223

~.D. Gasparini °, F. Crippa °, E. Regalia*, E. 5eregni% E. Bombardierf', G.L. Buraggi °

g. Leinsin~er, K. Scheidhauer, H. Denecke, P. Kragh, A. Haag, E. Moser and C.-M. Kitsch

D e p t s o of R a d i o l o g y and S u r g e r y , University Hospital, and Radiochsmical L a b o r a t o r y H o e c h s t AG, F r a n k f u r t / M a i n FRG

°Nuclear Medicine Division and *Surgical Oncolo. gy "A" ~ivision - National Cancer Institute of Milan, I t a l y

Depts. of Radiology a=d Surgery, Univ. of Munich, Klinikum GroBhadern, Munich, FRG

Tc-99m LABELLED iNTACT MUN~CLUNAL ANTiCEA ANTIBODY FOR S U C C E S S F U L L O C A L I Z A T ION O~ T U M O R R E C U R R E N C E S T h e p u r p o s e of this c l i n i c a l s t u d y was to d e t e r m i n e the d i a g n o s t i c e f f i c i ency of T c - 9 9 m l a b e l l e d M A b in p a t i e n t s with recurrent eRA-producing tumors. I n t a c t m u t i n g or in sell c u l t u r ~ prod u c e d IgG1 M A N B W ~ 3 1 / 2 6 ( B s h r i n g w e r k e , FRG)directed agains~ a protein componen~ of CEA ( a f f i n i t y ~ 0 " 0 M -) was l a b e l l e d with T c - 9 9 m u s i n g the free t h i o l g r o u p m e t h o d of S c h w a r z g i v i n g a l a b e l l i n g y i e l d o f > 9 5 % as d e t e r m i n e d by H P L C and an i m m u n o r e s c t i v i t y o f > 9 0 % . 4O p a t i e n t s w i t h r e c u r r e n c e s of d i v e r s e t u m o r s (col o r e c t a l 3 3 ; c - c e l l ca 3 ; b r e a s t ca 2, lung ca 2) s u s p e c t e d due to r a i s e d seru~ C E A [ ~ = 1 8 7 n g / m l ) r s c e i v s d 2mg of M A b lab. elled with 1.1GNq of T c - 9 9 m . W h o l e bod~ (1,6,~2-24h),planaz ( 4 - ~ 4 h and 18-26h) a n d E S T ( 6 - I ~ h p . i . ) i m a g e s w e r e obtainei R e s u l t s . O v e r a l l , 4 6 / 5 0 (92~) of k n o w n m e t a s t a s e s or r e c u r r e n c e s w e r e see~ with visualization of t u m o r s as s m a l l as 0.7cm. In a d d i t i o n , 11 o c c u l t l e s i o n s w e r e d e t e c t e d in the p r o s p e c t i v e l ~ s t u d i e d g r o u p and c o n f i r m e d in the f o l l o w - u p . T h e s p e c i f i c i t y was 88%, the a c c u r a c y 90%, and the p o s i t i v e p r e d i c t ive v a l u e 91%. O p t i m u m i m a g i n g t i m e s w e r e 6 - 1 2 h v.f. w i t h m o s t l y w e l l cont r a s t ~ d t u m o r s . N i g h q u a l i t y ECT s l i c e s p r o v e d s u p e r i o r to p l a n a r i m a g i n g in the t h o r a x , l i v e r and p e l v i s . We c o n c l u d e that the h i g h d i a g n o s t i c accuracy obtained with Tc-99m labelled a n t i - C E A a n t i b o d y is v e r y p r o m i s i n g and seems to be a d e c i s i v e step in the m o r e p r a c t i c a l l y o r i e n t a t e d use of i m m u n o scintigraphy.

ROLE OF IM~MUNOSCINTIGRAPNY IN LOCALRECURRENCES OF COLe-RECTAL CARCINOMA: COMPARISONWITH OTHER DIAGNOSTICMETHODS

SIGNIFICANCE OF IFRdUNOSCINTIGRAPHY (IS) USING SPECT AND 131-1 LABELED MONOCLONAL ANTIBODIES (MAN) TO CEA/CA 19-9 IN THE FOLLOW-UP OF COLORECTAL CANCER

The "in vivo" applications of anti-CEg monocIohal antibody (MoAb) F023C5 and its fragments in :olo-restal cancer, was previously reported by fur group. A pilot study performed on 51 patients lith 64 lesions, permitted us to establish the ligh sensitivity (about 90%) and specificity of ilmunoscintigraphy (IS), particularly: in detec:ton of local relapses and abdominal metastases )f cole-rectal cancer. Furthermore, these data Cere confirmed by a multicenter t r i a l organized ~y Italian National Research Council in which ~4 patients with 684 tumor lesions of CE~ se:feting tumors were examined. The aim of this ~tudy is to establish the role of IS in patients ~ith SUSbect local relapse of cole-rectal carciIome in comparison to other examination teehnilues, Thirty-eight patients, previously submit:ed to surgery showing an elevation of circula;ing CEA (confirmed by two consecutive determinations), were studied, f i r s t l y by IS and sub~equently by CT scan, NMR, US and with other ~ecessary investigations. F(ab')2 fragments of =023C5 radiolabelled with 1311 were used. A com)arisen was made between the sensitivity and the ~CCUFaCy obtained by each examination. ~reliminary results seem to confirm the high iiagnostic efficacy of IS in comparison with CT ~can and ultrasonography Cn detecting local re:urrences of cole-rectal carcinoma (IS 87% vs ~4~ of CT scan and 31% of ultrasonography).

In the follow-up of patients with primary resooted coloreetal cancer an early deteetio~ of all tumorsites is essential for further therapy Especially before planning hepatic artery infusion chemotherapy, imaging modalities are applied to exclude extrahepatie lesions. The aim of the study was to validate IS compared to ~CT and histology in visualization local recurfancies (LR), liver metastases (LM), paraaor~ie llymph node metastases (LNM) or peritoneal carmcinosis (PC). The study included 80 patients. In these patients tumorprogression was suspected by clinical status or fncreased tumormarker ~evels (ERA, CA 19-9). After i,v.-applieation ~f 131-I labelld MAB to CEA and CA 19-9 (2 mg I(ah')2; 70-140 MBq) SPECT-i~ges were perforled between 4 to 7 days p.i. All findings were :ompared to the results of subsequent surgery. [n histologically confirmed LH (N=28) sensitizity of IS was 93%, in LM (N=36) B7%, in LNM ~N=S) 88% and i~ PC (E=9) 78%. In 7 petients LR ;as visualized by IS inspire of normal levels )f CEA and CA 19-9. By TCT, only 50% of lR were letected. In all other cases, TCT could not lifferentiate LK from postoperative sear. Sensitivity of TCT in IM was 75%, in LNM 50% and [n PC |~g. Both methods showed false positive results. Speeifity of IS in detecting LR was ~5% (2/15 false positives: ovaria, cystes), in LM 93%, in LNM 92% and in PC 93%. This presented data shows that IS using SPECT can contribute addlt{onal informal%ion especially for detecting extrahepatic tumorsites of colorectal zaueer.

4

5

G. Mariani, C. Rosa, L. Dcnato

A. B i s c h o f - D e l s l o y e , B. D e l a l o y e , A. S t u d e r . W. g i l g i e n , S. C u r c h o d , m~ P e t t a v e l , J.C. Givel, F. M o s i ~ a n n , Buchegger, J.P.Mach,

R.P. B a u m , Hotte~ott, H 5r

A. H e r % e l , M. L o r e n z , C. A. S c h w a r z , F.D. Maul, G.

CNR Institute of Clinical Physiology at the Uni varsity of Piss; Piss (Italy), and Joint Progra, in Nuclear Medicine, Harvard University Medical School, SWRL; Boston, Massachusetts 02115 (USA)

NDIAGNOSTIC EFFICACY OF TUMOR RADIOIF~UNOSCINTIGRAPHY WITH MONOCLONAL ANTI-CEA FO%3CS-F(ah') VERSUS STANDARD X-RAY AND ULTRASOUND Patients' data pertaining to a multicente clinieal trial (supported by the Italian Rationsl Research Council) on the accuracy of tu~oz mmunoscintigraphy (ISO) By means of monoclonal mti-CEA FO23CS-F(ab')% were made ~vailable b9 :he projeon coordinator. Out of the total 542 ~atfents9 200 were selected for the presen[ ;rUdE, aimed at comparing the diagnostic perforlento of ISG with those of standard x-ray or US. All 200 patients (131 with gastrointesEinal ;aneer, GIC, and 69 with lung cancer, ha) had )een submitted to x-ray, whereas in a more re;%rioted group of 70 OIC patients ISG was compared with mono- or bidimensiona[ US. Patients ~ere selected on the basis of proven presence ol [umor lesions (evidences independent from ISG, :-ray, or US). Thus, results of the tests being ~valuated could only be either true-positive or [alse-negative, and were then compared solely in ~erms of relative sensitivity. ISG sensitivity was twice that of x-ray ir ~IC patients with tumor lesions smaller than 2 5m (iO0~ vs 43.6%), while the difference was not ~o relevmnt for lesions larger than 2 em (69.6~ rs 58.7%). In the LC group, ISG performed be%re* ~han x-ray for lesions both smaller (76.9~ vs ~3.6%) and larger Lhan 2 cm (g3.3~ vs 60%). IS6 )ensitivity wms far higher than US in GIC pati!nts with lesions smaller than 2 em (IOO~ vs ~7.4~) where~s in was lower in the larger lesior ~roup (63.8% vs 66~). These results confirm the high diagnostic ralue of ISG as compared to conventional nonin,asive techniques, particularly for tumors smaller than % cm. The relatively poorer performance )f ISG with tumor lesions larger than 2 cm me) ,erhaps depend, in GIC patients, on the higher )roportion of liver metastases at such stage.

m

~ausanne

University,

Imperial Cancer Research Fund Unit, ICRF, St Mark's Hospital, City Road, London EC1

Switzerland

~ADIOZMMUNOSCINTIGRAPMY (RIB) PRODUCING TUMOURS:A PROSPECTIVE

M.Granowska. P,Riehman, g.E.gritton, S.J.Mather, E.Sobnack, J.E.iass, $,Clayton, J.M.A.No~thover.

IN C E A STUDY.

In o r d e r to e v a l u a t e the v a l u e of RIS in C E A producing tumours we e v a l u a t e d 9rospectively 61 patients, ii with ~uspected primar~ (PR), 21 with suspected recurrent t u m o u r s (RA). RIB ~as p e r f o r m e d w i t h o u t k n o w l e d g e of the p r e s u m e d d i a g n o s i s . 29 f u r t h e r p a t i e n t s (RE) s h o w e d discrete symptoms and/or Eaising serum CEA, before definite ~iagnosis. A total of 296 possible t u m o u r s i t e s w e r e e v a l u a t e d : p e l v i s (P) 61, abdomen (A) 5B, liver (h~ 57~ t h o r a x (T) 60, b o n e (B) 60 and c o m p a r e d to the r e s u l t s of the u s u a l d i a g n o s t i c procedures, surgery and follow-up. 7 2 / 8 8 t u m o u r s i t e s and 1 9 3 / 2 0 8 d i s e a s e free r e g i o n s w e r e c o r r e c t l y i d e n t i f i e d . 6/9 patients considered free from tumour (0.5-2.5 y follow-up) had negative studies. 18/27 studies detected correctly single, 17/25 multiple lesions. Lesion detectability was somewhat i n f e r i o r in RB patients w i t h less advanced disease (72~) than in the o t h e r g r o u p s (88 and 91% for PR and RA). It has to be menbionned h o w e v e r that i0 l e s i o n s w e r e s h o w n m o r e than l month earlier than with the usual diagnostic procedures which did not show 6 other t u m o u r sites. 7 w e r e false negative on RIB, 4 of t h e m w e r e visualized >6months after RIS. This technique seems to be a v a l u a b l e tool in the diagnostic work-up of p a t i e n t s with CEA producing tumours, even in thoss which are n o t yet detectable by the usual diagnostic procedures.

UK

A NEW MONOCLONAL ANTIBODY FOB RADIOIMMUNOSCINTIGRAPHY, RIS, OF COLOBECTAL CANCER: PRIA3 ,ABELLED WITH INDIUM-ill. PRIA3 is a monoclonal antibody against a fixed surface antigen on colonic columnar cells developed by the ICRF. It was labelled with InIii 80Mgq using the bicyclic anhydride DTPA method. SIS in 14 patients showed images of comparable quality to those with In-lll antiCEA but with much less muoosal uptake in the colon. Analys~s of surgical specimens showed an average tumour uptake of 0.0265% injected dose, ID, per gram, similar to In-Ill anti-eRA. TumouP to mucosa ratios, average 14:1 (range 1.7-%7.O)were three times greater than the tumouP to mueosa ratios obtained with anti-CgA. Moderately differentiated tumours showed similar uptake but poorly differentiated tumours showed better uptake of PRIA3 than with antiCEA. Normal and involved node uptakes were similar, unlike anti~UEA where normal lymph node uptake is much ~peater. Blood clearance of PRIA3 showed 51% remaining at 24 hours and 33% at 48 hours, similar to anti-CEA. Preliminary studies of per rectal lymphscintigPaphy via triple suhmucosal injection alongside the tumour in 3 patients showed persistent lymph node retention in some aoPto iliac nodes suggesting a possible r61e in staging outside the surgical field. In conclusion In-lll PRIA3 is a suitable monoelonal ~ntibody for eoloreetal radiolmmunoseintigraphy with some advantages over anti-CEA.

224

JL Martinet, JD Huret, F Peron-Magnan, B Mazoyer, JC Baron, H Leo and A Syrota.

T ~ K u w # r t *, H.W. Lange ~, K.-J. Langen I, H. Herzog *, A. Aullch ~, L.E. Feinendegen t

K~=J~ Langenl, N. Reason ~, T. Kuwert z, E. Berzog*, J.C.W. K i w i t ~, E. Rata ~ , W.J. Beck ~, L.E. Feinendegen*

Service Hospitalier Fr~ddric Joliet, Dgpartement de Biologic, Commissariat £Energie Atomique, 91406, Drsay, and Service Hosplt~lier Un~versitmlre Hopital ~ednte-An~e, 75014, Par]a, France.

I) Institute of Medicine, Nuclear Research Center J~lich, Fag. Departments of 2) Psychiatry and 8) Neurology, Unlversity of D~sseldorf, FRG.

I. Institut f~r Medizin, KPA Jdlich GmbH, 5170 Jglich, FEG 2. Neurochirurgische Klinik der Universit~t Ddsseldorf, 4000 Dgsseldorf, FRG

CENTRAL D2 DOPAMINERGIC RECEPTOR STA. rus ASCERTAINED BY PET AND 7EBR-BROMO, B P I P E R O N E IN U N T R E A T E D SCHIZOPHRENICS In order to test /n vivo the hypothesls of a D~ top&m~nergic receptor increase in the striatR of schiz@ phrenics, we used P E T and 76Br-Bromo~plperone in I~ mode patients ful~l]ing the D S M lit criteriafor schie~ )hrenic disorder. Nine patlents were drug-naive and 3 were drug-free )r Rt least one year. The striatum-cerebe[hum (S/C 1 ratio was used as a validated index of the striata] D2 receptor densiby. P E T daba were compm'ed to those ol t sex ~nd age matched control group. N o signJ~c&nt difference between the S/C ratios el ~he bwo groups was found. W e also did not found a dgni~cant correlation bebween the patient individual 'C ratio and the D S M III types, or the positive and/o* Inegative s y m p t o m scores. However, the S/C ratios el ;ubchronic or chronic patients wlbh acute exacerbation 'mean 4- s.di = 2.34 4- 0.20) were significantly higher ';hen both the S/C ratios both ofchron~c patients (1.83 O lB) (p=0001, t-test), and bhe S/C ratlos Of bhe ,controls (2.05 4. .22, p=0.05); the mean &gas of the ;hree groups did not differ signifcantIi: These data suggest bhab the striation D 2 receptor tensity is altered neither in our group of schizophrenics as ~ whole, nor in relation to the intensity or the lqUallty of the psychotic symptoms. They do suggest bhe poes b ty that state dependanb vaMab es cou d be related to changes in the sermitlvity of ~he striRtal D 2 receptors.

10

CEREBRAL GLUCOSE CONSUMPTION M E A S U R E D BY PET IN PATIENTS WITH PSYCHIATRIC A N D N E U ROLOGIC S Y M P T O M S OF HUNTINGTON'S DISEASE The aim of this study was to eompnre patterns of local cerebral metabolic rate of glucose (LCMEGIu) measured by PET in patients (P) with Huntington's disease (HD) witB or without psychiatric or neurologic symptoms. LCMRGIu was determined in 17 P with HD and II normal controls (C) using the high resolution PET scanner PC 4096-15WB (in-plane resolubion l of 5 ram) and the ~"F-deoxyglucose (FD6) m e thod. The P were divided in 4 groups: I. P with a family history of HD and behavioral changes Itypieal of HD. but without chorea or psychosis (HB; n=5) - 2. P with chorea, but no psychiaI trlc symptoms (HC; n=8) - 8. P with chorea, dementia and without psychosis (HDC; n=4) - 4. I P with chorea and psychosis (HPC; n=6). Differences of compared ROt-data were considered as significant for p<0.026 (statist. prop. ANOVA). Compared to C the lentiform nuclei had signi'ecantly decreased L~MRGIu in all 4 groups, whereas LCMRGIu in bhe eaudate nuclei Was significantly decreased only in HC, HDC and HPC and not in HB. HPC additionally had decreased LCMRGIu in the thalami and all evaluabed cortical regions except the visual corbex; these regions were not different from C in the other P groups. Between NC, HDC nnd HPC no sight,cant differences were found. LCMRGiu in the caudste nuclei and in bhe lenbiform nuclei was significantly higher in HB than in the other P groups. Thus, different patterns of LCMRGIu related be psychiatric symptoms in HD could be identified: hypometabolism of bhe lentlform nuclei seems to accompany early behavioral changes In HD, cortical and thalamic hypometabollsm appear to be related to psychosis in ED.

11

L.Widdn I, G.Blomqvistl, S.Stone-Elander~, Chr. ~ , P.Rolandl, O.SolinS, M.LLndqviSt 2, B,t~ngstrgm6~ F AiWiesel,~

T. Muwert * , M . Bennerici i K.-J. Langen * , ~ ] & ~ r & o ~ I, g.. Steinmetz ~, A. Aulich s, G.E. geinendegen *

Depto or Iclin neurephysiolegy,2rleuroredinlogy,~psychiatry and psychology of the Karolinaka institute, 4Karolinska p h ~ y , S~helm, 5Tur~ medical cyclotron laoorabory, andddept-of o~geqic ch~stry, university of Uppsa/a

1)Institute of Medicine, Nuclear Research Center d~lich, 5170 J~lich. PEG. 2)Department of Neurology, University of DQsseldorf, 4000 Ddsseldorf, Fag.

PROBLEM5 IN MEASUREMENTSOF CEREBRAL METABOLIC ~ATE OF GLUCOSE. Aim: To compare 18F~=L=oxyglucose(18F DG) and 11C-glucose, ~iformly labeled (U11C~Ic) or labeled selectively at pssibion I (I-11C-glc) as tracers for determination of the ~rderal metabolic rate of glucose (O~g/o). ~etl~ds: PET studies - approved by ~ ethicaZ cc~mzbtee 3f the Karolinska hespitai- ~ere psrForn~d on 11 healthy subjects. DRglc was determined with the above tracers. In addition arterio-venous diFFer~rces for the brain of 11C3]2 as well as o£ glc and oxygen v~re measured as was the ~ i ~ c ~ l cerebral bluod flow, using 15 O-~ater or 110 Flucr~thane as tracers. This ailu~ed us to celculato the averac ~rebral 02- (C~02) and g l c ~ t i o q according to the Fi~k psirciple. ~ t s : With 1-11C~ic the average loss of 11C~2 was le th~ 5 ,% 15 min after bolus inj~tim, i e much less than ~ith UIIC-glc.O~Rglc obtained with the Fzck prirciple or ~ith 18FD6 " ~ about ~ % larger ~ that detained aith 1-11C~ic or UIIC-glc (after correcbioq For loss of figCOg). Ho~ever~ the rabio between the average O~glc~ ob~ rained with 1-11C-glc, snd 0 ~ 2 shertly after bolLtS znjectloq was > I/6 but decreased to I/6 within 15 rain which seems ~o indicate that iaihially there was a mixture of oxidative a~d non-oxidative giLccSe metabolism with profaction of e g lactate ~ py~vate. The exth~ction (E) of I 110~glc at steady slate ~ s > E of cold plasma-glc ~ide is explained by a negative A-V~ifFer~ce of 11C-m~t~bokites other th-~ 11C~02. £on~: About 20 % of O~glc is non-oxic~tive. ~Rglc detained with PET we;~ursr~nts of I~ ~ uptake or according to the Fick prznoiple ~ess~res the tote1 glc-uptake ~nereas with the tracer I 11C~10 one measures c~ly the u~id~ti~e b r e ~ - ~ of glc.

CEREBRAL gLUCOSE CONSUMPTION PATTERNS MEASURED BY PET I N P~TIENTS WITH TRALJMIC INFARCTION

Patients with thalamic infarctions (TI) have wide array of s~ptoms d e s p i t e only small structural damage visualized by E-ray CT or NMR. The purpose of this study was to investigate the value of positron emission tomogra ~ pbic measurement of cerebral glucose consumption in this patient group. Local cerebral metabolic rate of glucose (LCMRCIu) was determined in 4 patients with TI osing the high resolution PET scanner SCANDITRONIX PC 4096-1BWB tin-plane resolution of 5 mm} and the LeF-deoxyglucose (FDG) method. 28 regions of interest were evaluated and ratios between the TI ipsilaterdl and contralateral regions {I/C ratios) were calculated. These data were compared to the c o r r e s p o n d i n g data from 11 normal controls, x-ray CTs and ~ R scans were available in all 4 patients. X-ray CTs and NMR scans were normal except for small unilateral lesions in the thalamus. LCMRGlu was decreased below the normal value in the TI of all patients. LCMRGlu of the other regions was in the normal range. Again in all patients, the I/C ratios of the cerebellum were increas#d, the I/C ratios of the frontal, parietal and temporal cortex decreased compared to control indicating crossed cerebellar and ipsilateral cortical diaschisis. This correlated well with the clinical symptoms of these patients, i. e. mild contralateral hemiparesis and a variety of behavioural changes. These results indicate that - contrary to structural imaging methods as x-ray CT and ~ R - functional imaging by PET permits objective evaluation of the remote effects caused by TI.

EARLY EFFECTS OF INTRAARTERIAL CR~d~OTHERAPY IN PITIENTS UITN gRAIN TUMORS STUDIED WITB PET: PRELIMINARY RESULTS

Surgery and radiotherapy of malignant gliomas has been enriched in the last years by intraarberial chemotherapy. The purpose of this study was to test for early metabolic effects of intraarterial cerebral perf~sion therapy with the n i t r o s u r e a ACNU {iaACNU). - In a first series, g patients with malignant I gliomas, of which 6 had been pretreabed, were studied prior to iaACNU and within 1 - 3 days I thereafter using positron emission tomography. 5 patients were examined for glucose consumption (rCMRGIR) with tsF-2-Deoxyglucose with one patient being sbudied again following a radiotherapy course with a repeat i a A C ~ admiI nistration to months later; in 4 patients cerebral perfusion (rCEF) and oxygen consumption (rCMROz) was measured ~sing the xsO steadystate inhalation method. - The one tumor without prior treatment initially showed an elevated rCMRGIu and exhibited a 20 % reduction after the first iaACNU, then a further 33 @ reduction after radiotherapy and no further response after the second iaACNU. 4 patients with prior treatment did not show an iaACNU induced change of rCgRGlu. Regarding rCBP and rCMROs no i a A C ~ induced change was observed irrespective of pretreatment. - The data indicate that rCBF and rCMRC~ appear less sensitive than rCRRG1, in monitoring response to iaACN~. In addition, tumor pretreatment seems to obviate the metabolic expression of effects of continued therapy.

12 Meyerl G.-J., Schober, O, Gaab, M.R., Dietz, H, Hundeshagen, H Dpts. or Nuc;ear Medicine and Neuro Surgery, Medical School Hannover, D-3000 Hannover 61~ FR. Germany

MULTI-PARAMETER PET STUDIES IN BRAIN TUMORS. The physiologicalFunctionor individualbrain lumors has been analyzed by three psrameters: bloodflow (IBo-wster), glucose utilfoalian tiff- FDO) and amino acid uptake (11CMathionine). All data were analyzed in three relative ways using a) tumor region over contrslatersl re~ion ratios, b) tumor region over average white matter and, c) gcay matter ratios. In some tumors relative blood flow measurementswere obtained by 99mTc-Hr~PAO erECT. Patierds selected Far this study had medium to high grade (IH/IV) gliomas, astroc,/tomas, or oligogendro-gliomaa, All measurements ware carried out prior to surgery. Bistolegy was obtained from authentic tumor ~mplas. All/umors shewedratios ~> I in [arms Of amino acid uptake by all analytic methods The ms]crib/of tumors of qrede III showed a ratio < 1 For glucoseutilization by methoda) and c) This was matchedby a deceasedb]sod flow in most cases. Using methodb) about half ef those tumors showed a relic ', I for gluosse utilization. This again was matched usually by lha blood flew rati,;s obtained with the corresponding method Only some high grade gliomas (IV) exhibited g~ucoseutilization ratios ) ; by oil analytical methods Theeeeases shewedmatchedhigh blood flow ra~ios as welb We conclude that amino acid uptake is the best positive funadon dascr;#hon agentfor brain tumors The variing gluo~e utilization in brain tumors is usually matchedby corresponding blood flow charastaristiosDifferentreefhods of analysisdo not improve !he charasterisaUon of tumor functionsignificantly Therefore measoremen~ of amino acid uptake is the method or choice for clinicallyorienledrouifneanalysisof brain tumor~, which usually does act allow a multi parameter approach [or each patient

225 13

15

14

Holker S,, Porenta M.

Kononenko I., JauhA,, Fidler V.

A.Bonazza,G.Petracca Ciavmrella,PG. PaleaniVettori, V.Annese, V.Fruseiante, S.Modoni.

~

i, V . G o l d o n i I, D . V r b a n e c g, o t k v i d I, K . P a v e l i d 2, C l i n i c a l H o s p i t a l "Dr M . S t o j a n o v i 6 " Zagreb, Y u g o s l a v i a

University Clinic for Nuclear Medicine, Ljub lj aria Faculty of Electrical Engineering Ljuhljana EXPERT SYSTEM's DEVELOPMENT IN THE MANAGEMENT OF THE THYROID DISEASES

Ospedale "C.S.S."

t23 I INSULIN IMdBINS IN NOR~dLS~ ]N HEP~TDPhTICPdTIENT~

u__

Insulin receptors have a lidespread distribution on lest tissues. L~31 insulin is a purifind preparation that has been intreducnd ID illn~ the in vivo evaluation of insulin interaction ~ith its 'eceptors (Sodeyez'e3l.Sistributien pattern of t~31 ins,i~ Ig heaiN iubieEts a,d in IY pts.mith proven chroni~ hepatic disease (3 porto:oval sbunt,k cancer-cirrholis,d ~irrhosis,2 alchoolk steatosis~ ~as eva]usted.Nprmal patients had all normal blood glucose valuestr~ raIltiarlty for diabetes~ norIal oral @]~cose tolerance test an~ no ;linicat and heiatocheaic~] evidence of liver and/or re~al disease. lepatndatic patients /ere.About 30-dO 8Bq (0,8-l.k iCi)of 1~3 I ins. m a 1.5-~.5 co. vo]ule v,ere injected in an arl vein. J~(quisition lag ilendiately started by storNR lnduential frzees.ROl~ lore draw ,n left ventricle, kidneys, bladder and the lost pitt Df liver, :arefu]|y av0idin@ kidney 0vertappi~. in normal patients eest 0f ctivity appeared in the liv~ ~ith a T~ax at ~-T(N|e 5.&" 8],7~). I eeln t~ if 15' ~as T0u~ on liver =urve.Bean time from the 75S of :aunts on the sscendin~ phase of the c~rve a~'/hX of c~,lle|inn the Ilscending p~aselt?~-?5)~ai IO.3P (~D .Bd, ES.~) .Kidneys eere ~e]l !vident at the end of the study be:ause insulih Ind its fra~lmnts ire fittratnd sod then reahsorbed by tubules.Urinary bJmdder became ~vi~enl since from the first linutes of the gaudy and its activity •eflects probably excrekion of o~[y free iodine. Spleen ~as lore or ass slightly evident, probably because of a physiological pooling ~f blood ceils. In hepatopatic patients distribution p~ttern mas ,lien characterized by a delayed appearance of the activity in the aver but especially a lore prolonged descending phase Ilonger ttI. his was veil expressed hy the mean L75-7~ that Mas l&.J7 (9S 1.5, iS.3B),Kidneys ~ere moTe scarcely visua]iznd due probably to Conger iver retention tile sod tumor rate of arrival Df inSlllin fra~lents md free iodine. Urinary bladder is tess and later evident for the ~amereasun.Spleen is often larbnd]y eyident especially ~ben underyin9 disease results Jn splenoiega[y .ith zncreased f l ~ . It is nel lear if this has to be interpreted lere]y as s vascular effect. hose figures clearly sho~ thet t23] ins. has a definite different ehavio.r in norla] and hepat~pakk patients and dearly separates :he imp @rDUpS.RO#the role of 123-1 its in identifyng other sublasses of hepatic disease re,sins to be deteriinnd.

16

17

The diagnostic process in the Outpatient Clinic for Thyroid Disorders is composed of procedures as history taking, physical examination and laboratory te~ting. Our intension is to develop suhexpert systems for each phase ol the diagnostic process and to build them in a~ o n llne system for everyday routine First attempts were made with laboratory tests using 15 of 500 possible attributes, stored in the data base, for each of 926 patients first examined at the beginning of the year 1986. The decision trees were constructed by the ASSISTANT system of automated learning of diagnostic rules, using 70% randomly chosen cases as learning and others as testing set. Qe postulated 4 mutually exclusive classes (hyper, hypo, euthyroid and healthy). The comparision was made between the accuracy of the single decision tree, the selection of good rules, hierarchy og subtrees and the domain specialists (using the same 15 attributes). The be@t results [accuracy of 74%) was achieved when the hierarchy of trees was used. Analysing the results and the data, the position of TSH in the root segment of all trees were found, but this attribute was present in only 36% of patient's records. ~e can conclude that the hierarchy of sub£rees is a good method, which could be used in development of an expert syste~ and that the accuracy is excellent (91%), ff the attributes in the root segment are present. The fact, that the ASSISTENT program put TSN in the root segment confirms the high informative value of this test for determination of the thyroid function and is now used as the hasie test fn our clinic.

P.SgNNEIDER,

P.BERGER, K.
Institute "R.Bo~kovid" Yugoslavia

S.Giovanni Eotondo (FG)

F.A.KBAFAGI, B.SHAPIRO, S.MALLETTE,

Zagreb,

AUTOCRINE TUMOR GROWTH REGULATION BY T H E I N S U L I N G R O W T H F A C T O R I (IGF I) A N D THE HPIDER}IAL G R O W T H F A C T O R (EGF) T h e r e is a g r o w i n g b o d y of e v i d e n c e t h a t g r o w t h f a c t o r s m i g h t m e d i a t e tuor a u t o s t i m u l a t i o n . In this s t u d y two g r o w t h - p r o m o t i n g m o l e c u l e s IGF I a n d GF d e r i v e d f r o m h u m a n tlL~or t i s s u e s ere d e t e c t e d b y the radioirm~unochemica] ~ethods (RIA) in 15 p a t i e n t s s u f f e r i n g rom melanoma and i patient with hemangiosarcoma.

~

~

h~-man p r i m a r y h e m a n g ~ o s a r c o m ~ w a s derived from a patient with severe hypog l y c e m i a . T h e c e l l line e s t a b l i s h e d f r o ~ this t u ~ o r s e c r e t e d IGF E in a ~er~/n-free c u l t u r e m e d i u m . A p p l i e d o n ~ephacryl-S-200 IGF I w a s e l u t e d in t w o ~ e a k s , m o l e c u l a r w e i g h t o f 160 gog a n d ~OOO daltons. ~GF from human primary e l a n o m a c u l t u r e w a s m e a s u r e d in a seru~ ~ r e e - m e d i u m . A p a r t of m e l a n o m a t i s s u e ~as homogenised ultracentrifuged and the EGF a c t i v i t y in s u p e r n a t a n t w a s de~ e c t e d . On e l e c t r o p h o r e s i s a s i n g l e hand ~ a s o b s e r v e d at same p o s i t i o n as p u r i f i e d E G F s t a n d a r d ( m o l e c u l a r W e i g h t 600D ~altons). E n h a n c e d D N A s y n t h e s i s in h u m a n tu~or cells incubated with 3H-Thymidine t e r e x p o s u r e to IGF I s h o w e d 136% greter s t i m u l a t i o n c o m p a r e d w i t h c o n t r o l n d a f t e r e x p o s u r e to E G F 263% b i g e r timulation than control. T h e p r e s e n t e d d a t a s u p p o r t the h y p o esis t h a t t u m o r a s s o c i a t e d g r o w t h faC t o r s p l a y a r o l e as (autocrine) g r o w t h romcting molecules in melanoma.

I

I! r

18 J.C.SISSON.

IM.D. 8rnos, B. S~:mpiro, 8 0 l ~ e r , AJ. Bouffard, F. Khofegi end I. Francis.

Dept. of Nuclear Medicine, Univ.of WGrzburg * Children's Hospital, University of WOrzburg

Division of Nuclear Medicine, University of Michigan Medical Center, Amn Arbor~ Ml 49109, U.S.A.

F.R.G.

I

ITHE INFLUENCE OF LONG TERN CALCITONINE DEFICIENCY ON TRABEGULAR BONE DENSITY (TBD) AND TOTAL gONE DENSITY (BD)

low dose 1E5-I CT scanner. One c r o s s - s e o t i o n a l slice was taken at the distal radius of the nondominant forearm, located 5% of the ulnar length proximal of the ulnar tip. Monomeric calcitonine before and after stimulation with calcium, parathyroid hormone, osteocalcine, 25-OHD, alcaline phosphatase and ether iparameters were evaluated. Secretion of monomeric oalcitonine was expectedly reduced or missing in patients. TBO and go were significantly Ireduced in male but normal in female patients. patients SD normals SD

BD

male female male

0.705 0.694 1.055

0.09 0.09 0.17

0,794 0.682 1,175

0.15 l/cm 0.08 ilcm 0.15 itcm

female 1.067 0.19 0.98 0.09 i/cm Me conclude that there might be an influence on sceletal demineralization in male thyroidectomdzed patients but not in female. Thls icould be explained by a higher normal caleitonine level found in healthy men. Further investigations are in progress to monitor indi-

;v'~d,l~l Pnllnw-lln

a~r

I

THE EFFICACY OF 13tl-6D-IODOMETHYLNORCHOLEST£ROL (NP-S9) SCINTIORAPHY IN THE EVN.UATION OF THE

CUNI(~d_LYSILENTADRENALf~S,S.

The role of calcitonine in humans is still not clearly known. In a cross-sectional study 56 subjects, 39 patients and 20 normal controls were studied. The patiants (25 women, ll men) had undergone thyroidectomy due to the diagnosis of thyroid cancer (24 papillary, 30 follicular) i to 15 years before. All patients received thyroxine replacement therapy in an adequate suppressive dose. All subjects were selected to be in a low age range in order to minimize age dependency in bone miner~l content. None of t5e females were postmenopausal. We measured TBO and Bg at Ithe distal radius by means o f a s p e c i a l l y b u i l t

TBO

REDUCTION OF (I-131)-METAIODOBENZYLGUANEDINE (MIBG) UPTAKE BY LABETALOL.

The Delmrtmant or Intorrml Medicine, Division of Nnolanr Medicireand The Deportm~,t of Rediole~, The University of M chigan Medical Center', Ann Arbor, Michigan, USA.

i,hy~nid~ntnmy

1-131 MIBG has proven to he an effective agent for the scintigraphic location of pheochromocytomas, neuroblastomas ~nd some other neuroendoerine tumors. ~ptake of MIBG is inhibited by blockade of the neuronal catecholamine uptake pathway ("uptake-l") and by drugs which deplete catecholamine storage vesicle contents, but it is not significantly affected by conventional alpha- or beta-adrenoreceptor blocking drugs. Labetalol is an antlhypertensave agent with both alpha- and beta-bloeking properties which has been used to m~nage patients with suspected pheochromocytomas. We report 8 patients with known or suspected pheochromocytomas in whom concurrent or recent therapy with labetalol significantly reduced uptake of 1-131 MIBG into salivary glands, liver and spleen. Tumor uptake of MIBG wRs also reduced in 2 of the 3 patients who were proven to have pheochromocytomas. In one case, the effect of lahetalol persisted for 36 hours after the drug had been discontinued. Return of normal tracer uptake was observed 7 days after drug withdrawal in m further case. The inhibitory effect of lahetalol on MIBG uptake is likely to be due to the drug's little-known additional properties of uptake-i blockade and depletion of storage vesicle contents rather than to its alpha- or beta-adrenergic blocking ~ctions. Labetalol therapy should be stopped for several days (preferably I week) before undertaking 1-13] MIBG scintigraphy; conventional alpha- and beta-blocking drugs may be substituted.

To ~ the role of NP-59 scintigraphy in the chatantorizatien of the silent adrenal me~s, 119 euedrerml i~atients (156 women end 61 men)with uniletorol ( 5 6 r i ~ t end 63 loft) edvorml rnee~ on al~bmienl CT were edministored I mCi of NP-S9 iv Pnolerior, teterol end anterior e@dominal scs~s (50,000 counls/image) were ebteined 5 to 7 de~ Iofer, CT wes pavformed in 6 6 to erase e known or suspantoci neopimm, 43 were studied for abdomir~l pain while the remaining I0 were evetueted for pleurol/abdominol effusion (4), rerml insufficiency (3), bocl( pain (2) end re~roporitoeesl fibrosis ( I ). Ol~[p'~s of adenomo w m mode in 82 (biopsy in 12, odrenalcotomy in 14 i~ in the remainder" no change in CT eppcoranno for at lenot o 6 HO interval). Intvg-edreonl neoplesms/spnoe-occuwir ~ lesions were see. in 26 [metestetic lur@ ( 1 2 ) , colon ( 2 ) , lyrnphoma/leskemia (3), edpananorU~l omcinonla (2), fibrous hieticoytome (2), g~licoeurome ( l),

neuroendcorine tumor ( I ) end adrenal cyst (3)]. Thoro wore 't pepledrenel metestmes (3 ranet, I lung) no~ 5 o~enet paeudofumors (o myeletipama, rofropepitencol Ihemetomo, renal c~t, Ganb'ic verix and gestric lei~nY~la) NP-59 depicted 76 of 82 ~enomes as l@torelizing 511 activity to the oide of the maSS co CT (cenmr~nl scan), while in 6, bileteret symmetric NP-59 irn~ncj was seen. In 26 patients with spaco-occuwing lesions N P - 5 9 u p ~ e letoroli~s:i to sMe opposite the mees (discordant scan) seen on CT. TWO lntPa-adranal neoplasms (lung and re.gl, esch less that 2 cm in diameter)lacked sufficient asymmetry to e identified . ~ i t i v i t y (11~/TP-H:N); 26134 WaS 76%, ~ecificity

(I~I/TN+FP)j

85185

WaS

100%

8C~dP~/

]N+II~/TN+]~+FP+FN); 111111g Woo93%. Thus, NP-59 to Ificaceous in the characterization of incidanletly dis:svored eu~rerml ramies.

226 21

20

19 EOSSEIN-FOUCEER CL #, ROUSSEAUJ. #, LECOUFFE F. #, REGAL R. &, CARNAILLE B. *, VENEL M. #, PROYE C. *. MARCEANDISEX. #. # Serv/ee Associd de Mddecine Nucldaire, * Service de Chirurgie Adultes Est, CHU Lille - 59037 Lille - PRANCE & Lab. PHASE, CNRS, 67037 Strasbourg - FRANCE A NEW INTRAOPERATIVE

CdTe DETECTOR

We

report the development of a new C d T e probe that is suitable for use in a surgical context.

The main physical characteristics of Cadmium Telluride detectors are a large bandgap (1.5 eV) to reduce thermal noise, a high atomic numbe.{ Z (48-52) coupled with a high density (6.06 g/cm ~) to increase sensitivity, and solid state ionization chamber operation with low bias voltage (50 V). Our detector is I mm thick whith s sensitive area of 25 ram2, and operates at room temperature. These characteristics give it better handiness than NaI scintillators, Si or Ge detectors, in an intra operative purpose. In order to reduce microphonic and electrical noises, both detector and preamplifier form a single module, weighing 160 g. with a diameter of 25 mm and a height of 130 ram, connected to the portable PHA unit. The low noise level (less than 1 cpm for energies above 16 KeV), the very high efficiency (near i00 %) for low energies and the adequate spectrometric resolution (about 16 KeV), the very high efficiency (near 100%) for low energies and the adequate spectrometric resolution (about 14% in the 15-140 KeV range) give it excellent sensitivity to 125-I (approximatively i eps for 1 nCi up against collimator). No saturation occurs up to 10000 cps, far removed from the usual count rate clinically used with excellent time stability. The collimator mainta/ns spatial sensitivity with a 75° angle. Use of 125-I has numerous advantages in surgical context : easy labelling, l o n g period enabling to choose optimal delay between injection and surgery, possibility of contact detection without tissue attenuation and with a light collimator. We report various eliBical applications : total thyro~dectomy (probe sensitivity would permit detection of a 1 mg thyroTd fragment), osteoTd csteoma resection, phlebothrombosis detection, tumor detection through monoclonal antibody, etc.

22 A J Gree,, R H J 8egent, K D Sagshawe C ~ c ~ Rem~rc h Campaimn IJLboratorl~, D e ~ r t m ~ t of K4e41c~I OncolcH~, Ch~lnQ Cross Hospital. F u l h m Palace Road. London W(3 8RF

Mazlmmm Likelihood Remonmtructlon incorporating Line Spread Function Data Accurate dot merry in Redlolrnmunntherapy (NIT) I requlrem quanlHaflve Single Photon Emission Tomegraphy {SPET) st late time points when the sinogram I couat dertsity is k)w. Conventional fiHered back projectle, (FBP} reconatructlon gives poor quad~titoflofl in these comdRlens. We have developed a projector-hack projector for use in a maxheurn likelihood (ML} Rerative SPET recmlntructlon algorithm which Iecorl~rates measured line spread function (Isf} data. Lsf's were measured between 1 and ,50 cm from the sur#ace of u hkJh sensNIvRy 1311 collimator in air. I0 Mcts being take. for each measttrement. The data were saved on computer as a two-dlmenslenal array. The projectorback projector aJgorlthm was developed to use this array as a look-up table to calculate the contribution of each sioagram bin to each phial of the tomogram. The projector-back projector was Incorporated In a ML algorHhm (Shepp at el, 1982). Phantom and HIT patient data were recorded st a range of alnogram count densities. Scatter was corrected for by the method of Jaszczak et al (1984). ML reconstructions were performed with the LSF projector-back projector ~md compared with FBP reconstructions, The improvement offered by ML reconstruction was seen to Iecrease with decreasing count density. in con¢iosion, we have shown that, in situations where It is important to achieve quantitative SPET from poor data, such as when developing ardlhedy directed cancer therapy, measured camera parameters can be used to improve the accuracy of the reconstruction algorRhm.

F.Zito, C.Rossettl,

G.LuciEnani,

Iscituto S.Raffaela, Riomediche Avanzate Milano, Milano, Italy

F.Fazlo

Istltnto ,Teenologie C.N.R., Universlt~ d~

QUANTITATIVE AUTORADIOGRAPHY USING A DIGITAl SCANNER LASER AND A BARIUM FLUOROHALID PLATE.

Quantitative autoradioEraphy (QAR) is technique to measure functional and/or metabolic parameters in animal models. It is currently performed by placing tissue sections onto X-ray films which are analyzed by densltomerry after development. We report the application to the study of brain physiology of a~ alternative method for QAR based on the use of imaging plates in whdeh the radiation sensitive material is europium-actlvated bari~fluorohalid (EaFX:E~). The BaTX:Eu plate does not reoulre the conventdonal photographic processing and the ionizing radiation absorbed can be released and quantified as laser stimulated luminescence by a digital lasex scanner (ULS). The scannin E time for s igcmxg4cm plate using a 100um pixel size is 1 min. This technique has a good uniformity, stability and signal to noise ratio. TC validate the use of this system For measurements of local cerebral glucose utillzatio~ (LCGN) with the O-14 deoxyglueose method we analyzed rat brain tissue specimens both by conventional N-ray film QAR and by ~aFX:Eu i plate autoradiography. Deflsitometry of the X-ray films was carried out with a rotating drum densitometer. The images obtained from BaFX:Eu plates and DLS were analyzed by a mini computer. Rates of LCGU assessed by the ~wo systems showed substantial agreement tn all the brain structures examined. The results of this study demonstrate the reliability of a system based on the use of BaFX:Eu plates and DLS for measurement of LCGU. The use of this technique in combination with other radioactive tracers for evaluation of additional physiological parameters is under examination.

J.R. Prince and C.G. M u m ~ University of Oklahoma Health Sciences Center and Oklahoma Teaching Hospitals 9~0 NE 13th Street Oklahoma City, Oklahoma 73126 U.S.A, CONTRAST-DETAIL CURVES IN RADIOSCINTIGRAPHY: MEASUREMENT AND ANALYSIS Contrast-detail (C-D) curves are increasin Ely being used as a psyehophysieal measure of image quality in radiologlcal imaging. However, there is a paucity of information relating to radioscintlgraphy. Furuher, utilization of C-D curves has been hampered by inadequate curve tinting methods, We report the measurement of C-D curves for count densities ranging from 200-4000 cts/em g obtained on a Siemens ZLC camera with a LEAP collimator. A logistic function, (I) dm : dl/[t-EXP-(EX)] was applied to the weighted regression analysis of these C-D curves. In equation I, dm is the minimum percepnible signal diameter in a~ array of targets at contrast X. Notation d~ is the saturation value of dm and E is a regression parameter. The area-under-the-curve tAUt) was used as a figure-of-merit (FOg) by innegfating the logistic function over mathematically and clinically acceptable limits. C-D curves utilizing Tc-99m iiRagi~g of detail diameters ranEing from 0.7cm me 3cm at object contrasts ranEing from 5.6% no 78,4Z yielded r 2 values from 0.95 me 0.98. The AUC's differed by a factor of 2 over the range of count densities used and it was demonstrated that count densities over 1000 did not improve ;performance. It was concluded that the logistic function dis a robust model of C-D curves in radioscintigraphy, the AUC is a sensitive FOM and no improvement in image quality is apparent at mount densitdes exceeding i000 using the experimental paradigm reported here. These conclusions are consistent with subjective clinical experience.

24

23 R.J. Jaszczak, C.E. Floyd,

Z- Lien E, K.L. Greet and R.E. Coleman

Departmen~ of Radiology Duke University Medical Center Durham, North Carolina USA

ONE BEAH SPECT: AN ACQUISITION GEOMETRY TO INCREASE DETECTION EFFICIENCY Cone beam collimation [iaszczak, et al 1986] man improve photon detection for brain and heart SPECT. We have investigated the imaging properties of a cone beam (CB) collimator (focal length = 50 cm) using a filtered hackprojection (PEP) algorithm, and have compared its performance with a commercial parallel hole (PH) collimator. Two iterative methods, Bayesian image processing (BIP) and ~ x i m u m likelihood (ML), were assessed for convergence properties using simulated projections. Reconstructed spatial resolution, using a 15 em radlus-of-rotation, ranged between 10 and ii ~ for both collimators. At this distance the point source sensitlvty for the CB collimator was a factor of 3 times the sensitivity of the PH collimator. The CB volume sensitivity, measured USlng a 17 cm die. spherical source was a factor of 2 times the PH volume sensitivity. Cone beam phantom and patient scans demonstrated decreased statistical noise. Both iterative methods resulted in similar image quality between 5 and 20 iterations; however, the BIP approach resulted in improved convergence to the source distribution at higher iteration numbers. Cone beam SPECT has the potential to improve SPECT by optimizing the use of the active de~eetor area, and the use of itera~ive strategies offer the potential to improve the reconstructed image by eliminatin E or minimizing inaccuracies observed using FBP. Jaszez~k RJ, Floyd, Mangles SH, Grsar EL, C o l e ~ n RE: Cone beam collimation for SPECT: An~lysls, simulation, and image reconstruction using filtered backprojection. Med. Phys. 13:484-489, 1986.

E. Henze, G. Graf, g. Clausen, ~ c h , N.E. Adam

R. geller,

P.

Divisions of Nuclear Medicine, University of Ulm and Central-Hospital Augsburg, Germany A HEW PROJECTION OF SPECT DATA ANALOGOUSLY TO THE X-RAY ORTSOPANTONOGRAM: TEE ORTNOPAN TOMOSCINTIGRAN {OPTS) Accurate regional correlation of facial bone hot spots to dental x-ray findings is difficult because of the highly different projection techniques, i.e. multiple planar or SPECT sclntigrams of the skull vs the unique orthopan tomogram (OPT) display in dental x-ray. To improve correlative imaging a new projection algorithm was developed that uses $PECT data for orthopan-tomographic projection, and that allows 1:1 superimposition with the OPT. 14 SPECT slices covering the upper and lower jaws were obtained by 180 degrees rotation from right to left lateral in 32 steps, wlth lO see/frame and a 64x64 matrix. Mandibular SPECT slices were superimposed resulting in a horseshoe-shaped structure. The 2 open ends of this horseshoe were connected hy a line, and a reference point was determined in the middle. From that point the both halfes of the horseshoe (or of the jaws) were divi@ed into 8 segments according to the number of teeth. All SPECT slices were then masked'by Ithe individual segments, thus allowing an orthopan reconstruction. The empty hand between both jaws, reflecting the non-radioactive teeth on the final OPTS, can be used for displaying a scale with the individual tooth number. Applied in more than g0 studies at our institution the OPTS has proven to be superior in exactly localizing facial bone hot spots, and it has become the preferred docomentation means by our dentists, although - expectedly - it did not increase the sensitivity in detecting jaw bone affections.

227

25 R.C. Waloviteh, J. Makueh, G. Knapik, A.D, Watson, S,J, Williams.

27

26 M.Franeeschi,M.Picard,R.E.Zimmerman,J.F. ~--~,A.G.Jones,B.L.Helman

g.I. DuPont De Nemours Co., N, Billerica. MA. Brigham and Women's Hospital, Boston, MA, USA

RETENTION OF Tc99m-ECD IN THE BRAIN IS RELATED TO IN VlVO METABOLISM. Te99m-L,~-ethyl cysteinate dimer (EGD) is being studies clinically as a marker of regional cerehral perfusion. In humans Rod non-human primates, ECD e~Snihits rapid brain uptake and prolonged retention (tll~ > 20 hours) with rapid renal clearance. Since ECD is a diester, it was hypothesised that metabolic transformation of the complex may he essential to its )harmaeokineSic behavior. In-vitro incubation in homogenates of monkey brain cortex results in the rapid conversion of ECD to a single more polar complex. Studies in the same system with the Tc99-1abeled complex show this metabolism to be enzymatic (Vmax = 38.8 pmol/min/mg wet wt. and Kd ll.05uM). Analysis of the Tc99-ECD metaholite suggests it to be the monoaeid, Imono ester complex. In contrast, while the D,D-ECD isomer is also well-extracted by the monkey brain in-rive, is is not retained (tll2 < 30 minutes) and is not metabolized in-vltro. Subcellular distribution studies in monkey brain one-hour post L,L-ECD administration show more than 70% of She activity to he localized in the cytosolie fraction and to be in the form of a metaholite~ When the metaholite was injected intravenously l~to a monkey, it failed to cross the blood brain barrier. These results suggest that rOD is metabolized rapidly in the brain by a specific enzymatic pathway to a polar complex which is trapped.

28 G. Demonceau, J. Leveille, M. De Roe, R. Walovitch, S. Williams, A. Taillefer, J.M. Douesnard, R. Cantineau, P. Bite. university of Liege, Leuven (Belgium) and Montreal (Canada), du Pont de Nemours (USA).

COMPARAISON OF TC-99M-ECD and Tc-g9M-HM-PAO : FIRST HUbiAN ~ S ~ T S . We have coryared, in human, two Tc-99m labelled CBF imaging tracers : ethyl cysteinate dime: (ECD) and h e x ~ t h y l p r o p y l e n e oxime (HM-PAO). A~out I GBq of ECD or 560 MBq of H~-PAO were injected intravenously to 6 volunteers. Whole body biodistribution was assessed from static views up to 24 hours after injection. During t/ads time, 4 tomographie studies were initiat~ at 20, ioo, 240 and 36Oth min. In 4 volunteers the grey-to-white ratio was obtained iteratively untill 120 min. After labelling, the radiochemical purity assessed by R~LC was higher for ECD (98%) than for HM-PAO (95%). ECD is stable in vitro at least for 24 ho~rs. Both tracers revealed similar high uptake as soon as 2 min after injection but washout of ECD was faster (Tl/2 17h) than HM-PAO (Tl/2 : + 7th). B~ain-tosoft tissue ratio was higher for ECD than for HM-PAO; this difference increases with time. Grey-to-white matter ratio was higher with ECD (2,2) than with HM-PAO (1.6). The pattern of activities in vascular territories was similar for both tracers. BiodistEibution of ECD showed lower activities in the lungs, liver, gallbladder and muscles. The u r i n a ~ e x c r e t i o n (more than 75% of the injected dose at 24 hours) was higher than of HM-PAO. So the absorbed dose was lower. We conclude, from these preliminary results, that ECD seems more convenient for clinical use, due to its high stability in vitro, high grey to white matter ratio, lower activity in soft tissue and more favourable dosimetry.

B~AIN WASHOUT OF Tc-ggm-L,L-Eq~YL CYS~EINATE DIMER (ECD) IN NORMAL_VOLLUTEERS grai~ w~shout of a new b~ain agent Tc-99m-ECD was studied in five healthy volunteers (ages 22-34).Thepatients were injected at rest in a quiet room (6.5-1~nCi).Anterior and posterior whole-body in~ges ( 2 0 ~ n / m ) were acquired at 5 and 30 m/~, I~2,4 and 2q hour with a GE Star cam camera using low energy whole-body collima tor.A 25Bx1024 ma~Pixwas used.The b p a i ~ r e melted in the field of view for 2 m/~utes. SPECT acquisition was also performed using a long bo~e collimator (fi4x64-matrix, 360 degrees, 64 projections, 30 seconds pep projection) .Whole brain anterior and posterior, left and right s m ~ l te~nporo-parietal anterior and postemior, eerebellar a~d facial ~OIs were drawn at each time point on the plarlar images. Whole bra~n as well as seven symetrical ROIs were drawn on transverse SPECT slices.The initial brain % injeeted dose (ID) was 5.8+-1.0% a~d b~ainwasbout ~ s slow (<25% in 4 bouts), while the irdtial facial % ID was 3,8+-0.5% but its washout rate ~ s very rapid (58% in the first boUT). %Plana~brainwashout relative to g . o g ~ 1.00hr: 8% 2.0Ohm: 18% 4.OO~e: 21%

%SPECT brain wasbout relative to o . 2 g ~ 0.g2hr: 14% g.12h~: 17% 3.13hr: 22%

A true ~ a l n washout rate was underestimated at fi~st hour on the planar images.Brain washour rate is ~ela~ively stable one hour after injection of Te-99m-ECD.In a clinical set-up, a standard brain SPECT acquisition (64xgg sac) can be performed at any time i hour afte~ injection.

29 G. OEPEN, L. HERMLE, H." BOTSCH, M. FUNFGELD

I ~SY.CHIAT~I~CNH~E~I~R~T;T~KLIN~GAND

INCREASED RIGHT-HEMISPHERIC (BH) STRIATOLIMBIC UPTAKE OF 99m-Tc HMPAO IN MESCALINE-INDUCED SCHIZOPHRENIC-LIKE PSYCHOSIS

1. L~veill6*. G, Demoncenu ~'~, P. Rite ~ , M. Be ~oo***, R. Taillefer~, B,A, BsrBes8 ~ e ~ , R.A. ~orBnn t t ~ . R.C. Walloviscb ~ * ~ ~6tel-Dimu de Montreal, Montreal, qu~bec,Csnad# ~niversity Hospit~l, Liege. Belgium w~ J.Z. Gas~buiberB, Leuven. Belgium **~ E.I. DuPonf de Nemour & Co. (Inc.), North Billerica. MA * * ~ BRAIN TOMOGRAPgY IN NUCLEAR MEDICI~E W~fn A N~W AGKNT: ETHYL CYSTKINATE tIMER (99mTc ECD). The purpose of this study was to evaluate th~ in rive stability of a new brain perfusion ima sing abetS, the Tc-ECD. EIght male adult volunteers were Injected with 25-30 mCi of Tc-ECD. S~ (rotating camera) and whole-body imaging were performed up tO 6 hours snd whole-body study was repeated at 24 hours sfteF injection. Dynsmim planar brain imaging (0-20 min. post i.v.) served CO evaluate i~itlal br~in uptake. Four other adult volunKeers ~ere studied using a multicrys~al dynamic SPECT to de,ermine the Bray-go-whl~s (G/W) matter ratios. The initial facial soft tissue, g~snds uptake and washout are rapid. In contrast tbe rapid brain uptake (4.6% et g minutes post injection) is stable. The G/W matter ratio OM 4.5 and 7.0 cm is 2.5 with a smsll predominance of occipital over frontal region without any slgni~icant change in neuroanatomlcal distribution. The clearance from the braln over ~he course o~ the study is slow with a T~ of 20,8 hours. Blood activity remains below 10l and the lung contained less than 3~ of the injected dose at 70 minutes poet injection. Tc-ECD cleated rapidly through the ;rena~ system wizb urinary output at two and twenty-four hours accounting for 50 and 70~ of the I.D. respectively. Yi~al nig,s~ blood and afire chemistries remained normal Repeated ~PECT imaBing s t u d i e s showed an unchanged diS~ribution pattern of the activity o~ertime. In :onclusion, t h e Tc-ECD appears t o be stable and useful to assess reBionsl cerebral blood flow in humans.

3O I~ ' U.Schmidt, G.Notohamiprodjo, K.Vyska, O.Busse. ] Institute of Nuclear Medicine, Heart Center North Rhine-Westphalia, Bad Oeynhausen, FRG.

ASSESSMENT OF REGIONAL PERFUSION RESERVE BY USING Tc-99m-HMPAO AT DIFFERENT END-TIDAL COz-LEVELS

T h e p r e s e n t s t u d y investigates possi~ble ~e--la~

tions between basal ganglia hyperactivity and abnormal hemispheric asymmetry in schizopbreni~ as a first step towards a more flexible model of brain laterality alterations in schizopre nia. Following induction of a schizoprenielike psychosis, caused by intake of .5 g Mescaline .(M) sulfate, 6 healthy male volbnteers were studied neurophysiologically (SPECT) and neuropsychologically (tachistoscopic visual half-field tests) for "primary" alterations in hemisphere functioning. Test-results were then statistically correlated with results of earlier tests, done in a nonpsychotie state. The 99m-Tc-HMPAO SPECT, undertaken at the peak of the psychosis, revealed a marked right-sides striatolimbic increase of 9Sm-Tc-HMPAO uptake under M in comparison with that found earlier unter control conditions (p= .036). In parallel with the neurophysiological changes, repeatedly monitored RH capacity to recognize tachistoscopicslly-presented face stimuli was reduced, possibly because of competition or interference between the RH demands of the testing material and the RH demands on the subject .imposed by the drug-induced visual hallucinations. RH performance was f u ~ h e r disturbed following tachistoscopic presentation of distracting emotional stimuli, much as has been found with schizophrenic patients. To the extent that a M-induced psychosis faithfully mimics a true schi ophrenic psychosis, the possibility is raised of a state of primary striatolimbic hyperactivi. ty of the RH in acute schizophrenia, with LH dysfunction and later neurophysimlogical alera_+ions as secondary, dependent phenomena.

Decreased cerebral perfusion pressure is widely compensated by mobilization of the perfusion reserve mediated by local CO z balance. The question is posed whether an increase in arterial CO z would change Tc-99m-HMPAO uptake so that this could reflect peKusion reserve_ z7 investigations (based on two consecutive injections o[ g mCi Tc-99m-HMPAO at tilt[trent end tidal CO -levels except for 4 controls range: 2. 7 - 7.a vol~) were carried out in z3 individuals; I3 of them had ACI stenoses > 754 (CVD), 6 had no significant extraeranial stenoses, but multiple coronary vessel disease (MVD), 4 were normal volunteers (NS). Tc-99m-HMPAO cerebral uptake at hypercapnia exceeded that at normo-/hypocapoia by 35.8% on average. The individual increase in uptake (dU) depended linearly on the CO -difference obtained in the respective situation (r~ean difference = 2. 3 void). In CVD dU was 9-7 ± 8% and in NS 33_+7.3% per % change in COz-cOncentration. There was no correlation between flU and uptake relative to the injected activity. No significant dKferences in dU between frontal, tempotoparietal and occipital cortex were observed. On the basis of reproducibility testing, if was found that an increase of > lo% of overall cerebral activity in an individual subject can be regarded as significant (SD = 54). Within a range of 3 - 7 void, changes in endtidal CO -concentration produce significant alterations ingTc-99m-HMPAO uptake. Thus, perfusion reserve is re[lectod by the increment o( activity uptake per % change in COg-concentration.

228 31 H.Feistel, F.Wolf

32 H.Stefan,

33

G.Platach,d.Bsuer, I[ Leinsin~er, P. Schmiedek, T. Kreisig, Einh~upl, g. Moser amd C.-M. Kirsch

Institut fdr Nuklearmedizin und Neurologiscbe Universit~tsklinik der Friedrich-Alexander-Univerait~t Erlangen- N~rnberg, Erlangen, FRG Tc- 9 9m-}RdPAO-SPECT DURING FOCAL EPILEPSY

SEIZURES

k. Cnetm~au, J.F. tectal, p, Peltier, e. Bipoche N. T e u e n ~ , C, DiEabel.P.A,I~/%tlr

Dapts. of Nuclear Medicine, Neurosurgery and Neurology, Univ. of M~nich, Klinlkum Gr0~haderr Munich, FRG OF

~CEEESROVASCULA~SEEVE CAPACITY (CVEC) MEASUIRED BY 133Xe-DSPECT - A hrEWAPPROACE TO DIAGNOSIS AND TREATME~ OF C~KONIC CEILbBKAL IgCEEMIA.

We report on e i g h t patients suffering from epileptic seizures, who underwent preneurosurgical diagnostics to localize t h e e p i l e p t i c f o c u s (five t e m p o r a l lobe [TLE], t w o f r o n t a l l o b e [FLE], o n e m u l t i f o c a l e p i l e p s y ) . A n i n t e n s i v e monit o r i n g w a s p e r f o r m e d in all p a t i e n t s b y means of v i d e o camera, long term EgG and a s p e c i a l emergency call system, which was installed to provide inunediate reaction. After onset of the s e i z u r e 12 m C i T c - 9 9 m - H ~ P A O were pro ~ pared and injected within two minutes, in s o m e c a s e s w i t h i n 30 s e c o n d s . B r a i n EPECT was performed one h o u r l a t e r in nuclear medicine department with S I E M E N S R O T A C A M E R A (6 ~ a n g l e , 64 m a trix, 1 mln/proj .) , semiquantative evaluation was done according to PODREKA' s algorithm by means of regional perfusion indices. In all patients interictal SFECT was performed under EEGcontrol ruling out s u b c l i n i c a l c o u r s e s of a t t a c k s . Results up to now show not only the m o n o f o c a l (7 p a t i e n t s ) or the multifocal regions (i p a t i e n t ) , but also contralateral hyperperfusion and asymmetric cerebellar pattern. Even if in conventional surface EEG no activity may be registered, the corresponding ' n o n i c t a l * S P E C T s h o w s a r e a s of a l t e r e d perfusion. Controlled ictal SPECT may be helpful to l o c a l i z e t h e e p i l e p t o g e n i c f o c u s in TLE a n d in m o n o f o c a l FLE with respect to n u r o s u r g i c a l excision. The first patient operated in the meantime is f r e e of a t t a c k s now.

The efficacy of bypass surgery compared to meIdical therapy ig patients (pts) with cerebrovascular disease again is a matter of =on, Pcverse discussion. Previous s=udies usually neglect f~mctioual data. The aim of the present study was to involve rCBF values (ml/|OOg/min) at rest a~d after pharmacologlcal stimulation (~rCBF = CVRC) tO assess the perfusion status of the brain. The study included 26 normals and 55 pts with occlusion of the internal carotid artery, In normals, we f~una a negatfve correlation of ~ rCBF after i.v.-~njeetion of I g aeetazolamide a~d rCBF at resting conditions: ~ r C B ~ = -0.5 TCEF + &2; r = - 0,7~. A ~ange of + 2 SD from this regression line (95%-~oleranca interval) was considered normal. Equidistant (5 ml/T00g/min) curves to the lower confidence line defined re,gee of small, moderate or severe DV~C-reductlon. In ~8 pts (~7%), CVRC was reduced on the diseased side. The extent of reductlon, howeve¢, did not correlate to the findings of transmlssion-CT, because 12 of 21 pts (57%) wi~h ~ormal CT-sca~s presented moderate to severe CeRC-reduction. In contrast, CVRC corresponded to the extent of arterial collateralisation as documented b y cerebral panangio~raphy. In 31 pts EC/IC-bypass surgery was performed. In follow-up studies (3-12 months Ipostoperatively) CVRC increased especially in pt~ who had a severe red~etion preoperatively. Therefore, combined measurements of rgBF at rest and CVEC is a sensitive, non-invaslve me~hod for the diagnosis of (even bilateral) ca~rebrovaseular disease and can be helpful t= identify pts with hemodynamlc ischemia, wh~ m~ benefit it from EC/IC-bypass surgery.

34

35

iM. Odavi~, M. Elakovid, M. Djukni~, Z. Jankovid M. Rastovac, and N. Bojanid:

I

Centre R. GAUDU(~EAU,4~O35 NANCES Cebex, FRANCE

ROLE CF ]~dUNCSCINIZG~ApHYUSING ~N 111-LABQJ~ MONCf[ONAL ~ D I E S A G A ~ T (2~ AND/OR CA 19-9 IN PRO~pEC~ SIUDES CF GDLORECTALC~RCINCHA~CL~P~C~

Tee results of zn~-~scinti~,aphy (IS) in visual/zi~ suspected l~currencesof Colorectal c~ncer were c o ~ blindlywith those of co~ubed ton~aphy (CT) and L/ltr~oncgraphy (US) in I p~psctive stu~ of 35 patients~ About Img of F{ab')2 f r a ~ t s of anti.tEAand/or CA 19-9 labeled with 111 5Z3g ~f /n 111 was injectedin~ psEiemts (14 with anti-tEA, 17 ~ith 19-9 ~:d 4 with both 8ntibodies). I Tu~or ~srker levels were significantin 33 patients, and 8 ~thwed associatedelirlical~igns such as p~in. Three days after injection, ~odo~al and pelvic plan~ sc~ntig~aphyand SPECT reCOrdir~s~ perforI~ed. To I obtal~ ~tc~nieal l~r~b~ks, ~he ~ views were done

with the patient ~ the ~ e pssition us~ Tc 99m-labeled DTPA, colloids and M)p. ~ s t ~ t i c subtractionwas performed for hepatic psreneh~m~ Surgical biopsy or althicalcourse dsIing at l~ast 6 m~ths was the h~s~s for Ileal diagnosis. Sensitivity of 13 was B3 % fo~ liver metastas~s, 50 % for extrahepatic abds~ tL~sOrs~ 93 % for pelvic recurrences. ~hree peritoneal c~relnc~sswere n0t visualized.8eca~se of IS subtraction there were false-positivesfor the liver, with specificityof only 7~ %, whereas ~br extrabepstie specificitywas 100 %. For US, sensitivitywBs 3~ % for extrahepatic re~/rrencesand 9 1 % for Liver m~tastases ; overall specificity was 100 %. For CT, overall s~sitivity was 50 %, with better results for the liver (71%) ; overall specificityw ~ 97 %. Tn~e data 1s u ~ t that IS, with an overall sensitivityof 82 %, dS ~ ~ ~ the ~ i a l ~ ~st be~o~ in prospectivestudy of cclorectalrecurrences.

l

C APHILE, PG DE FILIPPI,R SAPONARO,A OOMANDONE M CAHENA,M EACCEGA.

INSTITUTE OF NUCLEARMEDICINE M M A, Crnotravska Str. ~7 (Bsnjica) I I 000 B E 0 G R A D (Yugoslavia)

Fond. Cllnica Lavoro,Nucl. Med.gerv. PAVIA; H.delle Molinette,Nucl.Med.Serv. TORIMO; ITALY

)IAGNOSTIC AND PROGNOSTICRELIABILITY OF THE IRADIOIMMUNOSCINTIGRAPHY(RIS) IN COLORECTAL CARCINOMA

RADIOIMMUNODETECTION WITH iSl I MoAb tEA AND 19-9 OF GASTROINTESTINAL TUMORS AND THEIR METASTASES.

The aim of the study was to assess diagnostic r e l i a b i l i t y or RIS using MoAb CA 19.9 F(ab')2, mti-CEA F(ab')2, IMACIS-| International CIS, i n patients with celorectal carcinoma. Prospective clinical t r i a l was performed in 6B patient~ using RIS, and tumor markers (CEA, TPA, CA 19.9 every six months. No side effects were noticed a f t e r application of labeled monoclsnsl antibod es. Uslng ~deolslOn matrix" system, the following results were achieved: sensitivity 90.g8%, specificity 59.23%, accuracy 82.35%; faIse-posirive results was 18.18%, and false-negative re'sulfa was IT.Bg%. Predictive value of the positive test is 82,61%, and predictive value of th( Inegative geat is 8|.82%. Chi-squere is 26 15B, and contingency coefficient: D : 0,527. There are high s t a t i s t i c a l l y significant correlation between clinical findings and immunoscintigraph~ lappearance. The diagnostic validity of tEA, TPA, and CA |9.9 serum concentration were particularly useful in suspected and obscure cases. The combined measurement of TPA end CA 19.9 serum ilsvels has shovm to be much more diagnosticaly useful than measurement of CEA level alone. LiVer ~etaatasea was true positive in 71.42%, and true negative in I00,0% of cases. Radioimmunsscintigraphy has shown to be very luseful, nonrisky, easy to perform and reliable diagnostic procedure in following of patients with colorecta] carcinoma treated surgically.

We report the Tesults of a work undertaken by two nuclear medicine oentres to assess the clinical usefulness of radioimmunodetection (HID)with an immunocooktail MOAt tEA and 19-9, F(Ab')g labelled with 131 I{Imacis i). In sa pts with malignancies from the gastrointestinal tract(128 t ~ o r altos)Ha scintiEraphic studies have been performed.Multlpl¢ overlappinE views were taken st different times after administration(Ill MEg) in about half the cases until the 10th day.Final diagnosis was confirmed by surgery ~nd/or US,CT,Xray,endoscopy. Test performance results:Sensitivity .74,Specificity ,6S,Accuracy .gS,Ppv .93,NPV .32.Test sensitivity was bette~ in the detection of abdominal,pelvic and hepatic lesion than in the lung's. Tumor visualization was obtained as early as 4S-96 hrs p.i.,while late~ scans,with a worsenin E of the signal to noise ratio.did not offer real advantages. Scan positivity was related to the rate of increase of circulating antigens with time rather than to theic absolute value.False positive results could be attributed to technical artifacts due to accumulation of labelled compoundsin the caecum and rectal ampulla. Therefore RID with this immunocooktail seems to off~? real advantages in the clinical ~ana~ gemest of pts with gastrointestinal tumors,although a negative scan cannot rule Gun the presence of local or diztant recurrences.

36 H.Felstel, F.Wolf

W.J~ger,

E.M.Paterok,

I n s t i t u t fur N u k l e a r m e d i z i n Universit~tsfrauenklinik

N.Lang,

und

Friedrich-Alexander-Universit~t Erlangen-N~rnberg,Erlangen, PRG 'REGAI ~ RESECTION GUIDED BY ANTIBODIES (IODINIZED) A NEW PROCEDURE FOLLOWING IMMUNOSCINTIGRAPHY TO LOCALIZE MINOR RESIDUES OF OVARIA~ CANCER 14 p a t i e n t s w i t h o v a r i a n t u m o u r h a d b e e n s u b m i t t e d to the surgical p r o c e d u r e we call R E G A I to a s s e s s t r e a t m e n t r e s p o n s e to chemotherapy. All patients got computertomography, immunoecintigraphy and clinical examination. Tumour marker level of C A - 1 2 5 h a d i n c r e a s e d in s e v e n patients. Radioimmunodetection was per ~ formed with '131-J-labeled monoclonal antibody OC-125 ( F(ab'2)-fragments). Scintigrams were taken between third and sixth day p.i. in p l a n a r technique. Between eighth and 13th d a y p.i. R E G A I was initiated. For detection of i n t r a abdominal micrometastases a collimated hand scintillation detector was used (Derthold, Munich, FRG). Scintillation was c o u n t e d d u r i n g s u r g e r y a f t e r s e v e r a l peritoneal washings. Positive countrates w e r e a s s u m e d to be 50 % h i g h e r t h a n b a c k ground noise. Tissue samples were removed from those suspicious areas, additional blind punctions were obtained. F r o m 173 b i o p s i e s 69 p r o v e d to be m a l i g n a n t . In 88 randomly performed excisions o n l y 13 showed micrometastasos, b u t 56 o u t of 85 REGAl- tissues. From nine histologically verified cases of metastatic involvement only four could be visualized macroscopically. Three patients showed micrometastases in s p i t s of normal ttimor m a r k e r levels. REGAl t e c h n i q u e s e e m s to be of b e n e f i t in ' n o - m a r k e r ' p a t i e n t s e n d in p a t i e n t s with negative immunoscintigramm a n d increa~ed tumourmarker levels. r -

-

-

229

37

38

39

F._Orippa°, M.~sparini °, E.Seregni°, M.Presti °°,A.Marin~°°~ R.V.Fontanelli°,L.Landoni °°% M.I.Colnaghi °, G.L.Bu~aggi°

S.Lmstoria, p.D'Amico, Nansi, M.Salvatore.

°National Cancer Institute of Milan, Italy - °° I l l Obst. and Gyneac. Clinic of University of Milan, Italy - °°°Univ. Dbst. and G~naE. Clinic, S.GarardoHospital, M~nza, Italy

]/¢~NDS;INTIGRA~IYflF ~ ~ wnH I%0 MB~O(I(I~. ~IIIBODIE~; RA'18 AN) 0C 125 F(ab') 2

40 D.PECTASIDID.K.PATERIOTIS,L.TZIMIS, X~,P.NATEIS,P.ABAPANTONI.J.TAYLO] PAPADIMITBIOU,~.EPENETSS,A.ATHANASIOU, .KOUTS O B . 6Pept. o~ ~cAlear M e d i c i . . . . d I st D e p t of P a t h o l o g y , M e t & x a Cancer Hosp.Piraeus. Imperial Cancer Bee.Found. Hammermith Hospital. ABDOMINAL CT-SCAN VENSUS IMMUNOSCINTIGBAPHY WITH 131-I LABELLED NoAbHMFO2 & HMFGI(Fab')2 IN T H E D E T E C T I O N OF R E S I DUAL DISEASE IN O V A R I A N CANCER PATIENTS In 15 p t s w i t h o v a r i a n carcinoma w h o suceesfully completedtheir chemotherapy and were clinically in c o m p l e t e or p a r tial response, the 131-I labelled MoAb HMFG2 and HMFGI(Fab')2 w~s ~dministered intraperitoneally. All pts were scanned at 2 4 - 9 6 h p o s t - i n . ~ e c t i o n . T h e immunosci" ntiKraphy results were compared with t h o s e of a b d o m i n a l CT-scan and those of gnd look laparotomy.Blood and urine s~m lea w e r e c o l l e c t e d for pharmaeokinetic studies.In 12/15 pts the immunoscan sho" w e d a r e a s of i n c r e a s e d uptake, indicating the presence of r e s i d u a l disease. The abdominal CT-scan wQs normal in 4/1~ pie,In 9/12 who undergone 2nd look lap~ rotolay, t h e o p e r a t i o n findings w e r e similar with tho~e of t h e i m m a n o s c a n results (100~).In contrast o n l y in 6 / 9 p t s (67~) the 2nd look operation findings were similar w i t h t h o s e of t h e a b d o m i n a CT-scan results.In the re~t 3/15pts the 131-I labelled HoAb stooed in t h e a d m i nistration a r e a d u e to t h e p r e s e n c e of extensive symDhyses.The hi,heat activit of t h e a d m l n ~ s t e r e d d o s e of 1 3 1 - I d e t e c t e d in t h e b l o o d at 154 p o s t - i n ~ e c t i o n a n d &t 2 ~ h t h e a c t i v i t y had fallen in 50% Of t h e i n i t i a l dose.On t h e o t h e r ha nd t h e h i g h e s t activity in t h e u r i n e sa mules detected at 7 S h p o s t - ~ n j e c t i o n , Conclusions. I. I n t r a D e r i t o n e a l idministration of 1 3 1 - I l a b e l l e d MoAb can detect with high degree of ~ c c u r a e v the presence of r e s i d u a l disease in o v a r i a n cancer pts. ~. T h e i m m u n o s c a n is s u p e r i or, c o m p a r e d to a b d o m i n a l CT-scan in the detection of r e i d u a l disease'.

N.Panza,

L.

2nd l ~ U.211 Centre Ren~ C,audusheeu, Nantes, FRANCE.

Early recurrence and/or m~tastases ~-~taction is an important problem in the monagsl~nt of ovarian cancer and on this sub ject two fmmr~scintigrephic trials are in progress at the Nuclear l%=4icire Division of the National Cancer Institute of Milan (INT). l?e forTmr trial is a retrospective study to evaluate the clinical utility of ~Dv]8, a new m~lonal antibody (NbAb)with high tumor specificity against human ovarian narcinam, selected by the Exbarimmtal Dnco]oc/y "E" of ~NT3r:4 la~eUed with 1-13l by S~rin Biemadfca, Sa luggia. At present, 19 patients with advancedovarian carci F~mS are evaluable. M]v18vas injected intravenously (16) or intraperitoneally (3) (m~anac~inis~ered activity 2.73 TCi or IOl.Ol ~Bq, masnM~Abquantity 0.544 rag) and the i,T~noseintigrephic results ~re comparedwith laparothemy. Preliminary results indicated that M3vl8 is a suitable reagent to study ovarian caroinam. rne lattE trial is a prospective study with the 1-131 ~Ab OC 125 F(ab' )~ (CIS), basedon scintigraphy m~qitaring )f ovarian carcinc6~as in patients v~o have previously ~ndergone s~gery. Tne inmmoscintigraphic results Were Fx~paredwith surgical 2~d lock. At present, 20 patients are .Waluable. Ft~b vas injected intravenously (meanac~iniste ed activity 3 mCi or I l l ~gq, n~anr~b quantity l mg). reliminary results gave 2 false positive patients and 6 alse negative ones. H~ver, it has to b~ noted that ~ng the false negative cases, only 3 patients bad elevated eu.n~ levels of CA 125 antigen.

G.Pacilio,

P. Peltier, J.F. Cqatal C. Curtet, P. Tne~.ez. Medical School, Rational Cancer Institute and Cardarelli Hospital, Naples, Italy,

B72,3 1-131 IM~NOSCINTIGRAPHY

CC~?ARATIVE DIAgnOSTIC ACemP&CEOF IM~DNOSCINYfh~J~HY USI~ OC 125 MONO~NAL ~NT~BODY (Feb) LAB~/D WITH IN-111 A~D 1-131 IN T:~ S ~ PATIOS. ~everul studies ~ v e shown the diagnostic accuracy of 1-131 OC 125 MAb. However, as the radioph~ical char~cteristins of 1-131 aze less favorable than those of In-111, the present study was undertaken to 0ampere the d~agnostic accuracy of In-111 and 1-131 OC 125 MSh in pelvic exa~D/~tio~s in the same patients. ~C 125 F(ab') 2 f r a ~ t s were injected IV into 18 patients with ovarian serous carclr~Tms, accordir~ to the following protocol : injecttoo of I/~-111 OC 125 at day 0, platter scin~igrapby (PS) a~d ~nisaion c~uted tomography (ECT) r~cordings follow~d by 1-131 0C 125 inJectios at day 3, PS and ECT recordir~ Lsirg the sa~e p~-ameters at day 6. The ECT and PS i~s~-s were blindly linterpreted by E observers (01,02), and the results were th~ compared with the final diagnosi~ (su~&~ry or latient's co~s~). Pelvic tumor ~r=s confirmed in 13/18 latients. With In-111 0C 125, 01 found 15 ECT and 6 PS • ~ges positive~ and 02 I0 ECT and 5 PS ; 01 found ~ ECT md 2 PS false-positive, and 02 1 ECT and 0 PS. Onterotserver r~producibility was v e ~ good for ECT (17 :oncord~) and moderate for PS (10 concordances). ~ith 1-131 OC 125, 51 found 7 ECT and 10 PS i n ~ s lenitive, and 02 6 ECT and 8 PS ; 01 fo~d 3 ECT and 3 ~S false-positive, and 02 1 ECT and 2 PS. Interobse~ver .eproducibility was ~oderate for ECT (10 concordances) ~d good for PS (13 cone0rdances). :ndium 111 ECT, ~ave more accurate results than 1-131 ~CT, 1-131PS or In-111PS, whereas 1-131 ps was tatter ,bsn ~-111 PS.

IN OVARIAN CANCEl

B7~,3

is a monoolonal antibody (MAb) recognizin~ a tumor associated glyeoprotein (TAG72) expressed on the cellular surface of epithelial cancer. In particular, B72 3 binds to all the most I diffuse ovarian carcinoma, includin~ serous and I mutinous histotype. BadioimmunoscintiEraphy i (RID1 wss performed in 37 patients afer i.v. ad~ ministration of iii MBq of 1-131 B72.~ (speci- " tic activity; !E5MBq/mN). ~Snole body ~nd spot I i m ~ e s were obtained during ~ 96 hours period post-injection. Patients were divided in 3 groups; i) 17 with prima~y tumor and aseites before surgery and/or chemotherapy; ~) IO with minimBl or bulky disease after a therapeuticml approach; S) iO disease-free, from clinical, serological and radiologioal point of view, at the time of RID, after surgery and/or chemotherapy. Positive results were obtained in 15 out of 17 patients of group I and in 6 out of ]O in the second Stoup. In £roup 3 m f~ise ~ositive wms observed in a patient stud~ed gO days afte~ a surgical second look. gig results showed good agreement with X-ray CT and ultrasound findings with a better capability in differentiate tumor rather post-surH~cal fibrosis. i

42

41 }]UGLO D., LECOUFFE P., ROUSSEAU a., PRANGERE T., LAFITTE J-J., MARCBANDISEX. Service Associ~ de Mgdecine Nuclgaire Unit4 d'Imagerie RMN DE~partement de Pneumophtisiologie CHU L i l l e - 59037 L i l l e - France

NMR AND ISOTOPIC MEASUREMENTS OF LUNG WATER CONTENT Pulmonary edema is related to an increase in lung water. I t may be quantified by many techniques such as impedancemetry, absorptiometry, X ray, CT scan among which isotopic dilution m e t h o d is t h e b e s t v a l i d a t e d . Measurement of lung water may also be done using proton NMR imagiag. A NMR study was performed on l0 normal volunteers after it had been validated using )hantoms, Pulmonary T1 being about 600 ms at 0.5 T, a CuSO4 (0.45g/i) solution in 70 % U20 and 30 % H20 was used as a reference ; it was put in a PVC tube placed under the patient's arm. This reference was also used to correct spatial inhomogeneity, 10 to 14 axial 2g-ram images in format 120x128 were done contiguously on chest using 2 SE sequences (500/28 and 3000/28/4 echos), with cardiac gadng and respiratory pseudogating, Volume and percent of water in each lung were calculated from ROIs. A study of extravascu~r ]Ling water expressed as fraction of blood flow and of blood volume was done concurrently, using 123]odoAnflpyrine and 99mTc-HSA from an adaptation of the method Of FAZIO (J N M 1976, 20, 81). Our NMR results were 15.4 % _+ 2.4 (17 % in Mc LENNANrs 6 subjects : Br J R 1907, 59, 553), with a good correlation with T2 (r~.74, p .05) but no correlation with T1 values. Difference between left Bnd right lungs was 6 %. The range of isotopic results was much wider : difference between lungs was 24 %, mostly as a consequence of the mathematical fittingS.

Q~O.SLOSMAN

~

A. DONATH,

Nuclear Mndectne Division, Hopltal cantonal unlversltaire. 211 Geneva 4, Sw~lzedand.

THE USE OF METAIODOBENZYLGUADINE (MIBG) FOR THE EVALUATION OF LUNG ENDOTHELIAL CELL FUNCTION." The combined use of propranolol (pRoP), a basic [IpophUic ~,mine, and norsplnephrine (NE), a blogsnic amine has been ~valuated In human for the assessment of pulmonary endolhelIBI ;ell funcdon and tung funclional vascular sudace. Using the solated perlused lung model, we have observed thai HIPOM and MP has p opadies similar lO those of PROP, and MIBG similar to hose NE. A non invaslve method has been proposed for clinically I ~va u.,,fing he r pu ,'~onary extredion. We used the model ~.f ;solated psrfused lung of rals to tesl [f MISG 1-131 lung extraction ' (%E is ) dependent of Iho pulmonary vascular sudace available Lo the blood pool and 2) dependent of the slmubaneous adminstraion of iMP 1-125. MIBG (1FM) and IMP (1 and 10 ~M accumulations were studied after a 2-rain peHuslon to(lowing I a t0-mln perfuson wth Krebs-Rlnger albumin buffet. Lung o0ntent of radloiod ne acllMy per g of lung was measured. %E IMP and M BG were exp essed as % of total perfused a,~tivlty. The loss ~f pu monary vascular surface was simulated by broncho-vascular ligatures and was expressed as % of Iotal lung weight (%W). In normal ¢~ndiUon, %E MIBG was 9.1 ± 1,1% (mean ± SO, n=8), An inverse linear relaIIonshib was observed between %g and % W (y.O.1O-0.08x R-0,75, p<0.0Ol, n-20). WUb a S0% loss of sudace, %E MIBG decreased to 4.1 ± 2.1% (.4.462. p<0.001, n=13). With the simultaneous inlusion of IMP (1pM), ws still observed the linear correlation between %E MIBG and %W (y=5.ao-004x, R =0 5 3 b<0.05 n=15), but we observed also an inh bidon of the %E MIBG fonmlon o~ the IMP concentration; [t w~,s observed In normal ¢ondklon (%E MIHG.5.7:E1.6% wsh pM and 2.0±0.5% with 10pM o1 IMP) as well as In all expsdmBnts wilh ligxtures; in addition no relationship between the %E IMP and °/oW was observed. In concuson these results confirm 1hat %E MIBG does not only re act the endothelial celt function but also depends of the pulmonary vascular suNacs available Fudhermore, an inhibition of %E MIBG omcurod with lhB addition of IMP. Therefore, the simullaneous evaluatlo, of their lung emtacgon Is nol possible and another proeedure such as the kinetic analysis ol MIBG extrac0on Is required to differentiate eudolhellal function and pulmonary vascular sudace perused. • daam of the Swls~ National Pundal~On lor Scientific Research Ro 3.985-e,80.

230 44

43 L.61anl, M. MiniaU, 5. Petruzzelli, A Fontane, M. Pistolesi, C, @iunt~ni, C.N.R. Institute of Clinical Physiology, Plsa,=and U University of Rsme, Italy. LUN6 RETENTIONOF IODOBENZYLPROPANEOIAMINEA5 AN INDEXOF NONRESPIRATO~YLUN8 FUNCTIONSIN MAN,

The b~o nempou~J N,N,N'-(rlmetbyI-N'-(2-1wdroxy3-methyl-$-iodopenzyl)-1,3mprapanadi~nine (HIPDM) is tokenup by the lungs wffhu hlohllasoetobloedr=',tlo.Wg studied In man the lung kineti~ of I.v. tn)ested 1231-HlPOM. Time ectlvtty gurves wgrs regarded over the lungs by ~ m g camera for 90 rain after InJeotlen In 83 suhJeots: 13 normal non smokers (NS), 12 asymglomatic smokers(5), I I pgtlents with lung cencer (C), 23 with chronic oOstrucUve lung dlsea~ ((]OLD), Ig with interstltiel lung dis~ce (ILD) and 5 with eduH respiralccy d i s t r ~ ~'n~'ome (ARD5), Ni~W-oi~ per cent of COLD en~ C patients and 48% of ILD patients were current smokers. The First gemportent was cempleled by 30 rain niter injesUon, indiceUng rapidly reverelhle HIPDrl tung distribution. The ~enond component was cherastericed by a slower monoexponenliul decline of redioactJvih/, csmpatible with o mare slable cellul~ blndinp We o~mputed the m ~ time

('/) of Ihis component as an index of HIPDri Tungretention: N5 5 C COLD fLO ARD,S T(hre) 7.2 ±gO 1.1

12.2'"

2.1

12,7,"

4.3

I0.7. 2.9

9.6"

2,8

25.1... 4.7

*p<0,05 cemparedto NS; ='p
Lung relention Of HIPDM Wee not correlated with function tests end PaOZ Siene masl ofCOLD and C patients were smokers, lung persistence of HIPDH could be related to smoke esposurg, Howeves,smoke had no apparent effect on HIPDM lungcls~"ance In ILD potlentg (t: I0.2 ± 3.6 hrl in smokers re. 9.2 ± 2.2 hrs In nonsmokers). Pesslslsm:eof HIPD~ in the lung m~ reties( an increasedlung oellulorilylnoucad by emokJngor by acute and ~ronle InFlummatory p r o c ~ or may be expresslonof 9 ~11 mgt~oollc dysfgnctlon.

C.~chueminhen, W.Mosehallsky

2 IJ.J.P. de LimaT, A.M.S. Pereira, and M.F.BotelhoI

g.Danilov, A.Martynov, A.Klibanov~ A.Slinkin~ I.Sakharov, V.Muzykantov, ~.Malov, V.Sergienko, V.Torchilin

Department of Nuclear Medicine, University Clinic of Radiology, Freiburg, FRG USSR Cardiology

L~b. R~dlolsotopos, F~c. de Mediclna, Universi. Coimbra De0. E1~cUronica e [elecomu. UniversidBdede Aveiro

.

~[,

~

~

I.

with a little noise.

Center

IMAGING OF LUNG VESSELS USING Ill%NL A B E L E D M O N O C L O N A L A N T I B O D Y TO ANGIOTENSIN-CONVERTING ENZYME

Inhalation selntigraphy with Te-Sgm labelled aerosol (aerodynamic mean diameter (AMD) 0.48 urn) is used as a substitute for ventilation seintigraphy w~th inert gases. However in pts with obstructive airway disease the radioaerosol deposition does not follows the regional ventiintinn distribution. To overcome this problem, ultrafine particles (AMD below 0.001 urn) are needed.

M o u s e m o n o c l o n a l a n t i b o d y (MoAb) a g a i n s t h u m a n a n g i o t e n s i n - c o n v e r t i n g enz!nve (ACE) ~as r a d i o l a b s l e d w i t h l l l I n v i a D T P A ~ i t h o u t s u b s t a n t i a l loss of a n t i g e n b i n d i n g c a p a c i t y . This M o A b d e s i g n a t e d 989 c r o s s - r e a c t s w i t h rat a ~ d ~ o ~ k e y A C E .

In this study the principles of particle generation by evaporation of Tc-99m pertechnetate were investigated in order to make this process more effective and less expensive. Evaporation was performed in a h e a t resistent chamber, filled either with dried air, oxygen, nitrogen or argon. Various materials were used for the cruieible: platinum foil (melting point 1769 C), molybdenum (2610 C), tungsten (3367 C) and graphite sheets (3727 C). Th~ er~ialble was he,ted ~p electrically (maximum 21 V, 288 A) in three steps to evaporate i.) water, 2.) NaCI and 3.) Te-99m pertechnetate. Depositlon of radioaeres01 in the bronchial system was measured both in a lung phantom and in patient~ I. Two-step evaporation of Te-S9m pertechnetate together with NaCI a t 1500 C gielded a low efficiency and larger particles due to a hyg~cscopie partiele growth. 2. Three-step evaporation above 25~ C in a metal cruinable removed all NaCI but produced neverthegess larger particles because of volatile metal oxides. Oxidation could be prevented neither by nitrogen nor by argon (99.99 % purity). A high evaporation yield and extremely small particles were obtained in a graphite cruicable. 4. Th/S yield was even more improved by oxygen instead of nitrogen or argon. These ultrafine, non-hygroscoplc particles proved perfectly suitable for ventilation studies even in pts with severe obstrucUve airway disease.

K. Liewendahl, K. Kairemo, A-L. Irownell, U. Aronen, M. M~ntyl§

After intravenous injection lllIn-9B9 ~as s e l e c t i v e l y a c c u m u l a t e d i n t o r a t l u n g s (i0 to 20 f o l d h i g h e r accumulation t h a n in b l o o d in o t h e r o r g a n s ) . N O dama. ~ i n g e f f e c t s o f M o A b 9B9 i n l u n g s w e r e o b s e r v e d p r o b a b l y due to the f a c t t h a t the M o A b 989 h a s no c o m p l e m e n t - f i x i n g c a p a c i t y . T h e k i n e t i c s of l u n g s acc~LmUlation and blood clearance was studied for l l l I n - g B 9 - a n t i b o d y . H i g h l y specific a c c U m u l a t i o n of l l l I n - 9 H 9 - a n t i b o d y in lungs after intravenous injection into Macaca Rhesus was monitored by gammai m a g i n g . I m a g e s of l l l I n - l a b e l e d a n t i b o d y b i o d i s t r i b u t i o n in m o n k e y l u n g not i c e a b l y d i f f e r f r o m the i m a g e s o f b i o d i s t r i b u t i o n of 9 9 m T c - l a b e l e d a l b u m i n m i c r o s p h e r e s . This d i f f e r e n c e assu/nes t h a t r a d i o l a b l e d M o A b 9B9 m a y p r o v i d e i n f o r m a t i o n c o n c e r n i n g the s t a t e of the s n d o t h e l i u m of l u n g c a p p i l a r i e s in cont r a s t to the c h a r a c t e r i s t i c s of the blood f l o w i n the c o r r e s p o n d i n g a r e a s which is p r o v i d e d b y 9 9 n ~ c - m i c r o s p h e r e s . A p p l i c a t i o n of this p h e n o m e n a for d i a g n o s t i c s o f m a s s i v e d a m a g e of endotheliL~n, s a r c o i d o s i s , and h e m a n g i o m ~ s are dis-

Icussed.

48 P. BlOdc( I, D. Beoquart 2, J. Van Meerbeeck3, M . ~ , A. Vrencg(en1 Depa~te

, METHODFOR THE UErRCTIONOF FUNCTIONALSHUNTSgN THE PULIONARYCIRCULATION method for the quantification of the non effective pulmonlery circulation, b~sed upon the deconvolutionoU the iirst mass curve of the actlviUy on the pulmonary area afteran in iectlon oR 2-~ mCi (74-~B MBq) 99mTc-MAA is OescribeO. "h~ prlnclple of the method Us in Fig. The input E is divi{ed by the upper flow (l~blrinth without activity retentlon] md the lower flow (full retenLlon of the activity). The ac:Uvity variations detweenthe traced lines in The Uwobran:bee are Ns e Np. The summation of those Functions is S. The 'uneUion gn that is the summation response Uor a normaliseO nput En (delta function) can he oblained Oy deconvolutlon. ;n is toe summation oU a step ~unction and a Fast dilutlon ;urve. When tug upper branch ls ,of present, Sn is a step :unction. h determtnatlono~ the area oF the dilution curve, :he corruspondingmean transit tlme,and £o the amplitude oT :he step function a11ows the calculatlon oF the ratio bet~een the flow of the two brancUes. In the pr~ctlc~1 silua:ions o~ the study oF pulmonary collateral circulaUionwUth 19mTc-MOA, the upper branch represents the arterlo-wnous ;hunts, Brigthe lower brancU the lunctionlngpulmonary parem Iuima. In tug present study, B GE ~OOT Gamma Camera and a ~ova ~g DG Computer wUlh hom: made ~oTtware Uas been used. Icquisition is made in frame mode (~g~Sg), with O.g sec per ~rame, anO during BD sec. cog's for lungs and subclavia are $rawn and deoonvolution is carried out.lhis metUod has been ~sed in 30 patEents incLuding B group of 8 normals. The re;ults of tug pBIiente with co116teralcirculationconflrn~d Oy pneumooraphy,show the interest oF this method. The uood statlsticgand the ~ ~m virtual absence of bacHgr! : ~" ound, touether with the

Research

GENERATION OF ULTRAFINE Te-99m PARTICLES FOR INHALATION SCINTIGRAPHY

47

46

45

of Nuclear Medicine (i), O n O o l o ~

Division of Nuclear Medicine and Opt. of Radiotherapy and 0neology, Helslnki University ICentral Hospital, Helsinkl, Finland

Hospital, B-2520 Edeg~n, BelgiL~a

IEXPERIENCE WITH IZ~In-LABELLED ANTI-CEA-ANTIIODY FOR IMAGING LUNG CA~CKR M~TASTASES

EVALUATION OF N~JRON SPECIFIC EADLASE IN UNTREAteD LUAU ~d~UJRS.

T4 patients with epidermoid or adenoma~ous pulmonary cancer were imaged with llZln-l~belled monoclonal anti-CEA-antibody (BW 431/31). All patients were imaged twice (i-g d), For image enhancement pulmonary end liver-spleen subtraction was performed in all patients using sgmTclabelled radiopharmaceuticals: ~IAA and tin-colloids. All 14 primary tumours were positive and also metastases were detected. None of patients had liver metastases in subtraction images, ultrasonography or g-ray computed tcmography (CT). There were a total of 43 kns~m primary or metastatic lesions, of which 42 (98%) could be detected. We found 3 unknown lesions, which were all subsequently verified histologically and radiologically, Other radiclogieal methods were applied to the sDudy of 34 lesions detected by i~unoscintigraphy. Two cases had brain metastases (planar and SPECT images were recorded), also visualized in CT. Pulmonary subtraction was found to be important for exclusion of pulmonary perfusion abnormalities and facilitate the interpretation of the images. When using sultraction we found in four patients 9 lesions, later verified to be pulmonary metastases, that were not detecteU in non-subtracted images. The lesions were also better delineated in pleura, medias~inum ang pericardium in subtraction images than in unprocessed planar i~unoscintigr~phy images. We conclude that detection of lung lesions by immuncscintigraphy is improved when using subtraction techniques, and irmaunoscintigraphy itself is a useful method of staging n o n ~ i e r ~ cellular pulmonary cancer.

(2) and ~eumDlcgy ( 3 ) , Antw~-p U n i v e r s i t y

In order to investigate its v~lue in ~ t r e a t e d lung carcinoma, ~ determined serum neuron specific enclose (N~E) in 60 patients witch histologically proved b r ~ a l carcinoma, of whom 27 (= 45%) had ~ a l l Cell lung cancer I(S~C), and 33 (= 55%) non ~vall cell lung ~ancer ( N S ~ ) . T ~ groups were again sub~ v i d e d in nm~-m~tastatic (Mo) and metastatic [M+) t ~ u r s , according to the results of the 3(aging procedure at the time of diagnosis. Zn untreated tm~our~, increased ~ NSE levels (> 12.5 ag/ml) were almost exclusively Observed in SCLC: a higher percentage was fourz in M+ cases (14/14 = 100%) than in M O ce~es (10/13 = 77%). In only one case of ms(asiatic ~SCLC ~ NSE w~s fomnd to ha slightly increased (i/14 = 7%). In n~n ~ t a s t a t i c NSCLC ~o increased NSE values ~ observed. WSE co~en%~-ations were found to ha higher in he(asiatic dise~se, as ~ 1 1 in SCLC as N S ~ . Statistic analysis (Wilcox~n rank ~ test) ~howed that t/%ese d i f f ~ were highly :igflificant (p < O,01) as well between M O 2rid ~+ for the same t ~ o u r type, as between both h m o u r types for the some stage. ~Dreover, h~E was found to be s valuable parameter in the follow up of SCLC, as well in limited Bs extended dlse~se. qowevef, some restrictions have to be made: - in ~hixed SC-NSC In/no~L~ lOW NSE levels m y ~ive the false i ~ r e s s i ~ of r ~ s s i o n , wb/le the NSC o ~ n e ~ t in fact progresses - haemolysis m y ~xtifici~lly increase t-he NSE valueS in s e x ~ through r ~ l ~ of red call NSE raking these comments into accota%t, NSE must be z~r~qidered a v~luable par~neter in ~he investi7 a t i ~ of it~gg cancer, as well for classification (S(~C - NSCLC), as for m o n i t o r ~ of SCLC.

231 49 M Gvsemans, J. Mertans, W. Vanryckeghem, A. Hermanne, R. Van Den Stean, M. Van Houdt. Vrije Univers~talt Brussel - Cydo~'on Dept. Laarbeeklaan 103 - 1090 Brussal

51

50

J. Stevovic, V. Bosnjakovic, J. Horvat, B.D. ~ k o v i c and S. Pavlovic

N. g. Dahlr. S. g. Hessle~ood & g. g. Jack"

medium UND~STA~IDINGTHECHEMICal~ B : ~ S l l C S OF THE BUT~FK)PHEk~)NE GROUP IN NL:LkqOR ECEPTC~q ~4~T#C-OM~TS ALLOW~ TO DEYELOP APPP<)PPLe~TE S~BSTPL~TESFOgNUCLEOPHILiCRN)~ FLUOF~WAllON leF-S~perone, hem been used as a 1racer for D~ receptor mapping in the br'~n with PET "Fheone step radio~ynthe~ds of tsF-Spiperone via the non4soto~c exchange on *:NOfSpiperone (NOfSpip) in alkaline condt]ons, presented as a hi~ yield synthesis and as the most promising alternative for the complex rnultistep synthesis, failed when ~ied by different groups. Therefore t~F-Spip is actually abandoned for N-fluoroalkyl Spiperones. This paper shows that NO=-Splp is not a suitable subs'cute for a one step nudeophilic radoflushnatmn. N%-Spip and

PREPARATIONAND PgOTEIh gIhglNG 0P PEhlAVALENT T~ BMSA

y-CbpNO~-butyrophenone(NO ~BP; the but~ro~lanone tail of spiperese) totally inhibit the radiofluorinal~on of cyclopropyl-p-NO ~-phenylketone (NO~PK), an achvaled rnolecUle which in absence of these compounds shows a labelling y~d of st least 90% As ke~ie~d analogues of NO2-Spip and NO=BP do not show this inhibi'don, the enhanced encl-tautomer form of the butyrophenone in NO~-Sp~p is supposed to cause the failure of nudeophilie racfofluorinal]on when using NO2-SPip as a subs~ate. Thanks to this knowledge alternshve subsb'ates for a high yield one-pot preparation of N-laF-alkyl Splp by drect exchange can be proposed. Kstalised N-X-alkyl Spip ia an appropriate subs@'ate for this purpose. On one hand the ~apping" of teF" by the enol tautomer ia avoided and on the other hand the isotopic radiofluorination of the subslrate is inactivated by the keial form.

52 T . R . C a r r o l l L. J. M a h e u , S. J- M i l l e r , S. M o u s a , a n d S. J. W i l l i a m s E. I. d u P o n t d e N e m o u r s & Co., M e d i c a l Pr o d u cts Dept., Diag. Irnag. Div., N. Billerica, MA

gentavalent

technetium D~k (Tc(~)OMSkl has been recently used as a tumuur seehing agent, particularly in medullary oarctno,~ of the thyroid and squam~us cell carclnoma of the head and neck. An atkaIi,e p~ has bee, reported to be necessary for its preparation and some authurs specify the need for a low stannous ion c~.tent. We have investigated the effect of pg~ stannous ion and BMSAamount on the formation of fc(V)h~h. At constant BHSA and stennous ion content, Formation of To(V)DMSA, dBtermtned by TLC and eleetrophoresis, $nerBased wlth pH reachlng a plateau at pH B (yielg 95%)Further experiments at pg 8 showed formation wa~ independent of atannous ion co~fenl (11-~0 u) and DMSA

content (O.]h-5.~ mg).

k% pg 5-5, Tc(~)DMSA formation was dependent on ~ith 71 ug stannous chloride the yield was 9J.T~. but fell to 5%when~0 ug was used. Protein binding of IC(V)DMSAhas been comparedwith Tc(III)~MSA. the widely used renal imaging agent_ Protein precipitation using I ~ TCD was unsatisfactory, the level of binding detected increasing with the sampJe size used. stannous foe content.

Plasma volbme (ml) O-d d5 o

=~

%

Tc(V)g~d in pren£pltate 32.0 (z.6) 66.1 (~.~) 77.z ( t q )

Gel Tiltratlon on Sephade* G-25 M could not be used. ince Te(IU)BMSA WaSPound lo bind to the column (g~.6% lot ~pplied activity), whereasTc(V)DMSA was completed eluted. Satisfactory analyses performed by equilibrium dialysis

showed 9~.8% (S.D. 65) proteln blndhng of (LD. 0.~) for Ic(V)~MSk binding levels between the agents helps to explain their distinct biodistributions.

