Leucocytes scan gives a nice topographic description of the lesions and of their infectious heterogeneity. In extreme cases leucocytes and 67Ga scans are in good aga'eement. In some doubtful cases, accumulation of leucocytes without positivity of 67Ga scan could either indicate severe inflammatory response, or be early indicator of cutaneous infection. We are now considering theses hypothesis in bernt patients candidate for skin graft.

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PRELIMINARY CLINICAL APPLICATION OF 99mTC-HM-PAO LABELED LEUKOCYTE FOR IMAGING. Gu Zhao-Xiang, Lin Xiang-Tong. Department of Nuclear Medicine, Huashan Hospital, Shanghai Medical University, Shanghai 200040, P.R. China.

EXPERIENCE WITH TECHNETIUM LABELLED WHITE CELLS. P.J.Sullivan, J.Lising, Nuclear Medicine Dept., Woden Valley Hospital, Canberra, Australia

In this study, 6 patients were detected by using labeled leukocytes with 99mTC-HM-PAO for imaging. All scintigraphy of 3 patients with inflan~matory lesions were positive. One patient with carcinoma of the colon and hepatic metastasis showed 99mTC-WBC uptake in the area of local lesion. Preliminary clinical application suggested that 99m TC-HM-PAO labeling and reinjection of leukocytes should become a helpful procedure for the scintigraphic detection of inflammatory lesions in clinical practice.

Over the last 6 years we have been performing Tc-99m stannous oxide colloid labelled white cell scanning for the detection of both inflammatory and infective conditions. Predominately most of our work has been involved in the assessment of patients with inflammatory bowel disease. A definitive paper was published in Gastroenterology in October, 1988. This study showed excellent correlation between fecal excretion and histologic score of mucosal biopsy specimens (rS= 0.84, p 0.001) and with the Crohns Disease Activity Index (rS= 0.87, p 0.001). The peak uptake time, i.e. the time to reach maximum uptake within the bowel both visually and on computer generated R.O.l. correlated well with histological scoring (rS= -0.84, p 0.001). We have found white cell scanning to be a very useful test in the assessment of inflammatory bowel disease. Its efficacy in other inflammatory or infective conditions has also been excellent. Its role in clinical conditions such as post operative infections, boney or joint infections, appendicitis and collections has been understated and underutilised. We would like to present clinical examples of the above conditions to show its clinical applicability and usefulness in diagnosis in acute conditions. In summary Tc-99m white cell scanning is easy to perform. The labelling method is performed on whole blood, and shows a high labelling efficiency. The results obtained show that it should become an important part in the diagnostic workup in patients with either inflammatory or infective conditions.

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216A

MODIFIED HAMMERSMITH PROTOCOL FOR TECHNETIUM-99m HmPAO LABELED LEUKOCYTES. L. Karalasin~am, S.D.Ripley, Metropolitan 9eneral Hospital, Windsor, ON, and W.C.Porter, Wm Beaumont Hospital, Royal Oak, MI.

INTRAOPERATIVE BETA PROBE FOR DETECTING TUMOR DEPOSITS USING 1-131 AND 1-124 LABELED MONOCLONAL ANTIBODIES (MOAB). F, Daqhiqhian, K J. A Kairemo, S C Rubin, M Federici, S M.Larson Memorial Sloan-Kettering Cancer Center, New York, NY

The Hammersmlth Protocol (HP) was modified to increase the Labeling Efficiency (LE) of T o - 9 9 m H m P A O leukocytes (WBC's) an d reduce the volume of Whole Blood (WB) required for labeling. The HP used 80ml of WB to achieve a 50% LE. If 50ml or less of WB is used the LE decreases to 35%. HP was modified by using: 1. 3040ml W-B; 2. platelet poor plasma (PPP); and 3. degassed saline (DGS) to prepare Tc-99m PanPAO and for hypotonic lysls (HL) of EBC's. 40ml of WB was drawn into 7ml ACD and 5ml hetastarch. RBC's were sedlmented over 30mln. A mixed WBC/RBC pellet was obtained at 300Gxbmin yielding a WBC pellet, which was then suspended in Iml PPP. l.llCBq of pertechnetate was added to a vial of HmPAO. The mean of Tc-99m HmPAO LE was 88% (• 4ml of Tc-99m HmPAO were added to the suspension and incubated for 15min. With unbound removed, 185-370MBq Tc-99m WBC was resuspended in 5ml PPP and injected. The mean LE was 51% (• Images were obtained on iO patients. 5 were positive for inflammatory bowel disease (IBD), 2 for abscess localization (AL), I for osteomyelitls (OM), and 2 were negative. Bone, Indium and Gallium scans were also obtained in OM and AL patients. In-lll WBC was matched by Tc-99m WBC, but nonspecific bowel activity was routinely noted. Conclude that HP has been successfully modified achieving an equal LE with 50% reduction in WB. The sensitivity is equal to In-lll WBC, but specificity is felt to be less for IBD.

Sunday, August 26, 1990

We have studied in nude mouse and rat models positron and electron emitting radioiodinated MoAb (~X35) using a beta-probe, This probe (positron and electron sensitive) was used for detecting 1-131 (B-) and 1-124 (B+) labeled MoAb in ex rive and in rive samples. This probe consists of a plastic scintillator (3 r~n x 3 rrm) coupled to a PHT through a light guide, The proper energy threshold was set to reject ganmm generated counts and therefore nmking the probe sensitive to short range beta r a y s T h e animmls had either intraperitoneal or subcutaneous hunmn ovarian cancer xenografts (serous cystadenocarcinoma), MX35 MoAb is expressed by this ovarian ca cell l i n e The results of probe counting were compared with those of gannm in~ging (in vivo), surgical findings (ex/in rive), and well counting The probe counts showed a high degree of localization of radio-labeled MoAb after 2 days following injection, The sites identified by probe corresponded with those seen on gamma /nmging and at surgery, The probe was found to be sensitive to beta rays and highly insensitive to ganmm rays and therefore inmmne to distant radiation sources In ovarian cancer diffuse superficial peritoneal metastases are corrmon This technique may provide a new specific means for detecting micrometastases during second-look staging relaparotomy,

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217

INTRAOPERATIVE CANCER DETECTION: RAPID BLOOD CLEARANCE USING 1-125 LABELLED BIOTINYLATED MONOCLONAL ANTIBODIES AND COLD AVIDIN. G.Paaanelli. P.De Nardi, P.Magnani, M.Stella, L.Pennacchioli, F.Zito, A.G.Siccardi, V.Di Carlo, F.Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy.

POSITRCN EHISSIC~ T(I~OGRAPHY (PET) FOR DI~f~NCSIS OF CANCER METAST~ES USING 1-124 LABELED MONCCLC~AL ~/q/IBODY IN A NUDE RAT MODEL K.J.A.Kairemo. F. Daghighian, A -L, Brownell, S. C. Rubin, M. Federici, K.S. Pent low, S.M. T-arson. Kemorial Sloan-Kettering Cancer Center, New York, NY and Massachusetts General Hospital, Boston, H-~

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. Twelve patients with colorectal cancer were injected i.v. with 1-3 mg of cold avidin, 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 57% in 10 minutes and by 62% 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.

PET is the most accurate functional mmaging modality and when combined with specific ~r,r~!nological targeting, it might provide a n e w specific and sensitive radiolnlnunoscintigraphic tool. T6 investigate this w e injected intravenously nude rats bearing subcutaneous or intraperitoneal human ovarian cancer xenografts with 1-124 labeled MX35 monoclonal antibody (doses 200-300~Ci). This I~31 subclass antibody reacts with this ovarian cancer cell line lnmmnohistochemically. Imaging was performed at 3-4 days using a high resolution positron emission tomograph (PCR-I) with a spatial resolution of 4.5 nmn. The slice thicknesses were 0.5 and i cm, 40-70,000 coincidence pulses were obtained/frame. The imaging results were compared with those of computerized tomography and histology With PET it was possible to localize spleen, heart, liver, and kidneys accurately, The intraperltoneal tu/nors were identified with PET imaging and correlated with tissue sa,mpling. Our findings suggest that PET 3_maging of tumor wi~h 1-124 labeled .,.M~_35 monocloPml antibody may be useful in hu..~andiagnostic and therapeutic applications

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219

E V A L U A T I O N OF I n - l l l AND Tc-99m L A B E L L E D MONOCLONAL ANTIBODY FOR PRE-OPERATIVE IMAGING IN PRIMARY COLORECTAL CANCER. L Golberg, A J . B . McEwan, W. Brzezinski, E. Wiens, A.A. Noujaim, M. Longenecker, T. Sykes, G.D.MacLean. Cross Cancer Institute, Edmonton, Alberta, Canada.

TECHNETIUM LABELLED MONOCLONAL ANTIBODY 170H.82 IN R A D I O I M M U N O GUIDED C O L O R E C T A L SURGERY -A CASE STUDY. L. Golberg, A.J.B. McEwan, W. Brzezinski, E. Wiens, A.A. Noujaim, B.M. Longenecker, T. Sykes, G.D. MacLean. Cross Cancer Institute, Edmonton, Alberta, Canada.

Using monoclonal antibody 170H.82, the results of preoperative radioimmunoscintigraphy, intra-operative localization and pathological findings were compared. 170H.82 is a murine monoclonal antibody derived against synthetic TF (ThomsenFriedenreich) antigen and has been shown to be reactive with the majority of adenocarcinomas in-vitro. Eight patients with primary colon cancer received infusions of varying doses of radiolabelled MAb 170H.82. In six cases l l l In was used and in two Tc-99m was used. Pre-operative imaging with planar and SPECT was obtained on all patients. In the group where 111-In was used, SPECT was done 6-10d post infusion and identified all known primary tumors. Planar images revealed 4 of 6 tumors. On two occasions 111-In SPECT images revealed presence of tumors not suspected pre-operatively. In the group where Tc99m was used as a radiolabel, SPECT was done 24h post infusion and identified 1 of 2 tumors. However, in both patients receiving Tc-99m 170H.82 imaging was reported to show abnormal areas of tracer accumulation which could not be confwmed surgically. All patients underwent standard surgical exploration and resection and imaging findings were verified. We feel that the sensitivity of imaging for the particular monoclonal antibody used depends on time between infusion and scanning. In-vivo behavior and biodistribution of a given antibody should dictate choice of the radioisotope.

170H.82 is a novel IgG1 monoclonal antibody with previously shown reactivity to the majority of adenocarcinomas in-vitro. It was derived against synthetic "IT (Thomsen-Friedenreich) antigen in the beta configuration. We have shown it to be clinically useful for gynecological radioimmunoscintigraphy of metastatic disease. The patient was a 65 year old female with confirmed adenocarcinoma of the colon. She had previous anterior abdominal resection of recto-sigmoid with subsequent colostomy and presented with obstructing recurrence at site of anastomoses. Antibody was labelled with 1850 MBq of Tc-99m and infused over 30 minutes while monitoring HR and BP. Planar images were obtained immediately and at 24 h and abdominal SPECT at 24 h. Surgery was performed at 48 hours aided by a RMD CTC-4 cadmium telluride (CdTe) miniature gamma probe. Biopsies taken at surgery were counted in a well counter and cts/min/gm calculated. The use of both pre-operative SPECT imaging and intraoperative gamma probe greatly assisted in localization of lesions. Planar images demonstrated two areas of abnormal uptake of activity; one in the right S.I. joint, the second a large complex mass in the pelvis. All sites visualized on imaging were pathologically confirmed. Positive biopsy sites included ovary, fallopian tube, large bowel, and a segment of small intestine. Pre-operative localization with planar and SPECT imaging and intra-operative localization with the CdTe probe greatly facilitated appropriate surgical management. This investigation has shown Tc-99m labelled 170H.82 to be a promising agent for radioimmunoscintigraphy of metastatic adenocarcinoma and can be particularly useful when used in conjunction with a miniature gamma probe.

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221A

QUANTITATIVE IMAGING OF 1-124 LABELLED ANTIBODIES USING POSITRON EMISSION TOMOGRAPHY. K.S.Pentlow, M.C.Graham, N.K.V.Cheung, R.M.Lambrecht, R.Finn and S.M.Larson. Memorial Sloan-Kettering Cancer Center, New York, NY, USA and King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

I M M U N O S C I N T I G R A P H Y IN P A T I E N T W I T H C O L O R E C T A L CANCER RECURRENCES AND REGIONAL HEPATIC CHEMOTHERAPY. A. Kroiss, Ch. A u i n g e r , J. Schfiller, W. Weiss, M. Wirth, K. Dinstl, a n d A. N e u m a y r . K A R u d o l f s t i f t u n g , Vienna, A u s t r i a .

Positron emission tomography (PET) could be useful not only for the diagnostic imaging of antibodies but also for quantitation leading to improved dosimetry during radioimmunotherapy. Most commonly used positron emitting nuclides do not have suitable half l i v e s or chemical properties, lodine-124 has such properties and a half l i f e of 4.2 days, but has not been widely used because of i t s complex decay scheme. Measurements made cn PET scanners under r e a l i s t i c conditions using body sized phantoms and 1-124 labelled antibodies in animals bearing human tumor xenografts have shown that 1-124 can be successfully imaged and quantitated. Spatial resolution showed a degradation of less than 2 mm F~VHMcompared with fluorine-18. D e t e c t a b i l i t y of small spheres was only s l i g h t l y worse i f imaging time was increased to compensate for the lower positron abundance. L i n e a r i t y of observed versus actual a c t i v i t y within regions was maintained. Satisfactory q u a n t i t a t i v e imaging was carried out using spheres of various sizes and a c t i v i t i e s in d i f f e r e n t background a c t i v i t i e s within head and body sized phantoms. Similar measurements were made over one week with rats bearing human neuroblastoma and injected with 1-124 labelled 3F8 antibody. Thus, q u a n t i t a t i v e imaging of 1-124 labelled antibodies over several days appears to be possible under r e a l i s t i c conditions.

The aim of t h i s s t u d y w a s to p r o v e t h e diagnostic accuracy of immunoscintigraphy (IS) in p a t i e n t s (pts) w i t h c o l o r e c t a l c a n c e r and recurrences, especially in p t s with regional hepatic chemotherapy. IS was performed with Tc-99m labeled monoclonal anti-CEA-antibody (BW 431/26; B e h r i n g w e r k e FRG). T h e i m a g e s w e r e d o n e 4 t o 6 hrs and 24 h r s b y p l a n a r s c i n t i g r a p h y a n d b y SPECT. IS w a s done in 14 p t s with c o l o r e c t a l cancer, 21 p t s w i t h c o l o r e c t a l cancer recurrences, 5 pts with urinary b l a d d e r cancer, 1 p a t w i t h p a n c r e a s cancer. T h e l e v e l s o f C E A w e f o u n d b e t w e e n 3.1 a n d 1400 ng/ml. In the g r o u p of the c o l o r e c t a l c a n c e r r e c u r r e n c e s w e f o u n d a s e n s i t i v i t y of 92 % and a s p e c i f i c i t y of 94 %. B e c a u s e o f t h e s e g o o d r e s u l t s w e p e r f o r m e d IS in 18 p t s with regional chemotherapy in pts with surgically implanted hepatic artery catheter. In 18 p t s w i t h m e t a s t a s i s of t h e l i v e r w e f o u n d ll "cold" l e s i o n s a n d 7 "hot" l e s i o n s . In ii p t s w e f o u n d l o c a l r e c u r r e n c e s , in 6 pts we f o u n d c a r c i n o s i s p e r i t o n e i , in 1 p a t m e t a s t a s i s of t h e b r a i n and t h e lung. The results were concordant by clinical indices, b y e n d o s c o p y , b i o p s y , r a d i o g r a p h y and s o m e t i m e s s u r g i c a l s p e c i m e n s .

221B

222

RADIOIMMUNODETECTION OF CANCER WITH A NEW Tc-99m CEA MONOCLONAL ANTIBODY Fab' AGENT: RECENT RESULTS. D.M. Goldenberg, H. Goldenberg, S. Murthy, D. Front, R.E. Lee, E. Nigginbotham-Ford, J.A. Horowitz, L.C. Swayne, T.C. Hall, C.M. Pinsky, and H.J. Hansen. Center for Molecular Medicine and I~unology and Department of Radiology, New Jersey Medical School, UMDNJ, Newark, NJ, Morristown Memorial Hospital, Morristown, NJ, and Immunomedics, Inc., Warren, NJ. A carcinoembryonic antigen (CEA) monoclonal antibody (MAb) Fab' fragment has been labeled with Tc-99m by an "instant" labeling kit. Initial studies have indicated the safety and efficacy of this new cancer imaging agent, especially the ability to image small lesions early, particularly with SPECT (Goldenberg et al., JNM 30:809, 1989; idem., Sem. Nucl. Med. 19:262, 1989). The NP-4 (Immu-4) MAb used shows lower binding with circulating CEA than is found with other CEA MAbs, and is CEA-specific. A series of patients with diverse cancers producing CEA have been studied with the new CEA-Tc kit, eva~uating image results at 3-5 h and at about 24 h by planar scintigraphy and with SPECT alone at the early imaging times. In a series of over 40 patients with known or suspected disease, radioimmunodetection (RAID) was capable of correctly disclosing over 90% of the known sites, even tumors less than 1 cm in diameter in the liver and in other difficult areas. The new lesions revealed only by RAID are being followed in order to determine the specificity of this new cancer detection kit. Imaging results at 3-5 h after injection of 1 mg Fab' labeled with 10-20 mCi of Tc-99m sufficed for accurate tumor imaging, comparing very well to 24 h RAID studies or to CT scans.

Sunday, August 26, 1990

HUMAN LUNG CANCER IMAGING USING 1-131-LABELED MONOCLONAL ~NTIBODIES S.C. Wang, C. Chou, X.B. Shi, C.Z. Yao and F. Li. PU~C ~ospital, Beijing~ China The purpose of this study is to prepare and characterize 1-131 labeled n~rine antibodies (V~Abs) directed against human lung cancer and to evaluate their efficacy in tumor localization. Anti human lung cancer McAbs 2E3 and 6DI were developed by cell fusion method. 2E3 (igG1) and 6D1 (lgG2a) reacted with a 67 Kd and 30 Kd cellular antigen respectively. ~le affinity constants were determined by Scatchard analysis. The specificity of the McAbs was studied by immunohistochemistry, cell immunochemistry, in vitro binding assay and biodis~ribuCion in tumor-bearing nude mice. The McAbs were sorongly reactive wigh lung giant cell carcin~na, lung adenocarcinoma and lung squamous carcinoma, but did nog react with hepatic~ gastric carcinomas and nont ~x~ lesions. For clinical evaluation, i0 patients suspected of lung tumor underwent radioirmmlnoimaging~ after intravenous injection of a mixture (2mg) of 2E3 and 6DI labeled with I-]31 (74 mBq). Among these patients 11 were subsequently proven to be lung cancers, 4 noncancer lesions and another lymphoma by endoscopic or surgical biopsy. Immunoscintigraphy was true positive in 8 of the 11 lung cancer patients (73%) and true negative in all 4 patients without lung cancers (100%). However, positive image was also observed in that patient with lymphoma. The overall diagnostic accuracy was 75%. Our results suggest that McAbs 2E3 and 6DI are promising agents for imaging of lung cancers. More clinical trials are still in progress.

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RABIOI~INIUNOIMAGINiJ IN NUDE MI/TE BEARING THYROID CARCINOMA UGING ANTI-THYROBLOBULINMONOCLONA[ANTIBODY Lupin 0 [.i,5hengtin9 Li,Xiaolmi Zhang, YanLin 9 Xiao The Third C l i n i c a l College, Norman Bethune University of ~tedir. a[ Science, Chang Ehun. Ji kin, P.R. ghina.

SUCCESSFUL TREATMENT OF REFRACTORY NON-HODGKIN~S LYMPHOMAWITH RADIOLABELED MONOCLONAL ANT~BODIES. D.M. Goldenberg, J.A. Horowitz, T.C. Hall, D. Izon, R.E. Lee, V. Steimle, K. Burger, R.M. Sharkey, E. Belisle, C.M. Pinsky, and H.J. Hansen. Center for Molecular Medicine and Immunology, UMDNJ, and Immunomedics, Inc., Newark, New Jersey. B-cell, non-Hodgkin's lymphomas are curable in, at most, 65% of patients. Standard therapy utilizes multiple drug regimens and in certain cases combined modality treatment~ Since lymphomas are systemic at diagnosis and extremely radiosensitive, we have undertaken a pilot therapy trial using an anti-B-cell murine monoelonal antibody (MAb), IMMU-LL-2, tagged with 1-131. All patients had been heavily pre-treated and were felt to be chemotherapy-resistant. Responses have been seen using from 6.2 mCi to 68 mCi of 1-131 ou intact IgG MAb (0.2 mg - 2.8 mg). LL-2 (EPB-2) was raised against the Raji cell line. The exact antigen site or chemical character is net known. 2/4 patients injected with approx. 50 mCi for therapeutic intent have had partial remissions. In addition, one patient injected with only 6 mCi of 1-131 for imaging had a biopsy-proven durable response. This patient has subsequently been retreatd with i0 mCi 1-131 (0.6 mg IgG) and again had a response. Myelotoxicity has been the dose limiting finding and no other significant side effects have been identified. These initial clinical results indicate that B-cell lymphomas are responsive to radiolabeled LL-2 MAb. Further studies are in progress. (Supported in part by NIH grant CA 39841.)

This paper aims to investigate tile use of radieimmunoimagi~t9 ia the diagnosis of thyroid carcinoma. The distribution of 1-125 labelling anti-tilyroglobutin monociona[ a n t i b o d y ( l - f 2 5 a n t i - T G ~,tc.~b)in normal mice was measured. The nude mice modal bearing f o l l i c u l a r , p a p i t t a D and mednttar> thyroid carcinoma were made and tile d i s t r i b u t i o n of 1 - 1 2 5 amti-TG McAb im bearing tumor nude mir.e arid RII using blood-pool background subtraction technique were performed. The r e s u l t s show: 2dhrs a f t e r injecting 1 - 1 2 5 anti-TG McAb in normal mice the radioactivity, mainly remain in c i r c u l a t i o n ( a b o u t 50%), tower r a d i o a c t i v i t y hl other tissues. Radioactivity in orafted f o l l i c u l a r anti p a p i l l a r y thyroid rarcinonla were highest, l . 3 t times and 3. % times to that of blood, respectively. No sionifh:ant accumulation of r a d i o a c t i v i t y in medullary thyroid carcinoma. The accumulation of 1 - 1 2 5 by folLicuLar an.I p a p i l l a r y thyroid tamer was much more than those of the other tissues. We conclude thai the a n t i - T G Nct~b for the diagnosis of f o l l i c u l a r and p a p i l l a r y thyroid carcinoma kind ei.qni firant value.

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Radioisotopes Production Department,

Nuclear Research

Centre, P.O.Box 765, Baghdad-Iraq. Authors: Rodriguez~N ;Ysla,R;Herrera,A; Gonzales,L;Ladr6n do G u e v a r a , N . Summary : Our group has developed a lymphocites label l i n g t e c h n i q u e w i t h tc99m-~vl PA0. The v i a b i l i t y f o u n d o s c i l a t e d b e t w e e n 96 a n d 98 % r o a c h i n g a l a b e l l i n g e f f i c i e n c y of 37 to 40 %. Comercial yorkshire female pigs were studie~o Biodistribution w a s d o n e i n two of them. Heterotopic kidney an pancreas transplants were performed with different unrelated donor The m o n o n u c l e a r s cells were isolated accord i n g to t h e B o y u m m o d i f i e d t e c h n i q u e u s i n g t e l e b r i x 38. A f t e r one h o u r of i n j e c t i o n of l y m p h o c i t e s labelling we observed a definit activity in kidney and pancreas suggesting rejectiong reaction. The histopathological verification was oerformed. ~ h e r e w a s a g o o d c o r r e l a t i o n in h u m a n b e i n g studies. In c o n c l u s i o n , w e c a n s a y t h a t the t e c h n i q u e of l a b e l l e d l y m p h o c i t e s w i t h t c 9 9 m - H M P A O results practical and sensible on a fast rej e c t d i a g n o s i s of p a n c r e a s a n d k i d n e y t r a n s p l a n t . I t s l o w e r cost, s c a r c e i n v a s i v o n e s s a n d l o w r a d i a t i o n d o s i s m a k e s it a n o p t i o n a l t e c h nique in organ transplants.

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Radioim/nunoassay of Human placental lactogen as diagnostic test in pregnant- women. The resent study was designed te know what factors contro i~ed the levels of hpl in maternal serum so that physiological studies could be undertaken in both normal and abnormal pregnancies. It was found that the concentration of hpl was varied between patients at the same time of gestation. Human placental lactogen concentration were measured in the blood of 4.4 ~g/ml women in three trim~ sters of pregnancy to judge how estimations of hpl could help in the management of a~ obstetric population in Iraq~ It was found that the e x p e r i m e n t population with a mean hpl levels of 0.38, 2.51 and 6.48 ~g/ml for first, second and third trimester, respectively. The mean of all population was 4.4 ~g/ml. The concentrations of hpl were 0.22,5.20, 4.33 and 10.33 ~g/_~l for ectopic pregnancy, diabetic, hypertensive and twin pregnancy, r=spectively. The results of the study indicate that hpl concentrations are useful in predicting the result of pregnancy. Also that hpl" is a valuable prognostic measure in women with 'complicated early pregnancy and a reliable index of viable pregnancy. * D~pe. of Gynecology and obstetrics, Medical City, Baghdad University

Sunday, August 26, 1990

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EXPRESSION OF THE HUMAN GENE PS2 AND OF THE PROTEINTM FOR WHICH IT CODES IN BREAST CANCERS. 3. GRENIER*, F. GUILLEUX% 3. FAUQUE** and P. CHAMBON***

DETE[~\IINATIOh ~ J SIGNIFICanCE OF A N ~ C~P~O.IYD~TE ~TIGElq C~ 50 IN T~E SE~Ubi OF PATIENTS wITH C~qCLR

The m e c h a n i s m s by which estrogens induce and s t i m u l a t e the growth of c e r t a i n breast c a n c e r s are still little known. One gene, the ps2, and the protein for which it codes a r e under the

control of estradiol. We are trying to find out whether its study in the cytosols of some breast tumors might permit to improve the diagnosis of hormone-dependence. Originally, the term ps2 was used for a cDNA clone the quantity of which increases when estradiol is added. The ps2 gene codes for a protein also named ps2. Out- retrospective study deals with the ps2 radioimmunological evaluation (C.I.S. Bio [ndustrie) in 209 cytosols of breast cancers for which estrogen and progesterone receptors had been measured, using R.L. techniques. Then, the cytosols had been kept in liquid nitrogen. Several classes and subclasses are studied : - ER + with RP + and PR- subjects - ER- with PR + and PR- subjects The discussions bears on the subclasses related to ps2 deterruination and on the+quality of the additional data for the + identification of ER and PR breast cancers non-responsive to hormonal t h e r a p y .

Mo Qi-zhong *, Dr.R.P.Baum *w, Dr.A.Hertel** and Prof. Dr. G. Horn*, Dr. G. S c h n o r r * ~ * Shanghai College of Tranditional Chinese Medicine, Shanghai, China. ~ Nuclear Medicine Division of Radiological Centre, Frabkfurt, University Hospital * ~ Radiochemical Laboratory, Hoechst Company West Germany. The concentration of ser~/m CA-50 in 227 patients with cancer and 40 healthy subjects were determined by a solid phase radioimmunoassay with the PdA-g~aost CA-50 assay Kit(Behringwerke). The CA-50 P~IA dose response curve is essentially linear f ~ m approximately 0.1-120 U/ml. Analysis of the data obtained demonstrated excellent perforTaance characteristics of the CA50 ?~IA. The assay is very simple to perfor~n and can be comleted in one working day. Since the interassay reproducibility and the assay recovery are both satisfactory at the high end of the curve. The CA-50 P~IA provides reliable results, even for clinical samples with high antigen concentration. comparison of the CA-50 and CA 19-9 assays showed significant correlation between the two parameters for colorectal, pancreatic and liver cancer. The CA-50 assay was more sensitive and specific thaxl C& 19-9 and A~s

*3. GRENIER, F. GU1LLEUX : l~aboratoire de Radioanalyse C.R.L.C. - Rue de la Croix Verte - P a r c Eurom~decine 3409# Montpellier C~dex 2 (France) * ' 3 . FAUQUE : Cis Bio Industrie, BP 17i, 30205 Bagnols/C~ze (France) ***P. CHAMBON : LGME du CNRS, [nstitut de Chimie Bio,logique - Facult~ de M~decine, 67085 S t r a s b o u r g ( F r a n c e )

Based on a co:nbination of the assays for CA50,CAI9-9,CEA, their positive rates were raised to 91.3 ,76 ,84 in colorectal,pancreatic,liver cancer respectively.

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BIODISTRIBUTION OF AN ANTI-CEA MONOCLONAL ANTIBODY LABELED WITH Gd TO HIGH SPECIFIC ACTIVITY WITH POLYLYSINE AS A MULTIFUNCTIONAL LIGAND. G. Westera,, R. Schwendener, G.K. von Schulthess, Department of Radiology, Clinic for Nuclear Medicine, University Hospital, 8091 Z0rich, Switzerland

TUMOR IMAGING BY P O S I T R O N EMISSION TOMOGRAPHY USING A 1-124-LABELED ANTI-CEA MONOCLONAL ANTIBODY.

The usual way to increase the amount of labeling metal in a monoclonal antibody (MAb) is by increasing the number of bifunctional ligands. This hampers the immunological activity at the specific activities required, because too many loci in the antibody are occupied. Therefore we have prepared a multifunctional ligand by substituting polylysine with DTPA which is coupled to one site in the MAb using N-succinimidyI-S-acetyl thioacetate (SATA) to give PolyMAb. This product was saturated with Gd, labeled with Gd-153, resulting in the introduction of 30 40 Gd per MAb. An anti-CEA antibody (IgG) and its F(ab')2 fragment were lhus gadoliniated, injected into nude mice, bearing a CEA [~roducing tumor and their biodistribution measured after 3-4 resp. 1 d. The relative uptake was very low in the tumor : 0.1 0.3 %id/g, although the in vitro binding activity remained high at 70-80%. High uptake was found in the liver (especially for total IgG: 45 %id/g (F(ab')2:4 %id/g)), in the spleen (IgG: 37%id/g, F(ab)2:3.5 % id/g) and in the lungs (F(ab')2:15 %id/g, IgG: 2.5 %id/g). No contrast enhancement was observed in a magnetic resonance imaging study, with 1 mg of the Gd-PolyMAb. More carefully controlled site specific high specific activity labeling will have to be developed to be useful in vivo.

S u n d a y , A u g u s t 26, 1990

G.Westera, H.W. Reist*, F. Buchegger**, A. Pfeiffer, G.K. von Schulthess, J.P. Mach***. Department of Medical Radiology, Clinic for Nuclear Medicine , University Hospital, Z0rich, * Paul Scherrer Institut, Villigen, ** Ludwig Institute for Cancer Research and *** Institute for Biochemistry, University of Lausanne, Switzerland PET may improve localization and quantification in radioimmuno diagnosis with monoclonal antibodies (MAb). 1-124, because of its 4.15 d halflife presents a convenient radiolabel to test the feasibility of this concept. We have labeled the human-mouse chimaeric MAb CE 4-8-13 (provided by Ciba-Geigy), using the chloramineT method, with 1-124 (produced at the University of Manchester (Dr. H. Sharma)) and injected 100 uCi (100ug) into nude mice, xenografted with the CEA - producing colon ca T-380-54 (tumorsize 0.2 - 0.5 g). After 4 days PET imaging was performed with a CTIECAT scanner,collecting 2.25 mio events. The images showed, in the appropriate transversal planes, excellent tumor localization .Two tumors, which were implanted on the back of the same mouse about 2 cm apart, were clearly seen separately, indicating very good spatial resolution. Further experiments are needed to determine if radio immuno PET with labeled chimaeric anti-CEA MAb will be useful in clinical conditions for quantification of tumor dosimetry.

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The Clinical Application of Tc-99m Labelled Monoclonal A n t i b o d i e s , I-NiFG1 and SM3 in O v a r i a n

DETECTION OF COLON CARCINOMAWITH I N - I l l ANTICARCINOEMBRIONIC ANTIGEN (CEA) MONOCLONALANTIBODY (MoAb). I. Zanzi, S. Lichtman, V. Vinciguerra, M. Yoshida, S. Kroop, W. Robeson, N. Kamdar, B. Babchyck, D. Margouleff. North Shore University Hospital-Cornell University Medical College, Manhasset, New York, U.S.A.

Cancer Granowska M, Jobling T, Britton K E, Mather S Naeem M, Shepherd J H St Bartholomew's Hospital, London ECIA 7BE, 13]<

J,

The difficulties in ovarian cancer management after initial surgery are related to the determination of the effectiveness of chemotherapy and the demonstration of recurrence or metastases, for

u l t r a s o u n d and x - r a y CT a r e not s p e c i f i c . The u s e f u l n e s s of m o n o e l o n a I a n t i b o d i e s a g a i n s t the human m i l k f a t g l o b u l e HVIFG g l y c o p r o t e i n a n t i g e n in t h i s c o n t e x t was in c o n t r a s t to i t s low s p e c i f i c i t y for ovarian cancer at primary presentation. SM3, s t r i p p e d mucin a n t i b o d y 3, was d e v e l o p e d to overcome this. The p r o g r e s s i o n of r a d i o l a b e l from 1-131 t h r o u g h 1-123 and I n - i l l l e a d to the a d o p t i o n of Tc-99m. Using a m o d i f i e d Schwarz t e c h n i q u e , Tc-99m l a b e l l i n g of b o t h tlVfFG1 and SM3 h a v e been a c h i e v e d and r e m a i n s t a b l e in v i v o w i t h no Tc-99m u p t a k e in the u n b l o c k e d t h y r o i d o v e r 24 h. S t u d i e s in 7 p a t i e n t s w i t h 600 ~ q (15 mCi] Tc-99m BMFGI and 9 with Tc-99m SM3 with imaging at 5 min, 3, 6 and 24 h and SPET at 5 h show high quality images with tumour definition at 6h and often earlier, with confirmation at 22h. 12 true positive ovarian and endometrial cancers were found and 4 true negative images in non malignant conditions were shown. There were no f a l s e p o s i t i v e or f a l s e n e g a t i v e r e s u l t s in this small series. The a d v a n t a g e s of Tc-99m RIS a r e low c o s t , low r a d i a t i o n and r e a d y a v a i l a b i l i t y . A result within 24 h of request makes radioirrmunoscintigraphy a routine test.

The role of the I n - l l l - l a b e l e d Anti-CEA MoAb ZCE025, an intact murine Ab, in detecting metastatic or tumor recurrences was evaluated in 18 patients (ptsl with known adenocarcinoma (colon 12, rectum 4, and unknown o r i g i n 2), increased CEA and either normal or equivocal CT/MRI. Planar and SPECT images of chest and abdomen were obtained at 3 and 6-7 days following an average I.V. dose of 5.8 mCi of the radiolabeled MoAb and 40 mg of unlabeled Ab. Radiolabeling e f f i c i e n c y was g3%. Results were confirmed by surgery (5 pts), CT, and/or extended follow-up (113 pts). Administration of MoAb was safe. The MoAb detected 29 abnormal lesions and 7 questionably abnormal f o c i . S e n s i t i v i t y was 0.88 and s p e c i f i c i t y 0.67. MoAb scan was more conclusive than CT in I0 lesions. In 2 false (-) MoAb studies, Ct pulmonary nodules measured 7mm and hepatic foci ~ I cm. SPECT did not detect a substantial number of additional lesions as compared to planar scans. I t improved the accuracy of l o c a l i z a t i o n and the degree of cert a i n t y in evaluating the lesions. For hepatic lesions, subtraction technique with Tc-99m M i c r o l i t e improved d e t e c t a b i l i t y of lesions. Overall, MoAb scan improved the detection of tumor recurrence in the patients studied.

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CLINICAL ASSESSMENT OF IMMUNOSCINTIGRAPHY USING 1-131ANTI-CEA AND AZTI-CAI9-9 MONOCLONAL ANTIBODY COCKTAIL D. Tsujino, T.Takahashi, S.Someya and Y.Sasaki ~ St.Marianna University and Gunma University ~ Kawasaki and Maebashi ~ Japan

IMMUNOSCINTIGRAPHY WITH IN-Ill LABELED ZCE-025 MONOCLONAL ANTIBODY RECOGNIZING CARCINOEMBRYONIC ANTIGEN IN PATIENTS WITH COLORECTAL CANCER K.Endo, Y.Watanabe, T.Nishikawa, T.Saga, H.Sakahara, M.Koizumi, T.Nakai, M.Hosono, Z.S.Yao, S.Maetani, T.Tobe and J.Konishi. Nuclear Medicine and Surgery, Kyoto University Hospital, Kyoto, Japan

Clinical usefullness of 1-131-antiCEA and anti-CAlg9 monoclonal antibody Fab' 2 cocktail (IMACIS i provided by International CIS, France) was assessed in 45 patients with various cancers. Three mCi of IMACIS i was administered i.v. by drip infusion taking 30 min.. Scintigraphies were taken by a scintigllation camera starting from the 3rd day post injection and continued, if necessary, till the lOth day. Thirty four out of 45 cases(75.6%) revieled increased accumulation of radioactivity at least in one of proven cancer sites. Positive immunoseintigraphy of primary cancer sites was obtained in 20 cases of 40 patients(50%). Metastatic lesions were detected in 20 cases among 28 patients(71.4%). Positive cases in 31 patients with cancers originated from digestive organs 25 cases, that is 80.7% positive ratio. Nine cases of 14 patients with cancers of non-digestive organs showed positive immunoscintigraphies(6h.3%). There were 12 cases in which hypervascularity was observed by angiography and necrosis in tumors was detected by CT. All 12 cases revieled positive immunoscitnigraphy. Our results indicate IMACIS i shoule be usefull to be used for the detection of cancers, especially metastasis of cancers originated in digestive organs.

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In-lll labeled ZCE-025 MoAb reactive with carcinoembryonic antigen(CEA)clearly visualized human colorectal cancers xenografted in nude mice. Dose escalation studies showed that i0 ~g Ab (equivalent to 30 mg Ab in humans) is superior to 0.7 ~g or 100~g Ab per mouse. This Ab-dose effect on the biodistribution of In-lll ZCE-025 was specific to ZCE-025 and there was no effect by adding control MoAb. Three mCi (Iii MBq) of In-lll ZCE-025 at doses of 42 mg were intravenously administered in 5 colorectal cancer patients without any adverse reactions. Immunoscintigraphy obtained 3 days after infusion demonstrated tumor in all patients including 3 patients with normal serum CEA concentrations, and detected 6 out of 7 tumor sites. Lymphnode metastasis missed by CT scan was demonstrated by Ab scanning. Cancer-to-normal colon tissue ratios, obtained during surgery at 7 to 9 days after Ab administration, ranged from 3.1 to 10.4, but small tumor of 0.5 cm was not detectable. Immunohistochemical analysis demonstrated that all eolorectal cancer tissues were reactive with ZCE-025, in spite of normal serum CEA levels. All patients developed human anti-murine Ab(HAMA) in their serum 3 weeks after infusion. These results suggest that immunoscintigraphy using In-lll ZCE-025 of 42 mg dose is useful and promising for detecting colorectal cancer even in normal serum CEA levels, but HAMA is detectable at 3 weeks after infusion.

Sunday, August26,1990

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RADIOIMMUNOSCINTIGRAPHY OF COLON CANCER ~IETASTASES WITH 1-131 B72.3 MONOCL,ONAL ANTIBODY. ,.RR.Reilly, +M. Papa, +J. Kirsh, +H. Stern, S. Houle. Toronto General Hospital and +Mount Sinai Hospital, Toronto, Ontario, Canada.

IMAGING OF COLORECTAL CANCER IN TAMARINS USING 1-123-LABELED NONOCLONAL ANTIBODY WGHS 22-2. Y-C.C. Le___~e, J.E. Crook, L.C. Washburn, E.C. Holloway, T.T.H. Sun, M. Henke, N. Clapp, and Z. Steplewski*. Oak Ridge Associated Universities, Oak Ridge, TN, and *The Wistar Institute, Philadelphia, PA.

Monoclonal antibody (mAb) B72.3 is specific for several adenocarcinomas including colon, breast, ovary and lung. The objective of this study was to determine the optimum time p.i. for imaging metastases in patients with colon carcinoma following i.v. injection of 1-131 B72.3. Three patients with hepatic metastases and one with intraabdominal metastasis were first skin-tested for hypersensitivity with B72.3. No reactions were noted. The mAb was labelled with 1-131 to a specific activity of 2.5 mCi/mg using the Iodogen technique. After purification, the radiochemical purity was 96-98%. The mAb was tested and found to be sterile and pyrogen-free. Each patient was injected i.v. with 2 mCi (0.8 mg) of 1-131 B72.3. Anterior and posterior images of the skull, chest, abdomen and pelvic areas were obtained at 3, 24, 48, 72 and 168 hrs p.i. using a large field of view gamma camera fitted with a medium energy collimator. Initial images revealed "cold" defects in the liver in the 3 patients with hepatic metastases. Later images at 168 hrs demonstrated uptake of radioactivity in these areas which correlated with known tumour sites as determined by CT and clinical findings. Tumour site uptake was also observed in the patient with intraabdominal metastasis. Tumour/normal liver ratios were 1.2-1.4 at 168 hrs. Despite pre-treatment with Lugol's iodine, there was some uptake by thyroid and stomach indicating in-vivo deiodination. No adverse effects due to mAb administration were observed. We conclude that 168 hrs p.i. is the optimum time for imaging colon cancer metastases with 1-131 B72.3. Further studies are planned to evaluate the pharmacokinetics of this mAb.

Diagnosing colorectal cancer in its early stages would lower the mortality rate. The cotton-top tamarin, Saguinus oedipus, serves as a useful animal model for studies of human colorectal cancer because this New World monkey is the only known nonhuman species which has a high incidence of spontaneous colorectal cancer. The mouse anti-human monoclonal antibody WGHS 22-2, with specificity for human colon adenocarcinoma, was used for the study. Radioimmunoassay showed the cross-reactivity of WGHS 22-2 to the TAC-I antigen on tamarin colorectal cancer cells. The antibody WGHS 22-2 was radiolabeled with 1-123 by the chloramine-T method to a specific activity of 3.5 mCi/mg protein. Unreacted radioiodide was separated from antibody-bound 1-123 by HPLC. Seven animals were studied (three with confirmed colon cancer, two with suspected rectal or colon cancer, and two controls). The thyroid was blocked by oral administration of potassium iodide (1.3 mg in 0.5 ml) one day prior to and immediately before IV injection of the radioantibody. Serial images were obtained up to 72 hrs postinjection using a Searle Pho/Gamma V gamma camera. Excellent images of colon and rectal tumors in tamarins were obtained. This suggested that 1-123-1abeled monoclonal antibody WGHS 22-2 can be used for early detection of coloreetal cancer in tamarins, thus increasing the value of this animal model. (This work was supported by DOE Contract No. DE-AC05-760R00033 and by USPHS Grant No. CA 39706.)

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1MMUNO-SPECT USING in-lll ANTI-CEA MONOCLONAL ANTIBODY FOR THE PROSPECTIVE EVALUATION OF BLADDER CARCINOMA AND ITS METASTASES.

IMMUNOSCINTIGRAPHY OF COLORECTAI, CARCINOMA WITH BW a31/26 MONOCLONAL ANTIBODYf CLINICAL RESULTS A. Muxi, M. Moragas, P.Bassa, R.Fern~ndez, M. Minoves, F. Pons, A.Garcia, F. l,ome~a, R. Herranz, J. Setoain Serv. Medieina Nuclear. Hospital Clinic. Barcelona. Spain.

R.P. Banm, W. Boeckmann, H. Schaldes, G. Herrmann, W. Kramcr, A. Hertel, T. Baew-Christow, D. Jonas, G. H6r. J.W. Goethe University Medica] Center, Frankfurt/Main, FRG. Localized invasive bladder carcinoma (BC) can benefit from radical cysteetomy whereas patients (pts) with lymph node involvement are treated by inductive chemotherapy first. Conventional imaging procedures, e.g. CT scan, are unreliable in the staging of BC. The purpose of this prospective study was to assess the diagnostic efficacy of immuaoscintigraphyin the pre- and postoperative evaluation of BC. Methods. 2 mg of the intact cDTPA coupled MAb BW 431/26 (Behriagwerke, F R G ] directed against a protein epitope on the CEA molecule (affinity 101D l/M) were labeled with 150-185 MBq h - l l l El3 at >90 % efficiency as controlled by HPLC and slowly injected i.v.3 anterior and 3 posterior planar images (1000 K/view) were obtained 2448 h and again 48-72 h p.i. using a digital LFOV Sophy gamma camera (173/247 keV peak) fitted with a HR parallel hole collimator (290 keV). SPECT of the abdomen and pelvis was performed 24-48 li p.i. (360 o >5000 k, Wiener filtering). 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 chemotherapyfrUR. The diagnostic aceurae] of Immtmo-SPECT was 89 % for primary untouched BC; 87 % for loc~l 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 immanohistochemicaUy whereas only 20 % showed elevated CEA serum levels (low secretors). Candusions. This prospective study demonstrates for the first time that SPECT using In-111 labelled anti-CEA MAb has a much higher sensitivity (> 80 %) for the detection of lymph node metastases compared to CT scan (<20 %) and is therefore useful for the preoperative staging and postoperative care of invasive bladder carcinoma.

Sunday, A u g u s t 26, 1990

We have performed immunoseintigraphy in 28 patients (68+/-9 years) with colorectal carcinoma 48 hours before surgery with a total of 51 lesion sites. In 22 patients the primary lesion was studied, in 5 the recurrences and in 24 we looked for the posibility of metastasis (MI) in liver. The antibody used was the BW 431/26 (Behring) labelled with 99mTc (85] MBq), which was proved to be the most selective antibody for CEA out of three different antibodies studied by immunohistochemistry. The scans were performed at 4 and 24 hours after the injection. After the surgery and histological study we found: n TP TN FP FN Primary lesion 22 13 0 1 8 Recurrences 5 4 0 0 i M1 Total

24 51

6 21

16 ]6

1 2

1 10

The BW 431/26 seems to be useful in the localization and extension of colorecta! carcinoma. The global sensibility ( S ) was 69.7% with an accuracy (A) of 76.6%. We obtained the best results in recurrences. The S was lower in primary lesions (S=61.9% A:59.1%), due to 4 FN in rectum, 2 FN by peritona! eareinomatosis and 1 FN by necrosis. The metastasis in liver (S.85.7% A=91.6%) showed like hot or cold lesions. We recommend to be careful with cold lesions, as they could represent also non neoplastic lesions.

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PET MEASUREMENTS OF F-18-DEOXYGLUCOSE (FDG) UPTAKE IN LIVER METASTASES.

EVALUATION OF REGIONAL CHEMOTHERAPY IN PATIENTS WITH LIVER METASTASES USING PET.

L.G. Strauss. A. Dimitrakopoulou, U. Haberkorn, M. Knopp, E Oberdorfer, W.J. Lorenz. German Cancer Research Center. Heidelberg, Germany.

A. DimitrakoDoulou. L.G. Strauss, U. Haberkorn, M. Knopp, R Schlag, E Helus, G. van Kaick. German Cancer Research Center, Heidelberg, Germany.

Morphologic information about metastases can be obtained by different imaging methods, while functional data are provided by PET. We used PET in patients with liver metastases (n=25) in order to determine the metabolic activity of the lesions prior and after chemotherapy. While eight patients received chemotherapy with fluorouracil due to colorectal cancer, three patients were treated with TNE Sequential images were acquired for one hour following intravenous injection of 370-444 MBq FDG. All images were iteratively reconstructed and a ROI-technique was used to obtain standardized uptake values (SUV) for the liver parenchyma and the metastases. We observed an increased FDG uptake in 80 % of the lesions, while in 19 % the FDG accumulation was within the normal range (,1.0 SUV). In 2 metastases hypometabolic areas were noted in PET. Multiple lesions in the same patient may have different FDG uptake values, indicating a different tumor metabolism. Follow-up studies demonstrated hypometabolic areas in lesions responding to chemotherapy. The results obtained from the Patlak evaluation correlated with the standardized uptake values one hour after FDG application. Therefore, endpoint measurements of FDG uptake 60 min p.i. are adequate for the routine evaluation of the metabolism in metastases. Our results show, that PET can be used to quantify the metabolic activity in liver metastases. FDG is a promising tool for the early detection of tumor response to chemotherapy.

Fluorouracil (FU) has found use for both intravenous and intraarterial chemotherapy in patients with liver metastases from colorectal tumors. We used PET and F-18-uracil to compare the uptake of the FU in malignant lesions and normal liver parenchyma after i.v. and regional tracer application. 0-15 labeled water was administered to evaluate the perfusion of the lesions. The evaluation comprises 30 examinations (intravenous and intraartedal studies) in 15 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 10 of 20 metastases using the i.a. approach, while in 3 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 noted a higher systemic toxicity in 22 % of the patients. The accumulation of the perfusion tracer 0-15 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 cannot be used to estimate the FU accumulation in metastases. The results of the ongoing study show, that PET with F-18-uracil should find preferential use to optimize the regional chemotherapy.

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P O S I T R O N E M I S S I O N T O M O G R A P H Y (PET) W I T H F-18D E O X Y G L U C O S E IN T H E I M A G I N G A N D S T A G I N G O F BRONCHOGENIC CARCINOMA

USE OF POSITRON EMISSION TOMOGRAPHY FOR OPTIMIZED THERAPY MANAGEMENT OF PATIENTS WITH LUNG TUMORS

M.V.Knopp, LG.Strauss, U. Haberkorn,A Dimitrakopoulou,H. Bischoff, D. Branscheid,F. Oberdorfer,H. Ostertag,G. van Kaick German Cancer ResearchCenter, Heidelberg,West-Germany The staging of bronchogenic carcinoma with conventional techniques remains limited compared to surgical staging with an overall sensitivity reported in the range of 50-80%. The aim of our study is to use PET with a metabolically active compound, F-18-1abeled deoxyglucose (FDG), to detect increased uptake in neoplastic tissue and to delineate active tumor from surrounding tissue end to compare with the conventional T-staging. 20 patients which had completed clinical staging for bronchogenic carcinoma were studied prior to surgery. Histologic evaluations of 16 patients are currently available comprising 12 malignant tumors and 3 benign lesions. The 12 malignant end 3 benign tumors were correctly identified due to their different FDG-upteke values. In 5 out of the 12 malignant tumors, PET correctly changed the T-classification (3 smaller, 2 larger) compared to the previous staging whereas 7 agreed. We conclude that FDG-PET imaging of bronchogenic carcinoma can be used to improve the preoperative staging end shows great potential for improving the sensitvity.

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M.V.KnODD. L.G.Strauss, U. Haberkorn,A. Dimitrakopouiou,H. Bischoff, H. Manke,F. Helus,W. Maier-Borst,W.J. Lorenz German Cancer ResearchCenter, Heidelberg,West-Germany Positron emission tomography (PET) with F-18-deoxyglucose (FDG) allows quantification of the metabolic activity of tumors prior and during chemo- or radiation therapy. The goal of our study is to use PET for early evaluation of the changes in tumor FDG-uptake as response to the given therapeutic treatment protocol and compare those changes in uptake to the change of tumor volume as determined by plain film or CT. Each patient is studied prior to therapy with subsequent follow up starting after the second chemotherapeutic cycle or 1/3 of the radiation dose. FDG uptake was quantified by the standardized uptake value (SUV) as determined by ROI measurements and adjusted for injected dose and body volume. We studied 25 patients prior to therapy. 17 patients finished the follow up period, 14 receiving chemotherapy, 1 radiotherapy and 2 a combined protocol. We found a direct correlation (r= 1.0) between decreased uptake and clinical response (12/12) and unchanged or increased uptake with no response to therapy (5/5). In those 5 patients the tumor volume decreased in 4 and remained unchanged in 1. The tumor volume remained unchanged in 4 end decreased in 8 of the 12 patients showing response and decreased FDG-uptaks after therapy. Our results indicate that the change of FDG uptake to therapy is more reliable and sooner available than the evaluation by change of tumor volume. PET enables a selection of patients not benefiting from the given therapy (5/12) at an early time during therapy end thus facilitates optimized therapy management.

Sunday, August26,1990

242

243

I M A G I N G O F N A L I G N A N T T U M O U R S IrITH I N D I I ~ - l l t - L A B E L E D L I P O S O M E S - FIRST C L I N I C A L RESULTS.

II@ILrNOSCINTIGRAPHY N I T H 1 3 1 - I - L A B ~ L ~ f J ANTI-SHCG-ANTIB O D I E S IN THE F O L L O W - U P OF T E S T I C U L A R T UI~OURS.

B. Briele, A. Hotze, A. Bockisch, M. Graefen, J.P. Hartlapp, W. Roedel, and H.J. Biersack; Dpts. Nucl. Med., Oncology and ENT, Univ. of Bonn, W. Germany

B. Briele, A. Bockisch, A. Hotze, P. Oehr, N. Jaeger, H.J.Biersack; Dpts. Nucl. Med. and Urol., Univ. of Bonn, W. Germany

This prospective study has been performed to evaluate the clinioal usefulness of In-111-labeled liposomes as a tumour imaging agent. Twelve patients (11 males, I female; mean age: 59 yrs.) with proven malignant tumours (pharyngeal carcinoma:6 ; malignant melanoma:3 ; bronchial carcinoma:2;Non-Hodgkin-Lymphoma:1 ) were investigated with labeled liposomes. Results of liposome scanning were compared with X-ray, CT, MR, US and Surgery. Liposomes (VS 102 (100rag) ; Vestar Inc.,USA)were labeled with 18.5-37 MBq In-11 l-chloride. Labeling efficiency was calculated by paper chromatography (75% - 92%). Scintigraphic images were obtained 30min., 6h, 24h and 48h after i.v. injection (and 72h in I pat.). 15 different tumour localizations were found in 10 patients. 10 localizations were identified by liposome scanning (true pos.: 10). 7 of these lesions were found to be positive only on the late scans (24h, 48h and 72h p.i.). 5 tumour localizations were not visualized by. liposome scintigraphy (false neg.: n=5 ; Non-Hodgkin-Lymphoma: I, pharyngeal-ca.: 3, bronchialc a . : I ). Further evaluation of the clinical value of this new method is necessary. Late images (24h, 48h and 72h p.i.) seem to be of the highest diagnostic value.

This prospective study was performed to evaluate the usefulness of the RID by comparison of RZD-results with CT, MRI, ultrasound and surgery. Twelve patients (mean age: 28.4 yrs.) with proven HCG-positive, malignant testicular tumours were investigated following surgical treatment and chemotherapy in order to detect suspected tumour recurrence. HCGlevels were elevated in all patients excepted one case (questionable CT-finding without HCG-elevation). Complete anti-~HCG-antibodies (Zymed, San Francisco, USA) were labeled with 74 MBq 131-I and administered as an i.v. infusion. Scintigrams were obtained 4, 5 and 6 days p.i.. Blood pool images were performed on the 5th day including subtraction images to provide correct anatomic localization and to exclude false positive results due to increased blood pool activity. There were 14 different sites of proven tumour recurrences in 10 patients. 9 tumor localizations were confirmed by RID (true positive:9; paraaort.:5, retroperit.:2, lung:l, brain:l). 4 localizations were not detected by RID (false negative:4; liver:2, lung:l, paraaort.:1). In 3 cases, RID results were true negative: no accumulation of labeled antibody in ~HCGnegative teratoma tissue (I case) and normal findings on the RID scan in agreement with other imaging modalities (2 cases). Although RID with anti-~HCG-Ab does not seem to detect tumour recurrence very reliably, it might provide additional information. More experience with this method is required.

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245

EFFECTS OF STREPTAVIDIN PREADMINISTRATION ON BIODISTRIBUTION OF BIOTINYLATED CEA ANTIBODY M A B 35 I N T U M O R - B E A R I N G N U D E M I C E I. N o v a k - H o f e r , R. H e y e r , P. Bl~iuenstein and P.A. Schubiger Paul Scherrer Institute, C H - 5 2 3 2 Villigen-PSI, Switzerland

INTRAOPERATIVEDETECTIONOF MONOCLONALANTIBODIES IN COLORECI'ALCARCINOMA P. LECOUFFE,B. CARNAILLE,L ROUSSEAU,J-p. TRIBOULET, Ch. PROYE, X. MARCHANDISE' ServiceAssociddeMddr162 Nucldai~,SerAcede ChirurgicGdndralrctEndocrinologiqur CHU de Lille- 59037LILLE-FRANCE

Biodistributions o f biotinylated anti C E A antibody M a b 35 ( M a b 3 5 - B H Z ) and 125I-labelled streptavidin (SV) were investigated in nude m i c e bearing tumors o f L o V o hu colon adenoc a r c i n o m a ceUs. M a b 35 was derivatized at carbohydrate sites with biotin h y d r a z i d e yielding fully i m m u n o r e a c t i v e and stable conjugates. Streptavidin was iodinated with the iodogen m e t h o d to a specific activity of 5 m C i lz~I-SV/mg. M i c e (2-3 animals p e r e x p e r i m e n t ) bearing L o V o tumors were injected i.v. with either 50 g C i 12sI-SV alone or after p r e t r e a t m e n t s for v a r i o u s times with 100 g g M a b 3 5 - B H Z . 125I-SV alone s h o w e d rapid ( m a x i m a l after 6 h), strong (14.7 + 2.2 % i.D./g) and p r o l o n g e d (up to 7 days) kidney retention. P r e t r e a t m e n t for 24 h with 2 m g o f unlabelled S V did not affect the m a s s i v e kidney accumulation, w h e r e a s i.v. injection o f unlabelled SV together with z2sI-SV r e d u c e d kidney uptake to 2.03 • 0 . 2 1 % i.D./g. Simultaneous injections o f 0.5 nag or 0.1 m g S V r e d u c e d kidney uptake to 6.54 + 0.42 % and 13.53 _+ 0 . 4 1 % i.D./g respectively. T h e s e results s h o w that SV uptake into kidneys can be blocked by unlabelled SV but SV binding to sites in the kidneys cannot be displaced. 12SI-Mab 35 biodistributions s h o w e d best t u m o r / o r g a n ratios after 3 - 5 days (5 - 6 % i.D./g in tumors). W h e n m i c e w e r e pretreated for 3 days with M a b 3 5 - B H Z , followed by 48 h o f ~zsISV, 1.4 +0.07 % i.D./g w a s found in tumors and the localization index ( M a b 3 5 - B H Z + IzsI-SV/nSI-SV) w a s 3.5. C o m p a r e d with u n m o d i f i e d M a b 35 the tumor/liver ratios w e r e l o w e r (1.6 v s 10.5) and the tumor/blood ratios w e r e similar (2.6 v s 2.5). Simultaneous injection o f 0.1 to 2.0 m g unlabelled SV with 125I-SV for 48 h resulted in loss o f specific t u m o r uptake. T h e results show that the strong kidney uptake o f S V cannot be blocked by administration o f unlabelled SV without c o m p r i s i n g t u m o r uptake.

Sunday, August26,1990

Evaluation of clinical interest of radioimmunoguided~..~ection,mainlypromoted by HAWXINSand coll. (Arch.Surg.1986,121: 1391)needs further dam. We describeclinicalresults obtained in 30 patients with colorectalcarcinomathat were to benefit from a curativ~or a palliativetreatment ; we used a hand-held Cadmium te]luride probe ; surgery was undergone 5 day~ after 125 iodine labelled moncclonal anfi-CEAF(ab')2i~jection(50r mieroCi). Ten men and 20 women,age 39 - 74, have been studied since April 1987. There was no second-look.Stagingof 20 colon cancers (right side : 6, left : 14) and 10 rectal cancers was as following: DukesA : 2, B : 7, C : 17, D : 3 and villouspolyadenomatouslesion : 1. CirculatingCEA determinationwas high in 7 casesonly(whileCA 19-9was raised in 3 other cases).

Over 38 tumoral locations, 32 were correctly identified by hitraoparativr radioirnmunodetection,lesion/healthytissue ratio being largerthan 1.5.These locationswere detected in the primitivetumor in 25 cases, in the liverin 2 cases (over 3 hepatic lesions), in gangliain 3 eases(over 3 locations),in peritoneumand in gallbladderin 2 cases.The 6 false negativeresults in 5 patientswer~attributed to some tr difficultiesin approachingthe probe close to the lesion (prostate : 1 case, posterior liver : 1, lower ~cturn : I) ; other advocatedreasonsof failurewere a secondinjectionof monoclonalmurinrantibodiesin I case, a low Dc=kesstaging in another, a high thyroidal activityin spite of thyroid Lugs] blockade in 1 case. Over 11 non tumoral lesions, there was 1 false positiveresult rcgistrcd with ovarian/healthytissue ratio being I5 ; ten other lesionshad a ratio lowerthan 1-~. In the conditions of our study, sensitivitywas 84 % and specificitywas 91%. There was no correlation betweenantibodies anti-CEAuptake and circulating serum CEA activity; there was no quantitative relation between uptake and tumoral staging. In clinical practice,

there was vcty little gain in pdma~/ sargcz7, Interest of recurrence managementis currentlyunder evaluation.

the intraopcrativ= detection in

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246

247

Tc-99m Radioirnnunoscintigraphy, RIS, in Colorectal Cancer Oranowska M, Mather S J, B r i t t o n K E, Northover J M A

RAOiOINHUNODETECTION IN THE FOLLOW-UP OF BREAST CA,~CER. A PROSPECTIVE STUDY USING ANTI-CEA ANTIBODIES. L. Campos, H. Pajares, T. Cambil, J. F r e i r e , I. Vale ~ . Security Social Hospital, C~diz, Spain,

ICRF Unit, St Mark's Hospital, London ECi, UK The

introduction of RIS

into routine use requires a

completed report within 24 hours of the r e q u e s t . The ready a v a i l a b i l i t y , low cost of Tc-99m and simple Sohwarz procedure for Tc-99m l a b e l l i n g now achieve this for c o l o r e c t a l cancer. PR~A3, a rnonoclonal antibody against a columnar c e l l surface e p i t h e l i a l antigen which is not shed, has been used p r e v i o u s l y s u c c e s s f u l l y with I n - l l l as radiolabel with uptake three times that of anti CEA. 2mercaptoethanol antibody molar r a t i o of 1000:1 is used to open the S-S bonds and the product is stored frozen. A methylene diphosphate bone kit and Tc-99m is used to radiolabeI PRIA3. 15 mCi (600 ~ q ] is given iv with imaBing at 5J, 3, 6 and 22 h with SPET at 6 h, High q u a l i t y images of tumour uptake are seen at 6 h confirmed at 22 h. No unblocked thyroid uptake is seen over 24 h confirming in vivo s t a b i l i t y . 35 p a t i e n t s were studied. 19/19 primary colorectal cancer, 8/8 local recurrences, 3 with liver metastases, were p o s i t i v e . 5/6 without recurrence were negative with one equivocal r e s u l t . 2 villous adenoma were p o s i t i v e . 4 local recurrences were found by imaging Dukes' C p a t i e n t s at 1 year follow up when p a t i e n t s were CEA or symptom negative and 4 when p a t i e n t s were CEA or symptom p o s i t i v e . Tc-99m PR1A3 is taking i t s place in the r o u t i n e management of coloreetal cancer a f t e r primary surgery.

248 IMMUNOSCINTIGRAPHY WITH Tc-99m LABELED MONOCLONAL ANTI-CEA-ANTIBODIES, CEA TISSUE EXPRESSION AND SERUM CEA LEVELS IN PATIENTS WITH SUSPECTED BREAST CANCER Lind P, Smola MG, Ratschek M, Hoff M, Langsteger W, K61tringer P, Steindorfer P, Eber O. Internal Department, Barmherzige Briider Graz, Austria The discrepancy between serum CEA levels and CEA tissue expression in patients with breast cancer is a well known phenomenon. Wheras immunohistochemistry shows positive CEA expression in 70-90%, the serum CEA levels are often in the normal range. In 33 women with suspected breast cancer or recurrence we performed immunoscintigraphy and SPECT with a Tc-99m labeled monoclonal anti CEA antibody (MAb BW 431/26). After injection of 1100 MBq Tc-99m MAb BW 431/26 planar and SPECT images 6 and 24 h p.i. were done. The results of anti CEA immunoscintigraphy, mammography, serum CEA levels and immunohistochemistry were evaluated according to the histology of the tumor. In 17 out of 33 patients histology verified breast cancer (pT1 In--4], pT2 [n=ll], pT4 In=2]), in 16 patients lipoid necrosis or cystic mastopathia were responsible for the suspicous mammographic findings. Immuno-SPECT showed 14 right positive, 3 false positive, 11 right negative and 5 false positive findings (sensitivity 82%, specificity 69%). In contrast serum CEA levels were slightly elevated in only 3 out of 17 patients with histologically verified carcinoma (sensitivity 15%). Suprising were the results of immuno-histochemistry; only in 2 patients with breast cancer tissue CEA expression could be demonstrated. Maybe the occupation of the CEA epitope by the in vivo injected antibody was responsible for the negative immunohistochemical results. According to our experiences with this Tc-99m labeled monoclonal anti CEA antibody, immunoscintigraphy is well suited as an additional method in the diagnosis of breast cancer and recurrence. Preoperative serum CEA levels give no support for the differentiation between benign and malign tumors.

S62

22 patients with surgical treatment because of breast cancer, has been studied with monoclonal antibodies anti-CEA l a b e l l e d with 131-! in i n t r a venous i n j e c t i o n . All patients have a serum tumor markers control CEA and CEA 15,3. We obtained some plane images 4, 7, lO days p o s t - i n f u s i o n . A d i u r e t i c agent is administered in the course of patient evaluat i o n . Ant er i or and p o s t e r i o r thoracic and hepatic views are employed. We found a good c o r r e l a t i o n between the r a t i o of the serum tumor markers and the inmunoscintigraphy. We have not employed substractioning d i g i t a l techniques. The analysis ef method inmunoscintigraphy i s : The s e n s i t i v i t y is 0.80, the s p e c i f i c i t y is 1.00, the positive p r e d i c t i v e value is 1.00, the negative p r e d i c t i v e value i s 0.70 and the exactitude is 0.86.

249 HUMAN BREAST CANCER IMAGING WITH 16 =~ (123)-IOD0 II ~ M E T H O X Y - 1 7 ~ F. THERAIN,

J.

GROS, D.DEBRUN, CH

Orl6ans,

M.T.

ESTRADIOL GUILHEM,

France.

16 ~ Iodo II ~ M e t h o x y 17 ~ E s t r a d i o l p r e s e n t s good characteristics as a p o t e n t i a l i m a g i n g a g e n t of b r e a s t c a n c e r . Its b i n d i n g a f f i n i t y r e l a t i v e to t h a t of e s t r a d i o l m e a s u r e d at 4 ~ C on e s t r o g e n r e c e p t o r s and at 37 ~ C on M C F 7 c e l l s was r e s p e c t i v e l y 50 % and i00 %. Its t i s s u e d i s t r i b u t i o n in i m m a t u r e f e m a l e r a t s s h o w e d u t e r u s to b l o o d and u t e r u s to non t a r g e t t i s s u e s r a t i o s of r e s p e c t i v e l y 87 • 12 (n = 5) and 94 ! 22 (n = 5). T h e s e r a t i o s r e d u c e d to 2,2 and 6,0 w h e n the a n i m a l s were treated simultaneously with excess unlabeled estradiol, demonstrating a high specialty. Tile I derivative can be p r e p a r e d w i t h i n a few h o u r s w i t h an o v e r a l l r e c o v e r y of up to 70 % ( b a s e d on i o d i d e ion) and a s p e c i f i c a c t i v i t y of m o r e t h a n 500 C i / m m o l e . The f i r s t c l i n i c a l s t u d i o s in p a t i e n t s w i t h b r e a s t c a r c i n o m a i n d i c a t e t h a t t h i s non invasive technique would provide useful information about the r e c e p t o r s t a t u s of the t u m o u r s in vivo.

Sunday, August 26, 1990

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251

CLINICAL VALUE OF CA15-3 AND CEA IN BREAST CANCER ~,M.Rodrigues, J.B.Weinholtz,F.Fernandes,G.Ramc M.Rosario Vieira.Nuclear Medicine and Surgery Departme Instituto Portugu~s Oncologia,Lishon,Portugal

BREAST CANCER AND DIFFUSE SKULL ACTIVITY IN BONE SCINTI-

The AA. conducted a prospective clinical trial to a sess the value of the tumor markers CA15-3 and CEA(IRM in 71 breast cancer patients(pts).Three pts died and 2 were lost for follow-up.A total of 128 CA15-3 and 118 CEA determinations,with an average of 3 determinations per patient,was performed in 43 pts classified in stag~ 5 pts;stageII 23 pts;stageIII i0 pts and stageIV 3 pts. During follow-up (2 years) 5 pts developed regional recurrence and 5 pts,sistemic disease.As control groups,w used 90 normal individuals and 13 individuals with henig pathology of the breast. RESULTS 1 2 3 4 5 6 10.3 16.1 18.9 20.8 363.9 CA15-3 13.4 +4.5 +4.9 +12.7 +6,8 +760 ~Ulml) +5.2 CEA 0.8 0.9 0.6 1.2 3.6 3.6 +I.I +0.4 +1.6 +7.4 +4.3 (nglml) +0.7 l-Normal;2-Benign pathology of the breast;3-Stage I; 4-Stage II;5-Stage III;6-Stage IV In stage I,II,III,all together,median values of CA153 were statistically different(p 0.001) from those in stage IV.In stageIII only 9% of CA15-3 values were above normal vs 50%,in stageIV;for CEA,we found 15% abnormal values in stageIII vs 30%,in stageIV.CA15-3 was high in I/9 determinations and CEA in 3/7,in 5 pts with local recurrence;in 5 pts with sistemic disease CA15-3 was high in 8/17(47%) determinations and CEA in 5/13(30%). The measurements of CA15-3 and CEA were within normal values in pts with regional disease.A raise in tumor markers should be considered as sign of sistemic disease modifying the prognosis and therapeutic strategy.

GRAPHY:A PROSPECTIVE STUDY. M.Rodrigues,L.Salgado,M.Rosario Vieira,J.Bivar Weinholtz F.Fernandes. Inst PormguSs Oncologia, Lisbon, Portugal. 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 findingwithradiological patterns and biochemical parameters of bone metabolism(measurements of serum ealcium,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,lO had osteolytic lesions,lO 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
252A

252B

REEVAJJUATION OF BONE SCANNING IN BREAST CANCER. A.H. Elgazzar, A. Omar, E. Higazi, H.M. Abdel-Dayem, Y.T. Omar. Dept. of Nuclear Medicine, Kuwait University, Kuwait Cancer Control, Kuwait.

DETECTION AND TREATMENT OF BONE METASTASES IN DIFFERENTIATED THYROID CARCINOMA.

Routine use of bone scintigraphy in early clinical stages of breast cancer is still a subject of much controversy as the yield of positive scans varied widely in the literature. We have undergone a retrospective study on 255 patients with breast cancer attending the same oncology clinic between 1986 and 1989 who had pretreatment bone scan. All bone scans were done by whole body spot views using extra large field of view gamma camera 3-4 hours after i.v. injection of 20-25 mCi of Tc-99m MDP. Results of bone scans were as follows : Clinical # of stage pts. I IIA IIB

26 69 73

# of positive scans i0 27 29

# & % with benign dis. 8 (30.7%) 19(27.5%) 18(24.6%)

# & % of metastat. disease. 2 (7.6%) 8 (ii.6%) 11(15.1%)

The yield in stages I and II were higher than majority of the reported values and is in agreement with several reports with relatively higher values. To conclude bone scan should be done routinely pretreatment for all clinical stages of breast cancer.

Su n d a y , A u g u s t 26, 1990

Herry JY, Dufeu E, Lescouarc'h J, Siemen C, Bernard AM, Ben Hassel M, Kerbrat P, Langlais F, Allannic H. Pontchaillou, Rennes, FRANCE. Bone metastases were demonstrated by I 131 total body scintigraphy in 12 patients with differentiated cancer of the thyroid. Lung metastases were also seen in four cases and skin metastasis in one. Following thyroid hormone withdrawal, scans were performed with 3 to 5 mCi of iodine and after Iodine treatment (100 mCi). All secondary Iocalizations were detected. All the patients received one or more courses of I 131 therapy (100 to 1100 mCi) combined with surgical resection in 3 patients who each had only one metastasis, chemotherapy (one case) and radiation therapy (5 cases). Long-term remission has been obtained for one patient who underwent resection of a metastasis of the ribs. In the other two cases of surgery (costal metastasis and a tumour of the pelvis treated by extended resection, bone allograft and total hip replacement) a recurrence occurred less than 2 years after surgery (bone metastasis in one case, bone and lung in the second). One patient with bone, lung and skin metastases failed to respond to a cycle a Mifoxanthrone. Seven of the patients in our series are dead (6 died within 5 years) ; four are under I 131 treatment and only one is in complete rem}ssion (12 years after surgical removal of a costal metastasis). Our results confirm the bad prognosis of thyroid cancer when bone metastases are present. I 131 treatment has little effect on bone secondaries. Whether used alone or combined with radiotherapy Iodine 131 did not sterilize any of the bone metastases in our series. I 131 does, however, slow disease progression. Resection is justified if there are only one or two operable metastases : the evaluation of disease spread must be thorough and includes, in particular, scintigraphic exploration following administration of 100 mCi of I 131.

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253

254

LA SCINTIQ~APH2~ 0SSEUSE DANg LE TRAITEMEYf DE L'0ST~O-SARCOME

BONE SCINTIGRAPHY AND SERUM TISSUE POLYPEPTIDE ANTIGEN (TPA) LEVELS IN EVALUATION OF BONE METASTASES FROM NASOPHARYNGEAL CANCER (NPC). FX Sundram, Dept of Nuclear Medicine, Singapore General Hospital, Singapore.

G.C. Mussa, A. BraehDel Preyer, C. De Filippi, IstiiTdto di Puericultura - Universit~ di Torino

L. gilvestro

Avec la scintigrsphie osseuse au 9gm-Tc FDP pendant le traitement chimioth~rapentique preoperatoire il est possible de r~aliser t~ne tr6s bonne valut~tion de l'activit~ m~tabolique-fonctionnel de la n~oformation du ost4o-sarcome de faQon ~ fournir 8u chirurgien un utile information pour tm intervention chirur~icale ad~guat et en m ~ plus conservatif possible.

temps le

Du 19@6 chez le Centre de Medicine Nu-

cleaire Infantile de l'Universit~ de Turin ncus avons 6tudi~ avec la scintigr~0hie 86 enfants avec un diagnostic histologique de ost6o-sar-

Bone is the commonest site of distant metastases in NPC. 233 patients with biopsy proven NPC had bone scintigraphy within two months of the initial diagnosis; they also had blood taken for estimaLion of serum TFA before the bone scan. The aim of the study was to evaluate TPA as a screening test for metastases.

come, qui ont 6t& trait~ avec de Cisplatintm (CDDP) 40 mg/mZ/die tout droit dens l'art~re pour valuter l'efficacit~ du tralte~ent localment

~ C i / ~ de 99m-Tc NDP et viers evalu~e l'arriv6 de l'indicateur radicactif et son premier cercle. S~uceessivment on prendrat des scintipho %ms apr@s 5', apr@s 2 heures c ~ d toujoars 16 membre frappe svec

30/233 (13%) of the newly diagnosed NPC patients had evidence of bone metastases on bone seintigraphy, while 85/233 (36%) had elevated levels of TPA beyond 112 U/I. The mean TPA levels for T1 + T2, T3, NO + NI, N2 + N3 Stages were respectively 119, 179~ 90 and 193 U/I. In patients without metastases, the mean TPA was 112 U/I, and 290 U/I in patients with metastases. However of the 30 patients with known bone metastases only 22 (73%) had elevated TPA levels. Conversely only 30/85 (35%) of patients with elevated TPA levels had evidence of bone metastases. In patients symptomatic of bone metastases however~ 83% had elevated TPA levels.

le controlsteral. En chaque cas exanin6e en n~ne temps ant ~t~ rslis6e la sointi~caphie

Conclusion:

dans le tuneur. Les enfants qui ont effectu~ la chimioterapie (CT) (18 m~les et 18 rifles avec un ~ge entre les 4 et les 17 ans) ont present6 une looslisation initial an niveau du f@nur en 20 cas (17 a niveau dis%ale), de la tibia en ii cas (7 a niveau prossimale), de l'hum@rus en 3 cas et en 2 patients du p~ron~. Les patients viers mis sous le oollimateur de la geTmac~ra positio n6e sur la faGon frapp~e par la tumeur; la dose achninistr4e est 200

osseuse st l'art#riographie du membre frappe. A cette ~tude est evidente que la simuliane execution des investigations scintigraphique et arteriographic~/e Dermis une bortne pr~vision de la reponse au traltement initial, permittand au cnirurgien par con-

TPA is not as useful as bone scans in predicting bone metastases because the serum TPA levels are raised in late tumour and nodal disease, regardless of absence of metastases.

s~quant an approche operatoire le milleur possible.

255

256

CHONDROITIN SULPHURIC ACID (CSA)-~C-99m AS A BONE TUMOUR SEEKING AGENT. O. J. Degros si, T. Watana]3e, P. Oliveri, E. B. Deg ros si, C. Devo to,H.Garcla del Rio and M.O.de Goncalves, Htal Alem~n and Inst. Roffo, Buenos Aires, Argentina.

IMAGING FOR FOLLOW-UP OF HEAD AND NECK CANCER PATIENTS. J Muz, RH Mathog, GA Kling. Departments of Radiology and Otolaryngology, Harper Hospital and Wayne State University School of Medicine. Detroit, MI, USA.

In 68 patients (p) with both primitive or secondary bone diseases and 5 normal volunteers,724-925 MBq of CSA-Tc-99m were administered iv and bone scintigraphy was carried out 2 to5 and 24 hs afterwards;48 hs later, MDP scintigraphy was carrien out. Ten p with chondrosarcoma(CH) and I bone sarcoma of chondral rece showed increased CSA activity in positive MDP areas with similar size and shape;one of these p with a tibial CH presented in CSA study a positive area in femur bone marrow (not seen in MDP study,confirmed at pathological study),and another 3 p with bone and/ or lung metastases of primitve CH,in the follow up show e d positive CSA studies,negative with MDP. Liver and kidney metastases of primitive CH did not concentrate CSA.Two cases of chondroma did not show signfficant CSA increased concentration. Ten bone sarcoma and 25 p with bone metastases of breast and prostate primitive tumours,positive with MDP,were negative with CSA.Two Paget's bone disease did not present significant CSA uptake in positive MDP areas ; 10 p in different evolutive stage of osteoarthritis ,show in the pre-radiological stage a decreased CSA uptake and in the other stages, similar figures than MDP. These results indicate that CSA could be a promising tumour seeking agent for bone tumours of chondral rece as indicative for surgery extension and in the follow up.

The purpose of this presentation is to evaluate the usefulness of scintigraphic imaging for assessment of swallowing function in patients (pts) with head and neck cancer (HNCA). Scintigraphic studies were performed with patient in upright position who swallowed 2.5 mCi (92 MBq) of Tc-99m sulfur colloid diluted in I0 ml of water. During swallowing, data were acquired from regions of the oral cavity and pharynx for assessment of the oral transit time and pharyngeal transit time. In pts who aspirated, the percentage of aspiration was calculated by dividing the number of counts from the region of aspiration by counts of the total dose given to the patient and multiplied by I00. The oral transit time, pharyngeal transit time, and detection and quantification of aspiration were used as criteria for scintigraphic assessment of swallowing function. A total of 118 examinations were performed in 37 pts with HNCA before and during treatment with either surgery, chemotherapy and/or radiotherapy. The scintigraphic results were correlated with clinical findings. Both scintigraphic and clinical studies indicated a worsened swallowing function in 12 pts and improvement in 13 pts. In ii pts, both studies revealed mixed changes. There was disagreement between scintigraphic and clinical findings in only i patient. We conclude that scintigraphy is a useful method for objective assessment of swallowing function in head and neck cancer patients. Results obtained from scintigraphic studies correlate well with the clinical course of patients with head and neck cancer.

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SCINTIGRAPHIC QUANTIFICATION OF TRACHEOPULMONARY ASPIRATION IN PATIENTS WITH HEAD AND NECK CANCER. J Muz, RH Mathog, R Nelson, LA Jones Jr. Departments of Radiology and Otolaryngology, Harper Hospital and Wayne State University School of Medicine, Detroit, MI, USA.

Tc-99m METHOXY ISOBUTYL ISONITRILE (MIBI) HEAD AND NECK SCINTIGRAPHY IN NASOPHARYNGEAL CARCINOMA: DETECTION OF PRIMARY AND CERVICAL METASTASES. R.S. Liu, S.H. Yeh, M.N. Ng, S.H. Yen, C.H. Hsu, K.Y. Chen, and H.D. Chu. Veterans General Hospital and National Yang-Ming Medical College, Taipei, Taiwan.

The purpose of this study was to detect and quantify tracheopulmonary aspiration (TPA) in patients (pts) with head and neck cancer (HNCA). For these examinations, the patient (pt) swallowed 2.5 mCi (92 MBq) of Tc-99m sulfur colloid diluted in i0 ml of water and scintillation camera-computer images were acquired. In pts who aspirated, the percentage of TPA was quantified by dividing the number of counts from the region of aspiration by counts of the total dose given to the pt and then multiplying by i00. Of the 125 pts with HNCA that were examined with scintigraphy, 51 (41%) had TPA. In 63 pts with HNCA but without tracheostomy, 15 pts (23%) showed TPA. In the group of 58 pts with HNCA and tracheostomy, 34 pts (58%) demonstrated TPA. In 4 pts in whom the tracheostomy was surgically closed, TPA was demonstrated in 2 pts (50Z). Among 58 pts with traeheostomy, there were 7 with a removable tracheostomy obturator. These pts were examined with the tracheostomy plugged and re-examined with the tracheostomy unplugged. In the majority of pts examined with the tracheostomy unplugged, the increase in TPA varied up to tenfold, as compared to examinations obtained with the tracheostomy plugged. These findings indicate that pts with a tracheostomy should be watched for TPA. In conclusion, pts with tracheostomy aspirate more often and in larger quantities when the tracheostomy is unplugged. This observation may be applicable when feeding pts with HNCA and tracheostomy. Scintigraphy is a useful modality for detection and quantification of tracheopulmonary aspiration.

Tc-99m MIBI has been shown to accumulate in carcinoma of thyroid and bronchogenic carcinoma. This study assessed the detectability of nasopharyngeal carcinoma by Tc-99m MIBI scintigraphy. Fifteen mCi of MIBI were injected intravenously. Planar and SPECT studies of the head and neck were performed in sequence at 2 hr after injection. The result was positive in case the radioactivity in the lesion was higher than that in the scalp. Twelve normal subjects and 13 proved patients (pts) with nasopharyngeal carcinoma (undifferentiated carcinoma in 4, non-keratinized epidermoid carcinoma in 7, keratinized epidermoid carcinoma in 1 and anaplaetic epidermoid carcinoma in i) were studied. We detected 12/13 tumors by SPECT and 4/13 by planar imaging. No false positive result (0/12) was obtained by either method. The sensitivity and specificity were 92% (12/13) and 100% (12/12), respectively, for SPECT study, and were 31% (4/13) and 100% (12/12), respectively, for planar study, i0 pts had cervical metastases. SPECT detected 4 (40%) and planar scan 2 (20%). No relationship existed between the histological type and radioactive uptake. In summary, Tc-99m MIBI SPECT can reliably detect primary nasopharyngeal carcinomas with a high degree of sensitivity, whereas the sensitivity for tumor detection on planar images is inadequate. Neither SPECT nor planar imaging is sensitive enough to detect cervical metastases.

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259 OUR ]D~I]~CE TIA_q~E) ~

IN T~E FOI/J3W-4/P OF ~}D/I~OID D J ~ ' F ~ (T[]C) ~ ~}]ALILT[A~-201

P. Uriarte, G. Mara6a, C. Sanjuan, M.C. Marin, M.J. Argdeso, J. Ortiz Mouliaa, J. Ortiz Berrocal. Clinica Puerta de Hierro, Madrid, Spain We present our experience in the follow-up of select~d cases of TDC using thallous chloride T1 201. We have studied 23 patients with pathological diagnosis of TDC, surgically treated, administered varying doses of I 131, and subjected to whole-body imaging i0 minutes after iv administration of 3-5 mCi of TIC1 (TI

201). Eleven patients were studied with evidence of local reculq;ence or metastasis of TDC, based on the existence of elevated serum thyroglobulin levels (group I, n=2), palpable cervical tumor (group II, n=4) or focal I 131 uptake (group III, n=5). In six patients, T1 201 scan revealed unknown tumoral localizations (2 in group I, 3 in group II and 1 in group III). Twelve patients in whom presence of tumoral tissue was not suspected were studied. Five presented thyroid remnants which took up 1-131, but did not take up T1 201, and seven presented no evidence of normal or cance~Dus tissue. In no case was there evidence of pathological thallium deposition. We conclude that the T1 201 scan is useful in cases of TDC with elevated thyroglobulin and negative I 131 scan, with or without palpable lesions. It does not appear to be reliable in cases with positive I 131 scan, nor in those in which there is no evidence of the existence of tumoral tissue.

Sunday, August26,1990

DETECTION AND TREATMENT OF LUNG METASTASES IN DIFFERENTIATED THYROID CARCINOMA. Herry JY, Dufeu E, Lescouarc'h J, Siemen C, Bernard AM, Allannic H. Pontchaillou, Rennes, FRANCE. Lung metastases were visualized by 1-131 total body scintigraphy in 20 patients with differentiated cancer of the thyroid. The scans for 15 patients were positive with a dose of between 3 and 5 mCi. In the 5 other cases, an uptake by lung metastases was demonstrated by total body scan obtained after administration of 100 mCi. Plain chest X-ray was normal in 8 cases and showed micronodules or macronodules in 12. All the patients received one or more courses of I 131 therapy (100 to 500 mCi). In 14 cases, no tung uptake was observed after final course of I 131 therapy. At the end of treatment, Tg levels were non detectable. Six patients are under I 131 therapy :lung uptake of iodine has decreased as has the Tg levels. Recurrence occurred in 2 patients (lung was involved in 1 case, liver in the other). Four patients died : tumour-related in 2 cases, from myocardial infarction (1 case), and from a cerebrovascular accident (1 case). Lung function was not modified in any of the patients. Our study gives a survival rate of 95 % at 5 years (19 patients out of 20). It also confirms that lung metastases respond well to iodine therapy but that late recurrence does remain possible even when complete remission has been obtained.

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EFFECTIVE USEFttA~SS OF 99m-Tc-I~A (V) IN DETECTICN OF OCCULT RECURRKZ~ OF ~DULLARY THYROID CARCI~KI~A

IMMUNOSCINTIGRAPHY OF MALIGNANT MELANOMA WITH F(ab')2 FRAGMENTS OF ANTIMELANOMA MONOCLONAL ANTIBODY (MoAb) 225.28S LABELLED WITH Tc-99m A.Nogueira,M.Ros~rio Vieira,R.Santos,J.Bivar Weinholtz, J . A m a r o , N u c l e a r Medicine,Surgery and Dermatology Departments,Instituto PortuguSs Oncologia,Lisbon,Portugal

M.R. Csstsllani*, A. Rodari*, F. C ~ o ~ F. @ippa*, E. Bombar~ieri* - *Nuclear Medicine Div. - ~ Dept., Istitute Nazionale Tu mori , Milan, Italy. The medullary thyroid carcinoma is a rare tumor with relatively slow evolution. A persistent elevation of serun calcitonine levels may appear'e several months before clinical or radiological evidence of recurrence. 99mTc-I~A (V) scintigraphy is a prcmising method to detect a recmmre~ce of disease. Aim of the study is to focalize the value of this examination in the deteotion of occult metastases in selected patients with increasing elevation of serum calcitonine levels without other signs of disease. i0 examinations (J~jected activity: 555-7z~3 MBq) in 8 patients without clinical (or on Rx-chest standard examination) appearance of dis ease ene month -15 years after radical t ~ i d e c t c m y were performed. The serum ealcitcrd/ne levels ranged between 103 to 22218 pg/ml. The scans were positive in 6 studies. These positive finding~ were always localized in tpper mediastinun and were later confirmed by CT or MR imaging. In one case with negative findings the disease has not yet been localized (follc~v-up 6 months), I~ the other three cases the disease became clinically evident 8-12 months later. No false positive results are observed~ In conclusion in our experience DMSA (V) scan is a very suocess-

Twenty patients with malignant melanoma were imaged with F(ab')2 fragments of antimelanoma monoclonal antibody (MoAb)225.28S labelled with Te-99m.Patients were placed in two groupsiThe low suspicion group (8 patients) consisted of patients with no evidence of disease. In 4 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.ln this group a total of 45 sites demonstrated localization of radiolabelled antibody;40(88.8%) corresponded to known sites of the disease;5(ll%) 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.

full ~sging method to detect occult metastases (mostly in mediastint~n) in case of increasing of serum calcitonine levels. In case of a negative flndings, the studies must be repeated every 6 months or if a clinical appeareDce of disease occurred.

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PRELIMINARY CLINICAL EVALUATION OF IODINE123 N-(2-DIETH YL A M I N O ETHYL) 4-1ODOBENZAMIDE IN THE DETECTION OF MALIGNANT MELANOMA (MM) AND METASTASES. J. Michelot,** J. Bonafous , A. Veyre,. M.F. Moreau, G. Desplanches ,. G. Meyniel, R. Plagne . ]NSERM U**71, C l e r m o n t - F d , Centre Jean

I M A G I N G O F T U M O U R S W I T H R A D I O I O D I N A T E D tPA A N D uPA. S.-L. Karonen. H. Aronen, P. Nikkinen, A.-L. Brownell, J. Lindgren, and K. Liewendahl. Division of Nuclear Medicine, University Central Hospital, Helsinki, Finland.

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s t u d y was to e v a l u a t e the usefulness as a n e w imaging agent in M M (Brevet n ~ PV 8901898, 14/02/1989, France). We r e p o r t a preliminary clinical study in 14 p a t i e n t s , Group I : 3 patients with primary melanoma, Group II : 1 p a t i e n t in clinical remission of MM. Group HI : 9 p a t i e n t s with metastases, Group IV : 1 p a t i e n t with oesophagus carcinoma, The patients were imaged at 6 and 24 hr after i.v. injection of 10 mg of iodobenzamide labeled with 5 mCi (187 MBq) of 123-iodine. Anterior and posterior whole body images (Statport, O.E.), static images and tomoscintigraphy were obtained. While many lesions ....

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were compared evaluation and by group I, s c a n s w e r e positive i n 2 out of ] c a s e s , in g r o u p I] w e d i d n o t d e t e c t any lesion. In g r o u p Ill we visualized one known brain metastasis ; an unknown area of metastasis was identified i n the liver of o n e p a t i e n t a n d in t h e l u n g o f a n o t h e r one ; an unknown iliac node was visualized ; on the same patient a known left axi]]ary n o d e w a s seen but a right one, unsuspected, was identified ~ multiple unsuspected nodules were discovered in t h e last patient of group ill. S c a n w a s n e g a t i v e in the patient of group IV. In t h i s study of 14 p a t i e n t s 10 s c i n t i g r a p h i e s were positive. The primary melanoma not visuaIized had a Bresiow Indiee = 0.1 mm. In four cases we detected unsuspected l e s i o n s . to the results obtained other imaging methods.

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Recently tissue plasminogen activator (tPA) and urokinaselike plasminogen activator (uPA) have been shown to be associated with neoplastic growth. To study the accumulation of radioiodinated plasminogen activators in experimental tumours we injected intravenously 131-I-tPA or 131-I-uPA into nude mice bearing colorectal carcinoma (SWl 116) or malignant melanoma (WM9). The control mice received an equal amount of nonspecific 131-1-1gG or 111-In-labelled monoclonal antifibrin antibody fragments (59D8). To test the specificity of the accumulation we also injected unlabelled tPA intraperitoneally 30 min before the injection of 131-I-tPA. Imaging with a gamma camera was performed after 1 h, and 1,2, 3 and 5 days. We observed strong accumulation of radioactivity after administration of 131-I-tPA and 131-I-uPA in both types of tumours. The target to non-target ratio increased up to 5 days. No uptake was found in control mice after injection of 131-1-1gG. After injection of 111 -In-antifibrin fragments radioactivity was observed mainly in necrotic tumour areas. Labelled tPA could be displaced by unlabelled substance. The mechanism of the accumulation of PAs in malignant tumours is unknown but our results indicate that binding to fibrin in the stroma of tumours is not the only explanation.

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IS DIGESTIVE CANCER DETECTION BY RADIO-IODINATED TRANSFERRIN POSSIBLE OR NOT ? A.C. Prost, F. M6n6gaux, J.M. Vidal, P. Langlois, J.O Jost, J.J. Duron, J.P. Chigot, G. Chomette, J.C. Legrand, P. Vayre, and A. Aurengo. C.H.U. La Piti~-Salp~tri~re, Paris, France.

TC-99M HM-PAO STUDY IN HELA CELL TUHOR XENOGRAFTS IN NUDE RATS. WJ Shih, H. Meier, Q. Liu, P. Oehr, J. Pollack, B. Briele, A. Hotze, HJ Biersack. VA and Univ. of [
Transferrin (Tf) specifically recognizes transferrin receptors (Tf-R) the density of which is increased in replicating cancer cells. The aim of this study was to quantify the Tf-R number in digestive cancers. Crude membranes prepm'ed from surgical pieces were incubated with 1-125 Tf in presence of native Tf. Scatchard analysis evidenced a larger Tf maximal binding (Bmax, nmol Tf/g proteins) to 23 colorectal (C) and 2 gastric (G) adenocarcinoma, 1 oesophagal epidermoid cancer (O), 1 breast carcinoma liver metastasis (L) and 1 pancreatic sarcoma (P) than to paireC normal tissues (p<0.01) having similar dissociation constant values. 15

Tc-99m HM-PAO, a cerebral blood flow imaging agent, has been localized in primary and metastatic brain tumor, melanoma, bronchogenic carcinoma, and laetastatic bone tumor, and has been proposed to be a tumor imaging agent. To evaluate Tc-99m HM-PAO to be localized in a tumor, four nude rats with Hela cell tumor xenograft (3 X 4.5 cm in size) in the right thigh (4 weeks after innoculation in the tumor) underwent the study. One hour after IV injection of 300 uCi Tc-99m HM-PAO, a total body image with 150,000 counts was obtained for each rat. The information was also stored in a computer. The planar images of the rats showed very high activity in the internal organs of the chest and abdomen, prominent activity in the tumor-bearing thigh and less activity in the contralateral thigh. Semiquantitatlve data calculated tumor-bearing thigh to contralateral thigh, liver, and chest were 1.81, 0.27 and 0.34, respectively. Counts/min/gm of the tumor, liver, kidney, spleen, lung, heart, and blood of one sacrificed rat were obtained; individual organ-to-blood ratio were as follows: tumor 0.15, liver 1.43, kidney 2.90, spleen 0.21, lung 2.63, and heart 1.07. The tumor uptake was apparently less than that of internal organs but greater than that of the contralateral thigh. Greater uptake in the tumor bearing thigh than in the contralateral thigh is explained by that the larger volume of the tumor had the greater perfusion. These results indicate that Tc-99m HM-PAO is not suffioiently localized in tumor to be used as a tumor imaging agent for Hela cell tumors.

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IN V I V O B I N D I N G OF 1 - 1 2 5 - G A S T R I N TO S P E C I F I C RECEPTORS ON HUMAN GASTRIC AND COLON CARCINOMA XENOGRAFTS. R . S e n e k o w i t s c h , K . - W P a s c h e r t z , G . R e i d l , H.W. Pabst. N u k l e a r m e d i z i n i s c h e K l i n i k , T e c h n i s c h e Universit~t M~nchen, FRG

APPLICATION OF ISOTOPE LABELLED ANTI-MBP MONOCLONAL ANTIBODY FOR IN VIVO DIAGNOSIS OF CANCER

T h e g a s t r o i n t e s t i n a l h o r m o n e , g a s t r i n , is s u p p o s e d to s t i m u l a t e t u m o r c e l l p r o l i f e r a t i o n in v i t r o a n d in vivo. T h e a i m of the p r e s e n t study was to assess the gastrin-receptor status i n h u m a n g a s t r i c a n d c o l o n i c c a r c i n o m a x e n 0 g r a f t s i n v i t r o a n d to c o r r e l a t e t h e rec e p t o r d e n s i t y w i t h t h e in v i v o t u m o r b i n d i n g of 1 - 1 2 5 - g a s t r i n i n j e c t e d i n t o n u d e m i c e bearing human tumors. Using a seven point S c a t c h a r d a n a l y s i s a s p e c i f i c b i n d i n g of gastrin (binding capacity 14-88 fmol/mg prot e i n , K d = 8 n m o l / l ) w a s o b t a i n d for g a s t r i c s p e c i m e n s a n d a l s o f o r s o m e o f t h e t u m o r s investigated. The biokinetic data after injecti o n of 2,5 ~ C i of 1 - 1 2 5 - g a s t r i n s h o w e d a r a p i d e x c r e t i o n of t h e h o r m o n e l e a d i n g to a w h o l e b o d y h a l f - l i f e of o n l y 2h. The m a x i m u m u p t a k e in t u m o r s t h a t h a d s h o w n an e l e v a t e d r e c e p t o r d e n s i t y in in v i t r o s t u d i e s w a s o b t a i n e d at lh p.i. r e s u l t i n g in 3.1% i n j . d o s e / g of t u m o r t i s s u e . B e c a u s e of t h e f a s t b l o o d c l e a r a n c e t u m o r - t o - b l o o d r a t i o s of 2.3 w e r e a l r e a d y obta i n e d w i t h i n 6h p . i . . T h e r a p i d in v i v o b i n d i n g of r a d i o l a b e l e d g a s t r i n to t u m o r s of t h e gastrointestinal tract demonstrates a chance to visualize the receptor status in vivo also w i t h s h o r t l i f e d r a d i o n u c l i d e s , as p o s i t r o n e m i t t e r s . T h e b i n d i n g of r e c e p t o r b l o c k e r s t h a t m a y i n h i b i t t h e s t i m u l a t i n g e f f e c t of g a s t r i n c a n p o s s i b l y a l s o b e e v a l u a t e d b y PET.

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i 2 5 4 ~<. Mohari~ sO. K6vesi, B.Fekete, I. Szilv~sl, IL. Kocs~r, ~G. Tigyi 9Natl. Res. Ins + ,Radiobiol. Radiohyg., Budapest. ~Semmelwelo Univ.Med.Sch.Oept~Max.Fac.Surg.Budapest. "Central State Hosp.Bud~pest.~III.Phys.Clin.Postgrad. Educ.Med. Budapest.'Biol. Res. Ctr. Hung. Acad,Sci. Szeged.Hungary. According to our previous work the myelin basic protein /MBP/ used in our experiments seems to be a common carcinoma antigen reacting with all epithelial malignancies. MBP antigen has been used in humoral leukocyte adherence inhibition assay/H-LAI/. 93,4% of the cases gave positive reactions, while there were no falsepositivity among the controls. In the in vitro immunohistochemical study the antiMBP monoclonal antibody bound only to the cancerous tissue, but not to the controls except of the brain. After this in vitro study the menoclonal antibody was iodinated with 151 isotope, with chloramine T method. Lewis-tung cancer mice and Walker mamma cancer rats were treated intravenously with the labelled monoclonal antibody. Repeated gamma camera radioimmunoimaging and scintigraphic studies were done for five days. lhe results showed that the isotope labelled menoclonal antibody had bound specifically to the tumorous tissue and furthermore had net transfered through, the blood - brain barrier.

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IMMUNOSCINTIGRAPHY OF HUMAN TIrMORS TRANSPLANTED NUDE MICE WITH RADIOLABELED ANTI ras p21 MONOCLONAL ANTIBODY. Y. Katoh, N. Ishii, M. Shima, K. Nakata, Y. Kusumoto, T. I
SPECT IMAGING OF Tc-99m 170H.82 MONOCLONAL ANTIBODY IN PATIENTS WITH PRIMARY AND METASTATIC ADENOCARCINOMA. L. Golberg, A.J. McEwan, A.A. Noujalm, B.M. Longenecker, T. Sykes, G.D. MacLean. Cross Cancer Institute, Edmonton, Alberta, Canada.

Anti ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. 1-125-1abeled RASK-3 was injected into nude mice with either human colon cancers (FCC-I or BM-314) or lung cancer (KNS-62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 1-125-1abeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity ard % injected dose per gram in the tumor were significantly higher than other organs by day 8. The specific localization index expressed as 1-131-RASK-~ / 1-125-eontrol monoclonal antibody Jn tissue divided by 1-131-RASK-3 / 1-125-control monoclonal antibody in blood, was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine -paraformaldehyde which confirmed the intracel]u!ar localization of ras p21. The mechanism by which anti ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non necrotic cells. Tbese results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of variety of human cancers.

170H.82 is a novel IgG1 monoclonal antibody derived against synthetic TF (Thomsen-Friedenreich) antigen. It has been shown to bind to the majority of adenocarcinomas in-vitro and appears to be a clinically useful agent for imaging metastatic disease. Eighteen patients were imaged with this compound after administration of 2-16 mg. MAb labelled with up to 1500 MBq Tc99m. Whole body planar images at times 0, 3-6 h, and 24 h post injection were obtained. SPECT imaging was optimal at 24 h. Of patients imaged; 8 had primary adenocarcinoma of unknown origin, 5 ovarian, 4 colorcctal, and 1 bladder adenocarcinoma. Images were correlated with clinical, surgical (where applicable), and radiological findings. The superior resolution of SPECT imaging over planar imaging enabled detection of smaller lesions and/or added information about tumor extension and size of lesions in 12 of 18 patients. It has proven essential in detection of a significant number of lesions where overlying organs such as the liver, spleen, kidneys, bladder and colon, with high concentrations of the radiolabelled MAb, obscure visualization of possible tumor uptake. SPECT imaging showed para-aortic lymph disease in 9 of 18 patients imaged which could not have been appreciated by conventional planar imaging alone. From this investigation, Tc-99m labelled 170H.82 appears to be a promising agent for radioimmunoscintigraphy of metastatic adenocarcinoma. SPECT imaging greatly enhanced diagnostic sensitivity, particularly in the para-aortic region.

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TUMOR PHARMACOKINETICS OF 5-FLUOROURACIL (5FU) IN WALKER 256 ADENOCARCINOMA IN RATS USING NONINVASIVE 19F NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY (NMRS). A. Ei-Tahtawy and W. Wolf, Radiopharmacy Program, University Southern California, Los Angeles, CA, USA

PET USING F-18 FDG AS A PREDICTOR OF PROGNOSIS IN MALIGNANT LYMPHOMA.

In order to gain a better understanding of the trapping of 5FU in responsive tumors, we have estimated the pharmacokinetio parameters of various subsystem models of 5FU in the Walker 256 tumors in rats using the noninvasive data obtained with in vivo 19F NMRS. Rats, anesthetized with Ketamine and Rompun, were placed in a 4.7T magnet (CSI, Huntington Research Institute), a 1.5 cm surface coil tuned to 19F was positioned over the rat's tumor implanted in the forearm, and a bolus of 150 mg/Kg 5FU was administered. 1200 FID's were collected at 20 KHz spectral width with a pulse [15 usec] optimized for maximum signal, at 188.360061 MHz. The external reference standard was 1,2-difluorobenzene. Both 5FU and the anabolites nucleosides + nucleotides (FNUC) were observed, as well as some catabolites at later times. Excission of such tumors, 1 hour after a bolus of 5FU, extraction of the acid-soluble fraction and of the RNA, yielded 63% of 5FU, 9% of nucleosides and 26% nucleotides, and 1.8% of 5FU following hydrolysis of the RNA fraction. This compares very closely to the values obtained from the radiopharmacokinetic estimation of 52% free 5FU and 43% PNUC, and 3.7% 5FU in the high molecular weight (HMWA) anabolite fraction. These data document that noninvasive pharmacokinetics is possible at tissue and organ sites, and should be used for drug monitoring studies, either alone or in conjunction with 18F-PET.

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J. Okada, K. Y0shikawa, K. Imazeki, g. Un0, J. Itami, S. Min0shima, Y. S. Uematu, and N. Arimizu.

Chiba University Hospital, Chiba, Japan. Positron emission tomography (PET) using F-I8 fluorodeoxyglucose (FDG) was studied in eighteen p a t i e n t s with p r e t r e a t e d malignant ]ymphoma in head and neck region to evaluate the c l i n i c a l u s e f u l n e s s as an imaging procedure for p r e d i c t i n g the prognosis. Tumor to normal s o f t t i s s u e c o n t r a s t r a t i o s (TCRs) were obtained on the reconstructed PET image a f t e r 60min following i n j e c t i o n of FDG (148MBq) in f a s t i n g s t a t e , and glucose u t i l i z a t i o n r a t e s (GURs) were calculated by graphic method using multiple-time uptake data (Patlak, 1983). These data were compared with pathological diagnosis which graded into three groups of malignancy, prognosis and Ga-67 s c i n t i g r a p h y . TCRs were higher than 2.6, and all malignant lymphomas were c l e a r l y visualized on PET. Increased GURs of tumors were also demonstrated. Difference of TCR and GUR between H0dgkin's disease and nonHodgkin's lymphoma was not s i g n i f i c a n t . Especially

in a high grade case and two intermediate grade cases with poor prognosis, higher TCRs and G~Rs were observed,

whereas

10w TCR and GUR were shown

in a low-grade case. Good correspondence was demonstrated between glucose metabolic s t a t e and prognosis. Comparing with Ga-67 s c i n t i g r a p h y , a tumor with size of 2.hx0.8cm, which was d i f f i c u l t to be pointed out on Ga-67 planer image, was shown evidently in PET. FDG can be expected as a tumord e t e c t o r and a p r e d i c t o r of prognosis in malignant lymphoma.

Sunday, August 26, 1990

273 EVALUATION OF Ca-67 SCINTIGRAPHY OF THE CHEST IN LYMPHOMA PATIENTS. I. Zanzi, L. DeMarco, R. Sollazzo, S. Kroop, V. Vinciguerra, M. Lesser, M. Desai, W. Robeson, D. Sherr, and D. Margouleff. North Shore University HospitalCornell University Medical College, Manhasset, New York, U.S.A. Forty-eight patients (pts) with Hodgkin' s Disease (HD) (25) or non-Hodgkin' s lymphoma (NHL) (23) were prospectively evaluated pre-therapy with Ga-67 (planar and SPECT) scintigraphy and CT scanning (2 HD and i0 NHL pts, > 3 years from initial treatment). Interval between these two modalities was less than 45 days in all p t s . Most of the pts received I0 mCi of Ga-67 citrate I.V. followed by 48 hours and further delayed planar views and by SPECT at 72 hours. Site to site comparisons of Ga-67 and CT chest abnormalities were made using CT as a standard. Planar and SPECT images were compared independently of each other. Differentiation of sites of Ga abnormalities between hila and mediastinum was difficult even using SPECT. Therefore, differentiation between mediastinal and hilar localization was not attempted. In the 25 pts with HD, SPECT revealed a sensitivity of 0.90 and a specificity of 0.50 (corresponding values for planar images were 0.81 and 0.50). In the 23 pts with NHL, the values for SPECT were 0.86/0.63 and for planar, 0.57/1.00, respectively. In 4 pts, Ga-67 views demonstrated diffusely increased tracer activity in both lungs, not detected by CT. We concluded that SPECT complemented and moderately improved the evaluation of pts with lymphoma when compared with planar images.

274A TITLE VALUE OF ROUTINE MULTIORGAN RADIO~dCLIDE S C A N N I N G I N C A S E S OF C A R C I N O ~ OF LUNG A B S T R A C T : - In o r d d r to d e t e r m i n e t ~ utility of r o u t i n e m u l t l o r g a i n s c = n n i n g of brain, l i v e r & b o n e in d e t e c t i n g m e t a s t a s e s in clinically asymptom=tic patients o f carcinom~ of l u n g a r e t r o s p e c t i v e a n a l y s i s of 4 0 patients was performed. AmoMngst asymptom~tic p ~ t i e n t s w e f o u n d no p o s i t i v e s c a n s in 2 4 p a t i e n t s w h o had u n d e r g o n e liver sea ning and no p o s i t i v e s c a n s in 1 4 p ~ t i e n t s w h o h=d u n d e r g o n e b r a i n scantling. H o w e v e r , in 15 a s y m ? t o m ~ t i c p t i e n t s w h o had u n d d r g o n e bone s c i n t i g r = p h y , 7 p a t i e n t s h~d e b n o r m = l scans. R o u t i n e bone s c i n t i g r = p h y is useful adjunctive procedure for deciding further m~nageme nt in c ~ s e s of c a r c i n o m ~ of lung b e c a use of its s e n s i t i v i t y in d e t e c t i n g m e t a s t a s e s in a s y m p t o m a t i c p ~ t i e n t s . , w h e r e as r o u t i n e l i v e r end b r a i n s c a n s are n o t f o u n d to be of value.

Dr. Sanjay Raina, Dr. Narender Nair c/o Radiation Medicine Center BARC, Bombay 400012 India.

274B

274C

USE OF QUANTITATIVE RADIONUCLIDE LUNG IMAGE AND LATERAL POSITION TEST IN PREDICTING INTRATHORACIC METASTASES OF LUNG CANCER. Wang Weinine, et al. Department of Nuclear Medicine, Zhong Shan Hospital, Shanghai Medical University, P.R.China.

LYMPHOSCINTIGRAPHY LESIONS. A.Gar~, R.Inculet, Victoria Hospital,

The lateral position test inaccurately measures differential ventilation of the lungs when the mediastinum and diaphragm are unmohile. The quantitative radionuclide lung image correlates well with differential ventilation but are not dependent on mediastinal and diaphragm movements, then the lateral position test may give discordant values for differential ventilation from that of the quantitative radionuclide lung image. All of the patients with lung cancer had no evidence of metastases by the conventional chest xray. Before thoracotomy 22 cases of lung cancer were prospectively evaluated by comparing the relative ventilation of the involved lungs as determined by quantitative radionuclide lung image and lateral position test. Fifteen patients who had no evidence of intrathoracie metastases had equal ventilation by quantitative ventilation lung image and lateral position test (r=0.66, p<0.01) or quantitative perfusion lung image and lateral position test (r=0.98,p<0.01). Seven patients with intrathoracic metastases had unequal ventilation as determined by quantitative ventilation lung image and lateral position test (r=0.11, p>0.05) or quantitative perfusion lung image and lateral position test (r=0.005, p>0.05). We conclude that the lateral position test used in combination with the quantitative ventilation lung image are both valuable in predicting intrathoracic metastases, but the later combination is superior to the former.

Sunday, August 26, 1990

OF P E R I P H E R A L

LUNG

A. M a t t a r , M. L e f c o e , London, O n t a r i o , C a n a d a .

S t a g i n g of l u n g c a n c e r , p a r t i c u l a r l y in r e l a t i o n t o l y m p h a t i c spread, is of p r i m e i m p o r t a n c e for its t r e a t m e n t a n d l o n g t e r m prognosis. However, intrathoracic lymph n o d e s a r e d i f f i c u l t to assess. R a d i o g r a p h y evaluates size but not drainage patterns or n a t u r e of p a t h o l o g y . M e d i a s t i n o s c o p y a l l o w s a s s e s s m e n t of the m e d i a s t i n a l b u t n o t of t h e l o b a r or h i l a r nodes. In 18 p a t i e n t s (pts) w i t h p e r i p h e r a l l u n g n o d u l e s (PLN) u n d e r g o i n g p e r c u t a n e o u s b i o p s y w e p e r f o r m e d l y m p h o s c i n t i g r a p h y in an attempt to visualize lymphatic drainage. At b i o p s y T c - 9 9 m Sb2S3 c o l l o i d w a s i n j e c t e d in the P L N a n d i m a g i n g s u b s e q u e n t l y p e r f o r m e d a t 0.5-1, 3-4 a n d f r e q u e n t l y a t 24 hours. In 13 (72%) pts n o l y m p h a t i c d r a i n a g e o c c u r r e d . T h i s s t a t i o n a r y p a t t e r n (SP) w a s a s s o c i a t e d w i t h 8 p r i m a r y c a n c e r s (6 > 3cm and 2 < 3cm), 3 m e t a s t a s e s a n d 2 b e n i g n lesions. In 5 (28%) p t s r e g i o n a l l y m p h n o d e s were visualized; the PLN was primary c a r c i n o m a in 3 p t s (i P L N > 3 cm) a n d b e n i g n in 2. O v e r a l l , 77% (14/18) of t h e P L N w e r e m a l i g n a n t , a n d of t h e s e 79% (11/14) w e r e a s s o c i a t e d w i t h t h e SP. In c o n c l u s i o n , t h e S P o r t h e p a t t e r n of nodal flow from PLN appears to be dependent on t h e n a t u r e of t h e lesion. M a l i g n a n t lesions, e s p e c i a l l y l a r g e o r m e t a s t a t i c , a r e likely to be associated with the SP whereas small primary carcinomas or benign lesions m a y be a s s o c i a t e d w i t h e i t h e r p a t t e r n .

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IMMUNOLYMPHOSCINTIGRAPHY AND PEROPERATIVE GAMMA-PROBE DETECTI(IN IN BREAST CANCER USING 1-131 B 72.3 LABELED MONOCLONAL ANTIBODY K.J.A.Kairemo, M.S.Kestila, R. Haapiainen, T . E T . Korppi-Tormnola Helsinki University Central Hospital, Helsinki, Finland

TREATMENT OF THYROID CANCERWITH 131 I IN EUROPE MJ Delis]e, C Gibo]d, IJG Reims, N Schlemberger, V i ] ] e j u i f FRANCE EORTC Thyroid Cancer Study Group

B72.3 monoclmnal antibody which reacts with TAG-72 glyeoprotein recognizes many types of breast cancer We, therefore, examined primary breast cancer patients after injecting subcutaneously into all interdigital spaces of both hands equal doses of 1131 labeled monoclonal IgGl antibody (Sorin Biomedioa, Italy), The total radioactive dose varied from 1.7 to 2,6 mCi (63-96 MBq). All patients were imaged 4-8 times at 0-14 days preoperatively and once postoperatively using a high energy collimmtor (Siemens Rota Ganmm, camera), Oblique projections for axillary areas were studied in every session and the imaging results were compared with surgical and histology findings, The patients were studied pre- and peroperatively using hand-held gannnaprobe. Radioactivity in blood and urine samples was also measured,Preliminary results show that inm~nclymphoscintigraphy could be used to detect axillary lymph node infiltration in prin~ry breast cancer using this antibody. The radioactivity found in lymph node metastases is up to 24 times non-infiltrated lymph nodes. The inrnunolymphoscintigraphic approach provides improved tumor/non-tumor ratios compared with intravenous mnm~noscintigraphy in axillary lymph nodes, Inmuunolymphoscintigraphy is easy to perform and may serve as a complementary tool in staging prinmry breast cancer,

AIM : In 1988-1989 a survey on the treatment of differentiated thyroid cancer with radioiodine was undertaken in Europe. A short questionnaire was sent to Nuclear Medicine Departments with 3 main topics a) the most frequently used therapeutic strategy : systematic total thyroidectomy and radioiodine ablation or treatment modalities based on the knowledge of prognostic factors, b) optimal dose of 1311, c) radioprotection methods. METHODS : Files were distributed through a national representative in Western Europe and d i r e c t l y elsewhere. Questions concerned number of patients treated during I year, number of doses, indications, preparation and dosimetry, practical conditions and radioprotection. RESULTS : 120 responses were collected from 20 countries (Austria, Belgium, Czechoslovakia, Denmark, France, FRG, GDR, Greece, Hungary, Iceland, Israel, I t a l y , the Netherlands, Norway, Portugal, Spain, the Soviet Union, Sweden, Switzerland, Yugoslavia). In 1988, 5500 patients were treated with 6500 high doses of 1311. This represents a cumulative a c t i v i t y of 650 Ci. Indications for 1311 treatment were as follows : Ab]ation doses a) systematic administration following total thyroidectomy, 45 %, b) after incomplete or impossible surgery, 6 %, c) after satsifactory surgery but because of unfavorable prognosti c indicators, 7 %. Treatment doses : d) for a persistent or recurrent tumor, 14 %, e) for distant metastases, 22 %, f ) for increased Tg level without other evidence of disease, 4 %. COMMENTS : Systematic ablation doses are prevalent. Doses are standardized more often than calculated. Physiscians administer 1311 treatment. The number of shielded rooms is 0-I0 per center. Patients are hospitalized for 4-5 days. The exposure dose rate on the patient's skin at the time of discharge ranges from 0.5 to 20 mR/h. PROSPECTS : To underline the importance of prognostic factors and risk group concept. To promote a better evaluation of radiation doses in tumor tissue. To propose a general improvement in radioprotection. This appears necessary in view of the huge cumulative amount of 1311 administered each year.

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MEASUREMENT OF IN-VIVO DOSE-RESPONSE RELATIONSHIPS IN RADIONUCLIDE THERAPY FOR THYROTOXICOSIS USING PET. M.A.Flower, A.Ai-Saadi, V.R.McCready, C.L.Harmer, B.Pratt, B.Cronin, J.Mundy and R.J.Ott. Thyroid unit of the Royal Marsden Hospital, Surrey, UK.

RE-186-V-DMSA: A NEW RADIOPHARMACEUTICAL FOR THERAPY OF MEDULLARY CARCINOMA OF THE THYROID Clarke S E M+, Blower P*, Allen S J+, Blake G M+, McKeeney D B+, Lazarus C R+, Singh J*, Page C++ +Dept. of Nuclear Medicine, Guy's Hospital, London, SEI, ++Dept. of Nuclear Medicine, St Thomas' Hospital, London, *Biological Labaratory, University of Kent, Canterbury

With acknowledged problems in assessing thyroid mass and hence radiation dose, our policy has been to give 75 MBq 1-131 at 6 monthly intervals to patients with Graves' disease until they become euthyroid. Recently 35 patients have had their functioning thyroid mass determined from an 1-124 PET scan, and the radiation dose to the thyroid has been calculated (with an accuracy ~20%). The clinical response of these 35 patients has been assessed at 6 monthly intervals. The results show that patients who receive a low dose (<20Gy) at their first treatment have a high probability (64%) of still being toxic at 18 months, independent of the number of extra treatments. In contrast, patients who receive higher doses (<40Gy) at their first treatment have a high probability of control (50% became euthyroid and 40% became hypothyroid) at 18 months. The probability of becoming euthyroid increases more rapidly with increasing dose than the increasing probability of becoming hypothyroid. A dose >40Gy needs to be delivered to minimise the chances of remaining toxic after radioiodine therapy. A dose of >60Gy involves a 40% probability of becoming hypo thyroid. We now propose to change our strategy. In future, a PET tracer study prior to radioiodine therapy will be performed to enable a prescribed thyroid dose of 50Gy to be delivered to patients with Graves' disease. Further 1-131 therapy will only be considered if patients are still toxic at 12 months.

S70

Re-186 is a beta emitting radionuclide (Emax=l.07 MeV, T i/2 = 3,8 days) with 10% of disintegrations leading to emission of 137 KeV gamma rays. Tc-99m-v-DMSA is known to show high uptake into medullary carcinoma of the thyroid (MCT), suggesting that substitution of Tc-99m by Re-186 might lead to a useful therapeutic agent in patients with MCT. We have performed a tracer study in a 47 year old male patient with nodal and skeletal metastases from MCT to examine the kinetics and dosimetry of Re-186-v-DMSA and to evaluate its therapeutic potential. Following imaging, whole body counting, measurements of urinary excretion and whole blood and plasma concentrations were performed for 7 days. 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 Tc-99m-v-DMSA. Excretion was through the kidneys, with a plasma clearance rate of 20mls/min. Whole body dose was 0.05Gy/GBq, bladder dose IGy/GBq, kidney dose 8Gy/GBq and tumour dose 3Gy/GBq. The results suggest that, with pharmacological modification to eliminate Re-186-IIl DMSA renal uptake, Re-186-v-DMSA may prove a useful therapeutic agent for treating MCT.

Sunday, August26,1990

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APUD TUMORSSTUDY AND TREATMENTWITH 131-I MIBG ,G.Lago,A.Bianco,G.Mart~nez,F.Garc~a,M.Beretta, ,F.Mut,M.Gonz~lez,J.Gaudiano.Centro de Medicina Nuclear,Hospital de Cl~nicas,Montevideo,Uruguay.

TRAPPING OF 5-FLUOROURACIL (5FU ) IN HUMAN TUMORS : 19F NMRS PROVIDES A FIRST ON-LIME AND R E A L - T I M E ASSESSMENT OF CHEMOTHERAPEUTIC RESPONSE. W. Wolf, C.A. Presant, M.J. Albright, K.L. Servis, R. Ring III, C. Wiseman, D. Atkinson, R.L. Ong, Mark King, D. Blayney, A. Ei-Tahtawy, M. Singh and J. Shani Radiopharmacy Program & Dept. of Chemistry, University Southern california, Wilshire Oncology Medical Group, and Siemens Medical Systems, Los Angeles, CA, USA

26 patients(11 males,15 females,19 adults,7 children) with tumors of the APUD series were studied with 131-I MIBG. 5 of them received 11 therapeutic doses(TD). A t o t a l of 47 studies were done.The tracer dose was 1,06 MBq/Kg.Planar images and SPECT were obtained.99mTc studies were performed to locate the hot spot. MIBG uptake was found in 17 patients:3 adrenal pheocromocytomas(ADR-PH),l mediastinal PH,1"in s i t u " recurrence ADR-PH,lophtalmic neuroblastoma(N),l cerebellar N 7 retroperitoneal(RTP)N,2 carcinoid tumors(CT),l chemodecto~a(CH). In 9 patients there was no MIBG uptake:3 were TN(I postsurgical control of capsule invading PH that showed uptake previous to surgery;1 RTP-N recovered;l RTP neuroganglioma in remission)and 6 were FN(1 ADR-PH in a boy that showed no uptake presurgery nor when restudied for an"in situ"recurrence;3 CH;I thyroid medular tumor) The TD were administered to 4 adults and 1 c h i l d with progressive disease:3N,l CT and I CH.One of the N received 2 TD in 5m.Another N 6 TD in 17m.The TD varied between 2,442-7,759 GBq. The results were:1)in a case of multiple metastases predominantly in bone of an extirpated RTP-N there was no response;2)a child with N with bone lesions had a 3m subjective improvement without change in total tumoral mass;3)an adult with a 4y recurrence RTP-N had 31m symptom free survival a f t e r 1st TD and 4m complete response confirmed by CAT a f t e r the 6th TD (total TD 36,504 GBq),but relapsed again and surgical treatment was attempted;4)in the CH there was a partial response; 5)the CT is in follow-up.

An evaluation of the pharmacokinetics of 5FU in the tumors of ll patients with carcinoma of the breast, colon, endometrium, cervix and kidney, using 19F-NMRS (Nuclear Magnetic Resonance Spectroscopy) in a 1.5 Magnetom MRI (Siemens) detected a long-lived tumor pool of 5FU in 7 out of ii patient tumors, including carcinomas in the pelvis, breast, lung and liver. The half-life of this tumor pool of "trapped" 5FU was 0.33-1.3 hours (20-78 min), much longer than the half-life of 5FU in blood (5-15 minutes). Neither the key anabolites of 5FU (fluorinated nucleosides, nucleotides, RNA or thymidilate synthetase), nor its catabolites, were detectable by I9F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the 7 patients receiving 5FU, or 5FU or FUdR plus leucovorin, 4 of 5 patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas 2 patients failing to show tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, enables investigators to study 5FU pharmacokinetics and metabolism in tumor in-vivo, evaluation of 5FU metabolic modulation, and might be able to guide therapeutic decisions.

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MONITORING RESPONSE TO CANCER THERAPY USING F-18 FDG AND PET. K. Yamamoto, S. Kubo*, K.Ono*, Y.Nagata*, Y.Magata*, T.Shibata*, Y. Yonekura*, J.Konishi*, M.Abe* and Y.Terada. Osaka Red Cross Hospital and *Kyoto University School of Medicine, Japan.

STRONTIUM-89 THERAPY IN THE TREATMENT OF DISSEMINATED SKELETAL M~ETASTASES R. Carretta, T. Malekian, P. Matin, Roseville Hospital, Roseville, CA

Five cases with hepatocellular carcinoma (HCC), 6 with metastatic l i v e r tumor, 1 with cholangiocarcinoma and 2 with pancreatic cancer were studied with PET study using F-18 fluoro-2-deoxyglucose (FDG) before and a f t e r cancer treatment. Before therapy, a l l of the cases showed abnormal accumulation at 1 hour a f t e r i n j e c t i o n of F-18 FDG. In 7 cases with l i v e r tumor who had adequate transarterial embolization (TAE) and hyperthermia therapy showed marked decrease of F-18 FDG uptake in the tumors, however 4 cases who were undercarried only the t r a n s a r t e r i a l infusion of chemotherapeutic agents s t i l l depicted abnormal hot lesions. In two cases with unresectable pancreatic cancer, i n t r a - and post-operative radiation therapy were performed. Radioactivity in the tumor regions markedly reduced and abnormal uptake was nearly undetectable in one case, while s i g n i f i c a n t changes were not observed in the other case. In the case with cholangiocarcinoma, the density of the tumor became lower in X-ray CT a f t e r therapy, but uptake of F-18 FDG was unchanged as before therapy. In two cases, F-18 FDG PET study could detect the recurrence of malignant tumors in the l i v e r e a r l i e r than X-ray CT. Since accumulation of F-18 FDG correlates to the regional glucose metabolism, abnormal regional uptake of F-18 FDG may suggest the presence of active malignant tissues. F-18 FDG PET study was considered to be useful for monitoring the response to cancer treatnlent and f o r early detection of recurrence of abdomi nal tumors.

Sunday, August 26, 1990

The use of Phosphorous-32 (P-32) for the treatment of skeletal metastases has been limited due to the severe hematological side effects associated with P-32 therapy. We have evaluated the use of Strontium-89 (Sr-89) for the treatment of painful skeletal metastases. Patients were treated with approximately 1.5 mBq/kg of Sr-89 intravenously after conventional therapies had failed. Patients kept detailed pain and medication diaries and were evaluated at regular intervals for extent of pain, quality of life, and changes in total body bone scans. Of the 60 patients treated with Sr-89, greater than 80% achieved some relief from the pain associated with skeletal metastases. The majority of these patients were able to reduce the frequency of pain m e d i c a t i o n and in a significant number were able to discontinue morphine or morphine derivatives. Additionally, quality of life improved in a large number of patients and resolution of skeletal metastases, particularly those of the ribs, were demonstrable. No significant depression of white blood cell count or platelet count was observed during the course of the study. A "flare phenomena" with increase in bone pain 36-48 hours after treatment was observed in a small percentage of patients. Retreatment at three month intervals was possible in 15 patients with some patients receiving up to four courses of therapy. Although Sr89 is not curative at the dose levels used in this study, significant pain palliation was achieved and a better quality of life attained in a vast majority of patients studied.

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Abstract withdrawn

QUANTITATIVE SUBCELLULAR D I S T R I B U T I O N

OF PLATINUM

IN

RAT TISSUES, FOLLOWING IV BOLUS AND IV INFUSION OF CISPLATIN R. Parti and W. Wolf, Radiopharmacy Program, University Southern California, Los Angeles, CA, USA An analysis of the subcellular localization of Pt (platinum) has been conducted in Sprague-Dawley (SD) rats, following administration of 6 mg/kg IV dose of cisplatin (bolus and infusion), in the liver and kidney of control animals, as well as in these same organs and in the tumor (Walker 256 adenocarcinoma) in SD rats. At 6 hrs after cisplatin administration, 2530% of the Pt in the kidney and the tumor tissue was localized in the nucleus and 70-75% in the cytosol. However, only 10% of the nuclear Pt in this tumor was bound to DNA, while 90% was bound to nuclear proteins, well in excess of any DNA-protein crosslinking. These results illustrate that in addition to the platination of DNA in these tissues, significant amounts of Pt is also incorporated into the nuclear and the chromosomal proteins (CP), as well as into other cytosolic fractions. The localization of Pt in the cytosolic fractions was highest in the kidney, followed by the tumor, and lowest in the liver, on a %ID/gr basis. The significance of such cytosolic, CP and nucleoprotein localization of Pt is not known at this time, but may be involved in the cytotoxic effects of cisplatin, as this drug is cytotoxic to tumors and kidneys, but not to the liver. The localization of cisplatin'in the subcellular fractions of liver, kidney and tumor showed a trend of being higher after IV infusion compared to the IV bolus administration of cisplatin. Studies in progress are directed to document how a radiopharmacokinetic analysis using 195mpt labeled cisplatin, may reveal such information in patients.

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USE OF PLANAR IMAGING FOR THE STUDY OF DRUG DELIVERY: THE BIODISTRIBUTION OF INTRAVENOUSLY INJECTED [C-11]MK-329. NJ Brenner, HI) Burns, HF Solomon, J Links*, W-s Eng, C Fioravanti, JJ Frost*, D Karr, J Walkow, RF Dannals*. Merck Sharp & Dohme Research Laboratories, West Point, PA, USA. *The Johns Hopkins Medical Institutions, Baltimore, MD, USA.

IMPROVEMENT OF THE SYNTHESIS METHOD OF [C-11]PROPYL KETENE BY USING HCL/HE GAS MIXTURE R. Fujii, *Y. Imahori, **T. Ido, T. Yagyu, H. Horii, K. Wakita, *S. Ueda and H. Nakahashi Nishijin Hospital, Kyoto. *Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto. **Cyclotron and Radioisotope Center, Tohoku University, Sendal.

The objective of this study was to use non-invasive imaging to determine the kinetics of clearance of I.V. administered MK-329 from the blood by the liver. MK-329 is a CCK-A antagonist which has been proposed as a potential treatment for a variety of indications, including irritable bowel syndrome, pancreatitis, and gastric motility. A n I.V. injection vehicle is required for some of these indications. Due to the high lipid solubility of these compounds (log P for MK-329 = 2.79), standard I.V. injection vehicles are not suitable. As part of an effort to develop an I.V. injection vehicle suitable for clinical use, we have been investigating the effect of fine emulsion systems on the biodistribution of lipid soluble compounds. [C-11]MK-329 was synthesized and incorporated into a microfine emulsion, and imaging studies were conducted in African green monkeys using a planar camera equipped with a high energy collimator. The results showed that [C-11]MK-329 was not rapidly cleared from the circulation by the liver but remained homogeneously distributed throughout the whole body for at least 1 hour post injection. Liver activity peaked at 16% of the injected dose 5 minutes post injection and remained constant at that level for at least 1 hour. These results suggest that this microfine emulsion can be a suitable I.V. injection vehicle for lipid soluble drugs, and that planar imaging can be used to study drug delivery using C-li labeled drugs.

We have been reported a new type of [C-II] labeled propyl ketene. We newly found out and report in this report [C-ll]propyl ketene synthesis technique using gas mixture of 0.1% HCI/He. We synthesized [C-ll]propyl ketene by using the method of Y. Imahori et al.(J. Lab. Comp. Radiopharm., 9, 1025-1034 (1989)) with some modifications. We used glass beads (imm in diameter) as a medium of the pylorytic decomposition, and used gas mixture of 0.1% HCI/He and He for dilution instead of the phosphoric acid. The reaction vessel was connected to the quartz glass column after produced lithium salt of [C-ll]butyric acid, and the gas mixture were swept into the reaction vessel. The vapor of [C-ll]butyric acid were extructed by ECI, and were carried into the quartz glass column(530~ The [C-ll]butyric acid was decomposed by pyrolytic decomposition, and the [C-ll] propyl ketene was synthesized. The total flow rate of the gas mixture was 70ml/min. (flow rate of 0.1% HCI/He was 5ml/min., and He for dilution was 65ml/min.). The esterfication of [C-ll]propyl ketene was analyzed by using PMTE(Phorbol 20-Methoxytrityl ether) as a standard. The total yield was about 22%, and synthesis time was about 25min. The concentration of HCI was important to vaporize [C-ll]butyric acid. The best concentration of HCI of this system was 0.007% as a mixture of 0.1% HCI (Sml/min.) and He for dilution(65ml/min.). We got stability and improvement of the yield, and synthesis steps were abridged. We synthesized [C-ll]phorbol esters and [C-ll]diacyl glycerol for the second messenger imaging by using this labeling technique.

$72

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AUTOMATED QUALITY TEST OF POSITRON EMITTING RADIOPHARMACEUTICALS IN A CLINICAL PET CENTER. M.Senda, M. Suehiro, T. Sasaki, H.Toyama, K.Kitani, K.Miki*, T.Hiroishi*, H.Snzuki*, T.Hiasa* and Y.Miyake~. Tokyo Metropolitan Institute of Gerontology and *Sumitomo Heavy Industry, Tokyo, Japan.

ENZYMATIC SYNTHESIS AND BIODISTRIBUTIONOF RADIOLABELEDINOSITOL, A POTENTIAL SECONDMESSENGER IMAGING AGENTFOR BRAINPET STUDIES. T. Sasaki, M. ~enda, K. K i t a n i , I. O. Umeda* ~d-H~-NTs-higori ; Tok~co Metropolitan I n s t i t u t e of Gerontology, Tokyo and -Teikyo University, Kanagawa, Japan.

In the hot laboratory of a PET center, positron emitting radiopharmaceuticals that have been synthesized should be checked for quality before being sent to the PET clinic. To facilitate routine supply of those short-lived agents, a computer-controled automated quality checkout system has been developed. The detecting part of the system consists of a dose calibrator, balance, liquid chromatograph (HPLC) with a radioanalyser, and test papers for pH and metal ions which are inspected by a small camera. Those devices are driven by two robot arms, which move along the tracks to carry the vials and suck and inject samples. The entire system is contained in a chamber and controled with a computer at a console in the next room either in full-automatic or manual mode. The action of the robot is observed at the console through two monitor cameras. This system can measure the weight (volume), radioactivity and radiochemical purity, and check pH and metal ions. Given the requested Dose, volume and scheduled injection time, the appropriate amount is diluted and separated into a vial for clinical use. This system can be applied to any in-house labeled agent, provides automated remote-controled quality inspection in conformity to the standards established by the Japan Radioisotope Association, and helps decrease the radiation exposure during the procedure.

289

Recently, p h o s p h a t i d y l i n o s i t o l ( P I ) has been considered one of the second messengers in the neurotransmission. To explore the p o s s i b i l i t y of imaging the PI metabolism using positron emission tomography(PET) in vivo, i n o s i t o l ( I n s ) , endogenous precurcer of PI, was labeled w i t h C-14, and biodistribution was studied in ddY mice, The [C-14]Ins was obtained from [C-14]glucose by three successive enzyme reactions: hexokinase(EC 2.7.1.I), i n o s i t o l phosphate synthase(EC 5.5.1.4) and alkaline phosphatase(EC 3.1.3.1). Each enzyme reaction reached almost I00 % y i e l d in 5 min. Uptake of C-14 radioactivities in the cerebrum, cerebellum and blood after IV injection of [C-14]Ins was shown as follows: lO min

60 min

(% dose/g) (% dose/g) Cerebrum 2.00+0.35 I . 66_+0.44 Cerebellum 2.20+0.36 1.82_+0.50 B1ood 4.32_+I. 30 O. 59_+0.28 The r a d i o a c t i v i t i e s in t h e ce re b ru m and t h e cerebellum was about 2.8 and 3.1 t im e s h ig h e r than t h a t o f the blood, r e s p e c t i v e l y , a t 60 min. I t was observed t h a t the r a d i o a c t i v i t y in the cerebrum was a t t r i b u t e d to Ins and metabolites o f PI. These o b s e r v a t i o n s suggested t h a t Ins could be la b e le d w i t h C - I I , which may be useful as a b r a i n diagnostic agent f o r the PET studies of the metabolism of PI and i t s role as a second messenger in the brain.

290

18F-LABELED TETRAHYDROCANNABINOL: SYNTHESIS, DISTRIBUTION IN MICE AND PET STUDIES IN A BABOON. G. MarciniakI, A. Charalambous• C.-Y. Shiue2,3, S.L. Dewey2, D.J. Schlyer2, A. Makriyannis• and A.P. Wolf 2. i. Univ. of Connecticut. 2. Brookhaven National Laboratory, Upton, NY. 3. Creighton University, Omaha, NE. Marijuana is a major drug of abuse. We have labeled its active component ((-)-8A-tetrahydrocannabinol: ZX8-THC) with fluorine-18 and studied its distribution and metabolism in mice and in a baboon. [18F]THC was synthesized from the corresponding multistep synthesized triflate with K[18F]/Kryptofix in 8% yield (EOB) in a synthesis time of 90 min. from EOB. O~ 3

H

~sCH2{ISF ]

"3c' [ze~]~ The uptake of [18F]THC in mouse tissues was high at 5 min. but radioactivity then declined rapidly in all tissues studied. Pretreatment of mice with m8-THC had no effect on the distribution of [18F]THC in different reqions of the brain. Following I.V. administration, [18F]THC uptake in the baboon brain was similar in the striatum, thalamus and cerebellt~n, and the clearance from these regions was relatively rapid. Radioactivity in the base of the skull, corresponding perhaps to the sella turcica increased with time, indicating in vivo defluorination may have occurred. These results suggest that the uptake of [18F]THC in mouse and in baboon brain is probably non-specific. Supported by USDOE and NIDA.

Sunday, August 26, 1990

Stabilization of Tc-PPm HMPAO M. Billinghurst, D. Abrams, M. Lawson, F. Vaziri Health Sciences Centre, Winnipeg, MB., Canada. Tc-99m HMPAO an important brain imaging radiopharmaceutical, is unstable in vitro. The two approaches to stabilize this radiopharmacetical were investigated. One approach prepared Tc-99m HMPAO in 85% ethanol followed by a I in 10 dilution with physiological saline. It was hypothesized that if the ethanolic preparation was stable the aqueous dilution could be done immediately prior to injection. However, the chelation reaction proceeded slowly in ethanol necessitating dilution at least 5 mln prior to use for the reaction to go to completion. Upon dilution the product was stable for up to 21 hours. Thus repeated dilutions immediately prior to use were unneccessary. Biological studies on mice s h o w e d that this p r e p a r a t i o n had the same b i o l o g i c a l distribution as cereter A second approach employed tartrate to stabilize the stannous ion at the relatively high pH at which the Tc-99m HMPAO is formed. By o p t i m i s l n g the t a r t r a t e c o n c e n t r a t i o n at approximately 0.01 M it was possible to obtain a T c - 9 9 m HMPAO preparation which retained a radiochemical purity greater than 85% for at least 3 hours post preparation. While, this was a considerable improvement, it was not as stable as the ethanolic preparation.

S73

291 IN V I T R O S T A B I L I S A T I O N

292 OF TECHNETIUM-99m

HMPAO

BY

CHILLING. J.R. B a l l i n q e r , R.H. R e i d * , a n d K.Y. G u l e n c h y n . Nuclear Medic~e, Ottawa Civic Hospital, Ottawa, Canada, and Victoria Hospital, London, Canada.

PREPARATION OF 99mTc-CARBONYL COMPLEXES FOR USE AS RADIOPHARMACEUTICALS J Bonnyman and J Baldas Australian Radiation Laboratory, Melbourne, V i c t o r i a

T h e 30-minute she/f-life of T c - 9 9 m H M P A O m a k e s it inconvenient to use and there is not y e t a stabilised formulation available. W e h y p o t h e s i s e d that l o w e r i n g t h e t e m p e r a t u r e should decrease the rate of ch~aical d e c o m p o s i t i o n of the complex and thus extend t h e shelf-life. Vials of H M P A 0 w e r e reconstituted with 2.2-2.8 G B q T c - 9 9 m (total volume 3 mL), f r o m w h i c h 1.5 m L w a s stored at room temperature (RT, 22~ a n d 1.5 m L w a s p l a c e d in a p r e - c h i l l e d lead shield in a r e f r i g e r a t o r (REF, 4ec). Radi0chemical p u r i t y (RCP) w a s m e a s u r e d repeatedly over the next 3 hours using the ethyl acetate extraction technique validated in o u r laboratory. T h e decline in R C P w i t h t i m e w a s fitted to a m o n o e x p o n e n t i a l function to determine the decomposition r a t e c o n s t a n t , k d. T h e k d for t h e R E F solution, 0.158 + 0.042 h -1 (mean + S D , N=4) w a s s i g n i f i c a n t ~ l o w ~ r t h a n t h a t o b t a i n e d at RT, 0.240 + 0.036 h (paired t-test, p<0.005). This allowed extension of t h e shelf-life b y a n ' a v e r a g e of 50%. T h e manufacturer recommends that the reconstituted kit be kept at room temperature, presumably d u e to t h e limited solubility of H M P A O in saline. However, precipitation w a s n o t o b s e r v e d in o u r e x p e r i m e n t s . Thus, cb{ll{ng m a y be a simple b u t effective m e a n s to relax t h e t i m e constraints o n t h e u s e of T c - 9 9 m

We have reported previously ( I ) that the use of formamidine sulphimic acid as a reducing agent f o r the preparation of~mTc-dithiocarbamate complexes can, on occasions, lead to the formation of the complex containing a carbonyl group. By using HPLC to monitor the r e a c t i o n , i t has been possible ~ develop a procedure f o r the preparation of Tc-complexes contalnlng a carbonyl group in good y i e l d and high p u r i t y . A f t e r separation, these complexes are stable f o r up to 24 hours. The b i o d i s t r i b u t i o n of these complexes in mice has been studied and the use of these complexes as radiopharmaceuticals is discussed. ~ m

.

.

Reference

(i)

Baldas J, Bonnyman J, Pojer P M and Williams G A (1982), Eur. J. Nuc. Med. 7, 187-189

HMPAO.

293

294

ESTABLISHMENT OF PHARMACOKINETICS PARAMETERS THROUGH COMPARTIMENTAL ANALYSES OF GENTAMICIN SULPHATE 99m LABELED WITH Tc,

TC-99M ALBUMIN [:OLLOID OR TC-99M NALLOCOLLOID BY IP INJECTION TO VISUALIZE ~;EDIASTINAL LYEPH [~ODES. ~J. Shih, J.J. Coupal, C. Coustatin, L Marsano, U.Y. Rye, P.A. DeSimone, A. Hotze, H.J. Biersa~k, Y. !;aruyama. VA and Univ of Kentucky Medical Centers, Lexington, KY, U.S.A. and Univ. of Bonn, Uest Germany.

O!ga G. de Carvalho;Maria A.T.M. de Almeida; Emiko Muramoto;Antonio S. Gouveia;Maria do Car;no C.Falcao. Institute de Pesquisas Energeticas e Nucleares, CNEN/SP - BRAZIL. Gentamiein sulphate is an aminoglycoside antibiotic type specifically used for treatment of infections produced by Gram negative bacterias but at the other hand it presents ototoxic reactions as a serious side effect. The main purpose of labeling gentamicin with 99m Tc was to obtain a radioactive tracer for eom partmental analysis of this antibiotic. The plasma 99m decay curve of Tc g#ntamicin was obtained and the half-lives calculated. Furthermore the apparent vol ume of distribution was determined and the residual radioactivity in the body determined too. The biological half-life and total dru~ clearance were ob ~m tained. ,"he distribution cf 7c gentamicin in rats was set in a two-compartments in addition to a retention one for the 24 hours time interval studied.

874

Tc-99m albumin colloid (AC) and Tc-99m nallocolloid (14C) have been used for liver-spleen imaging and bone marrow imaging, respectively. Mediastinal lymph nodes were incidentally visualized after intraperitoneal (IP) injection of 5 mCi for evaluation of Laveen shunt TcAC in a cirrhosis patient with ascites*. We replicated this in an animal model: Images over the chest and abdomen of 5 rabbits were obtained 4 hr after IP injection of 500 uCi TcAC or TcNC with 10-20 ml of normal saline. These images showed areas of radiotracer localization in the mediastinal region. We also reviewed 5 patients with ascites due to cirrhosis of the liver in 3 patients, colon carcinoma i, and ovarian carcinoma with extensive peritoneal metastases I. Sequential thoraeoabdominal images were obtained i~ediately after IP injection of 5 mCi TcAC and after 15, 30, 45, and 60 min and 2, 3, 4, and 24 hr. Mediastinal lymph nodes were visualized in 2 cirrhosis patients; none was visualized in 2 malignant ascites and i cirrhosis patients. Peritoneal implant cancer cells originating from, for example, colon or ovarian cancer, invariably would induce malignant ascites. Cancer cells in the abdominal cavity may enter mediastinal lymph nodes and establish metastases directly through the mediastinum or indirectly through the pleural cavity. Nonvisualization visualization may indicate lymphatic block and may also exacerbate existing ascites. The results suggest Tc-AC or NC may be recommended to be used as a lymphatic imaging agent for functioning status between the peritoneal cavity and mediastinal lymph nodes. *J Hucl Med 30:559-560, 1989.

Sunday, August 26, 1990

295

296

iNTERACTION OF SOME STERILIZING FILTER MATERIALS WITH I n - l l l LABELLED MONOCLONAL ANTIBODIES (mAb) o R.M. R e i l l y . Toronto General H o s p i t a l , Toronto, O n t a r i o , Canada.

RADIOIODINATION OF MONOCLONAL ANTIBODY INTACT ANTI-CEA.

Retention o f r a d i o l a b e l l e d p r o t e i n s by some s t e r i l i z i n g filter materials has been previously reported (I)o This phenomenon may also occur with radiolabelled mAbo The objective of this study was to compare the retention of In-111 mAb by four different commercial sterilizing Filters~ The filters were composed of cellulose acetate/nitrate (Millex-GS), polyvinylidene difluoride (Millex-GV and GV 4) and polysulfone (Acrodisc). The filters were first pre-wetted with 2 mL of saline or I% HSA in saline~ The mAb (in 2 mL of saline or I% HSA) was then passed through the filter and the radioactivity remaining bound to the filter and in the filtrate measured~ The effect of volume on retention was determined by flushing the filter with up to 6 mL of saline or I% HSAo When the mAb was formulated in saline, up to 90% of the radioactivity was retained by the Millex-GS filter. This radioactivity could not be displaced by flushing the filter. In I% HSA, the retention by the Millex-GS filter was only 26%. This was reduced to less than 10% by flushing the filter with an additional 4-6 mL of I% HSA. The Millex-GV and Aerodisc filters retained 15-23% of the radioactivity in the presence or absence of HSA. The Mi]lex-GV 4 filter exhibited the least retention of radioactivity (2-3%). In conclusion, in order to minimize retention of radiolabelled mAb on sterilizing filters, it is important to select an appropriate filter material, formulate the mAb in I% HSA and ensure that the volume filtered is at least 4-6 mL. Io Billinghurst MOW., Westendorf 18:746-747, 1977

B.A.J.

The introduction of monoclonal antibody technology and the development of alternative radiolabelling procedures accel~rated the use of antibodies as radio pharmaceuticals for diagnosis and therapy of human tumors. Convenience and simplicity are essential in radiopharmaceutieal preparations, where time and per haps expertise are limited. An intact Anti-CEA 4 CII IgG2a,K, prepared in the "Instituto Ludwig de Pesquisa sobre Cancer" S?-Brasil, was purified by affinity chromatography on protein-A-Sepharose(Pharmacia)Labelling of intact Anti-CEA was carried out by the iodogen(l.3, 4,6 tetraebloro 3a,6a diphenyl-glycouril) method. This radioiodination technique for antibodies which is rapid, simple, efficient and reproducible can be acomplished in most radiopharmaceutieal laboratories. Unreacted 131 1 was removed by anion exchange resin(Bio-Rad Dowex I-X8 ~00-200 mesh chloride form). The miniature chromatographic system, alsoyapid, accurate, simple, effi cient was elaborated to determine the labelling effi ciency and the radiochemical purity of Anti-CEA. The efficiency of incorporation of iodine into immuno globulin of the two preparations were 71 and 74Z. The specific activities were z$O and 50 )~Ci/jag. The radio chemical purity was 98% for both preparations.

NUClo Med.

298

297 PLASM~A. AND TISSUE DISTRIBUTION I ~ C O K I N E T I C S IN-Ill MURINE, ANTI-CEA MONOCLONAL ANTIBODY COLORECTAL CANCER PATIENTS. W.B. Webster. Jr., R.G. Carroll, S.J. Harwood. M.A. Morrissey, Bay Pines VA Medical Center, Pines. Florida.

OF IN and Bay

Five patients in a phase II clinical trial for detection of colorectal cancer were administered IV 2 to 40 mg of a murine, anti-CEA MAb labeled with 5-7 mCi of In-lll. Serial blood samples were taken days 0-8. One patient had increased circulating specific antigen. CEA (124 ng/m_l). Plasma pharmacokinetic parameters based on probability were calculated for the central and peripheral compartment. Mean times for transit (MTT), residence (MRT), compartmental cycling (n) and the probability of distribution (PRD) from the central to peripheral compartment are reported. Parameter Mean Range MRT (Body} 71.3 hrs 65.4 to 79.7 hrs MTT(Oentral) 9.7 hrs 5.4 to 18.0"@ hrs l~RT(Central) 50.5 hrs 36.3 to 56.4 hrs n Cycles 5.1 x "1.8 to 9.3 x PRD 80.5 % 90.3 to 64.9*@ % (* Patient with increased circulating CEA. @ P < .I) Conclusions: Activity from a single molecule spends 9.7 hrs in the central compartment (MTT(C)) cycling 5.1 times to the peripheral compartment -aggregate time (MRT(C)), 50.5 hrs. The probability of In-lll-MAb activity in the central compartment distributing to the peripheral compartment is 80%. There is a correlation for circulating CEA and MTT(C), n, & PRD (p < 0.05) showing increased circulating CEA increases MTT (C) and decreased distribution to peripheral compartment, PRD.

Sunday, August 26, 1990

Iracelia T.T. e Souza; Helena Okada. Instituto de Pes quisas EnergSticas e Nucleates CNEN/SP - B r a z i i .

A KIT FORMULATION FOR MIBG LABELED WITH 1-131 M.Neves, I.Castanheira, A.Paulo and L.Patr{cio, Laboratorio Nacional de Engenharia e Tecnologia Industrial - Estrada Nacional 10-2685 Sacavem-Portugal The aim of this work was to develop the MIBG in kit form ready for labeling with 1-131. The availability of the kit at local application avoids the problem of low stability. The kit includes 3 vials: A-freeze dried mixture of MIBG, CuSO 4 and Na2S205 . B-acetic acid. C-sodium acetate buffer. By a simple manipulation followed by heating at 150~ during one hour the labeling yield is~99%. The involved reaction is a nucleophilic exchange assisted by Cu(I) generated "in situ". Optimization of labeling conditions as concentrations of reagents, pH, temperature and heating time are s u ~ a c e n t to kit formulation. The performed quality control of 1 - 1 3 1 M I B G by HPLC and electrophoresis as shown a single peak. For routine control, paper chromatography assure the absence of free iodide. Biodistribution and adrenal uptake were evaluated in female mice. A rapid excretion from the body and a slow elimination from the adrenals were observed.At72 hours a.i the adrenal uptake in % of remaining activity in whole body was 6.1+--0.5. The uptake expressed in % of remaining activity/gram of organ was also evaluated for adrenals, kidneys, heart, liver, intestine, lungs and blood. Adrenals-to-other organs ratio ranged between 49.0• (kidneys) and 245.0• (blood). These results indicate highselectiveedrenaluptakeofthis developed kit.

S?5

299

300

PADIOC~CAL ~ ~ OF KITS ;.~t~,r.TrJ~ 99~Tc P R ~ D AT IR~/C~n~-SP.

P R E P A R A T I O N OF LABELED I O D I N E - 1 3 1 LIPIODOL COMPOUNDS FOR THE TREATMENT OF HEPATOMA. Jiunn-Guan~ Lo, W i n g - K a i Chan*, Wing-Yiu Lui** and Chin-Wen Chi**. I n s t i t u t e of N u c l e a r Science, National Tsing Hua University, Hsinchu 30043, Taiwan, R.O.C.

M.F.de Batboza, N.S.4~ Pereira ald C.P.G.da Silva. Ins

tltuto ~ P ~ q u i ~ s ~ e r ~ t i ~ Sag P~,_!o, Brazil.

e Nucleazes. cram - s~

The r a d i ~ c a l s are nmfclnely used in Nucle ar Medicine laboratories. A large number of these em~ ploy t / n ( I I ) z~agents to rer Tc(pertedmetate VII) to a l o ~ r valence state, themaby making it more able to ~ , ~ l e x f o n ~ n g x'eace_tens, The m l z ~ t a t u ~ , d

~mtm~

~ of 99mTc labelled om~ounds, using 3~4 (8 X i~0 as a support and 30% NaCl; 0.9%

NAG1; 85% MeOH and buffer phosphate as a solvm~ts, penlite to assay the radloohemlcal purity in few minutes after preparation. In ~ I t i o n , this method in~ in routine womk not only detsamdm~s zt~uced

99m Tc (pertedmetate) but also "~termines reeuoed 9Oj~c tmbound to the r a d i ~ c a l s (hydroZtzed reduced 99m T o ) . The lyophilized kits for labelling with 99m Tc p r o d t x ~ in routine at IP~/Q~EN-SP are: M~P; DIPA; HSA; G ~ ; HIES; Pyro; ~ A ; MIAA; Sulfurcolloid; ~ - 5 0 0 ; Cit.Sn end Fitate.

Padloch~mlcal T ~ t y ~ntrol of these kite were perfon~d at the first day after pzeparation and during 12 munths for de~ennlnlng their validity for use. All preparation showed high yield of labelling ~uring this period of time.

(95 - 99%)

301

302 IN-ilOU~E RETEODSFOR RULTI-DOSE REAGENTKITS F(R Tc-99m RRD] OPHARNACEUTI CALS

GarJmeLta vs Rayudu, Rush University Medical Center, I I [inois, U.S.A

Chicago,

In order to arrive at the most simple and safe methods of preparing reagent kits, threeapproachesare described: I. A three step multi-dosekit, 2. Sub-divisionof commercial liquidkits, 3. S u b - d i v i s i o n of co~mercia[s o l i d kits. The three step method in a clean air hood consistsof: A, Comp[exing agent in sterile water at requiredconcentration I 10mg/ml, B. Sn(I[) in Cone HCl,(I gram/ml)C. AdjustingpH to 5.56.5 in asepticcondition,additionof anti-oxidantImg/IOmlascorbic acid and bubblingwith N2. MDP, HMDP, PYP I~ > OTPA, DMSA, HSA GLUCO, NAG3, MAA PHYTATE, DISOPHENIM(

|with N2 add anti-oxidant, ~g.22 micron filterand

in sterile water and

| p a r c e l Sn(Ii) complexes

bubble N2.

~Adjust pH 5.5-6.5,bubble

k into vialsand freeze.

SnCt2, in conc HC[ 1

Commerciallyavailablesingle/multi-componentliquid kits such as Sulfur colloid can be split into 5 to 10 equal parts asepticallyand can be used safelyafter the labeledproductswere checked with ITLC. Commercially available freeze dried multi-dose solid k i t s such as 15-million particle containing MAA can be sub-divided w i t h micro-spatula into 15 p a r t s aseptically and the labeled substance can be used in patients after checking the quality with ITLC. This approach was tested in patients where ever the supplies are l i m i t e d and the kits were checked to be stable for 30 days.

S76

An i s o t o p i c e x c h a n g e m e t h o d w a s u s e d t o label the radioactivity of i o d i n e - 1 3 1 in LJpiodol. In g e n e r a l , t h e l a b e l i n g e f f i c i e n c y was found above 81.9%, and the radiochemical p u r i t y of l a b e l e d 1 - 1 3 1 L i p i o d o l w a s u p to 99. 0 9 1 . 0 % as e x a n i n e d b y t h e I T L C c h r o m a t o graphy. In a d d i t i o n t h e i n f l u e n c i n g factor s u c h as t h e h e a t i n g t e m p e r a t u r e , pH, a n d storage condition were studied and the optimum conditions for preparation of 1 3 1 I Lipiodol were determined. The treatment s t u d y of 10 h e p a t o m a p a t i e n t s w a s u s i n g l a beled 1-131 Lipiodol, which was infused hepatoma via the hepatic artery. A b o u t 70% of h e p a t o m a p a t i e n t s h a d r e s p o n s e to t h e t r e a t m e n t w i t h r e d u c t i o n of a - f e t o p r o t e i n a n d d e c r e a s e of h e p a t o m a s i z e s . The overall m e d i a n s u r v i v a l is 9 m o n t h s ( r a n g e 2 - 1 7 months). T h e m o s t i m p r e s s i v e a s p e c t of t h i s m e t h o d of t r e a t m e n t is the. r e l a t i v e l a c k of major side effects. * I n s t i t t u t e of B i o m e d i c a l Science, Academia Sinica, Taipei, R.O.C. ** D e p a r t m e n t of S u r g e r y , V e t e r a n s G e n e r a l Hospital, Taipei, R.O.C.

AUTOMATING RADIOPHARMACEUTICAL DISPENSING. A.T. Elliott, T. Murray, T.E. Hilditch. Western Infirmary, Glasgow, U.K. The critical radiation dose to staff preparing radiopharmaceuticals is that to the fingers. In our eentralised radiopharmacy, handling 29TBq of Tc-99m and 400GBq of 1-131, finger dose averages 50mSv per year. Imminent reductions in permissible dose levels provide impetus to reduce these levels. Some 85% of finger dose is due to sub-dispensing patient doses from stock solutions, and so effort has been directed at automating this part of the production procedure. A standard automated biochemistry system has been modified to be capable of puncturing closed vials. Its size permits installation in a standard laminar flow cabinet. It has been found capable of dispensing over I00 different patient doses per hour, with activity and volume errors 41%. This compares to the best manual results of 65 doses per hour with an error of 2-4Z. Sterili~y and pyrogenicity tests were negative and there was no evidence of radionuclidic or pharmaceutical crosscontamination between doses. The system is controlled from an IBM PC programmed in 'C' and has been modified to permit downloading of a dispensing schedule and calculation of decay factors. In addition to yielding reductions of over 50% in finger dose for present operations, the device will enable dispensing of other stock solutions such as TL-201 and the remote handling of alpha-emitting radionuclides.

Sunday, August 26, 1990

303

304

IMPROVED METHOD TO LABEL BETA-2 AGONISTS IN M E T E R E D DOSE INHALERS WITH TECHNETIUM-99m. J.R. Ba]]inqer, L.E. Calcutt, K.Y. G u l e n c h y n , a n d R.V. Hodder. Divisions of Nuclear Medicine and Respirology, Ottawa Civic Hospital, Ottawa, Canada.

BRAIN SEEKING Cu-62 LABELED BIFUNCTIONAL RADIOPHARMA CEUTICAL WITH ENZYMATICALLY METABOLIZABLE ESTER GROUP K. Matsumoto, Y. Fuj ibayashi, K. Wada, T. Takemura, Y.Yonekura, J.Konishi & A.Yokoyama. Faculty of Pharm. 8ci. & School of Med., Kyoto Univ., Kyoto, Japan

Lab~]]ing beta-2 agonists in a metered-dose inhaler (MDI) with Tc-99m allows imaging of t h e deposition of the aerosol in t h e t r a c h e o b r o n c h i a l tree. H o w e v e r , there are technical p r o b l e m s in t r a n s f e r r i n g T c - 9 9 m into a p r e s s u r i s e d cannister a n d e n s u r i n g t h a t t h e active ingredient is labelled. K o h l e r et al (Respiration 1988;53:65-73) d e v e l o p e d a m e t h o d in w h i c h p e r t e c h n e t a t e is e x t r a c t e d f r o m s a l i n e i n t o M E K , e v a p o r a t e d to d r y n e s s , s o l u b i l i s e d w i t h s o r b i t a n trioleate (Sp85), d i l u t e d w i t h f l u o r o c a r b o n , a n d t r a n s f e r r e d into an M D I w h i c h h a d b e e n chilled t o condense the prop~llant. It is believed that p h y s i c a l labelling takes place; t h e large e x c e s s of n o n p o l a r propellant forces the pertechnetate to associate with the active ingredient and solubiliser. W e improved the extraction procedure b y minimising volumes a n d using h e a t a n d a s t r e a m of n i t r o g e n to speed u p evaporation. Residual w a t e r w a s r e m o v e d as an azeotrope with acetonitrile. M o r e importantly, b y u s i n g ethanol r a t h e r t h a n S p 8 5 as s o l u b i l i s e r , w e obtained more c o m p l e t e a n d r e p r o d u c i b l e t r a n s f e r of T c - 9 9 m into t h e M D I (efficiency 80 + 6%, n = 24). M o r e o v e r , this m e t h o d d o e s not r e q u i r e addition of excess surfactant which could p e r t u r b t h e s y s t e m a n d thus it should b e b r o a d l y applicable to a variety of MDIs, in addition to the salbutamol and fenoterol M D I s for which w e have validated it. Studies with a test lung system have allowed us to evaluate the effectiveness of various spacers and aerochambers in i m p r o v i n g d e p o s i t i o n e f f i c i e n c y of t h e r a p e u t i c aerosols.

In our previous work, clinically applicable Zn-62/Cu-62 generator system has been developed. Using this generator, various biologically interesting Cu-selective ligands can be labeled. For brain studies, Cu-62 labeled bifunctional radiopharmaceutical inducin Z intracellular retention by ester hydrolysis was designed. As a stable Cu 62 chelate, the ligand, bis (N, N-dimethyldithiosemicarbazone) (DTSM2), was selected and an ethylester group was introduced into it (DTSM2-Et). In non-radioactive Cn as well as Cu-62 studies, the Cu-labeling of DTSM2-Et was completed by simple mixing of DTSM2-Et with generator eluate. Then, metabolic affinity of Cu-DTSM2-Et in the brain was basically studied by the analysis of the mouse brain homogenate; the reversed-phase HPLC studies revealed the presence of a more hydrophilic Cu-~rSM2 complex. However, such change was not detected in the protein-precipitated fraction, a possible indication of enzymatic hydrolysis of the introduced ester group. These basic results were reflected in in-vivo mouse biedistribution studies ; namely, the radioactivity retained in the brain, although its absolute uptake value was rather low. These results indicated that Cu-DTSME-Et could be a Cubifunctional radiopharmaceutical with ester hydrolysis-based retention in the brain.

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BIOLOGICAL BEHAVIOUR OF TECHNETIUM-99m LABELED MONOPHOSPHONATES DERIVATIVES

BIODISTRIBUTION OF THE p-(nlS-CARBOXYMETHYL)-AMINO METHYL CARBOXYAMINO - HIPPURIC ACID PAHIDA,

I.Castanheira, M.Neves, A.Paulo and L.Patr{cio, Laborat6rio Nacional de Engenharia e Tecnologia Industrial, Estrada Nacional I0 - 2685 SacavSm, Portugal

Elaine n. de Araujo;Maria A.T.M. de Almeida; Emiko Muramoto. Instituto de Pesquisas EnergStieas e'Nueleares, CNEN/SP - BRAZIL.

Currently used Tc-99m bone imaging agents are based on diphosphonate ligands which are oligcmeric or polymeric in nature and it seems that the smallest ones provide more favorable bone

A renal agent labeled with 99mTc and quantitatively secreted by the tubules has been sought for many years, To meet LLis peed a PAH analog (PAHIDA) has,been syn 99m thetized that yields a stable complex with Te using Sn(ll) reduction. This report describes biodistribution studies in rats of PAHIDA 99mTc. The compound is rapidly cleared from the blood with approximately 26% present i min. after the administration of the dose. The uptake dose/organ, showed that the kidneys have a selective performance in elimination. The urinary excretion is rapid,with 50% in the urine after 30 min. Gastro intestinal elimination of the compound is less than 8%. Protein binding determined by TCA precipitation method is high (35% in i min. and 50% in 50 min.). The eritrocits binding increase in time, arriving i0% in 60 min. The whole body analysis showed a retention of 50 and 20% of the administered dose, respectively at 30 and 60 min. after the administration dose. Rat urine analysis by ITLC chromatography suggest that the agent excreted is similar to the complex administered to the animals until 15 min. after the administered dose. Similar analysis of the urine after i5 min. showed a second peak that suggest the presence of PAHIDA metabolites.

uptake. Monophosphenatesligasds are expected to disfavor polymers formation. The aim of this ~ r k was to prepare some Tc-ggm-monophospheeste derivativesand correlate to biological distributionin mice. 7he ligands under study ~ere:(-)cis,l,2-epoxypropylphosphenicacid (~DPA), 1,2~ydroxypropyl-l-phosphenic acid (HPPA) and phenylphosphonic acid (PPA). Te-99m labelingwas performed at pH 2.5 and 6.8 using tin chloride as reductant. I ~ and paper chromatographywere used for analysis of TcO~4and TcO2 contents. All labeled compounds were highly excreted in urine being the PPA the less excreted. The presence of a phenyl group confering a less hydrophiliccharacter could explain this as well the low hepatobiliaryexcretion observed. At 3hr a.i the femur uptake were:65.7, 64.2, 78.1, 9.5 and 10.4% of that of ~[]Pfor EPPA(pH=2.5),HPPA(pH=2.5),PPA(pH=6.8),EPPA(pH=6.8) and HPPA(pH=6.8) respectively.~DPA(~{=2.5)and HFPA(~H=2.5) despite having a lower femur uptake exhibit a pattern of biodistribution similar to MDP. However at pH=6.8 a much lower femur uptake was found ~nile a signifiestivelycortical kidney uptake was observed (8._3i0~ and 6.2 + 0.9 expressed in % dose/organ)which indicates the influence of pH. It may be concluded that bone uptake is not only related to the monophesphonatederivative but is strongly controlled by the nature of monophesphenate-matalccmplex formed.

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307 A

NEW

308 Tc-99m

B-GALACTOSYLATED

ALBUMIN

MOLECU-

(GA) F O R T H E S T U D Y O F T H E H E P A T I C F U N C T I O N L.Manil,Y.Salmon,V.Lamy,J.Thornback,P.Rigo. Hop Jumet; CHU Li@ge; MEDGENIX Group,BELGIUM LE

A novel Tc99m-GA obtained by stannous reduction (GALACTOSCINT"),& available as a f r e e z e dried kit, has been proposed for functional liver investigation. The GA uptake kinetics w a s t e s t e d in 4 N o r m a l s & 27 p a t i e n t s u s i n g 2 doses (50~g tacer and 10mg non-tracer dose) i n j e c t e d a t 20 m i n i n t e r v a l . T h e hepatic time /activity curves were plotted for each dose. An exponential y=6-e*e-Bt was easily fitted t o t h e e a r l y p h a s e of t h e h e p a t i c c u r v e s , in order to compare the different c u r v e s in t h e same patients and between patients. 6 and were found to be unrelated to patient parameters (GGT,SGTP,Child Score(CS) ,Aminopyrine test (ABT),..). In c o n t r a s t , B values were correlated with the results of ABT and, for patients with severe disease, with CS. T h e greatest differences were found with the 10mg dose [Nls(n=4):4.50(X10-Smin-l)• steatosis(n=10):3.31• non-alcoholic cirrhosis (n=3): 2.02• alc cirr (n=8): 1.23• Smaller differences were seen with 50~g. The ratio B(50~g)/B(10mg) w a s g r e a t e r in p a t i e n t s (1.57• t h a n in N l s ( l . 3 6 • ces between the 10mg curves from different patients are a function of both blood flow & receptor activity. But differences between tracer & non-tracer d o s e in t h e s a m e p a t i e n t are related to hepatic receptor function. This test with a tracer & a higher non-tracer dose(50mg?) would help to differentiate hepatocyte-related from hemodynamic disorders.

HEPATIC PROCESSING OF GALACTOSYL NEOGLYCOALBUMIN IS SIMILAR TO THAT OF ENDOGENOUS ASIALOGLYCOPROTEINS. + x D. Billinqton , S. Gore , A.I. Morris x, I.T. Gilmore x and J.R. Thornback ~ . +School of Natural Sciences, Liverpool Polytechnic XRoyal Liverpool Teaching Hospital, Liverpool U.K. and ~ s.a. , Fleurus, BELGIUM. Plasma glycoproteins, after removal of terminal sialic acid residues to expose penultimate galactose residues, are endocytosed by a receptor radiated process into hepatecytes 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 (heDatlc 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 uD 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 heDatocellular injury) decreased uptake bv 50%. Dre-perfusion of livers with leupeptin (a ivsosomal nrotease 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 i-s processed bv the isolated perfused rat liver in a similar fashion to endogenous asialomlvcoDroteins.

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DIFFERENCES IN THE HEPATIC METABOLISM OF Tc-99m AND 1-125 LABELLED GALACTOSYL NEOGLYCOALBUMIN. X . M . ~ M S. Gore.. t A +I. Morrls , I.T. Gllmore P. Maltby , D. Billinqton and J.R. Thernback". +ROYAL LIVERPOOL TEACHING HOSPITAL, Liverpool, U.K. SCHOOL OF NATURAL SCIENCES, LIVERPOOL POLYTECHNIC, U.K. "MEDGENIX S.A. , Fleurus, Belgium.

RADIOPHARMACEUTICAL INVESTIGATION OF CYCLOSPORIN A CARDIOTOXICITY AND CORRELATION WITH HISTOPATHOLOGICAL FINDING. A. Owunwaane, A. Shihab-Eldeeb, S. Sadek, T. Junaid, T. Yacoub and H.M. Abdel-Dayem, Depts. of Nuclear Medicine, Pharmacology & Toxicology and Pathology, Kuwait University, Kuwait.

Galactosvl neoglycoalbumin (NGA) is a synthetic ligand for the asialoglyceprotein receptor (hepatic binding protein) which resides exclusively on hepateeytes. Uptake of Tc-99m-NGA allows assessment of liver function based on receptor concentration as well as dynamic liver imaging. However, most biochemical studies on the uptake and hepatic metabolism of asialoglycoproteins have used 1-125-1abelled ligands. We have undertaken, therefore, a comparative study of NGA uptake and hepatic metabolism in the isolated Derfused rat liver using both Tc-99m and 1-125 radiolabelled NGA. First pass hepatic uptake of a pulse (150 omol) of 1-125 and Tc-99m-labelled NGA was similar (37 + 3% vs 44 + 5%, n.s. ) showing that both radlolabelling methods did not alter receptor binding. Of the 1-125-NGA taken up, 82% of the 1-125 was released at the sinusoidal pole of the hepatocyte and reappeared in the perfusate (mainly as small M.Wt. metabolites) whilst 8% was excreted unchanged into bile and 7% remained in the liver lh after the pulse. Of the Tc-99m-NGA taken up, only 4% of the Tc-99m was returned to the sinusoidal pole of the heDatocyte whilst 40% was excreted in bile and 55% remained in the liver lh after the pulse. These differences in the hepatic metabolism of 1-125 and Tc-99m-labelled NGA cab be related to the different methods of attachment of the radiolabel to the ligand. The implications of these 'results to the diagnostic use of Tc-99m-labelled radioligands will be discussed.

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inspire of the well documented uses of CyA in preventing rejection of transplanted organs CyA has been reported to have toxic effects : nephrotoxicity, hepatobiliary toxicity and neurotoxicity. There are no reports of CyA toxicity to the native heart either in patients or animals. Hence the objective of this study was to use 1-125 HIMPD, In-lll ant• (In AM) and Tc-99m pyrophosphate (Tc-99m PYP) to study any cardiomyopathies associated with CyA and correlate the results with histological findings. Thirty six rats were used : 12 for each radiopharmaceutical (CyA and control 6 each). The rats were injected subcutaneously with 50 mg/kg (b/w) of CyA or equal volume of vehicle (control) for ii consecutive days. For In AM studies, they were i.v. injected with the tracer on the 7th day of treatment while for 1-125 HIPDM and Tc-99m PYP they were injected 1 day after the treatment. All rats were sacrificed 1 day after treatment. The hearts were excised and counted in a NaI well counter. Samples of the hearts were used for histological studies. The ratio of the uptake of each radiopharmaceutical in CyA treated to control rats were 2.49, 2.1 and 2.2 for 1-125 HIPDM, In-AM and Tc99m PYP respectively. The difference in uptake was statistically significant (p<0.05). Histological examination of the heart tissue showed interstitial oedema and focal vacuolation of the myocardium. The results indicate that CyA seems to have toxic effects on the rat heart.

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STUDY OF CYCLOSPORIN A NEUROTOXICITY IN RATS USING 1125 HIPDM AND CORRELATION WITH HISTOPATHOLOGICAL FINDING. A. Owunwanne, A. Shihab-Eldeen, S. Sadek, T. dunaid, T. Yaeoub and H.M. Abdel-Dayem. Oepts. of Nuclear Medicine, Pharmacology & Toxicology and Pathology, Kuwait University, Kuwait.

INVESTIGATION OF MULTIORGAN TOXICITY OF CYCLOSPORIN A (CyA) IN RATS USING 1-125 HIPDM AND CORRELATION WITH HISTOPATHOLOGICAL FINDINGS. A. Shihab-Eldeen, A. Owunwanne, S. Sadek, T. Yacoub, T. Junaid, H.M. Abdel-Dayem. Dep
Cyclosporin A (cyA) neurotoxicity has been reported in patients under CyA therapy and in experimental animals. 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 1125 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 with 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 autoradiogrsphy. 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 1125 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.

CyA is known to have toxic effects. Being lipophilic CyA can cross biological membranes and diffuse into various tissues. Because 1-125 HIPDM is also lipophilic, it was used to study tissue response in CyA treated and control rats. The 1-125 HIPDM uptake in the various organs was correlated with histopathological findings. 30 rats were studied; each was SC injected 50 mg/kg (b/w) of CyA or equal volume of vehicle (control) for 7 days. 20 rats (CzA and control i0 each) were used for biodistribution studies while i0 (CyA and control 5 each) were used for histopathological studies. For biodistribution studies, each rat was injected i0 uCi of 1-125 HIPDM and sacrificed 30 minutes later. The organs were excised and the radioactivity counted in a well counter. The liver, kidney and heart showed increase while the spleen had a decrease in the uptake of 1-125 HIPDM in CyA treated compared to control rats. The differences were statistically significant (p < 0.05). There was no difference in the uptake of 1-125 HIPDM in the lung and brain of CzA treated and control rats. Histopathological examination of the different organs showed fatty change in the liver but no significant changes in others except focal myocarditis in one test animal. The difference in the uptake of 1-125 HIPDM was assumed to be the tissue response to CyA thus indicating that CyA is toxic to liver, kidney, spleen and probably the heart.

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MYOCARDIAL Na,K-ATPase IMAGING USING 1-123 LABELED DIGOXIN. Y.Fujibayashi, Y.Takemura, K.Matsumoto, K.Wada, Y.Yonekura, J.Konishi & A.Yokoyama. Faculty of Pharm. Sci. & School of Med., Kyoto Univ., Kyoto, JAPAN.

36-CHLORIDE FLUX IN RAT HIPPOCAMPAL SLICES:A NEW PHARMACOLOGICAL ASSAY FOR DRUGS ACTING ON THE "GABA-BENZODIAZEPIN-CHLORIDE CHANNEL RECEPTOR".

Based on the high affinity of cardiac glycosides (digitalis etc.) to the Na,K-ATPase in the myocardium, radioiodinated digoxin was selected as a candidate for myocardial imaging, with particular interest for non-invasive monitoring of cardiac glycoside therapy. In basic study, 1-125 labeled digoxin derivatives having histamine residue for iodination were surveyed both in-vivo and in-vitro. In guinea pigs, 1-125digoxin-iodohistamine(bis(o-carboxymethylo• (I125-digoxin) showed selective myocardial accumulation. However, 1 - 1 2 5 - 1 a b e l e d d i g o x i n h a v i n g no sugar residue, showed scarce myocardial accumulation. In in-vitro binding studies using isolated kidney Na,KATPase, 1-125-digoxin showed high binding affinity to the N a , K - A T P a s e as H-3 digoxin. Also in in-vivo guinea pig biodistribution, 1-125 accumulation in the heart was completely inhibited by ouabain co-injection (0.5 mg/kg), a fall to 66.3 % of the control, while other tissues were unaltered. Based on these results, 1-123 l a b e l i n g of digoxin-histamine(bis(o-earboxymethyloxime)) was performed. C a r r i e r - f r e e 1 - 1 2 3 - d i g o x i n could be obtained by conventional chloramine-T method and HPLC purification. Using this 1-123-digoxin, heart was clearly visualized in dog seintigraphy study. Tissue counting study in this dog showed e x t r e m e l y high m y o c a r d i a l a c c u m u l a t i o n (left v e n t r i c u l a r m u s c l e / blood = 31.2, 70 min post injection). 1-123-digoxin have high p o s s i b i l i t y as a new type of m y o c a r d i a l diagnostic agent, based on Na,K-ATPase binding.

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M.Valli,S.Gassama,C.Rinaldi,R.Hdoye,R.Paulin. I.R.A.M.I.R. F a c u l t l de M 4 d e c i n e - M a r s e i l l e (France)-Lab. Biophysique,Facult4 de M 4 d e c i n e Dakar(Sinlgal). The stimulation of a s u b u n i t o f " t h e G A B A - B e n zodiazepin-chloride channel receptor complex" ( G B C C R C ) by d i f f e r e n t b e n z o d i a z e p i n e s increas e s C1 conductance in r a t b r a i n s l i c e s . 3 6 C I e f f l u x w a s m e a s u r e d at 3 7 ~ in o x y g e n a t e d phy_ siological saline.Hippocampal s l i c e s of 250 u m were preincubated 30mn,loaded f o r 3 0 m n w i t h 70 K B q / m l of 3 6 - C l - , t h e n passed sequentially every m n t h r o u g h v i a l s of n o n r a d i o a c t i v e medium. After obtaining a stable efflux rate(10-15mn), various benzodiazepines alone produced a significant • in 3 6 - C I - e f f l u x r a t e . T h e rank order for this enhancement of t h e C I conductance was clonazepam>lorazepam>diazepam. The results are consistent with the respective affinity for benzodiazepines binding sites. Furthermore,these effects were reversed bicuculine,picrotoxin and RO 15-1788.

by

Thus,this bio-radio-chemical m e t h o d s e e m s to b e an i n t e r e s t i n g pharmacological for the functional study and for radiopharmaceutical s c r e e n i n g of d r u g s a c t i n g o n t h e " G A B A - B e n z o diazepin-chloride channel receptor complex. Wong

E.H.

and

al.,Brain

Res.1984,303,267-275.

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CHEMICAL AND BIOLOGICAL INVESTIGATIONS OF A SERIES OF NEUTRAL LIPOPHILIC TECHNETIUM COMPLEXES DESIGNED TO MIMIC rCBF. J.R. Thornback, M. Deblaton, P. Clemens, P. Vandenbroeck, and G.F. Morgan. MEDGENIX S.A. Fleurus and I.R.E. Fleurus, BELGIUM.

QUANTITATIVE DETECTION OF SPEmqATOZOAN MIGRATION AND TRANSPORT BY IN VIVO MONITORING OF RADIOLABELED CELLS. A. Bockisch, S. AI-Hasani, F. Nettekoven, K. Diedrich, H.-J. Biersack, D. Krebs; Dept. Nuclear Medicine, Gynecol. Dept., Univ. Bonn, W.Germany

MRP20, N (-2 (IH pyrolylmethyl) )N' (-4-pentene-3-one-2) ethylene 1,2 diamine, is currently under investigation as a brain perfusion agent in Phase of clinical trials The general structure of the MRP series is shown in Figure 1 and to date ~-~ p. several ligands have been synthesised N~ ~ n //" 9 . . H HN which are modlflcations of this struc ~ -~ ture. A selection have been detailed ~ / / below Fig. I. In this oaper we pre- i_ /NH 0 : : ~ sent our studies on a series of t h e s e ~ E ligands. It illustrates the versatility of this ligand structure in mo~.-2.~. difying both the chemical and biolo~P~2.-2,R-R~,B. gical behaviour of the technetium ~RP~7..';.~'.E, complexes. MRP~B ,-2. ~-~'~ Lipophilicity of each ligand and ~p~,~.z.~~.cs complex was measured by octanol : saline partition and reverse phase HPLC. Values ranged from Log P=0.93 (MRP23) to 2.1 (MRP22), the Log P of MRP20 being 1.84. Those complexes where n:3 were unstable and showed insignificant brain uptake (MRP30, 0.07% i.d. at 30 min p.i.) whereas n=2, brain uptake was observed ranging from > 2% i.d. (MRP20) to 0.12% i.d. (MRP 22) at 30 min p.i. All the complexes are unstable and decompose via one of two routes either to TcO 4- or a secondary hydrophilic complex. This latter is t~ought to be the hydrolysis product Of the azomethine moiety as it has been observed in most of the series of ligands. We conclude that our MRP series of ligands show potential as future tracers for rCBF, and potential use in other fields of nuclear medicine.

For gentle and stable radiolabeling of spermatozoa (SP) Tc-99m-HMPA0 has proven to be an ideal agent. A total of 50 ~emal rabbit~ was scanned after insemination of 1.10 ~ or 100.10 ~ radiolabeled rabbit SP. 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 and passive transport, a mixture of In-111-oxine labeled avital and Tc-99m-H~PA0-1abeled motile SP was inseminated. A mixture of unlabeled and Tc-99m-HMPA0labeled SP allowed an evaluation of the influence of labeling on SP motility. Results: Thorough cross checks excluded a relevant degradation of the quality of the SP by the labeling procedure. SP located in the uterus, the fallopian tube, on periovary or intraperitoneal regions 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-HMPA0-1abeled 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 investigate infertility in human couples. With humans, conception with labeled SP must be excluded, although the spermatozoan dose is restricted to values well below 0.1 Gy.

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A PROPOSAL FOR HNIFIED SYMBOLS AND NOMENCLATURE IN TRACER KINETICS. A. Rescigno, A.K. Thakur, A.B. Brill, and G. Mariani. University of Parma School of Pharmacy, Parma (Italy); Hazleton Laboratories America, Inc., Vienna, VA; University of Massachusetts Medical Center, Worcester, MA; and University of Pisa School of Medicine, Pisa (Italy).

ESTIMATING ENERGY RESOLLrL~ON OF A SCINYILIATION D ~ R WITHOUt pOISE HEIGHT ANALYSIS. F.B. Atkins. George Washington University Medical Center, Washington, DC.

The resurgence in interest in tracer kinetics in biomedical research has been mandated by the availability of a host of new tracers labelled with radionuclides of short half-life and by the recent advances in functional imaging with techniques such as PET and SPECT. Uniformity of nomenclature is preferable for the concurrent development of new models to understand physiological functions in normal and diseased states. The terminology for tracer kinetics has therefore been re-examined with respect to the report of Brownell et al. (1968). An updated and consistent nomenclature is proposed for biomedical research that may be applicable to all disciplines which employ stable or radioactive tracers in kinetic investigations. In particular, definitions and symbols are rationalized concerning the terms of metabolic systems, tracer and tracee, pools and compartments, tracer and tracee differential equations, matrices, integral equations, connectivity and stochastic properties, order zero and first moments. Finally, the kinetic properties of noncompartmental systems are considered, and a glossary of terms is included as well. Although an absolutely uniform terminology is impossible to achieve, we feel that the sets of terms proposed here can be adopted in many cases, and can help, when necessary, in introducing new definitions. Brownell GL, et al. Nomenclature for tracer kinetics. Int J Appl Radiat Isot 19; 249-262 (1968).

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While the determination of detector resolution is easily accomplished using an MCA, most older ganmm cameras do not provide pulse height analysis of the energy signal. It would be useful to have a sirmple approach which does not involve spectral analysis or even a calibrated SCA, while providing an accurate estimate of the energy resolution. With this intent we can employ a model of the photopeak distribution, which has been shown to be well approximated by a Gaussian function. Next we require two radionuclides with uncomplicated ganma emission decay schemes having similar photon energies. Based on simple measurements of the system response for each radionuclide separately within two energy windows, each being centered on the two photopeaks, and the Gaussian model an estimate of the FW]~ can be obtained from: = 2. 355A/$1n(Cll" C22 )-in(C12-C21) where Csj are the counts recorded for the ith photon energy in the jth window, and Zkis the difference in photon energies. The accuracy of this approach depends on the photon energies, the window widths and centering precision, and limitations of the Gaussian model. However, its strength lies in its sirmplicity, namely that the formalis~ does not require knowledge of either the absolute or relative activities of the two radionuclides or of the window widths.

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EFFECTS OF INCREASING ANGULAR SAMPLING FREQUENCY IN MYOCARDIAL SPECT IMAGES*

A NEW COLLIMATOR SYSTEM FOR AN IMPROVED SPECT IMAGING OF REGIONAL CEREBRAL BLOOD FLOW BY Xe-133 INHALATION METHOD. A. Komatani v K.Yamaguchi, M. Kera, T.Takanashi, Y.Hirose*, Y.Higashi* and N.Yamaoka*. Department of Radiology, Yamagata U n i v e r s i t y School of Medicine, Yamagata, *Shimadzu Corp., Japan.

M.F.S.Rebelo I, C.C.Robilotta 2, R.Abe 1 1-1nstitute do Corag~o, Hospital das Cl~nicas, FMUSP, 2-Instituto de Ffsica, Universidade de S~o Paulo, S@o Paulo, S.P., Brasil. Myocardial SPECT imaging is a well accepted diagnostic method in most cardiac clinics. However, there is still some controversy regarding to the total angular sampling of data: 180g x 560~. In spite of the contrast artifacts (false-positive infarctions) and geometrical deformations, generated by an incomplete angular sampling, the reconstructions from 52 projections obtained in 180~ are preferred to those reconstructed from 64 projections in560~. The main reasons are the general increased contrast in those images and a reduced acquisition time interval. In order to assess the effects of increasing the number of projections, that is, the angular sampling frequency, in the quality of myocardial SPECT images, computer simulations and phantom studies had been developed. The myocardium phantom was placed in an elliptical phantom, simulating the human chest (the radio between the activities in these phantoms is 5/I). Ramp filtered back-projection was applied to produce the tomographic images. Both the computer simulation and the phantom study showed that the images reconstructed from the 64 low count density projections within 180~ are equivalent to those obtained from the 64 high count density projections witNn 360g. These results indicated that by halving the sampling angle from 5.6~ to 2.8g, geometrical and contrast artifacts introduced by the incomplete 180~ sampling in SPECT iamges can be significantly reduced, while maintaining the increased contrast in the whole image. * Work partially supported by CNPq, FAPESP, FINEP.

For an improved imaging of regional cerebral blood f l o w by Xe-133 i n h a l a t i o n method with a r i n g type single photon emission computed tomography (HEADTOME), a new c o l l i m a t o r and a data a c q u i s i t i o n program were developed. Xenon clearance method is one of the most r e l i a b l e way to obtain the absolute value of cerebral blood f l o w , because o f i t s simple model and few influence of gamma-ray attenuation. But the i n f e r i o r i t y in s p a t i a l r e s o l u t i o n o f the Xe-133 i n h a l a t i o n SPECT seemed to be the most d e f i n i t e weak point. We designed the space and length of tungsten s t r i p s of the r o t a t i n g c o l l i m a t o r to obtain I00 cpm per p i x e l f o r 1,850MBq (50mCi) of Xe-133 gas i n h a l a t i o n . This design was i n f e r i o r in s e n s i t i v i t y but superior in s p a t i a l r e s o l u t i o n compared with conventional highs e n s i t i v e c o l l i m a t o r . The stepping r o t a t i o n - a n g l e o f the d e t e c t o r r i n g was changed i n t o 1.4 degree f o r every 180-degree of c o l l i m a t o r r o t a t i o n . The a b i l i t y o f t h i s new c o l l i m a t o r system was as f o l l o w s . S e n s i t i v i t y was estimated by c y l i n d r i c a l pool phantom of 20cm in diameter f i l l e d with 37Bq of Tc-99m, and i t revealed 13.5kcps/37kBq/ml. Spatial r e s o l u t i o n was estimated in FWHM by Xe-133 l i n e source placed in the c y l i n d r i c a l pool phantom. The FWHM was 13o6mm at the center and lO.3mm at the point of 6cm apart from the center of the phantom. The a x i a l FWHMwas 25.0mm. This new c o l l i m a t o r system enabled to provide f o r more r e l i a b l e rCBF measurement e s p e c i a l l y at the basal ganglia region.

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CHARACTERIZATION OF COLLIMATORS FOR A SURGICAL D E T E ~ O N PROBE SYSTEM. J.W.Logus, L. Golberg, AJ McEwan. Cross Cancer Institute, Edmonton, Alberta, Canada.

V E R I F Y I N G HOLE A N G U L A T I O N OF C O L L I M A T O R S F O R SPECT IMAGING. R.S. S l o b o d a , H.R. H o o p e r , and J.W. Logus. Cross Cancer Institute, Edmonton, Alberta, Canada.

Miniature gamma probes are increasingly being suggested as intra-operative devices to aid the surgeon in the detection of tumor sites defined by labelled monoclonal uptake. Optimal choice of collimation for these detectors has not been clearly defined. We characterized 3 collimation systems at Tc-99m energies with such a probe. A cadmium telluride (CdTe) probe system (Radiation Monitoring Devices model CTC-4) was tested with 3 collimators: the supplied protective cover which offers minimal collimation, the supplied 0.5 mm parallel bore collimator and a 10 mm parallel bore. Maintaining the detector at surface level above a water tank, a point source of activity was varied in depth directly under the detector and at various offset intervals. A map of isocontours was then defined for the three collimation systems by the use of a radiotherapy dose interpolation program (ATP). Sensitivity was measured by varying the background to "tumor" ratio and testing the three collimators with various (0.5, 1.7, and 3.0 cm diameter) spherical phantoms. Contour maps derived for the 3 systems indicate that the width of the 50% FWHM contour at a point 2 cm from the collimators, was 50 ram, 25 mm, and 13 mm respectively. Relative sensitivity, was 100%, 15% and 7%. For a sphere diameter of 1.7 cm, and a sphere to background ratio of 10:1, a 50% reduction in observed count (relative to the count at 1 cm) occurred at depths of 1.7, 2.0, and 2.6 cm with the 3 collimators. Interestingly, reducingly the sphere to background ratio from 10:1 to 5:1 had minimal effect on these ranges for the 3 and 1.7 cm diameter spheres. We conclude the choice of appropriate collimation should be simplified based on the location, size and background activity, as well as the amount of time the surgeon is willing to spend getting significant counting statistics.

Sunday, August 26, 1990

C o l l i m a t o r s u s e d for r o t a t i n g gamma camera SPECT should satisfy minimum standards for hole angulation to avoid degradation of r e c o n s t r u c t e d image quality. We have measured the regional hole a n g u l a t i o n of five p a r a l l e l hole and one fan beam collimator geometrically, using a simple p h a n t o m a n d a n a l y s i s s o f t w a r e w r i t t e n in our institute. Four of t h e five p a r a l l e l collimators tested were deemed acceptable for SPECT i m a g i n g b a s e d on the f o l l o w i n g criteria: (I) a v e r a g e h o l e tilt < 0.35 degrees, (2) hole tilt s t a n d a r d d e v i a t i o n < 0.20 degrees, (3) a b s e n c e of a distinct hole tilt p a t t e r n in the c a m e r a ' s u s e f u l field of view. For the fan beam collimator, the focal length and e f f e c t i v e focal spot size were o b t a i n e d from the m e a s u r e m e n t s in a d d i t i o n to the r e g i o n a l hole angulation. Taken together with that of other investigators, our r e s u l t s i n d i c a t e that as m a n y as one in t h r e e c o l l i m a t o r s currently b e i n g u s e d in S P E C T i m a g i n g s y s t e m s may not meet a c c e p t a b l e performance standards. We p r o p o s e that equipment m a n u f a c t u r e r s institute a g r a d i n g s y s t e m for c o l l i m a t o r s in order to identify those which meet acceptable hole a n g u l a t i o n standards for S P E C T imaging.

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FACTORS AFFECTING THE ROUTINE MEASUREMENT OF GAMMA CAMERA UNIFORMITY. K.C.Younq, K.Kouris and H.Jadallah. Dept. of Nuclear Medicine, Faculty of Medicine, Kuwait.

M. L. de Cabrejas, J. C. Dima and O. J. Degrossi.

i'he quantitative evaluation of gamma camera uniformity is dependent on variations in the technique used, and this project evaluated the effect of some of these. Sequential intrinsic measurements were made on a g~mLa camera using a Tc-99m point source at 5,10 and 40 Mcounts. Then sequential extrinsic measurements were made on the same camera at the same count densities for different collimators. Each image was analysed to find the integral uniformity (IU), differential uniformity (DU) and corrected relative standard deviation (CRSD). The latter was calculated by removing from the relative standard deviation the contribution due to statistical fluctuations. For intrinsic measurements at 5,10 and 40 Mcounts the means and standard errors were 7.5!.1%, 6.6~.2% and 6.4% for IU, and 2.11J.03%, 2.11+.02%_ and 2.19% for CRSD, respectively. The corresponding values for extrinsic measurements with a collimator in good condition were 7.9~.2%, 7.2~.1% and 6.9% for IU, and 2.352.02%, 2.54~.02% and 2.6% for CRSD. A damaged collimator was found to have values of 12.0!.3%, 11.8+.2% and 11.3% for IU, and 3.02J.02%, 3.03+.01% and 5.1% for CRSD. The magnitude of the increase in IU and DU at low count densities has been established. The mean value of CRSD has been shown to be independent of count density. A collimator in good condition appears to add about 0.5% to IU and DU and 0.4% to CRSD. The contribution of a damaged collimator to the nonuniformity may be established provided adequate statistics are obtained.

GAMMA CAMERA EXTERNAL QUALITY CONTROL IN ARGENTINA. Abstract received in a form unsuitable for reproduction

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C O U N T RATE L O S S E S U N D E R E N E R G Y - W E I G H T E D ACQUISITION. S.L. Breen. M. Blais, T.D. C r a d d u c k , V i c t o r i a H o s p i t a l , L o n d o n , Canada.

ASPECT - A DEDICATED BRAIN SPECT INSTRUMENT. R.E. Zimmerman, A.P. Smith, S. Genna, B.L. Holman Brigham and Women's Hospital, Boston, and D i g i t a l Scintigraphics, Inc. Cambridge, MA, USA

M e a s u r e m e n t of c o u n t r a t e l o s s (CRL) is a s t a n d a r d p a r t of a n y s c i n t i l l a t i o n c a m e r a quality control regimen. Energy-weighted a c q u i s i t i o n (EWA) is a r e c e n t l y d e v e l o p e d m e t h o d of c o l l e c t i n g g a m m a c a m e r a i m a g e s t h a t u s e s t h e i n f o r m a t i o n c o n t a i n e d in scatter events to improve image contrast. At p r e s e n t , no s t a n d a r d q u a l i t y a s s u r a n c e p r o t o c o l f o r E W A is in use. Two s c i n t i l l a t i o n c a m e r a s ( S i e m e n s Z L C 7500) equipped with Weighted Acquisition Modules w e r e t e s t e d u s i n g s t a n d a r d C R L tests. A s o u r c e of T c - 9 9 m in s o l u t i o n w a s p l a c e d in a t h i c k l e a d pot. C o p p e r f i l t e r s of k n o w n attenuation factor were used to vary the i n p u t c o u n t r a t e (CR). Two-source tests w e r e a l s o c o n d u c t e d to d e t e r m i n e C R response. CRL measured under normal single frame acquisition agreed with manufacturer's s p e c i f i c a t i o n s of 20% l o s s at a n i n p u t of 1 4 0 , 0 0 0 c o u n t s p e r s e c o n d (cts/s). Results c o l l e c t e d in d u a l f r a m e m o d e ( s i m u l t a n e o u s c o l l e c t i o n of E W A and s t a n d a r d a c q u i s i t i o n ) s h o w e d 20% C R L in b o t h a c q u i s i t i o n s a t i n p u t C R r a n g i n g f r o m 6 0 , 0 0 0 to 8 0 , 0 0 0 cts/s. C R L t e s t s c o l l e c t e d in s t a n d a r d and energy-weighted f o r m a t s do n o t s u f f i c i e n t l y d e s c r i b e t h e p e r f o r m a n c e of E W A s y s t e m s . T h i s l o w e r v a l u e of t h e 20% C R L m a y be d u e t o p r e p r o c e s s i n g o v e r h e a d in t h e e n e r g y weighted module.

ASPECT is a c y l i n d r i c a l Anger camera consisting o f a single crystal annulus of NalCT1) with 31 cm i . d . by 8 mm thick coupled to 63 PMTs. The output of the p r e a m p l i f i e r s is summed and used to gate 63 ADCs. The output of the ADCs is connected to a d i g i t a l p o s i t i o n analyzer f o r rapid computation of the corrected posi t i on and energy signals. M u l t i p l e image arrays can be stored corresponding to m u l t i p l e pulse height windows. The c o l l i m a t o r is a three section p a r a l l e l hole c o l l i m a t o r cut in a c u r v i l i n e a r fashion and permits an opening f o r the brain of about 23 cm. Measured parameters describing performance f o r Tc-99m in a 20 cm diameter water f i l l e d phantom appear in the table.

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Table Resolution Slice Thickness S e n s i t i v i t y (mt in a i r ) Sensitivity Energy Resolution ( a i r )

8.3 mm 8.4 mm 7.5 cps/uCi 2200 cps/uCi/cc 10.1%

The ASPECT has proven to be e s p e c i a l l y r e s i s t a n t to uniformity a r t i f a c t s since the p r o j e c t i o n data is averaged over a l l crystal p o s i t i o n s . Collimator correction data is acquired i n f r e q u e n t l y but f o r very high count d e n s i t i e s . The ASPECT has proven to be a r e l i a b l e , high r e s o l u t i o n brain SPECT imaging system.

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P H A N T O M FOR A N A L Y S I S

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K . T a m u r ~ , K . S a s a k i , M . K o b a y a s h i and T . K a t o . A k i t a University Hospital, AKita, Japan In o r d e r to e v a l u a t e S P E C T i m a g e q u a l i t y , w e have developed a new brain phantom containing multiple line sources. This p h a n t o m is a w a t e r - f i l l e d h e m i s p h e r e 22cm in d i a m e t e r , i n the half of w h i c h 23 t h i n parallel v e s s e l s ( 0 . 5 m m in d i a m e t e r ) c o n t a i n i n g rad i o n u c l i d e are a r r a n g e d p r o p e r l y as line sources. L i n e s o u r c e s are set p e r p e n d i c u l a r l y to axial, s a g i t t a l and c o r o n a l scan d i r e c t i o n s , s o that s p a t i a l r e s o l u t i o n can be e s t i m a t e d by m e a n s of I s o - F W H M c u r v e s . * U s i n g this p h a n t o m and d u a l h e a d s c i n t i l l a t i o n c a m e r a ( T o s h i b a G C A - 9 0 B - E 2 type) w i t h n e w l y dev e l o p e d s l a n t - h o l e c o l l i m a t o r s , w e c o m p a r e d the i m a g e q u a l i t y of t o m o g r a m s a q u i r e d by axial, s a g i t t a l and c o r o n a l scans. Our i n i t i a l e x p e r i e n c e r e v e a l e d that a x i a l scans was best in t h r e e scans b e c a u s e F W H M v a l u es and d i s t o r t i o n of the i m a g e w e r e m i n i m u m . A n a l y s i s of i m a g e q u a l i t y w i l l be e a s i l y p e r f o r m e d by this p h a n t o m not o n l y in SPECT but a l s o in PECT s t u d i e s . * I s o - F W H M c u r v e s w e r e o b t a i n e d by c o n n e c t i n g e q u a l F W H M v a l u e p o i n t s w i t h p o i n t s p e a d func t i o n of S P E C T i m a g e of line sources.

A general purpose mlcro-computer based quality assurance package designed to be used under an expert system shell P. Slomka A. Todd-Pokropek, Victoria Hospital, University of Western Ontario, London, Canada and University College Hospital, London, UK Quality assurance protocols which are highly automated, requiring little human intervention, seem well adapted both for use by a busy nuclear medicine department and in centres which possess little experience in instrumentation (sometimes " both). With support from the IAEA, a package has been designed which attempts to minimize operator intervention yet will provide intelligent responses in cases of abnormal functioning of a gam/~a camera. To provide the widest coverage of existing systems, the software package has been designed to run on a standard (IBM-type) microprocessor, where all the low level functions are written in C. The expert system component is designed in Prolog. The basic input data are the flood image. The package is designed to handle data from a variety of cameras (round, hexagonal, rectangular etc) and to compare the observed feature of the image with a predefined configuration. Thus, a data base is maintained of camera types, results, tolerance limits, and (in the extended) system, actions to he taken. This data base forms the interface between the low level image processing system and ~he expert system, which run autonomously. An important design aim has been to make the processing modules independent of the type of camera to be analyzed, and to have a common format similar to that used for Interfile for reporting of results. Examples are shown of the analysis of various cameras, with various types os defect.

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USE OF SENICONDUCTOR DEVIC~ IN RADIATION IHA6IN6

R. Ropolo, P~6~ ~ E!~!9~! Serv. 8 e d i c i n a N u c l e a r e , Osp. H o l i n e t t e , Torino, i t a l y Two dimensional r e c o r d i n g of radiation-emitters p a t t e r n s f o r l o c a l i z i n g and q u a n t i f y i n g r a d i o a c t i v i t y i s important in medical r e s e a r c h . In our work we study the f e a s i b i l i t y of a u t o r a d i o g r a p h y by means o f s o l i d s t a t e image s e n s o r s , p r o v i d i n g , in p r i n c i p l e s , s e v e r a l advantages over t h e c o n v e n t i o n a l approach. The way He have i s p l e w e n t e d i s to use the t h i n sensitive s i l i c o n l a y e r o f a charge coupled d e t e c t o r in c l o s e a p p o s i t i o n t o the r a d i o a c t i v i t y - l a b e l l e d specimen a s a replacement f o r n u c l e a r e m u l s i o n . Charge coupled d e v i c e s (CCDs) c o n s i s t of a b i d i s e n s i o n a l a r r a y o f p i c t u r e element s e n s i n g s i t e s embodied in a silicon wafer by MOS t e c h n o l o g y . The electrons r e l e a s e d by the passage o f a i o n a z i n g p a r t i c l e a r e collected in t h e p h o t o s i t e p o t e n t i a l H e l l s . CCD a c t i o n c o n s i s t in charge i n t e g r a t i o n a t the p h o t o s i t e s during a p r e d e t e r s i n a t e d t i m e - i n t e r v a l and in r e a d - o u t o f the c o l l e c t e d image, by p u l s i n g t r a n s f e r e l e c t r o d e s connected in p e r i o d i c manner, thus s h i f t i n g the potential Hell array. Inherent a d v a n t a g e s are: low n o i s e performance, good u n i f o r m i t y , high g e o m e t r i c accuracy, digital c o n t r o l o f image r e a d - o u t and p o s s i b i l i t y o f o b t a i n i n g a l s o an o p t i c a l image of the specimen. The CCD used N a s a THX 31138 modified a t our request. In t h i s way we gained a c c e s s to t h e whole sensitive s u r f a c e measuring 6 . 6 4 ms x 5 . 8 2 mm comprising 288x208 p i x e l s . A microcomputer was used a s c o n t r o l f o r t h e d e t e r m i n a t i o n o f time i n t e g r a t i o n and for the d i g i t a l i z a t i u n of the image. S e v e r a l images o f phantoms Has a c q u i r e d and good results was obtained in terms of resolution, Modulation T r a n s f e r Function and system l i n e a r i t y .

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AN APPLICATION OF MULTI-MODALITY DISPLAY AND PROCESSING TO PET AND MRL L.M. Bidaut. B. Poncelet, ULB-H@ital Erasme, Brussels, Belgium

CT AND RADIOLABELED ANTIBODY(AB) SPECT "FUSION" TO IMPROVE STAGING OF THE MEDIASTINUM IN PATIENTS WITH LUNG CANCER. E . L . K r a m e r , D.Reddy, M.Noz,R.Heelan, V.Rusch, M . G r a h a m , H.Kalalgian, I.Ginsburg, S.M.Larson. Memorial Sloan-Kettering Cancer Center, and N Y U Medical Center, New York, NY, U S A

Following the need of using, on the same patient, similar but complementary modalities such as PET and MRI for producing composite images and results facilitating evaluation and diagnosrs, a multi modality imaging and processing syste'~ has been implemented in our lab, mostly for brain studies. The system matching method 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 interpatient comparison through the alignment with a common "reference" template. Our application uses MRI to help 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 MRI also helps in identifying the different tissues types (e.g. fluid, gray and white matter), permitting the use of proper parameters when applying metabolic models calculations on the whole PET data set. Future development will include more efficient correction of metabolic data through the use of true structural data, and also the introduction of other modalities (particularly speclroscopic magnetic resonance which might be seen as the missing link) into the list of modalities the system is now able to handle. Also, more specific/automatized processings (acquisition, matching, display calculations) might be developed in order to accommodate specific pmtocols linked to different molecules and/or pathologies. 5-parts of which have been developed while at UCLA Division of Biophysics & NuclearMedicine,Los Angeles,USA

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OPTIMIZATIONOF LIVER IMAGING PARAMETERS FROM PHANTOM DERIVED RECEIVER OPERATOR CHARACTERISTICCURVE ANALYSIS Barb Bartkiewicz Walter Huda Yvonne McFarlane I. David Greenberg Health Sciences Centre and Manitoba Cancer Treatment and Research Foundation Winnipeg, Manitoba The relationship between gamma camera variables (counts per image, collimator type, distance from collimator) and diagnostic imaging performance was quantitatively investigated using Receiver Operator Characteristic (ROC) analysis, a College of Ameucan Pathologistslivcr phantom was used with a Technetiurn-99m flood source to generate aPllatera[ liver images with "cold lesions", Imaging was performed 011a wide field of view gamma camera equipped with a high resolutiura and allpuqmse collimator (Elscint Apex 415).These images were read by four Nl~clear Med iciue physicians and the areas under the resultant ROC curves computed. Areas urlder the ROC curves arc taken as a quantitative estimate of diagnostic accuracy. The average area under the ROC curve for the ]bur physicians reading the same 500 k standard image 6 times was computed to be 0.668 +_ 0.049. Increasing accuracy was noted as image counts increased from 200 k to 2000 k with the #reatest increase occurri~ag between 500 k and I000k (, area = 0.113);lesser degrees ofimprovcmerit occurred between 200 k and 51)0k (, area = 0.038) alqd 1000 k arid 2000 k (, area = 0.080). 500 k images sbtaincd with a high resolution its colnl?alcd to an all purpose collimator showed only mininnll improvement (* area - 0.014) despi~e a 2.3 fold increase in counting time requhcd. As expected, diagnostic accuracy dccl:eased with distance from the collimator. It is concluded that for liver imaging, one shou.ld ain't at obtaining individosI images with >- 1,000,000counts. For the system tested, use of a high resolution coltim:ator would no{ appear to be justified.

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Radiolabeled A b specific for lung cancer m a y help stage lung cancer in the mediastinum, but a lack of anatomic landmarks on the A b scan hinders interpretation. Matching o f CT to A b SPECT m a y overcome this problem. Before surgery, patients with non-small cell lung Ca had chest CT. Patients then received 30 mCi I.V. o f Tc99m N R - L U - 10, an Ab localizing in lung Ca. SPECT was acquired about 18 hrs later with Co-57 markers placed on the patient's chest. Dual energy windows, one each for Co-57 and Tc-99m, were used giving two sets o f projections. Reconstruction w a s performed yielding 6 mm-thick slices. CT and SPECT were analyzed with qsh, a general purpose image processing a n d display toolkit operating on a Microvax II with a graphics display.Using external landmarks identified b y the Co-57 markers, 3 CT and SPECT slices at corresponding levels were chosen and displayed. Pairs o f corresponding points on the slices were defined on SPECT, at fiduciary landmarks and at the b o d y edge using scatter, and on CT at corresponding anatomic features on these slices. A 2-D transformation describing the relationship between corresponding pairs o f points w a s defined. Regions o f interest over mediastinal and lung abnormalities were d r a w n on various CT slices and remapped onto the corresponding SPECT slice using this transformation. This allowed definition o f the anatomic site o f A b uptake. Results were compared with surgical/pathological findings. Sites o f intensely increased Ab uptake correlated with lymphadenopathy. Less intense foci on SPECT more often corresponded to blood pool. W e conclude that fusion imaging with CT and Ab SPECT permits direct comparison o f anatomic (CT) and radiolabeled A b localization (SPECT). This m a y improve interpretation o f radioantibody images and improve mediastinal staging in patients with lung carcinoma.

ORTIIOP/dg PROJECTION (OP) THE JAWS' B O B E S C A N S TECIINIQUE AND N O I ~ V A L I I E S . A. Bockiseh, R. K~nig, A. Hotze, B.Briele, K.-d. Biersaok; Dept. Nucl. Medicine, Univ. Bonn, W.Germany A computer code was developed, which uses conventional Single Photon Emission Computed Tomograms (SFECT) of the head, and performs a cylinder projection of the jaws, resulting in a planar representation. Since the structures under investigation are quite small, delicate data processing is necessary. ROIs which mask out soft tissue activity are generated semi automatically. The processed images containing virtually only the activity originating from the jaws are used for the cylinder projection described, which is performed by sector integration. From the projection images, relative activities are calculated for each dental region. The position of the regions are determined by anatomical models and calibrated by patients presenting localized dental disease. A computer code was developed, which allows a mostly automatic creation of the projection images and the numerical data. The procedure takes about 20 min with a Siemens Mikro-Delta computer and may be significantly speeded upby using the array processor. From 20 subjects with healthy teeth, normal values were obtained. The activity in the region of one tooth was normalized both on the value for the contralateral tooth, or the average value for the jaw. There was no right - i e f t asymmetry found. Results: Normal values relative to average jaw: Dental Regions. Upper line: Maxilla; Lower i.: Mandib. I 2 3 4 5 6 7 8

0.88(8) 0.88(7) 0.89(6) 0.93(6) 0.95(6) 1.15(5) 1.23(9) 1.23(11) 1.10(9) 1.07(8) 1.0~(6) 0.95(5) 0.~(5) 0.98(6) 1.06~) 0.98(10) Conclusion: The OP of the jaws is the adequate presentation to evaluate dental lesions. The set of normal values allows the sensitive detection of even slight changes in the odontogenic activity like early and chronic disturbences of the mineralisation activity.

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APPLICATION OF S U R F A C E OVERLAP CRITERION FOR REGISTRATION OF NUCLEAR MEDICINE IMAGES. p,r Y.Yonekura, S.Sasayama, N.Tamaki, Y.lwasaki, K . M i n a t o , J.Konishi, Y.Bizais*. K y o t o U n i v e r s i t y Hospital, Kyoto, Japan, and * Pro jet DIMI, Nantes, France.

F. Friedlander , J.L. Barat , and F. Meyer . *Centre de Morphologie Mathematique, Ecole des Mines, 35 Rue Saint-Honore, 77305 Fontainebleau, France. **Bordeaux University Hospital, France. It has been shown that in order to assess a reproducible measure of the left ventricular ejection fraction from equilibrium gated nuclear angiography images, it is necessary to automate the contouring of the left ventricular region of interest. A new method based on Mathematical Morphology is presented; The contouring algorithm uses morphological operators such as the erosion, the dilation, the opening, the watershed or the skeltonization operators. Two versions of the method are proposed. In the 2D version each image in a sequence is considered independently from the others; The operator initializes the detection of the contour by drawing an interior marker inside the ventricle and a polygonal exterior maz~er surrounding it. The area bounded by the two markers is considered a "row contour" for it is thicker than the real contour. A thinning algorithm is then applied to the row contour under the control of the laplacian image, resulting in the final contour. In the 3D versiton, the 16 images of a sequence are stacked up, resulting in a 3D image. The 16 left ventricular projections generate a particle in the 3D image, that can be segmented by generalizing the 2D algorithms. In the case of 3D, the operator initializes 3D interior and exterior markers, The method has been programmed on a SOPHA system. We show on a sample of 71 sequences that in both 2D and 3D cases, the reproducibility of the method does not suffer from the manual initialization. We also show hew this step can be automated~ Then we analyze the correlation of the new method with contrast angiography (r=0.81 for the 2D version, r=0.83 for the 3D version), and compare, on the same sample, this method to three commercially available fully automated methods (r~0o76). Finally we show how the method can cope with extremely__ pathological cases.

D e r i v i n g a d i a g n o s i s from medical images most often involve to relate i n f o r m a t i o n a v a i l a b e l in images p r o d u c e d by v a r i o u s m o d s l i t i e s and/or in various patients, and necessitate to register images at first. We have developped a new registration method based on the o p t i m i z a t i o n of s i m i l a r i t y criterion, maximizing the surface overlap of the images pair. In s u m m a r y , a s s u m i n g t h a t the i m a g e s to r e g i s t e r correspond through a geometric transformation (GT) , for various GT parameters, the difference image is computed, from which the h i s t o g r a m of i n t e n s i t y d i s t r i b u t i o n , in a region of i n t e r e s t (ROll), is derived. B e c a u s e of the p r o p e r t i e s of s u c h an histogram, maximizing its peak area is equivalleet to m a x i m i z i n g the surface o v e r l a p of the image pair. Thus the optimal registration transformation is the ST corresponding to the largest peak area value. The p r o p o s e d m e t h o d has been tested on a set of s i m u l a t e d i m a g e s a n d c o m p a r e d to the s t a n d a r d techniques, leading to the following remarks: the m e t h o d allows to s e l f - e v a l u a t e the q u a l i t y of' the results and to handle colored noise and small signal differences. Therefore, the surface overlap criterion was e v a l u a t e d on m u l t i m o d a l i t y medical images (ventilation Xe-133 vs perfusion Tc-99m lung scans, and FDG PET vs IMP SPECT images) . Results were satisfactory for these images and gave interesting insight about the choice of a registration ROI.

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' P H ~ DIM.K~S](Y@AL C~P~TFER SIMULATION OF SPgYFf IMAGING OF T ~ H ~ g r . A.S_ Boyers, R.L. E i s n e r , and R.E. P a t t e r s o n . Car.ly]e Fr~ne.r Hrt Ctr/Crawforfl Long IL~p o f Ftaory Univ, Dept~ o f ~ i c i n e (Co_r~liol) and Radiolo~/, s a t ] ~ i ~ , (~.

EARLY VS DELAYED Tc-99m MIBI SPECT : A PROGRAM FACIbiTATING THEIR INTERCOMPARISON. K. Kouris, M. Awdeh, H.M. Abdel-Dayem, I.M. Hassan, C. Constantinides, M. Nair, Dept_ of Nuel. Mad. Kuwait University, Kuwait

~ have developed a three dimensional compat~r simulation of the a(.~tAsiti(~l, processh~g, and q ~ n t i t a t i o n of SPECP myocardial pe.Yfusion imaging. T ~ ox~aputer model allows variations of the size, shal~% position, and orientation of the ~ a r t with r~_spect t~ the. acx~isJt~on arc of the simulated rota-tirol ~ camera s y s ~ . Quantitative results obtained from SPECf i m ~ of the myocardium are influenced by multiple technical factors; attenuation, noise, re~olutien, c~rdiac motion and patient motion degrade image quality and reduce diagnostic accuracy. All of these technical factors can be examined with the simulation. In clinical or animal studies it is ofte~ not possfble to quantify the effect of a variation of an individual parameter on the final S F ~ image qu~dity; wbereas, the. c o m ~ t e r simulation allows all of t]r~e parameters tx> be held constant while ~ H y one is varied. Isolating parameters in this fashi~, permits a quantitative eva/uation of these individual parameters t } u - o ~ a c ~ s o n of Bullseye displays. For example, t ~ r e s u l t ~ of the sJxs~lations hatter define relationships and provide limits on artifact production in ~PECI" from patient-related effects. ]]~ particular, the resu/ts of the simulations on patient motion provide an i m p o t e n t d a t a b a s e for clinical stndie.s of patients who show movement during the t.~c~e of f/~eir SPE(~F .,~e~gn. As with otlger simulafiords, this model appears to offer promise to guide. identificati~, of new ~ s e a r c h questions and education of personnel involved in a l ] a~I~x~t.q of S}~]T.

Sunday, August 26, 1990

lecent reports indicate that Tc-99m MIBI uptake in the myocardium may undergo washout and/or redistribution. We developed a program to enable a quantitative comparison between early (E) (lh) and delayed (D) (3h) Bullseye plots (BPs) from E and D SPECT studies acquired after a single injection of Tc-g9m MIBI at stress or rest. The acquisition and reconstruction parameters for the E and D studies were the same. The EBP is first decay corrected to the time of the D study so that in the absence of washout or redistribution the corrected BBP would be identical to the DBP. The two BPs are displayed side by side with their corresponding histograms underneath in 10% steps. Each histogram presents the no. of BP 'pixels' Vs %counts where i00% denotes max (EBP, DBP). In the second display each BP is transformed to a 5-colour image and corresponding histogram in 20% steps with respect to the same maximuml. In the third display, all BP pixels with counts in a user specified range are blackened and their respective number in the E and D BPs indicated. In another display the E-D and D-E images are displayed with negative values set to zero. Finally, the %(E-D)/E and %(D-E)/E parametric images are presented with histograms in 5% steps. The former reflects washout and the latter redistribution. Utilization of this program has produced evidence that there are significant changes in the distribution of Tc-99m MIBI uptake in the myocardium within a time period Of 3 h from injection.

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THE NAILIRAL OR INTUITIVE DISPLAY OF TI-201 MYOCARDIAL DISTRIBUTION. J.R. Perry, J.G. Ballard and B.M.W. Tsui. UNC Hospitals, Chapel Hill, NC, USA.

D~'I'ERMINATION OF CUTOFF ~ C Y OF BU'rr~I~WORTH FILTER BASED ON PNf)JEDTION IMAGE OOUNT IN SPECT STUDY. S.Minoshima, T.Shiina, J.Okada, K.Uno, Y.Kitakata, Y.Anzai, Y.Uchida, N.Arimizu. University of Chiba, School of Medicine, Chiba, Japan.

Polar coordinate, or bull's eye, display of Tl-201 myocardial perfusion and washout is an efficient method for displaying information from multiple slices of image data simultaneously. However, the polar coordinate display method is abstract and distorts the original images such that it is difficult for the referring physician m visualize what has happened to an area of interest seen on a slice image. A more natural, or intuitive, representation of this type of data would be to display the original myocardial tomographic images with additional visual aids employed to portray isotope redistribution. A method was devised to display similar tomographic slices from stress and redistribution datasets and utilize a special color table to demonstrate and quantitate TI-201 redistribution as a change in color. Tomographic images of diagnostic interest from the stress (or initial) and redistribution datasets are selected by the interpreter for quantitative analysis. The initial image is normalized for the video display so that the highest level of the display scale is adjusted to coincide with the maximum pixel value in the myocardium. The matching redistribution image is then normalized by mapping the image pixel values to the same display scale as determined for the initial image. These images are displayed side by side with a 16 level color strip utilizing the hot metal spectrum for the upper 50%, and the green and blue object spectra for the respective 50-25% and 250% portions of the display scale. A change in T1-20I concentration for a suspicious area of myocardium may then be quantitated by counting the number of color level changes, with each level representing a 6.25% change. Normalized color display of T1-201 tomographic images is simple to implement and provides a natural, intuitive form of image display for clinical use.

In clinical SP~L~r study, Butterworth filter was useful for reducing statistical noise. Cutoff frequency of the filter, however, was determined through trial and error because of unknown noise spectrum of the image. This investigation was undertaken to develop a simple method for determining cutoff frequency based on projection image count in SPECT study. Six projection image sets of different image count (8k to 30k per projection, 64 X 64 pixel~ 64 projections) were obtained over 360 degrees from cylindrical phantom (20 cm in diameter) which contained 5 cold spots (5 mm to 21 mm in diameter). Butterworth filterings with cutoff frequency from 0.234 to 0.390 / pixel (order of the filter was fixed 8l were applied to each set of projection images. Transverse images were then reconstructed using filtered backprojection method with attenuation correction. 60 sets of reconstructed images were finally obtained. In each reconstructed image, resolution was determined visually by counting the number of cold spots and the degree of statistical noise was represented as standard deviation / mean count in the uniform part of the phantom. From the point of view of evaluating images, image quality was required to be stable even if projection image counts were variable among patients. High resolution and high statistical noise (high cutoff frequency) or low resolution and low statistical noise (low cutoff frequency) were not suitable for practical reading. To decide optimal cutoff frequency, we devised resolution / statistical noise ratio (RS ratio) and projection image count vs. cutoff frequency chart. Under fixed RS ratio, which should be determined by clinical study, relation between projection image count and cutoff frequency showed a certain correlation on the chart. This result suggested that optimal cutoff frequency in each examination could be obtained from projection image count using this chart.

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RECONSTRUCTION OF SPECT IMAGES: COMPARISON OF FILTERED-BACKPROJECTION AND INVERSE FOURIER TRANSFORM METHODS. J.Darcourt ~, F.Martin 2, J.B6noliet ~, F.Lapalus 1. Dept. of Biophysics and Nuclear Medicine, CAL, Nice, France 2. Dept. of Astrophysics, University of Nice, France

SCATTER AND ATrENUATION CORRECTION IN SPECr BY USING DENSITY MAPS AND MONTE CARLO SIMULATED SCATrER FUNCI~ONS M Liun~ber~. S-E Strand. Radiation Physics Department, University of Lund, Sweden.

Reconstruction of cross section images from multiple projections is usually performed by filtration and backprojection (FB) of the raw data. We developped on a nuclear medicine computer (Simis Sopha Medical) a method using an inverse Fourier transform (IFT). For a given slice plane each projection is a profile of activity. The complete set of these profiles represents the cross section image in the projection space called Radon space (also called "Sinogram"). The reconstruction process consists in performing an inverse Radon transform to reconstruct the image from the data known in the Radon space. The projection slice theorem states that the onedimensional Fourier transforms (FT) of each projection are the corresponding sections of the cross section image in the Fourier space. Thus the reconstruction can be achieved as following: Radon space -FT---> Fourier space -IFT--->lmage. The results of this method have been compared with the classical FB method. The impulse responses (in pixels) of the two algorithms are 1.59 for IFT and 1.84 for FB. The errors in image reconstruction of 2 fantoms were mesured and were equal for both method considering the object itself. Considering the total field of view the errors were inferior with IFT than FB (0.75 vs 0.98 with the "hot spots fantom"). The signal/noise ratios were mesured for each method on in vivo studies (myocardiN, brain perfusion, liver, gated blood pool scans) and were found similar. We conclude that IFT method can be used as well as the classical FB method in nuclear medicine as long as computers are equiped with fast Fourier transform devices.

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Purpose: In nuclear medicine quantitative SPECT studies, based on a standard NaI(T1) scintillation camera equipment, today has a limited accuracy due to the effects of photon attenuation in the object and contribution of events in the tomographic images originated from photons scattered in the object. A new scatter and attenuation correction method is presented that is based on tabulated Monte Carlo simulated scatter line-spread functions for different depth and lateral positions. Method: A reconstructed emission map is used to estimate the source distribution in the object in order to calculate the scatter contribution in the projection data by using the appropiate scatter line-spread functions. The scatter is then subtracted from the original projection before applying the attenuation correction. The correction for photon attenuation uses maps describing the density variation in the object. Simulation studies have been done with a clinically realistic source distribution in both a cylindrical, homogeneous water phantom of different radius and in a non-homogeneous clinical realistic computer phantom, obtained from a Computer Tomography study. The simulation studies have been made for photon energies corresponding to TI-201, Tc-99m andln-lll. Results: The results show excellent quantitative results with an accuracy within • for most of the source positions and phantom sizes. It has also been also shown that the spread in the event distribution has been significantly decreased and that an enhancement in the contrast has been achieved.

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August26,1990

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A:~AI,:~I~ OF RADI011.~I,:b~ODETEC~0~[ OF .~IORS BY DIGITAL .~,~ULTI-SUBI~ACTI01~ -~EC!~QUE L~2oor~tory of R,~dioisotopes ],~edical Ao~{demie - Sofia (BG) A co :pu%er sssis%o4 p:'ogr~m ',,,ithdigital n u l % i subtraction technique (D:~Sq') has been d~veloped to ~.nn!~se the ~:A}'~-acoumul&%ion in tissues a%%~qued b~" %'~le cancer ,~nd }de inst.%erases. In 45 patients with liver me%~siases of ~.~oloreo%sl Carcinoma an exa0% topogTaphir loc~,~lisa%icn of metastases nr,d 0.beonoe of extl~ahena%io %umoF 4,-,posi{;s are prerequisites for cuP:~%ive p,9~%i~%1 ]:eps%eoT_cm~. i% w~s the aim of this s%~.t;~,r 50 eluoid:~%e %}~e u ~ of I,IAll-aocimut!ation }~efO~'e suz'giezl in%ePven%ion. ~ e ~,,~$-tec}miq~le :,,~%s c':to~.:n "L'a cive rise 9o artifactual positive r e ~ o n s ~ which could ])e ,~volded by expe~:ienoed clinicians. ~le digital mu]ti-sub%r~ot~,on technic!us (~]ST) is sho~rin c 9o%sn%i~l s.s m diagnostic tool~ because the ~,emainin Z ~o~}.ok~'ound activity of %he MAB-s~bs%~noe is sub%racted~ "~he bone-artefact of DL~J] (Indium-Ill connected in the me.prow) and k i ~ e y - ~ r t e f a c t are subtm~cT,ed u s i n g To-]~ne and To-k~dney markers and %he imp]~-nt~i:[om of MAP, in %~e hi,~:tological l~eal%hy tissues on %he liver non a%%aqued by the %minor ~re subtr~,c%ed u s i n g To-su!phoco~loid or diphosphon~%%. I~ olini0ml pPac%ioe is ~ need %0 kno~.~] the limits of sensivity and specificity of the .~e%hod~ i~.rtico.l~zry sines i% is likley %0 be of most use if sm~ll t~l:~or oD earl Z stages of recurrence c,~n be detec%ed~ since these are most ~m~enable %o %reeteman%. I% is of gr_ea% i~por%~noe • do%ermine%ion of the depth of deposit of l(AB-s~/be%~noe in d~terminin g ea~ v~ty fcrm:,tions and such of necrotic n~%ute u s i n g the Digital multi-suit%Pectin %ec}~li,lue (IZ[ST),

E X P ~ R I ~ N C ~ W I T H A N M S - D O S COMPUTER F ( ~ N U C L E A R ~ D I C I N E IMAG~ ACQUISITION AND PROCESSING. J.L.Dach, Memorial Hospital, Hollywood, FL., USA. Our previous reports dealt with the design and programming details of an MS-DOS IBM Compatible Computer interfaced to an analog gamma camera for routine clinical use. After three years of use at five sites across the country, we describe the strengths and pitfalls of such a system, and recommend specific quality control procedures. One major advantage of this platform has been the steady improvement in C Compiler programmingtools, as well as the increase in computer speed as evolution from the 4 ~4z 8088 to the 20 MHz 80386 chip occurred. The ease of altering the programming code allowed trial of new image processing ideas. One example was an improvement in the left ventricular edge detection algorithm for ejection fraction which gave the ability to interactively correct the position of an individual edge dot. Gates' method r e n o g r a m ( ~ R d e t e m m i n a t i o n w m s easily implemented in the BASIC language, Abundance of accessory hardware, for example, a $200 commercially available internal modem and communication software package provided remote image transmission as well as connection with a nuclear medicine electronic bulletin board service. One subtle error in the software went undetected because it occurred only at unusually low count rates of 50-100 counts per second resulting in non-uniform frame density. Therefore we recommend routine testing at both very low as well as high count rates. Migration to the new 80486 chip will probably further the utility of the MS-DOS Computer in nuclear medicine.

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APPLICATION OF A WELL-TYPE GE-DETECTOR IN BLOOD CELL SURVIVAL STUDIES. S.J. Oldenburg, M. de Bruin, R.A. de Vries and A. van de Wiel. Dept. of Radionuclide Techniques, University of Utrecht, Utrecht, The Netherlands.

DIGITAL ARCHIVES IN NUCLEARMEDICINE

Purpose of this study is to investigate the survival characteristics of different populations of blood cells simultaneously within one individual. The method can be applied to measure the survival times of combined populations of autologous and homologous erythrocytes or platelets. By means of a well-type Ge-detector with high energy resolution and also high photopeak efficiency both radioisotopes can be detected at once. Owing to the high signal to noise ratio activity concentrations down to 0,009 Bq have been measured. Red cells were labelled after incubation with Co-57and Co-58-tropolonate respectively, with initial labelling efficiency of 70%. Labelling of th~ platelets was performed by incubation of the cells with :n-lll- and In-ll4m-tropolonate, with a labelling efficiency of 60%. Comparing our labelling procedure with the well-known Cr-51 method, using identical populations of cells within one individual, a good agreement could be observed. However, there are also differences. The Coerythrocytes, injected in vivo, showed a strong initial decrease of activity, which has not been observed with the Cr-51-ery's. This has to be studied further. Due to the high sensitivity of the equipment low activities could be administered in vivo (18k Bq together for Co-57 and Co-58, and i00 kBq together for In-lll and In-ll4m), which led to low radiation doses (0,032 and 1,6 mSv respectively). Therefore, with our method it is possible to study more than one population of red cells/platelets within one individual, using low activities with a low radiation dose.

Sunday, August 26, 1990

F. Bitter, B.A. Bitter, R. Weller, L. Almasi*, E. Mate* and W.E. Adam. University of Ulm, Nuclear Medicine, Ulm, FRG, *Dept. of Nuclear Medicine, University of Szeged, Hungary. Currently the images of nuclear medicine institutions are stored on magnetic media. The documentation is done with hardcopies. Officially magnetic media are not accepted for documentation purpose and hardcopies do not allow further processing. The access to the original data is time consuming and personal intensive. There is a demand to store at least the original information cheaply, safely and direct accessibly. The appearence of the optical disks together with a jukebox facilitates digital archives at least for nuclear medicine. As a prerequisit it is necessary to connect all imaging devices through its data systems within a nuclear medicine institution to a local area net (LAN) forming a PACS (Picture Archiving and Communication System) Data compatibility must be fulfilled as well as a positive patient identification. Quality controls must provide for data security and reliability. An effective retrieval system must serve for fast access to the archives. Such a, local net in addition should be connected to the hospital information system in order to reduce the administration work in nuclear medicine. Since PACS currently is developed mainly for the other modalities ( S T , MR, DSA, DR) through the industry, nuclear medicine should participate in this development with its particular needs.

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A NETWORK SYSTEM FOR DATA PROCESSING AND MANAGEMENT IN A PET CENTER. H.Toyama, M.Senda, K.Oda, H. Hayashi ~ , H.Fujii ~ and H. A s a y a m a ~ % Tokyo Metropolitan Inst. Gerontology, ~Asahi Technocomputer Corp., ~ R i c o h Company LTD & ~"~,~Tokyo Electron LTD.

A Trial in Determination of Simple FDG Input Function

A new computer system has been developed to process and manage image data of PET and other modalities (XCT,MRI). The hardware consists of the following three parts; the main frame of a mini-super-computer 'CONVEX' and a super-mini-computer 'MieroVAX', the imaging devices of a PET camera and a GAMMA camera and two sets of image workstations 'STELLAR'. All devices are connected by ETHER network with TCP/IP protocol. The software consists of system management by the main frame, data ana%ysis and display by the image workstation, reporting system and the data base to manage and retrieve image data, study reports and patient information. The images of PET as well as other modalities are transferred to the main frame and are transformed into the ACR-NEMA format with definite size of header so that every image can be handled in the same way. Data processing is done by using a top menu and a multi-window system. To minimize interactions and to facilitate batch processing, the parameter used in image process and display are stored in the work-sheet files and a series of process protocols are recorded in the log file. Information upon each patient (name, history), PET studies (date, protocol) and scans (radionuclide, sampling time) are recorded in the data base according to a tree structure, in which one 'patient' consists of one or more 'studies' and one 'study' consists of one or more 'data files', which are classified into images, blood data, ROI, time-to-activity curves, etc. This system provides integrated data processing and management suitable for s PET center.

Kazuo WAKITA, Yoshio IMAHORI* Masato YAMASHITA* Norihiko MIZUKAWA*,Yohei ODA* Satoshi UEDA* Hitoshi HORII, Ryo F U J I I , Takehiko YAGYU, Tadashi INABA, Tadashi AOKI, Hisao MABUCHI and Hisamitsu NAKAHASHI Nishijin Hospital, *Kyoto prefectural Univ. of Med. It is most important to determine input functions in the analysis of human FDG (F-18-fluorodeoxyglucose) dynamics using PET (positron emission tomography). We have been employed a sequential arterial blood sampling tech nique requiring many blood samples and complicated manipulations. Initially we assumed that the input function (1)[arterial FDG time activity curve, C (t)] is composed by three exponential components as follows ; C ( t ) = A l ' e x p ( - / t l ' t ) + A 2 . e x p (-/~z't)+A3"exp ( - a s " t ) . . . . . (1) We tried to standardize the constants (A~, ~ , A2, az, A3, ~3) by averaging those from the sampling data of 35 subjects and evaluated on the least sampling numbers enabling the determination of the input function. We also evaluated the variations of those derived by indivisuaI differences and administrated doses. It was revealed that values, A3/A2"~I, az, ~3 had relatively constant means with S.D. (<25%). The equation (2) is obtained using those values for the equation (1) as follows ; C ( t ) = A c e x p ( - ~ ' t ) *Hl+Az'exp (-.2340 "t) *H2+1.07 "exp (-.0,177"t) "" (2) We could obtain relatively better results using this equation (2). It was revealed that there were at least no significant differences between K3 values obtained by the equation (1) and those obtained by the equation (2). It was also revealed that the eqution (2) required half numbers of samples, 10 samples, to obtain the similar results obtained by the equation (1) and reduced the computer calculation time.

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A NEW SPILLOVER CORRECTION METHOD FOR THE QUANTITATIVE MEASUREMENT OF MYOCARDIAL BLOOD FLOW IN CARDIAC PET STUDY. ~ M. Yamashita, S. Otsuka, Y. Kira, M. Kondo, H. Horli, K. Wakita, R. Fujii, H. Yamagishi, T. Yagyu, H. Nakahashi. Eyoto Prefectural University of Medicine, Nishijin Hospital, Kyoto, Japan.

RADON: ORIGIN, DETECTION, RADIATION EXPOSURE & RISK. ~.G. Velehik. University of Pennsylvania, Philadelphia, Pennsylvania, USA.

There are some potential difficulties, one of which is related to the simultaneous spillover fraction {SF) between the blood pool and the myocardium, for the quantitative measurement of myocardial blood flow (MBF) in cardiac PET studies using freely diffusible tracers such as H2lSo. The conventional direct subtraction technique using a separate CISO scan for the correction for SF in dynamic HzlsO study implies possible errors in the estimation of absolute HzlSO activity in the blood pool and the myocardium. We have newly developed a method for SF correction employing the same C150 scan and C'50 activity in the blood sample (CBLD) based on the theory that the two components of the bidirectional SF are equal. The clSo radioactivity in the ROI assigned to the left ventricular cavity (CLvRoI) and the myocardium (CMYoRO~) can be expressed by the following equations, CLvaol = CRLD * (I-SF) + CMs * SF C~yo~o~ = C ~ o * (I-SF) + CaLD * SF where CnYo is the Ciso activity in the myocardial vascular space. To validate this approach, we studied I0 normal subjects using dynamic scans after bolus injection of HzlSO and a separate equilibrium clso scan. Regional MBF and tissue fraction were calculated with a modified single compartment model and the nonlinear regression method using the serial blood pool and myocardial HzlSO activity corrected for spillover activity by SF and CMYo obtained from above equations with a given extraction fraction and partition coefficient. The obtained MBF and tissue fraction values were 0.91!0.17 (ml/min/g) and 0.73• (g/ml), respectively. The results showed that the tissue fraction value was close to a known recovery coefficient (0.7) due to the relatively thin myocardial wall and cardiac wall motion. This method may be useful for the quantitation of model parameters in cardiac PET studies in vivo.

S88

Recently there has been a great deal of publicity in the media and medical literature concerning the increased risk of lung cancer due to the radioactive gas radon, which accumulates in buildings. Nuclear Physicians especially, should be knowledgeable concerning radon and its potential health consequences and should be prepared to intelligently address the public's concerns regarding radiation exposure and cancer risk and be able to offer sound advice about detection and exposure reduction. Radon-222 (Rn) is a naturally occurring, odorless, inert, radioactive gas that is produced by the decay of uranium-238 and radium-226 which are found in soil. It may accumulate in houses where it decays to 4 short-lived radioactive daughters (Po-218, P0214, and Pb-214, Bi-214) resulting in exposure of the bronchial epithelium to alpha and beta particles respectively, and potentially an increased risk of lung cancer. The EPA has cited radon as the #1 environmental cancer risk resulting in 5,000-20,000 lung cancer deaths annually in the US. The NCRPM has doubled estimates of US radiation exposure from 180 to 360 mRem/yr due to the inclusion of the estimated exposure to radon that was previously omitted. Current EPA guidelines recommend an airborne radon concentration limit of 4 pCi/L. This is equivalent to smoking 1/2 pack of cigarettes a day or 300 CXRs/yr and approximately 10% of American homes have radon levels exceeding this limit. The source of radon, methods of its detection and measurement, and potential medical risks are discussed.

Sunday, August26,1990

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348

EXPOSURE LEVELS A R O U N D NUCLEAR MEDICINE PATIENTS (diagnostic)." J. Blanchette, L. Renaud and (2. Oaland. (Laval Hospital, Quebec, Quebec; Montreal Heart Institute, Montr~tl, Qu6bec; HOtel-Dien de Montreal Hospital, Montreal, Canada).

RADIATION EXPOSURE TO AMBULANCE

This study was undertaken to develop a simple model of the dose received by an individual in the close environment of a diagnostic nuclear medicine's patient. Measurements at three different distanCeS (2, 50, 100 cm) from the radioactive patient have been performed at four different levels (head, thorax, novel and feet) with a calibrated meter during 10 contiguous week days. 263 sets of independent measurements from 109 patientS at various time after the isotope administration have been realized. Several molecnles have been investigated. Exposure levels will be reported as a function of distance, time of administration and nuclear medicine exam. It will be shown that the exposure level at distance smaller than i meter is not isotropic, the thorax area being often more active than the abdominal one. Contact distances smaller than one meter are a reality for many hospital workers. These data support the observation that, if the workers are aware which patients are radioactive, they may adopt a practice that will reduce their own dose. Even if these workers are generally not classified as radiation workers, the collective dose reduction acheived might be significant. "(Work supported by Canadian Atomic Energy Control Board and Supply and Services Canada under contract 87055-8-4099/01-SS)

PERSONNEL DURING THE

TRANSFER BETWEEN HOSPITALS OF RADIOACTIVE PATIENTS. A.Rossi ~ , G. Guidarelli% A.Abbati% I. Adversi ~ R.P.Dazzani ~, L.Lembo ~ , and M.Pimpinella~% Ospedale Maggiore ~, ENEA**, Bologna, Italy. In a preceding work (Third World Congress of Nuc. Ned. and Biol. , Paris, 1982) the authors found the annual exposure %o hospital attendants from confined patients submitted to nuclear medicine examinations was between S and 23 mR. Now the authors extend their observation to the ambulance drivers and attendants, during the transfer between hospitals of radioactive patients studied at one of two departments of nuclear medicine in Bologna (500 OO0 inhabitants). Taking into account the driver cabin exposure rate ( E ) due to more radiating and i frequent examinations (i), the number of transported patients per examination in a year ( n ) , the number of i patients per examination per path (w) transported in a year ( n ) and the mean time of transport ( t ) i .W W relative to each path, the mean exposure rate is -E = ~ i Ei ni / ~-i ni The number of transported per path in a year is N = ~. n w i l,w and the driver cabin total e x p o s u r e in a year is

E=Z

gt

N

w w w From this, the individual valued dose equivalent is less than 5 mSv/y: result confirmed by a dosimetrio control for 6 months in driver cabin. No particular measure of radioprotection is considered necessary.

349

350

AN ANALYSIS OF THE SPATIAL PATIENT W I T H THERAPEUTIC

T. O r i t o .

S.i{oga,

DOSE I)ISTRIBUTI0N AROUND DOSE OF I 13].

A. Takeuchi,

O.Takeshita,

S. Suzuki

THE

EFFECTS OF 2-NITROIMIDAZOLE AND LEVAMISOLE ON RADIATION RESPONSE OF MICE.

and

A.L.C.H.VILLAVICENCIO and N.L. DEL FLASTRO. Divisao de Radiobiologia. Institute de Pesquisas Energeticas e Nucleares. CNEN/SP - Sac Paulo, Brasil.

}l.Toyama. Department of l~.aith Physics, Scilool of Hygiene, Fuj i t a ileal th Onivers ity, Tuyoake, ,Japan Patient, receiving therapeutic amount of rad:0active

s u b s t m l c e may be a s i g n i f i c a n t source of r a d i a t i o n , llowever, o n l y a few d a t a a r e a v a i l a b i e to e s t i m a t e the r a d i a t i o n exposure t o persons around the r a d i o a c t i v e p a t i e n t . The purpose of' t.Ms s t u d y is to g e t the s p a t i a l dose distribution around the p a t i e n t ~ i t h t h e r a p e n h c dose of I i 3 i which i s the only r a d i o n u c l i d e used f o r therapy in Japan .

T h e o r e t i c a l c a l c u l a t i o n s and experimental measurmenr,s were performed u s i n g A!derson Rand Phantom which had 3,.,s of I - ] 3 1 in the neck s e c t i o n t h a t had been r e p l a c e d by OR.INS type phantom. Three p a t i e n t s with m e t a s t a t m carcinomas, administra~.ed 100 , 88 and 90mCi of ! 131 respectively, were also i n v e s t i g a t e d , l i n e a r scanning ( ~ e d i c a l U n i v e r s a l Human Conuter ( Toshiba )) through the whole body of the p a t i e n t , dose r a [ e measurments a t two p o i n t s ( 50cm and 80cm ), and measurements of' s p a t i a l dose d i s t 1 ' i b u t i o n (Aloka ICS-151) around the p a t i e n t in the ward were c a r r i e d out immediately a f t e r a d m i n i s t r a t i o n of r a d i o n u e i i d e and two to twe!vedays a f t e r ' a d m i n i s t r a t i o n . At the time when the r e s i d u a l a c t i v i t y in the p a t i n t became

Agents which are able to modify radiation re sponse are of immediate practical interest to the radio therapist. Among them, several imidazole derivatives have been claimed to increase radiation response of radioresistant hypoxic cells. The effects of two imidazole compounds, 2-nitro-IH-imidazole and L(-)2,3,5,6 - tetrahydro-6-phenylimidaze (2,1-6) thiazole (levamisole), were tested systemically in order to determine the ra diomodifyingbehaviour in the whole organism. The drugs were administered ip 0.8 mg/O.5 ml two hours and 0.1 mg/ 0.I ml one hour respectively, prior a single 9 Gy dose 60Co irradiation. The 30-day survival data were recorded and qualitative and quantitative peritoneal cell analysis (macrophages, menocytes, lymphocytes, polimorphonuclear and mast cells) were performed. The results showed some radioprotective action for nitroimidazole at the whole body level (65% treated and irradiated survivors against 40% control only irradiated) and a mild sensitizer capacity for levamisole (30% against 50%). The peritoneal cell analysis showed also that radiation interfered in a differential way in the ki netics of the various peritoneal cell populations.

i5mCJ, which was the recommended value of maximum allowable

activity

a t d i s c h a r g e ( !CRP P u b l i c a t i o n 25 ) , e x p o s u r e r a t e

at the point 50ca apart from the patieet was 3.2mR/h in average of three cases. Maximum allowable period to be there not exceeding the dose limit recommended to a member of the public was 229 hours provided the attenuation of tile activity occured only physically.

Sunday, August 26, 1990

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351

352

RADIONUCLIDE VENOGRAPHY FOR DETECTING DEEP VEIN T~9OMBOSIS AND EVALUATING HEPARIN TREATMENT C. Cbou, J.Y. Xu, M.Q. Long and G. Lu. PUMC Hospital, Beijing, China

DIAGNOSTIC OF LUNG PERFUSION OMISSION AS COMPARED TO ISOTOPE PHLEBOGRAPHY OF LOWER KNEE DEEP VEINS P.Predi~, P.Drnovgek. Hospital Celje,Celje,Yugoslavia

Deep vein thrombosis (DVT) of the lower extremities is rather common in China, so it is desirable to have a convenient and accurate procedure for its diagnosis. 94 patients suspected of DVT were studied by radionuclide venography (RNV) using a whole body imaging syst~n after injection of 3-5 mCi Tc-99m-Dextran (147,000 daltons) in 5 ml normal saline into the dorsal vein of each foot. 1O of the patients were also examined with x-ray venography (XRV) for con-

firmation. After localization of the thrombosis, 18 patients were treated with small doses of heparin and a follow up study was performed 2-4 weeks later. The image patterns could be grouped into 4 categories: (i) Complete obstruction of the vein, either Ca) without formation of collaterals, 5 eases~ or (b) with collateral formation, 46 cases; (2) incomplete obstruction of the vein~ 14 cases% (3) Venous insufficiency~ 14 cases; and (4) Normal venous flow~ 15 cases. 90~ of the RNV results agree well with those of XRV. Follow-up studies after heparin treatment indicated that satisfactory clinical effects were usually accompanied by recanalization of the obstructed vein, forn~tion or improvement of collaterals. The authors conclude that the method described is a non-invasive, sensitive and reliable one for detecting deep vein obstruction and monitoring the efficacy ef heparin therapy.

353 PERSONAL COMPUTERSIN D ~ O S I S AND ~ M E ~ PU~O~Y EMBOLISM.

354 OF

E. Kotlyarov, R. Reba, Y. Epelbo~n; George Washington University Medical Center, Washington, D.C., U.S.A. A cc~prehensive diagnostic program was written for personal computers. It incorporated published data using ventilation/perfusion (V/Q) lung scans plus the author's experience with 196 angiographically proven studies. The strategy is based on segmental and segmental equivalent approach to interpretation of V/Q mismatch, the extent of ventilation abnormality, relative size of the chest x-ray opacifications and on the occurence of the "stripe sign". The program is designed to progress through a logical sequence for evaluation of ventilation and perfusion distribution organized as a seven level branching decision tree having forty different outcc~nes. The integrated probabilities of all the data are displayed on a Bayesian curve, indicating the precise posterior probability of pulmonary embolism (rE) for any given prior (clinical) probability of PE. The obtained post-test probability of PE is then used in Utility Analysis for defining an optimal manag~nent plan, by generating a written report of the test and suggestions for further diagnostic and therapeutic procedures, if indicated.

$90

According to literature over 95% of lung embolism results from the vein thrombosis of lower extremities. The studies of various authors vary in percentage to which the deep vein thrombosis of lower knee causes lung embolism. Our study involved analysis of iOO0 isotope phlebographies made in the last five years with the expressed blockade in deep veins in the region of lower knee. 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 so that the flow of tracer is achieved only in deep veins. 50 images are obtained by computer in 200 seconds (i img/sec). The isotope phlebography performed, we take the scintigram of lungs in 4 standard views and possibly in any additional one to establish the perfusion omission of either subsegmental or segmental type. Out of iOOO positive phlebographies of the lower knee 780 (78%) cases also had lung perfusion omission. 220 (22%) isotope phlebographies showed no lung perfusion omission. Positive findings of deep vein trombosis in the lower knee and positive findings of perfusion omission speak in favour of lung embolism. Our study confirms that a great number of lung perfusion omission results from the blockade of deep veins in the region of lower knee. Due to a high percentage of simultaneous positive findings of isotope phlebographies of deep veins in the lower knee and lung perfusion omission we beleive that in all patients suspected of lung embolism it is necessary to make at the same time the isotope phlebography of deep veins in the lower knee region as well as the lung perfusion scintigraphy with Tc-99m-MAA.

COMPOSITE PULMONARY SPECT SCINTIGRAPHY AND LUNG CT: AN UPDATE. G.W. Moskowitz and J.C. Vaugeois. Long Island Jewish Medical Center, New Hyde Park and Long Island College Hospital, New York, New York, U.S.A. The superimposition of cross sectional lung CT on companion images of pulmonary SPEC'T scintigraphy provides complementary structural and functional anatomy. The method has been report by Moskowitz et. al. (JNM 27:1038, 1986). A computer program was designed to read CT from a GE 9800 into a Siemens VAX 11/750 nuclear medicine computer system. SPECT was acquired on a Siemens ROTA dual head camera. The technique requires meticulous positioning of the patient so that corresponding cross sectional images are obtained for both imaging modalities. In order to closely approximate the SPECT cross-sections, CT should be obtained in the neutral or mid respiratory phase. Computer algorithm corrects for differences in size and orientation of the corresponding images. CT cross sectional image provide precise anatomic spatial relationships useful in defining the size and extent of pulmonary perfusion defects. CT can provide information concerning the etiology of perfusion abnormalities such as hyperaeration due to emphysema or bleb formation. Infiltrates and loculated plenral effusions are readily apparent on CT. A analysis of these studies had indicated that this technique enhances the information obtained from both SPECT and CT. The configuration and character of each perfusions defect can be readily defined and quantified.

Sunday, August 26, 1990

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356

GLOBAL AND REGIONAL EVALUATION OF MUCOCILIARY C L E A R A N C E F U N C T I O N IN B R O N C H I E C T A S I S T. I s a w a , T. T e s h i m a , Y. A n a z a w a , M. M i k i a n d M. M o t o m i y a . T o h o k u U n i v e r s i t y , Sendal, Japan

IMAGE PROCESSING FOR STUDYING MUCOCILIARY CLEARANCE MECHANISMS T. Teshima, T. Isawa, Y. Anazawa, M. Miki and M. Motomiya. Tohoku University, Sendai, Japan

Now mucociliary clearance or transport mechanisms function in t h e b r o n c h i e c t a t i c r e g i o n s of t h e l u n g s is l i t t l e k n o w n . T h e p u r p o s e w a s to s t u d y m u c o c i l i a r y clearance in bronchiectasis on global and regional basis. Twenty patients with verified bronchiectasis were studied by radioaerosol inhalation lung cine-scintigraphy and a quantitative analysis using ultrasonically generated Tc-99m-human s e r u m a l b u m i n a e r o s o l (dm of 1 . 9 7 ~ m w i t h ~g of 1 . 5 7 ) . G l o b a l l y q u a n t i t a t i v e p a r a m e t e r s indicated slight derangement in m u c o c i l i a r y clearance mechanisms but regional derangement was remarkable in bronchiectatic regions. Deposition of i n h a l e d aerosol in b r o n c h i e c t a t i c r e g i o n s w a s d i m i n i s h e d or i n h o m o g e n e o u s ; regional mucociliary transport was extremely deranged there showing stasis, regurgitation, s t r a y i n g a n d / o r z i g z a g m o t i o n s of m u c u s . W h e n v i s u a l o b s e r v a t i o n w a s n o t p o s s i b l e b e c a u s e of t o o l i t t l e d e p o s i t i o n of i n h a l e d r a d i o a e r o s o l , time-activity curves from the ciliated airways of t h e b r o n c h i e c t a t i c regions were helpful for evaluating regional mucociliary clearance function. Those from normal lung regions showed steadily declining curves, but those from the bronchiectatic regions irregular or abruptly rising or d e c l i n i n g or h o r i z o n t a l curves. These regional abnormalities in mucociliary clearance seem responsible for t h e bronchiectatic regions to d e v e l o p recurrent infections and hemorrhage.