A number of Tc-99m ether isonitrile compounds have been synthesized which show promise as myocardial perfuslon imaging agents. As a class, Technetium (I) hexakis (ether isonltrile) complexes generally exhibit high myocardial uptake and low background levels. This is best exemplified by the cation hexakis (2methoxy-2-methylpropyl isonitrile) Technetium (I) , [Tc-99m (MIBI)6] +, the technetium component in Cardiolite TM. The ether isonitrile class has been explored further, with some promising results. For example, the Tc-99m complexes of 1-methoxy-2methyl-2-propyl isonilrile and l-methoxy-3-methyl3-butyl isonitrile show excellent heart uptake (1.5% and 1.6% L D./organ at 30 sec. post injection in guinea pigs respectively), but also show early lung activity (9.8% and 7.2% respectively). This class of compounds has now been extended to include diether derivatives. For example, the diether complexes hexakis 12-(1-isonitriloeLhyl)-2-methyl1,3-dioxolane] Technetium-Rgm and hexakis (2,2,5trimethyl-5-isonit rile -1,3 -dioxane ) Technetium-99m display good imaging characteristics but slightly lower heart uptake (1.1% and 1,4% respectively) than the isonitrile complexes described above. It was anticipated thai through appropriate modifications, new ether derivatives could be synthesized with unique pharmacokinetic properties. The syntheses, pharmacokineties, and structure-activity relationships of these ether isonitrile complexes will be discussed.

ANTIFIBRIN ANTIBODY NETIUM ggm-Tc

(AFA) LABELLING WITH TECH-

We have developed AFA labelled by 131-1 and |23-I as a new agent f o r imaging the deep vein trombosis. The attempts were made to label anti bodies with 99m-Tc as a preferred agent f o r immunoscintigraphy. In this study two d i f f e r e n t techniques of ggmTc AFA'labelIing were applied. By the f i r s t technique AFA was coupled with cyclic DTPA anhydride (cDTPAA) in bicarbonate buffer and labelling was performed at d i f f e r e n t pH (4,0-5.38), At constant concentrations of AFA and cDTPAA, the labelling efficiency of DTPA-AFA with 99m-Tc varied from 60 - 96% depending on cDTPAA:tin mol ratios (1:1.5 - 1:3) Radiochemical impurity mainly attributed to 99m-Tc-DTPA reached the lowest level of 5-8% at mol ratio 1:3; ggm-TcO~ was found in trace. Thus prepared 9gm-Tc labelled DTPA-AFA did not preserve its immunoreactivity. By the second technique, 99m-Tc AFA labelling was performed in g]yeine buffer at pH 8.2-8,4 using the reduction of 99m-TcO~ by stannous chloride method. The labelling efficiency was > 90%; the radiochemical impurity due to g9mTcO~ was D~9%. In v i tr o studies revealed slight my ~ecreased s tabi l i ty of 99m-Tc-AFA after labelling with fraction reduced to 86% after 4 h. The immunoreactivity was preserved. 1 The labelling of AFA (antibodies) with 99m-Tc 1 in glycine buffer is a promising procedure f o r I the preparation of 99m-Tc-AFA with high label- 1 ling efficiency and preserved immunore~ctivity.|

ITc(fll)g~Sd (g:5) and 59-5~ (N=~). Difference in protein

53

A. Morguet, ~ ,

P. M. De Coster W. Wijns, F. Cauwe, C. Beekers~ J.A. Melin.

Center of Nuclear Medicine, University of Medical School, Brussels and Yvoir, Belgie.

1 54

Louvain

AREA AT RISK DETEF~NATION BY Te-99m MIni IN KEPER~USED MYOCARDIAL INFARCTION.

STRUCTURE-ACTIVITY RELATIONSHIPS F O R A N E W SERIES O F T E C H N E T I U M - 9 9 m E T H E R I S O N I T R I L E COMPLEXES.

Boris Kidric I n s t i t u t e of Nuclear Sciences Vinoa, University Medical School and Immunology Center, Belgrade, Yugoslavia

Ihe

Radiopharmacy Oepartmnt. Dudley Road Hospital, B~rmingham Department of Pharmacology. girminghamgniverslty

Uptake of Te-99m-2-menhoxyisobutyl isonitrile (MIBI) is =orrelate~ with regional myocardial blood flow (M~F). In the setting of reperfused myocardial infar¢uion, we tested the h~othesis that peat reperfusien MIni imaging e~ill reflects occlusion ~mF when the tracer is injected prior to reperfusion. Six anesthetized dogs unde~ent coranary occlusion (CO) for 2 hrs followed by 3 hrs af reperfusion (REpt = ~BF w as dete~ine@ by microspheres 20 min after CO and I00 min after ~P. MIni was injected 30 min after CO. Tomographi= imsgimg was performed during CO, Z and 2 hra ~fterREP. T~e size of tomographic perfusion defect was unchanged a~ter CO and REP. MIBI tisa~e conten~s from Ischemic and normal areas were compared in serial myocardial hiopsiss. Before RGP, ischemie MIBI content (expressed as % OF no~al zoner averaged 2& ~ 23 and was similar 27 f 19 at the end of PEP. Area aL risk (Pit was ~ssessed by in vivo dye injection and area OP necrosis (NEt by te~razoli~staln, l~mediately after ~acrifice, tissue samples characterized as Rl~ NE~ patchy necrosis (PA) and normal (NL) were counted for MIBI activity and MBF dete~ina=ion. Transmural values (mean Z SDt of these s~ples are ezpressed as % of NL: RI/b~b PA/NL NE/NL HIBI counts 37 Z 19 18 + 1 6 Z 3 MBF CO 34 Z II,~ 21 + iI 3 ~ I ** ~ F REp 75 Z 25 48 ! 14 50 + 15 In the 3 types of reper~used tissue (RI, PA, NEt, post KEP MIBI counts were similar to ~ F during CO and were nmt influenced by the increase of MBF after PEP. Thus, MIBI content in reperfused viable and necrotic myocardi~ accurately reflects regional MBF during CO when MIBI is injected prior to PEp, Clinically, MIBI imaging perfumed after REp would therefore pe~it to assess the area at risk, and the comparison with a la~er MIni 8can performed aE~er a new injeetlon would ~how the ~ount of salvaged myecardi~. ~*, p<.001; ~ , p<.01, vs MIBI and bLBF CO.

D. L. Munz, E. Voth, U. Tebbe, and O. Emrieh

Department of Nuclear Medicine and Department of Cardiology and Pulmonology, University of Odttingen, FRG

DOUBLE-TRACER MYOCARDIAL IMAGING USING INDIUM111 ANTIMYOSIN-Fab (AM-Fab) AND TECHNETIUM-ggm METHOXY-ISOBUTYL-ISONITRILE (MIBI) IN ACUTE MYOCARDIAL INFARCTION (AMI) In scanning AMI with monoclonai In-113 AM-Fab, anatomical localization of infarcted myocarddum proved to be often diffdcult or impossible, especially by applying SPECT technique. Therefore, we evaluated whether Tc-ggm MIBI zs a suitable agent for anatomical landmarking and exact AMI localization In B patients lets) aged 39 - 76 years with AMI confirmed by characteristlc ECG changes, left heart catheterization, and significant serum CK-MB elevation, intraindividual scintigraphic studies were performed. Each pt was injected intravenously with 74 MBq In-f11 AM-Fob 2 3 days after the onset of clinical symptoms and with 925 MBq Tc-ggm MIBI on the following day. 2.5 - 3 hr after the lest injection, double-tracer myocardial SPECT imaging was performed simultaneously using the 247 keV photopeak of In-

ill

and the 140 key peak of Tc-g9m. Spatial

reconstruction of the In-111 distribution by means of filtered backprojeetion was made possible using the Tc-ggm images for orientation. Two observers, respectively, analyzed scans and angiographic films and correlated local myocardial findings segmentally according to the AHA elassifzcation. The scintigraphic patterns corresponded well with the results obtained invasively. In conclusion, the use of Tc-ggm MIBI as a myocardial perfusion tracer proved to be essential for exact tomographic reconstruction and anatomical localization of segments accumulating In-lll AM-Fob. Furthermore, old infarctions could be differentiated from AMI by missing uptake of either agent.

232

55

56

57

J fincham*, d F Klopper*% H Wasserman**, WWeight*, S Wynchank*

A Syrot~, J Delforge, B M

~edical Research Council* end Department of Wuclear Medicine, University of Stellenbosch** Tygerberg, Cape, South Africa.

Biologie, Commissariat l'Energie Atomique, 91406, O~ay, France.

S.Del Vecchio,L.Mansi.N.Gagliardi,A.Petrillo, ~.Sofia,L.Carratu',M.Salvatore.

Mazoyer.

Service Hospitalier Frddgric Joliet, D~partement de

[HE BIODISTRIBUTIONOF 1-131RADIOLABELLED ~LASMA LOW DEBSITY LIPOPROTEIN [LDL) IN 9YPERLIPIDAEMIC VERVETMONKEYS

]attedra di Medicina Nucleare ]attedra di Pneumologia [I Facolta' di Medic~na - Naples - Italy ~edicina Nucleare-lstituto Tumori-Naples-Italy

IMPROVED ESTIR£ATION.OF RECEPTOR DENSITY AND BINDING RATE CONSTANTS USING A SINGLE TRACER INJECTION AND DISPLACEMENT.

)revious studies of the biodistribution of -adiolabelled plasma LDL have been limited to 12 hours after injection due to radiotracer Hfetime. Labelling of LDL with 1-131 enabled )iodistribution studies to be performed for 10 lays in normal and hypercholesterolaemic lervet monkeys. Ethical approval was ~eceived. Seven adult Vervst monkeys (4 ~aving had an atherogenic diet for at least 20 nonths and 3 controls) received 1-131 LDL by intravenous injection after appropriate :hyroid blocking. Whole body scans were )erformed for up to 10 days after injection. variety of blood cell counts and levels of ~ultipie biochemical compounds including :holesterml and 1-131 were obtained when imaging was performed. Urine activity was llso monitored. Using regions of interest, :ime variations of activity in heart and l i v e r Itissue were calculated. High levels of cholesterol were found in atherosclerotic ~onkeys, otherwise all results for cell lumbers and physiological blood compounds were ~ithin normal limits. The greater part of circulating I - l g l remained bound to LOL. The blood:hepatucyte activity ratio increased up to three fold between monkeys who had atherogenic and normal diets. Effective half l i f e in l i ve r of 1-131 LDL was similarly Iprolonged. These results are consistent with numbers of hepatocyte LDL receptors being down regulated in the presence of persistent increased plasma LDL levels and permit further mderstanding of LDL metabolism in the )resence of atherosclerosis.

We investigated the possibility of improving receptor model parameter estimation using a dlspIacement experiment in which an excess of unlabeled ligand (d) is

injected after a delay (tD) following injection ¢ff a trace amount of • #'+-labeled ligand. Simulations of labeled and unlabeled ligand kinetics were performed using the

non/inear rate equations:

qdM: C -- -k+x V - ,IB'~

-

M[ - M,)M] - k-,M[

M! and M~ are solutions of similar equations. The experimental data correspond to C] (arterial concentration) and M~ = M; + M] (quantity of bound and free radiotracer). V is the volume of reaction and B ~ the quantity of unoccupied receptors. The ef[ect of varying tD and J/J" on parameter uncertainties were studied in the ease of nC-MQNB binding to myocardial acetylchollne receptor using parameters ideatiffed in a dog experiment (B~,~,, = 17wnolg-X,k_t = 3.8min -~, ~ = 5.gprnol-~m{n-*.rnl, pV = O.29prno/ rnin-~g-] k = O.3min-Z}: tD(mln) O 20 50 did" 0 10O aS-., 6 .8 st_, 53 5 o,f,/v 35 11 (o's are expressed as

10 .4 31 29

i00 1,2 2.6

100O 3.9 4.7

I00 1.6 41

4.1

13

39

eoel~dents of variation (~))

The best parameter esticnates were obtained with dispIacement at 20 s i n and a J/d" ratio of 100.

58

59

[A. N- Serafini,

K~ Chateopadhy-ay, G. Sfakianakis,

IUniversity

J. Kotler,

L, Feun, D. Robinson, I

A. Heal, M. Dew*ujee, W. Sanz, P, Abrams, W, Nelp.

of Miami/Jackson Memorial Medical

C : n ~ : ~ Mwa~h~nFltornid. . . .

d NeoRx Corp . . . . ion,

] '

Kassel,

26 patients with Clinical Stage II or llI ~4 ~ere studied with 10-30 mCi of Tc-99m-F(ab) fra~ e n t s of a murfne monoclonal antibody lAb) NR~L-05 that recognizes the 250k dalton melanoma issociated antigen as part of a Phase Ill clini:el trial. The objectives were to assess the scintigraphic detection rate of known a~d occult ~elanoma. The antibody was supplied in kit form (NeoRx, Seattle,.Washing~on) and specifically labeled with Tc-99m using the blfu.ctio~al NgS2 chelate method of Fritzberg et al (JNM 27:957, 1986). Following 5asellne studids 40 mg unlabeled irrelevant Ab, 7.5 mg unlabeled specific Ab and 1Omg labeled specific P(ab) fragments were sequet tially infused over 30 minutes and scintigraphy performed at 7-9 ho~rs. No adverse or toxic reactions were noted. The kit was readily prepared with high labeling efficiency and provided s ~ e day images of high resolution. A total of 98 noncutaneous lesions were analyzable. 67~ of lesions >l cm and 100% o~ lesions >3 cm were seen whereas only 20~ of lesions less than 1 em were visualized. A total of 227 superficial cutaneous melanoma lesions measuring less ~han 4 ~ were not visualized. 16 previously unsuspected sites were imaged. 6/16 (37%) have been verified as ~Rd. Nonspecific tracer uptake was noted in sites of hyperemia such as active inflarm~ation (pneumonitis, skin ulcer, trauma) or persistent blood pool (varicolices). Sointigraphy with specific Tc-99m F(Ab) fragments appears promising in noncutaneous MM as an easily performed imaging method with no untoward or adverse toxic effects noted.

A. Bockisch, H. P. Oehr, H.-J Dept. Nucl. Ned. Universlty Bonn.

Biltz*, A. Motze, F. GrUnwald Biersack, and Dept. Dermat. (*), W. Germany

FRG

PECIFIC TC-99m-LABELED#2~TIM~LANOMAHLrRINE ~ONOCLONAL ANTIBODY (NR-ML-05) SCINTIGRAPHY IN ~ATIENTS WITH MALIGNANTMELANOM-% (MH),

lesions including @deno- end adsnosquamous lung osrcinomm.Pstients received 500 uCi (i00 ug) of 1-131 S72.3 through s fibsroptic bronchoseope. The radielsbeled MoAb was placed on the tumor mess under visual monitoring. Images were obt@imed w~th a LFOV gamma camera on line with sn imaging data analyzer within 2 hr of MoAb administration and daily up to 4-6 days.Plesma samples were obtained at 2-24-48-72-96 hr after MoAb administration and urine were collected up to 72 hr. Immunohistochemistry was performed on biopsy specimen obtained from the tumor one week later the antibody study. Scans showed retention of radioactivity at the tumor sites during all the study.No other organs were visualized with exception of some stomach and thyroid activity.Vascular compartment contained less than 1% of the administered dose at all time points.15~ of administered dose was excreted in the 2a hr urine ss free iodine.We conclude that intrab~enehial administration ~s e feasible technique end allows stable target of bronchial tumo~ protruding in the lumen.Furthemmore the low activity found in plasma end other organs suggests that this model may be used to delive~ therapeutic doses of MoAbs to lung cancer,

60

M.Fischer*, A.Elayan*, S.Antal**, E.Alex&ndrakis***, J.Petres** *Dep. of N u c l e a r M e d i c i n e , ** Dep. of D e r m a t o l o g y , *** Inst. o f P a t h o l o g y , St~dtische Kliniken, D-3500

[NTRABRONCHIAL ADMINISTRATION OF 1-131 B72.3 MONOCLONAL ANTIBODY IN PATIENTS WITH LUNG CANCEF In order to evaluate alternative therapeutic i Istrategy of lung cancer we tested the fe~sibili,ty of intrabronohial administration of rsdiolabeled monoclonsl antibody (NoAh) and the biodistribution of the rediotraeer. We used 1-131 H72.3,s murine IgGl remctive with many caroinomE

RADIOIMMUNOSCINTIGRAPHY

OF M E L A N O M A

Radioimmunoscintigraphy (RIS) w i t h monoclonal antibodies (MAb). is u s e d for s c i n t i g r a p h i c localization of m a l i g nant tumors and metastases. In a p r o s p e c t i v e s t u d y i00 p a t i e n t s w i t h s u s p i c i o n o f m a l i g n a n t m e l a n o m a or m e t a s t a s e s were investigated by RIS, u s i n g M M Y A h ( 2 2 5 . 2 8 S ) , a F(ab') 2 f r a g m e n t o f an IgGga against a high molecular melanoma associated antigen, radiolaheled with 9 9 m - T c . 59 w o m e n a n d 41 m e n , m e a n a g e 53,5 y e a r s , u n d e r w e n t R I S 1-24 h o u r s after tracer administration. 5 patients h a d to be e x c l u d e d b e c a u s e o f a p o s i t i v e s k i n test. In 89 p a t i e n t s t h e d i a g n o s i s was c o n f i r m e d by s u r g e r y a f t e r the RIS, in 9 p a t i e n t s R I S w a s p e r f o r m e d for e x c l u s i o n m e t a s t a s e s . 73 p a t i e n t s suffered from malignant melanoma, one from another malignant, 24 f r o m b e n i g n skin t u m o r s a n d 2 f r o m i n f l a m m a t o r y lymphnode affections. RIS was true p o s i t i v e in p a t i e n t s w i t h m a l i g n a n t a e l a n o m a in 7. e q u i v o c a l in 8, f a l s e n e g a t i v e in 35 a n d t r u e n e g a t i v e in 9 patients. In 27 l e s i o n s o t h e r s t h a n nalignant melanomas 2 false positive, 4 e q u i v o c a l a n d 21 t r u e n e g a t i v e R I g ~ere o b s e r v e d . In 2 p a t i e n t s a l s o d i f f u se t r a c e r u p t a k e in t h e l u n g or b o w e l tract was imaged without confirmed ualignancy. A strong relationship bet~een s i z e of l e s i o n a n d R I S r e s u l t s ~as o b s e r v e d . M a l i g n a n t m e l a n o m a s and metastases less t h a n 1.5 cm of s i z e m a y be m i s s e d b y RIS.

RADIOI/~R~0DKTECTIOB (E]~) AGA/~ST THE K&LIG NAIT ~ A I O I A A R T I 0 ~ 225.28S - A C01TROI/a~ CL~CAL STUDY. For more than 2 years we have performed RID xn patients with suspected metastases or recu rv rence of malignant melanoma using TECNEMAB K xj which is a Tc-g9m-lahelled F(ah')2-fragment of anti melanoma antibody against the surface antigen 225.28S. We administered 350 ug of antibody labelled with 740 M3q (20 mOi) To-99m and performed scintigraphy I to 24 hours after i.v. injection. Currently, a total of 42 patients suffering from 50 established metastases were studied. The results of BID were compared with clinical course, ultrasound, T-CT, and/or imm~uohistochemistry. Results: tr~e poe. tmeg. false pss. f~neg. pts (n=42): 22 13 2 5 les-(n=57): 31 4 3 19 I~munohistochemistry was positive in g out of I0 cases. In 81% of the patients metastases were excluded correctly, or at least I ~mown m e t a s t a s i s was f o u n d by RID. In the 4 patients, where the primary tumor could not be detected by any other means, the results of the BID were also negative. With respect to the number of lesions the sensitivity and accuracy of 62%161% was calculated. In app. 35% of the patients RID detected so far unknow~ metastases or could prove equivocal results of other examinations to be positive or negative. (x) TECNEMAB K, Ssrin Biomedica

233 61 K. Scheidhauer, G. heinsinger, E. Maser, C.M. Kirsch, O.E. Scheiffarth, K.G. Riedel, and F.H. Stefani.

Depts. of Radiology and Ophthalmolog F University of Manich, Fag.

IMHUNOSCINTIGRAPEY IN EYE TUMORS. Early diagnosis of malignant tumors is mandatory for a successful therapy. Eye selanoma is mostly a small-sized primary ocular tumor with similar antigenicity like skin melanoma. Therefore, immanoscintigraphy (IS) of eye melanoma was evaluated by both, planar and SPECT technique using the antibody 225.289 recognizing the high-molecular-weight melanomaassociated antigen. 51 patients were studied; size of lesions ranged from 2.0 to 12 mm (mean: 6.4 mm), measured hy ophthalmoscopy and ultrasound. Eye melanoma was diagnosed in 45 lesions, 6 lesions remained doubtfully. IS was performed 6 to 24 hours after i.v.-injection of 0.3 mg F(ab')~ fragments of the Igg~, monoclonal antibody ~25.28s labeled with 400 -i000 MBG Tc-99m. Scintigrams were acquired planar as well as by SPECT. Aoquisitisn time was up to 40 min with either modality. Is two patients, specificity of antibody binding was studied with doubleantibody/double-radioisotope measurements (Iniii labeled erA-specific antibody (F023C5). Antibody binding was proven by immuohistochemistry (immanofluorescence) in nine enucleate4 melanomas. 17/45 (38 %) documented intraocular melanomas were already visualized hy planar scintiqraph~. Using SPECT, 32/45 (71%) lesions were detected. Unhnown lesions turned out as: 1 melanoma, 3 nevi, 1 metastasis, 1 unknown: still in clinical follow up. Detectahility showed no correlation to lesions' size or localisation (nasal/temporal). These data confirm the potential of IS t o detect even small lesions ((12 mm) and to be helpful in differential diagnosis of intraocular tumors.

64 I.G. B~ttger*, A.C. Ludo'iph**, H. Herzog***, K.~. Langen***, G. Lottes*, and L.E. Feinendegen

~Nuclear Medicine and **Neurology Clinic, University of Mdnster, and ***Institut of Medicine Nuclear Research Center Jalich, F. R. G. INTERCOMPARISON OF REGIONAL CEP~BRAL BLOOD FLOW rCBF) AND CEREBRAL METABOLIC RATE OF GLUCOSE rCMRGlc) IN AM¥OTROPHIC LATERAL SCLEROSIS (ALS) ased upon earlier I-t23-BIMP SPECT findings, we studied ALe (cl~ssification: Norris-score) employing two additional methods, for rCBF and rCMRGlc,in 6 moderately affected patients: i) F-18-FDG, 222 - 363 MBq, with PET, reconstru¢ finn of t5 slices parallel to the aM-line; 2) Te-99m UM~PAG, about 500 MBq; and 1-123-BIMP 185 MBq, with SDECT, reconstruction of 12.5 mm slices in 3 standard and I reoriented transversal projection(~) through the lower parts ef the frontal lobes and the cerebellum, enabling calculation of a ratio cts/pixel fronto-tempo~al/ serebellar. Furthermore, somatosensory evoked ,otentials and neuropsychologic examinations frontal lobe alteration) were included. ~e 1-123-eIMP results were consistent with previous ones in 23 patients with ALS demonstratin reduced uptake, especially in the frontal lobes and were comparable to the TC-99m-HM-PAO studio Details are shown below: Pat. Age Norris-I HIMP HM-PAO | FDG y score cts f.-t / c e r e b . ~ o l / m i n X I00¢ S.S. 69 74 0.80 0.87 40.0 ~ 2.4 62 0.8a 0.96 83,9 ~ 5.1 ~.E. 72 M.B. 57 81 0.86 0.84 33.0 ~ 7.0 P.R. 65 76 0.94 0.93 36.9 ? 9.8 H.P. 37 0.85 .2 ~ 6.7 *Reference according to Biersack 0.9 - 1.1 (~ + 2s, n = i0), **mean cortical MaGIc, reference: 27.1 - 74.: (x ÷ 2s, n - 7) Furthermore, PET as well as SPECT findings reveal that ALS affects cortical structures/functions other than the motor region alone, rCMRGI¢ is not consistent with rCBF and may be (sub)normal or increased - at clearly decreased rCBF.

62

63

D. A C C H I A P P A T I

N. C E R U L L O * R, G U Z Z A R D I J.O. ~uret, 3.L. Martinet, @. Mszoyer, &. Lesur, S. Pappata,A. Syrota, J.C. Baron, T. Lem~eriere

CNR iNSTITUTE OF CLINICAL PHYSIOLOGY, PISA, (ITALY) * DEPT OF ENERGETIC ENGINEERING UNIVERSITY OF GENOVA, (ITALY) IANALYS~S OF THE PERFORMANCE OF A PET SCANNER THROUGH MONTE-CARLO SIMULATION AND EXPERIMENTAL COMPARISON This paper contains the description of a Monte-Carts simulation package developed with Ihe aim of predicting the physical performance of PET scanners. The package, named PETS~ (PET Simulation), is able to simulate Ihe emission and the annihilation of the positrons in a variety at scattering media, the transport of the pairs of photons and Iheir detection by a simulated 2 ring tomograph. The comparison between the simulated data and the experimental ones were obtained using the ECAT-I~I double ring whole body tomograph, constituted by 2 rings of 512 small BGO crystals. Among the most important parameters, efficiency, axial resolution and scatter traction perlormance {at differenl energy thresholds) have been evaloaled: the agreement between the Monte-Carlo prediction and the experimental measurements was very good, thus confirming the validity of PETSh As an example of comparison, the scanner etficiencies are quoled below. Using 20 cm diameter Lucite cylinders of variable length, filled with Ga-68, setting 250 KeV energy lhreshold and a slice lhickness of 2.95 cm, Ihe comparison gave the following resulls: CYLINDER LENGHT EFFICIENCY tTRUES) SEPTUM (cm) (Kcps/~Ci cm ) OUP IN

20. 8.

EXPERIMENTAL SIMULATED 59~3 +_5 63. +_ 3. 30.1 +_2 34. +_ 2.

The simulation of these experiments besides showing the validity of the method, is an important tool in the design ol Ihe system setup for Ihe clinical prolocols. Furlhermore, PETSI cabbies to simulate the detector rings per[ormance allowing ~o evaluate the various technological solutions during the optimization process of PET Scanners design.

65 E.Voth, M.Feldmann*, brewer*, D.Emrich

Serv. Sosp. P. J o l i o t , C~A, 91406 Orsa~,Frane~ Serv. P s y c h l a t r l e , Bop. L. MourJer(Parls VII) 92701 Colombes cedex, Prance. A SPECIFIC HETABOLIC ~ATTE&N BELATEO BALLUCINATORY ACTIVIT~ IN 9C~IZOPKB~dIA

TO TB~

The c o r t i c a l metaboli~ pattern of 12 s c h i z o p h r e nic inpatlents experiencing either crue o[ pseudo- h a l l u c i n a t i o n s was s t u d i e d u s i n g p o s i tron e m i s s i o n tomography (PET) and 1 B - f l u o r o - d e oxyglucose, PET scans vere collected tm subjects in testtr~ c o n d i t i o n v t t h eyes c l o s e d . 18F-D~ PET s t u d i e s vere a l s o performed i n a group of age-matched control subjects. A specific hypothesis eon~erning the h a l l u c i n a t o r y e ~ t l v t t y yes elaborated before data a n a l y s i s . This h y p o t h e s i s i n v o l v e d a p a r t i c u l a r imbalance between the activities of the p o s t e r i o r a s s o c i a t t v s (PA) and of the n o n - a s s o c i a t l v e sensory c o r t e x (NAS). Var i a b l e s were a p r i o r i s e l e c t e d for the s t a t i s tical analysis : the regional glucose m e t a b o l i c rates (rCMBGIu) in the PA region and in the NAS regions and the ratio of these cwo values. The smalysls revealed a s i ~ ' n i f i c a n t decre~e of the CHRGIu in abe FA cortex (p..05, Kruskal and gallis test) together mlth a marke~ Increase of the r a t i o PA/NA$ (p=.O04) ~n the patfent Mromp. ~e a l s o found s s i g n i f i c a n t increase of the metab o l i c index (the ratio of the rCMRGlu to the whole c o r t e x s e t a b o l i ¢ rate) i n the NA$ v i s u a l cortex (p<.O001) in the schizophrenic group, These results are In good agreement with recent PET saddles showing a reduction of the r ~ G l u in the posterior associative area in patients. Morever, the apparent imbal~nce between the PA and NAS cortex actlvit~es offers a £~nctlonal approach Of the hallucinatory phenomena whatever their sensory modality could be, This perticular pattern fs also tn agreement both wlth the c l i n i c a l phenosenolo~y of s c h i z o p h r e n i a and v i t h some psychophyslological t h e o r i e s developped about hallucinations.

66 Th.Henze',

D.

Her~ingsen t H. I , H. Bihl 2 , J. Allenberg 3 , I. A. 1 Born e , T. Steir~netz5 , A. Fries I , R. Reuther 5 1

Division of Nuclear Medicine and Department of Neurology ~ , University I of G o e t t i n g e n , F a g

Depts. of Neurology 5 (Mannheim Bospita112a~d University Bospital ) , Nuclear Medicine , Vas- | ruler S%L~ger~, pathology4, all University of [ Heidelberg , ~ IN/I~J

SIGNIFICANCE OF HMPAO-SFECT EARLY DIAGNOSIS AND FOLLOW-UP CEREBRAL ISCHEMIA - COMPARISON

111 -~DIL~t PLATET~T SCINTIGBAPHy AND HIS2CIEGICAL FEA_mUR~S IN PAT/aNTS ~[V2H SY~£~IQMATIC NAL (3%~CFfID ARTERY STENOSIS There is a long standing controversy as to which patients with symptomatic Inter~al Carotid Artery (ICA) stenosis should underg~ thr~arterectcr~y (TEA). Recent studies with 111-Indit~n Platelet Scintigraphy (PSC) in stroke patients showed a positive corTelation betsyn~c~%~tic ICAs a~d pathological platelet accumulations. The purpose of this study was to see whether PSC coUld identify those types of carotid stenose~ with a high risk of recurrent cerebral ischemia. We performed PSC in 21 patients with symptcznatic ICA I to 10 day~ prior to TEA. The surgical speclrens obtaLned Were examine5 by light microscopy. PSC shswed pathological platelet accna~ulations in 6 out of 7 plaques with moderate and predo~u/lant t h ~ t i c lesions. PSC u s also positive in 5 out of 6 plaques with acute ( ~ I week old) add fresh (1 to 4 weeks old) intraplaque he~norrhages. Su~erficially and deeply ulcerated plaques were PSC positive in 6 out of 11 and 4 put of 5 cases. - The carotid plaques were additionally categorized as stable or ~ s t e b l e based on the thickness of the fibrotic and hyaline layer covering the atherosclerotic lesion. Ynls proved to be the feature correlati#~ best (p
IN THE I OF ACUTE TO CCT

In s p i t e of the i n t r o d u c t i o n of cCT, t h e r e is a lack of e a r l y i n f o r m a t i o n a b o u t s i t e a n d size in a c u t e c e r e b r a l ischemia. B e c a u s e the d i s t r i b u t i o n of 99m-Tc-H~dPAO f o l l o w s the a c t u a l c e r e bral perfusien pattern, SPECT using H M P A O can v i s u a l i z e p e r f u s i o n d e f i c i t s d i r e c t l y a f t e r the s t r o k e . We therefore investigated prospectively 43 p a t i e n t s (P) w i t h a c u t e i s c h e m i c events: 7 w i t h TIA, 9 w i t h P R I N D a n d 27 w i t h c o m p l e t e d stroke (Ca). S P E C T a n d cCT w e r e p s r f o r m s d on d a y s I , 3 a n d 14, r e s p e c t i v e l y . SPECT was per f o r m e d a f t e r i n j e c t i o n of 370 FiBq of HMPAO using a rotating gamma camera. Results: On d a y 1 S P E C T d e m o n s t r a t e d ~ f u s e d areas in 28/34 P with c o r t i c a l i s c h e m i a (4/7 TIA, 6/7 P R I N D , 18/20 CS), hut only in 2/9 P (0/2 PRIND, 2/7 CS) w i t h ischemia in the c a p s u l e i n t e r n e . CCT on d a y 1 r e v e a l e d a c u t e i s c h e m i a o n l y in 4 P, a l l w i t h CS. In P w i t h TIA and PRIND, SPECT normalized in the f o l l o w - u p according to t h e i r clinical improvement. In P with CS, SPECT demonstrated variable perfusion patterns (hypo-, n o r m o - a n d hyperperfused areas) on day 3 and especially on d a y 14. H y p o d e n s e areas o c u r r e d in ths oCT in 4/9 P w i t h P R I N D a n d in 23/27 w i t h CS, m o s t l y o n d a y 3. Conclusions: In contrast to oCT, HMPAO-SPECT leads to e a r l y d i a g n o s i s of i s c h e m i c s t r o k e s a n d a l l o w s f o l l o w up. I s c h e m i a of the c a p s u l a i n t e r n e is m o s t l y not r e c o g n i z a b l e .

234 67

68

69

R. Bauer, E. van de Ftierdt, H. Stettmeier, H.R. Langhammer, H.W. Pabst

L. Troncone, V. Rufini, P. M o n t e m a ~ i ~, S.Bamba ee °

I. Brows and R.N. Carpenter

Nuklearmedizinische Ktinik, TU M0nohen Ismaningerstr. 22, D-8000 M0nchen 80

D e p ~ t a e n t s of Nuclea~ Medicine and RadioloR2 -o of the Catholic University of the Sacred Meart, Rome, Italy

IThe Research Laboratories, Cambridge Universit School of Clinical Medicine, Rills Road, ICambridg¢.

1131 MIBG THERAPY OF CARCINOID TUMOR OF INTESTINAL ORIGIN A 35year old patient with metastatic carcinoJd tumor of the small bowel had surgery and 4 cycles of poJychemotherapy which had to be stopped due to severe side-effects. Diagnostic MIBG scans ravealed tumor recurrence in the abdomen and muJtiple liver metastases. Tracer uptake amounted to about fourfold the intensity of the liver and exhibited a half-time double as long as in liver. Tumor mass of the liver metastases was quantltated by NMR imaging. Because sufficient MIBG uptake was documented, MIBG therapy was tried out. A first application of twice 3500 MBq 1131 MIBG was well tolerated by the patient, except for temporary deprasRion of leukocytes to minimum 1700 M/I. Calculated radiation dos~s were 1.9 Gy for whole body, 20 Gy for liver and 70-80 Gy for tumor (accopding to MIRD estimations). Following therapy, the patient reported improvement of phys[oal condition, and all the laboratory tests were normal. However, a NMR scan 4 weeks later revealed no change in tumor size. Two months later a second MIBG therapy was performed because clinical symptoms and laboratory tests indicated progression. The same radiation doses were achieved and the patient left our cUn[c in good condition. Conclusion:

#131-MIBG therapy seems to be promising in patients with oarcinoid tumor of intestinal origin, when other procedures are exhausted, but sufficient tracer uptake is ducumented.

7O 5ha. H, Park * ) , Ryung b. YOO ( - - ) , done J, Lee ** , June H~ Sub ( * * ) , Byung S, Kim (**) and Heung O. Choi ( * * ) .

CAN 1-13I-MIBG THERApy BE USEFULLY INTEGRATED IN FHE T P ~ A T ~ N T OF MEDULLARY THYROID CA. (MTC)? PP~LIMINARY~ESULTS IM 4 CASES. the treatment of MTC is s u b s t ~ t i a l l y based on ~he early surgical removal of the tumor. The I:omplement~y use of external ~adiothe~apy and/ )r I-lSl therapy is controversial and ~eputed ~carcely ~ffective. The recently availabIe 1-13] -MIBU could be potentially utilized either indi. I~idually, or intearated with conventional radio. erapy for the treatment of MTC, particularly hen in an advanced stage. Four cases of proven MTC, 1 female and 3 males, e r a ~ e 37-66, Undex-went 1-I~I-MIBG treatment i(sin~le doses of 3.7-7.4 GRq w~Fe lnjeoted by Islow I.V. infusion and repeated at 2-4 month in ervals).Th~ee pts. had residual/rect~rent tuors and 2 a disseminated diseBse(one with a re urrence as well).In addltion 1-131(3 c~ses)and/ Co-80(2 cases)therapy was performed. In one c~ Ise with widespread metastases ~ courses of 1-13] MIBG treahment(8,7 GHqlwere subst~*tially inef ective(only pain relief was a~hieved).In the o fhep 3 cases MIHG therapy(27 GHq,8 GBg and 6 OBq espeetdvely)inte~ated with I~131 Bnd(in m caes)with Co-EO slightly influenced distsnt met~ ~tases,but allowed a ~eE~ession(complete in 2 ca mes)of local recurrences. In these cases tumoral kers(CEA and CTIwere periodically determined. inteErated t~e~tment clearly brought about reduction in CT, whereas it b ~ e l y affected ~he CEA levels,The preliminar~ data indicate a ertain utility of the i n t e ~ a h i o n of MImG thera y in t~eatment of MTC,with prevalent effective ~ess on locoregional lesions.

I

l

~

;~e

71 ~ J ~ , A, RuoCei, J . H£1tunen, C..¢E~I_~.e~D~t~II of mou~:h 3,/ll~,p o~d •~'eeHnD.mmJ, ~teeon].'¢h ~eIl~;~e of FinJ.en¢[,

(*)Division of Nuclear Medicine, Thomas defEctson University Hospital, Philadelphia, PA., USA. (**)Depts. of Radiology, Internal Medicine and Cancer Center, Yogsei University Hospital 5eoul, Korea. A NEW THERAPEUTICMODALITYFOR VASCULARHEPATI( TUMORS USING INTRA-ARTERIALLY INJECTED 1-131LIPIODOL. Intra-arterial I y injected 1-131-Lipiodol (*L) is known to localize selectively in the hypervaGcula~ tumors such as hepatoc~l ular carcinoma (HCC) ( 1 ) . The purpose of t h i s c l i n i c a l study wee to asseGs therapeutic e f f i cacy of high internal radiation dose from *L in the treatment of vascular HCCs, Sixty-one patients who had inoperable HCC were treated with Intrahepatic arterial admin i s t r a t i o n of *L in single or multiple fractionated doses. HCCeare classified as massive (20 cases), multinodular (MN) (18 cases), and i n f i l t r a t i v e (1) (23 cases) types, Protracted tumor doses of lO,OOO rad (lOgGy) or higher were aimed in single or m u l t i p l e attempts. Following the therapy, patients were followed with computed tomographic (CT), serum level of AFP, and in 0ome caseG with Ga-67 scans, Smaller the tumor, the better the response; there was 82% respo.se for the tumors less than 5,0 cm in diameter, while only 22% response for tumors larger than lO.O cm in diameter, The massive type responded to this treatment best[ (75%7, followed by l~i {44%) and I (1.3%) types. This new therapeutic modality was able to d e l i v e r a high internal radiation dose and was most successful in patients with smaller, massive type HCCs. Thus, the new method may a l t e r the prognosis of patients with HCC. More importantly, the method was able to provide a q u a l i t y of l i f e with minimum risk and discomf o r t to the patients. 1, Park CH, Sub UH, Yea HS, et al: Evaluatior of intrahepatic 1-131 Ethiod~ on a patient with hepatocellular carcinoma. C l a n Nucl Med 19B6; II:51¢-517.

'UNDIFFERENTIATED THYROID CARCINOMA= PRELIHINARY STUDIES WITH A~TAT~NE-211 USING A XENOGRAFT MODEL Undlfferen~iated carcinoma of the ehyrold is assoclated with a poor prog~osls. Regardless of therapeutic approach, survival is often less thmn 6 months. Unlike differentiate~ thyroid carcinoma, radioIodi~e has rarely beeo found to sufficient to deliver a significant therapeutic absorbed radiation dose. of the Group VIIB elements, astatine though ~ore amp~oterie tha~ iodine, exhibits some similar physio-ebemical properties. It' :oncentrates i~ thyroid tissue to a high Degree, though the grecise mechanism has not been fully elucidatea (Rrowm, 1986). ~stati~e-211, of half-life 7.21 h, is a most ~uitahle isotope. It decays By the emisslo~ of[ orest 6.8 MeV meam energy u-particles of verase track lenBth ~6D Dm. The mean dose-' verage L E T of 211At is ~99 keV/p, which is ear optimum for endoradioDherapy. Preliminary bfodistribution and autoradioraphic studies have demonstrated significant take (11-23%/g) and retenCion of I.v. dministered [21lAt]-ascatide anio~ ib B/iS ndifferentiaeed human Ehyroid carcinoma enosr~fts in male MF1 ~u/nu mice. The uptake f radIolodine into these tumours was eRligible. These results wdll be discussed withI, the ontext of a possible role for astatine-211 is the management of anaplastic thyroid carcinoma.

f l

fp ~ t

row~ I. Astatine-211: d~ csncer therapy. 3 7 : 7 8 9 - 7 9 8 (1986).

its possible appllcatios Appl. Radiat. Isotopes

I

72 ~.N.HEOKE,E.v.d.LOREh H.J.~INONe, P.DARDODme, U.BUELL, Dept. Hucl.~ed.~II Cardiowsc. Burg. HHTHAachen~~ ],Med.Oinlc, Acid, Tea:h, HeaRt, Odrenr F~O

The ±a~¢a-a~:~lcaZaz ig~ee¢£on o." the ~rad a ¢ £ v e ~= t o o n p~ red e t~.¢~$ ~,n '~hdi t:_).latment~ o : r n e u ~ b o i d

.L~a~:a~e ttz'om 'nnp ~o~nt h a s D ~ V e p t ~ d the w ~ d e a p p e a l u s e o~ t h d meteor, Rocen~ly a new ~adieenermacmu~ic~, d ¥ l p r o m l u m - 1 6 5 - f a ;z'i a .._hyt~ro~ ~ 0 ¢ o~oa r a ( . a t e ( -1 5 - ~ q ~ ham ~een ~ ' ~ r g ~ c Z e d . z ~ e D ~ o i ~ a a e Oo vengue

D ~ a o a &~F o o n a l ~ e E a b l ~ ~.e~E ~r~#n t~at OZ o t h e z i l e t e ~ e m p=etvJ.oumly uFa~, T~e purpose o~ ~his ~ r k i s t b

~ u o v what a tetaz mxtra-arti~u~a~ ~,eakR(I~ ~ I , ~ O W ieen a n ~ i n t o w h l e h oz~an# t~lte a~tiv~y w i l l a c c u m u l a t e , a M wxta~, I:he ~eolat:&o~ d o l e eZ t h e ~a~ge~ e~gmn ~.i. A n w m e ~ h o d ham b e e n aeve~a~)ed, which enablmm a r e ~ st~atlon O~" t;~rLy a e ~ i v ~ t £ e e wbil~ m very _hi$ih ba¢Egzeund a o t i v £ t ¥ im ~Ee &enteric l ~ £ pac e te t~ 'c~t &a¢ ¢ o a x a 3 e i ~ me.amp=el, T~O ayo¢Igo ~gakaggm_ ~ ¢ e h whelm boay P . 5 1 ~ , &~¥9~iU,u29~. 891men 0.01~, k l ~ a y

UzU~.S m L:eQ';LOI~T l ~ h noae 0z010%. vono~l ]~o~ 0 . 0 1 6 ~ "and u = e a O.OO5~ O;~ t h e l:~J~¢t~(~ d o l e ~q~k~hin 4 h . T h e radia~iom ~oqe was S ~ a ~ l COl~l~l~ec~ 1;o t ~ e a o l e e e~ e o l d - 1 9 B and ~tt~c.tzmgO, The ~ v e r a ~ " dplm 'Co t h e ~ r i t i c a l oz_gant F a ~ I o p m A lymph Deem, was ~7 a iI w]~s 7 m in h ~ y h a m Deeu = e ) m ) ~ e a a t the ~mdiat~qn m~'noveotg~v O~" t h e k n e e uslnn golo19B ~ & n ~ } ~ t ~ r I v ~ - g 0 ~eppee~iv~, DV-165-¥ M.~. me,ms t e DO a a ~ & ~ l e r~dlophazmacm~tlca~ in the zm~mt~en ~ a o v ~ t e ~ . y . a l a e ~ n the c a l m o f t o ~png fe:~.~O p#ti~nta, beoaus~ itm ~xtra-arti~:ula¢ leaKago ~e v a z ~ OW.

PATHOLOGIOALFREE FATTY ACID TURNOVER iN CAD AFTER OYRFFON

LIHITEDEXEROIOB,DIFFERENTIALMETABOLICRATTERNOOENONOTRRTEOWITH 1-123PHERYLPEHTROECANOACIO I~ aiD) AND 5PECT, Regional cardiac free Jetty acid metaholi)mof hl patients IPl with angiogr@hicalI)documentedCAP and of tO controll (C) wa~ ut~died using IP, a radio - i)dinJkmdpaIiJtic acid analog,and sequential OPECT. imaginghas performedby leans of a dual head rotating ORECT system (RDTR Jl, Aiemens )aaHhonics).Oath camera head was rotlted IEOx in the stop and shoot mode. Acquisiti)nswere p~rForled 5q5 ~in, 35-55 mln and dE-DR min p,i. Imag~zwere reconstructed using coHerc~dlf available moftwarp withoul aki~nuitioncorrection. A)] P and 0 undlrwent mymptomlimited bicycle e~erci|e~the tracer hOOD - )00 NBd i,v.i Oeinp inied~O at peak stresJ. Norm than 99 X of left ventricu]ar segmentsof E showed homgenous traceruptake and rel~a~|, i~dlcatinghomogfnOUh FFA turnovmr in normal myocardium at peak e~ercJse and the immediateOo~texerci~e phase, AI] P With END exhibitedmetabolic abnormalities: )hY41 Had smp|enis with reduced tracer uptake +ollo.ed by prolonged tracer retention indicative of impaired region)l ~A oxidation. In =ompromsed myocardiul el 5/41 R, postexercisetracer uptake ,as homogenou|i segmentswith distinct fo[al tracer retentionI howewr, were observed in these P, indicativeel delayed FFA-oxidation. Persistentdefects were Found in 26/E~ R with documenidmVocardiz] infarction. In 75,1 h of segments, pErfused by ( 5o D ~tenoseO velsels, HomogeNous po)texerciEeuptakt was followedby ~=reasing 9e)~en~ activity, OkwkyFive percent and BD.h D o¢ segments in khe perlu~ior~ 6erritoryof )0 - 75 D and ) ?5 ~ obstructedvessels bad ~etabolic abnormaltie|. NehabolJc aOnormalltie| were Found with similar sensiUvity in patientswith or witheu~ei~=Vocardiographicand dinkcal evidenc~e+ stress inducedische~iasuggestingpresenceoh addi()onz] the. merely acute ischemka )ediat~d alterationso( rsgion~l cardiacenerg~ aekabolis¢, These Findings (~ogesLthat a]~eratJon~ oI [ardiac free Fatty ~etahol;smo~cur abunUanklyin

pitlents with CA) Quhiectsdto symptomhmited exercise. Different ~etaboIic patterns~demonstratedby the ~as~rihBdaoproachmay lead ~o an improved non-incisive characterization al ~hocardiu~ suUjected fe repetitivezschemicevents.

235

$.N,RmlWI,

75

74

73 B,F,Kntppl, ANik|ehH, S.kohlen, J.Kokkmeier.

Oept. Nuc. Med, RWTHAAGHEN, ! Nut, Med, Broup, Oak Ribge HaLl, Lab, Oak Bidge, lN I II Bept. Cardiol, and lnst, Clin, Exp. Nut, HEd. Untv Bonn, FBG

SUSTPlHBD 1-123 PHBNYLPENTABECbNOIEAC]O (IP) fXIRACTIDNANO RBTENTIBN IN REPERFUSEB MYO~AROIdH.

5uetai~ed early P-IB fluordeeoxyglu¢ose and C-ll palmitic aeib uptabe has be~n eh0wn to predict life tJes~e recovery Of reperfueebmyoc~rdi~m. Thu~, meLaboiicattiuity6 poetischemie myocardium W~S exalined by means Of IP, a radioiodlnateb paliiti¢ acid anllo~ in a coronary 0ctluei0n/ reperfueionLangendorfF swine beartmodeI.Eiohtbe|rts~ere inveetigaLed.~Hli~ationef plu~ose, FreeFsbtV acids (FF~),lactate and r~F Iml/|ine g~ H detereinedbV treeereicroepberee,wererepeaLeblyconLreliEd durinR a 40 min coronaryoc:iusiohand 30 mln reperfusion period in control and r~perfueed tise~e. ~ubekrate utilisaLion wae determinedby the Ftc~ ~ethod, [P was injected5 ion gef0rethe end o( reperfusion, Tissuewad anelyzedfor irreversihie damage by T1C stai~tnp,contentof IP anb {ractionalJeeorporatlonof IP :nto tissue lipids by radioactivitp assay ~nO sgend~rd bloche~ital techniques. Reversibleinjured ly0tardium~tili~ed during ischemie ~lueoee in preference to FFA and produted laet|te, Reper(~mibn increaeed FFA utilieation to a similar e~bent than plueose where~s lactate production ceased. RMBFwas persietently reduced in TTf-negative tisfue (5 vs 6 m(/~[n ~ g~l n.s.), reversiblyreducedin tbE borderzone (15 vS 32 ~l/min ! gmi p(,dll anb ge~eralIy stable in controltiSe~E 1110ve R!I mlfmin ~ g~; P),0d). IF uptake was .0~ % dosE;gmvS .2~g dose/gm (p (,01) ve ,gTl t doeE/gm(p(,Ol)in respectiveLiseue samples and Lhus clearlydieeriainateot~ntrol fr0mreversible injured and irreversible damagedmyocardium. The same~as true for fractional[P uptakein tiseueT8 (15.Y X vs ~I.7 ~; p(.0H vo 37.B ~; ~( .OIL Thesedlndingeshew preserved~ardia~FFA uLili~aLion and IP uptake in reversible iscbe~ic viable tiEsue and indicate a potential role Of IR-scintigraphy ior Early identificationol rEvereiblyinjuredreperfused~vocardium. Supported by grant IV B S gO0h 5185,Hinistryol Eoenoe aod Reoearch,NRNand QRN L, operated by US OeparlmenL of EnErgy, contract DE-ACO5-BgQB2140Owith MarLin MariEtta Energy EysLemg,Ioc.

76 G.Notohamiprodjo, G.S.The, K.Vyska, U.Schmidt, H.-J.Machulla, E.J.Knust, U.Gleichmann, R.KiSrfet, W.H.Knapp. [nstitute of Nuclear Medicine, Heart Center North Rhine-WestphaBa, Bad Deynhausen and Department of Medical Radiation Physics, University of Essen, FRG. REGIONAL MYOCARDIALE X T R A C T I O N OF zS-(p-I-zz3-PHENYL)-PENTADECANOIDACID IN PATIENTS WITHSEVEREAORTIC STENOSIS. - E F F E C T S OF VALVULARREPLACEMENT

Previous studies have shown decreased myocardial free fatty acid (FFA) extraction in hypertension. Now aortic stenosis is used to further evaluate FFA utilisation in chronica[ pressure overload and its treatment, ~a normal subjects (NS) and zo patients with aortic stenosis (NYHA Ill-IV) (Pts) were investigated. Left ventrtoular mass and wall thickness were determined by biplane angiography and echocardiograhy. Tl-zo~ was used as flow indicator and I5-I-I~3-phenyl)-pentadecanoic acid (IPPA) simultaneously injected as FFA-tracer. After corrections, Lhe IPPA image was divided by the Tl-~o* image. The values (count rate ratios) reflected the IPPAextraction fraction (IPPA-EF). In NS there was an exponential rclationship between IPPA-EF and workload. Thus, the patient data were normalized to the mean value of NS at the respective workload. Before surgery, IPPA-EF of Pea was reduced by 45 -+ zo%, while perfusion was homogeneous. 2-3 weeks after valvular replacement: IPPA-EF increased insignificantly to 64 ± I3%, and no reduction of the myocardial hypertrophy was yet percieved. 8 - i s mo later, IPPA-EF attained a signif icantly increased level, though below the normal range (~7 -+ ~5%)- These findings were paralled by a significant decline of myocardial hypertrophy. FFA utilisation is reduced in ehronical pressure overload without Tl-~o~ abnormality, this reduction is related to myocardial hypertrophy, it is reversible with delay after reduced ventricular pressure. IPPA-EF may serve to assess the degree of impaire, myocardial functioning due to valvular stenoses.

W.R.Thies, K.Vyska, G.Notohaniprcdjo, W.H.Knapp, W.Matthies, U.Sc~nidt, H.Meyer.

B. Geut!n~ K.-P. Kaiser, K. Grossmann Eivester B. 5Base, L.E. Feinendegen.

Institute of Medicine, Nuclear Research Cente J~lich, Jdlich, and Department of Cardiology, University of Ddssel~orf, D~sseldorf, FRG

METABOLIC BE~AVIOgR OF TgE ORTRO- AND PARA-ISOMERS O F ~axI-PHENYL-a-~C-PENTADECANOIC AC~ (oPPA, pPPA) Ig HUMAN MYOCARDIUM AFTER INTRACORONARY INJECTION

~°I-pPPA is a useful tracer of blood flow an~ long-chain fatty acid metabolism in the huma~ heart. Following injection of its ortho isome~ i~Sl-oPPA, the label is retained in the myocardium for hoers (T~/~ ) 200 min). It was the aim of this study to investigate the site ol this trapping of the label in myocardial cells im vivo. For this purpose OPPA and gPPA were double-labelled with ~alI on the pbenyl ring and ~"C in the ~-position. After intracoronary injectior of oPFA or pPPA in 3 individuals each group, undergoing coronary angiography (informed con,sent), blood samples were simultaneously taker from the aorta and the coronary sinus during 2C minutes. The samples were analyzed for the unmetabolized fatty acids and their labelled catabolites, short-chain ~atl-ghenyl carhoxylic acids and x4coa. Upon ~-oxidation ~ c o z is expected to rapidly lea~e the myocardium. T h e experiments showed a rapid ~etabolizatiom of pPPA. p - ~ I - c a t a b o l i t e s and ~4C0= appeare~ at the same rate and reached i00 % of the total ~0~I- and *~C-activity in the coronary sinus blood 8-i0 minutes after injection. ~n contrast the cataholites of oPPA constituted only 40-50 % of the total blood activity after 20 minutes, at the end of the experiment. Also here ,the ~dCO~/~*I-catabolite ratio remaine~ constant. Thus, oPDA is trapped in the myocardial tyrosol, and there is no selective trapping of iodinated catabolites in the mitochondria.

77 [

Clinic of Pediatric Cardiology and Institute of Nuclearmedicine, Heart Center North Rh/ne-Westfalia, 4970 Bed Oeynhausen, FRG.

FATTY ACID M ~ J ~ K ~ L I ~ IN CONGESTIVE AND ~ P H I C ~ICMYOPATHI~S IN CHILDR~W. The aetiology and pathQmechanim~s in beth types of cardiomyopathies (CM) are still unknown. In vivo measurements of myocardiml metabolis~n in C~4 are needed but there is hardly any information about this subject. Fzee Fatty Acids (FFA) are the main source oJ energy for the normal myocardi~n. We developed a double isotope method for external measurement of FFA-extraction rate (FFA-ER) in different myocardial regions. 201-TI was used for the determination of myocardial per. fusion and 15-(p-123 J-Phenyl)-Pentadecanoic-acid (IPPA) for assessment of the FFA uptake. The relati[m IPPA/TI reflects the FFA-ER. 8 pts with hypertrophic C~ (HCM) , age 0.2-20 years and 8 pts with congestive CM (C~M) , age 0.2 - 22 years were investigated. 8 patients w~re used as control group. The normal FFA-ER was taken to be 100%. In pts with HeM the global myocardial perfusion was normal with a slight increase in the hypertrophied muscle. The FFA uptake in hypertrophic areas, hcx~ever, was strongly diminished resulting in a reduced FFA-ER to 35%. In all pts with ~ the global myocardial perf~sicn was reduced. Small areas with a normal and a d/minished coronary blood flow were mixed throughout the whole heart. Si~/larly to the diffuse reduction in myocardial blood flow the uptake of FFA was also diminished (FFA-~ of about 90%) . The results suggest that in R(~ an insufficient increase of myocardial blood flow results in relative o~ge~n deficiency. In pts with CC~ diffuse obliteration of the very small coronary arteries is expected.

78 H_i_4 I~/_LER~iiRIAER ( I ) , R ~]NTZ ( I ) , R }4.AR3OR(2) R ~1024%%N(3)

Def. OF ~bcl~ Medicine (I), ~ . of ln~rr~l Medicine (2) O~,Of Radiology (J)~ tbi~rsity ~bspito/ M a ~ b u r g - ~ obrf, D-2000 Hamburg 20, ~tinistr. 52 R~IDI~MJ~I]]HZRkPy (}- srJ_ITARYLI~ER ~'T~ST/k~S BY ~ INTRATLM~L INSTILLATI{]N ~ T~£ [TcA-~NTIB[DY 131

CF

~31/26 E~rim~Ib~l studies on anlmalsdemonstratedthat gro~h of pa7creatic earcino.~scould be effectivelyreto~cbd by mesns of int~ttn~31 injectionof 131-icdinolabelledmor~ct~l antibodies (131 I~h). In ~ this int~atu~xal t~i~ has rot yet be~ ~lied to m~tsstas~ F ~ colo~ectsl ca~cinm~s, and syste,ie ~oplicstinnof 131 l-P~b did not ~=JJlt in 8~ effecti~ tunmJr ~iatic~ time, Me~x~: In b~o patients (Pl and P2), 131 I-~'Pb (antigUA ~ t i b ~ 131 14~4 43J/26, 8ehri~ Co.) ~e~ -tFa7s~ l y and unc~r s u x ~ i c ~ l guidance - mJltilccally injected into a ~ l i t ~ li~D metastasis of a colon c~ccinoma (VOlLmePl: Ii0 corn;P 2: la tom, t ~ r ~ l u ~ doublira] ti~B in P 1 and P 2: 1 - 1.5 moTths). The ~lied activity amountedto 5.I~ ~ in P[ or~ to 1.85 ~ q in P2. The study had been ~ by the local ethical cuTmittee. ResJlts: Canolic~tiu~sdid not occur. The Follo~up tim~ in P I and p 2 amounP~ to 2.5 and 2.0 months ~es~ti~ly. ~urtog this period both metast~s~ did not increase in vohme (co~outod to~x~a~hy). CEA serum crxt~h-atic~s ~eclired aCcer 131 I-M°b therspy to 66 ?: Bed 58 % res~sctivsly (in P 1 2.5 ~ in P 2 i.5 months after therapy) ~hen related to the resoectivevalues immediately before 131 I-M~b heerapy. D~tsiledkinetic studies in Pl revealed: lhe e?fe~tivehs/F-liFe-periedof int~tL~ral radlo~-tivity ~,~s2a h ( ~ h ~ l - 7~ ~ of 8oplied ~ctivity) and ~ ~ys ( D ~ [[ - 30 ~ of 8p~[i~ ~tivihy); t~ inL~tumut~l r~iatim dose a m u ~ to 503 Gy. lho effecti~ half-life-geriedof se~tm radio~"tivity~ss: phase I 12 hours, ~ I I 6 deys. The total body gsnrns-c~s~ (b~.our excluded)~ s ~,3 Gy (MIR]), the b e ~ 0.25 Gy. Co7clusiors: Instillation of 131 ~-P~b into ~ liver metastases ftcm colo~ecto/carclno~ssse~.s to be a safe pr~ceo~ and did e~ert - in emtr~st to systemic 131 g-M~b a~bicati~ - ~ si~ific~t t~m~r g ~ inhibifin~effect.

P.Riva*,S.Lazzaria,G.Moseatelli*,M.Agostini*,G.Sarti°,L.Rasciti*,G.Paganelli *, V.Spinelli*,S.Mengozzi°,R.Tassini*,g.ge veri*. • N u c l e a r M e d i c i n e D e p t . a n d I s t i t u t o Once logieo Romagnolo. o Health Physic Dept.- M . B u f a l i n i H o s p i t a l C e s e n a Italy. T H E R A P E U T I C A L A P P L I C A T I O N S OF H A D I O L A B E I L E D M O N O C L O N A L A N T I B O D I E S : A P H A S E II S T U DY IN C O L O N CANCER. iO p a t i e n t s b e a ~ e r s of l o c ~ l r e c u r r e n c e s and i n t r a b d o m i n a l ( m a i n l y liver)or d~ta~ metastases from colon cancer,who became resiste/zt to t r a d i t i o n a l t r e a t m e n t s , w e r e s e l e c t e d for t h e r a p e u t i c a l p h a s e II stud y p e r f o r m e d n y i n t r a v e n o u s ( l p a t . ) o r i~ t r a p e r i t o n e a l (9 p a t . ) a d m i n i s t r a t i o n of r a d i o i o d i n a t e d ~ p e e i f i o m o n o c l o n a l antib o d i e s . The M o A b s e m p l o y e d , c h o s e n on the b a s i s of in v i t r o i m m u n o s t a i n i n g e x a m i n a t i o n and in v i v o i m m u n o s c a n r e s u l t s , w e r ~ AUAl(ICRF-London)(2 pat.),BW494/S2(BEHRINGWERKE-FRG)(4 pat.),the FO23C5(SoPin Biomediea-Ttaly)(2 pat.)and B72.~(SorinItaly) ~ pat.). The m e a n d o s e o f a n t i b o dy w a s 1 7 , 2 m g . ; t h e m e a n dose o f 131I w a s 92mCi. 7 pat. w e r e s u b m i t t e d to 2 admini s t r a t i o n s and 1 pat w a s 3 time i n j e c t e d ~ No e a r l y or late side e f f e c t w a s o b s e r ved. All p a t i e n t s d e v e l o p e d ,after the f i r s t o o u r s e , a n t i m o u s e a n t i b o d i e s . In i p a t i e n t the t u m o u r g r o w e d u p ; i n 2 p a = tients only minimal temporary results ( p a i n d e c r e a s e ) w e r e o b s e r v e d ; a s l o w tum o u P p r o g r e s s i o n and l o n g s u r v i v a l w e r e o b t a i n e d in 3 oases. In 4 p a t i e n t s a sig n i f i c a n t c l i n i c a l i m p r o v e m e n t and a~ i~ s t r u m e n t a l e v i d e n c e of t u m o u r v o l u m e re duction(30-50%) p e r s i s t i n g f r o m S-to ii months was achieved.

236 7@

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=J.FI CgATAL, P. THEDREZ,J.C. gACDAVINI, D. NOLIBE, D. GUERREAU, G. PASCAL, J.P. SIMOEN, 'p. PELTIER~ A. CHETANNEAU, M. KREMER.

Lastoria, JA Carrasquillo~ A Raubitschek~ Colcher, JC Reynolds, ~D Neumann, A Molinolo, JP Simpson, W Sindelar, P gugarbaker, M ~{erino, Miller, E Glastein. J Sehlom, and SM Larson. ~tional

Institutes

of

Health. Bethesda, MD.

COMPARISON OF HIODISTRIBUTION OF 1-131 .FTER MULTIPLE IBTRAPERITOBEAL DOSES.

B72.3

~e have trea~ed five patients (pts) with eritoneal carcinomatos~s (2 with appendix, 2 :oloreetal and 1 ovarian cancer) with intfape-I Itoneal injeetdon of 1-131 B72.3 monoelonal ~ntibody. All tumors expressed TAg-72 antigen. The B72~3 was labeled at specific activities of ~,i + 1.5 mCi/mg. AII pts underwent a diagnostic ~tudy (I0 mCl, O.gS to 1.1 mg) and received therapy within 16 day8 of the diagnostic dose. two pt8 received 50 mCi and three pts received 8E to 100 mCi on 10 to II,T mg of 1-131 572.3. Loealiaation in tumor sites was seen in both the diagnostic and bh~rapeutie scans. The 1-131 ~hole body retention showed a trend toward morel prolonged retention with diagnostic than therapeutic doses: T 1/2 of 56.7 + 6.2 hours Eor diagnostic and 43.2 + 8.5 hours for therapeutic, Two pts had h~gh levels of anti-mouse antibodies (HA~A) at the time oE the therapy ose, and had a faster clearance (TI/Z) fro~ he whole body (50,6 vs 33 and 65 va 40.8 hours). Re,ions of interest were drawn both ~or the entire peritoneal cavity and for the ~oeal tumor sites. The biologic TI/2 in the ~hole peritoneal cavity was 43 ~ 13 hours, ~herea~ the TI/2 in t%~or Was longer. Peritoteal clearance for therapeqtfe doses was Easte~ ham for diagnostic doses in pts with HAnnA. he 1-131 B72.3 (intact Ig~) activity i~ the erum was near maxim~l by g4 hours ranging from rum B to 39% and fro~ 3 ~o 44% for the diagnothe and therapeutlc, doses respectively. In summary dlfferences in biodistribution and clear,nee were observed between initial and ~hsequent intrsperltoneal doses.

~

D, Colcher. O.A. Gansow, M.W. Mirzadeh, A. Rauhitsehek and J.

Laboratory of Tumor I ~ o l o g y and Biology, National Cancer Institute, N~tional Institutes 3f Health, Bethesda, ~IFFEP~ENCES IN THE BIODISTRIBUTION BE I N D l ~ kND YTTRIUM LABELLED MONODLONAL ANTIBODIES. The ~se of radiolaheled monoclonal anti~odies (MAbs) to detect and treat neoplastic disease iB ~ctiveiy bring pursued by many investigators, 131I has been the radionucldde most commonly used. Laheling techniques ~o~ permit metal to b~ eou led to proteins via bifunctional chelates. 9~X has often been s~ggested as a suitable therapeutic radio~ n~clide with ~llln ~ b (using th~ identical chelate) to be used as a tracer for in viv~ biodistrihution studies, despite the major diEferences i~ ~n and ~ chelate ch%mistxy- Th~ differences iN their physical properties, the Coordination H~L~ber (C,N.) o~ Y t t r i ~ being 8 or 9 v s 6 for In, may affect their in vdvo hiodistrlbution. We therefore investigated the biodistribution of In and y labeled MAb gTg.3 using 3 dlfferent chelates with maximum D.N. of fi, 7, and g (BCN-Bz-EDTA, CADTPA, SGN-Bz-HTPA, respectively). A t h ~ i c mice bearing the h~man colon carcinomas (LS-174T) were injected i.v. and sacrifi~d at ~ i o ~ s times and the distribution of In and Y labels compared. Previous in vivo studies have demonstrated low counting efficienc for bone with 9Oy; so we used the y-emitter ~gY as a tracer. Bey labeled B72.3 with CA and EDTA chelates gave 10% ID/gm in the tu~or at ~B hrs compared with 32% ID/gm of the DTPA-B72.3. Major differences were also seen in the bone wh~re g13% ID/gm of the CA and ~DTA conjugated 8y v s 2-3% ID/gm for DTPA. lllIn labeled MAb using all 3 cheIates yielded only g-3% ID/gm in the bone. Th~ m~jor difierenee~ in hone ~pt~ke with the Y-labeled MAb (using CA and EDTA) demostrgt~ the potential problems in using the bdodist~ibution of In-labeled MAbs to predict the dosimetry (espe~ally for bone marrow, the critical oreaD) of y labeled MAbs.

D.J. ~ r ~ t ~ e h , M. C~inol*, M. Gionet, D.A. Sie~, M. ~ s c k ~ , R, ~k~ter and T. Griffin . University of Mz~sachusetts Medical Center Worcester, ~%. M~mant sinai M ~ c a l Center*, New York, MY.

U.21I 1NSERM, NANTES, Dommissariat & l'Energie Atomique and Comp. ORIS Ind., SADLAy, FRANCE. I~/NOTH~gAI~:

FEASIBILITY STUDY OF INTRAPERITDNBAL (IP) RAD10IMMUNOTHERAPY (RIT) USING I n l l l - 0C125 MAb IN PATIENTS WITB OVARIAN CARCINOMA. The feasibiIity of performing RIT with radiolabeled MAb was assessed by studying biodistrdbutton of Inlll- OC 125 MAD after IP injection inte 19 patients with documented ovarian carcinoma. Patients were injected IP through a catheter with a 1.5 1 saline infusion containing intact In111- 0C125 MAb (Group I, n=7 patients), intac" In111- 0C125 MAb associate with 20 mg of unlabeled 0C125 MAh (Group II, n- 5 patients), intact nonspecifie immunoglohulin (Group liE, no3 patients) and Inlll- 0C125~ F(ab') 2 fragments (Group IV, no4 patients). During the operation, 1 to 3 days after injection~ the surgeon removeq 'fragment~ o~ t~L~or (large ~ o r s in 15 patients and small nodules in 3 patients) and normal tisq sues (blood, colon serosa, m~scle, fat, skin i and liver). In 3 patients tumor cells were sepa~ rated from nonmalignant cells in infusion fluidJ IExpression of CAI2S antigen in tumor fragments or modules and in the pellet of tumor cells was studied by im~unohistocbemistry (~H). For fragments of largo tumors, uptake values expressed in g injected dose per gram (xlO-3) were 7,6 14,7 (Group 1), 2.5 + 1.g (Group IP), 8.7 ± 10.6 (Group III) and 2.8-± 2,2 (Group IV). Tumor-tonormal tissue ratios did not exceed 6, regardless of tissue or group. For small nodules (lee Ithan t00 mg) ~nd clusters of malignant ee~ls, Itumor uptake values were 130 ± 75 (Group I) and 360 (Group IV). Tudor-to-normal tissue ratios Ir&nged from 4 to 2400. For small tumor nodules and clusters of malignant cells~ there was good Ioorrelation between tumor uptake and the percentage of stained malignant cells as determined lhy IB. The feasibility of IP HIT was doc~ented I for small : ~ o r nodules and ~icrometastases.

A. Morguet, ~rg~R,

PILOT STJDIES IN

A l t h ~ g h yttrium-90 (Y-go) is one of the ide~ radionuclides for ra dioi~unothel~peuti( applications, the lack of 9amm~-r~ys in it~ decay c ~ l i c a t e s the estimation of radiatior dose since its biodistribution c a r ~ h~ accurately d e t e ~ by external imaging. I; order to c a l c u l a t e radiation dosimetr~, limited clinical trial was conducted in patients with suspected or docummnted ~ a r i a cancer (scheduled for l a p a r ~ ) ~t th~ University of Massadnusetts Medical C~nter, %~le F(ab')2 fragm~-nts of anti-ovarian antilx~ OC-125 %~.re c ~ l e d with DTPA and %/qen labele~ with generator p r ~ Y-90. Prior to surge~ patients were injected IP with one mCi of Ygo-antibody. Size exclusi~ and ion e ~ ( HPIC analysis of patient ~scit/c fluid ar~ se/x~ sample~ sh~wed that in vivo t h e 2-goantibody c ~ l e x was very stable. Tote3 ~ir~ excretion of radioactivity over a i-: day period before surgery averaged 6% of th~ admini~ dose. At suzgery, ~ o r tlssu~ and other normal tissue bi~psied samples w e ~ obtained and radioactivity m e a s u r ~ in vit~ for accurate quantitation. B% of the inject~ activity was in serum, iD% in liver, 6% J~ bone marrow. The mean tna~or/norm~l tissu~ ratio varied between 3 to 25. In order cal~ulate radiatien dosimstzy, we a s s ~ e d a] instantaneous biodistribution, b) nl biological clearance from tissues and c) al: the radiations f r ~ y-g0 were absorbed with~ the tumor. One mCi of Y-90 delive&n approximately 50 rods to the tumor while th~ normal tissues receive ~pprexi~ately g z-ad~ These r ~ t s suggest that Y-90 labeled ~C-12! antibody ~ay be useful for the treatment ovarian cancer.

84

83

82 M Rosellf ~ s . Schlom

81

g. R. Karsch, W, MOller-SchauenKirchnar

i.P. Peycelono 3.R. Lusson.

V. Abrieu~ A. Veyre

3. Cassagnes. Medical Clinic and Nuclear Medical Department, University of TObingen, FB§

Centre Jean Perrm - CHRU Saint-3acques, Clermont-Ferrand - France

REVERSE REDISTRIBUTION (RR) IN THALLIUM-lOl MXgC~glgL SR£C~ i~gGIRg RR is not only seen on planar TI~2Ol myocardial scans but also on SPECT images. The phenomenon is discussed controversely. This study was undertaken to determine its clinical significance. Two observers evaluated 643 consecutive T1-201 myocardial exercise and redis tribution scans in SPECT technique. 90 of these patients demonstrated a persistent myo cordial defect, 93 a reversible lesion, 147 both patterns, and 38 RR (5.g %). The latter was graded and documented segmentally. Among the 48 segments (S) with RR 2 were anterobasol, i anterolaterB1, 15 apical, 6 diBphrag mal, 12 posterobasal, i sepbal and Ii posterolateral. 24 patients with gg reverse S had undergone left heart catheterization. Two observers analyzed the angiographies looking for wall motion abnormalities and coronary stenoses. The S of the eineventrdculograms ~ere compared with the corresponding ones of the Tl-201 SPECT and appointed to coronary perfusion areas. The following r~sults ~ere found for t h e S wzth RR: Transmural infarction 13/gg S (4b %) Nontransmural infarction 3/29 S (CO %) Coronary st~osis > 75 % 512g % (17 %~ Normal segment 8/23 S (28 Z) Conclusions: (l) Because RB is seen as ~ell on tomographic as on planar Ti-2Ol myocardial scans, it is supposed to be not only an artefact due to background subtraction. (2) 72 of the myocardial S ~ith RB ware associated with infarction or significant stenosis of mhs supplying coronary artery. This indicat8s that beside the persistent and the reversible defect on myocardial scans RR is a marker for signiflcant coronary artery disease.

TL-201 TOMOSCINTIGRAPHY DURING ISOSORBIDZ DINITRATE INFUSION (ISDN-SPECT) : A PREDICTIVE TEST FOR RECOVERABLE MYOCARDIUM The aim of this study was to compare the results of rest-TL-201 SPECT with those observed during 1SDN infusion, in patients with recurrent angina after myocardial infarction (MI), in order to detect viable and recoverable myocardium, that could be preserved by angioplasty (PTCA) or by coronary artery hypass [CABG). Rest-TL-2Ol SPECT (TLI) was compared to TL-20I SPECT realized during ISDN infusion (g mg/h for # hours), one week apart (TL2). The test was considered positive if the extent of the perfusion defect decreased between TL2 and TLI, and negative in case of unchanged defect ~[ze. lg patiemts with anterior M1 and lg patients with inferior MI (CX : B, RCA : 6) were included. 13 patients had a positive test (Gr 1), including g inferior MI and 5 anterior MI, and 15 had a Inegative test (Gr lI) including 9 anterior MI and 6 inferior MI, CABG was performed in g patients (GR I : 3, Gr II : 1) and PTCA in 15 patients (Gr I = 10, Gr II : 15). Successfull PTCA occurred in 7/15. More than one week after revascularization, 9 patients had control rest SFECT (TL3), without nitrates, TL3 was compared to TLI. In Gr l, 5/6 patients had an increased uptake, while in Gr 1l, 5/3 had unchanged uptake. Conclusion : TL-2BI SPECT during ISDN infusion compared to basal rest SPECT can detect viable and recoverable myocardium in an infarcted [zone, allowing CABG or PTGA ~ good results, defined by a decreased size of the perfusion defer% are observed after revascularization if the IS[IN test is Dositive.

l

237

85

87

86

G,Pra~asso, E.Rossetti, P.Zoli, g. Taddei, O.Carandente, M.gclammarella, P.Gerundlni, F.Fazio, S.Chierchia.

Division of Cardiology and Department of Nuclear Medicine. lstltuto ~cientifleo gun Raffaele, Milano, Italia.

F. Dr u n o t t e, M. N. • a u r e n s , G. b t e s c h e n k o ~risse,N.Sadeul,E.Aliot,J.Robert,J .H.Gilgenk#antz

) P. -

Service de M 6 d e c i n e Nucl~aire et s e r v i ce de C a r d i o l o g i e CHR N A N C Y (France)

J.L.DEMANGEAT ~, B.gRUNOT ~ , A.FACELLO *~, P.BAREISS ~* , A.CONSTANTINESC0 ~ Nuclear Medicine ~ and Cardiology ~ CHNU Hautepierre, Avenue Moligre 670£B STRASBOUEG CEDEX - FRANCE

Departments

I PAINLESS MYOCARDIAL ISCHAEMIA DURING ~I-201 STRESS TESTING IN PATIENTS WITH STABLE ANGINA. I In patients (pts) with effort angina (A) and coronary artery disease (CAD), the incidence of t s ~ p t o m a t i c ischaemia recorded ~urin~owereXercise :eat%no (ET) has been reported to be than :hat observed during dull activities with ~mbulatory ECG monitoring. ~ i s has led to the )ellef that ischaemia induced by increased lemand is more likely to he associateg with A. ge retrospectively analyzed the results of 89 71-g01 stress tests, performed in atlanta with ]AD aug chronic effort-relate~ A. After Lnjectlon of 74 MBq of TI-201 at oak exercise, ~ r e s s and rest images were collected in £he ~k~r, LAO ~5" and 70 e projections. All tests were }ositive for ischaemia by ECG criteria (> 0.l mV rectilinear or do~msloping ST s e c a n t ~ ) and :eversihle p~effusion defects on the TI-20I ;cans. A only occurred in 25 pts (28%) (group [~ while asymDtomAtie ischaemia was seen in 6~ [,~%) ( g r o u p = ) . The two groups were comparable [or age (5~ ~ 7 and 57 + 7 years) and for ~everity of ischaemfa developed during ET (max ;T& 1.5 + 0.6 and 1.6 ~h 0.9 am). However, fn roup 1 ~ t a l ET duration and flue" to 1 mm ST ~egment~ (6.0 + 2.5 and 5.& ~ 2.6 rain) were {hotter than i n ~ r o u p 2 (7.4 ~-2.4 and 6.2 + 2.3 rain) (p < 0 , 0 0 2 and p < 0.00I r e s p e c t i ~ l y ) . ~urthermore, in all pts of group i A followed : h e development o f diagnostic ST ~time to I ~m~ ;T ~ 5.A ~ 2.~, time to A 5,8 + 2.5 min). 'ersistent perfusion defects, indicating irevions myocardial infarction (MI) were seen on :he TI-201 scans of 16 pts of group 1 (64%) and :n 33 of group 2 (52%): 86% of these irreversible defects, were seen in regions ~djaeent to the isehaemic areas. In conclusion: ) in pts with stable A, the incidence of ~xereise-Jnduced asymptomatie ischaemia fs licker than that reported in the literature and limilar to that observed during ambulatory ECS ienitoring; 2) the reason for the dlscr{paney )etween our and others' experience osslbly :elates to the fact that A is eonsidere~ an end icier of ET and pts are usually brou~Elht to its levelopment eve~ when diagnostic ST c~anges are Llready present 3) The incidence of irreversible ,erfusien. defects suggestive of a previous MI ras slmllar in the two groups, in contrast with :he hypathesis tha£ previous myocardial necrosis "caulking in destruction of afferent fibers :ould account for painless ischaemia.

PROGNOSIS OF PATIENTS WITH CHEST PAIN AND NORMAL 2 0 1 - T H A L L I U M EXERCISE MYOCARDIAL SCINTIGRAPHY [he value or 2Ol-Thallium myocardial scintiqraphy to identify coronary events i n the two y e a r s after testing ~as a s s e s s e d in 1 6 7 p a t i e n t s . fomoscintig~aphy was obtained using a ~otating gammacamera arber injection or mCi of T h a l l i u m 201 at the end or xe~cise testing on a b i c y c l e . Images ~ere analysed at t i m e of t e s t i n g by 2 3r ~ e x p e r i e n c e d obsecvera. Bayes analyIszs w a s used Io c a l c u l a t e probability )F c o r o n a r y artery disease. Sensibility [So) of st~ese ECG was 60 % and .~peciFicity (Spa) 70%. ge and Spe o f ny . . . . d i a l s c l n t i g r a p h y .... both 80,.:ollow-up could not be o b t a i n e d inl5 ]abiemts. Mean time between testdng and ~tudy was 25.6+6.6 months. The mean ~ge o f p a t i e n t s was 5 5 + 9 . 9 y e a r s . Mean }reexercise probability--~as 38.8+25.4 % ~nd p r o b a b i l i t y after stress t~st was 12.7Z24.4 % probability after Thallium ~can w a s 1 4 . 5 + 1 7 . 7 %. ~o p a t i e n t d E a hh ~ a s n o t e d , 1 myocardial infarction occured, 2 patients underwent CAge, 1 underwent a coronary angioplasty. In one p a t i e n t coronary arteriography revealed a 50 % s t e n o s i s o f LAg. 18 o t h e r coronary arteriographies were normal. At f o l l o w up 5 8 . 6 % of patients were taking antianginal drugs. lln c o n c l u s i o n our study confirm that patients with chest pain and normal 281-T1 exercise myocardiai temose.intigraphy have a low r a t e o f non F a t a l cardiac e v e n t s (2 % / y e a r ) .

88

89

Mortelmans*, J. Vanhaecke ~ , E . Lesaffre ~ , G, Willems**, M. De Roe ~ , N. De Geest {, F. Van de Werf*. U.Z, Gasthuisberg, K.U.Leuven, B-3OOO Leuven, BELGIUM Rijksuniversiteit Limburg, 521S EA Maastricht, The Netherlands. ASSESSMENT OF THE EFFECT OF rt-PA ON VENTEECULAR FUNCTION AND ON INFABCT SIZE BY SCINTEGNAPHIC AND ENZYMATIC METHODS. In a double-blind trlsl 2ig pts with an acute myocardial infarction of less than 5 h duration were allocated either to lO0 mg ~t-PA given intravenously over 3 h (n=lld) or to placebo infusion (n=105). Infarct size was assessed by the cumulative myocardial release of e-hydFoxybutyr~te dehydrogenasa durlng the first 7S hours (HBDN QZg) and b y planar Thallium scintigraphy performed I0 to 22 days after the a~ute event. A total index of hypoperfuslon (TIi) was calculated using a circumferential profile method in comparison with a normal database. In the same period the global left ventricular ejection fraction (LVEF) was calculated by an equilibrium gated nuclear angiography (EGNA) performed after injection of 20 mCi of Tc-HSA. In rt-PA treated patients NBEH Q72 was 20% lower than in patients allocated to plezebo : 635 (90% range : 137-161£) OiL vs 791 (90% range : 234-]554) U/L, p < 0.05. Accordingly, TII was 2S% smaller in the rtPA g~oup than in the control group : 2356 (90% ~ange : 360-6264) vs 32E1 (90% range : 3E7-7598), p < 0.05. There was no difference in global LVEF between the two groups 54.5% (90% range : 27-74) VS 52% (90% ~ange; 28-691, p - 0.48. I Thus, the intravenous administration of rt-PA within 5 h of onset of symptoms signlIficantly reduces infarct size as assessed by 2 independent methods. With EGNA no effect on global LVEF can be demonstrated.

This study was designed to determine kinetics, uptake and wash-out rates of 2OlTI by the myocardium as a function of age, type and level of stress. In 212 patients with suspected or eonflrmed coronary srte£ M disease (CAD) was performed a Tl-scintigraphy at exercise (Ex- IBS pts) or after 0.A4 mg/kg Digyridamole (Dip73 pts). The myocardial uptake (M) and the background activity (g) were measured at the 7th, 15th, 23th mln and at the 4th hour (redistributlon). Patiants were divided into 2 groups according 5o the age : I [ < 6O yrs-152 pts), II (> 60 yrs-60 pts). The main results were the following : l) The maximum in the time-actlvity curve for M occurred early after Ex (around the 7tb min) but was delayed after Dip (around the 15th min). Thus the ~easured wash-out (W.0,) was dependent on the i~aging schedule. 2] M and S were significantly higher after Dip than after gx at all scanning times (7, 15, 2Bmn - 4hr) but M/B ratio was lower 3) Mg S end M/B were higher in group [I for both Dip and EX at all scanning times (inexpected result). I 4) The mean W.O. rates were lower after Dip than after Ex, and in group II compared with group I ~fter Ex. No age-dependance ,was found after Dip. 5) M was strongly i~fluented by the extend of heart rate increase during Ex. The myocardial uptake of 201TI ~fter Ex ~ppeared thus to be a complex function o£ age and heart rate increase ; D l p , leading to more homogenous and reproductible results, might be prefe~re~ in the elderly.

90

E.B. Cargill, H.H. B a r r e t t , R.D. Fiete, M. Ker) D,D. Patton, G.W. Seeley. Division o f Nuclear Medicine, University o{ Arizona Medical Center, Tucson, Arizor)a 85794, USA,

LIVER SCAN A N A L y ~ tJ~ING FRACTALS; A ~

2OlTI ~ Y O C ~ R D I A L U P T A K E AND W ~ M - O U T AFTEN E X E E C I S E AND D I P Y R I D A M O L E : AN E N % ~ S T I G A T I O N OF 212 C O H O N ~ Y PATIENTS AND THE INFLUENCE OF AGE.

[. R~ox, ~. Aguadd, V, H~rhinez-lbs~: It), C, N~rgarit {lh F,H, D~l~etk-~otad, ~uele~r Mediokne Serv£ce and Pediatric Hurger? D~p~rtment(lI, HoapJtBl Ge.~r~J and CiI~InB ]~fa~hi], ¢i~dad ~nitlrh 'V~II d'HebrdB', Barcelona. Spain,

01'ENSION

~OI~?IOHAPHIG CONTROL I~ PHDIATEIC L[VE~ TRASPLA~% Analysis o { radiocogoid liver scans i s usually based on a visual search 9or t e x t u r e abnormalitles: filling de{ects, uneven uptake, etc. We set about to determine whether f r a c t a l analysis could supplement the visual information ~n fee liver scan. Practals are o b j e c t s having the same general s t r u c t u r e over a range o f scales (e.g. coastlines, trees, bronchi; no dominant spatial frequency). The Fourier power s p e c t r u m (FPS) o f a f r a c t a l i m a g e is a s t r a i g h t line on log-log coordinates with a linear relationship between log (power) and log (spatial frequency). We inured t h a t the FPS o~ radiocolloid liver scans s t r o n g l y behaves like a { r a c t a l , suggesting t h a t the liver i t s e l f is ~ r a c t a l in nature, The FPS was a s t r a i g h t llne on log-log c o o r d i n a t e s (r>O.99) for all 70 liver scans studied; we found Pourier power spectrum slopes (FPSS) between -4,74 and -3.95 in normal livers, decreasing t o -3,6 to -d.8 in cirrhosis, and as low as -£.7 in metastatic disease. Normal and abnormal livers were significantly d i f f e r e n t (t=4.04, d~z29, p=O.O05). Furthermore, since the FPSS is independent o{ the number o~ counts in the image, the FPSS can be accurately estimated in l o w - c o u n t scans; the FPSS ~if~ered by less than IX when m e a s u r e d in a 5,COO:nun& image and a 5on,cOO-count image in the s a m e )atient, though noise was greatly increased. ge concluded t h a t (1) t h e liver is { r a c t a l ,n nature, {S) the FPSS o f the liver scan can be d e t e r mined with relatively few counts, an~ (B) the FPSS may aid in screening and in d i f f e r e n t i a l diagnosis Screening liver studies may De possible using radiocolloid doses in the 3-5 microcurie range.

hhienLB wi£h orthotopic liver tra~planladnn {OGTxl have been studied with bepatQbill~rl 6eintlg~apby (99mTc-hri~elkyii~inndi~cetic acid (TN-IDA}L dncludin~ liver bdood flo~ slu~I. Vascular 6tudl infnr|~ ~kout the ~teri~[ and the portal frRations of total heBatJ~ blnod [Io~. Liver per[usion mu~t b~ altered due to surgery, rejection or other recipien~ pathology. He~h.hili~r ~cintigr~ky mesures the hepatic exLr~ctinn, tke rsn~l ezctet£on~ Lke intrahepatic transit time and th~ ti~ing of h i l i a r y and inte~kinal ~ctiviti. lh ; o r b i t s tb~ detection ¢[ exLrabep~tin coaplkcaLLon~ llke bili~r~ oh~hruction, hiliar; leakage ~nd vas~ul~r kinking. We show our results in ZO ~edla~ric OLT~ age r~Ke eigkt ~ont~ 1o tkirteen f~ars. ~ perform ~6e ~[udf after an ~-~ bourn [s~[ng. V~scui~r study obtains ~[me-~ch[vlt~ nurve~ o~ ~Mnminal ~Drla, ~p]een, le~t kidneF ~nd llver. Bf ~ computer anal~i~. flttln~ ~m~a function o[ wsculBr peBk~ ~e c~leu[~e hepatic vamuuhH~tion indiueH. In normal uonditinn~, ~ obtain a scinti~rapkic Lunge ~erp ~ ~inutea (l to 4~ minut~J, If there is n~t biJiary o; intesti~ai a~tivity, hh~ det~otion~ ~I~ ~p~a~ed ~ Z, |, ~ and Z4 hours, We ~omp~re Lbe~n r~ulb ~ilh ghe reeipien~ evolution. In ea~e of rejection, ~e h~ve ~ound hepatic ~cularis~hio~ abnormalltieH ~s~nciated ~itb decreased hepatic extr~utin, a~d increased intrahepatio ~r~n~it time. [n ~w0 cases, ~ h~ve detected bili&ry leakage, In ~o c~Hes with port~l ~kroebosiH, ~e obserwd, [n the ~b~h blood Uo~I s~adL abaenne nf poc!~i [bw, In tb folln~-u~ studies, port~i flo~ ~ner~s~d, ~d in one Ga~, one pear after OLT~, liver per~usiun ~a~ ~or~al. Thi~ nnninva~iv~ ~eth0d has a ;re~t imporlanc~ no~ ¢;liy t~ indio~te su~getf fin our ezperie~ce in t~o patien~), but :l~o ~o darl[y the di~gnosi~ between rejection or surgical problem, and [h~refote we u~e tbi~ teohnlque llke a routine.

238 92

91

93

Ludwig G. S t r a u s s , John H. C/orius, Burkhard L e h n e r P e t e r Sehlag, F r a n z Oberdorfer, Frantisek Helus, Stefan A, B e y e r - E n k e , Rtidiger Port, G e r h a r d van Kaick

6. PO~G~LCNB~SlI~cVI(°), A. PA~FEGGL~(°°), S.DI L ~

G e r m a n Cancer Research Center, H e i d e l b e r g , W e s t Germany

(o) L a ~ of Nuclear M~ici~e-Vis P.Gi0vi0.15-~dls~e (°°)Institutof ~ i c ~ l Physi0pathel~y, LPcv~rsityM~ s

S C I N T I G R A P H I C S T U D I E S OF L I V E R IVrmTASTASES EROM C O L O R E C T A L C A N C E R U S I N G O-15 L A B E L ED WATER AND F-IR-URACIL.

Et~qICAL VALUE OF P ~ G I C A L ]Ehq~ ~LR~NG S E O J E ~ CtW~TITATI~E PEPAT~BIL/AqY~CIN~GR~PH?

)

To assess the d i ~ i c utility of ~he mrul~in test in ~resect~d pte. (gmu~ A 30 pts) and in pts. wi~h s a n biB_

The positron emission tomegraphy was used in 30 p a tients in order to assess the tumor perfusien and the ]ptake of F-18 labeled fluorouracil (F~j) in liver netastases from colorectal cancer, We w e r e able to >erform Four examinations after intraarterJal FU appli .'ation, while 36 studies w e r e carried out after i n t r a 'enous tracer injection. O-15 labeled w a t e r (30-100 mCi) was used Ior perfusion m e a s u r e m e n t s , followed by the application El F - i S labeled HuorouraciI (5-I0 mCi). F u r t h e r m o r e , in selected cases N-13-glu amass was used for the assessment of tumor metabolism. I A we r ng positron em ss on omograph was used for I data acquisition. Serial transversal scans w e r e obtained I for five minutes ( O - I 5 labeled w a t e r ) or 120 minutes (F-18-uraei[). An interative image reconstruction a l g o rithm was used and the tracer concentrations w e r e determined with a r e g i o n - o f - i n t e r e s t technique. All racer eoncen ra ons w e r e standard zed for the njec/ed dose and She body volume in order to get n o r m a l i z e d values. The final evaluation comprised 40 metastases in 30 patients. W e Found no significant correlation b e t w e e n the perfusion values and the concentration values 2 hobrs after F-18-uraei] injection. A significant corrclation was noted b e t w e e n the uptake of N - 1 3 - g l u tamate and F-18-uraci] concentrations. ~ e i n t r a arterial injection of F - 1 8 - u r a e i l was not followed by enhanced F U uptake in all patients. In spite of high tumor perFusion values the uptake of F-18-uracil remained unchanged after i n t r a a r t e r i a l tracer injection as compared to the intravenous injection of the zyt0static agent. The use of a modified t reat m ent protocol gave higher tracer concentrations in three patients. As our results demonstratc, P E T examinations with F - 1 8 Iracil can help to optinlize the therapeutic protocol in ,atients sufferin B from liver metastases.

der dyskires/a (g~oup B 20 pts.) and of the m m ] ~ - c ~ u lean test in cholecystectaTdzed pte. (£~up C 22 pte.) se~ueff~al h e ~ i l i ~ y stingier;by ( ~ ) wss c ~ e d out in ~ r t o r ~ pmjectim, after i.v. inj. of 3 ~Ci of Tc 9Sm~DA ~ d dynamic acqJisitinn vas r ~ Lsing digitel ~am~c~_ TE~ SEL0 linked to CST@UterMaps 5~]; analog h e p ~ l i ~ x~2es was cOmBined e v ~ 5 man. fo~ a total of 30 ~/n. ~cer visL~lit~ti~ of the biliaryr ~ c~rulein (0.~5 ~g/kJg, Takus, Free,italia-Carlo Erba) ~as i~ject~ L v . /~j in 50 ml O.~P/oNaCI in 18 nfin. u s ~ a S e ~ pe~fLr~/' ~mup C~ given 0.5 r~3 ~ i.v. inj. befc~ethe

lean, l ~ c ~ c t ~ e c~pacity of ~ gB]]~ladd~r was ass~ s~ Dy ci=teIT,i~ ~ eje~J~ f ~ ~ ~ activity t~ ~e cruse of the ~sll2ol~li~. In ch01ecystecto~izedpto. b_i empytir~ ~pacity was assessed by ~ the ejecti~ fracti~ of the ~ bile duct on fl-e activity/tim~ cu~e of ch01ed0c. Duede~al~astricreflux (DG~) was qu~ti fled used the i ~ x ~:mde~ by Wickrs~i~he. In the -~ p A the DGR was prese~ in the g[/~ of the asM~ptcmstic ~ . (range28~4[~ and in all symptomaticpts. (rB-~e4 ~ S~), In O~e ~ B the 83~ of pie. bed lo~r then ~xral gall-bledd~r ejectioq fraction (lessth~n 35 percent) after the ceruleantest. I n the &~up C £5~ of the pts. gave a de leyed resp~se to the mmT~ire-ca~ulein tes% and 2 ~ of ~ts. presented a very small a~ou~c of ~adi~accive bile in t e dueder~ after the test. The phe~acolo~ical test made kming SHS offers several edvantagas in clinical practice ~h s ~ i v i t y of the ~ wicb is ~ep~mducible, non i

rssiVequantitativea S S E ~

F~D,Haut~ g. B l t t n E r , R,P,gau~e ~,g~re g . g o t t E n r D t t , ] . B r a n d h o r i t I E.~tandke

Sch6rner, M Laniado, W Kornmesser, Bittner, H Henkes, B Sander, R Felix

D i v i s i o n s of ~ s n l r s l N u ¢ l e l r HEdicine and Rbdoaina] Surgery J . W . ~ o e t b ~ - U n i v E r i i ~ y Frankfurt~ FRg

FUNCTIOMgL PgTTEgg Of HEPATOBIL]~RY SPLIT PUNCIIONg AFIER LIVER TRgNBPLANIATIONn MEW gPPROACH gAgE9 ON A BIEKINETIC gN~LYBI$ WO ~alyiEd the k i n e t i c data of 22 I c - ? ? ~ - H I D g studie~ in t h e ÷=l]ow-up ~t ~ p a t i m n t J (~ oales, 1 ~eJale) Jfter llwr ~ransplantation (ITxO. ThE f i r s t HID~ study .as : a r r i e g out hI 0 daya attar LTw, gft#e i n j l C t i o n Of 7~-100 HEq Tc-?qm-HIDA a 40 mi. galmacsmera-computeracqgi$ition wa| s t a r t e d . Fro~ t h l ~ study we ¢IlCuZltld the half-life ol blood ¢limaaation (HL-BE)~ the h a l f - l i f e of liver invasion (HLLI], m ~ a n parehchymal t r a ~ s ~ time (HP-TT] ip alhUtEs and the percEnt|g= of b i h a r y retm~Lios a~tEr 40 sin (gET=40). Noroal values as Established in 51 p a t i e n ¢ | w i t h o u t Slyer d*sEase wErE! HL-B~CbO, H L ' L I ( 3 , NP-TI
I

~ h ~ s m of hlluL~ flow. I~h m~b~t faired ove~rdd'~ a'fl recei.v~d I~D ) ~ of 99n-To-HIE~~ ~

m~LC~OU~ ~

~

.

~n$~ne

~11~L~m. ~ c ~

of

Lobe, +he cc~n~ h e ~ c duct, the c m m ~ bile duct, ~ &xOan~ a ~ o~r t~e g a l l h b ~ . T m ~ i ~ t y cu~es ~"~ ~ . h amup;of ~ ~a~ie~ c ~ 5~ g cho~]~f~ at ~he ~0. mb~te of ~ullb]~er fillir~. 'Doing f~-tirg~ z ~ % reg~]~ pericdic~/ infl~ ~ s

~

~

~ .

~

of ~ ~

(3-5 cycles/;mt~e~)~ m ~ u r ~ , rr~a~: 13,I~ - 10,53 }~in. CS-L:g4rr~l.). '~tme la-~C ",ewes frequeltly~ivi~d into ~.~ ~xx% %sees. Periodicityof ~ e sa~e f~qt~(mc'y o~erve~ i n the e ~ e of esn~n Fe~ic drab, c ~ ~e

duct a~ ~

~ ~ne bep~c ct~e as ~]2. ~e

fa//irc a ~ ~ y ~ v,e~ ~ (r~lieal, in ac=on~ ~dth the biLim-y d ~ m:,VBTm~. ' ~ 1~.~"iS~,~&l~_ed'mr'~'fer of

(47 raUar~), b ~fl~copic ~ m ~ _ ~

(6 pts.) or by

peristalsish~s becom i m m d ~ l y f~sterz ~ m~mu cycle I ~ of ~ group ~ fr~ 12,16= 4,75 r:dm t;o 8,6~ - 3,~0 me.. ~ s m m ~ of isoto~ clean~ 9,~o 9*s d u o i ~ durirg ore rarind has ir~mms~d. l'~ c~clude th% ~ h i ] J ~ ducts ~ the g ~ ] / ~ have a az~:~'~ou~ ov.n p~ristaltic~ not edy of%c2 eatir~ but also d ~ i ~ f ~ n ~ .

of [~8, morphological a~d

95

94

I._~'i~i:;, A. I~'VAY

96 J.T. Ennis, J. Stack, O. Redmond, D. Carney, g. Hurson.

,artment of R a d i o l o g y , R u d o l f V i r c h o w tospital, F r e e U n i v e r s i t y of B e r l i n , test G ~ r m a n y

Institute of Radiological Sciences, Mater Nospital, Dublin.

C O N T R A S T E N H A N C E D NMR I M A G I N G OF B R A I N T U M O R S : E X P E R I E N C E S OF 200 C A S E S

THE ROLE OF MAGNETIC RESONANCE IMAGING IN THE MANAGEMENT OF OSTEOGENZC S/iRCOHA.

A d e c i s i v e a d v a n t a g e of NMR i m a g i n g lies in its h i g h l e v e l of soft t i s s u e c o n t r a s t . H o w e v e r , in s o m e c a s e s i m a g e contrast obtained with different plain NMR t e c h n i q u e s is n o t s u f f i c i e n t to obt a i n r e s u l t s w h i c h are c o m p a r a b l e with contrast-enhanced CT. T h e s e l i m i t a t i o n s l e d t h e i n t r o d u c t i o n of the c o n t r a s t agent Gadolinium-DTPA into c l i n i c a l NMR. >aSSents and m e t h o d s . - P l a i n and con: r e s t - e n h a n c e d NHR i m a g i n g (0.5 T Magn e t o m ) w e r e p e r f o r m e d in 200 p a t i e n t s w i t h i n t r a e r a n i a l t u m o r s . P l a i n NMR s c a d s w e r e o b t a i n e d u s i n g TI- and T2w e i g h t e d spin e c h o s e g u e n e e a . A f t e r iva d m i n i s t r a t i o n o f C.l mmol G a d o l i n i u m D T P A / k g BW T l - w e i g h t e d s p i n e c h o and FLASH scans were performed. R e s u l t s . - The e x p e r i e n c e s g a t h e r e d in t h e s e s t u d i e s s u g g e s t e d a v a r i e t y of c l i n i c a l f e l a v a n t i n d i s a t i o n s f o r contrast-enhanced NMR imaging: I. I m p r o v e d d i f f e r e n t i a l d i a g n o s i s : Usimg Gadolinium-DTPA, the differentiat i o n b e t w e e n e x t r a c e r e b r a l t u m o r s and highly malignant gliomas from several o t h e r t u m o r s (not a c c o m p a n i e d by a b l o o d - b r a i n b a r r i e r d e f e c t ) is p o s s i b l e 2. I m p r o v e d d i f f e r e n t i a t i o n between t u m o r and edema: W h e r e a s p l a i n NMR scanning permits differentlation in approx. 60% of the cases, c o n t r a s t - e n h a n ced NMN i m a g i n g a l l o w s f o r s u f f i c i e n t a s s e s s m e n t of t u m o r d e l i n e a t i o n in m o r e t h a n 90g of all c a s e s . 3- I m p r o v e d d i a g n o s i s of s m a l l t u m o r s and r e c u r r e n t t u m o r s .

This rare, aggressive neoplasm, with an incidence of 4 per 1 million, although rapidly invmslve, now has a better prognosis through limb salvage operation and more effective chemotherapy. Patients & Methods.. Ten patients with a h~opsy diagnosis of osteoge~ic sarcoma were included in the study. All patients underwent radlonuclide hone scan imaging, computerised tomographp and magnetlc resonance imaging, using axial, coronal and segittal projections with different pulse sequences. The age range was 9-2h years with a mean of 16.7. All lesions were in the lower extremities and the TI ~nd T2 weighted spin-echo sequences were performed i) prior Co the co~encement of chemotherapy; and 2) i~edlately prior to surgery, Changes in T2 values were quantatared following chemotherapy. P31 ~ R spectra were obtained from 5 of the patients, using a surface coil loealisation technique. Intramedullary extent of tumour was demonstrated by the chemical shift artefact of the t ~ o u r / normal marrow interface. Results. The main value of radionuclide scanning was in demonstrating satellite lesions MR was vastly superior to CT in determining the extent of marrow involvement prior to prosthes~ Changes in T2 measurements showed good correlation with tumour prognosis. MRI Spectroscopy was the most effective method of demonstrating adequate response to chemotherapy. Conclusion. MRI is a very accurate technique for determining intrameduilary extent of tumour T1 weighted (500/17) sequences are particularlp %~ to che~ ic s .aft ~sefp ~ due ......... T~ 1va~ . . .artefact. . . . . b .....C~.anges

239

99

98

97

•

J.T. Ennis, J, Stack, O. Redmond,

Institute of Radiological Hospital, Dublin.

Linden,A.*, g. Franke +, J.Smolorz*, ~W.gchicha*

D. Carney.

Sciences,

Mater

ASSESSMENT OF BONE MARROW INVOLVEMENT BY SMALL CELL LUNG CA/qCEK WITH SPIN-ECHO AND GRADIENT MR SEQUENCES. Standard criteria underestimate marrow involvement in small cell lung cancer and MRI was used to evaluate she signal changes in response to chemotherapy in patients with SCLC. Patients & Methods. Twenty-one patients wi~h biopsy-proven and 21 age-sex match controls war~ examined, using contiguohs coronal images obtained from the femoral and pelvic marrow. A I.bT Magnetome superconducting system, using TI and Tg spln-eebo sequences and two rapid gradient echo sequences, PISP iO ° (10/13) and FLASH 40 (10/14). Standard cancer staging procedures including CT, radionuciide ~one scan hone marrow gspirate and biopsy were performed. Results. In the abnormal marrow, three distinct patterns were observed~ i) multiple small discrete foal of i cm low signal intensit} 2) larger th~n I em marginased regions of low intermediate signal- and 3) diffuse, poorly defined regions of low to intermediate signal. T2 weighted images were less reliable, hut t h e rapid sequences showed all three patterns elea~ly, gone marrow abnormglity was identifis in i3 of 21 patients, compared to i of 21 usir Istandard criteria, Follow-up scans during and after chemotherapy showed varying patterns in response be chemotherapy. ~oncluslon. i) The incidence of hone marrow involvement by SCLC is significantly creater ]whenHRl is used. 2) Treatment response to the bone marrow can be monitored using MRI. 3) Lesions may be more readily identified with rapid sequences imaging because of the chemical ~hift effect.

P.Theissen*

* Institute of Clinical and Experimental Nuclear Medicine, University Hospital, Cologne + Medical Clinic I (Ontology)

Institute of glinical and Experimental Nuclear Medicine, UniVersity ~ospital, Cologne + Medical Clinic I (Ontology)

MR IMAGING OF BONE MARROW IN MALIGNANT LYMPHOMA: OOMgA~ISON WITH HISTOLOGY

MAGNETIC RESONANCE XM~GING IN PATIENTS WITH

In 124 patie£ts with malignant ly~phoma MR imaging of bone marrow of lu~osaeral are&, pelvis and both femora was correlated with the histological results of bone marrow biopsy of the lilac crest. Findings with both modalities were ciassified as normal, react&ve or indicative of malignant infiltration. In 62 patients results of MRI and his#elegy correlated completely. In 6 patients one of both methods indicated malignant infiltration with a normal finding in the reference method. In 4 of 14 patients with MR findings'indicatin¢ infiltration and normal or reactive histology MR results could be confirmed by rebiopsy, guided biopsy or post mortem studies• To evaluate the validity of these investigations we performed i0 post mo~tem MRI examina'tions of patients with malignant lymphomas. In 9 of i0 cases the MRI findings were confirmed by direct biopsy and histolog~ of suspect area~ In I case marked autolysis may have caused a false negative result• Conclusions: i. There is a positive correlation between bon~ I marrow MAI and histological changes 2 In case of different results between MRI and histology a new biopsy of the suspect area is necessary 3. We suggest that bone marrow biopsy is more egficient when guided by MR findings showing localisation and extension of malignant infiltrasion.