We have studied how mucus t r a v e l s by using radioaerosol inhalation lung cine-scintigraphy compiled from sequential I0 sec frame lung image data obtained in 64x64 matrices following inhalation of Tc-99m human serum albumin aerosol. To analyze the mucous transport in a more detailed fashion, the following methods have been developed; I ) Condensed image mode (CM); tracheal images condensed in column form are sequentially arrayed with time to see the mucus transport patterns, and 2) Trajectory mode (TM); a f t e r setting a point of i n t e r e s t (POI) on a hot spot on the trachea, a t r a j e c t o r y is drawn by sequentially searching the POI of the subsequent images. These methods were used to analyze the tracheal mucous transport in the dogs and normal human subjects to see the e f f e c t of smoking cig ar e tte s . In dogs a radioactive droplet was placed at the carina. In a normal non-smoking dog, the CM indicated a steep diagonal line with a gradient of 15mm/min, whereas in a dog who acutely smoked 5 cigarettes, i t showed a nearly horizontal line with a gradient of 1 mm/min. In the former the TM indicated a upward but spiral transport with the e f f e c t i v e transport r a t i o (ETR) (the distance between the s t a r t and end points of i n t e r e s t divided by the t o t a l actual pathway a mucous glob followed) of 68.7 %, while in the l a t t e r r e g u r g i t a t i o n , zigzag motions and stasis were observed with the ETR of 7.2 %. More or less s i m i l a r transport patterns were observed in humans following aerosol inhalation. The ETR was 12 % both in normal non-smokers and smokers. Our new methods enable us to get not only q u a l i t a t i v e but q u a n t i t a t i v e information on tracheal mucous transport in a more detailed or microscopic fashion.

357

358

MEASUREMENT OF TRACHEAL CLEARANCE RATES IN HORSES USING TECHNETIUM-99m SULPHIDE COLLOID (TC-99m SC) AND A MODIFIED GAMMA CAMERA SYSTEM L. Riddolls, R. Willoughby, G. Ecker and S. McKee. Equine Research Centre at the University of Guelph, Guelph, Ontario, Canada.

EARLY

Tracheal clearance mechanisms are assumed to play an important role in equine respiratory disorders. To establish tracheal clearance rates in horses, eight healthy unsedated horses of various breeds were positioned in a modified stock. Studies were repeated on 5 or more days. Following site preparation, local anesthesia and disinfection of the skin over the distal end of the trachea, 370 MBq Tc-99m SC was injected into the lumen of the trachea through a 0.91 mm O.D. x 8.9 cm spinal needle. A 40 cm flexible measuring tape, to which five Cobalt-57 spot markers are secured at 10 cm intervals, was attached to the ventral aspect of the horse's neck. Clearance was followed by taking sequential scintigraphs perpendicular to the neck at recorded interval~ using a scintillation camera system modified by attaching the yoke assembly and detection head onto the end of the boom of a hydraulic crane. From the images obtained on film, the leading edge of the bolus of Tc-99m SC and the centre of the spot markers immediately below and above the leading edge were plotted on a digitizer. These data were entered into a data processor programmed to calculate clearance rates. The overall mean tracheal clearance rate and horse-to-borse variability was 2.06 + 0.24 cm/min (mean -+ S.D.). The tracheal clearance rates within individual horses did not differ significantly (p > 0.05)~ There were, however, significant differences in betweenhorse clearance rates (p < 0.05). The injection of a tranquilizer reduced clearance rates by nearly 50%. Exercise did not appear to alter clearance rates.

Sunday, August 26, 1990

DIAONOSIS OF CHRONICOBSTRUCTIVEPULMONARYDISEASE USINO RADIOAERDSOL INHALATION SCAN. Johan S. Nasjhure, E. Soeriasoeaantriee, Zul Oahiana*, A.Hussein S. Kartamihardja*.Dept. of NuclearMedicine(el and Division of Pulmonolegy Oept.ofInternalMedicine(H) Schoolof Medicine University of Padjadjaran, Dan~n; Zadunesia. Chronic ObstructivePulmonaryDisease(COPO)is quitecommonin the developing

countries; the underlying factorsare namely cigarette smoking, chronic bronchitis, pulmonary tuberculosis,and air pollution. I t is necessary to develop a reliablediagnostictechnique,whichcan detectCOPD in its early and reversible stage;an easy to performand inexpensivetechnique is also desirable. The aim of this study is %o eva!uatethe usefulnessof radioaeroso! inhalationscan in diagnosingCOPO. Thirty eightof subjectsclinicallydiagnosedas havingCOPDparticipated in this study;theycomprisedof 33 male and IS femalewith a mean age of 52.95 years, Ten normalvolunteersservedas control. All participants underwent chest x-rayexaminations,FEV! test, in addition%o radioaerosol inhalation and perfusion scan. TNe radioaerosolinhalationscan was performed by using BARC aerosol generatorwith Tc-ggaphytateas radioactive particles, while perfusionscan was done using Tc-g9amacroaggregatedalbumin. Our resultssuggestthat radioaeroso]scan is most sensitivetechniquein the

early detectionof COPD with sensitivityrate of 89.5X, whileotherdiagnostic aodalities i.e. chest x-ray, FEVI,and perfusion scan havethe sensitivity of

63.2X, 42.1%,and 86.8Xrespectively.We concludethat radloaerosolinhalation scan can be used for early diagnosis of COPO,and this technique can be recommended to be using in the developing countries since it is relatively inexpensive and easy to perform.

$91

359

360

CLINICAL INVESTIGATION OF REGIONAL TC-99mDTPA AEROSOL PARTICLES PULMONARY ALVEOLAR PERMEABILITY IN CASES OF BRONCHIAL ASTHMA.

USEFULNESS OF VENTILATION AND PERFUSION SCANS PATIENTS WITH COLLAGEN-VASCULAR DISEASES. S. N. Kamata, K. Suzuki, S. Inokuma, A. Kubo, S. Tokyo Metropolitan Komagome Hospital and Keio Hospital, Tokyo, Japan.

T.0hishi, R.Saito, Y.Igarashi, Y.Yamagishi, and K.Ebata. Department of radiology, Nippon Medical School, Tokyo, Japan. Certify the clinical usefulness of Tc-99m DTPA aerosol nebulizing scintigraphy and investigated the regional pulmonary alveolar permeability compare with the analysis of pulmonary plane Xray photograms and pulmonary spirometry which performed in cases of bronchial asthma. Data collection was carried out in regular ventilation and gamma camera was fixed on dorsal direction. Regional alveolar permeability was estimated in subdivide ROIs prepared on the pulmonary fields. Following results were obtained:regional alve -olar permeability would he revieled that the minimal disturbances of peripheral air sacs earlier and more sensitive than plane Xray photogram and pulmonary spirometric analysis.

361 I N F L U E N C E OF R A D I O A E R O S O L CHARACTERISTICS ON PARTICLE FLOW THROUGH STENOSES. C.Schuemichen T . G e h r i g , Th. Krause, E . S t r a u s s . D e p a r t m e n t of N u c l e a r M e d i c i n e , U n i v e r s i t y of Freiburg, F R G Inhalation scintigraphy with radioactive aerosol has some well documented limitations. R a d i o a e r o s o l d e p o s i t i o n in t h e a i r w a y s f o l l o w s not only regional ventilation but is a l s o i n f l u e n c e d by p a r t i c l e size, a i r w a y g e o m e t r y and b r e a t h i n g m a n o e u v r e . In t h i s s t u d y it is s h o w n for t h e first t i m e t h a t b e s i d e s p a r t i c l e d e p o s i t i o n t h e p a r t i c l e f l o w i t s e l f is c h a n g e d in a o p p o s i t e w a y in l a m i n a r a n d e d d y flow b y t h e p h y s i c a l c h a r a c t e r i s t i c s of r a d i o a e r o s o l . T h i s w a s d e m o n s t r a t e d by a p h a n t o m of c o m m u nicating glas tubes with stenoses. The gas flow in all 7 s t e n o s e s w a s k e p t c o n s t a n t by v a r y i n g its length. A w e t s t a n d a r d a e r o s o l (AMD 0.45 um) a n d a d r y u l t r a f i n e a e r o s o l (AMD 50 A, e v a p o r a t i o n of T c - 9 9 m at 2500 ~ w a s used. T h e f l o w in t h e p h a n t o m w a s i n c r e a s e d s t e p b y s t e p f r o m 5 to 50 i / m i n a n d the p a s s i n g a e r o s o l c o l l e c t e d in b a c t e r i a l filters. U s i n g t h e d r y u l t r a f i n e aerosol a linear correlation was found between t h e input g a s f l o w a n d t h e a c t i v i t y in e a c h filter a n d t u b e as a m e a s u r e of p a r t i c l e flow. However using the wet standard aerosol, there w a s a r e l a t i v e i n c r e a s e (<40 %) of a c t i v i t y in l a m i n a r f l o w (<30 i/min) and a d e c r e a s e in e d d y f l o w (>40 i/min). This phenomenon w a s independent of activity deposition within the s t e n o s e s a n d w a s o b s e r v e d in s t e n o s e s w i t h a diameter below 3 mm. Hence, dry ultrafine r a d i o a e r o s o l y i e l d s m o r e p r e c i s e results.

IN Kosuda, Hashimoto. University

Pulmonary involvement is an important feature of collagen-vascular diseases and significantly contributes to mortality, but no investigators have reported the pathophysiological study of chronic interstitial pneumonitis by radionuclide methods. We studied 50 pts with collagen-vascular diseases with Xe-133 ventilation scans (V) and Tc-99m MAA perfusion scans (Q). Of 50 pts, 8 underwent the sequential studies at intervals of more than 3 months. Mean transit time (MTT) was calculated from the Xe-133 wash-out curve. V, Q images and MTT were compared with chest X-ray films and results of pulmonary function tests. Of 50 pts, 27 had no abnormal finding on the chest Xray films. Of the 27 pts, however, V and/or Q abnormalities were found in 16 pts(59%) , 22 pts(82%) , respectively. Every patient with abnormal findings on the chest X-ray film showed both V and Q abnormalities. Overall, Q abnormality was more frequent and severer than V one. Of the 8 pts with the sequential studies, 5 showed prolongation of MTT in concordance with deterioration of pulmonary fibrosis, suggesting airway occlusion as well as A-C block and Q abnormality. V, Q abnormalities were not necessarily relevant to DLco values. In 5 pts (10%), there were low V/Q mismatch areas in the pulmonary fields which were concurrent with high V/Q mismatch areas. In conclusion, ventilation and perfusion studies are useful in assessing the regional pulmonary function in patients with collagen-vascular diseases.

362 STUDIES ON TFE LOCATION OF AIRWAY STENOSiS iR9 ~THACHOLINE Ih[/AL~.TiON M.Sugita,

H.Nakamura,

O.Kitada. Department of

Internal Medicine, Hyogo College of Medicine, Nishinomiya,

Hyogo, Japan.

On 72 patients with respirator 3, disease, stenotie sites were conjectured from continuous changes of respiratory impedance and of pereutaneous oxygen partial pressure after rnethacholine inhalation.

To make our conjecture obviously,

observation on the topographic changes in ventilation and perfusion image was made in some eases using 81m-krwipton and 99m-technetit~m ~b%A. As a result, these 7E patients were divided into 4 groups, i.e.8 patients suE~estive of proximal respiratory stenosis,

ii patients suggestive of

distal r~spirator~y stenosis,

41 patients suggestive

of both proxi.vlal and distal stenosis and 12 patients without m]y apparent stenosis at either site. in the proximal stenosis, were atopic asthma. stenosis,

6 out of 8 patients

In the both proximaA arid distal

17 out of 41 were abopie and 22 out of 41

were non-atopic asthma. In the distal stenosis,

2 out

of ii were a~opic and 4 out of ii were non-atopic asthma.

$92

Sunday, August26,1990

363

364

FACTORS INFLUENCING CLEARANCE OF INHALED Tc-99m DTPA FROM THE LUNG M. Bracken, P. Pityn, M. King, M. Chamberlain and W. Morgan University of Western Ontario, London, Ontario, Canada

DIFFERENCE IN AEROSOL DEPOSITION PATTERNS DUE TO THREE DIFFERENT AEROSOL SIZES. M. M i k i , I. Isawa, T. Teshima, Y. Anazawa, and M. Motomiya. Tohoku University, Sendai, JAPAN

Clearance of inhaled DTPA from the lungs is a measure of i t s d i f f u s i o n from i t s s i t e of deposition in the r e s p i r a t o r y passages. Increased DTPA clearance occurs in smokers and in numerous r e s p i r a t o r y diseases. This promotes the hope that clearance may be used as an i n d i c a t o r of e p i t h e l i a l membrane damage, a l v e o l a r permeability or at least a non-invasive technique of monitoring lung i n j u r y . Our studies in normal volunteers and patients i l l u s t r a t e the dependence of clearance times on the s i t e of deposition. This in turn depends upon various, often u n c o n t r o l l a b l e , f a c t o r s including the pattel, n, depth and r a t e of breathing, the amount of mucus present, whether the subject is a smoker etc. Gross differences in sites of deposition are often imperceptible by visual inspection of immediate post v e n t i l a t i o n lung scans. DTPA clearance is also posture dependent with consequent differences in regional lung clearance and in some circumstances may be perfusion limited. Perceived clearance is a l t e r e d by the technique of measurement, B r i e f observation may suggest a single exponential whereas multiple components become evident on prolonged observation. Understanding of these f a c t o r s is necessary before DTPA clearance can be contemplated as a c l i n i c a l l y rel i ab I e measurement.

Radioaerosol i n h a l a t i o n lung deposition patterns are known to depend on various f act or s; size of inhaled aerosol, shape of airways, a i r f l o w rate, c a r r i e r gas, humidity, temperature, body position, etc. The purpose was to see whether t h e r e were any changes in the deposition patterns of inhaled aerosol in the lungs when 3 d i f f e r e n t aerosol generators, Mistogen EN-142, U l t r a v e n t and BARC (Bhabha Atomic Research Centre, INDIA) nebulizer were used on the same subjects, They generated aerosol with dm and og of 1.93 um and 1.52, 1.04 um and 1.71, and 0.84 um and 1.73, r e s p e c t i v e l y , 5 normal persons and 20 patients with various chest diseases inhaled Tc-99m albumin aerosols from each o f the 3 generators at d i f f e r e n t times with t i d a l breathing in the same s i t t i n g p o s i t i o n , and 4 views were taken. Besides visual comparison, 4 parameters were calculated; namely, a l v e o l a r deposition r a t i o (ALDR), Xmax i n d i c a t i n g the maximum point of the count p r o f i l e of a selected zone, Xmean the mean point of the count p r o f i l e and SD. In normals there was l i t t l e d i f f e r e n c e in d e p o s i t i o n p a t t e r n s among these i n s t r u m e n t s . In patients with COPD deposition patterns in the lungs were uneven with a l l the instruments according to the degree of o b s t r u c t i v e disturbance, and central deposit i o n patterns were less evident with the BARC nebulizer r e s u l t i n g in a b e t t e r penetration of inhaled aerosol to the lung p e r i p h e r y . Mistogen showed a tendency o f preponderant d e p o s i t i o n on the l a r g e r a i r w a y s . Ultravent showed the deposition patterns in-between. The l a r g e r the aerosol in size, the more proximally i t deposits. The deposition patterns using the so-called Techne-gas are now under study,(supported by IAEA)

365

366

A QUANTITATIVE ASSESSMENT OF REGIONAL VENTILATION BY MEANS OF AN I[JHALATION METHOD WITH CONSTANT CONCE!:~kATION OF Kr-~[m. T.ShimJda, T. Obata, Y.Mori, K.Kawakami. Jikei University,Tokyo Japan.

1-123 HIPDM PULMONARY IMAGIN~; DEMONSTRATES ELASTASE-INDUCED PUL~IONARY EMPHYSEr~,A. W.J. Shih, Y.L. Lai, J.J. Coupal, G. Simmons, C. Coulston, U.Y. Ryo. VA and University of Kentucky ~
Kr-81m gas has been used to assess the regional ventilation(V) in asthmatic patients. Conventional method of c o n t i n u o u s b r e a t h i n g of K r - 8 1 m gas, however, radioactivity in the lung changes with ventilatory speed. We developed a new method to inhale Kr-81m gas with constant c o n c e n t r a t i o n . This apparatus consists of a spacer and mixing fan e q u i p p e d between Kr-81m generator and the mouth. On phantom study, activity of Kr-81m was well correlated with v e n t i l a t o r y volume in the wide range of minute ventilatory volume(MVV, 31-101/min). On the other hand, in the conventional method, activity of Kr81m was decreased by increasing of MVV. Clinical study was p e r f o r m e d on asthmatic patients in attack.Changes of V after inhalation of b r o n c h o d i l a t o r was r e g i o n a l l y m o n i t o r e d by m e a n s of t h i s m e t h o d and regional V was q u a n t i t a t i v e l y calculated. Three oaces having severe attack show a further decrease of V in some hypo v e n t i l a t o r y regions. This enhances V/Q mismatch and PaO2 was decreased although indices of pulmonary function test were inproved. In remaining 7 patients, inprovement of V with bronchodilator was quantitativelyobserved in each region of bronchospasm. This i n h a l a t i o n study could contribute to a quantiative assessment of regional pulmonary function.

Chronic obstructive pulmonary disease/emphysema has been identified by diffuse decrease in pulmonary activity in the upper thi-d to one half of the lung using 1-123 hydroxyiodobenzyl-propanediamine (HIPDM); for this reason 1-123 HIPDM is proposed as a lung imaging agent. Its potential usefulness for the detection of pulmonary emphysema was evaluated as an animal model of elastase-induced emphysema along with Tc-99m MAA lung perfusion imaging. Long-Evans rats (200-250 gin.) were intratracheally instilled with 400 IU/Kg elastase under ether anesthesia. Four weeks after treatment, 15 treated and 15 non-treated rats were simultaneously imaged as follows: I~ediately following IV injection of 250-300 uCi Tc-99m MAA, the rats were placed prone side-by-side under a scintillation camera. The procedure was repeated 48 hours later using 250-300 uCi 1-123 HIPDM. Activity in the region of interest (ROI) over both lungs of the elastase-treated and the control animals was recorded after each procedure. Total counts pew ROI from each rat were measured which were normalized by lung volume. The normalized lung activity ratio was computed for each pair of treated/non-treated rats. The mean ratios of HIPDM and ~;AA were 0.847 and C.802, respectively. The results showed a significant decrease in uptake of both MAA (p
Sunday, August26,1990

S93

367 PULMONARY DEPENDENT

368 BIOGENIC UPTAKE MECHANISM: IS ON PH, L I P O P H I L I C I T Y OR PKA?

IT

S.F. Akber, K. K n e s a u r e k * . D e p a r t m e n t of R a d i o l o g y , UTMS, Houston, TX) * D e p a r t m e n t of R a d i o l o g y , U n i v e r s i t y of R o c h e s t e r , R o c h e s t e r , NY.

PULMONARY PERFUSION AT ZERO GRAVITY. S. Groth, D. Swift, D. Merrild, J. Mortensen, I. Evald, J. Vestbo, E. Bonde-Petersem, P.F. H~ilund-Carlsen and A. Rabol. Depts. of Nuel. Med. and Space Ned., Rigshospitalet and Glostrup Hospital, Denmark, and Dept. of Envir. Health, Johns Hopkins University, U.S.A.

The uptake and c l e a r a n c e of b l o g e n i c amines have been studied in the lungs of d i f f e r e n t species. The b i o g e n l c amines seems to bind to high a f f i n i t y sites located on the m e m b r a n e of p u l m o n a r y e n d o t h e l l a l cells. In the past, it was assumed that the a c c u m u l a tion of b l o g e n i c amines in the lung is due to the lower pH value in the p u l m o n a r y e x t r a v a s c u l a r space in c o m p a r i s o n to the p u l m o n a r y v a s c u l a r pH. However) i n v e s t i g a t o r s found that the d e r i v a t i v e s of p - c h l o r o p h e n l e t h y l a mine show a g r e a t e r r e t e n t i o n in the lungs than can be e x p l a i n e d solely by a pH effect. This fact is f u r t h e r i l l u s t r a t e d by L i n e t al who d e m o n s t r a t e d that the brain l o c a l i - z a t l o n of N - I s o p r o p y l - l - 1 2 3 - p ~ i o d o a m p h e t a m l n e (1-123 IMP) is not a f f e c t e d by pH v a r i a t i o n . Fowler et al p o i n t e d out that the high uptake of lung tissue for long chain amines such as o c t y l a m l n e was not i n d i c a t i v e of llpophillclty. Akber d e v e l o p e d the t e c h n i q u e to study p h a r m a c o l o g i c a l i n t e r v e n t i o n of b l o g e n l c amines in the dog lungs and o b s e r v e d active c o m p e t i t i o n b e t w e e n 1-123 IMP and p r o p r a n o l o l and mild c o m p e t i t i o n b e t w e e n 1123 IMP and ketamlne. It is c o n c l u d e d from the study t h a t uptake and r e t e n t i o n m e c h a n i s m of b l o g e n i c amines in the lung is d e p e n d e n t on pka rather than pH or l l p o p h i l l c i t y .

The effect of gravity (G) on regional pulmonary perfusion was studied by injecting lO0 MBq 99mTc-MAA in 7 healthy sitting subjects st 0 and 1 G. The injection of the 99mTc-MAA at 0 G was made on board a Gulfstream aircraft. Periods of 0 G lasting 23-26 s were obtained by varying the flight profile. The 99mTe-MAA was injected intraveneously st the beginning of one of the periods of 0 G and immediately flushed centrally by lO ml saline. The injection was always completed ~ithin lO s leaving 13-16 s for the 99mTc-MAA to be trapped in the pulmonary arterioles before the end of the 0 G period. After the flight the subjects were taken to the medical center and pmaced in a sitting position in front of a gamma camera. Posterior and anterior acquisitions were made. Within one week the 1 G measurements were made by injecting the 99mTc-MAA st the laboratory. Data were processed by calculating mean pixel radioactivity in individually created regions of interest in the upper (U) and lower (l) parts of the lungs. Average U/L radioactivity (and SD) of the posterior acquisition was: 0 G 1 G P Right lung 0.52 0.29 <0.05 (0.19) (0.063) Left lung 0.61 0.37 <0.05 (0.15) (0.i0)

369

370

NON-INVASIVE MEASUREMENT OF LUNG WATER USING Tc-99m-RBC AND Tc-99m-DTPA IN PATIENTS WITH CARDIAC DISEASE N. Yamamoto, K. Gotoh, Y. Yagi, S. Ooshima, Y. Terashima, K. Nagashima, M. lids, F. Deguchi, T. Saws, H. Tanaka and S. Hirakawa. 2nd Department of Internal Medicine, Gifu University, Japan.

SOLUTE TRANSFER ACROSS ENDOTHELIUM: DEPENDENCE O N TISSUE PERFUS 10N A M Peters and D Vassilarou, H a m m e r s m i t h Hospital, London WI2 0HS, England

Method : In patients with cardiac disease, we measured pulmonary blood volume (PBV) and extravascular lung water (EVLW) non-invasively hy double isotope indicator method using Tc-99m-RBC as non-diffusible indicator and Tc-99m-DTPA as diffusible indicator. Both PBV/BW and EVLW/BW were examined for their relation to (i) hemodynamic parameters (PA, RA, PAW and CO) measured with a floating catheter, (2) radiographic signs of pulmonary edema scored by Pistolesi's method and (3) pulmonary function tests performed within 24 hours of measurement of PBV and EVLW. Result : PBV/BW and EVLW/BW showed a slight positive correlation with P'--A(r=0.62, 0.56, p
S94

The results of the anterior acquisition were equally significant and suggest that substantial part of the topographical inequality of perfusion seen under i G is abolished during short periods of 0 G.

Hydrephilic solutes pass from plasma into the e x t r a v a s c u l a r (eV) space by d i f f u s i o n through i n t e r - e n d o t h e l i a l pores. The rate of t r a n s f e r (J) is a function of the p e r m e a b i l i t y c o e f f i c i e n t (P), c a p i l l a r y surface area (S) and the mean concentration of s o l u t e in the c a p i l l a r y , which i t s e l f is a function of solute e x t r a c t i o n (E), It can be shown that, as t i s s u e blood flow (Q) increases, J r i s e s e x p o n e n t i a l l y with a rate constant equal to PS/Q to reach a plateau, i.e. becomes independent of Q. When PS>> Q, the t r a n s f e r rate is l i m i t e d by Q but when PS<< Q t h e transfer rate is diffusion limited. SincePS/Q is equal t o = I n (IE), values of E can be specified at which Q is so much greater than PS that J becomes independent of Q, Thus, for E - 0.2, J is 90% of the plateau value, and for E = 0,I, 95% of the plateau value. Our aim was to measure E for Tc=99m DTPA in a t i s s u e Rol in the lumbar region below the kidneys in order to assess the extent to which DTPA transfer into the eV space is Q dependent, U s i n g a t e c h n i q u e p r e v i o u s l y d e s c r i b e d for the g e n e r a l m e a s u r e m e n t of e x t r a c t i o n f r a c t i o n , E was 0.29 (+ 0.06), i n d i c a t i n g that Q w i l l p a r t l y d e t e r m i n e the t r a n s f e r rate of DTPA, By measuring clearance of DTPA into the eV space, we have derived Q and calculated a PS product for DTPA in the sub= renal Rol of 1 . 2 m l / m i n / 1 0 0 m l . This is s l i g h t l y less than values published for s k i n and muscle in the experimental animal using the s l i g h t l y smaller molecules, sucrose and Cr-51 EDTA.

Sunday, August 26, 1990

371 SCINTIGRAPHIC CONTROL IN PEDIATRIC LIVER TRANSPLANT. I.Roca, S. Aguade, V. Martinez-lbanez*, C. Margarit*, F.M. Domenech-Torne. Servicio de Medicina Nuclear. Hospital General "Vall d'Hebron", Departamento de Cirugia Pediatrica*, Clinica Infantil "Vall d'Hebron", Barcelona. Patients with orthotopic liver transplantation (OLTx) have been studied in the Nuclear Medicine Service by means of hepatobiliary scintigraphy (HBS), pulmonary perfusion scintigraphy (PPS) and renography. MATERIAL AND METHODS: 30 children with OLTx (age range eight months to thirteen years) have been studied with HBS (99mTc-trimethyl-iminodiacetic acid (TM-IDA)), measuring liver blood flow study, hepatic extraction, intrahepatic transit time and the timing of biliary and intestinal activity. In 6 patients, we studied the existence of pulmonary arteriovenous fistulae (PAVF) with PPS previously to the OLTx, quantifying systemic versus pulmonary activity (QS/QP+QS). When high cyclosporin A (CyA) levels were found or when renal dysfunction were suspected, we studied tubular function and glomerular filtration rate by means of MAG-3 and DTPA renography. RESULTS: In 42 HBS performed in 30 children, 21 studies were normal, 18 showed low hepatic extraction and prolonged intrahepatic transit time and time of biliary and intestinal activity with clinical symptoms of acute rejection, 3 had extrahepatic activity during the excretion phase (biliary leakages), in 2 cases the diagnosis were portal thrombosis (pathological portal phase in liver vascular curve) and in one case we found duodenogastric reflux. We found PAVF in two children with hipoxemia. In 2 patients with transitory CyA high levels, we found prolonged transit time in Tc-99m-DTPA renography with normal Tc-99m-MAG3 renography. CONCLUSION: The noninvasive isotopic methods have great importance not only in the liver function survey to clarify the diagnosis between rejection and surgical complications, but also in pulmonary and renal dysfunctions.

372 IDA SCANS IN MONITORING OF LIVER M,R. Castellani*, C. Colcmbo~

DISEASE DUE TO CYSTIC FIBROSIS

E. Sere~ai*, M.G. Apestslo ~

*Nuclear Medicine Div., let. Tt~ori, Milano- ~

Pediatrics, Osp_e

da/e Policlinico, Mi!ano, Italy, A recent report (Gaskin K.J., N. En~l. J. of Med., 1988) indicated that the hepatobiliary scan showed evidence of common bile ducts stenosis in 96% of patients with liver disease due to cystic fibrosis (CF). 99mTc-trimethy]-Br-lda scan (IIIMBq) was performed in 20 pte af fectsd by CF with clinical or biochemical evidence of liver disease, In 9 pts the study was repeated as the baseline emgminstion, i0 months after the beginning of the therapy with hydrophilic 8nd eholeA~etic ursodeoxyehelic (UDCA) acid (15 m~/kg/day). A total of 29 stu dies was performed. Morphological pattern end some fuetion~l parameters (~/~ of hepatic wash-out, time of vislmlization of the intestine) were evaluated. At baseline, evidence of severe biliary obstruction was fot~d in 2 cas~; visualization of seccndm~y end tertiary bile duets in I0 and dilatation of common bile duct in 7. Gallbladder could not be visualized in 8 pts and it was enlarged with delayed emptying in 8 pts. The mean T/~ of hepatic wesh-out w~as 29 rain. The mean time of intestinal visualization wSs 13 rain. After UDCA therapy in the 9 pts with severe hepatic injury and common bile ducts stenosis these ftmctional times were respectively reduced frcm 40,0 r a i n . t o 29,2 rain. and from 22,2 rain. to 17 min. The morpholo~ic appearance at IDA scan improved ~mmrkably in all patients. None showed evidence of biliary obsh~etion. Dilatation of intra hepatic ducts end of com~ mon bile duct was reduced and the ~allbladder was visualized in all cases. In conclusion IDA scan is a very usefull method to evaluate the grade of biliary obstruction and to verify the clinical improvement after UDCA ther~43y.

373

374A

SERUM PEPSINOGENS IN CHILDREN. T. Shindo, T. Ota *, K. Kojima*,and K. Ishii ~ Kitasato Institute Medical Center Hospital, Kitamoto, Saitama, 3 a p a n / K i t a s a t o University School of medicine, Sagamihara, Ka~agawa, Japan ~.

.t.Boca! N.CobosZt S.Li~l t, 5.&guad~l N.BRIeda, J.Verdmw J.CaSIe|I, F.Porta, F.N.pomenech-Torn~. Servicio de H e d i c i n a Nuclear.Hospital General "vail

We could find few previously reports regarding normal levels of serum pepsinogee Group] and ~ ( P G I , P G ~ ) in children. Therefore we m e a s u r e d s e r u m l e v e l s of Pepsinogen Group l and ~ in various age of groups. [MATERIALS AND METHOD] Blood samples were obtained from 189 children and 7 aduls without gastrointestinal diseases. Serum PG I and Serum P G ~ were determined by a radioimmunoassay method. [RESULT] Group AGE n mean PG [ ~S.D. mean PG ~ ~S.D. l AT BIRTH 19 9 . 1 ~ 2.4ng/ml 3 . 6 • 3.6ng/ml 3-6DAYS 75 I0.2~ 3.0ng/ml 20.1• 9.7ng/ml IY> 4 32.2~ 5.6ng/ml 5 . 4 ~ 2.6ng/ml [~ I- 2u I0 38.8~ 5.2ng/ml 8 . 8 • 3.4ng/ml V 3- 6Y 25 36.8~lO.7ng/ml 7.4• 4.6ng/ml Vl 7-10u 28 35.2~ 9.Sng/ml 5 . 1 • 1.5ng/ml 11-14u 28 49.6~24.5ng/ml 8 . 6 ~ 6.1ng/ml 20-25Y 7 43.8• 6.7• 2.Sng/ml [CONCLUSION] PG I was low a t birth, rose abruptly during the early months of life,but somewhat reduced in levels up to age of I0 years. PG ] tended to increse again after puberty, but there was no sigoificant stastical difference in PG ] b e t w e e n the ~ , ~ , V , ~ , ~ and ~ groups. PG ~ was also low at birth, rose abruptly during the first week of life, reduced in levels during the early months of life, and remained in the same levels during the rest of life.

Pulmonary hypertension (YS) a p p e a r s in the evolution OF c h i l d r e n with pulmonary cystic flb~osis (PCF) as a s e v e r e c o m p l i c a t i o n . Phe early detection o f PH i s d i t F i c u ] ! with indirect t e c h n i q u e s as ECGj thorax radiography, ventilation and perFusion scintigrapbies and echocardiography (air trapping]. The a i m os o u r s t u d y i s t o s p e c i f y the role of the scintigraphic ventriculography (SY), with right ventricle ejection Fraction

Neumologla BARCELONA

l,

Cl~qica

I n.tantil

H I G I T VRNTB[CLK EJECTION FRACTIOM l l CYSTIC F I B J O S I H .

(HVEF) in the early detection of NAYKRIAL ANN N S T I O l : 24 p a t i e n t s d i a g n o s e d o f CPF and w i t h c l i n l c a l

"Valld~Hebr6n"

CIIILDREH w i f e

Pe

in

childre~

S E Y E B i PULMONARY

with

severe

PCF.

(4 t o 1~ y e a r s o l d , mean 9 y e a r s ) criteria of severity, have been submitted t o 6u (99mTc l a b e l l e d red blood cells)~ in the best left anterior o b D i q n e . RVRF have been c a l c u l a t e d , with semi-authnmatic metbod (reference normal values, mean 22 y e a r s , RYRF=46+/-6~). I n t h e week b e f o r e o r a f t e r SV, a l l the children are submitted 10 clinical evaluation (Sbwachman-Knlczycki clinical score)(s-K), thorax radiography (cbrispin and Norman s c o r e ) (RxS), arterial oximetry (pO2) and functional respiratory test (FRT). RESULTS : g o s i g n i F i c a t i v e correlation coefficient h a s been f o u n d b e t w e e n RYEF and a l l t h e o t h e r s t u d i e d parameters (C-W, RX6, pO2~ FRT a n d L V E F ) . The results compar severe scores of these parameters with pathological RYRF a r e d e s c r i b e d above : S-K

RxH T

pO3 (65

io I

.

. .... ' BVRF I >34 -

Silo [4

14

3

5

7

~ 14

.

FRT T .

.

.

13

3 tO 13

2

7 4

6

6

D I S C U S S I O N : T h e s e compared m e t h o d s a r e n o t o f c h o i c e to detect P8 e a r l y , and t h e y a r e n o t m e a s u r i n g t h e same as RYRF. We m u s t remark the discordant results Found b e t w e e n RY~F and t h e s t u d i e d

parameters. We

must

have

in

methodological found

in the

disapointing. determined

Sunday, August 26, 1990

pediatrics

R.Ortegal

d'Nebrdn"

mind

problems,

that

this

with

one

available

underestimation

method

of

has

some

RVEF. T h e o v e r l a p

results o f RYEF i n t h e l e s s and more s e v e r e s c o r e s a r e The v a l u e o f RVEF as a t e s t t o d e t e c t PH s h o u l d be

by

Iongltudinal

survey

of

these

patients.

$95

374B

3740

USE OF A AC-PC CUTANEOUS LANDMARK FOR PET AND SPECT STUDIES IN CHILDREN C. Raynaud, G. Salamon, J. Regis, C. Chiton, C. Rumeau, S. Tran-Dinh, C.A. Cuenod, O. Dulac, A. Leroy-Willig, M. Morel, L. Laflamme, M. Bourguignon and A. Syrota. Serv. Hosp. F. Joliot, C E A , Orsay and Neurodiagnostic Depart. Hosp. La Timone, Marseille, France.

Tc.99m HMPAO SPECT in neurologically

Among the proposed landmarks, for PET and SPECT, two survived, the orbito-meatal line (OM), and the eommissural line passing through anterior and posterior commissures (ACPC). Anatomists plead for AC-PC and most of neuro-anatomieal atlases refer to this line, but it requires MRI. OM line, although preferred because simpler to draw is influenced by the level of ear implantation more than by brain anatomy. MRI can now be more easily obtained, and we studied the possibility to use routinely AC-PC line. A group of 18 children aged from 2 days to 15 years, found a posteriori neurologically normal and without cerebral lesion, had brain MRI with a GE, SIGNA, 1.5 T. ON line was visualized using a plastic catheter filled with table oil. In 9 of them OM and AC-PC lines were parallel + 4 ~ mean distance between both lines was 30.2 mm +_4.2. In the others the angle between OM and AC-PC could be as much as 120 and distance OM to AC-PC is irrelevant. These results indicated that when OM and AC-PC were parallel, the distance between lines presented only small variations with age. In these children a l~ne parallel to AC-PC and drawn 30 mm lower, AC-PC

impaired neonates,

R. Denays, M. Toodeur, H.R, Ham, A. Piepsz, P. No~L Departments of Neurology, Radioisotopes and Pediatrics, St Pierre Hospital, Free Universities of Brussels, Belgium. In infants who have suffered perinatal trauma, tons and electroeencephaIographic abnormalities are poorly indicative of site of cerebral injury. Cranial ultrasonography is of considerable value in the identification of periventricular leucemalacia, periventricular-intraventricular hemorrhage, porenoephalic cysts and ventrlcular dilatation but is less useful to detect thalamic and parasagittal ischemic in}ury, an extremely commnn feature in asphyxiated term infants. In this work, Tc-9gm HMPAO SPECT studies of 10 neonates wifh severe impairment of limb, neck or trunk tone were compared to the studies of 15 infants in which SPECT was performed in the neonatal period because of the existence of risk factors (such as low birthweight or perinatal asphyxia) but whose neurological examination, electroencephalogram, cranial echography in the neonatal period and neurological outcome at 12 months were normal. Regional cerebral blood flow (rCBF) anomalies were demonstrated using Tc-ggm HMPAO SPECT in all the 10 neurologically impaired neonates. RCBF anomalies ranged from unilateral focal hypoperfusion to extensive bilateral hypoactivity involving cortical, thalamic or cerebellar areas. in the 2 patients with unilateral anomalies demonstrated by cranial ultrasound scan SPEC]- findings were congruent or more extensive. In one patient, bilateral thalam]c 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-9gm HMPAO could have a contributing role in the determination of site and extent of cerebral injury in neurologically impaired neonates.

(30 ram) line, could be used as well as O M line. For children having an angulation between O M and A C - P C lines, the use of A C - P C (-30 ram) line eliminated the error in localizing brain functional areas due to this angulation. It allowed to scan the brain always in the same antero-posterior plane, parallel to A C - P C that is considered to have relatively constant relationship with telencephalie structures (Talairach, J., Masson - 1967). A small device to mark on the skin the A C P C (-30 ram) line, and M R I acquisition procedure are described.

375

376

CEREBRAL VASCULAR MALFORMATIONS IN CHILDREN: THE ROLE OF THE TC-99M RED BLOOD CELL CEREBROVASCULAR STUDY. J.H. Miller, A. Khonsary, P. Stanley, L.S. Fishman, and S.D. Segall.

~EREBRAL PERFUSION ABNORMALITIES IN THERAPY RESISTANT EPILEPSY IN MENTALLY RETARDED PAEDIATRIC PATIENTS (TREMRPP). COMPARISON WITH EEG AND X-RAY CT. H.M. Abdel-Dayem, K. Nawaz, M.M. Hassoon, M.A. Rahman, O.E. Oiofsson, Depts. of Nuclear Medicine & Paediatrics, Faculty of Medicine, Amiri Hospital, Kuwait.

Vascular malformations and capillary angiomas of tr~ brain m~y p~_~ent in chilammod as a cause of seizures, stroke or may even mimic a malignant neoplasm when associated with hemorrhage and a parenchymal hematoma. Usually, these lesions are evaluated by CT, MR, and angiography. Rarely, the findings of these modalities may conflict or be inconclusive. In this circumstance, evaluation of the brain utilizing the Te-99m red blood cell (RBC) cerehrovaseular study (CVS) can be pivotal in the evaluation and clinical management of these patients. We have evaluated 66 patients with suspected cerebral vascular malformations on the basis of clinical examinations or other imaging procedures. There were 33 females and 31 males, ranging from 2 months to 20 years in age. Twenty-five (25) patients were found to have significant vascular malformations including arteriovenous malformations, capillary angiomas, Vein of Galen malformations, and the Weber-Mason syndrome. SPECT was used in five (5) patients which allowed clear definition of lesions. Although not the primary imaging modality for vascular malformations of the brain in children, the Tc-99m RBC CVS can have dramatic impact in the management of these children.

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identification of sites of abnormalities (Abn) in TREMRPP is a difficult and important task. Nuclear Medicine procedures has better accuracy than EEG and X-ray Ct in adult epilepsy. We examined 13 paediatrie patients (pts) (age 1-13 years), 5 males, 8 females with Te-99m HMPAO SPECT (15 studies), Ii had X-ray CT I and 12 had EEG (4 had EEG twice). All studies for same pt were within 2 weeks apart. SPECT studies were reviewed twice by two nuclear medicine physicians without any knowledge of the results of other teits. X-ray CT (i0 pts) showed cerebral atrophy only in 3 and was normal in eight. EEG was abnormal in all 12 pts examined. Epileptogenic spikes (EPS) were seen in 8 pts only. Tc-99m HMPAO showed 21 foci (21) of decreased perfusion in 9 pts, 9 foei of increased perfusion in 7 pts, (3 pts. had mixed lesions). Seven pts out of 8 with EPS have correlating foci of increased perfusion. The 8th pt had severe brain atrophy on X-ray CT and severe mental retardation. No significant inter or intraobserver variability was noticed. We conclude that Te-99m HMPAO is sensitive for localisation of sites of EPS in TREMRPP and that EPS are usually associated with foci of increased perfusion.

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NEUROTENSIN AND BETA-ENDORPHIN IN BRAINSTEM AND CSF IN SUDDEN INFANT DEATH SYNDROME. A. C o q u e r e l , M. B u s e r , F. Pfaff, J. Tayot. Centre Hospitalier Universitaire. Rouen FRANCE

TC 99 M MERCAPTOACETYL TRIGLYCINE (HAG3): NORMAL VALUES FOR KIDNEYS IN PAEDIATRICS AND ITS USE FOR INDIRECT RADIONUCLIDE CYSTOGRAPHY. I Gordon, H Gatanash, G Harris, P Anderson. Hospital for Sick Children, London, UK.

Experimentally NeuroTensin [NT) and BetaEndorphin (BE) induce long lasting apneas after injections in ventilatory areas. Apneas c o u l d b e t h e c a u s e of t h e S u d d e n I n f a n t Death S y n d r o m e (SIDS). I n c o n f i r m e d S I D S w e studied BE in CSF and NT and BE in various brainstem areas. B E w a s m e a s u r e d b y I R M A (Nichols) and NT by RIA (Paesel & Amersham). CSF were o b t a i n e d f r o m 21 S I D S 3 - 2 4 h a f t e r death and were compared to CSF of alive same aged infants and adults. In 6 cases of SIDS the brainstem was removed for BE and NT assays. Each was cut in 5 sections: Upper and Lower Mesencephalon (UMes and LMes respectively), Pons, Upper and Lower Medulla (UMed and LMed), each divided in 3 parts. CSF BE levels were [(n) m e a n • S . E . M . ] : i n S I D S (n=34) 298 • 50 pg/ml; control infants (n=30) 113 • 46 *; a d u l t s (n=20) 54 • 17 **. (vs S I D S * = p < 0 . 0 l , 9 * = p<0.001). In brainstems (pg/mg protein): regions: median intermediate lateral t~id: NT 2 4 , 4 • 7,7 32,2 + 1 2 , 4 70 • 22 BE 279 • 94 315 • 128 241 • 53 LMid: NT 91 + 47 195 + 80 170 • 70 BE 379 + 101 244 _+ 61 261 • 100 Pons: N T 101 + 58 19,9 + 10,5 22 + 22 BE 182 + 63 79 _+ 5 71 + 8 UMed: NT 4,4 _+ 2,1 2 7 , 2 _+ 5,7 1 4 , 8 _+ 5,7 BE 118 -+ 12 282 -+ 50 174 • 38 LMed: NT 0,8 + 0 , 2 22,6 + 7,4 4,2 + 1,5 BE 168 + 59 166 _+ 30 105 • 6 T h e l e v e l s a r e c o n s i s t e n t w i t h a r o l e i n SIDS.

One hundred and eighty children aged 3-15 years were referred for Tc 99m MAG3 dynamic renal scintigraphy (DRS) and indirect radionuclide cystogram (IRC). All children underwent a dynamic Tc 99m MAG3 DRS and 20-40 minutes later micturition in-front of the gamma camera computer was observed, the IRC. The volume and activity of the voided urine was measured. Peak urine flow rate, full bladder volume, residual bladder volume as well as estimation of the renal reflux in ce was calculated. Results: Fifty-one children had normal Tc 99m DMSA scans and renal ultrasound examinations, these children are the basis of the 'normal' data. The mean differential function showed the left kidney contributed 51.37% and the right kidney 48.6% to overall renal function. The % dose taken up by the kidneys at 2 mins was left=t0.7%, right=t0.35%. The ratio of kidney to background at 2 mins showed left=2.4 (SD 0.33) and right=2.3 (SD 0.29). All 180 children underwent IRC. Renal reflux was detected and quantified in 25.5% of children, the bladder and micturition parameters were calculated in all these cases. Conclusion: Normal values of renal handling of Tc 99m MAG3 in paediatrics are presented. Tc 99m MA@3 is a useful agent for semi-quantitative indirect cystography, renal reflux may be detected with greater accuracy because of the low kidney to background activity at the time of micturition.

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ASSESSMENT OF KIDNEY FUNCTION WITH RENAL SEQUENTIAL SClNTIGRAPHY FOR RECOGNIZING RENAL INVOLVEMENT IN CHILDREN AFFECTED BY URINARY TRACT INFECTION. G.La Cava, R.Sciagr~, M.Materassi*, R. lenuso**, U. Meldolesi. Dept of Nuclear Medicine, *Dept of Paediat r i c s , U n i v e r s i t y of Florence; **Dept of Radiology, Meyer Hospital, Florence, I t a l y .

DIRECT COMPARISONS OF CYSTOGRAMS BY RADIONUCLIDE AND RADIOGRAPHIC TECHNIQUES. C.McLaren, J.Sammons. Royal Canberra Hospital, A.C.T., Australia.

We t r i e d to v e r i f y the value of single kidney e f f e c t i v e renal plasma flow (ERPF) f o r recognizing renal involvement in children with u r i n a r y t r a c t i n f e c t i o n . We studied 321 renal units in 162 patients (age 20 days - 15 years, median 3.5 years), with symptoms and signs of u r i n a r y t r a c t i n f e c t i o n . Contrast urography demonstrated renal involvement in 85 kidneys. Renal sequential s c i n t i g r a p h y (RSS) was then performed and the single kidney ERPF was calculated from the 1-123 Hippuran clerance measured with our method, based on e x t e r nal measurements. The lower l i m i t of normalcy was 270 ml/min', i . e . the mean minus 2 standard deviations of the ERPF in a age-mathched group of healthy c o n t r o l s . Of the 85 a f f e c t e d kidneys 83 had abnormal ERPF, of the 236 healthy kidneys 231 had normal ERPF; t h e r e f o r e s e n s i t i v i t y and s p e c i f i c i t y were both 98%. The p r e d i c t i ve value of the p o s i t i v e t e s t was 92% and t h a t of the negative t e s t was 97%. We conclude t h a t single kidney ERPF measurement with RSS using 1-123 Hippuran is an accurate method f o r recognizing renal involvement in c h i l d r e n a f f e c t e d by u r i n a r y t r a c t i n f e c t i o n . I t o f f e r s the advantage over contrast urography of a b e t t e r dosimetry.

S u n d a y , A u g u s t 26, 1 9 9 0

In most comparisons the sensitivity of Direct Radionuclide Cystography (DRC) in detecting Vesico-Ureteric Reflux (VUR) approximates that of the X-ray procedure (XRC). However accurate comparisons have suffered because of the delay (up to 3 months) between studies in many series. To maximize pick-up and to provide an accurate baseline for follow-up studies both tests were performed at the same sitting. To date 50 patients suspected of having VUR (from 2 weeks to 10 years), average age 7 years, have been studied this way. With a single direct bladder catheterization, DRC is first done (with manometer recordings, gamma camera monitoring of filling/emptying of the bladder with computer enhanced images) followed immediately by XRC. If reflux happens DMSA scanning follows on the same day. Preliminary results confirm that DRC and XRC have similar sensitivities for VUR, however in approximately 20% of cases discordant results were found. Because of this variance, utilization of both tests is now routine in the initial workup of children with suspected reflux. This provides a more comprehensive diagnostic picture, with minimal additional radiation and trauma.

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381A

381B

C O M P A R I S O N OF P H A R M A C O K I N E T I C S (P) OF Tc99m DTPA INFUSION OF V A R I O U S INTRAOSSEOUS INFUSION SITES. G.J. Morrissey, D. Gravelle, N. Kisson, D. Warren and A.G. Mattar. University of W e s t e r n Ontario, London, Ontario, Canada.

DIAGNOSIS OF NEUROBLASTOMA 1 2 3 - I - M E T A I O D O BENZILGUANIDINE. O. C a b a l l e r o and J. Ferris H o s p i t a l la Fe. Valencia. Spain.

Intraosseous (IO) infusion of drugs is an alternative to intravenous (IV) administration when vascular access is compromised in patients, particularly pediatric patients. To assess the effectiveness of this technique we injected Tc-99m DTPA at various IO sites: humerus (H), femur (F), proximal tibia (T) and tibial malleolus (M) in a pig model. M e a s u r e m e n t s u s i n g a s c i n t i l l a t i o n gamma camera as well as v a r i o u s b l o o d samples included a) time appearing in the central c i r c u l a t i o n (CO), b) T 89 c l e a r a n c e from IO infusion site and c) blood c o n c e n t r a t i o n as percent injected dose (ID)/mL at 2(Table), 5,10,20,30 and 40 minutes. P data were c o m p a r e d to similar data for T c - 9 9 m DTPA infusion at an IV site (Table). P Site H F T M IV a) sec 15 18 22 18 16 b) m i n • 16• 11• 11• 17• --c) % ID/mL .04 .03 .03 .04 .03 This data suggests that the time to reach CC is similar from all sites. As well, the clearance from the IO sites is variable, but location dependent. The c o n c e n t r a t i o n of tracer reaching CC is not clinically d i f f e r e n t b e t w e e n the IO and IV sites. We c o n c l u d e that an IO infusion can access the cardiovascular system as e f f e c t i v e l y as an IV infusion.

123-MIBG PATIENTS

The children with neuroblastoma needs f o l l o w - u p after tumoral treatment with a s c r e e n i n g test that a l l o w e d us to v e r i f y the e f f i c a c y of therapy, the e a r l y d i a g n o s i s of local recurrence and/or metastasis. The introduction of 123-I-MIBG in c l i n i c a l practical, it has a l l o w e d to m a k e repeat studies in children. W e s t u d i e d 62 patients, all t h e y after t r e a t m e n t of neuroblastoma (surgery and chemotherapy that w e r e followed for four years (mean: T w o y e a r s and six months), 40 cases are in c o m p l e t e remission at present, a n d 22 of them had p e r s i s t e n c e or r e l a p s e of the disease. In all cases, we performed sequential scintigraphies w i t h 1 2 3 - I M I B G (i00 uC/kg), in a g a m m a c a m e r a e v e r y six m o n t h s . In total we have done 356 studies. M I B G - s c a n was normal in the 40 cases in complete remission, and p o s i t i v e in the 22 cases w i t h persistence or relapse of the tumor, a l t h o u g h we have o b s e r v e d h y p e r u p t a k e in all lesions. Finally, we have m a d e an analysis of the factors that could influence the nuclide u p t a k e in these patients: i. Size of surgical rests of tumor, and lack of e x p l o r a t i o n b e f o r e treatment. 2. Metastases lesions of bone m a r r o w and l y m p h a t i c system. 3. P r e v i o u s t r e a t m e n t wi'h~ c h e m o t h e r a p y .

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The aim of this report was to e v a l u a t e the diagnostic value of M I B G scan in c h i l d r e n with neuroblastoma. Forty patients with diagnosis as neuroblastoma proven by histopathological analysis, were studied after being distributed in the following stages: IV, 27 patients, III 8 cases, II 4 cases, and 1 in I. In each case sequential scintigraphies of head, thorax, a b d o m e n and pelvis were performed, and o c c a s i o n a l l y of skull and extremities, at 3,24 and 48 a n d hours with 123 I-MIBG (100 uC/kg). MIBG-scan, has b e e n p o s i t i v e in all cases of primitive tumors and hepatic-bone metastasis, so the index of p o s i t i v i t y has been 100%. The p a t h o l o g i c a l uptake of M I B G was intense, early (24h) and p e r s i s t e n t (72h). We c o n c l u d e that scintigraphy with M I B G has a h i g h s e n s i b i l i t y and specificity in N e u r o b l a s t o m a diagnosis. This justifies its inclusion in the p r o t o c o l of study of these patients, it must be the first exploration in these patients for diagnosis and stage.

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381C A D V A N T A G E S A N D L I M I T A T I O N S OF T H E SCINTIGRAPHY IN THE F O L L O W - U P OF T R E A T E D OF NEUROBLASTOMA. O. C a b a l l e r o and J. Ferris. H o s p i t a l La Fe. Valencia. S p a i n

WITH

THE ROLE OF THE TECHNOLOGIST IN THE STUDY OF MOVEMENT DISORDERS USING THE PET-FLUORODOPA TECHNIQUE. P. Schofleld. UBC/TRIUMF PET Program, Vancouver, British Columbia, Canada. Strlatal uptake of the L-dopa analogue F-18-fluorodopa is diminished In movement disorders. PET is the only technology able to measure (in vlvo) this reduction. As the technique is complex and costly it is essential the technologist be familiar with all aspects of the procedure. Precise calibration of the system (detectors, electronics, and mechanics) is performed daily. An understanding of the acquisition programs, and the ability to modify parameters and procedures are essential. Accurate positioning and meticulous blood analysis contributes to the success of each study. A knowledge of cross sectional neuroanatomy is desirable for ROI placement and an understanding of brain chemistry is an asset. Twelve sequential scans, i0 minutes in duration a r e routinely performed using the UBC/TRIUMF PETT VI tomograph. Prior to scanning, an arterial llne is inserted (by a physician) into the radial artery (for blood sampling), a venous catheter into the opposite antleubltal vein (for injection of tracer), and attenuation Scans performed. It is important the subject be very well prepared for thls lengthy procedure as total cooperation is vital. The teehnologlst's involvement in this exciting research program is challenging and rewarding.

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THE ANIMAL HEALTH TECHNOLOGIST'S ROLE IN CEREBRAL FUNCTION MEASUREMENTS ON NON-HUMAN PRIMATES BY POSITRON EMISSION TOMOGRAPHY (PET)

Tc-99m WHITE BLOOD CELL LABELLING WITH HEXAMETHOPROPYLENEAMINE OXIME (HMPAO): A C O R R E L A T I V E S T U D Y OF T H E V A R I A B L E S A F F E C T I N G LABELLING. J.A. SteDhenson, G.J. Morrissey, D.R. Gravelle and A.A. Driedger, Victoria Hospital, London, Ontario, Canada.

K. Hewitt, Division of Neurology, University British Columbia, Vancouver, B.C. Canada

of

Cerebral functions, such as dopaminergic neurotransmission, are examined in vivo using PET and L-6-fluorodopa (FD) in the brains of both human and non-human primates. The role of the technologist in such studies using cynomolgus monkeys begins with the health and welfare of the monkey before, during and after PET scans. The morning of a scan, a general anesthetic is administered and the cardio/respiratory function is monitored during the entire period of the experiment until recovery. Adequate knowledge of anesthetics and their properties and the course of action taken in the event of an emergency is a must. The PET measurements usually require bolus intravenous injection of the scanning agent and sometimes other pharmaceutical agents, and for this an intravenous catheter is usually placed in the cephalic vein. The measurements also depend on periodic blood sampling, and for this an indwelling catheter is placed, usually in the femoral artery. The blood samples so obtained are centrifuged to obtain plasma, of which measured aliquots are employed for radioactivity assay. In the case of L-6-fluorodopa (FD) uptake studies, the plasma is further analyzed to determine the relative FD and 3-0-Me-FD content by absorption on to alumina. Routinely the total protein, hematocrit and white blood cell count is determined to monitor the physical status of the monkey from scan to scan.

The a d v e n t of H M P A O has i n c r e a s e d the use of in-vitro labelling of human p o l y m o r p h o n u c l e a r l e u k o c y t e s (PMNL) w i t h Tc99m. This was a retrospective s t u d y to d e t e r m i n e t h e e f f e c t s of c e r t a i n v a r i a b l e s on the l a b e l l i n g e f f i c i e n c y (LE) e n c o u n t e r e d in 275 p a t i e n t s who underwent a Tc-99m leukocyte (WBC) scan. These variables i n c l u d e d i) the v o l u m e of T c - 9 9 m (mean • ISD 0.8ml • .7;n=252), ii) age of T c - 9 9 m e l u a t e (2.3hr • 1.3;n=244), iii) p a t i e n t ' s WBC c o u n t (12.4 x 109/L • 7;n=186), iv) b o d y t e m p e r a t u r e (37~ • 1.6;n=62), v) s e t t l i n g time (24min • Ii;n=27) and vi) m e d i c a t i o n s

(n=184). T h e r e w a s a low c o r r e l a t i o n b e t w e e n LE and v o l u m e of T c - 9 9 m (r=0.14). The o n l y significant c o r r e l a t i o n w a s w i t h the W B C c o u n t (r=0.37). Of 28 m e d i c a t i o n s o b s e r v e d only antihistamines (AH;n=56) had any effect. T h e LE of p a t i e n t s o n A H (58.8 • 1.67 • sem) d i f f e r e d s i g n i f i c a n t l y from t h e o t h e r s (52.6 • 1 . 2 4 ; p < . 0 1 ) . B a s e d on t h e a b o v e it w a s c o n c l u d e d t h a t the W B C c o u n t is the m o s t i m p o r t a n t f a c t o r a f f e c t i n g the LE of W B C w i t h T c - 9 9 m HMPAO. WBCs l a b e l l e d w i t h H M P A O is r e p r o d u c i b l e a n d r e l i a b l e o v e r a large r a n g e of c l i n i c a l and technological variations.

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COMPARISC~ OF ANT/DXIDANTS FOR IN VITRO STABILIZATION OF TECHNETIUM-99m HMPAO. S. Nardi, A. Proulx, a n d J.R. Ballinger. Nuclear Medicine, Ottawa Civic Hospital, Ottawa, C a n a d a .

PRACTICAL CONSIDERATIONS IN P R E P A R A T I O N OF TECHNETIUM-99m M I B I F O R C L I N I C A L USE. S. Gillespie and J.R. Ballinger. Nuclear Medicine, O t t a w a Civic Hospital, Ottawa, Canada.

The in vitro instability of T c - 9 9 m H M P A O makes in inconvenient to use. H u n g et al (J Nucl M e d 1988; 29:935) showed that H M P A O can be stabilized in vitro by adjustment of the p H to 6-7.4 and addition of an antioxidant (AO), gentisic acid (GA). However, G A is unstable at high p H and thus cannot be added to the kit itself. W e the/~fore evaluated 3 other A O s which are used in radiopharmaceutical kits: p-aminobenzoic acid (PABA), cysteine (Cys), and ascorbic acid (Asc). Lipc~hilic Tc-99m H M P A O was isolated from reconstituted kits cmto a C-18 SEP-PAK extraction cartridge and eluted in 1 m L ethanol, which was then diluted with 9 volumes of bicarbonate buffer (i0 mM, p H 6) contain/rig 1 mg/mL AO. The buffer without A O served as a control. Radiochemical purity (RCP) was measured repeatedly by the ethyl acetate extraction technique v~]~dated in our laboratory. T h e decline in R C P with time was fitted to a m o n o e x p o n e n t i a l f u n c t i o n to d e t e r m i n e t h e d e c o m p o s i t i o n rate c o n s t a n t k d. Under the conditions of p H and A O concentration stud~ed, G A and P A B A slightly improved the stability of HMPAO. Conversely, Cys and Asc greatly acce/erated decomposition and thus are u n s u i t a b l e for u s e in stabilizing H M P A O . T h u s , P A B A m a y b e a n a l t e r n a t i v e to G A for stabi//zation of H M P A O but optimal conditions of p H a n d c o n c e n t r a t i o n r e m a i n to b e d e t e m i n e d .

Although Tc-99m M I B I (Cardiolite R) offers advantages over TI-201, it also presents a n u m b e r of practical difficulties. It is less convenient, requiring preparation (including a boiling step), quality control (QC), and separate injections at rest (R) and stress (S). There is a limitation to t h e amount of activity and volume which can be added to a vial. The high cost of MIBI w//l necessitate optimal use. For the following analysis, it was assumed that 5500 M B q in 3 ml can be added to the kit and t h e first a n d s e c o n d d o s e s are 370 a n d iii0 M B q , respectively. A maximum of 3 pat/ents undergoing R and then S imaging (preferred sequence) can be studied from a single vial without exceeding the m a n u f a c t u r e r ' s specifications. With the S/R sequence, requiring 3 hr rather t h a n 2 h r b e t w e e n injections, only 2 patients can be studied per vial. W h e n setting u p a schedule, multiple generator elutions may be required during the day. Using 1 camera, 4 patients can be imaged comfortably between 0800 and 1300 hr, requiring 2 elutions but leaving the camera free for other tests in the afternoon. One camera could image up to 8 patients per day, but 2 generators wou~d be needed, each being eluted twice. Depending on demand, 1 day per week may be set aside for MIBI, preferably early in the week for higher generator yield. One major limitation in a small department is the availability of staff to take time during the day to reconstitute a kit; p r e p a r a t i o n a n d Q C r e q u i r e s ~30 min.

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NEED FOR SCATTER CORRECTION IN DUAL ISOTOPE IMAGING IS DEPENDENT UPON RADIONUCLIDE DOSES. C Smith, TD Ruddy, RA Davies, KY Gulenchyn. University of Ottawa Heart Institute at the Ottawa Civic Hospital, Ottawa, Canada.

LESION VOLUME DETERMINATION BY SPECT: ANALYSIS OF PROCESSING FACTORS FOR TC-99M AND IN-111. SW Walker, KY Gulenchyn, C Smith, RA Davies, TD Ruddy, University of Ottawa Heart Institute, Ottawa, Canada.

Dual isotope (DI) imaging has potential problems when using radionuclide combinations with similar energies. Significant down and up scatter may occur with combinations used for imaging myocardial necrosis and perfusion such as In-111 (172 keV, 247 keV) with TI-201 (70 keV, 164 keV) or Tc-99m (140 keV). Syringe sources of T1-201 (0.3 mCi), Tc99m (0.3 mCi) and I n - l l l (0.2, 0.3, 0.4 mCi) were counted with a LFOV gamma camera and a medium energy collimator. 20% windows were used for each of the isotopes (TI-201 70 keV, In-111 247 keV, Tc-99m 140 keV). Downseatter of In-lll, as a fraction of the counts in the In111 window, was 32% in the Tl-201 window and 90% in the Tc-99m window. Upscatter in the In-111 window was negligible (2% for TI-201 and .06% for Tc-99m). Using appropriate clinical dose approximations, downscatter of In111 (2 mCi) would contribute 13% of the recorded T1-201 (3 mCi) counts. Downseatter of In-111 (2 mCi) would contribute only 0.5% of the counts recorded in the Tc-99m (20 mCi) window. Thus, down scatter correction appears necessary for combined In-Ill/T1-201 DI imaging. However, down scatter correction will not be required for In-lll/Tc-99m DI imaging because of the relatively small scatter contribution. For DI imaging of myocardial perfusion and necrosis with I n - l l l antimyosin, a Tc-99m labeled radiotracer such as Tc-99m isonitrile would be preferable to TI-201.

In-111 antimyosin has recently became available for infarct imaging. Our purpose was to determine 1) the appropriate reconstruction filter, filter parameters and background subtraction thresholds for lesion sizing with In-111 and 2) whether these parameters varied from those of Tc-99m. SPECT phantom (Data Spectrum) studies using a medium energy collimator were performed with I n - l l l and Tc-99m. A 21 ml lucite sphere was filled with 5.4 uCi/ml and activity was added to the background to approximate a 6:1 target to background ratio. Reconstruction was performed using Butterworth (BW) (Nyquist (N) 0.3 - 0.8, filter order 3-9) and Shepp-Logan-Hanning (SLH) (N 0.3 - 0.9) filters. Lesion volume was determined from transaxial slices with thresholds of 10 -70%. Best lesion sizing with In-lll occurred using the SLH filter with N of 0.6 and threshold of 70% and the BW filter with N of 0.5, 0.6 and threshold of 60%. Best lesion sizing with Tc-99m occurred using the SLH filter with N of 0.3, 0.4, 0.5, 0.6 and threshold of 70%, 60%, 50% and 40% respectively, and the BW filter with N of 0.6, 0.7, 0.8 and threshold of 36%. Thus, 1) l n - l l l and Tc-99m optimum lesion sizing depends upon appropriate SPECT filter, filter parameter and threshold, 2) In-111 images require a higher threshold for optimal lesion sizing (This is likely related to the greater scatter of this radionuclide) and 3) filter, filter parameters and threshold must be optimized for each radionuclide so that clinical lesion sizing is accurate.

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ESTABLISHMENT OF PARAMETERS FOR ACQUISITION AND RECONSTRUCTION OF SPECT IMAGES OF CEREBRAL BLOOD POOL. C.M. Lau, R. Irvine, K. Gulenchyn. Ottawa Civic Hospital, Ottawa, Ontario, Canada.

IN-Ill ZCE 025 IF~v~JNOSCINYIGRAPHY IN "OCCULt' COLORECTAL CARCINOMA PATIENTS. H. Ahdel-Nabi, N. Evans, E. Farrell, R.J. Doerr, VA Medical Center, University at Buffalo, NY and S. Schweighardt, B. Merchant, Hybritech Incorporated, San Diego, CA.

This study describes the establishment of parameters and the development of a protocol for acquiring and reconstructing SPECT brain images to determine cerebral blood volume in the evaluation of cerebral vascular disease. Te-99m-HMPAO images were compared with those acquired with Tc-99m labelled red blood cells. All procedures were carried out using a Low Energy All Purpose collimator and repeated with a High Resolution collimator for comparison of image quality and total technical imaging time. Computer analyses and mathematical calculations were performed to arrive at an average cerebral blood volume of 4.1 mL of blood per cubic centimeter of brain tissue for six normal subjects. This value was comparable to published results. The established parameters and protocol for this study to be performed in a Nuclear Medicine department are presented in this exhibit.

$100

This study investigated the merits of Indium-lll (In-lll) labeled to anti-carcinoembryonic antigen (CEA) murine monoclcnal antibody (MoAb) ZCE 025 imaging in identifying "oecult" tumor sites in patients (pts) with high clinical suspicion of colorectal carcinoma recurrences (CCR). Seven pts had elevated serum CEA (range 6.4-51 ng/ml, normal 3.5 ng/ml) end negative radiographic and colonoscopic findings; 3 pts had elevated CEA (4.1-59 ng/ml) and suspected liver metastases (mets) by computerized tomography (CT). T~ere were suspicious CT findings in 2 pts with normal CEA. Each pt received 5.6 mCi In-lll labeled to 2.0 mg MoAb ZCE 025 plus 38 mg of the unlabeled MoAb. Patients were scanned 3-7 days following infusion by planar and emission computerized tomography (ECT). Sulfur colloid liver-spleen ECT scanning was also obtained in 4 pts. Seven pts had exploratory laperotomy 1-3 weeks following MoAb scan which detected CCR in 4 pts and liver mets (hot lesions) in 2 pts, all surgically confirmed. Liver mets were missed in 1 pt as well as a mstachronous cecal lesion in another. !n-lll ZCE 025 MoAb imaging sensitivity was 7~/o, positive predictive value, 88%. Two pts with negative scans had no surgical evidence for CCR. MoAb imaging was positive for liver mets in 3 pts, and lymph node mets in 2 pts; all tumor sites subsequently confirmed by CT scans during the ensuing 6 months. In 4/12 pts, m~tiple tumor sites were simultaneously detected by the MoAb scanning. In conclusion, the accurate localization of CCR end mets with In-lll ZCE 025 MoAb demonstrates the usefulness of this modality in pts with high clinical suspicion for recurrence.

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395

INDIUM-Ill IABEL~D MOAB DETECTION OF LIVER METASTASIS FROM COLORECTAL CANQ~R: HISTOPATHOLOGIC ~ IP~UNOSCINTIGRAPHIC CORRELATES. Ho A b d e l - N a b i . R.J. Doerr, V e t e r a n s Administration Medical Center, School of Medicine and Biomedical Sciences, University at Buffs/o, NY.

REGIONAL ACTIVITY VARIABILITY USING A TIME OF FLIGHT PET SCANNER. L. Cinotti, F. Lavenne, D. Le Bars, M. Chaze, K. Sasse, P. Landais, G. Galy, F. Maugui~re. CERMEP, Lyon, FRANCE.

Liver metastasis remain the co~onest site of colorectal carcinoma (CC) spread. Immunoscintigraphie detection of liver metastasis with Indium-lll (In-lll) labeled murine monoelons/ antibodies (MoAb) varies from 20 to 8 0 % . This study was conducted to determine the factors influencing liver metastasis detection. Eighty five pts with CC primaries were evaluated with anti-CEA MoAb ZCE 025 (n=39, group I); and anti-TAG-72 MoAb B72.3-GYK-DTPA (n=46, group 2) labeled with In-lll, Patients in group 1 received 5.5 mCi In-lll labeled to 2,0 mg plus 38 a~ unlabeled MoAb co-infused simultaneously; group 2 pts received 3.85 mCi In-lll labeled to 1.0 - 20~ rag MoAbo Histopathologic correlates of liver metastasis (size, differentiation (DIF), degree of necrosis) were compared to results of MoAb scans. Liver metastasis were confirmed intraoperatively in 16 pts, appearing as hot lesions in 8 pts, cold in 6 pts, and uptake equal to normal liver "normoactive" in 2. Histopathologie factors were; (i) size: liver lesions 1o5 - 2.0 cm appeared hot; (2) tumor DIF: moderate and well DIF imaged hot or normoactive, while poorly DIF appeared as cold, irrespective of size, (3) % necrosis present: 20% necrosis seen as hot lesions, 50% necrosis appeared cold; In conclusion, 50% of liver lesions appeared as hot lesions on In-lll MoAB seintigraphy. The most important histopat hologie factors related to successful Jammnoscintigraphy of coloreetal liver metastasis are size, degree of differentiation, and amount of necrosis of the lesion.

396 ATRIAL FOURIER ANALYSIS CAN DEMONSTRATE RETROGRADE VENTRICULOATRIALCONDUCTION IN SUPRAVENTRICUIT~TACHYCARDIA. P.Gonzalez, M.Ortiz, R.Lillo, I.Arambur6, T.Massardo, R.Oya~zun and S.Otarola. university of Chile. The goal of this research was to assess Fourier Analysis(FA) of atria for depicting retrograde ventriculo atrial conduction(RVAC), in patients(pts), with supraventricular tachycardias(ST)and concealed tracts, correlating to electrophysiology(E). Seventeen pts-7 males; mean age 38(16-65)- with ST and concealed tracts proved on E, underwent radionuclide ventricuiography with Tc-99m labelled red blood cells in best septal LAO view, in resting condition and during induced ST at E study, obtaining biventricular ejection fraction(EF) and FA. The ECG was normal in all. E r e v e a l ~ 12 left tracts and 5 in the septum. Resting left ventricular EF was 66+__11% (X+_SD) and 57+15% during ST (p=0.0003). Right EF was 52+--7% and 41+__~% respectively(p=0.0001). Mean heart rate was 83+22 b~m in basal study and in ST 187+23 b~n. Resting a~rial FA was normal in all and ven~ricular FA in 15/17, showing earlier left ventricular contraction in 2 with left tracts. During the ST, atrial FA demonstrated RVAC with earlier left atrium contraction in 12/12 left tracts. In septal pathways, FA showed both atria with early contractions in one pt, another with early left atrium activity and 3 were considered nondiagnostic. Ventricular FA was similar to basal study, described above. Concluding, Atrial FA can show RVAC during ST in concealed tracts especially left ones. This could eventually be used to locate the site of accessory tracts. Resting FA has poor sensitivity in concealed pathways. EF decreases significantly during ST.

Sunday, August26,1990

The noise to signal ratio (NSR) in PET imaging is usually estimated by the pixel to pixel standard error mean (SEM) of activity in an homogeneous image. It is theoretically lowered when pixels are grouped together. Therefore, we were interested to measure the improvement brought to the SEM when regions of interest (ROD are compared. 9 18 F-fluoride We used a uniform cylinder filled with a .87 mCl/ml solution. We collected 40.106 transmission and 100.106 emission events in l i s t mode using 2 out of 4 detector rings. Series of 256 x 256 images were reconstructed using Hanning and Cosine filtering (zero and negative derivative at the .25 m m -1 cutoff frequency) for .5, 1, 2, 5, 10 and 50 Mevents. Five circular ROIs (10 pixels radius) were d r a w n at increasing distance from the center. The interpixel and interROI relative variations were compared a n d presented as averaged SEM in percent to estimate the NSR in direct (dp) and cross (cp) tomographic planes. Hanning Images 0.5 1.0 2.0 5.0 10.0 50.0 SEM pixel dp 75.7 45.2 33.0 22.9 15.5 10.6 SEM plxel cp 47.3 39.6 28.6 16.9 11.6 8.3 SEM ROI dp 3.7 3.1 2.2 1.2 .95 .44 SEM ROI cp 2.9 2.5 2.2 / .85 .31 These results show an improvement by a factor of 13 to 26 when considering ROI instead of pixel SEM variations. SEM is also higher in dp than in cp due to the higher sensitivity of the latter. Two ways ANOVA showed no ROI position effect in dp or cp but a significant count/pixel (N) effect (p< .0001). A linear correlation (r = .97, p< .0001) was found between SEM for ROIs and the expected NSR proportional to N -1/2 only since the ROI size was constant. Compared to Hanning, Cosine reconstructed images demonstrated for pixels a 39% higher SEM which decreased to 22% for ROIs (p< .001). The interROI variability, more relevant for quantitation i n biological studies, is 10 to 20 times lower than the inter-pixel SEM whatever the count rate. It remains sensitive to reconstruction filters.

397 CLINICAL INVESTIGATION OF 99mTc TEBOROXIME (CARDIOTEC) Margaret M. LaManna, M.D. ,FACC, Riyad Mohama, M.D. , Lewis Slavich, D.0., Frank J. Lumia, M.D., Rite Lauderman, CNMT, Naipaul Rambaran, M.D., Vladir Maranhao, M.D., FACC Deborah Heart and Lung Center, Browns Mills, NJ Twenty-five patients mean age 58, underwent Thallium studies within 2 weeks of a 99mTc Teboroxime (Cardiotec) exercise stress and rest procedure. Patients achieved comparable exercise stages, %maximal predicted heart rate, peak systolic and diastolic blood pressures for both Thallium and Cardiotec. The electrocardiograms were compared. There were no adverse side effects noted. The correlation coefficient between Cardiotec and Thallium was high at 0.92 with a "p" value of less than 0.001. Total imaging time with Cardiotec was approximately II0 minutes, excluding treadmill time. The authors conclude that Cardiotec compares favorably with maximal stress Thallium imaging and provides considerable time savings.

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ALVEOLO-CAPILLARY PERMEABILITY (ACP) MEASUREMENT W I T H TC9 9m D T P A I N A S Y M P T O M A T I C P O P U L A T I O N . A I R P O L L U T I O N EFFECT. T.Massardo, P.Humeres, R.Paredes, E.Jouanne, P. Gonz&lez. University of Chile, Nuclear Medicine Center, Santiago, Chile

AS-76 DETERMINATION IN HUMAN HAIR USING NAA TECHNIQUE. A. Pazirandeh, M. Shahidi, Physics Depatment, Tehran U n i v e r s i t y , Nuclear Research Center Atomic Energy Organization o f Iran (AEOI), Department o f Dermatology, Medical Sciences o f Shahid-Beheshti U n i v e r s i t y , Tehran, Iran.

S a n t i a g o h a s a h i g h g r a d e of a i r p o l l u t i o n , especially during winter (W) . A w a r e o f t h e a b n o r m a l i t i e s o f A C P in s m o k e r s , we d e c i d e d t o co n d u c t a st u d y in an a s y m p t o m a t ic p o p u l a t i o n l i v i n g in S a n t i a g o a n d s u r r o u n d i n g s , w i t h T e g 9 m DTPA aerosol scanning. Three groups were studied: I)Adult group, (9M,SF} , living indifferent neighbourhoods e v a l u a t e d al 1 y e a r l o n g ; I Ia) A group of 8 healthy young males attending to a downtown highsohool (morepollutedarea) , of t h e s e 7 w e r e s t u d i e d a g a i n d u r i n g s u m m e r (S) vacation IIb) a n d III) a similar group coming from semirural places. All volunteers (non smokers a n d withoutbronoopulmonardiseases ), u n d e r w e n t Ultraventnebulization (40mCiofTcg9mDTPAfor 5rain). An a c q u i s i t i o n w a s t h e n o b t a i n e d f o r 15 rain. E x p o n e n t i a l m e a n h a l f t i m e l u n g c l e a r e n c e (T1/2) f r o m the first 7 m i n w e r e c a l c u l a t e d : GROUP(n) SITE SEASON AGE year T1/2min x+ds x +ds (range) I (17) control all 36.4+_9.3 98_+40 ( 4 9 - 1 8 6 ) IIa (8) downtown W 17.4+_0.5 47-+ 9 ( 3 2 - 6 1 } Ilb (7) S 17.9+0.5 110+_39 ( 6 8 - 1 6 8 ) II! ( 7 ) r u r a l W 17.1+0.7 69+26 (32-106) It was found a significant T1/2 difference between IIa and III inwinter (p=0.044) , their mean age were similar (p=0,47)0 The seasonal difference in group II was also significant (p--0.006) .TherewasnodifferencebetweenIand Ilb (p=0.76) and Ilb and III (p:0.08). Concluding, lung aerosol scanning is useful to detect asymptomatic air pollution effect on ACP.

Many have attempted to measure the accurate amount o f the t r a c e elements in human body (in blood, l i v e r , kidney, h a i r . . . . ) using diverse techniques to f i n d a base f o r sound judgement o f any i r r e g u l a r i t i e s in the organ f u n c t i o n , i f i t should be a t t r i b u t e d to beyond the t o l e r a n c e level o f some major elements. Not along ago, neutron a c t i v a t i o n analysis (NAA) employing very s o p h i s t i c a t e d equipment has enabled researchers to measure e s p e c i a l l y very s h o r t - l i f e r a d i o i s o t o p e s which have been produced by neutron i r r a d i a t i o n o f samples in an i r r a d i a t i o n f a c i l i t y of a research r e a c t o r s . Recently, M. Shahidi ( d e r m a t o l o g i s t ) came across a group o f p a t i e n t s having ski'n t r o u b l e ; he was suspicious o f Chroni~ Arseni'c poisoning, The c l i n i c a l examination i n d i c a t e d some symptoms such as raindrop pigmentation o f the s k i n , k e r a t o s i s o f the palms and soles. And also r e s p i r a t o r y d i f f i c u l t i e s , Dermatitis and Bullae f o r m a t i o n , Mee's l i n e s o f f i n g e r - n a i l s were observed. Desquamation o f the skin and other signs documented w i t h urine and h a i r e• TSese symptoms revealed t h a t the p a t i e n t s have suffered from chronic arsenic poisoning. We were r a t h e r sure of higher arsenic i n t a k e than normal by the p a t i e n t s . By analyzing t h e i r h a i r along with the h a i r o f an unaffected person using Neutron A c t i v a t i o n Analysis (NAA) technique we found higher accumulation o f arsenic in t h e i r h a i r than in normal h a i r . More i n v e s t i g a t i o n s revealed t h a t the p a t i e n t s were using local water which contained high c o n c e n t r a t i o n o f arsenic.

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COMPARISON OF INDIUM-Ill WBC'S AND T E C ~ I U M 99m HMPAO WBC'S IN THE DETECTION OF INFECTION. D.S. Rimkus, Cancer Foundation, Santa Barbara, CA USA

EFFECT OF EXERCISE SUPPLEMENTATION ON DIPYRIDAMOLE THALLIUM-201 IMAGE QUALITY. S. Stern, I.D. Greenberg, R. Come.

This study compared Indit~n-lll and Tc-99m HMPAO labeled W]3C's in a group of ii patients. White blood cells were separately but simultaneously labeled with In-lll and Tc-99m HMPAO in patients suspected of having infection. The studies yielded comparable results in all ii patients with 3 positives (ostec~nyelitis, soft tissue, septic arthritis) and 8 negatives. F~PAO-WBC's provided superior image quality at 2-4 hours, but were similar to In-WBC's at 18 hours. Gastrointestinal activity was apparent in all F~4PAO-WBC studies at 18 hours, limiting the value of the 18 hour images of the abdomen. Tc-99m HMPAO labeled WBC's may replace In-lll WBC studies, particularly when early (2-4 hour) results are clinically necessary.

Intravenous dipyridamole thallium imaging has become a valuable alternative to exercise thallium testing in patients unable to perform an adequate level of exercise. The quality of these images however suffers from a high level of infradiaphragmatic activity which makes interpolative background subtraction and subjectiveassessmentmore difficult. Several investigators have proposed that the addition of low level exercise- either in the form of isometric handgrip or low level treadmill exercise would improve the quality of the images. This study was undertaken to prospectively evaluate image quality both qualitatively and quantitativelyin threepatient groups - those receivin gdipyridamolealone (D), dipyridamole in combination with isometric handgrip (HG), and dipyridamole with low level treadmill exercise 0-M). Thirty patients were randomizedto D, HG, and TM groups and anterior images of the chest were obtained. Regions of interest were placed over areas of peak heart and peak liver activity, and representativeregions in both lungs. Another region of interestwas placed adjacent to the inferior wall of the left ventricle. Ratios of heart to lung (H/LUNG), heart to liver (H/LIV), and heart to adjacent infradiaphragmatic region (H/ADJ) were generated. Heart to total infradiaphragmatic activity was also graded semiquantitatively(SQ) by 2 independentobservers using a 3 point scale (1=poor, 2=average, 3=excenent). Resultsare as follows:

Health Sciences Centre, Winnipeg, Manitoba, CANADA.

n D 11 HG 10 TM 9 p HG vs D p TM vs D p TM vs HG

H/LUNG H/LIV H/ADJ SG 2.55 2.47 2.66 N.S. N.S. N.S.

1.22 1.15 1.78 N.S. <0,01 <0.01

1.46 2.1 1.53 1.8 1.93 2.5 N.S. N.S. <0.002 <0.02 <0.01 <0.01

We conclude that supplementation of dipyridamole testing with low leveltreadmillexerciseproducesa significantimprovementin image quality over that of dipyridamole alone, or dipyrldamole with isometric handgrip,

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CC~ARISON OF CARDIOLITE (Tc-99m-HIBI) WITH THALLI~-201 ~GING BY PLANAR A~D SP~'T TB3~IQUES FOR ASSFZS~T OF P A T I ~ WITH C O ~ Y ART~Y DISEASE. V. Ser.~enko, L. Samoylenko, A. Malov, E. Svirshevskii. All-Union Cardiology Research Center, Moscow, USSR

~adiolodtnated o<-butylhydorxybenzyl acohol as potential agent for benzodiazepine receptor imaging

a

Guo Zhengpin and Tan T i a n z h i Dept. of Nuclear Medicine, Medical Sciences. Chengdu.

West China University Sichuan, China 610041

of

To compare diagnostic accuracy of TI-201 and Cardiolite (Du~t) 52 patients (pts) with coronary artery disease (CAD) (24 pts. with previous HI and 28 pts. without HI) undergoing coronary angiography were studied with both TI-201 and Cardiolite planar and SP~CT i , ~ i ~ . TI-201 images were obtained at i0 and 240 rain. after a 2.0 mCi injection on stress testing. 5-7 mCi of Cardiolite was injected at the same exercise work load within a week of the TI-201 study. Imaging was performed from ene to three hours later. Rest study with Cardiolite was obta/ned one day later with the same acquisition parameters and the same dose. The localization of stable perfusion defects was identical in all pts. with CAD and previous HI on TI-201 and Cardiolite planar and SPECT images. Reversible perfusion defects were noted in 87.5% (21/24 pts.) ca planar TI-201 scintigraphy. Planar scintigraphy with Cardiolite correlated well with type of TI-201 defect in 79.2% (19/24 pts.) . SPECT TI-201 and Cardiolite showed similar results (87.5% and 79.2%, respectively). In pts. without previous HI the appearance of reversible perfusion defects on TI-201 pla~r scitigraphy was docmaented in 92.9% (26/28 pts.) and in 82.1% (23/28 pts.) ca planar Cardiolite. Ca SPECT TI-201 images the perfusion abnormalities were revealed in 92.9% (26/28 pts.) and in 85.7% (24/28 pts.) on SPECT Cardiolite. Thus, Car~olite and TI-201 correlate well on both planer and SPECF images for i) the presence and localization of stable perfusion defects in pts. with CAD and previous HI, 2) the deteetica of the perfusion akaormalities in CAD pts.

C~-butylhydroxybenzyl alcohol(G-018), a derivative of gastrodigenin(a effective component of Tianma, wellknown chinese traditional medicine) has been shown highly accumulated in mice brain. The tritium labeled G018 was found binding to benzodiazepine receptor. In the present investigation. 1-125 labeled G-OI8 with high specific activity(4.07xlO I~ Bq/mMol) and radiochemical purity(99%) was prepared by the method of chloramine-T. In a solusion of 5ug G-018 in 15% ethanol and imCi Na I. the reaction was initiated by addition of 100ug Ch-T for 5minutes at room temperature, then terminated with sodium thiosulfate. In contrast, the stable iodine labeled G-Of8 for MS and NMR spectra analysis was prepared as follows: 300ug Ch-T in aqueous solusion was added to a vigrously stirred suspension of 40mg G-Of8 in 15% ehtanol and 45mg potassium iodide, the suspension was continously stirred for 30minutes at 60 ~ The mixture was extracted by ether(3x2ml). Purification was carried out on a silica gel chromatography, which eluted by chloroform/methanol(7:3). The eluted fractions containing labeled compounds were pooled for removing of the solvent by negative pressure at 30 ~. One iodine incorporated into the ortho-position of benzyl ring in G-018 molecule was confirmed by MS and NMR spectra. In competitive binding, nonradioactive G~O18 and diazepam inhibited 1-125 G-OI8 binding to rat brain membrane competitively, which indicated 1-125 G-018 binding to benzodiazepine receptor. Following injection of 1-131 G018 to rabit, brain images were obtained at 1, 5, I0, 15mln with a planar camera. Radioactivity obviously accumulafied in the brain and retained for .15min. This results suggseted that radioiodinated G-Of8 is a potential agent f o r benzodiazepine receptor imaging.

404

405

A DECADE OF EXPERIENCE IN THE FOLLOW-UP OF PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA BY THYROGLOBULIN DETERMINATION

Synthesis of N o - C a r r i e r - A d d e d 1'F-and n C - L a b e l e d Methamphetamine and its Analoqs. C.Y. Shiue, G.G. Shiue, R. Sharma and M.P. Frick. Creighton University, Omaha, NE.

Fi. F r a n c e s c h i ,

M e t h a m p h e t a m i n e and 3 , 4 - m e t h y l e n e d i o x y m e t h amphetamine ("Ecstasy") are the w i d e n i n g u s e d illicit drugs. In order to characterize their in vivo b i n d i n g p r o p e r t i e s w i t h PET, we have synthesized [iSF]methamphetamine (ib) and its analogs. C o m p o u n d (ib) was s y n t h e s i z e d f r o m p - n i t r o b e n z a l d e h y d e with ZSF (K1aF/kryptofix, DMSO, 140~ 10 min), f o l l o w e d by K n o e v e n a g e l condensation with n i t r o e t h a n e (II0~ 10 min), reduction with LiAIH 4 and m e t h y l a t i o n with CH3I to give (ib) in -7% yield in a synthesis time of i00 min from EOB. Attempt to synthesize (2b) from (2a) r e s u l t e d in a low yield, tar-Labeled "Ectasy" (id) was s y n t h e s i z e d from 6-nitropiperonal in a similar m a n n e r in an overall yield of ~5% in a synthesis time of ~i00 min from EOB. M e t h y l a t i o n of a m p h e t a m i n e and 3,4methylenedioxyamphetamine with CH3I (DMSO-DMF, CH3CN, 150~ 5 min) gave m e t h a m p h e t a m i n e and Ecstasy in 40% yield. The synthesis of nClabeled methamphetamine, E c s t a s y and the studies of their in vivo b i n d i n g p r o p e r t i e s are currently under investigation.

Lj. L u k i n a c ,

Z. K u s i d , S. S p a v e n t i .

H u c l e a r Medicine a n d 0ncolop~ Clinic, D r M. Stojanovir Clinical Hospital, Zagreb, Yugoslavia

During last ten years serum thyroglobulin (TG) measurements were performed in the follow-up o f 248 patients with differentiated thyroid carcinoma. All patients had undergone surgical treatment and radioiodine ablation o f the thyroid remnant. Blood samples were obtained from all patients after T4 substitution withdrawal. In some, T G was measured during replacement therapy as well. Serum T G measurements were performed with the commercial TG RIA kit with the range o f 5-600 ng/ml. Sera containing T G antibodies were excluded from the study. Undetectable or v e r y low T G levels were determined in 195 o f 213 patients without residual tumor tissue. Elevated serum T G levels were found m the remaining 18 patients (ranging between 14 and 156 ng/ml). These patients are being carefully monitored. Increased T G concentrations were measured in all but one patient with metastases accumulating I- 131. In 21 patients with distant metastases TG levels were above 100 ng/ml, and in 4 patients with regional lymphonode metastases T G ranged between 20 and 63 ng/ml. Six o f 9 patients with nonfunctioning metastases h a d elevated T G (> 260 ng/ml), and in 3 patients T G was undetectahle (< 5 ng/ml.). In 9 patients T G levels were found to correlate with the progression o f disease or the success o f the treatment. It is apparent that T G determination in the follow-up o f patients with differentiated thyroid carcinoma is o f great value, especially in patients with nonfunctioning metastases.

Sunday, August26,1990

(2a) (lb) (lc) (ld) (2a)

R1 = R3 = R~ = R 1 = R s = H; R1,R 2 = OCH20; R1,R 2 = OCH20; x = NO2 (2b)

H; R2 = 18F R2 = I~F, R~ = CH3 R 3 = 18F; R 4 = H Ra = 18F' R 4 = CH3 x ~SF"

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406 BONE MASS BY DUAL PHOTON ABSORPTIOMETRY IN CHRONIC ALCOHOLISM WITHOUT LIVER CIRRHOSIS. H. Pumarino, P. Gonzalez, S. Oviedo, R. Lille, E. Bustamante, J. Santiba~ez and M. Rios. University of Chile Hospital. Santiago, Chile. Chronic alcoholism has been suggested as a risk factor for low bone mineral content. However, not many studies have documented its derangement by dual photon densitometry(DPD) in patients without liver damage. The goal was to assess global and regional bone mineral density(BMD) and total bone mass(TBM) in this condition using DPD. Forty eight alcoholic(A) (mean age=42; range:22-68) without liver cirrhosis, underwent whole body, lumbar spine and bilateral femur Gd-153 DPD. Their results were compared to 48 normals(N) paired by age. In addition height and weight were determined. In A blood tests revealed only mild hypomagnesemia in 8 cases. Results Mean + SD, were as follows: BMD (g/cm2) N A p Spine i. 06+0.13 1.07+0.13 NS Left Hip 0.97~0.14 0.99~0.13 NS Right Hip 0.96~0.12 0.99+--0.15 NS W. Body 0.93+0.08 0.92~0.08 NS TBM(g) 2492~314 2326~345 0.02 HEIGHT(cm) 170~5 164+7 0.003 WEIGHT 70~8 63~9 0. 003

407 TRANSFORMATION OF THE IRON ELECTRONIC STRUCTUREIN OXYHEMOGLOBIN FROM PATIENTS WITH LEUKAEMIA OR ERYTHREMIA H.LOsbtra~ah Division of Applied Biophysics, Ural Polytechnical Institute, Sverdlovs~ 6 2 ~ 2 , USSR Some possible changes in hemoglobin ( H b ) duaeing blood s y s t e m malignant diseases could he analyzed by exa~inatlon of the electronic structure of the active site. The s~unples of oxy- and deoxy-E{b f~om patients ~ t h leu]Eaeudas or ez~rhhremia were studied by Mosshaue~ (nuclear ~'-resonance) spectroscopy. The sEunples of normal adult and foetal Hb with different molecular structures w e r e studied fern comparison ~ t h patient's Hb. Results of M o s s b a u e r study showed that the iron electronic stmucture differed slight ly for normal adult and foetal Hb in both deoxy- and oxy-forms while that of fo~ patlent's Hb dlffered from normal adult Hb in oxy~form only. This fact could bo interpreted as consiquence of s ]ight differences in iron-ligand bonds for normal adult and foetal Hb and modifications of the distal heme region of patient's oxy-Hb. In this case the transformation of the iron electronic structure could ~efleet in particular the chan~es of the iron-oxygen bond which w e r e in aEreement ~ t h the changes of oxygen affinity and Hill parameter fo~ patient's Hb_ The cause of modifications of the active site strl/cture in patient's oxy-Hb ~s not clear yet. However, an examination of the iron electronlc structure transformation b y M o s s b a u e ~ spectroscopy could be a useful test to detect some modifications in patient's Hb.

Concluding, A patients without concomitant liver cirrhosis, have normal BMD in spine, femur and whole body. Total lower TBM cempared to N, can be explained by their smaller height and weight.

408 LOCALIZATION OF Tc-99m DIAMINE-DITHIOL(DADT)COMPLEXES IN RAT BRAIN. S.Stathaki, M.Papadopoulos, A.Varvarigou and E.Chiotell Is. Inst. Radioisotopes and Radiodiagnostics N.R.C.P.S. "DEMOKRITOS"I5310 Ag.Paraskevi, Athens, GREECE. Complexes of DADTs with Tc-99m have been proposed as promising brain perfusion imaging agents. The f o l l o winq d e r i v a t i v e s of HSC(CH~)~-CH~NHC(CH:)2N(R)C(CH~)2 S H ( 1 ) R : H , ( l l ) R : e t h y l - p y r r o ' r i ~ i n y ~ , ( l l l ) ~ : e t h y l - 3 ~et h y l p y r r o l i d i n y l , (~V)R:ethyl-3,3 d i m e t h y l p y r r o l i d i n y l and (V}R:ethyl-4,methyl p i p e r i d i n y l were tested f o r t h e i r brain uptake and w i t h i n brain d i s p o s i t i o n char a c t e r i s t i cs. In female Wistar r a t s , the compounds i n i t i a l l y showed s i g n i f i c a n t l y high but various brain uptake and r e t e n t i o n time as w e l l , a t time i n t e r v a l s from 2 to 20 rain a f t e r i . v . i n j e c t i o n . Subcellular f r a c t i o n s and postmicrosomal supernatant were obtained by d i f f e r e n t i a l c e n t r i f u g a t i o n o f brain homogenates, where DADT~sl content and p r o t e i n concentration were determined in each f r a c t i o n . DADT(s) a c t i v i t y was mostly recovered from the crude nuclear f r a c t i o n and postmicrosomal supernatant, while i t was declined by the time. Detailed analysis o f DADT(lll)showed that i t s 'highest s p e c i f i c a c t i v i t y was found in the t o t a l l i p i 4 e x t r a c t o f whole brain,which was s l i g h t l y ~ a f f e c t e d by the time. Further studies f o r the detection o f possible ~ e t a b o l i t e ( s ) o f DADT(lll)from r a t serum and brain were performed with HPLC and revealed i n t o a polar d e r i v a t i . we.of DADT(III) with the same chroma~bbgraphic p r o f i l e f o r both b i o l o g i c a l substances. As i t shown, i n t e r a c t i o n s o f DADT(s)with subcellu ]:r. struc~ure~ add l i p i d s may suqgest a new approach oT Dra~n Imaglng.

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409 BIOASSAY FOR TECHNETIUM-99m IN NUCLEAR MEDICINE TECHNOLOGISTS. R. Vanderwerf, M.E. King and M.J. Chamberlain U n i v e r s i t y Hospital, London, Ontario, Canada Shadow shield whole body counting has been used to study Tc-99m i nt er nal and external contamination in Nuclear Medicine technologists involved in radiopharmaceutical preparation (N=21) and radioaerosol studies (N=I6). I ndi vi dual s were counted twice immediately a f t e r the procedures; f i r s t in t h e i r working clothes and then a f t e r washing and changing t h e i r clothes. Gloves worn during the procedure were discarded p r i o r to the f i r s t measurement. Median i n i t i a l contamination was 6.8 KBq f o r the radiopharmaceutical group (RP) and 17.5 KBq f o r the radioaerosol group (RA). Median residual contamination was I . I KBq (RP) and 1.9 KBq (RA). Thus contamination of clothing accounted f o r approximately 90% of the t o t a l . Hats worn by RA technologists accounted f o r 0.7 KBq contamination. A worse case assumption that all residual contamination is i nt er nal and occurs on 250 working days per year y i e l d s 0.04% of the ALl f o r insoluble Tc-99m aerosols f o r RA. For the conditions studied occupational ingestion of Tc-99m does not warrant routine bioassay.

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PRELIMINARY STUDIES ON SEPARATING AND RADIOLABELLING MONOCYTES. W. Monq, G. Morrissey, D. Gravelle, J. Powe, A. Driedger, Department of Nuclear Medicine, Victoria Hospital, London, Canada.

Montz, R., M. Reuter, I. de Heer, R. Klapdor, Depts. of Nucl. Med., Gen. Surgery, Int. Medicine, Univ. - Hospital Eppendorf, 2000 Hamburg, Germany.

Human blood (27-37mL) was collected with 0.27% EDTA as an anticoagulant. Sedimentation of red cells for 1 hour to obtain leukocyte rich plasma (LRP) was facilitated by the addition of 3.5 mL of Hetastarch. Monocytes were isolated from LRP using a Nycodenz Monocytes (Nycomed AS, Oslo, Norway) gradient and resuspended in platelet poor plasma (PPP). The monocyte suspension was of high purity (80-90%). The yield of 3.7~6.0xi06 monocytes represented approximately 30-60% of total monocytes available. After washing the monocytes with PPP, the cell concentration was adjusted to 107 per mL for labelling. Both 99mTcHMPAO and lllIn-tropolone labelling have been evaluated (see table). No microscopic changes in cell shape and viability (trypan blue) were found after radiolabelling. These results suggest that both 99mTc-HMPAO and lllIn-tropolone have potential usefulness in monocyte radiolabelling. REACTION MEDIUM

99mTc-HMPAO lllIn-tropolone

ACD-PBS ACD-PPP

LABELLING LABEL EFFICIENCY RETENTION (%) 2 HRS (%) 54.5• 3.7 61.i•

84.0• 87.8•

*Supported by Victoria Hospital Research Development Fund.

Intraoperative abdominal Scintimetry with Tc99m-MAB EW431/26 - Preliminary Results. The immunoscintigraphic detection of tumor foci of ~ i cm fails even by SPECT owing to low contrast with background activity. In an intend to improve detection of macroscopically not visuable tumor spread, intraoperative scintimetry (IOSM) with a hand-held garm~a probe (Stratec, FRG) was performed in addition to SPECT 24-30 h p.i. of the Tc-99m labeled anti-CEA-MAB (Tc - MAB: BW 431/26 : BehringW., FRG) on ii patients with colorectal ca., Tumor specimens were measured in vitro in a gamma well counter. -After modification, the gamma probe originally designed for J-131, showed 20 fold higher sensitivity in detecting those activities of Tc-99m located close to the collimator hole, i00 cps corresponding to 0.005% dose Tc-MAB 24-30 h p.i. - The unfavourable high background activity affected both the in-vitro and in-vivo analysis: SPECT had been considered negative in 5 of ii cases. Invitro tumor/non-tumor (t/nt) r a t i o s > l . 5 were found in 5 cases, although tumor specimens had 0.010% dose Tc-MAB and more per g. In-vivo IOSM resulted in t/nt ratios ~ 1.5 in only 3 patients. But in most cases there was no coincidence of elevated t/nt ratios from the different methods. - In conclusion, the measurement technique of IOSM seems adequate, but clinical success will depend on a more specific enrichment of MAB in tumor tissue.

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BIOD1STRIBUTION AND RETENTION OF Tc-99m-HEXAMIBI EVALUATED IN T H E RAT. L. Andersson. B.A. Joensson, S. Leide', S. Mattsson', S.E. Strand. Departments of Radiation Physics in Lurid and in Maim6", Lund University, Lund, Sweden.

TECHNETIUM 99M TEBOROXINE MYOCARDIAL PERFUSION: A General Hospital Experience Using Single and Multidetector SPECT Cameras. R. Carretta, M. Kramer, P. Cronin, P. Matin. Roseville Hopsital, Roseville, CA.

Radiopharmaoeuticsls labelled with Tc-99m are in general characterized by giving low absorbed dose and effective dose equivalent. However, the introduction of new agents such as Tc-99m-HMPAO and Tc-99m.HEXAMIBI, where high activity is injected and the substances are excreted via the intestinal tract, makes dosimetric studies important. This is emphasized by the new discassion about risk estimations where the ICRP proposes specific weight factors for the gastrointestinal tract for calculation of the effective dose equivalent. The aim of this study is to investigate the biodistribution and retention of Tc-99m-HEXAMIBI in an animal model. The radiopharmaceuticsl was injected in rats and blood samples were taken and urine and faeces were collected during 48 h. The animals were sacrificed at different time points and tissue samples were taken for activity measurements. Approximately 50% of the injected activity is found in muscles and is cleared slowly. The maximum uptake in the gastrointestinal tract is about 30% 6 h after injection. Tne rest of the activity is mainly located in kidneys, liver, red marrow and heart (2-10%) showing a similar retention. Dosimetric calculations as well as comparison with human data estimated from scintillation camera measurements are under evaluation.

Technetium 99m Teboroxin~ (TBO), a new myocardial perfusion agent, differs significantly from Thallium201. One distinct difference is the rapid (less than 15 minutes) washout from the myocardium with no redistribution. This rapid washout affects SPECT imaging parameters and has raised the question whether TBO myocardial perfusion imaging could be routinely used in a general hospital setting. We have evaluated the use of TB0 in patients suspected of having coronary artery disease and have developed imaging parameters that can be used with either a single-headed or multiheaded SPECT camera. For single-headed system, SPECT images are acquired using either continuous rotation or stop-and-shoot protocols. Data acquisition time ranges from 12-15 minutes and the acquired SPECT images are processed according to a standard protocol. High quality TBO images can be routinely obtained using a single-headed SPECT camera and the images compared favorably with TI studies. Diagnostic quality TBO images can also be obtained with a multidetector system (Triad). Continuous 2 minute acquisition protocols produce high quality TBO images. Using i020 minute continuous dynamic imaging enables washout ratios to be calculated. Our preliminary results show that TBO myocardial perfusion can be readily performed in a general community hospital using either a single or multi-headed SPECT camera. Patient throughput is increased, washout ratios can be calculated, and diagnostic quality TBO images easily obtained.

Per cent of Inleoted activity ,=

o,t

(%)

~

,=

.... ;1~ Time after injection (11)

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CLINICAL USE OF INDIUM iii ANTIMYOSIN IN A GENEILAL HOSPITAL: R. Carretta, M. Kramer, P. Cronin, T. Malekian, P. Matin.

DEVELOPMENT OF INTERFILE FOR IMAGE DATA TRANSFER BETWEEN COMPUTERS COST-B2 Working Group #1, European Community, Brussels, Belgium The COST-B2 project is concerned with the development of quality control for nuclear medicine software. In this context, one of the major objectives is to develop test data sets or software phantoms that can be tested on computers from various manufacturers. To this end Working Group #1 has been assigned the task of establishing a file format to facilitate file transfer between systems. Of the various formats that have been proposed - ACRfNEMA, AAPM, GIFF, TIFF etc, the AAPM format has been chosen because of its readability. In its nuclear medicine form it has been called Interfile 1. Interfile consists of key value pairs which, if necessary, can be edited. One example is: patient name := The present format provides for transfer of static, dynamic, gated and SPECT studies. Future developments will include curve and ROI data as well as screen saves. An electronic file server has been set up where the latest version of key-value pairs is stored for direct downloading by electronic mail. Another major consideration is the form of hardware link and the software drivers for this link. It has been agreed that MS-DOS probably provides the best method in this regard and Kermit is widely available for a number of operating systems used in nuclear medicine that can be attached to IBM PC's or clones by RS-232 connection. A number of programs for transfer into and out of Interfile are either in development. Early programs for GAMMA-11, micro-Delta, Elscint and Toshiba are presently in the test stage.

The use of Indium iii Antimyosin was evaluated for its ability to detect myocardial necrosis in patients presenting with chest pain of uncertain etiology. The Indium Iii Antimyosin was injected within 24 hours of the onset of chest pain and planar and/or SPECT imaging was performed at 24 and 48 hours. Interpretation of the Indium iii Antimyosin scans were compared with clinical presentation, ECG, serum enzymes, and coronary angiograms. No adverse effects or human antimurine antibody responses were noted after the Indium iii Antimyosin injection. Of the 22 patients studied, 18 had positive Indium iii Antimyosin scans. All 18 were confirmed to have had acute myocardial infarction. Three of the four patients having negative uptake of Indium iii Antimyosin had no evidence of acute infarction. Indium iii Antimyosin is helpful in detecting myocardial necrosis in difficult to diagnose cardiac patients. It may also have prognostic implications when combined ~ith a myocardial perfusion agent such as Thallium 201.

1 CRADDUCK TD et ah A standard protocol for the exchange of nuclear medicine image files. Nucl Med Comm 10:703713 (1989)

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COMPARISON OF THE RENAL CLEARANCE OF TC-99M-MAG3 TO 1-131-OIH IN PATIENTS WITH RENAL DISEASE. 3.J.Kemp*, L.Reese, D.C.Kuhl, F.S.Prato*. Nuclear Medicine Department, St. Joseph's Health Centle, and *Medical Biophysics Department, University of Western Ontario, London, Ontario, Canada.

DELAYED L-PHENYLALANINE INFUSION INCREASES STRIATAL CONTRAST OF 6-18F DOPA PET SCANS. D.J. Doudet, C.A.--McLellan, R. Wyatt, T.G. Aigner, R. Adams, R. Finn and R.M. Cohen. Clinical Brain Imaging, NIMH, and Nuclear Medicine Department, CC, NIH, Bethesda, MD, USA.

To investigate whether MAG3 clearance can be used to determine effective renal plasma flow (ERPF) eighteen patients (7-86 yr',mean 50, s.d. 20), were simultaneously injected with 370 MBq of Tc-99mMAG3 (Mallinckrodt Diagnostica, free Tc-99m< 10%) and 20 MBq of 1-131-OIH (Merck Frosst, free 1-131<2%). Dynamic images were collected at 10 s intervals for 50 ruin for each isotope using a gamma camera (General Electric, Milwaukee) and a medium energy collimator. Blood samples were taken at 25 and 43 rain postinjection. Heart time-activity curves were generated by placing an ROI over the left ventricle. These curves were then fit with a bi-exponential and the two compartment (Sapirstein) model was used to determine the slow component slopes, the volumes of distribution, and the renal clearances. The MAG3 to OIH ratios of slopes, volumes of distribution, and clearances were (mean +1 s.d.) 1.24+0.16, 0.57+0.12, and 0.72+-0.16, respectively. Theslope and clearance ratios were significantly different than those published [1]. The clearance for OIH (ERPF) can be expressed in terms of the MAG3 clearance (CMAG3) either by a linear regression (ERPF = 105 + t.05(CMAG3); r=0.91) or by a quadratic regression (ERPF = -0.34 + 1.73(CMAG3)- 0.00080(CMAG3)2; r=0.92). This linear regression varies considerably from published results [1] and an offset of 105 ml/min seems unreahstic. In comparison, the quadratic relationship seems suitable because its offset is essentially zero. Further experiments on additional patients are underway to test the accuracy of the proposed quadratic relationship. A model is presently being developed to predict the clearance relationship by considering differences in renal extraction, protein binding, and radiochemical purity for the two compounds. [1] Jafri RA, Britton KE, Nirnmon CC, et al. J Nucl Med 1988;29:147158.

S106

Improved visual radiocontrast and ratios between striatum and posterior cortices have been achieved in the rhesus monkey with 6 - 1 ~ - D O P A using positron emission tomography. This was obtained by reducing the non-specific background activity resultin~ from the entrance into the brain of amino-acid 6 J F-methoxydopa the only 6-187-DOPA metabolite that crosses the blood brain barrier. The constant infusion of the cold amino acid L-phenylalanine, beginning 15 to 60 minutes after tracer injection, resulted in competition for the Iarge amino-acid transport system at the blood brain barrier and in a consequently important reduction of 6-18F methoxydopa background in the brain. By increasing initial 6-18F-DOPA availability, carbidopa pretreatmeut further enhanced the contrast between basal ganglia and DA-poor areas. The differences in striatum to cortex ratio between normal controls and animals with dopaminergic lesions were amplified in the 6-18F-DOPA scans with L-phenylalanine infusion with or without carbidopa pretreatment. The identification of striatal regions was facilitated in both normals and monkeys with nigrostriatal lesions. The improvements were dependent on the timing of the L-phenylalanine infusion. The time that L-phenylalanine has to be infused to yield the best results (contrast and ratios) is under investigation. The technique described here, safe and readily applicable to human subjects~ may help reduce the 6-18F-DOPA injected dose and prove useful in the idenfication of discrete dopaminergic areas.

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ADVANCES IN CONE-BEAM TOMOGRAPHY FOR SPECT, B.D. Smith, Ph.D., Electrical & Computer Engineering, University of Cincinnati, Cincinnati, Ohio 45221-0030.

99m TC antifibrin monoclonal antibody in the diagnosis of DVT P Peltier, CI Mezeray, Ph De Faucal A Bertrand, JI Barat, JF Chatal.

Cone-beam collimators have recently been shown to increase the photon count when large-field-of-view scintillation cameras are used in SPECT. This lecture will present several advances that have recently been made in cone-beam tomography which will further enhance its usefulness in SPECT.

99m Tc antifibrin monoclonal antibody ( T2Gls)was studied in 38 patients with suspected DVT. 35 patients were treated with heparin at the time of T2G1 s injection. The patients underwent US and/or Doppler and contrast venography. Planar scintigraphy of the lower limbs was performed immediately (PI) and 90 min after T2Gls injection, images of the legs, knees, thighs, and pelvis were recorded respectively with 1 min and 4 min pretime. Contrast venography and immunoscintigraphy (IS) images were blindy interpreted. 27 patients had recent thrombosis.Two IS interpretations were blindly performed : 90 min images (A) and 90 min images compared with PI images (B). Lecture A was considered positive if a hot spot was present. Lecture B was positive if a hot spot present on 90 image did not exist on PI image. The number of false positives and negatives was respectively 3 and 5 for A, 0 and 3 for B. The diagnostic accuracy (number of correcrt IS/number of patients ) increase (51)% to 79%) when 90 min images were compared to PI images. T2Gls is sensitive (78%) and specific (82%) for the detection of recent thrombosis. Thus T2G1 s is a promissing technic for the diagnosis of active DVT.

When cone-beam data is collected, the vertex of the cone is moved along some geometric path around the object. Perhaps it is not surprising to learn that sufficient information to produce an artifact-free three-dimensional reconstruction (without extrapolation) can be collected from certain geometries of vertices, and for other geometries it is not possible. .The "completeness condition" will be presented which specifies whether sufficient information can be collected from a given geometry to reconstruct an arbitrary object. Unfortunately, a circle is not complete. In addition, three novel reconstruction methods will be presented. Results from computer simulations will be presented that illustrate that all the reconstruction methods can be implemented. In particular, it will be seen that the most computationally efficient method, which is as efficient as Feldkamp's algorithm, produces images with substantially reduced z-directional artifacts.

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PARADOXICAL RESPONSES OF THE THYROID GLAND TO THE RADIO IODINE TREATMENT OF GRAVES DISEASE. B. Schober, P. Cohen and B. Lentle. Lions Gate Hospital, Vancouver General Hospital and the University of British Columbia. From 1971 - 1983 one hundred and sixty consecutive patients were treated in the Division of Nuclear Medicine at Lions Gate Hospital for Graves disease with individually calculated doses of 1-131. In addition to the customary tests, the effective half-life of 1-131 in the gland was determined. After the introduction of Te-99m perteehnetate for thyroid scans, the thyroid activity 20 minutes after the I.V. injection was determined; it is referred to as Te-99m trapping. Before treatment and afterwards as long a s the patient was cared for by the Division directly, scans and uptakes were frequently done. It was noted that the responses of the functional mass, the Tc trapping and the 24 hr. 1-131 uptake to the treatment were sometimes dissimilar. Not only did these three components decrease in different degrees but paradoxically, some increased. These responses show only slight dependence on dose. This can only be partially explained by the inherent errors of dosimetry.

ATTENUATION AND SCATTER COMPENSATION IN BRAIN SPECT.

Sunday, A u g u s t 26, 1990

D. Swerhone, L. Hahn, R. Sloboda*, C. McCreary, R. Kloiber. Div. Of Nuclear Medicine, Foothills Hospital, Calgary, Alberta. *Cross Cancer Institute, Edmonton, Alberta, Canada. Scatter and attenuation are two major sources of image degradation in SPECT preventing proper quantitation of tissue specific activity. In this work, we hsve been investigating a series of compensation methods for scatter and attenuation in Monte Carlo simulated and experimental data. The compensation methods include: Chang's iterative algorithm and Tanaka's method for attenuation, and for scatter, subtractive as well as deconvolution techniques. Currently, we are examining applications of holospectral scatter correction techniques. First, scatter and attenuation were modeled by Monte Carlo simulation tecniques. Next we developed a brain SPECT phantom with several separated compartments so as to distinguish between gray and white matter (specific activities of gray and white matter were in the ratio 3:1). A 3.2 mm alnminium band around the phantom simulated the skull. A comparison of the compensation methods on both the simulated and the experimental data shows that Chang's iterative method, together with scatter subtraction techniques, forms an optimal compensation package. For the phantom, after scatter and attenuation compensation, the specific activity ratio of two identically "hot" regions is improved from 1.76 to 1.09.

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A P P L I C A T I O N S O F C O M P U T A T I O N A L C H E M I S T R Y IN NUCLEAR MEDICINE R.J. Boudreau, M.D., Ph.D., a n d S.M.N. Efange, Ph.D. University of M i n n e s o t a , M i n n e a p o l i s , M N 55455.

F. Godinho, M. S. V. Fernandes, L. Oliveira, M. G. Cantinho. BONE MINERAL DENSITOMETRY USING

Modern super and super mini-computers now have the capability to execute large p r o g r a m s t h a t a r e t h e c u l m i n a t i o n of y e a r s of effort on the part of theoretical chemists and c o m p u t e r scientists. These programs allow one to calculate the structure and electronic properties of a m o l e c u l e w i t h an a c c u r a c y t h a t c h a l l e n g e s t h a t of e x p e r i m e n t a l m e t h o d o l o g y . They also provide different information than obtained from X-ray crystallography, which is an observation of t h e m o l e c u l e in t h e s o l i d state. Current approaches include molecular mechanics, semi-empiricalquantum mechanics, quantum mechanics, and density functional theory. This presentation will concentrate on the semi-empiric quantum mechanical methods and discuss how this methodology d i f f e r s f r o m t h e others. Specific examples to b e d i s c u s s e d a r e t h e s t r u c t u r e of MPTP, an a n a l y s i s o f t h e s t a b i l i t y of f l u o r i n a t e d and non-fluorinated derivatives of raclopride, a n d a n e x a m p l e of h o w s e v e r a l a n a l o g s of M P T P w e r e u s e d as m o l e c u l a r p r o b e s to d e v e l o p a m o d e l of t h e a c t i v e s i t e of m o n a m i n e o x i d a s e A a n d B.

424 COMPARATIVE STUDY

CONVENTIONAL GAMMA-CAMERA. Abstract received in a form unsuitable for reproduction

425 OF THE

ABSOLUTE UPTAK~ AND CORTICAL

DISTRIBUTION OF Tc-99m }~MPAO AND 1-123 I O D 0 - ~ A M I N E

(IMP) IN TWO G~0UPS OF NORMAL S ~ . C ~ _ _ _ ~ , J. Friede2, R . M . Dupont~ & S.E. Halpern 3 . 1U. de Sherbrooke, p.Q., zOH }btel-Dieu, Quebec, P.Q., 3V.A. Hospital and U. of California, San

AN IMPROVED METHOD FOR SCINTIANGIOGRAPHY USING RAPIDLY LABELED RBC IN VIVO: APPLICATION TO PANCREATIC TRANSPLANTATION C. Cobb, D.D. Price, and R.S. Hattner. University of California at San Francisco, California, USA.

Diego, CA. The aim of this study was to describe quantitatively the cortical uptal~ and distribution of }RIPAO in a group of 12 normal subjects, in comparison to the upand distribution of IMP (20"p. inject. ), previously measured in a comparable group of 17 subjects. After reconstruction of the transaxial SFECT images, quantitative maps of the cortical uptal~ were generated for each subject with "Cort-Ex", a program for the analysis and geomorphological presentation of brain SFECT data. The mean cortical uptake index was found to be equal to 0.688 (+ 0. 157) for }~{FAO as ~ to @.921 (_+ 0. 185) for IMP. However, with }~IPAO, the distribution of these index was remarkably far from normal. A pi~l by pixel comparison of the relative uptake of these tracers showed a fairly uniform ratio (~PAO/INP) of 70 to 80 % over the entire cortex with a significant increase to 85-95 % over the cerebellar area, After renormallsation of the data on the basis of the cortical uptake index, the distribution of ~ A O was found to be slightly more uniform and the residual variation on the relative uptake significantly less. We conclude that these results tend to reinforce the hypothesis that, in vivo, }~PAO is widely variable in its bioavailability making it almost useless for the absolute measurement of blood flow to the brain. Those results also indicate the need for more restrictive criteria in the assessmant of the distribution of I~'IPAO. The relatively greater cerebellar uptake remains unexplained.

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Scintiangiography is an important procedure to qualitatively evaluate organ perfusion, and is valuable in the transplanted pancreas. A new method of studying blood flow was tested in a group of pancreas-renal transplant patients. Half were injected with TC-99m DTPA and the other half with rapid invivo labeled RBC's. Ten patients were studied. Forty-four scans were performed (2-6 scans per patient). Six received DTPA and four invivo labeled RBCs. One frame/second anterior images of the inferior abdomen, composite flow, and 500K post flow static images were acquired. Comparison of the methods demonstrates that the image quality is enhanced using bolus Tc~99m labeled RBC. We think Tc99m DTPA is sub-optimal because of the end physiological distribution of the agent. Twenty percent remains in the extracellular space and only 5% in the intravascular compartment. The concentration is therefore diluted by 4 resulting in a blurrred vascular image. Rapid bolus injection of Tc-99m invivo labeled RBC results in improved image quality because it stays within the intravascular compartment. Composite scintiangiography (summed first-transit) yields images of higher diagnostic quality for this application and offers an improved method for studying post transplanted pancreas-renal blood flow.

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AUTOMATED QUANTIFICATION OF THE RIGHT VENTRICULAR EJECTION FRACTION (RVEF) IN MULTIGATED (MUGA) EQUILIBRIUM CARDIAC BLOOD POOL SCINTIGRAPHY. .A. Jouan, J. Verreault, G. Bissoa. Department of nuclear medicine and radiobiology, University of Sherbrooke,QC, Canada.

NEW TECHNETIUMCOMPLEXESWITH TETRADENTATETHIOIMINATO SCHIFF BASE LIGANDS S.G.Mastrostamati s, M.S. Papadopoulos p H. Vavouraki,

Many attempts have been made using MUGA studies for an automated quantification of the left ventricular ejection fraction but none for a similar approach for RVEF. Using the vectorial representation of a MUGA sequence, we propose a f~lly automated method yielding both end-diastolic (ED) and end-systolic (ES) regions of interest (ROI). Our method is based on the orthogonalization (Gram-Schmidt) of the three main typical temporal behaviors (ventricular, auricular and background noise) present in the sequence. This process yields a ventricular factorial image which is used to extract a primary ED shape. A linear operator is applied on the average and ES images to defiae accurately the interventricular region and the separation between the right ventricle and the pulmonary artery. The ED ROI well defined at this time is used to extract the ES ROI by applying a threshold on the profiles of an angular profiles network centered at the center of gravity of the ED shade. The obtained ES ROI leads to avoid the right auricular counts in RVEF calculation (Maddahi & al, Circ. 60,3~ 1979). Results of a pre-validation study comparing RVEF by our method on'MUGA and by first pass study in 24 patients : MITGA : 0.39~ 0.06 (SD) FP : 0 . 3 8 ~ 0 . 0 5 (SD) r~l~

FAsl

Kr

,,,

Y = 0.14 § 0.58X R =0.745

C.Stassinopoulou, E.Chiotellis, National Center for S c i e n t i f i c Research"Demokritos" 15310 Aghia Paraskevi A t t i k i s , Greece. Thioiminato complexes with technetium were synthesized. Ligands were of the following formula,

R

-

PH ( I I )

Synthesis was proceeded via tetradentate ketoimine by nucleophilic substitution with b i s u l f i t e ion. Ligand exchange method was employed for the preparation of Tc-g9(v) complexes with thiomine using Bu4NTcOCI4 as precursor and the ligand in stoichiometric quantities. The complexes were c r y s t a l l i z e d from acetone at OoC. Red-brown c r y s t a l l s were collected and analysed by NMR, IR, UV-VIS spectroscopies. Data for (I) given below: 1NMR(methanol-d4) (free ligand in brackets}:CH3-:2.68(s ) and 2.73(s) [2.18(s) and 2.50(s)]; -CH2:4.32(m) [3.83(m)]; : CH,6.96 (s) {6.22(s)]. IR(KBr) :964cm- i (Tc=O), UV-VIS:414nm(MeOH),487nm(CH2C12). Labelling of (1) in carrier added level yielded 75fo of Tccomplex which proved to be identical by HPLC analysis with authentic 99Tc(V) -complex. Biodistribution studies in mice showed a heart uptake up to 7.74% dose/g, 30min after injection and slow myocardial washout. Blood as well as hepatic clearance was also slow. Further investigation of thioiminato complexes formation with Tc-(III) is in progress.

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TRIPODAL N,S3-DONOR LIGANDSAS A NEW BACKBONEFOR REDUCEDTECHNETIUM

INFARCTED HEART UPTAKE AND BIOOISTRIBUTION OF RADIOLABELED ANTI-MYOSIN MONOCLONAL ANTIBODY IN RAT AND DOG MYOCARDIAL INFARCT MODELS. J. Rousseau, I H. Sikorska, 2 A. Gervais, 3 and J.E. van Lier. I ZDepartment of Nuclear Medicine and Radiobiology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada JIH 5N4, 2Rougier Bio-Tech Ltd., 8480 St-Laurent Blvd., Montreal, Quebec, Canada, H2P 2M6, 3 S e r v i c e de c a r d i o l o g i e , D ~ p a r t e m e n t de mgdecine, Faculty of Medicine, U n i v e r s i t y of Sherbrooke, Sherbrooke, Quebec, Canada JIH 5N4.

S.Mastrostamatis*, M.Papadopoulos, E.Chiotell is* F.C .Hunt**. * National Center for Scientific Research "Demokritos" 15310 Ag. Paraskevi Attikis, Athens, Greece. ** Australian Nuclear Science and Technology Organization Sydney, Austral ia, Tripodal tetradeI~ate N,S3 llgands and t h e i r complexes containing the MoOg:Tcore ha~e been reported~. In the present study we ihvestigate the complex formation of N, N-bi s (2 -mercaptoethyl ) -2 -ethyl thi oethyl amlme ( I ) with Tc(V). Synthesis of (1) was proceeded via direct mercaptoethylatlon of 2-ethylthioethylamine using ethylene sulfide. Labelling with pentavalent technetium, in c a r r i e r added l e v e l , was accomplished by ligand exchange using e i t h e r Tc-gluconate (A) or Bu4NTcOCI4 (B) as precursors. Complex formation o f ( 1 ) was monitored by UV-VIS spectroscopy, TLC and HPLC chromatography. The y i e l d of l a b e l l i n g was found 20% and 80%^~or method (A) and (B) respectively. Isolation of the ~Tc(V)-complex of (1)in c r y s t a l l i n e form was performed by method (B), in orderto determine i t s chemical structure. IR spectroscopy reveals the presence of Tc=O core at 945cm"1. The oxo-Tc(V)c ~ p l e x j p r e p a r e d by method (B) in c a r r i e r added level (9gTc+~mTc) and purified by HPLC, was biodlstribu(ed in mice at 30,60,90,120 mins p . i . . A c t i v i t y was found to be accumulated in l i v e r and lungs and cleared slowly by the time. Heart to blood r a t i o showed persistent values of approximately 0.4 at a l l time intervals. In order to investigate i f this new backbone can use as a basis for new technetium radlopharmaceuticals, further studies on a series of tripodal ligands are in progress. 1.J.L.Corbin, K.F.Miller, N.Parayadath, S.Wherland, A,E.Bruce E . I . S t l e f e l , Inorganica Chimica Acta 90(1984), 41-51.

Monday, August 27, 1990

A new mouse monoclonal antibody that recognizes ~and E-heavy chain of human slow skeletal muscle myosin was obtained. This AM antibody and its F(ab')2 and Fab fragments were labeled with 1-125 via the iodogen method and evaluated in a rat model for their potential use in infarct imaging. Non-invasive infarctlike myocardial necrosis in the rat was induced upon two s.c. injections with 15 mg of isoproterenol in 0.2 ml saline, with a 24 h interval. Distribution of 1125 in five equal transversal heart slices, which showed increased severity of infarction, was compared with Tc-99m-PYP uptake. The 1-125-1abeled AM F(ab')2 fragment showed the highest retention in the infarcted rat heart and this fragment was derivatized with DTPA for In-lll labeling. Comparison of images obtained with AM F(ab')2-DTPA-In-III and Tc-99m-PYP of infarcted dog heart, induced by selective obstruction of a c o r o n a r y artery, s u g g e s t that the In-lll l a b e l e d F(Ab')2 localizes specifically in infarcted myocardium only. This differential uptake pattern between the two radiopharmaeeuticals was particularly evident from images of 1 cm thick heartsliees, obtained via sequential imaging of Tc-99m and In-lll, of infarcted dog heart removed from animals which received both the In-lll labeled AM F(ab')2 and Tc-99m-PYP.