101

100

+

Llnde£, A.*, E. Franke , J. Smolorz*, P~ The--~sse~*, W. Waters*, V. Biehl +, H. Schicha*.

Magnetic resonance images were performed in 30 patients with histologically proved plasmocytoma to evaluate th~ extent of bone marrow !infiltration using Tl-weighted spin echo and fast field echo sequences• In 5 patients we found a sy~/aetrical spotty pattern of circumscript decreased signal intensity in bone marrow of lumbosacral area, pelvis and both femora. This pattern was absent in 15 examina- i ted normal subjects and 20 patients after radia~ I tion therapy. Only 7 of 102 patients with I other malignant iymphomas showed similar bone marrow abnormalities, most of them suffering from chronic lymphocytic leucemia. As ~ur findings correlated positively with the histological results performed by bone marrow biopsy of the iliac crest, we conclude that the described MR pattern is specific for bone marrow infiltration in plasmocytoma. Thus MR imaging might be a valuable method in addition to bone marrow biopsy in demonstrating localisation, intensity and extension of bone harrow infiltration and in facilitating diaqosis and follow up studies•

~

102 IG. Pagane±ll~

:.i. ZANCA I, P. BERNIER 2, N. ROSSI 1 i. Biophysique Lapeymonie

et [i@decine Nucl@aire, Hgp~tal MONTPELLIER

Department of Microbiology End Immunology, New York Medical College, Valhalla, NY 10595 (USA) OF BIOLOGICAL IN DIRI

TISSUES

AND TISSUE

CHABACTEHIZATIOR

Due to the kind of the studied phenomenons,

N!~N

I s l l o w s the observation of specific properties of bxological tissues which lead to a possible t~ssu characterizatlon ; furthermore, some of tbose properties are currently accessible to !]gI with relatively simple adequate methods• i. Characheri~ation with TI and T2 : BecauSe of- t-he E-e~t ~eco~er 9 between healthy and pathological tissue values, T1 and T2 appear to he poorly representative, hut itis very useful to measure in rive MRI T1 as accurately as possible We thus developped a routinely applicable p~oto'eel ~hich was able to rapidly supply precise measures of T1 and applied it Jn pelvis breast_.. '2. Temperature linked properties : ~/e observed in vitro an increase Jn T1 tissue v~ lues with temperature, accordin~ to the equation I1/T1 = (I/TlltexpiEal/kT). The activatio~ energy Ca' seems to characterize the lipid content of the tissue, or its malignity :ga' is about 2(gcai.~k-l.mol't)for healthy tissues, or non aalignant pathologies, about 4 for malicnant ones and about g to 6 for pure fat• 3. Water content index H' : We d e t e - - ~ m ~ ~ F l . ~ sequence whose inversion time allowed to cancel the fat signal. Applylng this sequence to breast MBI, we could define a water content index H' far more sensitive than the msm~ogPaphic one, and correctly correlated with the contrast enhancement observed after I ~ Ud injection. a. Contrast media : Using DOTA-Gd injections, ~ dymemic study inF/B allowed to define kinetic parameters according to a mammillary model, as : maximum-signal embed cement) time to peak, mean transit time•.• : we observed significative variations f o r e - - v a l u e s depending on the tissue,

[

S, Pervlz~,

£.BlVa~

Isiccardi$ and A.A- Epenet0s§. Ospedale gufalini, Cessna; §0neology GrOUp Hammersminh Hospital, London; &Societ~ ?rodotti ~AntihJo~ici, Milano; +SORIN Biomedica, Saluggia SDipartimento dl Biologic e genetics, Milano.

~

2, LaDe. H~JN, GDPC-USTL,

NMR PROPERTIES

G. ~owlison~,

F. UEio~e~io~,~. Naleo~a~i$, G. UEleide: g.~.

M. Temponi, T, Kageshita a~d S..Ferrone

A role for antiidiotypic alatibodies in immunoseintigraphy and radioimmunotherapy Labeling of monoclonal antibodies with radio-isotopes is associated in most, if not all, cases with a reduction of their immunoreactivity. Rgdiolaboled rnonoclonal antibodies which have lost their immune-reactivity may bind non specifically to cells which lack the corresponding antigen. This phenomenon may cause a high background when radiotaboled monoclonal antibodies to tumor associated antigens are injected into patients to visualize malignant lesions and to implement radioimmanotherapy. To overcome this limitation in the in-viv0 use of radiolabeled rnonoclonal antibodies, a method has been developed to purify imrnunoreactive monocloaal antibodies from antibody preparations following radiolabeling. In this procedure, radiolabeled rnonoclonal antibodies are incubated with insolabilized antiidiotypic rnonoctonal antibodies for 2 hours at 4eC. Bound antibodies are eluted with a pH gradient. Utilizing this procedure the immunoreactive fraction of rain or {2sI-labelcd anti high molecular weight-melanoma associated antigen (HMW-/V[AA) meRgE[oRal antibody (MoAb) 225.28, 763.75, TP41.2 and TP61.5 increased from 37.6% to 87.6%, from 56.5% to 91.6%, from 29.I% to 90.9% and from 61.6% to 96.0%, respectively. The increased immunoreacdve fraction was associated with a marked increase in the tumor/background ratio, when the lnIg-~nti HMW-MAA MoAb 763.74 was injected into human melanoma bearing nude mice. These results indicate that affinity chromatography on antiidiotypic antibodies represents a useful method to purify irnmunoreaetive anti I{MW-MAA monoclonal antibodies from radiolabeled antibody preparations. This approach may improve the sensitivity or irnmanoscintigraphy to visualize malignant lesions in patients wilh melanoma and the efficacy of rm:i oimmunotherapy.

'~--VlVO TUMOUR LOCALIZATION BY IBIOTINYLATED NONOCLONAL ANTIBODIES AND RADIOACTIVE STREPTAVIDIN. P r e l i m i n a r y work j n vitro and in a r a b b i t model had demonstrated the ifeasibility of a t w o - s t e p m e t h o d of radioaotivity d e l i v e r y to tumour lesions, based on t h e u s e of b i o t i n y fated MaD's, f o l l o w e d by radioactive a v i d i n (Int. J. C a n c e r , in p r e s s ) , In the present work, biotinylated MaD IAUAI w a s i n j e c t e d in n u d e m i c e b e a r i n g

l

intraperitoneaI cells line).

xenografts

of

LOVO

(a One

human adenocarcinoma cell day p o s t - i n j e c t i o n ~IIor itz~I-streptavidin was administered i.p. and f o u r h o u r s l a t e r t h e a n i m a l s

'were saorificed and t h e i r o r g a n s CQuntsd in e gamma-counter to evaluate the percentage of injeoted dose per s r a m o f t u m o u r snd t a r g e t to non-target ratios. For comparison purposes, two other groups of hude mice were studied after single administrations of radioactive N a b or of r a d i o a c t i v e streptavidin, respeotively. The results demonstrated t h a t t h e twos t e p m e t h o d is d e f i n i t e l y more efficient than the direct administration of r a d i o a c t i v e Mab's with respect to

a) the relative amount of radioactivity in t h e t u m o u r (24% vs 6% of the i n j e c t e d dose) a n d b) target/non-target ratios (which were improved, on

average, 6.5 fold). Autoradiography and direct peroxidase-streptavidin staining of histological sections demonstrated the presence and t h e specific distribution of biotinylated N a h ' s o~ t u m o u r c e l l s ,

240 103

105

104

P. Oehr, J, Westermann, U. Germer, A. Bockisch, H,J. Biersack

d e a n - M a r c Le Doussal, Marie Martin, Emmanuel Gautherot, Michel Delaage and Jacques Barber,

Inst. Mucl, Med. University Bonn, FaG

Immunotech S.A., Campus de Luminy, Case 13288 Marseille Codex 9, France,

SCINTIGRAPHIC TUMOR IMAGING WITH BIOTIN-CONJNGATED ANTIBODIES AND RADIOLABELED STBEPTAVIDIN

AFFINITY ENHANCED TARGETING R A D I O L A B E L E D D I V A L E N T HAPTENS.

The aim of our experimental study was to take advantage of the high affinity of streptavidin to biotin (K D = i0-~5 ) in scintigraphic tumor iJaging. We used nude rats bearing cytokeratin-positive solid BeLa cell carcinomas on their hind leg. The binding of monoclosal ~nti-cytokeratin antibodies to the tumor was demonstrated in vitro by immusohistochemical staining and in viva by means of rsdioimmunodetection with 125I-labeled antibodiss. The anzmals were preinjected 1.v. with "cold" biotin-conjugated anticytokerstin antibodies. At a later t±me 125I-laheled streptavidin was administered l.v.. In another approach the animals received an additional injection with a specific anti~antibody to the previously administered anticytokerstin antibody in order to reduce free antibodies in the circulation. In the streptavidin-biotin system the tumor could be localized within 60 minutes whereas it took at least three days with the directly labeled antibody. Using the anti-antitody the tumor could already he seen 15 minutes p.i.. A limitation of the system was some antibody-independent binding of streptavidin to the tumor as well as to other organs, especially kidney and liver. Our results demonstrate, however, specific antibody-dependent radioactivity uptake into the tumor. We assume that the in vivo application of the streptavldin-biotin system leads to improvement in diagnostic and therapeutical approaches,

Two step-techniques using antibody conjugates (DSC) with specificity to both t a r g e t cells and a h a p t e n c a r r y i n g radioisotopes should improve the efficiency oC i m m u n o s c i n t i g r a p h y and i m m u n o t h e r a p y . However excess free DSC may i n terfere with t h e specific localization of t h e hapten. A system ]n which t h e h a p t e n binds p r e f e r e n t i a l l y to cell s u r f a c e - b o u n d DSC should be much more efficient. Thus, DSC was prepared by coupling F(ab')2 f r a g m e n t s of a monoclonsl a n t i b o d y (mAb) specific for t h e ailelic mouse B cell a n t i g e n Lybg.2, to PaW f r a g m e n t s of an a n t i - g , 4 - d i n i t r o p h e n y l (DNP) mAb; d i v a l e n t and monova[ent h a p t e n s were obtained by col/piing DNP to peptides or to d i e t h y l e n e - t r i a m i n e pentaaeetic acid. Divalent haptena tightly bound to mouse spleen cells In the p r e s e n c e of DSC in vitro, and binding occurred w i t h h i g h e r affinity to cell-bound DSC than to soluble DSC: we refer to this effect as "affinity enhancement". Binding of m o n o v a l e n t h a p t e n s to t a r g e t cells was much weaker. Divalent h a p t e n s , l a b e led w i t h e i t h e r 125I or l l l i n and injected with optimal amounts of DSC, accumulated in the spleen of BALB/c mice as well as t h e 1 2 8 I - l a beled DSC. Monovalent h a p t e n s , u n d e r the same conditions, were m u c h less efficient. When lllln-labeled divalent hapten was injected ten minutes after DSC administration, spleen uptake was even higher (24 % of injected dose). In every" instances, both in vitro and in vivc binding occurred with the expected LybB.2 and DNP specificities. This suggests that indirect tumor radloimmunologlcal localization and t h e rapy, using DSC and radlolabeled h a p t e n s , may be d r a m a t i c a l l y Improved by t h e use of d i v a l e n t h a p t e n s and a f f i n i t y e n h a n c e m e n t .

106

915,

OF

107

D. Colaher, R. Mutate, M. Boselli, M. F. Minelli, D. Simpson-Milenic and J. gehlom

P. THEDREZ.M, KREMER,C. CURTET,C, SAI, D. GUERREAU,d,C SAC~VINIANDd.F, CHATAL.

Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda MD 20892

IN$ERM U 21 I, Nantes, end Camp. ORI$ Ind., Glf sur Yvette, Francs.

RADIOIMMUNOLOCALIZATION OF HUMAN CARCINOMA XENOGRAFTg WITH 872.3 SECOND GENERATION (CC) MONOCLONAL ANTIBODIES

BIODISTRIBUTIONOF IN-Ill OC 125 MONOCLONALANTIBODY(MAB) IN A NUDEMOUSEMODELINTI~PERITO~EALLY tiP) GRAFTEDWITH A HUMANOVARIANCARCINOMA,

i

The 57~.3 reactiv~ antigBn, TAG-72, has been purified and a series of second generation monoclonal antibodies (MAts), designated CC (colon cancer), have been characterized hy a range of in vitro immunological assays (Muraro et a T . submitted for publication). gi~ UC HAbs (CCII~ CC30, CC46, ccAg, CC83 and cog2) were chosen ~or analyses of the in vivo bfndlng to a human colon carcinoma xenograft. All 6 MAhs have been previously shown to he distinct from 872.3 and each other by a series of reciprocal competition BIAs, add all were shown to have a higher K a than 872.3. In this study we have demonstrated that all six CC MAbs evaluated are superior to B72.3 in an in vivo tumor targeting model, using human colon car---~inoma (LS-174T) xenografts in athymie mice, in terms of both the percentage of the injected dose of radiolabeled MAb delivered per gram of tumor and in to,nor to normal tissue ratios. Differences in the in viva bdndin B patterns and pharmacokinetics amonB the Cg MAts were also demonstrated. Thus, in light of the fact that B72.3 has been shown to successfully target approximately 75% of priraary and metastatic carcinoma lesions i~ a variety of different carcinoma types in several hundred patients, these studies serve as further evidence to support the clinical evaluation of the second generation CC ~[Abs, either alone or in combination with 872.3.

The aim of this work was to stud,/the biodiatribulion af In-111 intactOC 125 I'IAbwith known affinityfor ovarian carcinomas in e nude mouse model grafted IP

with a human ovarian career (NIH:OVCAR-3). Results are expressed in % of injected r~se per gram and in tumor-to-nontumor ratios. Tumor uptake 24h after IP injectionwas highor wlth In- I I I 00 125 i'IAb (28 ± 7.44) than with a nonepaslfic immunogloPulin (In- I I I N $ ) (6.86 ± 1.35). The kinetics of tumor uptake al~) differS, showing a please followed by a drop at day 7 with In-I 11 00 125 MAb and a decrease beginning at 24h with In- 111 NS. Tumer-to-normaltieeue ratios ranoed between 29 ± 1.10 and 4 ± 0.8=I with In- 11 I OC 125 DAb and between 9.46 ± 6.8,2 and 0.89 ± 0.29 with In- I 11 N$. Maxim~Jm tumor uptake was higher after IP (:50.77 ± 4.76) the~ IV (14.59 ± 2.70) injection. Insteadof attaining the plateau noted after IP injection,tumor uptake after IV injection remained low at 2h (2.11 ± 1.66), reaching its peak only after 96h. Comparatively, I- 131 0(3 125 injected IP, which reeched maximum tumor uptake at 2h (13.53 ± 4.25), showed tumor-to-tissue ratios ranging between 25.18 ~ 9.22 and 1.93 ± 0.99: the

rate of tumor uptake decreased, but the ratios remained elevated. Intraperitonaslinjection of 8 radiolabeled colloid sslutionshowed maximum tumor uptake at 96h (20.22 ± 5 35) but with very elevated nunspeciflc

uptake in liver (31,06 * 6.22) and spleen (55.23 , 14.11).

T h ~ rssults indicate high, selective tumor uptake of In-1 I I OC 125 after IP injectionand demonstrate the feasibility of IP r~ioimmunotherepy o~ ovarian

csroinomss.

E. Bombardzeri

Dept.Nuclemr Medicine, National Cancer Institute 2OiS3 Milano (Italy), Via Venezian i

CEA PRODUCTION AND E~eESSION BY HT 29 HUMAN COLON ADENOCANCINOMA CELL LINE UNDER DIFFERENT EXPgRIMENTAL CONDITIONS The immunoscintigraphic results mainly depend oz the availability of the tLuno? associated antiMer for the radlolabelled monoclonal antdhodies. Ce] lines derived from epithelial tumors than sacra te CEA provided us with the opportcunity to stud) the production and the expression of "the target CEA in defined experimental conditions. We demo nstrated that CEA p~oduction by HT 29 cell line modulated under different media of cultlnce (p~_e sence or absence of FB8, HB 1Ol synthetic serum free medium). The ppoduction of CSA also inerea sed in p~esence of cho2estemol at 25,50,1OO ug/ ml concentrations. The treatment with some biol( Eical response modifiers, such as recombinant ir Iterferon alpha(rIFNK ), beta (rlFN 6 ),and gamma (rlFN [), caused an enhancement of CEA synthesi~ in particul~ the activity of rIFN~ an rIFN 6 on lEA metabolism was much less remamkable than th~ demonstrated by rife ~ . The metabolic effect foz ~IFN~ was already evident at the dose of IO IO/n )n the contrary for rIFNs d and ~ only the high, st ~oses (iOOO IU/ml) induced a modest increase in lEA p~oduetion. Morphological ~alysis of cells •ith various eRA content seemed to correlate th( ]EA production with some aspect of the cell dif ferentiation. These findings s u r e s t that CEA ~xpression in cancer cells can be modulated in ~ariety of ways, and this observation must be t( Ken into accocunt in the immunodia~nostic and iml nutherapeutic application of the anti CEA mono zlonal antibodies. I

I

108 M.P. LAROCK, R. CANTINEAU, P. RICO

CHU - Liege, BELGIUM Tc HIM TO DEFINE THE EXTENDOF MYOCARDIAL ISCHEMIA AND EVALUATEVENTRICULARFUNCTION. Tc MIBI is a technetium (To) labeled i s o n i t r i le d e r i v a t i v e . We have taken advantage of the ihysica] c h a r a c t e r i s t i c s of Tc to combine vent r i c u l a r studies with the analysis o f perfusion. lle have attempted to evaluate the diagnostic performance of MIBI in patients (pts) with multiple vessel disease {VD) by comparison of angiography and of thallium scintigraphy. We have analysed global and regional ventricuf a r function by comparison of f i r s t pass ejection f r a c t i o n (EF) and gated tomography with equilibrium radionuclide ventriculography. We have studied 67 pts with CAD : 42 pts studied at rest and at stress and 25 pts with c l i n i c a l , biological and ECG signs of acute myocardial i n f a r c t i o n studied at rest with gated tomography. Angiographic control was performed in 37 pts :12 pts had one VD, 15 two VD and 10 three VD. The overall sensitivity for the detection of

myocardial infarction (MI) reaches 95% [43/45). The s e n s i t i v i t y for detecting individual vessel lesion at stress was higher in pts with previous MI (89%) than in patients without (86%). The correlation between the EF evaluated with the f i r s t pass technique and the EF evaluated with the equilibrium technique was excellent r = .98 for LV; r = .79 for RV). ly comparison of diastolic and systolic frames fated tomography provided the analysis of wall tion abnormalities and allowed identification of physiological thinning of the apex. Tc MIBI is a very promising perfusion agent to document MI and myocardial ischemia as well as functional information on global and retonal venbricular function.

241 109

110

C. I,'ANCA~SA, P. ~.~IE/9, O. PAHODI, G. ~UCETi, D. f~GLZA.

E.~enze, P. Hildebrand, D. Hellwig, E. glausen, R. Weller, D. Nanjura, F. Bitter, N.E. Adam.

0.1]I?~ITOTZ 07 CI//~CALp}h~lOI~', PISA, ITALY

University of glm, Germany

QUR~ITAT/VE MYOCARDIALIVAIL ~ O ~ E ; ~ ~IAL~IS BY EgoGATED ~.~{gXY-IUONIFYI~IS~ULF P~J~L~IC~ SCIN~IGRA~.

REGIONAL WALL NOTION ABNORNALITIES IN LBBB SPECIFIED BY BY QUANTITATIVE pHASE ANALYSIS.

9C~Te labeled ~9~oxy-tsohu~fl-isonitrile (i[gl] has be~n recountly introduced to ~tudy regional blood flow dis~ibutic~ in m~n.T,~e7also sllo~s E~-~ted acquisition. g]mce I,~[g[ is tr~p!~ iniD the l~{Oc~i~, systc-disstolIc ~dioectivity CheESes ~ppe~r related only to v~riation in CoLors recoveredby ~ e exte~al counting due t~ c}~n~es in wnll ~ c ~ , accor~ling to the }n~ti,ql v o l ~ effect. Based on d~is aSSL~,ticm,we in~xrx~Jc~dr~n algoz~/~n to ohfain quentltative iDfo~tion on regio~el wall ~ick~ning. k'e studied iB patients (pLs) ~ o uqder~t C~n~st venll-lculo~Jly heesuse of stt~pected isd~emic heart disease. 2ef~o~l i~ii ~tion (R~.~) sb~:~lities on con~asg ven~riculogc~]y were qusmtii~tive]~ sssessed by f~actional~lortening ~ , 12 rad/i both For 20 riper ~nterior and ~c) left anterio~ oblique projection.ECC-gai~d s~inti~r~n~,(le fr~-~s,~xfa nixel ~trix,r.D~elh~n I~.C(~ ooun~s on the c~ddiasi~lic fr'~e) ~,e~eaequi~:d i~q 'a~e ent~,ior, left ;~terior oblique ~0 and 7O project/onby s s:m]l field,moLlie~-~rern after injecticr~of 15 r,%Ciof I~n~ in control c~ditioms, g~* the enddimstolic and the codsystolic f~es, g angular pr~file~ v~re generated (60 t~dil, average c~t~/pixel for each s~lir~ redius). ;a~.] l,a~s assessed as re;zior~lsyst~lict h i c k ~ g (~q~T)acco~Jmg ~ ~19 fo~ia: (end~tolio cu~2%tprofile - enddiestmlic count profile)/ (eeddimstolic co~nt p~of/le) R 103. Five ~omnsl suhject~provided c~[z~l ~alu~-~of ~ST. To identify c~ssgnergic ~/~as,~[e ~ T h i s i ~ ~,.%s plott~odversus that derived fr~a com+~ol l~pulation (mea~-lSD); E, pl~/l~n,sls ~atio belch,,i ,,;asconsidered~s abnom~l (i.e, C~ss~er~), Tne 60 ~ST values were ave~qed to obtain !2 s e ~ n ~ 1 values e ~ a ' o l e wLU~ s~qilar v~il-ieuloL~a~ic r~gions. 7if~e se~eni.s c~,~l abnormal f~actio~l short,daD ~%~ile O7 Uad a [~ologi~l ~3T. ~he ~e~itivity, and specific~t 7 wez~ C6.~ End Cg.[T~, t~sQect~w~ly. In Donclusion: gate] i[,e~e~sof ~'IBI~A~c~edi~ distribution, ~st~iai~ with i~e prDi~sc~ etlgor~i}~, p~ovided)jective irlo~,~i.ic~ on ]
In LBBB radionuclide venfriculograms (RNV) it is difficult to differentiate between a pu~e LBgg-speci[ic septal wall motion abnormality and a ~ossihle septal infarction (MI), which would be a desirable diagnostic hint for the underlying disease, CAD or cardiomyopathy (CMP). Thus, ¢7 LBBB-RNV were analysed by quantitative B-sector phase and amplitude analysis with comDarison to normal space-time contraction p~ttern. 20 had remote anteroseptel NI. 7 had CMP and 20 had pure LBBB {no CMP or MI). From the many regional and global functional data discrlminant analysis revealed 2 parameters of high discriminative power {gilk's lamhda = 0.22, canonic correlation = 0.5). These 2 were the mean sectorial amplitude (NSA), a measure of global LV function, and the ssandard deviation of the sectorial phase (SDP)~ a measure of time-homogeneity of LV contraction- NSA and SDP allowe~ the true diagnosis in 17/20 MI-RNV's, in 6/7 CNP-RNV's and iN 19/20 ENV's with pure LBBB~ In addition~ phase anaylsis of the 3 septal sectors in comparison to the remainder 5 sectors showed a significant septal phase delay of 4.92+-5.3 SOU (S~andard Deviation Units in comparison to normals) in the 20 NI-patients, but a mild premature septal contraction o£ +0.75+-2.64 SDU in the 27 non-MI LBEB studies, resulting in a sensitivl:y of 0.75 and a specificity of 0.99 for diagnosing septal MI in the presence of LBBB. Thus, quantitative reqiona 1 phase and amplis~de analysis yields a~ditional important information in LBEB-RNV's not seen by visual interpretation alone.

12 E . V o t h , U . T e b b e ' , H ~ S c h i m h a , R. Sc-~der", K.L.Neuhaus', D.Emrich Div, of N u c l e a r M e d i c i n e a n d Div. of C a r d i o l o g y ' , U n i v e r s i t y of G o s t t i n g e n , F R G a n d I . S . A . M . S t u d y G r o u p "~

INTRAVENOUS STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION (ISAM): FOLLOWUP B Y 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 ~ { Y I.S.A.M. intravenous streptokinase in a c u t e m y o c a r d i a l i n f a r c h i o ~ - w a s a prospective placebo-controlled doubleblind multicenter trial. Patients up to 75 years of age were randomly allocated within 6 hours after onset of s y m p t o m s to either 1.5 million U of streptokinase (STK) in 60 min or placebo (PL). In a subset of 192 patients (95 STK, 97 PL) 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 w a s performed 4 w e e k s and 7 mc~ths after infarction. Results: ant.infarction inf.infarction STK PL STK PL n 39 42 5d 53 4 weeks EP(%): ~ 50.4 41.5 56.9 54.7 SD 15.2 15.0 11.0 12.4 p< 0.015 n.s. 7 months EF(%): ~ 52.4 43.7 56.3 56.6 HD 13.8 17.4 13.0 12.O p< 0.015 n.s. In p a t i e n t s with anterior infarction regional EF was higher in the STK g r o u p in a l l w a l l s c o m p a r e d to the PL group. Zn inferior infarctiom differences in r e g i o n a l E F o c u r r e d only in the inferior wall with higher v a l u e s in the S T K group. Conclusions: In enberior infarction ~ i n t m a v e n o u e STK improves left v e n t r i c u l a r function. This benefit is p r e s e r v e d up to 7 m o n t h s . In inferior infarction only little benefit of S T K c o u l d be demonsgrated~

113 P. Knesewitsch, C.-M. Kirsch, N.H. Goeldel, E. Moser

Department of Radiology and Internal Medicine, University of Munich, Klinikum groBhadern, FRG Value of Exercise-Equtlibrium-RadionucltdeVentriculography (E-ERNV) in the Early Detection of Adriamycln-Cardiomyopathy (ADM-CMP). Aim of this study was to compare the value of ERNV at rest (R-) and after exercise (E-) for early detection of ADM-CMP. In 348 patients (pts) with malignant tumors, 606 ERNVswere performed. In 90 pts, R-ERNVs were followed by E-ERNVs. RegulUs were evaluated s t a t i s t i c a l l y to detemine whether E-ERNV provides an e a r l i e r detection of ADM-CMPthan R-ERNV. To assess the l e f t ventricular function following parameters (R-, E-) were used: global ejection fraction (gEF), enddiastolic-, endsys t o l i c - , stroke volume (EDV, ESV, SV); peak f i l l i n g , peak ejection rate (pFR, peR). Increasing ADM-doses yielded a significant (p500 mg/m2, In contrast, s i g n i f i c a n t increases (p
111 LJ

Syohra,

DG Pavel,

E Olea

i v e r s i t y of Illinois,

Univ.

of C h i l e

I!

X P E R T IMAGES OF C A R D I A C R W M A

F u n c t i o n a l images, such as p h a s e and f a c t o r a n a l y s i s images, used for the diagnosis of c a r d i n g regional wall motion abnormalities (RW~) do not o f f e r a d i r e c t d i a g n o s i s of RWMA. They require experienced interpretation, r e p r e s e n t only a portion of r e l e v a n t idiagnostic i n f o r m a t i o n that can be e x t r a c t e d f r o m the r a w image data, and do not u t i l i z e experience g ~ i n e d on p r e v i o u s l y d i a g n o s e d cases. In o r d e r to o v e r c o m e these w e a k n e s s e s , we have d e v e l o p e d a new kind of images, the e x p e r t images:

i

I I

The e x p e r t images s u g g e s t the d i a g n o s i s at e v e r y p i x e l in one of seven d e g r e e s of RWMA. The c o m p u t e r is b o u g h t by a training data base of 80 cases, c o n t a i n i n g RWMA c l a s s i f i c a t i o n images dra~/n by physicians, traditional f u n c t i o n a l images, and a b o u t twenty new p a r a m e t r i c images. Normal cases were d e t e r m i n e d by p h y s i c a l examination, m e d i c a l history, u l t r a s o u n d , phase and f a c t o r analyses. The RW~IA cases were in a d d i t i o n c o n f i r m e d by b i p l a n e c o n t r a s t a n g i o g r a p h y . When the c o m p u t e r is given a new, "unknown" case, it e m u l a t e s the RW~ c l a s s i f i c a t i o n image as it w o u l d be d r a w n by a p h y s i c i a n , who bases his diagnostic drawing on radionuclide image data, and also on r e s u l t s of the o t h e r tests. The e x p e r t images offer a robust diagnosis of RWMA, and are Isuperior to p h a s e a n a l y s i s images, as the LS class error ( 1.2.

114 A. Cuocolo, F.L.Sax, J.E,Brush, S.L.Bacha:ach, M.V. Green, R.D. Neumann, E.O. Bonow. Department o f Nuclear ~ledicine and NHLBI, National Institutes Qf Health, Be~hesda, Md, USA.

EJECTION FRACTION RESPONSE DURING EXERCISg AND LEFT VENTRICULAR FILLING IN PATIENTS WITH ESSENTIAL HYPERTENSION. In many patients (p~s) with hypertension in the absence of coronary artery disease (CAD) left ventricular (LV) ejection frmction (EF) is normal at rest but may respond abnormally to exercise (Ex). This abnormal EF response may reflect altered LV loading or intrinsic myocardial dysfunction. To assess the determinants of the LVEF response to Ex in such pts, we studied 60 HTN pts with no evidence of CAD hy high-temporal-resolution radionuelide angiography at rest and during maximal supine Ex. All drugs were stopped at least 2 weeks before the study. Pts were separated into l groups; A (n=12) - pts with an increase in LVEP with Ex ~0.Ob; B (n=28) - pts with a change in LVEF with Ex <0.05. A and g did not differ with respect to sex, age, heerc rate, mean arterial pressure, LVEF at rest, and double product during Ex. However, peak filling rate (PFR) st rest, normalized to either end-diastolic volume (EDV) or sBroke volume (SV), and time to PFR (TPFR) were significantly different between the g groups: Gro~p A group B PFR (EDV/sec) 3.i+0.7 2.5+0.6 <0,01 PFE (SV/sec) 5.~0.9 4.2TO.g
242 115

116

117

Tzourio, C. Chiton, C. Raynaud, O. Dulac Mazoyer, M. Bourguignon and A. Syrota

K. Lauterbach, J,G. Copeland, R, Christensen, M.S] McCarthy, S.H. Paplanus, A.R. Graham, G,C. HoNeit],il D.D. Patton

N~

Division Of Nuclear Medicine, University o f Arizon Medical Center, Tucson, Arizona 85718, USA.

]Serv. Eosp. F. Joliot, CEA Orsay, France HBpital St Vincent-de-Paul and Inaerm Paris, France

N=~OVE~ PRE]~CllONOF ~ C tmldG DE~/ED p GRAMS (RNV).

~

1W/g~SPtANT REJECllON

OF R/~Y~JM.~LI)E MENT~Ct~O-

Cardiac t r a n s p l a n t (CTx) patients (pta) are o f t e n monitored "for r e j e c t i o n (Rj ) by the RNV, with a fall in l e f t ventricular ejection f r a c t i o n (LVEF) being the most commonly used criterion. We examined o t h e r hemodynamic parameters available -from the RNV to see whether others might be b e t t e r p r e d i c t o r s o'~ Rj. We reanalyzed 95 RNV's in 26 CTx p t s who had had %ram 0 t o 8 episodes o f R j, all documented by endomyocardial biopsy and successfully t r e a t e d . A fall in LVE£ c o r r e l a t e d on]), m o d e r a t e l y wlth Rj (r= -0,£4); on ROC analysis t h e area under the curve (AUC) was 0.659 ( p e r f e c t = f, random = 0.5), For the LVEF value i t s e l f %he correlation was even weaker(r=-O.f4, AUC=O,599). Though eJection and filling r a t e s also c o r r e l a t e d poorly with Rj , we ~ound a s t r o n g e r correlation using the derived ratio maximum ejection Pate / LVEF (r=O,BB, AUG=O.77|) and similarly for maximum fil]ing r a t e / LVEF (r=O.39, AUC=O.7TE). The times to maximum ejection r a t e (MXER) and real
118 C. Chiro~, C. Raynaud, 0. S. Tran-Dinh and A. Syrota

N.

Tzourio,

Depailmenls of Radioisotopes, Neurology and Pediatrics, St,Peler Hospital, Free University of Brussels, Belgium.

U29:

CEREBRAL BLOOD FLOW iMAGING OF BRAIN MATURATION IN HUMANS USING f23-1-IMP AND SPECT.

STUDY OF BRAIN MATURATION BY REGIONAL CEREBRA] BLOOD FLOW MEASURED BY SPECT IN THE FIRSt 20 MONTHS OF LIFE Regional cerebral blood flow (rCgF) was measurel by SPECT using TOMOMATIC 564 and go-133 il 20 children from birth to 2 0 months of a g e These patients were free of cerebral damage. All studies were performed in accordance wit[ the Fuhlic Hospital and the CEA ethica~ committees. For each patient~ 20 ~-thic[ slices distant by 40 and 60 ~m from th~ orbitomeatal line were studied. The mean GEl (mCFF) was calculated on these two entir~ slices and the rEBF was measured in 20 cortical and i suScortical regions of interest pel slice. The mCBF increased regularly durin I the whole studied period from 50 ml to 7( ml/lOOg/min respectively. At birth the highest rCBF value was foun( in the subeortical area concerning the s~riat~ and thalamus where it exceeded by 60 to 705 the mCEF ; cortical values were 30 to 40~ lower than rCBF except on the inferior parl of semsorimotor cortex, the primary ~isua] cortex and the temporal cortex where it reacher 'the mOgF. rCgF increased to mCaF value or higher durin] the let month in the ~iddle part of th~ sensorimotor area, at 2 months in the whol~ occipital cortex, at ~ months in the posteriol associative areas and between 6 and 20 month~ in the frontal region. ,The step by step cortical flow build up involve< successively the subcortieal area~ the primar~ ,cortices, the assoniati~e cortices. These~ steps seem to correspond to the histoloFica[ eortical maturation and to the ehild'~ ]psychomotor development. The observed sequenc~ confirmed and detailed that described wit] PET using local glucose metabolic rate (gnnal~ lof Neurolo~y~ 1987. 22~ 4: 487).

119 Dulac,

M. Rubinst~in, R. Denays, D. Haumont, H.R. Ham, A. Piepsz and P. No~l.

CBF studies in small children are hampered by the fast changes Of Ihe regional perfusion pattern in relation with brain maturation. The aim of this study was, lirslly, to describe the SPECT pallerrl ol brain maturation using a CBF tracer, 123-1-IMP (0.05 mCi/kg of p,Sn produced 1-123), and, secondly, fo irlvestigale whether the environment could exed an influence upon Ihe cerebral maturalion, by comparing age-matched term and prelerm infants. 15 prefers (gestalional age al birth : 24 to 38 weeks) and 17 term infanls were studied. The age at time of SPECT was respectively 36 weeks to 2 years and 40 weeks 1o 2 years. All of Ihe neonates were at risk to develop a neurological disorder. The older children suffered from various neurological diseases, SPBCT in newborns exhibited a marked predominance of thalamus and mesencephalon. with only slight occipital and parietal activily. Frontal cortex was barely recognizable. These cortical areas rapidly developped, The thalamo-parietal ratio exponentially decreased as a function of lime with a plaleau reached by lhe end of the 2nd month of life, Fronlo-oceipitgl ralio sleadily increased and the frontal predominance was settled after the 6th monlh. Allhough for ethical reasons all babies were potentially abnormal, SPECT pallern was found very closely and exclusively related to the gestaflona[ age. In preterms we found indeed no influence 01 the lenglh of exlra-uterine life upon the cerebral maturation.

120

J.Lumbroso, F.Gsermazi, O.Hartmann, Y.Rabarison, 5.Coocnaert , g.Lemerle, C.Parmentier.

~ y e s JSE, Babich JW, Carter R, Meller ST, Agr awal M.

Inserm U29 and Neuropediatrie Dept. Hospital St Vincent-de-Paul, Paris Serv, Hosp. F. Joliot, CEA, Orsay, France.

Services de H~decine Nucl4sire et d'Oncologie P4diatrique, InstJ~ut Gustave Roussy, Villejui£ and CEA-ORIS =, Gif-sur-Yvette; France.

The Royal Marsden Hospital, SUTIDN, Surrey, U.F Queen Mary's Hospital for Children, Carshalton, Surrey, U.K.

133-Xe BKAIN SPECT IN A SPECIAL TYPE OF UNILATERAL CEREBKAL MALFORMATION : SONTRIBUTION TO PROGNOSIS A~D MANAGEMENT ~emimegalencephaly (ERE) is a unilateral brain malformation ahat produces severe epilepsy that may be improved by hemispherectomy. In six patients, i day to l0 year old, with typical clinical and radiological signs of }LME, the regional cerebral flow (rCFF) was measured 5y SFECT using a TOMOMATIC 565 with 133-Xe delivered by IV injectzon. All patients hag also a RRI study at the same period. In all eases a hypoperfused area was found, it corresponded to the abnormal MRI region, the mean rCgF decrease was -38~. The other 3emisphere had normal rCgF and MRI images in 5 patients, but its integrity was doubtful in the sixth patient as suggested by focal cCBF defects and paraventricular heterotopias 3n MRI. In one patient, with left ~ E , rCFF ~as repeated 4 times. At day I, during suScontinu~us right discharges, the whole left hemisphere was 50% higher than the right side~ even ~n the areas usually i ~ a t u r e at this age. At 7 and 1O months the left hemisphere cCgF deereased and was approximately 35% lower ~han the right side in int~rict~l periods. Zrlilepsy remained intractable with severe ~sychomotor impairment and considering that ~he right reEF was normal, a left lemisrlherectomy was performed at Ii months. ~ne month later a eomplete cessation of seizures ~nd a marked psychomotor improvement was ~bserved. rcgF in the right hemisphere remained ~nchanged 1 month after hem~pherectomy. [CBF ml/100~/mn O l 7 M I0 M 12 M (after eft hemisph. 66 40 49 18 surgery) ight hemisph. 46 62 62 61 n HHF, rCBF seems essential to control the unetional integrity of the 'normal' hemisphere afore deciding surgery.

A COPPARISON OF THE SENSITIVIIY OF mlBG SCANS AND CYTO-HIS[OLgGY FOR THE D E [ t e f l O N OF BONE

i

QUANTITATIVE P ~ U R ~ OF UPTAKE OF M~BG IN C H I L D R ~ WITH NEUROBLASTOMA

NARRBNHETASTASES I N NEUROBLASTOHA. We compared the sensitivity of meta-iodobenzylguanidine (mIBG) scans and eyto-histology for the detection of neuroblashoma hone marrow metastases in s group of 70 children (3.7 i 3.3 y e a r s ) .

0re-hundred-fifteen

whole body scans were

carried out 24 hours after injection of 3.7 MBq/kg o£ i-123 mlBG (83 scans) or 0.7 HBq/kg of 1-131 mlBG (17 scans) or 0.9 to 4.5 GBq of 1-131 miBg (15 post-therapeutic scans). The scans were interpreted as positive For bone marrow metastases in the presence of any bony uptake of the tracer, even at the l e v e l or the metaphyseal complex. The cyto-histological examination of the bone marrow (CHBM5) was 3erformcd in two steps: (i) smears ob%ained from two iliac bones aspirates and, when nega'tire, (ii) ten bone marrow aspirates and 2 bone marrow biopsies. These modalities were done within less that 15 days of each other. The overall sensitivity of mlBG whole ~ody scans compared to CHBM5 was 90~. If we restricted the positivity of mIBG scans to posfive images only at the level of sternal or iliac bones, having no regard to other bony sites, we lowered the sensitivity of mIBG scans to 80%. In both eases, the specificity of mlBG scans was lower than 100~, due principally %0 the inability of the method to separa%e bone metastases from hone marrow metastases. We conclude that mIBG scans are I0~ less sensitive than CHBH5 when the two methods are compared to stage the same bone marrow site. However, mlBG scans may demonstrate positive bone marrow sites unaccessible to biopsy and brovide a better estimate of the extent of the disease.

This study was undertaken to correlate quantitative tissue uptake of mIBG and histopathology in neuroblastcroa (Nb). 6 children with Nb (2 at relapse) and I with ganglioneurc~(GN) received 0.SmCi intravenous 125I~IBG before surgical excision of their t~noura. Uptake of mIBG in the excised tissues ]w~s measured by scintillation coonting. Correction ~¢as made for radiochemical purity and self absorption, and the uptake was expressed as % injected dose (%I.DI and % ~ . D / g r ~ tissue. The inaterial w~s then submitted for histopathology. A relative value was also assigned to each s a ~ l e based on the ]%[.D/g, for a given patient, and this value was used as a reference for correlating m/EG uptake and tissue histology. The results are as follows : Mean %I.D/ Relative Patholog~ Pt. Range %I.D/g g tissue . mean value I. 0.0 90-0.877 0.0502 00.0 >90% U.NE 2. 0.0220-0.0448 0.028 55.8 >90% U.Nh 3. 0.0047-0.061 0.022 43.8 >50% U.Nh 4. 0.0034-0.017 0.0899 ]9.8 25% GN~ 0.0039-0.03 0.0077 15.3 <10% U.N~ 5. . 0.0013-0.0048 0.0031 6.2 <10% DgN~ 0.0017-0.0028 0.0022 4.4 G~ 8[ 0.0002-0.011 0.0029 5.8Control tissue (UNb = Undifferentiated Nb, GNb = C~nglioneuroblastoma, DgNb = Degenerating Nb) CONCLUSION ]_ Quantitative uptake of mIBG by INb varies within patients and within each to/nouz 2 Pbre undifferentiated Nb takes up more m~BG ~nd may be rmrre likely to respond to targetted radiotherapy with mIBG.

~

243 121 F,Claudiani, =B.De Bernardi L.Bertoleszi, *A.Garaventa G.Villaveeehia, B. SanSuineti. gueleaz Medicine Service Galliera Hospital - Genoa *Pediatr in hornets-once logY ImG.Gaslini - Genoa MIBG~azJ-THERAPY IN P~DIAT~ICNEU~OBLASTOMA Between February 'B6 an January "88 14 children affected b y relapsed o r resistent NB have been treated by BI~GZ±~J, two of whom had a new treatment on the oesasinn of a subsequent relapse. At treatment 2 Pts were in partial remission after ablative surgerY and ~ t o l o g o u s b o w e m a z r o w tress-plant, 2 Pts had large abdominal masses and 12 were in first (6) or subsequent (6) relapse. 12 Pts had undergone s~r~ery and autologous transplant. 34 cycles have been administered (4 - 9.1 mCi/cyele); 5 Pts had only 1 cycle, 2 had 2 cycles, 4 had 3 cycles and 1 had 4 cycles. The 2 twice-treated chdldzen underwent respectively 2+1 and 3+3 cycles at intervals of i0 and 12 mouths. In 14 c~nes it has been possible to evaluate ~ : complete remission in 2 oases (after S oyeles) at 6 and 1 mouth, partial remission in 2 oases (after 2 cycles) at 2 and 4 mouths, lower response in 1 case at 18 mouths. In 4 cases neoplastic stabilization at 10, 6, 5 and 4 mouths h g s b e e n obtained, and in 5 cases the ddsease relapsed. In 2 Pts hsem~tolo~ie tnxdcitv Was stnassessable (at 4 weeks); 4 Pts treated with less than 5 0 O 0 0 / ~ platelets showed lower values and 1 of them needed pl&telets transfusion (all 4 Pts had undergone ablative surgery and bone marrow transplant), 4 Pts showed platelet levels
124 TISON F.. L E R O Y B., HOSSEIN-FOUCHERCI., WEMEAU J-L.. MARCHANDISEX. Service Associ4 de Medecine Nuel4aire et Se#vice de M4decine Interne el Endecrinologie CEU Lille - 59037 L i l l e - France

BONE MINERAL CHANGES AFTER SURGICAL TREATMENT OF PR[MARY HYPERPARATHYR OIDISM Bone mineral content was studied by dual photon ebsorptiometry (NOVO 22) in 20 patients (17 female, 3 male ; age 30-76) before and 6 or 12 months after an effective surgical treatment. These patients had no associated bone disease ; they did not receive any medical treatment that could modify bone mineral c o n t e n t . Before surgery, vertebral (L2 to L4) bone mineral content was lower than in normal controls of the same age : on average -1.74 S.D. (± .9D) under controls. I t was not correlated with any clinical or biological data and this decrease was observed even with no radiological evidence of skeletal changes. After surgery, vertebra] mineral content increased significantly in 17 eases. After 12 months it was -1.12 S.B. (+_ 1,05) under controls. The increase appeared to be more important in the iirgt 6 months after surgery (+ 0.37 S.D. against + 0.16 S.D. in the next 6 months). The increase in vertebral mineral content was inversely correlated with the degree of initial demineralization (p&.05). Similar findings occurred at the femoral neck ]eve]. This rapid increase )n axial mineral content after surgery may be related to the efficacy of mineralization of the available osteoid surfaces which were in excess Jn bone of patients with hyperparathyroidism. It may however be limited and unable to correct completely the bone toss. Our findings suggest that early surgical treatment could prevent resistant cgteopenia in primary hyperparathyroidism.

123

122

J. Kotzerke, B. Henniny, R. Habenicht*, R. Sc~urzrock,

B. Lambert, M, Guyot, R. Jeandot, J. Caix, J.L, Demarquez, A,J. Brendel,

H6pital Univ. Pellegrin,

H. Hunde~hegen Ab~ilur~ Nuklearmadizin UM epezielle Bioph~ik, *Abteilu N Kinderchiroryie, Medizi nische Hnehechule Hannover, F.R.iGermang

Bordeaux, France,

LUNG VENTILATION AND PERFUSZON SCINTIGRAPHY IN TeE FOLLOW-UP OF REPAIRED CONGENITAL DIAPHRAGMATIC NERNIA (CDH) In order to evaluate the degmee of pulmonary hypoplmsia, and subsequent development of the lung and respiratory ~unction in children who had undergone surgical repair of B severe tell CEH within the first iE hours of life, we perfommed lung seintiGraphies (LS), at the abe of In-3 months in IB patients (pts) then at 1-2 years in 10 of these pts, and again at 5-0 lYeams in 6 of them. Regional pulmonary ventilation (V) was studied by using Xe-133. Pulmonary perfusion (P) was studied after IV injection of Tc Ogm-albumin~micmospheres. On the initial LS, g to the hernia side was 0ecreased in B/16 pts and ave#aBed 43.7 + 6.2 (mean Z SB) of the total V. In 9 pts, theme was tmapping of Xe-133 at the lower part of the left lung. P to the hernia side was deere6sed in ll/IB pts and avemaged 36.9 + 11,5 of the total P, For all the pts, seri~l lung X-Rays pemformed du~in~ the first yeam of life showed ~qualization of lung volume~, suEgesting a ~or~al left lun B ~#owth. After 1 year, V to the ~ernia side was normalized or remained normal, ~xeept for 2 of the I0 pts studied, and averaged 47.4 + 5.7 of the total V. Persistent trapbin6 of X~-133 in the left lun B base was found in 3 pts. P to the hernia side was still reduced in @/i0 pts and averaged 39,4 + 5,2 of the total P. After B years V was ~ormal in ~ii the B pts studied, whereas P to the hernia side remained decreased in 5/6 pts and averaed me.7 + 4.6 of the total P. These --findings show that durin~ the first ears following surgical eepair of a severe DH, there is an improvement of V and a 3ersistent impaired P to the hernia side, suggesting a primary vascular pulmonary hypo~lasia.

125 P, Martin, 5eertruya~n

ASSESSMENTOFTHEANDER~IN-HYNE5PYELOPLASTYBY RADIOISOTOPE RENOGRAPHYIN g4CHILDREN

IGbetruction d the pelviurateri¢ j unction (PUJO) is the most common form ofa malformationof the upper urinary tract. Indication for gurgergis based on the ctimcalcouree on the one handa,d diffeEentirangingrnehelitieeon the other. Renoyraphg (RG) Beon8 of thnee methede c o m b i ~ the nett malign of" morphological details with the aspecto oftubulaY function end drm nege. In the caecaof 941ofents(newborn - 14 yeere) with PUJO, the valueof ~ hag beenilluotrat~bU pro- a ~ puotoperative exami nations. RIGwne carried out with 125- I-OIH over o period of 50 mi hulas, i f reed be completed bg a diurasie-at~g(BRIG)of i5 mi auraswith applicationof fruoemide.Eslimotionofthe Effectiverenal plasmafl~ (ERPF) was only pertlu po~ible. pro-operative 01;[6Vas carried out on 55 childnan: a hecreaseofecilaltg in the pelvlnof 4~0 % or an elimi notion roteof <5,IGmax%/mi n are the typicalatoneof a Pm.Mowhich can congeq~ntluhe followedby a redued functionof the Iddnag. After suryerg 66 kidneysslx~gedan improvementin tubulGrfunctionwith en averacl8raig8of I O ~ of the r81Btive function.In 50 childrenthe ERPF ~ s maneorodin the progridthe pastgperativeorate,in I5/50 the flewinerea~mdabout lO0 ml/min/1,75m 2. A hecraaseaftheflow couldgnlU he atated i n one child, An i mprovemant Ofdrai n~e gould be obasrved in 85 out of 98 kidnege, in 21 casee the drei nage couldonlg be visualizedby DRG. In l3 cneas, PUeloplastghad produced no effect neither on the tubular function nor on the drai na£e. ~,n improvement of the renal funetione could he stated Up to s period of 2 years after guryer U. The combinationof Io%, radiationdase~with very ~gmficant glatemeotg forms the high vglua of the RIG.Summerizin,:j our anolyoEe we can therefore clearly see the importance of this mathodconcerainy ourgicglde8igionaend satimationgof eucceoful treatment of the PUJO.

126 P. (2),

Bergmann ( [ ) , J. Van M1 PUSS and J, C o r v l l a I n

(3)

Departments of Nuclear Medicine (I), Surgery (2) and Internal Medicine (3), Brugmann UnIversTty Hospital, 4, place A. Van g e h u e h t e n , I020 B r u s s e l s , BELGIUM LONG TERM EVOLUTION gF BONE MINERAL CONTENT (BMC) AFTER SURGEnY FOR PnIMARY

P. Blockx I, M. Driessens 2, G. M~3rtier~ and A.~enZ Depazlments of Nuclear Medicine (i) and Pt~sical M~iicine (2), Antwerp University Hospital, B-2520 Edegem, Belgit~n

PTTFAILS OF T}~REE PHASE BONE SCI}~TIGRAPHY IN THE STASIN~ OF REFLEX ~ A T H E T I C DYSTROPHY

HYPERPARATHYnOIDIM (I o NFT)

We showed p r e v i o u s l y ( I ) t h a t one year a f t e r surgery f o r primary hyperdarathyroidlsm, radial BMC measured by s i n g l e h ton absorptle~etry , . . . . . . . d by 7% iPn° t he e p l n h y s f s and by e~ I n t h e s h a f t , There w a s no c o m p l e t e c a t c h up to normal at I year and t h e Increase seemed to l e v e l o f f a f t e r I year In 5 p a t i e n t s f o l l o w e d up to 38 months, In t h i s study, 57 patients wlth I o aPT had 2 to 9 measuremenEs up to 106 months after surgery. Measurements were performed wlth a Me[sgaard I I 0 8 Bone M i n e r a l A n a l y z e r at t h e r a d ) a l e p ] p h y s l s and 5 em l a t e # at t h e r a d i a l shaft, For t h e e p l p h y s l s , the monthly Increment f i n e ) was high d u r i n g the f i r s t year pest s u r g e r y and decreased r a p f d l y t h e r e a f t e r . The r e l a E l e n between I n c r e m e n t and t i m e was b e s t d e s c r i b e d by a n e g a t i v e power f u n c t i o n : Inc (%)=2,46 x Months - , r 8 { r = . 5 4 , p ( O . 8 0 1 ) . The same t y p e of r e l a t i o n was observed f o r t h e radial shaft: Ine=g.71xM - , 8 2 (r=,65, p• O.OOl). There was no d i f f e r e n c e between t h e e v o l u t i o n In men a~d women. There was no correlation Between t h e age oF p a t r e n t at t i m e of s u r g e r y and I n c r e m e n t . The I n c r e m e n t at I y e a r was n e g a t T v e l y c o r r e l a t e d wTth t h e BMC values a~ the epiphysls; Inc~O.2g2xnMC- I ' (r=.46, p(0,01), u ne ~ I g n l f [ c a n ~ c o r r e l a t i o n was found a~ ~he r a d i a l shaft. To c o n c l u d e , t h i s s t u d y c o n f i r m s o u r p r e v i o u s . . . . . ~oss . . . . . [nbYlUS . . . . . . . . .p. e r t l y one ~ H~(T] ~ . . . .only reversible, a l s o In t h e long term even i f p a t i e n t s who had t h e more i m p o r t a n t bone loss w i l l r e c o v e r more. I, P, M a r t i n , P. Bergmann, C. g l l l e t , M. Fuss, P, K l n n a e r t . J. C o r v l l a l n . J. Van Geertruyden: Partially reversible esteopen[a after surgery or primary h y p e r p a r a t h y r o l d l s m , lArch I n t e r n Ned, 146, 689-691 (1986), 2. d D. R i d g e : P r e c i s i o n and c l i n i c a l application of p e r i p h e r a l single photon absorptlometry, in: Nenllnvaslve Bone Measurements: M e t h o d o l o g i c a l Problems, IRL Press, O x f o r d , E n g l a n d , J Dequeker and CC Johnston e g s . , 47-54, 1982,

S i n c e a f e ~ y e a r s , 3 - p h a s e bone s c i n t i g r a p h y wlth 99mTc-methylene diphe~honate ( ~ p ) has been advocated for differentiation between early and lobe stages of reflex sympat~hetic d y s ~ (KSD). Previous studies, however, lhaVe suggested that the "vascular" inflow phase may be c ~ n t g m ~ t e d by early bc~e uptske %0 a v e ~ large e - ~ t . ~his COuld lead %0 an staging of late RED c~.~e~. Indeed, 'these pa~/ents have a decreased blood flow in the 8ffected l~i(3n, which c ~ d be o b s c t ~ by I a r~3n-vasci~ar increase of bone tracer activityL To /nvestigate this, we c ~ a r e d %he early I iinflc~4 ctlrves for 99~Tc-~Dp and for gg~Tc h~nanl albumin (HSA), in a group DE six patientE with r e c ~ late stage RED. tin ~ of these patients an increased blood flow Was foL~Id in The affected limb (P/N ratio HSA: ~ d i g n = 93%, range 64 - 99%). When using ~ p , however, an increased tracer activity could be ob£erved in the affected lin~ lin 67% of The cases (P/N ratio NDP: n ~ i a n = i06%, range 74 - 148%). ~3re~ver, in all cases The P/N ratio wee higher for ~Dp than for HSA l(diffel~-nce + 6 - +5094, p4, eventually l e a d i ~ %0 an .~rroneous staging of the disease.

244 127 Hgflin

28 F.

U n i v e r s i t y of Berne, Dept. Medecine, CH 3010 Berne

of N u c l e a r

~ r , A. A. Malki, A. O ~ a z m e , M. Ei-Dadah, S. Mal~oud, M. Ei-Sayed and H,M. Abdel-Dayem. Depts. of Nuclear Medicine and Orthopaedic Surgery, Faculty of Medicine and MubarakAlKabeer Hospital, Kuwait.

Recent publications document the uptake of nanoneter-sized colloids (NNC) in sites of inflamnation located in the extremities. Ne have con~ucted a series of experiments to v e r i f y i f ~his can be explained on the basis of local ~yperemia, and to ~tudy the difference between Lhe behaviour of small solutes (gW<20K dalton) ~uch as Tc-99m DPD, and large structures such ~s NNC (size 30-50 nm). The former supposedly leave the intravascular space by diffusion through the basement membrane surrounding the ;apillary endothelium, whilst the l a t t e r seem ~o remain intravascular except whehe e.g. inflammation causes discontinuity oF the basesent membrane and extravasular spilling. Seven )atients referred on a suspicion of femoral ~ead necrosis but with healthy hands volunteered for a DPD asd NNC investigation. Each kept )ne hand immersed in a 42°C mater bath from 10 ~o 25 min after tracer injection and palmar ziews were obtained at 3 h (DPD) and 45 min [NNC). In the thermslly treated hand, bone uptake mas higher with DPD but no L/R difference was seen with NNC Cp<.OS rank test). In 5 more Ipatients with inflammatory lesions, DPD uptake was again uniformly higher but focal NNC uptake 'Yn the lesions had drastically improved under hyperthermia. We conclude that hyperemia yields better T/NT contrast on NNC scihtigraphy, that changes in local endothelial permeability may affect the bone scan and that the uptake mechaInism oF NNC in inflammatory processes is based on local discontinuity ef the basement membrane associated with the inflammatory process.

~VAJ~JKI'IUm ub ~&fE~J~l & ~I'I~S Oh AUUI~ b K ~ TAL (Sk) ~ S C L E DAMAGE (M-D) FOLLOWING TRAUMA BY In-11i ANTIMYOSIN (In-Ill AM) In-t11 AM has heen used to diagnose AMI myocarditis, adriamyeine toxicity and myocardial rejection. No previous report of A M u p I take in acute Sk M-D. It is important to kanw the extent of S k M - D secondary to fractures (fx) or in accidents. In-Ill k M w a s used in acute M-D in order to look for: (I) extent of d~mage at fx sites after closed or open reduction and (2) detect other sites of M-D. Whole body imagingwaa done 24 hrs after the I.V. injection of 2 mCi of In-Ill ~M i n 4 patients (5 studies) involved in accidents. The results are in the table : Diagnosis No of sites Scan result Clinieally~n-111 AM I. Spiral Fx it. femur +re 2 3+ 2, Rt hip F x & replac~ent +re 1 3 3. Hemarhhosis (it.knee) -re l~-~ negative++ 4. Multiple F~ +ve 3~ 3 ~* ................................... 7 9 + Repeated In-Ill AM study 4 weeks later showed decrease of uptske lesser ~han initial study. + + P o s t tra~atic swelling, h~ato~a, surgically proved to be h~narthrosis of ~nee. * F~ lt. maxilla, In-Ill AM uptake in adjacent muscle was detected retrospectively. ** In-Ill AM uptake was detected in Rt elbow muscles, but no Fx. The results indicate that In-Ill AM accumulates at sites of SkM-D; may b e u s e d to differentiate lesions with acute M-D from those without, and will have a role in predicting healing of fxs.

130

131

TARGETACTIVITY ENHANCEMENTBY THERMALLY INDUCED HYPEREMIAIN TNE SCINTIGRAPHYOF INFLAMMATIONIN THE EXTREMITIES

J. ABRAMOVICI, M. RUBINSTEIN

_A. van Dales l, A.F. Stemfoort 2, J.m. de Jongenok 3 and M. ds Schrijver 4.

D~part~ment des Radio-Isotopes, ImeIles Hospital, Brussels, Belgikm Tag9m-RAMOCOLLOIDS : AN ALTERNATIVE APPROACH TC DEAGNOSIS OF INFLAMMATORY LESIONS OF BONES ABE JOINTS. The recognition of bone and joint infection often relies upem~ nuclear medicine teck~iques8 Actually none of tAe convent~ongl m~thods (Ga ? I111-Leucocytes and Tc89m-MEP-thrse phase-bone scan) provide a suff~cient accuracy ~nd the need for a new agent is r~al. T~I~ rationale for this study was : 1. Nanocolloids have the copo~iZity t~ ~ i f ~ tbr~z~h a~ten~d capiZlnr~ walls and thus to accumulate in infZavmatory foci, in relation with the activity of the process. 2. The ~arly phas~ essentially reflects the blood flow and is no% hampered by a sign~f~ ca~t uptake phenomenon. The aim of our paper was to evaluat~ the diagnostic power of TeYBm-N~ocolloids-two phasebone scan (NCE) in bone ~nd joint inf~ction and ,to comber4 it to G~ E7 and Te~Bm-MDP (late phase (MDP). 89 patients (age:4-8Z) with a suspicion of oste myelitis (n=6?) or septic arthritis (n 22) have be~n included. Diagnosis was histologiaaZ{y or miarobiologica~ly confirmed in 80 patients. Al~ patients had NCS and f~DPand we performed Ga R7 in 39 cases. These procedures were perform ed as folZows : 1)NCS:2 second frames w~re solletted during 240 seconds after injection of 10 mCi, Static imag~s were performed 30 minute later. 2)MDP c~d Ga ~? saint~grc~hs w~re m a ~ Jrespectively 3 ~nd 48 hours after IV administration of respectively 15 mCi and 3 mCi. Sensitivity and s~ecificity were 95%-?7% for NOB; 87~-63% for Ga 7 and B3%-59~ for MDP. CZearly NCB is a performant diagnostic t~st I however, it must be e~phaslzed that that method is proJbably not suitabZ~ for dlfferentlag diaffnosis between sterile and ~ p t i c inflc~mnatory leslon~

29 P. H~lntz,Oh. Ehrenheim,H. Bellow, N. Railroads,K. Vyk~pil M. Celarlakl, H, Hunde~II~ Deportment of Nuclear Medicine, Clinic of TraumMology Institute of patheNx]y,end Deportmentof DiognosticRedioN~, M~ic~1 ~he~l of Henrmv~r,FRO OOMPARI~ON OF MR-II'IAOINB, BONE 6ClNTIaRAPHY,AND HIgTOL(~)IOhL FINDIN08 IN MALIONANTTUMORSOF THE I MUSCULO~KELETALSYSTEM

MR-imaging hec advancedin the preoperativedieg~m~isof bone end soft tissuetumors providing information about localization,

expansion, soft titus me~ end mnlreot differences befwecn tumor" endnormsl tissue. In 54 patienla (mie~enic ~emcome, Ewing~ ~:orns, ehendro~rcoma, histiocytom¢, flbrm~'ecma, lipo~rcoma) precurgical MR-imaging (Magnatom, 1,0 T~la, Siemens)wec ~ns using SE-lechnique end in some c ~ s chemical shift imaging.Adettienelly, Bedolinium-DTPA eca ~ntra~ agentweb

~pliml The normal end pathol(Ricalfindings in MRI were documented in T1- and 12- weighted Jmeges, proton density imec~e,calculatedT I- and T2-imagen ende T I-wei@%tedimage offer application of the contrect ~ t . The patients u n d ~ t functional bonescinligrepby with 99m-Tc-HDP, ultr~ound, end computed ~mo~fBphy, as well. In ~me ~ a ~cond imaging ef [he ~rgi~l specimenwe~ doneendoompm-edto the hiatopathelagic~l findings of the tumor. All ~

had a finel

histndiagI~is,

The high sensitivib/ (> 96%) of tumor MR-imping concerning the mueculoskeletsl ~ s I ~ w~ confirmed_Theclinic~l

value of Bn axBcl.pnsoperstive imaging by this mathag is obvious. 8ome tumor~ (ecteoGenic~ B , c~r~ec~:eme, ltp~m'c~s) were fm.lnd to have ~'a~is(i~ Imttm'ns in MR-imaging. Beyond this, MBI seems to be useful in the follow-Up of patientstr~ted with chemotherapy.

132 M.E. Rodeie. A.M. Peters, J.P. Lavender, H.J.F. Hed~ennand R.D.Neirlnekx.

Dopes. of Nuclear Medicine l , Orthopedic 2 and Rheumatology , Bleuland hospital, Gouda, The Netherlands and the Medical-Scientific Departnest , Solco Basle, Biersfelden, Switzerland.

Depts. of Radiologyand Medicine,Royal Postgreddate Medical 8chooh Hemmer'smlth Hecpitel, London and Amerehem International,Bucks.,England.

S-PHASE SCINTIGRAPHY SF Tc~99m NANOCOLL VS. Tc99m MDP IN ORTHOPEDICS.

IN~BTI~TION OF INFLAMMATORYBOWELDISEASE VSJNOTO-99m HMPAOLABELLEDLEUCOCYTES.

Ehe study was designed to compare the behaviour Df Tc-S9m Nanocoll with that of T¢-e9m ~DP in Patients with a variety of bone and joint somIplaints. Blood flow and blood pool Were studied by recur. ding 3S frames of is sac (S min) after i.v. inlJection of the radiopharmaceutical. Static images were obtained i-i,5 hr after injection of Nanocoll and 3 hr after injection of MDp. A total of loo patients were studied (with informed consent) including 24 arthroplasties, J 155 joint complmints and 21 miscellaneous bone complaints, in all cases g-ray studies were av~il~ble. JSased on S3 studies of which a final clinical diagnosis was obtained, the sensitivity of NaJnocell in detecting inflammatory (resp. infecteous) conditions was 88%. The specificity was S9%. These results were based on static scinti-I i Igraphy. The dynamic phase of MPP is hampered by rapid extravascular appearance of this small 1olecule. Hypersemic states and contralateral )verlosd may cause false positive cesults in hh~ Idynamic phase both with Manocoll and MDP. In infecteous loosening of arthroplssties and in Ispondylodiseites incidentally a diminshed uptake n the static images of Nanoeoll was recorded. [n Conclusion, related to the clinical outcome )f the sensitivity and specificity of static mages with 9am-To Nanocoll this may substitute bther more laborious procedures. Blood flow and blood pool images may he omitted,

Indium- I 11 labelled leucocyte SCanning is ectsbliohed as an ¢curate method for diagnecthO inflammatory bowel dlsecsBand ~'~satng it'sextent and severity. However, Indium-111 is expensive and not widely m,oilable,the techniqueInvolvestime consuming cellseparationby a skilledtechnicianand there is u relatively high rediatien dose to the patient. A new Te-99m chelate, HifiPAO (hexemetbyl propyleno amine oxlme) is a mederately efficient leucoeylelabelwith selectivityfor grenulos','tec.We have studied 100 patientswith known or suspected inflammatory bowel dlso~m after relnjectien of autologousTe-99m HMPAO ]ehelledgrenulecytec.As in Indium- ] 11 labelledleucocyteScanntsQ,activity is sawn in liver, spleen and bone marrow, but in addition, there is urinary and billary excretion of the free complex. Thls results in activity in the urinary tract,and eccecioneIIythe ~ll bladder,soon after reinjeclienand activityapp~riog in the c~len after ~I hours In normal patients. In patientswith inflamed bowel, however, intense,abnormal activity is visible in the first hour after relnjentlon, so ~of~ii~ de~5 not ari~. All pbttsflts wsrs imB~I~at l hour and 4 hours 68 patientshad abnormal sans showing Inflamed bowel. No false positiveor fals~ negative results mere encountered. "[hewhole body radiation dose to the patients was one third that which they would have received using Indium- I 11 labelledleucocytesend the superior image resolution facilitsted indeniiFicaIion of small bowel involvement. ReCto] involvement wec easily separated from activityin the urinary bladderby usa of the pelvicoutletview where necessary.

245 135

134

133 D.C. Costa, D. Lui and P.J. Ell.

Institute of Nuclear Medicine, University College and Middlesex School of Medicine, London, UK. RBDIOLABELLED WBC IN LOCALISATION OF IBD ANE DETECTION OF INFECTION - COMPARISON BETWEEN TC99m-HMPAO AND In-lll-ox~ne.

%. Moisaun, O. L o r ~ a l , J.F. B r e t a g ~ e , (.P. Ra~, Ph. Moulinoux, J. Le ~loirec, J . L . R a o u l , B. Lau]%ois, I. G a s t a r d , J.Y. H e t t y . ~entre Eugene M~rquis, ~HU, Pontchaillo~RENNES, FRANCE

Tc-99m-HMPAO and In-lll-oxine were used tc label white blood cells (WBC) and their e~icac~ was compared in the detection of inflammator~ bowel disease (IBD) and infection. 2 cohorts of wee were labelled, one with Tc-99m-HMPAD and th~ other with l~-lll-oxine and administered [iv.) tc each patient. Simultaneous dual radionuelid~ gamma camera studies were undertaken with the IGI 499AC/STARCAM system. An initial dynamic stud~ was performed on the thorax and abdomen for 3[ min (i min ~rames) followed by static images at dg-6O min, 3-4 and 18-24 hrs p.i.. 99 patient~ (56 females, 43 males) with an age range from to 81 years have been ~tudied. 41 were referre with inflammatory bowel disease (IBD), 18 wit~ chest infection, 26 with bone infection and i~ with other pathologic conditions, Good correlation {r=9.81) was found between £h~ 50% washout time from the ~ungs for Tc-99m-EMPA( [mean=4B3.O3 sec) and In-lll-oxine (mean=475.8~ sec) labelled WBC, with p=8.636. Concordan~ results were encountered in 71% of the IBD cases 94% - chest infection and BB% - bone infection. In 28 studies o~ Crohn's disease, 24 wel positive with TC-99m-~MPAO and only 19 with Inlll-oxine in tbP initial (30-69 min) plana; study. Tc-99m bowel activity was seen in 16% o: patients without known IBD at 30-60 min p.i., il 82% at 3-4 hrs p.i. and in 95% at 18-24 brs p.i With In-lll-oxine only 7% (30-69 min), 13% [3hrs) and 33% (18-94 hrs) showed thi~ characteristic. The data suggests similar kinetics for Tc-99m" HMPAO and In-lll-oxlne labelled WBC. Tc-99m-HMPA( - WBC may replace In-lll-oxine-WBC for th, diagnosis of IBD and infection.

INDIUM III-GRANULOCYTE SCANNING OF iNTESTINAL RESECTED SPECIMEN IN [NFLAMMATORY BOWEL DISEASE ~e i n j e c t e d 1 0 - 1 5 M B q of l l l - I n exine labelled granulocytes into 9 patients 9ne h o u r p r i e r to surgery for colonic c e s e c t i o n , to v a l i d a t e t h e s p e c i f i c i t y gf l l l - l n g r a n u l o c y t e scanning (lll-In ?N) in inflammatory bowel disease (IBD). We investigated one c a s e of tight colectemy for necplasia, o n e of ileal resection for Crohn's disease (CD) and 7 subtotal colectomies for ~icerative colitis (UC}. Two to 4 zours post injection, the resected 3olcn was washed before scanning. Radioactive uptake was calculated over healthy and disease macroscopic areas. 3olonic uptake w a s : 2% in t h e l o t p a t i e n t of w h i c h 1 , 3 % w a s c o n c e n t r a t e d in t h e t u m o r ; 0 , 8 % in CD, a n d v a r i e d f r o m 12% to 24% in U C ( m e a n : 17%). Pancolitis was scintigraphically visualized even in t h e 4 c a s e s of UC ~ h e r e t h e r e w a s no m a c r o c o p i c evidence of r i g h t colonic disease. Histologic findings demonstrated microscopic cryptic abcesses in these 4 cases ( r i g h t c o l o n i c u p t a k e w a s o n e t h i r d of all uptake). Autoradiographic studies zonfirmed that the lll-In r e m a i n e d in granulocytes in inflamed ~ucosa. This study confirms the specificity of l l l - l n P N in IBD (however uptake was p o o r in t h e c a s e of macroscopic i l e a l CD), the high PN t u r n o v e r in surgically treated UC and that microscopic disease can be v i s u a l i z e d by I l l - l n PN.

136

137

M.Verhas, S.Conti, S.Cadranel, G.Glupezynski, L.Van Tricht and M.Deltenre

P.R. Garg, H. Friedman, nd M.R. Zalutsky.

E. genze t P, Ealfertheiner, ~lausen, N.E. Adam.

N. Burkh~rdt,

N.

Divisions of Nuclear and Internal Medicine, University of Him and Hospital of Neu-Ulm, germany TEE C-14 UREA BREATH TEST FOR DETECTINg COLONIZATION OF QBNPYLOBACTER PYLORI IN YIVO. Common castro-intestinal Affections such as gastritis and ul~er may he c a u s e d by Campylo~ I 5acter pylori (C.p.) as dicoverad recently, A CO~ exhalation f~st after oral application of C-13 or C-14 urea has been suggested, siege C.p. has a high specific activity of urease enzyme which degrades urea into C0~ and NHI. A C-14 urea hreath test was performed in 34 patients who also underwent gastroscopy, urease quick-testing and hiopsy, 3 ~Ci C-14 urea were administered orally and the exhaled CO2 was trapped in i0 min intervals for 90 miB and measured. The integrated D-14 activity exhaled over 90 miB was calculated in %1 activity of the total d~se given. In all 14I subjects the maximum g-14 concentratiQn in the individual probes was reached within the 90 ~in collected; there was a wide range of exhaled radioactivity from 0.26 g to ~4.9 %.i In 14 patients serving as normal group with negative urease quick-test add negative C.p. histology, respectively, a mean of 0.61+-0.16 g was measdred resulting in a upper limit of normal of 0 . 9 1 % (mean+2Sg). Using 1 ~ as upper limit a sensitivity of 90 % (l~/2O pts) and a specificity of 85 g (12/14 pts) for detecting C.p. in the upper GD tract non-invasively by the C-14 urea.breath test was found. Applied in additionally 7 patients so far hefore and 3 days after a 3 week Jatrox regimen the g oI exhale4 activity fell from 5.6+-5.4 g to 2.1+-2.0 ~. Thus, this C-14 urea breath test shows great promise as a non-invasive and perhaps gua,titative test for C.p. eoloniz@tion and might become a routine tool in primary diagnostics add treatmenf follow-up.

138 8. Slade, D.D. Bigner

W. Gilgien, A. Eischof-Delaloye, J. Pettav~l, F, Mosimann, S. Waeber, L. Barrelet, B. Delaloye.

Duke University Medical Center, Department of Radiology, Durham, NC 27710, U.S.A. Hepital universitaire Brugmann, Universit~ Libre de Bruxelles

ACCURACY OF UREA C14 BKEATH TEST IN DETECTION OF CAMpYLOBACTER pYL0~I The presence of campylobacter pylori (CP) has been correlated with gastritis type B.0wing to the production of urease by this organism, an urea-C14 breath testj developped by Marshall allows the detection of the bacteria in the gastric mucosa.We have studied the fiahility of this new breath test on a population of 81 patients (mean age of 26,1+-18,1 years). Methodology: patients are fasting for 6 hr. After a control Ureath test sample and a standard breakfast of 300 cal- and admini@tratfon of i microcurie (37 KBq) of urea-el4, breath test samples of 5 min. are collected during 30 min.Kesults are expressed in cumulative % of administered dose corrected for C02 production and body area. Results: l.Patients with gastric endoscopy and ~ulbure for CP: 53 patients have been studied; 22 had a normal endoscopy and among them the culture was CP- for 19 with 15 patients 14C02 ~(1,2 SO:0,6 % ID);31 patients had a positive endoscopy for gastritis or 5ulbitis; in this group,29 patients had a culture CP+ and a positive breath test (ii~6 SD 4,8% ID).Considering the culture for CP as reference, sensitivity of the test was 97%~ speeificlty 76% and accuracy 89E 2. Asym.ptomatie _patients without endoscopic examination (n=28): for 28 patients without any actual abdominal pain~ 19 had a positive urea-el4 breath test (8,0 % SD 4,5 ID).Among them ii patients (39%) were parents of CP+ children suggesting a great number of CP colinizatlon in the healthy population. In conclusion, the urea-Cl4 breath test appears to he an accurate method for detection of gastric CP colonization and screening of symptomatic patients.

I

IASTATINE-2]I LABELED MONOCLONAL ANTIBODY: A POTENTIAL AGENT FgR RADIOIMMUNOTUERApY I Alpha-particle emitting nuclides such as the 7.2-h halogen astatine-2]] could be of articular utility for radioimmunotherapy eeause of the short range and high linear ,energy transfer of their radiations. We ~e~cribe the aslatination of 8]C6, an ancibody directed against a human glioma associated antigen, using an N-succinimidyl-3-(tri~ethy!stannyl)benzoate (m-MeATE) intermediate. ~statlne-211 was dry-distilled into chloroform Ifrom a cyclotron-irradiated bismuth target. m-MeATE was synthesized in 3 steps from ~-bromohenzoie acid. Astatine-211 in chloroform ~as reacted for 30 min with t-butylhydroeroxide (20 ~ m o l e ~ n d m-MeATE (1.5 ~mole). -succinimidyl-3-[~''At]astatobenzoate was ~solated by silica gel minieolumn ehroma~ ~ography in 75% yield, and then reacted for 15 min wi~h 350 ug of 81C6 in pH 8.5 borate. ~statine-21] 8]C6 was isolated in 50-55% yield psing a Sephadex G~25 column. Immunoreactivity as assessed in vitro hy incubation with D-54 ~uman glioma Tomorh--omogenate and as a control for nonspecific binding~ with rat liver. IBetween 8[-89% of At-211 8]C6 bound to D-54 tumor while only 10-16% hound to liver. Athymic Imice hearing D-54 tumors were injected with &t~21] 8]D6 and sacrifited at 16 and 24 h. At )6 h, tumor uptake was 27% per,g and tumor to Itissue ratios for blood liver kidney muscle and brain were 2, 7, 9, 26 and 88, respectively. Thyroid uptake of At-2]l was only 0.15% at 24 h, reflecting the inertness of the labeled antibody to dehalDgenation. These Iresults demonstrate that antibodies can be labeled with At-211 using m-MeATE while aintaining their specificity for tumors in itro and in vivo.

~

~

l

~

university Hospital, Lausanne, Switzerland.

ENHANCEMENT OF TUMOR/pARENCEYMA PERFBSION RATIO BY EETABLOCKADE IN LIVER METASTASES. Treatment of liver metastases with radiolabeled monoclonal antibodies, but probably also cytotoxic agents, is limited by the low t~mor to liver perfusion ratio (TLPR). The aim of the present study was to e x ~ i n e the influence of beta-blockers (BE) on TLPR. 8 patients, aged 54-69 years, with liver metastases from colorectal cancer were studied. All had a catheter put in the liver artery in view of tetraarterial (i.a.l chemotherapy. In i patient low basal heart rate (HE) precluded the efficient use of BB. gerfusion of liver metastases was estimated after i.e. administration of Tc-ggm labeled microspheres. TLPR were obtained on ECT sections by the ROI technique in dividing metastasis by n o ~ a l parenchy~a count rates, before and after SS (study interval : i-6, x 2.80 days). Patients A-E wer~ treated with Propranolol (3x40 ms) given orally. In patients F, O microspheres were injected when HR was decreased by 25 % during infusion of a short acting BB, Esmolol, [2gg-350 ug/kg/min) performed under close monitoring of vital parameters. Patients D and S had extensive ()50%), B and E important (>50%7 and A,C,F, limited liver involvement. M an TLPR Patients Eet~iockade SB/basal

D

G

0.1 g.5 1.0 0.7

B

E

g.5 0.7 1.3 2.3

A

C

F

0.7 l.O 1.2 1.0 2.0 2.4

Substantial increase of TLPR by HB ~ay be expected in all patients except those with extensive liver disease.

246 139

140 .

1

Se c a m a n i E. , M riani M.::, A. ~, P i s t o c ~ h i E. ~ , R i v e P'~3 S p r a zi E, , TattaDelll M. A G.~

Comandinl Siccardi

1 S o r l n g i o m e d i c a -- S a l u g g i a , 2 Ospedale Bufallni - Cesena, 3 Dipartlmento di E i o l o g i a e G e n e t i c a llnivmr~i I-.~ I~i Hi ]ann SPECIFICITY OF H U M A N A N T I - M O U S E IMMUNO 3LOBULIN RESPONSE TO M U R I N E MONOCLONAL %NTIEODIEZ I Fo m o n i t o r the i m m u n e r e s p o n s e r a i s e d in ~ u m a ~ s by a d m i n i e t r a t i o n Of m u r l n e MAbS ~or r a d i o i m m u n o d e t e c t i o n , we developed ~n E L I S A test for the q u a l i t a t i v e deter n i n a t z o n of h u m a n a n t i - m o u s e antibodle~ [HAMA), by c o a t i n g m i c z o t i t e r w e l l s witJ in i r r e l e v a n t m o u s e m o n o c l o n a l IgG. ~ven if the p r e s e n c e of HA/~A in parian ~era has not b e e n a s s o c i a t e d so far wit~ illergic reactions, the d e v e l o p m e n t oi ~AMA c o u l d be an impediment to repeat [mmunoscintigrapby or z a d i o i m m u n o t h e r a p ] ~'roln a s i g n i l i c a n t population Ot normal ~ u b j e c t s an a v e r a g e a D s o r b a n c e of 0.075~ F 0.0303 was found. As a CUt-oft, tn( ~ean v a l u e + 3 SD w~s establistled. 6 Large number of sere trom patient L D j e c t e d w i t h w h o l e lgG, ~ ( a b ' ) 2 and ~aD cere tesCed. M o s t of the r e s p o n s e ot thl ~uman anti m o u s e immsnogi obulins we.. I£ound ~o De directed against antiqenl( determinants on the constant region o~ mouse immunogloDulln r a t h e r than N(ab)~ )ortion ot the a n t i b o d y . k significant number oz sere foun~ ]egative in the a s s a y w e r e aiso testa( n otJler t h r e e d l l t e r e n t E L I S A systems, w h e r e ~he i r r e l e v a n t M A D w a s r e p l a c e d b~ mne specific antl-TAA M A b u s e ~ for uh6 in-vJvo studies. No slgni [icanl dlffe[eilces amo[lq the four E L I S A sy!~temE w e r e pu~ in evidence Therefore, th( i,[liTLune resporlse a p p e a r s in laost c a s e s C( ~te c r o s s - r e a c t i v e [atbel" [rlai: s p e c l f i ( o the moriocionai aritiDo
142

141

J.C. Reynolds. H. Sakahara,

J.A. Carrasquillo, ~.E. Lore, P.J. Maloney, M.T. Lotze, R.D. Neumann, S.M. Larson

Centre Rend GAUDUO~AU CHR NA~

NANTES FRANCE F ~

IMAO]~G V ~ k ~ THRC~I USING ANT/F~RIN MC~OO39NAL ANT/BODY Contrast veno~-aphy, an invasive Docedure, is the gold standard for vistslizafion of [eep venous thrc~bi (DVTI. Eowewer, on the bss~s Of in 'itro and animal ~mdal studies, it would appear that nI~inosointi~Taphie detection of v~nous thr~bi using s 11In-lateled mc~oclcmal antibody (NAb) (CEBA) is now 'easihle in b~ans, as indicated by the sensibivity ssulis r~porbed here. Method : ~,~ studied 3 patients rithout (~OU~ A) and 21 patients with DVT confirmed by 'enoE0aphy, includin~ 10 NhOhad he,aria therapy b~for8 ~2/ ir~ection (@~oup B) mqd 11 who b~d heparin hherapy ' to ~ E a~ber {group O). Veno~rams showed 18 thr~mbi B : 8, C : 10) of the leg (calf and pepliteal veins), 4 (B : ~, C : 7) Of the pelvis (ocIIIrmnfemoral and/or liac veins). An activity of 2,5 to 3,5 ~Ci of 111n-C22~ was Jajected inte an anpecubibel vein. nberior views of the leg and thigh (200 K counts) and he pelvis {3DE K comte) ~ere recorded in~nediataly, 3 nd 18 g abner injection. Images were interpreted in ~orance of ve~o~a~ results, with hot spots considered s positive. esulte : Im~nu~oseintJd~r~phy (IS) kms ~sitive in ~oup in all 10 uatiente , visualizing 8/~ leg, 7/? thigh and /~ pelvic thrombi. In ~cup C IS w~s positive in 8 out f 11 patients, visualizing 7/10 leg, 4/7 thigh ~nd 4/7 e/vie t h a i . qhe 3 false~ne~tive patients ted x~ive tilY~i of the leE, thigh and pelvis, with nlar~d COllateral veins. Is was he.tire in group a in ii 3 patients. 0~clusic~ : Iis~nosointi~aphy using I11~n antifihrin Ab is very useful in visualizing DVT, even in patients reabed with h~parin. ~he procedur~ could be ne~tive nly in the e~se of e n ] ~ d COllateral veins. ~ner~ no false pa~itive results.

Lastorla,

J.

J.A. Carrasq~illo, Departments of Nuclear Medicine and SUrEery ~ ~ational Institutes of Health, gethesda, MD

~urine Antibody Pharmacokinetics ~easurement of Antibody-antlbody

and In Vitro Complex.

In previous studies we showed that the ~bility of serum to form complexes with murine nonoclonal antibody (NoAh) was related to the human anti-mutant antibody (HAMA) levels as measured hy radioassay. Slate HAMA can cause rapid blood clearance of injected murlne antibody, we studied the relation of In Vitro complex formation to the rate of antibody clearance in HANA positive patients. Ten melanoma patients underwent imaging studies with 10 mCi and 100 mg of 1-131 9.2.27 a MoAb against the p250 tumor associated antigen. Serum radioactivity and the concentration of mouse IgG were measured in serial blood samples and gave comparable clearance data. Preinjection sara (0.19mi) were incubated with 1125 labeled 9.2.'27 (100ng) and evaluated for complex formation using size exclusion HPLC. The level of complex formed ranged from ii to 54%. Patients with high levels of complex had rapid clearance of 9.~.27 from circulation and increased liver to heart count ratios at 2 hours. The % dose of radioaetlvlty at 24 hours and the T i/2 beta were inversely correlated with the percentage of complex formed (r=0.831. p
143 P. p~LTI~ B. PLANCHON, PH. DE FAUCAL, M.D. ~DUZg,B. DUPAS,J.F. ~ATAL.

S.

Reynolds, R.D. Neumann, D. Colcher,J. Schlom, S.M. Larson.

M. Merino, R. Blasberg,

Department of Nuclear Medicine, National Institutes of Health, Sethesda, MD.

MEASUrEmeNT OF TAb-72 BY IN VITRO QNANTITATIVE AUTORA D IOGKAPHY USING MONOCLONAL ANTIgODY g72.3. In Vitro quantitative autorsdiography was used to measure the local concentration of ~he tumor associated glyeoprotein TAG-72 in human tumors. Eight micron sections from lung. colon, and breast adenocarcinomas were incubated with solutions of 1-125 labeled monoelonal antibody B72.3 ranging from 2.5 to 166 ambles/1. Excess unlabeled g72.3 was used to determine non-saturable binding. Adjacent H & E stained sections were used to define tumor areas. Autoradiograms from incubated sections were analyzed with a microdensitometer, Tumor region activities were compared to autoradiographic standards to give cOl/gram and pmoles/gram of labeled antibody bound to tissue. Computer analysis showed that specific binding of labeled antibody to tissue was saturable. TAG-72 concentrations varied from undetectable to 251 pmoles/gram. TAb-72 concentration in tumors was related to regional differences in tumor nell content. Autoradiographie images correlated with E & E morphology of the tumors and the antigen positive areas determined by immunoperoxidase staining. High concentrations of TAG-72 were found in mucin positive areas which included normal colon mucosa (also immunoperoxidase ,ositive). The binding constant of 1-125 g72,3 to sections of these tumors varied from 0.43 to 1.7 x 108 L/m. We conclude that the In Vitro quantatative autoradlography method will be useful in measuring the molar concentration of Tag-72 in tumor and normal tissue and that tumor architecture and mucin content affect the results obtained.

144

R M ~ n K . K l e t t e r , R.Dudczak, K.Goldschmid, steiner, E.Minar, P.Kalhs, P.Pokieser, H.Ehringer

5 De Ge~er~A. Bossu~ P, Van Den I~ande.

First Medical Clinic (Department of Angiology, Department of Nuclear Medicine), University of Vienna, A u s t r i a

Universily l-losp~al, Yrlle UniYersEeE,B~ussel% Belgium

I N - I l l LABELEDMONOCLONALANTIFIBRIN (AF) ANTIBODYSClNTIGBAPHY(SC) FOR DIAGNOSlS OF DEEP

IN111-LABELED ANTIFIB@INANTIBODIES IN THE DIAGNOSIS OF DEEP VENOUS THROMBOSIS: PRELIMINARYEXPERIENCE,

IVEIN THROMBOSIS(DVT).

The diagnostic accuracy of In-111AF (2-3 mCi i.v.)was evaluated in 28 patients with suspectec DVT (history 1-21 median 5 d.)using phlebograph) as a reference method. Because of ethical reasons 25/28 patients were on heparin therapy. Quality control repealed that q4-gg.5% of the isotope was protein bound. Images of calves (c), thighs (t) and pelvis (p) were obtained 2 and iF 8 patients additional l,g and 21 hours after injection with a gamma camera (LFOV, HEP collimator). Thereafter blood pool scintigraphy (Tc99m HSA) was done. No side effects were observed so far. AF-SC was interpreted by an observer unaware of c l i n i c a l information visually and quantitatively. In 15 patients phlebography identified DVT: c:3, c+t:7, t : 2 , t+p:2, c+t+p:l. 12 of these patients had positive AF-SC. 2 false negatives had small clots in a calf muscle veln (history l and 8 d, resp.), another one sufferec from a 16 days old DVT of t+c. For DVT with a history less then 7 d. s e n s i t i v i t y was ll/12 (gz%). The 21 hour images were less positive than the 2- and 5 hoar images. Extent of DVT as demonstrated by AF-SC correlated with phlebography. The s p e c i f i c i t y of AF-SC was 69%. The false positive patients suffered from varicosis and/or venous insufficiency. Probably due to collateral development and venous stasis qaantit a t i v e analysis of blood pool scintigraphy tended to decrease AF-SC s e n s i t i v i t y . The decision i f quantitative analysis is superior awaits Ifurther evaluation in a greater study populazion, however. Conclusion: In-t11AF-SC is a sensitive means Ifor diagnosing DVT (within 2-3 hours) even in eparinisized patients.

~

The potential of Indiurn-111.labeled moreclonal antifibrin anttedlas for visuallsation of deep venous tI~ombi (DVl') vfas studied in 11 patlanIs w11h a ¢Iinicatsuspicion of lower Imb DVT.

Feb ~agrnents of mol~se monoclonal antifibrin antbodies complexed with DTPAwere labeled in vko 74 MBq Im111. imaging was performed by a large field of Ylew gernma carnem equipped Y~th a medium energy parallel hole collimator. Care wag taken to position [~e ¢olli'natorprecisely parallelto t~e paBenls' Iint~s.Both In-111 peakg were used. Inages were I~ken 3 to 5 hour alteriri~ayenous ad/ninislralion of file complex. In 5 patler'~sm'~aging~ s repeated 2 4

hour later, to avoid disttzblng blood pool acUv~. Cor~rast phLMx~Taphy was done within 48 hours of the isotopicpr~edure.

It.gortirrrmd the preserve of DVT in 8 of U~e patients Inon~ 1 ofthesethe isobpic study was ir~erpretedas negate. Careful reirspect~n a postertori showed some abnormal inguinal act~'~ however, All io~t~r~s with neg~ive phlob09"gphy Imd g negatiYe antitibnn scan. None of the paI~en~ i~ese~ed any major die~on/o~ [rom the isotopicproced~e. W e conclude that In-111-arfdfibnn antl)od/ is a I~Omising n e w agent for tho nonim~sive detedcion of DVT.

247 145

147

146

[ H,J, .Ardngn, l.J. Heikkonen, K.J.A. Kairemo, M.J. MAntyl~

Departmbnt of Radiotherapy and Ontology, Helsinki University Central Hospital, Finland

I M M U N O S C I N T I G R A P H Y WITH I N - 11 I - L A B E L L E D MONOCLONAL ANTIFIBRIN-ANTIBODY FRAGM E N ' I S IN T H E DIAGNOSIS O F DEEP V E N O U S THROMBOSIS OF T H E L E G 14 unseleeted consecutive patients with suspected deep venous thrombosis were studied using I n - I l l labelled monoclonal antibody F a b - f r a g m e n t s (5gDS), which react w i t h fibrin but not with fibrinogen. The aim of this study was to evaluate the capacity of the antifibrin imaging in the diagnosis of deep venous thrombosis. Anterior images were taken of the calves and thighs. All patients were imaged at least twice (1-4 h, 20-2g h) and seven of the patients were studied also dynamically. The suspected leg of each patient was studied by contrast medium phlebography which was used as a diagnostic standard. Six patients had thrombosis verified by phlebography. All these patients had also a pathological uptake of the tracer in gamma images, The size and location of the thrombi detected by phlebography correlated well w i t h the antifibrin imaging findings in four cases. In two other true positive cases the early images showed decreased intensity of the femoral region, propably because of the nearly totally occluded femoral vein but the uptake to the thrombotic area in the cal£ was clear. Out of the three false positive cases one was treated with anticoagulants responding well and could represent a deep venous thrombosis not detected by pblebograpby, the second patient with false positive f i n d i n g had previous f e m u r endoprosthesis operation, the third false positive patient had no explanation for the uptake. A sensitivity o f 1OO % in the diagnosis of deep venous thrombosis was achieved. The specificity was 63 % and the accuracy was 79 %, Because of the high sensitivity the normal antiflbrJn images exclude thrombosis but after a positive antifibrin finding phlebography is still needed to confirm the correct diagnosis.

J.

Yiitanen,

M.

Vorne

R.

Mokka,

P~ij~t-H~me Central Lahti, F i n l a n d Tc-9gm-HMPAO DETECTION OF

I.

Toivio

Hospital,

LABELLED VASCULAR

LEUCOCYTES IN GRAFT I~FECTION

Tc-99m-EMPAO-iabelled leucocytes have recently been introduced as a new method for imaging inflammatory diseases. The aim of our study was to evaluate the diagnostic usefulness of Tc9gm-EMPAg-labelled leucocyte scintigraphy for detection of vascular graft infection. ~1 scans were obtained at sites of potential vasculagraft infection in 18 patients. Scans were carried out at 0.5, 2-~ and 18-24 hours. The scan was considered positive when graft area activity was at least as strong as bone marrow activity in the early 2-4 hours images and the delayed image also showed ,erked activity. 19 scans out of 9 patients were positive. 5 of them were sloe ~eriFied with positive Go-67 scan. With conservative therapy the patients were i~proving clinically and rescanning snowed diminishing activity in the graft area. After healing of the infection the scan became negative. There were 18 negative acans. 7 patients with negative graft scan showed an inflammation site other than vascular graft in leucocyte scan. Rest of the negative scans were in agreement with the clinical observations. In ~ddition there were 3 patients whose positive scans disagreed with the clinical situation. Recause mixed leucocytes were used, it is possible that Dlatelets could have accumulated i n these grafts. Our preliminary data indicate that Te-99m-EMPAO leucocyte scanning is likely to be clinically valuable for detection of vascular g~aft infection and follow up of therapy. However, further evaluation is needed.

FS Prato, G W1eenberg, TP Marshall, ~be],

P Ukslk, P

l

epartm~nts of Nuclear Medicine and Medicine, St, Joseph's Health Centre of London and Unlverslty f Western Ontario, London, Canada.

COMPARISON OF THE UIODIgTRIBUTION OF iSdGd-DTPA ND 99MTc-DTPA IN RATS. The optimal use oF gadolfnlum d l e t h y l e n e t r l minepentaacetlc acid (Gd-DTPA) as a contrast sent in ~ g n e t l c resonance i ~ g l n g (MRI) is

~

ependentonanunderstandingofitsblodistribution

~nd clearance. Since a great Pout the klnetlcs of 99mTc-OTPg,

deal

is known

it w a s decided ~0 cur.pare I t t o Gd-DTPA. Twenty-three mature gprague-Uawley male and ~emsle rats were simultaneously injected with race q u a n t i t i e s of gadolinium-153 DTPA and ~echnetlum-99m UTPA and 0.5 Inrnol/kg o f nonr a d i o a c t i v e gadolinium DTPA. Rats were s a c r i f i c e d t J minute, 5 minutes, 1O minutes, IS minutes ~nd 30 m i n u t e s a f t e r the i n t r a c a r d i a c bolus inJectton. The h e a r t , lungs, l i v e r , b r a i n , idney and blood were excisedg and counted in B ell-counter

to determrne

the amount

of the

i n j e c t e d m a t e r i a l in each or an and blood. In rder for the percent of t o t a l Injected a c t i v i t y o be determined, a technique was deveIop~d which ~11owed discrimination oF the [40keV 9emma-ray Df technetium From sum peaks of gat~Mlnium-153 ~hen the l a t t e r Is counted in a well-counter i t h 4~ geometr . A copper sleeve w i th a wall ~hickness of ~.5mm was placed between the ~ample tube and the Nal(Tl) well-counter. This reduced t h e frequency oF coincidence summing of ~S3Sd photons fro{. 32Z of the s i n g l e s events ~etected

between

40 end

IZOkeV

to

3~.

This

a l l o w e d for the accurate determination of both ~9mTc and 153Gd in the same sample provided a' a l i b r a t i o n sample of j u s t 99mTc was counted to determine down-scatter Into the 153Gd window nd a sample o f just lS3Gd w a s counted to

~

determlne the amount of coincidence counting nto the 99mTc window. Although the distribution Of the two OTPA co,~ounds was qualitatively similar, statistical analy!sis indicated that the amount of 99mTc deposited In the lungs was Ihigher than I53Gd (p=O=OgO), the amount of 99mYc deposited in the kidneys was lower than I53Gd (p=0.Og0d and the amount of 99mTe in the blood lwas higher than 153Gd (p=0.O022 , These results are consistent with the possibility that 99mTeIDTPA and/or its minor in%Duritles bind more to plasma IPr°teinSthan~es153Gd-DTPAand/oritsin%Durities. Our data indicates t h a t Gd-DTPA Is r e s t r i c t e d in its d i s t r i b u t i o n to the e x t r a c e I l u l a r space, is cleared by glomerular F l l t r a t l o n s l m l l a r to 99mTe-DTPA and is probably less l i k e l y to b i n d ~o plasma prote[ns than Is 99mTc-DTPA.

L

148 P. BERNARD'. C. CHAGNON*, A. LIOTARD', A. LELOUARN and H. PERRIMOND** • Unil~ d'lmegerie par Resonance Magn~fique. HFpital de la Timone. MarseJJle. *" Service d'H~msfologie P~distrique. HFpilal de la Timone. Marsei[le. FRANCE • MAGNETIC RESONANCE IMAGING OF IRON OVERLOAD APPLICATION IN TRANSFUSIONAL HEMOSIDRROSIS. Hemosiderin and hemoferritin, paramagnelic Iron complexes, drastically modify proton relaxation of tissues. Twenty-two palienls with transfusional hemosiderosis were examined by nuclear magnetic resonance imaging (MRI) on a Magniscan 5000 ( 0.5 TesJa). Fourleen thalascemia major (9-32 year-old) and eight Ihalasso-drepanocylesis (7-21 year-old), monthly Iransfused for at feasl five years, were studied. Two multiple spin-echo sequences were performed with Iwo different repetition times (TR 500 and 1500 ms). T1 and T2 measurements were done on liver, spleen (10 cases), head (in Syslolic arts diastolic phases), skeletal muscles and fat wilh a VAX 750 compuler (Digital Equipemenl). Results were compared to biological findings and total amount of Iranstusional blood. In all cases an enhancement of transversal retaxalion tale ( 1/T2 ) is found, and the value is belier correlate to tolal amounl of Iranslusional blood than ferritinemia. The longitudinal relaxation rale (1,'7"I) is paradox(rally reduced in patients with hemochromalosis (hemoferrltin deposits). MRI with prolon relaxation measurements (T1 end T2) appears to provide a good measure of iron deposits and, in some cases, Io roughty sopare Ihelr chemical forms.

149 ~D. A MOR . AN I13 , P. JERENSON 1 , D. DUROC I'3, MSYNOTA 1 . i. Service Mospitalier FrAd~ric-Joliot, Ddpartement de Biologic, CEA, Orsay, France. 2. INSERM U153, Paris. 3. Service de Cardiologie, HFpital Cochin, Paris.

ASSESSMENT OF 31p NMR SPECTROSCOPY IN MYOPATHIES BY LINEAR DISCRIMINANT ANALYSIS (LDA) 31p NMR provides information on the concentration of phosphate metabolites like inorganic phosphate (Pi), phosphocreatine (PCr), phosphomonoesterz (Pm) and ATP and on intracellular pH tn the muscle during rest, exercise and recove ry. Data from 7 control and 17 well documented muscle patients w e ~ used to assess the dia-~ gnostic accuracy of J~P NMR for myopathie~, ih~ latter included 6 McArdle's diseases, 5 type l-fiber predominances and 6 rhabdomyolyses. The diagnostic variables were Pi, PCr, Pm and pg at rest, Pi, Pm and pH at maximal exercise (PCr being a control for maximal exercise was then excluded) and recovery half-time of PCr (TI/2). LDA ~as designed to provide a diagnostic assessment tool. The first 2 diserimlnant functions [ were used to give a 2-dimensional plot of data. Eight less documented myopathies were compared to the diagnostic clouds previously obtained by LDA. The accuracy was so found to be 90 Z, the 2-diNensional combination of both discriminant functions p r o v i d i ~ 4 well-partitioned diagnos tic clouds. TI/2 date did not significantly [ chan~e the accuracy. The most discriminant variables were Pi and PCr at rest and pR a t maximal exercise. Eight patients diagnosed as "mitoehondrial myopathy" plotted on the 2 diseriminant functions were scattered over a half plane. Three were close to the cloud of type 1-fiber predominances. 0he was considered as normal. It is concluded that LDA m a y ~ e used as a h i g h accuracy assessment tool for ~ P NNR, I and as a diagnostic tool for less documented myopathies. It shows a heterogeneity of mito-I chondrial myopathies which P NMR might he able to further partition.

150 B.J.G. Daemen A.M.J. Paans, Ph.M. Elsinga, R.A, gieringa (*), A.V.T. gonings (*) and W. Vaalburg

Department of Nuclear Medicine, University Hospital, Institute of Radiopathology (*), University of groninEen I The Netherlands.

BYPERTHERMIA INDUCED SUPPRESSION OF SYNTHESIS IN TUMORS MEASURED BY PET

PROTEIN

Treatment of tumors with hyperthermfa (MT) leads to a reduction of cell metabolism and consequently to regression of tumor volume and delay in tumor growth. In rats with a subcutaneous rhabdomyosarcoma we measured the L-[I llC]tyrosine metabolism with a longitudinal positron imaging system. To caleutate the eorrectlons for change in blood flow 13NE3 was used• Before and after HT, which was applied locally by means of a radiofrequeney field (2.45 gHz) for IS minutes at 45=C and 42 ~, Ruth tracers were evaluated at the same regimen in the same rat. Incorporation studies, using L-ll-14C]tyrosine and different thermal doses at 42=C, 45"C and 47 °C at different time points after aT, were also performed. L-II-llC]tyrosine uptake before and after RT was 1.70 ~ 0.24 and 1.19 ~ 0.14 respectively (mean DARPET i s.d.), a reduction of 30% (P<0.02). No significant alterations in blood flow ware found. The tyrosine/13Ng3 ratio was reduced with 33% (P<0.1). L-[l-14C]tyrosine incorporation studies at 45*C showed, compared ire control, a 58% reduction in uptake and 51% reduction of incorporation into proteins. The total amount of protein incorporation is thus reduced with a factor of 4. lnhibitlon of protein synthesis is observed 2 hours after HT and almost restored after 3 hours. We conclude that L-[1 llC]-tyrosine has the possibility to predict the efficiency of hyperthermia for tumor treatment and therefor on tumor regression.

248 151

152

Ludwig G. S t r a u s s , John H. Clorius, Burkhard L e h n e i Peter Scblag, P e t e r Schmidlin, Ftantisek Helus, Stefan A- B e y e r - E n k e , G e r h a r d van Kaick G e r m a n Cancer Research Center, Heidelberg, W e s t Germany

153 G.KARCHER,L.PHILIPPE,P.PEYCELON,M.BOURGUIGNON,

EMATHIEU,J,C.MAYER,B.BACONNET,A.BERTRAND.

J,C. MAYER, G, KARCHER, E, MATHIEU, J. MAUBLANT, R. [Tfl, M. BOURGUIGNON, J.L. MORETrl, B. BACONNET, A. BERTRAND

Nancy, Tours, Clermont, Orsay, CorbeU, Dupont de Nemours-France.

Nancy, Corbe/I, Clermont, Toum, Orsay, Bobigny, anO Dupon de Nemours-Franoe

POSITRON E M I S S I O N T O M O G R A P H Y W I T H O-15 LABELED WATER AND F-18-DEOXYGLUCOSE ]N 3 O L O R E C TAL T U M O R S . Ipositron emission temography (PET) was used in p a - , Itients with suspected recurrent co[oreeta] malignancies in order to d e t e r m i n e the perfusion and Ihe m e t a b o l i s m log a soft tissue mass. O-15 labeled w a t e r (30-100 mCi was injected for per~usion imaging, whereas F-18=deo 'xyglucose (8-12 mCi) was administered in o r d e r to assess the tumor metabolism. Tracer concentrations ( n C i / m l ) w e r e evaluated with a r e g i o n - o f - i n t e r e s t t e c h nique and standardized for the injected dose and tbe body volume. Twenty-eight patients w e r e included into the final evaluation. The quantitative data of the P R T studies w e r e compared to the clinical results. The final diagnosis used for reference was based on surgery, biopsy or elinioal course. T w e n t y - o n e patients had a recurrent eolorectal tumor, w h i l e a soar was found in seven patients. In 19 from gl tumor patients a significant high P D G uptake was observed, while in two p a tients the ooeoerdration values overlapped with va]ues obtained f r o m soar patietats. The F D G concentration in the tumor one hour a h e r 1racer injection was two to three limes higher than in normal tissue Thi~ provides a superior delineation of the tumor region. The start dardized concentration values in scar patients were comparable to the normal soft tissue region, The p e r fusion values in most of tbe tumor patients were raised, but only at high perfusion values an increase of F D G uptake was noted. W e found no significant correlation between the perfusion o~ a mass and the P D G uptake. Therefore the differentia/ diagnosis b e t ween r e c u r r e n t colorectal lumor and scar necessitates the use of metabolic examinations. W e believe that P E T can be a useful adjunctive procedure in the dif- I ferential diagnosis of an unknown mass.

154

QUANTITATIVE EVALUATION OF MYOCARDIAL UPTAKE DEFECTS WITH THALLIUM AND Tc 99m-MIBI IN 67 PATIENTS WITH CORONARY ARTERY DISEASE.

COMPARATIVE STUDY BY TWO I N D E P E N D E N T OBSERVERS OF THE UPTAKE ABNORMALITIES OF 201 THALLIUM AND TC99m-MIBI IN 81 PATIENTS WITH CORONARY ARTERY DISEASE In order to carry out this study, 81 patients with proven coronary aRery disease underwentthe following protocol : 1) TI-SPECT at stress (3 mCi) and at redislribulion. 2) The days after MIBI-SPECT at stress (10 mCi) and 6 hours rater at rest (reinjeclJon of 20 taCit. 3) Coronary ar~eriography pedormed in the following' three weeks. Two indepeddent observers seberately interpreted the 81 TI-SPECT, and two days later the 81 MIBI-SPECT. Comparing the slices at stress and at rest, the 2 observers classed, as normal or abnormaJ, on the one hand the territories supplied by the left anterior descending adery (LAD), and on the other the tertttenes supplied by the right coronary and/or the circumflex arteries (RCA+ CX). The inter-obeervers reproducibility appears to be better with MIBI than with TI, as the following results indicate : TI : LAD 71/81 (88 %) RCA+ CX : 71/81 (89 %) MIBI :LAD77/81 (95°/=) RGA+ CX:79/81 (97%) In the instances where there was inter-observer disagreement, a joint reading was made with a 3rd obsewer in order to arrive at a eoncensus agreement. The interpretation of TI and MIBf were then compared. The agreement between he 2 racers is as follows : LAD ; 72/8t (89 %) RCA + CX : 72/81 (89 %) I in total, there is no agreement between the two tracers in 16 patients : in 3, TI was normal and MIBI was abnormal ; in 15 I patients,Tt abnormal and MIBI was normal. Among lhese 15 I patients, the coronary arteriography, if it is chosen as the "gold I standard", shows 9 false negative with MIBI and 7 false positive with ThalHum. However an increase in uptake ~bnormaHties between stress and rest was observed in 6 patients wilh Tt (reverse redistribution) and only in 2 patients with MJBI (Mecanism ?). I These results suggesl that, compared to Thallium, MIBI has better inter-observer reproducibility and specificity, but a slightly ower sans[ Mty,

156

155 G.BISi, M.T.R.De Cdstofam, O.M.San~m*,

J. MAUBLANT. L. PHILIPPE, E. MATHIEU, J.L. MORE~I, M,BOURGUIGNON, B.BACONNET,G.Ko~RCHE R, A.BERTRAND i Clermont. Tours, Co,ceil, Bobigny, Crecy. Nancy, Du Pont de Nemours-France.

IDIAGNOSTIC VALUES OF TC-99m-MIB[ AND TI-201 SPECT TO DETECT MYOCARDIAL ISCHEMIA : COMPARATIVE ASSESSMENT WITH CORONARY ANGIOGRAPHY IThe goal of this study was to compare diagnostic values of two myocardial tracers according to the location and the degree of s enosis on patients with proven coronary aderydisease, a I 148 patients underwent the following protocol within teriod of three weeks : 1)SitaRs and R e d [ s t r l b u t i o n I-I-SPECT (3 mCi) ; 2)Stress and Rest MIBI-SPECT 14+21 mCi) ; 3) Coronary Angiography (C,A.). Throe independant observers have analysed separately dlBI and TI scintigrams and have d e t e r m i n e d : l ) the )resence of defect ; 2)it's location (left anterior descend ng ]rtery (LAD) or right or circumflex aFtery (R/Cx) er f i t o r i e s ) . 3 A provided : 1)presence and location of stenosis (LAD or q/Cx) ; 2)percentage ol lumen narrowing : non significant 10-49 (N), Medium 50-89 (MS), Tight>go (TS). I For each patient tbe presence ol isohemia and/or necrosis ~as determined recording to stress and rest ECG and 3linical history. Among Ihe 48 pte we found : 78 ischemic lesJorls : 44 LAD 34 R/Cx 18 infaretg : 4 LAD 14 R/Cx gensitivgy and Specificity ot the two t/scars were determined for lormal and ischemic territories according to the degree ol ~tenosis: N,MS,TS and G = MS+TS. SENS[TIVrW % LAD FVCx LAD WCx 17N 18N 14MS 13TS 27G 3MS 1iTS 14G

MIB

76%

80%

79%

85%

82%

100% 73% 79%

94%

80"

71%

65%

78%

100% 55% 64%

These resume indicate : 1)sensitivity seems to be slightly interior for MIBI versus TI esp~ia[ly in the R/Dx territories ; 2) specificity seems to be befter for MIB versusT n heLADterrfories

E. MATHIEU, J. BOCHET N u c l e a r M e d i c i n e H. LARDOUX, Y. LOUVARD C a r d i o l o g y

A.P~I~i. Dep~tole~tof ClinicalP a t b ~ p h ~ y , NUSIS~ Medk*Jbe U r h , Uniwmity of Florence; Departmentof Cardiology,Careggi Hospital.F]Drence, ITALY, I SUPERIORI']~ OF WnTg-MIBI OVER 2OITL FOR SPECT EVALUATION OF C O R O N A R Y ARTERY DISEASE Amecg the i ~ o I d l ~ ded~tives prolx~ed fOE myocagd~ I,effusk, l~ studies,99mTc-2-~ox7 isob~tyl isomt0]e (99~TsMIBI) a~pea~ ve~memstlng, owmf to ~ ~ pulmor~'y hepa~cbac]'.gmu~ec~ity and ~ abserceof ~distn%u~, W~ testeditseffec~venessIn 6~e dte~nos~c~segsm,.=ntof 9u.~I gomrz&ry extety d~eese in 20 pa~n~ pmsemi~ withsymptoms suggestiveof effozXa~ina, A c c o M ~ ~ cofonar~ai~J~phy 3 sublet=had r~rfaalco.hazy &~de~, ? ha~ o~e-veggel,6 t~owuss~land 4 thre~-vessdd b e ~ fora to~ of 31 ~fectedvessel ten4~riss.T ~ resultsof s~ss ~Tc-MIBI scin~gmphy were compared wi~h ~ of st~g~ 2O~Tl,usiz~ bo~'iplecaraad torJ~&~'ap]~c(SPECT) i ~ . Dm'k~ s~ss s~ud]estlzega]r~ levelof exerc~e ~ msc]~d m all pa~nt~. A R o t ~ a ~ m (SL~USUS), eqmpI~l ~ t h U H R ¢olli~tor vus employS. SPECT ~ ~ f f o ~ d x¢~ doubk ;~.e~,m "s~ ~ shot" ]node,360"rots~a,g0 p~jeguous,mm~iw sl~odgm~for urz~e r~co~n. P ~ r ~c~'t~ w ~ ~¢uJred m 3 ~=-g,~ ~ I (a~edor, 45' and ?5' ]eft ect~dor o b ~ u s ) . T ' ~ m=rd.~ ~ z e I eval~ted c o n s i d e ~ the sidlevuscu]arterdlodus. I i

Planes

~e~we

The comparigon of the tomographic slices obtained with Thallium and with MIBI suggests that the uptake delects of MIBI ate often smaller than those of Thallium. In order to confirm this, we carried out a quantitative evaluation of myocardial uptake defects Jn patients with coronary artery disease. 87 patients were stubiBd by SPECT with Tharlium (stress and redistribution) and the forlowing d r y with MIBI (stress and rest after a second injection). The exlent of the uptake defects is evaluated using an automatic weigh{ed planimetry of "bull's-eye" images obtained by polar analysie ol "ematt-axis" sliCeR. Tbg defect extent is expressed by a score varying from 0 (norms( uptake) to 108 (no uptake). The correlation between the scores ol Thallium stress iTS) and MIB{ stress (MS) being as follows : MS~- 0.68 TS + 0.1 r = 0.85 mean MS = 10.6 mean TS = 15.9 The extent of the defects obtained with MIBI and Thallium are quge well oorreleted (r = 0.85) but the defects of MIBI are, on average, smalrer than those of TI (slope =0.68). This can be explained by the difference between the uptake mechanisms of the two tracers. The correlation between the scores of TI redistribution (TR) and of M1BI at rest (MS) is as follows : MR = 8.57 TR - 0.17 r = 0.77 mean MR = 4.9 mean TR = 6,6 Thus the uptake defects of MISI at rest are smaller than those obla;ned with Thallium redistribution (slope = 0.57). This can be explained by a S]OW arid incomplete redistribution ot Thallium in some patients : 30 % of the patients without necros)s having a posilive Thallium redistribution and only 7 % with MIBh These results suggest that the myocardial uptake of Thallium is more sensitive to stress ischemia than that ol MIBZ but that the uptake of MIBI at rest is more specific ot necrosis than that ol Thallium red[stdbution.

} "/4~

SPECT

I

~

Pkusx

I ~4~

I

I S~CT ~

'

We mey co~clude that ~ T e - M I B I is pmc'ocally az effeCt~w¢ ~°iTl, when plecar m ~ i ~ is emploTed, but appea~ mmm g e ~ i ~ e , '~thout l o ~ of specifisit~, using SPECT, us couldbe expectedcoraider~gthe f~ou~bis featuresof ~le ~acer~ of the labellt~m d i ~ n u s ~ e

Gilles de C e r b e l l H o s p i t a l gg Bd H e n r i Dunant 9TI08 CORBEIL-ESSONNES FRANCE

MIBI-Tc gRm VERSUS T1 201 DETERMINING THE NUMBER OF ARTERIES INVOLVED IN A COHONAROPATHY. Myocardial s c l n t i g r a p h y a c t u a l l y takes advantages of new r a d i o g h a r m a c e u t i c a l s and s p e c i a l l y

i f the Tc 9gm l a b e l l e d isonitrile compounds as t h e t e t r a k i s 2 methoxy i s o b u t y l i s o n i t r i l e (MIBI-T¢ 9gm or RP 30). lout purpose was to assess the a b i l i t y of such a t r a c e r to d e t e r m i n e how many c o r o n a r y arteries are i n v o l v e d in c o r o n e r o p a t h y ( i s c h e mla a n d / o r n e c r o s i s ) as compared to the TI 20] Irinding, the coronary arteriography being t h e r e f e r e n c e . T h i r t y p a t i e n t s undewent myocar= dial sointigraphies (RP 50 and TI 201 i n v e s t i I g a t i o n s ) aiw=ys b e f o r e c o r o n a r y a r t e r i o g r a p h y . The d e l a y between the exams was l e s s than I10 days. A l l the p a t i e n t s (23 men, 7 women ranging in age from 37 to 73 y e a r s , mean age 55 6 years) were suspected of c o r o n a r o p a t h y with clinical and electrocardJogrephical Findings, SPECT a c q u i s i t i o n s were done w i t h a t o m o g r a p h i c gammacamerB SOPHA MEDICAL (FRANCE) i n a semi e l l i p t i c rotational mode ( s t E~p by . . . . . . . . . . . . . . . . . . . . . . . . . j ...... l e t TI 201 s t r e s s and r e d i s t r i b u t i o n acquisit i o n s were p e r f o r m e d . A f t e r M I B I - T c ggm i n j e c tion, stres~ and rest (with reinjection) acquisitions were done. The c o r o n a r y e r t e r i o g r e p b y round r3 s i n g l e vessel. 5 bivessel, and g t r i v e s s e l diseases and 5 normal r e s u ] t ~ for 30 i n v e s t i g a t e d patients. With the RP 30 exam, we diagnosed 10/13 s i n g l e v e s s e l , 2/5 b i v e s s e l and 4 / 9 t r i v e s s e l disease, even when T1 2OI s c i n t i g r a p h y round g/]5 s i n g l e vessel, 2/5 bivessel and 3/g trivessel disease. In this preliminary study RP 30 seems as p e r f o r m a n t as TI 201 to d e t e r m i n e t h e number of a r t e r i e s i n v o l v e d i n c o r o n a r o p a t h y .

249 57 • Taillefer, L. Laflamme, G. Dupras, J. Gr~~ P h a n e u f , J. L~veill&, R.Essiambre.

iBtel-Dieu de Montreal and Institut de Cardiologie de Montreal, Montreal, Quebec, Canada DETECTION OF CORONARY ARTERY DISEASE WITH Tcggm METHOXY ISOBUTYL ISONITRILE (MIBI): CLINICAL COMPARISON WITH THALLIUM-201. The purpose oE this study was to compare MIB to TI~201 myocardial imaging in the evaluation of patients referred for Dhe investigation of chest pain. Sixty-two patients (48 men, 14 women, mean age 55 years) were prospectively studied with hoth TI-201 and MIBI planar imaging. Fifty patients had a coronary angiograpby. There were 68 significantly (~70%) stenosed coronaries. TI-201 images (anterior, 45 ° LAO and 70 ° LAO views) were obtained at 5 and 240 min, after a 2.2 mCi injection on a treadmill. MIBI was injected (10-25 mCi) within a week of the TI-201 study at the sBme exercise double product (21,600 ± 4900 for TI-201 and 21,300 z 4500 for MIBI, no significant difference). Imaging was performed one hour l~ter. Rest study lwas obtained 24-48 hours later with the s~me acquisition parameters and same dose of MIBI, IAnalysis was performed by 3 blinded observers. The left ventricle was divided intg five segnents in each image. Analysis of TI-201 and ~IBI results In 930 left ventricle segments showed an overall agreement in 826/930 (88.8%) segments. Correlation between the patient ~iagnosis on the TI-201 and MIBI studies showed sn agreement in 54/62 patients (87.1%). TI-201 revealed myocardial uptake defects in 26g segments detecting 50 of 68 (73,5%) significantly stenosed coronaries and MIBI detected 262 segments corresponding to 48 (70.6%) stenosed ~rteries. In conclusion, these results showed ~hat here is a high correlation between TI-201 and MIBI myocardial im~gin H in detection of coronar~ artery disease.

160 w. Brandau, B. Bubeck, N. Parekh ~ , M. Eisenhut, p. Georgi

Departments Of Nuclear Medicine and *Physiology University of Heidelberg

EICRETIO~ C B i P / C I ] ~ I I T I D $ OF Tc-gga-F~GI IN PATI~iTS Tc-99m-MASd i s discussed as a grcmisi~g substitute for r ~ i o i n E i a a t e d o - i c ~ h i I p . r i e (0~) in renal f ~ t i o n studies. Nevertheless s i ~ i f i c a n t pbe~aeokinetic d i f f ~ b e t ~ a both r ~ t i ~ s have been r e ported (i). ~ae ]u~wl~ge of these differences will be essemtial for the routine use of Tc-~%Sd, In order t~ evaluate the I~rmacekinetic data Of Tc-~Sd, w~ ~nthesiz~ the cm~x~M as descri~4 prevloBsly (2). • ~IE-purificati~ warranted that only Tc-~G3 with a raaiochemieal Ix~i~ of greater than99 g )ras usedin btman st~ies, simulthnem~ clea~aoce measurements o~ both raalo~ticals ~ e r steady state eo~ti~-~ revealed a clearance tatlO Tc-~3/I-131-0~ of 0.67 (r~124, r=0.94). Toe e~tracti~n efficien~es of OlB an~ ~ 3 were determined simultaneously in 6 patients by blood sampling of arterial ar~ ve~ous renal blood d ~ - ~ an operatic. ~me ratio of these extraction e/ficiencies w~s found to be nearly i~nti~l with the whole bo~y clearance ratio under steady state c~nditio~. ~is i~dicates that HAG3 is ~liai~ate~ ext~are~y j~t B~ little as OIH. iofusion of p - ~ ; u r i ¢ acid (PA~) ~uring the steady state clearance m ~ r ~ e n t s (n=21) decreased the clearance of Tc-MAG3 in a significantly greater extend Khan that of 0~, i~cating a l~-r a Z f i ~ i t y of Tc-~G3 to the tubular transport s~stem compared with 0~. This w5/l rmt be a limitatio, in the ~ of To-MASH, because even in transplant ;atients With extremly i~c 9a/re~ renal function the clear,nee ratio TC~GH/OIB is rather eo~tant. (i) B. Bubeck et BI. NUC. Comp_, 1@, 260, (1987) (2) W. BraiK]au et al. A~I, Radiat. Isot., 39, 121, (1988)

159

158 A. giordano.

M. Massaro*, M. Salvatord,

F. Di Fazio.

G. Galli.

S,Rortch, R.Sch~erzrock, G.Herrmann@, R.Haver~--'~ch÷, H.Hundeshagen

Institute of Nuclear Medicine. Catholic University of Sacred Heart. Rome *Dept. of Internal Medicine, and University Tar Ve~gata, Rome - Italy

Department of Nuclear Medicine and Department of Heart-, Thoracic and Vessel~ur~e~y + Medical School Hanover - germany

DIFFERENCES BETWEEN TI-201 (TL) AND TcSBm-MIBI (MIBI) IN DIPYRIDAMOLE MYOCARDIAL SDINTIGRAPHY

TRE VALUE OF TONOGRAPHIC MYOCARDIAL PERFUSION SCINTI~RAPHY (MPS) WITH 2@LTI- OR SgmTc-MIBI AFTER HERRT TRANSPLANTATION

Purpose oP this study is to compare TL and 'MIBI images in dipyridamole (DPN) myocardial scintig~amhy. Our interest was risen by the unexpected'finding of absence of reversibie defects (BD) in 7 consecotive pts. with hlgh pretest probability of CAD who underwent MIEI/DPR studleS: onl~ 5 fixed defects (FD) were observed out of 63 segments. Therefore we submdtlied 5 other pts. with high pro-test probability of CAD to the standard DPR procedure and injected simultaneously TL (2 mCd) and MINI (5 mot). TL early images were soon recorded; TL rest images and MIEI early images were recorded after 3 hours by contemporary dual-peak acquis ! tion; then 25 mot of MIBI were injected at rest and MIBI rest images were recorded after 2-3 hours• The Following results were obtained by qualitative analysis of planar scans: early images showed 12 TL defects and 5 MIBI defects (out of gS segments); rest images showed 3 TL and 3 ~IBI defeebs in full agreement ef segment and size; therefore 9 RD were demonstrated by TL. only 2 by gIBI. At pre~ent the reported mds match between TL and ~IBI early scans has no oh vious explanation; differences in extraction fraction at high flow levels may be involved. From the reported date we conclude that RIB1/ DPR studies should be interpreted with caution as the standard DPE procedure, widely validated For TL. may not be suitable for MIBI propertles.

161

(HTX)

After the f~r~t year vascular sc!aro~s aeems to be the determinant factor for graft survival zn HTN. Early detectzon of stanoszs of major vessels is essentzal ~n orden to perform PTC~ before £mfarction occurs. ~ngima does no± occur because of heart denervatlon and exercise ~Cg i s inconclusive due to RgB in most patiento (pisS, So MrS s~em~ to h~ the ~u~table nonznvaslVa test to reveal graft z~chemza. Up to now 45 DiS underwent I o m o g r e p n i c sxerotse and rest MPS ~nd coronary angzograohy (CA> to evaluate the usefulness of MRS as a follow up te~t after HTX. 4D of t h e MPS were done wlth 2DITI, the la~aat with SDmTc-MIBI (RR3g- OuPont), gzcycie exercise in a s~ecially destined ~rotoeol was chosen as a physiologl¢ way of work load. The studies were evaluated vi~u~lly and quantitatively. In 7/48 pts regional zschemia or infarction could be dBIected by MrS and confirmed by CA, 88mTc-MIBI wa~ superior concerning image quality compared wilh 2~ITI. None of the mazor vessel stanDByS weme mzsaed by MPS. However, the diagnos~s of d~ffuse ~olerosis was a problem despite washout analysis.

Bicycle e~arozse w~s dCfficult for some pts due to muscle weakness or lack of ~rainzng.

I

WB conclude ~hat MrS is ~ very useful test in the follo~ up a?ter HTN. It reduces th~ need for CA as it is very sensitlve in the detection of ±Nerapeutlcally important ~scbem~a.

162

W.G. MartiN, I.H. Wolf, K. Kempken, H.W. Pabst

E. M a h e r , S. O t h m a n , A. P.D.Diamond, D.S.Thakrar, H i l s o n , a n d P. S w e n y .

Nuklearmedizinische K l i n i k und P o l i k l i n i k r.d. Isar der Technische, Universitat MOorhen

Depts of Nephrology, Medical Physics, and Nuclear Medicine, Royal Free Hospital, L O N D O N N W 3 2QG, GB.

Tc-99m-MAG3 VERSTS 1-123-OIH: COMPARISON OF QUANTITATIV PARAMETERSIN RENAL FUNCTION, l , 22 patients a renal scintigraphy was performed by 1-123-OIH and Tc-g9m-MAG3 2 to 5 days later. The t o t a l and s p l i t rang) clearance were determined by the p a r t i a l sbilded whole body counting method and simultanigusly by a two-compartment analysis. The time a c t i v i t y curves derived from the heart and kidney regions were the base for a two compartementmodel for both tracers. The determination of mean t r a n s i t time was performed by deconvolution of renograms. I , Renal clearance: for renal clearance (el) a linear correlation was found: CI-MAG3 = -23 + 0,54 x Cl-I-123-OIH (r= 0,77), 2. For the s p l i t renal function ( l e f t kidney) (%) a linere correlation was_found too: %-MAC3 = 17 + 0,69 x ~-I-123-OIH (r=0,83). 3. The mean t r a n s i t time from 24 nonobstructed kidneys was 2,9 minutes for 1-123-OIH and 3,8 minutes for Tc-ggm-MAG3 in the same kidneys. 4. The transistionrate plasma to kidney (KI2) calculate from the two-compartment model was ]theory corretated for 1-123-OIH and Tc-ggm-MAC3: KI2-MAG3 = 0,02 + 0,61 x K12-1-DIH. 5. S p l i t renal function (%) derived from the two-compartment model (linear correlation): %-MAC3 = 0,7 + 0,89 x %-I-OIH (r = 0,94). 6. Volume of d i s t r i b u t i o n : for MAC3 a 17% lower volume of d i s t r i b u t i o n was found compared to 1-123-OIH, using the two-comartment model. 7. In 4 patients a reasonable l i v e r uptake was v i s i b l e 15 to 30 minutes p . i . Tc-99m-MAG3 seens to be a suitable radiopbarmaceutical for renal imaging especially in cases where no 1-123-OIH is available. Beside the lowered clearance, quantitative evaluation of renal parameters seems problematic, because of i t s nonrenal excretion.

FrBnkel, A.J.W.

CAPTOPRIL-ENNARCED 99m-Tc-DTPA SCINTIGRAPHY AS A S C R E E N I N G T E S T F O R UNILATERAL RENAL ARTERY STENOSIS. The value of Captopril DTPA Scintigraphy as a s c r e e n i n g t e s t f o r renovascular disease was studied prospectively in 47 hypertensive patients with possible Renal Artery 8tenosis (BAg) using the proposed Co-operative protocol (Oral Captopril 25 m g m 6 0 - 9 0 m i n s b e f o r e scintigraphy in a well-hydrated sodium-replete patient). Hl p a t i e n t s had a raised Creatinine level (>lHOumol/L). All patients had angiography (usually DSA): 15 h a d unilateral RAS, 2 h a d b i l a t e r a l HAS, a n d 30 h a d no renovascular disease. Captopril induced a fall in split renal function in the kidney on the s i d e w i t h R A S i n all p a t i e n t s with unilateral RAg (mean 51% (SD 22) f a l l i n g t o m e a n 4 4 % (SD 20) o f t o t a l OFR, p < O . O 0 1 ) . A positive captopril scintigram (defined as a f a l l o f 5% or more in split renal function) had a sensitivity of 87% and a specificity of 6 2 % in t h e d e t e c t i o n of unilateral RAg. The 2 patients with bilateral RAg had bilateral fall in GFR seen on analogue images, but with no change in divided function (as w o u l d be expected). This protocol a p p e a r s to o f f e r a good non-invasive screening test for t h e d e t e c t i o n of RAg.

250 163 AmM.Ai-Nahhas, CmC.Nimmon, K.EmBritnon, M.JmCarroll, MmA.Ai-Janabi, J.Bomanji, F.Fiore.

164 MARGARIDA RODRIGUES,M.JOS~ SAMPAI0,A,GOMES C ~ - ~ ~ E ~ ~ L I A NOGUEIRA,M.ROS~RIO

165 Oh. Ehrenheim, P. Hein~., H. H u n g ~ i ' ~

Servi~o de Medicirs Nuclear,Institute Por~ugu@s de Cncolog~ and Hospital d~ fl~z germelha, Lisbon, Portugal

Department of N~I~I" Medicirm M~I1~sI .~as) o~Hanrmvor,FRO Dept. Nuclear Medicine~ St Bartholomew's Hospital~ West Smithfield, London ECL, UK THE ACTION OF RAMIPRIL, A NEW ANGIOTENSIN CONVERTING ENZYME, ACE, INHIBITOR, ON RENAL AND INTRABENAL BLOOD FLOW IN ESSENTIAL HYPERTENSION During a placebo controlled drug trial of Ramipril a new ACE inhibitor (i0 mg dose) in 7 patients with essential hypertension, EH, eFfec tire renal plmsma flow, ERPF and eoFtical nephron flow, as a percentage of single kidney EEFF CN% and in ml/min, CNE, were evaluated. Patients with EH were given either 75 MBq 1-123-OIH or i00 Meq Te-99m FAH3 i.v. seated in Front of a compute~-linked gamma camera. Camdiae output (blood volumes per minute, CI) from first pass analysis, EgFF fcom single shot multiple s~mple OIH clearance or 1.5 times MAd3 clearance + go ml/min, CN% from the bimoda distribution oT parenchymal transit times by deeonvelution snalmsis were measured. Both ERPF and CNF were normalised to th~ placebo Cg values. With Ramipril mean blood pressure, g/F, was Ireduced from 179/i05 to IG6/88 (P~O.05); ERPF increased non-significantly, NS, from 498±57 ml/miN to 56~±57 ml/min (mean±SEN); CI fell fPo~ i . ~ ± 0 2 Co 1.36~0.I iNS); CN% rose from 186±2% to 91±2% iP=C.05); and CNF rose from 419±19 to 508±41 ml/min (P
166

~ I I R ~ O X I C ~ OF CYCLOSPORINEA IN ~SpL%NTEI E~DNEY."Z~I}~VALUE OF 99mTc - DTPA R ~ O G R A P ~ . ~ Significant progress has been achieved over the past two decades in the use of renal transplants Cion 8s a method of treatment for chronic renal Cailure. Since 1985 we followed the kidney transplant wi~ defined protocol that includes 99mTc-DTPA renc graphy(RN) on the 3rd,7nh and lOth days after sm gory and afterwards,whenever it is clinically i~ dicated.We analyse the morphological data and the time-activity curves generated from ROI's over the iliac artery and the transplant; a Perfusion Index (PI) is calculated. Phe treatment with cyclosporine A ( C N A ) causes s decrease in renal blood flow dn the days inmledi8 rely after transplantation sDecdally in cadaveri( grafts.The aC~ of this study is to evaluate ift~ nethod used,namely the values of the PI, can ident%fy the rejection group in spite sf the perfusion decrease described in patients treated kid

3SA, We selected 23 RN studies in 17 patients suh~itt~ ~o fine needle aspiration biopsy. Fhe PI in the rejection group (8 patients) was higher (i90,86 + 56.29) than in the CgA nephretc ~icity group ( 9 - p o t i e n t s ) ( 8 9 , 5 5 ± 4 3 . 2 0 ) ( p ~0,0055 ~e concluded that P% remains ~ good index for ~etection of acute rejection and that in CSA nehrotoxicity PI was in the normal range (PI belo~ 50). 1) Hilson g.J.W.~Maysey M.N.,Brown C.S.,and Ber£ek M,5.: Dynsmic rensl transplant imaging wit Tc-99m DTPA (Sn) supplemented by s transplant pe fusion index in che msnagmenC of rensl rransplsnt~ J.Nucl.Med. 1978 ; 19 : 994.

167

I . CASTANHEIRA and C.SANAS-OIMOPOULOU

G~DOLINIUM-OTPAIN MRINqD ggM-TECHNETIUM-OTPAIN EX/~MINATINOTHEP%RP~IONOf TRANSPLANTEDKIDNEY~

Functional scthti~sphy after the intraveroJs injection oF 370 MBq 9gm-To-DTPA ie used in the follow-up trmsplanted Wicmys. It provides information ebout perfusion and fupction o( the transplanted ~ n . As porama~natie contrast e~ont OadoHnium is eliminated W

of,

the the the

ki~eys = well ~ Tc-DTPA,a MRI stu~/with b~lu~ injection of Oado]lnium-DTP^ was performed In petloBts witN vascular problems ( complete sterm~is of the renal emery, fnferction of the kidt~/, thramPosia of the renal vein). The ~fnti~naphic ~t~ie~ ~ a audde~ dethrionation of the perfnai~l or circumscribed laskRof perfasion. g patients with trensplanted kidney~ underwent MRI examination wRh gradientecho sequen(ms(FLASH 3(?) using

e high resolution ~urfece coil in e n~prasentative coronal 8iico. After th~venous thJastlon of 0.2 rrll/kg OadellnlurnDTPAdataacOJisition with 3 imegas per miBute was done. The evaluation i~luOed e visual judgement as well as the in(erpratation OFcurv~ OF the signal intensity o/or the time. The ,igh resolution OFMRI chowsthe led( of perfusion at an

early si~e as B defect, wh~'eas be~nning reperfusim could be detected in the poriphew in the Fellow-up.

168 D. Terriers, P. Van den WJnkel. A, Hermanne G. De Backer

5.N.RESKE,F,&DEUTZ%B.SUZNNEM~NN,U.BUELL Dept. Radioisotopes, LNETI, Sacavem,Portugal Demokritos National Research Center, Aghia Paraskevi, 15310, Athens, Greece

AN APPROACH TO THE r4ECHANIS~I OF TECHNETIUrl-99m FOSFO)iYCIN RENAL TRANSPORT. A recently dev eloped 99mTc-radiopharmaceutical stannous Fosfomycin (F05) has predominant a f f i n i t y f o r kidneys at pH 6.8 and f o r bones at pH 2,5. The present inyestigat~on wag undertaken to determine the mechanism of FOS pH 6.8 handling by the kidneys. Whole-body autoradiographies of mice showed rapid blond clearance and excretion of Dart of the injected r a d i o a c t i v i t y through the kidneys. Another part of the radiotracer was retained in kidney cortex for some time ~s in the case of 99mTc-glucoheotonate (GH and 9~mTc-DHSA (OM5A). The excreted compound versus the injected one did not show any d i f f e rence when controled by electrophoresis, ITLC and reinjection to animals. Simitar to GH and in opposition to OMSA, neither acidosis nor alk£ losis had any effect on Fog kidney uptake and excretion. Probenecid (PB) reduced significantl2 the r a d i o a c t i v i t y retained in kidneys one hr after injection from 8 . I I ± 0.44% of injected dose in controls to 4.01 ± 0.54% and i t increased the urinary injection from 64.63 ± 0.65% of injected dose in controls to 74.36 ± 0.69% (P(O.O01)- A similar effect of PB on uric acid tubular transDert has been reported. High blood levels of uric acid hampered FOS-blood clearance and urinary excretion and increased the renal accumulation of radioactivity {P~0.01) suggesting comnetition of POS with uric acid for a carrier mediated transport. Evidence for active FOS-tubular transport is provided by the inhibi~ ling effecb of 2.4 -dinitrophenol on kidney uptake and excretion (P
VUB-CYCLOTRON, I_a~doeeklaan 103,1090 Brussels

DEPT,NUCLERR~EDICINEaND*UROLOBY,RWTH AACHEN~FR6

RESULFBOFDIURESI~NEPHRDGRRPHIN t OBSTRUCTIVEUROPAIHY

Nuresis nephrographyhas been shown bo categorize upper

urinary tra;te inb= ~ormal, obstructed 0r dL]~ted n0n-obetru0led in ~b~i S5 ~ o~pati~n~s, However, subtotal ure~era] obstru~i~on~aV =lieu eo=Br'oE~ual ¢~ow[hlmlgh [he ilolJO|e~ segJ~nt, r~sultingin a gartiai diureticreEpon~ ~d

00mpiicating interpretation o~ Piur~si~ nephrogram,Wethus e~a~ined results o~ diuree£~ nephrdgraphyin g2 paUente (gist wi(h obetructio% surgicaHy ~e~onstratsd within ~ weeks~4t~r a |ban~|rddiureeJs nepnrogram,~ter t,v, ~njecliono~ tO M0q l'I31 hlppuran,nehroqrame~ere obtainedhy me~ne of a LFOV ga=©a-camer~,TwentyminaRer ~rao~r iniBotion~2Q m~ L ~ Nero given :,v, and rBoordLngswer~ co,tinued~or ~dditional 15 min, ~lobal and d,Y~dedrenal hippora~-clear~neewere determioed according t0 Lhe OBERHAU~ENmethod, The ~t~retho e{(~cl w~ evaluated accordingto 0 LREILLgand resulhs ~ere divided into groups 0f C~% response (I}~ 5-1g %(II)~ 15-30X (lid and > ]O (IV~ respeotive]~.0iur~tJcrespons~e~ere (~'~8g:: h ,7 l,g 17/42ply), group [I: ti.~~ 4,2 ~ (1~142ptel, group IIJr l-i~l h[ppuranclearanceof af+eoted~idney ehowed ,o =igni6ica~tdiP+erenee~n group I - IV (h I~0 ~ 110 mI/mln, lh 147 ~ 65 mlYmzn, IJI~ ld4 ± ~8 ml/min, IV: 214~ dO ml/~in, Ip> .2 ,5i, eldudinI reduoed ren~l (unctiona~ potenti~l cause 6or the blunted diuretic respon|ein group I - Ill, S£~ilarIyglobal I cieeranoe~howed no +igni+zoantdiF(er~nce~between the groups. These daka indicatethat [he oampletespectrumo~ nearJy ~bsen~ to "normal"diuretJ0 ~esQon|e ~ay be encounteredin patients wlth surgicallyproven obstr~ttiw uropathy, thus cautious inbertpretati00 oF the dlunesisnephrogramie indioated and ~dditionaIanatomicalinformationi~ reguir~d For categorizingobstructJv~ w non-obstrucbiveuropathp,

A NEW METHOD FOR THE PREPARATION OF CARRIERFREE l) +-EMII-FINGBROMINEISOTOPES SUITABLE FOR THE LABELLING OF NEUROLEPTICS

Nudeophilic Br-# subsl~ution is a powerM tool for the prepa'~on of carrier-free 75Br and 76Br neurelepl~gs for PET applicati~s. However, as the reaction requires the avallibility of caTior-free rat~obromide solutions free of other halide carriers, of nilrogen diodes and of b'aces of target material, the mebhods desoribed in literature ere inferior (low reaction rates, poor yield) for the prepera~on of the ra~o~'acer sol.on. Therefore a new method was developed. It involves the Wrid~on of As metal targets ~ 75As ( 3He, 3n)75Br and ?SAs ((~ , 3n ) 76Br nuclear reactions) and dssdution of the metal in 30¢ H202 , followed by fast distilla~on of the l~'-radioisotopes. After addition of a reducing agent and ac~ustment of the pH the distillate is taken to dryness. The residu is ~lesdved in a smell volume of peracetic add and the resull~ng sdution is used for a fast aleatrophilic Br-H substitution on a highly activated subsCate ( i.e. 3,5-dimethytphend). Upon dathyiether ex~action of the labelled compound the organic phase is evaporated and the residue is well-mixed wi~ an appropriate amount of an organic sgbs~ate, Next a weighed fraction of the mixture is deslructed by means of the Schoniger oxygen flask combus~on. Tne carrier-free and highly pure radio~omide is taken up in a smell vdurne of NaOH. This final solution was succeofully applied for both, Br-I nudeephilic and for alec~ophilic substitul~on of Spiperone with very high yields.

251

J, Mertens,

R.Waege~ser

171

170

169 W.Vanryckeghem,

A.Hermanne,

Vnje Universitelt Brussd- Cydolron Dept. Laorbesklaan 103 - 1090 Bruszel Belgium NEW FAST PRODUCTION OF NCA 7~Br, 7SBr SUITABLE FOR NUCLEOPHILIC LABELLING OF BRAIN TRACERS FOR PET ;'BBr, ~Br labelled butFc~anones and henz~zepines showing hi~ brain receptor specificity ere at'~'active ricers for PET. Multi patient daily PET research requires high radoactive doses of ~'acer to be prepared. Trying described produc~on methods coupled to a 7SAs(XHe,xn)~,mBr reaction and applying the total batch of radobrornide for non-isotopic nudeophilic exchange results in low labelling yields due to the presence of s~"ongoxidaing entities. This paper describes an alternative method which is last, suitable for automshsation and which allows a high yield nudeophilic labelling. The bombarded 13 foil - As pellet sandwich is Vensferred to a vial containing 3 ml of 10% H=O=.Afler a few seconds of ulftasonication the water rinsed "fi foils are ~scerded. After dsaolving the As in the boiling ~O= solution 350 p.l of a 800 hydrazinchydrate solution are added dropwlse. Then the walls of the vial ere rinsed with 10 ml water.The obtained solution is passed through a prefEeated mini-column of AG 1-X8 in OFF form. The column is consecutively washed with 5 rnl 2M NaOH and 10 ml water and sweetly blown to "dryness" The radiobrornide is eluted with ~: 250 p.I 1M NAN%. A recovery yield oi" 75% of pure NCA radishromids is obtained within 45 min kom EOB. Using a total batch of "~Br for isotopic exchange on 2'-Br-Spiperone (100 °C) and non-isotopic exchange on lAMP (140°C) labelling yields ot respectively 85% and 60% are obtained within 60 rain,

172 I .. . [ 1 H . - F . ~ e e r , P . B l a u e n s t e l n , P.Hasleg , P.A,S~hu

J. Mertensl, L. Chdstiaens 2, J. Eersels 1, R. Cantinsau 2, C. Piron-Bossuyt t, A. Bossuytl, M. Guillaume~

A.i s c h o f - D e l a l o F e , B N. Oloachea-Toro, J. Bogousslavsky, R.F. Beer, P.A. Schubiger, F. Regli, B. Delaloye

1 VUB-Cyclotron 1090 BRUSSEL 2 Cent. Rech. Cyclotron Univ. Liege, Sart- Tilman BELGIUM

Centre Eospitalier Universitaire Vaudois, Lausanne and P~ul-Scherrer-lnstitut, R6renlingen, Switzerland

PURE N.C.A. 2'. 1231 . SPIPERONE, P R O M I S I N G TRACER FOR IN VIVO R E C E P T O R STUDIES W I T H SPECT.

FIRST EXPERIENCES IN NORMAL VOGUNTEERS WITH A 1-123 LABELED BENZODIAZEPINE (BZD) ANTAGONIST

A Di

T-125I -Spiperone was for the fwst time presented as a possible D e receptor tracer by Saji et al. 1987(1). Although the low specific activity (106 Bq/mmol) obtained by those authors through isotopic exchange, in vi~o binding and distribution in rat brain showed promising results. This paper describes the preparation of and the results obtained with pure N.C,A. 2'- [ - Spiperoae with very high specific activity ( 8.107I~q/mmol for I = t25~ at least 5.108 MBq/mmol for I = 123I). N.C.A. 2'- I Spiperone is obtained by Cu(I) assisted non-isotopic exchange on 2'-Br-spiperone as substrate in reducing conditions at 100°C. A labelling yield of + 90 % is obtained within 60 minutes. HPLC separation is carded out on a semi-prep 7 Iz RP 1g select B column. 2'- *ISpiperone is preconcenlrated and further purified on a Sep-Pak filled mini column and recovered in a small volume of acidified EtOH. Male Wistar rats of + 200 g were injected with 2.8 MBq 2'- 125I - Spiperone andt sacrificed 60 minutes post injection. Control rats were injected with respectively 200 ~tg spiperone and kctmaserine 30 minutes prior administration of the tracer, For the blanks a slxiatum / cerebellum activity ratio of 3.5 ~s obtained. The spiperone and ketanserine treated rats showed strlatum/cereb~llurn vaiues of respectively I and 2. This means that 2'- I - Spiperone shows D 2 and Sa binding characteristics comparable with Splpemne itself. Promising results of baboon brain SPECT studies with N.C.A. 2'- 1231-Spiperone are shown. 1 . Saji H., Nakatzuka h, Shiba K., Tokui T., Horiuchi K., Yoshilake A., Todzuka K., Yokoyama A. Radiotodkmted 2'-

Flumazenil is a BED antagonizt by eo~petiti~e interactlon on central BZD r~ceptors. The aim of the present study was to ~easure uptake of its 1-123 labeled analogue in brain and other organs, to study its cerebral distribution and to test the receptor-specificity of uptake. 9 healthy volunteers participated in the study approved by the efhical committee: in 5 subjects whole body distribution yes ~easured after 2 and 90 min, ECT was performed 30 min and 2 h, in i case even 24 h post injection. Displacement tests were performed by ECT first ~nder basal conditions, than after iv injection o£ 0.O5mg/kg cold Flum~zenil in 4 volunteers. W~sh-out from the brain was also recorded. Brain uptake was very fast, an activity plateau was observed at 7 min already. Organ distribution (mean!SD) in % of injected activity: 2 min 90 min Head S.28~I.02 7.07*0.74 Heart 3.60V0.40 0.96~0.19 Lungs 9.04~1.89 2,7871.03 Liver 16.26Li.47 4.89?2.44 Bladder 26.30~2.1@ As expected, highest activity was found in the frontal, pre- and posrcentral cortex, followed by the cerebellum and basal ganglia. Injection of cold Flumazeni2 was immediately followed by wash-out from the Brain with mean T1/2 of i0 min. 60-80% displacement of the 1-123-analogue was observed. These results indicate that brain uptake of the compound is high, rapid, stable and BID receptor specific.

174

173

b i g e r ' , E.Deisenhammer% B.Delaloye °, H . F i l l "

*R.C. Walovitch, *S J. Williams *R.A. Morgan, *S.T, Garrity, *E.H. Cheesman, **M. Doherty, **D,H. O'Leary, **T.C. Hill

2IPaul Scherrer I n s t i t u t ' 5303 WUrenlingen . ' CH 3Wagner Jauregg Krankenhaus ' Llnz ' A CHUV Lausanne CH U n l v e r s l t a t s k h n l k Innsbruck, A

*E.I. DuPont De Nemours & Co., N. Biller~ca, MA and **N.E. Deaconess Hospital, Boston, MA

FIRST STUDIES IN HUMANSWITH AN 1-123 LABELLED BENZODIAZEPINE, A RECEPTORBINDING TRACER

PHARMACOLOGY OF Tc99m ECD: BRAIN PERFUSION IMAGING.

Many compounds of the class of benzodiazepines are well investigated to be bound to central and peripheral receptors. A f t e r the completion of the previously reported animal studies using an iodinated benzediazepine antagonist IFlumazenil d e r i v a t e l the c l i n i c a l investigation was s~artcd. ~ho aim of the study was to show w~othor a s i m i l a r s p e c i f i c accumulation of the tracer can be found in the human brain as before in the animals. A second question was, in which diseases the radiolabelled Flumazenil der i v a t e is of diagnostic value. The substance was administered by intravenous i n j e c t i o n of 111-185 MBq (3-5 mCi) 1-123 Flumazenil derivate and 2-5 ~g cold Flumazenil in 5 ml 5 % glucose solution. D i s t r i b u t i o n studies in normal volunteers showed the following r e s u l t s . I . I n i t i a l uptake is s i m i l a r to the pattern of regional cerebral blood flow. 2. Later on the d i s t r i b u t i o n of the r a d i o a c t i v i t y i s parallel to the known d i s t r i b u t i o n of the benzodiazepin receptors, i . e . the uptake is high in the cortex and cerebellum, 3. The displacement of the r a d i o a c t i v i t y immed i a t e l y a f t e r i n j e c t i o n of cold Flumazenil proves the s p e c i f i c receptor binding of the radiolabelled substance. To judge the value of t h i s substance in the diagnosis of brain diseases patient studies were started. A few preliminary findings are given. The a l t e r a t i o n of benzodiazepine receptors in Altzheimer's disease can be visualized using 1123 Plumazenil derivate. In other cases (e.g. stroke, epilepsy, schizophrenia, neurasthenia) some differences are seen, but need further investigation to allow a s t a t i s t i c a l l y relevant statement.

Te99m-Z,L-ethyl cysteinate dimer (ECD) is a neutral, lipophilie complex with potential utility for hrain perfusion imaging. Dbrnamia planar brain imaging studies in anesthetized monkeys show the compound to be well extracted, with 95% peak brain aceivlcy ~4.7~ ± .8~ I.D.) being reached in less than i minute post injection. Washout of activity from the brain is very slow (tI/2 > 24 hours) hut background facial, lung, and blood activity clears rapidly To determine if brain distribution is representative of regional cerebral blood flow (rCEF), a rapid acqusition dynamic SPECT imaging study was performed in a rhesus monkey. Qualitatively, the images are representative of rOBF at up to 16 hrs. post-injection. To determine quantitatively that ECD is a marker of rCBF, dual-labeled autoradiography studies were performed in cynomologus monkeys. ECD was administered iv followed by iv administration of Cl4-iodoantipyrine one hour later. Autoradiographic images were digitized and the ratios of regional activities to corpus callosum were determined using a video-based autoradiography system. Cortical gray to white ~atter ratios are 4-5/1 for both tracers. In all brain areas studied, the distribution patterns of the ECD and C14 iodoantipyrine were ~imilar. Therefore. EGO has characteristics useful for the scinti~raphic assessment of regional cerebral perfusion.

A NEW AGENT FOR

eR.C, Walovitch, *K.M. Hall. *J.J. O'Toole. and *S.J. Williams, **M. Ficard, **M. Franceschi, ~-~R.E. Z i ~ e r m a n and **B.L. Holman. *E.I. Du Pont de Nemours & Co., N. Billerica. MA and **Brigham and Women's, Boston, MA. Te99m ECD METABOLISM IN NORMAL VOLUNTEER, Tc99m-L,L-ethyl cysteinate 6imer (ECD) is under clinical study as an agent for brain perfusion scintigraphy. Results in non=human primates and in vitro studies in human brain tissue suggest that the brain specificity and extensive renal clearance of ECD are due to its rapid metabolism via de-esrerization. Therefore, studies were performed to determine the metabolic profile of gOD in humans. In-vivo metabolism studies with ECD were performed in four normal males. The whole-hody distribution and blood and urine metabolism of the compound was studied for up to six hours post-injection. Imaging results show good brain uptake (6.8%ID) and slow clearance (<25% in 4 hours). Background facial areas and lungs clear rapidly. Venous blood kinetics are complex Blood activity increased to 7-B%ID by 2 minutes and a plaeeau at this level was maintained from 2-15 min. followed by clearance with a tj/a .of a few hours. The metaholic profile of ECD in the blood was studied by extraction of acidified venous blood with ethyl acetate: l-oetanol (50:50, v:v). The parent to metabolize ratio was i:i by 4 minutes and i:I0 by 60 minutes post injection. Therefore, che brain input function is gone within a few minutes post-injection. No correlation existed between the extent of blood metabolism and the brain rID. Urinary activity (75%ID by 6 hours) was only in the form of the de-esterified metaholites of EOD (mono and diaeid), These results ~uggest the pharmacokinetics of RCD to be related to its rapid de-esterification.

252 176

175 S. Vallathajesula, P. Stritzke, and ~ . 6oldm~ith

A. Steinstr~Ser, K. Bosslet, L. Kuhlmann and

A, Schwarz

Sinai School of Medicine, New York, NY, USA

HOECHST AG, D-6230 F r a n k f u r t / M a i n , FRG; BEHRINGWERKE AG, D-3500 Marburg/Lahn, FRG

Lipophilic neutral Tc-9Sm ccm~le~es of Bis-a~inoet~thiol (B~) and Diaminodithiol (~&I~f) l i ~ cro~s blood b~-ain barrier (BBB). A new derivative of this family of ligands, 99mIC-ECD (ethyl cysteinate d/me,r), Was recently developed by D,z~ont, We studied the ~narma~okinetics and biodistribution in four normal hi,man subjects. Following injection of lOmCi of TC-99m-E(D, anterior and p~-terior total body images were I I obtair~d at 5, 30, 60 min, 2, 4, 24 and 48 hours using a moving table at 20c~/min. Percent injected dose was calculated for different organs and tissues. Starting from 30 sac post injection 12 blood san#les were obtained over a 24 hr period. 24 h r u r i n e and 48 hr feces wee esllect~d.

Orq-an Blood Br~in LLesg I/vet

Fercent injected dose 5rain _30rain lhr 9.3 7.6 5,1 4,6 4.3 4.1 5.7 2.5 1.6 17.7 9.6 6.7

at 4br l.O 3.4 0.6 2.4

~he plasma clearance of the tracer is very rapid. Tc-99m activity excreted in urine was 60~ by 4 hr and in feces <8% by ~8 Itr. Brain activity is relatively constant during the first hour. If 8% of bl-ai~ vol%a~e is blood c~ly 0.2% of the total brain uptake (4.3% at 0.5 hr) is due to blood activity, qhe ratio of net cerebral to cerebral blood activity is = 20:I. Tc-g9m-ECD is rapidly extracted and r e t a i r ~ by the brain providing favorable oonditions for SPECT imaging.

178 L. Kuhlmann, A. S t e i n s t r ~ g e r ,

K, Bosslet

G. Martani, A.D. Van den Ahheele. C.N. Venkatesham~ A. Ealdany, g, leo, S.d. Adelstein, A.I. Kassis Harvard Medical School, Joint Program in Nueleal Medicine; S.W.R.L., Room 420~ 50 Binney Street; Boston, Massachusetts 02115 (USA)

INFLUENCE OF THE STRUCTURE OF ANTIGEN ON THE DETERMINATION OF IMMUNOREACTIVITY OF MABs

INTERNALIZATION OF INSDLINOMACELLS

Determination of i m m u n o r e a c t i v i t y of monoclona] a n t i b o d i e s i s commonly performed i n a c e l l - t e s t w i t h antigen excess, I f one assumes f o r the a n t i g e n - a n t i b o d y r e a c t i o n a b i n a r y "yes or no" condition, so i t would be s u f f i c i e n t for g e t t i n g a n t i g e n i c excess to have enough c e l l s fin the tube, i r r e s p e c t i v e how many epitopes are lamaged d u r i n g p r e p a r a t i o n of c e l l s . We observed i n c o n t r a r y to t h i s t h e o r y w i t h me p r e p a r a t i o n of t h e MAB BW 494/32 d i f f e r e n t ,inding kinetics and r e s u l t i n g from t h i s lifferent "immunoreactivities" (ranging from IO % to 70 %) corresponding t o d i f f e r e n t ways i f preparing the c e l l s u s p e n s i a n . In order to =ind the t r u e i m m u n o r e a c t i v i t y , we used the :allowing test: An a n t i i d i o t y p i c antibody i g a i n s t the BW 494/32 (which t h e r e f o r e bears ;he copy of the o r i g i n a l antigen as b i n d i n g ; i r e ) was coupled to sepharose p a r t i c l e s . These ) a r t i c l e s where used as " c e l l s " i n the b i n d i n g :est. The s u r p r i s i n g r e s u l t was, t h a t the int]body was f i x e d completely (immunoreactility~IgO %). A l l c o n t r o l s have been n e g a t i v e . [he f i x a t i o n of antibodies was much more t i g h t ;ban i t was to be seen i n c e l l t e s t , So i t can be concluded, t h a t a m o d i f i c a t i o n ; f the a n t i g e n i c epitope on c e l l s does not irevent the f i x a t i o n of antibodies c o m p l e t e l y , )ut a l t e r s the b i n d i n g k i n e t i c s and e q u a l l y the /alue a t t r i b u t e d as i m m u n o r e a c t i v i t y i n c e l l :est. The c e l l - t e s t for determining immunoreactivi:y of monoc]onal antibodies is a he]pfui tool in quality control, but needs to be validated For each antigen/antibody combination.

Monoclonal 305-IgM, originally raised against a tetraganglioside presen~ in fe~al rat brain, also reacts with the cell membrane of rat insulinoma cells RINm5F. Preliminary immunofluoresconce data shows that 305-IEM disappears from the surface of such cells when incubated at 37 ° C, The aim of the present study was ~o aseertaim ~bether this phenomenon is due to detachement of ~he antibody from, or to izs internalization by these tumor cells. HPLC purified 3G5-IgM was labeled with 1251. ~nd incubated with RINmgF cells either growing ,n Petri dishes or maintained in a cell suspenion 5both at g°C and at 37°E. I~ 1-305 bound onto NINmbF cells in the PetrJ fishes remained a~prox constant over 44 hours ;hen incubated at 4 C, whereas at 37°E activi~ ~as released back in the medium starting at ~ours. At the end of incubation at 37°0, radio~etiv'$~% in the medium included a high fractior ,f Na*=~I (15.7% versus 2.6% for bovine IgC, oz % for 3GS-I~M at 4°C). In the cell suspension, :ell-bound 1 51_3Gb_ig M also remained constant ~ver 24 hours at 4°C, whereas at 37°C i~ de:reased to 37.5% of initial binding. Concomitant )ieroautoradiography ~hnwed diffuse active depo;its withi~ ~he RINmgF cells following ineuha:ion wich 2 I-gg5-1gM a£ 37°E, but not at 4°C. These findings indicate that 3G5-1gM react~ qith a surface antigen on the RINmgF ceils, an( [s then rapidly internalized. Within the cells )Gb-lgH undergoes some metabolic processing following which Na1251 i s released outside th( :ells. We conclude that a n t i b o d y internalization is an important factor to be taken into account ehen assessing the potentials of monoclonal ~ntibndies for cancer diagnosis and therapy.

179

180

R.Schoening , E.Strau8 Department of Nuclear Medicine, University Clinic of RadloJogy Freiburg, FRG

HOECHST AG, D-6230 F r a n k f u r t / M a i n 80, FRG BEHRINGWERKE AG, D-3550 Marburg/Lahn FRG HIGH-SPECIFIC-ACTIVITY LABELLING OF IgG 250/183 WITH INDIUM-Ill For the most diagnostic procedures with I n - I l l labelled MaK the application of an activity of 75 - 150 NBq is sufficient. On average, this activity is bound to ] n*~ antibody. ~ thls level of specific activity is probably oct sufficient in sate areas of diagnosis, With the following example the high specific labelling of the [:,~K250/183 (~cd~rir~el-ke) is s l - ~ . li'e I~K 250/183 reacts with the antigen NCA-90 ~ i c h is found on the g.anulocytes of the p.:righeral blood. To obtain iofon~atien on the binding capacity of human granulocytes for this mTtibody we investigated the in vitro binding kinetics of the antibody by Scatchard analysis. I f the 50 % binding value on the curve is taken as broadly correspending to true conditions, 20 Pg of M~K 250/183 should be sufficient for 5 litres of htxnan blood. A study in man would thus require these 20 ~g to he labelled with 75/43q I n - I l l which corresponds to a ]enific activity of 3700 M3q/mg. In order to determine the ogtimJm anent of DIPA, w _=fformad a series of tests to see hew different amounts DIPA affected the immuonreactivity of the antibody. I t was found that the l ~ e d DTPA proportion can be up to 6 ,DI per m l IgG 250/183 without having any substantial affect on the inmuoclogica] pm[~rties, llmse antibody DIPA conjugates ~ r e used for the high specific activity labelling experiments, ~ achieved specific activities bet~=en 4500 and 9000 M~q/mg and activity yields of 70- 80 %. After purification by ultrefiltratiom the purity reaches values up to 98.9 %. In the cell-bindi~ essay the inmunereactivity decrease about 40 %. lhe high radiation ¢~ergy sesrs to be responsible for this loss of in~nore~ctivity. Despite of this influence other factors ~re under study.

177

NEW M E T H O D F O R M I L D J O D I N A T I O N O F SENSITIVE PEPTID C O M P O U N D S . Iodination of sensitive pepfJd compounds with chloramine 7~ lactoperoxidase or iodogen are well established labelling methods. Method: We lelctrolysed commercially available J-131, J-123, J-125 solution (up to 740 MBq) dil~l~ fed with 2-4ml destilled water at 12V, 4 12h witk )latinium (Pt) or palladium (Pd) electrodes at 00-40 ° C in a small glass chamber. The radio active iodine precipitated on the anode. The electrode was cleaned with destilled water anal cotton wool. Jodinat~on of peptid compounds (anti CEA moneclonal antibody), anti-pseudomonas none cronar, antibody, Gastrin I human# Insulin, Oxytocin Ornipressin and L-Thyroxin) arised by stirring the electrode up to lh with the corresponding peptid solution (0°-2O°C) Traces of Free iodide were withdrawn with a snail portion of anion exchange resin. The Cleaning step can be dropped, if J-Free inactive iodide is added to the peptld solution prior iodinatJon and if the iodinafion time is limited to a few minutes. Results: With this new method of )odination we succeeded so far in imaging small metastases of colon carcinom (human), experimental induced 3seudomonas abscess (rat) transplaoted human tumor (rat) with gastrin receptors and biodlstribution of J-L Thyroxin (rat). Advantages; 1. High specific activity. 2. unaltered ]mmunoreactivity. 3. labelling temperature at 0°C. 4. short labelling time. 5. no heterogeneous Ions. Experiments with copper or aluminium electrodes were unsuccessfu]. Obvionsly 7yrosin is the ]abelle0 group. The Pt-J and Pd-J bond is extremely tight. Neither by heating up to 200°C nor with organic soNents happens a notable toss of activity. Cleaning was performed with hot HCI conc. or "Kings-water".

MONOCLONAL

3G5-1gM

BY RAT

S-L. Karonen, N. Aronen, M. M~ntyla, G. Sievers p. Nikkinen, K. Kairemo, J. Gripenberg and K. Liewendahl Helsinki University Central Hospital, Dept. of Clinical Chemistry, University of Helsinki, Helsinki, Finland ACCUMULATION OF RADIOACTIVITY IN MALIGNANT I TISSUE AFTER INJECTION OF IalI-LABELLED TISSUE PLASMINOGEN ACTIVATOR (tPA) MAY BE DUE TO ~TABOLITES OF tPA We have previously reported on the accumulatior of radloiodinated recombinant tissue plasminogee activator (131I-rtPA) to various malignant ttmlours and the rapid elimination of the trace* from the circulation. We now report on the distribution of l~llrtPA in peripheral blood from 7 patients administered this radiopharmaeeutical, flood samples were drawn before the intravenous injection of tracer and 15, 30, 60, 150, 240 min, and 24 h after the injection. Dynamic images of the liver were recorded for the first 30 min and 24 h after the injection whole body imaging was performed for localization of malignant tissue. The peripheral blood cells contained 0.35% of the radioactivity 60 min after the injection. This cell-bound activity was found in the platelet and lymphocyte/monocyte fractions while only insignificant amounts were hound to the red blood cells. The distribution of radioactivity in the plasma was studied by exclusion chromatography using HPLC, The plasma radioactivity declined to 65Z at 4 h and thereafter more slowly to 22% at 24 h. A radiolabelled pro rein component of approx. 50 kDa, probably rebresenting l~II-rtPA, declined at the same rate. Simultaneously a radiolabslled protein component of approx. 6 kDa appeared reaching maximum at 150 min 5i% of total plasma radioactivity end thereafter decreasing to 25% at 24 h. Conclusions: I) l~iI-rtPA is rapidly degraded 'after injection to a smaller component(s) oft he size of approx. 6 kDa. 2) The radioactivity laccumulated by malignant tissue possibly represents one or more of the metaholites of lazIrtPA.

253

Am Ea@ri~anti, E. Pinori~ M. Ferdeghini ~ Servizio di Ematologi~-Clinica Medics i e Servizio di Medicina Nucle~re~ Universit~ degli Studi di Piss, Spedali S.Chiara, Pisa, Italy. iALIGNANCY

183

182

181

AND PDATELET ACTIVATION

~l~telets might play a role in tumor growth and ~issemination. In order to study platelet active ~ion in cancer, ~ thron~boglobulin (bTG) and pla [ ~elet factor 4 (PF4), two platelet-specific promains released into circulation when thrombocy~es are stimulated, have been measured in piasm~ ~y radioir~nunoassays (A~ersham and Abbott) in 41 :ancer patients(Do) and in 30 healthy subjects. twenty ps had breast cancer, 15 renalcareinoma ~md 6 miscellanea; 27 ps had evidence of distan~ 0etastases; no ps had clinical,instrumental or l~l )oratory signs of thromboemboiic disorders. Plas na ~TG (x±SD) was 42.7±16.7 ng/ml (range 18-93) [n cancer ps and 25.7±7.4 ng/ml in normals (StURent's t-test p<0.001); 17 out 41 ps (4~%) had ~TG levels above 40.4 ng/ml, that represents th~ ~pper limit of no~mals (x+SSD); 14 of them had Ristant metastases, the other 3 were apparently ~ree of metastatic involvement. No correlation ~as found between ~TG and platelet count. Plasma ~F4 was 6.3±3,3 ng/ml (range 1.3-13.6) in ps and ~.4±1.6 ng/ml in normals (p NS). Although PF4 is ~ecreted in parallel with 5TG during platelet a~ tivation, its level was not elevated: this might ~e due to the faster clearance of PF4 as compared to ~TG. In conclusion we have found evidence of in vivo platelet activation in a number of subjects with malignancies; since no ps studied had •ny sign of vascular thrombosis or of acute dis~eminated intravascular coagulation, high ~TG olasma levels may be the result of interactions Df platelets and cancer cells.

184

P Cummins, D Hamilton, R Cowan, H Sharma, P Nuttall, M Drmyson and D Crowther

Christie Hospital & Holt Radi~u~ Institute Manchester, England TREATMENT OF LYMPHOID CELL MALIGNANCY USING ZN-II4M LABELLED LYMPEOCYTES Animal experiments have shown that In-ll4m labelled lymphocytes can be used to control the proliferation of lymphocytic leukaemic cells. We have investigated the feasibility of using this technique in humans for the treatment of generalised lymphoid cell malignancy. Seven patients with actlve non-Hodgkin's lymphom~ were injected with tracer doses of between 1.4 22.7MBq autologus labelled lymphocytes. The cells cleared rapidly from the vasculature,with only 15% remaining in peripherial blood at 30 minutes, The total daily excretion was <1% of administered activlty. Bone marrow uptake was estimated from biopsy sa/aples and was found to he <5% of administered activity. Quantitative analysis of sequential gamma camera images from 3 patients who received the highest activities showed that radioactivity localised preferentially in the spleen and to a less extent in the liver. Activity in the spleen decreased slowly, with a biological half life of 34±9 days. Radiation dose calculations based on pharmacokinetic data from these tracer studies indicated that with acceptably low whole body radiation doses,circulating lymphocytes could receive therapeutic doses from the splenic radiation field. A clinical therapeutic trial of the technique is now underway. The first 3 patients received doses of 73,104 & 211MBq. Pharmacokinetic studies showed similar results to the tracer measurements. A significant therapeutic response (improvement in palpable disease and fall in white cell count)was only observed in the patient receiving the highest activity. Unfortunately thls patient also developed a profound thrombocytopenia and this may represent the dose limiting toxicity of this procedure.

185

g. S e n e k o w i t s c h , P.Schmid, ~.Kriegel, H.W.Pabst

S.Mbllenst~dt

~uklearmedizinische Klinik und Poliklilik d e r T e c h n i s c h e UniversitMt M~nchen, %bt.ffir N u k l e a r b i o l o g i e , G S F M~nchen,FRG ~ONTINUOUS APPLICATION V l A A N I.P, IMPLANTED MINI PUMP INCREASES TUMOR IPTAKE OF RADIOLABELED MONOCLONAL ANTI30DIES [n addition to t h e d i a g n o s t i c use of cadiolabeled monoclonal antibodies there are promising indications that 4Abs l a b e l e d w i t h a suitable radioisogope m a y b e a p p l i e d f o r r a d i o i r m n u n o t h e rapy. T u m o r u p t a k e of M A b s , h o w e v e r , is ~fhen to low to achieve radiation ab3 o r b e d d o s e s h i g h e n o u g h to d e s t r o y a l l ~umor tissue. In t h e p r e s e n t s t u d y a t gempts were undertaken to i n c r e a s e t h e i p t a k e of 1 - 1 3 1 O C 1 2 5 M A b i n i.p. g r o ~ing t u m o r s , t h a t h a d been established ~y i.p. i n j e c t i o n of 5 m i l l . c e l l s of a luman ovarian carcinoma. In p r e v i o u s studies it has been determined that humor uptake was much higher after i.p injection of t h e M A b c o m p a r e d to the i.v. i n j e c t i o n . Therefore 1 . 8 5 M B q of ~he M ~ w a s a p p l i e d e i t h e r i.p. or c o n ~ i n u o u s l y f o r 48 h v i a a n i.p. i m p l a n ted mini-pump. A f t e r a n o t h e r 24 h t h e motivity concentration in the tumor 5 i s s u e of t h e animals implanted with she p u m p s h o w e d a n i n c r e a s e of 40% in zomparison to the animals having receized a n i.p. i n j e c t i o n . First results on r a d i o i ~ m ~ u n o t h e r a p y a f t e r i.p, i n j e c t i o n ~f 34 M B q of t h e labeled MAb shewed a ceduction in t u m o r m a s s of m o r e than 50% 42 d a y s after beginning of the ~herapy. The i n c r e a s e of t u m o r u p t a k e ~f a MAb labeled with a suitable ~-emitter by continuous application via ~n i m p l a n t e d p u m p c a n p o s s i b l y lead to radiation absorbed dose which could Restroy the whole viable tumor tissue.

86

R. Taillefer, A. Gagnon, J. Gr~goire, L. Laflam~ee, D.C. Phaneuf, J. L~veill&.

U. Buell r P. Dupont, N.J. Kaiser, hans, R. Uebis, H.J. Simon

H6tel-Dieu de Montreal, Montreal, QuA~ec, Canada.

Depts Nucl Ned and Cardiol, Technical Univ. of Aachen, Depf lot Ned, Teaching Neap Dueren, FRGermany

Departments of Nuclear Medicine and Cardiology, Guy's Hospital, London, England,

EXERCISE/REST Tc-99m KKIBI-SPECT TO DIAGNOSE CORONARY HEART DISEASE (CHD): RESULTS OF g 4 HOURS PROTOCOL USING QUANTIFICATION

MYOCARDIAL PERFUSION IMAGING: SIGNIFICANCE OF ABNORMAL TC-99M MIBI EXERCISE LUNG UPTAKE.

COMPARISON BETWEEN REST-STRESS AND STRESS-REST INJECTION SEQUENCES FOR SAME-DAY INJECTIONS OF Tc-9gm METHOXY ISOBUTYL ISONITRfLE (MIel) FOR MYOCARDIAL TOHOGRAPHIC IMAGING. It has been shown that two MIHI injections (rest and stress) can be performed in an interval of less than few hours using two different doses of MIBI. In order to evaluate and compar, two sequences of MIBI injection, rest-stress (R-S) and stress-rest (S-R). 16 patients with either abnormal TI-201 scan or eoronarography were studied with both R-S and S-R protocols, The R-S was performed as follows: MIBI (7mCi) was injected st rest. SPECT study wesperformed 60 min. later (180 c . 64 projections, 30 see./ projection). Immediately after, patients were injected at peak stress with 25 mCi of MIBI. imaging was repeated 1 hr. later. Patients wer, submitted to the S-R protocol 3 days later: ima gins at 1 hr. after a 7 mCi injection at stress followed by an injection of 25 mCi of MIBI at rest (acquisition identical to R-S). Myocardia sections were reconstructed in the transverse, coronal and sagittal planes. A total of 288 sea meats were interpreted blindly by 3 observers. There was a~ agreement in 247/288 (85,8%) sag- i ments. However, 24 segments (8.3%) judged ischemic on R-S were called sear on S-R. Stress images from both protocols were judged similar in 15 patients, In 3 patients rest images were judged normal on the R-S protocol while they were found abnormal (false positive) in the S-R In conclusion, when using a short-time inter val between two MIBI injections, it is preferable to do a R-S sequence since the rest image performed initially represents a "true" rest study, which is not necessarily the case with the S-E sequence.

E. Klein-

Tc-99m HHIBI (bexakis-methoxyisobufylisonitrile), a potent myocardial perfusion marker, was employed, in a 4 brs protocol to elucidate its d/agnostic accurracy and the validity of dedicated quantification to evaluate CRD. 150 Ngq Tc-99m EHIBI were injected during maximal exercise (E}. i hr later, E-SPECT was done (2 heads, 2x180 ° orbit). Thereafter, 850 MEg Tc-99m HMIEI were injected at rest (R) a~d a second rotation was performed 2.5 hrs later (R-SPECT). 23 target-like ROI evaluated shortaxis cuts (2 pix) by computing a perfusion index at E (PIE, %regional ~ptake from myocardial maximum) and the relative coronary perfusion reserve (PR, half-life and dose-corrected regional uptake g-to-E related to ratios of upta~s-differences (E minus E) for minimum and maximum uptake areas). Correction of R images for remai,ing E cts was done. 40 pts with coronary heart disease (CHD] were examined. Coronary angiograpby findings subdlvided 2 groups (g: stenosis, O: occlusion). Visual findings displayed irreversible (I) or transient (T] myocardial defects. Sensitivity by visual findings was 84g (100% for O, 67-89% for graded S). PIE (norm: 100g) or PR (norm: 1.53±0.12) in CHD were (mean±gD)(*§p(.01): Anglo: gtenosis Occlusion Defect PIE(%) PE PIE(~) PE I SHill .65±.06" 32±10 .29f.18" T 71fli .6g+.14~ 57+11 .19±.ig~ indicating additional discrimination. We conclude, that Tc-99m HMIBI-SPECT may be employed in a 4 hrs, TI-201 like protocol with high sensitivity. Additional diagnostic access may be gained by computing a regional correlate tn the r n r n n a r v np)fu~nn ~ R ~ r v m

Y.C. Najm, M.N. Maisey,

A.D. T i ~ i s ,

E. 5owton,

Tc-99m MIBI is eharacterised by good myocardial uptake and rapid Lung clearance. Perslstenly increased lung uptake at i hour after exercise dosing was noted in some patients, and was thus investigated in 60 patients with coronary artery disease (group I) and in 10 normal volunteers (group 2). Lung uptake was considered as the mean activity in the left upper lobe of the lung and was expressed as a percentage of left ventricular activity as measured over the hottest myocardial segment, and was termed 'lung index ~. Exercise lung index was higher in group [ than in group 2 (37 ~6% vs 32±5%, p<0.001). Resting lung index was not significantly different between both groups. Normal exercise lung index was defined as less than or equal to 42% (mean for group 2 + 2SD). Accordingly exercise lung index was abnormal in 17 patients from group 1 (group IA) and was normal in the remaining 43 patients (group ig). In all patients 14 variables were evaluated. 0nly 3 were significantly associated with an abnormal lung index: the number of diseased vessels per patient (2.7±0.5 vs 1.8±0.8, p
254 187

,• PoOio*, •G. Castellano*, , MIT. Spinnler°, Righetti^, G. Avataneo*, G. Leone °, $. Ciaroni", P. Morello', G.L. Turco* "Servizio di Medicina Nucleate- Univetsi~ di ToIino (I) °Servizio di Cardiologia - Universit~ di Torino (I) "Centne de Cardiologie - HCUG - Gen&vs (CH)

MYOCARDIAL IMAGING WITH 99mTc-MIBI: CORRELATION WITH CORONARY ANGIOGRAPHY AND STRESS TEST ~gmTc-MIB] (RP-30) has been recently proposed as a new agen[ for

'myocardialimagingl RP-30is quteklyconcentratedin myocardtem,according Io blood Row and redialribu~n does not occur. We s~d~ed83 angteouspe~enm(pts - 10 I, 53 m), age 57±10 years (mean _+

1 8.Ol), S U S ~ O[ ~V[~ corcmaryartery disease (CAD}, ale of them wit~ a coronary angiography and a left vefltricutegrsphy. Planar scingg;aphic images were registered in two differenl days, in 3 incidences, after two inj~c~onsof RP~30:one al msl a,4 [he d/~er at ~e peak of a bydde sb'ess test. Co onary angi~J aphy was a~o real (slenos[s >_70% or al leaal one major coronary adery) in 42 pls. Among them, 19 pls had alreadysuffered from a previous myocardial infarction (MI), Coronary arleriogram was considered normal in 21 pts, 7 of which with MI, 8tress ECG was abnormal ST-segmenldepression -> 0.1 mV) in 21/42 pb having abnormalcoronary arturiogram and Jn 5/21 "normal" pls. The sthd/igraphic findings were considered abnormal if there was an hypope~tusionon Iwo cod/igous segmenls and/or in two incidences. We eva]ualed the correspondence b~twesn scinligrabhic findings and the tecalizagon of coronary artery stunc~thaed betweenslress ECG and RP-30 Ior~liza~onof abnormalthes iAccording fo coronary arteriogram, RP-3O specificity (Sp) was 81% in "normal" pte and raised up to 93% in ptu wilh both normal coronary angtegram and left vsntricalography.Persistent or Iransiso[ hypopertusten, I markers el scar or iscbemia, were p~esentin 39142 pIs with CAO (93%), while only 2f showedabnormalstress ECG.The overthlsenaliivily(8e) and 8p were good (73% and 7g% respec~vely)with single vessel disease p[s ~hewingthe best resufls (So 100% and Sp ~6% th pts with prior MI; 8e 82% and Ep 68% in ptu w/thou1MI). In mulfivesalaise~e pts it was gleandilbcug to establish which adery (RCA or LCx) perlus~s the cardiac segmenl abnormal on RP-30 images. With ]his purpose Iom~raphic tuabniquewas appliedin some pts and the first r~ults are underJnvestiga~on. ~P-30 images were abnormalin 21/31 pts with normal sb'e~ test (ECG or I symplon~): 15 of them showed significant CAD al coronary arturtugraphy. Among the remaining six, ~ve had a LAD stenosis _> 50%. Salnligraphio laldingswere normal in 3/32 p[s wan abnormalstress test: two among ~em did no[ show algnJgcanlCAD, while the other one bad a three-vessel disease. In pls with abnormal sb'ess ECG, Ih¢re was a good agreemenl between [he ECG and [he sein~graphicIo~llza[ion o[ abnormalities. !ConcltlsiOg. This prerimtearystud'/shows thai: 1. RP-30 has good gtehal I sensilte]ty and specificity in detec~ng CAD; 2. sensitivity and spec~city improvegreal]yin singlevessel disease pts, peNiculm'lyif LAD is involved; 3. [he physJ~l properties of mSmTcgive RP-30 new interesting prospects in a~esalng lea ventricuter thnctJenand pedormthgtumographicstudies.

190 KOTZKI P,O. I, COUBES p.3, ZANCA M. 1 , VALMIER j,2 .1 ROBSI ,,. , BALDY MOULINIEE M.2~ FREREREAO p.3 i- ~,~decine Nuel~aire, Lapeyroni@, Montpeliier, FRANCE. 2- E.E.G. et Explorations Fonctionneldes du Syst~me Nerveux, Gui-de-Chauliac, Montpellier, 3- NeuroehirurEie, Gui-de-Ch@ulisc, Montpellier. CONFRONTING OF 2~ORPHOLOGICAL (MEI) CEREBRAL I~dAGES WITH FUNCTION~AL ONES (CBF WITH H,qPAO SCINTIGRAPNY) : ~ETRODOLOGICAL ASPECTS The cerebral imaging henceforth depends on an efficient complementarity between morphological 'data (as obtained by CT scanning or ~RI) and functionnal ones (cerebral blood flow with isotopic methods). For the confronting to be effi~ cient and For a EOOd (clinical) interpretation "be be made,one has to insure a pe~i'ecb superimI positlon between the difFerent slices obtained from the different techniques, with the help of i a same standard for acquisition and processing of the images, We studied the possibilities of obtainin E the 'best juxtaposition with 3 methods : to impose, with a craniostatic system adaptec leo each patient, some ~uiding-ma~ks to make possibl~ the same positioning of the head durin beth acquisitlons. , To place around the craniost~tlo system a fixed tubular device filled up with a 99 mTc and CuSO~ solution mixture, thus permettinE a 3D registering in ~[RI and tomoscintigraphy. • To rotate in a second time, post-acqulsition the slices issued from R~PAO with help of !&HI sa~ittal or transverse scoot views, or with the tubular device. First results show that : • Anatomical location oF CBF anomalies, and their superimpositlon with the corresponding ones observed in ~EI are plainly improved, namely when compared to a systematic reorientaeion of the brain in tomoscintigraphy alone. • Reorienbation of the H2.[PAO slices from ~EI sagittal and transverse views is satlsFactory but the help of the tubular device oF the craniostatic system permits to adjust the slices dimensions and to prepare a real superimposltior on the TV screen. l

188

189

Q.S. Li, G. SoloN, D. Franceschi, H.N. Wagner,

Q.S. Li, Jr., L.C.

G.

5olot, Becker.

T.L,

Frank,

H.N,

Wagner,

Jr., L.C, Backer.

The Johns Hopkins "Baltimore, MD.

The Johns Hopkins Medical Institutions, Rmlf~mnrP Nn COMPARISON OF R9-30 AND SQ 3201h: MYOCARDIAL ' UPTAKE AND REDISTRIBUTION IN DOG8 WITH T~LPORARY CORONAKYARTERY OCCLUSION. P~P-30 (HF, Dupont) and SQ 32014 (SQ, Squlhh) are two promising but structurally different Te-99m perfusion agents bein E evalu~eed for myocardial imaging. In order ro compare the uptake and redistribution of Khese aEents , anesthetized dogs received radioactive microspheres (MS) after 1 min coronary occlusion to measure regional myocardial flow, along with IV injections of TI-201, and RF or S~. The activity of each ~racer was measured in myocardial seJ~ples taken from the ischemic zone, expressed as a fraction of nmnisehemic activity. At 5 mln post injection (no reflow), uptake of TI, RF and SQ were all hiEhly correlated with flow (TI-.0g+.57 MS, r-.99; Rg-.Of+.84MS, r-.99; SQ-.12+.76Me, r-.93), alKhouEh each tracer demonserated an excess of activity at low flows and a deficit ae h i g h flows. For MS<.20, mean tracer con~ent was 2.7 times M8 content for TI, 3.0 for R9 and 2.8 for SQ. For M8>1.0, the val~es were .93, .86, and .8~. In dogs ischemto for 6 min and reperfused for 3 hr, TI, RP, and SQ contents before reflow in the center of the ischemie zone averaged .17, .19, and .17. These values increased to .91, .23, and .48, respectively, arbor 30 m i n and Ko 1.02, .40, and .57 afeer 180 min. We ¢oncl~de; (i) eerly myocardial u~take of RF or SQ correlates highly with MS flow hut like TI, both tracers overestimate low flows and underestimate high ones, (2) both tracers demonstrate redistribution, with partial reversal of perfusion defects over time, (3) redistribution of SQ is greater Char RP, although both are considerahly less than TI.

191

Insbitueio~s

SERIAL REST ~D DIPYRIDAMOLE TOMOGRAPRII MYOCARDIAL PEKFUSION STUDIES WITH THE RAPIDLY CLEAKING Tc-99m AGENT 8Q 30217. SQ 30217 (SQ), a novel Te-99m perfaslon agent with rapid myocardial clearance, could allow serial studies of myocardial perfuslon without correction for residual background activity, To evaluate the feasibilley of this approach, anesthetized dogs underwent simultaneous injection of radioactive microspheres (MS) and 5-7mCi SQ, followed by tomographic imagln~ (30 VieWs over 150 °, 20 see/view, heglnnin E 1 mln post injection). In 6 dogs the circumflex artery was partially occluded and the dogs were studied at rest and followin E dlpyridamole (D). After sacrifice tissue MS content in the ischemic region was compared to scinClgraphic 8Q uptake (both expressed as a Ifraction of nonischemic region), A perfuslon defect was present in 2 animals at rest and Ideveloped or worsened in 5/6 after D. A~ rest, isehemlc zone activity averaged .55 for MS and .51 for SQ; after D the values fell to 1,30 and .53, respectively (p<.05 vs rosE) The dog with normal SQ imaEes also had normal flow by MS Flow and SQ were closely correlated (r-.55 for rest, r-.96 for D) but SQ consistently exceeded flow (p<.05) in the ischemic zone, In one do E with directly measured tissue SQ activity, the agreement between MS and 8Q lwas much better, suggesting that scatter from the liver may "have distorted bhe-- imaEes. IAdditional imaEing studies showed that after D, SQ uptake was increased (l. Tx) and clearance was faster (50% by 7,5 mln vs 20 miD). We conclude that SQ represents a premising myocardial perfusion agent with unique properties that may prove valuable in the clinical settle E ,

192

J,T. Kuikka O. Nousiainen Departments physiology, Finland

Medical

E.

Ldnsimies,

A.

Y l i n e n and

of C l i n i c a l P h y s i o l o g y and University Central Hospital,

KINETIC ANALYSIS OF EPILEPSY

Tc-99m

NeuroKuopio

B M Mazoyer, M Leva~seur, ~k Syrota, C Prenant, J C Baron, G Sette, B Verrey and Y Samson. Service Hospitaller Frdd~rie Joliot, DG.partement de I Biologie, Commissariat l'Enetgie Atomique, 91406, O r ~y , France.

HM-PAO IMAGING IN

R a d i o n u c l i d e b r a i n i m a g i n g has improved t o l o c a l i z e an e p i l e p t i c focus• Te-ggm HM-PAO has been used t o show both f r o n t a l and temporal lobe e p i l e p s y . The aim of t h i s s t u d y was t o validate HM-PAO as a marker o f c e r e b r a l blood f l o w (CBF) i n e p i l e p s y . Sixteen patients with clinical and EEG f i n d i n g s of e p i l e p s y were s t u d i e d in interictal st a q e . The mean age o f the p a t i e n t s was 25 y r ( 1 6 - 3 7 ) . The p a t i e n t was l y i n g i n su p i n e and 450 MBq o f Te-ggm HM-PAO was i v . i n j e c t e d . A dynamic s t u d y i n A P - p o s i t i o n was performed. Both hemispheres ( r e s i d u e } and the a o r t i c arch ( i n p u t ) were sel e c t e d and d e c o n v o l u t i o n t e c h n i q u e was used to f i n d the t r a n s f e r f u n c t i o n . S e i j e r s e n ' s method was a p p l i e d t o e s t i m a t e t h e f i r s t - p a s s extract i o n (E). I m m e d i a t e l y a f t e r the dynamic s t u d y a SPECT-study was u n d e r t a k e n . Transaxial slices were a n a l y z e d v i s u a l l y and w i t h an o p e r a t o r - i n t e r a c t i v e computer program u s i n g c i r c u m f e r e n t i al p r o f i l e t e c h n i q u e . Regional a c t i v i t y was expressed as p e r c e n t of maximal c e r e b r a l a c t i v i t y i n 12 segments. Regional r e d u c t i o n s below 2*SD of t h e normal mean were assumed to be p a t h o l o g ical. The r e s u l t s showed t h a t E was s i g n i f i c a n t l y smaller (0.74 + / - 0.03) i n the segments w i t h reduced CBF than i n c o n t r a l a t e r a l hemisphere (0.86 + / - 0 . 0 2 ) . A b n o r m a l i t i e s were p r e s e n t on 11/16 pts of SPECT-studies. Hypometabolism c o u l d be e i t h e r f o c a l ( 7 / 1 1 ) or d i f f u s e ( 4 / 1 1 ) i n the a f f e c t e d hemisphere• The r e s u l t s suggest that Tc-99m HM-PAO i s p a r t i a l l y diffusionlimited (E is not a c o n s t a n t ) and f o c a l SPECTf i n d i n g s were w e l l c o r r e l a t e d w i t h the EEG and clinical total locations.

I M O D E L I S A T I O N O F 11C-L-IVIETHIONINE P E T KINETICS IN T H E H U M A N BRAIN. We have tested the compatibility of 5 compartmenta models with nC-L-Methionine brain kinetics obtained in 16 fasted subjects. The following models were fit to 48 minute dynamic P E T data using the deproteirdzed arterial p l ~ m a as the input function: I : k,,kp,k~

kl,k~,ka,k~, III:kz,k,,k,,k,,k s IV: kl,k=,ka,ks,ke

%"J'v-. I(1 ~ k..J

Ks > k...J

II:

K6~

l Ks

(D

Using Akaike's Information Criterion (AIC), model I compatibliity was found less than other model compatibilitles (p _< •005, Sign test). Although AIC values did not differ for models II, III, and IV, 5 rate constant models exhibited larger parameter standard deviations values are mean in m i n -z :L s.d., k," in mi s i n -1 g-Z]; I II IlI IV kl .028 4- .006 .032 -4- .007 .033 4- .008 .033 4- .008 k2 .065 4- .016 .13 4- .06 .19 4- .12 .18 ±.11 ka .0554-.016 .12 d= .06 .17~=.14 .14=t=.07 k4 .015 4- .Off/ 10 + .19 k5 .066 t_ ,051 .14 :h .07 ks .050 4- .034 In conclusion, a m i n i m u m of four rate constants appears to be necessary and sufficient for an accurate description of nC-L-Methionine brain kinetics observed with P E T over 48 minutes in fasted subjects.

255 193 I) Inst. 0f Medicine, and 2) Inst. of Chemistry, ~ u c l e a r R e s e a r c h C e n t e r Jiilich, FRG ~HOLE BODY DISTRIBUTION OF THE D~R E C E P T O R LIGAND |~SFIFLUOROETHYLSPIP~RONE [Z~F]Flueroethylspiperone (FESP) has been used a s a l i g a n d for m a p p i n g of D g - r e c e p t o r s with 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) ( C o e n e n et al., Life Sci 40:8141987)). T h e p r e s e n t s t u d y d e s c r i b e s t h e w h o l e - b o d y d i s t r i b u t i o n of FESP, 1 6 0 - 2 6 0 MBq of FESP w e r e i n t r a v e n o u s l y i n j e c ted into 4 p a t i e n t s with slight e x t r a p y r a m i d a l s y m p t o m s . Using a PC4096 ~omograph w i t h a n optimum s p a t i a l r e s o l u t i o n of 5mm a n d s i m u l t a n e o u s l y m e a s u r e m e n t of 15 p l a n e s , s c a n s were a c q u i r e d of t h e b r a i n , t h e l u n g / h e a r t r e g i o n , the liver region, and the abdominal region. Attenuation c o r r e c t i o n w a s b a s e d on t r a n s m i s s i o n s c a n s u s i n g a r o t a t i n g p i n s o u r c e . Until 200 rain p.i, blood a c t i v i t y was m e a s u r e d by blood s a m p l i n g a n d u r i n e was c o l l e c t e d . Only 1% of the total administered dose (TAD) was found in the brain at 180 min. The high regioma] s e l e c t i v i t y of ~BFESP for t h e s t r i a t u m a n d p i t u i t a r y was c o n f i r m e d b y a n u p t a k e of 0.008% TAD p e r cm ~ a n d 0.004% TAD p e r cm 2, r e s p e c t i v e l y , in r e l a t i o n ~o a d o s e of 0.0007% TAB p e r cm ~ in t h e r e s t of t h e b r a i n . L i v e r u p t a k e was 19~ TAD a t 70 min a n d decreased to 16% TAD a t 200 min. T h e c o r r e s p o n d i n g d a t a for g a l l b l a d d e r w e r e 9% a n d ]4% TAD, 9% TAD w e r e f o u n d in t h e u r i n e a t 20O min. Two v e r t i c a l u n i d e n t i f i e d s t r u c t u r e s in t h e v e n t r a l p a r t of t h e a b d o m e n s h o w e d a r a t h e r h i g h u p t a k e of about 1% TAD. There is neglible uptake in the mart and in the lung, Blood activity decreased from 4% T A D at gO sin to 2.5% at 200 sin. A rather low bone uptake indicates a si0w metabolism forming free fluoride. Thus, the neuroligand I~eFI-FESP which proves to be v e r y u s e f u l for c e r e b r a l Dz r e c e p t o r mapping shows significant accumulation in a few c r i t i c a l o r g a n s , w h e r e t h e r a d i a t i o n dose is mainly governed b y the physical half-life.

196 R.BERBERIC~M.SUTTEN,

195

194

H.Herzog~, H.H,Coenen:, T.Kuwert ~, K,O.Langen ~, G.Stgcklin~, L,Feinendegen*

G. Blomqvist I, L. Erikssonl, 2, L. Farde3, ~ . Persson3 Department Departmem£ Department Karoiinska

oF Cl~n. Neurophysiology of Neuroradiology of Psychiatry and Psychology, Hospital

DETERMINATION OF RECEPTOR DENSITY, ASSOCIATIONAND DISSOCIATION RATE CONSTANTS FOR RADIOLIGAND5 WITH PET - A COMPARISON BETWEEN THE EQUILIBRIUM AND THE KINETIC APPROACHES

To o b t a i n the receptor d e n s i t y , gmax, the assoc i a t i o n and d i s s o c i a t i o n rate constants, ken and koff, and the equilibrzum dissociation constant KD (= kofF/kon) for the dopamine D2 receptor antagonist (11C)raclopride, and the (11C) labeled benzooiazepine antagonist RO IS-17gg, a kinetic analysis was applied to regional time-activity data obtained with PET. To obtain reliable estimates of the parameters, at least two experzment~ with different specific activities are requzred The analysis was performed in two steps; First the contribution of free radioligand was estimated and subCracted f~om the observed time-activity curve and thereafter the parameters were Tilted to the resulting curve. The time course of the activity of free radloligand was estimated eiiher through use of a reference region con sidered to be Free from specific binding~ or through use of the rate constants (kl and k25 For transport of the ligand accross the bloodbrainrbarrier. In case of gO ]5-1788 kl and k2 were obtained from an experiment with high speei Tic ~ctzvity (tracer dose) in cemblnation with protection, whereas in case of (11C)raelopride these parameters were obtained from an experiment with the inactive enantiomer (11C)-FLB472. To obtain kl and k2 the tzme-aetivity curve of the radioligand in arterial plasma is required. The results from this kznet~c analysis and From the traditional equilibrium method were compared In case of (11C)raelopride the two methods were Found to produce similar Bmax and KD. In case ol RO 15-1788 the two methods gave szmilar Bmax but somewhat different KD.

197 E.OBERHAUSEN

Radiologische Universit~tsklinik Abteilung for Nuklearmedizin 6650 Homburg/gaar Imaging o£ inflammatory labelled monoclonal antibodies.

lesions mzth Tc-ggm anti-granulocytes

In 15 patients with suspected inflammatory lesions we have performed scintipraphie studies with Te-99m labelled monoclonal anti-granulocytes antibodies in comparison with 111 ln-oxine labelled leucocytes. In 55 patients we have onlyused the Tc-99m-Mab, The Mab Bgaznst human granulocytes ~e used was the B~ 250/185 as a t~o component Nit From the RCL of the Farb~erke Hdchst. All patients examined were informed of the procedure and gave thelr consent. After znjectzon of the Tc-99m-Mab and the iii In-oxine labelled leucocytes scintigraphies of the mhole body were performed immediately, after 3-4 hours and 20-2h hours. At the same times the cell bound activity and total activity in the blood was measured too. In 60~ we found a positive result with both methods and in 40~ a negative one. This means, that there was a corespondence in a l l cases, The cell bound activity of Tc-ggm-Mab in the blood raised From 12% immediately after injection to 18% after 20 - 2~ hours ~ith s rather large deviation From patient to patient~ which was undependent from the leucocytes count per ul. Concerning ~hole body activity distributzon the#e was a high uptake of the Mab in liver and bone metro#. The uptake in the spleen #as less than with ill In-oxine leucocytes. Our results proof that 99m-Tc-Mab-antigrsnulocytes antibodies are well suitable For scintiqraphic visualization of znflammator lesions.

A.Steinstr~Ber, H.U.Schorlemmer, A. L.Kuhlmann, and K. Bosslet

G.Lucignani, K.Schmidt, E.Palombo, K.Mori, T.Nelson, and L.Sokoloff

T.Jay,

Istituto Teenologie Biomediche Avanzate, CNR, Milano, Italy; Laboratory of Cerebral Metabolism, NIMB, Bethesda, MD, U.S.A. REFINEMENT OF THE KINETIC MODEL OF THE 2[14C]DEOXYGLUCOSE METHOD TO CONFORM WITH INTRACELLULAR COMPARTMENTATION OF GLUCOSE-6PHOSPHATASE IN BRAIN The 2-[14CIdeoxyglucose ( D O ) method for measurement of local cerebral glucose utilization (ICMRglu) assumes that in the rat dephosphorylation of 2-[14C]deoxyglucos~-6 phosphate (DG6P) does not become a significant factor until 45 minutes after a DO pulse; thereafter it increases in magnitude. The observed time course of a lag preceding a progressively increasing loss of DC6P is consistent with a rate-limiting step ahead of the dephosphorylation of DG6P. Because of the recent report of the absence in brain of a translocase that transports hexose phosphates from eytosol to the cisterns of the endoplasmie reticulum, a 5 rate constant (5K) kinetic model was developed in which the loss of label occurs in two steps; 15 transport of DG6P from eytosol into the cisterns of the endoplasmdc reticular; g) hydrolysis of DO6P by G6Pase, Five rate constants were estimated from a group of rats administered DG and killed at various times between 2.5 and 120 minutes. IDMRglu was estimated by use of this model in a second group of rats killed between 45 and 12g minutes, and the results compared to values obtained by use of the original DC model (3E) and the model previously proposed for PET in which loss of DO6P is considered to be a first order process (4K model). ICMRglu was underestimated at times beyond 45 minutes by all the models, but less so by the 5K model. In conclusion, the 5K model, which more closely parallels cellular compartmentation, improves estima=es of ICMRglu when procedures longer than A5 minutes are required with quantitative autoradiography.

198 Schwarz,

A. L a u e - S a v i c , A. B d r n e r , D.L. M u n z , D. E m r i e h Department University

E. Voth,

of N u c l e a r M e d i c i n e , of G o e t t i n g e n , F.R.G.

HOEEHST AG, D-6230 F r a n k f u r t / M a i n , FRG; BEHRINGWERKE AG, D-3550 Marburg/Lahn: FRG TARGETING OF GRANULOCYTEg BY-A NOVEL MONOCLONAL ANTIBODY LABELLED WITH TC-99m The monoclonal CEA-NCA s p e c i f i c antibody BW B5D/I83 reacts w i t h more than 90 % of the d i f f e r e n t granulocytes found i n the peripheral blood. This antibody can be used f o r immunos c i n t i g r a p h i c d e t e c t i o n of i n f l a m m a t i c l o c i . I t e x i s t s as a ready f o r use k i t f o r l a b e l l i n g w i t h Tc-99m. A chemiluminescence assay was e s t a b l i s h e d to determine the a c t i v i t y of granulocytes by the rate of oxygen r a d i c a l s secreted. I t is shown that the function of cells is not affected by the MAb. With Cr-51 labelled tumor cells i t is demonstrated, that the MAb has no cytotoxic properties, neither of the cell mediated type nor complement dependent. An i n v i t r o b i n d i e g assay was used, t o q u a n t i f y b i n d i n g constant (2 x E9 I / m o l ) and number of s p e c i f i c epitopes on granulocytes (2 x E5). In case of complete s a t u r a t i o n of the epitopes, about l ms of the MAb would be f i x e d to the granulocytes of the p e r i p h e r a l blood (4 x E6 c e l l / m l , 5 I t o t a l b l o o d ) . But the i n v i t r o assay showed a 50 % b i n d i n g of MAb at concentrations being about 50 times lower. The d e t e r m i n a t i o n of r a d i a t i o n dose to humans can o n l y be performed i n d i r e c t l y . Taking as a basis on the one side the k i n e t i c s of a t u m o r s p e c i f i c antibody not r e a c t i n g w i t h any blood c e i l s , and on the other side the ~ehaviour of l a b e l l e d 9ranulocytes known from studies w i t h in v i t r o l a b e l l i n g methods, so i t =an be shown, t h a t the r a d i a t i o n dose is reduced to about 15 % compared w l t h Ga-67 or in-Ill (oxine). The antibody BW 250/]83 is a save a l t e r n a t i v e to in v i t r o l a b e l l i n g of granulocytes f o r J e t e c t i n g inflammations.

SIMULTANEOUS COMPARISON OF BIODISTRIH U T I O N O F IIIIN-OXINE G R A N U L O C Y T E S (OG) A N D 9gMTC-A/qTIGRANULOCYTE A N T I B O D Y (AGAB). S i n c e A G A b is m u c h m o r e p r s c t i c a l comp a r e d to OG, b o t h a g e n t s w e r e s t u d i e d s i m u l t a n e o u s l y in IO p a t i e n t s (pts) w i t h s ~ s p i c i o n of i n f l a m m a t o r y b o n e lesions. M e t h o d @ : S e r i a l m e a s u r e m e n t s of a c t i ~peripheral blood and over different organs and inflammatory l e s i o n s w e r e p e r f o r m e d d u r i n g 24 hours. Activity in s t a n d a r d i z e d ROIs over each organ and suspected inflamm a t o r y l e s i o n s w a s e x p r e s s e d as cpm/pixel. R e s u l t s : B i e x p o n e n t i a l d e c r e a s e of sca n p e r i p h e r a l b l o o d for A G A b w a s s i g n i f i c a n t l y f a s t e r c o m p a r e d to (OG): Fast comp.: 1.4 (4,5), s l o w comp.: 7.3 612.6] hrs. E x c e p t f o r h o n e m a r r o w , organ to b a c k g r o u n d r a t i o s ( m e d i a n v a l ues at m a x i m u m (4 hrs)) w e r e s i g n i f i c a n t l y l o w e r f o r A G A h c o m p a r e d to (OG); s p l e e n : ig 6515, liver: 14 6405, b o n e m a r r o w : 9 (55, k i d n e y s 3 (3), w h e r e a s it w a s in t h e s a m e r a n g e in inf l a m m a t o r y f o o l f o r b o t h a g e n t s (3.0). A c t i v e inflarmaatory foci c o u l d be l o c a l i z e d u n e q u i v o c a l l y in all i n s t a n c e s w i t h e i t h e r a g e n t (5 pts). Conclusions: From a biokinetic point of v i e w A G A b is s u p e r i o r to OG. A h i g h e r u p t a k e of A G A b b y b o n e m a r r o w m i g h t c a u s e d i f f i c u l t i e s to d e t e c t l e s i o n s i n s i d e o r c l o s e to t h e s e areas.

256

K.K.Solanki, S.J.Mather, Jones, E.E.Britton,

St Bartholomew's LoDdon, ECI UK

201

200

199 M.gl-Janabi,

Hospital,

A.K.P.

Heat Smithfield

SIMPLIFIED PREPARATION OF Te~99m HEXAMETAZIME LABELLED LEUCOCYTES AND QUANTIT~TION OF THEIR CHEMOTAXIS IN DIFFERENT PATHOLOGICAL STATES. A modified technique of Peters A,M., Lancet 1986 it: 946 has been routinely used within the Department. It requires only 20 ml blood and under an hour to produce a high activity yield (c.400 MEg) of labelled leucocytes. A rapid In-process chromatography with Whatmans DEal don exchange paper run in Butanone~ and a rapid method for leucocyte cbemotaxds has been developed. The ehemotaxis chamber is a pair of disposahle syringes, one containing labelled leucocytes and the other endotoxfn, attached to a unit containing two i0 micron filters. Second ~ilter from the leucocyte sgringe measures zbemotatic viability. In rive integrity of labelled leucocytes is shows by lack of lung sequestration and high splenic uptake. Successful imaging has been achieved in patients with abscess, inflammatory bowel disease and gheumatoi( joints. There is a linear relationship bePween leucocyte count and labelling efficiency in normal and abscess patient, but not with rheu~atodd patients. Significant differences in shemotatdc behaviour occur accordlng to the disease status. Patient No. mean on second s,d. P fil~er ~ormal 5 3.41 1.058 %bseess 5 7-71 1.897 ~0.05 Rheumatoid 5 19.27 3,130 ~0.01 Rheumatoid on cortisone 3 0.0 ¢0.05 ~hese variations dn behaviour should be taken into account when desdgning labelling protocols and patient studies.

202 l p,J,Vassi~skos,Ch.Plerrakess,N.PaliikaYskis,Th. Gori las,M.Pro rant i, B.Michalopoul on, G. Barbslias Depts of Nuclear Medicine,Medical Physics and Urology,UniversitY of Pstras Medical School, Pgtrae Greece,

KNOWLEDGE BASED SYST~4 (KBS) F0R RADIONUCLIDE RENOGP~M [RB) The aim s~ this study was to create a KBS applying in microcomputer using parametric quant i t a t i v e analysis of RR curve and well coded diagnostic rules based both ~n Nuclear and Clinical Medicine experts. Materisl~: Patients : Our electronic archive consists of 450 p a t i e n t s [94 were normals clinically and laboratory t e s t e d ) l , R R '~'TcDTPA was performed under a special detailed clinical protocol, Instruments ; Microcomputer 1,2 MB RAM with math co-processor and very high resolution graphics. Methods : The RR curve d i v i d e d in two sect i o n s (a,for a duration of 64 sec, and b,for a ,eriod of 26 min.), Four (4) different ,arameters were selected for the first section (blood flow) and nine (9) for filtration and excretion phase. From our data base of normals the mean values of the above mentioned larameters a n d the S.D.of those values was determined. A software program developed in Turbo Pascal T M 4.0 which creates the RR curve and automatically calculates the values for each parameter and this leads to a first separation between normal and abnormal values. The abnormal values stored in an archive which Js the data used from a~other program in Turbo Prolog~.Th~g pr0Eram consists of two level shells : the first one uses rules based on Nuclear Medicine classification of results from the analysis of RB cqrve, and the second uses rules based on clinical and other laboratory f~ndings, The combination of the above shells leads to ~n evaluation of renal functional abnormalities, Conclusion : Th~S system iS considered capable to diagnose abnormalities of the renal function and provide new more efficient values ~or the used ~arameters.

V. Ivangavid, D. Ivan£evid

Z. Ma~trovid,

Z. Ku~ter,

DepartmenC of Nuclear Medicine, University Hospital Rebro Zagreb,

Yugoslavia

99M-Tc-HM~PAO RED BLOOD CELL LABELLING: PRELIMINARY IN VITRO RESULTS Recently, hexamethylpropylene amine oxlme (H~-PAO) ~as been introduced as 9 promising leucocyte labelling agent and there have bean studies o, platelat labelling with ]B{-PAO as well. 99m-To - red blood cell (HBC) labelling is a wall essablished method in blood volume and b l o o d pool studies, its main drawback hei~g the elutlon of 99m-To from the RBCS. In Chls study we investigated the in vitro RED labelling propertles of HM-PA0 in order to examine 99m-Tc-HM-PA0 as a label allowing delayed blood sampling or imagdng with lower backgorund acltivdty. 2 ml of packed RBCs were incubated with rising concentratidns of BM-PAO up to 90 ug HM-PAO~ml packed RgCs. KM-pAO had previously been eomplaxed with 99m-To according to the manufacturer's prescription except for lower activities of 99m-Tc. The samples were washed twice in 20% autologous plasm~ and labelling efficiency was determined. After subsequent time intervals the samples were centrifuged, supernatant fractions withdrawn and counted for activity and the samplas were resuspendad to the original volume with 20~ antologous plasma. Calculations for net aluted activity were perfomed using a computer program. Labelling efficiency was always between 70 and 80% and the highest elution one hour after labelling was 3.52% with a mean value Below 2%. Within the investigated span no influence of KM-PAO concentration could be proved Our results indicate that RBC labelling with HM-PAO might be an alternative to the wide-spread I tinning methods, being less time consuming and having a more favourable elution profile. Since it is known that in vitro and in vivo elution of a RBC label may dfffer significantly comparative in vivo studies of the various methods will have to be perfomad

I-IMAGING THgOMBUS WITH BADIOLABELLED Feb' FRAGMENTS OF g MONOCLONAL ANTIBODY TO PLATELETS g simple rapid method, not requiring blood cell IsepaFatlon, is required fop plateleb labelling in tee d i ~ O s i s of DVT. We have previously PepoFged OUr preliminary clinical findings with an IV monoclonal antibody (P256), raised in mlce labelled with In-11~ and specific for the prlm~te platelet glycoprotein IIb/IIIa complex. ~ne effect of PH5~ and its F~b, fragment~ on in ~itro platelet function have been assessed by neasuring platelet aggregation in whole blood, )latelet rich plasma and gel filtered platelets. the F(ab')2 fragment caused consistently less ~ggcegation than the whole antibody, whilst the ~onovalent Feb' f r a ~ e n t bad no effect. The nonovalent Fat' fragment was therefore investteated For its ability to image thromhus in viv( ~fter labelling with In-11~, via the bifunettonal chelate DTPAm the P256 Fat' retained reactivity and specificity for p r i ~ t e platelegs. Tbrombus was induced in M.fascioularis by IV injection of iron microapheres and localised ~it~ an exterDally applied magnetic field. rhrombus was confirmed by veflography and imaged •ith In 111 P256 Fsh'. The v e n o g P ~ and scdntd~ram were both positive at I and 48 hr after 5hromhus induction. However after non-specific ~ntlbsdy, the scinCdgram was negative. These initial studies show~osd correlation between imagine with PH56 Feb' fra@~ent and venography ~or dotection of BVT.

f

204

203 J. R. Coveney,

A.W.J. Stuttle, C.J. 0'Donnell, N. Virji, A.M. Peters S.C. Harrison, G.J.P. Murphy, J.p. Lavender

G, D. Pileher and H. S. gobbin~

Department of Pharmacolngy & Toxicology Eallinckrodt, Inc. E a z e l w o o d , M i s s o u r i 630~2 U.S.A.