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CLINICAL EXPERIENCE WITH A NEW ANTIMYOSIN ANTIBODY L F Chert*, L R o s e n t h a l l * , RF Flanagan**, H Sikorska*** *Montreal General Hospital, **Merck-Frosst Canada Inc~ * * * R o u g i e r Bio-Tech Ltd A new mouse monoclonal antibody, 3-48, which recognizes the alfa and beta heavy chains of human atrial and ventricular myosin, and the beta chain of human slow skeletal muscle, has been developed. In t h e r a t i s o p r o t e r e n o l induced MI model and the canine model of selective obstruction of a coronary artery the antibody was shown to be specifically localized to the necrotic myocardium. 21 patients were in the clinical trial, ranging i n a g e f r o m 35 t o 79 yr. E a c h p a t i e n t received about 3mCi In-lllP(ab')2 antimyosin, and imaged 24, 48, 72 a n d 96 h o u r s later. Final diagnosis was based on the clinical, laboratory and ECG data on all of them. There was one autopsy confirmation and 6 had angiography. The studies were positive in 12/12 patients with Q-wave MI and 3/4 patients with non-Q-wave MI. 6 o f t h e f o r m e r group had streptokinase infusion. 5 patients had a diagnosis other t h a n MI; 3 w e r e n e g a t i v e and 2 depicted questionable uptake. The only complication was a transient rise in temperature in one patient. Overall sensitivity was 94%

POSITIVE In-111 ANTIMYOSIN SCINTIGRAPHY IN PATIENTS WITH UNSTABLE ANGINA. J.Lekakis, N.SJfakis, N.Vassilopaulos, H.Psichogiou, C h r . K a l l i o n t z J and P.Kostamis. Dpt off Nuclear Medicine and C l i n i c a l Therapeutics "Alexandra" U n i v e r s i t y H o s p i t a l , Athens, Greece. ~o examine the incidence and the p r e d i c t o r s o f a p o s i t i v e In-111 antimyosin s c i n t i g r a p h y in p a t i e n t s (pts) with unstable angina (UA) we p r o s p e c t i v e l y analysed 21 pts with UA and 8 pts with s t a b l e angina; pts were i n j e c t e d 2mCi In-111 on admission and scannJng was performed 48hrs l a t e r . Symptoms and signs i n d i c a t i n g the s e v e r i t y o f ischemia were monitored during the period between i n j e c t i o n and scanning. No p a t i e n t developed r i s e o f cardiac enzymes sugqesting myocardial necrosis. 6 (28%) pts with UA had a p o s i t i v e antJmyosin scanning; no pt with sbable angina had p o s i t i v e scanning. A l l 6 pts with UA and pos i t i v e scanning had signs o f severe ischemia ( 4 / 6 pts multi.pie episodes > 2/day, 3/6 pta pralonged > 10 min episodes, 2/6 pts STy> 3 EKG leads), while only 1/15 pts with UA and negative scanning had signs o f severe ischemia (p< 0.05). In conclusion 1) a s i g n i f i c a n t number off pts wJ.bh UA present p o s i t i v e antimyosin scanning without e l e vail.on o f cardiac enzymes 2) these pts usually present m u l t i p l e or severe episodes o f ischemia i n d i c a t i n g t h a t during these episodes minor myocardial nec r o s i s , undetected by enzymes, may happen.

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DETE',~T!ON OF MYOCARBIAL SALVAGE ~47TH COP~BZNED ANTi)ffOSIN A~ 9 THALLIUM Ib~GING K.Y. Gulenchyn, K.J. Ascah, T.D. Ruddy, W.L. Williams, C. Smith, S.A. Kearns, J.R. Ballinger, R.A. Davies. University of Ottawa Heart !nstitnte~ Ottawa, Canada.

1I 1In antimyosin antibodies uptake in patients with recurrent chest pain after coronary bypass. P. MARTIN*, B. PEPERSTRAETE**,J. PATERNOT* end M. VERHAS* Departments of Nuclear Medicine* and Cardiology ~*, Brugmann University Hospital. 4, pl Van 6ehuchten, B 1020 Brussels, Belgium.

Uptake of In-lll antimyosin antibody (AM) identifies myocardial necrusLs and TI-201 indicates viable myucapdium. Salvaged myocardium Following theombolytic ther'apy For myocardial infarction is characterized by endocardial necrosis extending towards viable ep~cardium. We, hypothesized that; areas of myocardial salvage Following thrumbolytic ther'apy would be identified as regions with uptak(" oF both AM and TI-201 demonstrating a mixture of necrotic and viable cells. S e w m patients were studied Following bhrombolytic therapy with 2D cehocardiegmaphy (days 1 and 7) and combined AM and T] 201 imaging. ~{ (80 MBq) was injected 24 hours follewing thr'ombolytic ther'apy. Planar imaging was carried out 24 hour's late>. Then TI-201 (110 YdBq) was i r ~ j c c t e d , f o l l o w e d 10 m i n u t e s l a t e r by d u a l i s o t o p e tumogr'aphy (180 ~ 32 p p o j e c t i o n s , 45 s e c o n d s ) u s i n g a me.dium e n e r g y c o l l i m a t o r a n d 20~ windows. I n 5 p a t i e n t s , AbI u p t a k e was Found i n r e g i o n s w i t h T1-201 u p t a k e ( s c ~ n t i g r ' a p h i c o v e r l a p ) . Wall motion curresponding to regions nf seintigraphic overlap ranged From normal to akinetie on day 1 with significant improvement by day 7. In the 2 patients with ~'egions of ~M uptake without TI-201 (no scintig~'aphic overlap) ~ corresponding wall motion was initially akineBic or dyskinetie on day I and showed no change by day 7. Scintigr'aphic ow~rlap of Av~ and TI-201 may identify r e g i o n s e f m y o c a r d i a l s a l v a g e and p r e d i c t s u b s e q u e n t improvement in wall motion.

In a preliminary study (Strasbourg IgBg), we found an uptake of I If In antimyosin Ab in ischemic parts of myocardial wall in a small group of patients without evidence of nffcrosis.To further assess the ability of the Ab to locate in ischemic myocardium, 42 patients with suspected recurrent angina,pectoris after a coronary bypass underwent a I I IIn antimyosin Ab planar scintigraphy. 3 incidences C0, 45, 90") were recorded 46 hours after the IV injection of 74 MBq of the tracer. The scans were analyzed by" two independent observers and compared to the findings of the control angiography. Results were as follow:none of the patients underwent adverse reactions. The general agreement between observers was g0%. 32 patients presented with a severe stenosis or obliteration of one or several bypass. 26 (87%) of them had an uptake in the correspondent territory at the scintigrephy (true *l In 3 cases, the scan involved a larger territory than that expected by angiogrsphy. In I case, despite a positive angiography, the $cintigrephy was negative. 10 patients had a normal angiogrsphy. 6 of them also had a normal scintigrsphy (true -). In the 4 last cases however, a diffuse uptake was observed. The scintigraphy and the angiography were in agreement in 34 cases (81%) (true + and true -). In 7 other patients (17~), the scintigraphy either overestimated the involved teritory or showed a diffuse uptake without evidence of ischemia (false§ There was only I false - case (2~). To conclude: 1 I fin antimyosin Ab have been described to be highly specific of necrosis. However, this study confirms our previous observation that, in case of ischemia, an uptake of the antibody is also present in ischemic parts of the myocardial wall and in some patients overestimate involved territories. Potentially, this could be responsible for interpretationproblems in case of differentialdiagnosis between angina peetoris and necrosis. More intriguing is the uptake in patients without evidence of ischemia or necrosis, nor any other cardiopathy, such as global cardiac failure,rnyocarditis or alcoholic

myocardiopathy.

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In-III-ANTIMYOSIN FOR RISK STRATIFICATION OF HEART TRANSPLANT PATIENTS DURING LONG TERM FOLLOW-UP. C. Duncker, I.Carri6, L.Bern~, M.Estorch. Hospital de Sant Pau, Barcelona, Spain.

SPECT BRAIN IMAGING USING N-ISOPROPYL-(Z23I)P-IODO AMPHETAMINE (Iz3I-IMP) ON PATIENTS WITH HEAD INJURY~ - - COMPARISON WITH X-RAY CT SCANNING - Ko Ishii, K. Nakazawa, H. Nishimaki, K. Yoda, T. Matsubayashi, M. Endo. Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.

llIln-Antimyosin (AM) myocardial uptake the first year after heart transplantation (HT) relates to the degree of rejection activity. To assess if AM uptake one year after HT could detect patients at risk of subsequent rejection during long term follow-up, AM s t u d i e s were p e r f o r m e d in 21 p a t i e n t s . P a t i e n t s were f o l l o w e d f o r a p e r i o d o f 18-+5 months ( r a n g e 10-28 months) a f t e r t h e f i r s t year. Routine controls included right ventricular e n d o m y o c a r d i a l b i o p s y e v e r y 4 months. A h e a r t t o lung ratio (HLR) was used for quantitative assessment of the AM scans. A cut-off point of HLR of I~58 (mean value in normals + 3 SD) was used to define abnormal AM uptake. Eight of 12 patients with HLR>I.58 one year after HT, presented with biopsy proven rejection (17 episodes) during follow-up. 1 of 9 patients with HLR -<1.58 one year of HT, presented with 1 episode of biopsy proven rejection during follow-up (p=0.01). The number of rejection episodes per patient during follow-up correlated with HLR at one year of HT (r=0.64; p<0.01). The 9 patients with HLR < 1.58 had 0.1 episodes of rejection per patient (I episode). 7 patients with HLR>I.58-I.75 had 1.6 episodes of rejection per patient during follow-up (8 episodes) (p<0.05). We conclude that persistance of AM uptake one year after HT indicates a higher risk of subsequent rejection episodes. Thus, AM scans are useful in risk stratification after HT.

SPECT brain images using 123D-IMP, were obtained from patients with head injury and were compared with those obtained from X-ray computerized tomography (X-CT) scanned on the same patients. Forty-eight patients with head injury, were submitted to z231-1MP SPECT examination. They are i5 to 78 years old (average 30). Most Iz31-1MP SPECT images were obtained within days after the injury but some were inspected twice some time later. X-CT studies on 34 patients were done within 2 weeks after IZ31-1MP SPECT. Patients were injected with 3 mCi tz31-1PLP intravenously. SPECT images were contructed from data recorded by a rotating gamma camera, staroam 400AC/T (General Electric Co.). Data collections were started at i0 minutes and 2 hours after the injection. Patients were categorized into four groups according to the difference between their SPECT and X-CT images: (i) Both showed the same degree of damage at the same site. (2) SPECT showed more prominent change than X-CT. (3) X-CT showed more prominent change than SPECT. (4) Each showed the damage at the different site. Thirteen out of 15 patients with amnesia, 20 out of 22 with loss of consciousness were categorized into either group (i) or (2), indicating that SPECT could be superior to X-CT to demonstrate cerebral dysfunction caused by cerebral injury. This study suggests that 1231-1MP SPECT is expected to show the correlation between symptoms and regional cerebral blood flow and that 1231-1MP SPECT is quite useful to evaluate the symptom associated with head injury.

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Tc-99m HMPAO BRAIN IMAGING POST HEAD TRAUMA EVALUATION OF THE CHRONIC PSYCHIATRIC SEQUELAE. R.H. Reid and M.E. Krelina. University of Western Ontario, London, and University of Ottawa, Ottawa, Canada.

CEREBRAL PERFUSION DEFICITS IN DYSBARIC ILLNESSES: FOLLOW UP STUDIES IN 18 DIVERS M.A. Macleod and G.H. Adkisson, Royal Naval Hospltal Haslar, Gosport, U.K.

Cerebral trauma may arise from many etiologies b u t in 4 5 % of c a s e s , they are secondary to motor vehicle accidents (MVA). The disability post head trauma can be dramatic, in p a r t i c u l a r the psychological chan@es that can be associated w i t h it. M a n y victims do not show significant changes on the CT scan initially but subsequently s u f f e r f r o m c h a n g e s in p e r s o n a l i t y , mood and affect. Thirty patients post head trauma related to MVA were investigated with Tc99m HMPAO cerebral perfusion SPECT imaging. I n 16 c a s e s t h e C T s c a n c o r r e l a t e d with neuropsychiatric testing. However in 14 o f the cases the CT scan did not reveal a significant abnormality whereas HMPAO imaging revealed sites of abnormality that were not suspected on the CT scanning which were in addition to sites of a b n o r m a l i t y noted on the CT or remote from the site of abnormality on the CT scan (ie. showed additional sites of abnormality). HMPAO imaging in a l l but 2 patients confirmed the neuropsychiatric site of suspected abnormality. The sites of abnormality were localized to the temporal and frontal lobes in most patients. Parietal lobe extension was a less common feature. Tc-99m HMPAO SPECT imaging in c h r o n i c psychiatric conditions post cerebral trauma can explain psychiatric changes which are not explainable i n p a t i e n t s w i t h n o r m a l CT.

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Long term neurological damage induced by diving has been suggested for some time and recent study in our department confirmed for the first time acute cerebral perfusion defects in divers follow~ng dysbarism. This paper describes a long term follow up study involving 18 such divers. In a recent series of 28 divers, cerebral perfusion deficits were demonstrated in every case of either cerebral arterial gas embolism (CAGE) or ~urological decompression sickness (BCS~I). Using ~ m 9~ m TO -Hexamethylpropyleneamine Oxime ( Tc -HMPAO) with single photon emission tomography (SPET) we repeated scans on 18 patients with demonstrated cerebral perfusion deficits following diving incidents. In patients with CAGE (n=4), 7 areas of reduced perfusion were noted on initial scans. In scans performed 1 week to 5 months later, 2 perfusion deficits had returned to normal, 2 showed improvement and 3 remained unchanged. New perfusion deficits were detected, however, in 2 patients. In patients with DCS (n=14), 33 perfusion deficits were noted initially. In scans performed at intervals from 1 to 18 months later, 4 deficits had returned to normal or near normal, 13 more showed notable improvement and 12 remained unchanged. New perfusion deficits were demonstrated in 2 patients and, in one of these patients, 2 previously noted deficits has increased in size. This study continues but indications are that the effects of CAGE and DCS II on cerebral perfusion are persistent in the majority of cases.

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REGIONAL DISTRIBUTION OF METHYL-[*SF]FLUORO-DOPA IN HUMAN BRAIN IN VlVO A. Gjedde, G. Firnau*, C. Nahmias*, H. Kuwabara, J. Reith, S.E. Garnett*. Positron Imaging Laboratories, Montreal Neurological Institute, Montreal, Quebec and *Department of Nuclear Medicine, McMasterChedoke Hospital, Hamilton, Ontario.

BIOLOGICALLY CONSTRAINED ESTIMATE OF DOPA DECARF3OXYLASE IN HUMAN BRAIN USING 18-F-FDOPA AND PET. H Kuwabara J Reith, A Gjedde. Positron imaging Labolatories, Montreal Neurological Institute, Montreal, Canada.

MethyI-DoPA is a common metabolite of DOPAin the circulation of humans, particularly those treated with DOPA for symptoms of Parkinson's Disease. MethyI-DoPA itself is not subject to significant metabolism and therefore excreted. Since methyI-DoPA is not metabolized in the mammalian organism, it provides an index of the relationship between large neutral amino acids in the circulation and in regions of the brain. It is of particular interest to determine the distribution of large amino acids in between the striatum and the circulation because of the comparatively high-rate of synthesis of dopaminefrom tyrosine in this region: Does the dopamine synthesis measurably lower the content of large neutral amino acids in the st6atum? The question was answered by positron tomography of a male volunteer known to be in good health, injected with 6mCi methyl-[*SF]fluoro-DOPA. Two regions,striatum and occipital cortex, were selected for analysis by the equation

M(T) = Kle -(K~/V')T Z T C.e(K~/vr

(I)

where M(T) is the regional content of radioactive methyl-[lSF]fluoroDOPA, [{l the unidirectional blood-brain clearance of the tracer, and Ve the partition volume. A 4% vascular compartment was subtracted prior to analysis. The results are listed in the Table. Region Kt V, ml hg- t min-~ ml hg-1 stdatum 2.15:E0.05 51.7:1:0.4 occiput 2.703:0.13 48.8/:0.6 Thus, the partition volumes and hence the total neutral amino acid pools of the two regionswere identical.

The estimate of DOPAdecarboxylase (DDC) activity (k3) in human brain using 18-FDOPAand PET is essential to the understanding of the dopaminergic system in rive. However, FDOPA metabolites in plasma obscure the analysis. We evaluated the use of the following biological constraints to improve the estimate; little regional variation of the partition volume (V~ = K1/k2) within a subject; a common Ve value and a fixed BBB transport ratio (2.3) between FDOPA and 3-O-methy[-FDOPA (OMFD); negligible regional variation of catechoI-O-methyltransferase (COMT) activity in brain. We analyzed 22 brain regions of five elderly healthy volunteers (age 47-68 years); the cerebellar (2) and cerebral (18) cortices and the striatum (2). With carbidopa, plasma 18-F activity was practically confined to FDOPAand OMFD. In cortex, Ve averaged 0.69-0.89 ml g-l with coefficients of variation of 10% in each subject (a Kl-k2-k3-Vo fit). In stliatum, uncertain k3 estimates were associated with Ve values t!:.t exceeded the brain water volume. When a mean cortical Ve ie of each subject was used (a Kl-k3-V0 fit), k3 was 0.065 4U.014 min -1 (mean -F SD) for striatum and 0.008 ~: 0.004 min -I for cortex. Plasma: FDOPA I

O~FD

II Brain tissue: k KI~:~ k2 FDOPA 3 [DDC] Metabo]ites It ~ k5 ICOMT] K I ~ : I :=~ k2 OMFD

Tile use of a pre-determined cortical Ve value improved the estimate of DOPA decarboxylase activity in human brain with PET.

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IMAGING D2 RECEPTORS WITH SPECT AND 1-123 IODOLISURIDE B. Mazi~re, C. Lee'h, M. Bourguignon9 H. Chabriat, C. Raynaud, M. Levasseur, A. Syreta. Service Hospitalier Frederic Joliot~ CEA, 91406 Orsay, France.

HIGH PREVALENCEOF CHOLECYSTITIS IN PATIENTS WITH NONVISUALIZATION OF EXTRAHEPATICACTIVITY BY CHOLESClNTIGRAPHY. C,S. Ahn, and D.E. Tow. Veterans A f f a i r s Medical Center, Brockton/West Roxbury and Harvard Medical School, Boston, Massachusetts, USA.

In vitro and in vivo pharmacological studies on rats and baboon have previously shown that 1-123 iodolisuride (I-123 ILIS) has very high affinity and specificity for dopamine D2 receptors. For imaging purposes, 4 mCi of the 1-123 ILIS were injected in healthy volunteers (5) (after administration of sodium perchlorate). Using a dedicated SPECT device (TOMOMATIC 564), tomographic images of the cerebral distribution of the radioactivity were obtained in 15 min. The brain kinetic study, revealed that the best contrast between the specific and the non specific uptake was observed 2 hours post injection (striatum to cerebellum radioactive concentration ratio S/C : 2.0 • 0.4). Due to the abscence of data correction for partial volume effects and y-ray absorption, the SPECT value of this ratio is underestimated. To obtain a more realistic value, the experimental ratio data have been roughly corrected using the results obtained with a human head phantom filled with various 1-123 activities (the phantom S/C ratio varies from i to i0). Once corrected, the mean calculated S/C ratio in controls is 7.6. When 123-I ILIS was injected to patients treated with high doses of haloperldol, it was impossible to see any specific fixation at the level of the striata (S/C : i.I). Using a conventionnal rotating y-camera, a good quality image of the distribution of the radioactivity in the whole brain was obtained in 30 min (S/C in controls : 3.2). Using such an imaging system, a lower value of S/C (1.8) was measured in a patient with clinical evidence of progressive nuclear palsy.

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The significance of nonvisualization of entire extrahepatic a c t i v i t y by radionuclide cholescintigraphy has not been well established in predicting gallbladder disease. We have r e t r o s p e c t i v e l y reviewed a t o t a l of 363 consecutive patients who had hepatobiliary scan using technetium-99m diisopropyliminodiacetic acid (DISIDA) since 1983. Twenty-two patients (6.3%) demonstrated this pattern for at least 4 hr despite good hepatic uptake. All of these 22 patients were male with a mean age of 68 due to dominant e l d e r l y male population of our i n s t i t u t i o n . Twenty-one of the 22 patients were operated on. All of the 21 surqical cases were acutely i l l with pain in the upper abdomen. Twenty patients were confirmed to have calculous cholec y s t i t i s (14 acute, 6 chronic) by pathological examination. Of these, 16 had common b i l e duct (CBD) obstruction. Three patients without CBD obstruction at the time of surgery did have stones in the neck of the qallhladder or cystic duct. One patient had acute acalculous c h o l e c y s t i t i s and no stones in the CBD. One patient who was not operated on was considered to have intrahepatic cholestasis from h y p e r s e n s i t i v i t y reaction to proca~namide. We conclude that a DISIDA cholescintigraphy with nonvisualization of entire extrahepatic a c t i v i t y despite good hepatic uptake in acutely i l l e l d e r l y males with pain in the upper abdomen is highly predictive of acute or chronic c h o l e c y s t i t i s (21/21+1:95%), CBD obstruction is also often seen in this scintiqraphic situation {16/16+5=76%),

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GAtJ~]~DD~ V O L I ~ IS (~.ATJ~ AND GAM~LADD]~ ]~TtTLNG RATE IS LESS IN LARGE PEOPLE BOTH OBESE AND NON-OBESE USING SMALL AND ~ LIQUID FAR~J"fMEAI.B. W.C.Vezina, D.M.Grace, L.C.Hutton, W.Y.Chey. University Hosp. London, ON Canada and The Genesee Hosp. Rochester, N Y U . S . A .

ARE BILE ACID MAt_ABSORPTION OR BACTERIAL COLONISATION SIGNIFICANT IN CROHN'S DISEASE? MV Merrick, HJ Nylhin, MA Eastwood. Dept. of Nuclear Medicine and Wolfson Gastro-lntestinal Unit, Western Generat Hospital, Edinburgh. U.K.

Imp~iredgallbladder (GB) emptying m a y b e a factor in pathogenesis of gallstones. Obese people have an increased incidence of gallstones but there is no evidence of this in non-obese large people. We measured fasting GB voltm~s (vol) using realtime ultrasound and emptying using T o - 9 9 m D I P I D A with a low calorie fatty meal (200 ml 10% cream, 374 kcal) and with a high calorie fatty meal (1200 ml ice cream in a commercial liquid meal, 1600 kcal). Fasting GB vol using an ellipsoid model were greater in the large subjects, morbidly obese 41 (3766) ~[, median (95% confidence) and large normals 40 (27-43) ml, than in average-sized subjects, 17 (1421) m/ (p=.03) (corrected for multiple comparisons). study #I: Effect of low calorie meal (N=I8 for each group). GB emptying was slower in the large subjects obese and non-obese: % remaining in the GB 90 m in after the meal, 33 (• in obese, 48 (• % in large non-obese versus 19 (• % for the averaEesized subjects (p<.05). study #2: Effect of high calorie meal. Obese (N=I4) and large normals (N=II) consumed the larger meal to determine if gallbladder emptying could be improved. Gallbladder emptying was similar to the small meal, with the % remaining in the gallbladder being 42 (• % for the obese and 42 (• % for the large normals. F~gting gallbladder volumes are greater and postprandial rate of emptying is less in obese and non-obese large subjects.

46 patients with proven Crohn's disease, whose symptoms had failed to respond adequately to conventional treatment, but who had not undergone any resection or by-pass of the small bowel, and 26 patients with a partial small bowel resection for Crohns disease, were investigated for evidence of bile acid malabsorption and of bacterial colonisation. The retention of Se-75 SeHCAT (23-selena 25-homocholate taurine) and of Co-58 B12 was measured 7 days after oral administration, using a shadowshield whole body counter. 11 (42%) of the patients with a resection had low B 12 retention, indicating either an extensive distal resection or colonisation, but only six (13%) of those without, in whom it predicated cotonisation. 23 (88%) of the patients with resection had bile acid malabsorption, evidenced by a retention of less than 5% at 7 days. One, with a proximal resection, was within normal limits and the other two. with limited resections, fell into the equivocal range (between 5% and 10%). Twenty (43%) of the patients who had not had any resection had 7-day retentions less than 5% and thus had significant bile acid malabsorption. Three further patients were in the equivocal range. We conclude that, although bile acid malabsorption is not a usual feature of Crohn's disease, it does occur in some unoperated patients and may exacerbate the diarrhoea. Thus SeHCAT retention should be measured in any patient with Crohn's disease whose symptoms are difficult to control, but is not indicated routinely in other patients. Colonisation is tess common both in operated and unoperated patients with Crohn's disease, but may be a cause of B12 malabsorption.

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IDIOPATHIC BILE ACID MALABSORPTION IS NOT RARE. MV Merrick, AJKWilliama, MA Eastwood, Dept. of Nuclear Medicine and Gastro-lntestinal Unit, Western General Hospital, Edinburgh, U.K.

EVALUATION OF PORTOSYSTEMIC COLLATERALS IN PORTAL IIYPERTENSION BY ABDOMINAL BLOOD-POOL SPECT. T. Kashiwa$i, H. Fukui, K. Kimura, T. Kozuka, N. Sato T. Kamada, M. Azuma, N. Mitsutani, and T. Koizumi. Osaka University Hospital and Osaka Kosei-Nenkin Hospital, Osaka, Japan.

Between 1982 and 1989 the 7-day retention of Se-75 SeHCAT was measured in 181 patients with chronic diarrhoea, unexplained after full and extensive investigation using all established diagnostic modalities. 121 of these had a 7-day S,eHCAT retention greater than 15% and thus had no evidence of any abnormality in the rate of bile acid turnover. 21 had a 7-day SeHCAT retention of between 10% and 15%. Their clinical features were typical of the irritable bowel syndrome, and none of the 8 treated with cholestyramine showed symptomatic improvement. It is therefore concluded that these patients did not have bile acid malabsorption and that the previously suggested lower limit of 15% should be revised downwards to 10%. 13 patients had a 7-day retention between 5% and 10%, six of whom were improved symptomatically by treatment with bile acid chelating agents; all 23 patients with a SeHCAT retention less than 5% at 7 days responded. The latter group had a characteristic illness with intermittent watery diarrhoea, large volume frequent liquid stools, commonly nocturnal diarrhoea, but no constitutional upset, ttwas not possible to distinguish the patients with bile acid malabsorption exclusively on the basis of the clinical symptoms, or of investigations other than SeHCAT retention. We conclude that the measurement of SeHCAT retention is useful, appropriate and necessary in patients with chronic diarrhoea for which no explanation has been found on other investigations. The identification of 29 new cases (16% of all patients with unexplained diarhoea) as having idiopathic bile acid malabsorption in a single centre in an eight year period indicates that this treatable condition is not rare if properly sought.

Monday, August27,1990

SPECT was performed with Tc-99m autologous red blood cells(RBCs) in 58 patients with liver cirrhosis to evaluate the development of portosystemic collaterals. Endoscopic examination also was performed to compare SPECT findings with endoscopic findings on esophageal varices. Twenty mCi of Tc-99m RBCs labeled by the in vivo technique was given intravenously, and tomographic imaging of the intraabdominal vascular blood-pool was performed. For each patient, 64 views were obtained over 360 ~ of elliptic rotation at 30 sec/view, and each view was stored in computer memory as a 64 x 64 matrix. Endoscopic examination was performed within one week before or after SPECT study. The portosystemic collaterals such as coronary vein, short gastric vein or splenorenal shunt could be clearly visualized by SPECT. The coronary and short gastric veins were observed in 36 and 9 patients respectively. In the case of 17 patients whose coronary or short gastric veins could not be observed by SPECT, esophageal varices were small. In 2 patients without esophageal varices, the coronary or short gastric veins were visualized by SPECT. In ii patients with splenorenal shunt, only one patient had severe esophageal varices and others had no esophageal varices or only small ones. These results suggest that SPECT is useful for the noninvasive evaluation of portosystemic collaterals in portal hypertension. Furthermore, the combined use of SPECT and endoscopy rather than the use of either technique could provide us with more useful information for the care of patients with portal hypertension.

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CLINICAL APPLICATION OF PET STUDY IN CHRONIC LIVER DISEASE. Y. Kuniyasu, S. Higashi, Y. Niio, S. Okada*, M. Ohto*, K. Imazeki**, and N. Arimizu ~*. Teikyo University School of Medicine, Tokyo, Japan and Dept. of 1st Internal Medicine* and Radiology**, Chiba University School of Medicine, Chiba Japan.

CLINICAL AND EXPERIMENTAL INVESTIGATION OF THE REPRODUCIBILITY OF BONE MINERAL CONTENT MEASUREMENTS OF LUMBAR SPINE AND FEMORAL NECK WITH THE DUAL PHOTON BONE D E N S I T O M E T E R O S T E O T E C H 300 J. F r o h n , T. W i l k e n , J. H a p p , S. Falk, R.P. B a u m , G . H 6 r J.W. G o e t h e U n i v e r s i t y M e d i c a l C e n t e r , F r a n k f u r t / M a i n , F R G

We have developed a liver scanning agent in convenient kit type for use of positron emission computed tomography (PET). The labeling procedure for Ga-68-mierospheres can be completed in 10-]5 minutes using NEN generator coupled with an acetate buffer system. Forty six subjects with chronic liver diseases, including 5 normal cases, were evaluated for PET imaging of the liver. The volumes of the liver and spleen were calculated as an index of reticuloendotherial cell function using the method of summation of the liver and spleen in each slice. They were compared with the volumes of the liver and spleen by X-CT which were calculated within ] or 2 weeks of PET imaging. For the volumes of the liver, r was 0.95, and 0.98 for the spleen, respectively. The volumes of the liver and spleen by PET were compared with different chronic liver diseases. The volume of the liver decreased significantly in patients with liver cirrhosis and the volume of the spleen increased with progression of chronic liver disease from chronic hepatitis to liver cirrhosis. The corrected liver uptake of Ga-68-microspheres using differential absorption ratio decreased significantly, with progression of chronic liver diseases, but the corrected uptake of the spleen did not significantly increase in chronic liver diseases. In conclusion, PET imaging of the liver with Ga-68-microspheres is useful for pathophysio]ogical stydy of chronic liver diseases.

A reliable e a r l y d e t e c t i o n of o s t e o p o r o s i s c a n b e a c h i e v e d p r i m a r i l y by l o n g i t u d i n a l studies o f b o n e m i n e r a l c o n t e n t ( B M C ) . T h i s type of follow u p r e q u i r e s a h i g h r e p r o d u c i b i l i t y of the m e a s u r e m e n t s . T h e objective o f o u r investigation was to d e t e r m i n e t h e p r e c i s i o n o f r e p e a t e d m e a s u r e m e n t s of B M C with t h e u s e of G d - 1 5 3 d u a l p h o t o n a b s o r p t i o m e t r y ( D P A ) . W e d e t e r m i n e d t h e p r e c i s i o n o f s e q u e n t i a l studies o n the b o n e d e n s i t o m e t e r O S T E O T E C H 300. T h e m e a s u r e m e n t s w e r e r e p e a t e d instantly a f t e r o n e a n o t h e r a n d w e r e p e r f o r m e d o n a v a r i e t y of a n t r o p o m o r p h o u s l u m b a r spine p h a n t o m s a n d o n blocks m a d e f r o m c a l c i u m hydroxy a p a t i t e . W e also d e t e r m i n e d t h e i n f l u e n c e of t h e s t r e n g t h o f t h e G d - 1 5 3 s o u r c e a n d of p a t i e n t positioning. S e q u e n t i a l studies w h i c h w e r e r e p e a t e d instantly~on v a r i o u s p h a n t o m s y i e l d e d a p r e c i o n b e t t e r t h a n -+ 0.01 g / c m A F o r the l u m b a r spine studies p e r f o r m e d in the a.p. p r o j e c t i o n t h e r e w e r e n o significant differences b e t w e e n t h e values o b t a i n e d with t h e p a t i e n t s legs fiat o n t h e table, a n d with t h o s e w h e r e the p a t i e n t s legs w e r e e l e v a t e d o n a c u s h i o n ( p = 0 . 0 5 ) . A comparison of measurements performed on the femoral neck c a n result in d e v i a t i o n s d e p e n d i n g o n w h e t h e r the p a t i e n t ' s leg w a s r o t a t e d i n w a r d s or o u t w a r d s ( m a x i m u m d e v i a t i o n m e a s u r e d : 11,8 %). W i t h a G d - 1 5 3 s o u r c e w h i c h w a s o n e m o n t h old, the s t a n d a r d d e v i a t i o n ( d e t e r m i n e d with t h e H O L O G I C l u m b a r s p i n e - p h a n t o m ) w a s 0.44%; with a source w h i c h was 12 m o n t h old, the s t a n d a r d d e v i a t i o n w a s 0.68%.

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INTER-UNIT VARIATION OF BONEDENSITONETRY SYSTEMS. M. Fischer and B. Kempers. St~dt. K1inken. Kassel, FRG

SELECTIVE EVALUATION OF THE VERTEBRAL BODY BONE MINERAL DENSITY [BMD) MEASURED BY DUAL ENERGY X-RAY ABSORPTIOMETRY. D.O. SIosman R. Rizzoli. A. Donath et J.-Ph. Bonjour. Geneva University Hospital. 1211 Geneva 4. Switzerland.

The aim of the study was to evaluate the intra- and inter-unit variation of bone densitometry systems (BD) of d i f f e r e n t companies using an animal spine encapsutated in soft tissue equivalent materiat as phantom f o r cross calibration. 3 vertebras of the phantom were measured several times with BDs using either radionuclide source (n=6) or an X-ray tube (n=4). To exclude the inaccuracy of BDs caused by overlying soft tissue, the phantom was measured with overlying water and/or f a t . Whereas the i n t e r - u n i t variation was upto 20%, the intra-unit variations were less than I% in all systems but 2 with a coefficient of variation of 2 or 5%. Overtying the phantom with water (4 and 8cm) and or f a t (3.5 and 7cm) d i f f e r e n t results were observed. Some BDs showed CVs of about 8-10% compared to basal vatues, others were not influenced by soft tissue. During a tong-term measurement of the phantom with two BDs the CV was less than 2%. The inter-unit variation of bone densitometry systems is due to various calibrations whereas the under- or overestimation of bone mineral content depending on d i f f e r e n t overlying soft tissue may be caused by d i f f e rent software algorithms. The software f o r calculating soft tissue and bone are significantly d i f f e r e n t and results are not d i r e c t l y comparable. Because of these differences a comparison of BHC values from d i f f e r e n t BDs is problematic. Therefore we b u i l t a phanto~ with cylindric bodies with d i f f e r e n t hydroxyapatite content and one f a t equivalent body f o r cross calibration of BDs. By using such phantoms a standardization of BDs should be possJbte.

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BMD of lumbar (L2 L4) vertebrae in antero~posterior view (BMDap) with d u a l - p h o t o n a b s o r p t i o m e t r y m a y be overestimated by osteoarthritis or aortic calcification which are common in elderly. To overcome these pitfalls, we have developed a technique to measure l u m b a r {L2-L3) spine BMD in lateral view (BMDIat} with the new technology that uses X-ray beam (QDR-1000,Hologic}. We investigated its precision, its ability to evaluate age-related bone m a s s loss and to discriminate between BMD in normal a n d in osteoporotic subjects with non traumatic vertebral fracture. In vitro, reproducibility of lumbar spine phantom BMDlat measured in air a n d expressed by the coefficient of variation of 6 repeated m e a s u r e m e n t [CV) was 0.3%. Simulating soft-tissue thickness with water (26 cm), CV was 1.0%. In vivo, CV of 20 paired BMDIat measurements after repositioning in 20 healthy volunteers was 2.8%. Peak bone m a s s values of lumbar spine BMDap a n d BMDIat were obtained in 27 healthy volunteers (20-35 yrs). Compared with mean BMD in 50 healthy subjects [without risk factor or fracture, 60-75 yrs), the age-related bone loss was 37.6% a n d 21.7% in LAT a n d AP views, respectively. A pathological BMD threshold was defined in AP a n d LAT views as the 90 percentile of the BMD value in 22 patients with vertebral fracture associated to minor or no trauma. In 169 consecutively screened women, 39.1% h a d BMD values above threshold, 47.3% h a d at least AP BMD below threshold a n d 13.6% h a d only LAT BMD m e a s u r e m e n t below threshold; therefore they would have been considered as false negatives if only BMD measurement was done in standard AP view. In conclusion, our results indicate that BMD measurement in LAT view is feasible, more sensitive to age-related bone loss t h a n BMD in AP view a n d c a n overcome artefacts associated with lumbar spine AP view.

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D U A L - E N E R G Y X-RAY (DEXA) A N D Gd-153 D U A L - P H O T O N B O N E DENSITOMETRY (DPA): S T U D Y OF PRECISION AT T H E LEVELS OF SPINE A N D F E M O R A L NECK. D.O. Slosman ~ Sandoz, R. RLzzoli,A. Denath and J.-Ph. Bonjour. Geneva UniversityHospital.1211 Geneva 4. Svatzerland.

COMPARISON BETWEEN DUAL ENERGY X-RAYS ABSORBIOMETRY (DEXA) AND QUANTITATIVFE COMPUTED TOMOGRAPHY (QCT). B: Bagni, F. Pansini, V. Valpondi, Ospedale S. Anna, Ferrara, Italy.

Precision is a major factor in the follow-up of bone mineral density (BMD). We have compared both in vitro and in vivo performances of 2 dual-energy X-ray absorptiometers (Hologic, QDR- 1000 and Norland, XR-26) and 1 d u a l - p h o t o n bone a b s o r p t i e m e t e r u s i n g G d - 1 5 3 (Norlan d, DPA-2600). In vitro, the precision expressed a s the coefficient of variation (%CV) was studied using spine a nd hip phantom immerged u n d e r various water depths (6 m e a s u r e m e n t s for each cm of wa le r up to 27 cm) to mimick soft tissue thickness. From 0 to 27 cm of water, %CV increased from 0.1 to 2.5% for DPA, from 0.2 to 1.4% for QDR and from 0,4 to 3.00/0 for XR; in addition the mean%CV of all 26 series of m e a s u r e m e n t s from to 0 to 25cm of wa te r was 1.0+0.7% for DPA, 1.1_+0.7% for XR, higher t h a n for QDR: 0.5_+0.4% (mean+SD). Thus, %CV of spine BMD (BMDsp) was dependent on the thickness of water for both DPA, XR and QDR, b u t not to the same extent. For femoral neck BMD (BMDfn), from 0 to 19 cm of water, %CV increased from 1.1 to 6.2% for DPA, from 0.6 to 3.1% for QDR and from h 0 to 2.0% for XR. In vivo %CV was assessed for BMDsp and BMDfn in 34 healthy v o l u n t e e r s (6 m e a s u r e m e n t s with repositioning, pe r site a n d volunteer) using XR, QDR and DPA with a 9 months old (os) and a new Od-153 source (ns). With DPAos, DPAns, QDR a nd XR respectively, mean%CVs were 3.8%, 2.1%, 1.0 and 1.2% for BMDsp and 2.4%, 2.0% 1.8 and 1.8% for BMDfn. In cc,nclusion, %CV of DPA is dependent on the activity of Gd-153 source. DEXA which h a s the a dva nta ge of a faster s c a n n i n g time t h a n E,PA, displays a gr e a te r precision at the spine but not at the femoraI neck level. Finally, both DEXA i n s t r u m e n t s (QDR a nd XR) give precision in the same extent at the 2 sites investigated.

102 patients who received QCT exam because of a clinical indication (postmenopausal osteopenia) of bone losse were also studied with DEXA. The DEXA esam were performed from 1 to 2 months after the QCT examination. The patient sample includes pre and postmenopausal women. The QCT exam were performed using an anatomical hydroxiapatite phantom. The data analysis shows a linear fit between QCT and DEXA (r=.774 p<0.001); whose equation is: QCT = 207 x DEXA -60.711 The correlation between QCT and DEXA is very high but the meaning of the figure obtained is quite different because QCT measures only the trabecular bone while DEXA measures the total bone in the spine.

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TOTAL BODY ~ D REGIONAL BONE MINERAL BY DPA IN PATIENTS ON HEMODIALYSIS: COMPARISON WITH INTACT-PTH CONCENTP~AT ION . H. Sere, N. Watanabe, R. Futatsuya, T. Kamei, and M. Kakishita. Toyama Medical and Pharmaceutical University, Toyama, Japan.

DMSA SCAN: A FIRST LINE INVESTIGATION OF URINARY T R A C T INFECTION. K. Me/is I,J. Vandevivere 2, A. Jespere I, C. Hoskens I IChildren's Hospital and 2 AZ Middelheim, Antwerp, BELGIUM

Total body bone mineral (TBBM) and regional bone mineral density (BMD) in the head, trunk, pelvis, lurabar spine, arm, and leg were measured by dual photon absorptiometry (DPA) with a Noland DBD 2600 in eighteen normal male subjects (age: 36.7~+5.3 years) and twenty-seven male patients. The patients were classified into two groups according to plasma intactPTH concentration: 13 males (age: 37.8f5.3 years) <73 pg/ml (A group) and 14 males (age: 36.1~8.5 years) >73 pg/ml (B group). TBBM/H (g/cm) and TBBMD (g/cm2) were also calculated. TBBM/H had the best correlation coefficient with intact-PTH (r=-0.60, p<0.01). NO significant differences in regional BPZD of any sites were noted between the ncrmals and A group. However, B group showed a significant decrease in the regional BMD of all sites. In contrast, TBBM indices were significantly decreased in both patient groups, as described below. Index

Normals Patients on hemodialisis In=18~ PTH<73 (n=13) PTH>73 ~n=14) TBBM 2620.0-+282.5 2294.2-+204.0 1937.6-+369.3" TBBM/H 15.3-+1.4 13.5~1.2"* Ii.5~2.0"* TBBMD 1.000~0.085 0.915~0.054** 0.812s ~91 ~* * p<0.05, ** p<0.Ol to norma.ls From this study we conclude: i) TBBM indices are inversely correlated better with plasma intact-PTH concentrations than regional BMD. 2) TBBM indices are significantly decreased in both patient groupa even though plasma intact-PTH concentrations were normal. 3) Measurement of TBBM indices is essential in patients on hemodialysis.

Monday, August 27, 1990

Over a 3,5 year period 147 children (39 boys and 88 girls; 99 under 5-years of age)underwent T c - 9 9 m D M S A scan (DMSA). The images were acquired with an all purpose- or pinhole collimator, in the posterior and both posterior oblique projections. W e compared the D M S A findings with the clinical history, intravenous pyelography (IVP), micturating cystourethrography (Me) 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 D M S A and US, 93 had IVP and 81 MC. In the P-group D M S A w a s + in 6 9 / 1 2 0 kidneys whereas 27 were + on US. In the U-group D M S A w a s + in 2 7 1 1 2 4 kidneys with only 6 + on US. In the P-group D M S A w a s + in 4 9 / 8 4 whereas 17 were + on IVP. In the U-group D M S A was + in 12/54 whereas 3 were + on IVP. In the P-group 33 kidneys showed vesicaureteral reflux (VUR) on MC with 8125 IVP +, 8/33 US +, and 24133 D M S A +. 23/33 showed a grade Ill or higher VUR. In the P-group 63 kidneys showed no VUR with 13/51 IVP +, 21163 US +, and 34/63 D M S A +. In the U-group 13 kidneys showed VUR on MC with I14 IVP +, none US +, and 5113 D M S A +.Those 5/13 D M S A + showed a grade Ill or higher VUR. In the U-group 57 ,i:Ineys showed no VUR with 6140 IVP +, I 1/57 US + and I 1/57 These re.sultssuggest that I~ D M S A is more sensitive than IVP 9~,,J US m the early detection of renal scarring, even without LIInicoI -~;iynsof acute pyelonephritis 2 ~ scarring seems to occur ,~,the .Jn:.,-enceof VUR more often than generally estimated 3 ~) OE.~,,~~s a useful first line investigation of UTI in children and can oe helpful in selecting patients who require a Me.

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A S S E S S M E N T OF S E P A R A T E RENAL F U N C T I O N BY THE HIPPURAN!-123 A C C U M U L A T I O N INDEX (AI) IN N E O N A T E S AND INFANTS WITH URINARY TRACT DISORDERS. D. Reymond, A. Bischof-Delaloye, B. Delaloye, N. Genton, CHUV, Lausanne, S w i t z e r l a n d

THE IMPORTANCE OF INDIRECT RADIONUCLIDE M I C T I O N A L C Y S T O - U R E T E R O G R A P H Y (IRMCU) IN THE E V A L U A T I O N OF PEDIATRIC V E S I C O - U R E T E R A L REFLUX (VUR). P. Capasso, A. Bischof-Delaloye, N. Genton, B. Delaloye N u c l e a r Medicine, Pediatric Surgery, CHUV, Lausanne Switzerland

With diagnosis of u r i n a r y tract m a l f o r m a t i o n s being made by p r e n a t a l ultrasonography, the decision on early surgery depends in part on the p r e s e n c e of concomitant functional impairment. In older children the AI, w h i c h is d e f i n e d as the ratio of 30-90 sec. b a c k g r o u n d corrected kidney a c t i v i t y to injected activity (in %), estimates reliably individual kidney function. It was not clear if this was also the case in neonates and young infants. From March 1983 to D e c e m b e r 1989 we p e r f o r m e d 140 renograms in children during the first year of life. 40 p r e s e n t e d with isolated v e s i c o - u r e t e r a l reflux, 20 with ureteropelvic and 20 with u r e t e r o v e s i c a l junction obstructions; 14 had duplications of the upper urinary tract, 13 p o s t e r i o r urethral valves, 12 dysplastic kidneys, 4 bladder extrophies, 2 hypospadias and 9 m i s c e l l a n e o u s disorders. In 54% the anomaly was bilateral, in 42% unilateral. In 4% involvement of the urinary tract could be ruled out. The average AI in these latter patients was 11.24 + 1.99 (ISD). These figures are identical with the normal values obtained in older children (11.04 + 1.96). In the other patients the AI v a r i e d a c c o r d i n g to the type and degree of the disorder and presence or absence of c o m p e n s a t o r y h y p e r p l a s i a of the c o n t r a l a t e r a l kidney. The lowest values were observed in dysplastic kidneys and in patients with urethral valves. I n d e p e n d e n t l y of the age of the children, AI is a useful p a r a m e t e r in the evaluation of urinary tract m a l f o r m a t i o n s not only during initial staging but also during follow-up.

The not i n s i g n i f i c a n t gonadal i r r a d i a t i o n received during a standard m i c t i o n a l c y s t o - u r e t h r o g r a p h y (MCU), an essential part of the initial w o r k - u p of children p r e s e n t i n g with u r i n a r y tract infections, has w a r r a n t e d the search of other tests for the follow-up after m e d i c a l or surgical treatment. Since these children usually u n d e r g o r e g u l a r controls of their individual renal function using either 1-123 hippuran, T c - 9 9 m DTPA or T c - 9 9 m P~G3, the I~MCU offers an alternative which does not involve either a c a t h e t e r i z a t i o n nor any additional irradiation. In order to evaluate this method, we c o m p a r e d the results of IRMCU to those of MCU and cystoscopies p e r f o r m e d during the initial w o r k - u p of 49 c h i l d r e n (98 renal units), 32 girls and 17 boys, aged 1 month to 13 years. With MCU we o b s e r v e d that a V U R was b i l a t e r a l in 20 cases, unilateral in 23 and absent in 6. In all cases with a reflux stage III-V end in 8/13 with stage I-II, the I ~ C U was positive. Stage I VUR is not expected to be seen by this m e t h o d due to o v e r l y i n g bladder activity. In 14/35 cases showing no reflux on the MCU, the IRMCU was pathologic. Of these 14 cases, I0 p r e s e n t e d a l a t e r a l i z a t i e n and/or m e a t a l dilatation of mild (n=4), m o d e r a t e (n=5) or severe (n=l] degree, 2 p r e s e n t e d a granular cystitis and 2 a v e s i c e - u r e t h r a l dyssynergy. These results show that the IRMCU is a sensitive technique for the follow-up of VUR and that it usefully completes the radionuclide assessment of the individual renal function.

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RELATIONSHIP OF VESICOURETERAL REFLUX, P-FIMBRIATED E. COLI AND ACUTE PYELONEPHRITIS IN CHILDREN. M. Maid, H.G. Rushton, B. Jantausch, and B.L. Wiedermann Children's National Medical Center, Washington, D.C.U.S.A.

RENAL FUNCTION IN ANTENATALLY D I A G N O S E D HYDRONEPHROSIS - LONG TERM FOLLOW-UP OF CHILDREN MANAGED CONSERVATIVELY OR SURGICALLY AM Peters, HK D h i l l o n , H Gatanash, I Gordon and PG Ransley. Hosp!tal f o r Sick C h i l d r e n , Great Ormond

Acute pyelonephritis in children is commonly assumed to be associated with reflux. Recent reports have suggested that acute pyelonephritis in the absence of reflux is common and it has been attributed to the presence of P-fimbriae in certain strains of E. coil We studied 94 patients hospitalized with febrile urinary tract infection (UTI) to determine the relationship between reflux, P-fimbriae, and acute pyelonephritis and to evaluate the diagnostic reliability of commonly used clinical and laboratory parameters. Based on a previous experimental study, we used 99mTc-DMSA renal scan as the standard of reference for diagnosing acute pyelonephritis. Acute pyelonephritis was documented in 61 (65%) patients. Reflux was demonstrated in 32% of the total group and in only 39% of patients with acute pyelonephritis. Of the 70 E. coil urinary isolates, 70% were P-fimbdated including 65% of isolates from patients with scan documented acute pyelonephritis and 75% of isolates from patients with normal DMSA scans. Although a trend was noted, there was no significant difference in the incidence of P-fimbriated E. coli in patients with positive DMSA scan and reflux (50%) compared with those who had positive scans without reflux (72%) [P =0.15]. Statistical analysis of clinical and laboratory parameters commonly used in the diagnosis of acute pyelonephritis revealed that these variables, either singly or in any combination, did not adequately predict the presence or absence of parenchymal involvement. These data show that: (1) acute pyelonephritis in the absence of demonstrable reflux is common; (2) febrile UTI in children is commonly associated with P-fimbriated E. coli both in the presence or absence of reflux; (3) the presence of P-fimbriae alone does not fully explain the pathophysiology of renal parenchymal invasion by bacteria in the absence of reflux; and (4) diagnosis of acute pyelonephritis in children with febrile UTI based on the clinical and laboratory parameters is unreliable.

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Street, London, Wl, England, It is i n t u i t i v e that c h i l d r e n with h y d r o n e p h r o s i s , in whom obstruction cannot be excluded on d i u r e t i c renography, should be c o n s i d e r e d for p y e l o p l a s t y , p a r t i c u l a r l y if they have impaired renal function. In many such c h i l d r e n , the h y d r o n e p h r o s i s is detected by u l t r a s o u n d d u r i n g the antenatal period, We s t u d i e d the effects of s u r g e r y on renal function and drainage in 29 c h i l d r e n with u n i l a t e r a l , a n t e n a t a l l y diagnosed, hydronephrosis. Thirty=eight other patients with this diagnosis, who, for v a r i o u s reasons did not undergo surgery, were also studied. Patients were studied on 2-6 occasions at ages ranging from I month to 5 years u s i n g t e c h n e t i u m - 9 9 m DTPA d i u r e t i c renography, Kidneys that c o n t r i b u t e d less than 43% of total function were considered to have imapired function, O b s t r u c t i o n was defined on the b a s i s of the response to f r u s e m i d e and b l a d d e r emptying, u s i n g two sets of c r i t e r i a : s t r i c t and l i b e r a l . A l t h o u g h drainage improved in 9 / 2 9 following surgery, there was no s i g n i I i c a n t improvement in function, even when only those p a t i e n t s with s t r i c t l y defined o b s t r u c t i o n and i m p a i r e d function were considered. In the non-operated group n e i t h e r function nor drainage changed s i g n i f i c a n t l y , even in those with obstruction. Indeed, in the same group, in 6/38 p r e s e n t i n g with i m p a i r e d f u n c t i o n , and in 7 / 3 8 w i t h s t r i c t l y d e f i n e d obstruction, function improved s i g n i f i c a n t l y . We conclude that DTPA d i u r e t i c r e n o g r a p h y is u n r e l i a b l e for d i a g n o s i n g obstruction in this age group and that a randomised controlled t r i a l to determine the benefits of s u r g e r y is justifiable.

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INFLUENCE OF URETERAL DILATATION ON KIDNEY WASHOUT AT DIURESIS RADIONUCLIDE RENOGRAPHY (DR) IN CHILDREN : THERAPEUTICAL IMPLICATIONS. F.Jamar, F-X.Wese, C.Beokers and L.Piret. Cliniques Universltaires St Luc, UCL, Brussels, Belgium.

LOW LEVEL RADWASTE DISPOSAL D. Brill, Geisinger Medical Center, Danville, PA, USA

The aim of the study was to evaluate the relationship between kidney and ureter washout during DR with regards to the therapeutic choice. 14 children (age: 9d to 9y) undergoing DR presented an abnormal image of one or both ureters (17 units). All studies were performed with DTPA Tc-99m in well hydrated supine children, with a bladder catheter. A washout index (T~) was determined for both the kidney and ureter. We consider as non obstructive (NO) a T~ < 15min, obstructive (O) T ~ > 20 min and intermediate, T between 15 and 30 min. Table shows agreement between the T ~ (min) for kidney (K) and ureter (U). K\U >20 <20 >20 5 i (16 min) <20 0 Ii The 0 T~ was observed in 4 cases of megaureter and in one neurogenic bladder. In one additionnal patient with poor renal function, the kidney T~ was clearly 0 while ureter T~ was indeterminate. Diuresis should be considered as inadequate to conclude. The NO T~ was present in various lower urinary tract disorders The correlation between the kidney and the ureter T~ was good (r = 0.7; p<0.01). Despite of gross pyelic dilatation and an 0 kidney T~ no patient underwent surgery for PUJ obstruction. Follow-up demonstrated regression of the hydronephrosis after lower urinary tract correction. In conclusion,when DR demonstrates an 0 kidney T~, no therapy should be decided without knowledge of the ureteral status and the ureter T~.

Low level radwaste (LLRW) disposal has become an important issue in the last decade, but progress in siting repositories has been very slow. Medicine is a generator. While clinical activities rarely generate much disposable waste, medical/ pharmaceutical research and production of radiopharmaceuticals do. On the other hand, nuclear physicians have a responsibility to speak out on matters of public health and safety. Medicine's goal is to find a safe, rapid, and economical solution to the LLRW issue with preservation of all benefits. The USA produces ~ 200,000 m3 LLRW annually, 10-15% of the volume (0.1% of activity) from medical uses. With disposal costs expected to escalate as high as $6,000 per m3 by 1993, the impact on society of limited or lost services could be severe. Still, safety is the most important matter. The key issue is isolation of wastes from the biosphere for a period of time sufficient for the radiologic hazard to dissipate. Most of the radionuclides (RN) are either short lived (< 5y) or present in trivial amounts (< ImCi/y). Only six fall outside these limits. More radioactive LLRW are usually physically stable or can be solidified to prevent migration. Soil chemistry may also prevent dispersal. Elimination of contact with water removes the most common vector of spread, and is the ultimate strategy in waste isolation. Numerous containment strategies have been proposed, many of which are feasible with presently available technology. Much is known about environmental behavior of RN and numerous sites could serve to safely isolate LLRW, especially when combined with sophisticated containment.

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OCCUPATIONAL EXPOSURE TO NUCLEAR MEDICINE TECHNOLOGISTS AS MEASURED BY TLD BADGES AND RINGS. A 17 YEAR RETROSPECTIVE STUDY. J.W. Logus, T. Kotchon. Cross Cancer Institute, Edmonton, Albevla, Canada.

EVALUATION OF THE INFORMATION NEEDS OF HEALTH WORKERS ABOUT THE INDUSTRIAL AND MEDICAL, NUCLEAR AND RADIOLOGICAL RISK. J.C. Artus, R. Granier, J.M. Vinot, Y. Tardy, H.Frossard et le Groupe Regional de Reflexion et d ' I n f o r m a t i o n Nucleaire et Sante (GRRING), C.R.L.C. Parc Euromedecine M o n t p e l l i e r , France.

A retrospective study was carried out to determine if a recently perceived increase in Nuclear Medicine Technologists TLD badge readings was significant and, if so, what factors were responsible. The department, which is located in a cancer treatment center, maintains TLD records dating as far back as 1973. Annual average dose estimates for all full-time technologists actively involved in diagnostic and therapy procedures were obtained from TLD badge readings, with corrections made for absences. Finger ring readings dating back to 1979 were also analyzed. An attempt was made to relate annual doses received to factors such as the amount of radionuclide ordered for the department, the types of radionuclides ordered (Tc-99m and 1-131), the number of procedures, and the number of work units generated. The 17 year average badge dose estimate was 2.14 _+ 1.35 mSv (mean _+SD). The first year had the highest figures of 5.35 • 0.40 mSv, while in 7 of the last 8 years, the average dose has been under 2.00 mSv. However, an increasing trend has been observed over the last 3 years (1.07, 2.17, 1.82 mSv). This appears to correlate with increasing numbers of 1-131 therapies (7 in 1980, 42 in 1986, and 83 in 1989). Relating annual dose received to work units per technologist or to number of procedures per technologist was not found to be an appropriate method of analysis due to increasing rime required for procedures and variations in the method of calculating work units. Finger rings were not worn by all technologists frequendy enough to provide reliable average dose estimates. The evidence suggests that the increasing number of therapies are the cause of the recent upward trend in technologist badge dose. Accordingly, changes to the preparation and administration of I-131 patient doses have been incorporated. These include: improved shielding at preparation stations, a better shielded dose calibrator, and a ~mialadministration of therapeutic iodine via oral capsules.

Monday, August 27, 1990

The preoccupation of the public about the r i sks associated with a c t i v i t i e s using i o n i s i n g r a d i a t i o n involves an e f f o r t o f information necessary to the acceptance and development of t h e i r medical and indust r i a l a p p l i c a t i o n s . Because of the possible health consequences, health workers, f r e q u e n t l y misinformed, are however concerned, and must be normally an i n f o r mation r el ay and to ensure a c c e s s i b i l i t y and his credibility. A regional groups of r e f l e x i o n , nuclear information and health, formed by local s p e c i a l i s t s , has the goal to answer to the questions of health workers. To precise the information needs, II 000 questionnaires were sent to every physician, pharmacist, d e n t i s t and v e t e r i n a r i a n of a southern region of France (Languedoc Roussillon: 2 045 000 peoples) near a major nuclear site. There were ten questions regrouped in three categories: knowledge level about the r a d i o l o g i c a l r i s k , wish to p a r t i c i p a t e in the information o f the public and help in case o f accidents, access to information sources. The answers were numerised from 1 to 4, from negation to a f f i r m a t i o n . Results analysis include: percentage of answers, by professionnal categories and based on the geographic l o c a t i o n (distance from the nuclear s i t e ) and the preoccupation o f the p o l i t i c i a n s or associations. S t a t i s t i c a l a n a l y s i s , based on epidemiological consi der at i ons, of the 3 200 answers, permits to b e t t e r define the information requests o f health workers, about the r a d i o l o g i c a l r i s k and the adaptation of the information to the public request.

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OCCUPATIONAL DOSE TO NON-MONITORED PERSONNEL FROM NUCLEAR MEDICINE PATIENTS* L Rcnaud, J. Blanchette and C. Galand. (Montr6al Heart Institute, Montr6al, Qu6bec; Laval Hospital, Qu6bec, Qu6bec; H6tcl-Dieu de Montreal Hospital, Montr6al, Canada).

RADIATION SAFETY ANALYSIS OF A SELF-SHIELDED CYCLOTRON BASED ON RADIOISOTOPE DELIVERY SYSTEM J.W. Swanson, J.C. Mantil, C.D. Peterson, M.P. Jacobs & R.L. Willett. Kettering Medical Center, Kettering, OH.

We report the results of a survey designed to measure and assess the radioexposure by nuclear medicine patients, on a selected group of nonmonitored hospital personnel in their working environment and to verify whether the ALARA principle is being observed. More than 800 workers in three participating hospitals (171, 340 and 560 beds) weared TLD badges during a 6 months period. Concurrrently, the various hospital areas have been surveyed daily with calibrated meters to assess the radiation pattern inside the hospitals. No alarmous situations have been found. However, occupational doses in excess of 1.3 mSv have been observed for a six months period. Doses observed wiil be reported by category of workers, workload and hospital's profile of the distribution of the nuclear medicine's patients. These data support the observation that personnel exposuce may be reduced by a better awareness of those patients which are radioactive, a better training how to deal with these and by resequencing some medical l~rocedures when acceptable. (Work supported by Canadian Atomic Energy Control Board and Supply and Services Canada under contract 87055-8-4099/01-SS)

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536 A MULTI-USE PJ~DXQACTIVEIODINE TRAP

G a r i ~ t L a v s g a y u d u a n d E r r l e s t U. Fordhm gush L~niversityNedicat Center, Chicago, ILLinois, U.S.A A simple rechargeable, Less expensive, e f f i c i e n t radioiedine trap was designed to f i t the needs of: I . Radioiedination, 2. Safe handling of radioactive iodine liquids and capsules for diagnostic and therapeutic use, 3. Temporary storage and handling of shipments of radioactive iodine by radiation safety personnel.

The trap consists of 230 cubic inches of stainless steel cylinder 5"x11" (p-902) f i l l e d with 6-14 mesh coconut charcoal and

Collins Motor glower with 1/10 HP (p-S53-p) supplied by Warren E. Collins, Brain Tree, Mass., and an 8" diameter plastic funnel from an auto parts store. The inverted funnel was clamped at variable heights like a dome either in a laminar flow hoed or conventional fume hoed depending on the application and connected to the bottom inlet of the trap and the top outlet is connected in sequence to the Suction blower with a rubber tubing. The routine use of trap consists of turning on the suction blower throughout the radioactive iodine handling under the funnel; when not in use, it is safe to store in a fume hoed behind a shield. The trap can be tested periodically with a mini charcoal trap kept at the outlet and measuring it. No activity was detected in the thyroid and urine of personnel involved in radioiedination and handling of therapy doses, and the trap is portable. The trap is also useful for radioactive

noble gases.

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The commercial use of positron emission tomography (PET) for c l i n i c a l imaging and e v a l u a t i o n of physiologic process has been a reality since the mid 1970's. The development of s m a l l , selfshielded cyclotrons and radiopharmaeeutical delivery systems has made PET a viable diagnostic modality i n the c o m m u n i t y based hospital setting. At Kettering Medical Center we are preparing to open the first clinical PET facility in our area. From the outset, radiation safety controls were designed into the facility wherever possible. Proto~ and neutron induced activation hazards were evaluated in addition to target activation and failure. Air handling systems were designed to provide safe environmental use, storage and discharge of radioactive gases. Solid Ge-68 transmission ring sources were specified to limi~ contamination during source changes. The possible adverse effect of high energy annihilation photons on images produced in normal and rotational gamma cameras was considered. Local and remote reading area and st~ck monitoring was evaluated. Requirements for a safe working environment were developed through a team approach involving government regulatorsj administrators, clinicians, design engineers, and medical physicists.

COMPARISON OF TI-2ol SCINTIGRAPHY, EXERCISE STRESS TEST AND HOLTER MONITORING IN DETECTING SILENT MYOCARDIAL ISCHEMIA IN ASYMPTOMATIC POSTINFARCTION PATIENTSM. Samar~ija, B. Strbo, M. Jembrek, F. ~ustovid, D. Ivan~evid. Clinical Rebro, Zagreb, Yugoslavia

S. Te~ak, Hospital Center

For patients who have had an infarction the standard method of detecting residual myocardial ischemia, including silent ischemia, is the exercise stress test. The purpose of this study is to determine the role of Holter monitoring and thallium-2ol scintigraphy as initial screening procedures. The submaximal exercise stress test, planar thallium exercise scintigraphy and Holter monitoring were performed 1-3 months after the infarction. Thallium scintigrams were processed by ADAC software. The myocardium is divided into five equal segments. 34 patients (3o men and 4 women) with the acute myocardial infarction were selected. None of them had painful ischemic episodes before or after the infarction. 12 patients had a negative response on all three tests. 22 patients showed Ti-2ol redistribution: 3 of them showed a painless ST-segment depression on Holter monitoring, 2 had a positive exercise stress test and 6 had both tests positive whereas ii patients had only T1 scintigraphy positive. The patients were followed for 18 months approximately and the diagnosis was confirmed by coronary arteriography in 5 patients. We may conclude that by using Ti-2ol scintigraphy we were able to detect signs of silent ischemia in more than twice as many patients as by using exercise stress test and Holter monitoring. The number of positive responders to the exercise test and Holter was almost the same, and all of these patients had a thallium redistribution.

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EVALUATION OF MYOCARDIAL VIABILITY BY SMALL DOSE REINJECTION OF THALLIUM-201 IN EXERCIZE-STRESSED MYOCARDIAL PERFUSION IMAGING.

A NEW k~SHOUT RATE DISPLAY METHOD FOR DETECTION OF SUBENDOCARDIAL INFARCTION BY THALLIUM-201 SPECT. M.Jamzad, A.Uchiyama (Graduate School of Science & Eng. Waseda Univ. Tokyo Japan), H.Toyama (Tokyo Metro. Inst. of Gerontology) and H.Murata (Div. of Nuclear Medicine Toranomon Hospital, Tokyo).

T.Toyama, N.Takahashi, T.Odori, Y.Ishii and School, Fukui,Japan.

T.Nakashima, T.Matsushita, K.Torizuka. Fukui Medical

AIM: in thallium myocardial perfusion imaging, myocardial viability has been evaluated by the presence of re-distribution of thallium in delayed image 3 to 4 hours after exercise. Recently, it was shown by PET studies that some cases with ischemim heart disease which showed equivocal redistribution in delayed image were confirmed to have still viable myooardium in that area. To improve this equivocal finding we try to evaluate myocardial viability by addtional injection of thallium (reinjection), whenever the presence of redistribution is appeared to be equivocal in the delayed image~ Subjects and methods: Thirty patients with ischemic heart disease were involved in this trial. We reinjected 1/3 initial dose of thallium. Results: Improvement after reinjeetion was observed in four cases which otherwise interpreted equivocal redistribution. Conclusion: Reinjection of thallium after taking delayed image with equivocal redistribution improved the diagnostic capability to define viable myocardium in thallium myocardial perfusion imaging.

The purpose of this study is to calculate and display the washout rate of myocardial slices on the pixel basis which can detect the subendocardial infarction, its location, extent and severity. The LV is divided into i0 short axial slices in early and delayed stages by using the Thallium-201 myocardial SPECT images. For each slice, the two regions of myocardiu~n corresponding to the pericardial and endocardial are selected automaticaly. The pericardial and endocardial parts of each slice are divided into 16 and 32 equi-angle sectors, respectively. The washout rate of pixel(i,j) located in sector k, (k=-l, ..48) of an early slice is calculated as follows: Washout Rate(i,j) = ((E(i,j) - Dk) / E(i,j) ) x I00 Where E(i,j) is the pixel meant and Dk is the mean count of pixels located in sector k of delayed slice. A normal washout rate limit is calculated for each of the 48 sectors in a myocardial slice by using the data obtained from i0 normal volunteers. The output of this method are i0 washout rate images having the same shape as i0 early myocardial slices. In actual display all pixels which washout rate are greater than their corresponding normal limits, are shown by one color. Other pixels are shown by a color which represents the severity of abnormal washout rate. We have applied the Bull's eye and our methods on several patients with subendocardial infarction. There were cases wJ%ich Bull's eye method could hardly detect the subendocardial infarction, but our method showed the location, extent and severity of infarct.

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RADIAL LONG-AXIS TOMOGRAPHY FOR RECONSTRUCTING OPTIMAL LEFT % ~ T R I C U L A R LONG-AXIS ~ IN THE CARDIAC SPECT.

ISCHEMIC CAVITY DILATION OF LEFT VENTRICLE ON DIPYRIDAMOLE THALLIUM-201 IMAGING: A MARKER OF TRIPLE VESSEL DISEASE. Y. Takeishi, I. Tono-oka, K. Tsuiki, and S. Yasui. Yamagata University, Yamagata, Japan.

Y. I s h i d a , K. Kimura, T. Morozumi, A. Tani, M. Hori, A. K i t a b a t a k e , T. Kamada, Y. Nakamura, T. Kezuka. Osaka U n i v e r s i t y Medical School, Osaka, Japan. The optimal l e f t v e n t r i c u l a r (LV) l o n g - a x i s (L-A) view tomograms may be those r a d i a l l y s l i c e d around the I-A of the left ventricle. We developed a new algorithm for reconstructing the radial L-A (R-L-A) tomograms in TI-201 myocardial and Tc-99m-RBC gated blood pool SPECTs to estimate myocardial perfusion and LV wall motion (WM) in the same L-A view plane. After determining the orientation of the L-A and reconstructing the short-axis view tomograms using standard techniques, the tomographic data were transformed into the polar coordinate system where the origin marks the position of the L-A. Based on the transformed data, we reconstructed R-L-A tomograms, i.e. midventricular L-A view tomograms circumferentially spaced at 6" intervals around the L-A. In TI-201 SPECT, the reconstructed horse-shaped R-L-A tomograms were q u a n t i t a t i v e l y estimated with the circumferential profile analysis. In Tc-99m-RBC gated blood pool SPECT, for LV end-diastolic (ED) and endsystolic R-L-A tomograms reconstructed based on the ED L-A, LV contour was determined with an appropriate cut-off level and %regional wall shortening (%RLS) was measured by the modified centerline method. The TI-201 distribution profile and the %RLS were then displayed as Bulls-eye maps. When the technique of R-L-A tomography and the quantitative data analysis described above were used in patients with coronary artery disease, myocardial regions with impaired WM but without TI-201 defects (hibernating myocardium) were clearly demonstrated.

Monday, August 27, 1990

To investigate the significance of transient dilation of left ventricle (LV) on dipyridamole 20IT1 imaging (DP-TI), we performed both DP-TI and radionuclide angiography (RNA) with DP on 72 patients (pts) with known angiogram. The presence of perfusion defect and washout abnormality were judged by Bull's eye polar maps for the detection of coronary artery disease. And we chose 3 slices of short axis image, then the radial 60-point count profiles were created for each slice. A distance between two count peaks which corresponded to LV wall was measured, and the average of them was calculated (LVD). A ratio of LVD (DP/ delayed) was determined as a LVDR, and a LVDR > mean+ 2SD value of normal coronary pts was defined as abnormal. Sixteen pts showed the abnormal LVDR and 14 of them (88%) had 3 vessel disease (VD). A sensitivity and a specificity for identifying 3 VD by either defect or washout abnormality were 75% and 75%, respectively. While, a LVDR had the sensitivity of 70% and the specificity of 96% and was more specific than Bull's eye analysis. In these 16 pts with abnormal LVDR, LV end-diastolic volume and ejection fraction measured by RNA did not change after DP infusion. We assumed that cavity dilation on DP-TI image reflected diffuse subendocardial hypoperfusion induced by DP rather than actual LV chamber enlargement or worsening of LV wall motion. The additional analysis of the LVDR can provide the complementary information to the traditional assessment of DP-TI and the LVDR will be a new useful marker of 3 VD.

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MYOCARDIAL SARCOIDOSIS : DIAGNOSTIC ACCURACY OF MIBI 99 Tc vs 201 T1 SPECT. D. Le Guludec, .J_L_ Moretti, D. Valeyre, N. Caillat-Vigneron, D. Sadoun, P. Tellier, J.P Battesti, A. Neuman - Hop. AVICENNE, Bobigny, France Myocardial sarcoidosis causes rest thallium defects which often improve after dipyridamole infusion. We compared MIBI vs TI SPECT in 19 pts ( 5 males, 14 female, age 43.5) with proven sarcoidosis and clinical or ECG features suggesting cardiac involvement. The procedure was : injection at rest of 3 mCi of TI I0 min before SPECT, then 8 mCi of MIBI one hour before SPECT, and 4 hours later 20 mCi of MIBI after dipyridamole infusion (DIP MIBI) and one hour before imaging. All patients with abnormal TI (N= I I) and two with normal T1 had abnormal MIBI images. 12113 pts with abnormal MIBI images showed partial or total improvement of defects after dipyridamole. Six pts had both normal T1 and MIBI SEPCT images. Moreover, defects were better defined on MIBI than T1 scan, except for the inferior wall. In our pts with clinical suspicion of myocardial sarcoidosis, 68 % were confirmed by MIBI SPECT ; these results are consistent with those of the litterature (histological diagnosis). Conclusion : I- MIBI SPECT is better than TI SPECT for the diagnosis of myocardial sarcoidosis. 2- Our results strongly support the hypothesis of microvascular impairment, consistent with a low coronary flow but a normal coronary reserve (Am J Med, 1988, 85 : 189).

CORRELATED REGIONS OF CEREBRAL GLUCOSE UTILIZATION IDENTIFIED BY FACTORANALYSIS. Z. Szabo, E.E. Camargo, S. Sostre, I. Shafique, B. Sadzot, J.M. Links, R.F. Dannals, H.N. Wagner, Jr. The Johns Hopkins Medical Institutions, Baltimore, MD.

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THE INFLUENCE OF BIOLOGICAL AND TECHNICAL FACTORS ON THE VARIANCE OF GLOBAL F-I8 FDG BRAIN METABOLISM. E.E. Camarqo, Z. Szabo, S. Sostre, I. Shafique, R.F. Dannals, H.N. Wagner, Jr. The Johns Hopkins Medical I n s t i t u t i o n s , Baltimore, MD.

150-H20 POSITRON EMISSION TOMOGRAPHY CEREBRAL ACTIVATION PARADIGMS: LIMITATIONS OF CEREBELLAR NORMALIZATION TECHNIQUES. J.M. MOUNTZ, D.C.M. TENG, J.G. MODELL, M.W. WILSON, M. DOLBERRY University and of Michigan and V.A. Medical Center, Ann Arbor, MI.

To investigate the influence of biological and technical factors on variations of global and regional cerebral metabolic rate of glucose (CMRgl), 42 F-18 FDG PET studies were performed on 12 male volunteers (23-40 yrs). We calculated the variance/covariance of the following parameters: CMRgl, six parameters of the blood clearance of F-18 FDG, time of injection, peak time of blood a c t i v i t y of F-18 FDG, six components of the operational equation (blood glucose concentration brain activity, two i n t e g r a l s , numerator and denominator). There was high correlation among these six components, except for blood glucose. However, correlation between the CMRgl and the individual components of the operational equation was poor. The i n t e r and intra-personal CMRgl variances were 13.2% and 7.0%, respectively. In contrast, variances of the numerator and denominator of the operational equation were 34.6% and 32.6%, respectively, and were always in the same direction. No correlation was found between CMRgl and the technical factors in the numerator and denominator of the operational equation. A weak correlation between CMRgl and the biological factors, blood glucose concentration and time of injection, was found, but this would not explain the t o t a l CMRgl variance. Since the t e c h n i c a l and b i o l o g i c a l factors investigated cannot explain the variance of CMRgl, i t is l i k e l y that other biological factors are important determinants of the variance.

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Factor analysis of CMRgl can be used to identify different functionally related regions of the brain during performance of various mental tasks. Forty-two F-18 FDG PET studies were performed in 12 normal male volunteers (23-40 yrs) under resting conditions, with minimal sensory input. The PET studies of the same subject were performed with conditions kept as reproducible as possible. For each study CMRgl was calculated in 24 regions, and factor analysis was applied to the resulting data set. Two factors accounted for most of the total variance. Factor I comprising temporal, cingul ate cortex, caudate, putamen, thalamus, frontal, a region at the inner convexity of the occipital cortex (cuneuscalcarine) accounted for 70% of the total variance. Factor II comprising cerebellum, visual and parietal cortex accounted for 10% of the total variance. Clustering of these regions was less efficient i f partial correlations or average weighted data were used. Of interest, is the fact that most of the regions that comprise Factor I are part of the limbic system, as defined by Paul MacLean. Factor II comprised structures related to sensory and motor a c t i v i t y .

The cerebellum is often used for "normalization" of cerebral blood flow (CBF) in functional cerebral imaging. The utilization of this method is based on the assumption that the cerebellar blood flow is independent of regional cerebral activation. It has been shown, however, that motor imagery can cause cerebellar activation in the absence of coordinated motor activity in humans (1). The goal of our study was to maximize cerebral activation in subjects without motion and to determine if cerebellar activation (as measured by an increase in cerebellar blood flow) occurred. Seven subjects were scanned in a TCC PC-4600 tomograph in a rest-activation-rest-activation-rest repeated measures paradigm after the I.V. injection of N30 mCi 150-H20 (2). ANOVA was used for statistical analysis. The results showed a correlation between the activation state and cerebellar blood flow (p=.057). In conclusion the assumption that cerebellar blood flow is independent of cerebral activation is contradicted by this experiment; therefore "normalization" of r-CBF to cerebellar blood flow may introduce artifacts. Features of this experiment (anxiety and desire to flee during activation scan) support the possibility that cerebellar blood flow may be affected by motor ideation. 1. J Decety, et. al. Motor Imagery Activates the Cerebellum: A Single-Photon Emission Computed Tomography Study with the Intravenous 133 Xe Injection Method. J Cereb Blood Flow Metab, 9, $742; 1989. 2. JM Mountz, et. al.: Positron Emission Tomographic Evaluation of Cerebral Blood Flow During State Anxiety in Simple Phobia. Arch Gen Psychiatry, 46, 501, 1989.

M o n d a y , A u g u s t 27, 1990

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THE C~OMORPHOLOGICAL APP[~0ACH: A NEW TEC[fi%Q~/EFOR THE EXTRACTION OF QUANTITATIVE DATA AND PRESENTATION OF THE RESULTS IN BRAIN SPECT IMAGING. G. Lamoureux. R . M . Dupont and S.E. Hal~ern. U. de Sherbrooke, Sherbrooke, P. Quebec, V.A. Hospital and U. of California, San Diego, CA.

Interactive 3-D display in 99m-TcHMPAO brain SPECT. M, R u b i n s t e i n , J. Braeckeveldt*, A. Collier-Geulette*and J. Abramovici. Departments of Radioisotopes and Neurology*, I.M.C. Ixelles, Brussels, Belgium.

absolute brain uptake of a tracer would be easy to measure with SPECT if it was not for the tremendous amour~b of data generated, ar~ the 3-dimensional variability of the brain anatomy. In order to facilitate the quantitative armlysis, the presentation and the interpretation of the data, we have elaborated a surface pepping technique, based on a 3-dirf~nsional spherical transform of the data, w~_re the cortical activity of each hemisphere is represented by a polar map centered on the temporal area. For the sake of simplicity, the outer surface of the bralz, was defined by an iso-active contour and the surface to be mapped was of a const~;t, thickness. By' an extension of tYm~ principle, we have been able to literally "peel out" the brain like an onion by defihing for each inner layer an outer surface (e.g. a given % of the outer radius of the brain) and a thiclvness, thus permitting a simultaneous evaluation of the i n n e r structures of the brain. We: have found that, after a proper color encoding of the quantitative results, such a representation did provide the user with a more natural perception of tk~ extent and relative ir~portance of a deficit. This angular mapping technique was also found to diminish to a large extent the inter-individual variations in brain a n a t o ~ and to lend itself easily to the creation of a star,lard data h~se ( average map and matched standard deviation map for each "layer" of the brain ).

In addition to activity-related informations, pure topographic description is of major diagnostic importance in neurological clinics. In order to test the clinical usefulness of 3-D surface display (3-D), we reviewed 99m-TcHMPAO SPECT of 66 consecutive patients with regional cortical hypoperfusions. 56 had cerebro-vascular disease (CVD) and 10 various disorders, including dementias and mass-occupying lesions, all assessed by clinical and/or radiological work-up. 3-D surface images were generated in 1282 matrix with software allowing real time manual adjustment of threshold, shading, angle of view and depth cut. Threshold value was interactively set so that the cortical lesion primarly defined on orbito-meatal and coronal slices clearly appears. In patients with infarcts of anterior and posterior cerebral arteries (ACA and PCA), 3-D revealed the typical pattern of terminal territory. In middle cerebral artery (MCA) strokes, 3-D disclosed 5 topographic patterns of cortical defect: sylvian valley, temporal lobe, pre-rolandic and postrolandic areas and whole sylvian territory. 3 territories of watershed lesions were identified: between ACA and MCA (parasagittal and frontal) and between MCA and PCA. The overall 10 vascular patterns were in concordance with the documented hemodynamic, embolic and thrombotic strokes. Non-vascular lesions were easily distinguished on 3-D, either by an atypical distribution, or shape. In conclusion, 3-D enhences the specificity of 99m-TcHMPAO SPECT findings provided a m a n u a l threshold adjustment is performed, which is a t i m e - c o n s u m i n g procedure. An interactive software is mandatory for routine use. We think that technique is suitable for cortical lesions only.

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548

PARAMETRIC IMAGING OF REGIONAL CEREBRAL VASCULAR RESERVES. MV Merrick~ CM Ferrington, AR Naylor, A Notghi. Western General Hospital, Edinburgh, U.K.

INFLUENCE OF DIURETIC THERAPY ON CLEARANCES POST CAPTOPRIL (ACEI) IN RENOVASCULARHYPERTENSION (RVH): H.B. Lee and MD.Blaufox, Albert Einstein College of Medicine, Bx, NY.

Because cerebral blood flow is usually maintained appropriate to local metabolic needs by reflex changes in calibre of resistance vessels, reduced arterial pressure or a local increase in pCO2 is compensated by vasodilation. Substantial fluctuations in regional blood volume thus occur without corresponding alterations in flow. In cerebral vascular disease the most important indicator is not the flow at any instant but the ratio of flow to volume - the cerebral vascular reserve (CVR). This is the reciprocal of mean cerebral transit time (MCTT) and indicates the proximity of any point to failure of compensation. MCTT is not the mean transit time (MTT) of an IV bolus through the head, which reflects all organs between the sites ob=injection and measurement, but the difference between MTT of an IV injection when measured at the aortic arch and the head. We have created parametric images of MCTT following bolus injection of pertechnetate, HSA or Au- 195m complex. The range and allowable asymmetry for hemispheric and regional values has been established in 106 normal subjects. Hemispheric values have been compared with peak and mean transcranial Dol~pler ultrasound (TCD) velocity measurements under basal conditions and during hyper- and hypo-capnia. The coefficient of variation is 5.7%; the values of MC'I-F do not differ significantly from PET measurements of rCBF and rCBV or following intraarterial injection. Hemispheric MCTT and end-tidal CO2 and CVR and mean (Doppler) velocity in the MCA are linearly correlated. MCTT is significantly prolonged in stroke, the changes preceeding CT evidence of infarction and indicating the extent ,of the ischaemic penumbra. MCTT increases before there is clinica! evidence of spasm after subarachnoid haemorrhage. Criteria which identify patients at highest risk of intraoperative stroke during carotid artery surgery have been developed, Parametric imaging of MCTT appears to be a more sensitive method than regional blood flow measurement for the prediction of high risk groups in cerebrovascular disease, is quicker and easier than TCD and gives quantitative regional information not otherwise available.

Interference of antihypertensive Rx is a major concern of application of ACEI in the differential diagnosis of RVH, To clarify this, clearances were done on rat models of RVH with and without diuretic Rx. Frequent use of diuretics in hypertensives is a concern in ACEI renography. 280-300 gm male rats with 2 kidneys, 1 clamped (2K1C) and 1 kidney, 1 clamped (1K1C) were studied. Group 1 was studied pro and post ACEI without diuretic,gp 2 was studied after 4 mg Hydrochlorothiazide (HCTZ) daily for 7-10 days. BP fell after ACEI in all rats. GFR fell after ACEI in the clamped kidney but not the normal kidney. ERPFdecreased in 1K1C in both groups but in 2K1C the decrease was not significant. ERPF in the normal kidney increased after ACEI. There were no significant differences between groups in GFR or ERPF after ACEI with or without diuretic therapy. The results are summarized on the table:

Monday, August 27, 1990

BP (mmHg) con t capt

Group No HCTZ 1K1C(CK) 167 2K1C(CK) 169 (NK)

152" 141"

GFR (ml/min/100gm)

ERPF (ml/min/100gm)

con__]t~

con.__tt caDt

n

0.36 0.27* 0.20 0.10" 0,38 0.37

1.17 1.05" O.61 0.37* 0.95 1.12"

19 19

HCTZ 1K1C(CK) 178 149" 0.33 0.18" 1.20 0.80* 11 0.20 0.10" 0.67 0.48 7 2K1C(CK) 187 182" (NK) 0.35 0.37 1.02 1.22" * = p < 0.025, CK = Clamped Kidney, NK = normal kidney These data suggest that valid results may be possible with ACEI even in patients receiving diuretics, However because of potential hypotension, efforts to withdraw diuretics should still be considered in all patients.

S121

549

550

Captopril s c i n t i g r a p h i c test in renovascular H y p e r t e n s i o n (RVH) E. Br i a n z o r l i * , G. V a l e n t i n i * , P. P i n c i a r o I i * , ~ . C i c c a r e l I i * * ~E. Capponi** * N u c l e a r M e d i c i n e and * * N e p h r o l o g y Dept.Osp USLI5- M a c e r a t a , I t a l y

CAPTOPRIL RENAL SCINTIGRAPHY WITH Tc99m MAG3 FOR DETECTING RENAL ARTERY STENOSIS.

I n RVH has been r e p o r t e d by s e v e r a l A u t h o r s that Captopril induces changes in renal f u n c t i o n and improves t h e r a d i o n u c l i d e r e n a l scan a c c u r a c y . The o b j e c t o f our s t u d y i s t h e e v a l u a t i o n o f the c l i n i c a l u t i l i t y of the test a f t e r two y e a r s o f o u r e x p e r i e n c e s . For t h i s reason we s t u d i e d 31 p a t i e n t s mean age 46.7 y y , r a n g e 36-68 . Each p a t i e n t s underwent two dynamic renal scintigraphic study the fxrst before the oral administration of captopril,the second two hours a f t e r the f i r s t s t u d y and almost one hour a f t e r c a p t o p r i l (50mq) . A n g i o g r a p h y was obtained i n a l l patients-.We considered the test positive the q u a n t i t a t i v e reduction within i - 3 minutes a f t e r i n j e c t i o n o f DTPATc99m i s g r e a t e r than lOZ.The r e s u l t s o f our s t u d y a r e summarized i n the f o l l o w i n g t a b l e : X-Rays stenosis

DTPA 3

before (captopril) +

negative 11 .............................................. malformation without 3 stenosis 2 -

after -

-

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . +. . I n o u r s t u d y a c o r r e l a t i o n was f o u n d between s c i n t i g r a p h i c response t o c a p t o p r i l and Xrays findings except in cases of severe monolateral abnormal baseline DTPA. We observe two false positive test in renal artery abnormality. The t e s t appears t o be u s e f u l as s c r e e n i n g i n d e t e c t i o n o f RVH, i f s u s p e c t e d . F u r t h e r m o r e it i s necessary t o e v a l u a t e t h e emodinamic status in malformation of renal artery.

M.Dondl, P.Zagnl, C.Corbelll, S.Fanti, A.Zuccala , F.Loslnno, R.Franchl, N,Monetti. Nuclear Medicine, Nephrology and Radiology S.Orsola-Malpighi Hospital, Bologna, Italy Converting-enzyme inhibition (CEI) improved both sensitivity and specificity of renal sclntigraphy for diagnosing renal artery stenosls (RAS) in renovascular hypertension. The aim of this study was to evaluate the use of the hlppuran-analog Tc99m MAG3, instead of the conventional renal agent DTPA, for detecting RAS by means of renal sclntlgraphy after CEI in 49 hypertensive patients, some oh which with high plasma creatinlne levels. The study involved a renal scan carried out one hour after oral admnistration of 50 mg of Captopril. Where the study turned out absolutely negative, RAS was ruled out. In cases of abnormalities, a second study in baseline conditions was repeated 24 hours later. All patients were further submitted to renal arteriography where 29 proved to have no RAS, 12 unilateral RAS and 8 bilateral RAS. For the detection of RAS>50% sensitivity was 90% and specificity 91%,-the positive predictive value 71% and the negative predictive value 97%. Similar results were already obtained from our group using Tc99m DTPA. Our experience proved T c 9 9 m MAG3 to be effective for detecting RAS. In particular it was very effective in cases of severely impaired renal function where DTPA was very likely to be of little help.

551

552

The Q u a n t i t a t i v e E v a l u a t i o n of O b s t r u c t i v e N e p h r o p a t h y w i t h Te~99m MAG3 by Parenchymal T r a n s i t Time I n d e x , PTTI, and Output E f f i c i e n c y , OE%, of the Frusemide Response, FR B r i t t o n K E, Nirnmon C C, Miceva S, J a f r i R A, C a r r o l l M 3, Bomanji J St B a r t h o l o m e w ' s H o s p i t a l , London EC1A 7BE, UK

USE OF F A C T O R ANALYSIS FOR P R E D I C T I N G / R E F I N I N G RESPONSE TO LASIX S T I M U L A T I O N D U R I N G R E N A L STUDIES, _D.G. Pavel, A. Montes, P. OrelIana*, E. Olea*, E. Michaels. Univ. of Illinois Hosp. Chicago; Catholic Univ. Santiago, Chile*.

Tc-99m MAG3 has been used r o u t i n e l y in o v e r 1000 p a t i e n t s w i t h one m i n o r s i d e e f f e c t . The ' c o l d ' MAG3 t e c h n i q u e of f r e e z i n g the p r e p a r a t i o n in 4 s e p a r a t e capped s y r i n g e s i m m e d i a t e l y a f t e r t h e b o i l i n g s t e p has r e d u c e d the b u i l d up of the l i v e r s e e k i n 8 i m p u r i t y from 0.4% to 0.006% p e r h o u r e x t e n d i n g i t s time f o r use to 8 h o u r s . The h i g h count r a t e s o b t a i n e d a r e excellent for the diagnosis of obstructive n e p h r o p a t h y , even w i t h poor r e n a l f u n c t i o n b o t h by PTrI (abnormal >156s) w i t h good s t a t i s t i c s for d e c o n v o l u t i o n a n a l y s i s , and by FR q u a n t i t a t i o n . S i n c e the m e a s u r e d change i n a c t i v i t y w i t h time i s the b a s i s of d e t e r m i n i n 8 the FR, t h i s r e s p o n s e i s a l s o c r u c i a l l y d e p e n d e n t on the amount and r a t e of u p t a k e of a c t i v i t y by t h e k i d n e y . To j u d g e w h e t h e r the FR i s appropriate to the l e v e l of r e n a l function, the c u m u l a t i v e i n p u t i s t a k e n as the i n t e g r a l of the l e f t v e n t r i c u l a r b l o o d c u r v e f i t t e d to t h e s e c o n d p h a s e and the c u m u l a t i v e o u t p u t as the d i f f e r e n c e between t h i s i n t e g r a l and the a c t u a l k i d n e y c u r v e . The c u m u l a t i v e o u t p u t as a p e r c e n t a g e of the c u m u l a t i v e i n p u t at 30 mins g i v e s the o u t p u t e f f i c i e n c y , OE%, which i s n o r m a l l y o v e r 75% and c o r r e c t s t h e FR f o r t h e l e v e l of renal function. C o r r e l a t i o n s b e t w e e n PTrI and OE% were s t u d i e d in 42 p a t i e n t s g i v i n g r = - 0 . 9 9 , P < 0 . 0 0 1 . Tc-99m MAG3 w i t h PTTI and OE% a n s w e r s the d i a g n o s t i c p r o b l e m of o b s t r u c t i v e n e p h r o p a t h y .

S122

In evaluating obstruction vs. dilatation, Lasix (Lx) stimulation may yield equivocal results or m a y generate results d i f f i c u l t to reconcile with clinical status or, at times, cannot be performed. This study proposes to evaluate the i n f o r m a t i o n resulting f r o m Factor Analysis (FA) of a pre-Lx 1-131 H i p p u r a n study of 21 minutes (1 min frames) and, when available, of a 35-40 s i n . acquisition which includes the post Lx phase. Processing was done on both kidneys simultaneously as well as on the abnormal kidney(s) alone. The goals to evaluate were: 1) predictability of Lx response based on a 21 s i n . (pre-Lx) processing; 2) r e f i n e m e n t of the Lx response; 3) explanation for incongruent Lx response. Results: 34 Lx-RRS studies were considered as h a v i n g adequate indication (i.e. did not have significant spontaneous renogram downslope at 20 sin.). In 7/34 RRS the post-Lx phase was also available for processing. In 16/34 FA of pre-Lx study (21 min.) was able to predict post-Lx n o r m a l or equivocal response with only 1/16 false (-) prediction (in that particular case there was enough evidence to indicate that the standard Lx stimulation/response was incongruent for several reasons). In 18/34 the prediction was of abnormal response with 3/18 (17%) false (+) predictions. All 3 were cases with GFR < 30ml for the respective kidney. In 5/7 demonstration of multiple pelvo-calyceal kinetics, helped refine the i n f o r m a t i o n f r o m Lx response. Conclusion: FA can be a reliable predictor of normal and equivocal response to Lx. It can also be a good predictor of a b n o r m a l response but only if GFR > 30 in respective kidney. This opens up the possibility to evaluate obstructive disease in cases where Lx was not given. FA also helps in r e f i n i n g response to Lx and in detecting/explaining incongruent Lx responses.

Monday, August 27, 1990

553

554

USE OF THE IMPULSE RENOGRAM FOR MONITORING THE PROTECTIVE EFFECTS OF PGE 1 AND SOD DURING R E N A L ISCHEMIA. Z. Szabqt G. Torsello, U. Neumann, H. Vos-

Tiqe l Y m P n O S C l n t l g r a p a l c l a V e S ~ i g a % i o n s i n t n e mas b r e a s t c a r c i n o m a s : e x p e r i e n c e of t h e J u l e s B o r d e r

berg and L.E. Feinendegen. Dusseldorf FRG.

P B o u r g e o i s , W M a l t h e l e F , h ,P ~an H o G t i e and J . F r u n l l a g S e r v l c e s of N u c l e a r ; ~ , e d i c l n e R a d i o t h e r a p y and S ~ r g e : y Institute J u l e s Border., UaLverslt& Lzare de Bruxeiles

Heinrich Heine

University

Ischemic renal damage after surgery for thoracoabdominal aortic aneurysms, renal artery stenosis and renal transplantation, is a severe complication which m a y lead t o renal failure and end lethally. Purpose of this experimental study was to investigate the efficacy of different drugs such as prostaglandin E 1 (PGEI) and superoxide dismutase (SOD) in protecting the kidneys from ischemic damage. For this purpose, kidneys were exposed to three hours of warm ischemia in v~vo. 23 dogs were investigated: 1 with normal kidney function, 6 ischemic pretreated with saline (NaCl) , 9 ischemic pretreated with PGEI, 6 ischemic pretreated with SOD. On the third postoperative day renal function was measured by the parameters of the impulse renogram for 99mTc-MAG~ (tubular excretion) and II3mIn-DTPA (glomerular filtration). The discriminating power was higher for the parameters obtained with MAG 3 then with DTPA suggesting greater significance in the changes of the t u b u l a r component. Both PGE 1 and SOD improved the mean p a r e n c h y m a l t r a n s i t time (normal: 167 sec; NaCl: 418 sec; PGEI: 252 sec; SOD: 240 sec) as well as the e x t r a c t i o n fraction for MAG 3 (normal: 74 %, NaCI: 28 %, PGEI : 46 %, SOD: 54 %) and DTPA (normal: 27 %, NaCI: 13 %, PGEI: 24 %, SOD: 43 %) significantly. In c o n c l u s i o n , both PGE 1 and SOD mitigate the effects of ischemia onto the kidneys as documented with the parameters of the impulse renogram of MAG 3 and D T P A and b o t h of them may be useful for protection of the kidneys during major abdominal vascular intervent ions.

on

S i n c e s e p t e m b e r 197S, a l l admen a a h q l [ t e d i n o u r i n s t l t U - _ i o n fOl" l-aa!etlon t n e c o g y of a n a [ o i ; , o J a = l i g l e g l c a i ! : l eg[aui!srlea areast c o r c l n o [ n a s n a v e d n a e r g o r e i y m c r ; o s c i n z l g r a p i ~ I C l n v e s ~ z g c : I o r , s Of :no internal mammary (Z[-]) a r c c i l i l o r y (Ax) noaes by means a f 9PraTe i a b e i e a m i c r a aria n a a o c c i l o i d S ii'1 noae I n v a s i o n ads d e m o e s t r o t e a m o r p h o l O g i C a l 1 ! / Oy ]~;,I l y I , 4 o n o s c l n ~ l g r a o n y ~ I I L S c ) I'd 3IZ Of the c a s e s one ~r, l s f i n d i n g ,.{as d e p e n a e n t on ERe c i l n l c o [ S [ C g l n g of cne tUmOr, On i+S S I Z e , on tlBe e x [ e n $ of t h e d i s e a s e i n i n e o x l l l a a n d on i t s e; easg lPcalisotlon. Patients altn pasltlve t;"ILSc e < , h i b l ~ e d t o o %lilies higher generailsa~zanand d e a u ~ , - r a t e s (20% v e r s u s 40% add i ; % v e r s u s 252 r e s p e c : I v e ~ y ) even ~.men O t h e r p r o g n o s t i c factors ~ a l a n e or c o m o l n e p ; '~ere t a k e n zn=o a c c c ' ~ n t AS f a r as t h e a n a t o m i c a l c o a t F l b u t i o l ' , s d r e COnCernea o u n i q t e it'; c n a i n was fomsd in 82 of t h e c a s e s ana t;',e i n t h e tiI.~ede!a.,,ec vlsuolisatlon of t h e two c a o l n s a l l o w e d t h e d e m o n s t r a t i o n of a c r o s s l n g lYmpll f l m ~ in 20% of a l l p a t i e n t s Hm'~e~e~, ~ i t n r e f e r e n c e of t h e c l a s s i c a l limits of t h e i r r a d i a t i o n flelas apoliea ijp tO 78 i n o u r l n S t l t U t l O P , iM napes nave been f a u n a 3CCOrOlng :O t h e K i n a o f l r r a g l a ~ l a n tecr, nique OUtSide tnelr limits in ISE tO 5qZ of e r e c a s e s one i n b o r a e r l i n e P O S i t i o n i n ~% tO 19~ , PostoPerazi,'e iymanosczntigraohic controls o f the a x i i l a a f t e r tilr:e a e i a y e o i n t e r c o s t a l { i c ] and i n t e r a l g Z Z a l (~d) I n j e c t i o n s of tne colloids nave d e m o n s t r a t e a r e s t a b a l Ax nodes i n as R1ucn as three gallants OUt of f o u r , t n l s f i n a l a g b e i n g r e l a t e d ai~1ong o t h e r s to t n e s Q r g e o n e x p e r i e n c e O c c u r r e n c e o f u p p e r [lI;Iaede;,la ( a l E ) evens is sl!ghtiy i n l g n e r i n t h e g r o u p s of a a t z e n % s i r r a d i a t e d on t h e i r o o e r a t e c axii!a ( Z a , S Z v e r s u s Z.~.aZ) aLE O c c u r s

aurlng the fol!o~-up in 347. of the cases ~nere the interruption of t h e l y m p h a t l c d r a i n a g e o f t h e l i m b had aeen d e l n o n s ~ r a ~ e d a f t e r interdlgltal Injection w h e r e a s P a t l e n t s ~ i t h Ax nodes v i s u a i i s e a after this injection d e v e l e a P e d ULE o n l y in 22.4% of cases. W i t h r e g a r a t o t h e p r o b l e m of n o d a l r e l a P S e S , t h e Y o c c u r r e d m e r e l y i n c a s e s ~ i t h IM nodes i n v a s i o n as d e m o n s t r a t e d bY I M L S c or i n t h e g r o u p s of women w l < n v i s u a l l s e d residual Ax n o d e s , i n case of a n a t a m o p a t h a l a g l c a i l y d e m o n s t r a t e d Ax I n v o l v e m e n t but ~IthOut postoserGtzve irradiation of t h e e X l l l a . TaKing into account these results. 1 [ i s c o n c l u d e d t h a t ~he Zym#iloscintigragnic lnvestigatlons of t h e lift and Ax nodes r e P r e s e n t a m a n d a t o r y p a r t Of t h e management of b r e a s t o a r c i a o ~ a bearing petlen~s Hlth dieg~OStlC, therapeutlc aad p r o g n o s t i c ima~icat sons,

556

555 CLINICAL

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LYMPHOSCINTIGRAPHY VS INTRAOPERATIVE INTERNAL M A M M A R Y C H A I N B I O P S Y IN H U M A N B R E A S T C A N C E R . R.Benti, P.Gerundini, M.Giacomelli, C.Archili, A.Bruno, L.Gianolli, D.Ayala and A.Bissi. I s t i t u t o H. S. R a f f a e l e , M i l a n , Italy. Prognostic and clinical implications of internal mammary lymphatic chains (IMC)s invasion were evaluated by comparison between parasternal iymphoscintigraphy (PL) and intraoperative ipsilateral IMC biopsy in 53 p a t i e n t s w i t h b r e a s t c a n c e r . In a l l p a t i e n t s w e r e p r e o p e r a t i v e l y o b t a i n e d t w o p l a n a r PL, 90 min after time-spaced bilateral subcostal i n j e c t i o n of 2 0 - 3 0 M B q of T c - 9 9 m h u m a n s e r u m albumin nanocolloids. PL studies were evaluated as normal, suspicious or abnormal by c o n s e n s u s of i n d e p e n d e n t o b s e r v e r s . I p s i l a t e ral IMC biopsy was inadequate in 6 cases (ii%). T e n p a t i e n t s (21%) h a d I M C i n v a s i o n a n d f o u r (9%) p r e s e n t e d I M C c h r o n i c i y m p h a d e n i t i s onlyo A l l t h e s e s u b j e c t s p r e s e n t e d an a b n o r m a l or s u s p i c i o u s p a t t e r n in t h e o m o l a t e r a l PL. Specificity, accuracy and sensitivity of PL for m e t a s t a t i c i n v a s i o n of I M C w a s 84%, 87% a n d 1 0 0 % r e s p e c t i v e l y . B i o p t i c a n d PL r e s u l t s c h a n g e d the s t a g e in 8 (17%) a n d i0 (21%) subjects respectively (P N.S.). Our data support the p r e - e m i n e n t role of P L v s IMC biopsy in the diagnostic and prognostic evaluation of I M C m e t a s t a t i c involvement in human breast cancer, considering the lower i n v a s i v i t y a n d t e c h n i c a l i n a d e q u a c y r a t e (0% vs 11%) of PL w i t h o u t l o s s of s e n s i t i v i t y .

Monday, August 27,1990

CLINICAL RESULTS OF B R E A S T C A N C E R DETECTION BY IMAGEABLE ESTRADIOL (I-123 E2). D.F. Preston, J.A. Spider, R.A. Baranczuk, C. Fabian, K.G. Baxter, N . L . M a r t i n , W.R. J e w e l l , R.G. R o b i n s o n . University of Kansas Medical Center, Kansas City, Kansas, U.S.A. Twenty-five women with known or high probability of breast cancer received high specific activity (greater than 10,000 curies/millimole) ]-123 E2 and underwent SPECT imaging of the breasts and axilli to determine if breast cancer could be visualized in viva. Fifty lJCi/kg of 1-123 E2 was injected intravenously (approximately 3mCi per patient.) In three p a t i e n t s , SPECT imaging was performed 20-minutes following injection. In 22 patients, imaging was performed two hours following injection. All acquisition and image processing used standard commercially available programs and equipment. Using focal 1-123 E2 uptake as the visual criteria, SPECT demonstrated 8 of 9 cancers in the breast. Four tumors were ER +, three were ER- and two of undetermined ER status. There was one false/negative of known ER status and two false/positives, both in patients who had recently been treated, one with radiation and one with tamoxifen. Clinically, they were without disease. Four of four metastasis were seen. Six of six axillary nodes present at the time of imaging were seen. There were eight "false/positive" axillary node sites. One patient with mediastinal and bilateral axillary uptake and normal CT two years ago is now seen to have mediastinal and axillary involvement with breast cancer. The high level of"false/positive" axillary node uptake may actually reflect early diagnosis of disseminated disease. CA-15-3 levels, breast aspirates for aneuoploidy were correlated with scan numerical measures of scan uptake and histological findings. Receptor imaging o f breast cancer has clinical promise.

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557 Tc-99m-NCA BONE MARROW SCANS IN PATIENTS BREAST CANCER AND SUSPECTED BONE METASTASES. C. Duncker, I. Carri6, M. Estorch, LI. Berne. Hospital de Sant Pau. Barcelona, Spain.

WITH

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-99m-labeledNCA (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 p a t i e n t s ; I I : 1 2 p a t i e n t s ; I l l : 8 patients; IV:8 patients) and suspected h o n e 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 b o n e marrow defects in 25/32 (78%). Bone marrow invasion was l a t t e r confirmed in 23 of these 25 patients (p
THE ROLE OF GALLIUM-67 SCINTIGRAPHY FOR STAGING AND EVALUATING PROGNOSIS IN P A T I E N T S WITH H O D G K I N ' S DISEASES AND NON-HODGEIN LYMPHOMA. C.~azak_i, T.Hiromura, H.Ikeda, R.Koshiba, and K.Itoh*. Sapporo General Hospital, Hokkaido University*, Sapporo, Hokkaido, Japan. The value of Ga 67 scintigraphy in confirming a stage and presuming a prognosis was estimated in 109 cases consisting of 15 p a t i e n t s with H o d g i k i n ' s diseases and 94 with non-Hodgkin's lymphoma. Four hundred twenty-one Ga-67 scintigraphy were carried out. Ga-67 citrate was given in a dose of 2 mCi/adult, and whole body seintigraphy was performed after 72 hours. If necessary spot images were added after 96 to 120 hours. We evaluated if the finding of initial Ga-67 sintigraphy of 109 cases had advanced their clinical staging or not. As a result, stage I moved to II in I, to Ill in 3, stage II to Ill in 2, to IV in i, stage Ill to IV in 4 . There were i] eases(10.1%) changed to advanced stage. Follow-up Ga-67 scintigraphy was carried nut after initial study of 66 cases with non-Hodgikin's lymphoma. Survival rates were compared between 36 patients who showed positive finding at least once in longitudinal follow-up Ga-67 studies and 30 who continued to show negative finding. In the former group two- and five-year survival rate were 31.2% and 9.4%, that for the latter group were 85.2% and 75.5%(Kaplan-Meier method). There was a statistically significant difference between the two groups

(p
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560

CLINICAL EVALUATION OF THE VALUE OF PROSTATIC ACID PHOSPHATASE (PAP), PROSTATIC SPECIFIC ANTIGEN(PSA)AND BONE SCAN IN PROSTATE CANCER PATIENTS. M.Rodrigues,L.Salgado,M.G.Ramos,J.Vilhena Aires and M.R. Vieira. Nuclear Medicine and Urology Departments,Iastit~to Portugu6s de Oncologia, Lisbon, Portugal.

CLINICAL RESPONSE AND TOXICITY FOLLOWING HIGH DOSE 1-131 ANTIBODY TREATMENT OF LYMPHOMA. W.B. Nelp, J.F. Eary, O.W. Press, C.C. Badger, PJ. Martin, F.R. Appelbaum, D. Fisher, B. Porter, I.E. Bernstein. University of Washington Departments of Radiology and Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA and Battelle Pacific Northwest Laboratories, Richland, WA.

PAP and PSA axe 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 pts. 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 statiscally different (p
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We are currently evaluating the potential value and toxicity of single high dose 1-131 antibody therapy in non-Hodgkins lymphoma, starting with patients in relapse following previous therapy. Doses up to 658 mCi of 1-131 labeled to whole antibody have been given in an escalating fashion based on the estimated highest dose to any normal body tissue (except marrow) - e.g. 1000 Rads (3 pts Gr-I) 1500 rads (3 pts Gr II ) 1575 Rads (1 pt. Gr-M). Tumor doses were greater, ranging up to 4000 Rads. Four patients experienced mild nausea 1 to 3 days post therapy. There has been no acute or long term renal, pulmonary or hepatic toxicity. Two patients developed delayed hypothyroidism despite blocking with stable iodide during therapy. All patients had severe marrow toxicity with estimated marrow doses ranging from 250 to 450 rads. The Gr I patients required platelet transfusions with spontaneous recovery of function 40 - 50 days post therapy. Gr 2 and 3 patients had more severe aplasia and were successfully treated with re-infusion of stored autologous marrow. The 7th patient has just been treated (Gr. III) and is not yet evaluable. The three Gr I patients had complete remissions lasting 4, 6 and 12 months. They have subsequently been treated with additional total body irradiation and autologous marrow transplant and are again in remission. Two of three Gr. II patients have complete remission at 9 and 14 months post therapy. The third Gr. II patient had a partial remission only and died nine months later. We are encouraged by these results that give higher doses to tumor than that achieved by total body irradiation and show no toxicity to normal tissues (nonhematopoetic). Dose escalation studies are continuing.

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A N A L Y S I S O F T H E F A C T O R S A F F E C T I N G THE R E S P O N S E TO RADIOIMMUNOTHERAPY IN G A S T R O I N T E S T I N A L TUMOURS:A P H A S E II TRIAL.

Z-i 1 ~-CHLOROMETHYL-I 7~-IODOVINYL ESTRADIOL, A VERY HIGH AFFINITY ESTROGEN FOR RADIOIMAGING AND TARGETTED RADIOTHERAPY OF ESTROGEN RECEPTOR (ER) POSITIVE TUMORS. M. Zeicher, J. Ouivy, A. Delcorde, P. Henrot, M. Deblaton, R. Pirotte, A. Vsrbist and J. Frfihling. MEDGENIX S.A., Fleurus, IRE, Fleurus and INSTITUT BORDET Bruxelles, BELGIUM.

P.Riva*,S.Lazzari+,V.TisonO,G.Franceschi * G.Moscatelli*,G.Sarti+,A.spinelli*,P.Morigi ~ G.Vecchietti*,C.Mazzotti+and D.Tirindelliw 9 Istituto Oncologico Romagnolo and Nuclear Medicine Dept. Cesena+ Health Physic Dept. e Pathology Dept."M.Bufallni" Hospital Cesena w Rome Italy 20 p a t i e n t s with gastrointestinal cancer (18 colorectal and 2 gastric) were submitted to Radlcimmunotherapy (RIT). Most of patients were in a d v a n c e d s t a g e o f d i s e a s e . Several Monoclonal Antibodies were utilized(AUAI,B72.3 BW494/32,FO23CS),they were labelled with I131 and were given,in most cases,intraperitoneally Many patients received multiple treatments. The toxicity was v e r y m i l d . The outcomes obtained are:7 Progressive Disease (lasting 6.4 months as m e d i a n time),5 Stable Disease (8.2 months),5 Partial Remission (5 m o n t h s ) , 3 Complete Remission (CR)(9 months). The factors which resulted favourably affecting the r e s u l t s w e r e :I) a q u i t e short time elapsed since tumour diagnosis and RIT;2)a strong immunohistochemistry positivity (> 2 p l u s ) ; 3 ) previous multiple chemotherapy courses;4) repeated RIT cycles; 5) a c u m u l a t i ve radiation d o s e t o t h e t u m o u r > 5 0 0 0 cGy; 6) a q u i t e l i m i t e d e x t e n s i o n of the disease which had to be confined in t h e p e r i t o n e a l cavity,with number of recurrences less than 5 and with their diameter <2 cm.

AUGER electrons emitting radionuclides like 1-123 release most of their energv 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 11 ~-chloromethyl- 17d-iodovinyl estradiol. This molecule has an affinity for the estrogen receptor I0 times higher than estradiol and an affinity for the plasma sex steroid binding protein 400 times lower than estradiol. In 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 human tumor grafted onto nude mice were obtained. As evaluated by the ROI method, the specific tumor uptake was reduced to 5% and 6.5%, if excess cold estradiol and cold Z isomer respectively were coinjected with 1-123 labelled Z isomer. In vitro cytotoxicity of the I-]23 Z isomer was assessed using a clonogenic assay and a modified MTT assay. The Z isomer was 1000 times more toxic for MCF7 human breast carcinoma cells than for human bone marrow cells. Our data suggest the estradiol receDtor could be a suitable site for radioimaging and for targetted radiotherapy. This work is sunnorted by an Furo~ean EURFK~ ~rant (~U/I~I/I~).

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TREATMENT OF METASTATIC BREAST AND P R O S T A T E C A N C E R IN B O N E W I T H STRONTIUM-89. R.G. Robinson, D.F. Preston,M. Schiefelbein,N.L. Martin, J.A. Spicer, K.G.Baxter. University of Kansas Medical Center, Kansas City,Kansas, U.S.A.

SAMARIUM-153 EDTMP AND RADIOSENSITIZING CHEMOTHERAPY FOR TREATMENT OF DISSEMINATED SKELETAL METASTASES. J.H. Turner, P.G~ Claringbold, A.A. Martindale and P. Sorby. Fremantle Hospital, Western Australia and the Australian Nuclear Science and Technology Organization NSW, Australia.

W e have utilizedStrontium-89 as therapy for painful osseous metastasis from breast and prostatecancer. W e have treated 242 patients with Sr-89 under a physician-sponsored IND, including 192 with prostate cancer and 50 with breast cancer. One hundred fifty prostate and 36 breast cancer patients survived at least 3months and had adequate follow-up data for analysis. An additional 37 patients were studied in a Phase I-II dose ranging trial. One hundred eighteen of 150 (79%) patients with metastatic prostate cancer responded with decreased bone pain and improved quality of life. Thirty of 36 (83%) patients with breast cancer noted improvement. The combined response rate in these 186 IND patients was 80%. All IND patients received 40pCi/kg. Twenty of the 37 Phase I-II patients received Sr-89 in doses ranging from 5585pCi/kg. All 20 who received ~ 55pCi/kg improved. The majority of patients received additional Sr-89 treatments. No patients developed life-threatening hematological toxicity from the first Strontium treatment. Strontium-89 is an e x c e l l e n t p a l l i a t i v e systemic radioisotopic therapy for metastatic breast and prostate carcinoma in bone when administered at a dose of 40pCi/kg body weight. Somewhat higher doses may provide further increase in response rate with acceptable hematological toxicity. The best palliative dose of Sr-89 is probably 5060pCi/kg. There is no longer any reason for these patients to hurt.

Monday, August27,1990

A clinical trial of Samarium-153 EDTMP demonstrated efficacy for the relief of pain from disseminated bone metastases and in 15 of 34 patients treated with Sm-153 EDTMP at Fremantle Hospital there was radiographic and bone scan evidence of regression of skeletal metastases.* To maximise antitumour action concurrent radiosensitizing chemotherapy using 5-FU, adriamycin and mitomicinC was studied in a prospective series of 15 patients receiving Sm-153 EDTMP therapy. Chemotherapy regimens comprised single bolus IV doses of adriamycin or mitemicin-C, or a 3-day infusion of 5-FU. Retrospective comparison with patients previously receiving 200 cGy radiation absorbed dose to marrow from Sm-153EDTMP alone showed no increase in myelosuppression in the patients given 5-FU. The maximum tolerated doses of adriamycin and mitomicin-C were 12 mg/m 2 and 3 mg/m 2 respectively in combination with a Sm-153 EDTMP marrow dose of 200cGy. Dose-limiting toxicity was reversible myelosuppression,, predominantly delayed thrombocytopenia. Pain relief assessed at 6 weeks in the chemotherapy group was complete in 4, good in 8 and poor in 3 patients which was comparable with our previous results using Sm-153 EDTMP alone. Longer follow up is required to document radiographic and scintigraphic evidence of enhanced tumour regression. * Ref. A Phase I Study of Samarium-153 Ethylenediaminetetramethylene Phosphonate Therapy for Disseminated Skeletal Metastases. Turner JH, Claringbold PG, et al. J. Clin. Oncol. 7:12 1926-1931 (1989)

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P32 TREATMENT IN ELDERLY AND YOUNG PATIENTS

EVALUATION OF Tc-99m HMPAO SPECT IN FOCAL EPILEPSY. MR Newton, KI Lee, SF Berkovic, MC Austin, PF Bladin, WJ McKay, Departments Nuclear Medicine and Neurology, Austin Hospital, Heidelberg, VIC, Australia.

~M CRITCHLEY, *P MALTBY, ~ DAVIES Departments of *Nuclear Medicine and ~ Royal Liverpool Hospital and University of Liverpool, Liverpool UK In spite of the advent of new radiopharmaceuticals for the diagnosis and treatment of disease, the number of patients treated with P32 in this Nuclear Medicine Department over the past 5 years has remained constant. 152 patients, 81 males, 71 females were referred from this hospital and from other hospitals in the region, 125 with polycythaemia rubra vera and 27 with essential thrombocythaemia. Patients received an IV injection of 3 MBq/Kg P32 sodium phosphate in isotonic solution. Repeated administrations were required in some patients; the maximun number of doses given was 13. In total 218 administrations were given, most to elderly patients; of these 8 underwent a leukaemic transformation. Most P32 administrations in the elderly are non-controversial but the young pose particular management problems. A 25 year old female with a history of 6 spontaneous miscarriages, essential thrombocythaemia, a decidual vasculopathy and a determination to have several children was referred and treated with P32. Treatment with P32 is useful, cost effective and easily performed. It is readily available and patients seen in the OP clinic can have their red cell, plasma volume tests and treatment with P32 all on the same day. Close liaison between the departments of Haematology and Nuclear Medicine allows effective follow-up and further treatment when indicated.

We have evaluated Tc-99m HMPAO SPECT in patients with refractory temporal lobe epilepsy by studying blood flow patterns in the interictal, ictal and postictal periods. Over the last three years 61 patients underwent SPECT studies as part of their investigation for temporal lobe surgery in our Comprehensive Epilepsy Programme. The postictal and ictal studies were done when patients were undergoing video/EEG monitoring, and interictal studies were performed when the patient had been seizure free for at least 24 hours. Unilateral temporal hypoperfusion was occasionally found in interictal scans, whereas all ictal studies (10 patients) showed marked increases in temporal lobe perfusion with variable diminution of flow in other cortical regions. Of 61 postictal studies (injection 1-20 minutes after seizure end, mean 3.5 min.), 48 (79%) showed hypoperfusion in the lateral cortex of the offending temporal lobe, often with residual hyperperfusion in the mesial temporal structures in the first few postictal minutes. The lateral cortex perfusion deficits were evident up to 20 minutes postictally. Confirmation of the visual assessment was made by determination of the count ratios in regions of interest (expressed as discharging/normal side). Ratios in the lateral temporal cortex were 1.0 +/- 0.06 interictally, 1.36 +/- 0.18 ictally and fell to 0.91 +/- 0.08 postictally. These patterns of peri-ictal blood flow have proved valuable in the locaIization of seizure focus and provide physiological evidence ancillary to the EEG findings. The rapid switch in blood flow at the termination of discharge also provides further insight into the nature of human seizures.

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Has Te-99m HMPAO brain SPECT a place in the routine workup of epilepsy? M. Rubinstein, J. Braeckeveldt*, N. Franck*, G. Vanhaelen* and A. Collier-Geulette*. Departments of Radioisotopes and Neurology*, I.M.C. Ixelles, Brussels, Belgium.

A Tc-99m-HM-PAO INTERICTAL STUDY IN SEVERE PARTIAL EPILEPSIES: CORRELATIONS WITH ANATOMICAL AND ELECTROPHYSIOLOGICAL DATA. M.O. Habert*, L Parietti**, M.L. Piketty*, R. Lebtahi*, S. Askienazy*, C. Munari*. Hospital Sainte-Anne*, PARIS. Universitaria di PAVIA**.

Highly selected series of PET and SPECT studies have reported a great ability to detect and localize epileptical foci, in particular with a typical interictal pattern of hypo-metabolism or perfusion. In order to assess the place of Tc-99m HMPAO brain SPECT (BrSp) in the routine work-up of seizure disorders (SD), we studied 29 consecutive patients with various SD: 23 were performed interictally and 9 post-ictally (< 72 h); 3 had both studies. 25 mci of Tc-99m HMPAO were given under 16 channels scalp EEG monitoring during at least 15 minutes after the injection. SPECT data were analysed unaware of the EEG findings. Differences between symmetrical regions greater than 15% were considered significant. Hypoperfusions were rejected in presence of CT abnormalities (4). Overall interictal BrSp sensitivity (S.) was 13/23, equivalent to the presence of spikes (10/23; ns). Combined S. rised up to 17/23, which was not better than EEG alone when sharp waves were also considered (19/23; ns). All SPECT abnormalities were focal: hyper in 10 and hypo in 3. The presence of SPECT lesions was independent as severity or type of SD. Conversely post-ictal BrSp was positive in 8/9 (7 focal hyperperfusions and 1 large area of hypo). They included all patients with positive EEG. All focal abnormalities present in both EEG and BrSp were spatially congruent. In the 3 patients with post- and inter-ictal study, BrSp disclosed totally reversible postictal focal hyperperfusion. In conclusion, Tc-99m HMPAO SPECT is competitive with EEG only when performed postictally. Therefore we think it is not of great benefit for the assessment of suspected seizures, unless performed immediately after the event. In our series, we found an unexpected high frequency of interictal hyperperfused foci.

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Regional cerebral perfusion was evaluated interictally by single photon emission tomography (SPECT) using Tc-99m-HM-PAO as a tracer in 24 patients (range 9-35 yrs. mean age 23.5 yrs) suffering from severe partial epilepsy. The aim was to correlate the SPECT data with anatomical (CT, MRI scans and stereotactic biopsies) and elcctrophysiological (interictal, ictal scalp EEG and stereo-EEG) findings. SPECT was carried out on a sagittat plane (32 angular views recorded in a 64x64 matrix) from nasion to occiput. Reconstructed brain slices were evaluated visually for regions of marked asymmetries. A perfusion defect was found in the site of anatomical lesion in 8/16 patients. If a site concordance was found between SPECT and interictal EEG abnormalities in half of patients (slow waves: 10/20, spikes and/or sharp waves: 10/20), the proportion of topographic agreement was decreasing when comparing with the localization of initial discharge (scalp EEG: 6/16) and with the epileptogenic area (EA) as determined by SEEG (3/10). These results underline the necessity of a correct definition of the EA when evaluating the interest of SPECT brain perfusion studies in drug-resistant epileptic patients.

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569 FIRST CLINICAL RESULTS OF A MULTTCENTER-STUDY WITH IOMAZEN1L P.H. Hasler t, P.A. Schubiger t, H.-F. Beer t, P. Bliiuensteint, A. Belder 2, M. Cordes 3, E. Deisenhammer4, M. De Rod 5, E. Moser 6, I. Podreka7, G. Riccabona 8, O. Schober 9, P. Van Rijk t~ E.A. van Royen n, G.K. von Schulthess t2 tpanl Scherrer Institute, Villigen PSI, Switzerland; 2St. Gallen, Switzerland; 3Berlin, West-Germany; 4Linz, Austria; SLeuven, Belgh2m; 6Freiburg i.Br., West-Germany; 7Vienna, Austria; 8Irmsbruck, Austria; 9Miinster, West-Germany; t~ Netherlands; nAmsterdam, Netherlands; t2Zurich, Switzerland. Iomazenil (ethyl-7-iodo-5,6-dihydro-5-methyl-6-oxo-4Himidazo [1,5-a][1,4] benzodiazepine-3-carboxylate; Ro-16-0154) is a benzodiazepine antagonist. In earlier published papers it was shown that Iomazenil labelled with 1-123 fulfilled all the conditions for a radiopharmaceutical with a high benzodiazepinereceptor affinity, especially the pharmacological properties, bindir~g saturation and displacement by its fluoro analogue (Flumazenil). All these results led us to test the usefulness of Iomazenil in the diagnosis of brain diseases where benzodiazepine receptors are involved. In a multicenter study patients with a focal epilepsy were selected because a reduced benzodiazepine receptor binding had been demonstrated in such cases. The protocol included a blood flow image, e.g. performed with Perfusamine, and the Iomazenil study 24 h later. The SPECT imaging was started 30 min. after the injection of Iomazenil. In 71 cases the same images were obtained with Perfusamine (or Tc-99m--HMPAO) and Iomazenil. In 21 cases clear differences between the two images were observed. In a subgroup of patients, all suffering from the Lennox-GastautSyndrome, the foci were clearly visible only in the Iomazenil images, whereas the perfusion tracer showed a normal distribution as observed in healthy volunteers.