Tc-99m HgH~ AND ~-131 o-IODOHIpPURATE (DIE) TRANSPORT KINETICS IN RAT KIDNEY SLICES The renal transport mechanism o[ Tc-99m HAG 3 was compared to that of 1-131 0IH in terms of Michflelis-Henten parameters and the dissociation constant for probenecid, an inhibiter of organic anion active transport. Renal cortical slices (O.5-mm thick), from female Sptague-Dawley r~ts, were incubated at r o . ~ t p m p ~ l a t . r o i n Rn o~yge.~m~d C r o s s Taggart medium for 30 mln in the preSen¢~ I~[ 1-131 OIE Or Tc-99m HAG~. Specified substrat~ levels were established with c a r r i e r OIg o r Tr-.99 HAG 3 - Nonenzymatlc accumulation was assessed using dinitrophenol and iodoa~etate. In i n i t i a l experiments, with 1-131 OIE at 200-800 pH, Vma R and leer0 Km values for uptake (mean±s.e.m.) were 26±3 nmol/min/mg wet tissue and 2.2B±0.IO log ~B. In later experiments, with 1-13~ OIE at 12.5-~00 pM, these values d r o p p e d t o 9.9±0.6 and 1,789±0.002, indicating a concentration dependence of enzyme kinetics, Tc-99m HAG 3 , at concentrations slmil~r to those of latter UIH experiments, gave similar V., x and logz0

K values: 9.8±1,0 nmol/min/mg and 2.70±0.13 l ~ g pH. Probenecid log~0 Ki values were 1.32t0.16 l o g uH f o r 1-131 OIE and 1.13±0,16 l o g pH for Tc-99m HAGs, suggesting that the transporter is the same for both tracers. We conclude that Tc-99m HAG3 and 1-131 OIH, at similar concentrations, share a common renal organic anion transporter, and display similar enzymatic velocity and saturation parameters with t h e transporterAt higher substrata concentrations, 1-131 OI~ might recruit additional subclasses o f transporters (with lower affinity for hippurate-like substrates), or might diffe~entially saturate contraluminal transporters.

A. Verbruge~, G. Bormans, B. Cleynhens, Hoogmartens, A. Vandecruys, M. De Roe.

M.

l University Hospital Gas~huisberg, RadJopharmacy and Nuclear Medicine, B-SODS Leuven, Belgium.

SEPARATION OF THE ENANTIO~BS OF ggmTe-MAG 5 AN~ THEIR RENAL EXCRETION IN A BABOON. 99mTc-MAG fl (I) has a square pyramidal complex structgre and can thus be supposed to exist as a mixture of two enantiomers. To obtain I in pure enantiomeric form we have first prepared the esters of benzyl MAG with (R)-and (S)-seo-guOH. L~belling wit~ 99mTc yielded for both esters a mixture of two diastereomeric 99mTc-MAG -see-but-esters (II), rasp. II-SA+II-SB and ~I-Rg+II-gg. The diastereomers were separated by RP-HPLC (Eosil CIgHL) and hydrolysed by Boiling for 1 min in O.5N NaOH. This final product was purified by ~P-HPLC (Zorbax EPlgl. On theoretical basis one can predict that hydrolysis of II-SA and II-RB will result in the same enantiomer of I (I-SA or I-RE) whereas the other dsomer is obtained after hydrolysis of II-SB or II-Eg. Racemization of the I-ensntiomers during the hydrolysis step is probably minimal, as postulated from similar experiments with isolated isomers of 99mTcMA-gly-ala-gly. I-SA, I-SB, I-RA and l-gB were evaluated in a baboon by gamma camera studies. ~n the study of I-SA and I-SB blood samples were taken during 60 mid to calculate the plasma clearance. I-SS was found to be superior to I-SA as shown by a faster elimination from the kidneys, a steeper plasma disappeacanoe curve and a 20% higher plasma clearanse value. I-RA, on theoretical basis identical to I-SB, yielded also a more favourable renogram than I-HS, in agreement with the above mentioned theory. These first results indicate that one of She isomers of 9gmTc MAG o is extracted from the plasma a~d excreted ~y the kidneys more efficiently than the other isomer*

257 205 A. Verbrug~en, G. Bormans. A. Vandecruys, L. Verhaegen, P, Devos, M. De Roe. University Hospital Gasthuisberg, Radiopharmacy and Nuclear M~decine. B-3000 Leuven, Belgium, COMPARISON OF 89mTc MAGAG-DA AND 99mTc MAG 3 IN HUMAN VOLUNTEERS. During a studg of methyl substituted Uerivatives of B9mTc MAg 3 it was found that the DA isomer of BBmTc mereaptoacetylglycylalanylglycine (99mTc MAGAa-CA. I) shows superior renal excretion characteristics compared to 99mTc MAC 3 (It) in mice and baboons. We have now evaluated both renal agents, purified by RP-BPLC, in a human volunteers in a paired study. A mixture of 18.5 Mgn (0.S mCi) of I o~ II with 1.85 Meq (0.05 mCi) of iS1[-Hippu~an (OIg) (internal hzoloEical standard) was injected intravenously, Pl~na~ images were acquired during 30 min with a LFOV eameca and the ~enograms for I o~ II were constructed f~om the data. Blood samples were taken at regular intervals during 60 min to construct the plasma disappearance curves and calculate the plasma clearance for I, II and OIH. U~ine was collected at 35 min and B5 min p.i, In each volunteer, the time to max. ~enal uptake (Tmax) and time to half this max. is shorter for I than for II. Mean Tmax = 2.92 + O.4 min for I, and ~.5 + 0.9 min for II. Residual penal activity after 30 min is in each case lowest with I, Mean u~inary excre~ lion after B5 min is 107.a + 3,S% of OIH value for I and B7.0 ! 1.4% for II. In each volunteer plasma clearance is highest with I. Mean plasma cleacance is 75.a + 4,SM of OIH valu~ for I versus 67.5 + 5.0~ for II. Liver is slightly visualized with II but never with I. It is concluded that 99mTc MAGAG-DA is superio? to 80mTc MAa 3 as a substitute fop Hippuran, but its preparation ~equires an HPLC purification ate n.

208 P.Thelseen,U.$echtem, A,Ltnden, H.H.Hilger,H.behlcha.

207

206 K.K.Solanki, A,Ai-Nahhas, K.E.Britton

I

St Bartholomew's Hospital, West Smithfield London, ECI UK "COL~" Tc-99m MERCAPTO ACETYL TRIGLYBINE, MAC 3 The main obstacles to Tc-99m MAG~ kits (Mallinckrodt) becomln~ more widely used are the belling step and the maximum of one hour shelf life of the boiled p~oduct. We have demonstrated the value of pre-reeonstltuted labelling and boilinB procedure, that is by separating the addition of Tc-99m to the MAC3 kit from the sub sequent boiling step. These modifications enable individual patient doses to be obtained for up to four hours, which fits better into routine wo~k. FuFther modifications to this procedure have now been tested to enable the stock solution to be used throughout the day and to guarantee a sufficiently lon~ shelf life of the preparation afteT boiling. It was observed that the stopage temperature had a ma~ked influence on the quality of the p~epa~ation. UtillsinB these findings the new protocol involves s freezin s step which enables the preparation to be used throughout the day. Further, by storage of the boiled product at below IO"C the produeC still had an hour's shelf life even afte~ boiling of the rout hours post pre-reconstitution ~liquot. ~his ?evised p~otoeol fo~ the p~eparation and ~toPage is very convenient and should eneour~Ee routine usage of Tc-99m MAG3, so that its excellent imaging and renal fUnCtion qu~nti~ation characteristics may be exploited to the Cull in renal nuelear medicine.

209

~

J.L. ;CALLEGO ~ . L . ~ B A I. ;CALVe C. ; O . ~ J.

~ CL~C~

pUER~% DE H I ~ . -

C. ; M A ~

NI%DBID.- SPA/~

OF MAG-3 IN THE ~ OF ~ STUDY ~/TH DTpA.

T~ANSPL~IT.-

ar~ I1~I%y publ/shed papers that c~i1par~ ed results with O ~ and M%G-3. As one ~f the r a d / o p ~ t l c a l c~maonly used in the st ~ y of renal tranSplant is D T P A , ~ have c ~ ~ e resu/ts with DrPA ar~ M~=-3 knowing that the take and e l / ~ a t i o n n~chanisms of both t-racer different. ~aterial an~ ~ t h o d : ~ hav~ studied a total of Zl patients with renal transplant. Both studies 3 a ~ been realized in a period of 48 hrs..The order of practicing the studies has been aleatory. %s in the days after transplantation the kidney _ ~ c t i o n n~y be very v~riable,w~ have rejected those studies with very different renal function. rhe e v ~ u a t i o n of the activity curve has been cor sldering:Uptake 1-3 m/n.T peak, T~eak+10 mi~. ar~ the perfusion curve in the first minute ~esults:May be clasiffied in 3 groups i.- Pts ~ith satisfactory, renal function:The information obtained with both tracer has been s/miler but the v~lues of the activity curv~ are differents uptake elimin T.peak ~I~A 1.55_+0.78 1.42+0.22 4.3+0.86 ~AG-3 1,76+0.28 1.57+0.26 3.6~0.67 2 .- In patients with ~ p a i r e d renal-fl/nction the ~ g is high a ~ the curves a~d I/r~g~s ar~ ofte~ %on diagnostic with DTPA.Wlth MAC-3 the higher =-Xtraction efficiency g i ~ s better i ~ g e s and cu~ ~es (Uptakel.32_+0.11 / 1.26_+0.09 Elim:!.28+0 07 1.18+0.08 in patients with ATN or rejection ~ hav~ not ob ~ained different renal patron. The morphology of the acti~ity curv~ is s h a r e r wit MAC-3 and less ~kg can be seen (Uptake: 1,53+ 0.12/1.25+0.09) [n perfn/sion studies the activity curv~ has been ~harper wth DTPA but the values of T peak have more or less the same.

210

IP.Thelssen. U.bechtem, B.G,",nger, R.Kux, A.Linden, IH.H.HIIger, H.Schicha.

P.Theiesen, U.Sedhtem, A.Linden, U.Mennlcken, H.H.Htlger, H $chtcha

Department of Experimental and Clinlcel Nuclear Medicine and Medical Clinic III University of Cologne

Department of Experimectsl and Clinical Nuclear Medicine and Medical Clinic Ill University of Cologne

Department of Experimental and Clinical Nuclear Medicine, Medical Clinic III,and Doper truant of Pediatric Cardiolo~/, University of CoI~na

MAGNETICRESONANCEIMAGINGWITH GRADIENTECHO SEQUENCESFOR FUNCTIONALASSESSMENTOF THE HEARTAND THE GREATVESSELS IN 250 PATIENTS

DYNAMIC MAGNETIC RESONANCE IMAGING IN PATIENT5 WITH AORTIC AND MITRAL REGURGITATION

EVALUATIONOFATRIAL SEPTALDEFECTSAND ANOMALOUSCONNECTIONOF PULMONARYVEINS

New gradient echo SequenCes improve the temporal resolution of magnetic resonance imaging (MR/) and allow visualizationand quantification of flow phenomena. In contract to spin-echo images, the~ dynamic magnetic resecance (dMR) images display blood with higher signal intensity than myocardium. In patients with valvular heart di.seaee (N=66) dMRI displ~/ed the presence and extant of valvular regurgitation. The volume of regurgitant bleed flow correlated well with qualitative angiegraphis grading of severity, In patients with valvular stenoses the narrow jet of blood is seen passing through the immobile leafletsof the valve. Dynamic PIRI was useful in patients with aortic disease (N=49) demonstrating false and true lumina, distinguishing slow flow from thrombus, and identifying sites of entry and reentry In aortic dissection. In cases of aortic coerctetion depiction of disttlrbedblood flow highlights the functional consequences of the narrow segment. In patients with coronary artery disease (N=60), dMRI permitted quantification of leftvectricular well thickening, threedimensional calculation of volumes, and ~ s m e c t of bypass graft patencv, Improved depiction of coronary arteries is possible because of enhanced cantrost beween blood and mvu~mrdium, There were several advantages of dMl~I in patients with congenital heart disease (N=30) including easier identificationof intra- and axtrasasdiec shunts, quantification of shunt volumes, end distinction of abnormal vessels from lung tissue. In most patients with paricardial disaaea, cardiomyopathias, or cardiac tumors (N=45) dMR] added information to the spin-echo examination, for example better differentiation of pericardial fluid and calcification. Therefore, this new technique has considerable botential for the diagnosis of heart disease and especially the quantification of cardlas function.

BY DYNAMIC MAGNETIC RESONANCE IMAGING Dynamic magnetic reeonanca imaging (dI'IRI) was performed in patients with a~rtic l'egurgttation ( N= 14) and/or mitre r~urgitation (N=13) documented and graded for ~erity by angiegrapby and @ normal persons (nl). Using a gradient echo technique with low /flip angles and short repetition and echo times dMR offers improved temporal resolution compared to spinecho-sequences. On dMR images turbulent retragrede blood flow through inc~mpetect valves causes signal less of blood thus permitting detection of the valvular defect. To determine the severity of regurgitation by dMRI areas and volume of signal lees were analyzed on transverse sections cover tng the entire heart.

I

Aortic regurgitation: nl

0 O

mild 4±3

moderate 15~8"

22±1"*

10.9

43*22*

95~16"

IMitral ragurgitatiOn:nl

mild

moderate

severe

max. area (am2) max. volume(om3)

seveca

max. area (ca2) 0 6±2 13±6"* 34±2** max. volume(ca3) 0 12±4 42=L19"* 169~I** * p < 0.05 vs nl, mild, moderate, ** p < 0.05 vs mild All regurgitant lesions were visualized in dynamic images. A slightly better correlation was found for the volume than for the area of signal loss. Analysis of the regurgitect jet, characterized by signal loss on dynamic magnetic re~nanca images, permits a semiquantttative eesecement of severity of left sided regurgltect lesions. Three-dimaosional determination of the jet volume is a passible edvantage of MR/ compared to other noninvesive methods.

G.

Spin-echo ($E) magnetic resonance imaging (MRI) (N=22) and grediect-eeho dynamic MR/ (dMRI) (N = I I) was performed in 22 patients with angiographically (N=Ig), echecardlograp h~celly (N=3), and/or surgically (N=12) verlfied atrial septeT defect (ASD)(21 ) and/or disconnected pulmonary veins (5). Type of defect and pulmonary venous connection ware determined by inspection of transverse M R images. ASD wee visualized in all patients on BE- Images and the type of ASD was correct ly Identified[primum ASD N= I , secundum ASD N: 17, sinus venasus defect (SVD) N=3]. Three left upper pulmonary veins (PV) could not be Identified.Anomalous PV return Into the superior vena ceva or right alrium was demonstrated in the 3 patients with SVD. TWo patients with a Scimitar syndrom had a right lower PV entering into the inferior veno cave One of these patients also had a eacundum A S O Dynamic MR/showed lees anatomic detail in eomporlsen wlth GE-images. However, the direetion of shunt flow was clearly demonstrated on dMR imagos, Thls was useful in small AGD which were difficultto differentiate from the fessa oYalis an SE-images. Due to high signal intensity of dMRI, distinction of PV from bronchi also was 1asilitated, Combined SE-MRI and dMRI has the capability to completely charasterize the anatomical and functional ednormaIItias in ASD. Compared to other imaging madalitias, MR/ has advantages in the diagnosis of SYD and Identificationof anomalous PV connections.

258

211

212

FS P r a t e G Wisenberg L Diesbourg, TP M a r s h a l l , oJ Drost, 5g C a r r o l l , B O ' N e i l ,

213

K.Tatsch, W.Schrbttie, C.M.Kirsch, P.Knesewitsch, E.Moser

Departments of Nuclear Medicine and Medicine, St. J o s e p h ' s HealthCentreof London and Unlversit~ of Western O n t a r i o , London, Canada.

Division of Nuclear Medicine, Department of Radiology, Unicetsity of Munich, Mtmich, FRG

DETERMINANTS OF CONTRAST IN MRI OF NORMAL, ISCHAEMIC AND INFARCTED CANINE MYODARDIUP FULLOHING A CONSTANT INFUSION OF Gd-DTPA. To Improve MR[ t i s s u e d i s c r i m i n a t i o n betweer non~l, ischaemic and i n f a r c t e d ~ o c a r d l u m w~ i n v e s t i g a t e d t h e e f f e c t on NMRt i s s u e parameters produced after c o n s t a n t I n f u s i o n o f the c o n t r a s t a g e n t Gd-DTPA. Separate c a n l n e l ~ x : l e l s o f Ischaeml~ ( c o r o n a r y a r t e r y o c c l u s i o n less t h a n l h ) anc I n f a r c t i o n ( o c c l u s i o n m a i n t a i n e d f o r I - 4 days) were s t u d i e d f o l ) o w I n g a 20mln i n f u s i o n o f C~:IOTPA ( O . O l - O . O Z m m o 1 7 k g / m l n ) . A n i m a l s wer~ s a c r i f i c e d immediate]y a f t e r t h e termination of the Infuslon In=4 for Ischaem(a and n=3 for I n f a r c t i o n ) or a f t e r a Zmln washout p e r i o d (n=3 for schaemla and n=2 For I n f a r c t i o n ) . 5ample~ oF t h e myoeardium were e x c i s e d and t h e F o l l o w t n { Parameters were measured: 1) t i s s u e concentratior of Gd-DTPA ([Gd-DTPA] by scintlilation countinc of the tracer ISSGd-DTPA, 2) reglonal myocardial blood Flow RHSF) by a radioactive mierospher~ technique, and 3) Tl and T2 relaxation times b) NMR s p e c t r o s c o p y at 6.4MHz. For dogs s a c r i f i c e d i n l ~ e d t a t e l y a f t e r I n f u s l o t [Gd-DTPA] was Independent o f RMBF and [Od-DTPA] was the same In ischaemic and normal t i s s u e s l b u t averaged 60% g r e a t e r i n i n f a r c t e d t i s s u e . For t h e 2mln d e l a y e d s a c r i f i c e [Gd-DTPA] wa~ reduced i n all tissues, was higher in ischaemi¢; than normal tissues, was greater than 60% tr infarcted compared to normal tissue and decreasec exponent a l y w i t h RMBF In a l l t i s s u e s . If on(I assumes t h a t each r e g i o n o f m y o c a r d i u m i~ n d e p e n d e n t l y inked by RRBF t o t h e r e s t o f th~ Gd-OTPA i n t h e body and t h a t Gd-DTPA i s bein£ cleared from the body by Rlomerular ffltratfon,l then the exponential rela¢ionship between [GdDTPA] and RMBF i s p r e d i c t e d , in a l l t i s s u e s , TI and T2 relaxation rates were linear witl ~Gd-DTPA]. Therefore the slgnal intensity It Tl-wei h t e d " images will be directly relate( to Gd-BTPA]. ~e c o n c l u d e that " T l - w e i g h t e d " MRI o f th, [ h e a r t taken at or near the end of a 20mir constant infusion w i l l allow d e l i n e a t i o n o i l Infarcted from normal and/or Ischaemic tissue. I f after t h e end of t h e i n f u s i o n a d d i t i o n a l images a r e t a k e n ( e . ~ . I0 Images a t I Image/mln), I t h e n n a p a t i e n t wmth normal k i d n e y f u n c t i o n , I Ischaemlc r e g i o n s c o u l d be u n i q u e l y d e l l n e a t e ¢ and i n f o r m a t i o n r e g a r d i n g RMBFc o u l d b e d e t e r m i n e d . I

I I

214 J . G U I L L E T , C. ROLE. Y, IMBERT, P_ D U C O S E, D U F O N T , E. VARLAN, g. V A L E N Z A , F. B R A M A R Y . S e r v i c e s de E i o p h y s i q u e M 4 d e c i n e N u c l 4 aire et M ~ d e c l n e I n t e r n e , C e n t r e H o s p i taller d'AGEN,47023 AGEN Cddex FRANCE Otis I n d u s t r i e - S a c l a y 91192 G I F / Y V E T T E FRANCE HMDP 9 9 m T c L A B E L L E D C O L L O I D A L A L U M I N I U M P H O S P H A T E (CAP) AND S U C R A L F A T E (S) A R E T H E Y S U I T A B L E T O D I A G N O S E AND F O L L O W UP OESOGASTRODUODENAL U L C E R A T I O N S ?. E n d o s c o p y is the r e f e r e n c e t e c h n i q u e fo~ the d i a g n o s i s of o e s o p h a g e a l , g a s t r i c an( d u o d e n a l u l c e r a t i o n s . H o w e v e r , i t is an i n v a s i v e m e t h o d w h i c h is not o f t e n w e l l t o l e r a t e d . R e c e n t l y 9 9 m T c l a b e l l e d col!loidal b i s m u t h . C A P and S w e r e s h o w n to h a v e an a f f i n i t y w i t h d i g e s t i v e t r a c t ulcerations. M a t e r i a l and m e t h o d . In v i t r o e x p e r i m e n t s g a v e H M D P 9 9 m T c as the b e s t l a b e l l i n g for C A P and S. C A P and S w e r e i n g e s t e d by 69 f a s t i n g pa t i e n t s , I n g e s t i o n and g a s t r o - d u o d e n a l 'emptying w e r e r e c o r d e d by a c o m p u t e r i z ~ , g a m m a - c a m e r a (Apex 415 ECT E l s c i n t ) . Results. For u l c e r a t i o n s d i a g n o s e d b y f i b r o L c o p i ( lexamination,results from r a d i o n u c l i d e i s c a n s are l l w i t h CAP: S e n s i t i v i t y 70~ Specificity 96,0%,Positive Predictive Ivalue 88,5~, N e g a t i v e P r e d ± e t i v e v a l u e i ,90,3~.2)With S, t h e s e v a l u e s are 57%; I )05%; 75%; 8 0 , 9 % . Ji )isoussion and conclusion, I Phe s e n s i t i v i t y of r a d i o n u c l i d e s c a n is too l o w to be c o m p e t i t i v e w i t h E n d o s c o - I )y, e s p e c i a l l y in d u o d e n a l ulcer. MoreI ) v e r , r a d i o n u c l i d e s c a n o n l y g i v e s locat i s a t i o n of u l c e r a t i o n w i t h o u t any i d e a )f h i s t o l o g i c a l data. In fact. o n the ~pper d i g e s t i v e tract, the true i n d i c a tion m i g h t b e the f o l l o w up of some )enign u l c e r a t i o n a v o i d i n g s o m e fibro! zopic e x a m i n a t i o n .

EVALUATION

OF

ESOPHAGEAL

MOTILITY

DISORDERS: COMPARISON OF A PARAMETRIC IMAGING TECHNIQUE WITH A STANDARD ESOPHAGEAL TRANSIT STUDY

[n order to assess the value of two different methods for evaluation of esophageal motility disorders a recently introduced esophageal para-

metric imaging (EPI) technique was compared to a standard esophageal transit study (ETS). 78 patients with different forms of esophageal dysfunction were studied by EPI and ETS. For EPI 15-20 swallows at 20 second intervals were recorded. For image ewluatlon 10-12 esophageal regions of equal size were established. Parametric images were created using a special space-time matrix. In ETS transit time of a single bolus was calculated using the time-activity curve obtained f m m a single esophageal region. With both methods the passage ol liquld and solid bolos was investigated. EPI-results for liquid (L) and solid (S) bdius were more frequently pathologic (L:45/Yg;S:66/7S) than i T S - r e s u l t s (L:gd/78;S:55/7S). A considetab]e number ET°fS cases showed pathologic EPI but normal (L:I4/42;S:I~/2g). The combination of normal EPI but pathologic ETS was rare (L:5/28;S:2/8). Using a solid bolus motility disorders were more sensitively detectable (EPh68

ETS:55) than by a liquid bolus (EPh45;ETS:36). In contrast to ETS, EPI visualizes the bolus passing the esophagus and defines various image patterns:cumulation, oscillation, retrograde motion. In the detection of motility disorders EPI is

more sensitively and reliably than ETS. This applies to both liquid and solid bolus. The advantage of EPI is that the diagnosis is not only based on a single but on multiple swallows. Furthermore, EPI provides defined image patterns end distinguishes various forms of esophageal motility disorders.

215 LECOUFFE P.. VERRIEZ O., HOSSEIN Cl., LACOSTE P., DEVEAUX M., MARCHANDISE X. Service Associd de M~ecine Nucldaire et Service d'Endocrinologie et Diabdtologie (Pr P.FOSSATI). CBU Lille - 59037 L i l l e - France

INFLUENCE OF CALCIUM LOAD O N INTESTINAL P E R M E A B I L I T Y T O 51 C r - E D T A IN C H R O N I C P A N C R E A T I T I S To 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 woutd be strongly influenced by calcium diet. Seven healthy adults (aged 29-22) acted as [controls. Twelve male patients (aged 39-60) with chronic pancreatitis but no associated disease and no NSAI treatment were investigated twice beCore [therapy as they received in a random sequence either a 1200 mg or a 300 mg calcium diet ; they were studied again on a 300 mg calcium diet after a two month pancreatic enzyme therapy. According to Bjarnason's technique, 24 h urinary lexcretion of 51Cr-EDTA 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 siffnificantly higher (p<.02) in patients on a high calcium diet (2.50 % ± .87) or on a low calcium diet (3.63 % % 2.15). The difference between excretions on high and low calcium diet was statistically significant Ip(.0.05). Excretion on a 300 mg diet was lower after treatment (p<.05, 2,23 % +_ 1,04). Our results suggest an abnormal intestinal permeability in patient with chronic panereatitis. Although no strong correlation was found between amount of stool fat and excretion of 51Cr-EOTA, intraeeliular 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 ~equenee of two first tests was variable. ~helation of calcium appears to influence Iramatically test result : so luminal calcium loa'd must be taken in account to assess exactly intestinal permeability to 51Cr-EOTA.

I P.

THOUVENDT

~ O H ~

M-H.

LAURENB,

Aq. KSOBICKA,

L-J.

J-M. ANTDINE.

Department o~ Nuclear Medicine, University of N a n c y , 18 Rue Lionnoie, 5~OOO NAN~Y Fpance. GASTRIC EMPTYING PATTERN: MATHEMATICAL MODEL TO CHOICE7

WHICH

The aim OF t h i s study was to Find a m~tbematieal model that best d e s c r i b e s the g a s t r i c emptying (DE) p a t t e r n f o r I d i f f e r e n t Foods. I 3Ba GE kinetics on 12D Volunteers lhave b e e n examined ~ccording to the Ip~rtioipants and/or the food properties as f o l l o w s : solid f o o d s of different consistencies op sizes with or without a stendmrd meml, i n m sedentary or a sportive type of subjects, during a p h y s i c a l effort o r at rest; liquid foods of different energetic ~alues or osmolsrities in "normal" subJets; semiliquids of different viscosity in subJets lwith/withcut lactose inholer~noe. Bcintlgrsphies were p e r f o r m e d e v e r y 1U mn e v e r s period of 3 hours, matbemetioal models~ e.g. linear (D), inverse cubic root [E), legistio (L), Gompertz (GI, power exponential (F) and m o d i f i e d e x p o n e n t i a l (MI have been used in o r d e r to a d j u s t the e x p e r i m e n tal curves. The d e g r e e of a d J u s t e m e n t was determined by means of the mean dUadratio standard deviations. For the solid foods; no m o d e l oen be emphasized as ~ particularly suitable to follow the BE kinetics. For the l i q u i d ~oods with d i f f e r e n t energies or osmolarities, the limear model appears to Fit B e o u r e t e l y . Pop the semiliquids foods, m o d e l s p and M a p p e a r to be the best For l a c t o s e intolerant subjects, whereas models M a n d D f o r l a c t o s e - a b s o r b i n g subjects. l

216 D DE N A R D O , M A N T O L I N I . G P I T U C C O , P GALLO *,G S C I B I L I A * ~ . A G M A C C E I A E E L L I **. A CASSISI **,Q C A S E T T A * * , G B I A N C O S*, 0 MARIN0 *~ V CAPUTO. IV S E R V I Z I 0 DI MEDIClNA NUCLRARE

I S T I T U T O P I ANATOMIA PATOLOGICA * I S T I T U T O DI C H I R U S G I A DEL C U O S E E G ~ O S S I VgSI **. I U N I V E R S I T A ' DI S O M A I N D I U M - I l l A N T I M Y O S I N (FA8) IMAGING HUMAN CARDIAC TRANSPLANT FOLLOW-UP.

IN

To e v a l u a t e I n - l l l m o n o c l o n a l Antimyosin FAB ( m A m ) i m a g i n g as noninvasive m e t h o d to d e t e c t r e j e c t i o n w i t h m y o c y t e necrosis,g2 scintigraphic studies were p e r f o r m e d 48 ~ 72hrs b e f o r e e n d o m y o c a r dial b i o p s y ( b x ) in B c a r d i a c transp l a n t p a t i e n t s . All pts, but 2,underwent reheated scintigraphie studies; adverse reactions have not b e e n noted. I m a g e s wereacguired 2 4 - 4 S h r s a f t e r the iv injection of 2 mCi of I n - l l l mAm. We considered positive f i n d i n g o n l y the intense myocardial u p t a k e b o t h f o c a l and d i f f u s e , on c o n d i t i o n that ventricular c a v i t y was e v i d e n t as c e n t r a l u n l a b e l e d are~. No f ~ l s e n e g a t i v e r e s u l t w ~ s obtained, gn the 10 p o s i t i v e s c a n s bx revealed: moderate acute rejection with m y o e y t e n e q r o s i s in 2 . m i l d rejection without myoeyte n e c r o s i s in g, m y o c y t e n e c r o s i s as a c o n s e g u e n c e of toxic or i s c h e m i c i n j u r y in 6 . T h e s e s t u d l e s suggest that In-lll mAm imaging may be a valuable noninvasive surveilgance method in c ~ r d i a c t r s n s p l a m t a t i o n pat i e n t s and c o u l d d e c r e a s e the n u m b e r of bx in p r e s e n c e of n e g a t i v e r e s u l t s . On the o t h e r hand, in p r e s e n c e of p o s i t i ve f i n d i n g s bx is mandatory in o r d e r to obtain morphological diagnosis.

259

~17 W.H. K n a p p , U. S c h m i d t , G. N o t o h a m i p r o d j o , K. V y s k a , D. F a B b e n d e r .

219

218 l. Carrid, L.Bern~, H.Ballester, [,,Abadal, H.Estorch, DiObradol:, M.Gindatmm, Departments o[ Nuclear Medicitm und Cardiology, Hospital de Sent Pau, Barcelona. Spain,

I n s t i t u t e of N u c l e a r M e d i c i n e and D e p a r t m e n t of C a r d i o l o g y , H e a r t C e n t e r North Rhine-Westphalia, Bad Oeynhausen C O M B I N E D U S E OF I n - I l l A N T I M Y O S I N ANTIBODIES AND TC-99m-MIBI FOR THE A S S E S S M E N T OF P O S T - I N F A R C T I O N MYOCARDIAL VIABILITY The p u r p o s e of t h i s s t u d y w a s to identify stunned myocardium, ischemia and necrosis following acute myocardial i n f a r c t i o n (MI) a n d lysis. In 14 p a t i e n t s 2 m C i I n - l l l a n t i m y o sin a n t i b o d i e s (AMAB) w e r e i n j e c t e d 1-4 d a f t e r the o n s e t of MI a n d lysis. I m a g e s w e r e t a k e n 24 h l a t e r u s i n g two e n e r g y w i n d o w s in at l e a s t 2 views. Then, 20-30 m C i T C - 9 9 m - M I B I w e r e r a p i d ly i n j e c t e d t o g e t h e r w i t h the o n s e t of d a t a a c q u i s i t i o n ( f r a m i n g - r a t e : 1/16 s), to o b t a i n f i r s t - p a s s w a l l m o t i o n i m a g e s In the same p o s i t i o n , T c - 9 9 m i m a g i n g was c a r r i e d o u t 45 m i n later. The following patterns were observed: ( I ) a c c u m u l a t i o n of A M A B m a t c h i n ~ a def i c i t in M I B I u p t a k e and s e g m e n t a l w a l l motion abnormality iN=3), (II)no a c c u m u l a t i o n of A R A B and no r e g i o n a l M I B I d e f i c i t , b u t i m p a i r e d w a l l m o t i o n (N=2), ( I I l ) p o o r a c c u m u l a t i o n of A M A B , s m a l l concordant MIBI deficit and large wall motion abnormalities iN=5), ( I V ) p o o r a c c u m u l a t i o n of A M A B , s l i g h t w a l l m o t i on a b n o r m a l i t i e s and l a r g e M Z B I d e f i c i t iN=4). The r e s u l t s of a n g i o p l a s t y iN=8) and the c l i n i c a l h i s t o r y r e v e a l e d the following correlates: effectiv~ lysis with stunned myocardiuml(II-III), pers i s t i n g i g c h e m i a (IV), i n e f f e c t i v e lysis with e x t e n d e d n e c r o s i s (I). T h e c o m b i n e d use of A R A B and M I B I ~rovides e x c e l l e n t i m a g e q u a l i t y a n d 'aluable i n f o r m a t i o n for t r e a t m e n t ,

220 R. Z i m m e r m a n n . W.H. K n a p p , F. Helus, M. K a p p , F.-J. Neumann, H. Tillmanns, P. Georgi, W. Ktibler. Departments of Cardiology and Nuclear Medicine, U n i versity of Heidelberg, end G e r m a n Cancer Research Center, Heidelberg, Federal Republic of Germany.

M-13 LABELED G L U T A M A T E AS A MARKER OF C H R O N I C MYOCARDIAL I S C H E M I A

Purpose of the study was to evaluate the clinical significance of myocardial scintigraphy with N-13 labeled glutamate and to investigate the behavior of poststenotie N 13 glutamate uptake after successful pereutaneous transluminal c o r o n a r y a n g i o p l a s t y ( P T C A ) . T h a l l i u m - 2 0 1 imaging (5 s i n and S h after injection) and N - t 3 glutamate scintigraphy (10 s i n after injection) were performed after symptom-limited bicycle exercise in 28 patients with single-vessel disease of the left anterior descending coronary artery (LAD). Poststenotic tracer uptake in the perfusion bed of the L A D (septum) was normalized to the tracer uptake in the nondiseased left circumflex territory (postarolateral segments) by c o m p u ter-assistad definition of regions of interest (LAO 30* view). In 15 patients with previous myocardial infarction, deficient poststenotic N-13 glutamate uptake correlated closely with thallium-201 uptake in both initial and redistribution scintigrams (p<0.0Ol). By contrast, in 13 )atients without previous myocardial infarction, poststenotlc N-13 glutamata uptake increased w i t h d e creasing thallium-20l uptake (p<0.05) and was correlated with percent thallium-201 redistribution (p<0.01). Seventeen patients were reinvestigated within I wk after successful PTCA and both thallium-2Ol and N-13 glutamate uptake were found to be significantly increased (p<0,01). Twelve of the 17 patients were reinvestigated 6 me later, and 9 were found to have a patent LAD. Wherel as poststenotic thallium-201 uptake stayed virtually constant during the 6 me study period after PTCA (p<0.05), N-13 glutamate uptake returned below the pre PTCA level after 6 me, thus approaching normal levels. Hence, the different time courses of poststenotie N - t 3 glutamate and thallium-201 uptake indicate prolonged alteration of myocardial amino acid metabolism despite successful restoration of regional perfusion.

I l I1 - INDI U M - A N T I E Y O S I N MYOCARDIAL

DAMAG£

IN

SCANS PATIENTS

TO ASSESS IN FOLLOW-UP

,FTER CARDIAC TRANSPLANT. lll-lndiulii-An~imyosin (AN) scans were used assess myocardial dal,age all patielltS ill ftlllow-up ariel caldiac transplant (CTp), 0.5 mg of RIi DI0-Fab-DTPA labeled with 2 mci ol ludittm ~ere i ] l j e c t e d alld scans obtaSued aL 24,t, fl ,and 720 pos~-lnjection. 62 5 e t t d i e s in 24 )atients, 7 days t~ ~e months alter CIp, have been done, with ~ maximmn of 5 studies wimlin 4 months in t:~(, patients, Btullal]antb]lurine antibodies (HAMA) have always been undetected in p[ttients wacb repeated injections. Visual analysis of the scans oI0en showed dlf#use AM uptake iu the myocarditml even in presence of a negative right ventrl.eular biopsI (Rvbx). The calculation o f a m I o c a r d i u m Co h m g r a t i o (AN index) eo qualttify ,IN uptake is pr~po~ed. c a l c t t l a t e d A~I i n d e x art 8 unfilial s u b j e c t s a t 4Bh posC-injet!tiun was I.~6±0.04. In the grc~up of paClents after CTp, AN index aC ~Rh teas 1,79±0.3, AM. indexes in chis group correlated with NVbx scores: Tn iS pat ieucs wich BVbx of rejectiun (scol'e 3), AH illde,~ i;Rs ] II)OZ0,3~, Ill 2i }acieuLs wich BVbx wich inglammacor} infiltrates h u t leEthmt[ iny¢lttyle dulllage ( s c e n e s 1 - 2 ) , AM itt,i~x teas 1,77ie,25 (p=NS), Ill 21 3ut.ie.ts wlrh u,nma] Rt'bx (s,m'e n). AM index was [ , b l ± O , 2 0 (p=n,04 vetslts scales ]-2; p=gino] velsns scare 3), Calculated A}I illdexes correlated well tqirh graded (4 sLap) visual a l h t ] p s i s (l=(Ji82[~; p=O.[IO1). AH s c a n s appeal: to p r , w i d e a i h ) U - i l l v a s i v e ilteth~ld to d e t e c t itlEUUaEdiat c e l l tlalllage lille [o al]ograit rejeetiml. The e v o l v i n g p a t t e r t l s o f .~1 u p c a k e i n i l t d i v i d u a l patients c o u l d I.,e u s e f u l Sn d e t e r m i n i l ~ g p a t i e n t meuagel,teld.

221

R.Schoening* H.gotsch,** Th. Krause*,E,Srau8* *Dept. Nuclear Medicine University Freiburg FRO **St,Josephs Hospital Freiburg FRO

IMAGING OF EARLY HUMANMYOCARDIALINFARCTION WITH Tcg9m- MAG3

Purpose: A cheaper,permanent available,murataRid and better method for imaging of early myocardial infarction,compared to I n l l l - e n t ~ y o s i n RAg,Tc- I 9gm-pyrophosphate(PPi) and the d -marked con;fast media (CM). tethod: Experimental acute muscular necrosis was .nduced in the rat (male Spraque Oawley 180-200g) ~y intramuscular injection of O,3mlaethylalcohol 'O%(for easy preparation coloured by black ink) nto the right hind thigh or s.c. administration if isoproterenol hydrochloride dissolved in sal~e [30mg/kg),24h later 3.7MBcq Tc99m-HAG3=mercapto]cetyl-triglycine was injected into a tail vein. )ynamic imaging with a gamma camera was donewith n thefirsthoL~, after lhrtbeanimals were sacrified m d the organ distribution measured.Ten patients Jp to 1 week post infarction received doses from Lg5-555MBcq(=5-15mCi)Tcggm-MAG 3 freshly prepared ~y use of the second eluate.Planar O-gh,seven~B-hole double isotope computer scintigraphy wfth T12ol end SPECT were performed O.5-3h pi Results: In animal studies the maximum of necrosis u p ~ k e is reached within 3minutes,followed by slow washout and rapid biood clearance. Ther~ is no significant bone uptake, necrosis/~cle ratioo~ p i > 2 0 , In human studies wi~h lo~d~ses of Tc~"-~C~ ,sucessYulimagiog~ be done /2h pi;~th high cbses l-3hpi. Coqoaredto Tc~U'I-ppithe visualisation of the necrosis s ~ to sh~ better f~tting to the area of

~e~io~ F ~

~ompared to J$2~arkedcontrast media.

222 D.Fa__wet,J.E.Wolf,M.Comet. Service de Biophysique et M~decine Nucleaire, Centre Hospitalier R~gional el Universitaire GRENQBLE - FRANCE.

Department of Nuclear Medicine, and NRLDI, National Institutes of Health, Bethesda, Bd.

I

s ~

of z~pid renal e x ~ z ~ 2. ~o bone u~ke end better fittzog to iofarcteda ~ , c o m ~ t o T c ==' PPi. 3.Lo~ F~i~

I

Quantdtation of myoearddal blood flow/metabolism requires knowledge of arterial (A) time laetivity curves (TAg). Such measurements are difficult because rapid A sampling is required. In cardiac PET A sampling may be replacad hy LV cavity measurements during imaging, requiring in turn a large number of images to be reconstructed for a high temporal resolution TAg. We investigated replacing A sampling with LV cavity measurements during bolus NH 3 dnjections. We tested the algorithm of Huesman (H)(Phys Med Biol 29,'84) allowing TAC's to be created from list mode data (saving at least a faetor of 30 in time). This rapid method was tested in 3 dogs (D) and in a dynamic cardiac iPhantom (P). Each D was injected with a 20 mCi bolus of NN 3 and data collected an sated llstmode. A samples were drawn each 2-3 see for 50 see and counted in a well counter. LV cavity TAC was generated directly from 5sec slnograms using H algorithm. Because of the high speed this was faster I b i n n a n g h a r d w a r e available, than using the list mode data directly. The P Itests utilized a cardiac P (Data Spectrum). Bolus injections of FI8 were made into the pump supplying the LV. Outflow "A" samples were collected each 2 sec. Lg TAC's were created erom images reconstructed each 2 sec and (for speed comparisons) from 2 sec sinograms using H. In D, agreement between LV cavity and A samples was good when gated and smaller unga ~ed volumetric aOI's were used. Significan~ size effects were observed, greater late (myocardial NBs>blood NH 3) than early. In P correlation between LV cavity PET activity and "A" samples was high (r=0.99), after appropria

pi~t~ i~ ~

co~pared to In lil-anti~mTosd~. 4.p~nent available

A. CUocolo, S.L. gacharach. R.O. Bonow, ~Carson, M.V.Oreen, E.F.Unger. C.Sheffield. S.D. Stein, E.g. Finn, P. Eersc0viteh.

RAPID ARTERIAL BLOOD CURVES BY CARDIAC PET WITH NO ARTERIAL S ~ P L I N G AND NO IMAGE RECONSTRUCTION.

~=~i~o

OO~ll~m:Tc - ~ is exce~ent f ~ imaging of early myo~srdial i~m-ci~.l./~dvarr~ge of early scinti~apby because

INFLUENCE OF ADRENERGIC BLOCKING AGENTS ON THE MYOCARDIAL UPTAKE OF 123 IODINE METAIODOBENZYLGUANIDINE ( i231-MIBG ) I231-MIBD, a norepinephrineanalog,has been recently iropased to study the myocardialcatecholaminemetabolism, The aim of our etudy wo0 to evaluate the influence of edrenerglc blocking agents on the myocardial 123I-MISG uptake. 4 mCi of Ig3I-MIBD were iniectedto 50 pai.ieni,e( tO controlaand 40 myocardial infarction- MI) and a LAD 45 ° ecintigredhy oF the heart was abtained 4 h p.L ROts were drawn BrOUnd the healthy leftven[ricule(LV) and around a mediastinalarea The Lg to mediastinalROle asLivityper pixal ratio was calculated, In order to study the relationship bet,weanthe myocardialuptakeOf 123]-MIBG and thecoronary bleadflow, 2 mClof2OIT ' Iwere iln)astedIV to 40 patients( I0 controlsand 30 MI patients)and a LAO view was obtained 15 rain laterThe resultswere as follows:

I 123-1"111~0 ControlsIn-tO) MI with hedarin ,in=el

1.76 ± 0.16 1.70 ~ 0.20 iNS)

201ll 2,36 ± 0,30 2.41 ± 0.36iNS)

MI with metoprololin=41 t 53 ~ 0.14 iNS) 2,43 ± 0.42 iNS) MI with ledetalolIn=3) 0 MI with amiodarohain=3) 1 45 ± O.04{piO,01)2,28 ± 033 (NS) MI with calciumblockers (n=I9) 150 g 0.20(p<0,05)2.52 ± 0,28 (NS) in=2) g i

Drugs have no influenceon lhe myocardialupi,akeof 2°III but decreasethe myocardial uptakeof 123I-MIBG , esp8elall _ y the Labetalol In concluaion I~ any interpretationof 12oI-MIBG ecintigraphiasshouldtakeintoaccountthe drugsthathave bean administeredto the patients,2- the 123]-MISG heart imaging is a most interestingtool to study In v~i'o in man the mechanisms of ecUon af drugs.

260 223 ?. HERLET) D. AGOSTINI, M.H. BOORGHIGNON, J.P. IICHALET, B. JOUVg, D, LEL--L~HC~ ~. - ~ A I G N E , ?. VERNANT, H. VALETTE, D. LE GULUDEC, C, {AYNAUD, A. S[ROTA. ~ervlee Hospitaller Fr~d~rle Joliot, )~partement de Riologle, CEA, Orssy, et CHH (ondor, Cr~teil, France.

~SSEgSMENT HF MYOCARDIAL SYMPATHETIC STORES IITH 1-123 META-IODOBENZYLGUANIDINE (HIBG) IN ~ONGESTIVE HEART PAILURg AND NORMAL VOLUNTEERS. [-123 MIB~, an analog of norepinephrine, has )een used to map s c i n t l g r a p h i c a l l y the adrener# e nervous system in man (RISgON). Consequen;ly, I-i23 HfEG myocardial scintlgraphy may be lsed to assess myocardial sympathetic function Ln congestive heart failnre (CHF) which is cha"aeterized by an excessive sympathetic tone, a Iowa regulation of cardiac myocyte beta receptors, and a d e p l e t i o n of myocardial sympathetic stores, lg p a t i e n t s ( a g e 4 ~ ± l g ) Vlth d i l a t e d eardiomyopathy in CEF - NYHA II or III and left ventricnlar ejection fraction < 40 ~ (4 Ischemic. 3 alcoholic, ii idiopathic) and ? normal vol~nteers (aRe 32 ± 7) were scintigraphically studied at rest after intravelnous lnJeetlon of 4 mCi of 123-I-HIBG. ECG Eared images were recorded during i 0 minutes, 4 hours after injection, in the anterior view in 64 x 64 matrix forest) 16 frames per cardiac cycle. A static image was also created as the sum of each gated series. Cinematic display showed a clear myocardial motion in the volunteers and very little change of activity in patients'heart area. Regions of interest were manually created over the heart area and in the upper medlastinum. Heert (H) to mediastinum (H) ratios were computed over the static image. The H/M ratio in volunteers was 2.16 5 0.38 and in the patients 1.19 ± O.15 (p
226

224 J.C. Maublant, D. Fagret, P. Peycelon, J. Verdenet 3.C. Cardo%M. Come L A. Veyre C%ntre 2can Perrin, Clermont-Fertand~ and the UniversiTy Hospitals of Grenoble and Besancon France r l - 2 0 l SPECT AND GATED CARDIAC BLOOD POOL IMAGING IN ACUTE MYOCARDIAL INFARCTION : RESULTS OF A MULTICENTER TRIAL 2OMPARING HEPARIN AND A NEW FIBRINO LYTIC AGENT Infarct size (IS) was measured by TI-20I SPECT ~nd left ventricular ejection fraction (LVEF) ~as calculated from gated blood pool scintigraphy n a series of 231 patients (pts) presenting with a <5 hours myocardial infarction (MI) and randomJy ~ssigned to an intravenous treatement hy heparin hep) or acyl plasmJnogen streptokinase activator :omplex (APSAC), a new fibrinolytic agent. 15 was measured by using a 35% isocount line to delineate the normal myocardium and a hand drawn contour to delineate the defect, lntetobserver reproducibility of the method was 0.95 for all the pts, 0.87 for the inferior MI, and 0.95 for the anterior MI. At contrast coronary angiography the patency rate was 33% and 73% in the hep and APSAC groups, respectively. The scintigraphic results were the following (m+_sd) : [g(% of total) LVEF(%) APSAC hep APSAC he~_ overall 13~li ** i9±1# ~3±12 * 39±12 anterior MI 18+_15*~ 27±16 38±I3 * 32~13 inferior MI 10+_7 12±8 t~7±8 #5~_9 • p<0.05 * * p<0.Ot In pts with patent or obstructed coronary arteries, LVEF was #5+~1 and 36+13, respectively, (p(0.001) and IS was 12+9 and 2J+1~ (p 0.001). There was significant negative correlation between IS and LVEF ( r=-0.73, p<0.01). It is c'oncluded that ia) APSAC significantly improves the cardiac [unction and decreases ]5, (b) TI-201 5PECT a useful method for 15 measurement.

227

225 u.--Sueli, w. Crosse, E. K£elnhaus, S.N. Reske, R. Uebis, H.D. Lo, H.J. Simon

Depts Nucl Ned, Cardiology and Cardiovascular Surgery, Univ. of Aachen, Dept Interbal Med., Teaching Hospital Dueren, YR Germany TI-201-SPECT TO DEFINE MYOCARDIAL SCARS: A RETROSPECTIVE STUPY 1N COMPARISOH TO ECG, WALL MOTION ANALYSIS (NMA) AHD INFARCT-HISTORY. TI-iOl myocardial SPECT is employed to document results of hypass-surgery or PTCA. However, some authors report on pegsistent myocardial defects (scars) which show redistribution or normal TI-201 uptake subsequently to such treatment. By employing a quantifying targetlike (33 ROt covering six 2pix short axis cuts) regional evaluation of TI-201 exercise/ Irest-SPECT, reflecting vitality (Of:% uptake to maximum), wash-out (NO: %loss between exercise and rest 13 hrs)) and redistribution {RD: gO corrected TI-201 gai~ rest vs exercise) we established a co~stellation of these 3 parameter to describe a myocardial scar within a routine Tl-201 exercise/rest protocol. Data from 25 pts with old ()g wks) transmural infarction (OMI, 14 of these apical), positive Q-wave in ECG and a- or dyskinesis in WMA (echography, CVG) were evaluated. Pour constellations (A-D) were separated (A: center of OMI; B: adjacent ROIs; C: surrounding transient ischemic area; D: normal) from 25 ORI and 25 surrounding areas (values: mean ~SD). s:p<.01 A B C D VI(%) 26.7±7 s 49.3555 48.15 7 s Ig0 gO(%) 28.0519 44.3±11 s 20.5~14 s 42.9±9 RD 14.619 S 2.4~ 5 S 49.8517 s S.356 We thus conclude that a myocardial scar is characterized by the combination of constellations A and B (extremely low VI adjacent to a ROI presenting isolated high gO) found i~ close proximity. A) may reflect Tl-kineties in tissue which is scarred, surrounded from or mixed with myocardial cells (g) with inadequate Tl-binding and/or high capillarizatioB. The simple description of a "persistent defect" is not sufficient to confirm a scar.

228

P. Pegcelon, 3.R. Lusson, B. Citron, Ph. Kohler, A. Richard, 3. Maub]ant, 3. Ponsonnaille, A,Veyre, 2. Cassagnes

R.J. Hicks, E. Laufer, V. Ealff, and M.J. Kell~. Department of Nuclear Nedlcine and Clini0al Research Unit, Alfred Hospital, Melhourne, Australia.

Medicine*, Landeskrankenhaus Feldkirch, Medical

Centre 3ean Perrin, University Hospital, Clermont-Forfend, France. USEFULNESS OF TL-2UI-TOMOGRAPHY F O R THE DETECTION OF RESTENOSIS AFTER SUCCESSFUL CORONARY ANGIOPLASTY

DIFFERENCES fN RESULTS OF ECHOCARDIOGRAPHIC AND Ti201 sCINTIGRAPHIC DlPYEIDAMOLE STRESS TESTS

INFL~ OF BETA BIDC
The aim of this study was to compare prospectively the value of clin)cal angina, exercise ECG (ETT) and stress-redistribution-T12Ol-SPECT for the detection of restenosts after successful PTCA, which is defined by a less than 50% residual stenosis, withoutany complication. 85 patients (70 men, II women), mean aged 5g.9 (33-78) were prospectively incJuded. 12 ~at ents had a non transmura[ myocardial infarction r3 had angina. 85 P T C A were performed : LAD=57, ~CA-Ig, LCX=IO. All patients were controlled ~iter PTCA (6.3 months) by ETT (,>75% of preJicted maximal heart tare, under medical treat"nent), T1201 5PECT and coronary angiography CA). Restenosis was defined as 50% or greater fiameter narrowing of the previous dilated artery. t was observed in 22 lesions (26%) : LAD=I7, ~CA=#, LCX=I. IR patients had recurrent angirla, with 13 restenosis ; ETT was abnormal in 18 :ases, with 10 restenosis ; TI201 SPECT showed t reversible defect in 27 cases, 18 had a restemoiis. The diagnostic value of the three non invasive echniques is expressed in % : Angina ETT 5PECT ;ensitivity 50~5 82 ;pecificity 89 87 86 Positive predictive value 69 56 67 Negative predictive value 85 82 93 Conclusion ~ 1) SPECT has a higher predictive value than ETT and recurrent angina for the ~etection of restenosis. 2) A negative 5PECT is highly suggestive of a good result. 3) StressSPECT can be used to follow-up the patients; only in case of positive test, control CA has to be performed,

We assessed the simultaneous effect oF intravenous dipyridamole (0.56 mE/Kg in 4 mlns) os regional wall motion (RWM) as assessed by two dimensional eehocardioNrsphy (ECHO). and on regloaal myocardial perfusion as 8ssessed by T1201 sci~*tigraphy, in 35 patients referred for dipyridamole stress tests. Test anginal symptoms were noted as presumptive indicators of true ischemia induced by dipyridamole. Elinded ECHO and TI2Ol results were compared in the 31 patlents with adeguate ECHO studies. Coronary angloErams ordered on clinical grounds revealed no false positive test results. Prior infarcts were present in 15/31 pts. Test anginal symptoms occurred in 11/15 pts with~ hut in 0/16 pts without a prior infarct (p<0.00t). ECHO and T1201 results correllated with test anginal symptoms as followe: ? Test Anginal symptoms Yes (]I) No (20) Reversible RW~4 abnormality 8/tl 1/20 Reversible TI201 detect 9/11 10/2g (H=NS) (p
Beta blocking (BE}and calcium ante~nints (CA)medication W-as described tm mask perfuslon defec~ in stress Ti-2oi myocardial sclntigraphy(Ms) . Since MS in out pat. often has to be performed during ~ and CA medicat/on, W~ evaluated the real influence of these drugs cn MS in the diagnosis of coronary artery disease (CAD) and compare~ scintigraphic findings with coronary angiographic results. 13 pat. (1o m, 3 f; age 34-58, ~=52) ~ BB meal/cation s h c ~ d after supIne bycicle testing an exercise tolerance of 3o-lcc%~=9o%)ard 5oIco%~=g8%)of the ~ax/mal heart rate value. 5 pat. showed perfusicn defects in MS which corresponded well to angiogr~aph/c results (2 lvessel disease(VD) , 2 2-VD, 1 3&VD) .2 ~at. had cardiomyopathy and 6 pat. hypertrophy of myocardium. 14 pat.(1o m, 4 f; age 41-64, ~=54)ttnder CA i~edication showed exercise tolerance of 29-Ioo% (~=75%)and 6o-Ioo%~=81%)of the ~axi~al heart rate value. Perfusion defects in MS corresponded with angiographic results in 8 pat. (I IW , 4 2-VD, 3 3-VD). I pat. had card±omyopath ~nd 5 pat. hypertrophy of my~,~rdium. 5 pat. (3 m, 2 f; age 44-72, ~=58) with both ~n and CA nedication showed an exercise tolerance ,of 5o-loo&~=6o%)and 55~95%~=83%) of maximal heart rate %~lue. Ab]%orr~l MS %ran d~Dnstrated in 3 pat. (I I-VD, 2 2-VD)with CAD and 2 pat. with hypertrophy of myccardium, In conclusion CAD can be identified by MS despite BB or/and CA medication. No false negative MS could be observed in th/s study. Well known p e r f ~ i o n defects in ~at. with hypertrophy of myocardium can also be de~Dnstrated in MS despite medication with BB or/and CA.

H. Fritzsche ,E.Hil ibz-=nd,M.Kargl, W. Eenzer*, ~.MtR~iberger#*. Department of Nuclear Medicine and Internal Un/versity Clinic**, Innsbruck, Austria.

261 229 P. NORELON, F. ANDRE, J.L. glCHER, T. MUNSCH, Q. DENTAN, J.L. PELLETIER, P. LOUIS and J.E. BOUHEY CARDIOLOGY DEPARTMENT, DNIVERE~TY HOSPITAL and NUCLEAR MEDECINE DEPARTMENT, CENTRE GENOGESFRANCOIS LgCLERC DIJON (FRANCE) EVALUATION OF CORONARY ARTERY DISEASE (CAD) BY DIPYRIDAMOLE (DIP) THALLIUM (T1) SPECT IMAGING IN PATIENTS TAKIN~ BETA-BLOCKERS (BB). It has been suggested that sensitivity of exercise Ti imaging for diagnosis of DAD could decrease in patients taking BS during the test. The aim of this study was to evaluate the influence of beta-blockade on results of DIP TI ERECT imagin G . We performed a DIP SPECT with DB and a coronary angiogram in d8 consecutive patients with actua] or suspected CAD (13 with myocardial infarction Eclntigr~ms were interpreted usin G vlsual criteria. 23 out of 24 patients with significant CAD 50 W diameter n~rowing) were identified by SPECT (sensitivity : 9E %), 2 normal patients had a false positive scan (specificity : 8E %j. In the 13 patients with single vessel CA0, one was not detected (a EO % stenosis of LAD), 9 were correctly identified and 3 were suspected of double vessel disease by SPECT. 8 cut of 9 patients with double vessel CA0 were correctly recognized, one was considered as one vessel disease. The g patientS with tciple vessel CAD were interpreted as two vessel disease, the poor accuracy in prediction of triple vessel 3AD by T1 imaHin G is well known. ~e conclude that DIP SPECT imaging can be per~ormed in patients taking BB without attenuation in sensitivity o~ specificity and with ~ood evaluation of vessels involved.

232

231

230 M. FARAfiGI, g. TgONNART. P. O. MESSIAN, P. ASSAYAG*, P. VALERE*, Servlce de Mgdeeine nuel6alre, Beaujoa, F-92110 CLICgV. * Service de Cardlologie, EEpltal F-gEflO CLICHY.

AUBNY*, B. BDK.

G.Cantinho, R. Ferreira, R. Rebelo, L. Rotes, F. Godinho

gDpital

BeaUjon.

DIPYNIDAMOLE THALLID~ MYOCAROIAL IMAGING (DPD-T) FOR DETECTING CORONARy STENOEES IN PATIENTS WITH VALVULAR HEART DISEASE : ASSESSMENT OF DIAGNOSTIC VALUE, The diagnostic utility of DPD-T in prediction c o r o n a r y artery disease (cAD) was evaluated in 34 valvular patients (E3 aortic, 11 m l t r a ] , age 63 ± ii) undergozng coronary a n g l o ~ r a p h y because of c h e s t p a i n (n = 21) or advanced age (> 40 f o r men and > 50 ~or women) p r i o r to v a l v u l a r surgery, A p l a n a r DPD-T w i t h r e d i s t r i b u t i o n Imagine and a c o r o n a r y a n g l o g r a p h y (CA) were both performed within 8 days. Positive criteria were : > 50 % stenosies at CA and systematized defect af DPD-T, The results of each test were read by two observers. Planar scintlgraphic images were obtained on 3 or 4 i n c i d e n c e s and processed for masking and background substpaotion. 13 p a t i e n t s had CAD a t angiography. DPD-T was positive in I0 patients (all with chest pain), DPD-T was negative in all as~ptomatlc patients (although 15 % had CAD) and lO symptomatic patients (18 • CAD). DPD-T value for detecting CAD was : S e n s i t i v i t y = 69 %, S p e c i f i c i t y = 95 ~. positive p r e d i c t i v e v a l u e (pPV) = 90 ~, negat i v e p r e d i c t i v e v a l ~ e (NPV) = 83 %, 3 out o f the 4 f a l s e n e g a t i v e races h a d a o r t i c disease. The only false positive case was a woma~ who had a mitral stenoszs. The PPV o f chest p a i n alone (52 ~) was i n c r e a s e d t o 90 • i f a s s o c i a t e d with posltive DPD-T. Positlve DPD-T therefore Is highly predictive of CAD. Inversely IS % of t h e asymptomat i c patients and 18 % of the symptomatic patients presented a CAD even thnugh the DPD-T was negatlve.

233

Department of N u c l e a r Medicine; D e p a r t m e n t of Exer c i s e Physiology. C . C . U . - Lisbon U n i v e r s i t y - P o r t u g a ~ P U L M O N A R Y U P T A K E OF 201-TL IN T H E EYALUAT ION OF SEVERE L E F T V E N T R I C U L A R DISFUNCTIO~ BEFORE C O R O N A R Y SURGERY Perfusion studies with 201-TL allow an accurate evaluation of areas of myocardial ischemia but do not give information about the degree of LV disfunction (D)after exercise (Ex).Pulmonary uptake of TL(PU)has been related with the degree of LVD.Inthis report we quantitate PU of TL which we compare with other indices ef LVD. 23 patients (p) with severe coronary artery disease(CAD),selected for surgery, werestudie~ 5 m after i.v. 2 mCi of TL, at maximal Ex in PA,LAO and tat. Emission computed tomography(ECT)wastake[ after planar(Pl)images(1).Reperfusion(R)were taken al 3 h. Index o~ PU(Pl) was the reason between the c~In~ /pixel in a ROt of heart and lung in PA, TL uptake by right V(RV)and LV was also quantitated. The followin variables were considered: heart rate(HR),double product (DP),time(Tm)of Ex, age, LV ejection fraction (LVEF),nr.of segments (Sg)withchanges of motion,hr. of diskinetic Sg (DISK),nr.of lesions(Le)inECT after Ex and R, total of vessels(VT)~nr, of major Le(MLe)in coronary angiogr~hy . Results: Pl after Ex was correlated(DR) (p~0.05) with LYEF, DISK,DP ~Tm_~ofEx and MLe, 10 p had PI Ex ) .50__~(A) with LVEF=0.33;the others (n=13)(B) LVEF= =0.47. PI Ex in A CR with DISK,Tm of Ex (p<0.05). In ECT of TL Ex average nr. of Sg with Le was 6 (A);d(B) In ECT of TLR nr. Sg with Le was 3 (A); 2(B). PIR CR with HR, Dr(p<0.05). PI Ex/PIR CR with LVEF(p<0.051 TLU in RV had no CR with any variable. I Concl~sions:l) In p with severe C A D PI Ex was ~in 43%. 2) P with PI Ex>0.5 had # L V E F (0,-3-3);thosewith Pi Ex{0.5 had normal L V E F (~0.45). 3) P1 Ex C R witt Jnr. DISK Sg and PP. 4) N o C R was found between Pig and variables evaluated. S) PI Ex C R with variables t h a t are indices of LVD.

!34

R.T. Go, W.J. M a c l n t y r e , J . L . King, P.K. Rehrn, J.K. O ' D o ~ l , D.A. Underwood.

Fraile M. Castell J., C~ndell J., D ~ F M .

H.VALETTE, M~.BOU~GUIGNON, D.AGOSTINI, D,LE GULUDEC.

Cleveland Clinic Foundation Department of N u c l e a r M e d i c i n e 950D E u c l i d Avenue C l e v e l a n d , Ohio g9106 U.S.A.

M~pital General Vall d'P~bran, Barcel~

EHFJ-CEA,

EFFECT OF TRALLIUVV201 SPECT MYOCARDIAL I/V~Oli~ ON FREQUENCy OF SUBSEQUENTCORONARy ANCIOGPJ~°HY RELATED TO CA,TEGORY OF REFERRAL. Thallium-201 SPECT m y o c a r d i a l imaging (TI-SPECT) is no l o n g e r performed o n l y as an initial s c r e e n i n g t e s t b u t is now i n v o l v e d i n many o t h e r aspects of p a t i e n t management, i n our institution more Ti-SPECT s t u d i o s a r e now per[o~med a f t e r a n g i o g r a p h y has a l r e a d y been done t h a n b e f o r e a n g i o g r a p h y is performed. T h i s s t u d y has been d e s i g n e d to d e t e r m i n e i n w h i c h of these v a r i o u s clinical referral c a t e g o r i e s is t h e r e { l a n c e of the r e f e r r i n g clinician sufficient to p r o v i d e a d e f i n i t i v e d e c i s i o n f o r p a t i e n t management w i t h m i n i m a l r e f e r r a l s f o r subsequent a n g i e g r a p h y . I n a t h r e e month p e r i o d 62~ p a t i e n t s were r e f e r r e d by C a r d i o l o g y f o r TI-SPECT and of t h e s e 276 p a t i e n t c h a r t s (~9%) v ~ r e r e v i e w e d . One h u n d r e d and seven p a t i e n t s (39%} had TI-SPECT to r u l e out CAD b e f o r e a n g i o g r a p h y was c o n s i d e r e d . Eig~nty-four s t u d i e s (30%) e v a l u a t e d p a t i e n t s w i t h r e c e n t CABG a n d / o r PTCA and 85 s t u d i e s (31%) were done to evaluate patients w i t h remote CASG/PTCA or known c r i t i c a l or s u b c r i t i c a l CAD. Of the 107 s t u d i e s performed on p a t i e n t s w i t h o u t p r e v i o u s a n g l o g r a p h y 96 were n e g a t i v e of w h i c h o n l y two had subsequent a n g i o g r a p h y . In the r e m a i n i n g 169 p a t i e n t s , 65 s t u d i e s ~ e r e n e g a t i v e and o n l y one p a t i e n t had subsequent coronary angiography. Of the total 95 p o s i t i v e s t u d i e s 11 (9%) of t h e p a t i e n t s had subsequent a n g i o g r a p h y . These d a t a show t h a t TI-SPECT has r e s u l t e d i n a low f r e q u e n c y of subsequent c o r o n a r y angiegraphy in all categories, indicating a h i g h l e v e l of r e l i a n c e and c o n f i d e n c e i n b o t h positive and n e g a t i v e TI-SPECT in p a t i e n t n ~ n a q ~ r ~ n t and d i s p o s i t i o n .

In d%s ~ t of same r ~ c ~ i b u t i ~ on the ~ i m n a~al)~is of ~ i s , t h e efficacy of ~alium s f ~ fast is r e , r i b . T e a reported variability in S~sitivity (~) and Specificity (~p) is exceedingly i ~ (P~,1987) and ~ ~xsi~ian a f ~ D i ~ (Dia,m~,iSST) is Se and Sp ~ as a ¢uatinsus fhnctign of the p r ~ i l i t y of pos~$ive +~t r~-ult (p(~÷)). This simply cam=e fm3m ~ e fsct t~t B~y~' ~ r ~ m cau be m - ~ in ex~x~s Se and S p m ~erms o£ P(R+) and Predictive ~u~cy.Baslc is tb~t the latter can be ~ r i v e d frum a ~ of ~ t i a ~ t~en in a n ~ . T~Js,~e have calculated the "oo~cted valuta!' Fac both Se and ~p Jn 5V3 patients s~pecind of G~D.73 of whm~ unde~-

0.50 In the 75.P(~+1 was 0,58 i n the ~hole se~e~,~d 0.66 i n t~e v ~ i f i e d ~'~up.Afet~ cm~u~_cn, Se ~ecz~oed from 0.97 in O.96,~hile ~p ~ (as expected) Hr~m0.72 to 0.7~. PostUre and Negative Fredic~ve ~ ~m~ also ~crr~=~ed (O.~ and O.95,r~peetively compared in ~igin~ ~ l u e s of 0.79 and 0.97). A l ~ c ~ h some r~ca~t ~ r e t i c a l d~jectians a-e far~sem (Tavel.1987),~e feel that such ~ , = ~ t i a n i ~ c e d r e ~ri~-,~tar~s in ;x-actine,f~ ~ is no better ~prz~ch to the m:blm of tc~wir~ d~e o c t a l t~Zium t ~ t etTicac~.It dlould be gmod practice in include the so-called 'Gil~t ~j~i~' of mn~nmogrphy patienin wha~ r e ~ ~n J~edi~ ~ efficacy. A,Bermmn ~S:Tne a 4 T i ~ of c~rdi~=scul~ nuclear ~licine e ~ sindies,S~iMed 1967;17:10a-120. )iamm~d ~A:Pexer~xl ~yes' Silent N~jori~y,h~Cardiol 1987;

57:11~o-ii79.

~avel~,Enas NH.~ods J~:S~itivi~y aad ~oecificity of ~t;Can ~le "Silent ~ i ~ ' spe~k?.A~JCardiol 1987; 90:1167-I/69,

P.MERLET,

0rsay, France

VALIDATION OF AN ALGORITHM DF AUTOMATIC DETECTION OF LEFT EPIEARDIAL EDGES ON THALLIUM 201 IMAGES. For reproducible, reliable, quantltation of defects on thallium scintigrams one needs automatic detection of the epieardial boundaries. The algorithm accomplishes a 12 = radial search from the geometric center of the myocardium. On each profile the maximum downslope is selected as the epicardlal edge with continuous control of the radii. The algorithm has been tested on planar images (anterior,LAD 45°,LAO 65 =) in 80 patients and on short axis tomographic images in i00 patients hoEh at stress and rest. The edge detection was performed twice to assess the reproduetibdllty (R). The automatically generated ROls were compared with the 45f dsocontour. A trial was considered as successful when the ROI appeared to enclose all and only the left myocardium. On planar images we had 442 successes (92%)- These failures (8%) were due to large anterior defect and high background value. The RDI determined hy the isocontour had only 35 % success rate in determining an accurate closed contour. The comparison of 2 successive determinations showed a good R of ROI size (slope = .95~.02) and counts (slope s .96~.03).In the second group there were Ig8 successes, The fail~res (6%) happened in noisy images (large myocardial infarction and low exercise level), The 45% isocontour determinaDion of the ROI was suceesseful in only 17% of the cases. The comparison of 2 successive determination also showed a good R of the ROI (size:slope= .95+.02 ; counts : slope=.94~.02). In conclusion this algorlthm give satisfactory results in routlne.

262

235 A.C. Tweddel,

236 W. Martin,

I. McGhie,

I. Hutton

237

IL;nd,P., Eber,B.*, Fluch,N.*, Brandt,D.*, ~steger,N., Klein,W.*

9. ;,~rzullo.

University Department of Medical Cardiology, Royal Infirmary, Glasgow, Scotland

Department of Internal Medicine, Hospital Barmherzige BrUder Graz-Eggenberg *Internal Medica] School, U n i v e r s i t y of Graz

C.N,R. I~ZTITCIE C~ C L ~ C A L ~[fSIOIf~Y, PISA, ITALY

ACUTE PERFUSION

T]-2OI-HYOCARD SPECT IN THE DIAGNOSIS OF SILENT MYOCARDIAL ISCHE~IA

C~ARATIVE VAU~ OF RADI~ZCLLDE V E h Z ~ I C ~ ~[ALLIL~%~I ScIr~Y(I%%mHV 1~.; vAse~srIc ISC}~7,JA

IMAGING FOR INFARCT SIZE

In patients with acute coronary artery oeclusioz flow markers can reliably detect the site of infa~otion. Gated Thallium-201 imaging was used to provide an estimate of infarct size in 120 consecutive patients scanned acutely at a mean time of 86 minutes from arrival at hospital, using a mobile Gamma camera, following an intravenous injection of 60 MBq of thallous chloride Infarct size was estimated in the 82 patients subsequently proven to have myocardial infarction and correlated with clinical (Norris Index) and enzymatic (Peak CK and CKMB release curves) estimates. In patients with first infarction there was a significant correlation between perfusion and enzymatic estimates of infarct size - r-0.7 (p<0.OOl) for 22 patients with anterior infarction and r=C.5 (p
Today, painless fores of COronary heart disease are summerized under the tere "silent myocardial ischBmia". In the absence of clinical signs suggesting th5 probability ef coronary ischBmia, a stregelined diagnostic approach for prBcise clarification proves to be difficult. In symptomfrse patients, positive ergometric results correlate with coronary stenosis only in about 25 % of the cases. Thus, the question arises whether the need for coronary angiography can be established more precisely by TI-2Oi-Myocard SPECT in these patients. The aim of the study was: (I) to examine the accuracy of Tl-~O1-Myocard SPECT in silent myocardial iscbemia established via angiography,and (2) to compare a positive TIMYOCARO-SPECT with the coronary angiographical results in symptomfree patients with positive ergometry and/or risk factors. SPECT was performed in~ediate]y after maximum ergometer load and 3 hours after injection by elliptical scanning over 180 degress. In patients in whom silent ischaemia had been established anDiographically by a coronary stenosis >75% (n=16), significant stenoses in excess of 75% corTespogded mostly to reversible defects, subtotal stenoses or complete occlusions correlated with irreversible defegts. In the lower probability group (symptomfree patieBs with risk factors and/or positive ergometry), the positive TI-SPECT findings (n=27) could be confirmed by aBgiography in more than70%.

239

238

W. Martin, Jure Fettieh. IRor granjeo

Matjag Singovee,

I. McGhie,

I. Hutton

THALLIUM AND ECG STRESS TEST IN HYPERTENSIVE WOMEN WITH CHEST PAIN Chest pain is relatively common complaint in middle aged women and proper evaluation of this simptom is difficult as prevalence of coronary artery disease (GAD) in wom~n is low. The prognosis of associated CAD and hypertension (HT) is worse than in hypertension alone, especially in women, who tolerate HT better than men. The aim of the study was to compare the results of noninvasive ECG and T1 stress tests in nommotensive (NT) and HT women with chest pain. 61 HT (RE> IBO/90), mean age 50,5 years, and 72 NT (RE < 160/80) women, mean age 4g,4 yearsj were evaluated. Patients with previous myocardial infarction, mitral prolapse, valvular disease and ea~diomyopathy were excluded. Typical angina, atypicel anginm and atypical chest pain were distributed evenly in both groups. ICompared with coronary 8ngiography results T1 imaging proved to be most accurate to diagnose !CAD in HT women, with slightly more false positive results in HT than in NT group. ECG stress test yielded high number of false posiItive r~sults, while resting ECO w B s not diagnostic. P~evalence of CAD in HT women was not siRnifieantly higher tham in NT group (15/61 and 16/72 respectively).

IRUonyaVlrii~iYr DmaerPy,rtGl nstgo°f 'Msd~t lalnCardi°l°gy '

Is MYOCARDIAL

IBCHAEMIA

REPRODUCIBLE?

Perfusion imaging is frequently used to assess the effects of either mechanical or pharmacological interventions. It is therefore important that the determinants of the reproducibility of these images are known. We studied 12 male patients with arteriographically documented coronary disease (CAD), in whom gated thallium imaging was repeated following symptom limited maximal exercise testing on an erect bicycle ergometer and a supine ergometer. In a further 5 male patients (again with CAD) scans were performed following 2 symptom limited maximal erect ex~rcise tests, 4 weeks apart and a third test performed to the same worg load as the initial test. Scans were reported visually semiquantitatively by 2 observers, from the gated images for 3 left ventricular segments from the • • . o anterlor project±on, 3 from the 45 left anterior oblique (LAO) and g segments in the 75 c LAO, The mean difference between observers was 2 f 2%. Between the scans performed erect and supine, there was agreement in 66% of segments, with similar variations involving the septum as inferiorly. In the 5 patients who performed 2 maximal tests, in iO segments of 50, disagreement occurred; thus in 20% of segments the diagnosis changed. Similarly. the diagnosis altered in 18% (9/50 disagreements) of segments between the maximal exercise test and that performed to the same work load. In only 50% did disagreement occur in the same segments. In conclusion, when using perfusion imaging to assess an intervention, cognisance should be taken of the reproducibility of the site of defects, due presumably in part to the variability of myocardial ischaemia.

I

Aim of this study was to corpare toe usefulness of radionualide ventriculoHraphy (~NA) and thalliu~wgOl scintisr%thy I in ~le detection of site ~nd ezghemt of ischemia in pati~ntsl Ipts) w i ~ vmsospBstic ar~ina (VA).i,~ evaluate~ 21 pts with VA characterized by ST elevati~] on ~ne ir~erior lends ~ I J isolated ri~t coronary 8rte/~ disease (iS pts, G r ~ I) or ST elevatic~ ca the Bnterinr leads ~nd isolated left ~ta~ior descending artez~ disease (H pts, (Youp If). Both I Jscintigr~nic s~dies were per~or~] in basal conditions I ~nd du~i~ spc~f~eous or e r ~ v i n e induced isch~ia in Isepapate but supe~impossble episodes. ~ A ~ performed in I LAO orojectinn while the 3 stonc~] vi~s were used in thallit~ studies. Left v~nthicular (LV) wall i~tio~ and I ejection fraction (EF) C h ~ du~ing isthemis were derived from ~ data. In Group I 10/13 pt.~ (IT/o) ~ w e d reversible LV dyssyne~ies; LVEF fell ~ ~ 6 D 52_+5 (p<.Oh)- Inl G r ~ II 8/5 pts (lO~g) d~cr~tratod LV dyssynergi~ durir~ ischemia; LVEF fell from $2+6 to ~ (p<.Ol). TnelliL~ anmlysis shewed rever~ibls LV defects in i0/13 pta (7~/o) of I and in 8/8 pi~ (lO~g) of Group il, ell with L~ ischemic ~y~s~nar~ies. The 2 tee/-~iq/es exhibited I00~,~I oonc~ in the detacfion or the ~clusion of LV isdlemia and 81% agreement in its regicrml localization by the analysis of [AN projection. Ehe availability of I multiple projections in parft~ion si~dies permitted to detect additional defects of the anterior wall, ~lide could not be visuelized by ~NA. in a pts of Group II ~nd to correctly loc~lize in~erior or apical isch~mia.Fr~ ~ . ri~1i v~ntricul~ (RV) f~ncticn was ~ assessed; ~lis ventricle never visualized in thallium sindi~s. In ~ 1 12/13 pts(~) showed RV isthemic dyssyne~gies;V~F~ fell f ~ ~ _ 9 th ~ (p<.Ol). In Group II no HV functional ch~age demcr~tr~ted dt~i~ isdle,da. In ocnclusicn:in pts w i ~ VA, ~qA and ~lalliL~ scinti~rs~%y ar~ s~ser/mposable t e c ~ q u ~ in the detection of LV ischemia but ocmplem~nta~y i~ its regional localiz~tion; RNA prOVides Bdditic~al information on the LV Klob~ impairment ~nd the possible e x t ~ i ~ of isch~mia to the r~ht v~st~icle.

l

240 A.C. Tweddel,

Gorazd gntoli~,

Departments of Nuclear Medicine Bnd Cardiology, University Medical Centre Ljubljana

~,D

I

M.A. Antar~

R.A. Remhish, A.U. B u a t t i

Univ. of Conn. Health Center, Farmington, CT and V.A. Medical Center, Newington, CT 06111 U.S.A. PULMONARY UPTAKE OF THALLIUM 201 AND WASHOUT AFTER EXERCISE AND DOBUTAMINE STRESS TEST.

Increased lung uptake after exercise Thallium imaging has teen correlated with an exerciseinduced elevation in left ventricular filling pressure and is associated with worsening of the prognosis. DobuDamine Thallium scdnti ~ graphy has bpen proposed as an alternative test for detecting coronary disease, especially in patients who cannot exercise or who exercise inadequately. To evaluate Thallium lung uptake and washout after exercise and dobutamine (DO) induced stress we studied 22 patients ~ith coronary artery disease; (12 ERER and 10 DO). The exercise test was a symptom-limited tread mill according to Bruce protocol. At peak exercise, 3 . O m C i were injected I.V. For dohufamine test, DO w a s infused in incremental doses; 5, i0, 15 and 20 mg/kg/min. Thalllum scintigraphy was started during the maximum dose tolerated. Del~yed views were obtained 3 hours later. The computer images were evaluated visually and quantitively by ROI technique. These views were imaged (LAO 45 Q , LAO 60 ~ , Anterior); each view was divided into 5 segments for computer analysis. Fo~ exercise and DO tests, Mean % Lung washouts were 29.6 ! 6.8 and 27.5 ± 14.0, hut myocardial washout in peak segments was 43.0 f ii,74 and 27.2 ± 11.7 respectively (p<0.OOl). Mean lung count (per pixel) was markedly reduced after DO compared to EXER; 46.1 ± 5.0 and For well I 90.5 ± 9.7 respectively (p<0.001). perfused myocardial segment, a similar decrease in mean count was found (p~O.O01). Hence the ratio of lung to peak myocardial uptake did not change. The data suggests although the absolute pixel count of lung Thallium activity after DO was decreased (halved) the washout rate did not change compared to that after EX.

263 243

242

241 . BOTSCH, H. WEIDEMANN; A. ZAHARESCU

I. E ~ ,

H

~4J Hohm~med, IM Hassan, C Constantinides, Y Kewan, M Nair. G Cherian, }~ Abdel-Day~,

A. ~5'~, ~. ~ R

Depts. of Nuclear Medicine and Cardiology, Kuwait University and ~ H , Kuwait.

[IHALLIUMt-~ ~ ~ V I S U A L ANALYSIS (VA) AND LUNG/HAERT (L/H) RATIO, CORRELATION WITH POSTEXERCISE PULMONARY CAPILPARY PRESSURE (PCP).

Increased TI-201 lung activity has been ohserved on early postexercise images in patients ~ith left ventricular failure (LVF), In 76 pa~ tients (pts) postexercise Ti-201 L/H ratio and ~CP were compared and a significant correlation ~as fouod (r=O,71). 27 pts with normal 'PCP (< 25 ~m HN) showed normal lunguptake evaluate( ~y VA. Two had an L/H ratlo greater thah 0,48. Sonsidering l/H ratio 0,48 as the upper limit of normal, the specifity for esseesment of LVP ~as 93~ (L/H ratio) rasp. 100% by VA. The sen~itivities of VA and L/H ratio for LVF were as VA follows: = 49 (PCP 25 mm) 36/49

73%

[/R ratio 40/49 84%

e conclude: T1-201 L/H r a t i o correlates with CP. Severe LVF (PCP > 30 mm) can be detected by /H ratio as well as by VA, while in moderate VF lung uptake is-normal in some patients. mphasis is given to the high specifity of the 1-201 lung analysis.

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l~+~/~ ~ h ~ afbe~ ~ne emr~_ize. ',h co~llde %h~ ~ D~p~" period for ~

245

244 ~. Master, N. Gruber, L. Alm&si, Gz~sz, S. Kov~cs, L. C s e r n a y Institute

Department Department Gy~rgyi Hungary

ix~t~-~ise

of of

of

K.

Nuclear Medicine, Cardiac Surgery, 2nd

Medicine;

Medical

Albert Szent-

University

~z~ged,

201~TL STRESS INVESTIGATIONS PATgENTS UNDERGOING BYPASS SURGERY The e÷glciency og stress ~cintigraphy wa~ examined

IN

20t-T1 in 31

patients who u n d e r ~ e n t aorto-coronary bypass s u r g e r y (ACBS;. In a l l p a t i e n t s , b i c y c l e e x e r c i s e 201-TI scintigraphy was per&ormed before t h e i r cardiac c a t h e t e r i s a t i o n . One week b e f o r e and m o s t l y 3 weeks a f t e r ACBS, d i p y r i d a m o l e (DIP) ~tress scgntigraphy was performed. Both types of TI studies were repeated & month~ a f t e r s u r g e r y . S c l n t i g r a m s were e v a l u a t e d v i a maximal circumgerential activity and washout profiles as compared t o narmal l i m i t s (mean-2SD)~ determined i n t h e same 20 young h e a l t h y v o l u n t e e r s for bicycle

and DIP stream s c i n t i g r a p h y separately. R ~ s u l t s : N o s i g n i f i c a n t d i f f e r e n c e s ~ere found between normal a c t i v i t y profiles a f t e r b i c y c l e and DIP s t r e s s . The mean washout a f t e r b i c y c l e s t r e s s was s l o w e r than a f t e r DIP, b u t t h e d i f f e r e n c e was not signigicant. The s e n s i t i v i t y of bycicl= stress TI s c i n h i g r a p h y before s u r g e r y was 29231=94%. The s e n s i t i v i t y of DIP 201-TI scintigraphy before surgery was 2B/31=90%. Changes a f t e r surggry were found i n 26 tales. Co nclusions from bicycle exercise s c i n t i g r a p h y and alP s c i n t i g r a p h y were i d e r , t i c a I 6 months after surgery i,11 2S131 cases~ but 9 patients demonstrated a slow washout i n DiP I scintigraphy, w hich c o u l d not be observed i n b i c y c l e s t r e s s s c i n t i g r a p h y .I Conclusion= B i c y c l e and DIP s t r e s s T1 s c * n t i g r a p h y are a l t e r n a t i v e methods i n I t h ~ m o n i t o r i n g of myocardial p e r f u s i o n .

SB~Iv~T-AL DIAGNOSTIC ACCURACY (SDA) OF SPECT DIPYRIDAMOLE TI-201 (DP TL) pERFUSION STUDY IN OOMFARISON WITH EXERCISE SPECT TL(EK TL) 1N PATIESFfS (Pts) WITH CAD. Intravenous (IV) DP has been suggested as an alternative to EK TL for myocardial imaging ~41). To determine the SDA of SPECT (DP • ) MI we compared two groups of Pts with IND. [0 had (DP TL) by 4 sin infusion of 0.568 mg/Kg )P. The mean age 47+9 years, 15 male and 5 f ~ l e . 24 male Pts~ mean age 46.7_+10 performed symptom limited (EX TL) studies. All had coronary angiography 2 weeks after M1. SpECT icquisitlon, 32-views, ]80 shortly after DP Lnfusion or (EXIt) and repeated 3 hrs later. ketlvity in 4 myocardial segments (S) was assessed vis~ally ~nd by Bullseye by 2 trained )bservers. The h a ~ y n a m i c changes due to IV DP were as follows: ~/min Syst.BP(~m H~) Diast.BP(m~ H~) ~est 66 + 20 135 ~ 2 1 8~ + 9.4 )P 91 ¥ 19 121 ; 24 81 ¥ l1.6 ~P) < 0-001 < 0.501 < 0--01 ~PECT ( ~ TL) ~ d (DP TL) correctly id~tified H of 96 and 69 of 80 segments respectively. ~ne comparison results are in foll~ing table: Sensitivity% S p e c i f i c i ~ Accuracy_ ~t. EXTL 85 100 88 77 86 80 ~ept.~TL 90 75 88 DPTL 85 86 85 ~at. }~/fL 86 90 88 DPTL 92 86 90 i n f . K~£L 93 100 96 DI~L 93 80 90 ;lo- ~L 100 96 98 ~al DPTL 92 100 95 We conclude that SPECT IV (DP TL) has _=qually good accuracy as (EX TL) in diagnosing ~nd localization of CAD.

246

E. Moser, g. Noefling, C.M. Kitsch, P. Knesewitsch and A. gtaeblein

M . B A Z A N * . T.GILLET'*, G.TESSONNIER**, G.LE CORFF', C.de LAFORTE*, P.J. BERNARD"

Dopes. of Radiology a~d Medicine I, Umiv. of Munich. Klinikum Grosshadern, Munich, FRG

• Service d'H~matologie et Cardiologie Isotopiquea. H6pital de la Timone. Maraeille. "" Service de Cardiolegle. H6pllal de la Timone. Marsei,e. FRANCE

FOLLOW UP OF C~-PATIENTS AFTER PTCAAND PERSISTING DEFECT PRIOR INTERVENTION USING TISCINTIGRAPEY In planning percutaneous transluminal coroner ~ngioplasty (PTCA), it is essential to know. whether a persisting defect (PD) in the TIseintigram after exercise (Ex-Tl-Sc) corresponds to avital myoeardium or severe ischemia but vital tissue. 47 patience (pro) scheduled for PTCA and having PDs prior to this interventlon, were included. 47 ptS had a history of myocardial infarction. Most of the pts (34; 72%) belonged to the angina pectoris class llI and IV. The scintlgramwere perfo~ed i ~ e diately after threadmill exercise and three hours later using 75 MBq (2 mCi) 201-TIchloride. For a visual evaluation, a viability score was established ranging from I to 5 (t: normal; 5: PD)- In 19 p=s (40%); PD was present even after PTCA. In ~he remainder (28 pts; 60%) PTCA resulted in a score-improvement. In A p t s (9%) a normal result in the Ex-TI-Se was present after PTCA. 45 pts were reclassified with lower angina pecsoris (classes I and gI). As a conclusion, PD in Ex-TI-Se is not necessary equivalent to avital myoeardium. It can also be caused by severe myocardial ischemia. As ~ consequence, PD in Ex-Tl-gc is not a contraindicaEion against coronary intervention.

DtPYRIDAMOLE-TL20f SPECT IN ASSESSMENT OF CARDIAC RISKIN VASCULARSURGERY. We assessed symplomallc,electrocardiographlc, scintigraphic findings in 102 consecutive patients (97M,5F) referred for aortic reconstruction surgery with aorlic cross-clamping. 45 patients were considered to have symptomatic coronary artery 'disease (CAD) on history or electrocardiographic evidence of previous myocardial infarction, AH patients underwent Oipyridamole-Thallium 201 SPECT (D-SPECT) by 4 mn infusion of 0.57 mg/kg .There were 60 patients with normal scans, 42 with abnormal scans. 21 with redislribuRon, 21 with persistent defects.Four cardiac posboperalive complicalions occurred, two deaths, one myocardial infarction, one angina,The incidence of complications was similar, for patients wilh symptomatic CAD (?J45), as for whose who were asymptomatic (?/57). Comparison of D-SPECT results and cardiac events:

Normal Abnormal Redist Defect D-SPECT No of palients Complications

60 0

42 4 p<0.03

21 3 p<0.02

21 1 NS

The results suggest that abnormal D-SPECT scintigrams with good redistribution are found to be superior in predicting post operativs cardiac complications than the presence of abnormal exercise or resting eleotroco,rdiogram and symptomatic CAD.

264 247

248

K~P:. EaisgK t , E. r e s t e r =, K. Grossmann *, A. gtorcb-geeger t, g. Geuting z, B. L6sse 2 L.E. Feinendegen ~

M Kaoo. R.Zimmermann, H.Tillmanns, M.Eisenhut, B. Bubeck, H.Aehenbach, W.Saggau, G.MalI, W Klibler. Departments of Cardiology, Nuclear Medicine, Cardiovascular Surgery and Pathology, University of Heidelberg, Federal Republic of Germany.

i) Institute of Hedicdne, Nuclear Research Center J~lich, 5170 Jdlieh, FRG. 2) Dept. of CarddolONy, University of Ddsseldorl, 4DO0 D~sseldorf, YRG.

MYOCARDIAL IODINE-123 PHENYLPENTADECANOIC ACID EXTRACTION IN PATIENTS WITH S E V E R E C O R O N A R Y A R T E R Y DISEASE

ORTHO -*zs I-PNENYLPENTADECANOlC ACID (OPPA): BASIC BIOCHEMICAL ASPECTS AND CLINICAL APPLICATION. OPPA is readily taken Up by the human myocardium and retained there for hours (T~ ) 200 Min.). The clinical use of oPPA was tested with SPECT in 42 Patients with coronary artery disease (CRBI. To elucidate the prolonged retention the distrihutioa of lahel in lipld fractions was measured in rat myocardium with a~d without blocking of transport into mitochondria. The clinical study was performed with ~z~Ilabelled oPPA in 42 patients with CAD diagnosed hy coronary angiography (i VD/II r 2VD/14, 3VD/I1, minimal changes/5 and 1 normal). aPECT was performed with 180~-rotation after an overnight fast, bicycle exercise and injection of 111-195 MBg oPPA. The rat experiments revealed that oPPA remained maiul~ dn the free g~tt~ acid poolt blocking of the carnitin shuttle had no significant effect on the distribution of lahel io the lipid-fractions. Thus the trapping site of oPPA is the cytosolic lipid pool confirming Iindings in man. - The clinical study showed a sensitivity of 90% for the ' detection of CAD (stenoses >50%); specificity was 60%. The trapping of oPPA in the eytosolie lipid pool is advantageous especially for time consuming SPECT-studies. The combination with the better imaging qualities of iasI leads,[ as shown, to a high sensitivity in the detection of CAD. The low specificity might be explained by myocardial metabolic alterations for various reasons, which warrant further elucidation.

To assess the diagnostic reliability of myocardial iodine123 phenylpentadecanoie acid (IPPA) extraction, 14 symptomatic patients with multiple-vessel coronary artery disease were investigated. 160 MBq IPPA and 75 MBq ThalUum-2Ol (TI-201) were injected simultaneously during symptom limimd exercise test. Planar imaging was performed in the AP, LAO 30 = end LAO 60* view at 5 min, I br and 4 hr after injection using dual-channel analysis with energy settings at 160 keV for IPPA and at 75 keV for TI-201. After interpoladve background subtraction, regional and global myocardial IPPA extraction was estimated by calculating the count rate ratio between IPPA and TI-201 in the initial scintJgrams (normalized to injected dose). Global myocardial IPPA extraction amounted to 43.5_-+6.,*%in the total study group and was inversely related to the extent of coronary artery disease: myocardial 1PPA extraction decreased with rising gensini score (p~0.05). However, IPPA extraction was also inversely related to both exercise ]eveI and maximum heart rate achieved during stress test (p<0.O5). Despite high overall correlation between the regional uptake of both tracers (r=O 96, p<0.001), segmental analysis of IPPA and TI-2Ol uptake in patients with previous myocardial in' farclion revealed a significantly larger defect size with IPPA ($7+_21") as compared to TI-201 (65+_17~, p
250

251

l.M.Hassan, M,M.J. Mohammed, C. Constantinides, S. Sadek, M. Nair, N. Belani, A.M. yousef and H.M. Abdel-Dayem. Depts. of Nucl. Med. and Cardiol., POM, KT Univ., and Chest Hosp., MPH, Kuwait.

SF/~AL ANALYSIS OF SPECT Te-99m METHOXY [SOBUTYL lSONITELLE@2-30) AND THALLIUM201 (TI-20]) MYOCARDIAL IMAGING IN ISCH~IC HEART DISEASE(IHD). Te-99m RP-30 is under evaluation to replace TI-201 for myocardial imaging. We compared both in 24 patients. All had stressrest TI, RP-30 and coronary a~giogr~phy (C~A_) within a period of 3 weeks. All had history of 1HD. CA s h ~ e d 7 with 3 vessel disease(VD). 10(2 VD), 6(~ VD) and one normal. The protocol for RP-30 allows for first pass (FPRNA). rest and stress studies in s ~ e day. Patients were exercised to s ~ e level for both tests. 96 segments were analysed for both studies. All were read by 2 trained observers and disag~e(~ent was solved by a third observer. The ~esults are shown in this table: Segment %S~nsitivit~ %Specificity %Accuracy TI RP-30 TI RP-30 "21 RP-30 Anterior 8-5 75 TOO 100 ~ 79 Septu~ 90 90 75 100 88 92 Lateral 86 93 90 90 8g 92 Inferior 93 87 100 89 96 88 Global 100 100 96 100 98 100 Segmental agre~ent between TI/RP30=90/96 (93.8%). EF calculated from FPRNA was 50% + 10% for Rt.V and 45.7% + 10.7% for L~, vers~s 49.1% + 9.6% for LVEF calculated from CA (r = 0 . 8 5 [ . We conclude that Tc-RP30 is a useful substitute for Ti-201 and has the advantage of calculation of LVEF from FPRNA in addition to assessing the status of myocardial perfusiGn.

I

R.Campini, M.Galli, W.Bencivelli, N.Franchetti Par~

Depts.Nuelear Medicine and Cardiology, "Clinica del Lavoro" Foundation, Institute of Care and Research, Medical Center of Rehabilitation, VERUNO (NO) - Italy 99mTc-MIBI VERSUS 201-T1 SCANS IN THE ASSESSMENT OF MYOCARD AL ISCHEMIA INDUCED BY DIPYRIDAMOLE TO ascertain the relative effectiveness of 99mTc-MIB[ in the detection of myocardial ischemia induced by Dipyridamole(DP), 14 pts (12 post-Ml) with positive DP Thallium scan repeated DP test with 99mTc-MIBI within 1 week. The same protocol was used. Anger, haemodynamic and ECG alterations were statistically comparable in both tests and 13/14pts were identified as isehemic by MIBI-DP. Fifteen myocardial segments were identified by 2+1 observers in the 3 standard proiections , and classified as normal(N), ischemlc(I) or scar (S); Thallium vs MIBI segmental readings were: THALLIUM S I N 19mTc-MIBI S 14 6 1 21 I 2 6g 11 81 N 5 11 92 108 Tot. 21 N5 104 210 Thus MIBI and Thallium results are higly :orrela~ed ()(,2=195,p<.00001);174/210(83%) classifications were in agreement(kappa=0.70+.04). A similar evaluation by vascular territory gave the same degree of agreem ent (K appa=.68 +0.07 ). nterobserver disagreement was 14%(8~ for TI).

I

infer m aMttlloBIn- vDPy ScClions'g: ~ oaP ~nYf o rPr°;iidens p rdoiagndmb~ Thallium; however the discrepancies observed in th s study shou d be nvest gated more n depht.

249 ~h,C,Arvieux, D, Fa(~ret. P.Y,Brichon, F,Duboi~, P.Pilichowski, J E,Wolf, J.PJ%thieu, P,Cuchet, M,Comet

Service de Biophysique el: Hedecine Nucleaire, Centre Hosplta]ier R~gional et Universitaire. ~pNnBLE - rp~rE A STUDYOF FAsMYOCARDIALrIETABOLISMBYEXTERNAL DETECTION.VALIDATIONOF A COMPARTMENTAL MATHEMATICAL MODEL IN DO~ A quantification cf the relative importance of the storage and of the mitachondrlel deoredation of lhe FAs taken up by the heart allows on gssessmsnt of their myosardiel metabolism. To oblain thesevalues from a my~,ardial Lime-activitycurve obtainedby externaldetectionafteran IY injectionof 1231 labelled 16 iodohexeqecenoicgrid (IHA), we developed a 4-compartment mathematicalmodal :compartmants 0, I, 2 and 3 representtnqplasmaticINA, intraceliularfracIHA, its asteriftedforms and iodides,rsspectivelygridthe k21 and k31 ere the turnover constgnt rate a[ stackaga grid mltachondrlal degreq~tion, In order to validate this medal, a I st serie of dogs (5 x 48 h-fasted end 4 under glucose pgrfusion) underwsnt 1 h external detection after on IHA IV lnJactlon, and on a 2nO saris of dogs (5 tastedand ~I with glucose) myacardial binpsies were performed to analyse the intracaIlular distributionof 1231activity.The malhematicalanalysisat"ths myacardiel time-actieitycurve that is obtginedby external dalaclion Indlggtesn esterificationratio (k211k21 +k31) equal to 0.18 ± 0.09 for fasteddogsand to 0.32 :~0.09 far glucosedogs.Tbe intracellularanalysisalsoindicatea higher storagsfor glucosedogs(65,9.14 ± 9,000 ceuntslg.mCi)than for facleqdogs (50,680 ± 13,000 caunts/g.mCi).The proposedmglhematicalmodal is thus validatedon dog & v/W and can ba eqp]ied[e [hsextsrnaldeteclioncurvesob(ained in mgn.

252 Q~,

R. S e ~ , O M

Sa~oro*,F GleeS,C,OalR~i,

Depe,runentof C~cal Pa~phy#iob~j, NuclearM ~ i e ~ umt, un~vexsityof Fbrence; * l)epm~nem of CaMiobgy, Cexeggi Hospital.F]olence,ITALY.

C O M B I N E D ASSESSMENT OF CARDIAC PERFUSION A N D FUNCTION WITH WmTe-MIBI: COMPARISON WITH RADIONUCLIDE V E N T R I C U L O G R A P H Y MyOc~a~/scint~mphy (MS) ~ Z0tTldoes not eJlo'vall evakla~n of left wnti~'xl]ar functlon; mdioll~clxle~nTf~uk~raphy (RNV) undel e~arcieepmsent~ limRat~o~*~for comm~ ~ d ~ e (CAD) diagno~ becauseof reklively lov specificity.The ~ of 99~Tc-kba~d ~ e ~ shoeM aUov IM siml~e.t~ousassessmentof mY~cardkl perft~on ex~ kfl wnNie~ar funcuon,~ lair beil~studiedby flint-passRN~. To verifyt~ feasibility of thiseombimd a p p ~ h , we studied18 p~e~s ~ symp~o~ of s~biean~ma. An pauents~ e r ~ n t co~)ne.lye,ngio@~phy:15 veto effacedby C A D and 3 ~ norrmleorone~ arte~s. M S ~ W~Te-MIBI ~ RNV were performed atlest~ att~ sortielevelof dyl~or~ exaleise.F~'1~rmorn, themma~ of lestfir~-l~SSR N V vi~h ~ T c - p ~ R c ~ t ~ ar~ ~ W~Tc-MIBI ~ m corniced Jn oMer ~o ~at b'~eir reproducibility. AccoMi~ ~o m~oaaMiel acm~mphy with ~Tc-MIB] 15 pa- i tisnuwere coneetlyclassifiedas ] ~ (2/3)or a~ ~ffectedby CAD (13 5);21 of 3 revolvedcorooe~ ~r'd~or'~es ~em Menufi~l,StressR N V gave a pa~ologicresult[ e ~ n f ~ o n (El')I incre~s_<5%or appes,~ancsof ~ n'~lJo~abnomeli~sl ~ 14 pa~en~s'withCAD, but alsom t~ 3 palms withouta o m ~ y obsu'm~n; mgJ~al wall m o ~ n m~ages a l ~ d ~ mcogni~n of 16 affec=d~m~o~s. The rela~n eoeffiOem~atwasnO~e fir~ passR N V mee.~mme~ perfonnM ~ ~Te-MIBI ~ ~ T c - I per~hre~e, ~ r = 0.96(p < 0.00001)for ~ leftV~nMi~Ul~, EF e~l r = O.74 (p < 0,0005)for~ kff ven~'iculare~-dJ~o]Jc vol%~e, For thedisgnoet~eveluauonof C A D 99~Tc-MIBIM S appears satiate ~ s~sa R N V and even s~pe]'Jorm t]~reaognitio~ of effacedvascukx~n~or~s; fux0~ermole,like~atTl,it sesn~ m be more specific,On the elliot h~l, first-peasR N V ~ilh ~Tc-MIBI is bJ~hly re~bie. A sombined ~ e i ~ o n of perf~ioll~I functionwith the a d . ~ e o n of a sh~k ~mcer appearsd~ereforefeasible.

265

J.M. CASTRO BEIP~AS, M.E. RIOJA MARTIN, M.L.P.AMIREZ VERA, A CP~ESPO DIEZ.

ISERVICIO DE MEDICINA NUCLEAR. HOSPITAL RAMON Y CAJAL. MADRID. SPAIN. EVALUATION OF Tc-99 MIBI SCINTIGBAPHY I~AGNOSIS OF CORONARY DISEASE.

255

254

253

IN THE

GKOCKKR D. , PI~KENTZ P.. GEANBEON d.* SCHOTT B.. FINCF.ER J.L.**

I

* I N S T I ~ T DE PHYSIQUE BIOLOSlQUE ~. rue Kirschleger 67085 STP.KSBO~/RG CEDEX ~* SERVICE DE C ~ I O L O G I E - HOSPICES CIVII~ i, place de l'H6pital 67091 STRASBOURG SEDEX

PURPOSE OF THIS PAPER: A) CompariSon between th( aiagostic accuracy of the TI-201 and the Tc-99 aIBI scintigraphy in the diego--is and localize Oion of miocardium infarct (MI) B) Correlation-between the trea~ill test with TI-201 in comp~ ~ison with Tc-99 MIBI in the diagnosis and mane aement ~n coronary disease. ~ATERIAL Abed METHODS: A) Scintigraphy with TI201 and Tc-99 MIBI was performed in 25 patients In 11 also was performed scintigraphy with ant~ nyosin monoclenal antibodies and 6 Tc-PYP. Cor~ narygraphy was done in 10 patients in within a ,ontO. B) Tread/~ill test with TI-iSI and Tc-99 ~IBI was done in 16 patients in no more than a ~eek in between both studies,.reaching the s~me rate of exercise in both cases in each patient. =oronary angiography was performed in 11 p a = ~ient5 in not a longer period than three months after exercise. RESULTS: A) 25 patients (10 trans MI, 5 ~ net 9I, 2 no MI]. Segmental correlation between T1201 and Tc-99 MIBI was 90%. Sensitivity (S) and Specifici'ty (Sp) was g5% and 91% for TI-201 and 100% and 100% for Tc-99 MIBI. B) 16 patients (13 had previous MI, 3 no MI). 11 with coronary an~iography, 2 had normal vessels and 9 coronary ~isease, Correlation of the myocardial see]tents for k~th tracers was 92% after stress and ~8% resting. S and sp was 92 and 100% for TI-201 an( 88% and 100% for Tc-99 MIHI. 2ONCLUSION: The results show the Tc-99 MIBI as good tracer for the diagnosis and localizatio~ ~f ischemia and evaluation of MI, S and Sp are similar to TI-20~, althouqh further experience is needed, There are other advantages derived o: using To-99, availability, better count rate an, image quality and no time dependence for study after injection.