Type

Benzodiazepine

Binding Sites

in Brain

A. Takada, S. Mitsuka, M. Diksic, and Y.L. Y a m a m o t o (Neuroisotope Laboratory, M o n t r e a l Neurological Institute, M ontreal~ Canada) There are two types of benzodiazepine binding sites in m a m m a l i a n brain t i s s u e ("central type" and "peripheral type"). P e r i p h e r a l type benzodiazepine binding sites (PBBS) are sparse in n o r m a l nervous tissue, However~ PBB5 have been r e p o r t e d to be p r e s e n t in high c o n c e n t r a t i o n s in rodent glial t u m o r s and human gliomas. To c h a r a c t e r i z e peripheral type binding in brain tumors, we e x a m i n e d rat brain tumors

(C6 gtioma and AA-ascites tumor as a metastatic tumor) and 8 human gliomas (2 benign gliomas, 6 malignant gliomas) from patients. Kd and Bmax of these tumors were determined using in vitro autoradiography by means of computer-based image analysis system. (3H) PKI1195 was used in this study. In aH tumors, high specific binding was observed and had excellent topographical correlation to areas of histologically verified tumor. Kd was 22.87 + 2.9# (nM), 8.05 + 0.7#~ and 6.92 -Z 1.29 in C6 glioma, A A - a s c i t e s tumor and normal r a t cortex. Bmax was #.30 _+ 0.76 (pmol/mg tissue), 1.39 + 0.1.5, and 0.15 + 0.03 in C6 glioma, A A - a s c i t e s t u m o r and r a t cortex. 'l=he value of Bmax in C6 glioma and A A - a s c i t e s tumor was 29 or 9 t i m e s higher than in r a t cortex. Kd in human gliomas (7,2# + 2.96) was higher than in normal human c o r t e x (3.9.5 + 0-38) and Bmax in human gliomas (1.26 + 0.2#) was also s i g n i f i c a n t l y higher than in human c o r t e x ('0.35 + 0.0#), These s p e c i f i c bindings to brain tumors shown in this study suggest t h a t these p e r i p h e r a l benzodiazepine ligands might be useful for imaging ol glial and m e t a s t a t i c tumo~:s and ligands conjugated with p o t e n t i a l l y c y t o t o x i c a g e n t s could be utilized as t h e r a p e u t i c drugs,

Monday,

The aim ofthis sludy was lo inveslJgate the pharmacol4netc behavior of 1123-1omazenil and the benzediazepine receptor dislribu~on in pa~ents (pat) with complex-par~al epilepsy (cpe). Pafenls and me~ods:Twenty-ive pat.were examined. Two were normaJ volurf~er& 12 had cpe, 10 had had an amygdalo-hippocan-oec~rny (abe) and 1 had a Lennox Syndrome. AJI pat were stJdied wi~ SPECT afer Tc-99m-HM-PAOi.v. and wi~S PECT 35 min. ater i.v. hjec~on of ca. 5mCi I-123 Iorra7enil. In 12 paUime-ac~vity cunyes ofthe brain, lung& liver and !4dneys were acquired ur/d120 min. p J,onoe un~124 h. pJ. (ind. serum sample 'cd4ng). The percent biodi~bu'don was e s P Y . h three pat a displacement study was perbrmed with cold Flumazenil. LeSright and co~x-frontal white mater raids were calculated. Results: Maximum ac~Jvitywasachieved 10-12min. pJ.and about 8,5%1.D. was present in the brain 75rrin. p.i. There is a biexponer~al decay overthe brain.One houraf~r displacement with 0,35, resp. 0,02mg/e,g Flumazenil ~qere remained about 25%, resp. 50% ofthe inltal adivity in the brain. In pat with cpe the expecled ir~riclai hypoperfus~on was found but no asymmetrical ac~vityof bmazenil. Three out of 5 mat ~ suspec~ cpe showed a decreased aOJvityin one temporal lobe in boUqs~dies. Pat. alter ahe showed the ex#ected defect at the site of opera,on in both saJdies, three had a region with hyperperfusion cranial to the de,kit. C~ndus~on: Since bmazenil concen~a~on in the brain rejects benzodiazepine receptor cistrib~on that depends on perfusion etfecls, only appropriale quanUlca~on will reveal regions of recepior ooncenlratons disproporlionate to lbw. To this end, we propose two cli~rent approaches. A ra~o recep10r- 10 perlusion-SPECT oould represent the true receptor density. Displacement s~udies may also yield the recep~r density.

572

571 Peripheral Tumors

1-123-1OMAZENL-SPECT OF THE CENTRAL BENZOOIA2EPINERECEPTOR R Haldemann*, A. Pfeiffer*, H.G. Wieser**, Y. Bidk*, P A Schubiger***, G K yon Schulthess*, Clinic und Polic~nic of Nuclear Me~dne*, Clinic und Polidinic of Neurology**, UnivePs~yHospital Zunch, Paul Schemer ins~ur**, Wurenlingen, Switzerland

August

27, 1 9 9 0

A FIVE YEAR EXPERIENCE IN COMBINED ULTRASOUND AND PARATHYROID SCINTIGRAPHY AND ITS IMPACT ON SURGICAL MANAGEMENT. L.B. Arkles. T. Jones, T.J. Martin, B. Hodgkins, G.D. Gill, M.A. DeLuise. Departments of Nuclear Medicine, Endocrinology and Surgery, Repatriation General Hospital, Melbourne, Australia. Full neck exploration is routinely performed for parathyroid adenoma in most hospitals, even where there has been pre-operative localisation. The necessity for this is debatable. This study documents our experience over the past 5 years with parathyroid localisation with combined ultrasound (US) & TI-201/Tc-99m parathyroid subtraction scintigraphy (PSS) in 110 patients. There were 55 patients who proceeded to operation, and a total of 72 adenomas were removed. The sensitivity, specificity and accuracy of sequential US and PSS in the total study was 83.3%, 95.6% and 90.9% respectively compared to 90.7%, 96.6% and 95.1% in file 43 patients with primary parathyroid adanoma. 'llae combined results were superior to PSS or US alone. Correct localisation was achieved in 5 cases of secondary hyperparathyroidism with solitary recurrent adenoma. 28 of these patients subsequently had a limited neck exploration (LNE), 25 full neck exploration (FNE) and 2 sternal splitting. The average operating time for LNE was 63 minutes and FNE 12l minutes. There were 7 patients with recurrent disease, 5 of these following FNE and 2 LNE. There was 1 missed adenoma (retropharyngeal) in the LNE group in a patient with 2 primary adenomas (1.9%). No cases of hypocalcaemia were noted in the 28 patients with LNE compared with 2 with persisting hypocalcaemia in the FNE group. Combined US and PSS is helpful in the pre-operative localisation of parathyroid adenomas and is of particular value in primary and recurrent secondary adenomas. The results suggest that accurate Iocalisation may obviate the need for routine FINEin the majority of patients with primary and recurrent secondary parathyroid adenoma. The necessity for routine FNE requires review.

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574

TECHNETIUM-99m SESTAMIBI FOR PARATHYROID IMAGING. M. O'Doherty, A. Kettle, C. Wells, R. Collins, A. Coakley. Kent & Canterbury Hospital, Canterbury, Kent, U.E.

OOMP,~!~ONBE~VEEN "MDREGI~!"AND"INrf~T''PTHASS~,YSINTHEREO::gNITI~I.AND FOLLOW-UP OFHYPOPAqATHYROIDISMAFTERTHYROIDSURGER'~. O.ler,rdsi, KMedi, F.M~eucci, M.Rono~lla, F.~la, RGiordmi, F.Mosca and R.Bimchi. Istituto dl Fis]ok~j Chm[a del C~R, Oenl?o dl Med~cTnaNuclei'e, Istltuto dl PaTot~a Chirurgi~IfedIstituto diClinicaMedi,caI!,Uni,,~'sita diPi~,Pisa,It@/.

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 18 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 18 patients who had surgery, ii had adenomas (i0 positive with Tc-99m sestamibi, 8 positive with TI-201, 1 missed on both scans) 5 patients had hyperplastic glands (12 positive glands identified with sestamibi, i0 with TI-201) and two patients with metastatic parathyroid carcinoma had abnormal uptake with both agents. 6 patients (2 adenomas, 2 hyperplasias, 2 carcinomas) were given tracer doses of both TI-201 and Tc-99m sestamibi shortly before the removal of the abnormal parathyroid tissue, and uptake in this was measured. This biopsy data showed higher uptake of sestamibi than thallous chloride in abnormal parathyroid tissue. Thus Tc-99m sestamibi appears superior to TI-201 for 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.

575 ASSESSMENT

~:#a'~t/roid]sm. I-~e4r the etm,geneityd tie irnmur~'~cti',~ PTH cir-aul~ingfort% confuses the interpret]on of the results of omvmt~al RIA t&-hnlqtJes Mmeover ire d~slopmmt d8 vg'i~' of PTH irrlmu~ for differmt ro~ors d the ~'rnone (N md C lerrnlnal, m~l-sgion(rnm), mta~t (1-84) PTH) ocmpl~aies tie r-ecogmt~q of their trte diegr6tic utiiii~', tn Crda" to e~aluate81 the:e prr we stuciir:d 68 i.s pc4.]ents (pts) subrn]tt~dtototal tr~/rOldeClEmv(T]', n=7), ~ total tiqyro~deAomv( NT7, n=35) cr omithyroidectomy (TT, n=26) Saurn cmr.mtratia-6 d (1-84) PTH, mm PTH, C~idt~qin (CT)andtotalC~iaurn(C~)werern4rdsuredpreop~velv,oJr'l~surgeryandafter4-8!2-16-2r163 hours(hrs)fromi:r~mrfing of oper~1on, thin e~erv 7-15 d&,s f~ 2-3 mm~s, &~rum (1-841PTH W'dSd~erm]r~l ~, a 2 site IRMA~sa~, mm PTH 6rdCT wsrs rneasurf:db/RIA.TF~ rnaln results are r~rted in the table: I~ n=62 ~dore Intrlsur(~ 72hrs 1 5 c ~ s 45d~s 5urcer-~ 1-84)PTH~,m~ 308_+92 282• 1 3! 2_+94 29.8+_104 3l 2-+94 3INTT mmPTH r~"ml 042• 0.38• 0,39+8,9 0.41-+0.7 0,40• 6,-r C,arnEq!l 46-+06 44t07 4.2+_05 43+_06 42_+04 2SET CT ~'ml 6.4_+4.2 7.8_+5.1 6.4_+4; 72_+3.8 8.14-4.5 2~ n=6 6efcre_. intFrJ~Jrq /2nrs_ 15~ 45rJ%~_~jr'qE~, / (I-$4)PTH,I:~/ml 29,4_+5J 7.5+3,0 4,1_+3.5 14.8_+50 26.1• 4h77 mmPTH rg/rn! 0.39_+0,060.35• 0.30_+0080.3!_+0.09 0.36_+0,I0 1T~ ,~ mE@", 14• 4,0• 3,5• 3.7+0.4 4.2_+0.5 iET CT ~/ml 6!_+2,2 75• 6,8-+4,1 71-+3,8 7 6_+3.2 Irl corciuslofi our d61a,-.~[}~5_t ] ) rnm PTH ~ ;s of llrn11,!d dlS~_f..6tlc utlhi~ In ~ i~s'tigu,~t.~.nnof ~/roidi~rn after th/roid r&'~ect.im; 2 ) ( ! - 84 ) PTM a~/~ m a.l~uate ser6;uwt~ ~I soeclflClty fa" tl-e %rEe:nng artl follow-up d i~st-s~rgicai b,.,.-~a~.t~/roidism; 3) hir~ predidi,n ~,%ro~tic inform~ims, cm beobtair~ !rorn ( ! - 84) PTH ssrUffl detr~rrilr-atlor; durlrgtrl~flrsthrsafl~ ceer~t~on

576 OF

THE

SAFETY

AND

EFFICACY

OF

IODO-6-CHOLESTEROL. I. Rendak, R. Taillefer*, A . A . D r i e d g e r , J.M. MacLean;, B. C. L e n t l e ~ and M. Picard*. University of Western Ontario, London, University of Montreal*, University of M a n i t o b a ~, B r i t i s h Columbia', Canada. Iodo-6-cholesterol, is a n e w a d r e n a l imaging radiopharmaceutical recently made commercially available in C a n a d a as an alternate agent to NP-59 (6 - b e t a - i o d o n o r c h o l e s t e r o l ). An o p e n label, m u l t i c e n t e r , crossover d e s i g n s t u d y of 30 p a t i e n t s w i t h s u s p e c t e d a d r e n a l c o r t i c a l d i s e a s e w a s p e r f o r m e d to assess its u s e f u l n e s s in a c l i n i c a l setting. Fourteen female and 16 male patients r e c e i v e d 37 M B q of 1 - 1 3 1 - i o d o - 6 - c h o l e s t e r o l and w e r e i m a g e d 2-3 t i m e s up to ii days. Scans were interpreted as normal (21) , h y p e r p l a s i a (3), a d e n o m a (3), a l d o s t e r o n o m a (2) or p o s s i b l e l e s i o n (i). Correlation with other diagnostic modalities (ultrasound, CT scan, s u r g i c a l biopsy, NP59 a d r e n a l scan, a r t e r i o g r a p h y or v e n o u s sampling) a n d final d i a g n o s z s w a s o b t a i n a b l e in 17 p a t i e n t s only. E x c l u d i n g cases w h e r e no c o r r e l a t i o n was possible, sensitivity equaled 71% and specificity 100% ( a c c u r a c y = 8 8 % ). In conclusion, iodocholesterol s c i n t i g r a p h y is s u c c e s f u l in a s s e s s i n g size and function of adrenals and compares f a v o u r a b l y w i t h NP-59.

S u p p o r t e d by F r o s s t R a d i o p h a r m a c e u t i c a l s .

S128

Alter th/roid~ior,.y,i-,~1:8~IcaTfia rzcurs with a relativeS,hicjqfrT:g..mcy.T~e rnear:~J~t d PTH in ~erum is O'~l~rsBJess~tlalfor-ire (]16grlC61Sof 9JSpl~IEd

1-123 I N S U L I N B I O D I S T R I B U T I O N S T U D Y IN V I V O E V A L U A T I O N OF I N S U L I N B I N D I N G DEFECTS. A CASE OF T Y P E A I N S U L I N R E S I S T A N C E . F.Dosio, N.Dozio, A. Savi, P. G e r u n d i n i , F. Fazio, P .Micossi, G. Pozza, F. S o d o y e z Goffaux, J . C . S o d o y e z . H. S. Raffaele, Milan, Italy, U n i v e r s i t y of Liege, Belgium. Metabolic and h o r m o n a l features of a 16 years old girl affected b y severe insulin r e s i s t a n c e c o n s i s t e d in m a r k e d h y p e r i n s u l i n e mia (200-350 ~V/ml), hypergljcaemia (25-400 mg/dl), absence of r e l e v a n t level of anti insulin receptor antibodies or anti i n s u l i n antibodies. In v i t r o the red b l o o d cells d i s p l a y e d a m a r k e d l y r e d u c e d 1-123 T Y R A 14 insulin binding. Insulin binding to liver receptors was investigated in vivo by scintillation scanning. One mCi of 1-123 insulin was i.v. injected and a dynamic acquisition was performed for 30 m i n b y a gamma camera. The biodistribution was c h a r a c t e r i z e d b y lack of b o t h liver u p t a k e of the l a b e l e d h o r m o n e (maximum liver u p t a k e 4% of the i n j e c t e d dose at the ist m i n v e r s u s 21.1 + i. 7% at 6th min in i0 normal volunteers) and liver metabolization. C o n s i s t e n t l y the a c t i v i t y curve of the h e a r t did not show the r e b o u n d o b s e r v e d in normals. B y c o n t r a s t the u p t a k e and d e g r a d a t i o n of the t r a c e r by the kidneys, m a i n l y a n o n r e c e p t o r m e d i a t e d process, show no m a j o r a b n o r m a l i t i e s . Defects in insulin binding can be readly demonstrated and c h a r a c t e r i z e d in v i v o b y a liver r e c e p t o r s u s i n g 1-123 T Y R A 14 i n s u l i n and s c i n t i l l a t i o n scanning.

Monday, August27,1990

577

578

LITHIUM-ASSOCIATED THYROTOXICOSIS. V.M. Varma D.C. Sweeney, and R.C. Reba, George Washington University Medical Center, Washington, DC.

NEHTROPHIL KINETICS UNDER NORMAL AND SEPTIC SHOCK CONDITIONS IN A BABOON MODEL.

Six patients on long term Lithium therapy for various psychiatric disorders were referred with signs and symptoms suggestive of hyperthyroidism. Thyrotoxicosis was confirmed by 1-123 two, six, twenty-four hour uptakes and serum thyroid hormone levels. All six patients responded to a single dose of RAI-131 therapy. Thyroidal abnormalities, such as euthyroid goiter and hypothyroidism are reported to occur in 7 to 30 percent of patients on Lithium Carbonate therapy. Twenty-five patients with hyperthyroidism have been described, mostly after long term Lithium therapy (AJM 80:1245-1248, 1986). This review identified only one patient who became hyperthyroid following a short period of hypothyroidism following eight years of Lithium therapy. Of our six patients, two of these patients were initially diagnosed with hypothyroidism, several months before the thyrotoxic episode. Although, it is well known that Lithium affects several steps in the process of thyroid hormone synthesis and metabolism, the pathogenesis of Lithium-associated thyrotoxicosis is a clinical phenomenon that is not well understood. We believe these cases represent a definite entity and are not a result of mere coincidence.

I C Dormehl, M Maree, D Cromarty, H B6ckman, L Jaccbs, E J van Rensburg, J G Kilian. AEC Institute for Life Sciences, University of Preteria The purpose was the correlation of neutrophil kinetics with the pathogenic course of septic shock in the baboon model, using scintigraphy. In-111-tropolonate labelled autologous neutrophils were used in six normal 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 neutrephil 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. Table I Study 10 rain 40 min 60 rain 180 rain Control 30• 6 60• 10.3 68• 14 72• 19 / LU N G ~ G r o u p A 3 16 32 59 ~Group B 5 19 32 60 / / C o n t r o l 182• 275• 275• 226• L I V E R ~ Group A 20 107 161 339 ~Group B 99 161 255 361 Control 375• 625• 775• 900• / S P L E E N ~ G r o u p A 300 400 1015 2500 Group B 150 316 368 366

579

580

EVALUATION OF MYOCARDIAL ISCHEMIA AND REPERFUSION INJURY USING In-111 LABELLED GRANULOCYTES: EFFECT OF IBUPROFEN. M.A. A n t a r , S. Hoory, D. Bandypadhyay, D.K. Das, R. Engleman, H. Otani and R. Clement. ClevelandClinic Foundation, Cleveland, OH, and Univ. of Connecticut, Farmington, CT.

PLATELET CONSUMPTION IN CONTROL AND HEPARIN BONDED OXYGENATOR DURING EXTRACORPOREAL CIRCULATION WITH In-lll LABELED PLATELETS I N i% PIG MODEL. G. P a l a t i a n o s , M. K. D e w a n j ee,

Myocardial ischemia and reperfusion myocardial injury fol lowing coronary revaseularization are associated with inflammatory response resulting in massive influx of polynorphonuclear leukoeytes (PMVs) and free radical production. We used an isolated in-vivo pig heart model to evaluate I n - l l l labelled PMN influx after myocardial infarction (MI) and reperfusion, with or without pretreatment with ibuprofen (IBU), a nonstroidal anti-inflammatory agent. Thirteen pig hearts (7 IBU, 6 control) were subjected to a) normothermic regional ischemia, (LAD reversible l igation), b) hypothermic cardioplegic infusion, and c) normothermic reperfusion, 60 min each; to imitate surgical revascularization post MI. Ibuprofendose was 50 uM prior to LAD occlusion. 120-130 uCi of I n - l l l labelled PMlqs were injected into the circulation at the start of the reperfusion. Experimental hearts showed higher concentration of I n - l l l labelled neutrophils in the isehemic regions supplied by LAD compared to the well perfused areas (2-4 times those normal areas). In contrast, after ibuprofen, there was inhibition of PMVs influx in the LAD ischemic regions. Ratio of mean a c t i v i t y of control to ibuprofen treated pigs was 100:31; P ~ 0.001. The findings suggest that the influ:c of I n - l l l labelled PMlqs is increased during myocardial reper-'---~ fusion and is inhibited by ibuprofen and that ~-scintigraphy, can be useful in evaluating in-vivo changes in neutrophils influx during ischemia and reperfusion and monitoring the e f f e c t of drug therapy.

To evaluate the effect of s u r f a c e heparin i z a t i o n (SH) o n p l a t e l e t c o n s u m p t i o n (PC) in t h e o x y g e n a t o r d u r i n g c a r d i o p u l m o n a r y b y p a s s (CPB), we placed i0 a n e s t h e t i z e d Yorkshire pigs on n o r m o t h e r m i c C P B (right atrium" t o aorta) for 3 hours. All pigs were injected with autologous I n - l l l l a b e l e d p l a t e l e t s ( 3 0 0 - 4 2 0 uCi), 24 h o u r s p r i o r to C P B a n d w e r e s y s t e m i c a l l y h e p a r i n i z e d ( A C T > 4 0 0 sec) p r i o r t o c a n n u l a t i o n f o r CPB. C P B w a s i n s t i t u t e d w i t h a r o l l e r pump, a h o l l o w - f i b e r m e m b r a n e o x y g e n a t o r (HFMO, B e n t l e y CM-50) a n d a n a r t e r i a l f i l t e r (AF, B e n t l e y 1025). I n g r o u p I p i g s (control, n=6) C P B s y s t e m s w e r e u n t r e a t e d . In g r o u p II (n=4) t h e i n t r a l u m i n a l s u r f a c e s of the CPB systems were treated with heparin for SH ( D u r a f l o II) .C a r d i o t o m y s u c t i o n w a s n o t u t i l i z e d . P e r c e n t o f i n j e c t e d r a d i a t i o n d o s e in H F M O a n d AF, b l o o d l o s s d u r i n g C P B (BL) a n d p e r c e n t c h a n g e in p l a t e l e t c o u n t s (PLC) , a t 3 h o u r s o f CPB, a r e tabulated below. Values are mean +SD. Group I G r o u p II H F M O (%) 0.75+0.55 2.44+1.71 A F (%) 0.96--+0.51 0.49+_0.39 BL(ml) 225--+178 200-+154 P L C (% c h a n g e ) -7.8 -21.7 S H d i d n o t r e d u c e PC o n H F M O a n d B L d u r i n g CPB. (Supported by DOE and FHTIC).

Monday, August 27,1990

M. K a p a d v a n j w a l a , S. Novak, G. Kaiser, Sfakianakis. University of Miami, School M e d i c i n e , M i a m i , FL, U . S . A .

G. of

S129

581

582

KINETICS AND IN VIVO DISTRIBUTION OF IN-111 LABELLED PLATELETS IN PATIENTS WITH UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA. N.W. Louw. State Hospital, Windhoek, Namibia.

THROMBOLYSIS M O N I T O R I N G - A SMALL STEP BEYOND IMMUNOSCINTIGRAPHY. G.J. Wang, Z.H. Oster, P. Som, and P.O. Zamora. Brookhaven National Laboratory, Upton, NY, SUNY, Stony Brook School of Medicine, Stony Brook, NY, and SUMMA Medical Corporation, Albuquerque, NM.

The literature is somewhat controversial about the cause of thrombocytopenia in falciparum malaria. The aim of this study was to investigate the kinetics and in vivo distribution of In-Ill-labelled autologous platelets in patients with uncomplicated falciparum malaria. Three healthy volunteers and seven patients infected with plasmodium falciparum took part in the study. Autologous platelets were labelled with In-lll oxine. Platelet survival and platelet recovery were calculated, as well a s the percentage of In-Ill labelled platelets in the liver, the spleen, the heart and the rest of the body at equilibrium and at the end of platelet survival. The results show that platelet survival was significantly shortened, probably due to a combination of hyperplastic reticuloendothelial system as well as damage of the platelets due to immunological and/or other factors, e.g. uptake of the malaria parasite by the platelets. Contrary to the conclusion of other authors, the results also indicate that no significant abnormal pooling of platelets occurred in the spleen at equilibrium. Interestingly, early sequestration of platelets took place in the liver.

Thrombus immunoscintigraphy with Tc-99m labeled monoclonal antibodies is presently undergoing intense clinical evaluation. Reports on clinical trials of radiolabeled antifibrins are very encouraging and results of antiplatelet antibody evaluations are forthcoming. If studies can be performed and a diagnosis is made within the critical "lytic window", of 4-6 hrs., the imaging procedure can be used as an adjunct with thrombolytic therapy. We are presenting preliminary results on the feasibility of using im~nunoimaging for monitoring thrombolysis. In vitro studies were performed with standardized clots incubated with Tc-99m-50H.19 and re-incubated with streptokinase (S-K), urokinase (U-K), or tissue plasminogen activator (t-PA). The effects of these thrombolytic agents on the labeled antibody and possible interference of aspirin (ASP), coumadine (COU) and heparin (HEP) in thrombus immunoimaging were also investigated. The decrease in clot-bound Tc-99m-50H. 19 activity after S-K, U-K or t-PA was proportional to the decrease in clot weight. ASP,HEP and COU did not interfere with clot-binding of Te-99m-50H.19. Thrombolytic agents did not affect the stability of the radiolabel or immunoreactivity of 50H.19. These results indicate that Tc-99m-50H.19 is a potential agent for monitoring thrombolysis in addition to thrombus immunoimaging.

583

584

PERIPHERAL BONE MARROW UPTAKE OF Ga-67 IN CHRONIC ANEMIA. H.K. Lee, J.J. Skarzynski. Mount Sinai Services-City Hospital Center at Elmhurst, and Mount Sinai School of Medicine, N.Y., U.S.A.

STUDY OF REGIONAL CEREBRAL BLOOD FLOW DURING ENTIRE CHILDHOOD AND ADOLESCENCE WITH Xe133 C. Raynaud, C. Chiton, B. Mazi6re, N. Tzourio, M. Zilbovicius, M.C. Masure, L. Laflamme, B. Mazoyer, O. Dulac, M. Bourguignon and A. Syrota. Serv. Hosp. F. Joliot, CEA, Orsay and INSERM U29 and Pediatric Dept. Hosp. St-Vincent-dePaul,Paris, France

Although increased bone marrow uptake of Ga-67 (BMUGa) in transfused or iron overload patients has been reported, a systematic observation of BMUGa pattern in a series of anemia patients is desirable. We analyzed whole body Ga-67 images of 50 consecutive patients (Age 21-67, M/F=24/26) with special attention to peripheral BMUGa, and correlated with the presence and types of anemia. Average dose OF Ga-67 was 6mCi and scans were done 48 to 72 hours after injection. Typical BMUGa was diffuse and bilaterally symmetrical. Humeri and femori were most commonly involved in the peripheral BMUGa. Central BMUGa of spine, sternum, ribs, scapula, skull and pelvis tended to parallel the peripheral BMUGa in many patients but was not as dramatic or discriminating as peripheral BMUGa. All BMUGa were recorded according to a grading scale of 0-III to represent none, faint, definite, and intense degree of uptake respectively. 26 patients had at least a pair of long bones showing grade II or III. All of them had chronic anemia of either hypochromic or microcytic types. 4 had recent transfusion. Of the remaining 24 patients with grade 0 or I, 18 had no anemia, 3 macrocytic, and 3 normoeytic hypoehromic anemia of mild degree. We conclude that peripheral BMUGa occurs consistently in chronic hypochromie or microcytic anemia with or without transfusion.

$130

Regional cerebral blood flow (rCBF) modifications accompagnying brain maturation were found during the first 2 years of life (J. Nucl. Med. 1988, 29:273 and 29:893). The present work extended the study to the entire childhood and adolescence, rCBF was measured by SPECT and Xe-133 in 42 children considered a posteriori as neurologically normal. Nine cortical functional regions were delineated according to Brodmann areas and measured, results were compared to those of a control group of young adults (n = 32, mean age = 22Y). Global CBF (mCBF) at birth had the same value than in adults, then increased to a maximum of 180 % of adult values at 5 years, and decreased to adult values at about 15 years. Functional region rCBF(s) were at birth lower than adult values, then followed the same pattern than mCBF. Because of the global increase in rCBF, to better define the sequence of the regional modifications each value of rCBF was normalized by dividing it by corresponding mCBF. Adult values were then reached, first by the posterior unimodal associative region, which is the parieto-temporo-occipital carrefour, at 3 months, by sensitivomotor region at 4 months, posterior heteromodal associative region, which is parietal, at 6m, auditive and Wernicke region at 8m, primary visual cortex at 10m, temporal pole at 18m, and later frontal regions, with associative prefrontal region at 2Y and associative laterofrontal and Brocca regions at about 9Y. When the correction for mCBF was not applied, the timing was shorter, every rCBF reached adult value before 15 months, and results were closer to those obtained with 18F-FDG.

Monday, August 27, 1990

585

586

A BRAIN DAMAGE MARKERWITHPROGNOSTIC VALUE IN N E W B O R N S : N E U R O N - S P E C I F I C E N O L A S E I N CSF. A. C o q u e r e l , E. J e a n n o t , A. L o e b , C. Fessard. Centre Hospitalier Universitaire. Roue~FRANCE

Tc-ggm HMPAO SPECT in spastic cerebral palsy.

Hypoxia-ischemia during the per• period could be dramatic but at this time clinical and EEG examinations give uncertain prognostic arguments and imaging informations a r e t o o l a t e . N e u r o n - S p e c i f i c E n o l a s e (NSE) is a brain specific cytosolic enzyme. Its CSF l e v e l i n c r e a s e s as t h e n e c r o s i s volume after experimental lesions. We tested whether CSF NSE level in newborns was predictive of neurological outcome (established with clinical, EEG and CT Scan or Echographic e x a m i n a t i o n s ) a t 1 m o n t h (A) and at 1 year (B). N S E a s s a y c o n s i s t e d i n a ILIA ( P h a r m a c i a ) (IC 50 % : 1 1 . 5 ng/ml). 119 newborns were studied: 94 had no brain suffering or a transient fetal distress without EEG or i m a g i n g a b n o r m a l i t i e s ( g r o u p IA) and 25 h a d confirmed brain damages (group IIA). 58 infants were re-examined 1 year later : 43 w e r e n o r m a l (gr.IB) a n d 15 h a d neurological disorders (gr.IIB). CSF NSE values were r e s p e c t i v e l y ( m e a n • S.E.): g r . I A = 10.2 • 4.3 v s g r . I B = 2 4 . 2 i 18.6 ( p < 0 . 0 0 0 1 ) , a n d gr.IIA = 11.5 • 5.5 vs gr.IIB = 32.4 • 20.1 (p<0.001). Cut off value is 17 ng/ml. S e n s i t i v i t y (Se), S p e c i f i c i t y (Sp), Positive a n d N e g a t i v e P r e d i c t i v e V a l u e s (PPV and NPV) w e r e f o r g r . A a n d gr.B, r e s p e c t i v e l y : S e 52 & 80 % ; S p 94 & 95 % ; PPV: 72 & 86 % ; NPV: 88 & 93 %, a n d t h e r e l a t i v e r i s k (k) were 6 & 12.6 respectively. We conclude CSF NSE has a high prognostic value at birth.

R. Denays, M. Tondeur, V. Toppet, H.R. Ham, A. Piepsz, M. Spehl, P. Noel. Departments of Neurology, Radioisotopes, Pediatric Radiology and Pediatrics, St Pierre Hospital, Free Universities of Brussels, Belgium. The outlook for cerebral palsied children is determined by the severity of the motor problem and by the presence of associated disabilities whose early detection remains a medical challenge. By means of Tc-99m HMPAOSPECT we have investigated 13 cerebral palsied children aged 13 months to 12 years. Six were suffering from spastic hemiplegia, five from spastic diplegia and two from spastic tetraplegia. The degree of handicaps varied from mild (no interference with function) to moderate (some aid needed to perform daily tasks) and severe (considerable aid needed to perform daily tasks). Interhemispheric asymmetries (right-left analysis) as well as bilateral and symmetrical reduction of cerebral blood flow (antero- posterior analysis) were considered in the analysis of SPECT studies. In hemiplogic children, SPECT hypoperfusion was, on the right-left analysis, congruent with CTscan findings in the 4 children with large sylvian perencephalic cysts. In the hemiplegic child with cerebral atrophy limited to the eontralatsral parietal cortex, the SPECT study showed a more extensive abnormality, including the superior motor area. In the hemiplogic child with normal CTscan, there was no demonstrable reduction of cerebral blood flow in the motor codex but a left parietal hypoperfusion suggesting the existence of somesthetic disabilities. In addition to the abnormalities revealed by the right-left analysis in hemiplegic children,the antero- posterior analysis demonstrated a bilateral hypoactivlty in the prefrontal areas in the child with severe mental retardation. In di- and tetraplegic children, the CTscan of the head was normal or only showed cerebral atrophy. In these patients, the right-left analysis of the SPECT study dit not demonstrate significant asymmetry, except in 2 patients with marked left sylvian cerebral atrophy on the CTscan and congruent temporo-parietal hypoperfusion on the SPECT study. On the antero-posterior analysis, 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 is a valuable complementary tool for s thorough neurological assessement in spastic cerebral palsy.

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CHILDHOOD-ONSET EPILEPSY STUDIED WITH (99m-Tc) HMPAO SPECT. L.A. O'Tuama, M. Mikati, J. Ulanski, S.T. Treves. The Children's Hospital and Harvard Medical School, Boston, MA.

Blood flow SPECT in seizure disorders in childhood, a preliminary evaluation.

Previous SPECT studies of cerebral blood flow (CBF) in epilepsy have predominantly considered adult seizures, which differ etiologically and prognostically from childhood-onset epilepsy (COE). To study clinicoelectrographic correlates of CBF in COE, we obtained (99m-Tc) HMPAO SPECT (7-17 mCi) in 18 patients (2.2 to 27 years). Focally asymmetric (FA) CBF was found in 14/14 partial complex, but not in other seizure types. CBF ipsihemispheral to the EEG focus showed (a): interictally: (n=10) relative decrease (RD) (6) or increase (RI) (4); and, (b) ietally: (n=3), RI (n=3). Relative to the EEG focus, FACBF was (a) interictally: coextensive (n=4), more extensive (n=3) or discordant (n=5) with SPECT findings. Ipsilateral RICBF was noted in Kleffner-Landau syndrome, temporal lobe dysgenesis and medial temporal sclerosis. In COE FACBF is highly prevalent and yields information not obtained from structural imaging, or clinicoelectrographic data. HMPAO SPECT is an important adjunctive test for seizure focus localization during patient selection for epilepsy surgery.

Monday,

August27,1990

M. De Roo, J.S.H. Vles, E. De Mandt, B. Ceulemans, P. Casaer. Pediatric Neurology Unit and Nuclear Medicine, U.Z. Gasthuisberg, Leuven, Belgium An increasing number of reports stress the value of blood flow SPECT for the localization of an epileptogenic focus in adults. In order to determine wether Tc99m HMPAO bloodflow SPECT is a usefull adjunct to conventional surface electroencephalography (EEG) and X-ray CT in pediatric patients, 48 children were explored in the i n t e r i c t a l phase. EEG revealed no functional abnormalities in 9 patients, CT showed no pathological findings in 27 cases, while brain SPECTwas normal in lO patients. In 5 out of 9 patients (=55%) with a normal EEG, SPECT showed focal abnormalities. In 18 out of the 27 patients (=66.6%) with a normal CT-scan, SPECT revealed abnormal findings. In 4 of the 48 patients (=8%) EEG and CT-scan were normal, whereas brain SPECT was not. In the patient group suffering from different forms of partial seizures (38 cases), the EEG showed diffuse abnormalities in lO cases, whereas the SPECT revealed a focus. From our results we conclude that SPECT imaging is a useful adjunct to EEG and X-ray CT with in about 50% of the patients accordance of the SPECT findings with either CT or EEG abnormalities. The role of SPECT f o r the confirmation of the diagnosis of epilepsy in childhood being established, the value of this additional information for the patient management remains to be evaluated.

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COMBINED 201-Tl/99m-Tc-HMPAO IMAGING IN PEDIATRIC BRAIN TUMORS. L.A. O'Tuama, M. Janicek, M. Scott, S. Sallan, N. T a r b e l l , J. Ulanski, R.T. Davis, S.T. Treves, The Children's Hospital and Harvard Medical School, Boston, MA

ALTERNATIVE FORMULATIONS OF TECHNETIUM-99m HMPAO.

Thallium-201 thallous chloride (TI) gives excellent functional delineation of many adult brain tumors (Kaplan, JNM 28:47, 1987). To obtain preliminary data on ( I ) T1 behavior in pediatric Brain tumors; (2) the relationship of T1 uptake to cerebral blood flow, we studied II children (4 s e r i a l l y ) with SPECT: T1 ( I . 3 - 1 . 8 mCi), followed (n=7) by 99m-TcHMPAO (8-18 mCi). In 8 cases, tumor status was uncertain at MR imaging. T1 was markedly increased with confirmed recurrence (cerebral glioma (n=3), medulloblastoma (n=l)) and with c l i n i c a l l y suspected recurrence ( n : l ) . T1 uptake was normal in recurrent oligodendroglioma (n=l). In T l - a v i d pts, HMPAOwas decreased at the same s i t e (n:2), or in the contralateral hemisphere (n=2). With radiation injury (n=l), T1 was minimally increased and HMPAOwas decreased. Total removal of tumor (n=4) showed normal or minimally increased T1 uptake, with normal HMPAO (n=2). Serial trends in T1 uptake at tumor sites paralleled the c l i n i c a l course. Conclusions: ( I ) Increased T1 uptake reflects functional a c t i v i t y of childhood brain tumors; (2) HMPAOdoes not improve diagnostic speceficity but demonstrates additional functional affects.

J.R. Ball~nqer and K.Y. G u l e n c h y n . Ottawa Civic Hospital, Ottawa,

N u c l e a r Medicine, Canada.

T h e in vitro instability of T c - 9 9 m H M P A O m a k e s it inconvenient to use. A 30-rain she/f-life after r e c o n stituticn is too short to allow determination of r a d i o chemical purity (RCP) and in~:~cion of the r a d i o p h a r m aceutical in techn/ca/ly difficult situations. O n e of the factors implicated in this instability is n u c l e o philic attack b y chloride ion p r e s e n t in saline a n d HCI used to dissolve the HMPAO. Kits w e r e prepared containing 0.5 m g H M P A O a n d 10 f~rog S n C I 2 d i s s o l v e d in v a r i o u s m e d i a a n d s t o r e d zen u n d e r a nitrogen atmosphere. A q u e o u s f o r m u l ations were at p H 9. Kits were reconstituted with 2-3 G B q Tc-99m, R C P w a s d e t e r m i n e d r e p e a t e d l y u s i n g an extraction technique validated in o u r laboratory, a n d the d e c l i n e in R C P with t i m e w a s fitted to a m o n o exponential function to d e t e r m i n e d e c o m p o s i t i o n rate c o n s t a n t , k d. V a l u e s o b t a i n e d for k d (h -1, m e a n + SD, N = 3 - 5 ) in v a r i o u s m e d i a were: fluoroborate, ~.177 + 0.013; d e x t r o s e 5% in water, 0.411 + 0.021; e t h a n o l 10% in water, 0.157 + 0.028. T h e s e w e r e n o m o r e stable t h a n t h e c o m m e r c i a l formulation. G r e a t e r stability w a s a c h i e v e d w h e n t h e kit c o n t a i n e d I m L 100% e t h a n o l which was reconstituted with 3 m L T c - 9 9 m in saline, 0.088 + 0.020. In e t h a n o l m e d i u m , t h e a m o u n t of S n C l 2 a f f e c t e d stability: 3 M g , 0.094 + 0.009; 10 ~ g , 0 . 0 6 5 + 0.012; 30 ~ g , 0.030 + 0.012. SnSO 4 offered no advantage over SNC12,0.090 + 0.018. These results suggest that an ethanol-based formulation m a y b e a practical a l t e r n a t i v e to allow g r e a t e r s t a b i l i t y of T c - 9 9 m HMPAO.

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INITIAL HUMAN RESULTS OF A NEW BRAIN PERFUSION AGENT : TC-99m-MRP20. J.R. Thornback, R. Pirotte, A. Chirico M. Carroll, G.F. morgan and A. Bossuvt. MEDGENIX S.A., I.R.E. Fleurus, V.U.B. Brussels, BELGIUM

TECHNETIUM-99m COMPLEXESOF 1,8-DIAMINE-3,6-DITHIAOCTANE (DDO) DERIVATIVES: SYNTHESISAND BIOLOGICAL STUDIES

MRP20 (N(-2 (IH pyrolylmethyl) )N' ( (-4-pentene-3-one2)) ethylene 1,2 diamine) is a ligand designed to complex technetium with the formation of a (TcOL) compound. The neutral complex is formed by stannous reduction of pertechnetate in the presence of the ligand and after filtration, yields the desired complex in > 90% radiochemical purity. The lipophilicity of this compound was found by octanol : saline partition and reverse phase HPLC. We evaluated the biodistribution and SPECT imaging characteristics of Tc-99m-MRP20 in eight adult male volunteers. Blood and urine chemistries were examined 10 min before and 24h after injection and remained normal. Vital signs were monitored and no adverse reactions were found. Acquisitions were made on a Siemens TLC camera and processes using a Sopha $2000. The brain uptake reached a maximum within one minute of injection and after an initial decrease of 10% due to blood clearance the brain activity reached a plateau after 5 min p.i. The % injected dose in the brain at 15 min p.i. was 5.2 (s.d 1.6) which remained at this level over the 7h of the study (4.9%) (s.d 1.5). The distribution of activity in the brain was not seen to change over 24h. The whole body studies showed considerable retention of the tracer in the skeletal muscles (20% i.d.) and > 2% i.d. was retained in the myocardium. The mechanism of uptake and retention is believed to be lipophilic diffusion into the brain matter followed by rapid hydrolysis of the azomethine moiety which gives a charged secondary complex unable to cross the BBB. In conclusion, Tc-99m-MRP20 is a neutral complex which is rapidly extracted into and retained by the brain and is suitable for SPECT imaging.

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Th. Maina, E. Chiotellis National Center for Scientific Research "Demokritos" 153 10 Ag. Paraskevi Attikis, Athens, Greece In our search for developing lipophilic complexes of Tc-99m, we synthesized new multidentate ligands, derivatives of 1,8-diamine-3,6-dithiaoctane (DDO). The radiochemistry of this class of compounds was investigated by HPLC and isolated complexes were biodistributed in animal species. The ligands synthesized were of the general type: R] R2NCH2CH2SCH2CH2SCH2CH2NR3R4 where RI:R2=R3=H, R4=H DDO (1), n-C4H9 ( I I ) , i-C4H9 ( I l l ) , C6H5 (IV), morpholinylethyl (V), piperidinylethyl (VI) and RI=R3=H R2=R4=C2H5 (VII), sa l i c y l y l (VIII), cyclohexyl (IX), RiR2N=R3R4N=morpholinyl (X). Labelling was accomplished by reduction of pertechnet~e by sodium borohydride in the presence of the ligand. ~mTccomplexes were isolated from the reaction mixture by organic extraction. Reverse phase HPLC revealed for most compounds the presence of various technetium species, differing in l i p o p h i l i c i t y (P.C~. 0.3-77.5). The radioactive components of each 99mTc-DDO derivative were administered in mice. Biodistribution v a r i ~ with the substituent (R) of the ligand. Lipophilic ~mTc-DDO complexes were accumulated in lungs (up to 35% dose/organ) at early time intervals. Certain complexes were also retained in brain and heart tissue. Of particular interest was found 99mTc-morpholinylethyl-DDO complexes. Biodistribution of this derivative in mice revealed brain/blood ratio 0.199-2.254, 2-120 min p.i. respectively.

Monday, August27,1990

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594

IN VIVO AND IN VITRO RADIOPHARMACOLOGY OF Tc-99m-CPI. S. Verdera, A. Leon, E. Leon, F. Mut, C. Oliveira, M. Beretta, F. Garcia, A.G. Jones *, J.F. Kronause * Centro de Investigaciones Nucleares y Centro de Medicina Nuclear, Montevmdeo, Uruguay. Harvard Medlcal School and Brigham & Women's Hospital, Boston, MA, USA.

RADIOLABELED MONODISPERSE POLYSTYRENE PARTICLES FOR VENTILATION STUDIES D.H. Hunter, M.J. Chamberlain, P. Pityn and P. Culbert University of Western Ontario, ~ O n t a r i o , Canada

In vivo and in vitro radiopharmacological studies using a lyophilized reagent kit of Cu(2-carbomethoxyisopropylisocyanide)4BF 4 with SnCI 2 as the reducing agent were performed. HPLC analysis of Tc-99m-CPI in plasma and excretion products was made to determine its chemical behaviour in vivo and the mechanisms involved in its biodistribution. Human Biodistribution was studied in i0 normal volunteers with 21 mCi (777 MBq) Tc-99m-CPI. A 60 min dynamic study followed by a gated study in 3 projections and 24 hour images were acquired with blood & urine samples also taken at serial intervals. The complex undergoes hydrolysis in vivo to the more hydrephilic anions that exist in plasma free of protein binding. Metabolites in humans as characterized by HPLC and FAB-MS consisted primarily of the mono and di hydrolyzed species~ are excreted rapidly and in high percentage via the biliary and urinary systems. In humans the half-times for myocardium, kidney and liver were 2.6 hrs, 17min and 37 min respectively. Myocardium/inng and myocardium/liver ratios were 3.5 and 1.0 at 90 min P.I.. Relative myocardium distribution was 74% lateral wall, 71% septal wall, as referred to 100% of the inferior wall of 45 ~ LAO projection. Global myocardinm uptake was 2-3% of injected dose and total urinary excretion was 30% (20% in first hr.) . In summary, Tc-99m-CPI exhibits outstanding characteristicts for non-invasive cardiovascular evaluation. Supported by I.A.E.A. Tech. Assist. URU/6/017. With thanks to A.M. Robles, E. Touya & CIN and CMN staff.

We h a ve developed a simple method of producing radioaerosols f o r studies of v e n t i l a t i o n physiology and pathology based on labeling of functionalized polystyrene p a r t i c l e s . Particles are available (Polysciences) as t i g h t l y monodispersed suspensions in a wide range of sizes from submicronic upwards with several possible functional groups. Studies with amino functionalized p a r t i c l e s were directed towards attaching a chelating agent to the p a r t i c l e s by a covalent bond to the functional group. This closely p a r a l l e l s sim ila r e f f o r t s to label monoclonal antibodies. The p a r t i c l e s used are not cross linked and as a re su ] t are extremely sensitive to heat and organic solvents thus l i m i t i n g the chemistry to that which can be performed in aqueous solutions at room temperature. The best results were obtained using a three step synthesis using Deferoxamine mesylate as a chelating agent and gluteraldehyde as the coupling agent. Leaching tests showed loss of the label to be negligible. Several d i f f e r e n t radionuclides are available as labels. The p a r t i c l e s have been used in human studies in which 1 and 3 micron p a r t i c l e s labeled with I n - l l l and Tc-99m respectively were inhaled simultaneously and t h e i r d i f f e r e n t i a l deposition studied by lung region. Greater penetration of the larger p a r t i c l e s was demonstrated p a r t i c u l a r l y at the apices9

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596

~KFFlIFTERS OF (]I,IfFATHION~{ HETABOI,ISM: EFFECT (}N [ABEIi,ING OF ~LY~'k3RPHt)NU(I~AR I,EI.'tg• P. L. Zabe ] . h.H. { ~ e e l o v s k y . N. J . Car'abe t.t . [.in i v e l ' s i ~y

INTERACTIVE TEACHING AND TESTING SYSTEM FOR HANDLING NUCLEAR MEDICINE EQUIPMENT

Hospital, L,ondon~ OnLar'h~. Canada

M.V.Knopp, M.Martens, S.Polzer, G.Layer, A.Knopp, G.van Kaick German Cancer Research Center, Heidelberg, West-Germany

i ! has b e e n p r o p o s e d that g l u t a l h i o n e ma> b e im.o]ved in the retention of Tc-99n, HMPAO i n v a r i o u : ~

tissue.~, To test wi~ether glutathione (GSIt} ran) be i nvo]\ ed wi th the retention mechanism of T~z-99m H>IPAO i l l I)ol )']llOl'[)}lOnlJ~!]{~aI' ] e u k o o y i es{PHNL , two modi f i e f s ,~f GSH m e t a b o l i s m w e r e i n c u b a t e d labelling * ; i t h Tc-99m I-~,lPAO.

w i t h PHN-I, [ ) P i e r t o DI.,-buthionine sulfoximine

(BSOi is an i~gJbitor of intraeelkular GSH synthesis while diethy] maleate (DF~I) covalent ]3 binds

Frequent software changes in computerized nuclear medicine equipment requires detailed training of the medical and technical staff as well as testing their proficiency. In order to facilitate this without interrupting regular work schedules, we developed an equipment independent simulating software on a

~,gth GSH i n t h ~ p r e s e n c e o f g l u t a t h i o n e tr'ansferases. ~JNI, fFOIII healthy v o l u n t e e r s We)l'@ sepai~'atEx{ by

MS-DOS compatible PC. The software simulates the

density gpad[ent e e n t r l f u g a t i o n on Perooli/plasma

alphanumeric screen of the computerized equipment and

g~'aditm|s. Tile c e l l s were t h e n [ n e t l b a t e d f o r 3 h~" w i t h 5 m,H BSO Ln p l a s m a o r 45 rain. wLLh 2 % DEM i n p l a s m a

expects the input in the same form as the simulated device

with 0,1% T~.'a'en 80 and 0.4% etha~lo]. Centre] DINI, were Jtl(2uE}alexJ ill the ! ] F e s e n e e of p l a s m a a]one o r p l a s m a

requires. We use the equipment simulator for several different gammacamera and tomographic equipment. The teaching part of

w i l h 0. I% T~veen 80 a n d 0.4% e t b m o l . C e l l s weee washed w i t h p h o s p h a t e b u f f e r e d s a l i n e p t ' i o r t o a 15 m i n u t e [n,mJ[mtJon w i i h Te-99m h~IPAO. The l a b e i l i n g efficiency was d e t e r ' m i n e d .

the program is divided into modules including acquisition,

Inhibition of synthesis of GSH with BSO was fotuqd to have no effect of the lahe]]Jng efficiency of P}INI, with Tc-ggm HHPAO. Slow natural depletion of GSH may not al]o~. ~i observable ehange since a large excess of g]utath[one wou]d stil] exist, relative to tracer quanta ties of Te-99m HMPAO. DEH resulted in a 87 + 3 % decline in the ]ebelling efficiency of Pg_INL with Tc-99m HMPAO. These results may indieat:e that glutathione is involved in tire intr'aeel]ular retention of Tc-99m HMPAO in po])cnorphonuelear leukoeytes.

used by the operator to perform the requested task. A report is

Monday, August 2 7 , 1 9 9 0

processing and special procedures. The testing part of the program evaluates the commands given as well as the approach printed after each test session specifying any incorrect commands as well as not efficient approaches used by the operator. The dialog is software independent and can be modified easily to a foreign language. Since the introduction of this system we improved the level of proficiency of the operators, shortened the necessary training time and were able to evaluate objectively their performance.

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597 THE OPTIMIZING OF RADIONUCLIDE BONE IMAGING S.B. Jong, C.C. Wu, G.T. Peng and C.C. Yang Dep. Of Nuclear Medicine, Kaohsiung Medical College, Kaohsiung, Taiwan, ROC. The image quality of radionuclide bone imaging will be affect by: radiopharmaceutical dose, time interval between injection and imagxng, body weight of patients, ganama camera scaning speed, and sensitivity of gamma camera. In this study we recorded the radiopharmaceutical (TC-99m-MDP) purity, time of radiopharmaceutical pre[~ring, dose of radiopharmaceutical, time olradlopharmaceutical administration, time of imaging, body weight of patients, and scaning speed of gamma camera. The sensltivity of gamma camera were checked by a phantom. The imaging quality were evaluated by ROI technique (set ROI in L4, L5 and leg muscle, then calculate the ratio Of L4-1eg and L5-1eg), and evaluate the performance Of image by our doctors in 4-grade scores. We collected more than 1200 of images and compared those parameters with ROI index and doctor-score index. We conclude that: (i) doctor-score index are somewhat rohgh but are corelated to ROI index; (2) radiopharmaceuticals dose are well corelated to image rfOrmance, and a dose of 15 mCi is reasonable r a 60kg patient; (3) time interval between dose administration and imaging is a very important parameter, and 2-3 hours interval will have good performance; (4) the lower scanning speed of gamma camera the better performance, in our laboratory (with a TOSHIBA GCA-90B) 40 min/sec is reasonably accepted. Whole body bone scannlng is a very common test for the routine use. The higher dose the better result, and the slower scanning the better. But with the consideration of ALARA and economic loading, we should have a trade-off. In this study we offer the criteriae for choice.

~o

598 SCATTER CORRECTION CALCULATION FOR DUAL ISOTOPE IMAGING OF TL-201 AND IN-111. C. Smith, TD Ruddy, KY Gulenchyn, RA Davies. University of Ottawa Heart Institute at the Ottawa Civic Hospital, Ottawa, Canada. To determine the need for scatter correction (SC) in clinical dual isotope (DI) tomographic imaging, cardiac phantom studies (Data Spectrum Corporation) were performed using 0.3 mCi I"1-201 alone and combined with 0.2, 0.3 and 0.4 mCi In-111. These studies were acquired using dual isotope (DI) tomographic imaging (64 x 64 matrix, 32 projections, 45 seconds per projection, 180 rotation). Varying degrees of down scatter correction from 0% to 50% in 10% increments were used. Images were reconstructed using a Butterworth filter (0.5 Nyquist, filter order 5.0). Oblique angle slices were created and five regions of interest (ROI) were applied to all studies in identical slices and locations. The total counts in the ROIs for the scatter corrected data (SC) I.k~. 9 ,.~o_ were compared to the TI-201 decay corrected data (TI) using ~' linear regression analysis (SC = a + (b)(T1)). Results: Similar data "~ . . . . . " ....... were obtained for all three amounts of In-111 (data for 0.3 5~i5~ ' mCi In-Ill/0.3 mCi TI-201 (b].gc~ 9 shown). We conclude that 1) scatter correction is necessary for .6 9 TI-201/In-111 DI imaging and 2) the amount of scatter correction '~ ~ ,to ,% 3b ,b sS- necessary is about 20% and does 5c (x) not vary for the range of activities used in this study.

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600

DEVELOPMENT OF ENEREGY SPECTRAL ANALYSIS METHOD IN DUAL NUCLIDE IMAGING. Y.Hirasawa, Y.Mori, T.Shimada, K.Kawakami, N.Katsuyama*,T.Shibahara**,R.Ban**. Jikei University School of Medicine, Tokyo, *Ryukyu University, Okinawa, **Shimadzu corp. Kyoto, Japan.

RAPID D E T E R M I N A T I O N O F R A D I O C H E M I C A L PURITY O F TECHNETIUM- 99m HMPAO. A. Proulx and J.R. Ballinger. Nuclear Medicine, O t t a w a C i v i c Hospital, Ottawa, C a n a d a .

A dual nuclide imaging is recently applied to gain the scanning time. A new method to discriminate each photon spectrum in dual nuclide imaging was developped. Dual nuclide imaging of TI-201 and Tc-99m could be applied for imaging of p a r a t h y r o i d adenoma, t h y r o i d c a r c i n o m a and myocardial infarction. Scattered enery spectrum of these two nuclides were separated by energy spectral analysis (ESA) method. Firstly scattered s p e c t r u m of TI-201 was stored in computer. Secondly mixed scattered spectrum of TI-201 and Tc-99m was acquired. Factor analysis program was applied to image the area with energy spectrum of TI-201 or Tc-99m. The ESA could separate each scattered spectrum in a phantom in which two nuclide was arranged with partially overlapped. This method has two advantages (1)negli-gible artifact due to patient movement, (2) less effect of scattering of each energy. This method was clinically applied to parathyroid scintigraphy. We experienced a small parathyroid adenoma which was detected only by the ESA. The ESA could make dual n u c u l i d e imaging of T c - 9 9 m and TI-201 more effective.

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Because of the short shelf-life of T c - 9 9 m H M P A O after reconstituticn, it is important to h a v e a rapid method to determine r a d i o c h e m i c a l p u r i t y (RCP). We have previously reported an extraction technique (El) for this purpose (J Nucl M e d 1988;29: 572-3). A few drops of H M P A O are added to a test tube containing 3 m L ethyl acetate (EtOAc) and 3 m L saline which is then capped and vortexed for 1 min. The phases are allowed to separate and the top layer (EtOAc) is transferred by pipette into a fresh tube. The 2 tubes are assayed in a dose calibrator and R C P is calculated as activity in EtOAc divided b y total a c t i v i t y in b o t h tubes. To make this procedure even mare rapid and simple to perform, w e h a v e modified it (E2) as follows: I) distilled w a t e r is u s e d in p l a c e of saline for greater stability; 2) vigorous manual shaking for 20 sec provides results equivalent to vortexing for 1 min; 3) centifugation for 5-10 sec speeds separation of the phases; 4) instead of transferring t h e t o p layer by pipette, it is simpler and quicker to transfer the bottom layer (water) using a syringe with a spinal needle. The results of E1 and E2 were not significantly different: El, 83.1+9.7%; E2, 84.1+ 9.2%, n=13, paired t-test. Linear regression of the 2 sets of data produced a line with slope 0.997, intercept 0.8%, and correlation coefficient 0.949 (p<0.001). The modified method produces results equivalent to the original but can b e completed in <2 m i n u t e s .

Monday, August27,1990

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IN SEARCH OF PULMONARY ASPIRATION: MILK SCAN vs RADIONUCLIDE S A L I V A G R A M .

RAPID BLOOD CLEARANCE OF A NEW Tc-ggm LABELED ANTIFIBRIN CONJUGATE. M.A. Nedelman, R. Boutin, J. Lister-James, R.T. Dean and H.J. Berger. Centocor, Malvern, PA. Slow blood clearance has made the development of practical Tc-ggm labeled immunoscinttgraphic agents difficult. We have recently developed a method of increasing the blood clearance of antibody Fab' fragments by forming their conjugates with asialo-~Iacid glycoprotein (as-AAG) and radiolabeling them w~th Tc-99m via a bifunctional chelator containing a cleavable linker (Tc-ggm Fab'-RP-3 conjugates). We have compared the imaging properties and pharmacokinetics of Tc-99m labeled antifibrin antibody T2GIs Fab'-RP-3 (n=3) and direct labeled Tc-ggm T2GIs Fab' (n:11) in a canine model of acute venous thrombosis. Venous thrombi were produced by injecting thrombin into veins temporarily occluded by balloon catheterization. Fifteen minutes after thrombosis, 20 mCi/O.5 mg of Tc-99m T2GIs Fab'-RP-3 was injected i . v . Thrombus-toblood (T:B) and thrombus-to-muscle (T:M) radioactivity (cpm/g) ratios were 4.6 _+ 2.5 and 52.7 _+ 26.6, respectively for Tc-99m T2GIs Fab'-RP-3 at I hr and 9.5 +_ 8.9 and 94 + 45 respectively for Tc-99m T2GIs Fab' at 4 hr.. Blood h a l f - l i f e was 2-3 minutes for Tc-99m T2GIs Fab'-RP-3 compared to i hr for direct labeled Tc99m T2GIS Fab'. The major route of Tc-99m Fab'-RP-3 elimination was the hepatobiliary system. Although absolute uptake of Tc-99m T2G]s Fab'-RP-3 in the thrombus was apparently 8-fold less than that of direct labeled Tc-g9m T2GIs Fab', definitive scintigraphic images of thrombi were seen as early as 15-30 minutes post-injection with Tc-99m T2GIs Fab'-RP-3. Thus this new technology may allow the development of Tc-99m labeled immunoscintigraphic agents having extremely rapid blood clearance.

M.M. Maher, M.G. Velchik, and S. Heyman. The Children's Hospital of Philadelphia, Philadelphia,

Peunslvania.

The detection of aspiration is of paramount importance since it may result in recurrent bacterial pneumonia or a severe chemical pneumonitis that may be life-threatening. Radionuclide techniques have been introduced in an attempt to enhance ones sensitivity compared to conventional barium studies (barium swallow or v i d e o f l u o r o s c o p y ) . We have recently introduced the radionuclide salivagram as a sensitive technique for the detection of aspiration. In order to compare the sensitivity of the traditional milk scan and the radionuclide salivagram we retrospectively compared our results in 599 milk scans and 96 salivagrams for the detection of aspiration. For salivagrams, 300 ltCi of Tc-99m-Sulfur Colloid in < 100 Isl was placed on the anterior tongue and permitted to mix with the patient's saliva. For milk scans, lmCi of Tc-99m-Sulfur Colloid in milk was administered orally. Imaging was performed in the supine position and either anterior (milk) or posterior (salivagram) projection with a gamma camera equipped with a high sensitivity collimator including the month and stomach in the field of view. For both, analog images were obtained @ 1 minute intervals x 1 hour and computer images @ 30see/image x 1 hour. Milk scans included a dynamic swallowing phase, anterior and posterior 5-rain static lung images @ 1, 2, and 6 or 24 hours. Aspiration was detected in 25/96 (26%) of cases with the salivagram but in only 24/599 (4%) of milk scans. The better sensitivity of the salivagram for the detection of aspiration is probably due to the greater concentration of radiopharmaceutical administered (125 ~.Ci/ml vs 5 I.tCi/ml). We therefore recommend that the salivagram be used in preference to the conventional milk scan when one is in search of pulmonary aspiration.

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In-111 ANTIFIBRIN MONOCLONAL ANTIBODY FOR IMAGING LEFT SIDED ENDOCARDITIS VEGETATIONS IN A RABBIT MODEL.

DETECTION OF INTRACARDIAC ACTIVE THROMBUSWITH Ga-67DFO-DAS-FIBRINOGEN. T.Suzuki, T:Yamazaki, M.Takahashi, K.Masuda, M.Hamazu, H.Ohnishi, l.Yamamoto, R.Morita, T.Inoue, K.Mitsunami and M. Kinoshita. Shiga Medical School, Ohtsu, Shiga-Pref, Japan.

P. Peltier, G. Potel, M. Kremer, AY. Delajarte, D. Baron, T. Schaibie, HJ. Berger, JF Chatai. INSERM, Nantes, France, and Centocor Inc., Malvern, PA. In-111 antifibrin monoclonal antibody (C22A), which reconizes fibrin but not fibrinogen, permits imaging of venous thrombi. In this study we tested the ability of In-111 Fab fragments of antifibrin (AF) to produce images of fresh fibrin-rich vegetations in a rabbit model of experimental endocarditis. Endocarditis was induced in 4 NZ female rabbits by catheterization of the carotid through the aortic valve and injection of E. coll. Six days later, In-111 AF was injected IV. Blood samples were obtained 15,30,60 and 90 min and 2, 3, 4 and 24h after injection. Radioactivity per gram of each sample was determined to evaluate serum half-life of In-111 AF. After the planar image of the open heart was recorded 24h post-injection, the vegetations were removed and samples of blood, ventricles and tissues were taken ,weighed and counted to determine In-111 radioactivity per gram of tissue. The mean half-life of In-111 AF was 2.9h. Planar images cteady showed all vegetations. Vegetations-to-tissue ratios averaged 4 (blood), 5 (ventricles), 0.07 (kidney), 2.9 (liver), 14 (muscle) and 9.3 (skin). These studies suggest that In-111 Fab antifibrin is a potential agent for detecting endocarditic vegetations.

Tuesday, August28,1990

The evaluation of active thrombus, newly forming thrombus in the cardiac chambers is very important in determing the i n d i c a t i o n and the therapeutic effects of anti-coagulant. We then t r i e d to detect the active thrombus in the heart and evaluated the preventive effect of anti-coagulant for thrombus formation, using Ga67-DFO-DAS-fibrinogen(Ga-67-fibrinogen), which was a bifunctional chelating agent and had demonstrated to accumulate in a r t e r i a l thrombus more than venous thrombus,in contrary to the conventional labeled fibrinogen. The subjects were II patients with mitral valve disease, and 17 patients with myocardial i n f a r c t i o n ; in a l l patients ultrasonography(US) was performed. The scinti-images of the a n t e r i o r , LA030~ LA045~ LA060~ and l a t e r a l views of the heart were taken by a gamma camera, 96 hours a f t e r the venous i n j e c t i o n of Ga-67-fibrinogen(2mCi). In 5cases of II patients with mitral valve disease, thrombus in the l e f t atrium was visualized with Ga-67-fibrinogen and the thrombus in 3 of 5 cases were c e r t i f i c a t e d by US; in only 3 of g patients given anti-coagulants, the thrombus was recognized with Ga-67-fibrinogen, but in 2 of 2 patients wihtout anti-coagulants. In I0 cases of 17 patients with myocardial i n f a r c t i o n , thrombus in the l e f t v e n t r i c u l a r was visualized with Ga-67-fibrinogen, and the thrombus in 7 of I0 cases were c e r t i f i cated by US; in only 2 of 9 patients given anti-coagulants, the thrombus was recognized with Ga-67-fibrinogen, but in a l l of 8 patients without anti-coagulants. Ga-67-fibrinogen was more sensitive to detecting thrombus than US, and could demonstrate i t s activeness and prove the preventive e f f e c t of anti-coagulant.

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605

606

A MULTI-CKMP~AL MODEL FOR DESCRIPTION OF 1-123 MIHG MYOCARDIAL KINETICS. M. Pabinovitch, C. Rose, L.F. Chen, D. Fitchett, J. Burgess and L. Rosenthall. Montreal General Hospital, Montreal, Quebec, Canada

1-125 MIBG SPECT IMAGING IN NORMAL SUBJECTS: HETEROGENEITY IN MIBG ACTIVITY DISTRIBUTION WITHIN THE MYOCARDIAL IMAGES. .P.Kostami s, J.Lekakis, D.TsinJkss, Ch. Pslsistides, N.Vsssilopoulos, Ch. Papsmichse], S.Gersli and Sp. Moulopoulos. Dpt of Nuclear Medicine and Clinical Therapeutics "Alexandra" University Hospital, Athens, Greece.

The goal was to describe 1-123 MIHG myocardial kinetics with a m u l t i - c c ~ t m e n t a l mathematical model. SPECT was performed serially over 24 hours in 33 healthy volunteers and ii cardiac transplant patients after i0 mCi of 1-123 MIHG I .V.. Twenty volunteers (GpI) received 0.3 mg of oral clonidine 3 hours before tracer injection, 13 volunteers ware untreated (Gp2) and all transplant patients (Gp3) received clonidine. Serial 1-123 MIHG blood counting was also performed in 5 Gpl volunteers and all Gp3 patients.

T.v. s e ~ + 0.5 Hr. 2222 + 2.0 Hr. 2286 + 6.0 Hr. 2251 0.5-2 Hr. -2.18 2.0-6 Hr. +0.32 *Acctmm~ulation in +p
Gpl

~

G~/

+ 532* 2160 • 369 396 • 294% i 528 2196 i 410 196 • 158~ • 531 1947 • 423 i 4.37** -1.29 i 5.22 +32.5 • 17.1e • 2.09 +2.92 i 2.43+ counts/voxel, **Efflux In %/Hr., compared to Gpl

A mammillary model incorporating blood pool, lung, liver and sympathetic nerve c o ~ r t m e n t s with 50% kidney excretion over 24 hours was developed. The model identified a small (15-20%) rapidly effluxing non-neuronal myocardial MIBG con~partment in man. It is also confirmed that clonidine significantly retards myocardial MIBG efflux.

1-125 MIBG seintigraphy has been used to delineate abnormalities of adrenergie innervation in human myocardium but characterization of a normal pattern is lacking. To determine a normal MIBG distribution to myocardium 15 normsL volunteers, 55-52 years old, were injected 5mCi of 1-125 MI8G and SPECT imaging was performed I and 2hrs later. I vertical long sxJs and /4 short axis views were snalysed and variation in MIBG distribution > 25% was characterized as nonhomogeneous uptake. 6/15 subjects showed homogeneousMIBG uptake in both I and ghrs images, while 9/15 showed intraimage heterogeneity; All 9 subjects showed reduced uptake to the apex while 2 also had defects to the inferior wall and I to the lateral wall. MIBG washout from I to 2 hrs ranged from 0 to 50% and varied unpredictably between wails and subjects. In conclusion: I) apical defects during MIBG SPECT imaging are common and should be interpreted as normal variant 2) washout rate cannot help in delineating a normal pattern.

607

608

1-123 METAIODOBENZYLGUANIDINE (HIBG) IMAGING FOR EValUATING SEVERITY OF HEART FAILURE IN PATIENTS WITH CONGESTIVE CARDIOMYOPATHY. T. Morozumi, Y. Ishida, A. Tan• H. gate, M. Her• A. Kitabatake, T. Kamada, K. Kimura, T. Kozuka. Osaka University Medical School, Osaka, Japan.

VALIDATION STUDIES OF C-II NMSP PET MEASURES OF DOPAMIN AND SEROTONIN RECEPTORS IN NEUROPSYCHIATRIC ILLNESS. D.F. Wong, D. Young*, L.T. Young, B. Chan, E. Mink• D Burckhardt, P.D. Wilson*. R.F. Dannals, A.A. Wilson, H . T Revert, T.K. Natarajan, E. Shaya, G. Pearlson, L. Tune, H. Singer, A. Gjedde+, H.N. Wagner, Jr., Johns Hopkins Med Inst., U Maryland*, Belt, MD, Montreal Neurol Inst+.

1-123 Metaiodobenzylguanidine (I-123 MIBG) is an analog of norepinephrine (NE), which can be used to image the sympathetic innervation of the heart. To test whether alterations in the s y m p a t h e t i c innervation relates to exercise capacity in patients ( p t s ) with congestive heart failure, we performed 1123 MIBG myocardial imaging in 7 pts with congestive oardiomyepathy (CCM, NYHA class II to IV). From the data of initial (15 min) and delayed (4 hr) imagings after an intravenous injection of 1-123 MIBG (3 mCi), the percent washout rate (%WR) of 1-123 MIBG and the heart to lung ratio (H/L) of tracer activity were determined in the anterior planar images. Regional inhomogeneity of 1-123 MIBG uptake was also estimated by the coefficient of variance (CV) of segmental radioactivities in the short-axis tomographic images. Exercise capacity was evaluated by oxygen consumption (V02) at anaerobic threshold (AT) determined with respiratory gas exchange analysis during bicycle exercise. In result, the %WR ranged from 40% to 73% in these pts and inversely correlated with V02 at AT (r=-0.79, p<.05) and with LV ejection fraction (r=0.55, NS) determined by echocardiography, whereas the H/L and CV did not significantly correlate with them. These results suggest that accelerated 1-123 MIBG myocardial washout, which may indicate the impairment or t h e h y p e r a c t i v i t y of c a r d i a c sympathetic nervous system, relates to reduced exercise capacity in pts with CCM.

S136

We have continued to validate our D2 dopamine (DA) receptor Bmax PET quantification methods with C-ll-3-Nmethylspiperone (NMSP). These methods have shown elevations for drug naive schizophrenics, psychotic but not non-psychotic bipolar patients, and some Tourette's patients. C-II labeled metabolite corrections derived from our model were compared to direct HPLC measurements (up to 6 blood samples per PET study) in 21 normals or patients with schizophrenia, bipolar disorder, cocaine use, Tourette or Lesch-Nyhan syndromes. The mean of the differences between HPLC and modeled corrections were not significantly different from zero and no diagnostic group effect was evident employing a variable component model for intraclass correlation. Average plasma protein bound C-If NMSP was 94.54%. No significant difference was noted between 32 patients and 6 controls nor between patient groups. Preliminary studies demonstrate robust resistance of [3H]-NMSP to competition with endogenous dopamine compared to [3H]-raclopride binding in rat sir• We have addressed logical problems in constructing simulation studies (SS) to compare Bmax by our previously published method (PM) and exact algorithms. Preliminary SS using eaudate and cerebellum curves for the PM and using only eaudate curves for the exact method (EM) demonstrated similar results over a moderate noise range. Initial SS for $2 serotonin reversible binding suggest the importance of low specific activity injections.

Tuesday, August 28, 1990

609

610

NEUROSPECT IN COCAINE A ~ S E = rCBF AND }MP/~) FIM)INGS. I. Mona, B. Miller, K. Garrett, L. Leedca, I. Khalkhali and A. Djenderedjian, Departments of Neurology and Psychiatry and Division of Nuclear Medicine, Harbor-UCLA Me:]. Ctr., Torrance, CA, U.S.A.

C-14-COCAINE DISTRIBUTION; SPATIAL AND TEMPORAL CORRELATION WITH PHARMACOLOGICAL EFFECTS. P. Som, Z.H. Oster, N.D. Volkow, D.F. Sacker, D. A. Weber. Brookhaven National Laboratory, Upton, NY and SUNY at Stony Brook, School of Medicine, Stony Brook, NY

We describe t h e use of SPECT to evaluate patients (pts) with neurologic and psychiatric complications from acute cocaine intoxication. We measured (rCBF) with Xe-133 and generated high resolution images by means of Tc99m-~P~) SPECT. Previous experience at Our institution has suggested that many of the neurological complications from cocaine are primarily vascular and cocaine is a c ~ n cause for stroke in a young person. Pathophysiology of cocaine-induced neurological and psychiatric changes include vascular spasm, cerebral vasculitis and increased catecholamine release. We studied 15 pts age 27+5 years, 9 males and 6 females, who consulted the Emergency Room for: severe anxiety, mania, hallucinations, psychosis, seizures, stroke, hypertensive encephalopathy. They had positive urine screens only to cocaine; history was negative for other drug usage. Within 48 hours of the last cocaine dose, Xe-133 rCBF was 56_+11 ml/min/100g (normal 60-80) while evidence of focal hypoperfusion with Tc99m-HMPAO was as follows: Frontal Bilateral 9/15

Parietal Bilateral 7/15

Temporal L R 3/15 1/15

Multifocal Deep Superficial 6/15 10/15

In conclusion, i) rCBF was significantly depressed in only 2 out of 15 pts., 2) 2/15 pts. had normal brain perfusion, 3) there ware multiple focal gray matter lesions deep and/or superficial, with frontal and parietal bilateral hypoperfusion in 13/15 pts.

In vitro studies have demonstrated that cocaine binds to norepinephrine (NE), dopamine (DA) and serotonin (SE) transporters. This prevents reuptake of neurotransmitters (NT) and a raising level of NT in the synaptic cleft. Characterization of cocaine binding in vivo was investigated by us using specific NT re-uptake blockers: desipramine to block the SE/NE and GBR to block the DA transporters. Three stages of whole body distribution of C-14cocaine are observed: I) an initial localization in brain, spinal cord, heart and adrenals over the first 2-5 min post injection (mpi), 2) a gradual accumulation in kidneys and liver (5-10 mpi) and clearance from organs showing early localization, 3) excretion into the urine and bowel (20-30 mpi). Results suggest that cocaine binding in the brain is mainly to the DA transporter sites whereas binding to the heart, adrenals and kidneys also occurs in the NE/SE transporters. Liver and the gut uptake was non-specific since it was not prevented by desipramine or GBR and probably represent metabolites of the labeled cocaine. The binding of cocaine in different organs could represent the first stage of the mechanism of organ toxicity secondary to cocaine abuse. The temporal and spatial distribution correlates with the clinical effects of cocaine. (Research supported by U.S.DOE Contract No. DE-AC0276CH00016)

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QUANTITATIVE ]-123-IMP SPECT IMAGING PRE & POST THERAPY FOR LATE ONSET DEPRESSION. M.G. Velchik. P.D. Mozley, A. Kumar, C. Dnnham, A. Alavi. University of Pennsylvania Philadelphia, Pennsylvania, USA.

T H A L A N I C ASYMMETRY OF R E G I O N A L C E R E B R A L FLOW D U R I N G E M O T I O N A L S T I M U L A T I O N

Late onset depression is a common disorder affecting 3% of the general population >60 years old. The mechanism of depression, eleetroconvulsive therapy's (ECT) beneficial effect, and SPECT scan patterns in these patients still remain to be elucidated. We conducted this study in order to quantitata 1-123-IMP SPECT scan changes before and after therapy (antidepressant drugs or ECT). Five patients (2M, 3F; 71-90 years old; mean = 77) diagnosed as having major depressive disorder (DSM-III-R) by a psychiatrist, were studied with 1-123-IMP SPECT scans before and after ECT or anti-depressant drug therapy. Approximately 30 minutes after an IV injection of 5 mCi of 1-123-IMP, a brain SPECT scan was performed with a LFOV gamma camera (GE STAR CAM TM) equipped with a slant hole collimator (360 ~ rotation, AOR = 6 o, 40 san/view; 20% window @ 159 KeV) . Images were reconstructed into coronal, transaxial, and sagittal projections and ROIs were generated from which corresponding ratios were obtained using the carebellum as a reference. The pre-ECT SPECT scan was characterized by a global decrease in radioactivity supratentorially, especially in the frontal region but with relative sparing (normal-increased radioactivity) in the cerebellum. The post-SPECT scans however, demonstrated a significant (p <__ 0.001) improvement in the mean supratentorial]cerebellar ratio of radioactivity pre ( 0.822 + 0.035) vs post-therapy (0.876 + 0.041). This was supported by an improvement in the patient's mean Hamilton ( p r e = 19.4 =t: 3.7; post = 6.2 • 2.6) and clinically documented improvement. These preliminary results suggest a relative decrease in the supratentorial/cerebellar ratio in patients with clinically documented depression that improves post-therapy. Our preliminary findings may have important potential implications with regard to the diagnosis and management of these patients.

Tuesday, August 28, 1990

BLOOD J

NAVETEUR J . , ROUSSEAUX M . , R O Y J . C . , H U G L O D . , S T E I N L I N G M. UNIVERSITES OF L I L L E 1, L I L L E 2 , L I L L E 3 and C . H . R . U . ; L I L L E ; FRANCE The hypothesis of hemispherical specialization of e m o t i o n a l f u n c t i o n s has b e e n r a r e l y investigated with regional Cerebral Blood Flow (rCBF). One of the p u r p o s e of the present e x p e r i m e n t was to c o m p a r e rCBF recorded durlng neutral-and averslve auditory stimulations. S u b j e c t s w e r e 20 right h a n d e d h e a l t h y females w l c h were d i v i d e d In low and hlgh trait-anxiety subjects as assessed by the C a t t e l l ' s self a n a I y s l s Sheet (1958). rCBF was measured by the X e n o n i n h a l a t i o n m e t h o d using a dedicated SPECT tomocamera (TOMOMATIC 6 4 ) . S e v e r a l p a i r e d ROIs w e r e d r a w n at 3 tomog r a p h i c levels on s u p e r f i c i a l and d e e p areas. The m a i n e f f e c t o b s e r v e d as a f u n c t i o n of the a u d i t o r y s t i m u l a t i o n was a significant i n t e r a c t i o n w i t h the slde of the b r a i n In the thalamus : the a s y m m e t r y a p p e a r e d to be of o p o s l t e d i r e c t i o n d u r i n g the neutral (R > L) and emotlonal (L > R) s t i m u l a t i o n s . This c h a n g e was due to a d e c r e a s e of rCBF In the right side from the former to the latter sit u a t i o n w h e r e a s the teft rCBF s e e m e d similar in b o t h c o n d i t i o n s . Thls e f f e c t was not inf l u e n c e d by the subjects' anxiety. It Is dlsc u s s e d w l t h r e g a r d to the hypothesis of an higher sensitivity to e m o t i o n s of the right slde of the brain.

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R E G I O N A L C E R E B R A L BLOOD FLOW TRAIT-ANXIETY SUBJECTS

IN

HIGH

AND

LOW

NAVETEUR J, O V E L A C Q E, R O Y J . C . , S T E [ N L I N G H UNIVERSITES OF L I L L E I,LILLE 2, LILLE 3 AND CENTRE H O S P I T A L I E R REGIONAL. LILLE .FRANCE.

CHARACTERIZATION OF THE ELECTROMECHANICALACTIVITY OF THE PROXIMAL AND DISTAL STOMACH USING SCINTIGRAPHY. J.L Urbain, A. Vandecruys & M De Roo.Gaathuisberg University HoepitaLBelgium.

In t h e p r e s e n t experiment, regional Cerebral Blood Flow (rCBF) was measured, by the Xenon inhalation technique using a DSPECT system in I0 h i g h a n d i0 low t r a i t - a n x i e t y subjects as a s s e s s e d by the CattelI's Self Analysis Sheet (1958). All were volunteer right-handed and healthy fema|es, rCBF was recorded during neutral and aversive auditory stimulations. Heart Rate and End-Tidal PaC02 were recorded contlnously during the d a t a a c quisition. State-anxlety was retrospectlveIy assessed. High trait-anxiety subjects were mainly among high state-anxiety subjects. 6 paired R O I s w e r e d r a w n on t h e t h r e e b o m o g r a phic levels on superficial and deep areas. The data were anaJyzed using ANOVA methods. Results showed reduced r C B F as a f u n c t i o n of trait state-anxlety in m o s t of t h e r e g i o n s of i n t e r e s t taken into account .barring the frontal c o r t e x a n d the t e m p o r a l lobes. This effect did not interact with the emotional content of t h e a u d i t o r y stimuJations. A gIobaI d e c r e a s e of r C B F is then infered which c o u l d be d u e to a s i g n i f i c a n t hypocapnia linked to a n x i e t y . It c o u l d be c a n c e l e d in t h e frontal cortex and temporal lobes consequently to a n a n x i e t y - i n d u c e d increase of rCBF.

The purpose of this study was to develop and validate a new sointigraphic method to visualize and characterize gastric motility. Ten healthy volunteers were studied After an overnight fast, each subject ate a standardized test meal consisting of scrambled egg labeled with 3 mCi of Tc-99m-$c, bread and water. Immediately after ingestion of the meal, each volunteer sat between the two heads of a dualheaded gamma camera interfaced to a computer. Sixty four by 64 matrix with a 2.6 acquisition zoom list mode images of the etomach were acquired for 5 minutes at 15, 31, 61,91 and 121 minutes. Each set of list mode images was refrained in 250 msec. decay- corrected geometric mean images. A ROI was drawn around the antrum and antral time-activity curves were generated. Data were analyzed using first harmonic Fourier function to determine the frequencies (F) and the amplitude (A) of antral contractions. A curve-peak finding algorithm was then applied to each time-activity curve to indicate the slar't of every gastric cycle. List mode images were relramed 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. Repeatedly viewing the 20 frames of the pseudo-gated image in rapid sequence on the computer gave the dynamic motion of the gastric walls. The first harmonic Fourier analysis of the time-activity curve in each gastric pixel location of the 20 pseudo-gated images allowed for the determination of the pixels which had the eame relative timing during a gastric contraction. Assembling those pixels with the same timing during the gastric cycle in a color scale created phase images. The cloeed 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 for that cycle. Correlations between the antral time-activity curves cycle and gastric contractions were validated in 5 dogs using simultaneous isotopic and serosal electrogaatrographic resordingsJn volunteers, F increased with the emptying process. In contrast, A decreased progressively during the emptying course.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, contractione originate in mid-corpus and propagate aborrally to the pylarum This is in agreement with results obtained by other investigators with invasive technique.The scintigraphis test can be used to noninvasively and quantitatively characterize gastric motility and to delineate the spatial sequence of gastric contractions.This tool can be applied to study the pathophyeiology of gastric emptying in various motor disorders.

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616

THE SOLID-LIQUID GASTRIC EMPTYING: IS LABELING OF LIQUIDS USEFUL ? J.L Urbain, J.A. Siegel, V. Van den Maegdenbergh A. Vandecruys, L. Mortelmans & M. De Roo, Gasthuisberg University Hospital, Leuven, Belgium.

GASTRIC EMPTYING AND DRUG ABSORPTION OF A NAPROXEN PELLET FORMULATION. J.G. Hardy, G.L. Lamont, D.F. Evans, A.K. Naga, and O.N. Gamst. Queen's Medical Centre, Nottingham, U.K. and Nycomed Pharma, Oslo, Norway.

In this study we have tested the contribution of the labeled liquid phase of a physiological solid-liquid test meal in the evaluation of various gastric motor disorders. Forty patients were studied: 10 idiopathic dyspepsia (ID), 10 diabetics (D), 10 patients with proximal gastric vagotomy (PV) and 10 patients with a Billrcth II procedure (BII). Ten healthy subjects (C) matched for age were used to define the normal range of emptying. Gastric emptying of solids and liquids was determined after an overnight fast using Tc-99m-Sc scrambled egg and water with ]n-111-DTPA, respectively. Simultaneous anterior and posterior images were recorded for 2 hours using a dual-headed gamma camera and corrected for decay and downscatter. Geometric mean data were generated, Solid data were analyzed using the modified power exponential function { y =1- [1- e -kt] 8} to determine the lag phase (TLAG, rain.), the emptying rate (ER, min.-1) and the half emptying time (T 1/2, min.), The ER and T 1/2 were also determined for the liquids using a single exponential function. Results are summarized below (mean _+SEM) for the different groups.

C ID D PV BII

TLAG 29_+4 50_+9 36+11 47-+10

SOLIDS EFt 3.31 +1.t5 1.88+0.4 1.47+0.3 2.42-+0.43.24-+0.6

T1/2 46+5 87_+11 85-+13 78-+8 32_+7

LIQUIDS EFt 2.83+0.15 1.90-+0.3 1.48-+0.2 1.98_+0.2 3.00 + 0.6

22_+4 44-+6 53-+8 28_+3 26_+7

No significant difference was observed between the solid and liquid emptying rates in any group. T 1/2a differences between solids and liquids were accounted for by the solid lag phase. Using the T1/2'e control range values (mean -+ 2SD) to classify individuals into normal or abnormal, no patient with a normal solid emptying had an abnormal liquid emptying but 7 patients with an abnormal solid emptying were considered normal based on liquid emptying. We conclude that 1)the liquid phase of a mixed solid-liquid test meal is emptied from the stomach at the same rate as the solid phase after the solid lag period 2) liquid emptying is less discriminative than solid emptying to evaluate gastric emptying in patients with various gastric motor disorders. LabeJing of the liquid phase of a test meal increases radiation exposure without providing additional information.

S138

The aim of this study was to relate the gastric emptying of an enteric-coated naproxen pellet formulation to absorption of the drug. Gelatin capsules containing 250 mg naproxen in the form of enteric-coated granules, doped with samarium oxide, were radiolabelled by neutron activation. At the time of dosing each capsule contained i MBq Sm-153. Eight healthy subjects were each dosed with a radiolabelled naproxen capsule and a pH-sensitive radiotelemetry capsule on two occasions; after breakfast and whilst fasted. On a third occasion the subjects received a non-radiolabelled uncoated naproxen formulation whilst fasted. Blood samples were taken and analysed for the drug. Following dosing of the fasted subjects, more than 50% of the enteric-coated pellets emptied from the stomach within i hour. When dosed after breakfast, the mean time for 50% pellet emptying was 3.i h. The mean times for small intestinal transit following dosing under the fasted and fed conditions were 4.4 h and 4.9 h, respectively. The highest pN recorded in the stomach was 4.0. The pH in the small intestine rose to at least 7.3 in all subjects. The onset of drug absorption was fastest from the uncoated formulation and slowest from the coated pellets taken after breakfast. The total amount of drug absorbed was the same on all three occasions. It is concluded that the enteric-coated pellets provide a reliable dosage form for the administration of naproxen.

Tuesday, August28,1990

617

618

SHORT AND LONG TERM ORAL INTAKE OF ERYTHROMYCIN IMPROVES GASTRIC EMPTYING IN GASTROPARESIS DIABETICORUM. J.L Urbain, E. Vancutsem,J. Janasons, G. Vantrappen, M. De RoD. Gaathuiaberg University Hospital, Leuven. Belgium.

GASTROINTESTINAL TRANSIT AND POUCH EVACUATION IN PATIENTS WITH

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 gastroparesis diabeticorum after acute IV adminiatratian, The purpose of this study was to assess the effect of short and long term oral intake of Erythromycin using the dual radionuc]ide technique, Twelve diabetics patients with gaetroparesis symptoms were studied. A baseline study was first performed in each patient, followed by a second test after an 15 min. IV pedusian of 200 mgr, of Erythromycin starting 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. ti.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 downscatter. Regions of interest were manually drawn around the stomach for each anterior and posterior Tc-99m and In-111 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 + SEM) : SOLIDS LIQUIDS 60' 120' 60' 120' CONTROL RANGE 35-+5 9+3 17+3 4+1 BASELINE 75_+21** 54+24" 51 -+16"" 27-+11 ** IV ERYTHRO 22-+15~~ 6-+5~ 21-+15~176 9-+10~176 3 WEEK ORAL 61-+18 28-+20~ 49+20 20-+6~ 3 MONTH ORAL 61 -+18 28+20" 49-+20 20-+6~ **p< 0.005 versus Controls ~ ~p< 0.0005 IV and ~ p< O.05versus Baseline IV Erythromycin overnormalized gastric emptying and abolished the co-called solid-liquid discrimination phenomenon. Compared to baseline, gastric emptying of both solids and liquids remained accelerated after shod and long term oral intake, but the effect was less striking than after the IV perfusion and the distinction between solid and liquid curves persisted. Erythromycin appears to be a promising oral gaatrokinetic drug which could be useful in gastroparesis diabaticorum to better regulate the absorption of food and to improve the blood glucose control. Compounds with the gastrokinetic effect and without the antibiotic activity should open the door for the hormonal treatment of delayed gastric emptying.

619 THE

ASSESSMENT

RESTORATIVE PROTOCOLECTOMY A B Mostafa. L K Harding, K 8 Hasie, N J Tulley. N R Smith, M R B Keighley Department of Physics and Nuclear Medicine, Dudley Road Hospital and Department of Surgery, Queen Elizabeth Hospital, Birmingham. England. Restorative protocolectamy (pouch formation) preserves normal anal function in patients with severe ulcerative c o l i t i s . As the frequency of evacuation is l i k e l y to be related to the rate of gastrointestinal transit, we have assessed gastric emptying. i n t e s t i n a l t r a n s i t and pouch evacuation in 15 poach patients and in 6 ileostomy patients who served as controls. Following an overnight fast each patient consumed a standard 99Tcm-DTPA labelled meal. Anterior abdomen imaging using a gamma camera and computer began when the meal was started, and following complete ingestion alternate 2 minute anterior end posterior images were obtained at 15 minute i n t e r v a l s f o r a minimum

period of 6 hours. The pouch was identified on the left lateral image and each time the patient requested to defaecate they were seated on a radiolucent commode and 30 second images were acquired. The frequency of defaecatinn was recorded ever 2G hours. Computer images were corrected for positioning, decoy and scatter. Stomach emptying T~ was calculated from the geometric mean of a n t e r i o r and posterior, time a c t i v i t y curves (TAC). and the e f f i c i e n c y of pouch evacuatlon from the pouch TAC. There was no

significant difference in T~ values between ileostomy controls (Av. 57 m[n. range 25-144) and pouch patients (Av. 52 min, range 29-100; p>O.05. Mann Whitney). and the frequency of defaenation did not correlate with gastric emptying (P>O.05 Spearman Rank). The average ef ficiency of pouch evacuatlon was 47% (range 207~). Those who emptied their pouch less efficiently had more frequent defaecation (r=-0.77. p>O.01, Spearman Renk). Our preliminary results suggest that the frequency of evacuation is related more to efficiency of pouch emptying than to gastrointestinal transit.

620 OF

COLON

TRANSIT

IN

ADULTS

USING

In-111 DTPA AND COLON ACTIVITY PROFILES. R.Smart, R.McLean, J.Wilson, S.Barbagallo, D.Gaston-Parry, N.Lyons, D.Lubowski, D.King, C.Bruck. Depts. of Nuclear Medicine and Colorectal Surgery, St.George Hospital, Kogarah, NSW, Australia Colon transit scintigraphy is a promising new technique in the investigation of constipation. We have investigated the use of the non-absorbable tracer In-111 DTPA and activity profiles to describe the passage of the bolus through the colon. After an overnight fast, 4MBq of the tracer was given orally and anterior and posterior views of the abdomen were obtained at 6,24t48,72 and 96hrs. Geometric mean images were used to assess retention of the tracer in the colon. Profiles of the activity distribution along the colon from the caecum to the rectum were generated and displayed graphically. The mean position of the activity in the colon, expressed as a percentage of the total colon length, enabled the position of the retained activity to be expressed a single parameter. The time to 50% clearance (T50) was used to quantify the clearance rate of the tracer from the large bowel. Eleven normal controls and eleven constipated patients were initially evaluated by this technique. The mean + SD of the TSO values for the controls was 28.6 + 11-~I hrs, significantly different from the constipated group, 67.8 + 24.6 hrs, (p<0.001). A further 150 patients have -since been studied and the results have proved of great value in clinical management.

Tuesday, August 28,1990

R A D I O P H O S P H A T E A S S E S S M E N T OF A S Y M P T O M A T I C C E M E N T L E S S P O R O U S C O A T E D HIP P R O S T H E S E S L. R o s e n t h a l l , M. E. Ghazal, C.E. B r o o k s Montreal General Montreal, Canada

Hospital,

McGill

University,

A c r o s s - s e c t i o n a l s t u d y of 50 a s y m p t o m a t i c A M L h i p i m p l a n t s w a s u n d e r t a k e n to d e t e r m i n e the t e m p o r a l c h a n g e s in M D P a c c r e t i o n w i t h the age of the i m p l a n t . A g e of the p r o s t h e s e s r a n g e d f r o m 2 to 49 m o n t h s . All were primary i m p l a n t s and d i d not h a v e t r o c h a n t e r i c o s t e o t o m i e s or g r a f t a p p l i c a t i o n s . By c o m p u t e r a n a lysis, r a t i o s of the f e m o r a l stem, s t e m tip, intertrochanteric zone, g r e a t e r t r o c h a n t e r , lesser trochanter and adjacent calcar, and n o r m a l f e m u r to the r e f e r e n c e s a c r o i l i a c j o i n t and contralateral equivalents were obtained. It w a s f o u n d t h a t i m p l a n t s of less t h a n 12 months duration had significantly higher r a t i o s t h a n t h o s e m o r e t h a n 12 m o n t h s . Beyond 12 m o n t h s t h e r e was a w e a k or no c o r r e l a t i o n of the v a r i o u s r a t i o s w i t h the age of the i m p l a n t ; i n d i c a t i n g s t a b i l i z a t i o n of b o n e activity. On a v e r a g e the s t e m r e m a i n s 1.10 (sd 0.24) times h i g h e r t h a n the n o r m a l femur, and the a c c r e t i o n at the tip e x c e e d s the s t e m by a f a c t o r of 1 . 3 9 ( s d 0.35) a f t e r 12 m o n t h s .

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622

BONE SClNTIGRAPHY IN CEMENTLESS HiP ARTHROPLASTY 6 YEARS AFTER IMPLANTATION L.Eckart, M.Gericke, B.Gr6nert, R.Reyes, R.Felix Free University UK Rudolf Virchow, Berlin, FR Germany

OSSEOINTEGRATION OF CEMENTLESS TOTAL HIP ARTHROPLASTY: QUANTIFICATION WITH DIPHOSPHONATE BONE SCINTIGRAPHY M. Gericke. L. Eckart, A. Lemke, R. Reyes, R. Felix UC Rudolf Virchow, Free University of Bedin, FR Germany

99mTc-bone scintigraphy is acknowledged as a highly sensitive and specific method in detecting loosening processes in cemented hip arthroplasty. 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 hiemechanical 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" scinfigraphic pattern 50 patients from a prospective study underwent a clinical, radiological and scintigraphical investigation 6 years after cementless hip arthroplasty (titanium/aluminium/vanadium stem, polyethylen socket, System Zweym611er) 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 scinfigraphies 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. Conclusion: In about 40 % of the patients an increased reactive osteoblastic activity could still be detected in the femor 6 years after cemenftess hip arthroplasty without clinical or radiological signs of loosening due to bony ingrowth of the titanium alloy stem and also radiologically visible biomechanical adapfion. 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 cementless hip prosthesis typical scintigraphic patterns have to be established and correlated to the radiographs to avoid misinterpretation of the images. The acetabular region with the polyethylen socket showed no increased osteoblastic activity after 6 years.

623 I N%-E S T I GAI~0R- I ICDEPENDENT QUANTITATIVE SCINTIGRAPHY IN PATIENTS WITH ENDOPROSTHESIS O F T H E H I P (HTEP) .

In cementless total hip arthroplasty (THA) the secondary fixation of the prosthesis through osseointegratiori is necessary to achieve long term stability. In postoperative management and evaluation of painful hip arthroplasty it would be very helpful to know the normal course and duration of the bony ingrowth of the implant. The aim of our study was to quantity the osseointegration of the prosthesis.with 99mTc-diphosphonate 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 99mTc-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, Conclusion: 1 week after THA scintigraphic activity largely depends on bone trauma and hyperperfusion, after 3 weeks the beginning osseointegrafion is mostly responsible for the osteoblastic activity. 6 months later the osteoblasfic activity decreased but is still enlarged due to ongoing bony ingrowth and adaption on biomechanical needs. After 12 months the decrease of osteoblastic activity continues but is still enlarged compare to normal bone, A different scintigraphical behaviour may be a sign of non-integration of the prosthesis or loosening processes especially if there were met by clinical or radiological findings.

624 BONECEMENTLESS

D. arecht-Krauss, C.T. Trepte*, B.A. Bitter, F.Bitter, S. Glatz, W.E. Adam and W. Puhl* University of Ulm, Nuclear Medicine and Clinic of Orthopedics*, Ulm, FRG Since several years cementless hip replacement has ben prefered to achieve better long term results. Dimension, duration and course of bonereaction is different to those of cemented BTEP. In order to solve this problem and to diagnose instability of hip 32 patients were studied by quantitative bonescintigraphy. Beside clinical and radiological investigation scintigraphic studies were performd regularly up to 3 years postoperativly. Quantitative evaluation was done by computerassisted gradientimaging, defining ROI's investigator-independently. Count-density ratio of different regions of HTEP were determinded. The most important of all the calculated values where the Shaft_op/Shaft_nop (Sop/Snop) and Diaphysis_op/Diaphysisnop (Dop/Dnop) ratio. In 21 patients an identic follow-up curve was observed to an level of 1.26 • 0.13 for Sop/Snop and 1.38 • 0.23 for Dop/Dnop on year postop, ii patients demonstrated values of Sop/Snop of 1.72 • 0.44 and Dop/Dnop of 1.84 • 0.45 one year postop. 7 of them showed loosening of the hip intraoperatively. 3 years after the hip replacement we found a Sop/Snop of 1.04 • 0.14 and Dop/Dnop of 1.12 • 0.14 for the normal group. The pathological group showed values of 1.84 • 0.45 and 1.81 • 0.41. 5 patients underwent surgery by loosening of hip prosthesis.

QUANTITATIVE DETECTION OF CHANGES IN THE PATIENTS WITH HIP ENDOPROTHESIS P.Predi~,

Hospital Celje, Celje, Yugoslavia

In diagnosing the instability of hip endoprosthesis the main problem is early diagnosis for the purpose of possible repeated surgical correction. Often, there is no correlation between clinical symptoms and other examination methods. Therefore, we have introduced in the 3-phase-bone scanning of both hips with Tc-99m-DPD also the quantitative assessement of relative perfusion in the artery phase (3T) in order to impartially establish and follow up perfusion changes. 52 pts with a hip endoprosthesis were submitted to the 3-phase-bone scanning with quantitative assessement of 3T. In the follow up period 25 pts underwent a repeated study. In 34 pts with a stable hip endoprosthesis 3T ranged between 0.18 and 0.41. The study was repeated in 16 pts and 3T showed stable low hip perfusion amounting from 0.18 to 0.36. In the group of 18 pts with observed changes, i.e. hip instability, 3T ranged from 0.62 to 1.31 indicating increased perfusion of the surrounding tissue. In 9 pts of this group who underwent a repeated study we observed the increase of relative perfusion so that 3T in this group ranged from 0.74 to 1.92 indicating the worsening of state. We can conclude that the 3T quantitative diagnostic is an unbiassed method in diagnosing, following up and defining early changes of hip endoprosthesis, and anables us to decide on proper treatment.

We conclude: cementless HTEP demonstrate another bonereaction than cemented one. An increased traceruptake on the tip of the shaft is not identical with loosening as by cemented prosthesis. Quantiative investigator-independent bone scintigraphy is therefore a sure and objective method in diagnosis and treatment of hip loosening, especially if radiological signs are absent.

S140

Tuesday, August28,1990

625

626

ROLE OF BONE SCINTIGRAPHY IN DIAGNOSIS AND PROPHYLACTIC MANAGEMENT OF PARAARTICULAR OSSIFICATIONS AFTER TOTAL HIP ARTHOPLASTY L.Eckart, M.Gericke, C.Otto, F.l<&stner,J.Pannhorst Free University UK Rudolf Virchow, Berlin, FR Germany

IMPAIRED LEFT LOWER LOBE VENTILATION - AN ISOTOPE STUDY OF MECHANISMS. MS A l e x a n d e < , J C l e l a n d , BL H e n d e r s o n , AM P e t e r s , JMB H u g h e s , a n d JP L a v e n d e r . H a m e r s m i t h H o s p i a l , L o n d o n W12 0HS, E n g l a n d

Ectopic ossifications after total hip arthroplasty (rHA) 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-diphosphonata sequence scintigraphy 7 days, 3 weeks and 6 months after cementless THA. Radiographs were done 3 weeks and 6 months affer 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. Conclusion: 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 affer 3 weeks and ineffective methods can be ruled out without waiting 6 months for the radiographic examination.

We have shown p r e v i o u s l y a s i g n i f i c a n t correlation between cardiac enlargement and reduced left lower lobe v e n t i l a t i o n on r o u t i n e V/Q scanning. In a prospective s t u d y on 19 p a t i e n t s with large hearts a marked improvement in left lower lobe v e n t i l a t i o n was seen in the prone compared with the s u p i n e position. A l t n o u g h t h e r e was a s i m i l a r change in normal v o l u n t e e r s t h i s was less marked. In order to e l u c i d a t e the mechanism of this change 1 l p a t i e n t s with enlarged hearts were studied, the change in the difference in signal at r i g h t compared with the left base being expressed as a r a t i o on p a s s i n g from supine to prone. ]n those showing a reduction in v e n t i l a t i o n at the left bases using inhaled K r - S l m the r a t i o on moving f r o m supine to prone was 2.40 (+0.46) r e p r e s e n t i n g a real increase at the left base (no changes were seen at the r i g h t base). No change was seen with intravenous Tc-99m MAA acting as a marker of lung position (0.96 +__0.08). or in regional lung perfusion u s i n g intravenous Tc-99m MAA and the peak of the injected Xe-133 curve (1.1 + 0 . 2 1 ) . There was also no change in v e n t i l a t o r y turnover, and thus no evidence of air trapping, from the injected Xe- 133 washout curve (1.35 +_ 7 t). Combining the Xenon washout and Krypton data to produce an index of volume change produced a s i g n i f i c a n t r e d u c t i o n at the left base (3.05 f. 1.7). This suggests the mechanism of the phenomenon may he due to lung compression and alveolar closure, and that a change in p o s i t i o n reverses this closure and thereby improves lung v e n t i l a t i o n and gas exchange.

627

628

QUANTITATIVE LUNG PERFUSION SCINTIGRAPHY IN THE FOLLOW-UP OF SINGLE LUNG TRANSPLANTATION. O. M e s s i a h , H. M a ] , C. S l e i m a n , B. A n d r e a s s i a n , B. B o k . H e s p . B e a u j o n , Clichy, France.

CLINICAL EVALUATION OF Kr-81M INHALATION STUDY WITH DEAD SPACE. S.Tominaqa, T.Shimada*, Y.Mori*, K.Kawakami*. Juntendo Urayasu Hospital,Tokyo, Japan. *Jikei University, Tokyo, Japan.

The

diagnosis of rejection after single transplantation is difficult and requires transbronnhic biopsy. Serial quantitative perfusion scintigraphies were performed in 7 patients transplanted for severe emphysema (5), fibrosis (1) and h i s t i o c y t o s i s X ( 1 ) . The f o l l o w - u p l a s t e d from 6 to 24 months, and 61 a n t e r l o r and posterior views were analyzed. A "transplanted ratio" (TR) was estimated for both i n c i d e n c e s as the number of counts over the transplanted lung, on t h e t o t a l number r e c o r d e d on b o t h lungs. The p o s t - o p e r a t i v e v a l u e of TR was 6 9 . 5 -+ 7 % and r e m a i n e d u n m o d i f i e d when no c o m p l i c a t i o n occured. In c a s e s of r e j e c t i o n {n = 9 e v e n t s ) , a similar decrease in TR was constantly o b s e r v e d on b o t h anterior and posterior views. After immunosuppressive therapy, TR r e t u r n e d to p r e v i o u s v a l u e s In c a s e s of b r o n c h i a l o b s t r u c t i o n due to isehemie problems, t h e d e f e c t s i s more limited and TR d e c r e a s e s q u i t e o n l y i n one incidence. Lung p e r f u s l o n s c i n t i g r a p h y i s of h e l p in monitoring single lung transplantations. lung often

Tuesday, August

28, 1 9 9 0

A new inhalation technique of Kr-81m gas was applied to e v a l u a t e the p a t h o p h y s i o l o g i c a l abnormality of ventilation. Kr-81m gas(370MBq) was continuously s u p p l i e d through a mouth piece (without a dead space) VE, or with 500ml of dead space, VL, in II0 p a t i e n t s h a v i n g v a r i o u s lung diseases. Patients were divided in four groups by a combination of distribution pattern of Kr-81m gas obtained by these two inhalation techniques. G r o u p I: No v e n t i l a t o r y d e f e c t found in e i t h e r techniques. Group 2: Lager defects found in VE than VL. Group 3: larger defects larger found in VL than VL. G r o u p 4: No r e m a r k a b l e d i f f e r e n c e found in defects in either techniques. Most of the cases of group 1 were normal by pulmonary function test and chest X-ray. Finding of group 2 reflects early airway closure. This group represents the cases of remission of bronchial asthma, small air way disease or pulmonary congestion. In group 3 restrictive disease or o b s t r u c t i v e desease obstructive particularlly emphysema, were included. Patients with severe obstructive desease or o r g a n i z e d change of p u l m o n a r y parenchyma were categorized in group 4. Among various methods involved in ventilation study with Kr-81m gas, an inhalation technique combined with dead space, and without dead space is quite useful to e v a l u a t e a pathophysiological c h a n g e of various pulmonary diseases.

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63O

HI6~ PROBABILITY OF P ~ N A R Y EMBOLISM IN THE YOUNG PATIENT WITH LOCALIZED PLEURITIC CHEST PAIN AND SMALL SUBSEG~4ENTAL PERFUSION DEFECT. E.Kotlyarov, R. Reba; George Washington University Medical Center, Washington, D.C. U.S.A.

IMAGING

Multiple diagnostic criteria published during the last decade consider small (less than 25% of a pulmonary lung se~nent) subsegmental perfusion defect with or without ventilation mismatch as a low probability for pulmonary embolism. During the last eight years we have observed 9 cases with single small subsegmental perfusion defect in a young patient (less than 45 yrs. old) referred for a ventilation and perfusion lung scan With complaints of sudden localized pleuritic chest pain. Each subsequently had pulmonary angiography performed. Seven of the nine patients (77%) had angiographic evidence of pulmonary embolism (intral~m3inal clot) in the area of the perfusion defect. Four patients had pleural effusion on the chest x-ray, and two of those patients had no angiographic evidence of pulmonary embolism. Conclusion: A single small subsegmental perfusion in the young patient with localized sudden pleuritic chest pain should not be interpreted as low probability of pulmonary embolism, and pulmonary angiography should be considered to finalize the diagnosis.

631 COMPARISON OF TECHNETIUM-99M AEROSOL AND KRYPTON 81M FOR VENTILATION STUDY IN DIAGNOSIS OF PULMONARY EMBOLISM

P. PELTIER, PH. DE FAUCAL, A.CHETANNEAU, JF CHATAL. NANTES, FRANCE. 99m TC - C aerosol (Technegas) was evaluated by comparing 99mTc - C images with those obtained with 81m Kr in the same patients. Method : Twenty-five patients (10 with COPD) with suspected PE were studied. The patients, in dorsal decubitus, inhaled 99mTc-C radioaerosol using the method described by Burch. Immediately after inhalation, 4 ventilation views (ant,lop,post top) were recorded with 200 k precounts. Immediately after the last view, the patient remained in the same position and inhaled 81mKr at tidal volume.The same 4 views were then recorded with 200 k precounts. All images were recorded with a medium energy collimator. 99mTc - C and 81mKr images were blindly compared for : (i) qualitative quality o! ventilation images, (ii) quantification of penetration (PI) and heterogeneity (HI) indices, and (iii) ventilation interpretation. Results : The difference between the mean PI of 99mTc-C (0.91) and 81 mKr (1.04) was significant (P < 0.03), as was the difference in mean HI between 99mTc-C (23) and 81mKr (14) (P = 10"4). 81mKr images were considered either very good or good quality for all patients. In 9 patients with COPD, 99mTc - C images showed moderate bronchial uptake in 6 patients and clearly apparent uptake in 3. For 3 patients ventilation interpretation of 99mTc-C and 81mKr images was discordant. Conclusion : Submicronic 99mTc-C radioaerosols, though not to be considered as gases, enable good quality ventilation images to be obtained in nearly all cases and provide results similar to those obtained with 81mKr. Differences between the quantitative parameters for assessment of the two radionuclides are not evident in most cases on ventilation images.

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PULMONARY THROMBUS

WITH

INDIUM-Ill

LABELLED ANTIPLATELET M O N O C L O N A L ANTIBODY. IE [ a c k s o n , A W J S t u t t l e , A11ison, a n d J P L a v e n d e r ,

BL H e n d e r s o n ,

AM P e t e r s ,

DJ

We have recently d e s c r i b e d an I n - I l l labelled Fab' fragment of the monoclonal antibody P256, which has a high a f f i n i t y for the Ilb Ilia I i b r i n o g e n receptor on platetets and can be used to i d e n t i f y venous t h r o m b o s i s . The aim of t h i s s t u d y was to d e t e r m i n e the s e n s i t i v i t y of P256 for i m a g i n g p u l m o n a r y thrombus. To image p u l m o n a r y t h r o m b o s i s , we s t u d i e d s i x patients with p u l m o n a r y a r t e r i o v e n o u s malformations who have undergone percutaneous transvenous embolization. In-I 11 P256 was injected i m m e d i a t e l y a f t e r embolization in three p a t i e n t s , and 3, 18 and 24 hours post embolization in one patient each. Images were a c q u i r e d at 12 hours a f t e r injection. In three patients, all lesions were demonstrated by p l a n a r imaging. In one patient, two major lesions were seen out of a total of six that had b e e n e m b o l i z e d . The f o u r u n d e t e c t e d e m b o l i z e d malformations were at the left lung base and were obscured by high splenic activity, In two patients, those injected at 18 and 24 h o u r s following embolization, none of the s i x embolized malformations were detected. We conclude that I n - I l l P256 is able to detect t h r o m b u s in the p u l m o n a r y a r t e r i e s in a h i g h proportion of eases, but only when injected soon a f t e r thrombus formation.

632 INTRAARTERIAL Y'I-FRIUM-90 GLASS MICROSPHERES FOR INTERNAL RADIATION THERAPY OF HEPATOCELLULAR CARCINOMA. S. Houle, K. Yip, F.A. Shepperd, L.E. Rotstein, K. Paul, K.W. Sniderman. Toronto General Hospital, Toronto Ontario, Canada. Internal radiation therapy with hepatic artery injection of Yttrium-90 glass microspheres (Theraspheres) was evaluated in 16 patients with hepatocellular carcinoma. A hepatic artery catheter was placed percutaneously under fluoroscopic guidance in 15 patients and surgically in one. Prior to treatment, the presence of extrahepatic shunting was assessed by injecting Tc-99m human albumin microspheres or macroaggregates of albumin (MAA). In six patients significant shunting to the lungs was present. One patient also had significant shunting to the stomach. These patients could not be treated because significant radiation damage to the lungs or stomach would have resulted. In the remaining 10 patients, the therapeutic dose ranged from 1,500 to 6,300 MBq. The intrahepatic distribution of Y-90 was assessed by Bremsstrahlung scanning. No toxicity was observed except in one patient who developed a gastric ulcer shortly after treatment and believed to be due to gastric shunting not seen on the MAA scan. Tumour size reduction was not seen after treatment. In two cases, tumour growth was halted for several months. Two patients are still alive after 46 and 146 weeks. The other patients survived from 3 to 92 weeks, average of 23 weeks. Y-90 glass microspheres can safely deliver large internal radiation doses to hepatic tumours as long as extrahepatic shunting can be excluded. Extrahepatic shunting is frequent with hepatocellular carcinoma and is the main limitation to this form of radiation therapy.

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MICROENCAPSULATED B EMITTING RADIONUCLIDES FOR THE TREATMENT OF TUMORS BY RADIOEMBOLIZATION

CRITICAL EVALUATION OF 1-131-LIP[ODOL THERAPY FOR HEPATOCELLULAR CARCINOMA. C.H. Park*, H.S. Yoo**, J.H. Suh**. *Thomas Jefferson U n i v e r s i t y Hospital, Philadelphia, PA, USA, **Yon-Sei U n i v e r s i t y Hospital, Seoul, Korea.

J.J. LE JEUNE, A. ERMIAS, P. BEAU, R. PERDRISOT, POULIQUEN, J. LEGER, A. LE PAPE , P. JALLET. ( C.H.U. ANGERS, C.H.U. TOURS - FRANCE)

D.

We present the results obtained by radioembolization of mouse B16 melanome using encapsulated colloid Rhenium 186 (Re 186). Selective chemoembolization of tumors is well known and has been described several times but to date the carrying of 13emitting radionuclides has not been widely investigated. This study concerns the preparation properties and use of biodegradable microcapsules labelled with colloidal Rhenium 186. This radionuclide is characterized by a reasonably long physical half life of 90 h and a strong 13emission (1Mev). A single gamme emission of 137 Key made possible the study of capsule biodistribution the acquisition of scintigraphic images and the evaluation of the dose delivered to the tumor. Biodegradable mierocapsales, I0-I5~m in diameter are manufactured by inteffacial polymerization of isobutil-cyanoacrylate encapsulating Re 186 previously dispersed in an organic phase. Microcapsules are injected in the single pedicular artery of B 16-melanom~ induced in mice (C57B 16/J strain) and metabelie follow up is assessed by 31P. Magnetic Resonance Spectroscopy (MRS) on a AM 200 WB BRUKER spectrometer and by measurement of tumor size. The results demonstrated that more than 90% of the radioactivity injected remained within the tumor. After delivery a dose estimated at 75Gy to the tumor, there was in MRS an increase followed by a decrease of NTP/Pi and PCr/Pi ratios. Furthermore tumor volume measurements showed arrested growth until day 3, then slow but progressive growth until day 8 with however a clear differencebetween treated and non treated tumors. In conclusion our results showed that mdioembolization with high activity can be used on the treatment of focalized rumors.

I n t r a - a r t e r i a l l y i nj ect ed radioiodinated Lipiodol (*L) or Ethiodol (*E) has been used in the treatment of h e p a t o c e l l u l a r carcinomas (HCC) in recent years, since i t is s e l e c t i v e l y l o c a l i z e d in vascular HCC. The purpose of t h i s r e p o r t i s t o c r i t i c a l l y evaluate i t s i n d i c a t i o n s , side e f f e c t s , l i m i t a t i o n s and e f f i c a c y in the management of HCC. Since February 1986, more than I00 p a t i e n t s with vascular HCC were treated with *L or *E alone or in conjunction with other m o d a l i t i e s . Following the treatment, p a t i e n t s were evaluated with follow-up examination, serum alpha f e t o - p r o t e i n (AFP), u l t r a sound (US), Ga-67 scan, computed tomography (CT), angiography, biopsy and surgical resection, whenever feasible. The smaller the vascular tumor without shunt, the better the therapeutic response. Large ( >4.5 cm in diameter) tumors treated more e f f e c t i v e l y in conjunction with i n t r a - a r t e r i a l chemotherapy, t r a n s a r t e r i a l embolization (TAE) and byperthermia. Intratumoral shunt can be evaluated by scanning chest and abdomen f o l l o w i n g hepatic a r t e r i a l i n j e c t i o n of Tc-99m MAA. Side e f f e c t s from the treatment include f e v e r , nausea, vomiting, pain in upper abdomen and elevation of l i v e r function t e s t s . These are mild and tolerated well by the patients. In summary, radiolabeled L or E can d e l i v e r high i n t e r n a l r a d i a t i o n to small vascular HCC without a significant shunt and the t r e a t m e n t may p l a y an important r o l e f o r large HCC in conjunction with other e x i s t i n g therapeutic m o d a l i t i e s .

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I 131-LIPIODOL IN THE TREATMENT OF H E P A T O CELLULAR CARCINOMA 9 R ESULTS OF A MULTICENTER PHASE I I STUDY OF FIFTY P A T I E N T S .

COLLOIDAL IRRADIATION

J.J.LE JEUNE, P.BOURGUET, G.VICTOR, F.THERAIN, B.LEMAIRE, H.COLLET Angers, Rennes, Toulouse, Orl6ans, Lille, M o n t p e l l i e r (FRANCE) W e conducted a multicenter phase II study to assess the therapeutic efficacy of I 131-Lipiodol in the treatment of hepatocellular carcinoma (HCC). Fifty patients (47 men, 3 women) with inoperable HCC were entered into the trial. According to OKUDA classification, 18 patients had stage 1 d i s e a s e et 32 had stage 2. D i a g n o s i s was c o n c e r n e d histologically (n=25), cytologically ( n = l l ) , or by a serum A.F.P. level > 500. A thirst injection of I 131-Lipiodol was given one to four weeks prior to the therapeutic injection to study biodistribution. Efficacy was assessed by tumor size, A F P levels, and survival. 55+14 mCi were injecte6, 15 patients received 2 injections and 2 had 3. Dose delivered to the tumor as well as to the liver and lungs was estimated in all cases~ Our results confirmed that I 131-Lipiodol, was well tolerated. Pain disapeared in 8 out of 11 patients. The A F P levels and/or tumor size showed : 0 complete responses, 20 incomplete responses, and 10 partial responses (for one of the 2 parameters), i.e. a level of 60%. Survival, at 6 months, at 12 months and at 2 years, was 60%, 31% and 23% respectively. In conclusion, our results have encouraged us to continue the treatment of HCC with I 131-Lipiodol and to carry out a phase III trial.

T u e s d a y , A u g u s t 28, 1 9 9 0

186Re IN THE ENDOCAVITARY OF CYSTIC CRANIOPHARYNGIOMAS

S. Askienazy, B. Turak, M L . Piketty, C. Munari, M D . ~ ~ b t a h i , A. Dilouya, JP. ChodkJewicz C/4. Saints-Anne, Paris, Fz-ance Mortality and morbidity of the surgical removal of craniopharyngiomas remains high. Since the majority of these ben,/n, slow growing tumors are totally or in large part cyst/c, treatment of the cystic component is the major part of the therapeutic attitude and simple aspiration has not proven to be an adequate treatment. In order to prevent recurrence intracyst/c injection of colloidal 13 ~m itting radioisotopes is currently perfon~ed in several centers. The main risk of this procedure is the irradlat/on of vital neighbouring areas by the cyst, and brain, liver, kJdneys, and bone marrow in case of leakage of the cystic contents. W e used 186Re colloidal sulfur to treat 41 patients harbouring cystic cranio-pharynglomas. This choice was based on a) [3 emission has a mean penetration of about imm, thus sparing vital neighbourisg areas b) g a m m a emission (137KEY) allows perfect survey of the radiolactive distribution in a search for possible leakage, c) T 89 (90~ h) enables the delivery of the total dose over a shorter period and a sooner reaspiratJon of cystic contents. Protocole is as follow: a)Inject/on of a test dose in the cyst. b~rain, liver, kidneys ~ a g e s are made at 0~4~B,72~96 hours pi. to verify cyst tightness and co//o~d absorpt/on on cyst walls. c)In absence of leakage injection of a therepeut/c dose (0,7-1~GBq) depending on cyst volume and % of retention d) new follow up and in case of leakage (activity in subarachnoid space (SAS)), liver, kidneys aspiration and washing of cyst and SAS. We have found 186Re colloidal sulfur to be a satisfactory radioisotope preparation for use in the stereotactic treatment of cystic cran~opharynglomas.

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TREA~ OF RHE~V~TOID ARTHRITIS WITH Y-90 EVALUATED BY QUANTITATIVE Tc-99m k~4PAO WBC AND Ga-67 SCAN. S.J. Wanq, S.H. Yeh, C.H. Kao, J.L. Lan, D.Y. Chen, and M.S. Lin. Veterans General Hospital, Taichung, Taiwan.

CEREBRAL BLOOD FLOW IN HEALTHY SUBJECTS WHOSE AGES RANGE FROM 1.3 TO 80 YEARS : SENSITIVITY TO AGE, BRAIN SIZE AND GENDER. A. Komatani, K.Yamaguchi, T.Akutsu. M. Kera and T.Takanashi. Yamagata University S~hool of Medicine, Yamagata, Japan.

This investigation assessed Tc-99m ~94PAO WBC (Tc-WBC) and Ga-67 knee uptake indexes before and after Y-90 treatment in patients with intractable rhet~natoid arthritis (RA) and to correlate the uptake indexes with the clinical score. Sixteen knee joints with RA were treated with intraarticular injection of 5 n~Si of Y-90 silicate colloid (Amersham) flushed with 50 mg of hydrocortisone. Clinical score, quantitative Ga-67 and Tc-WBC knee uptake indexes were obtained before and three weeks after treatment. A clinical score w-as derived from subjective and objective scores. Subjective scores were imp r o v e ~ n t and pain (at rest and on exercise) compared to the pretreatroent state. Objective scores were effusion, knee size and movement. A-P view of knees w~s obtained at 24hr after injection of 5 mCi of TcWBC and 48hr after administration of 3 mCi Ge-67. Quantitative knee uptake index %gas performed by establishing and comparing radionuclide accumulation within regions of interest over the knee and a remote area of soft tissue. Our results showed that 9/16 (56%) had a good response and that 7/16 (44%) had a poor response to Y-90 injection. There was poor correlation between clinical improvement and the changes of Ge-67 and TcWBC knee uptake indexes (r=0.46, 0.14, respectively). In s~aTery, clinical improvement was apparent in 9/16 (56%) of Y-90 treated knees. Both the changes of Ga-67 and Tc-WBC knee uptake indexes have a poor correlation with the clinical ir~rovement.

Cerebral blood f l o w was measured in 56 h e a l t h y subjects who ranged in age from 1.3 to 80 years. The Xe-133 inhalation method with ring type single photon emission computed tomography (SPECT) ; HEADTOME was used. These values were corrected f o r end-tidal C02 concentration that had an excellent c o r r e l a t i o n with PaC02 and was one of the most s e n s i t i v e f a c t o r s to change cerebral blood flow. The brain-size index was obtained by measuring the l a t e r a l and antero-posterior diameters from the SPECT images. The mean cerebra] blood flow in children less than f ive years of age was approximately twice that found in a d u l t s , The mean c e r e b r a l blood f lo w decreased rapidly w i t h age u n t i l 22-24 y e a r s o f age. Thereafter, there was a slow decrease and a negative c o r r e l a t i o n with age was found, In adults, the mean value o f the c e r e b r a l blood f l o w o f females was s l i g h t l y higher than that of males. In contrast, the brain-size index of females was s i g n i f i c a n t l y smaller than that in males. There was a s i g n i f i c a n t negative c o r r e l a t i o n (r=-O,40, p
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ASSESSMENT OF CEREBRAL PERFUSION RESERVE BY THE ACETAZOLAMIDE TEST USING Te-99m HMPAO SPECT. H. Matsuda, S. Higashi, K. Kinuya, K. Hisada, J. Yamashita. Kanazawa University Hospital, Kanazawa, Japan.

A GEOMORPHOLOGICAL DFSCRIFfION OF THE ABSOLUTE UPTAKE, CORTICAL DISTRIBUTION AND WASHOUT OF 1-123 IODOAMPHETAMINE (IMP) IN A GROUP OF NORMAL SUBJECTS. G. Lamoureux, R.M. Dupont, J.C. Gillin, W.L. Ashburn & S.E. Halpern. U. de Sherbrooke, Sherbrooke, P. Quebec, V.A. Hospital and U. of California, San Diego, CA.

A new m e t h o d using brain Te-99m HMPAO SPECT imaging was developed for evaluating cerebral perfusion reserve by the acetazolamide (DIAMOXR;D) test. The Ist SPECT study was performed for 15 min to obtain baseline images after 3 rain p.i. of 555 MBq of HMPAO using a high resolution system (Toshiba, GCA9300A). At the same time as the start of the Ist study, 1 gm of D was intravenously injected. Immediately after the stop of the Ist study, 925 MBq of HMPAO from the same vial was additionally injected. Three minute later the 2nd SPECT study was carried out for I0 rain. After reconstruction the tomographie images in the Ist study corrected for data acquisition time were subtracted from the images in the 2nd study to obtain those during the D t e s t . This subtraction technique gives independent SPECT images before and during the test. Besides regional fl0w changes were quantitatively e s t i m a t e d . T h i s m e t h o d was a p p l i e d to 14 p a t i e n t s w i t h c e r e b r o v a s c u l a r d i s o r d e r s . Mean r e g i o n a l f l o w i n c r e a s e b y D w a s 18 --+ 7 Y. in t h e u n a f f e c t e d c o r t e x . A d d i t i o n a l information about the perfusion abnormality of focal ischemia over baseline studies was obtained by the test in 13 o f 14 p a t i e n t s (93%); b a s e l i n e n e g a t i v e v . s . D positive in 5 c a s e s , b a s e l i n e p o s i t i v e v . s . D more positive in 7 c a s e s , and b a s e l i n e positive v.s. D n e g a t i v e in o n e c a s e . In c o n c l u s i o n t h i s m e t h o d s e e m to be p r a c t i c a l l y useful for evaluating regional brain perfusion before and during the D test as a consecutive study with a short period of approximately 30 min.

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The aim of this study was to describe quantitatively the cortical uptake and distribution of IMP in a group of 17 subjects, selected from a normal control pool. SPECT imaging was done 28 ~dnutes, 2 hours and 4 hours after injection of IMP. Quantitative maps of the cortical uptake (outer 2.4 cm of brain) were generated for each one with "Cort-Ex", a program for the armlysis and geomorphologieal presentation of brain SPECT data. Based on the individual cortical m~ps, we calculated a mean uptake (MU) and a standard deviation (SD) r~p for each time period. Washout (WO) maps for t ~ 2 0 2hrs and the 2@'-4hrs time intervals were calculated from the MU maps. In this group, the global uptake of the cortex was reduced by 13 % at 2hrs and by 19 % at 4hrs. At 2~', the MU was maxirou~j in the occipital, cerebellar and supra-temporal areas, The distribution of the tracer became more uniform with time The SD was maximum around the eerebello-occipital area at 2 @ , becomir~ maximum in the cerebellum at later ti~s. T~ WO was maximum around the cerebellum, the md-sagittal line and the supra-teml~ral areas. To further assess the potential utility of this data, the IMP studies of a few patients with l~own disease were evaluated in terms of their relation to the MU map +/- 2.5 SD; the areas known to be abnormal were clearly depicted. We conclude that this geomorphological approach looks irconlising for the quantitative assessment of IMP uptake and distribution over time. Ck~r study further suggest that normalization of data based on cerebellar IMP uptake could induce an extra and unnecessary bias.

Tuesday, August28,1990

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THE INFLUENCE OF WASH-OUT TO 1-123 IMP CBF IMAGING K.Kimura, H.Moriwaki**, K.Hashikawa*, A.Uehara*, T. Kozuka*, M.Matsumoto** and T.Kamada**, Biomedical Research Center, *Dept. of Nucl. Med. and * * I s t Dept. of Med., Osaka U n i v e r s i t y Medical School, Osaka, Japan.

TEST-RETESTCOMPARISONOF REGIONALCEREBRALBLOODFLOW (rCBF) ACTIVATION DURINGA SPATIAL LOCATIONTASK. CL Gradv, JV Haxby, B Horwitz, MB Schapiro, P Herscovitch, RE Carson, SI Rapoport. Nat. Institutes of Health, Bethesda, MD, USA.

Introduction: In general, the a c q u i s i t i o n of Nisopropyl-(l-123)-p-iodoamphetamine (IMP) image is started at I0 - 20 min a f t e r i n j e c t i o n and continued f o r 20 - 40 min. During a c q u i s i t i o n , the brain r a d i o a c t i v i t y is r e l a t i v e l y stable. But t h i s stable state ~s made by the equilibrium of the wash-in and wash-out. For precise q u a n t i t a t i v e measurement o f cerebral blood flow (CBF), the regional dynamics in t h i s period should be considered. Methods: In 5 p a t i e n t s with chronic cerebral vascular di'sease, we acquired dynamic images o f brain r a d i o a c t i ~ i t y by SPECT and a r t e r i a l blood r a d i o a c t i v i t y By continuous withdrawl during f i r s t 33 min a f t e r intravenous i n j e c t i o n of 3 - 6 mCi IMP. The SPECT system used is 4-head r o t a t i n g gamma camera which has been developed by us and has good s e n s i t i v i t y and r e s o l u t i o n . Assuming t h a t IMP could be a kind of d i f f u s f b l e t r a c e r with slow clearance r a t e , the regional wash-out rate and CBF were calculated. Results: The average wash-out rate (described by h a l f t i ~ e ~ n d CBF o f one s l i c e including the basal ganglia were 4g.6~12 (min) and 34.8~18.7 (ml/lOOgr/min), r e s p e c t i v e l y , In the regional image, the h a l f - t i m e of IMP was varied from 19 to more than 120 min and showed negative c o r r e l a t i o n with CBF (r=-O.86,p
To examine reliability and inter-subject differences in patterns of rCBF activation, rCBF was measured using (O-15)water and PET (Scanditronix PClO24-7B) during repeated performance of two visual tasks, a spatial location and a control task. Our previous work has shown bilateral superior parietal activation during the the spatial task relative to the control task. The present study compared rCBF activation in repeated visual tasks in 11 young subjects (25 _+4 yrs). Images were smoothed to 9 mm resolution and normalized to whole brain CBF. Five regions of interest (ROIs, 48 mm2) were placed in the superior parietal area in each hemisphere (85-95 mm above the inferior orNtomeatal line). For each ROI, the 2 control task values were averaged, and this mean subtracted from each of the 2 spatial location rCBF values. A 3-way ANOVA revealed no differences in overall levels of activation between subjects, but there was a significant difference between subjects in pattern of rCBF activation (subject x region x hemisphere interaction, p
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THE EFFECT OF KETANSERIN ON GLOBAL CBF AND CMRO2 DURING ANESTHESIA. 1) KS Olsen, 1) B Chraemmer-Jorgensan, 2) L Henriksen, 2) J Rosenorn, 3) H Dige-Petersen. Glostrup Hospital, Dptms. 1) Anesthesiology, 2) Neurosurgery, 3) Nuclear Medicine. U n i v e r s i t y of Copenhagen, Denmark.

ANTI-GRANULOCYTE IMMUNOSCINTIGRAPHY (Tc-99m MAb BW 250/183) IN PATIENTS WITH SUSPECTED INFLAMMATORY PROCESSES. P.Lind, G.Binter, P.K61tringer, H.P. Dimai*, R.Passl* and O.Eber. Internal Department, Barmherzige Briider Eggenberg Hospital, Graz-Austria *Department of Accident Surgery (AUKH) Graz, Austria

In search of the ideal hypotensive drug for neuroanesthesia Ketanserin is being evaluated. It is e new antihypertensive agent, acting primarily as a serotonin antagonist, and possibly being able to induce systemic hypotension without intracerebral vasodilation. Ue, therefore, studied the effect of Ketanserin on CBF and cerebral metabolic rate of O~ (CMRO_) in patients with. 9 Z, Z out cerebral dzsease durzng nzdazolam/fentanyl anesthesia and lumbar disc surgery. CBF and CMRO 2 were measured four times in each of 10 patients (22-54 y): 1) Awake, 2) after induction of anesthesia, 3) during anesthesia and Ketanserin (bolus dose 0.15 mg/kg and 6 mg/h infusion), 4) during anesthesia, Ketanserin, and hyperventilation to test the C02-reactivity. Bloodpressure was kept constant by angiotensin infusion. CBF (initial slope index) was measured by a 5-detector equipment for 15 min after Xe133 i . v . R~sults: ~ean CBF was reduced from 52 to 33 ml x 100-- ~ min-- ~by 38%) and CMRO~ from 3.9 to 2.8 ml x 100 g x min (by 28%) after induction of anesthesia (p < 0.05). No significant changes occurredlafter Ketanserin. The COp-reactivity was 2% x mmHg- . Ue conclude that Ketanserin is a potensislly useful drug in hypotensive neuroanesthesia inducing no increase in CBF. The C02-reactivity was preserved.

T u e s d a y , A u g u s t 28, 1 9 9 0

Antigranulocyte immunoscintigraphy with a Tc-99m labeled monoclonal antigranulocyte antibody (MAb BW 250/183) was performed in 66 in-patients in order to prove or exclude inflammatory processes. The examination was indicated in 29 patients because of suppurating processes of inner organs, in 20 patients because of postoperative inflammatory soft-tissue processes and in 17 cases because of suspected osteomyelitis. After labeling with Tc-99m 555 MBq Tc-99m MAb (0,5 mg antibody) were slowly injected intravenously over a period of 5 minutes. Planar and/or SPECT images (Elscint Apex 409 AG) were performed 6 and 24h p.i., in some patients 18h p.i. Leucocyte immunoscintigraphy proved inflammatory suppurating processes in 30 cases (true positive) and excluded them in 30 cases (true negative). The findings were false positive in 4 patients and false negative in 2 patients. In 20 patients human anti mouse antibodies (HAMA) were determined 2-6 months after anti-granulocyte immunoscintigraphy. Anti-isotypic HAMA's were found in 2, anti-idiotypic HAMA's in 1 out of 20 patients (15% positive HAMA response). According to our experiences sensitivity (94%) and specificity (88%) of immunoscintigraphy with Tc-99m MAb BW 250/183 is very high and therefore, well suited for the identification of leucocytic inflammations. Apart from the optimal gamma energy of Tc-99m, the simple in vivo labeling offers decisive advantages over leucocyte demonstration with In-ll 1 oxine or Tc-99m HMPAO. Leucocyte scintigraphy can thus easily be .performed at any time, also in routine nuclear medicine laboratories.

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ANTIGRANULOCYTES I M M U N O S C I N T I G R A P H Y (IS) USING DIFFERENTLY LABELED MONOCLONAL ANTIBODIES (MAB). J.Th. Locher and K.Seybold K a n t o n s s p i t a l Aarau, Switzerland.

99mTc-HMPAO-LEUKOCYTES (WBC) SCINTIGRAPHY IN THE DIAGNOSIS OF BONE INFECTION M.Moragas, A.Nuxi, A.Pavla, J.R.Gareia, A.Catafau, A.Gareia, F.Lome~a, R.Herranz and J.Setoain. Serv.Medieina Nuclear. Hospital Ciinic. Barcelona.

In 1986 we have shown that infections could be imaged using iodinated anti-CEA Mab-47. The aims of this study were to critically discuss the recent r a d i o c h e m i c a l developments and to proof their clinical relevance. Newly developed compounds could be labeled with Tc-99m(Tc-mab) and/or are more stable in vivo (I-mab).Both factors are clinically important because of the improvement of the quality of scans and the b e t t e r a v a i l a b i l i t y of the compounds. IS was p e r f o r m e d in approx. 250 pts. with osteomyelitls, arthritis 9 infected hip prosthese, inflam/natory bowel diseases and soft tissue abeesses. P l a n a r s c i n t i g r a p h y and SPECT were performed at 4 hrs after injection of either 3 mCi I-mab or 30 mCi Tc-mab (BW 250/183). 20 exa miaations were repeated with both agents. We found in both m e t h o d s a similar image quality of scans and, therefore, an almost equal functional behaviour of the granulocytes. Using Tc-mab the liver activity was higher, but the datas of tracer kinetics were comparable. The overall accuracy of both methods was 97% maximal s e n s i t i v i t y was 100% for bone infections and 92% for other infections; s p e c i f i c i t y was 92%. The longterm inlmunoreaction in pts. having undergone single or repeated IS was studied using two different HAMA tests.All IgG and IgM serum levels r e m a i n e d unchanged. We conclude that the Tc-mab is more advantageous for routine use, but I-mab is p r e f e r a b l e in some chronic CaSeS.

Spain

The utility of 99mTc-NMPAO-WBC in combination with 99mTc-MDP hone scan (BS) in the diagnosis of bone infection has been assessed. Two groups of a0 patients (p) (45 sites) have been studied: A) 25 p: 25 joint prosthesis (PT) and 5 endoprosthesis (n=30). B) 15 p with clinical suspicion of osteomyelitis. All Patients underwent a scan at 5 hours after the injection of 99mTo-HMPA0-WBC. At 48 hours a BS was made to localize the lesions detected with the WBC scan. As bone infection we considered a leukocyte bone uptake not justified by bone marrow activity, congruent or not with BS. Photophenic defects were net taken into account. Diagnosis was confirmed by clinical, surgical and/or microbiological findings. The results were: n TP TN FP FN The 3 FP were an aseptic Group A 90 15 12 9 0 trocanter bursitis, a Group B i5 4 8 0 2+1" knee PT recently implanted 45 19 20 3 2+i* and an aseptic loosening of a hip PT. The 2 FN were 2 Candida infections with a positive 67Ga scan. A Port disease* showed a photopenie defect on WBC scan and increased activity on BS. The sensibility (S) and specificity (SP) were 85.4% and 86.9% respectively. 99mTc-HMPAO-WBC scan shows a high S for bone infection, being an alternative to ll]In WBC scan. The SP is high, but can be lower in patients with orthopedic pato!ogy. The combination of 99mTc-NMPAO-WBC and BS can be one of the most advisable methods to be used for bone infection diagnosis

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BRAIN DAMAGE IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) POSITIVE INDIVIDUALS ASSESSED WITH

Tc-99m HMPAO SPECT IN A I D S D E M E N T I A COMPLEX. G. S c o p i n a r o , G. V i l l a , R. Z o c c o l a , :M. A z z i n i a n d mR. G a r a v e l l i . Nuclear Medicine Service and *Infectious Diseases Department, General Hospital, Alessandria, Italy

99Tcm-HMPAO/SPET.

D.C. Costa, M. L. Hall, R. Miller, J. Shields, J. Heavens, P.J. Ell. Institute of Nuclear Medicine, UCMSM, London, UK. Neurological involvement in HIV patients may be manifested by: 1) intracraneal space occupying lesions - SOL - (toxoplasma, lymphoma) and 2) encephalopathy-dementia complex (EDC) with no identifiable organic lesion. We investigated the perfusion patterns of 37 HIV patients, 18 with SOL and 19 with (EDC), in order to assess their brain damage, and compare it with psychometric evaluation. They were all male with an age range from 22 to 55 years and had CT brain scanning within 1-3 weeks of the brain perfusion study with HMPAO/SPET. This was carried out with the IGE 400 AC/STARCAM system, following predefined acquisition and processing protocols on routine use in our Institute. In patients with SOL, HMPAO/SPET demonstrated the site of lesion surrounded by a large area of reduced brain perfusion matching the oedema and midline shift seen with CT scanning. The findings in the EDC group included a wide range, in severety and extension, of cortical perfusion deficits. These, mainly located in the frontal, high parietal and temporal lobes, were more extensive than the degree of cortical atrophy observed with CT scanning. In addition, they correlated with the psychometric score for each patient. In conclusion, this work demonstrates that HMPAO/SPET identifies patterns of impaired brain perfusion in HIV patients with SOL which differ from those encountered in the encephalopathy-dementia complex.

S146

AIDS dementia complex is a well-defined neurological manifestation of the HIV infection. Its anatomo-pathological pattern is cerebral atrophy, gray and white matter abnormalities and vascular changes, and the main symptom is progressive dementia. SPECT with Tc-99m HMPAO has proved to be an useful tool in s t u d y i n g Alzheimer and multiinfarctual dementia, and its use has been recently proposed in A I D S - d e m e n t i a . We studied with Tc-99m HMPAO SPECT 40 Pts (38 drug addicted, 2 homosexual, 9 HIV+, 17 ARC, 14 AIDS) and a control group of 5 drugaddicted seronegative Pts. We found positive results in 6 3 % S P E C T , 25% CT, 0% neurological tests of dementia in H I V + phase, versus 71%, 3 6 % 5 1 4 % in ARC phase and 93%, 100% and 86% in AIDS phase, while all c o n t r o l Rts were negative. Control group is too small to exclude with all possibility of doubt cerebral blood flow impairment caused by drug damage but nevertheless we think that SPECT examination with 99mTcHMPAO has an important role in assessing CBF changes in earlier stages of A IDS-disease. These changes are probably forerunners of definitive cerebral damage and may be important markers of the advancement of disease.

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PULMONARY INFECTIONS IN HIV PATIENTS : DIAGNOSTIC VALUE OF LUNG 99MTc DTPA CLEARANCE (DTPA-LC)

A FUNCTIONAL DESCRIPTION OF THE SCATTER RESPONSE FUNCTION FOR SCATTER COMPENSATION IN SPECT. E.C. Frev a n d B . M . W . Tsui. University o f North C a r o l i n a at Chapel H-ill, Chapel Hill, NC, USA.

P Peltier, F Raffi, H Dutartre, B Milpied, JF Chatal. NANTES, FRANCE. To d e t e r m i n e w h e t h e r early d i a g n o s i s of p u l m o n a r y infection in HIV s e r o p o s i t i v e patients can be made by DTPA-LC, 38 non-smoking HIV+ patients were explored by D T P A - L C and b r o n c h o a l v e o l a r lavage (BAL). D y n a m i c acquisition of 60 sec frames was recorded during 20 min after 99mTc DTPA aerosol (Venticis II) inhalation. T 1/2 was calculated on the first 10 min of the washout curve, with background correction. Normal value of DTPA-LC T l / 2 was 60+ 15 min (20 healthy volunteers). BAL d e m o n s t r a t e d pneumocystis carinii (PC) in 9 patients, cytomegalovirus (CMV) in 7 and Streptococcus p n e u m o n i a e (SP) in 1. Seven patients had no clinical (CLN) or chest x-ray (CXR) abnormalities s u g g e s t i v e of lung interstitial d i s e a s e . DTPA-LC T1/2 w a s abnormal in 6 patients (BAL isolated PC in= 2 and C M V in 4). DTPA-LC T1/2 was normal in 1, w h e r e a s BAL isolated CMV. Ten patients had CLN+, including 5 with CXR+. DTPA-LC T1/2 was abnormal in all these 10 patients. BAL isolated PC in 7, C M V in 2 and SP in 1. When BAL isolated a lung pathogen, DTPA-LC T l / 2 was abnormal ( 1 6 / 1 7 ) . All PC infections with or without clinical or CXR abnormalities had abnormal DTPA-LC T l / 2 . Thus,in HIV+ patients 99mTc DTPA lung clearance is very useful for detection of lung infection, even at a preclinical stage.

651

Scattered radiation in SPECT results in a loss of i m a g e quality in terms of both quantitative a c c u r a c y and contrast degradation. S e v e r a l o f the p r o p o s e d c o r r e c t i o n t e c h n i q u e s , i n c l u d i n g c o n v o l u t i o n s u b t r a c t i o n , d e c o n v o l u t i o n a n d iterative reconstruction, require k n o w l e d g e o f the properties o f the scatter response function. W e have used Monte Carlo (MC) simulation to generate scatter line r e s p o n s e f u n c t i o n s (SLRF) for T c - 9 9 m sources placed at various positions inside a water-filled cylindrical phantom. Data w a s also generated using various energy windows. The resulting S L R F s were fit with fitting functions consisting of various combinations o f half Gaussians and the fitting parameters were plotted as functions of the source position. The S L R F s were also c o m p a r e d to S L R F s generated with sources imbedded in a semi-inf'mite slab in order to study the effect of the geometry o f the scattering medium. Several important observations were made. First, the shape of the S L R F is relatively independent o f baseline settings in the range 118-126 keV. This independence is important for p r a c t i c a l applications. Second, the S L R F is significantly a s y m m e t r i c f o r s o u r c e p o s i t i o n s not f a r f r o m the axis o f symmetry. This m a y significantly limit the effectiveness o f some scatter compensation schemes which are based on convolution and deconvolution. By studying the parameters o f the fitting functions as functions o f source position and the geometry of the scattering medium we have found trends that agree qualitatively with simple physical models. The consistency in these trends indicates that a position-dependent functional description of the S L R F is possible. This parameterization is important in characterizing the scatter response function and is necessary in order to devise and evaluate scatter compensation schemes in SPECT.

652 COMPTON-SCATTERING CORRECTION BY CONSTRAINED FACTOR ANALYSIS .l. MAS. P. HANNEQUIN*, R. BEN YOUNES, B. BELLATON, R. BIDET Laboratoire de Biophysique et de M~decine Nucl6aire, CHU Jean Minjoz, 25000 Besan~on-C6dex FRANCE *Centre d'Imagerie Nucl6aire, 74 000 Annecy, FRANCE

An important fraction of gamma rays which Compton scatter within the attenuating medium fails in the photopeak acquisition window degrading the contrast of Nuclear Medicine images. The aim of this study is the removal of these scattered photons by a novel approach based on constrained Factor Analysis (FA) of energy spectra. The acquisition of all the photons which have reached the detector is required for the process. So, either a listmode or a multi-windows acquisition is performed. In the later case, FA is computed on the series of N energy images. Two oblique factors are extracted, one representing the scatter and the other one a combination of photopeak and residual Compton information. The use of these rough factors leads to unrealistic factorial images as demonstrated by Houston. The innovative idea is the substitution of the combinated factor by a theoretical pbotopeak factor. The projection on the initial energy series of this constrained new factor and of the Compton factor extracted by FA gives the correct factorial images. The first one represents the unscanered information and the other one the whole Compton scattering. This method is tested on MONTE CARLO simulations and real phantoms, both on planar and SPECT studies. In order to quantify the improvement in scattered events rejection, comparison with the Jaszczak's weighted subtraction method is performed. The new recombination algorithm is more efficient than the two energy windows method, particularly in SPECT studies, moreover after attenuation compensation with the modified Chang's iterative procedure.

Tuesday,

August28,1990

QUANTITATIVE ANALYSIS OF SCATTER REMOVAL ALGORITHMS. D. Gaqnon, A. Todd-Pokropek*, N. Pouliot,

L. Laperri~re, A. Arsenault, J. Gr~goire, G. Dupras. Montreal Heart Institute, QC, CANADA, *University College, London, UK. Reduction of Compton scattering degradation of nuclear medicine images should improve the ability to obtain reliable quantitative estimates. We compared three de-contamination technique: the 10% asymmetric high window (AH), the dual window (DW) and the Holospectral Imaging (HI) with the conventional, unprocessed 20% window (20%). Data were obtained by imaging a series of 9 coplanar vials with predetermined activity using different amount of scattering medium (plexiglass). Figure-of-merit in our quantification analysis is the accurary of the activity ratios as predicted by the regression line computed on the 9 points obtained by drawing regions of interest (ROI) on the image. ROl's included 99% of the total activity on the Compton-free image. Four main conclusions can be stated: 1) there is a systematic degradation of the quantitative accuracy in the conventional image as more scattering material is put between the sources and the camera; 2) all the scatter removal techniques evaluated produce more accurate results; 3) HI has the highest accuracy of the three methods while the DW technique offer a better precision; 4) as the amount of scattering medium increases to 12 cm, the proportion of the total activity included in the ROl's drops to 72% for the 20% window image, to 83% for the DW, to 82% for the AH and to 86% for HI. This experiment clearly shows the importance of adequate scatter correction. Increase in contrast and contrast-to-noise ratio are ither ways to characterize these techniques. Improvements in quantification could have a major impact on nuclear medicine imaging techniques.

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654

WIDE ENERGY BAND IMAGING AND ITS CONSTRAINT ON A CONVENTIONAL GAMMA CAMERA. D. Gaqnon, L. Laperri~re, N. Pouliot, A. Arsenault, J. Gr~goire, G. Dupras. Montreal Heart Institute, QC, CANADA.

SIMULTANEOUS IMPROVEMENT IN IMAGE QUALITY AND ABSOLUTE QUANTITATIVE ACCURACY IN CARDIAC SPECT. B.M.W. Tsui, X.D. Zhao, E.C. Frey, G.T. Gullberg*, J.R. Perry and W.H. McCartney. Univ. of North Carolina at Chapel Hill, Chapel Hill, NC, USA and *Univ. of Utah, Salt Lake City, UT, USA.

Conventional gamma cameras are designed to be optimal only within a narrow range of energy. Severe signals distortions arise when the energy window is opened to accept ALL the events. Optimal implementation of full spectrum acquisition techniques therefore requires additional corrections for off-peak images regarding the energy consistency, spatial distortion, spatial registration and uniformity. Uniformity of the energy response is needed to ensure accuracy in the image evaluation for a given energy. This correction is done by producing a table of the offset between the mean energy detected by each pixel to the image mean and correct the photon energy accordingly at the acquisition time. Spatial distortion and registration correction is more sophisticated and requires a complete re-sampling of the image. With a marginal loss in resolution, counts concentration around the photomultiplier eentres, that cause spatial distortion and overall X- and Y-magnification factor can be corrected for by finding a new coordinates system, with varying pixel size and non-orthogonal location, in which the distorted image wilt appear straight and uniform. Residual nonuniformity is handled by a simple inverse matrix multiplication. The computation of correction coefficients and their application on a wide energy band acquisition demonstrates the feasibility of extending the optimal performance of conventional cameras in terms of uniformity and spatial distortion while maintaining adequate spatial resolution.

Simultaneous improvement in both reconstructed image quality and quantitative accuracy of cardiac SPECT has been impeded by counting statistics, non-uniform attenuation distribution in the chest region, and space variant detector and scatter response functions. A new compensation scheme has been implemented, which incorporates models of attenuation distribution and detector response function in the projection/backprojection operations of the iterative ML-EM algorithm. A computer generated phantom which provides realistic simulation of both the anatomy and TI-201 uptake in the chest region was used in evaluating the reconstruction technique. In the noise-free case, both quantitative accuracy and reconstructed image resolution improved with iteration number. Quantitative accuracy leveled off after about 50 iterations, but spatial resolution continued to improve even after 500 iterations. With Poisson noise added to the simulated projection data, the inclusion of detector response compensation showed improved image resolution and decreased image noise compared with attenuation compensation alone at low iteration numbers. After a large number of iterations, the improvement in spatial resolution was offset by a more rapid increase in image noise. With choice of appropriate stopping criterion, the iterative reconstruction technique provides simultaneous improvement in image quality and quantitative accuracy in cardiac SP~CT without the artifacts and distortions found in more commonly used image reconstruction and compensation schemes.

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C O R R E C T I O N F O R S K U L L A T T E N U A T I O N IN Tc-99m HMP A O SPECT B R A I N IMAGING. B.J.Kemp, F.S.Prato, G.W.Dean', and R.L.Nicholson. Nuclear Medicine Department, St. Joseph's Health Centre, and Medical Biophysics Department, University of Western Ontario, London, Ontario, Canada, and "Nuclear Medicine Department, Royal Victoria Hospital, Montreal, Quebec, Canada.

IN VIV0 MONITORING OF PULMONARYENDOTHELIAL CELL FUNCTION IN SHEEP WITH NON-CARDIOGENICPULMONARYEDEMA. D.O. S l o s m a n D.R. Morel, K. G u n n i n g , P. Masouy~, P.M. S u t e r a n d A. Donath H6pital Universitaire. 1211 Geneva 4. C H . MetaiodobetL.,~lguanidine (MIBG) is a n i o d i n a t e d a n a l o g of g u a n e t h i d i n e Ihat h a s a s i m i l a r l u n g e x t r a c t i o n p r o c e s s t h a n n o r e p i n e p ' m u e . A n o n - c a r d i o g e n i c p u l m o n a r y e d e m a m a y be reduced m sheep by infusion of E. coli endotoxin which is k n o w n to a k e r e n d o t h e l i a l cell integrity. We investigated in vivo the t i m e - c o u r s e of f i r s t - p a s s MIBG l u n g e x t r a c t i o n (%E) in s h e e p d u r i n g endotoxemia. In 5 chronically i n s t r u m e n t e d awake sheep, 1-123 MIBG (250~C1/ml) a n d T c - 9 9 m red blood cells (RBC, 500 IlCi/ml) were s i m u l t a n e o u s l y injected i / v b y b o l u s a n d aortic blood sampling w a s obtained (1 sec per sample for 90 sec) to allow %E m e a s u r e m e n t at the p e a k of the RBC dilution curve done s e q u e n t i a l l y for 24 h r s a f t e r the s t a r t of a c o n t i n u o u s E. coli endotoxin infusion (20 n g / k g / m i n for 2 4 hrs). We observed a n early p h a s e with t r a n s i e n t i n t e n s e p u l m o n a r y v a s o c o n s t r i c t i o n associated with a t r a n s i e n t t e n d e n c y of %E to decrease (see table). T h e r e a f t e r , a n i m a l s develloped a n h y p o t e n s i v e s h o c k with p e r s i s t e n t p u l m o n a r y h y p e r t e n s i o n , a 50% d e c r e a s e d systemic v a s c u l a r r e s i s t a n c e , a 2-fold i n c r e a s e d i n t r a - p u l m o n a r y s h u n t a n d a 6-fold i n c r e a s e d p u l m o n a r y l y m p h protein clearance. This w a s a s s o c i a t e d with a progressive r e d u c t i o n of %E o c c u r r i n g a s a function of time (n=34, R2=0.786). (mear~+sd; * p<0.05 from t= 0). Time 0min 15-30 60-120 180-300 420-600 24hrs MAP 94_+15 94_+9 87_+4 87_+18 72_+16 66_+2 MPAP 17+2 38-+11" 2 9 ! - _ 5 " 29-+4* 31_+5" 305-_2* %E 36-+11 29_+2 34_+14 31_+7 2CA6" 15+5" Progressive %E decrease observed d u r i n g the first 24 h o u r s after the s t a r t of e n d o t o x i n i n f u s i o n s u g g e s t s t h a t MIBG m a y reflect the loss of l u n g endothelial cell integrity due to endotoxin shock. %E MIBG m a y be f u r t h e r investigated for the non-invasive monitoring in clinical settings .

In Tc-99m H M - P A O SPECT imaging of the brain the gamma rays from the radionuclide will be attenuated by the brain tissue and the bone of the surrounding skull. However, the effect of the skull is not considered in first-order attenuation corrections of brai n images. An experiment was performed in which a human skull was filled with a uniform mixture of Tc-99m in gelatin and imaged. It was found that the images were overcorrected in the centre with respect to the periphery when compensated for attenuation using a water/tissue coefficient of 0.12 cm 1. Additional experiments conducted on phantoms in which the head was simulated by cylinders filled with uniform Tc-99m in water and wrapped with aluminum (to mimic the bone) show a 5% overestimation in the activity at the image centre. Computer simulations confirm experimental findings and indicate that the apparent overcorrection in the image centre is in fact an undercorrection at the periphery caused by increased attenuation at the edges of the projections where there is a greater path length through the bone. Consequently, a correction technique which uses the effective bone and tissue attenuation coefficients (0.21 cm "~ and 0.12 cm "~ at 140 keV, respectively) was developed to compensate for both the bone and tissue attenuation in the projections. The method is robust and only requires an estimate of the patient's skull thickness. A 25% over/underestimation in skull thickness will produce a 1% error in uniformity. The correction will improve image uniformity and increase the count density of the images, thereby producing a better estimation for the absolute quantitation of the amount of activity present in the brain.

$148

Tuesday, August 28, 1990

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LUNG VESSEL INJURY: EVALUATION USING RADIOLABELED MONOCLONAL ANTIBODY TO ANGIOTENSIN - CONVERTING ENZYME

DETECTION OF ALTERED PULMONARY EPITHELIAL PERMEABILITY BY A MODIFIED TECHNEGAS

S. D a n i l o v , E . A t o c h i n a , H.Hiemisch, A.Andjan, G.Deichman, V.Muzykantov. USSR Cardiology Research Center, Moscow USSR. Radiolabeled monoclonal antibody (MoAb) to a n g i o t e n s i n - converting enzyme (ACE), n a m e d 9B9, a c c u m u l a t e s very specifically and efficiently in t h e r a t , h a m s t e r , m o n k e y a n d human lung. Since ACE localizes on the luminal surface of vascular endothelial cells, we prop o s e t h a t d a m a g e of t h e l u n g m i c r o v a s c u l a r endethelium m i g h t c h a n g e t h e v a l u e of t h e l u n g accumulation of M o A b 9B9. A i m o f t h i s s t u d y w a s t o e v a l u a t e t h e M o A b 9B9 s p e c i f i c l u n g a c cumulation on the rats with pneumonia (as a model of AIDS complication) and on the hamsters with experimentally induced lung metastas i s (as a m o d e l o f l u n g t u m o r ) . After development and verification both of the models mixture of I-I25 labeled specif i c M o A b (9B9) a n d I n - I I I n o n s p e c i f i c MoAb (the s a m e i s o t y p e ) w a s i n j e c t e d i/v, a n d b i o distribution of r a d i o l a b e l s was estimated on e x c i z e d o r g a n s . In t h e b o t h c a s e s M o A b 9B9 lung accumulation dacreases rather significant: f r o m I 6 , 7 ~ 0 , 6 5 % o f i n j e c t e d d o s e / g in c o n t r o l t o 7,I + 1 , 3 5 f o r r a t s w i t h p n e u m o n i a , and f r o m 2 3 , I +_-I,9 to I 5 , 7 ~ 1 , 2 f o r h a m s t e r s with lung metastasis. W e c o n c l u d e t h a t M o A b 9B9 l u n g a c c u m u l a t i o n m i g h t s e r v e a v e r y s e n s i t i v e m a r k e r of l u n g vessel injury during different lung disorders.

TECHNIQUE. P. Monaghan t H. Van der Wall, D.W.J. Maokey and I.P.C.Murray. Dept. of Nuclear Medicine, Prince of Wales Hospital, Sydney, NSW, Australia. Technegas (TOG), an ultra-fine dry aerosol, has gained ready acceptance in eentres utilising it for ventilation studies in the investigation of pulmonary embolism. This popularity reflects the speed and simplicity of administration, the peripheral penetration superior to conventional aerosols and the image quality associated with excellent counting statistics because of the prolonged retention in the lungs. The clearance time of the radioactivity can, however, be markedly altered by replacing the pure argon atmosphere, in which the carbon particles are generated, with a 97% argon/3% oxygen mixture. Half-time pulmonary clearances (T89 achieved with this technique were compared with those obtained with conventional Tc-99m DTPA aerosol in 17 patients. Interstitial lung disease was suspected in 7 while 10 patients had AIDS, in 5 of whom opportunistic infection was present. In the 10 patients in whom the DTPA T89 was normal (mean 54.2 min, range 27.2 - 132.5 min), the TcG T89 was 9.7 rain (range 8.2. - 15.2 min). The group of 7 patients in whom altered pulmonary permeability was demonstrated by a short DTPA T89 (mean 8.8 rain, range 3.6 -11.9 rain), also had accelerated TcG T89 (mean 4.1 min, range 2.25 - 5.65 min). The shorter TcG T89 may induce some overlap between normal and abnormal patients, particuIar]y in smokers in whom DTPA T89 is usually more rapid. However, the advantages of the Technegas procedure are such as to warrant extending the evaluation of this method, particularly to ascertain its value in serial studies in individuals suspected of having opportunistic infection or other diffuse lung pathology.

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660

INTERSTITIAL PNEUMONIAAND PULMONARY EPITHELIAL PERMEABILITY Y. Anazawa, T. Isawa, T. Teshima, M. M i k i , and M. Motomiya. Tohoku University, Sendal, Japan.

Tc-99m HMPAO AND Tc-99m DTPA RADIOAEROSOL CLEARANCE MEASUREMENTS IN IDIOPATHIC PULMONARY FIBROSI S (IPF). S.H. Yeh, R.S. Liu, L.C. Wu, N.J. Peng, and J.Y. Lu. Veterans General Hospital and National Yang-Ming Medical College, Taipei, Taiwan.

The purpose was to study the r e l a t i o n between the pulmonary e p i t h e l i a l permeability and DLco, DLco/VA, Pa02 and LDH in patients with i n t e r s t i t i a l lung d i s eases and how the pulmonary e p i t h e l i a l permeability changed in patients f o l l o w i n g r a d i a t i o n therapy. Ten patients with i n t e r s t i t i a l pneumonia and lO patients with malignancy treated with r a d i a t i o n therapy were studied. Tc-99m DTPA a e r o s o l generated by a j e t n e b u l i z e r ( U l t r a V e n t ) (mass median d i a m e t e r : 1.04 micron, geometric standard deviation: 1.71) was inhaled in the supine p o s i t i o n f o r 3 minutes. R a d i o a c t i v i t y was measured with a gamma-camera from a n t e r i o r l y f o r 30 minutes in the same p o s i t i o n . The data were sequent i a l l y recorded to a computer every lO sec. Time act i v i t y curves corrected f o r physical h a l f l i f e from the regions of i n t e r e s t s (ROls) were analyzed f o r the i n i t i a l 7 minutes s t a r t i n g from t h e i r respective peaks, Each curve was simulated to a single exponential funct i o n and a h a l f time clearance ( T I / 2 ) was calculated. In patients with i n t e r s t i t i a l pneumonia there was no r e l a t i o n s h i p between the TI/2 and DLco, DLco/VA, Pa02, and LDH. In p a t i e n t s who developed r a d i a t i o n pneumonitis the TI/2 became smaller when abnormal d e n s i t i e s appeared on chest x-rays and the TI/2 became l a r g e r when pneumonic densities disappeared f o l l o w i n g s t e r o i d therapy. Although true pathophysiologic s i g nificance of pulmonary e p i t h e l i a l permeability is not known yet, i t could be an index of a n o n - r e s p i r a t o r y lung function.

Tuesday, August28,1990

The clearance rate of inhaled aerosols of a lipophilic complex, Tc-99m HMPAO, was studied and compared with that of hydrophilic complex, Tc-99m DTPA, in 9 normal subjects (N) and 8 patients (pts) with IPF. The subjects in supine position with their back against the scintillation camera breathed aerosols for 2 minutes and pulmonary radioactivity was monitored for 30 minutes thereafter. Percentage clearance per minute (k) in each lung was calculated from the power exponential fit of data after the peak of each curve. Tc-99m DTPA clearance (k = 1.31 -+ 0.13%/min, SEM) was not different from that of Tc-99m HMPAO (k = 1.32 -+ 0.27%/min, p > 0.25) in N. However, the former increased to 2.0 +- 0.23%/min, and the latter decreased to 0.55 -+ 0.12%/min in 8 pts with IPF (p < 0.001, DTPA vs. HMPAO). By regression analysis with the multiplicative model, both of them fairly correlated [r = -0.71, Y = exp(0.08 - 0.851nX), p < 0.005] with a change in the clearance in the opposite direction in all 8 pts. In IPF, Tc-99m HMPAO clearance decreased to 0.55 -+ 0.12%/min (p < 0.025 vs. N) with a sensitivity of 0.87 (7/8) and a specificity of 0.89 (8/9) at the cut-off value of k = 0.6%/min. In summary, the clearance of Tc-99m DTPA and Tc-99m HMPAO changes in an opposite direction in IPF. The increased clearance of Tc-99m DTPA may result from the damage to the tight intercellular junctions, and the decreased clearance of Tc-99m HMPAO may be due to the loss of cellular integrity in IPF. Tc-99m HMPAO aerosol may be useful for permeability study in IPF.

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PULMONARY EPITHELIAL PERMEABILITY VERSUS

NEW RADIOIODINATED RADIOPHARMACEUTICAL FOR SPECT STUDIES OF MYOCARDIAL ADRENERGIC FUNCTION : [I-123]IODOMETARAMINOL. K. Kawai, S. Nishiyama, Y. Fujibayashi, H. Saji, Y. Yonekura, J. Konishd, A. Kubodera, and A. Yokoyama. Science U n i v e r s i t y of Tokyo, Tokyo, and Kyoto University, Kyoto, Japan.

67 Ga UPTAKE IN CHRONIC INTERSTITIAL LUNG DISEASE (CILD) N. Caillat-Vigneron,J.L.Moretti.D. Valeyre, D. Le Guludec, D.

Sadoun, J.P, Battesti. Hop. AVICENNE,Bobigny2rance. The clearance rate (Cr) of aeroselized 99mTc-DTPA i s u s e d t o investigate pulmonary epithelial permeability in CILD, In most of these diseases an early alveolitis is usually associated with impairement of lung functions, An enhancement of 67 Ga uptake characterizes the cellular inflammatory infiltration and assesses the disease activity, 67 pts (36 males, mean age 47,2 * 173 ys ; 31 females, mean age 4 8 , 0 + 163 ys) suffering from CILD of diverse origins underwent 99mTc-DTPA lung regional clearance measurements and 67Ga scanning. The distribution of aeroselized 99mTc-DTPA on posterior view of the lungs is heterogeneous in 30 pts out of 67 and mismatched with a corresponding high 67Ga regional uptake in 16 pts out of the 30, The extraction of clearance curves from the peripheral part of this mismatched region provided abnormally low values for the Cr. Our findings suggest that, 1- a high proportion of patients with CILD exhibit an heterogeneous distribution of DTPA clearance in their l u n g , 2- in some c a s e s inflammation involvement due to an airway disease or localized perfusion impairement could affect the peripheral distribution of aerosolized 99mTcDTPACr. In such circumstances the DTPAalveolar epithelial permeability may be considered falsely normal.

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663 [I-131]IODOTROPAPRIDE

: A CEREBRAL

DOPAMINE

D2 RECEPTOR

LIGAND.

R. Cantineau, P. Damhaut, A. Plenevaux, C. Lemaire, M. Guillaume. Cyclolron Research Center, Liege University, B-4O00 Liege, BELGIUM Iodinated receptors ligands have been developed for the study of the neurotransmission system of the living human brain by single photon emission tomographty (SPECT) (1,2). Tropapride, iodotropapride and bromotropapride are substituled benzamide antagonists which have shown high affinity and selectivity to dopamine D2 receptors (3). [I-131] iodotropapride was synthesized at the no-carrier-added level (n.c.a.) by nuc[eophiIic substitution on the corresponding brominated analog in order to validate on animals the binding properties of Ihis new radioligand. The labeling was based on a nucleophilic exchange Br-I in the presence of Cu I and an excess el the reducing agents (gentlsinic acid - citric acid - tin sulfate] (4}. The reaction was conducted in a sealed vial under nitrogen Ior 30 min at 160~ Free iodine was removed from the reaction mixture by the use of sap pak cartridges. 11-131] iodotropapride was isolated from the unreacted bromoderivalive by HPLC considering that the bromo-compound showed non negligible affinily tot dopamine receptor sites. The chromatographic separation was carried out on a semi-preparative Bondapack C18 column with the following eluent : methanol / acetonilrile / waler / triethylamme / acetic acid - 16/16/66/1/1. [I-131]iodolropapride was obtained at a no-carrier-added level (no uv detection of the bromededvalive by HPLC) wilh an overall yield of 50%. Preliminary animal studies were carried out to evaluate the binding properties of [I-131] iodotropapride as an in rive dopaminergic tracer. General blodistribution in rats indicated that 0.45% of the injected dose appeared quickly in the total brain and remained constant during the first two hours showing a significant retention by brain tissue. High initial uptake was identified in lungs, liver and kidneys one hour after injection. The thyroid uptake was low suggesting a good in rive stability el the compound. Regional brain biodistribution showed a very high uptake in the striatum. The activities in the frontal cortex and the cerebellum were relatively low involving an in vivo dopaminergic specilicity of the radioligand. The striatum/cerebellum ratio was strongly increasing wilh time and reached values Of 11 and 21 at 60 and 120 minutes respeclively. No plateau appeared even 4 hours after injection. Uptake in the striatum was saturable and could be blocked by pretreatment with known D2 antagonists such as spiperone, The non specific binding el [I-131]iodotropapride to dopaminergic sites was very low. This was demonstrated by in vitro inhibition experiments. Human studies will be performed using [I-123]iodotropapride and SPECT. 1. Kung H.F. Guo Y.Z., Billings J.J.. Xu X . Mach R.H., Blau M. and Ackerhalt R. Int. J. Nuct Med. Biol. 1980; 15, 195. 2. Saji H., Shiba K., Saiga A., Tokui T., Nakatsuka I., Okuno M., Yoshiyake A, and Yokoyama A. J. Label. Compds. Radioparm. 1988; 26, 95. 3. Rumigny J.F., Strolin Benedetti M. and Dostert P. J. Pharm, Pharmacol. 1984; 36, 373. 4. Medens J., Vanryckegbem W. and Cadsen L Prec. 2nd Eur. Symp. on Radlopharmacy and Radiopharmaceuticals . Cambridge ; 1985.

$150

The myocardium, being under the control of the adrenergic neuron, highly takes up noradrenaline (NA). We attempted to develop new radioiodinated radiopharmaceutieal for SPECT studies of myocardial adrenergic function using a false transmitter, metaraminol (MA). 1-123 or 1-125-MA was efficiently prepared under non-carrier added conditions by the conventional chloramine-T method and was easily purified. In mouse biodistribution studies, 1-125-MA showed high and rapid accumulation in the myoeardium. In the homogenate analysis of the 1-125-MA injected mouse myocardium as well as other tissues, 1-125-MA was metabolically stable, especially resistant to enzymatic deiodination in vivo. The decrease of m y o c a r d i a l 1-125-MA accumulation by treatment with desmethylimipramine, reserpine and 6-hydroxydopamine indicated that the I125-MA accumulation mechanism was similar to that of C14-NA; 1-125-MA was taken up into the adrenergic neuron by uptake-i transport system and stored within the amine storage vesicles. The highly accumulated 1-123-MA in the myocardium within 5 minutes after intravenous injection was visualized very clearly by planner and SPECT studies in dog. Thus, 1-123-MA showing high myocardial accumulation, high stability in vivo, and similar accumulation mechanism of C-14-NA, indicated to be a new radioiodinated radiopharmaneutical based on the specific structure of the false transmitter, for SPECT studies of myocardial adrenergic function.

RADIOIODINATION OF PROTEINS BY A NEW CONJUGATION TECHNIQUE WITH ACTIVATED METHOXY PHENYL

I S O T H I O C Y A N A T E . M . K . Dewanjee, A.K. G h a f o u r i p o u r , W.Ganz, K . M c C a r t h y , A . S e r a f i n i , G . S f a k i a n a k i s , U n i v . o f M i a m i S c h . o f M e d i c i n e , M i a m i , F L , U.S.A. R a d i o i o d i n a t e d p r o t e i n s l a b e l e d b y t h e Nhydroxysuccinimide, are found u n s t a b l e in vivo; on the o t h e r hand, t h i o u r e a b o n d f o r m e d b e t w e e n a c t i v a t e d p h e n y l i s o t h i o c y a n a t e and t h e u n p r o t o n a t e d C - a m i n o g r o u p of l y s i n e g r o u p of t h e p r o t e i n is found s t a b l e in vivo. The p a r a m e t h o x y p h e n y l i s o t h i o c y a n a t e (PMPITC) w a s r a d i o i o d i n a t e d b y the c h l o r a m i n e - T or I o d o g e n method. The l a b e l i n g e f f i c i e n c y was (40-55)%. The r e t e n t i o n t i m e s of r a d i o i o d i n a t e d P M I T C (RPMITC) and free iodide e l u t e d w i t h 50% a c e t o n i t r i l e from a C-18 r e v e r s e p h a s e c o l u m n w e r e 7.6 and 1.7 m i n u t e s r e s p e c t i v e l y . T h e P M P I T C (RPMPITC) w a s e x t r a c t e d w i t h e t h e r a n d e v a p o r a t e d to d r y n e s s . A f t e r d i s s o l v i n g in DMSO, it w a s c o n j u g a t e d to the m o d e l p r o t e i n s : c a n i n e a l b u m i n and g a m m a globulin. The p a r a m e t e r s of c o n c e n t r a t i o n of PMITC, oxidant, p r o t e i n and p H w e r e o p t i m i z e d and the i m m u n o r e a c t i v i t y w a s c h e c k e d by the a f f i n i t y column. T h e c o m p e t i n g h y d r o l y s i s r e a c t i o n c o u l d be m i n i m i z e d b y conj u g a t i o n at the p H r a n g e of 6 - 8 . T h e c o n j u g a t i o n e f f i c i e n c y was (35-45)%. A s p e c i f i c a c t i v i t y of 2-10 m C i / m g was obtained. The s h e l f - l i f e of R P M P I T C w h e n s t o r e d in e t h e r at 4~ w a s 60 days. This c o n j u g a t i o n m e t h o d p r o v i d e s a s i m p l e t e c h n i q u e of r a d i o i o d i n a t i o n of p r o t e i n , p e p t i d e and o l i g o n u c l e o t i d e , d e v o i d of a c t i v a t e d p h e n o l ring. ( S u p p o r t e d by DOE and FHTIC).

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EFFECT OF LIPOPHILICITY ON BIODISTRIBUTION IN THE MOUSE USING 1-123 LABELLED GLUCOSE ANALOGUES. T. Lutz, D. Lyster, H. Dougan, T. Rihela, M. Hudon, Cohen, and W.R.E. Jamieson. TRID~F/UBC/VGH/LGH, Vancouver, British Columbia, Canada.

SYNTHESIS OF NIGH SPECIFIC ACTIVITY 1-123 mlBG* J Amartey, J Fayad and R M Lambrecht. King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia.

P.

Much research has been involved in the developement of radiolabelled glucose derivatives as heart imaging agents. Presently, [F-18]-2-deoxy-2-fluoro-D-glucose is being used as a heart imaging agent, but it would be advantageous if there was a non-positron radiepharmaceutical which was available to all nuclear medicine departments. Megata et. al.(Nuel. Med. Biol. 14, 7, 1987) have shown some localization using 2-O-(piodebenzyl)glucose. We wanted to determine if iodine position effects heart uptake. For these reasons we have synthesized and studied the isomeric series of 2-deexy-2-O-(iodebenzyl)glueoses (I-123-IBG) and 2deoxy-2-N-(iodobenzoyl)glucosamiaes (I-123-1BGLN). Octanol:water partition coeffients show increasing lipophilicity as one proceeds from ortho- to meta- to para-iodinated glucose analogues (as displayed below). ortho meta para IBG 0.44 • 0.01 0.56 • 0.03 0.66 • O.O1 IBGLN -0.83 • 0.01 0.18 • 0.01 0.28 • 0.01 Results for the IBG series in the mouse heart indicate a trend of increasing uptake with increasing lipephilicity, with a maximum heart:blood ratio seen for para-IBG (1.24 at 15 minutes post injection). The maximum heart:blood ratio in the IBGLN series is seen for 2-1BGLN (36.0 at 1080 minutes post injection). This is not the most llpophilic of the series, which suggests there may be some transporter affect. It would appear that iodine position, and hence lipophillcity, is one of many factors which influences heart uptake.

In view of the increasing use of 1-123 mIBG in the assessment of adrenergic nerve intergity in the myocardium, there is the need to obtain a very high specific activity agent by a reliable, routine synthetic method. We have optimized the production of mIBG labeled with 1-123 by using modified literature methods involving the solid state exchange reaction on "cold" mIBG in the presence of ammonitnn sulfate. Various reaction parameters were systematically studied. The key to optimization of the radiochemieal labeling reaction was the molar ratio of ammonium sulfate to sodium hydroxide present in the sodium 1-123 iodide. Experiments were done with 1 to i000 micrograms of mIBG. The optimum ratio was 10:1 for i00-I000 micrograms of mIBG. The radiochemical yield drastically decreased in presence of I0 micrograms and less of reagent. Heating temperature and time for the reaction were optimum at 150~ and 2 x 30 minutes, respectively. The radiochemical yield was generally 95%. However, any unreacted Iodide-123 and sulfate were removed from the radiopharmaceutical by passage through a mini-Dowex anion exchange column. This method consistently produced 1-123 mIBG of purity greater than 99% and of specific activity higher than 1.85 GBq/mg (>50 mCi/mg). Typically 3.25 GBq of 1-123 iodide is used to produce i0 unit dose vials of 200 MBq. The synthesis of 1-123 mIBG has been optimized to make effective utilization of 1-123 and ultimately to make the radiopharmaceutical available in the Middle East. *This research was supported in part by a private grant from Sheik Abdulrahman All Ai-Jeraisy.

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SYNTHESIS AND EVALUAT[ON DERIVATIVES AS POTENTIAL

OF NEW IODINE-125 RADIOPHARMACEUTI-

CALS FOR MALIGNANT MELANOMA~ M.F. Moreau, ] . M i c h e l o t , A . V e y r e , J. P a p o n , Y. M i c h e l , .i.E. M a d e l m o n t D. Geden~che, G. M e y n i e l . INSERM U 71, C l e r m o n t - F d , CIS ] n d u s t [ i e , G i f - s u r - Y v e t t e (France) T h e p u r p o s e o f t h i s s t u d y was to i n v e s t i g a t e the affinity for melanoma of a series of iodinated compounds and to e v a l u a t e their potential as m e l a n o m a imaging agents. I-~-Y-C

H 2 C H 2 N ( C 2 H s ) 2, H C I

Y = -CH(C6Hs)-O-;-CH20_;_O_;_CONH_; The synthesis of the radJoiodinated derivatives labeled w i t h 1-125 was p e r f o r m e d from the correspondent amines using the Sandmeyer reaction or the Wallach triazene method (Brevet n ~ PV 8901898, 14/02/1989, France). Their selectivity for melanoma has been qualitatively demonstrated by a u t o r a d i o g r a p h y o f w h o l e body s e c t i o n s and quantitated by coun[ings of tumors and selected tissue using C57BL6 mice bearing B16 melanoma and athymic mice bearing malignant melanoma heterotransplants. N - ( 2 - d i e t h y l a m i n o e t hyl) 4-iodobenzamide (y C O N H ) has been s e l e c t e d by i t s h i g h e s t m e l a n o m a a f f i n i t y : tumo[ u p t a k e = 6.5 Z ] D / g one hr p o s t - i n j e c t i o n , tumorto-blood ratio 19, t u m o r - t o - l [ v e r r a t i o 5, t u m o r - t o - b r a i n ratio 46, tumor-to-lung ratio 10 and t u m o r - t o - m usc]e r a t i o 48, 12 hr p o s t - i n j e c t i o n . In a s e c o n d step t h e r a d i o l a be][ng o f t h e a m i d e w i t h h i g h - s p e c i f i c activity was a c h i e v e d by i s o t o p i c exchange reaction to a l l o w s c i n t i g r a p h i c s t u d i e s in m i c e . F r o m 6 to 24 hr a f t e r i . v . i n i e c t i o n high u p t a k e in t u m o r t i s s u e t o g e t h e r w i t h r e l a t [ v e t y low uptake o f m o s t o f t h e o r g a n s due to r a p i d c l e a r a n c e of t h e a m i d e resulted in t u m o r i m a g i n g o f good q u a l i t y . This imaging study clearly dispiayed specific concent[ation in m e l a n o m a w h i c h is v i s u a l i z e d w i t h a good r e s o l u t i o n , about 4 mm f o r the p i n h o l e c o l l i m a t o r .

Tuesday, August 28, 1990

A NEW M E T H O D FOR M E A S U R I N G OF SKIN PRESSURE. H.Itoh, T. Shimada, Y.Morf, K.Kawakami Jikei University, Tokyo, Japan.

PERFUSION

We developed a new technique for measuring the skin perfusion pressure (SPP) by Xe-133 clearance and studied the SPP in diabetics. Our method has two f e a t u r e s compared with the c o n v e n t i o n a l method, i) A small cuff was used not to disturb venous drainage. 2)Decreasing pressure method was applied instead of increasing pressure method. The SPP was measured in 20 normal volunteers and 66 diabetics. Xe-133 saline (0.01ml, 100uCi) was injected into the skin of the pretibial region. The depot was coverd with a small cuff. The cuff was inflated quickly to stop the peripheral blood flow, the deflated gradually while monitoring its pressure. W h e n the c u f f p r e s s u r e f a l l s to a certain point, clearing of the Xe-133 by the blood folw starts. This point of pressure was considered the SPP. The skin blood flow was clculeted from the clearance curve of this Xe-133. The SPP was 33.5+7.2cm H O in normal subjects, 25.4+8.7cm H O in the d i a b e t i c s . The skin blood flow was also s i g n i f i c a n t l y d e c r e a s e d in d i a b e t i c patients. The low SPP in the d i a b e t i c s may be due to the steal p h e n o m e n o n of the b l o o d flow t h r o u g h the arteriovenous shunt vessels that dilate abnormally due to diabetic neuropathy. The blood flow in the c a p i l l a r y bed is, therefore, d e c r e a s e d in the diabetics. The simultaneous measurement of the SPP and the skin blood flow is useful to assess the impairement of peripheral circulation.

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BASIS FOR MYOCARDIAL ISCHEMIA DETECTING RADIOPHARMACEUTICAL: ROLE OF PCr SHUTTLE. K. Horiuchi, K. Ochi, K. H a m a m o t o and A. Yokoyama. Kyoto University, Fac. of P h a r m a c e u t i c a l Sciences. Sakyo-ku, Kyoto, Ehime University School of Medicine, Ehime, Japan.

SUBSTRATE UTILIZATION OF THE SKELETAL MUSCLE IN CARDIOMYOPLASTY : A PILOT STUDY IN DOG USING PET. C. De Landsheere, A. Rijnders, F. v/d Veen, J. Hodiaumont, G. Del Fiore, M. Guillaume, C. Lemaire, G. Heidendal, H. Wellens, P. Rigo, Maastricht, The Netherlands and Liege, Belgium.

In our search for the development of myocardial ischemia detecting radiopharmaceuticals, i n v o l v e m e n t of the p h o s p h o c r e a t i n e (PCr) shuttle, a reserve of high energy phosphate (HEP) bond was estimated. Since TI201 myocardial imaging is a valuable clinical tool in distinguishing non-ischemic, ischemic but viable myocardium, the c o r r e l a t i o n b e t w e e n PCr shuttle and the biological behavior of T1-201, was considered. In the present work, rat m y o c a r d i u m t i s s u e - s l i c e model was employed using a frequency variable microslicer (Dosaks, Japan)(300 um), and cellular uptake of TI-201 independent of blood flow was correlated w i t h HEP (ATP, ADP, AMP, Cr, CrP) m e a s u r e m e n t (reverse-phase C-18 HPLG), in control and injured slices (ischemic). Preserved metabolic function was detected in the control slices while injured slices s h o w e d very interesting results. Data showed a decrease in the concentration of HEP with the degree of injury well correlated with loss of T1-201 uptake ability; while the F-18-FDG, used as an experimental control showed an increased accumulation. However, if slices were returned to oxygenated incubation media, the ATP, ADR, A M P and C r e m a i n e d constant w h i l e only that of PCr r e c o v e r e d along the incubation time depending upon the degree of injury. Of particular interest being the follow up of the TI201 uptake along the recovery of PCr. Further studies relevant to this finding is now under progress. Thus, this implication of PCr shuttle in the TI-201 uptake might serve as a basis to build up a necessary conceptual notion for further development.

Substrates utilization by the skeletal muscle used for cardiomyoplasty and submitted to synchronized electrical stimulation could provide information on its degree of transformation. This study aims to define perfusion with potassium-38, glucose utilization with (F-18)-deoxyglucose (FDG) and oxydative metabolism with (C-ll)palmitate. Five mongrel dogs were studied at various intervals (2 weeks and 6 months) after cardiomyoplasty. Four dogs were sacrificed shortly after the final PET study. PET data were compared to hemodynamic and echocardiographic measurements and to autopsy findings. The 3 tracers showed normal myocardial uptake. High FDG uptake dysproportionate to flow, suggesting anaerobic metabolism, was observed, early in the skeletal muscle of all dogs and late, in 3 dogs. No significant palmitste activity could be demonstrated at the site of the skeletal muscle, in any dog (n=3). Perfusion study did not allow the identification of the transposed muscle, except in one dog. Increase in EF and/or contractility was observed in 2/5 dogs. Autopsy revealed (partial) muscle atrophy in the 3 dogs without hemodynamic changes. The site of the extracardiac FDG corresponded to the remnants of viable muscle tissue. In one dog, autopsy showed complete degeneration of the transposed muscle; this muscle was not visualized by any tracer. This pilot study suggests that PET may be used to demonstrate the viability of the transposed skeletal muscle. Glucose seems to be the preferred substrate in early studies and for some cases later.

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COMPARTMENTAL MODEL FOR DELINEATION OF MYOCARDIAL C11 -ACETATE KINETICS, A.Buck,G.Westera*, G.Hutchins, M.Schwaiger. Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI., * Division.of Nuclear Medicine, University Hospital ,Zurich, Switzerland.

ESTIMATION (II tilE. ISCHEMIC THRESHOLD FOR THE PRESERVATION 01, H~OC'ARDIAL CONTRACTILITY AND METABOLIC ACfI~ITY USING H21sO, ISFDG and PET. Y. Oda, M.

Previous analysis of acetate PET data relied on exponential fitting of myocardial C-11 clearance neglecting C-11 acetate recirculation. In order to correct for C-11 blood activity, we employed a compartmental model for the analysis of dynamic C-11 acetate PET studies of 6 patients with varying heart rate pressure product (DP, 6000-16000). Myocardial time activity curves (TAC) were fitted to a 2 compartment (Kl,k2) and a 3 compartment model (Kl',k2',k3'). The results were compared to monoexponential fitting of myocardial TAC with (p.') and without (~) the addition of a constant. The measured C-11 blood activity (cam) was corrected for C-11 CO2 activity according to the following formula: ca=cam-A*(1-exp(q*t). A and q were determined such that C l l - C O 2 activity accounted for 80 % of total blood activity 20 min p.i. (previously published data). Ca was assumed to represent only C11-acetate activity. The results, presented as the mean rate constants RC [min-1], were correlated with DP as a measure of MVO2, yielding correlation coefficient r. ~' k2 k2' RC 0.074 0.097 0.180 0.165 r 0.28 0.18 0.92 0.94 The rate constants calculated with the model are significantly higher and correlate better with DP. These data emphasize the need for a model approach, which accounts for input function variability to adequately estimate myocardial oxygen consumption with C11-acetate.

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Yamashita~ S. Otsuka, Y. Kira, H. Horii, K? ~ , R. Fujii, H. Yamagish}, H. Nakahashi, M. Kondo. Kyoto Prefectural University of Medicine, Nishijin Hospital, Kyoto, Japan. To assess residual myocardial blood flow (MBF) and glucose utilization in pathological Q wave infarcted areas with abnormal wall motion, we studied I0 normal subjects and 30 patients with prior myocardial infarction using PET with HzlSO and ISFDG under resting and fasting conditions. Myocardial activities were determined from serial PET images and spillover of blood volume H21sO activity was corrected by subtracting a separate C150 scan. Regional MBF was calculated by fitting the time activity curve with a modified single compartment model. 18FDG images correlated with H21SO images were visually analyzed by two experienced observers. A total of 60 regions with abnormal wall motion were selected for assessment. The residual MBF values in infarcted regions demonstrated a significant decrease compared with the normal MBF values (0,59_+0.17 ml/min/g vs. 0.94_+0.09, p<.OOl) and also demonstrated a significant decrease in accordance with the severity of wall motion abnormalities (A: mild hypokinetic, 0.78+_0.17; B: severe hypokinetic, 0.61+0.09: C: akinetic, 0.49+0.08; D: dyskinetic, 0.39_+0.081. 34 regions (97%) in-groups A and B showed residual MBF values higher than 50% of those of normal regions, while 16 regions (64%) in ~roups C and D showed values lower than 50%. In the SFDG study, 4 0 r e g i o n s (67%) demonstrated increased ISFDG uptake under resting and fasting conditions. Furthermore, increased ISFD G uptake was observed in 33 regions (94%) in groups A and B, whereas 7 regions (28%) showed increased ~~FDG uptake in groups C and D (p<.O01). T h i s d a t a s u g g e s t s t h a t a l m o s t 50% of normal mean m y o c a r d i a l b l o o d flow v a l u e , which i s a b o u t 0.47 m l / m i n / g , may be t h e i s c h e m i c t h r e s h o l d for the p r e s e r v a t i o n of myocardial c o n t r a c t i l i t y and m e t a b o l i c a c t i v i t y in t h e Q wave i n f a r c t e d a r e a s .

Tuesday, A u g u s t 2 8 , 1 9 9 0

673

674

COMBINED ASSESSMENT OF MYOCARDIAL PERFUSION AND METABOLISM BY ECG GATED HIGH RESOLUTION PET: COMPARISON TO MRI AND HISTOPATHOLOGY. A.L. Brownell R.I. Petfigrew, F. Holmvang, U. Spencer, R. McKinstry, H. Kantor, J.F. Southern, C.W. Stearns, C. Burnham, B. Rosen, and G.L. Brownell. Massachusetts General Hospital, Boston, MA.

Changes in phorbol ester binding to protein kinase C in the rat neostriatum and neocortex following middle cerebral artery o c c l u s i o n

This study was carried out to determine the relative value of high resolution positron emission tomography (HR-PET) and MRI in identifying and quantitating regions of ischemia and infarct in dog heart. Quantitative studies of blood flow with N13 ammonia and glucose utilization with F-18 2-fluorodeoxyD-glucose (2FDG) were performed in 10 dogs for 3-5 hours post LAD or LCX coronary artery ligation and 3 normal dogs. Cardiac gating was used to obtain time resolved 5 mm thick transverse sections at 40-80 msec intervals throughout the cardiac cycle with a spatial resolution of 4.5 mm using PCR-I. MR imaging was performed at 0.6 T. Both Cine MR imaging and static MR imaging with spin echos were performed. After imagLng, histopathologic studies (HP) were performed. All areas of infarction by HP showed a PET pattern of decreased perfusion and glucose utilization. Wall motion of these segments could not be assessed. On MRI, these regions showed no systolic thickening and some diastolic thinning. All areas of ischemia on HP showed a PET pattern of decreased perfusion and increased glucose utilization. Marked relative hypokinesis was seen on dynamic 2FDG comparable to that seen in Cine MRI. HR-PET as performed in this study may aid in the identification of viable myocardial segments at risk.

Y., Yamamoto, Y.L., One, S., Hosaka, T., Shimauchi, M.: Montreal Neurological Institute, Canada Imahori,

An implication of prompted excitatory amino acids (EAA) receptor action in the development of neuronal damage has been suggested. A study for ischemic change manifested by a particular membrane process could be approached from the aspects of phosphatidylinositol (PD response and protein kinase C (PKC) system, since these second messenger system links to EAA receptors. We report here the temporal changes in 3H-PDBu binding following the middle cerebral artery occlusion (MCAO) by using triple autoradiographic technique for the simultaneous measurement of CBF, CMRglc and PDBu binding recently developed. The ischemia-induced hyperglycolytic state, which appeared 2 hours after MCAO, was attenuated with NMDA antagonist (MK-801), suggesting that such hypermetabolism is one of the aspects which manifested by excitatory toxins. An increase in PDBu binding in the neostriatum can be observed 3 hours after MCAO, accompanied by the regression of glycolytic hypermetabolism. These events are not in accord chronologically but are in accord regionally. In the vulnerable neurons in layer 5 and 6 of neocortex, MCAO produced an increase in PDBu binding; however, these changes appeared from earlier time after the MCAO. This correlates to the distribution of neuronal damage and probably reflects the selective vulnerability of neuronal cell. We suggest that PKC is the key enzyme converting these signaling on PI response to the cellular damage via protein phosphorylation.

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COMPARISON OF HIGH RESOLUTION POSITRON EMISSION TOMOGRAPHY AND MRI WITH HISTOPATHOLOGY IN STUDYING OF INFARCT IN RAT BRAIN. A-LBrownell., M.A. Moskowitz, R. McKinstry, M. Kano, B. Rosen and G.L. Brownell. Massachusetts General Hospital, Boston, MA.

CORRELATION OF 1-123 IMP BRAIN SPECT WITH CAROTID DISEASE IN TRANSIENT ISCHEMIC ATTACKS. J.A. Lan, P.M. Katz, S.L. Heller, D.M. Rosenbaum, L.M. Freeman. Montefiore Medical Center/Einstein College of Medicine, Bronx, N.Y.

This study was performed to demonstrate the value of high resolution positron emission tomography (HR-PET) compared to MRI and histopathology to evaluate infarcted regions in rat brain. Studies were carried out in 11 infarcted and 3 normal Long Evans male rats. To produce cerebral ischemia the main branch of the middle cerebral artery was permanently ligated above the rhinal fissure and both common carotid arteries were occluded for 90 min with clips. This procedure produces focal ischemic stroke in the right temporal cortex. Quantitative study of glucose utilization was done using F-18 2-fluorodeoxy-Dglucose and the positron tomograph (PCR-I) with a spatial resolution of 4.5 man. Immediately after PET-study, static MR imaging was performed at 0.6 T with Technicare Teslacon. T2 weighted imaging were done. After imaging animals were sacrified and brains were stained with triphenyl tetrazolium chloride (TrC) solution to identify affected areas. All areas of infarction by TIC showed a PET pattern of markedly decreased glucose utilization in middle cerebral artery territory on the right side. MRI showed in the area markedly increased signal HR-PET as performed in this study demonstrates that it is possible to study glucose utilization in rat stroke model in vivo and non-invasively.

Tuesday, August28,1990

Patients with carotid territory transient ischemic attacks(TIA) were evaluated with 1-123 IMP SPECT(SPECT) to correlate deficit volume on SPECT with the presence of a hemodynamically significant(HDS) carotid stenosis. 13 consecutive patients were evaluated up to one week after a TIA by early and delayed SPECT and CT, and the findings correlated with cerebral angiography and/or carotid duplex scans. A lesion was considered HDS if one or more of the following criteria were present: residual carotid lumen~
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MAPPING OF THE SUPRATENTORIALLESIONS (SL) ASSOCIATED WITH CROSSEDCEREBELLAR DIASCHISIS (CCD) USING Tc-99m HMPAO. J.P. Soucy, M. Primeau, R. Ouellette, J. Lamoureux, S. Danais, F. Lamoureux. H~pital Notre-Dame, Montreal, Canada.

EVALUATION OF CEREBRAL VASCULAR RESERVE IN CHRONIC OBSTRUCTIVE CAROTID DISEASE USING SPECT : DETECTION OF "MISERY PERFUSIBN" AND DECIDING THE INDICATION OF EXTHACBANIAL-IN'~CRANIAL BYPASS

We previously have communicated our results on the l o c a l i s a t i o n of SL associated with CCD in a small (M-42) group of patients. Since then, we have extended those observations to 217 patients (118 M, 99 F) submitted to a t o t a l of 238 tomograms with Tc-99mHMPAO, a l l of them showing CCD; 140 CT scans were available for comparison. Our results were divided in four groups: II the whole group of patients; 2) studies showing SL with both HMPAOand CT scan; 3) studies with SL on BMPAO not seen on CT scan; 4) HMPAOstudies with SL but without CT scan. Group

# studies

CCD

1

238

§

2

64

+

3

76

~

4

98

~

Motor SL 74 81 21 14 24 32 29 35

(31~) (34"/.) (33%) (22%) (32%) (42%) (30%) (36%)

Non Motor SL 15 68 I0 19 3 17 2 32

(6%) (29~) (16%) (30%) (4%) (22%) (2~) (33~)

CCD was very s i g n i f i c a n t l y (Chi square t e s t , p
SURGERY. H. Toyama, G. Takeshita, h. Takeuchi, H. Maeda, K. Ejiri, K. Katada, N. Ishiyama*, T. Kanno*, and S. Koga. Departments of Radiology and Neurosurgery*, Fujita Health University School of Medicine, Toyeake, Japan. lo evaluate cerebral vascelar reserve by regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and rCBV/rCBF rati.o, 24 patients with chronic occlusion or severe stenosis of the internal carotid or the middle cerebral artery (21 patients with unilateral cases, 3 patients with bilateral cases) of normal or with on!y lacunar infarction on X-ray CT were studied using ring type SPECf " ~ " . Wemeasured rCBF with Xe-133 inhalation and rCBV with Tc-99m red blood ceils. rCBV/rCBF ratio was calculated using these two values. Nineteen out of 27 lesions (70 %} showed decreased rOBE in large middle cerebral artery territories of the affected hemispheres. But of those patients, 9 lesions (33 %) showed increased rCBV and remarkably increased rCBV/rCBFratio. Decreased rCBF, increased rCBV and remarkably increased rCBV/rCBF ratio can be assumed as the s t a t e of reduced cerebral vascular r e s e r v e - s o called "misery perfusion"us reported in PET studies: The extracranlalintracranial (EC/IC) bypass surgeries were performed on 3 cases of chronic unilateral internal carotid artery occlusions which were assumed as the "misery perfusion". On a l l 3 cases. postoperative SPECT showed improvement with increased rCBF, reduced rCgV and rCBV/rCBF ratio in the affected hemisphere in long term follow-up. In conclusion, measuring rCBV as well as rCBF using SPECT is very significant to detect the reduced cerebral vascular reserve -"misery perfusion" without PET, and to decide the indicatan of EC/IC bypass surgery.

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COMPARISON OF ECD Tc 9 9 m AND IMP I123 SPECT IMAGING IN SUBACUTE STROKES. J.L Moretti, P. Cesaro, C. Belin, G. Defer, A. N e u m a n , P. Delaporte, D. Le Guludec, N. Caillat-Vigneron - CHU PARIS BOBIGNY - CHU H. MONDOR CRETEIL FRANCE 13 patients (6 f e m a l e s m e a n age 72 • 9 ys, 7 males) w e r e s t u d i e d after t h e occurence of a middle cerebral a r t e r y stroke. Each p a t i e n t w a s injected i n t r a v e n o u s l y w i t h 800 MBq of 9 9 m Tc-ECD a n d 300 MBq of 123 I-IMP (I d a y b e t w e e n injections). Tomoscintigraphic acquisition by rotating g a m m a c a m e r a w a s s t a r t e d after ECD or IMP : ECD (n=13), 30 • 15 m i n for e a r l y IMP (n = 13), 258 • 57 min for delayed IMP (n = 13). All p a t i e n t s s u f f e r e d of h e m i p l e g i a a n d / o r aphasia, CT scan w a s p e r f o r m e d b e t w e e n I to 24 d a y s after s t r o k e ) w e r e positive in all cases. For e a c h p a t i e n t all slices w e r e analyzed for each t y p e of acquisition (ECD and IMP) a n d compared. The main r e s u l t s w e r e : 1 ) SPECT b r a i n i m a g e quality w a s b e t t e r t h a n IMP in 4 cases, e q u a l in 7 a n d inferior in 2. 2) In general, p a t i e n t s i m a g e d w i t h ECD 3 h r s post injection s h o w e d b e t t e r contrast a n d d i s p l a y e d m o r e clearly t h e h y p o p e r f u s e d area t h a n p a t i e n t s i m a g e d at 1 hr. 3) ECD a n d IMP s h o w e d h y p o a c t i v e a r e a s r e l a t e d to t h e neurological s y m p t o m s wich are larger in size t h a n t h e CT h y p o d e n s i t y .

L A B E L I N G OF D I E T A R Y FIBERS: AN IN VITRO STUDY W I T H IN VIVO C O N F I R M A T I O N IN A N I M A L A N D H U M A N . P. Thouvenot, J-M. Antoine, P. Maincent, A. Bertrand, Department of Nuclear Medicine, University of Nancy, France.

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Tile aim is to labeldietary fibers in order to study their gastric e m p t y i n g and their colonic transit, as well as their influence on the transit of the meal. Pea, beetroot, bran and barley fibers were labelled with Indium- 111 oxinate. I n v i t r o s t u d y : the a m o u n t of radioactive m a r k e r remaining bound to the fibers, after 6 hrs of incubation in the gastric juice, varied between 77 and 92% depending on the nature of fibers. I n a n i m a l : groups of 6 rats were placed in metabolic cages and fed exclusively on labeled fibers and water (after 48 hrs fast). After a further 48 hrs they were sacrified. The level of RA in the faeces and intestine was found to be greater than 9 8 % . There was no traces of RA neither in the blood and urine nor in any other organ, irrespective of the origin of the fibers. I n h u m a n : 12 healthy subjects were provided, at a one week interval, with a meal containing pasta, to wich 20 g of In labeled fibers had been added. The fibers were either mixed directely with the meal or introduced during the preparation of the meal. Scintigraphies of the abdomen were taken every 30 min during a period of 12 hrs, as well as one at 24 hrs. 211e fibers reached the left flexura of the colon after approximatively 10 hrs. The level of RA in the faeces exceeded 9 0 % a n d whilst less than 2% was found in the urine. The transit of fibers and their influence on the transit of different foods can be explored using this technic.

T u e s d a y , A u g u s t 28, 1990

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RADIONUCLIDE ESOPHAGEAL TRANSIT STUDY IN DETECTION OF ESOPHAGEAL MOTILITY DYSFONCTTON: COMPARISON WITH MANOMETRY. R. Taillefer, M. Jadliwalla, E. Pellerin, E. hafontaine, A. Duranceau. Departments of nuclear medicine ann thoracic surgery. Hotel-Dieu de Monnr6al, Canada.

THE UTILITY OF PROVOCATIVE RADIONUCLIDE ESOPHAGEAL TRANSIT IN THE EVALUATION OF NONCABDIAC CHEST PAIN. R.E. Ellowau M. Jacobs, M.F. Nathan, J.C. Mantil. Kettering Medical Center, Dayton, OH.

Radionuclide esophageal transit study (RET$) has been d~ve!oped to assess motor tunctlon of the esophagus. The purpose el this study was to compare RETS to esophageal motility studles (EMS) io detecLion of motility dlsorders. A total of 109 consecutive patients without previous history of surgery on the esophagus anderwent both RETS and EMS within one month of each other. All patients were referred for esophageal symptoms and their esophageal investigation also included radiology, 24 hr. pH-metry anO endoscopy. RETS was performed in supine position following ingestion of 15 ce of water labeled with 1.0 mCi of 99mTc-sulfur collo~d. Computerized data were acquired at 0.5 sec intervals for 2 minutes. Tlmeactiwty curves were generated for hypopharynx,esophagus (4regions) and gastric tundus. All EMS tracings were diagnosis was divided into 3 categories: reflux dlsease, primary motor disorders and non-cardiac chest pain. Using EMS as the standard, the results of RETS were as follo~:s: I- Reflux disease (n=48) II- Motor disorders (n=39) III-Non-cardiac pain (n=22) IV- Global results (n=]09) No clinically In conclusion, the screening of esophageal

SENS. 92% 97% 77% 92%

SPEC. 91% 100% 88%

f.n. 2 1 3 6

f.p. 2 2 0 4

significant lesions were missed by RET$. RETS is a useful non-invas~ve test for of patlents with symptoms thought to be origin.

683

We a s s e s s e d the d i a g n o s t i c u t i l i t y of the radionuclide esophageal transit (RET) of aqueous Tc99m sulfur colloid when preceded by an injection of edrophonium (ED) in a g r o u p of patients with noncardiac chest pain. Twenty subjects were referred by their primary care physician or cardiologist in a community hospital setting after evaluation for chest pain resulted in a negative cardiac evaluation. Provocative RET studies (P-RET) were performed by combining the two techniques as described by Russell (Gastroenterology 80: 887,1981) and Richter (Annals Int Med 103:14,1985) respectively. The first swallow, preceded by normal saline served as a control. ED, 80ug/kg preceded the second swallow. Patient symptoms during p-RST were determined. 55% of patients had abnormal studies: 30% had abnormal baseline RET (transit tin~ >15 seconds) and an additien-al 25% had an abnorn~l ED response. This was either abnormal transit time (10%) or reproduction of typical pain (15%). Where the transit time was measurable, ~3 was found to prolong it in 80%, and shorten it in only 13%. A control group of normal volunteers had no abnormalities, nor did ED significantly prolong transit time. We c o n c l u d e that P - R E T provides additional information to baseline RET, and its simple technique is well tolerated by patients with noncardiac chest pain. ED also appears to prolong transit time in patients with noncardiac chest pain.

684

BOLUS SPLFITING BY LOWER ESOPHAGEAL SPHINCTER

(LES) I. Bofilias, H. Langhammer and H. W. Pabst Clinicof Nuclear Medicine, Technlsche Unlversit~t of Munlch,FRG Summarising the various sointigraphic techniques which have recently successfully contributed to the better understanding of the mechanisms of the esophageal motility disorders we distinguish between the single and the multi swallows parametric methods. These use colloid/Liquidor semisolid meals labelled with 99roTe. Although the single swallow technique (Bolus) may show considerable intraindividual variations (Klein et al. 1987, Bartlett etal. 1987), it is accepted, that suitable bolus application may contn'bute to resdts which are desdy related to the organ response. Comparing the time activity curves between upper and lower esophagus we found bolus splittiag in all normal cases (n = 9), whereas no such splitting was observed by sderodermla (n = 14) and aehalasia (n = 12). This bolus splitting induced by LES is clearly observed by choosing extremely short aequisiliun time (<.25 see/frame). This time restriction requires usually a rather coarse dynamic frame mode accluisitioa (32x32 pixels /frame). Due to a) the significant lost of spatial resolution and b) the .~m~lhaess of the organ exteusioa (LIES) we developed a software packet which includes a) org~ ~]1~ment algorithms, b) overlay tedmiqaes, whieh displays both x-ray esophageal rdevant features and the aligned esophageal scintigram. Thus, the delination of LES is better ~ocalizod. The bolus splitting may be used as a qualified criterion for normal motih'ty function of the LES. Obviously, LES fulfils a protection motility mechanism for gastrium. It enables gastrium to test food acceptance only by a part of bolus.

Tuesday, August 28, 1990

IMMUNOSCINTIGRAPHY

WITH

GRANULOCYTES

ANTIBODIES IN PATIENTS WITH NECROTIZING PANCREATITIS. A.Kroiss, P. Sporn, Ch. Auinger, M. Kolacny, E. Redl, Ch. A r m b r u s t e r , G. Edelmann, and A. Neumayr. KA R u d o l f s t i f t u n g , Vienna, Austria. S e p t i c c o m p l i c a t i o n s are the p r e d o m i n a n t cause of d e a t h in n e c r o t i z i n g pancreatitis. As surgical i n t e r v e n t i o n is m a n d a t o r y in the case of s u p e r i n f e c t i o n of n e c r o s e s e a r l y d i a g n o s i s is e s s e n t i a l for survival. The a i m of this s t u d y was to p r o v e the clinical r e l e v a n c e of m o n o c l o n a l g r a n u l o c y t e s a n t i b o d y for this d i a g n o s t i c question. T h e i m m u n o s c i n t i g r a p h y (IS) w a s p e r f o r m e d w i t h i0 mCi (370 MBq) T c - 9 9 m l a b e l e d a n t i b o d i e s (Abs; BW 250/183; Behringwerke, FRG). The images were d o n e 4 hrs and m o s t l y 24 hrs planar. 13 pts s u f f e r e d from a severe a c u t e p a n c r e a t i t i s u n d e r i n t e n s i v e care c o n d i t i o n s (7 female, 6 male; a g e 50 • 15 yrs). In these pts w e p e r f o r m e d 27 i n v e s t i g a t i o n s : in 4 pts only once, in 5 pts twice, 3 pts t h r e e times and in one pat four times. A s all pts w e r e o p e r a t e d the r e l i a b i l i t y of IS c o u l d be v a l i d a t e d b y b a c t e r i o l o g i c a l cultures. In ii pts we found a true p o s i t i v e r e s u l t and in 2 pts a n e g a t i v e result - t h e s e 2 pts s h o w e d just edema of the p a n c r e a s and no s u p e r i n f e c t i o n at the time of operation. O n l y in 1 p a t w i t h 2 i n v e s t i g a t i o n s we found a b o r d e r l i n e level of HAMA's. In c o n c l u s i o n : IS w i t h g r a n u l o c y t e s A b s seems to be a i m a g i n g m e t h o d to d e t e r m i n e the c o r r e c t m o m e n t of s u r g i c a l intervention.

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686

COMPARATIVE SIIIDY OF CROP~'S DISEASE USING MONOCLONAL ANTIBODY BW 250/183 AND IABEIAZ9 ~ O C Y T E S

IN VIVO DETERMINATION OF THE GL
J. Ramos, M.J. T a b u s , M.J. Arggeso , P. Uriarte, I. Castej6n, L. Abreu, J.O. Berrocal. Nuclear Medicine and Gastroenterology Services, Clinica Puerta de Hierro, Madrid, Spain We present our results with 20 Crohn's disease (CD) patients studied with monoclonal antibody (MAB) 250/183 and leukocytes labeled with either indium (IL) or 99m-tecllnetium (TL), to see if MAB can substitute labeled leukocytes (LL) in the study of CD, thus avoiding the risks of handling and labeling leukocytes and saving time as well. Material: Twenty CD patients; MAB-99m Tc at a dose of 250-400 MBq; LL (250-400 MBq). Methods: ist: study with MAB; 2rid: LL study. Results: Of the 20 patients, CD activity was detected in 14 (in 13 of whom both methods ware effective) : in 6, only at the level of terminal ileum (TI) ; in asce/%ding colon (AC) in 3; and in TI and AC in 3; 1 patient had activity in TI and AC with both MAB and IL, and in sigmoid colon and descending colon only with MAB. Only 1 case was positive with IL and negative with MAB at the sigmoid level. In the 6 patients in whom DC activity was not detected with either method, the CADI was <150 at the time of the study. Conclusions: a) The findings with MAB and TL are similar in intensity and extension, b) IL findings are less intense and defined, possibly due to the physical charactaristics of lll-In, which may not detect small lesions, c) We prefer the use of MAB to avoid the manipulation of the leukocytes and possible problems arising with labeling.

An in vivo n~thod to measure the glomerular filtration rate (GFR) based solely on image processing of the standard DTPA renogram was developed by simplifying an in vivo method described previously by Rehling et al. We compared an in vitro technique based on 3 blood samples at 150,180 and 210 mn, with the in vivo method in 36 pts (13 men and 23 women), with a mean age of 55.2 and an average GFR of 71.3 ml/mn (range 0 to 150). The in vivo method is based on the relation between early kidney uptake of DTPA and GFR, and the use of the aortic blood pool as a depiction of background activity. The only manipulation required is the tracing of regions over the aorta and kidneys but no background regions, and no laboratory manipulations. Results: Regression analysis showed a correlation coefficient of 0.92 between both methods, and inter observer correlation of 0.98 and an intra observer correlation of 0.99. Bolus geometry and partial subcutaneous infiltration did not affect the reliability of the results. The only limitation is an underestimation of the GFR in pts with a height (cm) to weight (kg) ratio inferior to 2 (pts who are both obese and short). Conclusion: It is possible to measure the GFR reliably on the standard KfrPA renogram solely by image processing and independently of bolus geometry.

687

688

UNIFIED SINGLE-INJECTION, SINGLE-SAMPLE RENAL CIZARAk[~ METHODS FOR BOTH CHILDREN AhD ADULTS. C.D. Russell, E.V. Dubovsky, J.W. Scott, Univ. of Ala. in Birmingham and V.A. Med. Ctr., Birmingham, Ala. USA.

INTER-OPERATOR ERRORS IN BLOOD FLOW ASSESSMENT IN RENAL TRANSPLANTS. k.C.Young, I.Hassan, N.Bellani and H.M.Abdel-Dayem. Dept. of Nuclear Medicine, Faculty of Medicine, Kuwait.

Develolm~ent and validation of simplified clearance methods has required multiple blood samples obtained over a substantial time interval, difficult to obtain for children. To minimize the data r e q u i r ~ t , there must be scaling for patient size. A scaling technique is presented and evaluated ~ r e . The sample time was chosen according to patient weight w and area A from the forn~la wt/A (t constant). The clearance F per unit area was F = a + bx + cx**2 with x = I/wp and p the plasma concentration in fraction of administered dose per unit volume. The pararc,eters a, b, and c and t were chosen for best fit. Parameters for iodohippurate (OIH) and Tc-99mDTPA clearance were first computed using adult data truly, and then cross-tested against pediatric data frQm the literature. Close a ~ t was found between observed and predicted clearances for the pediatric data (r = 0.93 for pediatric OIH using constants calculated from adult OIH data, and r = 0.93 for pediatric diatrizoate using constants calculated frc~ adult TC-99m-DTPA data). In conclusion, b y means o f proper scaling, pediatric single-sample renal clearance methods can be developed using data mainly from adults. Measuremerits in a small number of pediatric patients are required to confirm and refine the method for each radiopharmaceutical of interest. The same for~mlas can then be used for both adults and children.

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 i0 patients, within 24 hours of surgery and subsequently during rejection. In each study a bolus injection of 8 mCi of Te-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 measurements were analysed to find the inter-operator errors. PI 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 10.9%, 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. Nucl Med Com 8:823-837,1987 ** J Nuel Med 29:1656-1661,1988

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Tuesday, August 28, 1990

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690

FUNCTIONAL URETERIC IMAGING IN DILATED NON-OBSTRUCTED OUTFLOW TRACT S AIAD, C PAGE, C RUFF AND T NUNAN St Thomas' Hospital, London.

FUNCTIONAL URETERIC IMAGING/NORMAL PARAMETER S AIAD, C PAGE, C RUFF AND T NUNAN St Thomas' Hospita], London.

The aim of this study was to assess the role of ureteric imaging in patients with dilated nonobstructed renal outflow tracts. 27 ureters in 18 patients were studied. All 27 ureters were associated with dilated outflow tracts. Standard renography was performed using 80 MBq of 99m Tc MAG3. Frusemide was given at 20 mins and a further i0 mins data was acquired. Ureteric images were acquired using 2.5 sec frame times and 64 x 64 matrix by dividing the ureter into 6 regions of interest and expressing the activity in each region in a time-space matrix. 15/27 ureters were studied pre and post diuretic injection. Prior to frusemide all 15 ureters had visible ureteric activity at the time when renogram curves were still rising. All ureters had good response to lasix with a diuresis excretion index (DEI] greater than 20%. This was associated with the presence of frequency of >2 wave/min in 13/15 ureters before injection.

Functional ureteric imaging allows ureteric peristalsis to be visualised Jn a timespace matrix. In order to study various disease states, it is necessary to establish the norma] patterns of ureteric peristalsis. We have studied 33 normal ureters in 28 patients. Prior to ureter processing, normal ureters were selected according to the following criteria - All had a normal renogram on the re]evant side. - There was no indication of clinical disease in either the kidney or the ureter on the side used. - There was no indication of clinical disease on the other side which might affect the normal side, eg dilated system, urinary tract infection. 80 MBq of TC 99m MAG3 were injected IV and data was collected over 20 minutes with frame time of 2.5 sec and 64 x 64 matrix. Ureteric images were acquired by dividing the ureter into 6 regions of interest expressing the activity in each region in a time-space matrix. Both the urine volume and the flow rate were assessed.

Our preliminary results indicate that ureteric imaging may provide clinically useful information in the assessment of dilated non-obstructed tract.

The following characteristics were considered as normal parameters. i) Antegrade peristalsis. 2) A frequency of peristalstic wave of .8-4/min. 3) Regular wave pattern with up to 20% variation in time. 4) Direct relation between the peristalstic wave and the urinary flow rate.

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CLINICAL EVALUATION ON CORTICAL SCARRING BY Tc-99mDMSA SPECT IN PATIENTS WITH CLINICAL EPISODE OF URINARY TRACT INFECTION. K Itoh, Y Asano, K Nonomura, and M Furudate. Hokkaido University Hospital, Sapporo, JAPAN.

RADIOIMMUNOSCINTIGRAPHYOF MALIGNANTMELANOMA. M. Fischer, J. Spitz, J. Petres. St~dt. K1iniken. Kassel, FRG

Post lasix, the number of peristaltic waves/min in all 27 ureters positively correlated with DEI.

The usefulness on clinical application of renal S P E C T u s i n g T c - 9 9 m - D M S A was e v a l u a t e d for the detection of cortical scarring in patients (pts) with episode of urinary tract infection. A total number of 108 scintigraphies, planar alone is 38 and 70 pairs of planar and SPECT, were carried out in 95 pts (age ranged from 2 months to 65 yrs, average being 14 yrs). In all but four 4 pts, vesico-ureterie reflux (VUR) was disclosed by radiographic micturating cystography and 45 pts had already received surgical treatment for preventing reflux. SPECT (64 x 64 matrix, 360 rotation, 6 degree per 1 step for 20 sec each) was performed after obtaining a planar image 2h post-injection with pts lying supine and the digital c a m e r a was p o s i t i o n e d p o s t e r i o r l y b e n e a t h the kidneys. Coronal section images corrected of a renal axis rotation to the body axis was re-constructed. P o s i t i v e r a t e of f u n c t i o n i n g c o r t i c a l d e f i c i t demonstrated by recent radiographic pyelography (IVP), planar images and SPECT images depended on grading of VUR. In overall cases, positive rates of IVP, planar and SPECT were 15% (27/177), 41% (74/182) and 61% (82/134) respectively. SPECT could provide superior cortical resolution particularly in the kidneys with no or a low-graded VUR, which maintained relatively good parenchymal uptake of DMSA. However, SPECT was also positive in 5% of the kidneys in i0 young normal volunteers. Tn-99m-DMSA SPECT is a useful means to enhance sensitivity for the detection of cortical scarring in reflux, although it may tend to decrease specificity.

Tuesday, August 28, 1990

This prospective study was done to evaluate the v a l i dity of anti-melanoma MAb 225.28S labeled with g9m-Tc as imaging agent for malignant me]anoma and melanoma metastases. 174 patients (94 females and 80 males) with suspicion of malignant melanoma and/or metastases were studied. In 147 patients malignant melanoma was confirmed by surgery, in 69 of them p r i o r to RIS. 10/147 suffered from malignant melanoma and metastases. In 28 patients metastases were observed during follow up a f t e r surgery. In 32 primary tumors and 29 lymphnodes immunohistochemistry was performed. Patients underwent whole body scintigraphy and single spot imaging of areas of i n t e r e s t 1-24 hours a f t e r i . v . administration of 9gm-Tc labeled MAb 225.28S. 60 patientswere investigated twice within 24 hours with SPECT. The highest rate of false negative results was observed in lesions with a diameter less than 2 cm. Immunohistochemistry was p o s i t i v e in 27 primaries, negative in 5, whereas RIS was p o s i t i v e in 10 and negative in 27 cases. By immunohistochemistry 3 lymphnode metastases were i d e n t i f i e d p o s i t i v e l y , by RIS only 2 of them. Our experiences using anti-melanoma MAb fragments 225. 28S f o r RIS suggest that there is a strong correlation between tumor size and tumor imaging. We conclude that MAb fragments demonstrate the potential for l o c a l i z i n g tumors, but MAb 225.28S show minor s e n s i t i v i t y in small malignant melanomas and melanoma metastases.

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RADIOIMMUNOSCINTIGRAPHY OF SMALL CELL LUNG CARCINOMA USING THE T c - 9 9 m LABELED MONOCLONAL ANTIBODY NR-LU-10. C.E. Neal, M.R. Baker, T.L. Swan, R,D. Cu11, J.G. K a t t e r h a g e n , a n d K. Sullivan, Memorial Medical Center. Springfield, IL a n d NeoRx Corporation, Seattle. WA.

DETECTION OF OVARIAN CANCERUTILIZING 1111n-CYT-103 RADIOIMMUNOSClNTI GRAPHY A.N. S e r a f i n i * , D.G.Gallup**, R.Vargas-Cuba*, D.East*, B.V.Sevin*, H.Averette*, T.Hardin**, R. Schmelter***, R.Maguire***, G.N.Sfakianakis*. *U. of Miami, School of Mad. Miami,Fl. **Med. Col l . of Georgia, Augusta, GA. ***Cytogen Corp. Princeton, N.J., U.S.A.

This s t u d y is done to e v a l u a t e the u s e of a r a d i o n u c l i d e m o n o c l o n a l a n t i b o d y for s t a g i n g p a t i e n t s with small cell l u n g carcinoma. The p a t i e n t s were evaluated u s i n g T c - 9 9 m labeled m o n o c l o n a l a n t i b o d y (MoAb) F a b f r a g m e n t (NR-LU-10) w h i c h recognizes a glycoprotein expressed i n s m a n cell c a r c i n o m a of the lung (SCCL}. Patients with a diagnosis of SCCL were evaluated with CT of the brain, chest, a b d o m e n a n d pelvis, chest x-ray, radionuclide bone s c a n , b o n e m a r r o w a s p i r a t e , a n d MoAb imaging. The patients received 10 m g of the MoAb labeled with 15-30 mCi of Tc-99m. P l a n a r imaging w a s obtained 14-17 h o u r s later of the head, chest, a b d o m e n a n d pelvis, as well as SPECT imaging of the chest. Eight (8) consecutive MoAb s c a n s on patients with SCCL were performed. MoAb i m a g i n g detected 1 1 / 1 5 (73%) k n o w n or s u b s e q u e n t l y c o n f i r m e d i n t r a t h o r a c i c lesions, 3 / 3 (100%) s u p r a c l a v i c u l a r n o d e s , a n d 7 / 8 (88%) b o n e m e t a s t a s i s . Overall, MoAb i m a g i n g d e t e c t e d 2 1 / 2 6 (81%) k n o w n or s u b s e q u e n t l y p r o v e n lesions. More i m p o r t a n t l y , t h e MoAb i m a g i n g d e t e c t e d t e n (10) l e s i o n s t h a t w e r e p r e v i o u s l y u n s u s p e c t e d , b u t s u b s e q u e n t l y confirmed, sites of m e t a s t a t i c disease. In addition, t h e MoAb i m a g e s identified eight (8) u n s u s p e c t e d a n d u n c o n f i r m e d sites of possible b o n y m e t a s t a t i c disease. These results indicate t h a t MoAb imaghng with NR-LU- 10 h a s a high detection r a t e a n d m a y be a p r o m i s i n g a d j u n c t in the staging of SCCL.

The safety and e f f i c a c y of an intravenously administe~'~ radiolabeled monoclonal antibody (MoAb) B72.3 ( ~ Z l n - C y t - 1 0 3 ) f o r the radioimmunodetection o f cancer was studied in a group o f patients with ovarian cancer. The group consisted o f 8 pat i ent s with 18 known preoperative lesions suspected o f being cancer and 3 patients with no known preoperative lesions but with a high c l i n i c a l suspicion f o r recurrence. ~ i s i n g l e dose of ~IIIIn-cYT-103 labeled with 4-5mCi o f ~ I n - C Y T - I 0 3 was administered intravenouslyover 5-10 minutes with no adverse reactions being detected. All patients underwent whole body planar imaging on 2 occasions between 2 and 7 days a f t e r i n f u s i o n . All pat i ent s went to surgery within 15 days f o l l o w ing MoAb scan to confirm the presence or absence o f tumor detected by a l l preop staging modalities. Ovarian cancer was proven p a t h o l o g i c a l l y in 12 o f the known preop lesions with 90% (11/12) p o s i t i v e on MoAb scan. MoAb demonstrated I0 a d d i t i o n a l unsuspected l e s i o n s , 9 confirmed malignant p a t h o l o g i c a l l y . In t o t a l MoAb scan was p o s i t i v e in 95% of 20 lesions confirmed malignant. Three patients suspected to have ovarian cancer presurgery had benign lesions (serous cystadenoma, pelvic inflammatory disease, theca lutein cyst)which were p o s i t i v e on MoAb scant I Preliminary r e s u l t s suggest that "'~In-CYT-I03 MoAb scan appears promising as a safe single noninvasive t e s t f o r the detection of ovarian cancer.

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1MMUNOSCINTIGRAPHY (IS) USING DIFFERENT APPLICATION ROUTES OF A Tc-99m LABELED MONOCLONALANTI-CEA-ANTIBODY IN THE STAGING OF PATIENTS WITH LIVER METASTASES BEFORE PARTIAL HEPATECTOMY. N. R i l i n g e r , D.L. Munz, H. Niemann, H.J. I l l i g e r , and H.J. HalbfaB. Municipal Hospital of Oldenburg and U n i v e r s i t y of GSttingen, FRG.

INITIAL CLINICAL EXPERIENCE WITH Tc-99m 170H.82, A NOVEL PANADENOCARClNOMA A.J. McEwan, G.D. MacLean, B.M. Longenecker*, Lo Golberg, T.R. Sykes*, and AoAo Noujaim*, Cross Cancer I n s t i t u t e and * U n i v e r s i t y of A l b e r t a , Edmonton, A l b e r t a , Canada.

I t was the aim of t h i s study to determine the value of portal-venous ( p . v . ) , i n t r a - a r t e r i a l ( i . a . ) or intravenous ( i ~ v . ) IS in the detection of l i v e r metastases before p a r t i a l hepatectomy in 36 patients (pts) with c o l o r e c t a l carcinoma. The Tc-99m labeled anti-CEA monoclonal antibody (MAb) i s an IgG1 i n t a c t molecule and reacts e x c l u s i v e l y with a protein epitope on the CEA complex. The l a b e l i n g procedure with Tc-99m i s described by Schwarz and coworkers (1987). Immediately a f t e r angiography and i . a . contrast CT (20 pts) or p.v. contrast CT (6 p t s ) , 700-1200 MBq of the Tc-99m labeled MAb were administered via the i . e . catheter. In 10 pts the MAb was i n j e c t e d i . v . Planar scanning with a gamma camera was performed as f o l l o w s ; sequential scanning during the f i r s t 5 mins., a f t e r 10-20 mins., 4-6 and 18-30 h p . i . , supplemented in special cases by ECT procedures. In 25 of the 36 pts metastatic deposits were discovered. IS detected 47/77 l i v e r metastases, 9/10 lymph node metastases end 3/3 l o c a l recurrences. In 2 pts IS was the only approach to delineate lymph node metastases. Although only 61% of the liver metastases were detected by IS, it was still found to be the decisive method of excluding extrahepatic tumor deposits before partial hepatectomy.

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We have developed a technique f o r generating monoclonal antibodies (MAbs) against synthetic carbohydrate antigens. One of these, designated 170H.82, was derived from the terminal disaccharide of asialo-GM1, the beta anomer of the ThomsenFreidenreich antigen. This MAb reacts in v i t r o with over 90% of adenocarcinomata tested. I t has been r a d i o l a b e l l e d with Tc-99m using a m o d i f i c a t i o n o f the Schwarz method. Eighteen pat i ent s with primary and metastatic adenocarcinoma have been imaged (unknown primary-8, ovary-5, c o l o r e c t a l - 4 , b l a d d e r - I ) a f t e r administration o f 2 mg MAb l a b e l l e d with 1200-1500 MBq Tc-99m. Images were obtained immediately a f t e r i n j e c t i o n and at 3 and 21-24 hours. SPECT imaging was r o u t i n e l y performed at 21-24 hours. Planar imaging showed p o s i t i v e uptake in most primary and metastatic s i t e s in 15 p a t i e n t s ; uptake in l i v e r metastases was c o n s i s t e n t l y less than in extrahepatic s i t e s . One negative image was a true negative, another a f a l s e negative, and a t h i r d was associated with an unknown primary. Tomographic imaging enhanced s e n s i t i v i t y in a l l s i t e s , p a r t i c u l a r l y in the p e l v i s and p a r a - a o r t i c regions. Positive p r e d i c t i v e value about 90%. We believe we have demonstrated a novel Tc-99m l a b e l l e d MAb (170H.82) with p o t e n t i a l f o r r o u t i n e diagnostic use, p a r t i c u l a r l y when used with SPECT. Phase 3 m u l t i - c e n t r e studies are planned.

T u e s d a y , A u g u s t 28, 1 9 9 0

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IMMUNOSCINTIGRAPHY

OF COLO-RECTAL

CARCINOMA WITH AN ANTI

CEA MONOCLONAL ANTIBODY G.L.

Buraggi ~ , M. Gasparini ~ , E. Regalia*,

F. Crippa ~ ,

E. Bombardieri ~ , E. Seregni ~ , M.R. Castellani a - ~ ar Medicine Division and *Surgical Oneology "A" Division - Istituto Nazionale Tumori, Milano, Italy. A technique for immunoseintigraphy of adenocarcinoma was developed using the F02315 anti-CEA antibody and

its F(ab')2 and Fab fragments.

A pilot study performed

in a series of 61 patients with 64 loealizations of colo-reetal carcinoma allowed to detect 64% of primary carcinomas, 90% of local relapses. These results were confirmed by a more extensive mul ticenter study involving ii nuclear medicine departments. A series of 509 patients with 926 lesions of adenocarcinomas were studied. The overall results were: sensitivity 79%; specificity 96.7%; accuracy 82.2%; pre dictive value of a positive result 99.0%. In order to better evaluate the clinical utility of the method in the follow-up of patients operated for co is-rectal carcinoma a prospective study was planned. At present 48 patients with suspect local relapses were examined by immunoscintigraphy, TC, MRI and US. Sensitivity (S=90%) and accuracy (A=90%) of immunoseintigraohy were comparable to those obtained with MRI (S93%, A:85%) whereas CT showed less favourable values (S=69%, A=67%) and US even more unfavourable (S=36%, A=

CHANGES IN THE RADIOSENSITIVITY OF TESTES DURING FETAL DEVELOPMENT AND THEIR MODIFICATION BY 2 MERCAPTOPROPIONYLGLYCINE (MPG). P.K. Goyal and P.K. Dev. Radiation Biology L a b o r a t o r y , U n i v e r s i t y of R a j a s t h a n , J a i p u r , I n d i a . Pregnant Swiss albino mice were whole-body exposed to 0.5, 1.5 and 2.5 G y g a m m a radiation from Go-60 in the presence or absence of M P G during selective organogenesis and fetal growth periods (days 11.25 and 14.25, 16.25 and 18.25 after conception, respectively). After parturition, spermatogonia were scored in the seminiferous tubules of the testes of 4 w e e k s old mice in both the drug treated and untreated i r r a d i a t e d mice.

Gestating females e x p o s e d at 11.25 day with 2.5 Gy showed complete r e s o r p t i o n of e mbryos in both th e groups . With 1.5 Gy, in absence of t he drug, 11.25 day gestating females showed partial resorption (76.10%). Male o f f s p r i n g d e r i v e d from 14.25, 16.25 or 18.25 g e s t a t i n g females i n d i c a t e d t h a t the number of spermatogonia was s i g n i f i c a n t l y d e p l e t e d in a l l the e xpos e d g r o u p s . R a d i o s e n s i t i v i t y of the f e t a l t e s t e s was found to i n c r e a s e w i t h the a d v e n t of embryonic age as the d i f f e r e n t i a t i o n of gonad p r o c e e d e d . P r i o r a d m i n i s t r a t i o n of t he drug p r e v e n t e d re duc t i on in th e number of s pe rma t ogoni a . A s i g n i f i c a n t e l e v a t i o n in the count was o b s e r v e d in t h o s e e x p o s e d at day 14.25 or 16.25 of f e t a l age in a l l the d o s e s ; w h i l e th o s e e x p o s e d at day 18.25, a s i g n i f i c a n t d i f f e r e n c e in the drug t r e a t m e n t was noted only w i t h l o w e s t dose u s e d .

31%). These results were obtained with the use of F(ab')2 fragments labelled with 1311. A TCmTc labelled immunoreagent was recently prepared and its clinical am plication is now under study.

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ISOEFFECT DOSE ANALYSES OF AUGER ELECTRON EMITTING RADIONUCLIDES APPLYING THE RAT TESTIS AS A RADIOBIOLOGICAL IN VlVO MODEL J. Tennvall. G. Grafstr6m, A. El Hassan, BA. J6nsson, and SE. Strand. University Hospital, Lund, Sweden.

DIMINUTION OF CELLULAR RADIOSENSITIVITY IN THE PRESENCE OF CUMENE HYDROPEROXYDEDURING A UNIQUE GAMMAEXPOSITION N. Drancourt, S. Waultier, C. Fergeas, R.H. Paulin. I n s t i t u t des Isotopes (IRAMIR) - Faculte de medecine Marseille (France).

An evaluation of the sensitivity and reliability of two different in vivo radiobiological models applied to the rat testes, with special attention to thorough analyses of the mechanisms of the biological effect induced by an Auger electron emitting radionuclide, Indium-111, have been performed. The radiobiological effects of intratesticularly injected Indium-111-oxine or testes exposed to local X-ray radiation have been analysed. The plasma pituitary gonadal hormones FSH and LH revealed to be neither a reliable nor a sensitive model for this purpose regarding absorbed doses <5 Gy. On the other hand, "the sperm-head survival assay model" seemed to be both more reliable and sensitive. By autoradiogaphy, Indium-111 showed to be very heterogenously distributed within the testis; By cell-fractionation, 60% of the injected activity was found within the cell nuclei. These results confirmed that a high fraction of the emitted Auger electrons exerted influence on the spermatogonial cell killing. This "sperm-head survival assay model" will be used in future studies in order to evaluate the mechanisms of the biological effect induced by Auger electron emitters.

T u e s d a y , A u g u s t 28, 1990

Because of the rarety of studies on the r a d i o b i o l o g i c a l impact of r a d i c a l a r promoters, that are used in i n d u s t r i a l chemistry, on culture c e l l s , we measure the r a d i o s e n s i t i v i t y modifications of "vero" cells induced by cumene hydroperoxyde (CHPO) at non cytotoxic levels (C<3 mgr/l). The o r i g i n a l proposed protocol coincide with the exponential growth phase of the "vero" c e l l s . jO_ J~]

j3_

c e l l s were c u l t i v a t e d in l i q u i d medium 105/ml CHPO is added in one well on two simultaneous i r r a d i a t i o n with 60 Co of the c u l t i v a t e d cells with and without CHPO at the same growth phase ( ~ in situ dosimeters DPDS) automated cells counting by c o l o r i m e t r i c test.

For doses D between 1 and 5 Gy (LDso r 3.764) the r a t i o SH/S (cells survival i r r a d i a t e d with CHPO/cells survival i r r a d i a t e d without CHPO on the same plate) is >I. At equal dose, SH/S increase with C and for a fixed C, SH/S increase with D. So, CHPO appears to have a radioprotector effect that is very obvious for SH/S =I.4 obtained for C=2 mgr/l and D=4Gy. This surprising r e s u l t may be explained by the very e l e c t r o phylic character of the liberated radicals by the r a d i o l y s i s of CHPO, capable of catching the free radicals in water.

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BIOKINETICS AND TISSUE UPTAKE OF INDIUM-111 RADIOPHARMACEUTICALS EVALUATED IN THE RAT APRROACHING RADIATION DOSIMETRY AT THE CELLULAR LEVEL. B.A. J o e n s s o n a n d S.E. Strand. R a d i a t i o n P h y s i c s D e p a r t m e n t , L u n d U n i v e r s i t y , Lund, S w e d e n .

THE PREVALENCE OF THYROID DISEASE IN THE ATOMIC BOMB SURVIVORS IN NAGASAKI. S. Nasataki, N. Yokoyama*, S. Inoue*, K. Shimaoka*, H. Hirayu, and M. Izumi. The First Department of Internal Medicine, Nagasaki University School of Medicine, Radiation Effects Research Foundation*, Nagasaki 852, Japan

It was early recognized that Indium-Ill and the accompanying impurity In-ll4m give high absorbed doses to the patient after administration of a radiopharmaceuticaL It has also been demonstrated that I n - l l l is extremely radiotoxic when localized within or close to the cell nucleus, due to emitted low energy electrons daring the decay. In conventional internal dosimetry it is assumed that the radionuclide is homogenously distributed in the whole volume of an organ and therefore the absorbed dose to individual cells in the tissue is the same as the mean absorbed dose to the entire organ. Thus the knowledge of the localization of the rsdionuclide is easential in order to perform reliable absorbed dose calculations and to determine the radiation hazards. This study was undertaken to achieve more and necessary information about the biokinetics of In- 111 biomolecules, and to investigate the activity distribution and activity concentration in different tissues and part of tissues. In- 111 -chloride, -oxine, -tropolone, -platelets, -WBC and -F(ab')2-antibcxlies were injected into rats, which were followed up to 1 month. Activity in blood, plasma, urine, faeces and most tissues w as measured at different time points. Digitalquantitative whole body autoradiography was exeeuted to investigate the activity concentrations in tissues. Our results show highest activity uptake in rapid proliferating tissues (bone marrow, lymph nodes, testes and spleen) i.e. those tissues characterized as very radiosensitive. In addition, the radionucllde is retained for a long period of time. Also liver and kidney have a considerable accumulation of indium. The autoradingraphy shows that in many tissues e.g. spleen, liver, bone marrow and testes, the radionuclide is very inhomogenously distributed. The investigation demonstrate the importance of careful investigations of the pharmscokinetics including exploration of the activity distribution within tissues evaluated by quantitative autoradiogrsphy. The study confirm the need for an improved internal dosimetry and show the hmitations of the current conventional MIRD-dosimetry which may underestimate the absorbed dose because of unknown localization data.

703 THE DIFFERENTIAL THERMAL SENSITIVITY MALIGNANT M ICROCI RCULAT ION

The aim of the study is to investigate whether the prevalence of thyroid disease is different according to the sex and age at the time of atomic bomb explosion. The subjects were 771 atomic bomb survivors in Nagasaki and 971 age and sex matched controls. All subjects were examined physically by thyroid experts aud their serum levels of total T and T^,_I freeT4 and T^, TSH, TBG, thyroglobulin and an4tithyroid autoanti~odies were measured. Furthermore, high resolution ultrasonic scanning was performed in all subjects and aspiration biopsy in most of subjects with goiter. The prevalence of thyroid nodule and hypothyroidism was significantly higher in atomic bomb survivors than in controls. The prevalence of thyroid nodule increased as the rediation dose increased, whereas hypothyroidism was significantly higher in subjects exposed to less than 50 rad than in the others. When the subjects were analysed according to the sex and age, the prevalence of thyroid nodule was significantly high in subjects whose age at the time of atomic bomb explosion was below 20 years in both sexes and the prevalence of hypothyroidism was significantly high only in female subjects who were from 18 to 29. These results suggest that the late effects of the atomic bomb exposure on the thyroid is influenced by not only radiation dose but also the sex and the age at the time of atomic bomb explosion.

704 OF

NORMAL

AND

SERIAL CHANGES OF TL-201 SPECT AND MULTIGATED RADIONUCLIDE VENTRICULOGRAPHY IN THE PATIENTS OF DUCHENNE'S CARDIOMYOPATHY. S.Nagamachi, S.jinnouchi, H.Hoshi, K.Inoue, T.Ohnishi, S.Ono, H.Yoshimura. K,Watanabe.Department of Radiology. Miyazaki Mdedical College. Miyazaki Prefecture. Japan.

The goal of this project was to investigate the heat sensitivities of the microcirculation in murine muscle and five types of transplanted tumours. The degree of microvascular stasis in the left leg of mice (+ tumour) during heating was assessed by the rate of clearance of technetium, Tc-99m, bound as pertechnetate ion, TcO 4- following an intratissue injection. Average leg temperature was maintained at 43, 44, 45 or 46~ using a radiofrequency, 13.56 MHz, capacitor and 370C water. Leg temperatures were monitored by seven thermoeouples in a 3-dimensional configuration. Clearance rates were measured before heating and during heating at the following times: 20, 40, 60, 90, 120 minutes. KHT, a well-vascularized fibrosarcoma, had the most heat sensitive microcirculation. The same level of microvascular damage occurred following heating (at 43 46~ in half the time for KHT tumor than for normal leg muscle, and for both tissues a I~ rise in temperature was equivalent to reducing the heating time by a factor of 2, i.e. the effect depends on heat dose not absolute temperature. The tumours studied, in order of decreasing vascular sensitivity to heat, were: KHT, RIF, C3H mouse mammary carcinoma, human mamn~ry carcinoma (in i[mnune deprived mice), and SCCVII (an avascular squamous cell carcinoma). All tumors had vasculature which was more heat sensitive than normal murine muscle.

In order to examine the natural course of Duchenne's cardiomyopathy(DMD),Ti-201 SPECT and multigated radionuclide ventriculography with Tc-99m albumin were performed in 14 patients for 5 years. TI-201 SPECT imaging was obtained by a Siemens rotaing gamma camera (ZLC7500) equipped with a low energy parallel hole collimator interfaced with a dedicated computer(scintipac70A). Data acquisition was done from 32 projections. Hypoperfusion areas were evaluated on the reconstruction images(long axis and short axis) visually. Multigaed blood pool images were also recorded in left anterior oblique view. Assessment of regional wall motion were done visually. Sytolic and Diastolic parameters were caluculated from flow volume curve. Phase analysis was also done. Hypoperfusion areas were recognized primarily in posterior-inferior wall and anterior wall at the age of 12 and extended to lateral wall and septum with aging. Systolic parameters decreased with aging after the age of 15. Diastolic parameters also decreased gradually in most patients after the age of 15. But there were various pattern compared to the patern of systolic parameters. Hypokinetic changes of regional wall motions and phase delay were obsereved at the age of 16 and they became distinctly with aging. Follow up study with TI-201 SPECT and multigated radionuclide ventriculography revealed well the progression of cardiac involvements in DMD.

5.L. Brown, J.W. Hunt, and R.P. Hill. Ontario Cancer Institute, 500 Sherbourne Street, Toronto, Ontario, Canada M4X IK9

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Wednesday, August 29, 1990

705

706

RADIOISOTOPIC EVALUATION OF RIGHT VENTRICULAR P E R F O R M A N C E IN M U S C U L A R D Y S T R O P H Y .

ASSESSMENT OF RIGHT ATRIAL (RA) AND RIGHT VENTRICULAR (RV) FUNCTION BY KR-81M GATED BLOOD POOL SCAN -RA AND RV PRESSURE-VOLUME LOOPS WITH SIMULATANEOUS PRESSURE DATA-. M Ishizuro{ ~ , S. Watanabe ~, T. Yasue{~, N. Sugishita{~, H. Ohashd{~, A. Goto ~{~, M. Kondo{~{~, H. Ogawa~{~ and T. Hirano~{~. {~Division of Cardiology, Gifu Prefectural Hospital, {~{~Divisionof Radiology, Gifu Prefectural Hospital, {~{~Division of Cardiology, Hirano General Hospital, Gifu 500, Japan.

DEVAUX J-Y. ; EGU J-F. ; D U B O C D. ; G A U D I C H E O. ; C A L D E R A R. ; G U E R I N F. ; R I C H A R D B. C e n t r e Hosp. Univ. C O C H I N 75014 P A R I S FRANCE

Sudden c a r d i a c f a i l u r e is a p o t e n t i a l risk in the spine o s t e o s y n t h e s i s s u r g e r y for c h i l d r e n suffering of Duchenne de B o u l o g n e muscular dystrophy. Left ventricular function and myocardial p e r f u s i o n are c o m m o n l y i m p a i r e d in this d i s e a s e as r e p o r t e d by s e v e r a l p a p e r s . But the role p l a y e d by the r i g h t v e n t r i c l e in this c a r d i a c d y s f u n c t i o n is not d o c u m e n t e d . Right and left ventricular evaluation were performed by T c 9 9 m g a t e d b l o o d pool in n i n e patients (ages 8 to 21) at rest, during isoproterenol infusion and after recovery. Right e j e c t i o n f r a c t i o n (REF) c a l c u l a t i o n was corrected for right a t r i u m a c t i v i t y . Its m e a n value at rest was 45.5 • 13.3 (range f r o m 60 to 24%) d i f f e r e n t f r o m n o r m a l (p < 0,005). Results s h o w that, a l t h o u g h t h e r e is a t i g h t p a r a l l e l i s m b e t w e e n right and left r e s p o n s e to isoproterenol, the i m p a i r e m e n t of REF is not correlated e i t h e r w i t h the left d y s f u n c t i o n , ECG abnormalities or with the corrected r e s p i r a t o r y v i t a l c a p a c i t y . This s u g g e s t s t h a t isolated right ventricular dysfunction may contribute to h e m o d y n a m i c f a i l u r e in m u s c u l a r d y s t r o p h y and t h a t REF d e t e r m i n a t i o n s h o u l d be performed in the pre-operative check-up of these patients.

Quantification of right ventricular function has been difficult because of complex geometry involved. Kr-81m is ideally suited to right heart study because of (i) a physical half-life of 13 ces., (2) high photon yield and gamma ray energy of 190 Kes., (3) low radiation exposure, (4) exhalation from the lung and no activity of left heart. A computerized method for list mode data aquisition was developed to collect the gamma camera, ECG wave, and RA and RV pressure data, simultaneously. RA and RV volume curves were obtained, calibrating the time-activity curves with end-diastolic volumes calculated form the ejection fraction and cardiac output measured by the thermodilution method. From RA and RV pressure and volume curves, RA and RV pressurevolume (P-V) loops were created simultaneously. One spanning cardiac cycle of RV beat was separated into 4 phases as follows : The ventricular emptying phase, the early ventricular filling phase, equilibrium, and the late ventricular filling phase. One spanning cardiac cycle of RA beat was also separated into 4 phases as follows. The atrial filling phase, the early atrial emptying phase, equilibrium, and the late atrial emptying phase. RA and RV P-V loops were shifted after nitroglycerin sublingual administration. This new method is potentially useful in the study of right heart hemodynamics.

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SECTORIAL ANALYSIS OF THE LEFT VENTRICULAR DIASTOLIC FILLING BY RADIONUCLIDE ANGIOGRAPHY - APPLICATION IN ONE-VESSEL CORONARY ARTERY DISEASE (CAD) Ph. PEZARD, A. FURBER, Ph. GESLIN, J.J. LEJEUNE, A. TADEI, P. JALLET Nuclear Medicine and Cardiology departments - C.H.U. ANGERS - FRANCE

CONSTRICTIVE PERICARDITISAND LEFT VENTRICULAR FILLING IMPAIRMENT: A RADIONUCLIDE ANGIOGRAPHIC (RNA) STUDY. A. FURBER. Ph. PEZARD, Ph. GESLIN, J.J. LEJEUNE, A. TADEI, P. JALLET Nuclear Medicine and Cardiology departments - C.H.U. ANGERS - FRANCE The aim of this study was to evaluate how the analysis of the early and late filling of the left ventricle (LV) by RNA might contribute to the diagnosis of constrictive pericarditis (CP). Popul at i on: 9 patients with evidence of isolated CP, ages 28-64 years, in sinus rythm and without noticeable systolic LV dysfunction (LV EF:56 + 8%), valvular disease, hypertension or LVH were compared to15 normal age-matched subjects. M e t h o d s : 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 (FF1/3) 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 TFlY3 as the delay between the end-systole 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 and bearing in mind that each patient with CP had a smaller end-diastolic volume, these showed an increased early LV filling and a decrease of the atrial contribution as jud ged upon a higher FF1/3 (ns) and FF1/2 (p<0,05), a rise in the PFR (p
Global left ventricular (LV) diastolic filling abnormalities svently observed in CAD are not specific and are often absent if systolic function remains normal. The aim of this study was to assess how a sectorial analysis of the LV early and late filling may improve the contribution of radionuciide angiography (RNA) to the CAD diagnosis. P o p u l a t i o n : 29 patients with one-vessel desease and without systolic LV dysfunction (LV EF: 61 :t: 6%), valvular disease, hypertension or LV hypertrophy were compared to 15 normal age-matched subjects. M e t h o d s : From LAO acquisition with 16 frames par cardiac cycle, one global and 10 sectorial LV time activity curves and their first derivatives were constructed with 64 pts/cycle by Fourier transform. The parameters studied were filling fractions (FF) at 1/3 and 1/2 diastole and during atrial contraction (AFF), peak emptying rate (PER), peak filling rate (PFR) and peak atrial rate (PAR), PFPJPER and PAR/PFR. ratios, time of PFR (TPFR) and TF1/3 as the delay between the end-systole and the occurence of one-third filling. Filling asynchrony was assessed as the average of the absolute differences between global and sectorial values of TFI/3 and TPFR. R e s u l t s : Sectorial diastolic abnormalities were frequently observed and localized quite specifically in the sectors correspondlng to the involveal artery. Thus, sectodal TPFRand TF1/3 were prolonged in 62% and 59~ respectively of CAD patients and sectodal PFR was diminished in 65~ of the same. Prolonged relaxation in these territories led to an increase of filling asynchrony (p_
Wednesday, August 29, 1990

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RADIONUCLIDE VENTRICULOGRAPHY (RNV) AS A CARDIAC SCREENING BEFORE PERIPHERAL VASCULAR SURGERY. P.Heidenreich I), G.Graf I), H.Vogt I), H.Loeprecht 2) i) Inst.of Nuclear Hed., 2) Dept.of Vascular Surgery Zentralklinikum Augsburg (FRG)

IN V I V O L A B E L L I N G OF A N T I B O D I E S W I T H T c - 9 9 m BIOTIN. P.Oehr, Q.Liu, B . S c h u l t e s , M . A l t r e u t h e r , and H . J . B i e r s a c k . Dept. of N u c l e a r M e d i c i n e , U n i v e r s i t y of Bonn, D - 5 3 0 0 Bonn, FRG.

The preoperative estimation of cardiac risk in pat. with peripheral vascular disorders is often difficult. The assessment of cardiac function by the noninvasive RNV supports the management of these pat.. The purpose of this report is to examine the usefulness of RNV in detecting coronary artery disease (CAD). Me thod: 711 pat. were studied prior to operation for vascular disorders. Most had peripheral vascular disease severe enough to preclude an adequate exercise stress test. After in-vivo-labelling of red blood cells using Tc-99m RNV was carried out on three projections (AP, LAO 30 ~ and 70 ~ by listmode data acquisition. Data processing was performed by multiharmonic Fourier analysis of the representative heart cycle. Left ventricular ejection fraction (LVEF) and regional contractility were analyzed. Results : 54% of all pat. showed normal (LVEF=>55%), 33% a slightly (40%
S c i n t i g r a p h y can be p e r f o r m e d w i t h l a b e l l e d a n t i b o d i e s d i r e c t e d to a n t i g e n s in vivo. I m a g i n g is p o s s i b l e b e t w e e n 1-7 days a f t e r i n j e c t i o n of the r a d i o l a b e l . A l t e r n a t i v e l y , a n t i b o d i e s c o n j u g a t e d to "cold" a v i d i n can be i n j e c t e d and, l a t e r on, i d e n t i f i e d in v i v o by r a d i o l a b e l l e d b i o t i n as a s e c o n d a r y tracer. Due to the h i g h a f f i n i t y b e t w e e n b i o t i n and avidin, it is p o s s i b l e to use i s o t o p e s w i t h s h o r t h a l f - l i f e . So far, i o d i n e - and i n d i u m i s o t o p e s w e r e applied. Tc-99m, however, has a shorter half-life, improved imaging qualities, e a s y a v a i l a b i l i t y and a l o w e r price. In this report, the b i o d i s t r i b u t i o n of Tc99m b i o t i n is d e s c r i b e d . M o r e t h a n 90% of the i n j e c t e d m o l e c u l e was e l i m i n a t e d f r o m the b l o o d a f t e r 20 min. T c - 9 9 m b i o t i n was a c c u m u l a t e d in tumors. In rat e x p e r i m e n t s , there was o n l y b a c k g r o u n d in k i d n e y s and u r i n a r y b l a d d e r due to the c l e a r a n c e . P r e i n j e c t i o n of a n t i g e n s p e c i f i c a n t i b o d i e s c o n j u g a t e d to a v i d i n led to a h i g h e r a c c u m u l a t i o n of T c - 9 9 m b i o t i n at the a n t i b o d y t a r g e t t h a n the i n j e c t i o n of b i o t i n alone. The T c - 9 9 m b i o t i n m e t h o d a l l o w s i m a g i n g w i t h i n 3 min. a f t e r i n j e c t i o n of radiolabel. It is c o n c l u d e d that T c - 9 9 m b i o t i n b e c o m e s i m p o r t a n t for s c i n t i g r a p h i c i m a g i n g of m a l i g n a n t and b e n i g n d i s e a s e s .

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TUMOR RADIOIMMUNOTARGF:TING IN CEA POSITIVE PATIENTS WITH THE AVIDIN-BIOTIN SYSTEM. (~,paganelli. P.Magnani, F.Zito, E.Villa, M.Stella, L.Lopalco, C.Rossetti, M.Malcovati, A.G.Siccardi, F.Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy.

DESIGN AND USE OF RECOMBINANT ANTIBODY-METALLOTHIONEIN FOR RADIOIMMUNO IMAGING AND THERAPY.

One major drawback in antibody guided tumor detection is the high background due to non-specific uptake by normal tissue and blood. We describe a method to post-label biotinylated Mabs in vivo, when most of the non-tumor bound Mabs have been cleared. One mg of biotinylated anti-CEA Mab (FO23C5) was administered i.v. in 10 patients with documented CEA positive tumors (4 lung non small cells, 3 medullary thyroid cancer, 3 gastrointestinal tumors). After 3 days, 4 mg of cold avidin was injected i.v. followed 48 hours later by 200-300 mg of biotin labelled with In-111 (2-3 mCi). Whole body biodistribution was measured at 20 minutes, 2 and 3 hours post injection using the conjugate view counting technique. Tumors and metastases (including liver secondaries) were detected in all patients within 3 hours after administration of radioactive biotin on both planar and SPECT data; unknown metastases were also detected in 3 patients and confirmed by follow up. Tumor to blood-pool ratio was 2.4~K).5 and tumor to liver ratio 2.5+0.1 at 90 minutes after injection. Blood clearance of In-111 biotin had a multiexponential curve with a fast component with a T1/2 of 5+3 minutes. The urinary excretion of radioactivity over 2 hours was 58+5% of the injected dose. Radioactivity at two hours was 9+2% in blood, 1.5+0.7% in kidneys and 2_+0.2% in the liver. No evidence of toxicity was observed. Four patients developed a human anti-avidin immune response. The present approach may improve tumor localization providing immunotargeting few minutes after administration of radioactivity.