99mTc GATED TOMOSCINTIORAPRY WITH ~ETHoDY-ISOBOTYL-ISONITRILE (MIBI~ IN ISCHBHIC[ )ISEASE : R E G I O N A L A N D T E M P O R A L A C T I V I T Y CUBVEI ~.NALYSIg, [esolution ef tOmoEraphic images obtained with ~01 TI is degraded by the cardiac motion. New ~yocardial perfusion agents labeled with 99mTc, like 99mTc MIBI allow gated acquisition. In :omparison with 201 TI, NIBI has a substantially higher activity, because of the higher injected dose permitted by the short physical half life and superior dosimatry of 99mTc. 12 patients with myocardial infarction, zonfirmed by coronary anEiography, were s~udied at rest, 90 minutes after the intravenous injection of ~0 mCi of 99mTc MIgl. 30 views of [6 gated image~ were acquired from right ~nterior oblique to left posterior oblique. total acquisition time was 30 minutes. ~hort axls, long axis, and apical four chamber views were reconstructed from the transverse ~lioes and the gating provides 8 or 16 frames luring a cardiac cycle for each slice, Bet=oriel quantitative analysies of short axis ~lices were performed by using angular profile :urges. The defects are detected by the minimum ~f the regional activities curves. Their size ~epends on the time within the cardiac cycle ~nd the lesions appears as a more large extent )n the diastolic images. In ~he other hand the Lesions can be ohserved hy a cite mode frames ~isplay, The wall time activity curves reconstructed for each pixel can be analysed by Fourier Transform, X~ne size of myocardial infarction is estimated from the akinetic area ~bserved on the phase image. IN S O N C L U S I O N : Sa~ed =omography with MlgI permits beth analysis of perfusion and wall kinetics in evaluation of isehemlc cardiac disease.

256

257

£raun #4 iJlutcrr,:e] r;

~anabihiation Sc~,]o] HaceHepeOnl',,'e{$]ly -~r:~:ar5 ,T_'~!}L!'t'

COMPaRiSON OF PL~N/,R ,SPECT ~ D I;ATED-I~pECT STUDIES IN CAD WITH RP-$o < [-~--~6) I$ a n~w mynca!-d18]]n-i~gln ~ s,~enl%dth Ong~]ca] ~nd hi.dr,gird]properti*.apor-,it~ng ~,i~nq.~it~ _--~EET and Gated-Tomoyraplu4 Th~ isurpo.~aofthi:~::=tu,9~,~aat,~6ompare th~ sansith.ity of di~fer~[ll m,~ucordi~] ~m~yj~,: ro~thod~ with z,p-3q to assess the ~ccuraoy of toe looahzafionof ischemic areas ou~ [0 kno~,'ocoronarydlseasas I! n-ra)epatientswith enyin~r~phicdbjproved c¢,D v,'~r~ sludied ( mean age nf 53.61jaars) Un~ to two hums attar the injection of ~5-~13 mLi of ?groTe R~'-SO at p~a~ exercise ~ata were acquired P~anar images I~NT,L~O 40~,LLT), Gated-planar ima,aes (ANT-LAG 4F[), tomogrophic images (Toshiba 601, single-head rutating qamma camera 18Ff',6~',25Sac) and Gated tomLrgraphic i mayas (181-,~,5°,55 sac) Ware performed.24 h later, at r~?t, the patients received 10 mci of RP-50 and th~ i n-,aqioopeotocol nfas repeatedwithin 1-,5 hours 7 haiien(s had 20fTL tomogrspnlc myocardial sci ntigraphu. Planar and gated planar irn~goe we{-~ analized quantitati~,,ely.Transaxio],sagittaland coronal ,~bIwJa ~~:ea ',,.,'ere int~rpreteted aualitativeb 9 patients pathologic angiography and also RP--~O imagesThe sensitivityof gated-tomoWaS 100% for LAD,82~ for iCx and 7295 for RCA.But planar images had 45%,72~,72~.$tre~s testiag show 64~ correlation to aoyiogrsphy,64% to RP-SO.Gated tomographic images allow to compare diastolicand systolicframes and gated planar images reveal wall motion as well as ~rfuaian. We conclude that RP-5O is a sensitive mtJocordial perfuaiona~nt, becauseol high photon flux, suitablefor gaiti ng striae,as well as tomographic gatedimages.

(YgDARDIAL

II

G

M~er~=

G

Bailiet,

J

Division of Nk~elear Medicine, Medical Cen~r, Torrau~ce. CA, USA

V~%'SalCH[I~G~

KtlmerLls

Harbor-UCl/

IN M~DCa/~)IAL I~FARCTION.

We report on the feasibility and possibl6 ber~efits of perforating sirm/Itaneous 1~ evabuation of mycc.ardial perfusion and right an~ left ventr~culography after a single f~ i~jection of 20-30 mCi Tc99m H e x ~ b i (MIBI) IC~rdiolite TM, D ~ n t ) . 40 patients (IYCS) ~ r e studied at rest, 20 males and 22 fe~rales, their age8 were 57+11 yeasts. First pass ventric,/Ingraphy (FPRNA) was was o ~ i m e d after IV bolus /~jection of T~9£mI MIBI in 30 degree RAO v i ~ . The data was i ac~red in list mode and processed cor~entional ly for ejection fraction and se~.mentel wall motion (~). T ~ hours later, I conventional S P E ~ images of the n~yccardiL~n were gathered. Ftt~ther evaluation of F ~ was ac~lished by r~peating the study with 20 mCi T~9~ IYfPA after SPECT imaging had been c~leted. H e . I t s demonstrated similar LVEF for MIBI and Te DTPA: 44.+9% and 45.+_17% respectively. Correlation of ~M with n ~ r d i a l perfusion was a s ~ s s e ~ i~ 160 s e ~ n t ~ (a~terior, alack, inferior and posterior). Full a g r e ~ n t was four~ in 133 (83%} s ~ t s . ~ o ~ r v ~ d r~ormai perfusion and a ~ r m a l ~M in 18 (11%) s ~ t s in pts with cardiccmyo~thy. Abnormal perfusion and normal NM, in 9 (6%) s e ~ n t s , pr~le false negative ~ . One of us (IM) reported on high s ~ i f i c i t y of sJml/itaneo~ detection of ~erfusion and ~M abnormalities with dual i s o t ~ techniques. Tc99m MIBI pr~vides this possibility for studi~s both at rest ar~ at eKel,eise, with m x i m a l usefulness in the evaluation of l~riinfarction i s ~ h e ~ , a l ~ it is a very sensitive p r ~ - ~ / r e for early detection of MI in the ~R.

258

E. Henze= M. C l a n s e n , A. S c h ~ i d t , R. W e l l e r , P. Richter, M. Stauch, W.E. Adam.

IM Hassan, y Kewan, ~ Mohmn~ed, C Constantinides, M Nair, N Belani and F~4 Abdel -Daye~L

Divisions of Nuclear Medicine and C a r d i o l o g y , U n i v e r s i t y of Ulm, G e r m a n y

Dept. of Nuclear Medicine and Cardiology, Faculty of Medicine and C1nest Hospital, Kuwait.

V A L U E OF Tc-99m RP-30A AND QUANTIFICATION OF INFARCT C O M P A R I S O N TO C P K AND LVEF.

SPECT SIZE

FOR IN

In o r d e r to determine the value of T c - 9 9 m R P - 3 0 A for q u a n t i f y i n g the size of m y o c a r d i a l infarction i0 patients w e r e s t u d i e d so far 2 to 3 w e e k s after acute infarction using 180 degrees S P E C T and d a t a p r o c e s s i n g s o f t w a r e
ant

vs

x

vs ICFK VS LVEF vs I C P K

r 0.81 0.93 0.67

regression y = 3 , 2 4 x + 3.i y = -I,Ix ~ 87.8 y = - 0 . i x + 73.4

it m a y be c o n c l u d e d fro~ these data that T c - 9 9 m R P - 3 0 A t o g e t h e r w i t h SEECT s e e m s to a l l o w a c c u r & n e i n f a r c t sizing and might thus beco~e a primary d i a g n c s t i c tool in the q u a n E i t a [ i v e and prognostic pos~-infarct evaiuaEieA.

I LEFT V ~ I C L E (LV) S F / ~ A L WAIl MOTION ABNORMALITIES (SWMA): C O ~ A R I S O N BEI~4F~ I PHJLTIGATED T c - 9 ~ MIBI, CONTRAST V ~ I C L q J D GRAPHY (CV) AND CORONARY ANGIOGRAPHY (CA). T c - 9 ~ Methoxy Isobutyl Isonitrile (MIBI) n~itigated studies were compared for LV SWMA in 26 patients with IHD. They were read by 3 Nucl Med physicians and differences agreed on. Results were correlated with CV and with CA. Four segment(S) were available in each study for comparison~ Anteroseptal (AS) supplied by LAD, Lateral (L) by circt~nflex and Inferior (I) by RCA and Apical (A) with mixed supply. The interpretation was 0 = normal, l = hypo, 2 = akinetic and 3 = dyskinetic. The s ~ a r y of the comparison is in this table: AS Lateral Inferior Apical N--Ab N ~ N Ab N Ab CV TI ~ 23 ~ 19 7 5 21 MIBI 7 ]9 ]7 9 12 14 I 25 CA 8 18 11 (5 14 11 ..... When compared w i t h f i n d i n g of CA i n which an occlusion of more than 70% was considered abnormal the % sensitivity (St), specificity (Sp) ~ d accuracy (Ace) of both CV & RP-30 at rest is in the following table: AS Late Inf. Total CV~-30 ~-30 CV RP-30 CV RP-30 Se 67 72 13 47 58 83 47 66 Sp 63 25 9b 82 100 71 87 64 Ace 65 58 46 58 81 77 64 65 In 17/78 segments RP-30 was Abn. & CV was normal, in no segments CV was Abn & RP-30 was normal. We conclude that resting SWMA from gated RP-30 has higher sensitivity, lesser specificity and almost equal accuracy when compared with C~f. Both are not sensitive for detection of underlyin~ IHD.

266

259

260

1 F. 6ruzzene, S. Borziani, p, Clavario, FL Cabria, C. Brunobl IT, P . ~ s o n i , N. Schad, S. CapgnF~tto.

I

University of Sonora, Italy.

FIRST PASS #~ISIOGRAPHy~ M/OBARDIAL 5CINTIGBAPHY IN PATIENTS WIIH CORCiIARyARTERY DISEASE USIN3 99mTc HEXA4181.PRELININARyRESULTS.

I

261

P.Kostamis, N.Vassilopoulos, 3.Lekakis, S.Gerali, Ch. Kalliontzi, Th.Athanassoulis, 3.Germanidis, N.Sifakis, D.Tsinikas, D.Maintas, D.Tsigourakos and Sp.Moulopoulos. Department of Nuclear Medicine and Department of Therapeutics. Alexandra University Hospital Athens Greece. I DIPYRIDAMOLE GATED AND SPECT IMAGING USING Tc 9gm RP-]O IN PATIENTS WITH CORONARY ARTERY DISEASE.

Aim of our study is to evaluate regional fUF~tion and perf~sico of the left ventricle (L~) in patients {pts) with coronary after, disease [0%9) with asy~tomatic non diagnostic and/or high grade ischeuic treshold stress test. lO pts with CA)(8 pts with previous myocardial i~arction) under~_nt coronary angiegra#hy (CA), first pass radionuclide angiograbhy (FPRA) with m~Iticrystal detector (BAIRD 77) in RAID30 view and myocardial scintigraphy (~5) vath single crysta] detector (ELSCINT APC3) in anterior view, left anterior oblique 45 and 70 views. All patients were studied at rest and during exercise test. Wedivided LV into 3 coronary territories: ]eft anterior descending artery, circumflex artery and right coronary artery referring to coronary angiegreghy. ]4 territories per%used by normal coronary arteries were detected by both FPRAand 14S.Considering territories with occluded vessel: 8 were detected by FPRAand 7 by MS. Considering 8 territories with stenobic vessel: 7 were detected by FPRAand 2 by MS. In conclusion the new 9Oj~Tc HEX#rdIBI is useful in assessing both regional function and perfusien of the LV in nonral and infarcted coronary territories. FPBA provides us a (,qorereliable marker of regional ischmlia in territories with stecotic vessel in pts with asympttmaticnon diagnostic and/or high grade ischeTdc threshold stress test.

The usefulness of gated studies using fc 99m R P - ] O i n d e t e c t i n g coronary a r t e r y disease (CAD) as compared to p e r f u s i o n defects i s i n v e s t i g a t e d . Twelve (12) p a t i e n t s (pts) w i t h recent coronary a r t e r i o g r a p h y underwent p l a n a r (PL), SPECT and dual gated imaging (DG) 1-2hrs loiter dipyridamole (D) infusion (0.56 mg/Kg) and 24hrs later. Scintigrams were visually evaluated as normal or abnormal by consensus of three independent observers. 10/12 pts had significant DAD ( >50% diameter stenosis). 5 #ts had vessel disease (VD) 5 pts had 2 VD and 2 pie had I VD. 12/25 abnormal vessels were detected by PL scans, 17/23 by SPECT and 11/2] by wall motion lanalysis (WMA). Both SPECT and WNA correctly identified 2 pts with false positive PL scans. The combination of WNA and perfusion data correctly identified ] abnormal vessels which were false negative by PL. Sensitivity and specificity Cot PL~ SPECT, WMA and PL+WMA were as Followed: Sensitivity 52% 74~ 48% 65Z Specificity 69~ 100% 1009~ 69~ In B pts perfusion defects were better delineated in end-diastolic and in 2 pts in endsystolic image. Conclusion: The addition of wall motion abnormalities to perfusion defects increases the sensitivity of Tc £gm RP-]O dipyridamole t e s t in detecting CAD. End-Diastolic images are of better diagnostic quality than PL images.

262

263

G.L.Tarolo, V.Marino, tini = , M . R a d i c e =

A.Vignati, A . A l b e r -

Cattedra di ~ d i c i n a Nucleate, Cattedra di Semelotica M e d i c s ~ , Universit& degli Studi di Milano Left ventricle functional and anatomic changes induced b y prazosin treatment in mild to m o d e rate hypertension: evaluation b y equilibrium gated radionRclide angiocardiography. T o assess the effects of alphal-blocker praz( sin on the heart and whether a correlation exists between reduction of left ventricle hsnpertrophy and irnprovemeht of diastolic function, 11 previously ulltreated hypertensives ~vere studied before and after at least 6 months of therapy. T h e dru~ significandy reduced avera~e blood pressure (BF) values (163--+19 / 106+8 to 149+13 / 94+10). Left ventricular I m a s ~ (LV~4) w ~ s determined by ecSocardiogra phy, %vhile the diastolic function indices (pea~ filling rate~ first-third filling fraction and tiI m e to peak filling rate) w e r e calculated by an~ lysis of the time ac£ivity curve of the equilibrium gated radionuclide angioeardiography p r e ~ o u s l y fitted with Fourier 4 harmonics. N o n e of these parameters w e r e significantly improved in the group as a whole. In 5 patients w h o s e B F w a s adeguately and sustainly controlled b y prazosin LViv[ decreased (128.7 to 102.4 , p
I]~4 Wiseman, DS Dymond.

F. Scopi~aro*,F.Iorio*,N.Cassone~-~,B.Maugeri ~-~, A. Centi Colella* Section o£ Nuclear Medicine ,Dept. o£ Experimen(tal Medicine ~ V I I Medical Physiopatholo~y University "La Sapienza", 00161 Rome

I

INTIGP&PHY Rr£%I 9 9 m - T c H E X A K I B - 2 @ I E ~ t O X Y - 2 -

~Eq}~/LPROFYL ISONITRILE: EFFECTIVENESS IN MYOCARDIAL INFARCTION. ~9m-Tc hexakis-2~methoxy-2-methylpropyl isonitr_i ~e (MIBI) is proposed as a new agent for myocardial perfusion scintig~aphy, suitable For tcmo~ a p h i c (SFECT) and n~/itigated imaging (MUGA) ecniques,too. The aim of" this study is to evauate the usefulness o£ 99m-TcMIBI in myocardial nFarction.According to [~J Pont trial protocol I n o m n a l volunteers and 23 patients ~ith proved ronary artery disease (CAD) (18 with previous ocardial ische~ia) were studied using 99m-To BI. Planar static images were performed in the ole se~les,99m-TcMIBl MUGA was performed in patients and ELECT in 2 cases• Scar localiza~ion and size, and the regional wall motion (RWM) were evaluated. A comparative study ~as I;arried OUt a~ong 2OI-Ti,99m-Tc red blood cell I(P~C) MUGA and bidimensional echotemO(TFaphy [(ECHO). 99m-TcMIHI, 201-TI and ECHO showed a satisfactory agreement for localization a~d sizing ~£ scars. However, in 4 cases the scars size ~ s Dverestinuated by 99m-Tc~CIBI. In so tar ~ is ;oncerned, a complete agreement was demonstrated ~mong 99m-TcMIBI MUGA, 99m-TcRBC MUGA and ECHO in the perinfarctual areas, O ~ n g to the uptake ;haracteristics of 99n-TcMlBI, which labels 9effused Fm]Dcardial wall, it is not possible to _=valuate the RWM inside the scar, particularly Jiskinetic changes.

[

~

I

264 R Sobnack,

LI Dyke, KE Britton,

Departments of Cardlolo~y and Nuclear I Medicine, St Bartholomew's Hospital, London RCIA 7RE, UK,

MITRAL REGURGITATION AHRESSED SF COMPARISON OF ' EIECTION FRACTION WITH FORWARD FLOW. First pass radlonucllde sngiography has been I used to determine the severity of valvular re~ursitation by stroke count ratios, but the method is crucially ~epen£ant upon operator determination of re,ions of interest (ROI)~ We present a method in which the left ventrieular I ejection fraction (LVEF) is romp@red wlth the effective forward ejection fraction (FEF) as calculaled from a gamma varlate fit t o the LV time-ectlvlty curve, both methods bein E relatively unaffected by choice o£ ROI. t3 I controls and 7 patients with mitral regurgitation (MR) were studied, all with LV£F)30%, There wBs good correlation between LVEP and FEF in controls (r=,75, p<.0Ol). For th~ whole population regursltant fraction (EF) was calculated from RF=(LVEFIFEF)/LVEF, In controls the mean RF was -. 21-% 14. There was clear separation between controls and patients I moderate or severe MR, and between those with trivial M~ and severe M~R

.~

I

This technique offers a new method of delermlnin~ the severity Of mitral re~ursltatlon From first pass data alone.

I~[~i~R~

.... h i ; N . M o n e b t i ; F . T a r t a g n i *

Department of Nuclear Medicine and I n s i t u t e of C a r d i o v a s c u l a r Disease* R.Orsola-Malplghi Policlinic Hospital Bologna;ITALY

ILEFT VENTRICULAR VOLUME ( L W ) RESPONSE TO EXERCISE AFTER TH~OMBOL~TlC ~HEBAPM: RELATIONSHIP WITH TOMOGRAPHIC AND ENZYMATIC I N F E C T SlZE LW and ejection fraction (LVEF) were measured at rest and during exercise two to six weeks after an acute myocardial infarction in 48 pts who w e r e % r e s t e d with intravenous thrombolytic therapy 114+43 min~ after the onset of symptoms. Rl --pts (44%) increased end diastolic volume during exercise (Frank-Starling mechanism, group i) while 27 did not ~(group 2).The two groups did not differ with regard to age, sex, site of necrosis, time to initiation o£ thrombolysis, number of diseased vessels at coronary ang£ography. Droup 1 pts experienced early post-infarction angina more frequently (29% vs 4%, p=0.015) and showed a slightly increased patenc? of the in~arct size was significantly lower in group 1 [18.3+15.1 vs 28 2+23.3 grEq/m 2 , p=o.04gT; similarly - the e~tension of tomographlc thallium resting pcrfusion defects was lower in group 1 I(SPECT-SCO~E 6.3+4.? vs 9.5÷6., D=O.02?). This was in keeping with different values lof end diastolic volume at rest (group i: 158.5+65 ml; group 2: 194.2+69.8 ml; Ip-0.O~8). During exercise both groups attained similar levels of worMload and double product. Group 1 pts exhibited a significant increase of end systolic volume compared to group Z pts (+14.8&29.4 vs -5.6+15 5 ml,p=O.0017). LVEF, ~oth at rest an~ during exercise, did not differentiate the two @roups. Thus the radioisotopic evaluation of left venzricular volume at rest and during exercise provides useful information about residual ischemia a~ter izhrombolytlc therapy.

]

267

267

266

265 O , @ i t t n e r , F,9.Maul~ R.Etindke, M,Klepzig Jr, Q.Kober,

S,H~r,

D i v i s i o n s o~ Eeneral Nuclear ~eO~cine and Cardiology J , g . O o e t h e - O n i v e r s i t y F r a n k f u r t , FRO FOORIERANALYB[Q OF GATED RYOCAROtAL QC]NTIQRAPHY (TCqgm-I$0NITR[LE~ 1 t 2 o t l l

Kevln E. McCarthy, M a r g a r e t M. Parker, Anthony F, Suff{edini, Robert O. Bonow, B. W i l l i a m Choi, Ronald D. Neu~ann and J o s e p h E, Parillo. N u c l e a r Medicine, Critical Care and NHLBI, NIH,

~

~

N Md. B USA e 20092. t h

e

s

d

a

'

PEAK V E N T R I C U L A R FILLING RATE M E A S U R E S E N H A N C E D

gETENMINATIQN OF LEFT VENTRICULARREGIONAL FUNCTION QY QUANTITATIVEBECTORIAL~NALVSIO OF

IN NOPd~AL HUMANS.

AMPLITUDES 8ateti myocardial s c t n t i g r a p h y (ORQ) wal p~rformed in I~ p a t i e n t s to analyse ~he r e g i o n a l ]eft ventricular ~unction and t~ compare it with r=dionuclide wntriculogrlphy (RNV) and/or clinical Oata, Computerized a c q u i s i t i o n ~a~ done i t r e s t in LA0 45 v i e w with I~ ÷ r a v e l p~r ¢irdii¢ c y c l e #gr I0 limute¢ g l l n ~ i general pur?ose c o l l i m a t o r , tO p a t i e n t s a~ter previoiJ~ infarctfo. ~ l r l l n v e s t l g a t e d wiLh Tc-99m-]so~itriJe (MIB[=RP-3O) and a~ a d d l t i o n a t RNV

To define the normal r e s p o n s e to rapid volume i n f u s i o n (VI), 6 human volunteers were studied w l t h arterial and pulmonary artery catheters and simultaneous r a d l o n u e l l d e angiogrsms- Com purer assisted d e t e r m i n a t i o n of the diastolic peak filling rate was also performed. Noz~nal saline was dnfused at 66 m l / m i n to a total volume of 2067+228 mls. Pre and post m e a n values w e r e (P<.05 desig ~ nated*):right atrial pressure rose from 6 £o 12 mmHg*; pulmonary artery m e a n 12 to 21 mmHg*; pulmonary artery wedge (PAW) 7 to 17 mmHg*; heart rate 60 to 65 beats/min (NS); m e a n arterial pressure (MAP) 85 to 9~ mmHg*; cardiac index 3.1 to ~.2 I/min/m2*; systemic v a s c u l a r resfstance index (SVRI) 782 to 586 dynes sec cm -5/m2"; and p u l m o n a r y v a s c u l a r r e s i s t a n c e dndem 136 to 138 dynes sec cm-5/m2 (NS); LV ejection fraction .53 to .59 and RV ejection fraction.42 to .44 (NS); Stroke V o l u m e Index (SVI) 53 to 6~ ml/m2*; LV and RV end d i a s t o l i c volume 101 to 112 and 139 Co i~9 md/m2, respectively; and LV P F R 200 to 456 ml/see*. In response to VI: MAP, CI, and SVI i n c r e a s e while SVRI decreases s i g n i f i e a n t l y . N o w e v e r , E D V ] does not increase. Classical cardiac physiologl s~ates thas Vl enhances cardiac p e r f o r m a n c e by increasing preload. H o w e v e r , l n this study, EDV] (a volume measure of preload) does no~ increas~ w h e r e a s PAW and PFR are increased, Therefore, with V I in normal humans, LV P F R is a more sen~ iSive functional m e a s u r e of d i a s t o l i c preload effects thsn volume.

within

48h,

In b p=tiente with various ¢ardiac

diseases we used 11-29L f o r GMS. A l l p r e v i o u | ~¥ocardJal im~ar~tlon~

(It'12} Wer~

correctly l o c a l i | e d by 8gs. 1~o p a t l e n t l w i t h d i ~ u | e h y p o k i n e s l a (q-ves~e|-bypas~ I c a r d i o ~y~pathy) presented =~lti~le Functional iesigns, 7.0 patients a f t e r successful trans,l u e i n a r coronary anQioplasty or b/pool surQory • ithaut p r e v i o u l i n f a r c t i o n Were ~ou.d [~or~a]. I . each O{ 10 g a t i l n t l rectorial amplitudes ($~) in gHS were c o r r e l a t e d with gN in RNV a.d wlfh i i ¢ ~ o r i i l l j e C t [ O ~ ~ r a c t i o n (5EF), S t r o . p correlation we; (ou,d {~r OA=EN$ vmeSOl SA-RNV (r',9~), OO~Fariion ~ ~A-BMS and $EF lhm~ed a I ~ good {o~relat~en in ~ patients with ,nt~-ri~r wall in~tctioo (r=,B~) b~t no ¢~rrela-Sign i n 4 p a t i e f l t ~ w~lh p o s t e r i o r . ~ ) ] i . i ~ t c Lion (~W[) ( r . , 2 4 ) , When ulin9 r l - 2 o t the detlrmiaation gf the ROt wal t e l l c e r t a i n than ulln 0 htQI, lfl conclusion ~ e c t o r t a l a s p ] i t a d e a n a l y e f s ~f Ogg Nee h i g h l y s ~ n s i t l v ~ i n d e t e c t i o n of r e liana] hypo(unction, sfls IRONed the lamb e x c e l eat r H u l t s as se¢LorL~l RNV a s p l i l u d e s , QEF l a l ] e ~ ! s e n s i t i v e i~ d e t e c t i o n of PN].

268

269 M.B A Z A N * , P . J . B E R N A R D ' , G . F A U G E R E * ' G.TESSONNIER'*, A.SERRADtMIGNI*"

~. VEILLAS. K. TISSOT. J,g. BESSON. M. Ch~ZZL and o. Dt~AU.

Centre de M~dec=ne Nucl~a~e , Hop~tal Czr~io~eg~que , Lyon . France M E A S U ~ N T OF LEFT VENTRICULAR FLmCftON ~T E S T EX.ERCISE BY G A ~ D RADION~JCLIDE V ~ I C J L O G R A 2 H Y IN 50 PATIENTS WITH ORTHOTOPIC CARDrAC GBAFT , In order to usess che ventrlcutar fun¢tlon In ths follow-~m of orthozo~ic cardiac transplan~a~zon , we

have measured in a0 patients the left ventrlcular

ejection fTac:zon ( L.V.E,E ) a~ res= and dur:ng exercise ~ multlga~ed equilzbr:~ redionuc!iae ven~r~culogra~hy ( R.N.V. ) ~wo years ~fter sur~er~ . The mazn results ~ e as follows :

~.v.e.t.

-

1~~ . . . .

3~n~ eza=~a~oal s~udy shewed ~. ~¢~h eases =~ rasping m a x ~ l exercise ~ s~ni~i¢~n= decrease of L.V .E.F. values and an ~ncreaee o~ blo~d pressures wlth age, No ~i~nzfic~n~ correlation was found between L.V.E.F. ~nd the ocher p=r~e¢ers of ~he ~ra~t , to~ai ¢=id

~sohemlo time t r = - o . l z } : age ot =he donor t r - 0.255 ) : weight ~at:o - [ weight of the donor we~gh~ of the rececver )/weight of th~ donor [ r - O.19 ) . We conclude the= the [e~t vencr~cular funo~zon de~e~Ined by R.N.V. may be considere~ as ~u*~e n o ~ a l 2 years a~ter card~ac transplan~s=~on .

* Service d'H~matologie el Cardiologie Isolopiques. H6pRal de la Timone. Marseille. "" Service de Cardiologie. HQpital de la Timone. Marseille. FRANCE PHASE ANALYSIS IN DETECTION OF CONCEALED AOCES,SORy CONDUCDON PAll-IWA~. The ventricular phase analysis (VPA) is a aoninvasive melhod to tocalise bypass pathways in patients with preexcitation (PE) syndromes. In absencs of obvious PE , elecirophysiology study (EPS) helps 1o dislinguish AV nodal from accessory palhway reentrant supraventricular fachycardias (SVT). This study compares EPS dafas and Tc 99m ventricular phase analysis. Twenty seven patienls wilh documented SVF and normal basal EGG underwenl phase analysis during sinus rythm. EPS identified 3 groups of palients according to reentry circuit: 1) [eft Kenl bundle (10), 2) MahaTm fibers (5), 3) dual AV nodal pathways (12). Ectopic venlricular motion was detected by VPA. In firsl group: LV 9 (anferolateral 2, laleral 6, poslerolateral 1) and RV posterolateral 1. In second group: RV 5 (anlerior paraseplal 1, anterolateral 2, laleral 1, posterior 1). In third group, with normal paMern of conduction, an ectopic ventricular motion was detected in 2 palisnts. Thus, sensiUvity and specificily of Ihe method is 93 % and 83 %. A VPA during intracavilary pacing in 6 patients confirmed aocesso W palhways. These results indicate that VPA is a non invasive method able to Iocalise concealed accessory palhway in patients with S'V'F./~osenoe of PE seems lo be linked to a delayed activation of acc~3s~ry pathway.

E.VERNA~R.CASUCCI,G.RONCARI

' S e r v l z l o di M e d l c l n a N u c l e a t e e D i v l s i o n e dl ~ a r d l o l o g l a , O s p e d a l e Multizonale,VARESE

NUCLEARPHASE IMA6ING IN WOLFF-PARKINSON-WHITE SYNDROME: USEFULNESSOF'INTERVENTION'STUDIES Phase analysis of gated blood pool studies has been used to demonstrate the effects of abnormal ventrlcular pre-excltatlon on the blood po ol motion in many patlents(pts) with Wolff-Par klnsen-White(WP~)syndrome. This technlque has ~roved t o be a u s e f u l ] non . i n v a s i v e too! f c r ! ~ c a l i z a t l o n of t h e p r e - e x c i t a t l o n s i t e , However t h e s e n s t t i v l t y of phase a n a l y s i s i n d e t e c t i n g " p r e - c o n t r a c t l o n ~ areas may be a f f e c t e d by t h e

degree of abnormal conduction through the acc¢ sory pathway. In order to further evaluate the role of pha se analysis studies in clinical evaluation of WPWpts,we used both'basal" and "intervention ~ radionucllde imaging In 17 consecutive pts with WPW syndrome. Either planar(multlple view) or thomographic (SPECT)gated imaging of radio~ucllde anglography were performed.lntervention studles included:llrapid atrial paclngite increase thedegree of pre excitation) and 21induction of ortodromlc supraventrlcular tachycardia or 3)Ajmaline admi nlstration(SO-lO0 m g . i - v . l ( t o abolish conduction throughout the accessory pathway). The a b i l i t y of phase imaglng to detect and So calize the bypass pathway with respect to elec~ trophysiologlc techniques was substantially improved by'intervention" studies. Factors which increased or decreased the amount of pre-excita tion also increased or decreased the'phase adv~ ce" of the fpsilatera] ventricle thereby helplng to l o c a l i z e the bypass tract.

270 Y . C . Najm, S.V. Ellam, A.D. Timmis, M.N. Maisey, E. Sowton. Depts. of Nuclear Medicine and Cardiology, Guy's Hospital, London, England. SIMULTANEOUS EVALUATION OF LEFT VENTRICULAR FUNCTION AND PERFUSION: A NEW COMPUTERISED METHOD, Pe~fusion imagdng with Tc-99m MIBI p r o v i d e s good definition of the myocardial wall e d g e , especially with e l e c t r o c a r d i o g r a p h i c g a t i n g . This has enabled us to derive the a r e a of the left v e n t r i e u l a r c a v i t y in diastole and systole and automatically g e n e r a t e an index of left v e n t r i e u l a r function as an adjunct to t h e perfus~on examination. Eightytwo p a t i e n t s u n d e r g o i n g Tc-99m MIBI imaging were studied and the a r e a i n d e x g e n e r a t e d was c o r r e l a t e d with the ang~ographie ejection fraction (AEF) and the g a t e d blood pool radionuelide ejection fraction (RNEF). The correlation coefficient with the AEF was 0.90, p<0.001, and with the RNEF it was 0.86, p<0.001. These d a t a show t h a t routine functional evaluation of left ventr~aular function d u r i n g Te-99m MIBI perfusion imaging is clinically feasible, valid and f u r t h e r improves our previous measurements based on the subjective assessment of the fractional s h o r t e n i n g o e e u r i n g in the v e r t i c a l and horizontal axes only.

268 271 3.F. BOUVIER°,°% BEN BRAHIM°°, M. RIVOIRE°° A. BEN IAZIA °°, 3. DAMIDEAUX",°"°, ~. LAHNECHE °°. Clinique G&n&rale 7#000 ANNECY FRANCE ° C e n t r e L4on BERARD 69373 L Y O N Cedex 0g FRANCE °° ; Hopita[ Cardiologique 69003 LYON MONCHAT FRANCE°"% SEQUENTIAL EVALUATION OF ANTHRACYCLINI CARD1OTOXICITY USING MULTIPLE GATE[ BLOOD POOL SCINTIGRAPHY WITH OR WITHOUT DOBUTAMINE INFUSION,

]13 order to assess anthracydine cardiotoxicit) sequential evaluation of LVEF was obtainec using multiple gated blood pool scintigraph) perIormed after injection of 555 MBq (15 mC[ 99m Tc for labeling red blood cells in vJvo. When the result Ior the LVEF at rest was between #0 % and 50 % a dobutamine test wa_~ p e r f o r m e d , i e a dobutamine inlusion was hegur a t a level ol .5 p g / k g / m n increased at four minute intervals by 5 # g / k g / m n i n c r e m e n t and continuec until 2 0 p g / k g / m n if Iatigue, chest pain, dyspnea, hypotension or ischemic ECG changes did not appear. The test was considered as negative i[ an increase in final ejection Iraction was noted. Thirty-six patients, 29 women and 7 men aged 25-78 yrs (m =5# +i2) with advanced cancers and } control pat]ents were evaluated by radion u c l i d e cineangiography. T w e n t y - t i r e patients and 2 control patients benefited also from echoc a r d i o g r a p h i c examinations, Only 3 patients iresented a c o n g e s t i v e cardiomyopathy and for all these patients LVEF appeared to be less than #.5 %, at 1090, 581 and 550 m g / m z a n t h r a cyciine doses ; twice LVEF after dobutamine inlusion were perlormed and no increase was noted. For 6 patients LVEF ranged from #0 % to 50 % and dobutamine inlusion tests were ,erlormed. For all these an increase was noted I r o m 52 % to 82 % and no congestive failure appeared. In conclusion LFEV radioisotopic deter mination seems to be b e t t e r t h a n echocardiography to identily cancer patients at risk for congestive cardiomyopathy receiving anthracycline t r e a t m e n t and could be considered as a more sensitive method when a dobutamine infusion test is performed.

274 R.Rebelo, R. F e r r e i r a , T. P e r r e i r a , E. P r a z e r e s S~, A. N o g u e i r a . A . B a p t i s t a C. R i b e i r o

CCU Santa Maria H o s p i t a l . D e p t . o f N u c l e a r Medicine C a n c e r InstitUbe, Lisbon - P o r t u g a l

272

273

&.FACELLO ~, H.BRUNOT**, J.L.DENANGEAT ~ , ?.aAREISS*,

A.CONSTANTINESCO ~

Cardiology ~ and Nuclear Medicine ~ CNeU Hautepierre, Avenue Yoli~re 6709S STRASBOUSG-CEDEX - France

C, Bellini,~Bisi, R. Scia#ra ~epm'l. of Pat'hop~ysiolo~y,'-Nuclear Nediei. ~ i t ~ivEcsity of Flo,~r~e - Italy

Departments

LEFT VENYRICULAR DIASTOLIC FUNCTION IN

WHY NOTHP~6RIp?

~-EV~.~TI~ ~

~

~.TE~TI~ E;(EI~ISE FOR

PATIENTS W I T H CHRONIC ISCHENIC }~ART DISEASE BEFORE AND ON D I L T I A Z g M O R A L TREATMENT.

The effects of oral administration of diltiazem (dill on left ventricular diastolic function were assessed by radionuclide angiocardiography at rest in patients (pts) with a previous history of myocardial infa~ctlon ( M I ) . Eleven pts aged 57 ± S years were stud~ed before and at seyen days oral treatment (2aO mR/daily). Radionuelide studies were done in left anterior oblique projection ("best septal"), in a 64x64 matrix si~e, with 32 images/sycle forward-backward g~ted and a re~eotion window of Z 5 % of mean cycle length. Temporal resolution was 29 ± 5 msec. Paired Student t-test and linear regression analysis were applied. Results are noted as mean ± standard deviation. Oil induced a decrease in peak filling rate (PFR) : 1.7e ± o.52 to 1.49 ± 0.53 EDV/s (p~ 0.05), an increase in rapid filling diastolic asynchronism (assessed by the full width at half maximum of the time %o PER histogram) : 155 ± 46 to 214 ± $5 msec (p~0.05), a~d a little impairement in ejection fraction : 43 ± 11 % to 40 ± I0 % (p = 0.15 ; NS). This impairement was well correlated with ~ decrease in mean rapld filllng velocity (r 0.74 p ~ O.01). Peak emptying rate ~nd other time parameters showed no alterations. Thus, dil could be deletereous fo~ diastolic function by enhancing re~ional filling heterogeneity in pts with prior MI.

(Sp) are

reboPbod to be lo~* than dyml~icst~s as to variati(m of both ET aBd itall lotion (IJN), In oPd#P to define the difference in flia~ostJc [x~mr a~d in csbocity to I'B/eal a~ assign kq ab~o~alities bets~'ee, these strese~, 9~Tc equili~'i~ ~ngi~ardiogr~phy ~as peter=be at r~t, durin~ 1t6 and cycteergomter (CY) test in 23 subjects ~it~t~t heart d i ~ L ~ arid ih ~? pt~. The table reports 5% ~, boSitive and ~ a t i v e Ipvedictive val~s (PP~ a,4 ~Pg) a,d accuracy (flcc) cor~ideri~ is a b ~ r ~ l respor~: fl) 8 = decrease ~ith 1t6 !95. B) ~c i.cre~me ~ith

CY .(~, C) ~N ~orsenir~ duri.g 1{60PI?) d~rt~ CY, E) ~ ard/or C~ F) B a~dJoP9, .... fl

B C D

SR. . . . . . . . % . . . . . . 75 65.2 &3,7 82.6 78,a 10@ &?..7 10~

_my__ ......

~ ......

8~.8

53.6

72

91.5

67.9 67.6 7L.9

~.7 &%3 ~.0

10@

l~

Tt~ revealing abr~alities ~as 94.7¢ (71175 Fpts.l.agre~e,t 88.5The 4 dim i scordant82"6 pts. NR ~re~EP~Oby coPoPaPographic76"O diarist"7 J alse positive and 2 false r~gative of CY a,d 1 false ~ a b i ~ of

V

H6. The ~ t~4~ i , the e,tity eStilrabo OY~ ab,0r~lities i. ~/T5 pt~. (88~), Four of fhe ofher 5 discord.mr pts. hod =ore severe ~ t~senlng in CY than in 1t6, o~ had the 0ppo~ihe.

IH6 ~ aM 5p are quite like to CY if k~ I~dJfieatio~ ape c~tsideted ~ith ~ , Noeeov~"the agPselentin diagnosisof XN torse.ir~ e,tity arm lOCalization is h i ~ . ]his study co, FiW the availability of H6 as fli~g~tic test in C~, ~ith special ~gard Ire k~ ~rs~i.g.

276

275 l ~ g J

tsolelric exe~iee Nith har~grip (H6) is a. easy and safe diagnostic Lest for mm-onaryartery disease (C~) alfer~tive to d)~aic stresS. Its ser~itivity (Sn) arm s~ecificity

FLINT, WA LITTLER, HK DAVIES and

J.DARCOURT, J.L. LAGRANGE, J. BENOLIEL, O. MIGNECO, E. BESTAGNE, M. SCHNEIDER,

D e p a r t m e n t of C a r d i o v a s c u l a r Research, Birmingham University, East Birmingham I Hospital, Birmingham B9 5ST, UK.

HYBERNATING MYOCARDIUM - FUNCTIONAL RESERVE A F T E R I N O T R O P I C S T I M U L A T I O N E V A L U A T E D BY R A D I O N U C L I D E A N G I O G R A P H Y

Tc-99 m VENTRICULOGRAPHY DEFINES LEFT VENTRICULAR FUNCTIONAL RESERVE IN CHRONIC HEART FAILURE.

Evaluation of residual LV disfunction(ED) after myc cardia] infarction (Mills important for prognosis andmanagement. Inotropic stimulation (IS)is one technic used to evaluate accurately viable myocardium. 25 patients (p), all O~,36-69(56) with previous Mr(follow-u] 18-38 el;anterior (A) in 19 p; inferior (1) in 2;combin~ C) in 4. RD was documented by equilibrium E) RNA. Global (GL)ejection fraction (EF)was 29% (14-19%); 14 p had EE 30%.Rest ERNAin LAO and Lot; IS by i.v. perfusion (PER) of epinephrine (epi) in increasing doses of 4; 8 and ]2Jig/rain each 5 min monitoring heart rate (HR) and blood pressure (BP);ERNAstarte, at 15 m}n of PER with 12,ug, till the end of acquisitic~ Five segments (Sg) considered: antero-basal(AB); A-lateral(All; infere-apical (IAp); Septo ap (Sap); S~. Results: Changes in HR and BP during epi PER were not significant. GL E~>I0% in 5 p (A group); 29.4%~ 41.6%'~19% in 10 p (B) EF 26.1%->32.4%;in 6 p EF had no change(C); in 4 p EF # (D) 38.8%-~29.0%.For the 14 p with rest EEl30% in 10 p (71%) EFt'after IS. In group A 3 p had 6 Sg with no~'EF>10%;those Sg were related with necrosis E K G site. In B, 6 p had a total of 12 Sg with no contribution or # of regionalEFt 4 of these Sg had no relation with MISle~In C 13 Sg (49%) contributed to GL EF maintenance. For the GL study 16 p had 40 Sg with response to IS~ but only in 4 p (group D) a # of EF occurred. Conclusions: I) After tS GLl~F~in60% of p. This@ was>10% in 20% of p. 27In p with EF~30%,71%had positive response to IS. 3) Sg that did not respond to IS are mostly related to aecrotic area; the positive response found in 60% of p may be explained by p a t ~ necrosis surrounded by viable tissue. 4) 32% of Sg had negative response; their surgical excision may be the only way to improve cardiac performance. 5) The positive response to IS is accepted as a good prognostic index, which may explain the good survival rate in this series.

Haemodynamic and radion~clide estimates of left ventricular performance and functional cardiac reserve were compared in 16 patients with severe, chronic heart failure, H a e m o d y n a m i c data, using Swan-Ganz andl intra-arterial catheterS, mand r a d i o n u c l i d e data using ECG-gated To-99 ventriculography were collected s i m u l t a n e o u s l y . Data was collected at rest and then functional cardiac reserve was determined by the resDonse to incremental inotropic stimulatfon with Dobutamine (range 2.5-30pg/Kg/min). Cardiac index (CI) and cardiac power output (CP0) increased significantly from baseline values (B) on maximal inotropic stimulation (M); C 2.2+0.6 ( E ) v . 3.7+1.2 (M) L / m i n / m ~, p<0.00 a n d - g P 0 0.7+0.2 UB) v. 1,2+0.4 (M) w a t t s p<0.01; mean~SE. S i m i l a r l y 7 mean ejectio fraction (EFT increased from 26% (B) to 38 (H). The incremental increases in CP0 (ACP0] over baseline values correlated with the incremental increases in EF ~EF) both over the w h o l e range of infusion doses (r=0.52 p<0.001) and at the maximum dose (tSpg/Kg/mi~ t o l e r a t e d by a l l the p a t i e n t s (r=0.72 p<0.01). Furthermore, total regional wal motion scores improved p r o g r e s s i v e l y wit increasing d o s e s of D o b u t a m i n e and w e r e correlated with the improvements in EF at m a x i m a l i n o t r o p i c s t i m u l a t i o n , (r=0.72, p<0.01). Non-invasive assessment of left ventricular reserve using To-99 ventriculogrsphy therefore provides an alternative to invasive haemodynamic assesament in p a t i e n t s w i t h severe chronic cardiac failure.

M. FRENAY, F. LAPALUS CENTRE ANTOINE LACASSAGNE U.E.R. DE MEDEOINE DE NICE - FRANCE

LEFT VENTRICLE EJECTION FRACTION VARIATION DURING THORACIC IRRADIATION We report on the preliminary results (59 patients) of a prospective study of the acute effect el thoracic irradiation (T!R) on felt vuntr!a!e eiecticn fraction (LVEF). 27 patients underwent TIR including all mediastinum (M Group) (far lung cancer, lymphoma or oesophagial tumor), 16 left internal mammary chain (L Group) and 8 right internal mammary chain (R Group) (breast cancer). TIR did not include the heart in 8 control patients. They w e r e studied by gated radionuclide angiography at rest before starting TIR (GRA1), 15 days after the end of TIR (GRA2) and after more than 2 months (GRA3). LVEF was determined in left anterior oblique projection by automated left ventricle detection. The differences between the successive LVEF determinations were analysed for each patient by paired t-tests. The entire group including the heart in the TIR (M+L+R) showed a significant drop ef LVEF between GRA1 and G R A 2 (p
269 279

278

277 g.V.Satkevi~ius,J.Kiudelis,R.Navickas

K. Kouris, I.M. Hassan, B. Taha, R.H, Babar, ~ . Constentinides and H.M. Abdel-Daye~,

C.L.MAINI ( I ) , G.VALLE (2), C.STELLA (3), R.IOVINE (3), G.GOTERI (I)

Institute for C a r d i o v a s c u l a r Research,

Dept. of Nuclear Medicine, Faculty of Medicine and Ministry of Public Health, Kuwait.

(I) Cattedra di Medicina Nucleare, Universit~ degli Studi, Ancona (2) Istituto di Medictna Nucleare e (3) I s t i tuto di Igiene, UniversitA Cattolica, Roma

Kaunas, Lithuania, U S S R

A ~ S ~ . S S M ~ N T OF THE C O R O N A R Y BLOOD FLOW

BY THE FIRST PASS H E A R T S C I N T I G R A r H Y B~ORE AND AFTER C O R O N A R Y BYPASS SURGERY The purpose of this study was to estimate coronary blood flow /caR/ by c o m p u t e r i z e d first pass heart scintigraphy / F P H S / data p r o c e s s i n g using an original "MBP" software before and after c o r o n a r y bypass surgery /GAS/. 9 9 m - T c ~ l a b e l l e d red b l o o d cells end LAO 50 p r o j e c t i o n were used for F P K S in ~9 pts before CBB, in 29 pts a few days after CBS and in 51 pts one year later. Before CBS the overall CBF accounted for 7.1 t O.2 % of cardiac output /C0/ or 5.9 Z 0.2 % of diastolic left ventricle volume /DLVV/ per cardiac cycle /CC/. Throughout the first few days after CBS these figures did not chan~e, 7 . 3 ! 0.5 % end 3-5 i 0.2 % respectively. The values for coronary artery filling time and coronary bed capacity increased from 0.74 ~ 0.05 to 0.90 Z 0.07 s and from 28.1 t 1.1 to 32.~ t 1.5 % DLVV / p < . O 1 / respectively. One y e a r after CBS, the overall CBF was found increased /p < .O1/ to 8.1 t 0.2 % CO or to $.7 ± 0.2 % DLVV/CC and coronary artery filling time d e c r e a s e d to 6.87 O.0~ s /p < .01/. Therefore the c o m p u t e r i z e d FPHS dat~ p r o c e s s i n g enables one to assess CBS aftereffects upon the CBF.

COMPARATIVE CLINICAL h~ALUATION OF 374/5 T I ~ AND FUNCTIONAL IMAGE WITH PHASE AND AMPLITUDE IMAGES. The global T4/5 ti~e interval (derived from the global LV time activity curve TAC) is the time interval between late systole and early diastole corresponding to the 4/bth fraction of the stroke counts. A pixel's T4/5 time interval is similarly derived from the pixel's TAC. The T4/5 image is the pictorial representation of the pixel T4/5 values of all pixels within the LV boundary at end systole ES. Toe mean T4/5 value M is the mean of all pixel T4 values. We have established the normal patterns in 15 healthy volunteers and we have studied their ~rariations in 33 IHD patients(pie) all of whom had normal rest LVEF > 50%. Table 1 : Normals (15) IHD P~s(33) P M (mace) 197.0+ 23 254.0+35 0.001 M/RR 27.0T 1.9 27.5¥ 2.7 NS M/TF~ 66.5T 3.3 69.8T 5.9 0.02 M/T4/5 89.9T 6.6 I03.0TI0.7 0.0001 M T4/5 time en~ its normalise~ value to global T4/5 time significantly separate nommals from IHD pts (p<0.001 and <0.0001 respectively). We have assessed the % sensitivity, specificity and accuracy of T4/5 functional image in comparison to phase and amplitude (~=p.) images. Table 2: #rap. phase T4/5 ~mp. + T4/5 ~ t y 52% 27% 64% 70% Specificity 93% 100% 73% 67% Accuracy 65% 50% 67% 69% The smlsitivity of the T4/5 image in detectimg patients with I~D is higher compared to the ~ p l l t ~ e and phase images.

M.BAUD,R.FAIVRE,J.C.CARDOT,J.VERDENE¶

E.g.

BOURGUIGNON,

B.

VALETTE, D. LE GULUDEC, BERLET, D. AGOSTINI, C. BERT,

P.BERTHOUT,F.PELLIER,J.P.BASSAND.

B.C. G ~ G ~ , ~ . C. RAYNAUD and A. S~OTA.

Lab Med N u c l e t Service de CardLologie Hepital St Jacques . BESANCON. FRANCE.

Servi~e Bospitaller Frdd~rle Jollot, Ddpartement de Biologle, CEA, Orsay, France.

LEFT VENTRI~

VOLUME MEASUREMENT USING RADIONUCLIDE ANGIOGRAPHY

L e f t v e n t r i c u l a r v o l u m e s (LVV) w e r e d e t e r m i n e d in 200 patients using both left ventricular c o n t r a s t a n g i o g r a p h y LVCA) (SIMPSON'S rule) and r a d i o nuclide a n g i o g r a p h y (RNA). W i t h RNA, left ventricular volumes ( L W iso) were calculated as LV count rate calibrated with count rate of 5 m l of b l o o d collected from the patient prior to the acquisition. As regard to LVCA values, L~V iso were underestimated. This is due to g a m m a - r a y s a b s o r p t i o n : inside of the radioactive source(LV itself) which i n c r e a s e s with its volume, and inside of the chest wall, which depends on the body surface area (BSA).Multiple regression analysis l e a d to t h e d e f i n i t i o n of a r e g r e s s i o n e q u a t i o n allowing the c a l c u l a t i o n of the true L V V f r o m L V V iso, B S A a n d LV a r e a expressed as number of pixels (Npix).

VENTRICULAR ONSET DR CONTRACTION (VOC) AND ITS TEMPORAL RELATIONSHIP VITH TBE R NAVE TRIGGER (R) USING BULTIBARMONIC FOURIER ANALYSIS (MNFA)

OF GATED BLOOD

P00L IMAGES (GBP)

Phases images of the first harmonic (HI) Fourier analysis are mostly successful to iocallme VOC as the area of earliest phases without reference to R. Ne have used additional information from the second (B2) and third (as) harmonic to improve the modelization. 12 patients were selected for their normal left ventricular (LV) function from standard GBP (LV EF > 50 % and normal LV Bl phase pattern). Using the Fourier equations with a time resolution of 360 e per cardiac cycle, time of peak acceleration (TPA) was calculated for Bl, HI+B2, BI+Br+ B3. The average TPA value (aTPA) was obtained for each patient's LV. The mean and standard deviation of patients' aTPA were c a l c u l a t e d . Results obtained for Median and 3

Dimensional filters were corresponding to 180° : TPA HI

True L W ~

1.14BSA 1"425 NpixT M

as

HI+H2

follows with R BI+H2+H3

L W i S O 0"98 3 D

The values of L W estimated from RNA a c c o r d i n g to this e q u a t i o n correlate closely with L V C A v a l u e s (r = 0.95). Our sample of p a t i e n t s allows a refinement of this equation w h i c h has been previously established with a panel of 60 patients and an attempt to g e t a s i m i l a r f o r m u l a for w o m e n by adding breast attenuation correction. In c o n c l u s i o n , this non geometric method for L W d e t e r m i n a t i o n is w e l l correlated with LCA, reproductible a n d its use is easy in routine.

Radionucitde angiocardiography is commonly used for serial assessment of cardiac function in diabetic patients. Abnorma|ities of diastolic function at rest in such patients have been de scribed,but the meaning of a decreased PFR with normal systotic function remains rather specula t i r e . In the present study a "pattern recognition" approach, including principal component analysis and hierarchical duster analysts, has 'been used to evaluate the determinants of PFR i~ ,48 unselected diabetic patients. The results prove that: I- PFR shows a strong inverse depen dence from age which is its main determinant when the systolic function is preserved; 2- PFR shows an inverse dependence from the combined ~ffects of ventricular dimensions, wall motion ~nd angina; 3- the duration of diabetes in i t s e l f does not influence the PFR. These result~ lead to the fotlowing clinically relevant conch signs: A- PFR in young diabetic patients withcul angina and normal systolic function is usually unimpaired even i f the diabetes has been presenl For a long time; a decreased PFR in such patients is however a sign of latent ventricular dys function. B- A decrease of PFR in a middle-aged Dr old diabetic patient without angina and with normal systolic function is a very common event, but i t cannot be equated with latent ventricuIarl Jysfunction as i t may represent only an age-rela ted physiological change without special diagn~ stic meaning.

282

281

280

THE CLINICAL RELEVANCEOF PEAK FILLING RATE (PFR) MEASUREMENTAT REST IN DIABETIC PATIENTS

13B~lO °

Filter Median Filter

181"±10"

188°±8 °

t=16 p<,O01 t=12 p<.001 140°±13=

180=±9= 186°±I0" t=ll p<.OOl t=15 p<.O01

Variance analysis demonstrated significant TPA differences in comparison to HI. The 2 MHFA were not significantly different from each other though the 3 harmonic analysis indicates a phase beyond the R wave trigger. In conclusion : MBFA suppress the phase shift of B1 and restore the temporal relationship of VOC with R in normal patients.

A. Giordano, M. Massaro*, P. Zeppilli** Institute of Nuclear Medicine and **Centre of Sport Medicine, Catholic University of S. Heart, Rome * Dept. of Internal Medicine. University Tor Vergata. Rome - Italy BADIONUCLIDE VENTRICULOGRAPHY (RNV) IN ABRHYTH~0GENIC BIGHT VENTRICULAR DYSPLASIA: SCINTIGRAPHIC PATTERNS. I n t e r e s t around arrhythmogenic right ventricular dysplasia (ARVD) is growing ,due to high risk of sudden death in young people recently demonstrated. A~VD diagnosis requires evidence of yen tricula T arrhythmias, right ventricula~ (RV) enlargement with global or segmen~ al wall motion abnormalities. RhrV may have a role in the clinical setting as R V is often poorly visualized By echocardiography. Purpose of this study is to characterize t h e scintigraphie patterns of R N V in ABVD. 12 pts. with ARVD underwent equilibrium-IhNV at rest. R V global enlargement was detected in I0 pts., segmental sacculations in 4 (at apex or trlcuspidal region~, photopenic areas in 2 (thick R V traheculae), poor global contractility in 8, cinem o v i e segmental wall motion abnormalities in 9, anterior view Phase and Amplitude images abnormalities consistent with dyskinesis in 12. From the reported data we conclude that R N V displays a complete picture of multiple R V impairments present in ARVD; the evidence of R V dyskinesis in anterior view Phase and Amplitude images seems to be the ;most useful sign on the basis of i00~ sensitivity in our population.

270 283 tunen, g. H~ttunen~ S. S0imagallio

285

284

M, M~ntysaarl, E. L~nsimies,

J. Nuikka,

H, Nut-

[

o =oo J.F. B O U V ~ R ' , Y. LIENHART °° , M. BIVOIRE °~°

M. Helin, S. Rehnberg and

Departments of Clinical Physiology, Internal Medicine, Thoracic Surgery and Clinical Radiology, Nuopi0 University Central Hospital, Euopio, Finland EFFECTS OF CORONARY ARTERY BYPASS GRAFTING ON LEFT VENTRICULAR FUNCTION DURING ISOMETRIC EXERCISE Effects of coronary artery bypass grafting (CABG) on left ventricular function at rest and during isometric handgrip test were studied in a group of 58 male patients. Radionuclide ventriculography was used to measure left ventricular ejection fraction (LVEF). gpearman rank order correlations were calculated between LVEF and the characteristics of the bypass operation L?EF decreased significantly (p
286

F. De Oeez~z-.A. B t ~ ,

L. HuRhens, P.BMck.

° clinique G6nArale 74000 ANNECY. ~° H6pital Cardiologique

69374 LYON.

°oo Centre L6on BE~ARD 69373 LYON Cedex OSFRANCE

123 1 MIBG UPTAKE I~ HYP~TROPRIC CARDIOMYOPATI~ Nype~trophic cardiomyopathy (HIM) is primitive heart disease of unknown etiology 3ut could be considered as a dysembryoplasy. Fhe dominating part of catecholomines has 3een mentioned after histological studies ~ave demonstrated an excess of adrenergic tissues in such myocardium. For this reason B blockers have been used for treatment aithout according to the intra-tissue leve~s 3f the cateeholamines. Meta-iodo-benzFl-guaniSine (M~BG) has specific affinity to adrener31c tissues. We have studied 4 control atients and 5 patients with hypertrophic ardiomyopathy. 148 MBq (4 mCi) of 123-I-MIBG as intravenously injected and LAO scintigrahic images were performed 4 hours after ith a computer assisted gamma-camera. he uptake of 123-I-MIBG by the myocardium as at first expressed in comparison with he background by region of interest technique ~nd then estimated in kBq(uci) by calculations /sing a cardiac model. The radioactive iens±ty appeared siqniflcantly less in ~he NCM (ratios of 1.7 T 0.4 and 2.6 ± .6, p < 0.05) but no significant difference as noted between the absolute uptake activiies (45.6 ± 4.1 gci for the control patients nd 46.4 f 3.D for the patients with HCM). ~ese conflicting results could be explained a "dilution effect" due to the hypertrophy. e analysis of the radioactive densities or each region of interest (septum, lateral nd posteroinferior myocardium wall) showed n homogeneous uptake. These preliminary esults militate against the adrenergic ypothesis, gowever all the patients with CM were treated with calcium channel blockers r 6 blockers and a larger study with a areful standardization of medication must

l

l

287

Univea~ityHo~pittl,V~e Umven~it,Br.~seb.Be&turn /'Pt'0OARDIAL F U N C T I O N IN PATI~]TS W I T H ACUTE

NECROSIS:

COMBINED

RADIONUCLIDE

ASSESSMENT

'Ir~'I~CULOORApI,~

BY AND

ANTI-MYOELN FAg'S. •M m ~

~

fur¢~o.a, "n sta~e~ ~ pa~e~ts~ImittM m

1~¢~ ~ ~ h~-tll-kbe~ t ~ m ~

~m~mmm~ "w~h 74 M~q

Fab. &~ kern 24 ~ h4m"f~ey •'~m imet~ u s ~ a medlma earth,pe~el hob col~me~ aad both In-Ill peeks,hneges ,tn~.mobl~ed ta the 4S defteeMft a m m ~ ob~que (LAO) ix~si~m~Withoutm m d ~ thepa~em 740 M B q 'l'e-99m-Mb~delbumfmw ~ Injecledm~,enous]y and a ga~d ven~u]~ta~hy was pe~oimed m theLAO v~ew.l~ht eml ~ venUmder pe~etem drown meneelly on a a~elmn~us dlsp]eyof the e ~ . 4 ~ s ~ hame e~l the Foe~; ampoule and l~me ~me@s were o m l a ~ on theQ ~ . m ~ q n ~m~e. T ~ bit ,t~aUCb ~ divvied ~m ~mtmor, t l ~ ~'~ lxmex~ pare, each occup),~ a ti~l of @e bl~ venblcubr ~0maem. Wal~m o ~ n -, e~ch of ~ese pare 'w~ comile~l asme*lrk:m ~ , pmseam ol emp~de ~ p l z ~ almm=,s~e. la ~ ~lpmm~ mtatm~ ~,a ~ ) t m l ~ v e ~ titI~r i~t~t~t or a ~ m Z%-e~:m'. In 4 se¢,,ems O apical~ra I pome~br) mcao.~ 'v~ a~t eccompen~d by mte£~l wa~ d~ftm~on. 'witb~t m . I:n 2 pa~e~s tbesedJ~oMmma could be mMtM to inmate m f e r ~ s or ~ comluc~n tList~*.u:~, la th~ oth~ ~ t h ~ 'mtm e~-ab~l to '~oztlefl~t,

288

R. Zimmermann, H. Tillmanns, H. Bihl, A. Ernst, M. Kapp, P Georgi, W. K@bler.

H.P.Stoll*,M.Mfiller=,J.Dyckmans 2 , G.Brill I , R.Berbericht

F. Therein, P. Potin*, D, Debrun, d. Grog, M. Valois*

Departments of Cardiology and Nuclear Medicine, Uaiver$ity of Heidelberg, Federal Republic of Germany.

IAbteilung f~r N u k l e a r m e d i z i n • I n n e r e M e d i z i n III, K a r d i o l o g i e Universit~t des Saarlandes D - 6 6 5 0 Homburg/Saar; W . G e r m a n y

Service de M~declne Nucl4aire et Service de Cardiologie*, C.H.R Or]4ens Cyclotron d'Orl4ans (CERI) - France

INCREASED REGIONAL KRYPTON-SIre CONCENTRATION AFTER IV INJECTION OF RUBIDIUM-81 AT REST IN PATIENTS WITH UNSTABLE ANGINA

CALIBRATION OF RB-81-MEAStFRED REGIONAL M~OCARDIP.L B L O O D PLOW IN M L / M I N / 1 0 0 G BY C O M P A R I S O N TO W A S H O U T OF I N T R A C O R O N A R Y I N J E C T E D X E - 1 3 3

The present study was aimed to investigate whether ~ sessment of reversibly and irreversibly damaged myocardium could be improved by additional imaging of the K r - g l m distribution after bolus injection of Rb-81. The study population comprised 9 patients with ur~table angina pectoris, 10 patients with stable angina and 2 patients with normal coro~tary arteries. Within i0 days after cardiac catheterization and immediately following TI-201 rest scintigraphy, 1C0 MBq ultra-pure Kb-gl were injected intravenously at rest. Twenty minutes after injection, 91anar K r - g l m scintigraphy w ~ performed, followed by Rb-81 imaging (high energy collimator). As compared to TI-201 and K r - g l m images, Rb-81 images showed worse visualization of the left ventricle due to a higher tracer uptake in surrounding tissue. Regression analysis revealed a significant correlation between segmental T1201 and R b - g l uptake (p<.001). The 37% intercept, however, indicated overestimation of low flow rgtes with Rb-$1. Of 14 study patients with previous myocardial infarction, 9 patients revealed regional tracer uptake abnormalities with R b - g l , compared to C0 patients with K r 81m and 12 patients with TI-20L In 3 patients with unstable angina, however, an evident mismatch between regional TI-201 and R b - g l distribution, respectively, and the distribution of K r - g l m was obtained: in contrast to the reduced uptake of TI-201 and Rb-8C, Kr-$1m activity was increased in 3 myocardial segments with normal wall motion hut supplied by either completely occluded coronary arteries with collateral flow or coronary arteries with high-grade stenoses. Thus, in patients with unstable angina, R b - g ] / K r - 8 1 m scintigraphy might be an alternative to T1-201 rest seintigraphy in the differentiation of reversibly and irreversibly damaged myocardium. Yet, further work on appropriate collimation, image acquisition and data processing will be needed to further improve the diagnostic reliability of Rb-81/Kr-81 m studies.

Rb-81 accumulates in the myomardium after intravenous injection d e c a y i n g t h e r e to its i n e r t d a u g h t e r Kr-81m. T h e n o b l e gas is w a s h e d o u t by myocardial perfusion. Thus the r a t i o Kr : R b - a c t i v i t y in a c e r t a i n region of the m y o c a r d o n l y depends on regional perfusiop and can theoretically be calibrated in ml/min/100g. Calibration, however, o n l y l e a d s to c o r r e c t f l o w v a l u e s if the errors of t h e imaging system caused by different gantma-absorption are taken into account,

To

overcome these problems we carried out phantom studies simulating the a n a t o m i c a l relationships of the chest. 4 different phantoms corresponding to chest circumferences b e t w e e n 80 cm a n d Ii0 cm were scanned as scintigraphic zero-flow references. Flow was calculated by the equation • Fl(ml/min/100g)=F*(ln Rpb..-in RPeti [El=regional myocardial blood flow, F=proportionality factor, Rp~a.= R a t i o K r : E b in the p h a n t o m , RP.t = E a t i o K r : R b in p a t i e n t s m y o c a r d i u m ] . The results of 25 patients are correlated to f l o w r a t e s determined b y w a s h o u t of i n t r a c o r o n a r y injected Re-133. Washout curves could be registered by a mobile camera-system in the C a t h e t e r - L a b o r a t o r y .

ASSESSMENT OF MYOCARDIAL PERFUSION USING KRYPTON 81m IN PATIENTS WITH CORONARYARTERY DISEASE (CAD). 16 patients with anginal chest pain were submitted to coronary arteriography, and planar imaging was performed using a scint i l l a t i o n camera connected to a d i g i t a l imaging system. A 81m Kr-giucose bolus (5 m], 40 +10 mCI) was injected above the aortic valve at rest and during a t r i a l pacing, 11 out of the 16 patients were also studied after a spray of TNT (Trinitrotoluene}. A visualization score was established from D to 4 for areas corresponding to each of the 3 major arteries, on normalized sci,tigrams after background 6ubstraction. The Kr perfusion images correlate well with the coronary angiograms ( s e n s i t i v i t y = 94,4 ~, specificity = 92,6 %) Determining the location was perfect in cases of slgnificant i and 2-vessel CAD. The perfusion defects were suppressed by addition of TNT in 17 out the 22 areascorresponding to significant i and 2-vessel CAD. We can therefore conclude that a 81m Kr scintigram is areliable method for the study of I and 2-vessel CAD. The tracer has no effect in the circulation and the injections are easily repeatable. This method then seems p a r t i c u l a r l y interesting for studying the effects of various drugs on CAD : i t could evaluate i n d i r e c t l y the coronary vascular reserve and be applied to other heart diseases.

271 289 S.J. Wang, S.H. Yeh. L.C. Wu, J.L. Lan, M.S. Lin, S.Q. Lien, R.S. Liu and C.P. Chang

Veterans General tlospihal, Taipei and Taichung, and National Yang-Ming Medicsl College. Taipei I Taiwan EFFECT OF PHOSTAGL~NDIN E-I (PGE-I) ON PERIFItERAL CIRCULATION IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): ASSESSMENT BY Xe-133 MUSCLE CLEARANCE. In view of the occurrence of vasculitis with compromised peripheral circulation in SLE, thi~ study was undertaken to evaluate the vasodilating effect of PGE-I in patients wlth this disease. Ee-133 muscle clearance test was adopted from Pozderac e t a i . (Radiology 117:633, 1975). Data were acquired in frame mode after intramuscular injection (anterior tibia muscle) of 0.3 mCi of Xe-133 in 0.2 ml of saline for 20 min, A computer routine was used to calculate clearance half-time (T 1/2) in min and flow rate (Q) in mb/10g gm tissue/mi~. Nine patients with SLE nompllcating with vasculitis in ig legs underwent Re-133 muscle clearance study before and after daily IV drip infusion of 40 m g for three days. The results are as follows: Croup

Number T½(mean ± s.d.) Q(mean ± s.d.

Before PGE-I ig 42 ± 19" After PGE-I 18 24 ± 16 •p < 0.0! vs after POE-I

1.33 ± 0.54* 3.39 * 3.19

After IV infusion of PGE-I, muscle Xe-133 clearance was increased in 88% (16/18) of the legs. In summary, prostaglandin E-I increases peripheral circulation in SLE signiflcantly, ang may have a potential therapeutic use in vasculdtic leslons.

$. bemonceau,

M. Steggen, J.L. David, P. Bourgeois.

292

P. Ziegels, P, Pdgo, M. Brasseur, L. Baldelli, Y. Beguin, G. Fillet, R. Leclercq, J.C. Depresseux and

I

HUMAN BIODISTRIBUTZON AND PP,ELIMINA~Y RESULTS IN THROMBOPHLEBITIS WITH TC-99M-SM-PAO LABELLED PLATELETS.

l

In vitro platelets labelling with Tc-99m-RM-PAO takes advantage of the lipophilieity of the compound. Our first clinical results obtained with this tracer are reported in this paper. 300 REq of Tc-99m-IIM-pAQ labelled platelets are intravenously injected into 5 healthy vollh~teers and 12 patients clinically suspected of thrombophiebitis. Radiologic p h l e b o g r a p h y w a s obtained in all patients. Planar views in matri> 64 x 64 are taken in ~nterior and posterior views, each ~our unti/l the 6th, then twice day during 48 hours for volunteers. Images of ~atients are only made at the 24th hour. [ormal hiodistribution is roughly simil~m to that obtained with In-lll-tropolonat~ labelled platelets, except somewhat lower circulating activity and speen-to-live~ ratio. Intestinal and renal, but not cerebral p a r e n c h ~ t o u ~ a c t i vities were noticed. Converging results between phlebography mud l~belled platelets are obtained in g patients (6 positive - 2 negative), Three patients are only positive with labelled platelets, one only with phlebography. The later mismatch is interpreted ~s an old stabilized thzombus. In conclusion, nical interest ,latelets with lier detection. tients are now

prelimZnary results suggest cllfor t h r o ~ i detection of labelled ~ improved reliability and earExtensive studies on more pa~/ider progress.

+ 9 2 11 l* tO It Tot, tO 12 22** P h l e b o reviewed as unconclusive for site of AFI positivity. ** One patient with DVT in the 2 limbs. Phlebo/PLT + Tot. + 6 1 7 3 Z 5 Tot, 9 3 12**

One patient with DVT in the 2 limbs/ - Precise comparison with Phlebo demonstrated that AFI as ~ell as PLT delineate only "floating" bhrombi but in no case organised on( AFI/PLT + Total +

-

3(Phlebo+)

0

3

l(Phlebo+) l(Phlebo-) 2 4 l 5 lut of these patients, were PLT pictures more contributive than AFI ones in two cases and inversely in two other. I t is concluded that : - P L T as well as A~I represent a reliable wey Lo diagnose deep vein thrombosis. at the present stage of our experience, AFI seems to have a greater accuracy that PLT - Nevertheless, the two investigations seem to be compTementary. Results on larger population w i l l be presented Total

M. Sy and I, S, Seo

DEEP VEIN TBROMBOglS (DVT) OF POPLITEAL VEIN (PV): UPDATE OF TECHNIQUE AND CRITERIA. Non-visualization of deep veins associated ~ith abnormal collaterals on radionuelide veno~ram (RNV) indicates DVT. Faint or no~-visual[zation of a deep vein without collaterals may represent very early stage of obstruction if present in a symptosatic extremity, however, :his is in itself inconclusive if noted dn the asymptomstic extremity or observed with other zssoelated features such as superficial variees. ]nlike DVT of illac or femoral veins, collat~rals are less readily seen in patients with )VT of PV. Modified RNV technique and criteria znd prevalence of DgT of PV are evaluated. With 8mCl of Tc-99m Fertechnetate, diluted [n 10ec of ~SS (diluted large volume technique) into a vein of each foot, 3 second d~namic hmages are obtained. If PV in symptomatic ~xtrembty is not visualized, tight tourniquets zre applied above the ankle. If PV is still cot visualized, often accompanied by severe pain at popliteal region during injectzon~ DVT of PV Ls strongly suggested. Recanallzation of PV m d / o r disappearance of some collaterals on :epeat study appear to confirm the diagnosis. Cf 218 patients with abnormal findings itotal 1259 studies between Jan, '82 and )ct. 'gT) 67 had DVT of PV, single or associated #ith others. Seventeen of 23 with follow-up ~tudies showed recanallzation of PV and/or educed collaterals while 2 showed progression nd 4 showed n o changes. Detection o f DVT of PV is less cCnclusive by I 0utile RNV because of less collateral formsion. Its detection is enhanced~ however~ by sing the preceding modified technique and riteria,

lI

294

A.Bonazza, G,Petracca Ciavarella, M.Grilli, U.Fieola, VmFrusciante, F.Earbano,

0spedale

99mTc HMPAOLABELED PLATELETS (PLT) AND In111 LABELED ANTIFIBRIN ANTIBODY (AFI) FOR DEEP VEIN THROMBOSIS(DVT) DIAGNOSIS. Results of tne scintigraphic research of DVT performed with PLT (11 cases) and/or with AFI (21 cases, informed consent obtained in each cases) in 27 patients with sclntigraphically suspected or proven lung embol (LE) or with c l i n i c a l l y suspected or "obvious" DVT have been compared to X Ray phlebography (Phlebo) data Phlebo/AFl + Tot.

IW.

I D E P A R T ~ N T 0B NUCLEAR MEDICINE, THE BROOKLYN HOSPITAL, BROOKLYN, NEW YORK, U0A

293

P. Bourgeois, M. Stegen, P. ZieBelS and G. Demenceau*. Dept. of Nuclear Medicine, CHJ Bracops, Free University of Brussels, and Cyclotron Research Unit, University of Liege*.

[

Cyclotron Research Center, Sector of Nuclear Medicine, Laboratory of Sematology, University of Liege. eracops Hospital Bruxelles - Belgil~m.

f

-

291

290

"CmS.S."

g.Giovanni

Rotond0

(ITALY)

OilER Llfig ARTERIO$CINTt~PHYIN UI~RETICNEL~OPATHICARTEROVENOgS ;HUNTSEVALLIATIDN ncidence and severity Df atherosclerolic disease in diabetic mtients is by far more caM;datable than in normal population.The IJabetic lDzqer ]il~ ucrnlicreangtopathy along ,ith auroral)raiLslid/ ~r sensitive-motor;el neuropathy, could account for the ircreased ius[eptihtiity to physical and thermicaI microtraumz, because of the ihnnrmal local response to also briyiil injuries. It'S already wellnolo that in the diabetic patient with louffi" llm~ autonomic muropi%hy,th~ deteriorating of the l i t t l e nervous sywh~Lhedtc ;hers often leads to denervatinn of capillaries with consequent ,pen;rig of arterovenouslk-V) shunts, lhis conditin, impairs the dready altered eq.ilibriul in tissue perfusion pressure and :ontrihutes to the slov healing ef chrenic infections and ilcerations. ]n Drder to improve lower limb torpid lesions healingl ;imple elastic benda~e Was used to pro|ore flow i~ poorly reactive essels. Elini[a] rHultswlre satisfying, The shunt is supposed :~ have a size of about 15-20 p so that particles whzch normally |pact i~ the capillary bed 4about h g size) can pass through and ;top in a secend f)lter (liver, lung;. Small size microspheres )S-M! 'Og Df the particles %25 pm) can be used~ by inlraarterial njection, in order to detect shu~t~ presence by indirect lung tsualizabton. Five diabetic patients were studied, before and afbel !Iastic bendage,by tnjecbing [1I flgq {3 met)of gdmhc-S-HSin the omoral artery. Two palients ,ith leg circulation problems without clinical evidence of shunttn~ served as controls, b total body ~xamtna~ionwas then started in the anterior v)ew.Liver was isualited both in diabetics and cDntrols in variable extent.In the :we controls lungs were only slightly evident and the ratio between ;wo eguivalent ROle on tun@ and calf .as over 7 in both cases.ln iabetJcs lungs were always more or less evident with a ratfo anginA from O,B8 to I.OB. After elastic bondage of leg and Pool adios showed small but definite changes, ranging from ].be to 1.7B~ dong with clinical improvement. AJlbough it could be used only in ;elected cases, arberioscintjpraphy,if performed by s l i I f u l hands, ~ighl be an useful best in detecting IDWEr limb A-V shunbing as well !as in monilprlnp the effect of mechanical or pharmaceutical devices ;used to prevent or correct them.

Rite Oaesa, f. Intrierim, R. 6attusomI F. Perle, 9. Boemt, R. Dessert;l, A, Centi-ColellaI F, genedetti-ValenLinia

Nuclear Red;tins - Oepartient of Experimental Redicine - and I And Chair of Vascular SurgeryI University 'La Sapienza' game [Italy)

AADIORUCLIDE ANRIORRAPHY FOR GRAFTR'OF THE LOWER LIRgR

INVERTIRRTIO~ OF ARTERIAL

Purpose of this study was to assess role and reliability of radionuc[ide angiography [BAg in investigations Df arterial grafts of the lower limbs. TwenLysix patieqls operated upon and discharged from hospita! wiLh a patent graft were i~ve~t[gabed by RA h to 4g mnnths after e~rgerp. Arterial grafts were : 4 axiltofemoraI -btfeloraI (iwith femaropopltteal branch), ] crnssfelor~] [[ with aortefeloral bypass), 2 straight aorticI 2 aortoilia% ~ aortofemoral bifemoral, 7 Pemoropopliteal -Ltbial. Eight patients were asymptomaltc, at least one in each groug, and were used as controls. Eighteen had either residua~ or recurrenL symptoms. All were investigated, also by d i n i c a ] a,d Doppler C# examinations; 20 of them had Echoduplex and color-Doppler analysis and 14 had an angtography. Transit L/me wee recorded over selected areas of interest. RA correctly showed patency ol the grafts in 8 asymptomatic and in 13 symplomatic patienls, Rnreover in the ~esond group it was able Lo identfff Lhe causes mar symplnms either directly by images, or indirectly detecting a delay og transit time. Such causes were preexistent or nem obslruc[ion of ~uperficial femural artery or more peripheral disease in 9 cases and distal anastomotic stone,is in an aortofemoral bypass. In three remaining patienls of this group, in one case i t was precisely distinguished potency of an aorLoiliac graft tram obstruction of rigth e~ternal iliac artery; in 2 femor,popliteal bypasses paLency of the graft was shown on a blind stump of popliteal artery in one and on a single peroneal arterp in the other one. In these three cases RA was particularly useful since diagnosis could not be dDne by any other goninvasive tecnique. Occluaion of the graft or at one branch of an aortobifemoral bypass w~s correctly shown in 5 cases. Our preliminary studies show Lhat RA is rather sensitive in the serial assessment of arterial grafts and in early detection of causes for failure, Further investigations are needed in order to asses the reliability of the procedure in cases were mare distal grafts are gresenL,

272

295 E,J, Wang, l.g. IIwang, S.H. Yeh, L,C. Wu, R.S. Liu, M.N. Wu, and M.S. Lin.

Feterans General Hospital, Taipei and Taichung, ~nd National Yang-Ming Medical College, faipei, Taiwan. EFFECT OF PROMOSTAN (PROSTAGLANDIN E-l) ON PENILE Xe-133 WASHOUT. In view of the pharmacological effects of Promostan on vasodilatation and increase in blood flow,.this study was undertaken to ;evaluate the effect of Promostan on penile Xe-133 clearance in patients with erectile impotence. The penile Xe-133 washout study was adopted ~rom Nseyo, etal. (Urology XXIII:31,1984). )eta were acquired in frame mode after ~ubeutaneous injection of 1 to 2 mCi of Xe-133 in g.l ml of saline for 20 min, A computer routine was used to calculate clearance halfItime (T 1/2) in min and flow rate (Q) in ml/100 gm tissue/min. Thirteen patients with erectile impotence underwent penile Xe-133 washout studies Before and after daily IV drip infusion Of 40 mg of Prsmostan for three days. The patients after treatment had a significant decrease in T i/2 (mean * s,d.) from 14.9 ± 5,2 to 9.2 ± 3.6 (p K 0.01), and increase in Q from 3,6 ~ 1.2 to 6.1 ± 2.3 (p < 0.01), In smmary, IV Promostan slgnificantly increases penile Xe-133 clearance, and may have a potential clinical use in erectile impotence due to arterial insufficiency.

298 I AM Peters, P George, JM Hows, F Ballardie.

296

297

IA. Cuoeolo, S. Esposito, L. Celentano, M.Volpe

liP. Vecchione, g. Trimareo, M. Salvatore. llstituto di Scienze Radiologiehe, Cattedfa di Medicine Nucleate and i Clinica Medics, 2nd Medical School, University of Naples.

~

~

z

~

INHIBITION ON COMPUTED Tc-ggm DTPA GLOMERULAR FILTRATION RATE IN HUMAN HYPERTENSION. In an effort to improve the noninvasive deletion of renal ~rtery stenosis, we investfgated the effects of angiotensin converting enzyme (ACE) inhibition on renal function. Global and split glomerular filtration rate (GFN) were determined, by ssing Tc-99m DTPA, in El patients with arterial hypertension. In the first group of [O patients affected by essential hypertension GFR was assessed by both radlolsotopic technique and 24-hour ereatinlne clearance. The radionuclide computed GFR showed a signlficant correlation with 24-hour creatinine clearance determlnaLions (r~0.875; p
299

~

,S.Tamas,M.G.Cotul,D.L.Dumitrarear D e p t . o f N u c l e a r M e d i c i n e o f t h e 3rd Medical Clinic,School of Medicine, 3400 Cluj-Napoca,Romania

NON-INV~IV~ MEASUR~dENT OF MICROFASCULAE PERMEABILITY. A simple technique for measuring regional micro -vascular p~rmeahility (HVP) in ~ n would be useful, specially in clinical research. Technl iques u s i ~ intravascular (IF) labelled proteins measure only gross changes in MVP. Our technique measures MVP to DTPA, a much s m a l l e r molecule which diffuses between IF and extravascular (EV) spaces. Gamma camera Tc-99m DTPA renogTaphy was performed. If E(t] is the background-corrected renal curve and P(t) the cardiac blood pool curve then the.~slope of the regression of N(t)IPlt) on JgP{t)dt/Plt) represents GFE. The purpose of background subtraction is to remove the EV component; IV background is ellmated in the analysis. By applying the same analysis to a NOI placed below the kidney and limibiNg it to the interval 40-180 see, a regression slope is obtained which represents the clearance of Tc-99m DTPA from IV to EW spaces. We assume that over this period the return of DTPA to the IV space is negligible. Total GFR was measured by blood sampling up to 4 hr. If A and B are the regression s l ~ for renal and sub-renal hOgs respectively (both sides summed), then the DTFA clear, nee in the sub-renal NOl, which represents MVP, is B/E.GFi This value w~s reproducible in 5 patients studied on successive days. The spread of values in 10 cormsls ~ s narrow (59-+3D 6.9/ml/min 100 pixels]. A marked increase, which correlated slgnificsmbly (p
Department of Surgery, Chafing Cross Hospital, Fulham Palace Road, London~ W6 8RF MEASUREMENT OF CAROTID THROMBOOENICITY: OPTIMA[ METHOD Platelet deposition following carotid endartereetomy results in post-operative thrombosis and restenosis, but until recently could not be detected in vivo. We evaluated radiolabelled platelet deposition after endartereetomy and compared 2 methods of measuring thrombogenieity. Autslogous 11]In platelets were injected into 10 patze~ts, 2 days after carotid endarterectemy. Radioactivity over the operated and contealateral reference arteries was measured daily for 3 days by both Scintronix (LFOV) gamma camera and sodium iodine crystal and ratemeter. The daily increase of the ratio endarterectomy over reference was calculated and expressed as Thrombogenicity Index (TI). An independent observer identified platelet uptake on gamma scans in 8 of the 10 patients. Gamma imaging recorded mean (±sem) counts of 46.3 ± 4.3 per pixcel over the operated artery, which was significantly higher than 36.6 Z 3.9 over the reference (p<0.O0~). This difference was not identified by probe counting with count~ of 3.0 ± 0.8 x 10s and 2.9 ~ 0.8 x I0 s over the endarterectomy and reference respectively. Thrombogenieify from gamma imaging showed progressive platelet deposition with TI of 0.11 ± 0.02 but this was not identifled by probe counting with TI of -0.03 ± 0.03. There was no correlation betwees the values of TI calculate by these g methods of assessment (r=0.g2). Gamma imaging is the method of choice for assessing carotid platelet depositlon. Probe counting fails to identify localised thrombus perhaps due to the high background from circulating blood.

300 K.Tatsch, C.-M.Kirsch, P.Knesewitsch, R.Landgraf,* E.Moser Division of Nuclear Medicine, Department of Radiology and Clinic of Internal Medicine Innenstadt*, University of Munich, Munich, FRG

H ~ e r s m i t h Hospital & Royal Postgraduate Medical School, London, UK.

I

A C Meek, R A Harper, A Chidlow, M Salmon, C N McCollum.

RADI01SOTOPIO SIALOGRAPHY IN COLLAGENOSES A i m . T h e a i m o f t h i s s ~ u d y w a s the e v a Y~tion of the s a l i v a r ~ g l a n d s f a n c tien in eollagenoses.Material-metheds. Radioisotepic s i a l e g r a p h y o f the p a r o r i d s R S P w a s p e r f o r m e d b a s e d a n the sa llvary c~earanoe of 99mTc pertechnetare(37 MBq adm.l.V.),Slalograms w e r e oh talced ~hroagh leqaentlal scintlgraph~ T h e r e g i s t r a t i o n w a s c a r r i e d o n 30 m i n in b a s a l c o n d i t l a n a n d a l s o 15 m i n . s f tar o r a l s t i m u l a t i o n w i t h 5 g . s u g a r . 32 s a b j e c t s w e r e i n v e s t i g a t e d w i t h s~s tsmic lupus erythematosus SLE;reumatho id a r t h r i t i s R A ; a ~ s t e m i a progressive sclerosis SPS;nondifferentlated connee tlvltls NO.15 health~ subjects served as control.The sialogrsm has 3 segment corresponding to the v a s c a l a r p h a s e A, concentratlan phase ~,excretian phases induced by stimulation. Its qaantitstlve processing included the estimation of the p a r o t i d c o n c e n t r a t i o n index PCI = B / A ~ n d of t h e p a r o t i d s t l m ~ l ~ t e d e x cretlan index PSEl=C/B.Results; G r o u p No~ PCI P~EI Oontz°15 2.0-2,7 0.5-0.6 SLE 5 1.0-1.2 0 -0.3 RA 12 1.0-1.5 0 ~0.2 SPS 6 i. 0 - 1 . 5 0 ~-0.2 NC ~ 1.0-i.~ O -0.4 Conclasion.ln all collagenosis,a dec r e a s e of P C I a n d P S E I w a s d e t e c t e d . T h e s e d a t a s R g g e s t a n i m p a i r e m e n t of the p a r o t i d f a n c t i o n in c o l l s g e n o s l s , e v e r in s R b c ~ i n l c a l c a s e s .

ESOPHAGEAL PARAMETRIC IMAGING: A METHOD FOR DETECTING ESOPHAGEAL M O T I L I T Y D I S O R D E R S IN D I A B E T E S M E L L I T U S

Gastlointestinal motility disorders are a well known complication in diabetes mellltus and may be considered as part o~ a generalized autonomic neuropathy. In the present study esophageal motility in diabetics was investigated by esophageal parametric imaging (EPI) and compared to gastric emptying (GE) by a standard scintigraphic method. 22 insulin-dependent diabetics (14 women, 8 men; age 24-52 years; mean disease duration 18 years) with known autonomic neuropathy were studied by EPI and GE. For EPI 15-20 consecutive swallows of a liquid and solid meal were recorded. For image evaluation 10-12 esophageal regions of equal size were created using a [ special space-tlme matrix. GE was performed with a mashed meal. For evaluation the retention at 20 rain. and the 50% emptying time were [ calculated. In both methods Tc-99m sulfur colloid was used for labeling. i EPI of liquid bolus was normal in 8 and pathologic in 14/22. Using the solid bolus pathologic EPI was observed in 21/22 with only one single normal case. Gastric emptying was delayed in all patients. This results indicate that EPI performed with so id bolus detects esophageal dysfunction due to neuropathy more tellable than EPI with liquid bolus. Comparable results were obtained by EP[ with solid bolus and GE. Thus, EPI with solid bolus is an adequate alternative tar evaluation of gastrointestinal mot lizy disorders indicating autonomic neuropathy in diabetics.

273 301

302

303

Oob~T Am

L ~EStOJDO~D,m S. Hedeni,m F, Harbano,3 T. Federich @ V. tnnese~0 N. Oaruso~m b. Bonazza

Pastinszky,

mDepartmentof nuclear Medicine and Sadlotherapy 3 SepPrtmentof OastroenteroIogy and Digestive Endoscoty General Hospital 'CtO0SSLLIEVQdella OOFPtREHZA% 0. Giovanni Hotend~ IFtb IThLP

Dept.ot Radiology, and Surgery + , Pestgraduate Medical Scboo , B u d a p e s t Videoton Research Institut ~ H-1389 Budapest, P . O . B o x 1 1 2 , HUNGARY.

.Szi,v~eL,

,.

H. . . . . .

Paulo M.Costa F.Godinho, G,Cantinho,FernandesF.Veiga

~ I.

M. K u n

Propedeutica Cir~rgica - Institute de Medicine Nuclear Faculdade de Medicine de Lisboa

SOP~GEAL SCINTIGHHPHYUSEPOL~ESO IN QDSTRt-SOGPHHSEtLNEFLUX cinlitraphic evaluationof esophateal lransit is useful in the assessmentof both primaryand eecondaryesophateal motordisordera as acbalaeia~ dlffen esophagealspasmand scleroderma. Recenilpa chants in the normalscintipraphlc clearancehas been documentedin 6astro-tsophatealReft~m(HoberteonP.]. et Hl.~IfBh).He performed esophateal sclntigraphy (ES) bt liquid and solid mealtest in: ~t D~D: (OfM + lSF,meanage gt yrs.,range Id-7g),with a pathologkI~i ~g hrs, esophageal pH-metry (De Neester'e criteria, 1980) submitted also to esephatealendoscope,manometryand scin)igraphy. 31 pts. shewed grade l-II esophagitie. We excludedfrom thie treup the patients which showed esephateaImotordiekurbancesprimaryor secondary to sistemic diseases; SOnormal informed and consentie~ subjecte (IOM + lOF~ieanage g3 oo-.l wieh .....I HophatealpH-:elrp, endeec,pyand manomekry.EeBpbagealmanometr? mas perfBrmed by ~ low colplianee neumohydraulicsystem(fl,wO.)cc/min},No drut~were adminielereN hB hrs. before and durdnt the examinallon, tO wae performedon fastint patients by adlinisterin t I mCi t07 )Bq) of 9fmfc-sulphur colloid diluted in lO mh of water {liquid Lest) or mimedto scrambled egts (solid test) and acquirint i ft./set, unit] 70 so=. and then [ fr,/15 sec. until IO min. Our protocol is a modification of the ~mImud'etechnique, Activity-tile turves were carrie3 out from the whole eeophatusand from each of four considered segments{superia% mid~le, inferior esophagus and gastric fundus). The results in the t ~ groups, e~pressed as retention percentages,werecomparedby Student T test forunpairedd~ta. Nostabisticaldifference het~enStHpatients and control groupwas found in EOperformed by solid meal, while by liquid meal te~t mehave found these differences: All the OE~ ply, vs. controls: g (O.OO5at 15" 6~ pts, without esophatltis vs. condr,ls: p (0.005 at 15" anq 30" HERpie. with esophatiLisvs. controls: p
l}hTTF;;ie

304 E.

INTRAOESOPHAGEAL DETECTION OF B I L I A R Y REFLUX

Biliary reflux inio the oesophagus is I frequently observed after gastric surgery. Its contribution to the pathogeI n e s i s of r e f l u x oesopha£itis i s contro-I I v e r s i a l , pH m o n i t o r i n g Ts u n r e l i a b l e go d e t e c t bile reflux after gastric I surgery. Cholescin~igrapby is a r e l i a b le m e t h o d b u t t i m e - a n d s p a c e - [ i m i t e d . fn o u r s ± u d y a new n o n f m a g f n g m e t h o d to I detect bile reflux inLo the oesophagus I was e v a l u a t e d . A miniaturized 5i(Li) semfconductor detector was p l a c e d fnio I t h e o e s o p h a g u s L cm a b o v e t h e o e s o p h a - I gogastric junction. 2A p a t i e n t s with reflux oesophagFtFs were studfed, After intravenous m]ection of 2oo MBq T c - g 9 m HiDA [ n i r a o e s o p h a g e a ( count rates were continously recorded, Detector geometry was s t u d i e d by p h a n t o m e x p e r i m e n t s , n vive measurements were validated by simultaneous gamma c a m e r a s t u d i e s . Frequency, duration and extent of a c t i vity spi~es were evaluated. Characteristic petterns were found in patients with various t y p e of r e f l u x disease. Good c o r r e I a h i o n was f o u n d b e t w e e n d e tected reflux events and endoscopic findings. O u r m e t h o d p r o v e d t o be a retfabte iechnique to detect and characterize biliary reflux into the oesop h a g u s . As a c o s t - e f f e c t i v e method it may b e u s e f u l in }ohm-term m o n i t o r i n g of p a t i e n t s with suspected biliary reflux under various physiological and 3ostural

conditions.

305

Pasztarak,

L. S i m o n ,

.

RADIONUCLIDE

Eaophague-Sclntlgraphy in scleroder=la as a way of m o t l l l t y - d l a g n o s t i o s :A new d i a g n o s t i c m e t h o d gets r o u t i n e

TRANSIT

PATIENTS

In the p r e s e n t s t u d y the a u t h o r m e x a m i n a t e d in 253 d i a b e t i c s the f u n c t i o n of the e s o p h a g u s / t r a n s i t t i m e / w i t h a n e w n o n i n v a s i v e m e t h o d . A c c o r d i n g to our m e t h o d ths e x a m i n e t i o n is p e r f o r med in upright position used a semisolid mesl labelled with 2oNBq 99m-TcDTPA. Registration was done with s gsmma camera computer systsm. Data w e e e s t o r e d as 2 - s e c f r s m e s u p to 5 min. 253 p a t i e n t s w i t h d i f f e r e n t m e t a bolic stsges of diabetes msllitus were investigated. A close correlation has b e e n f o u n d b e t w e e n the e s o p h a g e a l func~ t i o n and the a c t u a l m e t a b o l i c c o n d i t i ~ o n of the p a t i e n t s , or the p r e s e n c e ofm peripheriml neuropathy, reepectively. Stable carbohydrate-metabolism has f a v o u r a b l e e f f e c t e s p e c i a l l y i n the insulin-treated group. Gastrointestinal complications s u c h as the s i m u l t a n e o u s o e c u r e n c e of r e f l h ~ e s o p h a g i t i s snd p e p t i c e s o p h a g e s l u l c e r are a l s o m o r e f r e q u e n t in a s s e s w i t h l a b i l e metabolism. The m e t h o d is c o n s i d e r e d to be s u i t a b l e f o r the d e m o n s t r a t i o n of n e u r o pstb~y and for the d e t e r m i n a t i o n of the e f f i c i e n c y o f the t r e a t m e n t . Its p e r f o r m a n c e im r e c o m m e ~ n d e d i n the m o d e n n treatment of diabetic patients.

tion curves(Lower thirdS:Mean transit time:No =IZ.b±b.Z,E=ZS.6±1¢.9[p40.05];6 patients > 2SD. Maximal transit time:N=12=.5±5.2,E=26.6±14.9 1 (p
P,Reul~nd

HUKLEARMEDIZI~ISCHE ABTEILUNG (Arztl. Dir: Prof. D r . U . F e l n e h RADIOLOGISCHE KLINIK TOBINGEN

ESOPHAGEAL

! A decreased c l e a r i n g c a p a c i t y and an abnormal f l o w r e t a r d a t i o n of t h e l i q u i d b o l u s have been found i n e s o p h a g i t i s . Bolus d i s p e r s i o n a l l a l o n g t h e e s o p h a g u s may i n f l u e n c e t i m e - a c t i v i t y curves and t h e p a r a m e t r i c images i n t h e d i s t a l segments where the d i s t u r b a n c e s are m a i n l y d~s !cribed. Based on the d e c ~ n v o l u t i o n a n a l y s i s a n e w approach to s t u d y essphageal f u n c t i o n is proposed. T h i r t e e n normal v o l u n t e e r s and f i t teen p a t i e n t s w i t h e s o p h a g i t i s were i n c l u d e d i n t h i s s t u d y . A 3cc w a t e r bolus mixed 113m- I n was ~ a l l o w e d a t once, i n supine p o s i t i o n and dryswallowa were performed on command a f t m 1 min e v e r y 30 sec u n t i l 5 min. The a l g o r i t h e m implemented f o r d e m n v o l u t i o n a n a l y s i s was w r i t t e n i n P a s c a l , u s i n g the r e c i p r o c a l of the i n p u t f u n c t i o n (upper esophageal t h i r d ) and runs on t h e STAR II-GE computer system. The appoximation of t h i s method is based on the mi n i m i z a t i o n of t h e l e a s t square method. RESULTS: L o w e r - t h i r d t i m e - a c t i v i t y curves i n ~ites/EJ were s t a t i s t i c a l y d i f f e r e n t froN normals(N):Mean t r a n s i t time:N=11 9~9 0 E:74 0 t 4 6 . 3 ( p < O DD1);13 p a t i e n t s have ~ a l u ~ s ~ 2SDZ FWHM:N=B.B~5.3,E=72.2Z107.4 p < O . O 5 ) ; B p a t i e n ~ ~ . Total c l e a r i n ~ t i m e : N : 4 9 . 6 t 3 0 . 7 , E = 2 6 B . 9 I TB5.1(p~om.OOl);14 patients > 2SO. Output tuna- I

~z ~tgNO!g~, m S. Hodoni,* F. BarbanojD T. Federici, t 0. Pe Cosmo, 0 N. S~rUSD, H H. Anneal Jsuch

L a b o r a t o r y of N u c l e a r M e @ i c i n e snd D e p t . of G a s t r o e n t e r o l o g y , County Hospital Szeksz~rd, Hungary

IN D I A B E T I C

OUTPUT ESOPHAGEAL FI~CTION BY OECONVOLUTION ANALYSIS (A STUDY IN ESOPHAGITIS).

306

J. T o r n 6 c z k y M.

STUDIES

I

A almple and accurate method is needed to dlagnoBe the esophageal motllity d l s o r d e r a w h l c h a r e c o n s i d e r e d an e a r l y symptom of visceral progression in sclerodermlc patlents. Sclmtigraphy ia now the established m e t h o d of c h o i c e in T ~ b l n g e n . We i n t e grate t h e dabs o b t a i n e d c o n s i s t i n g of the data in tlme-actlvlty diagrams and the d a t a o v e r c o m p r e s s e d displacementtlme-lmages. Our t e a t g r o u p consllted of 14 icleroderml¢ patlehts and 18 healthy control prebends, selected c a r e f u l l y f r o B a g r o u p of g ~ t r l c emptying study. All are g i v e n 38 HBq'gTc s u l f u r c o l l o i d in a s t a n d a r d o r a l mi~tufa. U~lng a gamma-camera, we o b t a l n a n a l o g u e i m a g e s e v e r y 15 e e c ( 2 8 i m a g e s ) and dlgltlzed frames every second 1 3 0 ~ f r a m e s ) . T e s t r e s u l t s were p o s l t l v e in 85,7X and questionable in 1 4 , 3 ~ . W l t h o u t u s e of t h e displacementtimgmlmsges it would have not bemn poselble to d l a g n o s e 5 of 14 p a t i e n t s corr~tly because The compressed displacdment-tlme-lmages very clearly show the e n t i r e e s o p h a g e a l d y n a m i c throughout the e x a m i n s t l o n , C o m b l n l n g our digitized method with standard analogues frames in e s o p h a g e a l sclntigraphy we got a highly sensitive and accuratf coutine ~ethod.

mOepart*ent of NuclearMedicine and Rahtotherapt I Departmentof Internal fledichne - tiebetes Center @ Departlentof 6astroenterolety and 9igestive Endoscopy Henera] Hospital 'OAShSOLLIEVSdella HOPFEHENZAN 0. Giovanni Hotondo (Fgb ITALY

IS ESOPHAGEALSCIHTISHOPAgA AEPHOtHOISLETECHHIOUE? OarbletL Bt Of. (IfBTI have retorted tbout reproducibiliLp of ecintigraphic esothateal transit teats in patients affeched by eeothagitis and in control eubj~cte. Theytraded motor dieorders ly an index (0,b2,3). In b/Ih controls and in 13/25 eeophagitie laLiente they founddteagreementbetweenconsecutivestudies, him ,f our work is to evaluate variations of liquid meal ecintigraphic feet (LMST}and solid meal scindigraphic tesE (gHHT)j performed eccordint to our usual schedule, betweenconeecetiyemeaeureme~ds in the sale individuals, Wehave evaluated bt LDOTOh patients (2 affected by achalaeia, 13 by tastroeeophateal reflux, 5 by diabt tee, h by several different diseases) and 3 cendTol subiects. 19 out of 2h patients an3 ~ out of 3 normal subjects studied bp LMNTwere a]SD ~valuated by SHUT. In all patienls we performed the study three tiles at five minutes inlervale, tach test wascarried out by adlinisterint to fastin t patient 500 uCi Df NtITC sulphur colloiddilutedin IS cC of water (LAST)or mixed to a fratmentof scrambled eflqs tSMST) ant hy storin t I sac, imagefor 73 see, and l then iS sac. gagesun ] 3 lin,

I

i Result~ according to IS" from (by LNOT) and bY IH~ST)eitherretenti LMO STnbp 13/-Per3 centare valuer were grated O to 3. Hbso]ukelpreproducible resulte were obtained control sudjecte and IglSbpatients) or hy SHOT (2/2 controls and

ld/lf patiente). Our results chows a tebter reproducitilitf as compared to tart]elf's daka. SHOTseems e l i t h t i y o r e reproducible than LAST. However, accordin t to our repults, lhile L,HT ie very sensitive in tastro-eeophagealreflux patients, HASTappears lore sensitive in diabetic patients evaluatiDn.

He conclude that both scintigraphic tests are euffichent]p reprodD EmOteand that however performinA lhree times the sdudy in the onS"eJatient el, . . . . d.f,.it . . . . iuatiooof .ethereal.for fuoc

274 307

308

l. Room, X, Pavia {l), G. kguadd, J. Oil-Veznet Boix-Gchoa (hi ~nd L Ortege.

[d}, J.

309

D. G a r c i a

Soils,

E. Pamies,

J.N.

J. S a l a b e r r i ,

J. Sanchez-Roman

Rodriguez.

NuoleRr Medicinegervice and Pediatri~ ~ur~sry OogartmenL It] Hospital General and CJi,hoa Infantil. Ci~dad Ganiterie "Vail d'Hebrdn'. HosgiLalClinicoProvincialli}. B~rcel0na, ~pain,

(U. Oolagenosis). Hospital Universitario Virgen de] goclo. Sevilla. SpaI~

gCINTIORdPHIC gWALLOWZHGIMAGEhg d SCR~RNH I GTECHNQ I U~TODETBCT GSOPHk0~ALDIgMOTILZTY,

STUDY OF ESOPHAGEAL FUNCTION WITH RN METHODS IN PATIENTS PROFESSJONALLY EXPOSED TO SILIOA

Gastroesoph~geal /GG] tract is studied in children with s~speoted esogha{e~l dheeotiliLg I~eourrent rodur~iLaLlonand repe~ted broncbisl dlse~ee},Our purposois to specifythe role of the scintigr~phioswallowingimage (SI} as ~ teal, not Lo diagnosereflux, huL Ln deLecLGG disoaeeend zpplieehleh. th~ iniLi~lstudyof this grougo[ children,~e choseLhi~ he~hnigue heuause of it~ very low irradleLhun, short tieestudy, easy prachlceand ophigsiaccopLabilityin children, Thirty-five ohildreo ere accepted by recurrent rsgurgitation, spasmodiu cough,asLhmeand recurr~nLbronchitis, The gtuup ~as formedhy 11 girls~nd R4 boys,with adee ~&ngin~ ?rum 5 months Lu 1] years ned lO months fzeRn ~ year lO monthsi. Our teohniqu~ie ~ eodi~icutionol lhe GG scinLi~r~phy,studyin[ only the HO seconds dyosBio study. GsophRge~l mutilihy is studied in t~o isolaLed swallows,apglying a cempuL~rprogram, ~hieh consbruuthhe gI of i~ and ~0 seconds, The gI ouL/ines Lhe es0gbsgeal zones withdls~utility, a/lowingdehereln~Lionof Lhe retenLdoo Lfue of Lh~ deglutod bolus and ger~il~Lo clas~i[ythe yesullsin fcur ~roups,g[ zod 2~ hour pHmetryresults are oo~p~red, Botht~sL ay~ concoydanL (nureslor ~hno~m&l} in !~/3~oases. The observed~ucuraey~ae !7,11 ~ for Lho globalscore (gG-OS)and 8g,57X for toua]Lice reflux (~TTi of ~he ~l hour gHmetry,~ensibivhty ~as i00 %in boLh cases, ~nd specificity i~ higher For global score(SO%} Lh~n Per ~TT (d0 ~1. The be~t corre]~tlonIgpearman'~jhas been found betweenthe Si and pH-G~ II : O.?ldl] and %TT (r : 0.7110]. Beth the Z4-hour gHeeLry and tte scinti~r~phle SI Lry to measure the severity of GGR in Lw~ dilferenL Ways: hh~ e~epha~eal DH v~riakions [ihs duration ~nd freqgensy in differentsi{uaLions} aed Lhs dgn~,icsof degluLion. We beliers ] that due to ks h~zelessne~s and lhs e~sy ~nd :~gid practice, Uhe seinhizrRphle gI should constitutea tseheioueor choice to dotecL esophageal dys~otilityin children,The ~isenue of false negaLiveresulLs,high senBitiviLysnd goodcorrelatzonco~p~nng with the ~4 hour-pg~eLry, suggests Lh~t iL could he ~ screening t~ehni~uein Lhe deLeotdon~ gE lrEt abnorm~ldLiosin uhildren wilt recurronbhr0nchhtisand G~ diseaee. I

We have proven that professional exposure to silica powder may be an important factor in development of collagen dls~ases with ~sophageal affectation. Many patie~Ls, on early stages, are asymptomatlc or have non-specific symptoms, so the~ are not correctly diagnosed. For their hlgh sensitivity, Rig techniques constitute an. ideal method to evaluate esophageal function in these individuahs, Included in the coilagenosis study proLoco], esophageal Function with RN was assessed in 25 patienhs proFesslonBlly exposed to silica. To study esophageal motility, the subjects swallowed 15 ml water containing 7.4 MBq ~SmTc-collold, Data were stored in l-see frames du r[ng the initial 60 seconds and then in 15-seeframes up to 10 min. Analysis was performed by computer drawn RDI corresponding to the entire esophagus and its individual thirds. ETT and ETR (Tolin) were calculated. GER studies were performed after ingestion of I I . I MBq 99m-Tc-col]oid diluted in 300 ml acidified orange juice. External pressure with an infhatable binder was applied. Data were con tinousIy stored For IO min. RH methods showed esophageal motility disorders in 17 patients and GER wa~ also observed in four of them, Only seven patients had esopha goal dysfunction symptoms. CoIIagenosis was di T agnosed in 20 patients (5 PSS, 2 SLE, 4 overlap syndroms and 9 undifferentiated C.). in conclusion, For the elevated number of patients without c l i n i c a l signs of esophageal involveme~t, RN techniques are very useful to stu dy these ind[vidua)s in high risk of bearing esophageal dysfunction.