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C. Das, C. Webb, A. Constantinescu, P.V. Kulkarni, and P. Tucker. Depts. of Microbiology and Radiology, The Univ. Texas Southwestern Medical Center, Dallas, TX, USA In order to utilize both the metal binding capacity of metallothionein (MT) and the specificity of monoclonal antibodies (Ab), we performed fusions of the appropriate genes followed by their expression in eukaryotic cells. Mouse y2b heavy and ~ light chain genomic genes that carry variable regions which convey binding specificity for the hapten phosporylcholine (PC) and for the iodiotype TI5 were cloned into positive selectable vector pSV2gpt. The heavy chain constant regions 3' to the hinge segment were replaced by the human MT-II gene, generating a F(ab)' MT chimera Murine J558L plasmacytoma cells 2 " which produce no endogenous Ab, were transfected with F(ab)'pMT construct. Structure of hybrid protein secreted by-selected clones was confirmed by mRNA sequencing. Protein was purified by affinity chromatography and was shown by RIA and FACS analysis to bind PC or AB-2 at affinities equivalent to wild-type TI5 Ab. Purified F(ab)'pMT protein, bound radiometals (Cd-109, Tc-99m, Cu-67) ~ither in solution (confirmed by gel electrophoresis) or following immobilization on western blots. Optimization of labeling conditions and biodistribution studies are in progress. Production of recombinant antibody-metallothionein potentially provide an alternate approach to antibody-chelate conjugates for radioimmuno imaging and therapy.

W e d n e s d a y , A u g u s t 29, 1990

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714

DIAGNOSTIC AND THERAPEUTIC DOSES OF RADIOLABELED MOUSE/HUMAN CHIMERIC MONOCLONAL ANTIBODIES. R. Meredith, M. Khazaeli, E. Plott, C. Russell, E. Harvey, R. Wheeler, M. Hardin, T. Baker, R. Orr, L. Allen, M. Salter, A. LoBuglio. Comprehensive Cancer Center, University of A l a b a m a at B i r m i n g h a m , V. A. M e d i c a l C e n t e r , Birmingham, AL and Centocor, Inc., Malvern, PA, USA.

FIRST USE OF A Tc-99m LABELED MONOCLONAL ANTIBODY DIRECTED AGAINST THE T-CELL RECEPTOR FOR THE

A phase I trial was conducted with the mouse/human chimeric monoclonal a n t i b o d y CO17-1A (C17-1A) in patients with GI malignancies. Patients were infused with a 5 mCi d i a g n o s t i c dose o f 1 - 1 3 1 - C 1 7 - 1 A a n d pharmacokinetics, b o d y d i s t r i b u t i o n and dosimetry estimations were conducted. In another phase 1/11trial five of the above patients received therapeutic doses (34-54 mCi) of 1-131-mouse/human monodonal antibody B72.3 (CB72.3). Our previous studies with single and repeated 400 mg doses of murine CO17-1A m o n o c l o n a l a n t i b o d y indicated an 18 hr T1/2 and rapid development of an immune response. Subsequently, our studies with the 10 and 40 mg doses of unlabeled C17-1A showed a T1/2 of 100 hr and reduced immunogenicity. Our current studies with I-131-C17-1A produced a similar T1/2 to the unlabeled C171A and metastatic lesions of greater than 4 cm were visualized. Following 1 month of observation with no adverse effects the patients received a therapeutic dose of 1-131-C-B72.3. The tocalizations were prolonged ancl more prominent with this reagent than 1-131-C17-1A No marrow suppression was observed with a total exposure of 50-58 cGY at 18 mCi/m2 dose. The circulating T1/2 of both chimeric antibodies was l o n g e r t h a n the respective T1/2's of t h e i r m u r m e counterparts. Supported NCI contract #CM87215, Centocor and NIH Grant #M01-RR00032.

The in vivo labeling of human blood cells with specific monoclonal antibodies, e.g. anti-granulocyte MAb, simplifies cell labeling and opens new clinical applications. This phase I/II study aims at the evaluation of a new Te-99m labeled anti-T-cell antibody for the diagnosis of transplant rejection. 0.1-1 mg of the intact IgG1 MAb BW 111 (Behringwerke, FRG) directed against a 50 kD epitope (Tll, CD2) on human T-cells (pan TERCF receptor present on 80 % of all PBL, < 1% of granulocytes, 95 % of thymocytes, and 20-30 % of bone marrow cells) were labeled with 370555 MBq Tc-99m by a kit procedure (efficiency >95 % (HPLC), no purification, preserved immanoreaetivity; 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 rain, 2-7 li and 21-25 h post injection. Intense transplant uptake was found in all patients with acute cellmediated kidney rejection (conf'wmed 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 imarunoscintigraphy using a Te-99m labeled anti-T-cell monodonal antibody can be used for the rapid and specific non-invasive identification of transplant rejection.

IMMUNOSCINTIGRAPHIC DIAGNOSIS OF TRANSPLANT REJECTION. R.P. Baum, A. Hertel, K. Bosslet, U. Moodorf, P. Hechler, A. Schwarz, L. Bergmann, P.S. Mitron, G. HGr. J.W. Goethe University Medical Center, Frankfurt/Main, FRG.

716

715 I II~6ING /HlbqL OF I M - i l l

~

~

d~NTI-EPIDK-

BRONIIN FttEroR (LCI~) l~--m~vlOR~ O I N P L

L~Y'I'IBODY (NPJ)) ~ IN F~TIENTS MI'I'H S G U ~ U S ~ LUI~ CARCINOMA. CR Divqi, S Welt, M K r i s , FX Real, SD3 Yeh, R B r a l l a , 3 Mendelsohn, SM Larson. Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

A Phase I t r i a l was carried out i n 19 patients ( p t s . ) with inoperable squamous c e l l lung carcinoma (SQC) using anti-EGF receptor mAb, mAb 2s (IgG1), labeled with In-111. 4 mg o f the labeled mAb was given by i t s e l f (3 p t s . ) or co-infused with unlabeled mAb f o r a t o t a l dose o f 20 mg, 40 mg (3 p t s . / dose l e v e l ) , leO mg t& p t s . ) or 300 mg (1 p t . ) . An i n i t i a l group o f 3 pts. was given 1 mg unlabeled mAb. No t o x i c i t y was observed at any dose l e v e l . Serum clearance was dose-related, being 2.1~ d o s e / l i t e r (D/L) at the 4 mg dose, 12.4~ D/L at the 20 mg dose, 21.4~ at the 40 mg dose, and 2g.6~ at the 120 mg and 300 mg doses. S i g n i f i c a n t and early l i v e r v i s u a l i z a t i o n was observed at a l l doses i n all patients. Tumor v i s u a l i z a t i o n was also doser e l a t e d : 3 o f 5 primary lesions were v i s u a l i z e d in 6 patients given 20 mg or less mAb; a l l primary lesions were v i s u a l i z e d i n 10 patients given 40 mg or m o r e mAb. Single photon computed tomography could be carried out at doses ~120 mg and improved tumor v i s u a l i z a t i o n . We conclude 1) mAb 225 i s safe a t the d o s e s studied and l o c a l i z e s i n areas o f known SQC at doses ~ 40 mg; tumor uptake and plasma clearance o f In-111-mAb 225 are dose-dependent. This mAb targets a novel class o f tumor-associated antigens - growth f a c t o r receptors. Thus images o f mAb 225 uptake may provide important information about features o f cancer biology that w i l l have relevance to prognosis or choice o f therapy.

Wednesday, August 29,1990

PET STUDIES WITH MODULATED FLUOROURACIL (FUI CHEMOTHERAPY IN PATIENTS WITH COLORECTAL CARCINOMA. A, DilTlitrakoooulou, L.G. Strauss, U. Haberkorn, M. Knopp, P. Schlag, E Helus, J. Doll, W. Maier-Borst. German Cancer Research Center, Heidelberg, Germany. Modulated FU treatment protocols including pretreatment with d,l-folinic acid have found use for chemotherapy of metastatic colorectal carcinomas, since more than 80 % of all patients fail to respond to the i.v. FU chemotherapy. We used PET to evaluate the effect of folinic acid pretreatment on FU uptake and FU metabolism. Double examinations with F-18 labeled FU were performed in ten patients. The first PET examination was performed without pretreatment, the second study was carded out with pretreatment (500 mg per BSA, followed by FU infusion). PET images were acquired continously beginning with the FU infusion for two hours. Only in one patient a 40 % increase of the FU metabolite concentration was noted after pretreatment. A correlation between the FU transport and the FU metabolite concentrations was observed in metastases with and without pretreatment. In one of eleven lesions the FU metabolite concentration following pretreatment was higher as estimated from the FU transport data. The FU transport was lower after pretreatment for the normal liver parenchyma, while no significant differences were observed for the FU metabolite concentrations. Our data demonstrate, that folinic acid pretreatment results in enhanced FU uptake in the liver parenchyma, while the FU metabolite concentrations remain unchanged. Since only in 1 of 11 metastases an increase in FU metabolite concentration was noted, PET should be used to select those patients who are likely to profit from pretreatment with folinic acid.

$163

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RESPONSE TO CHEMOTHERAPY WITH FLUOROURACI/(FU) AND PET MEASUREMENTS OF FU-UPTAKE IN PATIENTS WITH COLORECTAL CARCINOMAS.

PET STUDIES WITH F-18-DEOXYGLUCOSE (FDG) IN PATIENTS WITH MELANOMA PRIOR AND AFTER THERAPY. L.G Strauss. W. Tilgen, A. Dimitrakopoulou, U. Haberkorn, M. Knopp, E Helus, W. Maier-Borst. German Cancer Research Center, Heidelberg, Germany.

L.G. Strauss. A. Dimitrakopoulou, U. Haberkom, M Knepp, P, Schlag, E Helus, J. Doll. G. van Kaick. German Cancer Research Center, Heidelberg, Germany. Fluorouracil (FU) is used for chemotherapy in metastatic coIorectal carcinomas for more than thirty years. Since response to FU chemotherapy requires 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 16 metastases prior to FU chemotherapy. CT preceeded each PET study in order to determine the target area and to calculate the tumor volum~ 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=0.84) 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.

Different chemotherapeutic protocols are used for the treatment of patients with metastatic melanomas. We used PET in these patients to quantify the metabolic activity in metastases prior and after therapy. The evaluation includes 8 PET studies in 4 patients. CT examinations preceeded PET in each patient to determine the target area. PET studies were performed with intravenously injected FDG (370-444 MBq), followed by sequential imaging for 60 minutes. Standardized uptake values (SUV) were calculated from the iteratively reconstructed cross sections using a ROI-technique. The FDG uptake in lymph node metastases was 2.9-10.5 SUV prior to therapy. Lower values were observed in bone metastases (1.9 SUV). Comparable results were obtained in liver metastases (2.5-3.2 SUV). Follow-up studies after chemotherapy with fotemustin (200 rag, 30 min infusion) showed a 3 % decrease in tumor metabolism 90 minutes after chemotherapy. The decrease in FDG uptake was 9 % and 26 % one and two days after therapy and remained constant for one week. The median decrease in FDG 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 cytostatic effect can be demonstrated by PET. Therefore, different chemotherapeutic protocols may be compared on the base of PET studies.

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N-ISOPROPYL-P-[I-123] IODOAMPHETAMINE(I-123 IMP) IN INTRA-HEPATIC AND BRONCHIAL ARTERIAL CHEMOTHERAPY. C.Miyazaki, T.Hiromura, H. Ikeda and R.Koshiba. Sapporo General H o s p i t a l , Sappors, Hokkaldo, Japan.

E V A L U A T I O N OF T U M O R B L O O D AN~D T C - 9 9 M LABELED MAA CHEMOTHERAPY.

T.Nakashima,

minutes after intra-arterial injection of I mCi(37 MBq) of 1-123 IMP. The injected dose was measured by counting the syringe on the gamma camera. ROIs were assigned over whole lung, whole liver, normal tissue, t u m o r and lymphnode. The first arterial

circulation decided initial 1123 IMP distribution in the t a r g e t t i s s u e of the artery. 1-123 IMP accumulated in the primary ]ung and liver tumors, metastatic l y m p h n 0 d e and n o r m a l tissue. The concentration of the chemotherapeutic agent in the tumor might be estimated from % uptake of 1-123 IMP. In the bronchial arterial infusion study, 1-123 IMP uptake of the tumor, lymphnode and normal tissue decreased with time, whereas that of the liver i n c r e a s e d and of the contralateral normal lung was constant. In conclusion, the 1-123 IMP perfusion studies may reflect flow distribution and kinetics of c h e m o t h e r a p e u t i c agents, differing from that in the Tc-99m MAA study.

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T.Toyama,

T.Matsusbita, K.Terizuka. Fukui

N.Takahashi,

T.~ori, Y.Ishii Medical School, Fukui, Japan. R.Nakamura

As to arterial perfusion study on evaluating the d i s t r i b u t i o n of a c h e m o t h e r a p e u t i c agent, T c - 9 9 m macroaggregate albumin(MAA) has been used. H o w e v e r 1123 IMP as c h e m i c a l m i c r o s p h e r e may give different i m a g e s reflecting a d i s t r i b u t i o n and k i n e t i c s of c h e m o t h e r a p e u t i c agent. F r o m this point of view, an intra-arterial administration of 1-123 IMP after an arterial chemotherapy infusion in 28 patients with lung or liver tumor was considered. D a t a a c q u i s i t i o n w a s e v e r y 30 s e c o n d s for 60

F L O W M O D U L A T I O N BY KR-81M IN INDUCED HYPERTENSIVE

and

Introduction: Induced hypertensive chemotherapy (IHC) is to i n c r e a s e the ttunor bloc~ flow specifically augumenting the effect of anti-cancer d r u g s to the tumor, decreasing undesirable systemic s i d e effects, in which potent vasoconstrictor Angiotensin- ~ (A- ~ ) is usually used. Aim: To a s s e s s i n c r e a s e of tumor blood flow in induced hypertensive chemotherapy by nuclear medicine methodology. Subjects and Methods: Two c a s e s of m e t a s t a t i c liver tumor (primary:gastric and colon cancer) and one case of m e t a s t a i e sacral t u m o r (primary: rectal cancer) were involved in our study. Tumor blood flow was e v a l u a t e d by infusion of Kr-81m or Tc-99m l a b e l e d M$~A into tumor vessels through indwelling a r t e r i a l c a t h e t e r with or without angiotensin-~ (A , 2ug/min). R e s u l t s : T u m o r blood flow increased successfully after A - ~ infusion in all c a s e s . B u t in the c a s e s with chemotherapy induced myositis or pest operative fibrosis,blc~Dd flow in t h e s e a r e a s i n c r e a s e d also. Conclusion: Conbined nuclear medicine methdology with IHC r e v e a l e d that i) IHC is eKcellent method to augument targeting efficiency of cancer c h e m o t h e r a p y by increasing the tumor blood flow specifically, and 2) IHC a l s o i n c r e a s e the bl(x)d flow to inflamatory focus and f i b r o s i s requiring strict c a s e selection.

W e d n e s d a y , A u g u s t 29, 1990

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A NEW APPROACH TO LABEL ANTIEODIES TO GET PURE TUNOURSPECIFIC Ga-67 AND Y-90 LABELLED ANTISODIES RESPECTIVELY

Time coded collimator imaging for super resolution with a gamma camera . J,L, STIEVENART, J, FONROGET,J.B. GUILHEM Service de M~decine Nucl~aire - C.H.U. Amiens FRANCE

FOR EARLY DIAGNOSIS AND THERAPY OF CANCER S.K. Shukla a ' b , C. Cipriani a, H. Xie e, R.L. HuaC,Zh.Yao~ and G.F. Wange; a) Servizio di Medicina Nucleate, Osp. S. Eugenio, Roma; b) Istituto di Cromatografia, C.N.R., Roma, Italy; c) Shanghai Inst. Cell Biology, China We showed earlier (Lectures & Symposia, 14th Int. Cancer Congr., Budapest, 1986 (1987), Vol. 6, 345-355) that poor tumour specificity of variously labelled antibodies and their fragments in vivo is due to the large radionuclide impurities present in the classically labelled antibodies. Since the metal radionuclides or metals, used for labelling the antibody, are present in many ionic and neutral forms as well as in their polymerized form depending on the ligand present in the solution, we have now identified chromatographically which species in solution has the highest affinity for the antibody to label. The radionuclide or the metal is then isolated in that chemical form and made to react with the antibody. Thus, chromatographically and electrophoretically pure antibodies were obtained. In the present work we have labelled antihepatoma antibody fragment, hepama-l, with Ga-67 and with Y-90. Ga-87-hepama-i was found to bind specifically to the tumour in nude mice bearing human hepatoma. Oa-67 binds so strongly to the tumour that its image could be obtained up to 9 days p.i. The antitumour activity of Y-90-hepama-l, which is chemically similar to Ga-B7-hepama-i is being followed. The results so far observed showed tumour regression without toxicity.

A n e w method (TCCI) is proposed, the aim of w h i c h is to improve the spatial resolution beyond the intrinsic resolution and to lessen the effect of the scattered radiation. Its specificity is to use a moving parallel multihole collimator characterized by its septa t h i c k n e s s w h i c h is large relative to the holes diameter. The i m a g i n g process is a two step process : during the acquisition step this collimator is sequentially shifted along 2 orthogonal directions parallel to the dectector surface in order to scan the full field of view. For each position, the image formed is a set of more or less overlapping response functions, each of them coresponding to an individual hole. In the decoding step all the information collected this w a y is processed to reconstruct a single h i g h resolution parallel projection image. This method has been implemented on a classical gamma camera (FWHMi = 4 mm at 140 KeV). The image of a thyroid phantom demonstrates that a h i g h quality image enabling detection of 2 mm large cold nodules can be obtained, We conclude that TCCI is attractive for four main features : i. it allows to find a trade off between sensitivity and resolution o v e r c o m i n g the classical "collimator limitation" e v e n on a large field of view. ii, by l e s s e n i n g scattered radiation effect and by allowing a n o n uniformity correction, it is suited to quantitative imaging. iii. it can provide h i g h resolution images e v e n at h i g h gamma ray energies, iiii. it could be incorporated in a quantitative SPECT process.

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OPTIMIZATION OF COLLIMATOR DESIGN AND ACQUISITION PARAMETERS FOR CARDIAC T1-201 STUDIES. J.R. Perry_ and B.M.W. Tsui. UNC Hospitals, Chapel Hill, NC, USA

ATTENUATION CORRECTION EFFECTS IN THE MYOCARDIUM DUE TO MISALIGNMENT BETWEEN TRANSMISSION AND EMISSION PET SCANS. S.L. Bacharach, M.E. McCord, R.O. Bonow, A. Cuocolo, V. Dilsizian. NIH, Bethesda, MD

Collimator design and acquisition parameters for T1-201 SPECT were optimized in order to obtain the same image count statistics with 2mCi doses of T1-201 as are currently obtained with 3.5mCi doses without noticeable degradation in image quality. A new collimator was designed and constructed to improve efficiency by 24% with a 10% loss in spatial resolution at 15cm compared to a GE low energy general purpose (LEGP) collimator. Both collimators were made from microcast hexagonal hole core stock.

Quantitative myocardial PET imaging requires accurate attenuation correction. The large attenuation factors of the thorax and the attenuation discontinuities present there make it possible that small misallgnments between transmission (T) and emission (E) scans could cause large errors in the corrected emission data. We use Huang's methodology (JCAT 1979, 3:804) to investigate the effects of T and E misalignment in myocardial PET imaging. Both patient(18-FDG) and phantom (elliptical Data Spectrum with cardiac insert and wooden "lungs") were imaged with a Positron Corp. PC6.5 (21 slice, 7mm in-plane resolution) scanner, and underwent T scanning using a rotating rod source. Data were repetitively reconstructed with T and E misaligned from 0 to +-2.7cm (in .68cm steps) in both lateral and anterior directions. Each myocardial slice was divided into 8 sectors, and the percent difference between sector activity with T and E aligned and misaligned was computed. If T was moved anterior to E, posterior sectors decreased 12-20% per cm, while anterior sectors increased by 3-12% per cm, with a similar (but reversed and reduced) effect for T mispositioned posterior to E. For lateral mispositionleg (T moved right laterally from E), septal sectors changed very little (<2%/cm), while lateral freewall sectors decreased by 15-22% per cm. The effect was similar (but reversed) for misalignment in the opposite direction. Thus anterior misalignment introduced intersector inhomogenities as large as 15-32%, while lateral misalignment caused 15-24% intersector differences. Phantom studies gave insight into the origins of these effects.

Collimator LEGP New

Hole size 2.5mm(flat-flat) 3.0ram(flat-flat)

Leneth 4.1cm 4.5cm

Sental thickness - 0.3rnm 0.3mm

The 135KeV and 167KeV photon peaks were included with the 75 KeV peak (20% windows) during acquisition, providing a 25% gain in image count statistics compared to the commonly used single energy window at 75KeV. Data collection time was increased by 15% with 64 stops of 23 seconds acquisition each in a 180~ orbit from 45~ to 45~ compared to the currently used 32 stop, 40sec/stop protocol. The total acquisition time of 27 minutes was within clinically acceptable limits and allowed for a delay in the start of acquisition to 10-15 minutes to avoid the problem of "upward creep." The image quality obtained from a 2mCi dose of T1-201, the new collimator and acquisition parameters was as good as that obtained from using the LEGP collimator and the more commonly used acquisition parameters with a 3.5mCi dose of T1-201. The combination of using the new collimator and acquisition parameters is such that a 2mCi dose of Tl-201 provides the same image count statistics as a 3.6mCi dose with comparable clinical image quality, lower radiation dosimetry, and isotope cost savings.

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725 NEM 6ENEI~TLON OF: BUAL PARTICLE KEGATIVE fan r165 DUAL PURPOSE PROTON LINACS FOR NODERN PET CENTERS

Garimetta vs Rayudu, ILLinois, U.S.A

Rush University

Nedicat

Center,

Chicago,

Advantages of dual p a r t i c l e delivering cyclotrons from ion Beam Applications ([BA), Belgium and short and slim version of Linear accelerators for neutron therapy and radio nuclide production are being incorporated into newer PET centers.

commercially available proton/deuteron: 18/9, 10/5 - MeV negative ion machines permit: 8 target ports, dual target bombardment, target transfer at computer command and uses 5X lower power use: 40kg; than conventional machines. In addition, faster access for servicing due to low activation, closed loop cooling, 100% beam extraction makes the machine advantageous. Deuteron beams are required to produce gaseous F-18 and for the p r e d u c t i o n of 0-15, N-13 from [east expensive natural targets. Improvements in proton source design, radio frequency systems at Fermi National Accelerator F a c i l i t y (A. J. Lennox proceedings of LINAC conference, Williamsburg, VA, (1988) r e s u l t e d in shorter and slirrmer proton linac such as 40" diameter 80' long at TO-MeV w i t h 100 microamp beam current for neutron therapy at a dose r a t e of 200 rad/min at 190 cm and sir~Jltaneously for radionuclide production of Xe-127, 1-123, Fe-52, TL-201 at 70 MeV and C-11, N-13, 0-15, F-18 at lower energies. Lt u t i l i z e s 1/3 electric power of conventional machines: 200 kw, with no external radiation build up making it convenient for repair and target handling with minimal loss of machine time,

THE DEVELOP[iENT OF A HYBRID POSITRON C A ~ E R A USING BARIUM FLUORIDE CRYSTALS (BAF2) AND MULTIWIRE P R O P O R T I O N A L CHA/4BERS (MWPC) . R.J.Ott, J.Suckling, P.Marsden and J.E.Bateman, Royal Marsden H o s p i t a l and R u t h e r f o r d - A p p l e t o n Laboratory,U.K. We have d e v e l o p e d a small prototype p o s i t r o n camera which combines the high sensitivity of s c i n t i l l a t i n g crystals with the low cost, high spatial resolution of an MWPC. The benchtop system consists of a 10cm x 10cm square chamber filled with tetrakis d i m e t h y l a m i n o ethy]ene (TgIAE) vspour. The TMAE is a p h o t o s e n s i t i v e gas which at 60 degrees centigrade can detect the 200nm photons emitted from BaF2 crysta]_s during a s c i n t i l l a t i o n event (i). The combination of the fast light decay time (800 ps) and the use of the low p r e s s u r e gas reduces the timing resolution of the system. ~ e a s u r e m e n t s made with a single 8mm thick DaF2 crystal in contact with the MWPC show that a spatial resolution of 5mm and a timing resolution of <5ns is possible with a detection efficiency o f - 2 0 % for 511 keV photons. Simulation shows that we can increase the detection e f f i c i e n c y to >40% with a thicker crystal without serious reduction in the other parameters and that a large area detector can be made of m u l t i p l e crystals 20cm x 5cm in area with m i n i m a l edge effects. With a fast delay-line read-out system it will be possible to produce a large area p o s i t r o n camera capable of high count rate capacity (<50kcps) at a very modest cost. We are now designing a camera w i t h a sensitive area of 60cm x 40cm to replace the MUP-PET system in clinical use at the hospital (2). i. 2.

Bchotanus et al, (1988) NIM A269, 377-384. C h e r r y et al, (1989) EJNM 15: 694-700.

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AN U L T R A - H I G H R E S O L U T I O N PET CAMERA U S I N G SOLID STATE S C I N T I L L A T I O N DETECTORS FOR SMALL A N I M A L STUDIES. R. L e c o m t e , M. H4on, J. C a d o r e t t e , C. C a r r i e r and D. Rouleau. U n i v e r s i t y of S h e r b r o o k e , S h e r b r o o k e , Qu6bee, Canada.

Abstract withdrawn

New pharmaceuticals m u s t be t e s t e d in a n i m a l s prior to their use for clinical a p p l i c a t i o n in humans. PET m e t a b o l i c imaging of the small animal organs w i t h adequate qualitative and quantitative a c c u r a c y requires the h i g h e s t possible r e s o l u t i o n in 3-D in order to a v o i d p a r t i a l v o l u m e e f f e c t s . This can only be achieved with a carefully designed detector system using d i s c r e t e crystals and independent readouts. We d e s c r i b e a new u l t r a - h i g h r e s o l u t i o n PET scanner b a s e d on solid state s c i n t i l l a t i o n detectors. The c a m e r a is 31 cm in d i a m e t e r w i t h a p o r t a p e r t u r e of 13.5 cm, a d e q u a t e for small animals such as rats, cats or r a b b i t s . T h e b a s i c a s s e m b l y is a 10.5 m m t h i c k dual r i n g of d e t e c t o r s f o r m e d b y 256 R C A C 3 0 9 9 4 modules. The two detectors w i t h i n a m o d u l e each consist of one 3 x 5 x 2 0 mm BOO c r y s t a l c o u p l e d to one s i l i c o n a v a l a n c h e photodiode. Several rings of modules can be juxtaposed with a 13.2 mm inter-ring distance to p r o v i d e a large axial coverage w i t h o u t crystal coding. Signals from every single detector are processed i n d e p e n d e n t l y to derive timing pulses. Energy validation is p e r f o r m e d by gated i n t e g r a t i o n of the signals f r o m the two d e t e c t o r s w i t h i n a m o d u l e . All data a c q u i s i t i o n p a r a m e t e r s are fully programmable. Experimental data obtained with a simulation p r o t o t y p e y i e l d i n t r i n s i c F W H M r e s o l u t i o n s of 1.9 m m ( i n - s l i c e ) a n d 3.0 m m (axial). R e c o n s t r u c t e d images wi~h an isotropic r e s o l u t i o n of less than 3.5 mm FWHM over a n e a r l y I0 em d i a m e t e r f i e l d are o b t a i n e d . The ring s e n s i t i v i t y is 3.3 K c p s / # G i / m l for a i0 em diameter flood. P h a n t o m images have also b e e n obtained.

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Abstract withdrawn

EFFECTS OF CIGARETTE F R O M T H E LUNG.

SMOKING

ON

1-123

IMP C L E A R A N C E

K,Kato, T,Takahashi, S.Harada, T.Yanagisawa. Departlaent of Radiology, Iwate Medical University, Morioka, Iwate, Japan, 020. N-propyi-I-123-iodoamphetamine( I-] 23 IMP), originally developed as a brain scanning agent, is taken up by the lung. To evaluate the interaction b e t w e e n a toxic stimulus a n d IMP, w e s t u d i e d the effect of cigarette smoking on 1-123 IMP clearance from the lung. The subjects were 14 healthy volunteers: 5 non-smokers and 9 smokers. After the injection of I] IMBq of 1-123 IMP into the medial cubJtal vein, the time-activity curve for 60 minutes and the regional activity u s i n g 1 frame/minute and a 64X 64 matrix is recorded. The 1-123 IMP clearance curve was described as follows: C(t) Ale-Xlt+Az e-;zt (AI,A2: intercepts, and kl,kz: slopes of the exponential components). The 1-123 I M P clearance was delayed in smokezs, and both k I and k~_ were smaller in smokers. Also s significant correlation between k, ,k2 and the number of clgarettes consumed per day was found (r=0.81, r=0.70, respectively, p<0.Ol). In conclusion, this study suggests that the delayed clearance and retention of 1-123 IMP in the lung indicate lung metabolic disorders due to cigarette smoking. In the future, histological examination, including radioautographs, must be considered in order to confirm the distribution of 1-123 IMP in the lung.

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PROLONGED RETENTION OF 1-123 IMP IN THE DISEASED LUNG. H. Ikeda, S. Seino, M. Mariko, M.Komatsu, K.Takahashi, S.Yasui. The First Department of Internal Medicine, Yamagata University School of Medicine, Yamegata, Japan

ROLE OF Tc-99m MAA SCINTIGRAPHY FOR EVALUATION RIGHT TO LEFT SHUNT DISEASE. K.Nakada, H.Katsuura, E.Tsukamoto, K.Katoh, K.Itoh, M. Furudate, and T.Tanabe. Hokkaido University, Sapporo,Japan.

The lungs highly accumulate N isopropyl-p-[123I] iodoamphetamine (I-123 IMP) and slowly release them. We reported the abnormal retention of 1-123 IMP in the interstitial lung diseases (Ear J Nucl Med, 1989). In this study we compared the radiographic findings and the r e t e n t i o n of 1 - 1 2 3 I M P in p a t i e n t s w i t h the pulmonary sarcoidosis or the pulmonary fibrosis, before and after treatment. And we studied the adsorption of 1-123 IMP to the alveolar cells and to the leukocytes. 1.5 mCi of 1-123 IMP was injected into vein, and the image of regional a c t i v i t y was stored by 3 frames/ minute in a 32*32 matrix. The half time (TI/2) of 1-123 IMP release from the lung was calculated. The lung field of X-ray photograph was divided into 6 portion, and a quantitative score was assigned to radiographic finding (X-ray score). The leukoeytes and the alveolar cells (mainly macrophage) were collected from venus blood and by the broncho-alveolar lavage respectively. The prolonged TI/2 was observed in the lung field which had a high X-ray score. The X-ray score and the TI/2 value in the corresponding area had a positive relation. The TI/2 was shortened with the improvement of findings in the X-ray photos. 1-123 IMP was adsorbed by the alveolar cells, but not by the leukocytes. The results suggested the existence of binding site. It was considered that analysis of 1-123 IMP washout was useful for the estimation of changes in the lung. We reported that the injected 1-123 IMP was transported to the alveolar space ('89 ATS annual meeting). It was considered that the retention of 1-123 IMP in the lung was related not only to the capillary endothelial cells but also to the alveolar sells.

Wednesday, August 29, 1990

During the period from 1982 to 1989, 47 patients with right to left shunt(R-L shunt) disease were perfomed Tc-99m MAA scintigraphy to estimate R-L shunt rate(RLSR). After injection of 1-AmCi(37-148MBq) of Tc-99m MAA, whole body image and spot image of lung and kidney was scanned from posterior projection. Extrapulmonary uptake such as brain,kidey, or spleen was demonstrated in all patients, and RLSR was caluclated using the formula described below. A)RLSR=(Cw-Ol)/Ow x100 (%) B)RLSR=(4Ck-CI)/4CkxI00(%) Cw:counts in whole body Cl:counts in both lungs Ck:counts in both kidneys From the results of examination of 17 subjects without R-L shunt, it was suggeseted that when calculated RLSR value is more than 18%(Method A) or more than 12%(Method B), RLSR was siginificant. Correlation of RLSR between calculated by cardiac catheterization and Tc-99m MAA scintigraphy was generally good,r= 0.798(method A),and 0.791(Method B). In most of the patients 9 changes of RSLE and lung uptake were compatible with time course of the disease, especially before and after operation. Tc-99m MAA scintigraphy is a simple and noninvasive way in estimation of RLSR, and also usefull in following up of the patients.

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EFFECTS OF EXERCISE ON RIGHT TO LEFT SHUNTING THROUGH PULMONARY ARTERI0-VENOUS MALFORMATIONS.

RAOIOIMMUNOASSAY FOR MEASUREMENT OF TI4YROTROPIN RELEASING HORMONE IN BLOOD AND BIOLOGICAL SAMPLES

M W h y t e , AM P e t e r s , BL H e n d e r s o n , JE J a c k s o n , JMB H u g h e s , a n d DJ A l l i s o n . H a m m e r s m i t h Hospital, L o n d o n Wi20HS, England.

1 2 ~K. Mohari, Oy.A. J@noki, L. K6r6si, E.Tal l" , . . 9Natl. Res. Inst. Radlebzol. Radlohyg. Budapest. The Hebrew University of Jerusalem.

Pulmonary arteriovenous malformations (PAVM) are u s u a l l y associated with arterial hyoxemia at rest. hypoxemia worsens on exercise, possibly by increased peripheral oxygen extraction or by increased right to left shunting. We measure resting shunt flow by quantifying right kidney activity immediately following IV injection of Tc-99m labelled albumin microspheres (Chilvers et al Clin Radiol 1988; 39: 611). Assuming the right kidney receives 10% of cardiac output (CO) the shunt flow (S) as a percentage of CO is equal to l0 times the k i d n e y a c t i v i t y expressed as a fraction of injected dose, On exercise CO is redistributed and kidney: dose ratios cannot he used. We therefore related the change in S to the change in lung activity (L). If the ratio L (exercise): L (rest) is f then S(exercise) - l - f [l-S(rest)]. 7 patients (4f, 13-52 years) were studied. In 5 patients with multiple PAVMs (8 measurements) mean shunt increased from 32 L SEM 6 to 39 +_6 Z CO (p<0.05) at 50% maximum exercise. Mean shunt decreased in both of the 2 patients with single large PAVMs, from 24 to 17Z. This new quantitative technique appears acurate and suggests that shunt behaviour on exercise may depend on whether shunts are small and multiple, or single.

Thyrotrepin releasing hormone (TRH) pyroglutamyl-hietidyl-prolinamide was the first hypothalamic releasing factor to be purified and identified, by Burgus et al. (1970). 7.e e '.:out to develop a RIA system for the measurement of TR;I during drug treatment and in biological samples. To raise antibody, TRH was coupled to BSA at different BSA at different molar ratios (l:IO,l:5,1:4)usino diszotized benzidine (BOB).For coupling e~ficiency d~termination a tracer amount of 125-I-TRH was used. Thereafter, the crude conjugate was purified on a SephadexG-lO0 column and by dialysis. The final purification of the conjugate was done by HPLC. After repurificstion, the TRH-BOB-BSA conjugate was diluted with 0.15 M NaC1 so that the TRH concentration was 200 zug/ml. One ml of diluted TRH-BOB-BSA and comp!ette Freund's adjuvant were hemooenized, and 2 ml of this mixture was injected intracutaneously into 15 rabbits. Antibody to TRH was detected by RIA after the 4th immunization. We measured 40-50& total binding with our antibody. We were able to measure TRH the range of lOB pg-lO0 ng/ml. Tracer was prepared by a modified Greenwood-Hunter procedure. Using tracer and antibody developed in our laboratory, we measured immunoreactive TRH in rat hypothalamus ( 241 _+ 19 pg/mg tissue level) and adrenal homogenates (i12 + 14 pg/mg tissue level)anD in serum of healthy indivTduals (normal range was 1 to lO ng/ml).

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A N A L Y T I C A L AND CLINICAL E V A L U A T I O N OF A DUAL TRACER METHODOLOGY FOR SIMULTANEOUS SERUM FT 4 AND TSH ASSAY. A. Coli I , M. F e r d e q b ~ H ~ 2 , G. M a d e d d u 3 , C. P r o n t e r a 2 , F. Scarpato I . Nuclear Medicine Departments of La Spezia I , Pisa 2 and Sassari 3, Italy.

U L T R A F I L T ~ T I O N AS REFERENCE METHOD FOR FT4 K. L i e w e n d a h l , a n d S. T i k a n o j a , D i v i s i o n of N u c l e a r M e d i c i n e , U n i v e r s i t y of H e l s i n k i , and Minerva Foundation Institute, Helsinki,Finland

The combined use of FT 4 and "sensitive" TSH assays is regarded as a powerful diagnostic tool f o r cost-effective thyroid profiling. The validity of the SimulTRAC FT4 (Co-57)/TSH IRMA MAb (I-125) kit (Becton Dickinson) was e v a l u a t e d in 401 euthyroid subjects, in 461 untreated patients with a well defined thyroid dysfunction (176 with overt or subclinical hypothyroidism and 285 with overt or compensated hyperthyroidism). The analytical performances of this procedure, as r e g a r d s practicability, sensitivity and precision, appeared appropriate for clinical use. Limits for normality, when empirically set at the 2.5 th and 97.5 th centiles, were 8.0-18.6 pg/mL and 0.34-3.64 ~IU/mL for FT4 and TSH, respectively. When sensitivity, predictive values and d i a g n o s t i c efficiency were evaluated according to the Galen and Gambino approach, the "sensitive" TSH test proved to be definitively superior in discriminating normals from all patients with the considered pathological conditions. However, an undetectable TSH serum level constantly found in primary overt hyperthyroidism was also found in 79.4% of p a t i e n t s with p r e t o x i c adenomas or compensated hyperthyroidism despite the normality of both FT 4 serum levels and of metabolic status. In conclusion, the FT4/TSH simultaneous determination may be considered as an useful screening procedure; moreover it may provide, in conjunction with FT 3 test, a definite functional statement both in t r e a t e d and in u n t r e a t e d patients with thyroid dysfunction.

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E q u i l i b r i u m d i a l y s i s (ED) has n r o v i d e d the r e f e r e n c e m e t h o d o l o g y in free t h y r o x i n e (FT4) e s t i m a t i o n as this m e t h o d is c o n s i d e r e d n o t to a l t e r the b a l a n c e b e t w e e n free a n d b o u n d analyte. D i l u t i o n of s e r u m c a n r e s u l t in s ~ u r i o u s ly l o w FT4 e s t i m a t e s if d i a l y z a b l e i n h i b i t o r s of T4 b i n d i n g are p r e s e n t , a n d the type of d i a l y s i s b u f f e r u s e d is k n o w n to a f f e c t the FT4 e s t i m a t e by a l t e r i n g the a f f i n i t y of s e r u m p r o teins for T4. We h a v e t h e r e f o r e d e v e l o D e d a new m e t h o d for FT4 b a s e d on the use of u l t r a f i l t r a tion (U) d e v i c e a n d R I A of the free f r a c t i o n in the f i l t r a t e . In e u t h y r o i d h e a l t h y s u b j e c t s m e m n FT4 (U) w a s 24.2 p m o l / l a n d m e a n FT4 (ED) 14.8 p m o l / l . In h y p e r t h y r o i d a n d h y p o t h y r o i d p a t i e n t s U v a l u e s w e r e a l s o a b o u t t w i c e as h i g h as c o r r e s p o n d i n g E D v a l u e s . In s e v e r e n o n t h y r o i d a l i l l n e s s e s m e a n FT4(U) w a s 41.2 n m o l / 1 a n d m e a n FT4(ED) 1 9 . 8 p m o l / l . I m p o r t a n t l y , in n o n t h y r o i d a l i l l n e s s e s the m e a n U / D r a t i o w a s n o t s i g n i f i c a n t l y h i g h e r t h a n in the e u t h y r o i d c o n t r o l q r o u p i n d i c a t i n g t h a t the e l e v a t i o n in FT4 is n o t c a u s e d by w e a k l y p r o t e i n b o u n d a n d t h e r e f o r e d i a l y z a b l e i n h i b i t o r s of T4 p r o t e i n - b i n d i n g ; the e l e v a t i o n is p o s s i b l y c a u s e d by an i n c r e a s e in free f a t t y a c i d s as a s i g n i f i c a n t c o r r e l a t i o n w a s f o u n d b e t w e e n the u n s a t u r a t e d F F A / a l b u m i n m o l a r r a t i o a n d FT4. On the b a s i s of t h e s e r e s u l t s , a n d on theoretical grounds,we suqgest that ultrafi!tration i n s t e a d of e q u i l i b r i u m d i a l y s i s s h o u l d be u s e d as the r e f e r e n c e m e t h o d for FT4 in serum.

Wednesday, August29,1990

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A N O V E L V A S O A C T I V E PEPTIDE, E N D O T H E L I N , LIKE I M M U N O R E A C T I V I T Y IN H U M A N C E R E B R O S P I N A L FLUID. Y. Suzuki, H. Suzuki, S. Sato*, M. 0ka, T. T s u c h i y a , I, Iino, T. Y a m a n a k a , N. I s h i h a r a * and S-I. Shimoda. Dept. of E n d o c r i n o l o g y , D o k k y o Univ. Sch. Med., Mibu, T o c h i g i , * I n s t i t u t e of B r a i n and B l o o d V e s s e l s , M i h a r a M e m o r i a l H o s p i t a l , Isesaki, Gunma, JAPAN.

EVALUATION OF A SENSITIVE AND SPECIFIC RADIOIMMUNOASSAY FOR HUMAN GASTRIN AND ITS CLINICAL APPLICATION. V.C. Borghi, M.G. Peig Ginabreda and A. Bettarello. In_s tituto de Pesquisas Energeticas e Nucleares and Faculda de de Medieina da Universidade de Sao Paulo, Sao Paulo, Brasil.

E n d o t h e l i n is a n e w l y d i s c o v e r e d 2 1 - r e s i d u e p e p t i d e w h i c h is s y n t h e s i z e d by the v a s c u l a r e n d o t h e l i u m and e l i c i t s a p o t e n t v a s o c o n s t r i c tor action. To e l u c i d a t e the p o s s i b l e role for vasospasm often observed after subarachnoid hemorrhage(SAH), a specific radioimmunoassay for e n d o t h e l i n was d e v e l o p e d and e x a m i n e d e n d o t h e l i n like i m m u n o r e a c t i v i t y in h u m a n c e r e b r o spinal f l u i d ( C S F ) . Over i00 of c o n s e c u t i v e CSF s a m p l e s from 26 p a t i e n t s w i t h SAH (M/F;10/16, m e a n age 6 1 [ S D 9]), who had o p e r a t e d on 2.2 [2.0] days a f t e r the onset. T e n - 2 0 ml of CSF s a m p l e s w e r e e x t r a c t e d u s i n g S e p - P a k C18 c a r t r i d g e s (Waters). An a n t i s e r u m was r a i s e d against synthetic endothelin-l(Novabiochem) c o n j u g a t e d w i t h b o v i n e serum a l b u m i n w i t h g l u t a r a r d e h y d e . The c r o s s r e a c t i o n of the assay was o n l y o b s e r v e d in the o t h e r e n d o t h e l i n family. A c o n s i d e r a b l e q u a n t i t y of e n d o t h e l i n like i m m u n o r e a c t i v i t y was p r e s e n t in CSF from p a t i e n t s w i t h SAH. The c o n c e n t r a t i o n i n c r e a s e d from 0.4[0.2] at day 0-i to 2.2[0.6] p m o l / l at day 6 and then d e c l i n e d g r a d u a l l y . Most p a t i e n t s s h o w e d the h i g h e s t c o n c e n t r a t i o n b e t w e e n day 4 and day 6. This r e s u l t s u g g e s t that e n d o t h e l i n m a y c o n t r i b u t e to the g e n e r a tion of v a s o s p a s m o f t e n o b s e r v e d in p a t i e n t s with subarachnoid hemorrhage.

Successfull radioimmunoassay methods have been developed for gastrin and have permitted studies of changes in circulating hormone under physiological and clinical conditions. The present work describes a highly sensitive and specific gastrin radioimmunoassay employing a carefully prepared tracer, with great stability and quality comp_a rable with a commercial tracer. It also evaluates the operational characteristics of the assay and confirmes its validity by its application in the measurement of gastrin from very low to extremely high levels. Synthetic gastrin was radioiodinated by the chlorami ne T technique and purified on QAE-Sephadex A 25. The specific antiserum, 1611 raised in rabbits, was sup plied by Dr. J.H.Walsh. The technique employed was the dextran-coated charcoal radioirmmunoassay. The assay sen sitivite ~asofthe order of I pmol/l and the precision was 3.6 - 11.9% (CV, within-assay) and 2.8 - 10.1% (CV, between-assay). Recovery was between 82 and 100%. Fasting gastrin levels in subjects with Chagas disease, pernicious anemia, chronic renal failure and Zollinger-Ellison syndrome were greater than in normals (16.4 _+ 2.0 pmol/l; mean _+ SEM). Very low levels were determined in gastrectomized subjects. No significant difference was found between the determination of serum or plasma gastrin concentration in normals (p<0.05).

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A P P R O A C H E S T O TI~E D E V E L O P I ~ T O1~ R A D I O I I ~ U NODIAGNOSTiC TESTS FOR THE ARALYSIS OF FREE L I G H T C H A I N S OF I ~ U N O G L O B U L I N S IN VITRO

99mTc-SESTAMIBI (MIBI) MYOCARDIAL IMAGING IN DETECTION OF ISCHEMIC HEART DISEASE: COMPARISON BETWEEN INITIAL (i HOUR) AND DELAYED (3HOUR~ POST-EXERCISE IMAGES. R. Taillefer, M. Primeau, P. Cost• R. Lambert, Y. Latour Nuclear Medicine dept., HStel-Dieu de Montr6al, Canada.

N.Piven', l.Vigdorovich, Institute of B i o o r g a n i c C h e m i s t r y o f the B y e l o r u s s i a n Academy of Sciences, Minsk, USSR F r e e l i g h t c h a i n s of i m m u n o g l o b u l i n s ( B e n c e - J o n e s p r o t e i n s ) b e l o n g to the i m p o r t e n t f o r c l i n i c m a r k e r s of a s e r i e s of m a l i g n a n t d i s e a s e s s u c h as m u l t i p l e m y e l o m a , plasmocytoma, l~phoproliferative disordes, etc. T h e p r e s e n t s t u d y w a s u n d e r t a k e n to develop based on radio~nmunoassay principles test for determination of serum and urine concentration of free kappa- and lambdalight chains of human immunoglobulins. M o n o c l o n a l a n t i b o d i e s (I~{ab) w e r e t e s t e d as i ~ m u n o a s s a y s y s t e m c o m p o n e n t s . T h e p o s s i b i l i t y o f r a d i o l a b e l l i n g of M a b w i t h i o d i n e 125 w a s i n v e s t i g a t e d . P r e s e r v a t i o n o f I~ab specificity and antigen-binding ability after i o d i n a t i o n h a s b e e n demons%_~ated w i t h the h e l p o f ~ . l u n o e n z y m e a s s a y . ~b~per~uents o n ~b i m m o b i l i z a t i o n w e r e c a r r i e d o u t w i t h the p u r p o s e of p r e p a r a t i o n of L ~ m u n o s o r b e n t f o r " s a n d w i c h " - a s s a y , b a s e d o n u s e of two M a b p r e p a r a t i o n s s p e c i f i c to d i f f e r e n t e p i t o p e s o f the s ~ n e a n t i g e n . The r e s u l t s o b t a i n e d m a y s e r v e as a prereguisits for the development of assay s y s t e m of i ~ m n u n o r a d i o m e t r i c t y p e f o r a n a l y s i s of f r e e l i g h t c h a i n s of h ~ l a n i a ~ u n o g l o b u l i n s in b i o l o g i c a l f l u i d s .

Thursday, August 30, 1990

Previous studies have demonstrated that there is no slgnificant myocardial redistrkhution following MIBI injection at stress. In some studies, imaglng has been performed up to 6 hours after injection. The purpose of this study was to evaluate the myocardial clearance of MIBI and ischemic/normal wall ratios at one hour and at 3 hours after injection at stress in patients with coronary artery disease (CAD). Twenty-five patients with isehemic defects on 201-Thallium scans (n=13) and/or significant CAD on coronary angiogram (n=17)were prospectively studied. Planar images (3 views, 10min./view) were obtalned at 65 and at 190 min. after an injection at stress of 25 mCi of MIBI. A rest study was performed 2-6 days later. Ischemic/normal wall ratio and myocardial uptake and clearance were determined for each study. Blinded reading (3 segments/view) was performed by 2 observers. Ische-mir/normal wall ratlos were 0.73• and 0.83• (p 0.05) at 1 and 3 hours respectively (0.98• at rest). Myocardial wash-out was 25% for normal walls and 15% for ischemic walls (p 0.001). Segmental ana!ysls showed 48 and 46 ischemic segments at 1 and 3hours respectively. In conclusion, although only few isehemic segments were missed at 3 hours, s~gnificantly lower ischemic/normal wall ratios were found at one hour. Fastpr myocardlal wash-out from normal wall is responsible for the partial correction of this ratio. Ideally, imaging should be performed at one hour after MIBI stress injection in order to avold this pheoomenon.

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TEMPORAL CHANGES OF TC-99M MIBI MYOCARDIAL UPTAKE. A.R. Mahmoud, A.H. ELgazzar, D. Algabagi, H.M. AbdelDafem, Depts. of Nuclear Medicine & Cardiology, Kuwait University & Amiri Hospital, Kuwait.

WITH Tc99m-MIBI OF VARIATIONS OF PERFUSION IN THE ACU-

Recent studies from D.K. reported washout of Tc-99m MIBI from the myocardium when comparing one & three hours acquisitions after one single i.v. injection. The purpose of this study was to find out whether there are changes between early acquisition (5 min.) post injection & delayed imaging after 3 hours. Twelve patients were studied prospectively. All refere~ with diagnosis of IHD. All had rest & exercise injections of 10-15 mCi Tc-fgm MIBI on two separate days, All had two SPECT acquisition after each injection at 5 minutes & 3 hours after the i.v, administration of Tc-99m MIBI. Acquisition & processing parameters were the same in all patients and at all acquisitions. The heart to liver and heart to lung ratios were compared. The studies were interpreted by two experienced observers. The results show that there is significant change with time in the myocardial uptake of Tc-99m MIBI indicating significant washout. There was no change in Ht/L ratio between 5' & 3 hr. The Ht/liver ratio got higher at 3 hrs due to clearance of liver activity but liver activity was not a problem at early acquisition. Gastric & colon activity was a problem in 3 studies in delayed imaging. We conclude that there is myocardial washout of MIBI with time. Three hour imaging may not reflect perfusion status at the time of injection. Early acquisition is preferable and liver activity does not cause a major problem.

ACUTE

MYOCARDIAL

INFARCTION:SCHINTIGRAPHIC

EVALUATION

TE PHASE AND IN THE SHORT PERIOD FOLLOW-UP *G.Medolago; A.Piti; N.~espili; R.Gotti; *G.Virotta; F .D 'Adda ;A.Balduzzi ;D. Mazzoleni ;A. Casari ;*C.Bertocchi. DPT of Cardiology and Nuclear Medicine-Bergamo-Italy To evaluate if Perfusion Study (PS), in the acute phase of myocardial infarction, can correctly identify the extent of the area cf necrosis, we performed PSs with Tofgm-MIBI, in the follow-up in 38 pts,who,in the acute phase, underwent e rest PS with Tc99m-MIBI.AII the pts were at their 1 AMI.The stress PS was performed, on the average, afler ]18 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 gradlng of the perfusion defect (GPD) of the 2 rest PSs. In 33 pts SE was the same, in 5 was reduced; while GOP was the same in 21 pts, and improved in 17.Between these 2 groups, we found no significant differences about me~i interval at the I PS (62vs50hours), at the 2 PS (107vslSO days) and residual ischemia.At the i PS, 15 pts (39%) had transmural perfusion defects (TPDs) and 23 noTPDs; at the 2 (16%) showed TPDs and 32 pts noTPDs.

PS only

6 pts

CONCLUSIONS:I) PS of MI in the acute phase correctly identifies the area of necrosis. 2)the larger perfusion defect observed in the I rest PS is probably related to the areas of "stunned myocardium" in the acute phase of MI. 3)therefore we think that, to obtain a correct evaluation of the area of necrosis,it's ferable to postpone the rest PS about at the 3

preweek

from acute episode.

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PERFUSION (Tc99m-MIBI) AND METABOLIC (II23-IPPA) IN RECENT MYOCARDIAL INFARCTION BY SPECT IMAGING *G.Medola~o ;A.Piti ;

M.Tespili;

R.Gotti;

STUDY

*G.Virotta;

F. D 'Adda ; A. Balduzz i ;D. Mazzoleni ;A. Casari ;* C. Bertocchi. DPT of CardioloEy and Nuclear Medicine-Bergamo-Italy PET showed that metabolic tracers seem to be the most suitable in identifying viable myecardium,when compared to perfusion tracers. Recently a new gamma-emitter metabolic tracer, II23-IPPA, has been avaiiable for SPECT studies, presenting potential larKer 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 S 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 thor studies on larger populations are necessary to confirm the better effectiveness of II23-IPPA in identifying viable myocardium.

S170

Tc-99m MIBI IN THE DIAGNOSIS OF ACUTE MYOCARDIAL INFARCTION. M. Pajares,J.M. Freire, E. Otero, L. Campos, T. Cambil, C. Pifiero. Security Social H o s p i t a ~ S P A I N . The aim of this study was to evaluate the diagnostic a b i l i t y of Tc-99m MIBI in patients with acute myocardial infarction (AMI). We have studied, 2-19 days a f t e r admission:f08 patients with either stablished AMI (88) or angina (20), 90 minutes a f t e r i . v . injection of Tc-99m MIBI (15-20 mCi) at rest. Ima9es were collected by planar gamma camera from anterior, 45 ~ LAO and 70 ~ LAO proyections. For each patient 15 segments were visually assessed and were asigned to three anatomical regions: Anterior, Inf e r i o r and Posterolateral. The Tc-99m MI81 images were scored independently by consensus of two experienced observers using a 4 point scoring system (O=normal, I= equivocal, 2=moderate, and 3=sevre reduction of a c t i v i t y ) The observers were blinded to the c l i n i c a l history and the ECG tracings. A segment was considered abnormal i f the score was ~ 2. Perfusion defects compatible with myocardial necrosis were visualized in 75 of 88 patients with c l i n i c a l AMI. Of the 13 patients with score< 2,5 had previously r e c e i ved thrombolitie therapy, another 2 patients presented nonspecific ECG changes. Anal#sis:of the 324 t e r r i t o r i e s studied showed a sens i v i t y of 0.86 ( 8 0 / 9 3 ) , s p e c i f i c i t y of 0.99 (230/231), a positive predective value of 0.98, negative predective value of 0.94: and accuracy of 0.95. Of the I I patients with nonspecific ECG changes, 9 presented a perfusion defect suggestive of myocardial necrosis. We conclude that planar images with Tc-99m MIBI is a highly s e n s i t i v e method in the diagnosis and l oca ti o n of AMI.

T h u r s d a y , A u g u s t 30, 1 9 9 0

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ASSESSMENT OF MYOCARDIAL PERFUSION IN UNSTABLE ANGINA USING Tc-99m-METHOXY ISOBUTYL ISONITRILE SPECT IMAGING. J. Gr6goire, L. Bilodeau, G. Dupras, A. Arsenault, D. Gagnon, P. Th6roux. Montreal Heart Institute, Montreal, QC, Canada.

Measurement of Blood Brain Barrier integrity in A[zheimer Disease Using Cll-[nulin and Positron Emission Tomography

Twenty three patients with proven significant coronary artery disease, no prior myocardial infarction, and presenting spontaneous chest pain at rest were studied. Tc-99m methoxy isobutyl isonitdle (MIBI) (1 GBq) was iniected during the episode of chest pain and single photon emission tomography (SPECT) was obtained 1 to 6 hours later. SPECT acquisition was performed using 64 projections of 20 sec each over a 360 degree elliptical orbit. The MIBI study was repeated 1-2 days later when the patient was free of symptoms. Data were displayed in a two dimensional polar map ("bullseye') format divided into 25 equal sectors, Comparison of normalized sectodal uptake was made with a normal file. Sectors with uptake 2 standard deviations below the normal mean were considered abnormal. Defect size and intensity were combined to determine a global defect score, All MIBI SPECT studies obtained during chest pain were abnormal. Mean global score (-SD) was 7.2 _+ 4,2% during chest pain and 2.6 • 2.6% without chest pain (p<.O001). Residual perfusion defects without chest pain were seen in 17 (74%) patients. Therefore, MIBI SPECT study can estimate the amount of hypoperfused myocardium in patients with unstable angina. Hypoperfuaion appears almost 3 times more severe during chest pain than in its absence, The persistence of a MIBI defect between chest pain episodes could be caused by chronic ischemia from a severe coronary stenosis or decreased metabolic activity secondary to stunning from the acute painful episode, Even though it can not be ruled out, a residual perfusion defect while pain.free does not imply the presence of an acute or old myocardial infarction.

Fuji Yokoi, Toshihiko Hara, Masaaki lio, Takeshi Tabira, Masatake Uno, Hiroshi Shibasaki, Eijiro Satoyoshi National Center of Neurology and Psychiatry, Tokyo, and National Nakano Chest Hospital, Tokyo We measured blood brain barrier permeability and cerebral interstitial fluid volume in Alzheimer disease patients using C l l - l a b e l e d inulin (n~.w. 5000). The C l l - i n u l i n (815 mCi) was injected intravenously. PET scan started at the time of injection and continued up to 40 min thereafter. Arterial blood samples were collected during this period. The C l l uptake in brain was estimated after subtraction of blood contribution, measured separately with CII-CO, from the total C l t -i nul i n count in the brain. The rate of change of C l l - i n u l i n concentration in brain parenchyma is given by dR(t)/dt=kCp(t)-kR(t)/f; R(t):net parenchymal concentration of C l l - i n u l i n at time t(min), Cp(t):plasma concentration of Cll-inulin, k:permeability suface area product for inulin, f:interstitial fluid volume in unit volume of tissue. R(t) data were obtained as follows; R(t)=Robs(t}-rCPV*Cp(t), where rCPV is regional cerebral plasma volume, and Robs(t) is total tissue concentration of Cll-inulin. In patients with Alzheimer disease, both k and f were markedly high, which is consistent with the hypothesis that the increased blood brain permeability in brain of Alzheimer disease is the cause of increased deposition of blood-borne amyloid beta-protein (m.w. 4000) in brain of the disease.

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A OUANTITATIVE COMPARISON OF rCBF IMAGING IN DEMENTIA USING 99mTc HMPAO SPECT AND C1502 PET.

REGIONAL Tc99m-HMPAO UPTAKE IN DEMENTIA ALZHEIMER TYPE (DAT): CORRELATION OF rCBF-EQUIVALENT IN RELATION TO THE CLINICAL GRADING OF DEMENTIA

HG G e ~ e l l , NTS Evans, JAO Besson, D Roeda, J Davidson, PF Sharp, FW Smith, JR Mallard. University of Aberdeen and Aberdeen Royal Infirmary, Aberdeen, Scotland. The aim of this study was to compare 99mTe hexamethylpropyleneamineoxime (HMPAO) SPECT with regional cerebral blood flow (rCBF) imaging using C1502 and PET. As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data was compared quantitatively with three versions of the SPECT data. These were, firstly data normalised to the SPECT cerebellar uptake, secondly data linearly corrected using the PET cerbellar value and , finally data Lassen corrected for washout from the high flow areas. Both the linearly corrected (r=0.81) and the Lassen corrected (r=0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the nor~0alised HHPAO SPECT data and the PET data was non-linear. It appears impossible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.

Thursday, August 30, 1990

U. C~bhardt, F. Schn~u~, C. W~gner- Marclau, R. Bauer, H. W. Pabst R. Zimmer*, M. Haupt*, A. Kurz*, H. Lauter* Nuklear medizinische und Pa~chiatrische* Kliniken der TechniscI~n Universitit MUnchen

30 clinically diagnosed DAT were investigated, fulfilling McKhann criteria and had been assessed by MiniMental State Examination (MMSE). The seveMty of dementia was classified in 3 grades (mild: 21-26, moderate: 1320, severe 5-12 MMSE range). All examinations were performed 20-30 min. after i.v.injection of 550 MBq Tc 99-HMPAO. 6 slices reorientated parallel to OML were analyzed by ROl-technique. As an rCBF-equivaient we used the cortico-cerebelIarratio (CCR). I. rCBF-reductions correlate with severity of DAT: mild DAT shows significant changes only in left hemisphere temporo-parietal areas, moderate DAT shows additional rCBF-reductions in both hemispheres fronto-lateral, temporo-parletal and occipital areas, severe DAT shows further reductions fronto-lateral, temp.-parietal areas and additional once mid frontal. 2. The comparison of rCBF and MMS examination, performed by linear regression; shows significant correlations: left ant. temp.-paMetal area (r=0,74; p
$171

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ARE FINDINGS OF T~4PQROPARIETAL HYPOP~'USICU SPECIFIC OF ALZHEIMER'S DER~NTIA? I. Mena, B. Miller, K.

CORRELATIONS OF REGIONAL HMPAO BRAIN UPTAKE WITH DEMENTIA SCALES J.Darcourfl, O.Migneco 1, D,Pringuey 2, O.Ricq 2, M.Borg 3, F.Lapalus 1. Dept. of Biophysics and Nuclear Medicine, CAL, Nice, France 2. Dept. of Psychiatry - 3. Dept. of Neurology. University of Nice, France

Garrett, J. villanueva-Meyer, R. Gic~betti. Dept. of Neurology, Div. of Nuclear Medicine, Harbor-UCLA Medical Ctr., Torrance, CA, USA. Temporoparietal (TP) hypoperfusion (HP) in SPECT studies is a frequent finding in Alzheimer's dementia (AD). However, the specificity of these changes has not yet been determined. We have found bilateral TP HP in }~PAO brain SPECT imaging in the following nonAD situations: 2/20 normal aging volunteers, 1 post hypoxic dementia pt., 6/22 multiple infarct dementia pts., 1 pseudo TP HP in frontal seizures pt., and i0 patients with sleep apnea (SA). The pseudo TP HP in frontal seizures resulted from the absolute increase in frontal perfusion and relative TP HP, with normal absolute perfusion in these areas. SA is characterized by disordered respiration during sleep and is often accompanied by deterioration of memory and judgement. A comparison was established with 45 pts of AD. The SA group had mild neuropsychological impairment, their Mini Mental Status (MI~S) score was 27 (normal 30) compared 21 for the AD group. Xe-133 rCBF was measured quantitatively by means of a multiprobe system and HMPAO Tc-99m SPECT was performed 2 hours after IV injection of 20 ~ i . These studies demonstrated the following:

We analyzed the regional distribution of cerebral pedusion on HMPAOTc-99m SPECT images using 5 cortical areas: frontal (F), parietal (P), parietotemporal (PT), temporal (T) and occipital (0). 31 patients with primary

These findings suggest that the TP cortex may be particularly sensitive to hypoxia and/or hypotension and that HP to the TP cortex is not specific to AD.

degenerative dementia of the Alzheimer type (PDDAT) according to DSM IIIR are studied. The deterioration is mesured by different dementia scales: mini mental status (MMS), Blessed A and B (BLA, BLB) and global deterioration scale (GDS) While solving a visual task, the patient is injected HMPAO-Tc-99m in the IV line previously placed. One to two hours later the tomographic acquisition is started:126 64x64 projections o125 sec over 360 degrees, After reconstruction, the slices are analyzed in 2 ways. First a visual grading (VG) of the extension of the abnormalities for the 5 cortical areas is achieved by 2 observers on transverse cuts. A color scale with a threshold at 65% of the maximum as the normal limit is used. Second the ratios of counts of the 5 corlioal ROle overthe cerebellum are computed using a new approach. The non cortical pixels are set to zero and the sagittal cuts are computed and added together for each hemisphere, This leads to 2 laterm views of the cortical uptake on which the 5 ROIs are positionned. There is no correlation between F or O uptake and dementia scales with the 2 analyses. P uptake only correlates using the visual score (R=0.66; p<0.0001 with MMS). With both approaches there is a significant correlation of the scales results (MMS, BLB and GDS) with T and PT areas uptake. T vs MMS: R= 0.73 p <0.0001 by VG; R= 0.55 p=0.0014 by ROI PT vs MMS: R= 0.65 p <0.0001 by VG; R= 0.54 p= 0.0017 by ROI Tvs GDS: R= 0.59 p= 0.0015 by VG; R= 0.60 p= 0.0012 by ROI PT vs GDS: R= 0.70 p <0.0001 by VG; R= 0.54 p= 0.0046 by ROI This correlation is higher for the left hemisphere than for the right. We conclude that the severity of cognitive impairment in PDDAT correlates with a heterogeneous muitifocal degenerative process involing mainly T and PT regions which can be assessed by HMPAO-Tc-99m SPECT.

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752

VALUE OF DOUBLE TRACER BRAIN-SPECT FOR DIAGNOSIS IN AIDS-ENCEPHALOPATHY (AZDSE). I. Bangerl, P. Pohl, ~. _Ricc~q~ab.~_J!~Depts. of Neurology and Nuclear Medicine, University Medical School, Innsbruck~ Austria.

COMPARISON OF Tc-99m MAG3 AND 1-131 HIPPURAN FOR RENAL FUNCTION STUDIES K. Rootwe!t. Rikshospitalet Natiollal Hospital, uElo, Norway

AD SA

Temporal- Parietal (TP) Symmetrical Assymetrical 20/45 25/45 3/10 7/10

Frontal 20/45 5/10

rCBF 44 ml/min/100g 39 ml/min/100g

Previous reports described alterations of tracer-uptake of 123 I-IMP or 99m Tc-HMPA0 in AIDSE. To achieve a correlation of findings with both tracers we studied 22 pats. with ]85 MBq 123 I-IMP and 555 MBq 99m Tc-HMPAO by SPECT using an orbiting ZLC-Digitrac single head camera with microdelta software and identical image reconstruction programs. Results showed really cold areas in 12/22 pats. after 99m TcHMPAO, while with 123 I-IMP only 8/22 showed comparable defects. In 7/22 cases the localization of defects with both tracers was not identical, the intensity of uptake with both tracers was different in 10/22 pats. and identical only in 5/22 pats. 21/22 pats. overall showed abnormal uptake patterns while CT/NMR exams gave an abnormal finding only in 1/22 pats. SPECT-uptake patterns, however, did not correlate with clinical stages of AIDSE. They showed cerebral involvement in the disease already in early stages (I) and in anatomical correlation with clinical symptoms. Our data seem to confirm the hypothesis that HIV damages primarily endothelial cells in the brain producing local perfusion abnormalities.99m TcHMPAO-SPECT-studies can therefore be proposed as screening method for AIDSE.

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Twentyfive ad'~11t patients referred for clinically indicated renography were studied to see if Tc-99m MAG3 should replace 1-131 Hippuran. The patients s<~ffered from a variety of renal diseases and had ERPF values ranging from 88 to 650 ml/min 1,73m2. Single shot i.v. injections of 5 MBq 1131 Hippuran and 75 MBq Tc-99m HAG3 were given 30 mandates apart. Dynamic gamma camera images and thorax activity curves were recorded. Plasma disappearance rate for both tra=ers was followed for 120 man, and olearai=ces and distribution volumes calculated according to Sapirstein. No side effects occurred. Target to background ratio was 1.28 times higher (p<0.05) for MAG3 than for Hippuran. Kidney activity curves were less noisy, and the kidney scintigrams had markedly superior ~uality. Scatterplot of relative kidney ~<[nction cl Istered around the i~entity line. In one patient Hippuran yielded an erroneous result for split right/left kidney fu'Iction. Distribution volumes V! and V2 were both smaller for MAG3 than for Hippuran, and their mean sum 11.8 1 averaged 70% (p<0.05} of the Hippuran average. MAG3 clearances averaged 53% of Hippuran clearances. The clearances showed good correlation: Hippuran=27+l.8*MAG3 (r:0.95). Clearances as estimated from paired thorax activity curves were in fair agreement, as were ERPF estimations from net kcd~eY uptake measurements accol-ding t o ~h gel (Hippuran=12; 0.68 MAGi; r=0.8~). At present we use MAG3 (3 MBq/kg) as our routine agent for renogra~hy. ERPF is estimated accol-ding to Scnlegel. In addition plasma clearances are determined and reported in absolute values and as % of normal.

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BIOKINETICAL CHARACTERISTICSAND DISTRIBUTION OF Tc-99m-MAG3 IN HUMANS. B. Bubeck, W. Brandau~, P. Georgi, Depts. of Nuclear Medicine, Universities of Heidelberg and ~MUnster, FRG The replacement of radioiodinated hippuric acid (OIH) by Tc-99m-MAG3 is taking place and the knowledge of i t s pharmacokinetic differences is essential for the i n t e r p r e t a t i o n of c l i n i c a l findings. The determination of the plasma protein binding of Tc-MAG3 (n=50) reveals 90%,which means theglomerularly f i l t e r e d fraction of this agent is negligible. Simultaneous clearance measurements with OIH and Tc-MAG3 in steady state (n=124) resulted in a one t h i r d lower clearance of Tc-MAG3 than OIN, probably caused by the the high plasma protein binding. Competitive i n h i b i tion by p-aminohippurate (PAH) (n=20) showed a c l e a r l y higher suppression of t'~e Tc--MAG3 clearance than of OIH. Nevertheless, no difference could be observed renographically in transplant patients during periods of severely reduced renal function. Clearance determinations under furosemide diuresis (n=13) and measurements of l i p o p h i l i c i t y indicated no re-absorption of Tc-MAG~ during the passage through the nephron. Neither the simultaneous determination of the r e l a t i v e l i v e r a c t i v i t y of the respective agent ( n = l l ) nor that of the plasma extraction e f f i c i e n c i e s of Tc-MAG3 and OIH, which were measured by sampling of a r t e r i a l and venous renal blood durind surgery (n=6), did i n d i cate an extrarenal elimination of purified Tc-MAG3. A d d i t i o n a l l y , analysis of patients" urine (n=18) revealed neither metabolism nor in vivo-decomplexation of Tc-MAG~. Under consideration of i t s pharmacokinetic% Tc-MAG3 is suited not only for q u a l i t a t i v e but also for quant i t a t i v e renal function studies.

RADIONUCLIDE HYSTEROSALPINOGOGRAPHY IN INFERTILITY

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SCREENING FOR RENAL ASYMMETRY IN HYPERTENSIVE PATIENTS UNDERGOING MYOCARDIAL SCINTIGRAPHY. G.A. H u r w i t z , A.G. M a t t a r , J.E. Powe, A.A. D r i e d g e r a n d P. H o g e n d o o r n . U n i v e r s i t y of Western Ontario, Victoria Hospital, London, Ontario, Canada.

DUAL RADIOISOTOPE STUDYIN THE DIAGNOSISOF VA$CULOGENICMALE IMPOTENCE. A.A.ESEN, M.T.KiTAPCI, B.ERBA3,C.F.BEKDiK,D.REMZi. HacettepeUniversity Facultyof Medicine~,NI
T h e d e t e c t i o n of a n a s y m m e t r y in r e n a l perfusion/mass may have particular relevance in s i g n i f i c a n t l y h y p e r t e n s i v e p a t i e n t s (HTP) w h o h a v e s y m p t o m s of t a r g e t o r g a n d a m a g e . Previously we have established the reliability of quantifying differential renal function on TI-201 images obtained for 5 minutes at 1-3 hours after tracer injection in HTP undergoing myocardial p e r f u s i o n s c i n t i g r a p h y (MPS) f o r c h e s t p a i n symptoms. In t h e c u r r e n t study, w e p r e s e n t r e s u l t s f r o m a t o t a l of 140 H T P w h o w e r e evaluated for a possible renovascular e t i o l o g y a t t h e t i m e of MPS. The normal range for differential renal uptake was e s t a b l i s h e d in 30 n o r m o t e n s i v e c o n t r o l s a n d validated in 18 o t h e r H T P w h o h a d k n o w n renal angiographic status when referred for MPS. Of t h e s c r e e n e d HTP, 23 h a d s i g n i f i c a n t asymmetry of T I - 2 0 1 uptake (outside 99% confidence limits for normals) yielding.an incidence of 16+3%. R e n a l T I - 2 0 1 imaglng p r o v i d e d t h e f i r s t e v i d e n c e of a s y m m e t r i c renal perfusion in 5 cases confirmed subsequently by angiography a n d i0 o t h e r s confirmed by DTPA renography. The simple non-invasive nature of this screening t e c h n i q u e s u p p o r t s its s e l e c t i v e u s e as a n a d d e n d u m t o p r o t o c o l s f o r MPS.

T h u r s d a y , A u g u s t 30, 1990

J. H. McKillop, D. McQueen, H. W. Gray, R. G. Bessent, W. P. Slack. Royal Infirmary, Glasgow, Scotland. Current tests of Fallopian tube factors in infertility are restricted to anatomical assessment with no evaluation of tubal function. We have carried out radionuclide hysterosalpingography in 96 infertile women undergoing conventional investigations. Technetium-99m labelled albumen microspheres (mean activity 17MBq) were injected into the mucus around the uterine cervix but not through the internal os. Anterior and squat view ga~na camera images were obtained at intervals up to 90 minutes post administration and examined for spill of activity into the periovarian area or peritoneum, The radionuclide test correlated with the findings at laparoscopy in the diagnosis of tubal patency or blockage in 83 patients. In 9 patients where laparoscopy demonstrated patency but the radionuclide test suggested blockage, there was a high incidence of peritubal and tubal pathology which might be expected to affect function even in the presence of anatomical patency. Six patients had patency on the radionuclide test but laparoscopic blockage. Tubal spasm may be a factor in some of these patients. The radionuclide test may facilitate the detection of diseased but patent tubes and be a useful adjunct to laparoscopy with hydrotubation. We are following the patients to observe pregnancy rates.

A relatively non-invasivedual rodioisotopictechniquewas developed to evaluateetiologic factors of vaeoulogenicimpotencesimultaneously. Study was performed in 35 patients who complainedof impotenceand confirmed with peni] brachial index, dupplex ultrasonegraph, cevernosography,cavernosometry, pudenda]angiegraphy. After lnvivo conventional labelingof red bloedcellswlth 5me1Tc-99m pertechnatate 5mCi of Xe- 133 in saline was injected into the corpus cevernasum.The scintigraphlc study was obtainedat 1rain/frame prier to and after the intracavernous administration of papeverine(60rag)for 1 hour. By choosingthe regionof interest ever the penis, Tc-99m time activity curve was generated and then Tc-99m penegram index (TPI) was calculated by the formula: (Activity at 3.4 minutes - Activity at the I~gining) / Activity at the beglning. Xe- 133 panegramindex (XPI) was calculatedfrom Xe- 133 washout curve by the formula: (Activity at the time of peek pentle volume Activity at the endof study)/Elapsodtime. TPI was 1.647 + 0.656 for the centrol group (15man), 0.768• in the patients suffer from erteriegenic impotence (amen). Statistical difference was noticed between two groups with Students' t test (.01
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3-PHASE-SCINTIGRAPHY WITH NANOCOLLOIDS AND ANTI-GRANULOCYTE-AB IN ACUTE AND CHRONIC POSTTRAUMATIC SEPTIC OSTEOMYELmS

T E C H N E T I U M - 9 9 M LABELLED POLYCLONAL IGG IMAGING OF FOCAL INFLAMMATION. F. X. Sundram, S. E. Aw, A. S. W. Goh, E. S. Ang, Department of Nuclear Medicine, Singapore General Hospital, Singapore.

M. Gericke. L. Eckart, U. G6ke, J. Pannhorst, R. Felix Free University of Berlin, UC Rudolf Virchow, FR Germany Early diagnosis of postoperative septic ostaomyelitis in orthopedic sugery is quite important. Infection scintigraphy with 99mTc-labelled nanocolloids has been shown a reasonable method with high sensitivy ( 90 % ) and specifity ( 92 % ) in infections after total hip arthroplasty ( THA ) and bone operations and fractures with no dependency of nanocoll uptake on par'fusion and bloodpool. In our study we comprehended the behaviour of Tcegm-labeled nanocolloids in about 150 patients with questionable postoperative infections and we prooved the potential of this method in differentiating postoperative changes vs. osteomyelitis. 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. Results: The sequence scintigraphy with Tc99m-labsled 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 fdst 2 months after total knee arihroplasty, 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 patternthan the nancoolloids, In equivocal chronical cases of osteomyelitis the granulocyte scintigram showed different results. Some cases had exactly the same pattern than the nanocolloids, some showed more Iocalised enrichment due to high granulocyte accumulation. For clinical routine, we prefer the scintigraphy with Tc99m-labeled nanocolloids because of faster results, lower cost and radiation dose and less allergic risk than mouse anti NCA-Granulocyte-AB.

759 Tc-99m HSA f o r imaging inflammatory f o c i . M.L. Thakur, J. OeFulvio. C.H. Park, A. Epstein* and J. McAfee+, Thomas J e f f e r s o n Univ, P h i l a . . Pa, *USC LA. CA.+ HSC Syracuse, N.Y. A Tc-q9m agent a b l e t o l o c a l i z e i n f l a m m a t i o n ( i n f l .) w i t h i n 4-6 hrs of iv i n j e c t i o n would be h i g h l y u s e f u l . HSA was labeled with Tc-99m by the ascorbic acid reduction technique developed in our l a b o r a t o r y . Following HPLC and ITLC a n a l y s i s , 20 ug of HSA labeled with 40 or 160 uC,i Tc-99m was injected to groups of f i v e mice each bearing i n f l . l e s i o n in the r t . thigh induced by i.m. i n j e c t i o n of 50 ul t u r p e n t i n e (TPI or a 1:1 mixture of lOxE~ E, Col i and Entercocci (EC). Agents admin, s i m i l a r l y were Ga-67 as c o n t r o l , Tc-g9m polyclonal IgG, Tc-g9m a n t i n u c l e a r antibody, TNT-/, and 1-125-TNT-1. Four o r 24 hr l a t e r animals were imaged, s a c r i f i c e d , and d i s s e c t e d , At a hr TP abscess/muscle r a t i o f o r Ga was 4.8+2.1. I-]25-TNT-I 4 . 3 + I , Tc-g9m-TNT-I 3.5 + 1.8, Tci~g9m-lgG 3.9 + r~.6 and-Tc9gm-HSA 4 . 3 + I . With EC these were 2.6+0.7, 3.3+0.5, 3.4+0.(I~, 3~1,I and 4.1+N.6 r e s p l y . A t 4 hr Tiver upt-ake was-highest (25~+8.g and 16.5+!D.6) f o r Tcq9m-lgG and lowest (6+5~-I and 4 . 8 + 3 . # I f o r Tc-qQm~NT-], s i m i l a r to t h e e of 1-125-TNT-I. Results were also s i m i l a r f o r 24 hr groups. Data suggest t h a t al the b i o l o g i c a l p r o p e r t i e s nf p r o t e i n , f o l l o w i n g Tc-9qm l a b e l i n g , remain unchanged (as indicated hy the s i m i l a r i t y of d i s t r i b u t i o n between 1-125-TNT-1 and Tc9gm-TNT-1), b) Tc-9gm-HSA is a promising agent f o r imaging i n f l . f o c i giving as high abscess/tissue r a t i o s as Tcg9m-lgG, Tc-99m-TNT-1 and Ga-67, and c) leakage into the i n t e r s t i t i a l space from increased c a p i l l a r y p e r m e a b i l i t y of the labeled p r o t e i n s is the most l i k e l y mechanism of uptake.

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A Tc-99m labelled compound for detection of focal inflammation has advantages over Ga-67 citrate or In-lll leucocytes. The aim of this study was to note the usefulness of Tc-99m labelled human polyclonal IgG in detection of focal inflammation. DTPA-coupled IgG was labelled with Tc-99m. Initial results with 38 patients

suggest the following:

I) in the early p o s t - i n j e c t i o n phase, behaves as a blood-pool tracer.

the

Tc-99m

IgG

2) Optimal imaging is at 5 hours, beyond which time there is no increased IgG losalisat ion in the lesion, and T s - 9 9 m decay reduces image quality. 3) The study appears more than chronic infection.

promising

4) Tc-99m-IgG or a metabolite~ bowel, reducing the value inflammatory bowel disease.

in

acute

rather

is excreted into of the tracer

the in

5) The clinical response to antibiotic therapy is associated with a negative Tc-99m-IgG scan, while the Tc-99m phosphonate bone scan may still show increased activity. Tc-99m-IgG is detection of evaluation.

an attractive radiopharmaeeutical for focal infection and needs further

760 COLD LESIONS O C C U R I N G IN WHITE BLOOD CELL SCINTIGRAPHY. J.Th. Locher and K.Seyhold K a n t o n s s p i t a l Aarau, Switzerland. In cases of chronic osteomyelits the rate of false negative results of the white blood cell scintigraphy is r e l a t i v e l y high (up to 30%). Because of many factors (e.g. formation of pseudomembranes, high gradient of tissue pressure, necrosis) the migration of labeled granulocytes could be slowed down, thatthe diagnosis of an infection is missed. Several times we have seen a cold lesion on both p l a n a r scans and, even b e t t e r delineated, on SPECT images. This symptom occurs i n d e p e n d e n t l y of the choice of the tracer. However, using the Mab technique for the labeling of granulocytes (I-123 Mah-47, Tc-99m BW 250/183) the defect was seen only t e m p o r a r i l y on early pictures. G r a d u a l l y increased a c t i v i t y has been remarked on delayed scans, wht we called a "filling-up phenomena" of a cold lesion typical for a chronic abcess formation. This p h e n o m e n a m a i n l y occurs in cases of chronic osteomyelitis, but is also seen in abcesses under high pressure. No filling-up was found in non-inflam m a t o r y diseases. Three p o s s i b i l i t i e s are discussed for its explanation: a) Mab labeled granulocytes remain viable for a longer time than after in vitro labeling; b) cell antigens already present w i t h i n the abcess are labeled continuously; c) unbound IgG (labeled mab) is concentrated.

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INFECTION IN HIV POSITIVE PATIENTS IS MORE ACCURATELY LOCALISED WHEN STUDIES WITH 67Ga CITRATE AND THE NEW AGENT 99mTo- HIG ARE COMBINED J.R. Buscombe, R. Miller, H. Burley, D. Lui, P.J. Ell Institute of Nuclear Medicine, UCMSM, London, U.K. Patients who are HIV positive are likely to suffer from multiple infections. Localising signs are often absent and most patients present with persistent or intermittent pyrexin. Lymphoma may also present with similar symptoms. The aim of this study is to compare the results obtained in these patients using both 67Ga citrate and the new agent 99mT~-HIG (Human immunoglobulin). This is the first time that this agent has been used in HIV positive patients. 14 studies were performed on 13 patients, all male, who were known to he HIV positive. All patients were given 200MBq 99mTc-HIG. An anterior whole body scan and relevant spot views were performed 1.4 and 20 hours post injection. They were then given 200MBq of 67Ga citrate and the same views obtained 24, 48 and 72 hours post injection. All studies were performed in an IGE 400AC Starcam. The 57Ga citrate was positive in all 14 studies but infection was confirmed in only 9 studies. Lymphoma (B and T cell) was isolated in 2 patients, gout in 1 patient, recent fracture in i patient and no cause was found in 1 patient~ In all these patients the 99mTCHIG study was negative. Of the 9 studies in which the 67Ga citrate was positive 19 sites of infection were identified of these 13 were positive w i t h 9gmTC-NIG. 99mTC-HIG failed to localise diffuse chest infection in 5 patients and one partially treated CMV eye infection. In conclusion when compared with 67Ga citrate studies alone a combination of 99mTC-NIG and 67Ga citrate studies improves the specificitv of the scinti~raphic investigation of patients who are HIV positive and in whom infection is suspected without any loss of sensitivity.

CHAGAS' DISEASE: RADIONUCLIDE INVESTIGATION IN ASYMPTOMATIC PATIENTS. G,Lago,F.Mut,J.J.L6pez,R.Ponce de Le6n,A.Berriolo, D.Bulla,A.Bianco,A.Aznarez,R.Dalenz,M.Beretta,C.Heuguerot,M.Franca,J.Gaudiano,E.Touya. Centro de Medicina Nuclear and Departamento---d-e'l~Fe'dicina,Hospital de Cl{nicas, Montevideo, Uruguay. Chagas' disease is a h i s t i c and heamatic parasitosis endemic in extensive areas of Latin America. Rural and fringe populations are mainly exposed(around 60 m i l l i o n people) with about 20 m i l l i o n infected.The heart and smooth muscles are frequently involved. A group of 77 asymptomatic patients were studied,all with positive immunoserological reactions most of which detected in potential blood donors.Ages were between Ig -52y (~= 36y); 64 being males and 13 females. A t o t a l of 278 radionuclide studies were performed to explore v e n t r i c u l a r function(VF)in 76 cases,oesophageal transit(OT)in 51,gastric emptying(GE)in 23,upper urinary tract(UUT)in 52 and bladder function(BF)in 47. Seven patients(pts)had 29 follow-up studies 4 to 5 years l a t e r . VF was altered in 32/76 pts(42%),OT in 34/51(67%),GE in 15/23(65%),UUT in 37/52(71%)and BF in 35/47(74%). In 48 pts in which all procedures were performed,VF was found abnormal in 35%,0T and/or GE in 73% and UUT and/or BF 92%.Ali pts had digestive and/or urinary a l terations,45/48 cardiac and/or urinary,and 43/48 cardiac and/or digestive abnormalities. Fourteen out of 29 follow-up procedures showed worsening of previous a l t e r a t i o n s , 8 corresponding to the urinary system, 3 digestive and 3 cardiac. The authors point out the high s e n s i t i v i t y of these studies in detecting s i l e n t alterations of Chagas' d i sease,specially u r i n a r y ( o r i g i n a l contribution of our group communicated in 1984)and digestive dysfunctions.

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PULMONARY AEROSOL CLEARANCEMECHANISMSASSESSEDBY FACTOR ANALYSIS H. K6hn and A. Mostbeck Dept. of Nuclear Medicine and L. Boltzmann-Institute of Nucleer Medicine, Wilhelminenspital, Vienna, Austria

D. Merrild, S. Groth, P.E.G. Kristjansen and J. Mortensen. Departments of Nuclear Medicine~ Rigshospitalet and Glostrup Hospital, Copenhagen, Denmark.

E p i t h e l i a l clearance as commonly measured over the lung is always influenced to a varying degree by mucociliary transport depending on the q u a l i t y of the aerosol used. Factor analysis provides factor images and t i m e - a c t i v i ty curves of extracted p r i n c i p a l components corresponding to underlying s p e c i f i c anatomical structures, even i f these structures overlap. When applied to dynamic inhalation studies of eerosolized 99m Tc-DTPA with d i f f e r ant particle size, always two simultaneously operating factors with opposite temporal behavior, one corresponding to epithelial and one to mucociliary transport, were extracted. TCM (total communality or contribution of all extracted factors) and RCFI (factor contribution to recorded count rate) of the factor related to epithelial clearance were markedly higher with the small-sized particles (98 • 0.9% and 31.9 • 7.5%) than with the aerosol of larger particle size (79.5 + 8.8% and 22.4 • 12.6%, respectively), while background contribution was significantly greater with the latter (65.4 + 14.3% vs 32.3 + 9%). Time-activity curves obtained by factor analysis represent the temporal behavior of specific anatomical structures. Analysis of the time-activity curves related to epithelial transport (RCF1) revealed significantly faster clearance rates than that measured over peripheral lung regions (median: 2.2 %/min vs 1.35 Z/min n=16, p < O.OOl), indicating interference of other clearance mechanisms with the latter.

Thursday, August30,1990

INFLUENCE OF VOLUME ON PULMONARYABSORPTIONOF DTPA.

Pulmonary absorption of DTPA (diamine-triethylenepenta-aeetie acid) has been widely adopted as an index of pulmonary epithelial permeability. The aim of this study was to analyse i) iF measurements of pulmonary absorption are influenced by the amount of Fluid being administered to the lungs together with the DTPA and 2) if all DTPA administered to the lungs is equally accessible for pulmonary absorption. We instilled the DTPA (either 99mTe-DTPA or Illln-DTPA) into a lung segment oF 6 smokers in association with a bronehoseopy whereas in 6 subjects (5 smokers and one ex-smoker), the DTPA ~as inhaled as an aerosol. Pulmonary absorption of DTPA was calculated from the plasma DTPA content, as determined for 4-10 hours after the administration of the DTPA. We Found that the mean transit time for the absorption oF instilled DTPA, ~(L), across the pulmonary membranes ~as significantly (p
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L U N G T e - 9 9 m D T P A T R A N S F E R IN P A T I E N T S W I T H R E N A L TRANSPLANTS AND L U N G INFECTIONS. O 'DOHERTY M, B R E E N D, PAGE C, B A R T O N I, NUNAN T St Thomas' Hospital, London, UK.

PREDLINICAL EVALUATION OF A ~9~Tc-LABELLED ANTIFIBRIN MAB FOR THROMBUS DETECTION G.R. Boniface I, K.Z. Walker z, L.J. Milner 2, F.T. Lee I, W Harewood 3, G.J. Bautovich 3, A. Weedon 3, J.F. Thompson 3, A.F. Phippard 3, R. Waugh ~, P.G. Bundesen 4, D.B. Rylatt 4 ZAustralian Nuclear Science and Technology Organisation, 2University of Sydney, 3Royal Prince Alfred Hospital, Sydney, 4AGEN Biomedical Ltd, Brisbane, Australia.

We have a s s e s s e d the use of lung T c - 9 9 m D T P A aerosol transfer in patients (nonsmokers) w i t h renal d i s e a s e w i t h and w i t h o u t chest infections. 12 normal controls, 13 a s y m p t o m a t i c t r a n s p l a n t patients, 7 patients o n c o n t i n u o u s a m b u l a t o r y peritoneal d i a l y s i s (CAPD), 7 on Hae~mdialysis, 3 w i t h acute renal failure (ARF) and i0 renal t r a n s p l a n t (Tx) p a t i e n t s w i t h lung infections (7 P n e u m o c y s t i s c a r i n i i p n e u m o n i a (PCP) , i w i t h M t u b e r c u losis, 1 w i t h H influenza and 1 w i t h S p n e u m o n i a w e r e studied. E a c h p a t i e n t w a s s t u d i e d in the supine p o s i t i o n w i t h a gamma c a m e r a s i t u a t e d posteriorly. Aerosol was inhaled f r o m a V E N T I C I S d e l i v e r y s y s t e m until 6000 c/sec w e r e a c h i e v e d or 2 mins had elapsed. After 40, 1 min frames w e r e acquired, an IV bolus of T c - 9 9 m DTPA was given to a l l o w b a c k g r o u n d correction. A half time of transfer (T50)was c a l c u l a t e d in mins for each lung. T50 mins (SEM) R Lung L Lung Normal: 70(6) 69(6) Tx: 73(11) 75(13) CAPD: 74(14) 73(15) Haemo: 77(15) 82(15) ARF: 90(7) 88(5) BCP: 11(3) i0(3) Other infections: 64(15) 62(15) In the a s y m p t o m a t i c patients, the T50 v a l u e s w e r e normal. This suggests that in these patients the 'uraemic lung syndrome' did not apply. In the patients w i t h pneumocystis, the TS0 was fast b u t not as fast as in H I V +ve p a t i e n t s w i t h PCP. A p o s s i b l e e x p l a n a t i o n for this f i n d i n g is the p a t i e n t ' s steroid therapy.

767 A NEW AUTOMATIC METHOD FOR Q U A N T I T A T I N G DIFFUSE G A L L I U M UPTAKE IN THE LUNG. T. Simon, S. Pfeffer, E. Molina, R. Hubbard, R. Crystal. Clinical Center and NHLBI, National Institutes of Health, Bethesda, MD. Gallium-67 citrate localizes in areas of p u l m o n a r y inflantmation. A l t h o u g h qualitative and semiquantitative methods of describing diffusely i n c r e a s e d pulmonary activity are clinically useful, their imprecision causes confusion that could be c l a r i f i e d by a quantitative procedure. This study a p p l i e d a new automated quantitative m e t h o d to determine whether it d i s t i n g u i s h e d diagnostic groups with various pulmonary uptake patterns. The m e t h o d was tested by p r o s p e c t i v e l y on 14 consecutive subjects with diagnoses s u g g e s t i n g focal thoracic disease [F] (5 with lymphomas) and diffuse lung disease [D] (9 with interstitial lung disease) end 2 normal controls [C]. 48 hrs after 6 mCi (222MBq) iv Ga-67 citrate, whole body images were a c q u i r e d by a moving gan~na camera interfaced to a digital computer. Automatic software found the mean p u l m o n a r y 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] and heart [HEART]. An analysis of variance showed that LUNG d i f f e r e d by diagnostic groups (p<0. 001). LUNG/BONE v a r i e d by diagnostic groups (mean + SEM: F=0.62+0.03, D=0.70+_0.02, C 0.56+_0.07, p=0.05), and LUNG/HEART tended to vary by group (mean +_ SEM: F=0.81+0.04, D=I.01+0.06, C=0.82+_0.04, p=0.08). We conclude that this m e t h o d for q u a n t i t a t i v e l y describing the average pulmonary uptake of Ga-67 is easily implemented since it is automatic. Moreover, since the m e t h o d demonstrates s t a t i s t i c a l l y significant differences among distinct groups, it has diagnostic potential.

S176

The monoclonal antibody (MAb) DD-3B6/22 binds with high affinity (>i0-9 M -z) to the D-dimer (DD) epitope of human cross-linked fibrin. A 9gmTc-labelled Fab r conjugate of DD3B6/22 has been evaluated for the detection of vascular thrombi by radioimmunoscintigraphy. The MAb binds well in vitro to clots from human and baboon (PaDio hamadrvas) but not rabbit blood. A rabbit model was thus established by seeding jugular vein clots with sepharose beads conjugated with human DD. DD seeded clots were visualised by scintigraphy 30 min after injection of ggmTc-DD-3B6/22 Fah' with optimal imaging at 4-5h when clot uptake reached 0.304 • 0.106% injected dose/g. No upzake of label was seen in any normal tissue with the exception of kidney and bladder which form the route of excretion. No specific uptake occurred after injection of control MAb or in clots seeded with sepharose without DD. Thrombi were also formed by stasis in the superficial femoral vein of the baboon. Injection of ~Tc-DD-3B6/22 Fah' into animals bearing fresh or aged (up to 12 day) clots resulted in a clear specific image within 2.5 h. The presence of an occlusive thrombus was confirmed by venography. Pharmacokinetic profiles in rabbits and baboons confirmed the rapid excretion of 9~Tc-DD-3B6/22 Fab' from plasma. No BAMA response was demonstrated in 6/6 animals following 1 injection, and only low grade responses were seen in 2/5 baboons following multiple injections of conjugate. The 99mTc-DD-3B6/22 Fab' conjugate appears to have excellent potential for rapid scintigraphic detection of vascular thrombi.

768 SCINTIGRAPHIC IMAGING OF SARCOIDOSIS WITH RADIOLABELED D25

P. Diot, A. LePape, C. Jubault, G. Normier*, H. Binz,*J.L. Baulieu, E. Lemari6 Laboratoire de Biophysique cellulaire, Facult6 de M~decine, 37032 TOURS Cedex- France * Centre d'immunologie et de Biotechnolog[e Pierre Fabre, 74106 St Julien en Genevois - France Macrophages are able to interact both in vitro and in vivo with some bacterial proteoglycans. This property was applied to develop a new scintigraphic strategy using 99m Tc D25 for the imaging of lung granulomas and mediastinal lymph nodes, both observed during sarcdidosis and characterized by a macrophage infiltration. D25 is a well chemically characterized (34 Kda molecular weight) glycolipopeptide isolated from proteoglycans of Klebsiella pneumoniae membranes. When administrated by inhalation, it has been demonstrated to target electively macrophages in vivo. 14 patients were included in this study. 99m Tc labeled D25 was administrated as an aerosol to avoid the hepato-splenic uptake of micella which occurs after intravenous administration. Results were compared to Gallium scintigraphy. In 4 patients with a lymph node enlargement without any pulmonary involvement and in 2 patients with both a lymph node enlargement and a reticulonodular pattern, positive imaging of the hilar nodes were obtained with both D25 and Gallium scintigraphy. 4 patients only had an interstitial injurywithout any mediastinal lymph node. In all these cases, D25 showed an intense and diffuse activity in lungs whereas Gallium scans were subnormal in the same regions of interest. 4 patients were at the pulmonaryfibrose stage. 2 of them had a discrete and diffuse pulmonary fixation wereas the 2 others had no D25 fixation. In this study, all the positive images were observed as soon as 2 hours after inhalation. So D25 scintigraphy, a new technic easy to perform, appears to be efficient for imaging thoracic involvement of sarcdfdosis and could provide functional informations on the activity of the pathology.

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QUANTITATIVE IMAGING~rITH Te-99m-SESTAMIBI (CARDIOLITE) A N D TI-201: A N A P P R O A C H T O OPTIMAL ALGORITI~r FOR BACKGROUND EVALUATIC~.

COMPARATIVE ASSESSMENT OF Tc-99m METHOXY-ISOBUTYL-ISONITRILE (Tc-99m MIBI) and TI-201 IN MYOCARDIAL PERFUSION IMAGING. I. Cas~ns, V. Belloch, L. Insa and J. Ciudad. Nuclear Medicine and Cardiology Departments. Hospital Clfnico Universitario. Valencia. SPAIN.

A. Teresifiska. Institute of Cardiology, Warsaw, Poland. The new interpolative background evaluation algorithm for quantitative planar CARDIOLITE and Ti-201 perfu~on imaging has been proposed (D.D.Wstson, et al. JNuclMed 1988; 29: 955, AfoJ~Sinusas,et aL .TNuclMed 1989;39:1456). PURPOSE: 1 To examine accuracy of tlis new algorithm (NAlg) using compeer-simulated and phantom imagos and to compare the features ofNAI~' with desirable features of optimal algorithm (OptAlg). 2 to support the results of the

exan'~.natlonbyanalysis of clinical data and to assess the ta-iltty ofl~Alg in quantitative CARDIOLITEand T1-201 imaging. RESULTS: 1- and 2-.dir~ computer-simulated images and hantom tests with a locally increased extracardiac activity ExtraAct) . as a part of backgr.oound (Bkg) - overlapI~ng a myocardial wail revealed that: 1 KAIg can cause significant Bkg underestimation close to the Bkg boundary and then some overestimation (beinga function of gee~etrtcal relation of myocardita'n, ExtraAct and Bkgboundary); 2 OptAlg should allow for the range of overlap of the myocardium by ExtraAct. Rest-stress C A R D I O L I T E and stress-redisirtbu~.on TI-201 studle% after Bkg subtraction (NAIE), were analyzed u ~ g clrc~-nferential profiles. 255 segments were assessed in 17 men with coronary artery disease for perfusion defect reversibility or persistence. The segment to segment cc~nc~dence between CARDIOLITE and TI-201 was 76% showing the least v[~]oUe(87%) In the inferior segments in A P view. CCINCLUSIONS: I Analysis of computer-simulated image% phantom da~a and clinicalimages is indicative of low accuracy of NAIg. 2 OptAlg should include some features of NAIg. llke a wide plateau at the level of aver;~ge Bkg and a ral~d fall-off, where fall-offshould beg~n at the edge of ExtraAct, contrary to NAIg where it starts at the Bkgboundary. This compels to seeking an algorithm for automatic detection of the range at overlap of the myocardim-n by high ExtraAct.

There has been performed Te-99m MIBI and TI-201 myocardial perfusion studies in 35 patients referred for chest pain. Twenty-six of them had a coronary angiography. Two doses of 740-925 MBq each of Tc-99m MIBI have been administered at peak exercise and 24-48 h later (rest s t u d y ) . Planar imaging was initiated one hour after inyection. Studies with TI-201 (740 MBq) were obtained fallowing standard planar technique, with similar exercise level. Semiquantitative scores on extent and se verity of disease were obtained from visual a n a l y s i s ( V A T The left ventricle was divided into three segments in each image. Quantitative analysis(QA) was performed by eircunferencial profiles, after interpolative background subtraction. Sensitivity for detection the presence of coronary artery disease was 8 ~ ( V A ) and 92%(QA) for TI201 and 87% with VA and QA for Tc-99m MIBI.: We have obtained significant correlation (p
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772

Left v e n t r i c u l a r wall t h i c k e n i n g m e a s u r e m e n t using Tc99mM I B I a n d G a t e d SPECT: feasibility a n d c o m p a r i s o n w i t h o t h e r

Tc-99m MIBI DIPYRIDAMOLE SPECT STUDY IN PATIENTS WITH SINGLE CORONARY OCCLUSION AND GOOD COLLATERAL FLOW. J. Gr~.qoire, A. Serra, A. Arsenault, D. Gagnon, G. Dupras, R. Bonan, G. CSt~. Montreal Heart Institute, Montreal, QC, Canada.

i m a g i n g t e c h n i q u e s . M. Rubinstein, T. Ibrahim*, P. W a n e t and J. Abramevici. D e p a r t m e n t s of Radioisotopes and Cardiology*, Ixelles Hospital, Brussels, Belgium. High i m a g i n g q u a l i t y of Tc99m-MIBI allows g a t e d SPECT (GSPECT) with potential additionnal d a t a on left ventricle (LV) wall motion (WM). Rest GSPECT w a s performed 1 hour after injection of 900 MBq Tc99m-MIBI in 24 patients. 14 had h i g h p r o b a b i l i t y of CAD (>95%); 11 h a d a b n o r m a l r a d i o n u c l i d e a n g i o g r a p h y (RNA) a n d 12 a b n o r m a l bi-D echocardiography (echo); c o r o n a r y a n g i o g r a m (CA) d i s c l o s e d s e g m e n t a l hypocontractility in 2 w i t h normal RNA and echo. 10 had a low probability of CAD (<5%) and n o r m a l RNA and echo. 16 f r a m e s / c y c l e (64 sq matrix) are acquired on 180 ~ w i t h 30 steps of 50 s. from RAO to LPO. Short and vertical long axis (SA & LA) slices are reconstructed from end-diastolic (ED) and endsystolic (ES) frames. ES and ED LV t h i c k n e s s e s are computed from i n n e r and outer perimeters p r i m a r l y delineated after 30% BG s u b s t r a c t i o n . W a l l t h i c k e n i n g (WT) is t h e difference between ES and ED thickness. Functional images of the absolute WT are g e n e r a t e d from 32 r a d i a l s e g m e n t s for each SA a n d 1 L A slices. 8 p a t i e n t s w i t h n o r m a l RNA a n d echo h a d homogeneous WT; 2 h a d septo-basal lower WT. All p a t i e n t s w i t h r e g i o n a l WM l e s i o n s h a d s p a t i a l l y c o n g r u e n t WT abnormalities. However d y s k i n e s i a could not be d i s t i n g u i s h e d from hypokinesia. WT was diffusely lowered in p a t i e n t s w i t h global hypokinesia. WT was found concordant i n t h e 2 cases w i t h s e g m e n t a l abnormalities demonstrated only on CA. In conclusion, WT m e a s u r e m e n t can be p e r f o r m e d on a routine basis w i t h GSPECT and Tc99m-MIBI. I t seems to be a sensitive p a r a m e t e r of left ventricular function.

Thursday, August 30, 1990

The purpose of this study was to look at myocardial perfusion assessed by ~i'c-methoxy isobutyl isonitrile (MIBI) single photon emission computed tomography (SPECT) in patients with total occlusion of a single coronary artery and good collateral flow to the myocardial area normally served by the occluded artery. Twenty patients with typical angina were included in this study. All patients were treated with laser assisted coronary angioplasty (LACA). Serial SPECT studies were obtained at rest and after dipyridamole infusion (0.56 mg/kg for 4 min) 24 hours prior to and 72 hours after LACA. SPECT acquisition was performed 1 to 2 hours after the MIBI injection using the short protocol (0.4 GBq at rest, 1.0 GBq after dipyridamole). A two-dimensional polar map display was produced and divided in 25 equal sectors. Normalized sectorial uptake was compared to a normal file and values lower than 2 standard deviations were considered abnormal. A MIBI defect score was calculated taking into account defect size and intensity. Mean defect scores (+_SEM) were: Pre.LACA Dipyridamole 5.8+0.9%* Rest 3.4_+0.7% (*p<0.05 vs Rest, p=0.05 vs Post-LACA)

Post.LACA 3,6_+0.7% 3.0+_0.9%

In conclusion, decreased coronary flow reserve following dipyridamole infusion can be seen in a myocardial territory dependent on a occluded coronary artery. Vasodilated collaterals at rest which are unable to increase their blood flow following dipyridamole infusion could explain this phenomenon. Recanalization of the coronary artery appears to restore the coronary flow reserve.

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773

774

EFFECT OF MENTAL STRESS ON POST INFARCTION MYOCARDIAL PERFUSION EVALUATEDBY 99m-Tc MIBI.

TECHNETIUM-99m METHOXYISOBUTYL ISONITRILE IMAGING FOR SIMULTANEOUS ASSESSMENT OF MYOCARDIAL PERFUSION AND VEN'IRICULAR FUNCTION IN CHAGAS'CARDIOMYOPATHY. E. Kuschnir*. H. Sgammini*, R. Castro*, L Camin**. *Hospital Nacional de Clinicas, Cordoba, Republica Argentina. ** Dupont Biomedical Products, M.A.

R Giubbini, M Galli, R Campini, E Bosimini, W Bencivelli, L Tavazzi. Clinica del Lavoro Foundation, Institute of Care and Research, Medical Center of Rehabilitation - Veruno (Novara) Italy. Purpose of this work 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 peffusion 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 MIBt uptake defects in 99/360 segments. 48 of these developed a corresponding reversibleabnormality during MAS. 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 MtBI 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 decreasein absolute uptake of 99m-Tc-MIBI is observed after MAS in the majority of myocardial sites with reversible defects at visual inspection.

The assessment of myocardial perfusion and function is of diagnostic, prognostic and therapeutic importance in Chagas'eardiomyopathy. Thus, we studied the extent of perfusion defect (PD) and EF abnormality with a single radiopharmaceutical, Tc-99m methoxyisobutyl isonitrile (MIBI) in 22 Chagasic patients (pts) (24-64 years old), 11 without (group A) and 11 with cardiomegaly (group B). All pts underwent a bolus injection of 25 mCi MIBI under an Apex 415 Gamma Camera from which a first pass LVEF was calculated. After 90 minutes, three view perfusion images were obtained and divided into three segments (seg) each. Images were visualized by a 3 point system (0=nl, l=moderate, 2=severe PD). Group A pts also had exercise (Ex) MIBI. All pts underwent an Ex redistribution (RDST) T1-201 scan for comparison. Results: In Group A, EF was .58 -+ .06 (mean + SD); 7/11 pts showed a moderate (5 pts) or severe (2 pts) MIBI PD with a mean of 1.4 abnl segs/pt. Ex/rest MIBI scans showed identical patterns in all pts. In Group B, EF was .40 - .15. All pts had reduced MIBI uptake (6/11 with severe PD's), with a mean of 2.3 abnl seds/pt. PD findings by TI-201 were similar to MIBI in both groups. Segment by segment agreement with TI-201 was 89.4%. Conclusions:: 1) Chagasic pts without cardiomegaly have normal LVEF and minor PD's; 2) pts with cardiomegaly have reduced LVEF and severe PD's; 3) MIBI allows a non-invasive, comprehensive assessment of myocardial involvement in Chagas' cardiomyopathy.

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WEIGHTED INTEGRATION METHOD WITH CBV CORRECTION TO ESTIMATE rCBF BY PET. S. Ohta, E. Meyer, A. Gjedde. Positron Imaging Laboratories, Montreal Neurological Institute, Montreal, Canada.

A METHODOLOGY FOR ACQUISITION AND M U L T I M O D A L PROCESSING OF MRI AND SPECT CEREBRAL DATA. P.O. Kotzki, D. Mariano-Goulart, P. Coubes, O. Fajon, M, Rossi, D e p a r t m e n t of n u c l e a r medicine, Lapeyronie Hospital, Montpellier, France.

The methods used to obtain the images of regiona! cerebral blood flow (rCBF) rely on the assumption that the blood radioactivity component of measured PET data is negligible. The table shows CBF values estimated using the data from whole brain by several methods with or without a term ]7o for CBV correction. C B F ( m l h g - I min - I ) Normocapnia Hypocapnia

A full methodology is p r e s e n t e d for p e r f o r m i n g a standardized acquisition of brain tomographic images using single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). This requires three steps : - The use of a stereotaetic headholder and a spatial system of reference filled with apropriate contrast agent and coupled together to allow the r e c o r d i n g of the same tomographic sections using various imaging apparatus. - The simultaneous acquisition of s t a n d a r d i z e d references for the tomographic planes. - A computerized multimodal p r o c e s s i n g including : The transfer of the data on to an IBM PS/2 computer and conversion into MS-DOS standard. An interpolation software using Cubic B-Splines as basis functions for the interpolation. An algorithm for the alignment of images based on intercorrelation techniques. An algorithm for the multimodal analysis of functionnal and m o r p h o l o g i c a l images based on orthogonal factorial analysis. P e r f o r m i n g multi MRI acquisitions, it has been experimentally checked that the readjusment of the headholder between two sequences does not affect the parallelism and the r e p r o d u c i b i l i t y of the r e c o r d e d sections. In this condition, the m e t h o d o l o g y have been successfully tested over a p o p u l a t i o n of 15 patients with epilepsy secondary to structural lesions.

no CBV correction (n:4) (n:4) St Louis ( i rain) 55.9 3- 4.2 36.1 3- 2.0 Autoradiographic ( I min) 57.1 4- 4.3 36.8 J_ 2.1 2-weighted ( I and t) (3 rain) 54.6 3- 4.4 36.4 3- 1.8 CBV correction Fitting with Vo (3 min) 39.5 3- 3.3 28.8 3- 0.6 3-weighted (14 and v~) (3 min) 37.8 3- 3.2 27.9 • 0.4 There are significant differences between the values calculated by the methods with and without Vo (p<0.05) and a significant correlation between the values of non-linear least squares fitting with Vo and the 3-weighted method, expanded to include a term of Vo (r=0.998, n=8). This result indicates that the methods which ignore the blood-borne radioactivity may overestimate rCBF in some regions. The 3-weighted integration method, improved to prevent this error, is a computationally efficient approach to a statistically optimal estimation of rCBF.

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August30,1990

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778

INITIAL EXPERIENCE WITH THREE-DIMENSIONAL SURFACE DISPLAY IN BRAIN IMAGING IN PATIENTS WITH CEREBROVASCULAR DISEASES : COMPARISON WITH XCT AND SPECT IMAGES. J. Ishimura, M. Kawanaka, M. Suehiro, K. Tachibana, and M. Fukuchi. Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

THREE DImeNSIONAL QUANTITATIVE ANALYSIS OF CEREBRAL PERFUSION FROM HMPAO SPECT IMAGES: NORMAL AND PATHOPHYSIOLOGICAL DATA. A.J. McEwan, H.R. Hooper, T. Kotchon, P. McTeer, and P.M. Hooper *. Cross Cancer Institute and *University of Alberta, Edmonton, Alberta, Canada.

This study reports our initial experience of the clinical application of three-dimensional surface display (3DSD) in brain imaging with Tc-99m HM-PAO. Twenty-two patients with cerebrovasucular diseases (mean age i SD = 59 • ii) were entered in this study. All patient's X-ray computed tomography (XCT) showed low density area (LDA) in the cerebral hemisphere associated with their neurologic deficits. Twenty mCi (740 MBq) of Tc-99m HM-PAO was given intravenously, and 15 minutes later data were obtained at 64 projections in 360 degrees with 30 seconds per projecion. The SPECT images were reconstructed by the filtered backprojection method with the attenuation correction. The brain surface image was made from the isocount outlines of the SPECT images. The threshold of the isocount was 45% of the maximum count of the global pixels. The 3DSD was made from the surface image using the distance-shaded method. When necessary, the 3DSD without the upper structure was made by setting the unwanted data of the upper images to zero. 3DSD showed perfusion defects in all 13 patients with LDA extended to the cerebral cortex. In 6 of 9 patients with LDA around the basal ganglia only, perfusion defects were detected by 3DSD without the upper structure. In the remaining 3 patients without abnormal findings in 3DSD, it was difficult to reveal defects in SPECT images. This study shows that 3DSD is useful for evaluations of cortical defects stereoscopically and 3DSD without the upper structure is effectual to demonstrate inner defects of the brain.

A three dimensional interactive brain fitting programme has been developed to derive semiquantitative data from cerebral perfusion imaging using HMPAO SPECT. Seven regions are defined bilaterally and data derived from regional activity is expressed both as a percent of total cerebral activity and as a percent of cerebellar activity. To define normal ranges for cerebral perfussion this programme has been used to analyse data from 136 healthy volunteers drawn from a long term normal memory project. The volunteers were aged 35 - 85 years. The studies were independently analysed by four operators, and the data analysed using univariate and multivariate analysis. Using this data it is possible to define variations of cerebral perfusion patterns with age. A group of 13 patients with Alzheimers disease was also studied using this technique. This group was shown to have significant underperfusion of the temporal and parietal lobes (p < 0.01). We believe that quantitative analysis of NMPAO SPECT provides relevant data for a normal database and for pathophysiological diagnosis.

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QUANTIFICATION OF CEREBRAL BLOOD FLOW(CBF) USING Tc-99m HMPAO AND DYNAMIC SPECT. K.Murase, S.Tanada, K.Ochi, Y.Kimura, S.Sakaki, and K.Hamamoto. Ehime University Hospital, Ehime, Japan.

Tc-99m HMPAO BRAIN SPECr-TRANSCRANIAL DOPPLER (TCD):

The purpose of this study was to develop a kinetic model for quantitating CBF using Tc-99m HMPAO and dynamic SPECT, and to investigate its validity. The kinetic model consisted of 4 compartments with 5 parameters, i.e. the rate constants for the transport of the diffusible tracer from blood to brain(Kl),back diffusion from brain to blood(K2), conversion of the lipophilic tracer to a hydrophilic one in the brain(K3), conversion of the diffusible tracer to a non-diffusible one in the blood(KS), and the fraction of radioactivity attributable to the vascular compartment(fa). To estimate these parameters, the model equation was fitted to the time course data of brain activity using the nonlinear least-squares method. Following i.v. injection of 25 mCi of HMPAO, serial 40 sec SPECT scans were performed for about 20 min using a 4-head SPECT scanner. Simultaneously, arterial blood samples were obtained and the values were corrected for radiochemical purity, determined by thin layer chromatography, to obtain the input function. Prior to the HMPA0 study, CBF was measured by Xe-133(Xe-CBF). The calculated values for KI,K2, K3,KS, and fa ranged between 0.1-0.4 ml/g/min, 0.2-0.8/ min, 0.3-0.7/min, 0.06-0.1/min, and 0.01-0.08, respectively. A significant correlation was observed between K1 and K2(r=0.82). While K1 correlated well with Xe-CBF (r=0.92,n=82), K1 was underestimated(y=0.64x+0.03),suggesting that the extraction fraction(E) was considerably lower than unity. When calculating CBF from the relation KI=E'CBF, using Andersen's equation(J CBF Metab, p.$44,1989) for E, CBF by HMPAO agreed well with Xe-CBF (y=l.03x-0.02,r:0.92). These results suggest that quantification of CBF using HMPAO is possible using our kinetic model coupled with the correction for E.

Thursday, August 30, 1990

A NEW APPROACH FOR EVALUATION OF CEREBRAL PERFUSION IN CAROTID OCCLUSIVE DISEASE. M,~,T~ni, L. Fiori, G. Parenti, F. Marconi, C. De Gaudio, N.Molea. University of Pisa,ltaly. After carotid occlusion, collateral circulation is not always able to assure a normal cerebral perfusion with consequent chronical cellular impairment and greater risk of ischemia after embolic event. For compensatory system efficiency assesment and revascularization surgery(RS)selecting pts,we studied 127pts with carotid occlusion by CW doppler,TCD and CT scan. 33 pts underwent SPECT study as well,and were divided into two groups, in accordance with presence (G. l)or not (G.2)of a CT ischemic lesion.ln Ii of G.I-17 pts with TCD Vm simmetry on MCA,SPECT emphasized an hypoperfusional area corresponding to CT lesion, and clinical deficit was generally transitory.On the contrary,in 6 pts with TCD significant Vm asimmetry for a reduction of Vm on MCA ipsilateral to ICA occlusion(MCAi)and evi dent SPECT hypoperfusional area, stroke was the most frequent event. In G. 2 ( 16 pts) 3 different perfusional conditions were identified:(A)(4 pts) TCD Vm simmetry and negative SPEC~;(B)(8 pts)TCD Vm reduction on MCAi but no significant and/or no corresponding SPECT hypoperusional areas.Therefore in(A) no perfusional abnormalities can be identified, while they are visualized in (B);multiple angiographic lesions could be responsible for(C)perfusional states.Two(B) pts were submitted to RS and studied again after surgery.Brain SPECT and TCD may be promising techniques to identify haemodinamic situations not detectable by angiognaphy, and we stress their combined use for selecting pts for surgical treatment

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PULMONARY A N D INTESTINAL PERMEABIL1TIES IN CROHN'S DISEASE P. LECOUFFE, H. VENEL, D. HUOLO, J.-F. COLOMBEL, B. WALLAERT, X. MARCHANDISE Service Associ4 de Mddccine Nucl6air~, Clinique des Maladies de l'AppareiI Dignstif, Ddpartament de Pneumologie - C H U de Lille - FRANCE

QUANTITATION OF SCINTIGRAPHIC IMAGES IN CROHN'S DISEASE AND CORRELATION WITH CLINICAL AND LABORATORY INDICES W.Tindale. M.Giaffar, D.Barber, S.Senior, C.Holdsworth. Royal Hallamshire Hospital, Sheffield, UK.

A latent involvement of the lung is frequently described in patients with Crohn's disease (CD). Moreover intestinal epithelial permeability (IP) is known to be increased in CD. "me aim of this study was to evaluate both pulmonary epithelial (PP) and IP in CD. METHODS : We studied 17 patients (age 18-50) with CD. 7 and 5 patients with active CD had second evaluation of IP and PP rexpeetively when CD was quiescent. Healthy volunteers (age 21-45) acted ~is controls. Patients and volunteers were non-smokers, had no pulmonary symptoms and did not intake alcohol before IP test. PP was assessed using a DTPA-99mTc aerosol ( 0 . 8 ) . After 2 rain breathing in supine position, 60 s frames were acquired for 20 rain. T 1/2 (rain) were obtained from exponential fitting over the first 10 rain of pulmonary clearance cur*es (whole lung, apex, middle, base). IP was COncurrently evaluated from 2A h 51 urinary excretion of Cr-EDTA expressed as a percentage of the total oral dose.

R~SULTS :Mainresultsareexpressedasmean +/-s.d. Controls (n = 13).

Active C'D (n = 13)

T 1/2 whole lung

57.2 + / - ~ = 2

CD (n = 17) "

82.6 +/-24.3

"'

51.8 +/-39.4

T 1/2 apex

40.8 +/-16.6

""

63.1 +/-22.2

"*

32.2 +/-15.8

"*

45.3+/-24.1

"*

9.4+/-6.4

N.S. T 1/2 base % EDTA-51Cr

N,S.

56.6+/-40.4

**

75+/-6.3

""

N.S.

81.6+/-24.2 2.0+/-1.3

9 : p < 0.05

*" : p < 0.01 (Wilcoxon test)

T 1/2 was not significantly different in patients as CD was active or quiescent. The difference between 51Cr-EDTA excretions in active and quiescent CD was significant (p < 0.05). No ton'elation was found between IP and PP.

CONCLUSIONS :Our resultsconfirmincreasedIF inCD withinfluenceofdiseaseactivity and at first ~',~al a diffuselyincreasedpp inCD withoutanyobviousinfluenceofdisease activity.Itwouldbe ofhighinterestinCD phy~iopathology(commonmucosaldefect)and PP hastobc concurrentlyinvestigated withothersl~ngparameters.

We have developed a computer based method of image analysis for the quantitation of abnormal bowel uptake of Tc-99m hexamethyl propylene amine oxime (HMPAO) labelled leucocytes.The method involves the generation of a 'normal' or background image which contains only bone marrow, liver and spleen activity. Any patient image can be considered to be composed of this normal image on which abnormal gut uptake is superimposed. Scaling and subtraction techniques are applied, yielding a scan score (SS) which is a function of the activity and extent of disease. SS was raised (mean I03~22) in 21 patients with clinically active Crohn's disease as compared with (20~6) in 13 patients with inactive disease. A significant correlation was found between SS and Crohn's Disease Activity Index (rs 0.6,p 0.002) and between SS and Harvey & Bradshaw Simple Index (rs 0.4, p 0.001). Of the laboratory measurements, SS correlated with haemoglobin level Its 0.7, p 0.003), albumin level [rs -0.7, p 0.001), C-reactive protein (rs 0.7, p 0.001) and alpha-l-acid glycoprotein (rs 0.6 p 0.01). SS did not correlate with erythrocyte sedimentation rate (rs 0.2, p 0.7) or platelet count (rs 0.2, p 0.5). The results of this study demonstrate that computerised quantitation of bowel uptake of tracer provides an objective measure of disease activity which correlates with clinical and laboratory indices of Crohn's disease.

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In- 11 I-OXINE LEUKOCYTES AND Tc- 99mNONOCLONAL ANTIBODY BW 2501183.DUAL TRACER STUDY IN INFLAMMATORY BOWEL DISEASE J. Martin-Cumin; N. Roca; H.I. Segarra; C. Baliellas'; Y. Ricart; R. Puchal; J. Nora; L. Casais* y M, Ramos. Serveis de Medicina Nuclear i Gastroenterologia'. Hospital Universitari de Bellvitge. Barcelona. Spain.

99mTc-'HmPAO GRANULC,:]YTE'5 AND ~.CIWEL D]:'3EASES. *S. P.lc~loni+ *V. Frusc~ante, A. Mangia, A. G a b b r i e l l i . *F. Barbano, *G.Petr'acca Ciavare'l]a. *Perrorle [. Depts. o f *t.~uclear Medicine and ,Sastroenterr Gerler'a] Hospita] "CASA SOLLIEVO de]'la SOFFERENZA", S, gh)vallni Rotondo (Fg), I t a l { a

30 patients with suspiction of inflammatory bowel disease (IBD) have been studied (14 males), mean age 37 -+ 19 years. Patient autologous leukocytes were labelled with 588 uCi of ~tIn-oxine (IN) and reinjected simultaneously with 8.33-i mg of MoAb BW 258/183 labelled with 15-28 mOi of ~g=Tc (MoAb). Abdomen scans were obtained at 3-4 h (ES) and 18-24 h (LS) postreinjection. The liver (L), spleen (S) and bone marrow (BN)/background (Bek) activity ratios were calculated. The diagnosis was based on clinical, endoscopic and sometimes radiological data. RESULTS : Table I : Ratios of activity ~ ~In- oxine ~ g=Tc-NoAb L/Bck S/Bck BN/Bck L/Bck S/Bck BN/Bck 4h 5.3-+1,6 12.6-+5.9 3.4-+1.4 5.8-+2.3 7.2-+4.4 5.6-+2.8 24h 7.9-+2.6 18.7-+8.9 3.2-+1.6 4.1+I.3 5.3-+3.8 4.1-+I.3 Table 2 : Scintiqraphic diaqnosis Disease 1 ~~In-oxine ~ ~=Tc-NoAb ES LS ES LS Total + § + + Yes 16 14 2 16 @ 9 7 14 2 Not 14 0 14 @ 14 0 14 1 13

In the "last three year's we w~de]y used the .:jranu]ocytes label 1ing technique by 99mTc-HmPAO, pr'oposed by Peters and coworkers (The L.ancet, Octobei '25, 1986), for' a new scirlt~gr'aphic approach 'to the study of bowe'l di'seases as Cr'ohn's enteritis and ulcerative colitis. Eighty-three patients (35 a f f e c t e d by Cr'ohnls e n t e r ' { t i s and ~8 by u]cer'ati've c o ' l f t ~ s ) were studied by t h i s s c i n t i g r a p h f c method and, in 57 oi= them, endoscopy arid consequent b~opsy were a] so perfo~ mad, w h i l e i n the others i t was not f e a s i b l e f o r f e a r of i n t e s t i n a l wall per f o r a t ~on. Glal/L~locyte separ'ation and l'abell i n g was performed in accordance w i t h the Harre~rsm~th pro'tocol. I ~ g i n g was car'r'ied out a t 30 rain. and 3 h r s . , a f t e r the ] a b e ] ] e d c e ] i s r'e~njection, by acqu~rinq~ a two m'~llion counts images. Latter' in,ages are I~Ot useful because of b i ] i a r ' y rad~ophamaceutica] excr'etion and mueosa] gr'anu]ocvtes e x u d a t i o n i n t o ttle bowel lumen. Better' images were c6tained i f the examination was performed in acute diseases without influence of steroid therapy. Mean l a b e l l i n g efficiency was of #3%, w i t h no s~gnific:ant in v i t r o ce'lls modif'ication~ and in vi'vo ]ast{llcj pu]rllOllar'y r e t e n t i o n . I n a l l the p a t i e n t s checked a'lso by the endoscopy we found a good c o r r ' e l a t i o r l w i t h s c i n t i g r ' a p h i c results r'egard t o disease e x t e n t i o n and h i s t o l o g l c a ] aspects.

Overall agreement between both methods was observed in 142 out of the 150 bowel segments analysed, 94.6 ~. In summary, though slightly less sensitive than ~XllIn-oxine, the BW 250/183 seems quite accurate and represents a valid option for a quick and aseptic labelling without blood manipulation and may be used in the management of IBD patients.

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AUTOLOGOUS TC-99a-LEUCOCYTESCIN]IGR~PHiIN F'AIIE~S ~ITH HI6~ ORLOWPRODABkITYOF INTESTINALINFLAmmATION,

Tc-99m-LABELED LEUKOCYTES IN ACUTE CHOLECYSTITIS. M. V o r n e , I. T a l v i t i e , R. L a i t i n e n . P~ij~t~ t r a l Hospital, Lahti, Finland.