Servicio Hedic{na Nuclear. Dpto. Med. Interns

I

Sergi~nko V.B., Popov-a L.V. USSR Cardiology Research Centre, Acadeny of

rFOR THE D E T E R M ~ T I O N IJUICE A C T M T Y

OF PRJI~OLYTIC GASTRIC

The method is based On the d e t e ~ t i c n of ~roteolytic gastric juioe activity (PC=JA) by time of dissolution of protein capsule (PC) rlth a definite %mll thickness filled with 99m~c-pertechnitate solution (20-30 r~i/O.3-O.5 i). The gamma-camera detector is fixed over t ~ ~stric area and upon peroral PC introduction mouldings are made on the callouter for 25-30 d_n. The PC dilutic~ time is defined according ;o its radioindicater release. An a p p r ~ t s time range for PC dissolution :orresp~g to no~nal (N), high (Hi and low [L) PC~TA has been p r e d e t e ~ e d cn 342 gastric iuice samples in vitro. Scintigraphic studies re.re e ~ e d to clinical and laboratory fintings. Padionuclide PC~A d e t e ~ t i c n h~s been ~_rfom~ed in vivo in 43 patients, 17 of them u~d duodenal ulcer, 16 had gastric ulcer and LO had no ulcer at all. The time of PC dissoluLiom in nca~nal subjects with N FG/A ranged fr(zn .5 to 18 sin (16,5+1.5 mini p
G C I M T I G R G P H I D -OF - - -ESOPMGGEAL - - G T U G Y AMO6RSTMICE~PTYINRIN bIAGETIC! Rim of this work is ku vatiqule clinical usefulness of esophageal I(RR) and gastric scinkigraphy (GS) in the early de~eckion of autouz mkc ne~upathy i~I H di~detes c~licahinn. [R~ Gi dhabelic pat~ ents ,ere studhed by sotld meal mdntigraphic temt [SMST).~5 out of them also hy liquid |ea] scinkigraphic test (LMGT). GO control su~ subjects were studied by LH~T and ib by RMGT. h7 diabetics studied by GMMT ~ere als~ evaluated by cardiovascular ~ests ICT) for the presence of GN and subdivided in 3 groups: IG pts, classkfked as po sitive, 30 as negative and 3 as borderline. GG .as performed bi administering l ~Ci of Y%Tc-sulpbur colloid diluted in iO ml. ok water ILMGT) or mixed with a fragment Of |era|bled eggs (GHRT). Gcquiditiun wsm carried sot by sterin g l" fr. for 75" and thou IM' Yr. u,hkI lO min. Results were ewprmseedas retention percenkaqus. MR: ,e studied ? normal conbrols and IB diabetics snbdivided dy CT in 6CT+ and tROT-. Study was performed by administering a ~OO Eal. standard meal (90 gr. of rice, gO gr. of minced meaL, [~ gr. of oil and ~ gr. of chicken liver ~hat was kagg~ in vivu by I mCi of gga Tc-MC. ~quhsition wam carried out by storing 1 Bin. ant. and post. image every J~mkn. unit! 3 hrs. From ant. znd post. gastric Counts, c~rre[ked fur physicsJ decay, zas calculated geometric mean.gesutt! were exDrened aS percent of mazimumgastric activity. A ~iqukfj reduction of esophageal emptyi~ was Dgservedbefween normal s~ jec|e and all diabetic pts. ak hD',75',[~0" (p I O.~t), between controls |nd CT+ pts. at dO'JM'dGO" and iBO" (p (O.~lb aM he, tween CT+ and CY-MLS. at dO" (p ( O.OR)JY Lp (O.dl) a~ at IRO' (p (O.OOS). 65 results shoed a aarh~ diffmre~e between controls add DT+ gtS. at YO' (p ( O.OI),IOS'~IGO',llY,J~O'Ip (O.d~), 16g' and I~O'(p (0.01). NO dhffere~e Hs Mound in CT-pts. vs. to,trois. Om'vziuesYer gastric emptying Jn controls are quite similar ku those repurted hy ~y~scbaer| H ~ o I , but ha our dJdhetic8 we found values significantly different from controls until 18d' ~ereas guysschaert reports shQnhficant dhffere~ed until {~O'. DoT results shu~ toe suitability of solid vs. liquid meal in ES and the dtagn~s tic usefulness of EG and 6~ in ~ early dePection, The good correli kion of s~tntigraphi¢ reu[ts vith CT+ vaihdates the diagnos|ic rE liabkli~yof the radiorm(lide tests, although ESseus to be prefM rsbie to 65 because of its short duratio, and its easy perYorming.

312

311

310

e G. Modoni, ~ V~ [[g[GbDD~, e F. Marbano, f G. 8andolfi, I S. De Coslo, ~ T. Federici, m G. petraeca Cisvareila m ~partment of ~¢]ear Bedicine and Radiotherapy I Department of Internal Medicine - Diabetes Center @ Department of Gastroenterology and Digestive E,duscopy § Department of Dietnlogy Genera[ Hospital "CASkGOLLIEVOdelia GOPF~EMZR', S. Giuvannt Rotondo (Fg), ITGLY

N. Parr, S. Grime, S. Brownless, C. Mackie, M. Critchl~y. Corbelli C.; Zagni P.; Levorato M; Monatti N.; *stanghellini v.; *Corinaldesi R.; Servlzio di Medicine Nucleare e *Clinica Medico I. Poldcllngco 6.oriole - Malpighd, Bologna THE EfFHCT OE DIFFERENT ACQUISlTEGN ON, THE RESOLTG EMPTYING STUDIES VITE

PATTERNS BE BF GASTRIC RADIOISOTGPIC

TECHNIQUE. The radioisocopic methods are considered

the most~affidahle amongst the nondnvasive methods for the gastric emptying studies. The results nevertheless widely depend on some technl-cal factors. Amongst these factors never have been taken in consideration the frequents of the registration and the duration of the test. We evaluated by radloisotopic method the emptying of a well balanced meal [6D6 Cal.; liver marked with 99mTc-SC) in i0 healthy vol~nteers (HV) (7 m; 3 f; 25.8 ~6.7 y; m +SD) and 19 patients with functional dyspepsia (FD) (8 m; ii f; 41.2 +10.3 y). The radioactivity was registred with a computerized ga~u~acamera, performinq the acquisition in anterior and posterior views for.l' every i0' for 4hi For each study 3 different c u r ~ s were ~nalysed, calculated respectively on: a) all 2S acquisitions taken every 10'xD40'; b) 9 acquisipions at 30'x240'; c) all 14 acquishtiens (every i0') of the first 2 h. Every curve was analysed with biexponential formula and the results were ~xpressed as T1/2. The values obtaiaed with the different methods of acquisition were compared by nonparametric test of one way variance analysis. (mE+SD IQ 240'/10' 240'/RO' 120'/i0' 94 +24 99 +22 95 +2M fO 162--+66 1 6 7 - - Z 7 5 267--+134 The results g~t with the three me'hods of acquisition statistically were not different in the HV group; this is due to the substantial equality of the results. Instead, in the FD group the dispersion of data give statistically siqni~icant variatlons in the studies 10'x120'. The lO'xl2S' technique generally induce a high overestimation of TI/2 wlth a notable da~a spread and a diminished accuracy of the radiolsotopic method, specially Eor the orients with slow gastric emptying.

Departments of Nuclear Medicine and Surgery, Royal Liverpool Hospital and University of Liverpool, Liverpool, U.K.

GASTRIC EMPTYING IN MAN: F~SPONSE TO ~ ! N G WITH A LIQUID TEST MEAL. The gastroduodenal braking response is independent of small bowel resistances in vagally intact dogs. Following %runcal vagotomy with drainage (TV+D) small bowel resistances contribute to the hransition from rapid initial gastric ehptying (GE) to a subsequent slbwer Fhsse. This suggests that a second meal taken in bhe early postprandial period should empty at the same rate in vagally intact subjects, but slower in those with TV+D. 10 healthy human volunteers (HV), 12 patients lwith duodenal ulceration (DU) and 23 patients with rapid GE following TV+D (9 asymptomatic; 14 with dumping and/or diarrhoea) had GE I measured for 90 mine. following a drink f 300 mls. of 15% dextrose labelled with 9~Tcm DTPA. An estimate of GE at 30 mins. was made and an equivalent volume of labelled dextrose refed. Comparison of gastric activity (%) at d5 mins. and 45 mins. (paired 't' test) showed that refeeding did not significantly alter GE in vagally intact subjects (HV90+2.6 vs 91+ 2.8 mean i g~M: DU 75+..2.5vs 76+__2.--6)and -resulted in slower initial GE in asymptomatic patients with TV+D (36+4.2 vs 58+7.7, p
275 315

314

313 Paulo M,Costa, A.Freire, F.Godinho,A.Cervalhi~Fernandes.

UGOLOTTI g ~ NERVETTI A., SALAFFI RACCIOLI G. F. ~ AMBANELLI U. ~

F;~

I Proped~utica Cirurgicamlnstituto de Medicine Nuclear-Medicina I I Paculdade de Medicine de Lisboa SClNTIGRAPHIC GASTROESOPHAGEAL(GER)AND BILE-GASTROESOPHAGEALREFLUX (BGR]BER)SIMULTANEOUS QUANTIFICATION DURING 60 min. A COMPARATIVE STUDY WITH 24 pH MONITORING. The simultaneous evaluation of GER and BEg during one hour is supoaed to improve gammagraphic accuracy. To prove this assertion a compar a t i v e study between r ~ l u x indexes (obtained by e scintigraphic method we are improving)and the 24 hour PH monitoring sccrB~ were performed . Fifteen patients with r e f l u x esophagitia were included in. this preliminary study, Scintigraphic method:l)il3m-ln was i n t r a g a s t r i . caly mixed with ISOCAL-HCN(an enteric cquilibr~ ted meal~300 co)and used in the q u a n t i f i c a t i o ~ of GER;2)ggm-Te-HIDA was used as b i l i a r y market fob BEg an BGR quantification:3)Data were regi~ tered during 60 min and analysed by a STAR I I -GE computer connected to a 400#C camere;4)Ref l u x indexes (GER,BER and BGR)were obtained~y the respective regions ~nd a c t i v i t i e s of i n t e r e s t , CUTve-to-curve d i v i s i o n . 24 hour pH monitoring and scores according to De Meester (1974}, Results:In I0 patients the GER index and the p~ Scohe were correspondent. In 2 patients with r e f l u x esophageal stenosis the pM score were positive (65,6 and 20.6) and the GER index were within normal values. In 3 patients the pH scores were negative (10,8, 8.4 and 5.9) but the GER index were p o s i t i v e (2,3, 5.5 end 2.4 respectively-values } 2SDof mean normal values). These 3 false negative results were probably due to the high BGR and BEg disclosed by our method. In conclusion: The quant i f i c a t i o n of GER, BER and BGR dUTing the gas, t r i c emptying of an enteric equilibrated meal (50 min) seems to be an accurate approach to evaluate patients with esophagitis.

316 Carrier, L., Poitras, P.,

GASTRIC EMPTYING: EGGS AND LIVER IN ~IITRO LABELLING EFF%ZIENCY AND STABILITY W I ~ 97mTc-COLLOII 9~FUH (~mTc-SC), IIIIn~OXINE, ±±IIn-DTPA AND ---In-CHLORIDE. Measurement of the rate of gastric emptying of solid food necessitates the use of radioactive label which remains attached to the solids, The aim of our study was to determine the efficiency and stability of labelling food (egg ~hites, whole eggs , and liver) with different co--only ~sed radiomarkers, Methods: egg w h ~ s and y ~ l e egg ..... ~ e l l e d ~ r ? yith Tc SC, In-chloride, In-oxine and -I~%n-DTPA. Beef li...... labelled in v i t ~ with ~ T c - S C and rabbit li~$r in vivo with mTc_SC, lllln_ chloride and --Gallium. One gram of each of these was incubated at 37SC in 15ce of gastric juice (GJ) or RCI O.IN. At different times, each sample was eentrifugated. Total activity was counted in a dose calibrator. Supernatent was then filtered and the residual net counts ohtained. Results: the labelling efficiency andg~tab~ llty of the egg whites were good only for mTcSC: 90% at 15 min. to 83% at 3 hours in GJ and 100% to 95% with HCI. With other radiotraeers, the results were good at 15 mln. in GJ but ~ropped rapidly at 3 hours and were poor in HCI,

~gg~ l a b ~ n i n g . . . . . .

y

gggd i~

Gg

{ ~ F t~

95%) and HCI ~ 9 0 % to 96%) for mTe-SC, T1~nzhloride and ---In-oxine. It was poor for -~In]TPA, especially in GJ. With the9~iver, result~ ~ere very good and similar with mTc-5C in vi~ ~nd in vitro, Both in1~~ (99% to 95%) and in H( (98% to 97%) and for ~ In-chlorlde in GJ (97%). Labelling stabillty~ropped for all others [abels, especially Ga in HCI (94% to 74%), 3onelusion: from this, ~e now do gastricl~ptyim ~ t h 2 solid foods~9whole eggs ( ln:hloride) and beef liver ( mTe-SC) both Labelled in vitro.

SA Pedersen

& ML

Departments of Nuclear Medicine, Surqical Gastroenterology and Medical Endocrinology, University Hospital, DK-5OOO Nucleare-Ospedali

]Eeumatologia

Universit~

Niuniti

PARM~

di PARMA ** THE RELATIONSHIP INGOdense'AND Denmark.PLASMABETHEEN GLUCOSE

GASTRIC SCINTIGRAPHY WITH LABELED ISUCRALFATE:COMPA~D'WITH ENDOSCOPY BIOPSY

AND

GASTRIC EMPTYIN NORMAIS AND

widened our series, of patients randomly collected and we have compared the scintiscan results with those obtained through endoscopy, biopsy of the stomach and oN data. 116 patients, referred to our out patient clinic because of rheumatic complaints of different origin, underwent gastric scintlscan and shortly afterwards endoscopy assessments. 43 patients also had gastric biopsy and pM evaluation of gastric juice, Scintiscan giving uptake at 30,60,90,120 minute after oral ingestion of the tracer, we considered positive for gastric lesions.From compsson with the other techniquesl endoscopy Ifindings and biopsy data) the sesitivity the specificity and the diagnostic Irehability were respectively 73,6%,68,7~ ~2,6% and 7g~,71,4%,72%.None correlation ~as found with pH data.gcintigraphy with labeled sucralfate is thus a ~imple non raumatic and echonomical technique hich is useful for the evaluation of he gastric lesion

DIABETICS. Gastroparesis is a long-term complication of diabetes mellitus, but whether the actual plasma glucose value (PG) relates to gastric emptyinn rate (GER) is uncertain. GER is determined by a mixed meal: g lO0 g omelette of 1400 g,I tagged l~ith 40 MBq 99m-To-sulphur colloid and 150 ml l~ater mixed with S MBq III-In-DTPA. The effects of iv infusion of hypertonic glucose and hypertonte saline ~ere investigated in t~o groups of eight healthy humans each subject acting as his o~,Jn control. RESULTS: Glucose, and to less e x t e n t saline, reduced GER of solid. Glucose but not saline reduced GER of liquid. T~enty-six IDDM diabetics ~uithout other disease or medicine were examined. Based on PG t h e y v~ere d i v i d e d i n t o t h r e e g r o u p s : a) PG~}.S retool/1 (2 p i t ) , b) } . 6 < P G < i0 (15 pit) and e) i O < PG (9 ptt). Values within the 95% confidence limits of the linear regression line of GER on weight in 40 healthy humans were eonsi-I dered normal. RESULTS; Solids: ~) both had normal GER. b) 13 had normal, one had increased and one had reduced GER, c) eight had normal and one had reduced GER. Liquids: s) one had normal and one had reduced GER. b) ten had normal, one had increased and four had reduced GER. c) seven had normal and t~,to had reduced GER. CONCLUSION: The acute increase in plasma glucose in healfhy subjects had a substantial effect in reducing the GER of solid and liquid. Relationship between Pg and 6ER of solid sod liquid l could not be demonstrated in diabetics.

317

318

In previous preliminary

reports we described our findings in the diagnostic

i

~,Andreica~ D . D u m i t r e @ o u , .~ozul

Picard, D., Boivin, M., Chartrand, R., Picard, M.

Depts of Nuclear Medicine and gastroenterology, Hgpital Saint-Luc, Universitg de Montrgal, Montrgal, Quebec, Canada.

~oi~

Medicina

Oester-Joer e n d , LaTeen [

S.Tama~,

~ r d Medical Clinic - I n s t i t u t e of ~ e d i e i n e and Pharmacy, Cluj-Nspoea, ~omania

I R3SECTED STOMACH EVACUATION APTER TR~|TMENT WITH SALBUTAMOL(S) AND DOPAMINE (D): ASSESSMENT BY COMPUTED S C I N T I G B A P H The main pathogenetic link in the dumping syndrome is the h a s t y evacuation o f stomach contents into the intee tins. The authors proposed to quantify stomach e v a c u a t i o n in the p a t i e n t s with partial g a s t r e c t o m y by a computed scinti£rsphie technique (radiolabelled liquid meal). M a t e r i a l and method: The study included 17 patients w i t h gastric resection (ll w i t h P ~ a n operations, 3 aith B l l l r o t h II, end 2 with ReiohelPolYa), and one w i t h t r u n c u l a r v a g o t o m y + gaetroenteroanastomosis. S t o m a c h eva0uation was d e t e r m i n e d basally end arbor treatment w i t h S (betasagonist) 4mg orally 2 hrs before the test (n=12) and D c h l o r h y d r a t e ~ug/kg body w s i g h t / m i a for 30 min, the test duration (n=5). ~/2(mln) of gastric e v a c u a t i o n and long itudinal (LD) and transversal (TD) diametere(em) w e r e determined. Resalts:S p r o l o n g e d ~/2 from 6.41+2.72 ~.33+6.45 m i n (p
b ~

P. LECOUEFE, P. FONTAINE, CI. HOSSEIN, P. FIALDES, J. LEFEBVRE, A. CORTOT, P. FOSSATI, X. MARCHANDISE Services de M4decine Nucl~alre, d'Endocrinologie et Diabdtologie, d'Endocrinologie et M~tapolisme et Clinique des Maladies des Vales Digestives CHU Lille - 59037 Lille - FRANCE GASTRIC EMPTYING IN REACTIVE NYPOGLYCEMIA Rapid gastric emptying has been invoked as an etiologic factor of reactive hypoglycemia nevertheless it was rarely documented especial by radionuclide technique, We have studied 12 healthy volunteers (34 9.5 yr) and 10 patients (39.4 +_13.2 yr) with prow reactive hypoglycemia ; no subject had undergone gastric surgery, Hypoglycemic clamp had shown a normal responsiveness of all counter-regulatory hormones in patients. Gastric emptying was measured for 3 hours using gamma-camera imaging of a 474 Keel mixed meal ; solid phase (egg) was labeled by 99mTc-colloTdal sulfur (18.5 MBq) and liquid phase by 1111n-DTPA (3.7 MBq), Corrections for movement, Compton scattering and isotope decay were achieved. Curves were obtained from geometric mean of posterior and anterior data. An exponential fitting was performed on liquid phase curves. Half-emptying time was significantly higher ( p ( 0 . 0 1 ) in patients (47.3 + 20.3 din) than in controls (29.3 _+ 8.3 din). Two hour retained activity was significantly higher (p4 0.01) in patients (17.4 +. 10.7 %) than in controls (5.7 t 0.2 %). A linear fitting was possible on solid phase curves in controls and in 13/18 patients. Solid emptying slope was significantly lower (pg 0.02) in patients (44.5 _+ 23.3 %/hr) than in controls (54.4 + 13.7 %/hr), Three hour retained activity was l~gher in patients (10.3 +_ 16.4 %) than in controls (2.1 + 4.9%) without statistically significant difference. Rapid gastric emptying of solid phase was observed in 2 patients. Abnormal gastric emptying in reactive hypoglycemia is confirmed by these results. Nevertheless unexpected slow gastric emptying observed in m o s t patients may suggest the influence of gastrointestinal hormones (GtP,etc.) in physiopatho]ogy of reactive hypoglycemia.

276

319

321

320 D.L.Dumitrascu,S,Cotul,S.Tamss,S.Granescu Dept.of N u c l e a r M e d i c i n e of the 3rd M e d l c s l C l i n i c , S c h o o l of Medicine, 3400 C l u j - N e p o c a , R o m a n i a

S. GRAVILI - G. BRUSCAGNIN Servizio di Medicina Nucleate FASOUINO - M.E. BENVENUTI Centro gi Gastroenterologia

M.

OSPEDALI

CIVILI EIUNITI

-

U,Z. 6ASTHUISBERG,LEUVEN,~ELGIUM

VENEZIA

PDIT[ S[J£RdLF~TEIN EARTROOUODENAL ULCERDETECTIONdNg FOLLO~UP. 991To suers]fate (5F) is an already ~elt-kno~n peptic ulcer visualizing agent. [t adheres hp |he site Of lucosal ukeration hy forling insoluble co@loxes .ith exposer proteins in an acid lilieu, gTPg is Rener|Jly preferred to bglan serum a]buli, IH~) as an inlerlediate agent in the ]ahelinp reaction. Me used 991T[OTPh sucralfate to evaluaPe gastrpdu~denal utters in g5 patients. All ulcers sites had already been detected by endoscopic egg|inn~ Lion perfnrled a l i t t l e before the scJntLgraphic test. No one of the patients ~is receiving any specific therapy, Tventy"fnur pa|ientg had duodenal bu]b focalization, It gastric Localization (h lesser curvature.E cardia[.3 prepMorJc ulcers), gt] lesions ,ere in the acute slags ,iih an endoscopic size ranging frol b go E5 I1, Rfter an overnight feat 37-7b Rgq of 991To DTPg-$FIEorin EJolegtca Saluggia Italy) suspendedin lO l ] of Lap .afer ,.ere administered to patients. They ~ere invited to dring at least 500 Co,of ~aterduringthe tesl, StaLicanberiorviewswore Lakenin the upright gosition at 15-3O-hO-l~Pand ~in sole casess leg iinutes. ~ localized and persistent activity ,as detected in ~l out od Eg bulb and in at[ paslric localizaLions. Negative cases sho~ed a diffuse gastric acliyitf ,flich grevented a deflnite localization. Eleven patients with positive seinLigraphic test .ere studied again bel~een 3 and 9 =onthe after speciTic t~erapy and before the endoscopic contTol. In eight case~ foes] activity ~as no longer found .hi]e in 3 patients it ~as s~ill evident in dhe sage localization detected on the First e~alinatinn. NO patienL cneplained of digestive ~ylptolS, The clinical evidence, along ~Jth a negative sucralFafe tesi ]e~ us even avoid endoscopic control in very anxious patients, dithDugh gg|Te-SF can't be proposed as a s~bstitute for engos:ppy {need for biopsy in gastric lesionsl i t might be useful in regucing the noaber oT e~alinaLions,especially in psychologically hypeYreactiye patients.

THE E F F E C T OF N I F E D I T I N E ON THE DELAY E D GASTRIC E ~ P T Y I N G OF A R A D I O I S O T O P E ISOTONIC LIQUID ~ A L ~im. Previous data report the lack of ef f-~t of N l f e d i p i n e N in single dose on ~astric emptying GE in n o r m a l s~bjects. iven the relaxant a c t i v i t y on cardia f N,we w a n t e d to study its effect on elayed G E , p r e s u m i n g e similar activity n the p y l o r u a , i n ccmditiens w i t h f~nGionsl gastric outlat o b s t r u c t i o n . ~ a t e ~ . l o patients w i t h symptoms la~ggesting delayed GE,of different etic Ilogy,confirmed by a prolonged T/2 of [the GE carve of 500 ml eeline m a r k e d ~ i t h 37MBq ll3-Tn-DTPA were investigat e d . T h e y received after informed conIsent lc mg N t.i.d.for 3 d a y s , t h e n the r a d i o i s o t o p i c i n v e s t i g a t i o n was repeated.As control served 1O m a t c h e d healthy v o l ~ n t e e r s H r e c e i v i n g placebo,and 7 c o n t r o l l e d subjects with delayed GE pecelving ~etoclopramid M.Re~ulta~ere ~ x p r e s s e d in percent~al v a r i a t i o n of each individual h a l f - t i m e . T o t a l T/2 and )atrial T/2 of the proximal and distal ;astris segments w e r e considered; T/2 persentual v a r i a t i o n , m e a n + S E ~ proximal distal foray -i.7+I.0 +11.0+3.6 +8.2+2.9 -2.4~2.1 -o.2+~.I -1.6~1.I M -21.~±3.6 -43.E~+~,6 -21.~Z4.6

l

O o n c l a s i o n . A s N did not changed T/2~p ~ M changed it s i g n i f i c a n t l y IP O,O1),it ia saggeated that N hae no n f l a e n c e on GE,not only in h e a l t h y sub ieots,bat atso in cases w i t h f u n o t i o n a l satric outlet obetr~otion.

J,L URBAIN,A. VAN D6CRUY$.E, VAN CUTSEM,V. VAND6NMAE6DEN~ERSH.M, DE R00,

EFFECTOF CALORICCONTENTONSOLID AND LIQUIDGASTRIC EMPTYIN6

In ~is study, we hove evaluathd the effect oT the caloric contenL of a physiological LesLmeal on gastric emptying or solids and liquids, Sixteen healthy mete volunLeers divided in 2 equal age matched groups were studied, AFter an OVernight test each volunteer underwent the some tesL pro¢ndure, In the FlrsL gro~#, the volunteers received g meg[ censisUng of 2 pieces of"bread, 150 ml 0f In-11 t-DTPA water end I scrambled egg ladelled with Tc-99m-SC, ]%e second group was given the same meal but with 2 scrambled eggs. Slmultate0us anterian and bosLerl0r imggas were recorded i%r 2 hours using a duel-t~aded gemma camera and corrected for decay ~ d dewnsegtter, Solid geometric mean date were generated and analysed th determine the fag phase (]'LAG; mid). the empLylng rate (ERr 10-2/rain) and the hale emptying time (TI/2; mid). The ER and the TI/2 were als0 determined For the liquid date. Rasulte ~'e iummerizad below (mean ± SEt'l) For the two groups, S~IDS LIOLIIDS

11_AG

ER

TI/2

Carrier, L., Poitras, P.,

goivin, M., Pieard~ D., Chartran£, R., Picard, M.

Depns of Nuclear Medicine and gastroenterology, q~pital Saint-Lue, Universitg de Montrgal, ~ontr6al, Quebec, Canada.

J,Z. EA$~U[SBERG. LEUVFN.BELGIUM.

ER

Tt/2

]RONP I 2911.7 335-~0.28 43,~2.2 5.06±021 24+-S ~qOUPll 6I±3.3"" 2.18~z0.18"'83.6±83" 2,29±0.12" $9±~'"

EFFECTOFDISTAL STOMACHREMOVALON6ASTRfC EMPTYIN6. The purpose Or"this study was ~o belier cha,~acterJze the role og ths distal stomach in the emptying o1 a phyglological selid-liquid meal, Tep paLienks with proximal gastric vageLomy (PV) and 10 age matched hetiente with Bi}lroth II-~oux and Y surgical pr~edure (BOY) were compared to fo hselU~/controls (CENT).All paUenth were asympthmaUc sed cMsslfted In the Visick grade ItlasslrlceU~, ATt~" so overnight fast, Oasthto empt'/lng of solldg and liquids was determined using Tc-gCJ~-SCscrambled eggs ~ d In-I f 1-DTPA labelled water, Simultaneous ant~'Jor sad posthrior images were recorded r'or 2 houcs using a duaPl~aded g camera and ¢orcected For decay and downseaLter. Solid geometric mean date were generated and analysed to dstePmlne the lag phase (/'LAG; mink the emptying rate (ERr 10-2/man) and the hair emPLying time [TI/2; rain). The ER a~d the T f12 were also determined ToT the liquid date. Reselte are summarized below (mean +- SEH). SOLIDS LIQUIDS ]lAG ER TI/2 ER TII2 CONT 28.9+-4,4 ~24e0.37 46~+-5,$ 2.g5±0.21 25+-2,9 PV 49,5+-10' 2.59~0.48 80.7±6.6"' 1,98,0J7" 32+-2.4"" BJIY (-) 0.81±0,25" 153±38"" 1.06±0,19"'72+-20 =. (' p< .05. "" p< ,005 PV vs CONT} ("p< ,05. * " p¢,005 BIIY vs CONT and PV) In PV patients, gas&it empty~ngof solids =nd liquids was slighUy delayed and the prolongation of" the solid T1/2 was mMniy accounted For by S abnermel lag phase, In B,Y patlenl.s no lag phase was obsef'~d and the solid and liquid emptying was severely impglred. We concludeLbeLthe Inn phase is atTec~edby pro)drool vagetomy and Is methly det~mthed by the distal stomach. D~e distal atom~ch ~ppears also th be gssenUal Tor U~ normel emptying or a solid md liquid meal.

324

323

122

J.L UR[~AIN,F, PENNINCKX,J,A, SIEGEL,P. VANDFNBORRE,P. DEVOS E. VAN CUTSEM,V, VANDENMAEGDENBERGH. M. DE Rgo,

COMPARISON OF SIMULTAN~QUS GASTRIC EMPTYING OF g SOLlp1~OODS: LIVER C~mTc-COLLOID SULFUR) AND gGGS (*~In-CHLORIDE). A variety of radionuclide labelled solid foods have Been used to measure gastric emptyinl Solid materials empty from the human stomach at rates chat differ from the rate of emptying of liquid contents of the meal. Whether solid components of a mlxed meal behave in a uniform manner is unclear. Our aim was to determine the rate of gastric emptying of two solid foods with a mixed meal. We choose eggs and liver as solid compounds of meal because there are several differences between the two foods: high protein for liver, high fat for egg, desintegration properties. Methods: 15 healthy humans; normal body weight, ingested a 516 Kcal meal (55% CHO, 23% protein, 22% lipid~9mCOntaining 30 g of liver labelled with imCi of 1To-colloid sulfur and • ii one egg labelled wlth In-oxlne. For 3 hours (at 20 min interval) after the meal, a~terlor Lad posterior abdominal activity was imaged with L gamma camera. Time

20"* 1O0"

~O" 120"

60" 140"

80" 160"

-180"

Liver

91.4 51.3

85.5 ~2.0

71.9 34.9

62.5 29.0

-23.5

Eggs

88.8 49.9

81.6 39

73.0 31.7

61.8 25.7

-20.5

R. Jana% J. Klirne~zewd
Dept of Nuclear Medicine, Child Health Cantor. 04-736 Warsaw, Poland. SELECTIVE HYDROLYSIS OF INSULIN, C-PEPTfDE AND GLUCAGON BY GASTROINTESTINAL MUCOSAL CELLS, Specific tissue insuDnase is present in many body organs Jike kidney, liver, pancreas, blood cells and other. Little attention has been paid in order to explore the role of gastrointestinal mucosa in the insulin catab@l[sm,We have prepared the plasma membranes and cytoso] of rat mucosal ce0s of fundus, antpJm, small intestine and colon, lO-20,ug of protein of each preparation was incubated at 37°C from 0 mid. (control) tiJl 120 man. with 1-2 ng of the equimolar mixture of 1261 - labegod menu-, dJ- and trimer[¢ ++ insulin in 100 ,ul of the assay buffer: Tris.Hep~ 25 mM. Ca 10 mM Mg 10 raM, BSA 0.1%, pR = 7.4. In the incubation media the insuDn stabgity w~ measured using: 9% TCA precip[t[tabilRy test, Sephadex G25 gel chromatography, and insuUn imrnunoreactiviW assay, We have compared the degradation fates of insulin, glucagon and C-peptide also• The degradation half-times, in man., are shown in the tab.; F~ndus Antrum Duodenum SmallFnz, Colon M, C. M, C. M, C. M, C, M, C. TeA INS, RIA GLUe. TCA C-pEp. TeA

O. 21~5 30/.40. 15;~2 e. 11;~2 o. 1s~:2 o. e. 5d2 9+1 o. 4;51 o. 2+-1 o. arc1 o. e." o n. o. o, 5~1 o, 15+-4 o. 6o+-15 0. O, O. O, O, lS~2 O. 32~0 0. 5~2

~SEM,

M m~branes,

C = cyto=ol,

O. -- no d~gr~BTIon

(" p< 0.05; "" p< 0,005) ]nstric emptying of both the solid aM liquid phase wse sigeiflcanBy >r'olonqudin group II volunteet-s. For ~ solids the delay is accounted "or by a longer lag phase a.d a decramse in the equilibrium empLying "eth, No ataLisUcaiy aigniRcanLdifference was 0~semmdbeLween the mild e~d liquid e,Xotylng raths In both groJ.tp. ~/e conclude that the caloric co~tenbof the solid porUon oF mmo=l noL rely affects the amptylng or solids but also determines U~ liquid m~otylag ~xI th~L following the iniLlll solid I ~ phseo, the stomach ~mpUessolids and liquids at the sims rate•

*p
UnsensiZive to aprot[nin and PMSF membrane associated insultnasa had Km = 10. +-3.,uM, and it c ~ f d be inhibited with baclzra¢[n ED50 = 0.01%. CDK, hGf7, hGH, glucagon, somatostat[n and ACTH had lower affinity to the enzyme compared with in~ulln, Chromatoraphic s~Jdies have shown that the radioactive peak corresponding co the di- or trimeric insulin disappeared much faster then that of the monomer[c form of the hormone. Concrusion: gastrointestinal mueosaf celJs selectively hydrolyse insulin, C-peptide and glucegon. Polymeric form of [nsuJin are less resistant to this hydrolysis compared with monomerZc [nsuJin.

277 325

326

327

IE.

l, We___stera

Henzs, $. M~nner, N. Clausen, H. Kornhuber, g.E. Adam

D. Hellwi~,

]niversit~tsspltal Z~rieh (linik und Poliklinik f~r Nuklearmedizi ~ i m i s t ~ a s s e IOO ]H-8Ogl g ~ D i c h Switzerland

Divisions of Nuclear Medicine University of Blm, Germany

Jose dependent metaboli~rn of Ascorbic Acid ( ~ , Vitamin C) in man.

THE SCHILLING TEST CANNOT BE REPLACED BY AN ABSORPTION TEST glTN UNLABELED VITAKIN BI2

interest in the clinical benefits of high doses )f AA exists because it w~s s u ~ e s t e d (but pro)ably wrongly as ~ecently shown) that it ~dght ]ave an effect a~m/nst cancer. @e ~tu/died the metabolis~n of 1-14-C-AA in canoe )atlents with r e g a r d to I~-C-CO2 production in ;he exbmled air (using especially d e s i r e d 14IC-CO2 flow counte~) with various doses of AAcar~ier. ~t ora~ doses increasing from O.l to iO z AA, the percentage 14-6302 exhaled du~in~ the first 8 h~urs after ad~1inistPation increased from < 2.5 to 78%, if the patient took the A A b e f o r e breakfast. If the patient had eaten before, the bercentsge exhaled at high doses (5-1Og AA) dropped to iO - 15%. If a high dose (3~) was given i.v. no measurabl6 percentage of A A w s s exhaled, but the u~usl iO~ excretion over llrdn became virtually q ~ t i t a tire. No difference was observed between n o r ~ s and cancer p~tlents, but a connection between AA uetabolism and general health ~ noticed. At high o~al doses, AA is apparently split by the intestinal flops and at high i.v. doses it is quickly excreted to a large extent, ~ne present findings cast doubt on the benefit Df the aC~nlnistration Of high doses of Vitamin (

328

and Neurology,

lit was the purpose of this study to evaluate the diagnostic usefulness of an oral absorption test with non-labeled Vit BI2 suggested by a commercial distributor as an alternative for the more expensive Schilling Itest (ST). Plasma levels of Vit BI2 were measured with a commercial ~it before ~nd 4 hrs after oral administration of 1 mg vit Bl2 in 32 aormals, in 16 gts with normal ST and in 14 pts with abnormal ST. In normals, 767+-404 'pg/ml before and 1096+-776 pg/ml after oral Vii BI2 with a mean increase of 331+-453 ~g/ml was measuzed. Because of the obvious large variation no meaningful range for normal absorption could be established. In the 2 latient subsets, there was no gaussian distribution, with a meridian of Vii BIB llasma increase of 142 pg/ml, range 27 - 2668 ig/ml, in normal ST and a meridian of 244 pg/ml ranging from 40 - 2453 pg/ml in the group with abnormal ST. Statistical aonparametric analysis did not reveal any difference between the both groups. Assuming a minimum required increase of iOO pg/ml as suggested by the kit distributor, a sensitivity of only 27% and a specificity of 75 % was obtained. The lack of any diagnostic value of ~his approach might he caused by the known non-intrinsic-factor mediated absorption of approximately i% of any BI2 given orally even in complete intrinsic factor deficiency and by the relatively large amount of oral Vit g12 needed for a "cold" absorption test. The latter can, thus, not replace the Schilling test.

329 J. Martin-Comin;D, Bonnin;C. Baliellas*;M. Roca J. X i o l * ; J , Mora;P. Massanes* and M. Namas.

DIVISIONE DI GASTROENTEROLOGIA g *SERVIZIO SI MHDICINA NUCLEARE. OSPEDALE MAURIZIANO DI TORINO.

Serveis de Medictna Nuclear and Gastroenterologia*. Hospital U n i v e r s i t a r i de B e l l v i t g e "Princeps d'Espanya" Barcelona, SPAIN

a ro-

Gamma camera measurement of SeHCAT disappearance over the gallbladder area on 5-7 successive day~ fin fasting state after omal administration provides biological t~ fo~ BeHCAT in the enterohep~ tic circulation. A high diagnostic value for this technique in detecting bile acid malabsorption has been shown previously by us (sensitivJ ty 86%, specificity 93%, positive predictive value 9g%). We studied 7 patients with irritable bowel syndrome (IBS, diarrheic type: defined as having increased bowel frequency, normal bowel morpholoF~y, and faecal wet weight < 200 g/day) and ii patients with obscure diarrhoea ( faecal wet weight ) gee g/day; normal biochemistry; normal bowel barium Xray, endoscopy and histoloF~y.) Normal value for SeHCAT t~ was calculated as the lower limit of the 95% confidence interval for this test previously earDied out in 12 normal subjects. RESULTS: 3 out of ? IB$ patients had lower than normal NeHCAT t~, as iO out of il patients with obscure d i ~ r h o e a did. ~ONCLUSIONS: patients complaining of diarrhoea in whom no organic disease can he found should me separated in E groups on the basis of faecal ,eL weight. Bile acid malabsorption is an almost ~onstant finding in patients with obscure dla~~hoea but not in those with IBS, suggesting that different pathogenetio mechanism underlies these two syndromes.

Radiologische Klinik und Medizinische Poliklinik*, Universit~t Mfinchen, Mfinehen, FRG VALUE OF CA-67 SCINTIGRAPHY FOR IMAGING GASTROINTESTINAL AIDS-INFECTIONS Ca-67 seintigraphy (GSC) is an established method for detection of opportunistic pneumonia in patients with AIDS. Little attention, however, was focused on abdominal Ga-67-imaglng even though the bowel is known as major site of opportunistic infections as well. The aim of this study was to assess the role of GSC in the detection of intestinal AIDSqnfections. 25 HIV-positlve patients (age 24-50 years) with AIDS or AIDS-related Complex were studied. Anterior abdominal images were obtained in addition to the lung scans 48 and 72 hts after injection of 185 MBq Ga-67 citrate. CEthartics were routinely applied before imaging patients without diarrhoea. Pathologic Ga-67 uptake in abdominal images was observed in 1g/25 patients. Increased colonic activity was present in 12/i9, fore/ increase in paraaottal lymph nodes in 3/12. In 4/12 both uptake patterns were observed. Severe increase of bowel activity was due to Cy~omegalofirus, 2ryptosporldlasis and Entamoeba histolydca. 2/:~ with uptake in abdominal lymph nodes had atyplcal myeobaeteria. In 13/19 pathologic abdominal and lung uptake was found, with different pathogens in most eases, however. 6/19 patients with positive abdominal scans had no lung affection • t the same time. The results indicate a high incidence of intestinal involvement in AIDS-infections. Findings in abfominal scans help to guide col~noseopy and/or ~ool mierobidiogic studies. Since intestinal inlolvement may OCcur with or without h o g d f e c t i o n abdominal Ga-67 imaging should be a "~andatory part of each Ga-67 study in patients gith A/DS.

330

G_ALATOLA Gt, FERRARIS R., BABLOTTA A.,*PELLERITO R.,*COTTINO F., DE LA PIERRE M.

~ S 75-Se Homocholic Acid TauDine (SeHCAT) le in throwing light on pathogenesis of l"functional" diarrhoea ?

K.Tatsch, C.-M.Kirseh, P.Knesewitsch, H.J.WaJnryb ~ k e * , F.-D.Goebel* and E.Moser

USEFULNESS OF THE Se-75-SEHCAI TEST IN THE MANAGEMENTOF INFLAMMATORYBOWEL DISEASE (IBD). We have studied 14 patients (6 male) whose meat age was 37.2 + i7 years. Pive were diagnosed as having ulcerative c o l i t i s (UC), 6 with Crohn's disease with i l e a l involvement (CD) an( 3 patients had undergone i l e a l resection f I R ) . The Sehcat t e s t was performed a f t e r the oral administration of 10 pCi (370 kBq) of Se-75Sehcat. The abdominal retention of the agent was measured with a gammacamera equipped with a 140 KeV high s e n s i t i v i t y collimator, at 3 hours and 4 and 7 days post-administration. Fecal excretion was measured by feces c o l l e c t i o n throug days 0 to 4. In a l l patients a SchiLling t e s t was also performed. Results ; Sehcat retention (%) 4 day 7 day UC 71.2 ÷ 22.4 CD 22.5 ¥ 15.7 IN 3.0 ~ 2.4

52.7 + 34.0 8.3 ¥ 6.6 2.6 T 0.07

Fecal excretion(%) 14.0 + 15.3 72.8 ¥ 22.3 97.1 ¥ 3.4

Vitamine B-12 absorption was normal in UC, borderline in CD and markedly decreased in IR. In summary : I~ The t e s t may beuseful f o r the detection of i l e a l involvement in IBD. 2) Both procedures (gammacamera retention and fecal excretion) give s i m i l a r results and can be used according to equipment f a c i l i t i e s .

Co~belli C.; *lannone P.

Zagni

p.;

*Brignola

C.;

5ervizio di Medicine Nucleare e *Clinica Mediea I, Policlinico S.Orsola - Malpighi, Bologna

SUC@ALFATB (B) DECREASED INTESTINAL PEgMEABIL~TY TO CRLI-EDTA IN PATIENT WITH CROHN'E DESEASE. It is known that in Crohn's deseas, (CD), even if in remission there is an I increased intestinal permeability tel different molecules [ex: Cr51-HDTA, PEGS). In th~ opinion of some Authors, this fact may be of pathogenetic significance and attempts in reducing intestinal permeability should be made. s. an aluminium salt of polysulphated sucrose, used in the treatment of peptic ulcer, has been shown be bind selectively at the site of mucosal lesion forming a sticky, gel-like substance which inhibits zhe diffusion of Cl acid and pepsin into the u!cerus. S has shown the same properties at the setting of the ulcerations occurring in CD. .The aim of our work was to investigate wether S effectively decreases intestinal permeabillty in a group of patients with CD. Six patients (3 with colonic and 3 with ileo-colonic involvement; 3 males and 3 females, age 28 ~S y) with CD diagnosed following conventional criteria, underwent an intestinal permeability test using CrSI-EDTA as probe molecule. At the time of the examination, all patients were in clinical remission and without any treatment, In the urine collected over 24 h, mean urinary excretlon of CrBI-HDTA was 4.B5 +1.53% of the administred dose (normal values-< 2.6%, previously calculafed in 30 ~elthy Controls). After one week patients SteTted S (1 gr. x 4 times every day, for 4 days]. Intestinal permeability was then [eevaluated. The patients treated this way, ~xcreted significantly less CrLI-EDTA (3.34 ~0.B9~; p < 0.05; paired T test). Thus S in our work effectively reduces intestinal permeability in CD. This obser~atlon, if conformed, deserves further investigations.

278 331 JW Arndt, GE Crama-Bohbouth, AS Pena, HW Verspaget, IT Weterman, EKJ Pauwels, CBHW Lamers. Departments of Gastroenterology and Nuclear Medicine, University Hospital, Leiden, THe Netherlands. INDIUM-III-LEUCOSCINTIGRAPHY: MORE ACCURATE FOR LARGE tOWEL IBD THAN FOg SMALL BOWEL IBD. This prospective study was undertaken to evaluate the sensitivity, accuracy and pre~ dictive value of Indium-lll autologous granulocytes scanning for the assessment of the localization and extent of inflammatory bowel disease (IBD) of the smali and large bowel, Thirty-seven consecutive patients, 25 women and 12 men, median age 35 years (range 16 - 66) were studied. Twenty-nine patzents had Crohn's disease (2O with small intestinal localization including one with left-sided colitis, 9 with colonic involvement) and 8 with ulcerative colitls. A positive scan corresponding accurately in localization and extent with radiology and/or endoscopy and/or resection specimens was obtained in 16 of 17 patients with active colonic disease (sensitivity 94%), while the scan was negative zn the single patient with inactive colonic disease. The predictive value for colonic inflammation was 95%. In contrast, only ii of 16 Qatients with definite evidence of small intestinal disease Had a positive scan (sensitivity 6g~). In g patients with inactive small bowel disease the scans were negative and no false positive scans were found, giving a predictive value of 75% for this localization. Indium-ill labelled granuiocyte scintiEraphy is, therefore, useful in evaluating localization and extent of colonic disease. However, it is of little value in ghe assessment of small intestinal localization of grohn's disease.

334 C. SAWAS-DIMOPOULDU,N.TOUBANAKIS,I.IORDANOU

332 I . ;A~GUESO

M.Jo ; A B E D

0. B E R R O C A L

J.

CLINICA

EFFECT OF CORTICOSTEROlDSON THE BIOOISTRIBUTIOJ OF 99mTc-TIN-PHYTATEAND 99mTc-SULFUR-COLLOID Diagnosis of abnormal l i v e r function is strong~ sugoested a f t e r intravenous injection of 99mTctinZphytate (Phy) or 99mTc-sulfur colloid (SC) when the concentration of radiocolloids shifts from the l i v e r to other organs. However, change: in the biodi~tribution of Phy may be induced by blood -Cai+concentration independly of any l i v e r disease. In the present investigation we studied the e f f e c t of high doses of corticosteroids on the biodistributlon of l i v e r radio colloids. Mice received i,m. a daily dose of 0,25 to 2.5 mg Prednisolone for 4 days before the i . v . i n t . of the radiopharmaceutical. The treatment did not changed significantly SC biDdistribution but Phy-blood clearance was delayed (0.48 ± 0.08% of injected dose in control! at 30min comoaratively to 5.45 ± 1.45 % afteF treatment), Moreover , Phy uptake decreased s i g n i f i c a n t l y in l i v e r whereas i t increased in spleen, kidneys, lungs and bone marrow, The liver/spleen r a t i o of % injected dose Phy was reduced from 27.15 ± 1.50 in controls to 13.16 ± 3.95 a f t e r 4 doses of 0.25mg PZ, and 5.98 ± 1.41 a f t e r 4 doses 2.5 mg PZ. Spleen weight was reduced from 0.10 ± 0.01 g in controls to 0,040 ± O.OO5g in treated mice and an 8-fold increase waa shown in % injected dose Phy/1% b.w.t, of spleen tissue, wheres that ratio was not changed for SC. The concentration of mhy in kidneys , lungs and bone raarrow was increased to 2 or 3 times that of controls. Serum Ca+2 concentration was s i g n i f i c a n t l y increased from 7.6mg/dl in controls to 11.2mg/dl in treated mice; The data suggest that co,ticosteroids in high doses, are capable of indg£ing major changes in the biodistribution of ~ ' T c - t l n phytate that might be attributed erroneously to hepatic disease.

PUERTA

~. ;DEHARO J. ;

E. van de Flierdt. R. Bauer, H.R, Langhammer, H.W. Pabst Nuklgarmedizinische Klinik, TU MOnchen Ismaningerstrasse 22. D-8000 M0nchen 80

DE

HIEtLRO.-MADRID.-SPAIN

STUDYOF CROHNB ' ~IBEASEONTc-~,gmHM-PAOLELCOCYTESAND ]n-IIIOXINALEU~VTEB The purpose of thi.~ 5tudyq~ t{) asses tqe value of Tc-gq~ gM-PA[

leuc~y~e~ ITcl scans ~d Ih-lli-Oxine i~ucocyteh(In)~cans pahens with Crohn's disease, ~ T ~ c i 8 pts wit# CD ~ve he~n studied of ~ich ]2 ~,~e i~ active disease (C~> 150) ~d 6 did not ~D~ ~y activiLy ~ignal. ~ E,~plora~ioh protocol : AJC~trai af:iabeliin~ .~fftciencyhoLh radiotracers.Bi ~ci~tigr~phi~ exI~loratiton L4 an~ 2~ h/s'~f£er in'/ept~o~ with T: ~nd SPEC~ iF needS.C)48 hr~ a{ter,ln inyectlon was made FoHowing ~qe sam~

proc~du~ as in th~ T: cage,Fecal,excretion o~ In-lii-nxlna Leu:

~uan~f~cat on. ~SLP_TB:£]~endin@ on uptake intensity oi T: and in on the taxis]IsI WE h~ve defined fo~F ora~e~ of uptakin~ in cc~pmrm~i6n with th~ boneman-~'upk~:e.in 12 pts with Cl)AI) 150,scan~shoed positive upLake belh:~ith Tc and In ,'showing relationship d~tween high COAl and:Ill and IV grades in 6 pts.ln all of tne,,n ]Doges Iwere of ~p~hD~ qua[ity'with Tc rather that with in,being Bill of ~he~~qvq4~radei,thi~ :on]7 happenedin 6 pts in scanwith in. She eptake; seanninow&s~oreprecociouswith Tc as a11 o~ them are see~~ittin the'k~g first hpurs,~hiIs £t only happenedin 7 p{s with In,in 6 pts with CDA;~130, Tc -~za~Swere pz~'ItlVe in {WO CaS~Sl[%0 CBS~S ~ece positive ~ith Zni

I

COKCLUSZ@~S,-~]i the images cihcained.ith Tziare of sQ~ei-ioc" qua]it7 and morepF~OZiOL~S. ~T!:eprecociz/ uptake QOSe{'~reo in be*e! ~alceus thlm: thee v.e a,'e i'e£ii~' an a;i irdier~atzFvciseaseB be{s:'e a.q the so~e; ca~al9_=is:3ntamlnated n!th :~ ÷ezal ~aterial wzchviii net .alien uS ~Odeter,~:r,a E:IECL:} i m Z!Ze of the dao~ge,

CARCINOID TUMORS: SCREENING AND FOLLOW UP WITH 1131 MIBG 9 patients with suspected carcinoid tumors of intestinal origin (n=5) or with histologically proven tumors and preceding surgery or chemotherapy (n=4) w e r e investigated with 37 MBq iodine-131 meta-iodo-benzyiguanidine (MtBG). Anterior and posterior images of the abdomen and chest were recorded 24 and 48 h p.i.. 3 patients with suspected tumors did not show any pathological accumulation, in 2 of them also CT and ultrasound were negative. The other 2 patients in this group showed focal MiBG uptake in tumor tissue. No additional tumor sites were detected in these patients with other imaging modalities. All 4 patients with histologically proven tumors showed varying intense uptake in local recurrence or metastases. 4 patients of both groups had a second MIBG scan after therapy. In correlation to the clinical findings MIBG scintigraphy showed padial remission in two cases, no change in one and progression in another case. Conc/usions:

1) No correlation between tumor mass (evaluatee by CT and MRI) and intensity of MIBG uptake was found. 2) If MIBG uptake in intestinal carcinoid tumors has been documented, MIBG scintigrephy seems to be the modality of first choice for fallow up. 3) If intense and persistant uptake of MIBG ha.= been quantitated in diagnostic scans by means of ROI techniques, therapeutic applications of 1131 MIBG seem to be premising in selected cases with carcinoid disease.

336

335 0. Galli, CIL. Maini, P, Orlando, ~. T h o m a s e t

Demokritos National Research Center, Aghia Paraskevi 15310 Athens, Greece Nuclear Hedicine Dept, Areteion Hospital Medical School, Athens, Greece

333

r"

C, Cobelli*,

P. Heintz,Oh.Ehronheim,B. Oofti~(J,I'L H u n d ~

~.

[stituto di Medicina Nucleate, Unlverslt& Cattolica del Sacro Cuere, Roma. •CNR Institute for System Dynamics and Sioengeneering, Pedova, 99mTc-DTPA-OROSOMUCOID:

F[HST HUMAN STUDIES.

new radiopharmaeeutical f o r the study of the Liver, 99m-To-DTPA-asialoorosomucoid (AOM), has been experimented in a limited series of humans: three normal volunteers and thDee pathoiogical cases (i cholostatic cirrhosis; I malignant hepa tema in chronic hepatitis; 1 cholangitis with hepatic abscess). All patients were injected ~ith 5S0 micDog of AOM and activities ranging from 66 mBq to 105 MBq. Frame mode acquisition (60' with time resolution 30", 64xE4) and static imaging were performed by a LFOR gammacamera; ~iso blood and urine samples were collected. rhe hepatic uptake of AOM is remarkable (50-60% 3f the injected dose in lh) and rapid (max. at 10'-15') with excellent imaging; an appreciable amount of radioactivity is excreted by the kidaeys; an additional fraction is excreted througt the bile. No adverse reactions were observed. £he calculated radiation burden is negligible (3-10cGy/MBq*lO -S to the liver; 25-70 to the 31adder). For kinetic studies a font compartnent model has been applied; functional data so 3btained differ in n o r m ~ and pathological subacts. conclude that 99m-Tc-DTPA-orosomueoid is a suitable radiopharmaceutic~l for liver imagin E and functional study.

Deportmenlof Nuciesr M~itclne Medical Schoolof Hanenver,FR8

D I , ~ I 8 OF LIVER TUMORS - CLINIC/~. VALUE OF (~INIUM-DTPA /~ISTED MRI IN ADDITION TO SCINTI(~%~PHICHETHOOS 5sverml imeging msthoc~ aod especially their omabi~d aPpliestim sfe proven to be useful In the dlaItrmis e~l difforenUatJen of liver tumors:, ultraesruTepby, ruen~jen computed Imn~laphy, sequenttol ~ i l i e r y esinii(Jrapby (HESS), blood pool scintigrophy using g9m-Tc-leheled m'y~r~es m~l rnegnetic ~ im~jIng. The diaT~sis of bemengiomes and focal nodular ~ p asia of the liver e~cesd]nga sies of 2-3 cm in dlametor can rather he

~ured by the ~iofi~'ephic m ~ mentionedabove.MRI of the liver witllout contrast e~ent enables us yet to dtoom~e hemen~omembelow the smelle~ siz~ that could bedetectedin bloodpoolscintigrapbyme, if the 8PECTmeti'~I is employe(l 38 psttsnts with liver tumors (bepet~Sllulor cortisone, focal rea"Jler hyperplesla, m~ensma, hemengi~a B~l rnete~BBes}underwentMRI of the liver" before end after i.v. ll'~ten of 012 mllkg 8alolintum-DTPA in ~ldlttes to other imaging rnetho~. Writto. informed ooment was achievedin all cases.The r~rmsl B~ p~l~l~Jiesl fln~r~ in MRI were dOCumentedin T I - and T2- meighted images, proton density irn~, calculated T I- end T2-image6 and a Ti-mei~ted imageef~r 8pplicatton of the contr~t ~enl. The catoutotlm of the rel~(atim times dfd net provide ne~ ~rwmening the clifforentiofien Of the liver tumors Investigated,w ~ the ~opilc~lon of bedelintum-DTPAes omtrsst agent improves the z~clfity by disorimin~ing the merphelogic~l componen~ of the turners ( l ~ f u ~ d o r ~ , esu'~es, hem~es). The results of ~is ~tu(~ hell~/ us to devel® an actual diagram of dim:~tic wWs for liver tumor& In corto~nc ~ , cytoto~cal and histological e~eminatlen could be replesedby r~inv~ive imegmg methods in order to confirm the dlaQrmsla

279

i.@~aancl~lU, O.F.~mayGz,K.Ozker, ~.~sel, t.Uslu, T.Tur~]lu, R.Rizalar, H.Emir Departments of Nuclear Medicine and Pediatric Surgery, Cerrahpa@a Medical Faculty, tstanbul University, Turkey

! ~: [[P~{~D!g, m H. Hodoni, * F. tarbano,g S. De Cosmo, D V. Aeneas, mD. Bonazzar } U, Fic~la * Department of Nuclear tedicine and 9adi~tberapy D Department ~[ [nhernal Hedicine - Dt|hetes tenter @Department of Gastroenterology and tigestive Endoscopy 6choral Nnspital 'CADNSOLLIEVDde[[a 5O~EREtZA% g. ti~va~i Rotondo (FHh ITALY

EVALUATION OF PORTAL SCINTIGRAPHY USING Tc-99m FOR STUDYING PORTOSYSTEMIC COLLATERALCIRCULATION Ibis study is undertaken to demonstrate the v a l i d i t y of Tc-99m in portal scirTtigraphy (PS)for the early diagm)sis of portal hyperLeqsion because of the pmnpt a v a i l a b i l i t y of t h i s redioisotope,using a r a t model with portal vein ligature.Transferral PS was perFon~ed by intestinal a ~ i n i s t r a t i e n of 0.1 ml ToO4 (go ~Bq/100 g animal waight) by a t h i n rectal tube in rats with and without portal vein ligationAtcle-body images of rats wase obtained by a g~ camra interfaced to a computar.A dynamic study with afraTe rate of 5 see/image was acquired for 360 sec, Regions of interest: (ROl's) ware GeFerated over the r i g h t lobe of l i v e r (L) and the heart (N) and time-a~ivity curves mare obtained.frocirculationtimes (CT)frm

iFCce~ise to L and intestine to Hware calculated fron the peak aCivity times of these curves.Following this,ammEter gr~x~pOFrats with and Wlt]~DLrCpo~tal vein iigstien ware injedced with 0.1 ml Tc-99~-~VV~(5 FBq/iO0 g animal waitS) into the splenic pulp.Oynamic~le-~x~y in~gesware reserded into the discs in the sameman~eras trsnsrectel PS,static sciFfci~ama ~re cbtaiFed in eve~ 2 rain for 10 min.ROI's ~re generated over the liver ~ IUF~]Saed shunt i n ~ x was calcu]sted. After administration of TcO4 into the intestines the radioa c t i v i t y passed rap[dly through the intestinal and portal veins and enterod the intrahepatis portal branches in noFm~1 r a t e , l t reached to H each rapidly and CT to L was correspondingly delayed in rats with portal vein ligatise. In normal rats injected ~ i t h TC-99FFH~AA,capilIary perfusise of the l i v e r parenchy~a was visualized rapidly while lung was not (Shunt index---O)iln portal hypeF~sive rats the bolus bypassed the portal vein and entered portosyst~mic collaterals.Lang was visualized while acma~latien in l i v e r waS RI~Ch less. In cenclusion,transrectal PS with ToO4 is an easy ard safe technique providing quantitative ioformaticm of CT and visualization Of portal circulation.

AFlSESDH~T~=BALLt~OgER FDtCflON IH DIgtETED m of our worh ts to evaluate gallbladder function in diabetes. Ne we sbudied ~ diabetics (ate r~npo IN-TOyrs) and 7 normalCoD rol~ lage range l?-~?~s}. Diabetics were subdivided in bwo groups: positive IAM+) and negakive (~N-} as to the presence of autonomic neuropathy evaluated hy cardiovascular tests. 6 datients • ere cJasslfJed as positive, ~ as borderline and lb as negative. Cholescintitraphy: a gammacamera interfaced with a cumputer ,~s used to obiain imagesat a frame rate of I fr./min. Pabients were ieiected ~iit 3-5 ~CJ ~f dietbyl-iOH: at sixty min the gallbladder was stimulated by a slom iniection 15 mth.I of £CK (1 Ivy-~ot Unitlbg body meitht). Regi~s of interest were dra~ on the whole liver IHD! n , l b gel]blaNder (HOI n.Hb geritheral porhinn of right lobe (ROI n.3) far fTom gallbladder and biliary ducts, and a background region [tOI n.g) just above hhe ritht liver lobe, and finally (90[ n.D) ~n the portion of gallbladder over]abping liver. Data were corrected for physical decay and s~tracted of norlalJ:ed hathtroe~d. ~e ~ ] n.~ a~d R@] O.D were utilized to Bbtain a ratio index tn first 3 minutes of study. This ratio index was then utilized in order to subtract liver contribution to gall allbladder counts. Correcteg data were analized tu calculate t~l]bladder ejection fraction ( ~ ) , peak f i l l i n t rate (PFR) and )eab ejection rate [ ~ t ) . The fo]lowing title shows our results ~xpressed as means~ s0: ~o, EF ~H PER gontrols ? Hi.H+7.9 T7.O~LB.B 170.5~7H.l gl[ diabetics tD tl.6~g3.g f 7h.?~3t.D @6.7t70,6 gN+ b 2d.~2~,g e IIH.i~35.] ~ hh,3*33.t %NIb D~.3.37.1 hH.7~t8.7 [email protected]~tO.7 N: p (O.DDI h p (O.Oil l: p (O.O~ Ff, PFR, PEH impairmenh in diabetics are due IB digestive localiza kion ef AN. Nevertheless ~ i s lore sensitive than P ~ a ~ PHR. However obolescintigrapfly appears |! an effective ~thod to evaluH te digestive ~ in di~ehics in alternative ho esophegeal scintigrh php although more tiHCOnsuming and ~re e~pensive.

~41

340

~

339

338

337

.~D~_Y,

lorio E., Massa R., Cortesi E.*, AschelLer A.Mt ~ r o ~. Nuclear Medicine and Clinical Ontology ~, Dept. of Experimental Medicine, University "La Sapien za", 00161 Rome.

99m-Tc- MAA INIRA- ARTERIAL SCINTIGRAPHYIN PATIENTS WITH HEPATIC METASTASES, 21 patients affected by hepatic metastases From coloreetal cancers were submitted to scintigraphy with NAA-99m-Te w~ioh.was slowly injected (110/MBq/2ml), via an arterial permanent-catheter followed by ID ml of saline water. All patients were examined before chemioLheraphy: 8 of these underwent serial controls, in association with U.5. and PC. Tumor perfusion shows the Following patterns: a) ~n 10/20 patients a decreased central radioaetivily with hyperperFused border, b) zn 3/2g no border Found end e) in 6/20 only an increased radioactivity spreaded in the tumor. In one case no signific~n changes were observed because of milliple metastases sized lesser than 1,5 cm. Pulmonary Jptake waa present in 7 patients, gastric Iptake in 6~ pancreatic and spleen uptake zn 1. ]ompleLe displacement of catheter was diagnosed ~n 2 patients, whereas spasm and main arterial iranches stasis were observed in 2, Changes in ~etBsLases perfusion after arterial chemiothe;aphy occurred in 7/8 cases: 4 showed reduction if area of decreased radioactivity, 2 increase if diameter of cold lesions, I reduction of ~umor areas of hyperperFusion. 99m-Tc- HAA ~eintigraphy results the best way to demonstrate ;omplete displacement of catheter or zncomplete )no with perfusion of extrahepBtlc areas(stomach )ancreas) slag due to arteriolar spasm or pro~ressive arteritis. Changes of meLastases ~erfusion correlate well with U.S. and TC in ~emonstrating r~sulLs of ehemiolheraph~: the association with U.S. would be suggested as the nosL important diagnostic tool in following up ~f theee paLients.

342 C OR~OOIR, d-P HINON, R VA~]A~V~4B~(,

M BAUDOt, M tl~V~Z,P &RA~tflm,T CATAMO,R CALAY

3.Lumbroso, 5.Sidibe~ P~Rougier, P.Lasser, D.Elias, C.Parmentier.

Department of Internal Medicine,Hospital Barmherzige BrUdsr Graz-Eggenberg, Austria

art|outof HuclearMedtcihe ~..g. A. V~ALK D110 MonOtonyie Tille~l,n~L~IUM

IServices de Mddecine Nucldaire, de Gastrolentdrologie et de Chirurgie, Institut Gust~ve Roussy, Villejuif, France.

PLANAR IMAGING AND BLOOD POOL SPECT DETECTION OF HEPATIC HENAKGIOMA,

SmP.E.C.T. CHII~RIhIN DIFFUSEALCOHOLICLIVERDIS~K.

,W,, L i n d , P . ,

Klima,G.,

Kdltringer:P.

IN THE

The more and more frequent employment of ultrasound in preventive medical examination has resulted in a growing number of diagnoses of circumscribed hepatic lesions. As in the majority of the cases these are incidental findings in symptom-free patients, an accordingly streamlined, primarily noninvaeive diagnosis of these focal liver tumors is desirable. The study population consisted o f 16 consecutive patients with a total of 19 hepatic lesions, which had been depicted with US or TCT. All lg hemangiomas were associated with normal or decreased flow and delayed uptake of the radiotracer. The great advantage of Tc-g9m Blood pooI-SPECT vs, planar imaging (PS) is the detection of small deep-seated haemangiomas; the sensitivity for PS and SPECT for all hemangiomas was 10/19 (52 %) and 18/19 (95 %), respectively. For lesions 3 cm or smaller the sensitivity woe 6/11 (54 %) for planar and 10/11 (el %) for SPECT. Moreover, other than in TCT, SPECT diagnosis is possible also i in patients with intolerance reactions to contrast media or hyperthyroidism. These results show that SPECT constitutes a simple examination method, which can be performed any time, is hardly contraindicated, and can be considered an ideal complement to ultrasound (combined accuracy above 95 %) in the differential diagnosis of circumscribed hepatic lesions. I The patients, the majority of whom are symptom-free, can thus be spared the discomfort of fdrther unnecessary and partly invaNive diagnoses ( l i v e r biopsy).

Ain of the atudy: 1= to define the ~ r l a l adult ra~e of the quantified scinth~aphic criteria in HP~CI studies of the liver and spleen. 2' to ~e~e the eensitivihyof thee criteria in diffuse alcoholic liverdisease. 3' ho co.are 5PHL? and CI ~ i t i v i t y i ~ alcoholic l i v ~ d~ease either at the st~e of fatty aetalorphesi% or cirrhosis. Hateriah and aet~ode: • =KCT te~bedgue us~ a Butt~vothh reconstruction f i l t e r of 90 proj~tions, matrix size s4, acquired in elliptic step-and-shot lode 20 mirates afhez the injection of 185 ~ of a cca~rcial ~c99a radi~olloid (~Jbure~, ~olco). ~ diap~osis is based on the followin~critexia: volumeof the liverand the spleen, hepotic atte~J~ation value, heterogemity, pre~ce of ~cite~. Homl ~bjects inclu~ 22 ~n-alcohelic patients referred to exclude a ~tatic i n v o l v e ~ t of the ]ive~ fcom a primacy n~plas|; all of thai had a nonlal liver biology and a nor|a1 CT study. Aheoml subjects include 35 patze~th with a histological dia~ooais of ateatvsi~or cirrhosis, or with portalhypertension excluding all other etiologies. ~ulth: l~ ~ the SDeCificityin our noI1alRie flied to 95~, the eelsitivities of SP££~criL~ia are: livervolume 375, spleen VOile 66%, spleen-be-liver s~ecific uptake ratio ~ , bone J ~ x r ~ - t o - l i ~ m~zth~ uptake ratio ~ . s p l ~ n - t h - l i v ~ volulm ratio 46%, norJh~la~'eJ~.=ousliveruptake 26~, left-to-right hepoLic 1 ~ laxim~ uptake ratio 31% D" An aheorll~]itp score is ~leo comp~t~ by addi~ ts~et.h~ C~ num~.~ of 6thed~ deviations of e~ch crit~rioa value out of its ~ormal range. Thatscorehas an o~all se~mitivit,/Dr gh% aed cone]aLes withthe histological~zade of the d i ~ e , and in the cirrhoticsub,cud withthe Cheldclassification(r :.7OL D" ?be se~ztivlty of CT is louer in the whole alcoholic pou D (~PECT 9~I; CT ~%] as well as in the steato~is sub.sup /SPECT 8~% C~ 5@%), or in the cirrhosis sub.cup (SPECS[00%, CT 7~%). ~nclusions: 1' The splle~-to-]ive~ specific uptake ratio is the e'in~le most u~ful ~tCt criterion for the dia~p~usis of alcohohc hver dis~e. 2=.h eco~e . .based . on all the scintipaphiccriteriastillthprov~ eh@tly ~e seneatzvthy and can he used to state ~ severity o[ the disease. S~ I?e~e pt~J~=inar/ data co.fir= the supe~iorit D of t~e s¢i~t~ap~i¢ t~cheiq~e ove~ C~ in the ~ia~ssis of diffuse alcoholic liver disease at ~ll stages of seveI~ty. 4' As 11% of our ahnor=al euhjects have a normal liver hiolo~], ~PtC~ is Tecouended as a ecreeqi~ procedure in alcoholic patients before cor=ideration for live~ hiopoL

F.Guermazi,

I

SERIAL RADIONUCLIDE STUDY OF THE DISTRIBUTION OF CHEMOTHERAPY DELIVERED BY IMPLANTED DEVICES IN THE HEPATIC ARTERY

I

Intra-arterlal hepatic chemotherapy (IAHC) aims at delivering a high concentration of cytostatic agents to liver metastases with a lowered systemic toxicity. Two methods of IAHC ~ere evaluated in 59 patients having liver metastases From a COlD-rectal cancer and we tri~d to assess the inLra-hepatie distribution of the drugs using serial radionu¢lide scans. A first group (GRI) o£ 43 patients had an arterial access subcutaneously implanted (PAC) 311owing a disconLnueus~ chemotherapy by 5Fluorouraczl (I g/m once a week) using a portable pump. A second group (GR2) of 16 patients had an Infusaid gOB pump implanted, allo#ing the continuous infusion of 5-fluerodeoxyJridine (0.3 mg/kg/day during 14 days each 4 weeks). The radianuelide scan consisted of: (i) the injection in the arterial access or in the side port of Lhe InFusaid pump of 99mTc]er-LeehneLate (150 MBq) washed out by 10 ml af saline solution, Followed by (ii) 99mTc~erum albumin macro-aggregates (200 to 300 ~Bq). The obtained images were compared to the conventional liver scan provided by intravenous 99mTc sulfur colloid. The radionuclide scans detected the arterial Lhromboses occurring in 65~ of the patients in GRI, and Found the explanation of ~lmost all the problems related to the status )F the catheters or to extra-hepatic infusion. In the Lwo groups, we Found that Lhe pattern )f arterial vascularization of the metastases ~as correlated to the response Lo chemoLherapy and to the survival. We conclude that radionuclide monitoring ]f IAHC is a simple and highly contributive technique.

280

343 Sabah S. Tumeh, John C. Lipn~n, Carol B. Benson.

345

144 A. K r o i s s ,

K. H e r h o l z , J. 5 c h ~ l l e r , W. Weiss, K. D i n s t l ,

A. Neumayr. Department of P~diology Hamvard Medical School Brigham and Women's Hospital 75 Francis Street ~oston, ~A 02115 SMALL FOCAL LIVER LESIONS: EVALUATION BY 89m Tc-RBC SPECT. To determine the role of 99m Tc-RBC SPECT in evaluating s~all live~ lesions: we studied g4 consecutive patients (pie) who were r e f e ~ e d fo~ the eva~uation of such lesions. There were 33 patients with 42 cavernous hemangiomas (C.H,) ; 9 patients wlth metaetases~ i patient with cysts and one n ~ r ~ (total i~ lesions). The diagnosis of cavernous hemGL~lO~a was made by angiogrephy (4 pts)~ biopsy (3 pts) and mlinically (26 pts). The clinical criteria were a] normal liver function tests, b] it least an ultresound (Ii pts), CT (7 pie) or both (8 pts) suggestive of cavernous h~m~ngion~ and c) at least one year follow up. 20 mc~ of Tc-gSm were used to labell the ~ed cells by a modified in-vivo technique. A i frame/2 second for 2 minutes flow study ~as done and followed by 10 6 count planar ~na~es up to one hour. SPECT was done then. 64 projections encompassing 360 ° orbit were obtained. Data were reconstructed after unJormity correction, using a ~/np Manning I i l t e r . Of tile 42 C,H. : 8 showed decreased, 32 norm~l and 2 increased flow. One hour delayed Planar imaging (PI) depicted 27 C.H., while SPECT depicted 41. Of the 15 non C.H. lesions, 2 showed dec~eased~ 4 NUt,hal ~/id 9 increased flow. None showed increased uptake on PZ or SPECT. We Conclude that SpECT is more accurate in depicting small C.H. than P.I.

Institute of N u c l e a r M e d i c i n e , KA R u d o ] f s t i f t u n g , Vienna

CLINICAL APPLICATION OF MEASUREMENT OF LIVER BLOOD FLOW BY INHALATION OF XE-133. The aim o f t h i s s t u d y was t h e e s t i m a t i o n of l i v e r blood f l o w in p a t i e n t s w i t h hepatoma and l i v e r s e c o n d a r i e s w i t h a n o n i n v a s i v e Xe-133 i n h a l a t i o n t e c h n i q u e : we used an i n h a l a t i o n s y s t e m , an Anger camera and an o n - l i n e c o m p u t e r s y s t e m . A ROI o v e r t h e e x s p i r a t i o n - t u b e was used as t h e a r t e r i a l i n p u t f u n c t i o n and a ROI was p l a c e d o v e r t h e s p l e e n representing the portal vein input function. ~he edge d e t e c t i o n over l i v e r and s p l e e n was done by a p p l i c a t i o n of Tc-99m c o l l o i d i n t h e same p o s i t i o n after inhalatio£. L i v e r b l o o d f l o w was estimated w i t h a m o d i f i c a t i o n of Obrist~ algorithms. L i v e r blood f l o w was found to be 48.8+10" in 7 p a t i e n t s w i t h hepatoma. 5 ) a t i ~ n t s were resected and showed a l i v e r blood f l o w of 47.6+4.8* 4 weeks l a t e r and I p a t i e n t was Transplanted ( 3 7 . 8 " ) . L i v e r blood f l o w was found t o be 53.3+10.4" in 13 p a t i e n t s w i t h l i v e r secondaYies. In 8 p a t i e n t s w i t h s u r g i c a l l y implanted a r t e r y c a t h e t g r f o r r e g i o n a l chemotherapy we could compare the Xe-133 i n h a l a t i o n method and the d i r e c t a p p l i c a t i o n of 133-Xenon i n t o the c a t h e t e r (r=O.9). In conclusion, the method i s u s e f u l l in p r e d i c t i n g the f u r t h e r p o s s i b i l i t i e s as r e s e c t i o n , t r a n s p l a n t a t i o n and i m p l a n t a t i o n of hepatic a r t e r y c a t h e t e r .

( * m i / I 0 0 gm/min)

346 C. Dosoretz, and L. M. Lieberman

Blttner and G. H~r

M a u l , R. Standke,

Department of Nuclear Medicine, Sheba Medical Center and Sackler School of Medielne, Tel Aviv University, Tel Aviv, Israel

UTILITY OF SPECT FOR THE DIAGNOSIS OF LIVER KE~GIOMA ?ha diagnosis of hepatic hemangloma usln~ Tc-99m labeled KBC blood pool plangr imaging is well accepted. In order to assess the utility of single photon emission computerized tomography (SPECT) for this diagnosis we studied 14 patients referred Because of suspected heman~io~a seen on either CT or US scans of Dhe liver. SPECT studies were done with an ElsclnD APEX 410 digital g s ~ a camera in 64x64 matrix uslng a low energy high resolution collimator. DaD8 were reconstructed in 1 pixel (6.4 ~ ) " thickness usln~ back projection end a Hannlng filten Twelve of the 14 patdents had planar imaging %~th the same camera and collimator. Three of the 14 patients had lesions less than 1 cm on CT or US and were not visualized by SPECT or planar scans. In 5 of the 14 patients the diagnosis of hemanEloma was ruled out hy both 8PECT and planar studies. Six of the 14 patients were diagnosed as positive for hemasgioma by both SPECT and planar scans. However, while planar studies (as well as CY or US) showed only a single lesion in each patient, SPECT scans revealed 3 lesions in ipaDient, 2 lesions in 2 patients and i lesion in 3 patients. We believe that SPECT should be done for all suspected hemanglomas of the liver in view of the improved accuracy for lesions g:eater Khan 1 cm.

D e p a r t m e n t s of N u c l e a r M e d i c i n e sfro-znfestznal Surgery, Odense sity H o s p i t a l , Denmark.

Qvist, d Svend

and OaUniver-

POSTPRANDIAL GALLBLADDER FILLING I N I RELATION TO GASTROINTESTINAL MOTILITY CHARACTERISTICS. PURPOSE: To d e s c r i b e t h e a n t r a - d u o d e n a l motor activity p a t t e r n to w h i c h g a l l bladder Filling is related in the past p r a n d i a l s t a t e . MATERIAL AND METHOD: In e i g h t h e a l t h y m a l e s the antra/ and duodenal i n t r a l u m i n a l p r e s s u r e s were registered after the i n g e s t i o n of a tO0 g o m e l e t t e (1400 KJ) and 150 ml ~ater. I m m e d i a t e l y after the m e a l c o n t i n a u s iv infusion of 9 9 m - T c - H I D A (40 MBq in i00 ml s a l i n e per hour) began. Thereafter, c o n P i n o u s a n t e r i o r gamma camera recordings in 2 7 0 - s e c o n d - p e r i o d s wer~ performed. M o t o r a c t i v i t y index - the number of c o n t r a c t i o n s per 270 seconds ~as r e l a t e d to time a c t i v i t y curve From gallbladder area. RESULTS: The m e d i a n time From i n g e s t i o n o6 the meal to app e a r e n c e of s i g n i f i c a n t g a l l b l a d d e r rad i o a c t i v i t y ~as 3 hours (range: 2 . 4 - 4 . 2 h). G a l l b l a d d e r Filling began in telatdon to a d u o d e n a l p h a s e I-like p a t t e r n in five c a s e s and in r e l a t i o n to a phase III in one case. In t~o eases slight f i l l i n g ~as o b s e r v e d d u r i n g fed p a t t e r n ~otor a c t i v i t y but i n c r e a s e d in r e l a t i on to a phase IIl. A p h a s e I l l - r e l a t e d i n c r e a s e of an a l r e a d y s t a r t e d filling ~as o b s e r v e d in t~o more eases. In one case t r a n s i e n t f i l l i n g ~as o b s e r v e d during fed p a t t e r n . In five cases minor e m p t y i n g e v e n t s ~ere n o t i c e d and always in r e l a t i o n to an i n c r e a s e d m o t o r activity index. CONCLUSION: Significant p o s t p r a n d i a l r e f i l l i n g of the g a l l b l a d der ~as r e l a t e d Co a pronounced d e c r e a se i s d u o d e n a l motor a c t i v i t y or t o the reappearenee aE phase I I I ,

348

347 ~G~ ~FJJldhor's~, F,-D.

Erik O e s t e r - J o ~ r g ~ n s ~ n , Niels Lars R a s m u s s e n ~ Claus H o v e n d a i Arne P e d e r s e n .

Dlv. of General Nuclear Medicine, I U n ~ v e m s i % v ~ n ~ D ] ~ R I . W?~.~mlle~/M m~ COMBINATION OF LIVER SPLIT FUNCTION PARAMETERS OF COMPUTERIZED HEPATOBILIARY S E @ U E N T I A L S C I N T I G R A F S Y (SSS): rBE V A L U E F O R C L I N I C A L R O U T I N E U S E 5inca the first use Of 9 9 m T o m l a b e l l e d ~IDA in 1975 a l a r g e n u m b e r of RSS ~xaminstions has been performed in order t o e v a l u a t e nonlnvasively pratepatio, in%rahepatlc and posthepatic l i v e r diseases. The a i m of 5 h l s study ~ss t o f i n d o u t w e t h e r a c o m b i n a t i o n 3f a quaatltative data for B I D A ' s half life of l i v e r i n v a s i o n (HLLI = < 3.0'), i~s m e a n t r a n s i t time in live~ parenchyma ( M T T L P = < 51') and its h i l i n t y retention 40" after i.v. In~ecbion (I~T40 : < 15) is m o r e sensitive for differentiation nonlcteric liver

diseases than single parameters. ~e evaluated these Parameters i n

52 pts. with duodeno-gas%ral reflux hut ~ithout a n y liver disease (normals), In 12 pts. with liver cirrhosis (I), in 10 n o n i k t e r i c pts. with partial bile duct obstructlons (II) and in B PtS. with Daoarbazin treatment by reason of m a l i g n a n t m e l a n o m a ( I I I ) . In a l l pts. but the normals the HTTLP was o u t of range. T h e pts, of I s h o w e d an i n c r e a s e d t i m e f o r H L L I a n d normal BET40. The pts. of II p r e s e n t e d a m o r m a l R L L I b u t demonstrated the B E T 4 0 tO b e a b n o r m a l too. O n l y t h e pts. of III s h o w e d n o r m a l R L L I a n d P~ET4O b u t M T T L F t o b e out of r a n g e e x c l u s i v e l y . This illustrates that the combination of q u a n t l t a t i v e d a t a of H S S e v a l u a t i o n is clearly a b l e to devide various liver diseases and t h a ~ it is i R p o r t e n t for c l i n i c a l r o u t i n e ~se.

P. CAMBELLI, G~SPREAFICO , G. GADOLB SENVIZIODI MEOICINANUCLEARE OSPEDALEDI LEGNANO~ U.S.S.L.N. 70 LEGNANO-hTALIA

Is IT POSSIBLE THE GIAGNBSIS OF HEPATOMAS~ITM £9mTc RED BLOOD CELLSIMAGING? Since the appearance of fomal hepatic lesions on gQmTc coIlaids sclntigrams is not specific and i t is important Lo distinguish liver hemangiomas Prom other hepatic lesions prior to biopsy, a study was performedusing gBmTc labelled red blood cells in ]OA patientswiBh l abnormal liver sclntlgraphyand]or echopraphy. On 43 patients wiCh one or more hepatichomangiomas, all demonstrated increasedactivily on delayed (2 hours) blood-pool images, while dynamlc or early (5 min) static images showed varleble ackiviLy and were not useful in dlPPerentiatlnQ hemangiomas From other lesions. The BE non hemanghomatouslesions consistedof 17 meha static tumours, 24 cirrhotic nodules or focal steat0sis, 7 cysts and 13 hepat0mas. None o? the BaLients showed the scintigraphicpatterns oF hemanglomas and , with the exoepllon of hepatemas, all showed decreased activity in the early and delayed images. The sclntipqaphic patterns of hepatomas are variable. Seven of these patients showed an increasedblood Flow while delayed sclntigramsshowed a blood pooh decreased(6) or isoacllvo(7) compared with the surrounding normal Diver. Lesions with delayed blood pool de~reaseN need For Further investigations while an increased blood pool at 2 hours allows For the diagnosis of hemangloma. The diagnosisoF hepatomais posslhle when it is observed an increased blood glow with a decreasedor isoactive delayed blood pool

281

349

350 I,B, Wolf, P. ~ieland, J . H ~ e r l e , J, Kretschko, H,W, Pabst

I

M.Emter ?), K.Alexander I ) , D.P.Pretschner 2) ~shagen 2)

Nuklearmedizinische Klinik und Pollklinik rechts der Isar der Technischen Universit~t M~nchen

Medizinische Hschscbule Hannover I ) Department Angiology 2) Department Nuclear Medicine and Special Biophysics QUANTIFICATION OF THERAPEUTIC EFFECTS IN LEGS WITH VARIOUS VENOUS DISORDERS

FIRST EXPERIENCEWITH A POSITION SENSITIVE PMT COUPLED TO A Nal(TL)CRISTAL

Compression therapy is the o~dest and often the best therapy in venous disorders of the leg. The q u a n t i f i c a t i o n of the success of the therapy was not possible t i I X now because of methodic complications. With the ENGYMETRIC DOUBLE RADIONUCLIDE METHOD measurement of parameters are possible which are essential for a judgement. By marking erythrocytes and using a e x t r a o e l l u l a r marker measurement of the i n t r a v a s c u l a r - and the edema-space is possible. Special detec%ors and a mobile storage-unit was used, SO i n v e s t i gations were possible, f . e . while waTkinD. In a study investigations were done on patients with primary varCces and an adequate compression therapy and on patients with a severe postthrombotic syndrome using a z~nc-g]ue-bandsge.

A PMT -~ Was developed, which generates output signals depending on the position of the ohotoelectrle interaction on the cathode. -The anode consists of a grid of 18 wires independently in X- and Y-directlon. The elgnals are divided by a resistor chain for each direction SO that the position of the center of electron distribution on the last d)~node can be calculated. Measurements of the producer using a LED light source showed a spatial resolution of 0.3 ~ w i t h a gain factor of i0".

Changes in the calf during one hour sittin~ / (n=2O, lying=IZO%) in patients with primary varices -- compression 197~ ! 47% without 118% I 9% ]34% r 38% with 110% ! 7% d i f f . 63% (sign.) d i f f . 8% (sign.)

Changes in the foot durin~ half an hour walking I (n=lO, lying=t00%) in patients with postthrom- | bstic syndrsms intravascu]ar

]

edema-space compression 106% ~ 17% without 101% ~ 5~ 7R% r I0% with 94% t 5~ diff. 3Z% (s~gn.) diRf. 7% (sign.) __ With the DOUBLE RADIONUCLIDE ENGYMETRIC METHOD measurement of changes in both compartments - i n t r a w s c u ] a r and edema-space - has become I possible. Therefore quanbificazion of therapeutic effects is possible.

352 P. WANETj J. ABRAMOVIOI

O~partement des Radio-Isotopes, 7xelles Hospital, Brussels, Belgium DUAL-PHOTON ABSORDTIO~TRY WITH A GAMMA-CAMERA: ACCURACY AND REPRODUCIBILITY. We have used a g ~ a - c ~ e r a (glscint Apex 409) ~ d a Gadolinium source to measure the bone mineral content (BM~. Acquisition on patients is carried out simultaneously for both peaks (44 and 100 K e ~ with a high-~enaitivity collimator, g good visualization requires at least 10 MCount, which c~i be obtail~ed DI ? ~i~inwith 500 mci source. Absorption coefficients have been d~termined on ~ater and Calcium phosphate sanples. Intensitie~ are corrected for dead time, s p i l l o w r ~ d beam hardening. Accuracy has been measured on bone ~ e c i e s and netal foils. Results show a good field uniformity after corrections. Densities on bone ~pecies measured in 5 to 25 cm of water are cons rant to within 5 %. 40 patients have been compared with our system and Novo-BMCgSA. Results ~re in good agreement (r> 0,97). 5ong term precision has been measured on 2 bone ~hantoms and 4 volunteers. The ~esults show a ~ood reproducibility over a period of I year. Ube variation coefficient is less than 2 % and 1 % an bones and patients respectively. In conclusion~ BMB measurements with u ge2nma~ame2a seem to be accurate and reliable.

This PMT with a surface of 7 cm x 7 c m ~ s }coupled to a 5J8" Nal(Tll-cristai of same dimension. All measurements are performed with a polnt source of Tc-SPm, which scan the detector very close to its surface. The position depending variation of the Isisnals w~s 0.i04 V ] ~ for both directions. Uslng a 7 bit ADC with a resolution of O.Obl v at 4 V a theoretical spatial resolution of 0.3 can be calculated. It is however not possible tO assess from this figure what the real resolution will be.

The energy resolution of the detector is 17E FW]~ at l~O keV. The photopeak positio~ however depends on the position of the point source. A deplec~ent of 15 ~ f r ~ the center to the edge of the cristal results in photopeak shift of 17Z. The explanation for this fact is, that the resistor ~hain generating the position signals are c o n n e c t e d parallel. The photopeak shift can therefore be calculated from source position. Measurements confirmed this calculations. For the practical application of this detector a microprocessor has to correct the position dependin$ Z-signal. Without this correction the posslble spti~al spatial resolution can not be achieved. *l Samamatsu Photonies K.K

353 C. SOSEIBER*, H.A, MOLgNARI ~-w, A. GALI/~ANN ~-~ and J, CHA}IBRON*

* INSTITUT DE PHYSIQUE BIOLOGIQUE PACULTE DE HEDECINE 4, rue Kirschleger 670B5 STRASBOURG CEDEX ** CENTRE DE RECHERCBES NUCLEAIRES 6, rue du Loess STNASBOURG-ORONENBOURG CADMIWd-TELLDRIDE MINIATURE PROBEg FOR CARDIAC AND PERSPECTIVES Ambulatory monitoring Qf ven~ricular function parameters together with ECC data could be of some help in the management of patients with coronary disease. Oonventionnal INa probes are not suitable for this purpose bu~ a new small probe is now commercially available (VEST fro= CAPINTEDH). Semi-conductors detectors represent an alternative choice. The NM. service of the Institut de Physique Blologique has built with the detector group of Prof. gallmann at the Nuclear Research Center (Strasbourg) a cwo probe portable autonomous system using a P-type chlorine d~ped Cadmitzm-Telluride detector. Altough theoretical limitations of such single detector systems using INa devices are well documented in ~he literature, little inforlacion is available concerning specific limitations of such minia=urized CdTe probes. ~e have performed M~GA s=udles wi~h our system and correlated the results with a gamma-camera study taken as reference. We have studied 41 pa=ients with various cardiologic pa=hologies. ~ost of them have a dilated and/or dyskinetic left ventricule (LV) and/or dysrythmias. Af£er completion of the ganLma-camera study (g0mCi ~PmTc Alb%Lmin), the CdTe probe was placed on the patient's chest according to the LV actlvi~y r - 0.56 (y - O.78 + 15 ; n - 16) or fixed to the camera's collimator r - 0,85 (y 3,85 + 12 ; n - 25). For both a SO % diastolic :~un~s back-ground subscraction (EKES) was lard. No significant correlation was found when 5KGS was obtained from a second probe placed in the liver area. Specific technical problems lwlll be dlsc~ssed, These results emphasize the limitations of such a small single CdTe device, but posltionnlng and BKGS problems could be solved by the use of a 12 detector matrlx whose design will be presented.

351 ~.Rota Kops~, H,Herzog~, R.Gillessen~, Peber ~, A.Schmid ~, L.E.Feinendegen~

H.J.

I n s t i t u t e of M e d i c i n e , N u c l e a r R e s e a r c h C e n t e r Jfilich, FRG Fachhochschule (Polytechnic) Aachen-Jfilich, FaG 3N LINE M E A S U R E M E N T OF W H O L E B L O O D A N D PLASMA ACTIVITY CONCENTRATIONS USING A ~LASMASEPANATOR The determination of metabolic data measured by Ipositrun emission tomography (PET) is often based on models demanding a high sampling rate of both P E T and plasma values, In this case a icontlnuous withdrawal of whole blood and soDaration of p l a s m a is n e c e s s a r y . This paper des c r i b e s t h e t e s t s of t w o t y p e s of p l a s m a s e p a I r a t o r s a n d a d e v i c e f o r o n l i n e m e a s u r e m e n t of ~ h o l e blood a n d p l a s m a a c t i v i t y c o n c e n t r a t i o n s . In o r d e r to l i m i t t h e b l o o d v o l u m e w i t h d r a w n ~rom t h e p a t i e n t d u r i n g a t o t a l e x a m i n a t i o n t i m e of abou% 80 m l n t h e f l o w of w i t h d r a w n e d b l o o d Iwas to be <10 m U m l n . As a c o n s e q u e n c e of t h i s low f l o w o n l y t h o s e t w o p l a s m a s e p a r a t o r s c o m mercially available with the smallest volume ,(lml) on the blood side were tested. The filtration process was controlled by using rotating Ipumps I n t h e b l o o d a n d p l a s m a l i n e a n d b y m o n i t o r i n g t h e % r a n s m e m b r a n e p r e s s u r e (TMP) w i t h s e n s o r s o n t h e i n l e t , o u t l e t , a n d p l a s m a side. T h e o p t i m u m blood f l o w Was 4 , 7 m l / m i n a n d a stable filtration could be achieved at a plasma flow of 10% i n r e l a t i o n to t h e b l o o d f l o w f o r both separators. I n t h i s case t h e p l a s m a flow w a s 0 . 5 m l / m i n . S e p a r a t o r A h a d a s t a b l e TMP of 2.6 k P a , w h e r e a s s e p a r a t o r B s h o w e d a TMP I n c r e a s e f r o m 5.2 to i g k P a d u r i n g a t e s t of I 0 m i n , w h i c h i n d i c a t e s t h e d a n g e r of c o a g u l a t i o n . First tests with ~Ga labelled blood gave an imp u l s e r e s p o n s e o n t h e p l a s m a side w i t h a d e l a y t i m e of 8.4 m l n a n d a t i m e c o n s t a n t of 6.6 m i n , T h e s e r e s u l t s show t h a t t h e d e v i c e b a s e d on s e p a r a t o r A is a p p r o p r i a t e f o r p l a s m a s e p a r a t i o n under conditions as found in clinical studies, Additional correction programs are needed to take account of the time delay of the plasma Impuls response,

354 D D I Wright,

A D Chidlow,

C N McCollum

Departments of Surgery and Radiology, Cross and WestminsteP Medical School, W6 8RF

Charing London,

RADIOISOTDPE TIMING OF LOWER LIMB ARTERIOGRAPH~

MONPTORING PRESENT LIMITATIONS

Angiography is usually performed with X-ray exposures at pro-determined intervals. In severe arterial dis@ase, where circulation to the leg is slow, three or more series of films may be needed to achieve adequate N-rays. We developed and evaluated an isotopic method to time angiograi exposures_ Matched scintillation counters were placed on the upper and lower calf overlying the tibial ~rteries. Following 8rterial eannulation, ImCi ~f 99 Tc in 10 ml of saline was injected ever 3s. Radioactivity counts were fed to an IBM XT zomputsr, plotted and the ratio of distal to 3roximal counts calculated (Mu Med Software). ~he timing of the "best" Film was identified by radiologist and compared to the computer Jrediction. Correlation between isotope timing and "best" ~-rsy was closest when the ratio of distal over )roximal counts reached 0.7. When used to )redict the ideal time for exposure in nine zo~seeutive arteriograms this ratio was ~eproducible and correlated closely with "best" 7ilm times (r=O.gB, p<0.Ol). The ~ean (farm) ~redicted time was 16.33 f 2.2s compared to 'best" films at 16.44 ± 1.91s (range 9-24x). Such isotope techniques enable accurately timed X-ray exposure during angiography iPreserving cathode-r~y tube life and reducing film consumption.

282 355

356

357

C~4OBRO J.L.;I~ }~%RD J. ;~a2ARA G. ;CASTEJON I.; TABLe,CA M.J.;GALVAN R.;O.BERR3CAL J.

CLII~ICA ~

~

M.O, Koskinen Tampere Ufliversity Central Hospital Department of Clinical Physiology SF-33520 Tampere, Finland

KI~K~RD. M~DRID.~AIN

MONITORIZATICN OF V ~ q ~ R I ~

V O I Z ~ OJRVE.VSS2

ut/lization of a portable de~ector.VF.~] to study the ventricular v~lume curve beat by beat for a 1~-riod of 0 I=o 6 hrs, o f f e r s az~ -~Oz rant and va/ious infon,ation not only in t/~ st~ dy of coronary patients but to ohserv~ the heart response in d/fferents situations of heart ~ r k or after differents farr~ca. AND F~I~3D: We have studied 15 subjets (control 9~::~.p) and 7 patients with coronary artery disease. In the control group t/~ study has been dono dur3L~q an interval time o f 1.84~}.5hrs i n following situat/c~:rest,walk/ng,sta/rs and treadmill. ~he E.P. value has been corrected by the c~su3.ts o b t a i n e d w i t h g ~ a c ~ RE.~ULTS: I.- Control group I N ° E.F. Var.Vol ~DV E~V P~st 15 0.54+0.17 0.03+0.01 Walk 6 0,57~0,20 0,05T~.02 +3.2+2.1 - 2 . 2 + 0 . 7 Stairs 6 0.58"~O.23 0 . 0 6 ~ . 0 2 +5.8~-3.2 -4.3~-2.4 Tread6 0.65_+0.25 0.07{0.03 +223_~5.6 -6.7~3.2 II.- Coz~nary A r t e r y Disease We~t 7 0.32+0.18 0.02+0,01 Walk 7 0.33_d~O.O8 0,03~-0,02 +1.9+0,8 -i,1+0.4 Stairs 7 0.35+0.12 0.05~0,02 +2.1~0.8 -2,2~0.7 ~-eadm£117 0.33~_0.09 0.07{0.03 +1.8{0.7 +1.5T-0.7 Conclusions: With the portable heart detector is possible to study the variat/ons of the ventricu 1at functions in differents loa~s situations.Itis possible to evaluate the begininq and the gra de of heart response wSth far~aca or ergometric tests.It is not of Value for long periods of stu -ly. It iS very important to locate in right pos~ tlon the detector and without any mouvcm~nt.

358 IE.Rota Kops, N.Herzog, R,Dick, L.E.Feinendegen

•

A.Winkens,

[nstitute of Medicine, Nuclear Research Center ifilich, FRG

n~FLUENCE off SOM~ INS'I'I~LI~NTAL FAHAMETERS DN THE DETERMINATION OF QUANTITATIVE DATA [JgING THE PET-SCANNER Pc40g6-15WB A major aim of positron emission tomography [PET) is to obtain q u a n t i t a t i v e information of ~etabolic data. The measurement of these data Ls coRtrelled by the physical and instrumental Limitations of the PET-technique. This paper reports on the influence of various parameters ~n the determination of q u a n t i t a t i v e data. t h e measurements were done using a whole-body ?ET-scanner PC4096-15WE with an optimum s p a Lial resolution of about 5mm in the centre. For ~r~nsmlaslon measurements a r o t a t i n g pin source Ls used, which yields low r a t e s for random and ~cattered coincidences and on principle allows t h e determination of absorption factors even after tracer injection. The reconstruction is based ou filtered backprojection with selectable Ivalues of full width a t half maximum of the Ireconstructlon filter (WRF). The influence of WRF on the maximum and mean activity values was investigated using the wobbled mode. Changing the WRF from its lowest value of gram to 4ram and then to gram decreased the maximum measured a c t i v i t i e s by 29% and @g%,respectiwly, The corresponding mean a c t i v i t i e s decreased by 6% and 10%, respectively, The a c t i v i t y concent r a t i o n obtained in the a t t e n u a t i o n corrected, reconstructed images was underestimated by 5%, when the transmission scan was done after t r a ,cer lnjecUon. The analysis of p a t i e n t studies done with lSF~deoyxglucose showed a grey/white m a t t e r ratio of 3.7;1. This ratio is higher t h a n t h e ratio of g:l found with older scanners and is a consequence of a decreased p a r t i a l volume effect 4ue to the high resolution and the low s c a t t e r fraction of <5% of the P04096 scanner. The r e s u l t s s h o w ' t h a t the use of a h i g h - r e s o l u tion PET-scanner leads to only small errors in the determination of q u a n t i t a t i v e data,

]

•

QUALITY CONTROL OF ENISSION TONOGRAPHY - MEASURk-I~NTS IN FINNISH HOSPITALS 1987 Quality control measurement was carried out for 20 of altogether 23 Finnish single photon emission computed tomography systems (SPECT) in a cooperation project between hospitals; A cylindrical test phantom was constructed including non-active rods, hot line sources and an uniform section. For simplicity, only 99m-technetium has been used as radioactYvity. Imaging and reconstruction were performed in the same way in every case. Integral and d i f f e r e n t i a l uniformitles on the area of phantom were calculated both for central (CFOV) and useful fields of view UFOV) as in NDt~-standard. Relative depths of defects in images caused by the cold rods represent the contrast resolutlon. Full width of half maximum values (FWHM) of line sources represent the spatial resolution of the system. A computer program was written for semiautomatic analysis of images.

RESULTS: Integral uniformity

CF0V : UFOV : Differential uniformity CFOV : UFOV : Contrast for 30 mm cold rod : Spatial resolution (FWHM) :

Range 10.8 19.1 7.6 IE.5 23.7 13.4

~ -

36.3 36.3 24.7 24.7 68.D 26.5

% % % % % mm

Some malfunctions found in the testing show c l e a r l y t h a t laboratories have to put more e f f o r t to r~gular quality control.

359 A.Schmid,

j

~ I ~ . ~ P. C. Stanley, and W. R. Guth l e m ~ Oammascaics,2000 NuclearrJr~ve, Des Haines,IL.,U S A 60018

W.J. Maclntyre, T.S. Houser, B.J. Sulfa, O n r i s t i e and R.T. Go,

CV)LI,IMATOR ANGUI.ATION ERROR AND ITS EFFECT ON SPF,,CT. A simple radioisotope mchniqa¢ has h=cn devc.M;~ lO ri1¢asuzc~uIa~on ¢rror~ in cmlllmalOr @¢pla T~C oc~um compcms the measured poLnt source z~spo~se cfion (PSRF) with a lcssl ~qu¢~csfit to the t h e ~ n : ~ ] P&~F. Deviationsof th¢ data .from ~ e theo~fica]m~lei deper~ on Ib¢ soptal Iucallon ~ the angulatlon error VIY~IOi',With a I~ o1~i57CO sonrcg4.5 m dJslanlf1~rt ¢olIimn~,a compl~ pixgI-hy-plxglmap of s~r~1 re'ton can be obtair~l n 15 ndnntcs, The l~rge mh.-co to coJJJm~r distance g~.a tly magai.fi~ the:"~T¢ciof any aeptal =deviations, l~vigrioau of ~ 0,I" am rashly quanfitied. The tecimiqu¢ has b0cn v e r ~ through measurerncn[sca a uurnb~ of om'~gated foil oolllmat~. Pa:~at mcasureraents t ~ i m g d i f ~ n t o~/¢o~J~lmt~ g~ometries agrted on g pkd-by-pixd to.4- 0.05 RMS over the full collimator area. R¢sult~ we~: fotmd to be counI-indcpcnd~nl above 30 l m ~ .mint ooonm, and wore nol s~gaif~antb' alt~M b) ~J mdlioncount flood c ~ c d o m Angulafion errors ha Ihe loll commaKs-s stupid were found to I~ odeny,~l Jn (~mcdon 10~'lX~cd~r to the p~le~ of the individual foi g~ips and w ~ not coz~la~.xI with individual s~ps. M c a s ~ & v m ~ o ~ we~ small; typio]]y ~; 0.1 ~ " (P.~S). T ~ re'feet of random ~n=cfio~d ~ on spader r~solation in SPECT was eslimal~l by means of a ~omputtr slmMalica, R~omCucted .~olution for a ~ l a m d [2.AP (lowcn~gy ",ill pmpo~) collimator by only 1 ~ for an =sunmd =~Wa~on m ~ r al.tnbuti~ of 0.6" ~ /d/measurM sepml deviaticas feU comi=L*mblybelow this limit

360 J.H.

Cleveland C l i n i c Fo~ldation Department of Nuclear ML~dicine 9500 Euclid Avenue Cleveland, Ohio ~qI06 U.S,A. RAPID, LOW-COUNT QUN-ITY CCINTRgTECHNIQUES FOr SINGLE PHOTON~vllSSlON T(I~OQ~APMY. I A l t h o u ~ high count coJlection flood field~ and high resolution center of retailer measurements are needed to determine optirnun correction factors f o r single photon emissior I tcmography (SPEUt), c l i n i c a l measurements ot heart and brain are p r i m a r i l y performed witF low count rates, large pixel sizes ant reconstructed with smoothing/high Freq~enc~ roll-off filters. For d a i l y operation, acceptable quatit~ control procedures must ensure that the tomographic systems are operating w i t h i n l i m i t s at which no degradation of c l i n i c a l data w i l l occur. I t has been determined that this objective can be achieved with a three minute measurement of center of r o t a t i o n {32 oppesincj views of am o f f - a x i s point course at 5 seconds each) and a 10 minute measurement of uniformity {approximately 100 counts per pixe] for 3000 p i x e l s of a 64 x B 4 m a t r i x ) . Reconstruction of 2Ol-TI cardiac images and the Phelps phantom have shown that an average ~ixel deviation of less than one pixel can be tolerated with no loss of c l i n i c a l information. Uniformity measurements at 1000 counts per pixel average a standard deviation of g.5% with most SPECT cameras of ~qieh 3% is due to s t a t i s t i c a l v a r i a t i o n of the count rate alone, Regional v a r i a t i o n s less than an additional 2% can be tolerated with no production of a r t i f a c t s at the c l i n i c a l count rates and filter utilized. High resolution demands may make the requir~nts more stringent, however, the rapid, low count program described has provided a r e l i a b l e index of q u a l i t y assurance with less than ten minutes of corq3uterized operation.