N Salon. PR6ibe0n, MLlcbtenstein, JT Andrews. G Hebbarb,. Departments of Nuclear Medic:ne and Medic:he , The Royal Melbourne Hospital, Victoria, Australia. Auteiogous Tc-gge-ieucotvtescintigraonvis cansioeredto glve accurate localizat:onand a sem:-puancat:ve~u1~e to the activity of intestinal inflammation:n eatientswitP inflammatory bowel disease (IBb~. Out the value in ecreenina low-risk patiente for led has not been evaluated. AIMS: To examine the ~redicttve vaiue of positive studlee in the dection of inteetine] inflammationin patientswlth high and low probability of IBO. NETHOOS: 2g patients with a h~gh probability (previouslydocumented ISD) anp 58 witN aiow probabiiity of intest:nalinflammationwere studies. Autsiogeus leucocytes were labeiled usinb stannous colloid (iabellin9 e~fitiency > 95%) In 54, HMPAU in 29. beth aeouentiaJlv in 4. Studies were interpretedby one observer dhnded to toe chnical data. RESULTS: in natient~ with IBD. 4 posit:yes (14~) were falsely positive, in low orobab]litvpatients, all oos~ve studies (%i58, 44%) were ~aiseiv positive. Faise-positivee were therefore more common in iOW orobaPihtv than bIOh orobab~1ity groups (P=O.Oll,cni-sauarei, toe ~aise-~ositivitv rate (colloid 38% vs HMPAO30X) was inoenendent of the aetno~ of cell labelling ueeO. Seouential coiioid and HMPAOs~u~les in 4 patients yielded identicalresu|ts~hzie 3 oatients with false-positive studies had normai In-Ill-leucocyte acintidraphv. CONCLUSIONS:Appearanceof lc-99m in ~leum or colon occurs commonly in the absenceof intest:nai in61ameat~on anP cannot be reliably dishnquisheo from that assoc~ateo with inflammation, thus, Tc-99m-leucocvte scans are of no value :n screeninq for IBD and are o~ ~uestionabievalue ~n the assessmentof patientswith iDO.

The purpose of this study was to evaluate the effectiveness of Tc-99m-HMPA0-1abeled leukocytes in the detection of acute cholecystitis. Twenty-five patients with suspected cholecystitis were imaged with a gamma camera at 0.5, 2-3 and 4-6 hours following administration of labeled leukocytes. Abnormal gallbladder activity was found in 15 patients, and in 30 patients leukocyte imaging was negative. Serum C-reactive protein level (CRP) and blood leukocyte count (leuk) were higher in patients with a positive scintigram (CRP: median 110 mg/ml; leuk: median 11.1"109/1) than in negative cases (CRP: median 34 mg/ml; leuk; median 7.9"109/1). Ten of the positive and 4 of the negative cases were operated within 10 d a y s . Acute cholecystitis was found in 8 patients, and chronic cholecystitis in 2 patients with a positive scintigram; chronic cholecystitis was found in all 4 patients with a negative scintigram. In both cases of chronic inflammation and a positive scintigram the gallbladder was filled with pus. These preliminary results suggest that imaging with Tc-99m-HMPAO-labeled leukocytes can be useful in the detection of acute cholecystitis, especially when ultrasonography and other clinical findings are contradictory.

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CLINICAL STUDY OF 1-123 IMP PULMONARY IMAGING IN PEDIATRIC PULMONARY DISEASE M. Umeh@ra, M. Yotsukura, K. Minoura, N. WATANABE, H. Nakajima, S. Horiike, and K. Ishii. Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.

99mTc-HmPAO GRANULOCYTES AND BOWEL DISEASES. *S. Modoni, *V. Fr'usciante, A. Mangia, A. Gabbr'ielli, *F. Barl)ano, *G.Petr'acca Ciavaf'ella, *Perrone E. Depts. of *Nuclear' Medicine and Gastr'oenterology Goner'el Hospital "CASA SOLLIEVO d e lla SOFFERENZA", S. Giovanni Rotondo (Fg), I t a l i a

1-i23 IMP has been used for diagnosis and clinical of neurologic disease, however, high uptake of it by the lung is recognized during the first pass through pulmomary circulation. We studied clinical usefullness of 1-123 IMP pulmonary imaging in children with various puimonary disease. [PATIENTS A N D M E T H O D ] 1-123 IMP lung scans were p e r f o r m e d in 12 c h i l d r e n w i t h p u l m o n a r y disease; 3 b r o n c h i e c t a s i s , 3 bronchial asthma,l hypersensitivity pneumonitis, pulmonary alveolar proteinosis, rt-pulmonary artery agenesis, Werdnig Hoffmann disease, eosinophilic pneumonia, pulmonary embolism respectively and IO children with non-pulmonary disease. After a bolus injection of I3 mci 1-123 IMP via a cubital vein, dynamic imagings were obtained while on supine at I frame/sec for 90 sec, i frame/3Osec for 30mins, and static imagings were obtained at 2hr, 3hr, 4hr. [RESULTS] l)Wash-in phase was delayed in patients with pulmonary disease than in normal subjects. 2)The half time(Tl/2) of 1-123 IMP was prolonged, especially in diffuse lung disease. 3)Changes of TI/2 were useful i n d i c a t o r s for the f o l l o w up of c l i n i c a l slate in hypersensitivity pneumonitis. 4)Abnormal accumulation in d e l a y e d images was d e t e c t e d in localized p u l m o n a r y lesions. [CONCLUSION] Theses findings suggest that 1-123 IMP lung scan is a useful method for the evaluation of pediatric patients who are not cooperative and difficult to evaluate their pulmonary function by other tests. evaluation

Thursday, August 30, 1990

In the last three years we widely u s e d the 9r'anulocytes l a b e l l i n g technique by 99mTc-HmPAO~ proposed by Peters and coworkers (The Lancet, October' 25, 1986), f o r a new scintigr'aphic approach to the study of bowel diseases as Crohn~s e n t e r i t i s and ulcerative c o l i t i s . Eighty-three patients (35 affected by Cr'ohn's e n t e r i t i s and ~8 by u lce ra t ive c o l i t i s ) were studied by t h i s scintigraphic method and, in 57 of them, endoscopy and consequent biopsy w e r e also perfor.med, while in the others i t was not f e a sib le for" fear' of i n t e s t i n a l wall perforation. Granulocyte separation end l'abelling was performed in accordance with the HanYnersm~th pr'otccol. Imaging was carried out at 30 men. and 3 h rs. , a f t e r the labelled c e l l s r e i n j e c t i o n , by acquiring a tw~ million counts images.

Latter'

images

are not useful

because of b i l i a r y radiophamaceutical excretion and mucosal granulocytes exudation i n t o the bowel lumen. Better images were obtained i f the examination was performed in acute diseases without influence of steroid therapy. Mean l a b e l l i n g efficiency was of ~9%, with no significant in vitro cells lasting pulmonary retention,

modifications

In a l l the patients checked

and in vivo

also

by the endoscopy r e s u l ts regard t o disease extention and h i s t o l o g i c a l aspects..

we found a good correlation with scintCgraphic

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T H A L L I U M B E Y O N D T H E HEART: A PEDIATRIC EXPERIENCE. H. R. N a d e l , K. J. P o s k i t t , C. O. F l o d m a r k , British Columbia's Children's Hospital, Vancouver, British C o l u m b i a , Canada.

VALUE OF 131-I-MIBG 8CINTIGRAPHY IN DIAGNOSIS,STAGING AND FOLLOW-UP OF NEUROBLASTOMA8 T. C. Ferreira, A. Nogueira, L. Salgado, M. R. Vieira Department of Nuclear Medieine,Instituto Portugugs de Oncologia de Lisboa,Lisboa,Portugal

We evaluated T I - 2 0 1 u p t a k e o n 41 brain single photon emission CT s c a n s or whole-body scintigrams in 25 c h i l d r e n with possible malignancy. Pathology included central nervous system malignancy (n=8), b o n e t u m o r s (n=7), lymphoma or soft tissue tumors (n=9), a n d c a t s c r a t c h f e v e r (n=l). Osteosarcomas (n=4) a n d e x t r e m i t y Ewing sarcoma (n=l) h a d c o n c o r d a n t thallium and bone scans at diagnosis with negative thallium scans following chemotherapy, correlating with tumor n e c r o s i s at p a t h o l o g y . I n c o n c l u s i v e or negative TI-201 uptake occurred in pelvic Ewing sarcoma (n=2), m e t a s t a t i c choriocarcinoma (n=l), C N S m a l i g n a n c y (n=5), a n d c a t s c r a t c h f e v e r (n=l). Recurrent CNS tumors (n=3) s h o w e d concordant thallium and CT studies. Chest lymphoma and soft tissue tumors (n=9) h a d c o n c o r d a n t thallium and g a l l i u m s c a n s in 7 c h i l d r e n . T I - 2 0 1 is p r o v i n g u s e f u l in c h i l d h o o d osteogenic sarcoma, extremity Ewing s a r c o m a a n d in c h e s t l y m p h o m a / s o f t tissue tumor for monitoring efficacy of chemotherapy and distinguishing residual or r e c u r r e n t tumor from non-tumorous conditions.

Patient survival and therapeutic strategy for treatment of neuroblastoma is highly dependent on the stage of the tumour.We performed 63 studies in 41 patients(pts) with suspected or proved disease.19 pts were males and 22 females.The pts were aged 4,7y(im-16y).13 pts 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 GC GE4OOT coupled to a 8tarII computer:static images of 600s using a 128x128 matrix.When necessary bone,kidney and hepatosplenic area were acquired using 99m-To labeled products.gPECT was used as well. We found 25 sudies normal corresponding to 17 remissions and 8 pathologies other than neuroblastoma.38 studies were abnormal :18 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 10:lymph node involvement in 3,bone metastases in 3 and bone marrow involvement is 4. These results show the importance of 131-I-MIBG scintigraphy in initial and differential diagnosis,staging and evaluation of the response to therapy.

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I. Roca, S. Aguade, L. Marques, J. Botey, X. Pavia, G. Moragas, S. Mane, F. Porta, F. M. DomenechTome.

18 GLOBAL VENTRICULAR FUNCTION ABNORMAL IN MYOPERICARDITIS OF INFANCY AND CHILDHOOD? R.A. Hurwitzm A. Siddiqui, H. Wellman, Indiana University, Indianapolis, Indiana. USA

ESOPHAGEAL SCINTIGRAPHY IN CHILDREN WITH ASTHMA.

This study evaluated ventricular systolic performance and its relationship to diagnostic and prognostic significance in 21 infants and children with myopericarditis. Pts were 0.1-14 yrs (median, 3 yrs) at presentation. Right ventricular ejection fraction (RVEF) was estimated by first pass radionuclide anglocardiography and left ventricular ejection fraction (LVEF) was estimated by equilibrium ventriculography. The initial RVEF of 0.50 + 0.13 was not statistically different from our normal (0.54 + 0.06), but differed from the RVEF of 0.36 + 0.15 (p<-O.O05) of pediatric patients who presented with dilated cardiomyopathy during the same period. Though RVEF weakly correlated with LVEF (r=0.55), the RVEF was normal in 68% of myocarditis pts and was n e v e r < 0 . 3 0 . At follow up, RVEF increased to 0.54 + 14. Initial LVEF was abnormal in ii pts; group LVEF of 0.43 + 0.19 differed from our normal of 0.68 + 0.09 (p
Abstract received in a form unsuitable for reproduction

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THREE DIMENSIONAL REGIONS OF INTEREST IN ISOMETRIC RECONSTRUCTEDS.P.E.C.T. DATA. Michael L. Goris, Stanford U n i v e r s i t y School o f Medicine, Stanford, CA, USA

THE QUANTIFICATION OF PLANAR SCINTIGRAPHY USING THREE DIMENSIONAL MODELLING OF ORGAN SHADOWS, Michael L. Goris, Stanford U n i v e r s i t y School o f Medicine, Stanford, CA, USA.

Reconstructed S.P.E.C.T. data can be considered as isometric mapping of three dimensional d i s t r i b u t i o n s in a three dimensional matrix. Yet most tools f o r the q u a n t i t a t i v e analysis o f s c i n t i g r a p h i c data are geared towards planar (two dimensional) data, with the consequence t h a t S.P.E.C.T. data are analyzed as stacks o f 2-D images. We propose a system o f q u a n t i t a t i o n based on sampling within the i n t e r s e c t i o n o f three ortogonal ROl's drawn on XY, YZ, XZ cuts or p r o j e c t i o n s respectively. The t h e o r e t i c a l variance of t h i s i n t e r s e c t i o n volume from the intended volume can e a s i l y be determined f o r simple geometric forms, but in practice the integrated count values f o r organs ( l i v e r , spleen, heart) were r e l a t e d by the i d e n t i t y r e l a t i o n to those obtained from cumulative s l i c e a n a l y s i s , with a standard e r r o r o f the estimate o f 20%. The e r r o r , however, is mainly r e l a t e d to v a r i a b i l i t y in border definition. Furthermore, the i n t e r s e c t i o n method had the advantage of a higher coherence between s l i c e s since they are defined on the basis o f 3-D representations. We conclude t h a t the i n t e r s e c t i o n method is a viable a l t e r n a t i v e f o r 3-D ROl's.

A method to define b i o d i s t r i b u t i o n from planar s c i n t i g r a p h i c data is presented. Sampling regions or regions o f i n t e r e s t (ROls) are f i r s t defined as the p r o j e c t i o n contour of organs. From anatomical knowledge the three dimensional volume of the organ whose shadow has been traced is reconstructed. When the r el ev a n t organ volumes, including the whole body or relevant whole body p a r t , have been defined, the count rate density in each pixel is assumed to represent the sum of the product o f the p r o j e c t i n g organ p a r t i a l volumes times the t r a c e r concentrations in the underlying organs. The s o l u t i o n (the d e f i n i t i o n o f organ concent r a t i o n s ) is found by a matrix conversion. Validation is obtained in two ways. The f i r s t method is i l l u s t r a t i v e : an image is reconstructed from the defined volumes modulated by the computed concent r a t i o n s . This image, i f the method i s c o r r e c t , should be a crisp equivalent o f the o r i g i n a l data, and c l o s e l y s i m i l a r to i t f o l l o w i n g b l u r r i n g with a convolution kernel equal to the imaging system's point spread function. The second is a n a l y t i c a l : from reconstructed S.P.E.C.T. data, in which voxel values are d i r e c t l y proportional to organ concentrations, a planar image is reconstructed. Organ average voxel values are computed in the S.P.E.C.T. image with volumetric ROl's and in the reprojected planar image using the method described here. The methods should y i e l d the same concentration data, but f o r a scaling f a c t o r . The method has the advantage t h a t i t y i e l d s volumetric and concentration data which are d i r e c t l y applicable to MIRD type analysis.

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QUANT]TATIVE ANALY-'SIS OF MY(~.]A~)IAi, Pk'i~l.'UgJON ~]-CANS WiTH 3 i) I)I'API~Y. R.[, E i s n e r , A.S. >i,ye.rs, T . S . (]hu, J. Oar,~s, B. ( ~ r i ~ n , E . g . Pal-t~)'~on. {k~r]yle Fr.:latT ! M i v , ]~e~!• o:f

INTERACtiVE THREE-DIMENSIONAL VOLUME PERSPECTIVE IMAGE DISPLAYS OF INTERNAL ORGAN ACTIVITY CONCENTRATIONS AND OF MYOCARDIAL GATEO SPECT. J.R. Halama, R.H. Wagner, and R.E. Henkin. Loyola University of Chicago, Maywood, IL, USA.

Me~ih.'ine ((~ttxiioJ) alld }~di(;]o0~,, E{JSM, A t l a n t ~ , DigiD_{i De.sig]l Co.rp, Norcross. GA.

GA;

We~ h a v e d e v e i o m e d a p r ~ e s s i n g and 3 D d i s p i a y p r o F,ram f o r q u J _ m L i ~ t i v e a n a l y s i s o f tx)l,h ~Pl,,~;[' TI 2(}t and [{1' 3(I my*.xm)~]]:/] Derf1~sioh ~<:a*]~. TF~ softa4ar~.-P~lx~nd~'; }Afll's eye software p a ( ~ m m . Following aaUx~{J(: sel6etion of apical and hasa] s.[iee,s, endc~ard'lal (END()) and e p i o a r d i a l (Flq) edge_q are. determineJ ~s.i1~*, an automatic edge deflection a l g o r i t h m a p p [ i ( ~ t lx~ arr,TW'.~ determlnexl by (xmvertlng tk,ze [{Pk~;I'six)r% dKiS sJ i(.~q (~AA) from rex~.tan~alar U> l~>]ar c ~ x ) m i i n a t e s . -MaximJm (x)~mt pixels b~.t~,~,m ~]NL~]~*(t EPI as we]]. as %J~e.a v e r ~*,e rad:i~n~ (RI]AR) were det*]rmin(~i. Crii~;ria defin~l a[~tormaJ (atxzl) pixels at a f:,rivea]numl~.r of sta[~da~x] deviat.iozkq [SI)) [~x~[(y,~t.f~ me~r, norms], value.'; normal. ( r d ) p i x e l s had ~ ) a b o v e U f i s v ~ u e . D i s t i n c ! , at~tl r e g i o n s wewe. i d e n t , i f ic~d w i t k a " d e f ~ t - z o n e " c:J.u:sDet" f i h d ~ n g aLgori.ia~m. [ ~ . ' f ~ . t s e v e r i t y was dei.h~e~i &~, i.t~ a v e r a g e , number o [ 'gD i n a t m l re4,do*m, l ~ f c i : t exUea~t i s d e t e r m i n e d f r o m atXql zone and l{li%R f i l e s and cx stress t~J rest (RI'-30) a~uI &Rut Ix> nl ratios cxm~q~x] tx> &s.~ss redJstr:ih~t:io~ (TL 201 ) or e}~mmge (RP 30). To cirr~amvent %he, size and s}~ll~; d[stx)rtions s in c~nw~ntional 2.-0 Paal]"s-eye display.,: t,}~',cxx~nt aFr,-a~S al~9 pFojex2.~~gd ()rll~,a 3-l) r~)(Jel o f th(e ~P~.E~rL. [):ist,~]~et ab~t ~.gioru~ 'are. (~xi(~] on the. 3-]) i m a g e w l t h different (]o]ore.~d rwer]ay.q. '1'}~-. ~ 3 i) datm ar~ pp-.sen c~amic fo~t where:., mr~mh)r, {n a]] I.V wall:: is o~,',]y ~qsessed. WritAz#n 9n C ux*(le.rt2.e UNIX oi:.~r:~ tir~ system f~e. p~)gram ~s ~-as~d c] inh~a[ ly and in <~r all~]nal re,.se~r<}l.

Thursday, August 30,1990

Three-dimensional volume (3DV) images are generated by forward projection, after distance weighting (DW), of the highest count densities at all viewing angles of the SPECT image set. This method is useful as it preserves organ activity concentrations. To reveal internal organ activity the 3DV method can be modified to remove the front surface by multiplying the DW function by a step function shifted to a desired depth. Previously masked internal high count structures, and low count regions that appear as indentations in the cutaway view, are observed. Caudate nuclei were visualized in 3DV perspective from SPECT of cerebral perfusion, as well as intrahepatic ducts and internal cold spot tumors in liver SPECT. Shine through of distal high count areas may be evident and can be masked by increasing the DW gradient. With an interactive display, one can select a viewing angle, cut into the organ of interest, and set the DW gradient for best visualization of internal organ activity. Ventricular wall motion analysis from gated SPECT is complicated by the tomographic segmentation of the ventricular wall. A 3DV perspective display of the beating heart as it rotates has greatly simplified and enhanced the evaluation of wall motion. An interactive display program was developed that allows selection of a viewing angle from the rotating display and to adjust the heart rate independently. The efficiency of the algorithm allows 3DV images to be generated quickly on workstation microcomputers having an array processor, and should become readily available on nuclear medicine computer systems.

S183

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798

THREE-DIMENSIONAL (3-D) ANALYSIS AND DISPLAY OF DUAL ISOTOPE MYOCARDIAL SPECT STUDIES. Dilhuydy H. (I),

COMPUTER SIk'ULATI01 OF IMR~NOSCIITIGHA~S. A. Bockisch, St. Schmidt, R. Knopp, A. Hotze, H.-J. Biersack, Dept. Nucl. Med., Univ. Bonn, W. Germany

Martel Y. (I), Lemieux R. (2), McNamara D. (2), Choiniere P. (3) and De Guise J. (i) ; (1)Institut de G4nie Biomedical, Ecole Polytechnique de Mtl. (2)D4partement de M@decine Nuclgaire, H6pital Sacr@-Coeur de Mtl. (3)D4partement de G4nie Biom4dical, H6pital Sacr6-Coeur de Mtl. We present a general 3-D modeling method to quantify the extent of myocardial infarcts and the results of a ~hantom validation study. Up to now myocardial infarcts have been quantified by several methods using dual isotope SPEGT data. These methods consider tomographic volumes as stacked slices for display purposes and even sometimes for the quantitative analysis. 3-D display is well suited for emission tomoKraphy first because of the volumic nature of SPEC~ clara and secondly because of the low number of voxels. However to obtain quantitative results, the 3 -D method must be geometrically calibrated and validated. Two radiotracers were used for the simulations: T1201 the uptake of which reflects the healthy myocardial muscle and In-lll the uptake of which is theoretically specific for myocardial necrosis when bound to antimyosin Fab. A Data Spectrum heart phantom was immersed in a water filled cylinder to simulate the torso. Small compartments permitted simulation of one TI-201 defect and one In-Ill hot spot. The image data-sets consisted of a simultaneous dual isotope SPECT study with a 180 ~ rotation around the cylinder. These were transferred to a Personal Iris graphic workstation where 3-D image processing was applied. These automated operations consisted of tri-• interpolation scaling, SPECT PSF deconvolution, interpolative backKround subtraction and thresholding. A "connecting cube ~ algorithm was then used for the 3 -D geometr~zc reconstruction. Specially designed software allows the user to manipulate and measure the total phantom volume and the hot spot volume. The optimal thresholds were 37% of the maximum TI-201 pixel value and 58% of the maximum In-Ill pixel value. 3-D volume errors were 7% for TI-201 (with a thallium volume of i00 to 150 ec) and 10% for In-ill (with an indium hot spot of 2 to 5 cc). These thresholds with our 3-D reconstruction method allow a uantifieation of the phantom "infarct" volume. hortly this approach will be evaluated in patients.

~

Performing computer simulation, individual conditions for immunoscintigraphy should be optimized. The parameters are: radionuclide, kinetics of the radiopharmaceutical (antibody), localization of the suspected lesion, time of scan, accumulated counts. We therefore measured for a point source located in a water scatter phantom the transmission function for our gamma-camera operated with all available collimators. Homogeneous scintigrams were taken for various count rates between 50 kcts and 10 Mcts per image. Using anatomic tables and coronal section planes of the N~R-temogram of a volunteer, Icm thick sections of all relevant abdominal organs were created and stored in a 128x128 pixel m a t r i L The simulation was calculated as follows: I.) Addition of all organ sections in a plane of given distance to the collimator. The relative organ contributions were obtained from the animal model. A spheric tumor may replace the organ contribution at any place. 2.) Calculation of the contribution of this plane to the scintigram by using the measured transmission function, which is interpolated by a cubic epline function. 3.) Summing over all the planes (20 planes for a normal individual). 4.) Calculation of the statistical variance using measured statistical scatter from the homogeneous scintigram. By this procedure we calculated images, which simulate patient scans very well. Thus it can be calculated, which count rate is necessary to determine a lesion in a given localization and with known relative accumulations for the various organs and the tumor. By simulation, we can decide whether a lesion may be visualized in the anterior or the posterior projection best. In addition, the optimal labelling isotope can be selected by simulation calculus. The simulation procedure may be performed for any ecintigraphic technique, for which the relative organ accumulations are known.

799

8OO

THE RELIABILITY OF THALLIUM (TL) AS THE FLOW TRACER UNDER THE INFLAMMATORY INTERSTITIAL EDEMA CAUSED BY ACUTE REJECTING TRANSPLANTED HEART OF RAT MODEL, H. Matsuo, F. Tamura, S. Wstanabe, M. Ishiguro, N.N.Wagner Jr and A. Harskowitz. Gifu Prefectural Hospital, Gifu, Japan and Johns Hopkins Medical Institutions, Baltimore, Md, USA.

DIAGNOSTIC CORRELATION BETWEEN RAPID PLANAR TEBOROXIME IMAGING AND THALLIUM SCINTIGRAPHY: GENERAL CONCORDANCE AND A COMPARISON BY VASCULAR TERRITORY. R.C. Hendel S.T. Dahlberg, B.A. McSherry, J.A. Leppo. U. Mass. Medical Center, Worcester, MA

To test the reliability of Thallium-201 (TI) as the flow tracer under interstitial edema, we evaluated the relation between blood flow measured by microsphere (MS) and T1 uptake, using rat heterotopic allograft model in the various stage of acute rejection (n=26). After simultaneous injection of MS labelled with Sn-ll3 and T1 from the left atrium of recipient heart, followed by sacrifice. Sn and TI uptake of donor heart relative to the recipient heart was calculated as Sn uptake ratio (SnR) and T1 uptake ratio (TLR) respectively. The semiquantitative scoring of interstitial edema (ES) and myocyte necrosis (MNS) were made by cardiac pathologist from 0 (no) to 4 (severe) in a blind fashon. TLR, SnR, TLR/snR (T/S), MNS according to ES is as follow. ES0(N=7) ESI(N=5) ES2(N=5) ESB(N=5) ES4(N=3) TLR O. 77 O. 80 O. 66 O. 36** O. 16** SnR O. 64 i. 04** 0.93* O. 27** O. 13** T/S I. 26 O. 80** O. 7 2 * * i. 60 1.71 ,~tNS O. 28 i. O0 I. O0 2.00"* 3.00"* {" P
$184

Initial experience has shown a high degree of correlation between teboroxime (TEBO), a neutral Tc-99m complex and thallium ('i"1)for the detection of coronary artery disease. However, a comparison of scintigraphic vascular territories (VT) utilizing planar imaging with TEBO and T1 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 min 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 T1 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/TI injection protocols. Comparing results of both protocols, TEBO imaging demonstrated 68 segments with ischemia, which was more than present on serial TI 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 T1 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.

Thursday, August 30, 1990

801

802

Feasibility of SPECT perfusion imaging with Technetium 99m-teboroxime: Comparison to thallium-201 and quantitative coronary arteriography

CLINICAL SIGNIFICANCE REDISTRIBUTION IN THALLIUMTEST.

Richard M. Fleming, Richard L. Kirkeeide, Heinrich Taegtmeyer, David B. Cassidy Julio Rodriguez-Bird, Dale Jones, Yvonne Stuart, Francisco Velasco, Richard A. Goldstein

MUNDLER O. M D , FARAGGI M. MD, MD, FAUCHET M. M D . Nuclear M e d i c i n e Dpt, L a r i b o i s i e r e Paris, France

The University of Texas Medical School at Houston, Houston, Texas 77030 Technetium 99m teboroxime (TEBO) is a new psrfusion tracer that is highly extracted and rapidly cleared by the myocardium. To determine the utility of TEBO in the diagnosis of patients with suspected coronary artery disease, 18 patients underwent SPECT ima$ing with TEBO (20 mCi) at peak exercise and again 90 mlnutss later at rest. All patients had thallium stress SPECT studies and automated quantitative coronary arteriography (QCA) within 3 months of the TEB0 studies without intervening revascularization or infarction. Images were reviewed by 2 investigators blinded to clinical data. Coronary lesions > 50 percent diameter narrowing by QCA were considered significant. Of 13 patients with disease, TEBO studies were abnormal in 12 and thallium in I] (NS). In the remaining 5 patients without disease, the TEBO was normal in 4 and thallium in 3 (NS). When a lesion of > 75 percent area stsnosis was used as the standard, the results were unchanged. There was concordance between the TEBO and thallium studies in 14/18. These results sugsest that TEBO imagine has a sensitivity and specificlty similar to that obtained with thallium. The rapid biologic half life allows studies to be completed within 2 hours which should aide patient throughput.

OF 201

SPECT

REVERSE STRESS

KEDRA

W .

Hospital ,

Reverse redistribution (RR) phenomenon in T1 201 Stress test is usually defined as the apparition or the w o r s e n i n g of p e r f u s i o n defects seen with exercise study at the delayed study. For many authors RR has to be correlated with significant coronary artery disease. As we did not found the same correlation we reexamine this phenomenon. 542 T1 201 SPECT exercise studies were rewieved for RR and 32 (6%) were found to demonstrate RR (agreed by two observers independently). These patients all received 2 to 3 mCi (74 to iii MBq) of T1 201 intraveinously immediatly after achieving at least 80% of m a x i m u m heart rate, severe angina or dangerous e l e c t r o c a r d i o g r a p h i c a b n o r m a l i t i e s as determined by the attending cardiologist. Scintigraphy studies were performed iramediately and 4 hours later using classical T1 201 SPECT acquisition (180 ~ 32 series of 35 sec each, step and shoot . . .) . For the 32 patients with RR phenomenon : Group i : 15 had correlative coronary angiopathy, 9 had c o r o n a r y stenosis but without territory correlation. In this "group none had n o r m a l angiography and exercise imaging. Group 2 : 8 patients had normal c o r o n a r y angiography and normal exercise imaging. So, reverse redistribution significative definitions seems to be modified if T1 201 SPECT exercise imaging is normal. Apparition of defect during delayed study might be correlate not with c o r o n a r y artery but m y o c a r d i o p a t h y disease o r technical artefact.

803

804

C;~' THALLIL~-201 STRESS-REDiSTRIBb~fION >PfOCARDIAL SINGLE PHOTON k~MISSION CO_~P[TED T ~ A P H Y (SPECT) 24 HOLMS .-M~'I'~ STRESS "PEST BE INTL~PRETED? H. Arai, S. Saito, F. Inomata~ X. Aizawa and B. Adachi. Shonan Kamakura Hospital, Hsma~{ura, Kanagawa, Japan.

OCCURRENCE OF HIBERNATING MYOCARDIUM DIAGNOSED BY FLUORODEOXYGLUCOSE RUBIDIUM RATIO IS UNRELATED TO SEVERITY OF FIXED PERFUSION DEFECTS. T Marwick, WJ MacIntyre, R Covalesky, D Neumann, RT Go~ G Saha, A Beachler. Cleveland Clinic, Cleveland, ON, USA.

It is knowm that late redistribution is more sensitive to myocardial viability than 4 hours imaging. But it is not clear if we can interpreted on a good quality 24 hours after stress. So we underwent 24 hours thallium-20] stressredistribution SPECT in 90 patients(Pts}. Pts were consisted ~ith 34 pts with myocardial infarction(Ml), 31 pts with angina pectoris{AP) and 25 pts with normal coronary arteries. Three mCJ (111 MBq) of thallium-201 was injected for imaging. Imaging started i0 min, ~ hours and 24 hours after injection of thallium. The stress and ih study were imaged for 30 s per projection. Twenty-four hours study were imaged for 60 s per projection. In 76 pts (Group A) we can interpreted images on a good quality. In the other 14 pts (Group B) we can not interpretate. The mean total sampling counts in Group A was significantly higher than Group B. ( 5760+1140 VS. 4520+732 KC, p<0.0] ) The mean body weight in Group B was significantly higher than Group A. ( 72+12 VS. 56+9 KS, p<0.01) Fifty-nine pts (90.1%) of pts with coronar F artery disease(CAD) were in Group A. Incidence of late redistribution was 41.2% in pts with MI and ]2.9% in pts with AP. Conclusions; In most of pts with CAD we can interprete 24 hours image on a good quality. The quality of 24 hours image depends upon weight or total sampling counts.

Thursday, August 30, 1990

Persistence of myocardial viability after myocardial infarction requires the persistence of some residual perfusion. We used an index of metabolism corrected for blood-flow (PDG/Rb ratio), to assess whether the degree of residual flow correlated with the presence of "hibernating" (H) rather than infarcted (I) myocardium. Pts with clinically documented myocardial infarction and regional LV dyskinesis underwent Rb-82 PET perfusion imaging before and after dipyridamole stress. Myocardial viability was assessed using fasting, postexercise imaging of F-18 deoxyglucose (FDG) uptake. Normally perfused segments were defined by having Rb-82 counts within 20% of maximum, with 20% reduction after stress. The FDG and Rb counts from these sites were employed to define a normal FDG/Rb ratio (0.08~0o03), corrected to standard doses of 6GmCi Rb-82 and 10mCi FDG. The FDG/Rb ratio in ischemic tissue (reduction of local Rb activity _20% with stress), was elevated to twice normal. This degree of elevation of the FDG/Rb ratio was employed to identify H, which was present in 13 regions (FDG/Rb ratio 0.21_+0.08), with improvement of regional wall motion score after revascularization. I was present in 9 areas (FDG/Rb ratio 0.12~0.06, p_0.001), which did not show significant functionaI improvement after revascularization. In H, Rb-82 activity was 59% of that in normal tissue, and in S, Rb activity was 65% of normal (p=NS). Conclusions Viable tissue (H) occurs in 59% of areas with persistent Rb defects. These zones have a degree of residual perfusion, but cannot be distinguished from non-viable tissue (I) by perfusion imaging alone,

S185

805

806

THE USED OF Tc-99m-DTPA IN THE DIAGNOSIS OF TUBERCULOSIS MENINGITIS. K.S. Von Wenzel. State Hospital, Windhoek, Namibia.

i]]DIll,-1 1 I-IA}7s I-'LAT]~LET SCI!~TIC-RAPHY FOR DLT~CTIOK OF I}!T~ACARDIAC TIiROMI~I I~ THE C EREi~RAL E~fBOLISM. !i.N ishimak i, K. Ishii ,~<.]:qakazawa, S. Ko bayashi, S.l;ishiysms,K.Yoda and T . M a t s u b a y a s h i . S c h . of Med.Kitasato U n i v . , S a g a m i h a r a , K a n a g a w a , Japan.

The Technetium-99m-Diethylenetriamine-penta-acetic acid (Tc99m-DTPA) partition test was compared to the Bromide-82 (Br82) partition test in 22 cases. Of these, 7 patients were diagnosed by the clinicians as having tuberculosis meningitis, 9 patients had viral meningitis and 5 patients had septic meningitis. One normal control subject was also included. It appears from the results of this study that although the mechanism of transfer of substances across the blood-brain barrier as well as the factors affecting this, are still unclear, both Br-82 as well as Tc-99m-DTPA, cross the blood-brain barrier to a greater extent in the case of tuberculosis meningitis as compared to viral meningitis. Although the accuracy of the Br-82 partition test, if a critical ratio value of 1,3 were chosen, is 90.6% compared to 86.9% of the Tc-99m-DTPA partition test if a critical value of 3 were chosen, there are still advantages linked to the use of the technetium preparation. These include the availability, cost and lower radiation dose per MBq, as well as the possibility of brain imaging.

807 CROSSED CEREgELLAR OIASCHISIS (CCO) IN CHRONIC CEREBROVASCULAR OISDROERS L. P~vics~ T. Odczi, M. Bodosi and L. Csernay. Albert Szent-Gy~rgyi Medical University, Szeged, Hungary. Seventy-three Tc-99m HMPAO rCBF SPECT investigations were performed in 44 patients with chronic occlusive cerebrovascular disease. In 29 cases, there were also follow-up investigations. The patients neurological comdition and CT findings were compared with CBF results, in order to clarify a possible connection of CCO with the size and location of structural and hemodynamic disturbances of supratentorial lesions, and with changes in the neurological condition. COO was found in 14 of the 44 patients. In 7 of the CCO patients, the CT was normal. No connection was found between CCO, the location and size of the supratentorial CT and rCBF lesions, and the severity of neurological signs. In 12 patients with CCO, the control rCgF SPECT revealed a correlation between the changes in CCO and the neurological condition. It was concluded that in patients suffering from chronic cerebrovascular diseases no definite relationship can be found between the development of CCO and the supratentoria] morphological, rCBF abnormalities or the neurological condition. The data suggest that changes in CCD in individual patients may mirror the alterations in the neurological condition.

S186

Our study investigates the clinical usefulness of In-111 labeled platelet scintigraphy--as used in the diagnosis of cerebral embolism--to detect intracardiae thrombi. lOlatelet was labeled either with In-111 oxine or In-111 t r o p o l o n e . l n twenty-nine ( 22 patients) clinical suspected with c e r e b r a l embolisrf~,the In-111 labeled platelet w~s administered intravenously in dose of 37MBq. Seintigraphie images of h e a d , n e c k , t r u n k and thiths were obteined at 24-72 hours after tracer a d m i n i s t r a t i o n . S c i n t i g r a p h i e results obteined from 28 of the cases were compared with t w o - d i m e n t i o n a l eehocardiographie (2-]] echo) findings.The seintigraphic images obteimed for 14 (50.0%) of 28 cases revealed it~traeardiae a b n o r m a l i t i e s ; o f those,12 cases were of abnormal a c c u m u l a t i o n s and 2 were of intracardiac d e f i c i e n c i e s . B y contrast, the 2-D echo results indicated the presence of intraeardiae thrombi in 11 (39.3%) of the 28 eeses.i deteiled comparative analysis of those results thus suggests that platelet sciutigrsphy is useful for detection of intracardiac thrombi in cerebral embolism.

8O8 99mTc HMPAO STUDY AND THE FOLLOW UP OF THE ISCHEMIA POST SUBARACHNOID HEMORRHAGE.

F. TRANQUART*, P. GROUSSIN*, P.E. ADES**, D. BEKECHI*, Ph. ARBEILLE*. *M@decine Nucl@aire in vivo - INSERM U 316 (Pr. L POURCELOT).**Service de Neurochirurgie (Pr. JAN). CHU Bretonneau-TOURS~7044 FRANCE

After subarachndfd hemorrhage, the most frequent complication is ischemia. Up to now, it is very difficult to recognize the exact site and the extent of hyproperfusion with the usual exploration (Doppler, artedography, scanner).

We used 99mTc HMPAO to evaluate these complications and to assess the evolution of the hypoperfusion. Approximately, 15 mCi (555 MBq) 99 mTc HMPAO were injected to the patient as a bolus in a quiet room. SPECT imaging was performed with a Gammatome 2 Sophy camera. Data were collected in 64 projections with an acquisiNon time of 20 s/projection. On the reconstructed slices (6 mm thickness), we determined an index of symetry. With this method, we obtained these following results : - the site and the extent of hypoperfusion (often before clinical signs) were delimited, - the evolution of hypoperfusion with drugs was controlled, - the rejection of other possible diagnosis in case of neurologic deterioration.

Thursday, August 30, 1990

809

810

EVALUATION OF SPINOCEREBELLAR DEGENERATION BY SPECT USING N-ISOPROPYL-P(I-123)-IODOAMPHETAMINE. Y.Mori L T.Abe, H.G0to, M.Nagase , J.Harada, H.Nakabayashi, T.Yanagisawa, R.Wetanabe, A.Asahara*, K.Kawakami. Jikei University, Tokyo, Japan. *JR Tokyo General Hospital.

Tc-99m ECD: EVALUATION OF A P E R F U S I O N T R A C E R IN H U M A N S . A.Bruno, F.Dosio, R.Benti, A.Savi, G.Taddei, L.Maffioli, P.Gerundini. S. R a f f a e l e , M i l a n o , Italy.

SPECT using 1-123-1MP was performed in 5 normal volunteers and i0 cases with spinocerebellar degeneration(SCD), diagnosed by clinical findings or Xray CT. SCD cases were classified by grade of the symptoms:I:mild, II:moderate III:severe. Early and delayed images were obtained 20 min and 4hrs after injection of 1-123 IMP(lllMBq),respeetively. Radiodistribution in the brain was semiquantitatively evaluated. Regions of interest were set in the cerebellum , frontal, temporal, and occipital areas. Ratio of activity in the cerebellum to frontal area was calculated. This ratio was significantly small in SCD patients compared with normal volunteers in early and delayed scans, and correlated with grade of severity of symptom. The ratio was 80 to 90% in the cases of grade I and 60 to 80% in the grade II. It was less than 60% in the grade III. No significant change of the ratio was noted between early and delayed scan of SCD. IMP a c c u m u l a t i o n in c e r e b e l l u m of SCD patients may be decreased due to reduction of cerebellar perfusien and/or deficiency of amine r e c e p t o r . 1-123 IMP SPECT will be useful in diagnosis and patho-physiological evaluation of SCD.

NEW

BRAIN

L.Gianolli, I s t i t u t o H.

E C D is a n e w c o m p l e x of Tc for r e g i o n a l brain blood flow investigation with SPECT. Biodistribution studies (20 mCi i.v.) and SPECT imaging performed in n o r m a l v o l u n t e e r s after informed consent demonstrated a rapid brain extraction and retention (4% at 1 h); moreover a 50% d e c r e a s e of h e a d s o f t t i s s u e a c t i v i t y w a s o b s e r v e d w i t h i n 1 0 ' - 6 0 ' . In 4 p t s volunteers with stroke, Tc-99m ECD SPECT was executed showing in three cases a larger t o m o g r a p h i c d e f e c t t h a n o n t h e CT scan. N e x t we have compared Tc-99m ECD SPECT pattern and tomographic images obtained with Tc-99m HM-PAO, a tracer commonly used for brain perfusion. We have also considered neurological f i n d i n g s , EEG, CT a n d M R I scan. W e h a v e s t u d i e d 6 pts, 3 w i t h c h r o n i c s t r o k e (4 w e e k s prior) a n d 3 w i t h d e m e n t i a . I n a l l s t r o k e p t s the r a t i o b e t w e e n n o r m a l a n d p a t h o l o g i c t i s s u e was higher w i t h ECD; the defects size was slightly larger, but the difference versus HM-PAO was not significant. In d e m e n t i a pts also, SPECT was similar with both tracers. T h e r e is a g o o d c o r r e l a t i o n between the two s c i n t i g r a p h i c p a t t e r n s but, b e c a u s e t h e l o w e r facial soft tissue background, ECD imaging s e e m s to b e b e t t e r a n d q u a l i t a t i v e diagnosis easier. H o w e v e r , a c o m p l e t e e v a l u a t i o n of t h i s new Tc complex needs further analysis in a l a r g e r n u m b e r of c e r e b r a l p a t h o l o g i e s .

811

812

SPECT OF ACUTE KNEE TRAUMA. LP.C.Murra),, .]. Dixon and k. Kohan. Depts. of Nuclear Medicine and of Orthopaedic Surgery~ Prince of Wales Hospital. Sydney.

QUANTITATION OF SKELETAL MUSCLE NECROSIS IN THE LOWER EXTREMITIES. K. Yip, S. Houle, J. Tittley and P. Walker. Toronto General Hospital, Toronto, Ontario, Canada.

Australia.

In the assessment of acute knee pain following recent trauma, most frequently related to sporting activity, bone scintigraphy was performed in 51 patients, in 40 immediately preceding arthroscopy. Entirely normal studies occurred in only b, patients, the others demonstrating alterations resulting from a variety of injuries, often multiple in the same individual SPECI wa% therefore~ critical in providing delineation and siting of the abnormalities, not feasible with conventional planar imaging. Thus, it identified patellar localisation associated with a symptomatic bipartite patella or lesions such as a stress fracture or supra-patellar septurn. Multiple sites of focal uptake were frequently visualised at muscle or ligamentous insertions, most commonly that of the patellar ligament onto the tibial tuberosity, as well as in intra-articular areas of cartilaginous erosions. However, damaged anterior cruciate ligaments were only identified in 6/11 patients, occurring when there was avulsion of the tibial attachment. The most characteristic scintigraphic change resulted from meniseal tears~ diagnosed in 29 of ] ] patients in whom the lesion was suspected clinically. Only 4/54 menisci observed by arthroscopy to be damaged had normal scintigraphic appearances while the scan was considered abnormal in 5 arthroscopically normal menisci, resulting in a sensitivity of 88%, specificity of 81% and diagnostic accuracy of 85% for this common injury. Thus, while trauma readily induces scintigraphic abnormalities in and around the knee, the patterns of alteration associated with particular lesions can be identified by SPECT and provide considerable assbtance in management, in particular in determining the need for arthroscopy.

Thursday, A u g u s t 3 0 , 1 9 9 0

Non-invasive quantitation of the amount of muscle necrosis (MN) has been described in animals (1). We have modified this method to study 9 controls and 13 patients and to retrospectively examine the clinical significance of MN. 500 MBq of Tc-99m Pyrophosphate (PPi) was injected iv 48-72 hrs post ischemic injury. SPECT imaging of the calves was performed 1-1.5 hrs p.i., over 30 min with a 64x64 matrix and LEAP collimator. Transaxial sections (TS) were reconstructed. A background region of interest (ROI) was drawn over normal muscle in the non-ischemic calf. After background subtraction and excluding the tibia, the number of pixels in each TS with significant activity was determined by the threshold method. Volume was calculated by summing these pixels and multiplying by the voxel size. As previously described (1), quantitation is not accurate <20 mL of MN. As MN is a focal process, muscles with significant necrosis should show a large variance in the number of counts within each pixel. A ROI was drawn around the calf (excluding the tibia) in a representative TS. The variance within this ROI was calculated. For the controls, the mean variance=132+/-27. A variance > 159 was considered significant. For patients with MN, the mean variance was 181 +/-19. Volume of MN was compared to strength of ankle dorsiflexion. 6 patients have significant MN (volume=462+/-280mL). All except 1 (with a small amount of MN) developed foot drop. 7 patients have no significant MN. All except one (with nerve damage) have normal strength. We conclude that volume of MN has prognostic value. (1) T.-C.K.Yip et al, Nucl Med Commun, In press.

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COMPARISON OF BONE SCAN AND MR IMAGING IN TRAUMATIC VERTEBRAL FRACTURES

SCINTIGRAPHY FOLLOWING MOTOR VEHICLE ACCIDENTS. R.Reid. University of Western Ontario, London, Canada.

(~ Waaner-M, anslau. E val; do Flierdt, B AIIgayer*, St v Gumpp-enberg**, R Bauer, HR Langhammer, HW Pabst Nuklearmedizinische Klinik, *lnstitut for RSntgendiagnostik, **Chirurgische Klinik, Technische Universitglt, Munich, FRG Bone scan (BS) has proven to be a useful diagnostic procedure in detecting primary and metastatic bone disease as well as in evaluating skeletal trauma. MR imaging (MRI) seems to be more sensitive in vertebral metastasis. The aim of the study was to compare the diagnostic value of both BS and MRI in traumatic vertebral fractures (n=104) of different age (age of fracture from 0-1 me: 18, from 2-6 me: 7, from 724 me: 51, from 24-64 me: 28). All fractures were classified by BS according to radionuclide uptake in 4 groups: normal (GO), weak (G1), moderate (G2) and marked increased (G3). These results were compared with findings in MRI (T1 and T2 weighted images). Decreased signal in T1 images correlated either with marked increase in T2 (edema) or with loss of signal in all modes (sclerosis). Increased signal in T1 was only found in G1 representing fatty degeneration of marrow in fractures older than 12 me. All BS up to fracture age of 6 me were positive, 76% of them show edema in MRI. 0/12 GO, 3/48 G1, 12/34 G2"and 10/10 G3 fractures show edema. 1. According to pathophysiology, BS is more sensitive than MRI in detecting and follow up of fractures of the vertebra. 2. MRI may be useful as primary investigation in patients with neurological deficits and before surgical intervention.

Following motor vehicle accidents (MVA), many patients complain of very non-specific physical complaints such as pain in back, hands, knees, feet and temporal mandibular joint. During the momentary time of impact peripheral forces come to bear on the spinal column. These forces can cause shearing and damage to axons, blood vessels and soft tissues. Hyperextension flexion injuries also cause significant soft tissue injury to the spine and in more severe cases fractures. (Whiplash) types of injury and the physical and psychological disability resulting from them can be very difficult to evaluate as radiographs and CTs are frequently normal. Seventy-five patients referred for evaluation as a result of symptomatology following MVA, underwent bone scintigraphy for complaints of pain in the back, peripheral limbs and temporal mandibular joints. In acute cases bone scintigraphy revealed several patterns of uptake in sites of pain where no evidence of trauma was evident on initial radiographs. In 10 cases occult fractures were located, including 2 potentially unstable cervical spine fractures. To be useful scintigraphy should be carried out as early as possible post trauma because changes in the cervical spine and other sites can resolve within 6 months due to healing. In middle-aged subjects foUowupscans are necessary to differentiate degenerative from traumatic causes. Bone scintigraphy is useful in assessing post MVA trauma, pattern of uptake in the spine, limbs and temporal mandibular joints and can be explained by the forces acting on the body during the time of impact.

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TWO PHASE HONE SCINTIGRAPHY IN THE EVALUATION OF REFLEX SYMPATHETIC DYSTROPHY SYNDROME OF THE LOWER EXTREMITIES. C.H. Park, C. Intenzo and S.M. Kim, Thomas Jefferson University Hospital, Philadelphia, PA, USA

SCINTIMETRIC TRAUMA.

Reflex sympathetic dystrophy syndrome (RSDS) is a symptom complex of pain, swelling, dystrophic skin changes, muscular atrophy and contracture of an e x t r e m i t y , usually following some form of trauma. RSDS can affect upper extremities, lower extremities (LE) or both. The purpose of this presentation is to describe the methodology of two phase bone scintigraphy (TPBS) and TPBS findings of RSDS of the lower extremities. F o r t y consecutive patients suspected of having LE RSDS were e v a l u a t e d w i t h TPBS. TPBS c o n s i s t s of both immediate blood pool and 3 to 4 hour delayed bone scanning of the pelvis and entire LE using the whole body scanning mode. Followinng t h i s , a s t a t i c view of the feet in e i t h e r dorsal or plantar projection is obtained. A scan is considered p o s i t i v e for LE RSDS i f the p e r i a r t i c u l a r a c t i v i t y is e i t h e r increased or decreased in r e l a t i o n to the asymptomatic LE. RSDS is grouped into I, I I , I l l stages according to clinical symptoms and physical f i n d n g s . The s e n s i t i v i t y of TPBS in the diagnosis of LE RSDS is v a r i a b l e depending upon c l i n i c a l stages. Twentyf i v e percent of the patients in stage I had abnormal scans, whereas 85% of the patients in stage I I and 100% of the patients in stage I I I had abnormal scans. In summary, the authors p r e f e r to inspect a l l j o i n t s from the hips to the j o i n t s of the feet in a s i n g l e image and feel t h a t TPHS is a s e n s i t i v e method in the diagnosis of LE RSDS.

$188

EVALUATION

OF

BONE

REMODELING

AFTER

J. Spitz, K. Tittel, H. Weigand. Municipal Hospital, Wiesbaden, F R G Bone scintigraphy has become as important in benign conditions as in malignancies since Tc-99mlabelled P-compounds are available. But except for some experimental work there exist almost no quantitativ data about the bone remodeling after fracture in man. Material and method: 274 patients with 431 bone lesions of 1.} distal radius 2.) os scaphoid 3.) proximal femur 4.) spine 5.) os pubis. Age: 18-79 years. Scans were done some minutes to 24h after i n jection of 500-700 MBq TC-99m-NMDP i.v. and 1-100 days after trauma. 3-phase sointigraphy. Digital rcamera APEX 415 ECT. $cintimetric evaluation. Results: I.) Clinical data in man are in agreement with experimental data in rats, canine and baboons. 2.} Compared to normal bone lesions show rising accumulation values during 24 h. 3.) In the first weeks an increasing tracer accumulation at the fracture side is found. 4.) The peak accumulation is found 2-3 weeks after trauma. 5.) Bones in different localizations behave different as to the time of showing up in sointigraphy, intensity of accumulation (first days 1.1 - 3.9, at peak 2.0 - 7.0) and steepness of the slope (log~=0.O77-1.055). 6.) The remodeling process after fracture is no_~t age depending. Conclusion Bone scintigraphy truely reflects bone remodeling after fracture. Quantitative data improve the understanding and interpretation of scan results by adding specificity to the known sensitivity of bone scintigraphy.

Thursday, August30,1990

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HIGH RESOLUTION POSITRON EMISSION TOMOGRAPHY IN STUDYING GLUCOSE UTILIZATION IN ONCOGENE TRANSFORMED TUMOR XENOGRAFTS. A-L. Brownell. F. Kallinowski, P. Vaupel, C.W. Stearns, C. Burnham and G.L. Brownell. Massachusetts General Hospital, Boston, MA

PET WITH F-18-DEOXYGLUCOSE IN PATIENTS WITH ADVANCED HEAD AND NECK CANCER TREATED WITH SYSTEMIC CHEMOTHERAPY.

To determine phenotypic effects of oncogenes in vivo and non-invasively glucose utilization was studied using high resolution PET (HR-PET). Quantitative F-18 2-fluorodeoxy-Dglucose (2FDG) studies were carried out in four genetically defined tumors implanted into immunodeficient NCr/Sed (nu/nu) mice. The ras and myc transformed tumor lines (pEJ6.6, 12/40E, RAT1 and RATv-myc2) were !nvestigated in size matched tumors in 15 animals and in 2 normal animals using PCR-I with a spatial resolution of 4.5 mm. 2FDG utilization was also determined in three different size groups of pEJ6.6 cell line tumors. The glucose metabolic rate (GMR) was 9.7+/-1.3, 11.0+/-2.1, 12.4+/-2.4 and 13.4+/-2.2 in 12/40E, RAT1, RATv-myc2 and pEJ6.6 cell line tumors and 4.3 +/-0.8 umol/min/100cc in corresponding normal leg muscle. In different tumor size GMR values were 13.4+/-2.2 (V=363+/-70mm3, n=3), 16.9+/-2.8 (V=1277+/-69mm3, n=3) and 17.5+/-2.1umot/min/100cc(V=3074+/-38mm3, n=3) in pEj6.6 cell line tumors. The data obtained shows that the glucose consumption is significantly different in various ceil line tumors and the GMR correlates to tumor growth. Also the high resolution of PCR-I revealed the heterogenous distribution of 2FDG in large tumors. The work provides insight into oncogenic alterations by making it possible to evaluate the metabolic microenvironment of solid tumors.

U. Haberkorn, L.G. Strauss, A. Dimitrakopoulou, M. Knopp, A. Schadel, J. Doll. G. van Kaick. German Cancer Research Center, Heidelberg, Germany. F-18-Deoxyglucose (FDG) is known to be accumulated in metabolic active regions. Moreover PET using FDG gives quantitative information about the tumor metabolism and may be performed pdor and during the therapy. In 12 patients with proved tumors PET studies were done prior and after the first chemotherapeutic cycle with 12 mCi FDG. The patients received a standard combination of cisplatinum and 5-FU for therapy. Tumor and/or lymph node volumes were determined from computertomographic slices and the tumor growth rate was calculated assuming an exponential function. The PET-FDG images were standardized for the bcdy weight and the injected dose and a quantitative evaluation was done with a region of interest techniqse. Data about the glucose metabolism were available for 4 tumors and 11 lymph nodes, volumetric data for 3 tumors and 8 lymph nodes. We observed an increase in FDG accumulation in one case and a decrease in 7 lesions. In 7 cases no change of metabolism was found. Multiple lymph nodes in the same patient may show a different metabolic activity and also a different response to chemotherapy. In general tumors were more sensitive to therapy than lymph nodes. A high correlation was observed between the changes in FDG uptake and the tumor growth rate (r=0.9). We conclude that PET should be used for the therapy management and the evaluation of therapeutic effects in patients treated with systemic chemotherapy.

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PET WITH F-18-DEOXYGLUCOSE FOR THE ESTIMATION OF THE PROLIFERATIVE ACTIVITY OF HUMAN HEAD AND NECK CANCER.

DETECTION OF P H E O C H R O M O C Y T O N A BY PET. B.~ Shulkin, D.M. Wieland, B. Shapiro, M.S. Haka, K.D. Rosenspire, G.D. Hutchins, J.C. Sisson, M. Schwaiger, and D.E. Kuhl. University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A.

U. Haberkorn, L.G. Strauss, D. Haag, E. Seifert, A. DimitrakopouIou, M. Knopp, K. Goerttler, G. van Kaick. German Cancer Research Center, Heidelberg, Germany. Fl~K)r-18-Deoxyglucose (FDG) is widely accepted for the study of the glucose metabolism in tumor tissues. In the literature a relation between the FDG accumulation and the grade of malignancy is reported. Moreover it is oonjected that the glucose metabolism is related to the cell division rate and therefore to the tumor growth and aggressiveness. We performed PET studies with FDG (12 mCi} in 5 patients with histological proved cancers of the oro- or hypopharynx. In 3 patients perfusion data with O-15 labelled water (80-100 mCi) were available. After the PET examination, tumor specimens from the examined regions were obtained by biopsy in 4 patients. One-dimensional flow cytometry was done to measure the different cell cycle fractions. All tumors showed an increased FDG accumulation (2.5-4.7 SUV) as compared to normal soft tissue (1.0 SUV). Perfusion as demonstrated by the O-15 water images was also raised. Flow cytometry showed an increased number of S-phase and G2/Mphase cells in the tumor tissue (15-27% S*G2/M cells). FDG accumulation and proliferation rate as measured with flow cytometry were correlated. These preliminary results from our ongoing study show that PET with FDG is a promising method to estimate the tumor growth and aggressiveness.

T h u r s d a y , A u g u s t 30, 1 9 9 0

This investigation was undertaken to assess the feasibility of applying PET technology and a newlydeveloped tracer, C-If hydroxyephedrine (HED), to the detection and localization of pheochromocytoma. Four patients with malignant pheochromocytoma and one h y p e r t e n s i v e patient who d i d not have pheochromocytoma participated in this study. A dynamic acquisition was begun immediately following the intravenous bolus administration of 20 mCi C-II HED, a positron-emitting probe of the adrenergic nervous system. Subsequently, a rectilinear scan was performed using the PET camera to screen the chest and a b d o m e n for a b n o r m a l accumulations outside the areas imaged in the dynamic scans. Comparison was made to recent CT/MRI in 4 patients, and to M I B G scintigraphy (either 1-231 or 1-123 labelled) in 5. In 3 patients, PET scanning with HED clearly detected deposits of pheochromocytoma located by CT/MRI or MIBG scanning in the imaged regions. C o m p a r e d to M I B G scintigraphy, the PET/HED scans depicted more lesions with greater clarity. Abnormal foci were visible by 5 minutes with uptake c o n t i n u i n g t h r o u g h the 20 m i n u t e d u r a t i o n of the d y n a m i c acquistion. In the remaining 2 patients, both the PET/HED study and MIBG scintigraphy were unremarkable. We conclude that PET scanning with HED is a promising approach to the scintigraphic detection and localization of pheochromocytoma.

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822

F-18-DEOXYGLUCOSE IMAGING WITH PET IN IRRADIATED PATIENTS WITH RECURRENT COLORECTAL MALIGNANCIES.

PET EXAMINATIONS WITH F-18 LABELED FLUOROURACIL IN PATIENTS WITH LIVER METASTASES FROM COLORECTAL CARCINOMAS.

U. Haberkorn, L.G. Strauss, B. Kimmig, M. Knopp, A. Dimitrakopoulou, E Helus, W.J. Lorenz. German Cancer Research Center, Heidelberg, Germany. Although the radiation therapy has proven useful in patients with Iocoregional recurrencies of colorectal maignancies, there is still need of information about the tumor metabolism to evaluate the effectiveness and for therapy management. Eighteen patients with recurrent colorectal tumors were examined prior and after a combination of conventional radiotherapy (40 Gy) with neutron therapy (20 Gy). Follow up examinations were done up to 603 days after the therapy onset. We performed 70 examinations with F-18-Deoxyglucose (FDG, 3-12 mCi). In 50 cases data about the tumor perfusion as measured with 0-15 labelled water (80-100 mCi) were available. Concommittant to PET we measured the CEA plasma concentrations. The quantitative evaluation was done using a region of interest technique for tumors and normal gluteal muscles. We observed a high FDG accumulation in all tumors. In 11 of the 18 patients more than 3 follow up studies were possible. A 30-60% decrease in FDG uptake was found in 6 of these patients within the first 60 days after onset of therapy. FDG uptake values in the range of normal soft tissue were observed only in 5 of 11 patients. In 12 of 41 examinations an increased FDG uptake was associated with a normal CEA value and only in 2 cases normal FDG uptake values and increased CEA levels were found, indicating that PET is more sensitive than the measurement of CEA plasma levels. We conclude that PET can be used to evaluate the effectiveness of radiation therapy in patients with recurrent colorectal cancer.

A. DimitrakoDoulou, L.G. Strauss, U, Haberkom. M. Knopp, P. Schlag, E Oberdorfer, W.J. Lorenz: German Cancer Research Center, Heidelberg, Germany. Fluoruracil (FU) is an important chemotherapeutic agent for the intravenous therapy of liver metastases from colorectal cancer. CT was performed prior to PET in order to determine the target area. We used F-18 labeled FU to obtain data about the time-dependent accumulation of FU in liver metastases and the normal liver parenchyma. Images were acquired after onset of the FU infusion (12 sin) for two hours. Standardized uptake values (SUV) were calculated for the metastases, liver parenchyma and the aorta. The PET evaluation comprises 60 metastases in 37 patients. The mean maximum liver activity was 11.4 SUV (30 min. p.i.) as compared to 2.77 SUV (25 sin. p.i.) in the metastases. The mean FU metabolite concentration values 2 h p i were 3.9 SUV (liver parenchyma) and 1.39 SUV (metastases). We obtained a high correlation (r=0.8821, pq %) between the FU uptake (20 min p.i.) and the FU metabolite concentrations (2 h p.i.) in 57 of 60 metastases. The FU transport into the lesions was increased in 17 % of all metastases, but high FU metabolite concentrations were noted in only 9 % of the lesions. Our results show, that PET can be used to evaluate the different steps of the FU metabolism. Therefore, PET may find use to identify patients with low FU metabolite concentrations who are unlikely to respond to chemotherapy.

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824

AN ON-LINE DIGITAL INFORMATION AND ORGANIZATION SYSTEM INCLUDING LONG-TERM STORAGE IN NUCLEAR MEDICINE J. Spitz, R. Thiel. Municipal Hospital, Wiesbaden, FRG

NUCLEAR IMAGE TRANSMISSION-HARDWARE INDEPENDENT SYSTEM. R.E. Henkin, J.R. Halama, R.N. Wagner, S.A. Jones. Loyola University Medical Center, Maywood, IL. and Lehigh Valley Hospital, Allentown, PA.

Original PACS arm 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 80385 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-multitask system, w i n g UNIX and INFORMIX as the basic software. ~ - l i n e 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 aguisition 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 effective data administration, handling, scientific questions and reducing archiving problems.

S190

The ability to interchange images internationally without loss of quality is important for diagnostic nuclear medicine. Two systems have been developed that perform this interchange in a hardware independent fashion. The first of these systems, the Nuclear Image Transmission System (NITS), is a direct computer transformation. The algorithm is adaptable to any computer system, and produces .GIF files (Graphics Interchange Format). Once formatted, these files may be transmitted worldwide through the CompuServe (CIS) network and its gateways. Transmission times average from 2 to i0 minutes per study. Film capture has been employed using the TNTS (TeleNuclear Transmission System), consisting of a video camera and digitizer in a PC. The output is transformed to .GIF format and may be transmitted on CIS, or to any PC system. Any VGA system may view NITS or TNTS. To transmit dynamic images, GRASP technology is employed. GRASP packs cine files with color tables and display information prior to transmission. The GRASP run-time routine permits the receiving IBM compatible PC to display the dynamic nuclear study at the same rate it was captured at, independent of the clock speed of the PC. Patient studies are currently transmitted for teaching and consultation purposes between several hospitals. This improves the quality of patient care, because of the rapid availability of consultation from institution to institution.

Thursday, August 30,1990

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826

INTEGRATION OF PICTURE ARCHIV!NG COMUNICATING SYSTEM (PACS) IN A NUCLEAR MEDICINE DEPARTMENT. A NE~ OPPORTUNITY. B. Bagni, Ospedale S. Anna, Ferrara, Italy

CLASSIFICATION TF~GES.

Toda~ PACS installations in Europe are at least t~enty, most of them are commercial. In Italy eight FACS sites are activated, and in four cases they are connected to digital radiography sets and in a case to nuclear medicine devices. A very large PACS system has been implanted at the S. Anna Hospital is Ferrara and is connected to four nuclear medicine gamma cameras via optical fiber and ethernet local area network (LAN). Other de%ices are connected to the PACS via optical fibers (CT scanners, digital radiography, ultrasound ...). A data base management system provides manipulation and data retrieval. Diagnostic viewing stations are situated in each remote site and use high resolution catode tube displays (i024 x 1024 x 8 bit depth). In the central operating and viewing room a laser reader and a laser copy unit are available for digitizing and printing images coming from different periferal devices. The maximum capacity of the optical disk (O.D.) is 1.6 Giga Bytes. The mass memory is arraged in a Juke-Box like device containing 90 m.D.. Based on the first 6 months of experience, it appears that the integration of the whole diagnostic devices currently used in a Nuclear Medicine Department and in a General Radio!aqy Department is a unique opportunity for improving the productivity and the diagnostic potentialities.

OF

PATI"ENTS

BY

DIRECT

COMPARISON

OF

B.A. Bitter, F. Bitter, R. Weller, A. Tarkowska*, E. Henze, P. Kress, M. Clausen and W.E. Adam. University of Ulm, Nuclear Medicine, Ulm, FRG, *Department of Nuclear Medicine, Medical Academy Lublin, Poland. Building up digital archives for all the images from routine work the question arose, how images mr studies directly can be compared with each other. Using these digital archives where around i0 O00 RNVstudies are accessible the attempt is undertaken to generate "typical" images for groups of patients with similar behaviour. The left ventricles of different shape, size and orientation are transformed to a fixed ventricle (circle) . Now the direct comparison on a pixel base is possible from patient to patient. Mean ("typical") images of groups can be formed and compared. The comparison of patients with groups is facilitated. The euklidean distance ranks groups as well as patients and measures the distance form particular patients to groups. As paramters for the classification the fourier amplitudes and phases of the heart frequency are used. Data from a normal group (20), posterior ( 1 4 ) and anterior (23) wall infarctions, aneurysms (18 ) , light (17 ) and severe (17) aortic stenosis, aortic regurgitation (54) and conduction abnormalities ( 4 7 ) are processed. The ranking of the groups seems to be reasonable as well as the reclassification of the patients. For the individual evaluation the difference images from a particular patient to any group or any other patient may be transformed inversely onto the original left ventricle shape, size and orientation.

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828

COFADS - A MOVE TOWARDS QUANTIFICATION IN FACTOR ANALYSIS OF DYNAMIC STRUCTURES. A.S. Houston, Royal Naval Hospital Haslar, Oosport, Hants ~ U.K.

PHASE ANALYSIS FOR MOVING STRUCTURES: APPLICATION TO GATED MYOCARDIALPERFUSION STUDIES. Michael L. Goris, Stanford University School of Medicine, Stanford, CA, USA.

Factor Analysis of Dynamic Structures (FADS) has been shown to be a useful diagnostic tool in nuclear dynamic studies. The technique uses time information to separate overlaying physiological compartments in a purely objective fashion. Unfortunately it does not yield a unique solution and therefore cannot be used quantitatively. Several techniques have been suggested to overcome this problem, e.g. simple structure, spatial constraints. Constrained Factor Analysis of Dynamic Structures (COFADS) uses clustering of image data points in feature space and a suitable representation of background activity to provide additional constraints. This method has now been generalised to deal with most clinical situations. This paper presents the first attempt to relate quantitative results obtained using the method to results obtained using conventional subjective methods. Among parameters tested were mean transit time and GFR for renal studies and LVEF for gated cardiac studies. The success of the method depends heavily on the ease with which a suitable representation of background can be made. Neither the assumption of a uniform background nor interpolation based on pixels forming the background cluster appears to be universally acceptable.

In the original description of phase ( f i r s t harmonic) analysis, the pixel content of pixel J in frame K of a dynamic image is assumed to represent the content or volume of a stationary structure projecting into J at time K. In this paper we present a method in which the data are f i r s t transformed, such that A (J,K) represents the r e l a t i v e position of frame K of a structure which an image K=O projects in pixel J, but moves in time. Structures are defined as percentiles of a line integral going from a reference coordinate to the periphery, in a polar representation of the data. When the transformed image is subjected to phase analysis, pixel J contains the amplitude and phase of the motion of the structure present in J at time O. In this representation amplitude represents the amount of in- or outward motion, and phase the synchronicity of this motion. We have found this analysis to be useful to describe wall motion when the data are obtained through myocardial rather than cavity imaging, in which case the classic approach would not work. Our approach avoids the problem in the l a t t e r method, in which moving structures result in simultaneous inward and outward phases and amplitudes at the edges rather than on the structures. The method has been used to evaluate the resting function of segments abnormal in MIBI stress images.

T h u r s d a y , A u g u s t 30, 1 9 9 0

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830

STUDY OF I II-In-AMINOTHIOL COMPLEXES

IN-VITRO AND IN-VIVO STABILITY OF MONOCLONALANTIBODY (mAb) 2G3 LABELLED WITH In-111 AND Y-90o *R..M.o R e i l l y , +A. Marks, +J. Law, *S. Houleo *Toronto Genera] Hospital and +Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada~

C. Cotsyfakis, A. Varvarigou, S. Stathaki, M. Papadopoulos and E. C h i o t e l l i s Radiopharmaceutical Lab., N.C.S.R. "Demokritos" 153 10 Ag. Paraskevi A t t i k i , Greece A series of polyaminodithiol: (NxS2) were synthesized and evaluated for complexing In s+. The compounds studied were of the following general formula: NS-C(R, R) -CH2-N(R') - [CH2CH2-NH]x-CH2CH2-NH-C(R,R)-SH, where R:alkyl, R -H ethyl-(heterocyclic)-amines, X=0,1,Z. Synthesis of NxS2 derivatives has b e e n reported previously ( C h i o t e l l i s et a l . , 1988). In order to determine the change of indium complexes, the ligands were complexed with indium n i t r a t e in acidic pH (3.5-5.0). Hydrogen ions, released, were determined by titratium. Indium to ligand r a t i o equal to unit, indicated the formation of cationic indium complexes. Ligands were further labelled with 1111nC13 at the same range of pH and complexes formed were electrophoretic a l l y and chromatographically studied. Data obtained confirmed that most ligands form cationic complexes, with the exception of polyaminodithiols ( x : l , 2 ) . Biodistribution of the cationic aminodithiol indium complexes in mice showed a considerable heart uptake, varying with the ligand. The heart to blood r a t i o ranged from 2.0 to 7.0 at i hour p . i . Further SAR studies on aminothiol complexes with I n - l l l are in progress.

We are currently investigating radiolabelled mAb 2G3 for therapy of effusions of breast and ovarian cancer~ The objective of this study was to determine if 2G3 exhibited different stability in-vitro and biodistribution in-vivo when labelled with In-111 or Y-goB 2G3 was conjugated with eDTPA anhydride to a substitution level of 0.5-1.5 mols DTPA/mol 2G3 then radiolabelled with In-111 or Y-9O to a specific activity of 1-12 uCi/ug. The mean immunoreactive fraction (IRF) against MCF-7 ceils was 0.55 (0.25-0~ for In-111 2G3 and 0.25 (0o10-0.55) for Y-90 2G3o The IRF of Y-90 2G3 was highest at low specific activity, in 5% HSA and when the time between labelling and measurement of the IRF was minimized. There was no change in the IRF of In-111 2G3 over a I week period in-vitro. Loss of radiolabel in saline as measured by instant thin layer chromatography was 1o2 %/d for In-111 2G3 and 0.8 %/d for Y-90 2G3. Loss of radio]abel in-vltro in plasma as measured by an anti-transferrin column or by size-exclusion HPLC was 6.6-10o8 %/d for In-111 2G3 and 2.5 %/d for Y-90 2G30 Biodistribution studies at 24 h p.i. in normal mice demonstrated that In-q11 2G3 localized mainly in lung, liver, spleen and kidneys whereas Y-90 2G3 localized in ]iver, spleen, kidneys and bone~ There was decreased radioactivity in all tissues at 96 h polo except for Y-gO activity in bone which increased. We conclude that In-111 and Y-gO 2G3 exhibit different stabi]ity towards loss of immunoreactlvity in-vitro and loss of radio]abel both invitro and in-v[vo.

831

832

SIMPLE, RAPs HIGH-EFFICIENCY RAOIOLABELING OF HEMATOPORPHYRIN ANALOGS WITH In-lll OXINE. S.M. Karesh, T.C. Origitano, O.H. Reichman, and R.E. Henkin. Loyola University Medical Center, Maywood, IL, USA.

A NOVEL METHOD FOR THE LABELING OF PROTEINS WITH F-18. L.W. Herman, E. Livni, D.R. Elmaleh, A. J. Fischman, and H.W. Strauss. Dept. of Radiology, Massachussetts General Hospital, Boston, MA.

The survival of patients with malignant brain tumors is poor. Standard surgical therapy has not improved survival significantly. Recently, a porphyrin complex, Photofrin-II, has been developed to photosensitize cells for laser photodynamic therapy (PDT). To determine the optimal injection-to-surgery interval, our laboratory has developed a one-step radiolabeling technique designed to prepare In-lll Photofrin-II. Previous techniques for labelng porphyrins were time consuming, complex, and had yields varying from 65-95%. Our technique results in an average yield of 96%, achieved by heating the light-shielded mixture of the Photofrin-ll solution with sodium bicarbonate and In-lll oxine. The reaction is complete after 20 min in an oil bath maintained at 115-120 C. The pH must be maintained in the range of 6-8. Labeling efficiency drops off dramatically above or below that range. The radiochemical purity of the final compound was verified by both TLC and HPLC, Following terminal filtration and performance of quality control testing, the product is suitable for intravenous injection. Other members of the porphyrin family have similarly been labeled with high efficiency using this radiolabeling procedure. In surmnary, members of the porphyrin family, and probably other compounds with a square planar arrangement of nitrogen atoms, can be rapidly and efficiently radiolabeled using readily available In-lll oxine as the starting material.

S192

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 potenlial of labeled monoclooal antibodies. We have investigated two pentafiourophenyl (PFP) derivatives for use as reagents in the synthesis of F-18 labeled proteins. These agents were tested for the rapid labeling of liSA in relatively high yield. F-18 was incorporated into pentafluorobenzaldehyde, using the tetrabutylammonium (TBA) salt in DMSO, with a 60% decaycorrected 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-tetrafluorophenylpentafluorobenzoate readily incorporated F-18 under similar conditions, and reacted quickly with HSA, to give an absolute yield of 15% labeled HSA, in 72 rains., based on starting tetrabutylammonium fluoride (TBAF). This method appears to be better than existing methods in terms of overall yield and synthesis time. Biodistribution 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 rain. 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.

T h u r s d a y , A u g u s t 30, 1990

833

834

F-18 LABELED FLUCONAZOLE (F-18[FL]): SYNTHESIS, BIODISTRIBUTION IN RATS, AND IMAGING OF RABBITS. 1E. Livni, A.J. Fischman, D.R. Elmaleh, L. Du, H.W. Strauss, R.H. Rubin, 2RJ. Dahl, W. Robson, D. Margouleff, 3R. Liss, 4D. Webb, S. Ray, I. Sinclair. 1Massachusetts General Hospital, Boston, MA, 2 North Shore University Hospital, Manhasset, NY, 3Sears Associates, Boston, MA, 4Pfizer Inc., Sandwich, United Kingdom.

NONINVASIVE MONITORING OF THE DEGREE OF TARGETING OF DRUGS AGAINST AIDS: STUDIES WITH 18F-3 "-FLUORO3 '-DEOXYTHYMID INE. I.K. Wilson, S. Chatterjee and W. Wolf, Radiopharmacy Program, University of Southern California, Los Angeles, CA, USA

Organ 5sin 30min 60min 120sin blood 0.44 0.51 O.33 O.22 liver 2.57 2.58 2.87 3.40 brain 0.16 0.23 0.29 0.14 kidney 0.65 0.57 0.41 0.51 bone 0.39 0.43 0.43 0.43 muscle 0.26 0.33 0.34 0.31 When pharmacolgical doses are administered these concentrations are in excess of that required to inhibit growth of invading yeast. Whole body PET images of rabbits injected with F-18[FL] revealed the highest uptake in the liver and kidneys, and demonstrable accumulation in the other organs as well. This approach will allow us to delineate the in vivo distribution of FL in a variety of disease states.

3 '- fluoro-3 '-deoxythy~nidine (FDT) , the fluorine analog of AZT, is a potent agent effective against the HIV virus. Although its in vitro therapeutic index in HIV infected MT4 cells is 5 times higher that AZT (i), its narrower selectivity index appears to control its therapeutic effectiveness in the treatment of patients wit AIDS (2) . Because noninvasive nuclear medicine techniques are ideally suited for monitoring how much of the drug administered has targeted to the desired organ/tissue sites, we have developed a method for the radiolabeling of FDT with 18F. Starting with thymidine, its 5"-OH is protected by tritylation, the 3 '-OH is tosylated and inverted into the iyxo configuration. Fluorination with DAST, in the presence of 18F-, and detritylation, yields chromatographically pure 18F-FDT. Critical synthetic steps whose conditions need to be carefully controlled are the fluorination and specially the detritylat ion reactions. This compound can now be used to monitor drug targeting, so as to select which conditions of drug administration would allow adequate targeting to sites infected with HIV. This work has been supported, in part, by the State of California Universitywide TaskForce on AIDS. (I) E. Matthes at al., Biochem. Biophys.Res.comm. 15___~3, 825-31, 1988. (2] P. Hardewijn et el., J.Med.Chem. 30, 1270-8, 1987

835

836

TRANCIENT ISCHEMIC DILATION OF LEFT VENTRICLE OBSERVED IN D I PYRIBAMOLE - LOADED THALLIUM-201 MYOCARDIAL PERFUSION IMAGING (MPI ). T. Toyama* , N. Takahashi' , T.Nakashima* , T. Odori" , T. Matsushita', T.Tanaka'', Y.Ishii" and K.Torizuka*. *Fukui Medical School, **Fukui Cardiovascular Center, Fukui; Japan.

IMPROVING THE SPECIFICITY OF DIPYRIDAMOLE-THALLIUM IMAGING FOR CARDIAC RISK ASSESSMENT BEFORE NON-CARDIAC SURGERY WITH SEMI-QUANTITATIVE INDICES OF SEVERITY AND EXTENT. J. Lette, P. Rene, D. Waters, M. Cerino, M. Picard, A. Gagn0n, M. Ker0uae, M.C. Eybelin, and A. Levasseur~ Maisonneuve Hospital, St. Luc Hospital, Verdun Hospital and the Montreal Heart Institute, Montreal, Quebec, Canada.

Fluconazole is a new antifungal agent effective in the treatmentof systemic yeast infection. To study the in vivo pharmacokinelics of FL the drug was labeled with F-18 by a modified Schiemann reaction on the amino precursor. F ~gF F~NHz r~N H O r ~ '''

~N Ha s J

...... omnl.....

v

~g~

v

zH=,

N,Nb ~N

The biodistribution of F-18[FL] was determined in rats at 5,30,60, and 120 min ( % dose/gm).

Trancient ischemic dilation (TID ) was reported to be observed on stress MPI, immediately after exercise or dipyridamole loading. W e try to investigate w h e t h e r TID is related to severity of ischemic heart disease. Subjects and method: Subjects involved in this study were ii0 patients with suspected ischemic heart disease which comprised of 48 cases of one vessel disease (IVD), 30 cases of two vessel disease (2VD) ~ 19 cases of three vessel disease (3VD), and 13 cases of normal coronary angiographic findings. These patients underwent both c o r o n a r y ang• and d i p y r i d a m o l e loaded MPI (DLMPI). To evaluate the presence of TID, SPECT imaging was performed on each patient immediately after and three hours after d i p y r i d a m o l e loading, and all these data were visually compared. Results: T I D was observed 6.3% in IVD'S, 16.7% in 2VO's, 42.1% in 3%rD's, and there were significant difference by student T test, between IVD's and 2VD' s as well as 3VD' s. In all four cases with bypass graft surgery, TID was disappeared in follow up study. Conclusion: TID in DLMpI revealed to be a good marker of multivessel Coronary artery disease, with its sensitivity and specificity of 27% and 95%, respectively.

Friday, A u g u s t 31, 1990

Thallium-dipyridamole (Dip-tl) imaging is used to assess cardiac risk prior to non-cardiac surgery. Accepted practice is to operate on pts with normal (N) scans or fixed defects (FD) and to investigate those with reversible (coy) defects. We further subdivided pts with roy defects into subgroups, using a scoring system to evaluate the extent and severity of the rev defects. We prospectively followed 178 pts (76 women and 102 men), aged 32 to 85 (mean=62 yrs); 105 had a history of coronary disease, 91 (51%) were asymptomatic, 31 (17%) had atypical chest pain and 56 (31%) angina. Surgery included 120 vascular and 58 major general procedures. Scans were divided into 6 myocardial regions; roy defects were graded according to severity and extent using 4 indices. Results: There were 158 uneventful outcomes and ZO post-op cardiac events (7 non-fatal MIs and 13 cardiac deaths). The sensitivity and specificity of Dip-tl testing interpreted as either positive [rev defect(s)] or negative (N or FD) were 95% and 38%. The specificity could be markedly improved by using the indices to subdivide pts with rev defects into subgroups with a cardiac risk ranging from 17= to 90% (p
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838

NONINVASIVE DETECTION OF FREE CYTOSOLIC ADENOSINE IN THE ISCHEMIC HEART USING POSTRON EMISSION TOMOGRAPHY. M.M. Henrich I, A. Deussen 3, K. Hamacher 2, H. Herzog*, M. Borst 3, H.H. Coenen 2, G. St~cklin z, J. Schrader 3, L.E. Feinendegen I . i) Institut f6r Medizin, 2) Institut f~r Chemie i, KFA JOlich, 3) Physiologisches Institut, Univ. DUsseldorf, FRG.

A PROSPECTIVE STUDY COMPARING THALLIUH-201 IMAGING AFTER INTRAVENOUS ADENOSINE INFUSION AND EXERCISE TESTING IN THE DIAGNOSIS OF CORONARY ARTERY DISEASE.

Adenosine is known as a sensitive marker of cardiac ischemia. Recently a kinetic method for determination of free cytosolic adenosine was developed via measurement of S-adenosyl homoeysteine (SAH) after infusion of homocysteine (HCY) (adenosine + L-HCY = SAH + H20: Deussen et al. Circ Res 63: 250-261). The present study applies this approach to the noninvasive detection of ischemia using PET with I-[C-II]D,L-HCY thioiactone (Hamacher et al. J Nucl Med 29: 755). Animal experiments were carried out in 5 anaesthetized open chest dogs. The circumflex artery was stenosed (coronary flow -35%, mean distal coronary perfusion pressure -40 mm Hg). HCY infusion did not affect hemodynamic parameters. After the end of C-f1 HCY infusion, the tracer concentration in the blood decreased with a half life of 40 min. PET scans exhibited a clear delineation of the underperfused region. Under these experimental conditions k~ estimated from Patlak graphical linearisation is expected to be proportional to the free cellular adenosine concentration. Thus an increase of the free adenosine concentration by a factor of seven was calculated for the ischemic compared to the normal myocardium. The dose related uptake was 0.027%/cc organ in the kidneys, 0.013%/cc in the liver, and 0.007%/cc in the nonischemic myocardium. Thus the present method assesses regional changes in free adenosine concentration and may also be clinically useful for the evaluation of regional ischemia.

E. Coyne, P. Vande Streek, D. Belvedere, F. Weiland, L. Spaccavento, R. Evans, and R. Borchert, Wilford Hall USAF Medical Center, San Antonio, Texas. Adenosine produces vascular smooth muscle relaxation and dilatation of coronary resistance vessels. We compared the predictive value of intravenous adenosine coupled with Thallium-201 (Ad-TI) with that of exercise Thallium testing (Ex-TI) in the diagnosis of coronary artery disease(CAD). Forty patients with angiographitally proven CAD and 50 subjects with no angiographic evidence of significant CAD or low probability of CAD received adenosine at 140 mcg/kg/min for 6 min. The thallium dose was given 3 minutes into the infusion and single photon emission computed tomography was performed immediately and 4 hours after the infusion. No patient required termination or interventional therapy due to side effects of the infusion. Sensitivity Specificity -Predictive +Predictive Ad-TI 83% 78%* 85% 75% Ex-TI 78% 78% 81% 74% *(p=not significant) The predictive value of Thallium scanning after adenosine infusion compared favorably to exercise Thallium testing. The dose of adenosine administered in this study was well tolerated. Adenosine infusion with Thallium imaging appears to be useful in the diagnosis of coronary artery disease. This diagnostic approach may be of particular value in patients unable to adequately exercise on treadmill testing.

839

840

DETECTION OF ASYMPTOMATIC ISCHEMIC HEART DISEASE IN CEREBROVASCULAR PATIENTS BY DIPYRIDAMOLE THALLIUM MYOCARDIAL IMAGING. G.Carini, G.Di Pasquale, *A.Andreoli, S.Urbinati, M.Ruffini, A.M.Lusa, P.Grazi, ~ ~ G.Pinelli. Divs of Cardiology and *Neurosurgery, Bellaria Hospital, and ~ of Nuclear Medicine, S.Orsola-Malpighi Hospital, Bologna, ItaEy. Ischemic heart disease (IHD) has a critical influence on the prognosis of cerebrovascular pts.ln order to evaluate the incidence of asymptomatic IHD in pts with cerebral ischemia unable to perform a maximal exercise testing, we prospectively investigated 36 consecutive pts (19 transient ischemic attacks, 17 mild stroke), 28 males and 8 females, aged 45-69 yrs (mean 58.8) without angina or previous myocardial infarction.All pts underwent clinical evaluation, CT scan, cerebral angiography, ECG, and Dipyridamole Thallium Myocardial Imaging (TMI) (0.56 mg/Kg i.v. over 4', followed by 4' of handgrip and i.v. injection of thallium at 7th minute). Dipyridamole TMI showed a normal scan in 14 pts and a perfusion defect in 22 (62%) (reversible in 20, fixed in 2). The average number of scintigraphic segments with perfusion defects was 2.2 per patient (Thallium activity measured in 8 myocardial segments). Dipyridamole infusion increased the heart rate (HR) from 67+10 to81_+12 (p<0.001) and slightly decreased the systolic blood pressure (SBP) from 160+21 to 150+20; the following handgrip increased HR to 95+12 (p<0.001) and SBP to 169+25 (p<0.01). ECG showed ST segment depression with angina in 1 case and T wave changes in 4. Minor side effects were observed in 5 pts (dizziness in 3, flushing in 2), symptomatic hypotension requiring aminophyiline in 1. Twelve pts underwent carotid endarterectomy with uneventful clinical course. During a mean follow-up period of 16 months after discharge 2 pts with abnormal TMI had a fatal myocardial infarction. In conclusion our findings suggest that in over one half of pts with cerebral ischemia a silent IHD is present. Dipyridamole TMI can be proposed as a safe and reliable examination in the non invasive screening of those cerebrovascular pts unable to exercise.

POST-EXERCISE FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPBY RELIABLY IDENTIFIES ISCHEMIA IN DIPYRIDAMOLE INDUCED RUBIDIUM PERFUSION DEFECTS. T Marwick t WJ MacIntyre, D Neumann, R Covalesky, RT GO, E Salcedo, G saha, A Beachler. Cleveland Clinic, Cleveland, OH, USA.

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Positron emission tomography (PET) imaging of postexercise myocardial F-18 deoxyglucose [FDG) uptake may be used to directly identify ischemia. To determine whether dipyridamole-induced perfusion defects truly correspond to ischemic foci, 15 pts with angiographically documented coronary disease were studied by PET imaging before and after iv dipyridamole stress, using 40-60 mCi of Rb-82. A fasting, symptom-limited exercise test was performed separately, and 4-10 mCi of FDG was injected after return to pro-exercise heartrate, with PET imaging performed after a delay of 40 minutes. A FDG/Rb ratio was calculated for each area of interest, and corrected to a standard dose of 60mCi Rb-82 and 10mCi of FDG. Normally perfused zones (within 20% of maximum Rb counts) had a FDG/Rb ratio of 0.08+ 0.03 in identical regions of interest. A reversible perfusion defect was identified b y _ 2 0 % reduction of Rb-82 uptake with stress (n=lS) - these sites had a FDG/Rb ratio of 0.18~0.08 (p0.0001). The FDG/Rb ratio of ischemic tissue was 2.3+0.68 times higher (range 1.5 to 3.3) than normal tissue. Conclusion. Dipyridamole-induced changes in coronary perfusion correlate closely with ischemic areas documented by exercise-FDG PET imaging.

F r i d a y , A u g u s t 31, 1 9 9 0

841

842

PROSTATE SPECIFIC ANTIGEN (PSA) AND BONE SCINTIGRAPHY IN THE DIAGNOSIS OF PROSTATIC MALIGNANCY R.J. Iorns, M.A. Macleod, I.L. Jenkins, Royal Naval Hospital Haslar, Gosport, U.K.

RADIOIMMUNOLOGIC CA-19-9 TEST IN DIAGNOSTICS MALIGNANT PANCREATIC DISEASE.

Prostate Specific Antigen serum assay has been successfully used as an indicator of prostatic malignancy for several years. In addition it has been claimed that PSA values are raised in cases of Benign Prostatic Hyperplasia (BPH) thereby increasing the level of false positive values for malignancy. In this study we have compared PSA assay levels with bone scintigraphy in known cases of prostatic adenocarcinoma (ADC) and BPH. Data on 67 cases of histologically defined ADC and 73 cases of BPH are presented. In patients with ADC the ?SA level was normal in 6 (9%), equivocal in 8 (12%) and raised in 53 (79Z). Of the 45 bone scans performed in this group 29 were positive for metastases and 16 negative. In the group with 29 positive scans the PSA was raised in 23 cases, equivocal in 3 and normal in 3 cases. In the 73 cases of BPH, PSA levels were normal in 30 (~IZ), equivocal in 25 (34Z) and raised in 18 (25Z) cases. Bone scans performed in this group showed 5 positive for metastases and 16 negative. Of the 5 positive bone scans PSA was raised in 4 and equivocal in i. In the negative bone scans PSA was raised in 2 (one with chronic prostatitis), equivocal in 5 and normal in 9. We conclude that PSA is a sensitive indicator for prostatic malignancy, and the results suggest that patieots with BPH may have underlying malignancy and a raised PSA serum value cannot be dismissed as a false positive.

843 CLINICAL

L.I. Vinnitsky, I.A. Egorova National Research Center of Surgery, Moscow,

OF

USSR

Radioirmnunologic CA-19-9 test presents an important additional means of complex diagnostics of the malignant pancreatic neoplasms. Our experience included 314 patients with different surgical pathology of the abdomen. Malignant disease of the pancreas was verified in 70 of them (cancer of the pancreas, tumor metastases of various localization in the pancreas). In 65 patients with the malignant pancreatic disease CA-19-9 level proved to be significantly higher than that in patients with the benign pancreatic and abdominal disease. False-negative results were registered only in 5% of cases. Diagnostic sensitivity and specificity of the test was 92%. CA-19-9 marker can be successfully used for diagnostics and differential diagnostics of the malignant and benign pancreatic disease and for early identification of the recurrent tumors.

844 EVALUATION

OF

NEWLY

DEVELOPED

RIA

KIT

FOR

TUMOR MARKER C A - 1 3 0 T. Nakashima, T. Toyama, N. Takahashi, T.Matsushita, T. Odori, Y. Ishii and K.Torizuka. Fukui Medical School, Fukui, Japan. R. Nakamura,

Introduction: CA-130 is a newly developed RIA kit uti liz~ng two distinct monoclonal antibodies raised against lung cancer cell line, PC-3. It can measure the tumor marker CA130 which simulate CA-125, by simple one-step sandwich method. AIM: TO establish the diagnostic capability of CA-130 in various malignant disorders, and the variations in normal subjects. Materials and Methods: CA-130 kits were supplied by DaiichJ Radioisotope Labs. Sera from normal volunteers and patients with various malignant diseases were stock frozen at - 20 ~ C until CA-130 measurement. AS for females, periodical blood sampling was performed from 6 volunteers to check the serum CA-130 variation during menstrual cycle. Results: Normal range exist in 6--+2.Z U/ml in male (N=59 ), and 20-+ 5.3 U/ml in female (N= 6 ) showing similar distributions as CA125. But in females, periodical variations in accordance with the menstrual cycle were found, with highest value at menses. In malignant disorders, CAI30 value showed the similar distribution pattern as in CA125~ for example, higher value in ovarian cancer. There was no relationship with the value of CEA, or A F P r and slight correlation with T P A . Conclusions: CAI30 has similar characteristics as CA125, with much simpler assay procedure, Periodical variations during normal female menstrual cycle needs further study.

Friday, August 31, 1990

A NEW TUMOR MARKER (TATI) A N D I T S C O M P A R I S O N W I T H C E A , C a 125, C a 1 9 - 9 A N D C a 1 5 - 3 IN D I F F E RENT MALIGNANCIES. P. K o u t s i o u b a , L. G o g o u , E. T r i v i z a k i , P. P o zantzidou, P. N a t s i s . M E T A X A Cancer Hospital of Piraeus, Greece. Tumor associated trypsin inhibitor(TATI), has recently been discovered in a t t e m p t s to find new markers for gynecological cancer, but occurs in high concentration in t h e s e r u m o f patients with others malignancies. T h e a i m of t h i s s t u d y w a s t o c o m p a r e TATI and others tumor markers in m a l i g n a n t and benign disorders.We measuredCEA,Ca125,Ca19-9,Ca 1 5 - 3 a n d T A T I in 5 4 8 p a t i e n t s with cancer in different stages(88 ovarian,59 endometrial,156 gastrointestinal,180 breast,33 lung,15 urinary a n d 17 h e a d - n e c k cancer.Also we examined 55 normal sybjects a n d 70 w i t h b e n i g n d i s e a s e s . Increased values of TATI we odserved:49% in endometrial,47,5% in g a s t r o i n t . , a n d 42% in o v a rian cancer.We found elevated l e v e l s o f C E A in 35,9% of patients with gastroint, cancer,47,5% of C a 1 2 5 in o v a r i a n cancer,44,7% of C a 1 9 - 9 in gastroint, c a n c e r a n d 3 1 , 1 % of C a ~ - 3 i n b r e a s t cancer. TATI and Ca19-9 were positive i n 90% in pancreatic cancer,58,3% and 92,3% respectively in h e p a t o b i l i a r y cancer. In advanced stages of breast cancer the levels of all markers were u p p e r 50% a n d t h e r e c o m b i n a t i o n increased the diagnostic r a t e f o r c a n c e r to 8 5 % . According to o u r r e s u l t s , s e r u m T A T I is e l e v a t e d in 90% a n d 5 8 , 3 % o f p a n c r e a t i c and hepatobiliary c a n c e r as C a 1 9 - 9 . 1 n gynecological c a n c e r T A T I is c o m p a r a b l e with Ca125 and in the breast cancer with Ca 15-3.

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846

EVALUATION OF THE TUMORI~KER TATI I N H E A D AND NECK CANCER COMPARED TO SCC-ANTIGEN. R.Senekowitsch, A.LOrken, B.Clasen and H.W.Pabst. Nuklearmedizinische Klinik, HalsNasen-Ohren-Klinik,Technische Universit~t M~nchen,FRG

THE IMPORTANCE OF MONOCLONAL TUHOUR MARKERS IN NITAL GASTROINTESTINAL ANOMALIES.

With the most frequently used tumor marker in o t o l a r ! r n g o l o g y the S C C - ( s q u a m o u s - c e l l - c a r cinoma) antigen only a low sensitivity can be o b t a i n e d . T h e a i m of t h e p r e s e n t s t u d y w a s t h e r e f o r e t o e v a l u a t e the n e w R I A for T A T I ( t u m o r a s s o c i a t e d t r y p s i n i n h i b i t o r ) for d i a gnosis and therapy control of patients with h e a d a n d n e c k c a n c e r c o m p a r e d to S C C - a n t i g e n . B o t h a n t i g e n s e r u m l e v e l s w e r e d e t e r m i n e d in 55 h e a l t h y p e r s o n s , 45 p a t i e n t s w i t h b e n i g n d i s e a s e s of t h e h e a d a n d n e c k r e g i o n a n d 69 p a t i e n t s w i t h s q u a m o u s c e l l c a r c i n o m a of t h e h e a d a n d n e c k . T u m o r s t a g i n g w a s p e r f o r m e d acc o r d i n g t o t h e c r i t e r i a of t h e T N M - c l a s s i f i c a tion. T h e i n v e r s e d i s t r i b u t i o n f u n c t i o n s d e m o n s t r a t e a c l e a r d i s t i n c t i o n b e t w e e n the 3 d i f f e r e n t g r o u p s for T A T I w h i l e t h a t for SCC w a s n o t s i g n i f i c a n t . A t a s e n s i t i v i t y of 82 % ( c u t - o f f l e v e l 22 n g / m l ) T A T I s h o w e d a s e n s i t i v i t y of 48 % w h e r e a s t h e s e n s i t i v i t y f o r S C C w a s o n l y 3 1 % at t h e s a m e s p e c i f i c t y of 82 % ( c u t o f f l e v e l 2.3 n g / m l ) . T h e c o r r e l a t i o n b e t ween TNM-staging and TATI-levels revealed a s i g n i f i c a n t i n c r e a s e in s e n s i t i v i t y w i t h t u m o r e x t e n t . A t T1 o n l y 22 % w e r e t r u e p o s i t i v e w h e r e a s a t T4 t h e s e n s i t i v i t y w a s 57 %. E l e v a t e d S C C - a n t i g e n s e r u m levels, h o w e v e r , d i d n o t show any correlation with tumor extent. Theref o r e T A T I s e e m s to b e t h e b e s t a v a i l a b l e m a r k e r f o r h e a d a n d n e c k cancer.

31 patients (mean age=101.5~23.5 days) who have different congenital gastrointestinal anomalies (CGA) 9 aganglionic megacolon, 7 hyper.trophic pyloric stenosis ,5 anal atresia, 3 anterior ectopic anus,2 ileal atresia ,2 oesophageal atresia,l colonic atresia, l duodenal atresia,l omphaloeel were studied by measuring their serum concentration of monoclonal tumour markers CEA,CA 125,CA 19/9. A control group with similar age and sex distribution were used to compare with the results obtained from the pathologic group. Serum concentrations of CEA,CA 125,CA 19/9 were measured by IRMA using double samples. Preoperative diagnosis was confirmed in all cases postoperatively. We have not found any statistically significant difference between control and CGA group in CEA,CA 19/9 levels. However,we observed a significant increased values of CA 125 levels in CGA ( p<0.05 ).Table I. CEA(ng/ml) CA 19/9(U/ml) CA 125 (U/ml)

847 KINETICS OF MDP Tc-qgmINEXPERIMENTAL OSTEOSYNfHESIS FROM EXTERNAL GAMMA MEASUREMENTS L.de Morais, A. R.Nogueira, A.M. Baptists Fac~idade de Medecina Veterin~ria and Instituto Portugues de Oncologia de Francisco Gentil-Lisboa-Portugal Experimental osteosynthesis was induced by various surgical procedures (intracavittary pins,plates and screws and external hemitaxia) in dogs. An attempt is made to derive quantitative data clinical useful from external measurenleats after injection of HDP Tc-99m. The main objective of the study was to compare the clinical efficacy of rigid and non-rigid fixation in osteo synthesis.lt was hoped that the elastic and blastic tom ponents of the process could be related to relevant parameters derived from the kinetic results. The study was performed in 8 dogs,and the data obtained with a computerised gamma camera at 48 h,8 d,15 d,30 d, and 120 d after the surgical intervention. The radioactivity me]surements for 30 rain after injection of MDP -Tc99m could be well fitted to gamma functions. It could be concluded from the parameters of the gamma fuactions that this quantitative approach was quite use ful by its simplicity and rigor to follow the osteosynthesis process in agreement with the corresponding clinical results. Contrary to some published results the rigid fixation leads to a less active osteolitic component after 120 d of the fracture as could be concluded from our kinetic study results, and in agreement with the clinical,morphological, biomechanical, and histological studies per formed in the same animals.

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CONGE-

M. ERKILIC, S. ASLAN, M. MELIKOGLU. DEPARTMENT OF NUCLEAR MEDICINE AND PAEDIATRIC SURGERY AKDENIZ UNIVERSITY,FACULTY OF HEDICIh~B,ANTALYA,TURKEY.

CONTROL(n= 17) 2.58u 26.38;4.24 I0.9252.29 CGA(n=31) 3.76~0.89 33.29u 36.52u ...................................................... Table I. p<0.05 for CA 125. As a result of our study,we observed that the increased value of CA 125 level is not related with placental transfer and can be used as a diagnostic factor in the management of CGA patients.

848 QUANTITATIVE BONE SCANNING IN PATELLAR PAIN M.ERKILIC,A.T.AYDIN,B.KARAYALCIN,A.YILDIZ. DEPARTMENTS OF NUCLEAR MEDICINE AND ORTHOPAEDICS, AKDENIZ UNIVERSITY,FACULTY OF MEDICINE,ANTALYA,TURKEY. 34 Young patients (mean age:28 +5.56 years) who have patellar pain that is undetectable by other commonly used methods were studied by quantitative hone scintigraphy.As an objective index,patello-femoral ratio (PFI) was used in order to evaluate patellar pathologies. The scans were performed two hours i.v administration of 555 MBq 99mTc-Hydroxy Methylen Diphosphonate.The count information of both lateral views of knees were recorded on disk for further processing.4x4 pixel area were chosen both on central and subchondral region of patella.For femoral ROI,one third distal region was chosen and PFI was calculated after background substraction by formula; Patellar cnts./Patellar+ Femoral cats. PFI values in symptomatic and nonsymptomatic knees were shown in Table I. SYMPTOMATIC NONSYMPTOMATIC Central Subchondral ................................. PFI 71.2%9.7 86.278.4 55.273.4

(%) All symptomatic PFIs were significantly increased and subchondral ROils values were greater than central ones.This difference was statistically significant (p<0.05). Quantitative bone scanning by using especially subchondral ROils PFI is noninvasive and very sensitive method in the management of patellar pain.

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ASSESSMENT OF SKULL BASE INVOLVEMENT IN ~ASES WITH NASOPHARYNGEAL CARCINOMA--COMPARISON OF SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY WITH PLANAR SOINTIGRAPHY. Pei-Wen Wang, ChJang-Hsuan Li, Hue-Yong Chen. Chang Gung Memerla] Hospital, Kaohsiung, TaJwan, R.O.C.

QUANTITATIVE BONE SCINTIGRAPHY IN ASYMMETRIC PROGNATHISM. H W GRAY, L STASSEN, A EL-ATTAR, K F MOOS, R G BESSENT. Royal Infirmary and Maxillo-facial Unit, Canniesburn Hospital, Glasgow, Scotland.

The complex structure of the skull may cause difficulties in delectJon and localization of local bony invasion in cases with nasopharyngeal carcinoma (NPC), a neoplasm most commonly attacks Chinese and easily invades the skull base. Thlrty-nJne ps~Jents (31 male, 8 female; age 20-65, mean 47) with pathologJceily proved NPC before radiotherapy were simultaneously assessed with planar and SPE~T examJnaLJon of the skuli base. In planar sLudy, AP ,PA and both oblique views of skull were acquired using a LFOV r-camera (Starcam 400 AO) with h~gh resolulJon collimator at preset count of 350K and matrix size of 256x256. The SPEOT sIudJes were performed by the same camera with high resoiuIJon collimator rotating over 360 degrees. Sixty-four projections were obtained Jn a 64x64 matrix with an acquisition time of 30 sec per projeclJon. The results of the 39 cases were as feiisws:(1).Ten patients had normal SPECT and planar scintJgraphy.(2). Seven patients with limited bony lesion in clJvus and body of sphenoid had essentially the same posJ(Jve findings Jn both studies.(3). Eighteen palJents' SPECT studies were superior to planar, prov#dJng better anatomical localization and defining lhe full exIent of the lesions, especJaliy in the sphenoJd and peIrous bones. (4). Four patients' SPECT studies were abnormal while planar scJntJgraphy were norma~. Our findings supported the potenI~al of SPEOT to deteel lesions ~n the deep bones of the skull that can not be visualized clearly with Ihe planar scJntJphotography.

22 patients, age range ]I-33, presenting with asymmetric prognathism had radiographic and scintigraphic investigation of the temporomandibular (TM) joint to assess the role of quantitative scintigraphy in diagnosis and management. Imaging of lateral skull (128 x 128) using IGE Maxi camera and low energy high resolution collimator was performed 4 hours after 600 MBq Tc-99m MDP. 16 pixel ROI's were selected over each TM joint. Background was I pixel thick around joint area. Results were expressed as left:right differential uptake. The I SD error of individual joint quantitation was 12%. Quantitative scintigraphy correctly indicated condylar hyperplasia or mandibular hypertrophy in 16 of 22 (sensitivity 73%). Twelve studies showing a differential uptake of 60:40 or over were true positives. Scintigraphy compliments other techniques, assists in differential diagnosis and allows earlier surgery.

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IN VIVO MIGRATION OF IEUCOCYTES IN RHEUMATOID

SCINT1GRAPHIC PATTERNS OF ACUTE AND CHRONIC BRUCELLOSIS ON BONE SCAN.

ARTHRITIS


MA AL-JANABI, PJ MALTBY, K SOLANKI, M CRITCHLEY, KE BRITrON. Departments of Nuclear Medicine, Royal Liverpool Hospital, Liverpool and St Bartholomew's Hospital, London. UK Objective assessment of inflammation in arthritic joints relies on estimating warmth and swelling; the relationship between pain and the different components of the inflammatory response is poorly docunented. We have assessed inflammation in the joints of patients with R A a f t e r an IV injection of 500 MBq 99Tcm-~n~PAO. The knees of 5 normal volunteers and 1 3 p a t i e n t s w i t h R A w e r e imaged w i t h a gamma camera - computer system. 9/13 ware also imaged after i.a. steroi,d injection. Pain at the time of scanning was assessed using a visual analogue scale. All patients had a full blood profile performed together with thermogra~hy. Activity in the knee was also expressed a s p e r e e n t of injected dose (ID). All 13 patients showed significant neutrophil migration at 22 hours (mean 0.12% ID). 3 normal volunteers showed no uptake at 22 hours. There was linear correlation between reduction in pain scores and neutrophil migration in the injected knees (r--0.86, p=<0.001). There was no correlation between thermographic results and pain scores or white cell uptake. 3 patients were scanned sequentially over a period of 3 months where high pain scores and neutrophil migration preoeded clinical detection of inflammation by several months. Conclusion - This technique appears to provide a sensitive and quantitative method of assessing inflammation in individual joints with RA.

Friday, August 31, 1990

A.R. A1 Suhaili*, R.H. Bahar, S. AI Mohannadi. A.H. Elgazzar, A.R. Mouse, E. Higazi, H.M. Abdel-Dayem Departments of Nuclear Medicine and Medicine, Mubarak A1 Kabeer, Aden Hospitals and Faculty of Medicine - Kuwait, fawam Hospital, AI Ain, UNITED ARAB EMIRATES. Brucellosis is endemic in many countries, particularly in the Middle East. Radionuclide bone scan is a sensitive modelity to detect bone and joint involvement. The aim of this study is to find out various patterns of bone and joint disease secondary to brucellosis on bone

scans.

83 patients were studied, 31 with acute and 52 with chronic brucellosis. Bone scan were positive in 63 patients (76%), in 17/31 patients having acute (54%) and in 46/52 patients having chronic brucellosis (86%). 7 patterns were observed: I. Involvement of the entire body of one or more vertebrae especially at lumbar region (37%), 2. Focal area of high activity at the margin of vertebra 'caries sign' (295), 3. Multiple costovertebral joints and eostochondral junctions (13~), 4. Sacroiliitis (38%), 5. Osteoarthritis of large joints (33%), 6. Solitary focal area in a long bone (15%), 7. Involvement of multiple areas in the axial and appendicular bones simulating metastases (1%) We conclude that brucellosis causes certain scintigraphic patterns on bone scan. Nuclear Medicine physicians should be familiar with such patterns that can predict the diagnosis.

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Tc-99m-LABELLED CYSTEINE K. Ozker, B.D. Collier, A.T. Isitman, H.M.Abdel-Dayem, A. Sungur, A. Amac, N. Hoskan, N. Ardagil, I. Urgancioglu. Istanbul University and Medical College of Wisconsin.

In-lll PHOTOFRIN-II: A NEW TUMOR IMAGING AGENT FOR INTRACRANIAL NEOPLASMS. S.M. Karesh, T.C. Origitano, J.R. Halama, O.H. Reichmann, and R.E. Henkin. Loyola University Medical Center, Maywood, IL, USA.

Aminoacids labelled with positron emitters were used to investigate the tissue function at normal and neoplastic states by PET. Present study deals with the labelling of an aminoacid, L-cysteine with Tc-99m. Tc-99m-cysteine was synthesized by an electrolytic procedure involving an inverted serum vial, two tin electrodes (3 cm length) inserted through the rubber septum and 1 mA current, passed through a solution containing l0 mg L-cysteine and 1-3 ml Tc-99m-pertechnetate. Labelling efficiency was determined by paper and thin-layer chromatography (ITLC-SG, Gelman) and cellulose acetate electrophoresis. Using an electrical charge of 0.12 coulombs involving the generation of 74 ug tin, a labelling yield of 98.9-+1.9% was reached while no pertechnetate and only 0.6% hydrolized-reduced Tc-99m were detected. Biological distribution of Tc-99m-eysteine in mice demonstrated a selective uptake of the tracer in pancreas (2.5-+0.3%) expressed as % of dose injected/g tissue at i hour post injection. Concentration in the kidneys was high (10.2-+0.2%) while liver uptake was (1.9-+0.04%). No radioactivity was demonstrated in thyroid and stomach. In conclusion the described procedure provides a stable and pure complexation of cysteine with Tc-99m in physiological pH and mild conditions. Much lower quantities of tin is generated, in situ, avoiding the possibility of its hydrolysis. Marked uptake in the pancreas and in vivo stability strongly suggests that Tc-99m-eysteine may be a potential agent for pancreas imaging by SPECT.

Photofrin-ll is a photosensitizer used in laser photodynamic therapy (PDT) as an adjunct to neurological surgery for therapy of intracranial neoplasms. We have shown In-lll Photofrin-ll, a mixture of porphyrins, to be an effective agent in depicting the location of brain tumors. Synthesis of the In-lll complex in greater than 96% yield is achieved by a simple, rapid radiolabeling method using In-t11 oxine as the starting material. To date, patients with malignant gliomas and metastatic brain lesions have been evaluated. Prior to human investigation, this material was evaluated in a canine glioma model. Human studies were carried out using both static imaging and SPECT studies employing 3-D volume rendered displays. Excellent anatomical spatial correlation was demonstrated between SPECT imaging, contrast-enhanced CT, and contrast-enhanced MRI. Regions of intense focal uptake correlated with neoplasia as determined by surgical histopathology. The target to non-target ratio (tumor to surrounding brain), calculated from computer-generated SPECT data, averaged 5:1. This agent has potential for identification and volumetric analysis of intracranial lesions, permitting individualization of PDT planning by calculation of the optimal time window for photoactivation of the residual brain tumor.

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EXPERIENCE OF THYROID USING Clarke S E M, Department of SEI

IMAGING MEDULLARY CARCINOMA OF THE TC-99M (V) DIMERCAPTOSUCCINIC ACID (DMSA) Lazarus C R, Maisey M N Nuclear Medicine, Guy's Hospital, London

Tc-99m (v) DMSA is a new tumour imaging agent that has successfully been used to image patients with medullary carcinoma of the thyroid (MCT). Fifty two studies have been performed in 29 patients with histologically proven MCT at Guy's Hospital since 1986. Four patients with primary tumour were studied prior to surgery, 3 patients were studied after successful removal of the primary tumour and 22 were studied with biochemical evidence of recurrence, 8 patients were studied serially to assess progression of disease and 4 were studied before and after surgery. Twenty one of the 26 patients with disease had positive scans with 4 false negative scans and 3 true negative scans, i patient had a false positive scan (sensitivity 80%, specificity 75%). Two of the false negative scans were obtained in patients with moderate but stable elevations of calcitonin but no other evidence of recurrence. One false negative scan was obtained in a patient discovered on screening to have an abnormal pentagastrin response and a small volume tumour icm was subsequently removed. Uptake in local neck recurrence was frequently intense, hut uptake at sites of bone metastases was less marked. False positive uptake was seen in the sternum after surgery. Tc-99m (v) DMSA is a cheap radiopharmaceutical, producing good quality images and has been shown to have an acceptable sensitivity and specificity in the follow up of patients with MCT, contributing significantly to management.

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ANTI-CEA IMMUNOSCINTIGRAPHY (Tc-99m MAb BW 431/26) AND SERUM CEA LEVELS IN PATIENTS WITH SUSPECTED COLORECTAL CARCINOMAS AND RECURRENCES. P.Lind_, P.Lechner, W.Langsteger, G.Binter, P.Kfltringer, H.Cesnik and O.Eber Internal Department, Barmherzige Briider Graz, Austria With the introduction of Tc-99m labeled monoclonal antibodies against CEA a clinically relevant extension can be expected in the diagnosis of colorectal tumors by immunoscintigraphy (IS). This study comprises a total of 102 patients (primary colorectal carcinomas [PCC], occult neoplasms and suspicious colorectal recurrences [CR]), in whom IS with Tc99m MAb BW 431/26 was performed. After injection of 1100 MBq Tc-99m labeled MAb whole body scan 5 1/2 hours p.i. and SPECT of the abdominal region 6 and 24h p.i. were done. In the course of primary tumor identification (n=50), almost all operatively verified carcinomas (n=36) were confirmed and correctly localized by IS (sensitivity 94%, specificity 86%). In the diagnosis of recurrences (n=52) IS revealed an uptake in computer tomographically and coloscopically suspicious areas in 26 cases (24 fight positive, 2 false positive); in 26 cases IS was rated negative (23 right negative, 3 false negative). Especially in these patients, in whom transmission computed tomography (TCT) failed to give dear differentiation between scar and recurrence, IS was the method of choice to clarify the problem (sensitivity 92%; specificity 88%). Overall sensitivity of IS in patients with suspected colorectal carcinomas and recurrences was 93%, specificity 87%. In contrast to anti-CEA IS, the results of serum CEA levels were rather disappointing (sensitivity: 47% in PCC and 64% in CR resp.; specificity: 65% in PCC and 69% in CR resp.). According to our clinical experiences with this Tc-99m labeled monoclonal antibody anti-CEA IS plays a preeminent role in the exclusion or identification of colorectal recurrences. Therefore, in postoperative colorectal cancer care IS should be perfommd in cases with unclear-TCT, even if the serum CEA level is in the normal range.

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RADIOIMMUNOSCINTIGRAPHY OF COLORECTAL CARCINOMA UTILIZING THE MOAB CYT-103 LABELED w1"rH In-111.

SUCCESSFUL STAGING OF SMALL CELL LUNG CANCER (SCLC) WITH MONOCLONAL ANTIBODY. Wil B. Nelp, R.G. Griep, D. Salk, P. Abrams, V. Suppers, M. Hanley and a Multi-center Study Group; Division of Nuclear Medicine, University of Washington and NeoRx Corporation, Seattle, WA, USA.

C.E. Neal. T.L. Swan. M.R. Baker. R.D. Cull, J.G. Katterhagen. Memorial Medical Center, Springfield, IL. Eleven {11) consecutive patients with known or subsequently proven colorectal carcinoma were prospectively studied by CT. radiolabeled monoclonal antibody scans (MoAb), and surgical exploration to gauge the utility of this MoAb in the detection of primary or recurrent intra-abdominal carcinoma. Eighteen (18) distinct tumor sites were demonstrated and confirmed pathologically. The monoclonal antibody used in this study, CYT-103, is B72.3, site-specifically labeled with In- 111 by the GYK-DTPAmethod developed by Cytogen. Patients received either 0,5 rag, 1.0 rag, 2.0 rng or 20 mg of MoAb labeled with 4 to 5 mCi of In~ Planar images of the chest, abdomen and pelvis and SPECT imagizlg of the abdomen and pelvis were obtained 2 to 7 days after injection. 78% (14/18) pathologically proven malignancies were demonstrated by MoAb while CT interpretations suggested malignancy in only 39% {7/18) of these lesions. More importantly, MoAb demonstrated carcinoma in 27% (3/I 1) of the patients in this study where CT found no evidence of malignancy. MoAb and CT results combined to detect 15/18 (83%) pathologically proven lesions. Significantly, CT assessed 3/18 (17%) pathologically proven carcinomas as benign diagnoses. These results demonstrate that CYT-103 is a promising adjunct in the detection of recurrent or metastatic colorectal carcinoma.

The treatment of SCLC, 20% of all lung cancers, is critically dependent on staging to determine if there is limited or extensive disease. Standard clinical staging includes CT of the head, chest and abdomen plus a bone scan and bone marrow examination. In this phase III study 96 patients from 21 investigational sites had standard clinical staging compared to the results of a single total body survey using a Tc-99m labeled anti-lung cancer antibody (NRLU-10). The body survey was done 14 - 17 hours following injection of up to 30 mCi of Tc-99m labeled Pab. The procedure was safe and only 7% of subjects developed transient antiglobulins to NR-LU- 10. Analyses of the data using blinded review showed NR-LU-10 imaging alone identified 84% of patients with extensive disease with a positive predictive value of 98%. Any other diagnostic study alone had much less sensitivity and accuracy. Staging by antibody imaging alone was virtually as good as the entire group of standard clinical staging tests. In addition 15% of patients thought to have limited disease (standard tests) were upstaged to extensive disease following antibody imaging. We conclude Tc-99m-NR-LU-10 Fab imaging is an extremely effective and safe method for staging patients with newly diagnosed SCLC.

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METHOD OF EFFICIENT SPECT FOR BETTER IMAGING USING A ROTATING GAMMA CAMERA. M. Kaneko, H. Kawai, Y. Takehara, and M. Asumi. Hamamatsu University School of Medicine, Hamamatsu, Shizuoka-ken, Japan.

CORRECTION FOR HEAD MOTION DURING BRAIN IMAGING USING SIMULTANEOUS AND INDEPENDENT MEASUREMENTS OF HEAD POSITION: A FEASIBILITY STUDY. M. Green, R. Dextras, C. Grady and K. Kempner. National Institutes of Health, Bethesda, MD, USA.

in order to obtain better SPECT images we have developed three methods of efficient SPECT using a rotating gamma camera. The first one was originated in 1985 for the brain SPECT, which we called "Sagittal Scan". Closer to the head a gamma camera rotated over 180 degrees from frontal to occipital through vertical side of the head. Higher spatial resolution and 1.4 times higher sensitivity were obtained with this than those of conventional SPECT. One hundred twenty routine scans were performed from Nov. 1986 to Nov. 1989. The second one was for the body. Closer to the body a camera rotated over 360 degrees on two axes. Over the first 180 degrees on one axis from ventral to dorsal and over the next 180 degrees on the other axis from dorsal to ventral. The second method also enabled better SPECT image and has been routinely used since Dec. 1986 for the body SPECT. The third one was for small organs using pin hole collimator. This has been developed recently and could reveal details of hydronephrotic kidney in 7 month old baby, which was hardly obtainable with conventional SPECT. These three methods mentioned above were performed without any additional hardware but software in latter two methods and were considered significant for better SPECT imaging.

Mead motion during brain imaging reduces image quality and degrades image quantification. Practical attempts to solve this problem have focused on prevention: restraint of the head with straps, masks, enclosures of foam rubber or styrofoam, etc. Even with such methods, however, residual motion is still often sufficient to cause significant image degradation. We are investigating a method that can, at least in principle, reduce substantially this source of error while at the same time lessening the need for aggressive restraint of the head. The method uses simultaneous, independent measurements of the position of an object within the imaging field to correct the incoming scintillation data from that object for translations and rotations of the object away from some arbitrary starting position, eg. the average object position during the first 30 seconds of data collection. Translational and rotational data are obtained with an electromagnetic spatial tracking device that senses motions of a transducer attached to the object in relation to a stationary reference source. This correction scheme was tested on planar scintigraphic images of an object purposely moved (rotated through 60 degrees and translated + I cm in all directions) during imaging. While the "~lurred" images of this object were virtually unrecognizable, the corrected versions were qualitatively free of motion artifacts. Analysis of these data showed that residual blur was a fraction of a pixel. Thus, this method may prove useful in all forms of seintigraphic brain imaging by minimizing image blur due to head motion.

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HiGH RESOLUTION B R A I N SPECT WITH ACCURATE MODELING OF SPATIAL SYSTEM RESPONSE, ATTENUATION AND SCATTER. A.R. F o r m i c o n i , A. P a s s e r i , A. Pupi and G. Comis. U n i v e r s i t y o f F l o r e n c e , I t a l y .

POWER SPECTRAL ANALYSIS OF HFART RATE FLUCI~JATIONS USING A MINI-COMPUTER SYSTEM FOR NUCLEAR CARDIAC STUDIES:ASSESSMENT OF AUTONOMIC NERVOUS FUNCTION IN PATIF~TS WITH LV DYSFUNCTION. A. Tani, Y. Ishida, T. M o r o z u m i , M. Hurl, A. Kitabatake, T. Kamada, K. Kimura, T. Kozuka, M. Inoue. Osaka University Medical School, Osaka, Japan.

Our compensation of SPECT g e o m e t r i c a l system response with conjugate gradient i t e r a t i v e technique (Phys Med B i o l 34:698 4 , 1 9 8 9 ) , has been extended to compensate a l s o f o r s c a t t e r and a t t e n u a t i o n e f f e c t s . A set of line spread f u n c t i o n s was acquired in air. A set of line spread functions relative to the sole scatter component was a c q u i r e d by means o f a p r o p e r l y designed phantom. A m a t h e m a t i c a l model was fitted to these s e t s o f e x p e r i m e n t a l data i n order to take into account spatial variability of system response because of resolution, scatter and attenuation. The model was used to g e n e r a t e a s e t o f w e i g h t i n g factors which were included in the system m a t r i x for the r e c o n s t r u c t i o n . The algorithm was t e s t e d by m e a n s of phantoms (capillary, homogeneous and brain) as well as with patients brain perfusion s t u d i e s , showing that the compensation f o r a t t e n u a t i o n and scatter is accurate and object-independent. This a l g o r i t h m gave f o r the r e c o n s t r u c t e d point spread function a FWHM o f 8 mm w i t h an UHR c o l l i m a t o r . In the s a m e c o n d i t i o n s , the filtered backprojection g a v e a F W H M of 15 mm. These results d e m o n s t r a t e the p o s s i b i l i t y of o b t a i n i n g h i g h r e s o l u t i o n b r a i n S P E C T with accurately modeled attenuation and scatter compensation.

Using a mini-computer system for nuclear cardiac studies, we programmed the software of power spectral analysis (PSA) of heart rate (HR) fluctuations, and simultaneously assessed LV function (with radionuclide angiography, RNA) and autonomic nervous function (with the PSA) in 7 normals (NL) and in 16 patients with LV dysfunction, Ii with coronary artery disease and 5 with dilated cardiomyopathy. The PSA was done for serially recorded ECC R-R intervals during RNA at rest. After determining two major spectral components of the HR fluctuations, a low frequency (LF) a t e 0 . 1 Hz and a high frequency (HF) at~0.25 Hz., the normalized power of LF and HF components for total power was measured as indices of sympathetic and parasympathetic activity, respectively. The patients were divided into two groups based on LV ejection fraction (EF) at rest, 8 (Gp A) with 150% and 8 (Gp B) with <50% of LV EF. Results: n EF(%) AGE mean R-R(ms) LF(%) HF(%) NL 7 66• 47• 950• 29127 69• Gp A 8 64• 51• 9491153 31• 65• Gp B 8 33• 50i12 865• 65• 29~16" (mean• *p
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PC BASED QA AND PREVENTIVE MAINTENANCE PROGRAMS FOR NUCLEAR MEDICINE. D. Goodenough, F. Atkins, S. Dyer*, The George Washington University Medical Center, Washington, DC., and *The Institute for Radiological Image Sciences, Germantown, MD,

DEI'E~/~INATION OF THE Ps RANGE: THE PROBLEM OF SMALL SAMPLE SIZES W.D. Leslie, Health Sciences Centre, Winnipeg, Manitoba, Canada

This paper will discuss basic scientific aspects of PC based programs for quality assurance and preventive maintenance of Nuclear Medicine systems. It will start by discussing existing programs such as the original IAEA program for Computer Management of Preventive Maintenance "CMPM" and potential expansions to include Quality Control functions. In addition, aspects of the ECRI HECS(tm) program and the Dupont Nuclear Medicine Manager(tm) programs will be reviewed. It will be shown that although there are important functions in each of the existing programs, a need remains for integration and synthesis of data, as well as the largely overlooked function of Quality Assurance both at the instrumentation and clinical service level. Interesting ideas developed by an Advisory group meeting of the IAEC on this topic will be presented. Aspects of technical and functional specifications as well as modular and branching design will be illustrated. The status of the current program will be illustrated. Examples of general QA camera measurements and standard test schedules for stationary and SPECT cameras will be given including the traditional NEMA specifications as will as aspects of SPECT center of rotation, voxel size, resolution and object detail performance. Practical aspects of PC performance for standard protocols and interfaces will be discussed.

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The process of developing and validating a quantitative test includes determination of a reference r ~ e . Traditionally this has been taken as the mean • 2 standard deviations for a random sampling from a reference population. However, this method fails to recognize the substantial variability in the sample standard deviation for the small sample sizes frequently encountered in nuclear medicine. A new approach, which includes calculating the 95 per cent confidence interval of the standard deviation, recognizes three ranges of values: normal, indeterminate and abnormal. The principles are demonstrated using differential renal function in twelve potential relatedtransplant kidney donors. The technetium-99m-DTPA differential functions based upon integrated counts between 1 and 2 minutes gave a traditional range of 50 • 8 per cent, whereas with the proposed method the normal range was 50 • 5 per cent with indeterminate ranges of 58 - 63 and 37 44 per cent. These values are consistent with the wide variation in reference ranges reported in the literature. A nomogram has been derived which permits the power of the reference range determination to be easily calculated from the sample size. Analysis of the effect of standard deviation variability is advocated whenever small reference populations are used.

Friday, August 31, 1990