R-Srejic I, D-Popov2, I,Sori~i~3 and M,Zuvela4 IInstitute of General and Physical Chemistry, 2Institute of Biophysics, 31nstitute of Pathology,Institute of 3urgery Faculty of Medicine, Belgrade, Yugoslavia PERMEABILITY OF HUMANSTOMACHTISSUES FOR WATEP AND RELAXATIONAGENT. NMR STUDIES, Comparative NMR studies of normal and neoplasmi human stomach tissues are performed on the basis of relaxazion agent (MnEDTA2-) permeation rate and cell membrane dtffuslonai pernleability RA. for water. MnEDTA2- permeation is followed i n d i r e c t l y by measuring TINMR relaxation time for water protons during the relaxation agent entry into tissue. Two to four times higher [ permeation rate has been found for neoplasmlc I tissues, in v i t r o . P~ is determined in tissue samples saturated wi~h MnEBTA2-, by measuring I the longest T1 components, T~, s e n s i t i v e to the I exchange of water molecules through the cell [ membrane. Pd values obtained for normal stomach c e l l s , Pd=(1,7±0,3)xlO-3cm s-I and Iymphoc tea t Pd=(1,3~0,3)xl0-3cm s ' l are in good agreement w th the repotted va ues for individual human c e l l s ( e r y t h r o c i t e s ) . Pathologically altered tissues showed supstan~ialy higher (2-3 times) cell membrane permeability for water, Rapid manganesse entry into tumor c e l l s is also opserved indicated remarcable changes in membrane(s) properties.

283 361 Fnfestin, G.P.*, A. Linden + , G , Frie~aru~*, H. Schicha + . * Dep~rtment of Radiology, University Hospital Cologne + Department of Nuclear Medicine, University Hospital, Cologne

P~ENAL EXCRETORY FUNCTION: GADOLINIUM-DTPA E N ~ M C E D FAST DYNAMIC MRI VERSUS RADIONUCLIDE RENOGRAPHY Fast gradient echo MRI with breath holding enables ex~ination of the ki~ineys with improved image quality due to supression of breathing artifacts. Following intravenous administration of Gado!iniknn-DTPA dynamic studies with repeated imaging at short time intervals can be performed to assess excretory f~Lnction of the kidneys. In 25 patients with normal (n-5) and hydronephrotlc (n=20) kidneys fast dyne/hie M~I of the kidneys was compared to radionuclide renography. Signal intensities in the renal cortex and medulla were measured in operator defined regions of interest. Time resolution was 6 to i0 sec. with a 12B-256x256 matrix. The relative! signal intensity plots provided a semiquantitative assessment of renal ftknction and correlated well with radionuclide renography findings (r-O,80). Thus fast MRI offers for the first time the possibility of high quality morphological diagnosis combined with a quantitative functional examination of the kidneys.

364 K. Kourfs, A. Musa, B. Taha, H.M. Ahdel~ B . D . Collier+ Faculty of Medicine, K ~ a i t University, Kuwait and +Medical College of Wisconsin, Milwaukee. USA.

CORRECTION OF THE BLADDER ARTIFACT IN HIP SPECT. SPECT enables the earlier detection of avascular necrosis of the hip. However, the "bladder artifact" occurs in 25% of the studies r e n d e r i n g t h ~ p a r t i a l l y or totally uninterpretable. In these cases, visualization of the femoral heads in the reconstructed images is obscured by broad shadows projecting beyond the bladder. The nature of the bladder artifact has been investigated. It is caused by bladder filling during the study (64 projections. 20 sec each, 64 x 64 matrix). This violates one of the necessary conditions for image reconstruction f r ~ projections, that of timeinvariance during data acquisition; the data are inconsistent and the reconstructions are dominated by the artifact. A multi-slice computational correction method for the removal of the bladder artifact has been implemented. The correction method operates on the projection data prior to image reconstruction. It ~edifies only those segments of the projections that contain contributions from the bladder. A sinegram is generated for each slice. Profiles are displayed at 6 preselected rows allowing the user to interactively deCermine the apparent bladder e x t ~ t . Polynomials are fitted depicting the a p p a r ~ t bladder be~mldaries and correction is applied within these boundaries. The contributions of the increasing bladder radioactivity and ~olume taking as referemce the first projection are removed. Transaxial and coronal slices reconstructed u~ing the corrected tomographic dataset do not suffer from the bladder artiact; ~he pelvic b~nes including femoral eaas become vlsua~izem.

f

363

t62

RUMBACH L,. ARMSPACH J,P., GOUNOT D. COLLARD M., CHAMBRON J,

Linden, A.*, U.P, F~restin +, P. Theissen*, H. Steinbrich +, H. Schicha* Depart/none of Nuclear Medicine, University of Cologne Department of Radiology, University of Cologne

ENAL PERFUSION-ASSESS~IENT RESONANCE IMAGING

WITH RA~ID MAGNETIC

TO evaluate the potential of MRI in the diagnosis of renal perfusion and renal vascular disorders 15 healthy subjects and tO patients with renal artery stenosis were studied using: i. ECG-gated d y n ~ i e gradient echo images in cine mode to assess flow phenomena in renal vessels. 2. Dynamic sequences of single slices with breath-holding (time resolution ].5-3 see.) after i.v. a~inistration of Gadolinium-DTPA With ECG-gated dynamic flow i ~ g i n g renal ~essels could be visualized in all healthy ~olunteers as high signal intensity structures ~t the usual anatomical positlon. ;n renal artery stenosis signal intensities wet, ;imilar but irregularities of the vessel walls ~n~Joled the d i a ~ o s i s of vascular disease. ~n hen~Ddyn~ically significant stenosis there /as delayed appearance of Gadoliniurn-DTPA in the ;enal cortex and delayed elimination from the sedulla indicating diminished perfusien. ~ast dl~namic ~ I offers the possibility to >brain morphological and functional infor~ti~n .n renal vascular disorders. Further tec~nnical .mprovement and experience is necessary to ~ssess the clinical relevance of the method.

365 E. Eenze r M. Olausen, R. Weller, A. Schmidt, P. Richter, F. Bitter,

INSTITUT DE PHYSIQUE BIOLOCIQUE 4. rue Kirschleger 67085 STRASBOURG CEDF.K pARAMETRIC ANALYSIS OF LESIONS OF MULTIPLE SCLEROSIS BY MRI The cerebral lesions of MS are characterised by edema and demyellnationwhioh evolve as a function of time. The great sensitivity of M.Rl i~ d~e, amongst other things,to the differences in the relaxation time between the different tissues and their biochemical composition. In the present study we proposed to study the evolution of the decay curves of the magnetlsation T2. The relaxa=ion time T2 is determined pixel by pixel from the analysis of the decay curves obtained from a series of 128 images using OPMG sequences. The mathemacieal analyses show that the experimental data may be adjusted to a mono exponential fonction characterised by a T2 time oorLs~ant or by a hi-exponential curve (charaoterised by a long T2 and by a short T2). The white matter of subjects presumed to be healthy ls eharacterlsed mos~ often by a mono-exponentlal our-vs. In constrast, the cerebral lesions of MS shows a hl-exponentlal curves. This indlcates the exlstanoe of a= least 2 voxel eonstltuents. The values vary from one patient to another.but they change above all as a function of time. The patients which have a recurrent form of MS have variable relaxation tlmes.which are vat/ high at the start of an attack, while the variation of the relaxation times for the chronic or clinically stahillsed form of MS is low. Nevertheless. it is not possible to differentlate the plates of these diverse clinical populations of MS from the NMR data alone. In conclusion, quantitative MKI allows a better approach to medical imaging and allows =o follow the evolution of the T2 of the in vlvo plates as a function of time. In opposite from a physiopatholoNieal point of view this method does not by itself, under present conditions. allow che appreciation of the biochemical composition of the lesions or to dlfferentla~e the old plates from the others.

366 D. Mellwig, V.E. Adam.

Divisions of Nuclear Medicine and Cardiology, University of Ulm, Germany THE CONTRACTION FRACTION - A NEW PARAMETER FOB QUANTIFICATION OF LV FUNCTION FROM GATED PLANAR Tc-99m RP-30 STUDIES. An attempt was made in this study to retrieve an EF equivalent from Tc-99~ RM-30 studies. Nest-exercise gated planar LAO images were recorded. Within 2 days, a gated equilibrium ventriculography also at rest and n.aximum exercise was performed for LVEF correlation. All attempts to obtain a LVEF equivalent iron a geometrical inner-edge-detection approach failed because of the poor outline of the inner LV edge in the Tc-99m BP-30 studies. Instead, I count based methods with different appoaches for count density scoring were developed and ~alida~ed in a computer simulation ~odel. Using the fractional increase of LV systolic count density (SCD) in relation to diastolic count density (DCD} the ability of the h¥ to "contract" the myocardial activity %owards the LV center can be quantified aSll contraction fraction (CF) = SCD/DCD. In CF/EP data pairs obtained so far the 3 methods showed a good correlation of r = 0.93, with EF = 1.36xCf + 7: r = 0.88, with EP = 1.95 x CF - 0.8 and r = O.S4, with EP = 1.25 x CP - 16, respectively. In addition to the global CF, a new hybrid of a regional parametric CAD image can be obtained by multiplying the enddiastslic planar LAO image (regional perfuslon defect) by the amplitude image from the same gated Ts-99m PR-IO sludy (with a hypokinesia at the same sit~). In conclusion, a Tc-99m RP-30 resting perfusion SPECT should be followed 5 y a ~a~ed planar rest- exercise study, sincs the latter might already Field important in~ormations regarding exercise-induced ischemia and thus avoid second Tc-99m RP-10 injection.

r.Bettinardi,

M.C.Gilardl and F.Fazio.

lstituto San Raffaele, Istituto Tecnologie Biomediche Avanzate - C.N.R., Univ~rsit~ di Milano, Milano, Italy. I ~ G E RESTORATION OF SPECT PROJECTIONS USING SINGULAR VALUE DECOMPOSITION TECHNIQUE (SVD). Tomographic images from SPECT systems are degraded by several factors hut principally by the poor spatial resolution and low count statistics due to the collimation system. In this work the (SVD) technique has been applied, for resolution recovery, on SPECT data, in order to improve image quality. The image forming equation may he described, in a n~iseless environment, as a system of linear equations as l=(D)o, where o represents the source image, i the degraded image and D the blurring matrix (BM). The SVD consists in the pseudoinversion of the BM using the associated singular values (SV~) and singular vectors (BVC).The SgD allows to control the "inversion" of the image forming equation, in terms of a trade off between the amount of no~se and signal quality, using only a limited number of SOL and SVC in the restoration process. The SVD was applied to the projection sinogram before the reconstruction. The BM was generated by the line spread function measured in the centre of rotation of the SPECT system. The method was tested on simulated and experimental data at different counting statistics. The optimum number of SVL and SVC, used to restore the projections, was determined on the basis of image quality improvement, estimated on the restored reconstructed images. A significant improvement of spatial resolution, contrast and recovery without reduction of the signal to noise ra~io was found on cold and hot lesion studies. The results demonstrate the validity of the SVD technique in the restoration of the SPECT images.

284 367

3ept. of Nuclear Medicine, Faculty of ~edicime, Kuwait.

N.We~ler, ~ ,

M.Clausen, W.E.Adam.

Divisions of Cardiology, West-Germany,

]ALCULATION OF EJECTION FRACTION (EF) FROM DUAL G A T ~ SPECT MYOCARDIAL IMAGING WITH rc-99m ~'THOXY ISOBUTYL ISONITRILE (MIBI). Two SPECT studies at ~ and ES were acquired in 11 patients(pts) with I}~ one •our after the IV injection of 20-25 mCi rc99m MIBI. THe ES study started at peak Rwave for 50 millisec, and ED one for sm~e :period of time at descending slope of T-wane. THe gap between hoth was calculated from EO~ tracir~s. Acquisiton for 180 from LPO to RAO, 64x64 matrix, 32 projections, 60 cardiac beats per projection. Reconstructed short axis slices with one pixel thickness, attenuation corrected and Ramp Harming filter cut off frequency 0.5. A program was developed to display symmetrical ED and ES shortaxis slices side by side with or without a selected threshold level. A circle is defined aro~md the outer land inner margins of the slices at each cut starting from the apex towards the base. THe program calculates all pixels with no counts or counts below the threshold within the LV cavity and all pixels with counts in between the two circles in LV wall. The ED, ES volumes. EF and myocardial volume is then calculated. The total n~yocardial activity is also calculated and data were correlated with those from contrast ventriculography histogroms of no. of myocardial pixels against cccmts is presented for ED and E5. The program will encounter problems when there is a defect in the myocardial wall of more than 25% of the whole myocardial circle (4 pts>. Mean calculated EF (8 pts) was 59.2 + 12.5 % versus CV 59 + 9%. We have developed a new p r o g r ~ and d~mmnstrated a new application for Tc-99m MIBI.

370 T. J . S ~inks, T.Jones

369

~68

{.M. Abdel-Dayem, K. Kouris, I.M. Hassan, ~. Taha, C. Constantinides, M. Nair, N. Belani

E.Henze,

P.Kress

Nuclear Medicine University of

an Ulm

Q U A N T I F I C A T I O N OF T H E A R E A OF SIGNIFIC A N T H Y P O K I N E S I A IN T H E RNV AMDLITUDE FUNCTIONAL IMAGE ON A PIXEL-BY-PIXEI BASIS. In radionuclide ventriculograph~ (RNV) the F o u r i e r a m p l i t u d e (FA) funct i o n a l i m a g e d e p i c t s a r e a s of d e p r e s s e d Icontraction. Analysis has been mad~ by visual interprebation. In t h i s stud] quantification of significantly dep r e s s e d a m p l i t u d e s on a p i x e l - b y - p i x e ] b a s i s is s u g g e s t e d , s e r v i n g as an alt e r n a t l v e to sectorial analysis wlt~ its k n o w n s h o r t c o m i n g s . A semiautomatically defined left 'ventricular (LV) region of interes~ (BOI) is p r o j e c t e d on the FA. The ind i v i d u a l v a r i a n c e of size a n d s h a p 8 of the L V SOI is n o r m a l i z e d to a standard c i r c l e (St) w i t h a predefined, fixed radius (R). For this transformatio~ the c e n t e r of g r a v i t y is c a l c u l a t e d and 720 radii are a t t a c h e d / c o m p r e s s e d to in p o l a r coordinates. This procedure w a s a p p l i e d to our RNV normal group, Icalculating mean and standard deviatio~ for e a c h p i x e l of the SC. Individual patient FA are then color coded t¢ normal and three different levels of s i g n i f i c a n c e . In a reversed transform a t i o n the o r i g i n a l s i z e a n d shape of the LV is restored, allowing direct comparison with the normal FA. Q u a n t i . f i c a t i o n of the a r e a of sign i f i c a n t l y d e p r e s s e d c o n t r a c t i o n in the FA on a pixel-by-pixel basis allows visual interpretation of the result, w h i c h is l e s i o n oriented rather tha~ a c c o r d i n g to some g e o m e t r y (i.e. sectors).

171 M.C.Gilardi,

J.D.Heather

and I

MRC Cyclotron Unit, Ha~ersmith Hospital. London, UK, and Istituto Tecnologie Biomedichs Avanzate CNR, Istituto S.Raffaele, Milano. Italy. ASSESSMENT OF QUANTITATIVE ACCURACY AND QUALITY CONTROL IN PET The theoretical advantages of PET in enabling accurate quantitation to be made is well known. The aim of the present study is to define the practical limits of accuracy in vivo and to make ~n assessment of long-term stability for one of the latest generation of commercial positron scanners. The scanner consists of 8 rings each of 512 EgO detectors separated by lead septa and yields simultaneously 15 tran~axial image planes. The transaxial resolution for clinical studies is 8 ~ (fwhm) and axial resolution 7 ~ (fwhm). Quantitative accuracy 0/Oi/ml) in line and volume sources scanned in air or scattering media was better than 5%, indltating that attenuation correction (usin S a retractable Ge-68 rlng source) was being perfo~ med adequately and that the influence of seatter was small.The relation between image counts and system count rate deviated from linearity at a corrected count rate of about I Mops (total system) true coincidences. The variation of count recovery with object size was assessed with (a) a head phantom containing spheres and cylinders of varying dla~ecer and (h) a heart phantom with varying wall thickness. The count recovery for a 1 cm diam object was about 50%. Statistical noise was estimated using phantom measurements in which count densities, equivalent to those seen in clinical data, were reco[ ded. A daily cheek procedure of detector unifo~ mdty and stability, using a Ge-68 plan source, was defined as the system quallty control. It is concluded that PET is an a c c u r a t e method of measurement within the limits of resolution, count rate and statistics but with the modern multi-flog scanne;s care must be exercised in performing regular checks of stability, uniformity, calibration and normallsation.

J AA S.... g . M i P .... Had Coppens. A.W.F. Rutgers~** T. Wiegman~* W. Vaalburg~* and J. Korf*. Departments of *Biological Psychiatry, **Nuclear Medicine, sod ***Neurology, Oroningen University, The Netherlands.

DOSE DEPENDENT FEATURES OF DRUG-RECEPTOR INTERACTIONS OF THE DOPAMINE D2 RECEPTOR IN RELATION TO PET. The concept of tracers has two basic assumptions. First, the substance Co be traced (the traeee) and the tracer itselfs are indistinguishable to the biological system. Second, the amount of tracer is negligible as compared Co the amount of the tracee and does therefore llOU perLubaLe the biuiuglcal system. These assumptions are not true in tracer kinetic drug-receptor PET-studies. Because no traeee is involved, nothisg is traced. Statements on the absence of biological side effects can therefore not he based on the concept of tracers. That a drug at very low "tracer" dose does not behave as a real tracer, is demonstrated 5y computer simulations and by experiments with N-(llC)methylspdperone (NCMSF) in rats and men, ~he latter by PET. It appears that the curve of the striatal/cerebellar ratio against the dose is most steep at the lowest dose and that particular features of drug-receptor interactions, e.g. positive cooperativity are to he seen at doses, which are usually considered as "tracer" doses. In addition, we found that the striatal/cerebellar ratio of NCMSP-radioaetivity in vivo, at a very low dose, deviate from what is expected from assumptions, usu~lly made in dopamine D2 PET-studies: e.g. independent specific sites in the striatum sod no specific sites in the in the cerebellum. Conclusions on the striatal/cerebellar ratio, detemined with PET. without considering the actual dose and cerehellar activity are challenged. The experiments were approved by the Ethical Commision of the Faculty of Medicine of the Groningen University.

Valentin Fidler, Ninoslav Margetic, Natasa Budihna, Milan Prepadnik

University Clinic for Nuclear Medicine, Ljubljana, Yugoslavia

ABBEBSMEMT ~NALYBI8 MOVEMENT

OF OF

RENKL BPATIAL

FUNCTION B~ R/%DIOIBOTOPE

D y n a m i c r e n a l s c i n t i g r a p h y c a n h e analyzed using standard methods by determ i n i n g : a/ s h a p e p a r a m e t e r s of k i d n e y r a d i o a c t i v i t y c u r v e s , b/ t r a n s i t t i m e s from deconvolution technique, a n d c/ principal components from factor analysis. O u r m e t h o d is b a s e d o n d e s c r i b i n g t h e spatial movement of radioactivity through glomerular and collecting t u b u l a r s y s t e m . In p r e p r o c e s s i n g p h a s e t h e k i d n e y i n h o m o g e n o u s b a c k g r o u n d is subtracted by two-dimensional cubic spline function interpolation and sequential back-ground normalization. The average distance of radioactivity distribution from point of kidney outflow and oumulative eliminated radioactivity are computed for both k i d n e y s s e p a r a t e l y in e v e r y s e q u e n t i a l frame. The following quantitative results can be assessed: starting time of kidney radioactivity outflow, partial clearance, fraction of eliminated radioactivity per minute, transit time index of glomerular and collecting tubular s y s t e m t etc. Initial results of the methodology show an improvement over standard a n a l y s i s in d e t e r m i n i n g the size and position of obstruction and index of kidney clearance.

372 IBM TAFANI 4 , JC VENDIE ~ , Y LAZOETMES ~ , COULAIS ~ . B DANET " ~ , E GUINAUD ~ Service de Mgdecine Nucl~aire CHR TOULOUSE Purpan- France • Clinigue de Neurochirurgle OHM TOULOUSE Purpa •" Service de M@decine Nucl~aire ONE TOULOUSE Eangueil

Model for imaging opiate receptors in the human brain by single photon emlssion computed tomography

For imaging opiates receptors "in-vivo" by PET various authors have used systemic injector of IIc labelled opioid compounds(garfentanylDiprenorphine) in primate and man, The accession of new neurosurgical therapy for chronic pain by intra-cerebro-ventricular (ICV) administration of opiates have allowed us to utilize a more important range of label~c compouhds and to consider the study of human opiate receptors by SPECT. Indeed direct administration of iEBI label led opioid compounds in the human oerebroventrJoular system gives many advantages : - administration through ICV access port leads to avoid both the problems lied to the perlphera] metabolism and to the crossin R off the blood-brain-barrier of substances administra ted by systemic injection. - opiates receptors involved in the analge : sy by ICV morpinotherapy localized in the walls of the 3 rd and 4th ventricles are then immediat 1E accessible. - radiotracer specific binding can be shif ted after ]CV therapeutic morphine injection. - finally, much lower radioactive doses are sufficient. O,S to 1 mCi (18,5 to $7 MBq). In this study, we compare the scans obtai~c from ]O patients suffering from intractable pain treated by ICV morphinotherapy who r e e e J ~ d an iE31 Morphine or 123~-FK $3824 (a highly potent synthetic MeteokephalJn analogue) ICV ~dministration.

285 375

374

373 i

I Depts. of Nuclear Medicine, Faculty of Medicine and Chest Hospital, MPH, Kuwait.

~epartment of Nuclear Medicine and Psychiatric Clinic, University Hospital-Rebro ) ~ Z a g r e h

:.H.U. Purpan, Toulouse - France JENTRAL DECUBITUS : A GREAT IMPROVEMENT FHALLIUM 201 MYOCARDIAL TOMOGRAPHY,

ON BRAIN PEREUSION IN PATIENTS WITH DEPRESSIVE PSYCHOSIS (DP) ASSESSED BY Tc-99m HMPAO A~D SPECT

IN

Diaphragmatic attenuation in 201 T1 180°myo=ardlel SPECT results in reduced specificity in the detection of inferior wall (IW) abnormalities due to possible attenuation a~tifaets and ~idenimg of the standard deviation (SD) of IW naximum counts circumferential profiles (CPs). To test if ventral decubitus which should result J n shifting down diaphragm and subphreni~ 3rgan~ could be a solution to this problem, we ~ysfematically performed 201 T1 redistribution ~PECT studies in both supine and ventral positions. We compared homologous medloventricular thick short axis slices by visual ~nterpretafion ~nd CPs a~alysis. Among twenty patients a posterio~i considered as normal on the basis of normal stress ECG ~nd ceronary arteriography, i~ presented a more [or less reduced activity in the IW in the supine study, none of them in the ventral study. The mean normalized supine CP showed a minihum at gg % ~ id % (i SD) in the IW- The SD de:teased to Qround 6 % in the angers lateral part 9f the CP. The mean normalized ventr~l CF was almost horizontal without no significant minimum [n the IW and the SD remained almost constant ~round 6 % along the whole CP. We conclude that ventral position drasticaly improves sensitivity and specificity in the evaluation of IW abnormalities by suDpressing almost completely attenuation artifacts and, by the way, the effects of high individual variability in left phrenic and subphrenic anatomic onfigupation and stomach degree of repletion.

Hemodynamic changes in brain perfusion were assessed using Tc-99m HMPAO and SPECT in eleven patients with DP undergoing ECT in anesthesia. In order to evaluate the effect of ECT only, each SPECT study was performed twice: only in ~nesthesia and du~ing ECT in anesthasi~ too. A dual detector rotatlng gamma camera (Siemens ZLC 37) interfaced to an ADAC 33ooo computer was used 20 minutes after i.v. injection of 74o MBq Tc-99m }LMPAO. Analysing oblique sections parallel to the O-M line, the regions of interest over the frontal (F), temporal (T), parietal (P), occpital (O), basal ganglia (Bg) and thalamus (Th) areas for each hemisphere were defined. The average number of counts per plxel for each region was obtained and the ratios for the ipsylateral and contralateral hemispheres were calculated. In each patient during ECT a pronaunced decrease of perfusion was found in O, F and BE regions in comparison to the baseline study. The obtained results confirm our hypothesis about ishaemie effect of ECT on brain perfusion. The possible explanation of mechanisam of action will he discussed.

l

376 B.Saitta. A.Savi, P.Uerundinf, G. Ferlin.

K. Kouris, M. Nair, I.M. Hagsan, C. Constantinides, N. Belani, H.M. Abdel-Daye~.

J.P. ESQUERRE, F.J, COCA, S.J, MARTINEZ, ,R.F. GUIRAUD

~ , V. Medved , M. ga§i6, N. Topuzovi6, I D. Ivan~evi6

P.Zanco,

M.Clausen, E.MENgE, F.BITTER, W . E . A D A M . Divisions diology, Germany.

Ospedale di Castelfranco Venets, Trevlso, Italy. Istituto Scientifico San Raffaele Milano, Italy. COMPARISON BETWEEN 180 ° AND 360 = SPECT MYOCANDIUMPERFUSION STUDIES WITH Tc-99m MIBI. Perfusion myocardial SPECT studies ~ith Tc-99m MIBI with 180 ° (HAS to LPO) data collection was carried out and compared wit~ full 360 ° rotation in the attempt to optimlz lesion detection. We examined 6 patients wit no ceronar'y arterin~arctlon.diseaseand II o~atlent with myocardial 740 M g q Tc~99 MIRI were injected i.v. 1.5-2 hours ~efore dat~ collectfon. The -camera was fitted with a parallel hole c~llmator. Angular sampling w ~ 5.6 °, the matrfx size was 64x54 and the whoT~ acqufsition time was 30 min for both 180 ° an 360 ° revolutions. Transaxial slices we o~ reconstructed by the filtered hack-f~iter.rOjectio method using the Butterworth N~ attenuation correction was performed. Section~ parallel to heart axes were obtained fro transaxial tomograms. In the normal patients determfned the ROI (18xl8 ~ ) count ratio between the posterior and apical walls (P/A) in the transaxial slices. We have compared the counts in 4 myocardial ROl's (placed at 0",90°,180 ° and 270 ~ on the myocardial wall in a short axis central slice) wlth those In 4 background ROl's (each placed adjacent to the respective myocardial R0I) and we have averaged the resulting counts to calculate fma e contrast (heart counts - bkg counts dlvlded ~7 bkg counts). Due to the tlssue attenuatlon P/A ratio was lower in 180 ° sampling althougt not statistically different. Statistics and contrast images were b e t t e r in the 180 ° reconstructed slfce: counts in the m ocardim w a l l were l g - 2 0 Z more t h a n i n t h e 3~0 ° scan contrast range was 6.8 - 11.2 in the 180°scal and 4.0 - 5.3 fn the 360 ° scan. In infarcted patients defect to normal wall ratio was calculated in different planes depending o n the site of infarction, Thls ratio was signifieatively lower in the i80°scans (p
]

I ]

180 °

V~US

360 ° SPECTUSING

1 8 0 ° acquisition has been recommended for TI-201 SPECT and is preferred over 360 ° acquisition because of reasons related to the low energy of T1. RP-30 (Tc-g9m 2 metho~y Isobutyl Isonitrile) has been successfully evaluated for myocardial imaging. Being labelled with Tc-99m which has a higher energy than Ti-201 the questionwhether ]80 ° is better than 360 ° acquisition has been answered in this study. Ten patients (pts) were imaged after the i.v. injection of RP-30, They had two separate acquisitions in s ~ e setting one for 180 ° (5 pts) from 120 to RAO 32 projections. 64x64 matrix, 20 seconds/projection. The second acquisition for 360 ~ (I0 pts), 64 projections, 64x64matrix, 20 seconds/projection. We c(~pared six sets of processed image from 180 °, 360 ° and 180 = reconstructed from th~ 360 ~ acquisition, in all with and without use of attenuation correction. A profile was generated in the sane mid short axis slice, for all studies. The following parameters derived from the profile were compared: I) peak/valley ratio 2) Width at I/3maximu~ over peak of sept%~ ~ d lateral wall 3) Distance between the two peaks at I/3 maximum representing the LV cavity, The results indicate that 180 ° acquisition with use of a e r a t i o n correction i~ processing has the highest peak/valley ratio, narrowest width of sept~m at I/3 max. and widest LV cavity. We conclude that for ~ - 3 0 SPELT studies 180 ° acquisition from LPO to NAO and use of atter~/ation correction in processing is recommended and has an advantage over 360 ° acquisition.

378

177 P.Zoli,

CO~ARISONOF Tc-ggm RP-30.

of N u c l e a r University

P.KRESS,

B.WELLER

M e d i c i n e and Carof Ulm, West-

INTEG~tATED SINGLE-PHOTON EMISSIO] T O M O G R A P H Y (ISPECT): A F A S T A L T E R M A T I V ] FOR RADIONUCLIDE VENTRICULOGRAPH~ (HNV). G a t e d S P E C T in R N V e x a m i n a t i o n s ha= s h o w n p r a c t i c a l l i m i t a t i o n s , m a i n l y du, to time r e q u i r e m e n t s . A modified, fasl aqulsition/processing method is th, p u r p o s e of' this study. The projection data are acquire, f r o m D P O to RAG with only 16 step: ( a n g l e s ) and 16 f r a m e s p e r heart cyl~ in a 64 m a t r i x . D u r i n g processing all horizontal lines that contain th, v e n t r i c l e s (but as little atrium a~ p o s s i b l e ) are i n t e g r a t e d to one line A l l 16 l i n e s of the heart cycle are s t a c k e d on e a c h o t h e r into a new matrix, one for each angle. Following backprojection the sequence of the transversal slices represent a cine d i s p l a y o f the v e n t r i c l e s in an axial view. T h i s is e q u i v a l e n t to an imaginary camera position directly cranial of the heart, but e x c l u d i n g foreand background. The a c q u i s i t i o n time is r e d u c e d to 8 min. The a n a t o m i c a l d e f i n i t i o n of the v e n t r i c l e s is m u c h i m p r o v e d b y ISPECT, s u c h that s e p t u m h y p e r t r o p h y is easily v i s u a l i z e d , w h i l e in the same investigation the global ejection fraction (EF) a n d the r e g i o n a l EF at the apez m a y be a s s e s s e d . Left-to-right strok~ c o u n t r a t i o s s h o u l d be less h a m p e r e d b~ atrial contaminations. W e feel that ISPECT works technically, p u t s l i t t l e b u r d e n on the p a t i e nt, a n d adds i n f o r m a t i o n to the standard planar technique.

D.Brecht-Krau~,

W.E.Adam

/ n i v e r s i t y of u l m D i v i s i o n of N u c l e a r 7900 Ulm, F R G

Medicine

BloodpooI-SPECT in the d i a g n o s i s of h e p a t i c h e m a n g i o m a : w h a t is m o r e im)ortant, e a r l y or d e l a y e d i m a g i n g ? ? c - 9 9 m l a b e l e d red b l o o d cell b l o o d f l o w and d e l a y e d b l o o d pool i m a g i n g is w i d e l y a c c e p t e d as a r e l i a b l e , a c c u r a te m e t h o d for the d i a g n o s i s of h e p a t i c h e m a n g i o m a s . T w o c a s e s (i - h e p a t o c e l lular disease,l - metastasic disease) d e m o n s t r a t i n g l i t t l e m o r e u p t a k e of T c - 9 9 m l a b e l e d ted b l o o d c e l l s in the l e s i o n of the l i v e r o n l y in the e a r l y p h a s e (20 - 30 m i n u t e s p.i.) b u t not in the d e l a y e d p h a s e (2 - 3 h p . i . ) c a u s e d us to c o m p a r e the S P E C T imag i n g s of b o t h p e r i o d s . In a r e t r o s p e c tive s t u d y 55 h e m a n g i o m a s ( v e r i f i e d by h i s t o l o g y or CT) c o u l d be a n a l y s e d . E a r l y p h a s e (20 - 30 m l n p.i.) and the d e l a y e d p h a s e (2 -3 h p.i.) w e r e compared together. Nil 55 h e m a n g i o m a s d e m o n s t r a t e d h i g h u p t a k e in the d e l a y e d p h a s e . In 41 h e m a n g i o m a s a p o s i t i v e r e s u l t in the e a r l y and in the d e l a y e d p h a s e w e r e D b s e r v e d . 14 h e m a n g i o m a s i l l u s t r a t e d high u p t a k e of T c - 9 9 m l a b e l e d red b l o o d c e l l s o n l y in the d e l a y e d p h a s e (two u n t i l t h r e e h o u r s a f t e r i n j e c t i Dn). T h e r e w a s no h e m a n g i o m a s h o w i n g e v i d e n c e of f o c a l s e q u e s t r a t i o n of red ~lood c e l l s o n l y in the e a r l y p e r i o d . ~e c o n c l u d e d e l a y e d b l o o d p o o l i m a g i n g is the more i m p o r t a n t one for d i a g n o sing h e m a n g i o m a s of the l i v e r .

286 379

380

381

O. MESSIAN, MIM. YAVARI, J.FI FLEJOU*, Y. MENC**, J P. BENHAMOU***, B. 80K.

Bi N ~ g e l e - W 6 h r l e ( 1 ) , N i c k e l 01(~), ~aus W.(2), ~ n e r D.(1), H a h n K , ( I )

Liberato~e M . ( * ) , Baemi S . ( * ) , Di Roceo E . ( * ) , Pau ~.(++), Pigorini 6.(**), Scopina~o F.(*), Centi Colalla A. (+).

Services de MEdecJne Nuel~aire, * d'anatomopathologic, *t de radlologie, *~t d'h~patogastroent~roloHle, HGpital Beaujon, F-92110 Cl~cby.

D e p a r t m e n t o f N u c l e a r NedlClne(l) Department of Radiology (2) Johannes Gutenber~-University, Nainz, BRD

(*) Section of Nuciea~ Medicine, Department of Experimental Medicine, University I'La Sapienza" 00161 Rome;(+*) Nuclear Medicine Dept., Ospedale "C. Eorlanini", 00146 Rome.

IS THE 99m TD COLLOID SPECT USEFUL TO DIFFERENTIATE FOCAL NODULAR BYPSRPLASIA FROM ADENOMA OF THE LIVER ? Focal nodular hyperplasia (FND) and hepatic adenoma are two uncommon tumors of the liver. NO single imaging method permits an accurate discrimination between these 2 types of benign tu~ors. The aim o f this study based On 13 cases of benign tumors was to assess the results and the interest of 99m Tc colloid single photon emission computed tomography (SPECT). All patients were women, ~Ith a mean age of S6 ± 7 prs (range, 87-SO). Sloven of them were affected by FNH ; Five of which were confirmed by histology, [n the others, the diagnosis was based on concordance of all the tests with eiJnlcal and biochemical Features : two cases were ~denomas, confirmed by histology. In adenoma, the sclntigraphic appearance was a l a r g e circular well de]imited hypoFixatlon area in both cases. The CT scan appearances before and after administration of contrast medium was heterogeneous and sonograms showed hyperechogenielty in one case and isoeehogeniclfy in the other In FNH, SPECT showed hyperFixation Jn 3 cases, and hypofixation in 8 cases. Dynamic CT scan s t u d i e s showed a major t r a n sJent and homogeneous c o n t r a s t hyper enhan cement, associated ~ith a c e n t r a l hypodense scarf i n 6 cases. Sono~rams were not c o n t r i butive. However a SPECT h y p e r f i x a t J o n and/or a

transient hypervascularity with central scarr were detected i n 8 p a t i e n t s . In conclusion, 8FECT l s of interest in the diagnosis of benign liver tumors, providing a strong argument for FNN i n case o£ hyperfixation.

382

C O M P A R I S O N AND S E N S I T I V I T Y OR P L A N A R S C I N T I G R A P H Y A N D S P H C T - T E C H N I Q U E IN PATIENTS WITH CAVgRNOUS HEMANGIOMAS OF T H H L I V E R The c a v e r n o u s h e m a n g i o m a c a n he v i sualized using labelied red blood cells. In a r e t r o s p e c t i v e a n d p r o s p e c tive s t u d y 72 p a t i e n t s w i t h or w i t h s u s p e c t e d cavernous l l v e r - h e m a n ~ i o m a s w e r e i n v e s t i g a t e d hy b l o o d - p o o l - s c a n ning. In a d d i t i o n to the s e q u e n t i a l i m a g e s we u s e d a c o m p u t e r - s u b t r a c t i o n m e t h o d and in s e v e r a l o a s e s a E r E C T r e c o n s t r u c t i o n . We c o m p a r e d the plan a r scan and E R E C T w i t h C T a n d ultrasound. ]0 mCi (370 Ned) g 9 m - T c l a b e l led r e d b l o o d c e l l s w e r e i n j e c t e d a n d sequential images were acquired every 2 m i n u t e s d u r i n g a t o t a l time of 32 m ~ n u t e s . A f t e r w a r d s planar v i e w s in a n t e r i o r , p o s t e r i o r and r i g h t l a t e r a l position were performed. ErECT-Studies f o l l o w e d i I/~ - g h later. Cavernous hemangiomas show a typical p e r f u s i o n - p a t t e r n ; d u r i n ~ the f i r s t mdnutes we f o u n d a r e d u c e d a c t i v i t y w h i c h was i n c r e a s i n g later. M i n o r heman~iomas (
383

DI Dodi 5, S. Lon~arid, )i Anti~evif

DIAGNOSTIC ACCURACY DF SPET WITH 67-Ga-CITRATE IN THE ASSE5SMENT 0E MEDIASTINAL METASTASES ~LUNG CANCER. Planar scintigraphy and SPET were carried out using 67-Ga(1580 kBq/kg oF body weight) zn a series of 34 patients with brenohogenic carding ma but without ~adiographic evidence of hzla£ and mediastinal abnormalities. The s£udy was considered as posi£ive zf the mediasLinat r e g i o n showed increased activity at 72hrs aFte the injection of gallium. All patients unde~went thoracotomy and hzshological evaluation of excised specimens was pecFormed. Sensitivity, s p e c i f i c i t y , accuracy and, using Bayesian analy sis, prior (premtest) and posterior(post-test)probabilities of having mediastinal involvement For p l a n a r scan and SPET (P(D+/T+) and P(D+/T-) were calculated for several values of prevalencos o f disease. Planar scan gave a d i a g n o s t i c sensitivity of 52~ and a specificity of 89~ For detection of mediastinal involvement, whereas 5PET demonstrated a s e n s i t i v i t y o f 62~ and a specificity of 90~. Bayesian analysis of results demonstrated a higher post-test probsbi liLy of mediasLinal ~nvolvemen~ throughout the-range of pre-tesh p~obabzlity using 5PET. The discrim~nant Factor was maximum at the pre-tesL probability ranged between 35~ and 40~, where the uncertainty is high. 67-Ga study, while reducing the Ialse-positive incidence, plays an ancillary rGle to TCT for detection of hilat and mediastinal metastases of pulmonary carcinoma.

384 Kne~aur¢k K,, King M. and Glick S.

Hilditch , 3.KI Pavidson and A.T. ElJiott Department of Nuclear Medicine, University or Massachusetts Medical Center, Worcester, MA, USA

D~partment of Nuclear Medicine, Orthopedic Clinic University Hospital Hebre Zagreb, Yugoslavia

Pert

SPECT IN DIAGNOSIS OF LEGG-PSRTHES DISEASE. (COMPAKISON WITH p L A N A K A N D P I ~ O L E SCINTICRAPH~

DIGITAL FILTERING OF THE BLAOOER FROM SPECT BONE S~UDIE$ OF THE PELVIS

Bone scintigraphy should be routinely perfomed when Legs-Perches disease is suspected. In the last year SPECT was included in diagnosing of Chis dlsease with planar and pishole sc~nbigraphy We examined 17 patients with suspected Legg-Perthes disease. For all patient~ tomography was done 2-4 hours after i.v. app~.ication of 99mYc MDP usin8 LFOV E a ~ a camera with parallel hole ~nd pinhole collimator. SPSCT was perfomed with dual-head rotabing camera and data were )reprocessed by convolution filter smoothing an( :econstrucbad with Butterwor~h order 5 filter. ]utoff frequency for both was 0.8 of Nyquist frequency. Our results showed that seAsitlvy of SPECT was similar to pinhole scintigraphy and the both methods were mote sensitive than planal seintisraphy. [n comparison with pinhole sci~tigraphy SPECT better delineated the shape and ;ize of necrotic area and invol~ent of K r ~ h )late. Extension of necrotic aEea can be a ~ro~nostic sign of late complications as contra :Lure of hip, and invol~q~ent of g~owth plate influenced growth of the patient.

C l i n i c a l Physics , Royal I n f i r m a r y , Western I n f i r m a r y , 61asoou I

$PECT bone studies of the p e l v i s are often compromised by a r t e f a c t s uhich are produced by the presence u i t h i n the bladder of high and changing l e v e l s of activity. To reduce the levee of a r t e f a c t production a data processing technique for the removal of bladder a c t i v i t y , prior to r e c o n s t r u c t i o n , has been deveIoned. The method involves t h e r e p l a c e a e n E of count values in the b l a d d e r on all projection views by daEa u b i c h are r e p r e s e n t a t i v e of the a c t i v i t y in surrounding s t r u c t u r e s . This is achieved by performing a b i l i n e a r i n t e r p o t a t i o n of the data i n the p i x e l s around the perimeter of a r e c t a n g u l a r region which has been chosen to incIude the bladder. The p o s i t i o n of the bladder region on a l l proJecEion views can be determined by d e f i n i n g s sxnele region of i n t e r e s t on a sinogrmm vieu. This considerably reduces the time and labour involVed in a p p l y i n g the technique making i t s u i t a b l e for r o u t i n e use. The method was tested by examining a group of t h i r t e e n p a t i e n t s r e l e n t e d f o r examination of avascular necrosis of the femGraI head. The number of s t u d i e s in uhzch the t r a n s a x i a I sections uere not i n t e r p r e E a b i e uas reduced from G/13 to 1 / i 3 . For the coronal sections , u i t h o u t bladder removal , a f a l s e p o s i t i v e diagnosis of avascuiar necrosis uas made in [/13 s u b j e c t s due to the presence of cold area a r t e f a c t s = these uere removed in e l i cases by the data processing method, Thus , ~ignificant imppovements in image q u a l i t y 0ere observed , oartioularly with respect to the l e v e l of a r t e f a c t production , which increased the number of cases in ~hich a confident and c o r r e c t diagnosis uas made .

INVESTIGATIONOF GEOMETRICALDISTORTIONIN GRECT IMAGING

In some recent papers it have been shown thatsections obtained from 180 O sampling in SPECT 1'maging suffer From geometrical distortion.Mostly such studieshave taken intoaccount resolutioneffects only. Although the resolutioneffectscontributeto geometrical distortion in 180O sections it was hypothesized that the attenuation and reconstruction effects may also be slgniMcant factors In causing that distortion. To investigate resolution and attenuation effects in addition to reconstruction errects in SPECT, a set of point sources at different positions in cylinder or radius 15.24 cm were acquired and corresponding point spread functions (PSF's) were reconstructed. To investigate resolution effects, full width at half maximum (FWHM) and of full width at tenth maximum (FWTM) of these PSF's with difrerent sampling techniques were deteiTninated. The results or a theoretical point source study were compared with the intensity values of reconstructed PSF's for different sampling techniques, showing excellent agreement. The results of this comparison showed that the I BeO sections sufrer from great changes in sensitivity within the reconstructed section. This Is in contrast to 3600 sections were arithmetic and, even better, geometMc averaging or opposite projections preserves unirormity or sensitivity. This nonuniformity of sensitivity is a major cause of geometrical distortion in 1800 sections in addition to resolution effects. The results of clinical data in which the same sections were reconstructed rrom different sets of projections have confirmed our simulation and point source results. As conclusion we can say that 3600 sampling is favoured over 1800 especially ir BPECT is used For lesion sizing or determination of actual volume

287 387

186

385 B. BEN Y0~NES, J. MRS, B. BIDET

D'Agata A,Cefsratti C,Dortolozzi D.Cappelli G M.

Laboratoire de Biophysique et de M~decine Nuel4aire - C.H.E.

Lyre,

N.

A.Psall~das,

Venetsanakis, C.Hourdakis,

E.

Drakou*,

N.Touban~s

Jean Minjoz Araeteion Hospital, Athens University *Greek Anticancer Hospltal "Ag. S a v e s "

25000 BESANCON - C4dex - FSANCE

I

A NEW ALGORIT}RdFOD AUTOMATED BODY CONTOUB COD~ENSATION E F F E C T IN

DETECTION IN SPECT. In order to perform accurate quantitative studies in single photon emission computed tomography (SPECT), scatter and attenuation compensation are required. These corrections need the knowledge of the attenuator boundaries, A lot of contour detection methods were developped, working on the acquisitions (photopeak and seat ter windows) or, indirectly, on the reconstructed slices. The procedure presented here use the Compton projections, is easy to implement, and is very fast without secondary computation like Fourier descriptors. The algorithm can be divided into four steps : - smoothing and thresholding of the data, - computing the masks from the previous step, and "LOGICAL OR" between opposite masks, - back-projection Of the resulting masks, - automatic thresholdi~g of the computed slices. These binary contours are the true area of the attenuator. The results of the computer simulations and the real phantoms or clinical studies demonstrate the efficiency and the reliability of the procedure. This one never underestimate the attenuator area and the overdetermination does not excess a few percent in the worst case. This last condition is necessary when an accurate scatter and attenuation compensation are needed without oscillating solu'tions. The restoration of the count levels within the computed slices is good, even in the presence of noise. This approach allows correct determination of volumes and different parameters of clinical interest in SPECT.

388 ;. Riccabonat S. P a w e l k a , )'t~tter, P. E h l i c h

OF SCAq'FER A N D A B S O R P T I O N SMALL SUPERFICIAL ORGAN SPECT TOMOGRAPHY

In an attenuation correction SPECT procedure, the build-up of scattered radiation m u s t be t a k e n i n t o a c c o u n t . T h e p u r p o s e of t h i s w o r k h a s been to show that in cases of small organ reconstructions t h e r e is e compensation effect between scatter and absorption. Cylindrical, 1 0 - 4 0 n~n d i ~ n e t e r , homogeneous sources To-99m in 4 c m d e p t h of a w a t e r p h a n t o m w e r e u s e d for the reconstruction of t r a n s v e r s e sections. " h e a x i s of t h e s e s o u r c e s w e r e a l i g n e d w i t h t h e a x ~ s of r o t a t i o n . All tomographic examinations were perfor~ned w i t h a 20~ energy window centered on the p e a k of T c - 9 9 m , for 180~-camera rotation and 45 angles. Reconstructions were made with Hanning back projection filter. Frame size u s e d w a s 1 2 8 x 1 2 8 a n d z o o m e q u a l 2. Spatial distribution of activity across the uncorrected as w a l l as the post reconstruction corrected sections of t h e c e n t r a l p a r t of t h e c y l i n d r i c a l sources were measured and evaluated. An analysis, of th~ energ~z spectra obtained by an 180 rotation and step of 4 w i t h t h e a b o v e phantoms, showed the nl~er of prlmary photons that decrease and the scattered events that appear for each projection which were estimated by convolving the measured projection data with a source -in-air distribution function. "his technique showed that ~n cases of small superficial organs, as Th,y r o ~ d g l a n d , quantitative measurements can be made in uncorrected transverse sections with accuracy up to ~7~ because of the compensation between scatter and absorption effect.

389 M.

Oberlad-

H.D.Roedler, U.Lechel, *g.Leinslnger, eE.Moser Institut fur Strahlenhyglene des gundesgesundheltsamtes, 8042 Neuherberg und ~Klinikumgrog6adern der Unl .... it~tMgncben,

~niv.-Klinik f~r Nuklearmedizin und ~trahlentherapie, Innsbruck~ Austria

~ N S O L V E D P R O B L E M S OF D O S I M E T R Y ~HERAPY F O R M E T A S T A T I C THYROID [TCM)

OF 131 CANCER

I-

.31 I - t h e r a p y is a w e l l e s t a b l i s h e d me~hod f o r the m a n a g e m e n t of TCM. S o m e faiures to c o n t r o l the d i s e a s e , h o w e v e r , light be a t t r i b u t e d to i n a d e q u a t e d o s i netry. A c c o r d i n g to d o s i m e t r i c criteria, regional uptake {RU) in m e t a s t a s e s , tunorvolume(TV) and effective half-life (T/2) w o u l d be the d o s e - d e t e r m i n i n g par a m e t e r s , w h o l e b l o o d d o s e s s h o u l d be (ept 4 200 rad. We t r i e d t h e r e f o r e to c o ~ celate the p a r a m e t e r s mentioned above ~ith the c l i n i c a l c o u r s e of p a t i e n t s ~ith TCM. A m o n g a l m o s t 2 0 0 0 t h y r o i d c a n =er c a s e s s e e n in o u r s e r v i c e s we c a r e ~ully s t u d i e d i0 p a t i e n t s w i t h p r o v e n recurrences and/or metastases. TV was ~ s t i m a t e d by C T - s c a n ~ i n g a n d by E R E C T ~fter 131 I, RU w a s e s t i m a t e d o v e r ROI's ~fter 131 I in c o r r e l a t i o n with phantom ~tudies a n d e f f e c t i v e half-life by whole )ody r e t e n t i o n . W h o l e b l o o d d o s e s w e r e z a l c u l a t e d a c c o r d i n g to the f o r m u l a e of ~enua e t al. C l i n i c a l c o u r s e w a s t h o coughly evaluated. It b e c a m e a p p a r e n t ~hat the a p p l i e d m e t h o d s to deter~nine )primal 131 I d o s e s a r e i n a d e q u a t e : TV ~aried b e t w e e n C T - r e p o r t s a n d 131 I - S P E C ~23 %), R U e s t i m a t e s w e r e o b v i o u s l y ~rossly erroneous due to g e o m e t r i c factors so t h a t e v e n in p a t i e n t s showing a ~ood r e s p o n s e to 131 I - t h e r a p y in d o s e s )f 100 - 183 m C i a n d w i t h o u t h e m a t e l o g i =al c o m p l i c a t i o n s calculated tumor doses lever e x c e e d e d 2 5 0 0 f a d s , We t h e r e f o r e = o n c l u d e t h a t 1 3 1 I d o s l m e t r y in t r e a t nent o f T C M e v e n w i t h t h e m e n t i o n e d ~ e c h n i q u e s is an u n s o l v e d P r o b l e m ~ i n zorrP]ation with phantom studies.

COMPARATIVE EVALUATION OF PATIENT DOSE FSOMI IMMIFNOSCIMTIGNAPHY WITH SPECIAL ~EFERENCE TO' ADMINISTERED ACTIVITY The total body retention and biodistrlbution of 131 I-, Iii In- and 99m To-labelled monoelonal antibodies (MABs) was measured in more than 1DO patients with a scintillation camera by conjugate countin~ as a basis for evaluat m ing the radiatlon dose to the patient from immunoaclntigraphy. Our data are yielding the followin H values of effective dose equivalent per 100 MBq administered activity: approx~ately 25 mSv for 131 Iand for iii In-labelled anti-CEA I F(ab')p and 0.9 mSv for 99m To-labelled intact anti-tEA antibodies• From these results, it is concluded that a dose reduttlon by an approximate factor of 4 may 5e achieved by administering 800 MBq 99m Tc anti-SEA rather than 120 MBq 131 I- or Iii In-labelled anti-tEA. Conversely, if the short physical half-life of 99m Tc is preventln~ a correct diagnosis by the need to scan too soon after administration of, e.g. 800 MBq, an up to & times higher activity mlght be considered. This would result in an effective dose equivalent comparable to that f r o m 120 MBq 131 I or Iii In antl-CEA. However, the additional henefit from a 99m Tc iscan that is delayed by two half-times (12 h) still needs to be investigated. !Optimization of administered activity of 19gm To- (and 123 I-) labelled MASs may improve diagnostic results and - in comparison to ' labelling with 13| I or ill In - at the same time reduce the exposure of patients from !mmunoscintigraphy.

l

Nuclear medicine Unit,Florence,Italy

HYBRIDIZATION RADIOMETRIC ASSAY OF HBV-DNA USING 125-1 DNA PROBE Many authors stressed the elevated diagnostic value of spot hybridization for assay the circt lating level of HBV DNA. This tecnique therefo re is still indaginous and time~@onsuming and often not quantitative. The use of a standard curve of H~V-DNA and the counting of the spots allows a quantitative evolution of this techni= que also if the nick-translation using S2dCTP and/or 32dTTP,needs of a Beta counting of stan= dard and samples. The incorporation in the probs of a I25dCTP seems advantageous for the semplicity of Gamma counting and the longer survival time of this tracer.With the aim to evaluate this possibility,we make a nick trmnslation by i25dSTP.Usin g this probe we a s s ~ e d the mome s t a n d ~ d and samples with both the traoers.UsiD two nucleotides labeled by 32P and one nucleoti de labeled by 125I the yeld of incorporation w~ respeetivaly 42% andg8%,the specific activity of the probes 200 and 70 uCi/ug.The spots were counted respectively in Beta end in Gamma counter.The sensitivity evaluated by l.d,l. was respectively for 3EP and 125I 2.7and 2.5 n~ The values of HBV-DNA concentration in IS s e r ~ samples were tightly correlated (r=0.00,P 0.00] Because the same sensitivity and hight corrals= tion of this results,we belleve that the use of this tracer can be a new importsnt tool for the access of this sophisticated technique in diagnostic routine•

390 FS Prato, L geese.

Department of Nuclear Medicine, St. Joseph'~ Health Centre o f London and U n i v e r s i t y of Western Ontario, London, Canada.

/H~ W ~ / ~ U L~U~J~IC iRPA~I IN A LANAUI~ml"tA~HI~ HOSPITAL OF A PROPOSED REDUCTION IN THE ANNUAL DOSE L(MIT FOR MEMBERS OF THE PUBLIC. In an atten~ot t o be more in l i n e w i t h ICRP r e c o m m e n d a t i o n s , t h e Canadian Atomic Energy Control Board has proposed t h a t the annual dose I l l m l t f o r n~embers of the Public be reduced Fro~l 5mSv to tmSv. The econcf~Ic impact on a 530 be teaching,general hospital was projected b evaluating= i) the need for a separate waitin room For Injected outpatients and t h e i r relatives 2 the need f o r health care workers (HCW) to b designated as atomic radiation workers (ARW on wards where i n p a t i e n t s c o n t a i n i n g dlaonostic doses of 99m-Tc are cared For and 3) the required hospitalisation of patients receiving therapeutic doses of [3]-I and the deslgnatfon of t h e i r HCW. Data from doses to Nuclear Medlcine personnel

andtheoretlcaIcalcuIatfonssuggesttpatattendlng

HCW receive approximately O.O054uEv per MBq of ggm-Tc given to patlents. For the 5000 Nuclear Medicine outpatient procedures performed per year by our Nue]esr Nedicine Department, c a l c u l a t l o n s indicate that a v i s i t o r In the waftlng room would receive l e s s than O. lmSv, implying t h a t sep(arate waiting rooms remain unnecessary. Similar calculations for the 2000 inpatient diagnostic tests performed per year Indicated that HCW on the ward with the greatest r i s k would receive less than O . [ ~ v per annum Implying that s t a f f on such wards should not be designated as ARN. Under the present regulatlons, It has been p o s s i b l e t o t r e a t 13[-I t h e r a p y p a t i e n t s as outpatients p r o v i d e d they receive less than [.IGBq. However, i f the dose l i m i t Is reduced, t h i s threshold should drop to 220MBq to protect the f a m i l y members of patients frc~ r e c e t v i n g a dose in excess of ImSv. The Increased h o s p i t a l i s a t i o n necessary f o r our s e r v i c e would be 12O hospital days. Thls has the slde-effect of increasing radiation dose to HCW on the endocrine ward to an average of 0.4mSv which w i l l require these personnel to be treated as ARW. (Experience and theory @uggest that HCW of 131-I bherapy ~ a t i e n t s receive a p p r o x i m a t e l y O.ZTuSv per MBQ ivan.) I t is estimated that iowerlng of the general ub]Ic dose ]Imlts to ImSv w i l l result In anJ incremental cost of approxin~tely $60,000 CdnI i.e. 120 hospital days x $500 per day) andl result In a s i g n l f i c a n t increase in dose to HCWI of patients receiving [31-1 therapy.

288 391

393

192

Oorthea Ribe,

Department

The Norwegian Radium H o s p i t a l , Nuclear Medicine.

Department a f

ILAIEX DBSPOSABLE GLOVES ARE PERMABLE TO RADIOACTIVE MATERIAL USEDIN NUCLEAR MEDICINE. Since late ~utumn 1987 we have sIudied the contamination o f the hands after havi0g worked with radioactive material in routlne nuclear medicine employment. After working in the hot laboratory and af ter working with injecLJons, the ]aLex disposab l e gloves were removed. The hands were washedand a s c i n t i g r a m by a Siemens ZLC 3705 gamma~camePa without c o l l i m a t o r was taken. A three minutes exposure of the hands showed From 50 DO1 to 326 oog counts. A background exposure taVen beforhand sho~ed From 17 DUO to ~8 DO0. counts/ minute, The s c i n t i g r a m s were examined v i s u a l l y . V i s i b l e spots were taken as a sign or r a d i o a c t i ve contamination of the hands. Working place Hot lab Injection

~.I.Oshtrakh

Earriet Dige-Petersen

Total numbers of scinLlgPams 15 8

Numbers of scintigrams wlth spots 8 5

Because o f frequent contamination we applied Atrix hand lotion (glycerol/silicone) beneath the gloves to avoid adhesion of radioactivity Lo hhe s k i n . This gave the followzng r e s u l t s : Working • Atrix applied HotPlaCeln~ectionlabTot . No5950ofscint.

I[SCint'

Affix appl. No of-with126spots

Preliminary conclusion: Latex disposable gloves are permable to commor nuclear medicine radioactive matePial. Covering the hands with Atri× hand lotion grid I er the l a t e x gloves reduces the contamination o£ the hands a f t e r wash.

394 A . K . V a ~ l e n o ~ ~, B . S . F s d o r e n E o ~ I d A,N. Cabachenko ~Medical A~adomy~ Institute o~ Roentg e n o l o ~ y a n d Radioblolo~y,So£1a 1756 B u l E a r l a ~ a~id U S S R H e a l Z h M i n l s t r y I n s t i t u t e o£ B i o m e d i c a l P r o b l e m s ~ M o s c o w , USSR.

RBE AND A S S E S S M ~ T OF R A D I A T I O N R I S K S FROM HEAVY ~HARGED P A R T I C L E S

RBE for 9 GeV protons l 4 GeV helium lode, a n d 4 G m V eaA-hon i o n s was a s £ e s m ed b y the g e m e t l e d a m a g e i n d u c e d in male FI(CBAxC)yHL/6) mice and Wlstar rats. T h e IrmadlaJhlons w a r e c ~ r l o d out at Dubua synchropkasotron, USER. the y i e l d O f r e c i p r o c a l trallslocations i n d u c e d i n s p e r m a t o g o n l a of b o t h magm, al i a n species. C o m p a r i s o n was d o n e w i t h s t a n d a r d E a m m a r a d i a t i o n f r o m 60Co. R B E w a s d e t e r m i n e d b y the r e l a t i o n ship for coefficients for linear regression of dose-tr&nslocatlons yields of i o n l z i n g p a r t i c l e s a n d ~ a m m a r a y s . C o e f f i c i e n t s £ o r R B E in m i c e w o r e I . ~ 1.0 a ~ d I+~ [ o r p r o t o n s , h e l i u ~ ions a n d c ~ r b o n ions r e s p e c t i v e l y . In r a t s w e r e e s t a b l i s h e d 1.9 a n d 1 . 7 f o r )rotons a n d h e l i u m ions. M e a n v a l u e s w e r e accepted f o r ~ n e ;ic e f f e c t i y e n e s s o f p r o t o n s and helium i o n s e q . a l s t o 1.7 a ~ d 1,4 ~ I s p e c t l v e l y T h e pro~nost&c a s s e s s m e n t of t h e g e n ~ tic risk for man was based on the direct method. Coefficients £or RHE of 9 GeV proton~, 4 GIV helium ion~ and G e V c a r b o n Ions e v a l u a t e d b y ~he y i e ld o[ tr~nslocatlons in spermatogonia i n i i e e a n d ~ a t s w e r e 1.7, 1o~ ~ d 1.~ resp~tlvsly.

Nuclear

of Clinical

Medicine,

Physiology

Glostrup

and V.A. Semionkin*

D i v i s i o n of A p p l i e d B i o p h y s i c s a n d *Faculty of E x p e r i m e n t a l Physics, Ural P o l y t e c h n i e a l Institute, Sverdlovsk, 620002, USSR

and

Hospital,DK

B-52 AIRPLANE CRASH IN THULE 1968

WOSSBAUER EXPOSED

- A HE~LTH HAZARD?

STUDY OF O X Y H E ~ O G L O B I N TO G A ~ A - I I ~ D I A T ! O N

In e968 4 E-he,Zoo crashed on the ice outside %~nule airbase in Greenland. The area was c o n taminated by plutonium and tzitium. The subsequent cleaning up was performed by the US army and by Danish workers, Radiation ex~sure was judged insignificant and no follow up of the workers' health was planned. In 1986, however, Danish media claimed that former Tht~le workers had a higher than normal mortality, incidence of cancer, and certain undlagnosed diseases. A preliminary study of death rate and cancer incidence in about 130 workers supposed to be most exceed showed no difference fxom the expected level. Never-the-less, there was a public ~ d political demand for a health survey of all Thule residents and workers in 1968. The Danish Board of Health designed the following plan: l) Identification of the test group 1202 persons - and a control group of Thule workers - 3120 persons. 98.7% were identified. 2) Identification of health hazards - cancer incidence, death rate, causes of de~th, clinical symptoms in selected groups, hospitalisations and hospital diagnoses, plutonium measure ments in urine, and a request for all information available on the exposure, radioactive and other. The results obtained so far show no difference between the groups and no disease patterns. Exact information on the exposure has not been received. 3) Detailed design of the health survey. ~he situation is: No hypotheses as to health hazards have been confirmed, the exact exposure is not known, the secrecy due to the type of accident strengthens the p~blic demand for a high quality study. The ~Dlicy of cooperation with and information to workers, trade union, and the public is described.

R a d i a t i o n r i s k a n d r a d i a t i o n carcino0nesls become one of the main problem because of e n v i r o n m e n t a l factors and development of n u c l e a r medicine especia l l y a p p l i c a t i o n s of gamma-therapy. Inv e s t i g a t i o n s of the r a d i a t i o n demands of h e m e p r o t e i n s p l a y i n g specisl role iz Ibioenergetics are important in this problem. Therefore we are s t u d y i n g the effect of gamma-rays on o x y h e m o g l o b i n (Hb0 2) by M a s s b a u s r spectroscopy, Samples of human adult BYo02 in fresh e r y t h r o e y t e e were e x p o s e d to gam/na-iriradiation at the Poem temperatlL?e in the range of doses from 0.6 to 60 M r a d during 1 h. M a s s b a u e r spectra were m e a s u r e d at sample temperature 87 K. The results show that gamma-irradiatioz lof HbO 9 leads to d e o x y g e n a t i o n and protein d~struction. M a s s b a u e r p a r a m e t e r s of different components of the spectra of g a m m a - i r r a d i a t e d Hb0~ were evaluate6 a n d c o m p a r e d w i t h the r @ s u l t s of Massbauer study of X - i r r a d i a t e d Hb0o. Usin~ subspectra areas the q u a n t i t a t i v e relaItions of oxy- a n d deoxyforms of hemog l o b i n as well as s u p p o s e d products of p r o t e i n d e s t r u c t i o n were evaluated. It is shown that g a m m a - i r r a d i a t i o n leads to the same effects as X - i r r a d i a t i o n ef Hb02 does; it needs h o w e v e r some ~igher doses. HbO 2 d e o x y g e n a t i o n a n d d e s t r u c t i o n ~hich increase w i t h the increase of Ir#adlation doses indicate that these p r o c e s s e s could also take part in diskurbanee of cell b i o e n e r g e t i c s of the irradiated body.

395

396

F.Dermentzol~, E. Yiakoumakis,

S. Koutroubas, M. Paphiti

M Mutlu,M.TErcan Departments of Chemical Engineering and Nuclear Medicine, Hacettepe U n i v e r s i t y Ankara, TURKEY

Greek Anticancer Institute, Athens TecbHical EdoCation Institute, Piraeus

SHIELDING MATERIALS NE DEPARTMENTS

FOR NUCLEAR MEDICI-

KINETICS OF RADIOLADELLEDPLASMA PROTEINS AT INTERFACEWITH 910MAT[RIAL SURFACES

The attenuation of y-rays of 1-131, TC-99 m has been measured in various shielding and building materials. Besides the conventional materials, two n e w products have been investigated; a) the steel-punchings, available as b y - p r o d u ~ of industry, b) steel-concrete, whic[ is concrete including steel-punchlngs. Results: Half-Value

layers,

cm

(broad-beeam)

Material Nuclide Lead

Steel

Steel vanch.

Steel [bncr I (bncr i

1311

0.25

0.88

2.8

5.0

Bg"h~

0.025

0.45

1.0

2.5

]!&'Jck

~ble

Fx3rth

Sand

217 0.9 Glas~ I

1311

512

4.0

8.5

8.8

6.2

99mTc

2.5

2.6

3.9

4.1

2.3

/ Th . . . . products p .... d to cobe t?van-I zgeous for shielding with low s

i

Polymeric biometerlels ore widely used in s number of clinically important blood contesting implants and oevioes, such as oxygenaters, hesmo4ialysers, artificial hearts, etc. All these materials are subjected to a series of in vitro, ex rive and in rive tests before clinical applications When any material comes into contact with blood, the initial reaction is the deposition or plesma proteins on the material surre~ The adhesion of blood formed elements depends strongly on the type of protein )ayer For example, a predominant albumin adeorp(iBn leads to decreased plats]etadhesion, while e predominant deposition of fibrinogen leads to increased pletelet adhesion which may cause thrombus, or further, ombolus formation. OonsequenUy, the kinetics of blood proteins are the most important parameters in bieccmpatibility testing In this study, the kinetics, or in other wards, the adsorption rate constants or" 9gmTO-HSA, ggmTo-HSF end ;251-HSF on palyureUlane biomaterial surfaces were determined in a modified bead column test circuit By stimulus-responoo technique, The dynamic heheviour of radiolsbolled proteins was studied by obtoining samples after their passage through column and detecting the r~foactivity by a gamma scintillation counter (Sertodld, BF 5300, FRG), The kinetics or these tracers were evaluated in a model study with e characteristic equation or I e2J &J k L d &J EL &J This equation was solved using "Parameter estimation by OYbernetic Moment Technique', end then the odsorpHen rote constants of plasma proteins on different Biomaterial surfaces Were calculated, Inconclusion,themeesurerBentorthe kineticsor tracers,such as 99mTc-HOA, 99mTc-HSF and 1251-HSF is e relioble method for the ulvestigation or blood compatibility of biamsterlals, with o suI ode experimental set-up and e mathematical model

289 397

399

398

B. BeE, F. GUIRA~D-VITAUX, N. COLAS LINHART, A. UZAN', L. BARA "=, M.D. LAPOREST.

K.Mori, G.Lucignani, K.Schmidt, T.Jay, E.Palombo, T.Nelson, C.Kennedy, and L.Sokoloff

Nuclear M e d i c i n e , Hosp. B e a u j o n , Clichy, France, ' ' L a b . Pharmuka, G e n n e v i l l i e r s , F r a n c e "" Hematology, HBtel Dleu de Paris, France.

Laboratory of Cerebral Metabolism, NlbIH, Bethesda, M.D, U.S.A.; Istituto Tecnologie Biomediche Avanzate, CNR, Milano, Italy

HUMAN PMARMACOKINETIC STUDIES OF NEW 99m LABELLED LOW MOLECULAR WEIGHT HEPARIN PRAGNBNTS : RESULTS OP A STUDY IN NORMAL VOLUNTEERS. New low molecular weight heparin fractions (LMWH) have been increasingly used in the prevention of thrombosis. We labelled one of these LMWH, Enoxaparin ~R) , with Techne tlum 9 9 " . After in vitro quality controls, preliminary studies I n rats and d o s i m e t r l c evaluation, approval for pilot measurements i n human v o l u n t e e r s was g i v e n by t h e l o c a l E t h i c a l Committee. 4 volunteers received intravenously both S9~Tc l a b e l l e d h e p a r i n (gO mE - 200 MBq) and 9 9 " T c - E n o x a p a r i n (30 mg 200 MBq) a t 8 d a y s intervals. Blood samples were taken seriallE for measurements of anti Xa, anti I I a act/vlties, TCE, and radioactive eountings up to 24 h. Protein binding was assessed by eolRmn chromatography. Urine samples were also submitted to g e l filtration chromatography in order to identify from degradation products. Organ uptake vs tlme was evaluated using a gamma camera. Preliminary results show some discrepancies between biologic a n t i I I a and anti Xa r a t e s , as well as radioactive c o u n t i n g s . These results i n men are i n accordance with those observed in dogs ~sinE a s~E label. Eeparin clears faster from blood than Enoxa parin. EJodistributlons ate similar with m a j o r u p t a k e on t h e l i v e r , h e a r t , and k i d neys. T h i s method may be u s e d n o t o n l y in normal volunteers, buL a l s o in diseased patients, after IV or subcutaneous administration.

400 ; B. BOCQUE[ ; p. FIALDES ; A. KHAZARJIAN ; C. BONNEEOY ; FM. VANEECLO0 ; R, VERGNES. A ~ d e ~ g N ~ l ~ a i ~ g ; H~pital B ; CNR de Li£1g ( P r o f e ~ s ~ R, VERGNESI. ORL ; H~pital C. BURIEZ ; CHR de Li6£~ (Prof~ss~ur PIQUET). PREOPERATIVE ISOTOPIC STUDY OF THE PERklIACILITY OF THE EUSTACHIEN TUBE The ~ I m ~ e or s u c c ~ s of t ~ p a n o p l # ~ t y i~ dir~ct~£~ r ~ z d ;to t h z penmi~biLLty of the. Eust a c h i a n t~bz, t h a ~ i s to s a y t h ~ i n t e g r i t y of i t s pr~sAure ~quZiib~i~m f u n c t i o n , The s t u d y of t h e 9az t ~ n ~ f ~ r faom t h g p o s t e ~ r naSo-phaAynx t o w ~ d ~ t h e middle ~ i~ p o s s i b l e ~ h manomzt~g whiah i s a d i f f i c u 2 2 t~ahniqa£. Previou~ s ~ t d i ~ ~ v z p r o p o s e d t h g ~ z ~ o n of s~um ~Ibum~ labzi~ed ~h 99m T% i n a t 2 ~ Z g m p ~ i 6 approach to g t udy t h e t u b a l d~a~ f u n ~ L o n . We propose an o ~ g i n a Z m~thod t o £v~g thz Eu~tuc~ tube pr~s~re-¢qui2i5 r i ~ f~n ctio n by studyin@ t h e I r a n ~ f e r of 733 X~ faom t h ~ p O A t ~ o r n ~ o ph~Aynx to t h z midd£z ~ . M~thod~ : Th~ t ~ n ~ t u b a l mouvzm~2~ are a n a l y s ~ by~ling aL% wi~h 133 Xg (0.5 mCi.m~ -l] in t h e R o s e n m ~ l l ~ foAAa wi~h an a ~ t o p ~ i v e Syrin@£ ~nd an I t ~ A d ' s probe, The ~xamlnation l~t~ 3 ~ : 60 ~mo.pz~ of one s~aond zach and 6 i m a 8 ~ o~ 20 S z ~ o n d ~ zach w i t h a ~amma c a m ~ Thz ~ S ~ i s poS~iue i n ~a~e of non pa~sa~Q of thg ~cea ( ~ t ~ U ~ t i ~ n o f t h ~ prz~Su2.g ~u~2~Lib;~an f~n~tionJ, S u b j e c ~ and r ~ 5 ~ : '- No~ma~ : 2 (Thz f~n~t 2 ~ t h o , ' u ~ ) 2 - Pathologic, ENT t u b a l : 9 8 + 7 - Pathologi6 , ENT non ~ b a l 9 5 + 4 Post opem~civg r ~ u l J ~ : Tympanic ~ p ~ : 15 II ÷ 4 ~on r z j z c ~ e d : 12 ~ + 4 Rgjzcte~ : 3 0 + 3 o n a l ~ i o n : - Th£ r ~ u ~ ~r~ i d e n t i c a l t o t h o ~meZ,~4, - E o ~ t ~ c h n £ q ~ g - No p r v . d i a ~ u e va£Rz o f t ~ ¢ t g ~ . In agreement moth t h e

oh~siop~holopy.

NEOLIGIBLE INFLUENCE OF GLUCOSE-6-PHOSPHATASE ACTIVITY IN DEOXYGLUCOSE METHOD WITHIN FIRST 45 MINUTES CONFIRMED BY GRAPHICAL EVALUATION The 2-[14C]deoxyElucose ( D C ) method for measurement of eerehral glucose utilization (C~glu) assLLmes that products following DO phosphor~lation remain in the tissue during the experimental period. We have e x ~ i n e d the question of loss of labeled product hy the Imultiple time/graphic approach of Patlak et el. i Rats were a~inistered DG and killed at times hetween 2.5 and 120 minutes. Time courses of arterial DG concentrations were measured by scintillation counting, and 14C concentrations in brain structures at the kill time were determined by quantitative autoradiography. For each of the 23 cerebral structures ex~ined, the ratio of brain to plasmR 1dO concentration at the time of killing, Ci(T)/Cp(T), was plotted against the ratio of integrated arterial DG concentration in plasma divided by the final plasma DG concentration, ~T Cp(t)dt/Cp(T). This analysis shows that, followin E an equilibration period, there is a linear relationship between the two ratios as long as there is no loss of product. The results of this study demorLstrate that such linearity exists up to 45 minutes when DG is ac~inlstered as a pulse and up to 60 minutes when DG is a~inistered by a programmed infusion which maintains a constant plasma DG concentration. We conclude that loss of label has negliEible influence on the DG method during the prescribed experimental period of 45 minutes.

P. StrltzKe, S. EIIp~er, O.K. l ~ R.W. Solomon, S. Vellal~lajosula, W. Strauss, S.J. Goldsmith. Mount sinai School of Medicine, New York, New York, USA C~MPARISON OF E ~ C ~ D L U T I C ~ TEC~/IQUES ~P2kC~ STUDIES OF I ~ BILgeD FI/3W ( 1 ~ ) .

]~

K~ previously developed a t~mlporal decc~lvoluticn a l g o r i t ~ using o r t h ~ polynomials (POp method) specifically designed to c a l c u late the response of orqans (LRF=-llnear resp~rc=e ftmcticm) in p/xel time activity c~irves f ~ ~ C scintic~c s t ~ d i e ~ . T~e aJ/n of this stlrly was to ~ss~,s the d e p e n ~ of the estimated ~ cn s a ~ l i n g p a r - ¢ m ~ , partition blood volume (blood b a c k ~ BB), Poisson noise, and lagged output f L ~ i O n S using Fourier tl-a~ f c ~ (~T)-, de~x~ivolution (DD)-, and COP elgorit/~, in crmputer slmul~ted analytical f-macticr~. calc~/laticrs s ~ that the POP algorit/m~ is superior to other methods, and specifically can handle high noise levels and ~ in pixel time activity curves. ~]%is can be accomplished by minimizing the calculated from the '~ar spectrum,, estimated InF. We ~ l u y e d this c m ~ p t in a ,~ecbenic~l 3 pool circulation Dha~um", simulating heart (input O.L--'ve, TC), k i ~ (oaVpat C~L--'ve, oc) and liver. ~ 'w~as m e c ~ c e l l y adjusted t o vary between "roo t o 450 ml/min. IC -w-as normalized in acg~rd with measured blood activity and OC corrected for camera sensitivity. IRF is then i n m l / m i n . E s t i m a t e d ~ " u s i n g p o p s h e w e d good o ~ ' r ~ l ~ ¢ , i o n (n=15, ~ . 9 5 , y--4.63+.99x, Sx.y= 40.7). s i ~ t e d ~ time activity curve

non-linearities in the ir~ut-oatlmt e v ~ t s which disturb correlation and •mrisbLlity of the calculated flow rates. can be corrected by shifting time activity curve~ and applying the optimization criterion establi~he~. ~ m~thsd has been applied clinically, and flmctiunal images of effective remal p l ~ flow and transit times derived

ICS Patlak, RG BlasherE, and JD Fenstermacher: Graphical Evaluation of Blood to Brain Transfer Constants for Multiple-Time Uptake Data. J Cereb Blood Flow Meta~ol 3:1-7 (1983).

401

402

G.Petracca Ciavarella, A.Bonazza, L.VigliarolJ S.Modoni, F.Barbano, F.Dicembrino.

Ospedale "C.S.S."

S.GiovanniEotondo (ITALY)

ASAL IILIC~CIL]~ CLEM~E IN SEPIhL DEV]hTION asal lucociliary transport is a coeptew phenoae,oo nhich cln be ,influeKed by several physical,chuical and biological factors that, by air.king one or both ciliar and aucous c~ipon~nthj nay interferl uith clearance efficie~y.[t's ieportant to obtain information abool |ucocillary clearance in order th eva]uath ~ chronic disorders and dregs use~ to cure or prevent the|.This has been achieved eain[~ by sacc~rin or radionuclidic tests, t5 sub)e~tslJE Bate,3 f m l e iQe range I~-hg)were stcdied by radio~clidic test. Io one of t h n had 4lergi¢ or atepic dizthesis, serf in general health state and all ,ad n ~ l septu deviation.Me o.e m*s r~eiving any t ~ i c a l and/or • .~'al pharucMegica] treeThent in the last 7 days bedmre the test.Tee 50 pi.Jropslabout 1~ pCi)of QgDTc alhu|Jn IMA (size 10-Th ,m) sere releasnd,oJder visual control,on nasal flHr,close to the oeer turbi~lth head. The subject .as cNThrtably sights} vith the htn suppmrted by an hole-lade lMobi]ization system ned a side #f the face parallel to the aperture of the pin-hole col]isa~r of a :oeputertzed |az|a caNra.l(e vat asked in breath quietly,avoiding n i f f i ~ er aoving.~th sides were studied o~ the ~au day, a l l e l i ~ L 45' r n t , between tMtl.Thirty l'frames mrs dinuically stored in [ hhab4 N h r i s . F r a m uere then cinentically revieNed to correct !lectroeically for inwluntary |ovenents. Then the distance betveeo the DrJginary spot and the farthest point reached by the activity mn the frale iuediately precndin9 the passage into rhynepharJnz vas Hasured.Tl~ achivity ~eed could be calculated and a rlm~je ?.h-E/ in/sin NaS found.This figure is higher thaa those reported by other Authors, probably due to the use of I I ~ particles ,hath are mt at all absorbed and stimulate a more efficient (]earam:e.he pts. 13.3]) deiced to shoe any difference in the activity speed betveen sides.In 13 pts.(gh.Tg)a difference ran~ing fret O.5-7.g ~ / e i n NaS found. )nvariablp,epeed Was lower by the sth~tic side with no significant correlation ~ith patients" age.This finding s~porls the hypothesis that an anatoiical obstacle could block or at least slo~ up secretions flo~ and this can be made ~pree by chronic flngosis which frequently can be found in these patients. Radinnuc]Jde haSpciliary clearance test Dight be a safe and useful test to evaluate patients nith sepia] deviation a~4 chronic inflaesatory the.yea and mattering the effects pt drugs Dr other therapeutic approaches.

i1

A.M.J. Paans

B,J.G. Daemen, Ph,H, ElsinEa , V. Vaalburg

Department of Nuclear Medicine University Hospital Groningen The Netherlands. THE PROTEIN SYNTHESIS RATES AS CALCULATEDBY A COHPARTHENT MODEL USING CARBON-11 LABELED TYROSINE PET DATA. Of the amino acids suggested for the measurement of the Protein Synthesis Rates dOSE), carhon-ll labeled cytosine is favoured because of the relative small amount of meLabolites generated and the high fraction of incorporation into protein. These biochemical parameters are very important for the interpretation because the PET technique 'only' yields information on the tissue radioactivity concentration in a quantitative and dynamic way. Values for t h e plasma eomcentration can be obtained by analyzing blood samples. Prom these Lwo sets of data, plasma and tissue concentrations, the PSR is to be calculated using a mathematical compartment model. This model describes the reversible transport of cytosine from blood to tissue, the incorporation into protein and the non-protein metabolism. The main radioactive non-protein metabolite is llC-labeled carbon dioxyde, which is exhaled immediately. In this model the PSR is expressed as a function of the two measurable quantities: plasma and tissue concentration. The computer program we developed on such a model enables us both, the prospective calculation of the PSR and the adaption of model parameters to the measured data. This program is used to analyze the PSR in an in-vice tumor model in rats with biochemicaL data obtained with llCand lhC-labeled tyrosine. Also the effect of therapy on the tumor can Be translated into a change of PSR as will be shown. In order to minimize the inter-tumor and inter-animal variations the dynamic PET studies are performed with the same animal in two sessions, separated by a hyperthermla session.

290 403

404

405

~D.Brecht-KrauB,

H. Mutlu. K.A. Plskin, M. T. Ercan, h 0noel, C. F, Bekdlk, O, Erbengl, E. Piskln Oepar{mente oF Chemical Engineering, Nuclear Medioine, Virology end Molecular Biolo~, and Surgi~ Re~er'oh Center, HaoBitapeUniversity, Ankara, TURKEY

DETERMINATIONOF BIOCOMPATIOILITYOF POLYURETHANE(PU) SURFACES IN DYNAMIC EX ¥1VOSTUDIES The bio~mpgtlbillty of polyurethane (PU) biemotartals woo determined W measuring the adsorption of labelledplooma proteins In in vitroexperiments in our previousstudies.The extanl of caballed albumin (ggmTo-HaA) and fibninagen ( 12gI-HgF end g9mTo-HSF) deposition on the surfaces of coated and unosatea PU beads was determined in a modified bead cOlUmn system, using stimulus-reSponse toshnique, that resulted in charocterlsllg "d" curves. The purpose of the present investigation was ta determine the biooempatibflity of PU beeds by measuring their adsorption of ggmTc-BeA in dynamic ex viva experiments. 3 rats (eve. wt. 200 g) were enestheUzed by I.P, Injection of 37.5 mg nembutal in 0.25 el, Femoral A.V. shunt woo performed. Thebloodwascircutaled througha column pecked

wilh PU beads(Peltalhane. 2363-80 A. UpJoh, Polymers B.V.,The Nethertands).The tubing was wetted with heparine to prevent clotting. The experimeataI ~t-up was placed directly under the detector of a gammacamera (ZLC 75 with ~ointivtaw, $1emens). I mCl ggmTo-B~A In 0.5 m] was pulse injecteddirectlyinto the tube just before the blood r~hed the column. The acqusition woo started Immediately end 150 frames, each 32 s~ were obtained while the blood flowed with a rate of 3.5 ml/min. At the ~mpleti0n of the experiment 2 !R0) were drawn ever the column and the whole animal separately.2 curves were obtained.The equilibrium woo reeched after 60 rain in both oF them. The curves were analysed end the dynamic adsorption of ggmTo-B~A was calculatedas 2.91%134.5 om 2 of the PU beads. In conclusion,the resultsobtainedin thisstudy were in good agreement with in vitro experiments, demonstrating the usefulness of the animal model used and the stimulusresponse technique.

406 M-H.Laurens*,J.M.Devoisselle**,B.Weber ***,Ch.Marchal***,D.Coustaut**Y.Noschetto****,J.Robert* *Service de M 6 d e c i n e Nuc16adre-54000 Nancy ( F r a n c e ) - * * * C e n t r e Alexis Vautrin Yancy-**haboratoire de Biologic Cellu[aire et G 6 n 4 t i q u ~ et **** INSERM B-279 _ills (France)

HUMAN IMAGING AND TISSUE DISTRIBUTION OF i i i In-LABELED SUV LIPOSOMES Clinical trials of l i p o s o m e s 8s drug d e l i v e r y systems in human must be based on p h a r m a c o l o g y studies of empty lipommes : the aim of the study was to *rovide i n f o r m a t i o n on the b i o d i s t r i b u :ion and the clznical t o l e r a n c e to high level c o n c e n t r a t i o n of small u n l l a m e l lar v e s i c l e s (SUV) llposomes, i to 5 g oF total liposomal lipid 500 ml (NaCI~ 0.9~) were injected with 500 uCi of lll In-labeled liposomes For 5 hours to 6 patient~. The b i o d i s t r i b u t i o n was investigated by m o n i t o r i n g of liver and spleen radioactivity, by r a d i o n u e l i d e imaging and by blood and urine activity mesure during the 72 h Following lhe b e g i n n i n g oF infusion. No ~dverse effect was observed during the whole study. D y n a m i c study showed rapid liver uptake of labeled l i p o s o m e s over the First 24 h with a d e c r e a s e of blood a c t i v i t y (T1/2=7.S+O.Sh, c a l c u l a ted at fhe end oF infusion). Uptake is significant in the r e t i c u l o e n d o £ h e l i a l (RE) system: 58+9.4~ of the total injected activit~ in the liver and 6+1.7~ in the spleen. The l i p o s o m e s s ~ a b i l i t y was 98 ~ at 48h w~th cumulative urinary e x c r e t i o n inferior to SW o v e r 24h,

Yhe r e s u l t s p ro vi d e a baals For the use of l i p o s o m e s as safe drug carriers in the freatment of organs rich in RE Dells. Further studies with the same 5UV l i p o s o m e s c o n t a i n i n g a cyfostatie agent wlll be carried o0t,

K.P~aU,

U n i v e r s i t y of Olm D i v i s i o n of N u c l e a r 7900 Ulm, PRG

W.E.Adam

Internal mammary lympmosclntlgzaphy: it's u s e f u l in d e t e c t i n g i n t e r n a l m a m m a r y n o d e s i n v a s i o n in b r e a s t c a n c e r ? Internal mammary lymphoecintigraphy ie a simple m e t h o d i m a g i n g i n t e r n a l m a m m a r y l y m p h nodes. But there are m a n y p r o b l e m s in i n t e r p r e t a t i o n of scan. The a i m of the study was to d e f i n e d i a g n o s t i c c r i t e r i a e v a l u a t i n g i n v a s i o n or non-invasion of p a r a s t e r n a l lymphnodes 125 i n t e r n a l m a m m a r y l y m p h o s c i n t d g r a phies in p a t i e n t s w i t h c a r c i n o m a loc a l i z e d in the i n t e r n a l q u a d r a n t of b r e a s t were studied. AS n o r m a l c r i t e ria v i s u a l i z a t i o n of four l y m p h n o d e s right and left p a r a s t e r n a l c o r r e s p o n d i n g w i t h the a n a t o m i c a l r e f e r e n c e s was d e f i n e d . As p a t h o l o g i c a l criteria w e r e d e f i n e d : - no v i s u a l i z a t i o n of l y m p h n o d e s on the o p e r a t e d side, -no l y m p h node p r e s e n t in the first two i n t e r c o s t a l spaces. All the o t h e r cases w e r e t e r m e d as " s u s p i c i o u s " . 49 of 125 s c i n t i g r a m s w e r e e v a l u a t e d as normal. 29 of 37 d e m o n s t r a t i n g a non-visualization of one l y m p h c h a i n c o u l d be correctly identified as p a t h o l o g i c a l l o c a l i z e d on the o p e r a t e d site. 8 w e r e i n t e r p r e t a t e d as f a l s e l y p o s i t i v e . 19 of 39 of the o t h e r c a s e s w e r e c o r r e c t l y d i a g n o s e d p r e s e n t i n g nc l y m p h n o d e e in the two u p p e r i n t e r c o stal spaces. 20 of all 125 c o u l d n ' t g r o u p e d in our c r i t e r i a and w e r e excl u d e d . O u r r e s u l t s c o m p a r e d w i t h clinical d a t a and CT had a s e n s i t i v i t y of 100%, a s p e c i f i c i t y of 80.3% and an a c c u r a c y of 88.6%. We c o n c l u d e : In s p i t e of p r o b l e m s in i n t e r p r e t a t i o n . internal mammary lymphoseintigraphy i~ a r e l i a b l e m e t h o d in d e t e c t i n g mammar~ nodes i n v a s i o n in b r e a s t cancer.

407 I G LuciEnani.

V.J. Picken and J.R. Prince University of Oklahoma Health Sciences Center and Oklahoma Teaching Hospitals 9g0 N.E. 13th Street Oklahoma City, Oklahoma 73126 U .5.A.

Medicine

DETERMINISTIC vs S T O C H A S T I C M O D E L I N G OF RADIOPHA RMACOKINETICS: AN EXAMPLE USING 99m-Tc PERTECHNETATE

Deterministic models have been shown on theoretical grounds to underestimate the population means of pharmacokinetic parameters; howeverp the degree of underestimation has not been determined, To evaluate population means £or boil] stochastic and deterministic methods of data analysis, the SAAM27 program was used to I i t the data of 99mTc pertechnetate activity remaining in the blood (Irom five minutes through six hours) of seven patient which had received the ~harmaceutical 30 minutes after taking an oral dose of $00 mg of potassium perchlorate. A twocompartmental model was selected because this ,harmaceutical has been shown to f i t the model and because this model also fits the pharmacokJnetics Ior several other pharmaceuticals. The pharmacokinetic parameters from each subject were averaged to produce the stochastic model results. The counts from each timed sample were averaged between subjects and the resulting curve was also analyzed to yield the deterministic model results. The independent pharmacokinetic parameters obtained include the coeflicient C2 and exponents bI and b2 of the IunctJon: Blood A c t i v i t y = CI*EXP(blt) + C2*EXP(b2t). For the deterministic model C2, bl and b2 are 5g.$(+/-1.2), 9.1 (+/-2.1) I and 0.134(+/-0.005). For the stochastic model the results are 57.1(+/-3.3), 10.2(+/-2.1) and 0.135(+/0.021) respectively. The means of each independent parameter determined Ior each model were compared with the t test and were found to not be significantly different at an alpha ievel of 0.20. For the distribution ol 99mTc pertechnetate, the ~harmacokinetic data may therefore be pooled prior to analysis thereby minimizing statistical variations in the data without systematically underestimating )harmacokinetic parameters.

408 K.ecb~idt,

and L . S o k o l o f f

V;Dol gova-KO~'ubin,V.Bogdanova,S.Mi ceva, U. Vaskova,N.Simova,G.~estakov

IstituCo Tecnologie Biomediche Avanzate, CNR, Milano, Italy; Laboratory of Cerebral Metabolism, NIM~, Bethesda, MD, U.S.A.

Institute of Pathophysiology and Nuclear Medicine,Medical Faculty,Skopje,Yugoslavia

CRITERIA FOR SELECTION AND USE OF LABELED TRACERS FOR IN viva MEASUREMENT OF BLOOD FLOW AND METABOLISM BY IMAGING TECHNIQUES.

INVESTIGATIONOF Pc-RECEPTOR FUNCTIONIN PATIENTS WITH GRAVES' DISEASE

Physiological and biochemical processes can be studied in vivo by use of radioactive tracers land imaging techniques when the distrihution of radioactivity in the image reflects the rate of the process of interest. Strategies must be developed to select a tracer with appropriate biochemical and kinetic properties, and to optimize the input function and duration of the experimental procedure so that final tissue concentration reflected in the image is as linear as possible with respect to the rate of the process of interest. In this study, we have developed measures to evaluate the effects of the interrelationships among these variables on the specificity of methods for measurement of blood flow or metabolism. The degree of linearity between blood flow and tissue concentration is directly determined by the percentage washout of tracer from tissue. Final tissue concentration of tracers with a high Ki/k2 ratio (delivery rata constant/efflux rate constann) is approximately linear with rate of delivery, even ~t long experimental times. Conversely, tracers with ~ low Kl/k2 ratio require short experimental times and steeply rising input functions. The degree of li~earity between rate of metabolism and tissue concentration is small for all tracers at short experimental ~imes, At long experimental times tracers with high k2/k3 ratios (efflux rate constant/metabolic rate constant) produce images more sensitive to rates of metabolism whereas low kl/k3 ratios produce images more mensitive to delivery of tracer to tissue.

Utilizing a previously described radionuclide technique designed to evaluate immunospec i f i c Fc-receptor function(Eur J Nucl Med 1984~ 9:A-457),we have been able to examine the function of the splenic mononuclear phagocytic cells and size of the spleen in patients with Graves'disease,an autoimmune disorder in which hyperthyroidism results from the stimulator// effect of thyroid-stimulating immunoglmbulins. The a f f i n i t y of the splenic macrophages to Re-sensitized erythrocytes was expressed by the slope of the spleen curve(%/min).The size of the spleen was determined from the computer ima. ge by number of pixels converted in cm2. We examined 20 patients with Graves,disease and with TSH-receptor autoantibodies Citers ranging from 26,3% to 45,Z%(normal value below 15%). Fc-receptor ,w~diated clearance was accelerated in 14 of the 20 patients with slope ran. ging from 14 to 43,5%/min(normal value 10,14~ 1,42%].min).No one patient showed defective clearance.Splenomegaly was present in tO,ranging from 78 to 128 cm2(normal value 63,78f13,48 in LO position).Reduction of the spleen size with normal slope of the spleen curve was found in two patients. The results showed greatly augmented splenic Pc-receptor function in patients with Graves, disease in contrast to the other autoimmune disorders in which impairement of the Isplenic Fc-receptor function and splenic atrophy are p r e s e n t

l

291 409 A,PASPALIARIS, L.TZIMIS,K,VONORTA, A,PAPPAS, K.TZIORAS, L.PAPAGRIGORIOU, P,KOUTSIOUSA, P.NATSIS,P,SINGELLAKIS,PH.KALDRIMIDIS. Dept of Nuclear Medicine end Dept of Endocrinology,MBTAXA Cancer H o s p i t a l , Piraeus Dept o f Endocrinology,St.SAVAS Cancer I n s t i t u t e Athens THYROID FUNCTIONAND BURNINGHEAT (JULY 1987) A prolonged exhibition to cold,provokes an increase of thyroid homnones (T3-T4) and of the TSH,al though this does not hapen under warm c l i mate conditions. These data,in combination with the burning heat of July 1987 made interesting to investigate i f the abrupt and prolonged incre ~se of temperature hes any influence on t h y r o i d f u n c t i o n of i n d i v i d u a l s who t o l e r a t e d well the aurning heat and of those who presented thermo31exy.122 ind.of full age participated in the study.47 presented the hospital for regular thyroid function control, before the burning heat CLot I ) . 4 3 came the l a s t 3 days of the burning heat ( L o t 11).B2 were i n t e r n a t e d in hospital pre seating symptoms of thermopl exy ( L o t 111 ),Serum l e v e l s of T3,T4 and TSH have been determinated with RIA method. Levels o f serum albumin were nqrmal. I t has been found t h a t serum l e v e l s of r3,T4 and TSN o f Lot I I were s i m i l a r w i t h those o f Lot I ( c o n t r o l ) . C o n t r a r i w i s e i n d i v i d . w h o pre seated thermoplexy had an important increase o f . TSD and a concomibent decrease of T3 and T4 l e vels .From the f i n a l analysis of the r e s u l t s , 7 indiv.who presented weeks or months,before the study, t h y r e o t o x o c i s i s , w e r e excluded.(4 from L o t I I and 3 of Lot l l I ) . C o n c l u s i o n : I n f u l l age ind% thyroid function:l)is not influenced from burning heat, 2 ) i s a l t e r a t e d in thermoplexy (decrease of T3,T4, probably due to an increase of peri eheral metabolism and a balancing increase of TSH).

412 P. FIALDES ( I L M. D'HEKBOMEZ (i), T, MATHIEU 12), C. ARGENTIN (3), J.L. WEMEAU (2), J,P. DESSAINT (3), R. VERGNES (i).

(i) Nuclear Medicine, (2) Endocrinology, (3) l~unology, CHR LILLE, FRANCE TSH receptor antibodies in thyroid diseases.

Two Assays were studied to detect antibodies to the TSH receptor : - by stimulation of human thyroid function and detection of CA}Jr accumulation (Thyroid stimulating i~mmunoglobulins : rsl), - by ability to inhibit TSH binding to it receptor, this receptor assay used a solubili~ed TSH receptor from crude porcine thyroid mem ~ranes (Thyrotropin liiuding inhibitor i ~ u n o globulins : Tall). ~5 patients were studied : 42 Grave's disease (27 with and 15 without ophtalmopathy ; 20 untreated and 22 treated), 7 Hashimoto's disease, autonomus nodules, iO patients treated with amiodarone, 5 thyroid cancers and 22 other thyroid d i s e a s e ~ , In the case of untreated Grave's sara sensibility (se) was 0,86 (TBII), 0,95 (TSl) and speeifizity (sp) was 0,83 (TBII and TSI), There was a ~ignificant correlation between TBII and TSI in the 95 patients (p ~ OjOOOl) and in the Grave's liseases with (p = 0,0064) or without (p = 3,0036) =phtalmopathy. However these two assays are discordant in 13 eases (13,7%) especially ~n I0 patients with a Cliyroid disfunetion other tham Grave's disease. In caneera (n = 5) TBII ~ere always negativem but TSI positives in 3 ~ases (two patients have an associated Grave's ~isease). Patients (n = i0) treated with amio5arena have TSI positive in 6 e~ses and Tail in 5 cases, the discordant patient was treated alsc •ith corticoid. Be and gp are equivalents in these two assays. ~ignificant correlations are shown between TSI and TBII, but we obs erred some mismatching in ~ome patients.

411

410 A . M . S E G A L I N I ° - A. S I L V A N I ~

K.Hoharl*, Gy.A.J~noki ~, L.KOrSsi ~ and E.Tal~ "FJC" Nat.Res.lnsb.for Radiobiology and Radiohygiene Budapest P.O.Sox 101.1775 Hungary • ~ Hebrew University of Jerusalem, Israel

o S E R V I Z I O Ol MEDICINA NUCLEARE D I V I S I O N E D[ MEDIOINA GENERALE OSPEDALE DI GORGONZOLA ( ~ l ) IIRql 5~ SEASONAL VARIATIONS ON THE TSH, FT4 LEVELS IN NORMAL SUBJECTS,

FT3 AND

DEVELOPt~ZNT OF RIA 5YSTEH FOR MEASUREMERT THYROTRFLPIN RELEASING HORMONE (TRH) IN BIOLOGICAL S~PLES: PREPARATIONOF ANTISERUM ~ O TRACER

I t was d e m o n s t r a t e d cts serum levels of thyrotropin

also

have

spontaneous

that

thyroid

diurnal

variation

short-term

The p r e s e n t s t u d y was luate y e a r l y variation

in n o r m a l aubj~ h o r m o n e s an( and

variation.

u n d e r t a k e n to evai n free t h y r o i d

h o r m o n e s and TSH l e v e l s in healty subjec t s . MoPe t h a n 5 0 0 0 c l i n i c a l l y healty subjects ( m a l e and f e m a l e ) , ran9in9 in age f r o m 20 to 6~ years, were t e s t e d to a s s e s s FT4, TSH a n d , on o v e r 1000 o f t h e m , FT3 a l s o , Serum TSH, FT4 and ET3 was d e t e r m i n e d by RIA o r IRMA u s i n g commercial kits (TSH IRMA by C O r n l n g - K o n t e on, FT4 and FT3 by D P C - M e d i c a l S y s t e m ) ~ The v a l u ~ o b t a i n e d weme e v a l u a t e d to fl nd medium v a l u e and d i s l i r i b u t i o n ' s patt e r n month by m o n t h , Finally medium v a l u e s w e r e t r e a t e d by Halberg's cosinor method t o test p e r i o d city, Statistically significant yearly biological r h y t h m s was d e t e c t e d in v a r i i i l i o n o f TSH and FT3. No s t a t i s t i c a l l y s_ 9nificant r h y t h m c o u l d be f o u n d f o r FT4 Our o b s e r v a t i o n shows t h a t TSH l e v e l s a re highest i n summer (medium v a l u e in the year ranging from 1.5 to 2 . 0 pU/ml) while in summer FT3 l e v e l s a r e l o w e s t (medium v a l u e t a n g l e 9 from 2.5 to 3.3 pg/ml). We t h i n k that reference values s h o u l d be c o m p u t e d a c c o e d i n 9 t o t h e p a t -

413

The accurate determimatdon of IRH /k-pyroglutamyl-L-histodyl-L-prolinamide/ in serum and other biological samples might be an important diagnostic loci in medicine. As the main action TRH stimulates the secretion of TSH and has the highest Gonoentratien in the median eminence. High IRH levels were measured also iR the pancreas, gonads, amniotic fluid and breast milk. Our research work aimed at to davelope RIA system for measurement TRH. To raise antisera synthetic TRH was conjugated by diazotation with bovine serum albumin (BSA). 18.5 % of the IRH applied became conjugated with BSA as judsed by the measurement of 125-I-TRH added fo the reaction mixture dn order to measure coupling efficiency. The conjugate was dialysed and purified on Sephadex g-lO0 column. The such a way purified TRH-BSA conjugate was rested by HPLC. The IRH-BSA immuno~en was administered to rabbits for immunization. Tracer preDaration was carried out with a modified Greenwood-Hunter procedure. The labelled TRH was purified on a BIO-GEL P-6 column. For raddoimmunoassay (RIA) second antibody separation was used. With the antisera obtained from the Wedfzman Institute of Science, Israel, we were able to measure immunoreactive TRH in rat adrenals. As compared to the 2~i ~ 19 pg/mg tissue level measured in the median eminence the adrenal medulla and cortex contained 50 ~ lO and 62+14 pg/mg (mean + S.U,). Our RIA system has been developed ~ r the determination of TRH levels in human serum and plasma.

414

~.Urgancic~tu, F.()z, ~.Onsel, i.Uslu, BJJz

D e p a r ~ t s OF Nuclear Medicine and Pathology, 2errahpa~a Medical Faculty, tstanbul University, Turkey

A. Franke and K. Oeff Gemeinschaftspra xis f~Nuldearmedizin, Berlin,F.R.Germany

CYTOLOGICALCHANGESOF IIHYROCYESAFTERP~IOIOGINE IIHERAPI Effects of radiation therapy on the thyroid cells wene investigated in 120 patients,B2 male and B8 f ~ l e who had received a total dose of 6-30 mCi 1-131,Fine needle aspiratien biopsy(FNAB) has been performed during the past5years with 96.i4% accuracy when compared with surgery inBOBcases llle patients were divided into four groups and were investigated.50 OFt h ~ were 0-I year,30 OFthegn were 1-3years,20 oI th~n mare3-IO years and 20 of then vane i0-20 years after the radioiodine(Rl ) trealmant .llqere was no cl inical evidence and findir~s to trace the realigeaney in these patients .lhnee main typesofcmatrelgrnupawereselected:a)IntheFNABof 200 euthyroid patients,the thyronytes(TR) sho~d sparce but tiny chromatin pattern and had ~r~lli nuclenl i;b) In those of 1604 patients with hypoactive or onofonctienal sol itary nodules,the pattornof chrnmatinwasmaretinyor inconspicloua than the fonTer greup;c)In those of 50 patients with hyperthyreidi~ i t Was seen that the TR had densely but finely reticular chronatin structure and nuclecli were slightly enlarged.ln all onr~;rol groups,the nuclei were slightly enlarged and they showed slight anisokaryosis, In t.he FNABafter applications of l-i31,thnee types of nuclear changes ~ere observed: 1-Tre thym%ytes that had regular,finely distriN~ted c h r m a t i n strnctene and had small nuclei .2-11~ thyrmaytas that had tiny ineonspicious chrmaatin pattern and ~Tell nuclei.3-1~e frank anisekaryobic TR that had coarse chroratin wnichwas c l ~ in ~ center of nucleus were observed a~Dng the normal TR.It is well known that Ist and 2 nd types of nuclear changes are seen inmany thyroid lesions except thyroid t u ~ r s and Hashimato's thymiditis.llle third type of nuclear changes could not be taken as a finding of rralignant transfomation,sinse few ~nisokaryotic cells were present among onrnal TR.Moreover, :oarse chromatin which is clumoed in the center of nucleus (progressing picnosis) is considered the hallmark of regressive changes,l~ere was no specific pattern due to elapsed since RI treabrent, ;onclusion: In examining FNABafter 1-20 years of RI tneabTent lid net reveal any sign of malignont changes.ITesethyroidal ]ell changes depending on RI vane similar to the findLr~s )f euthymid and hypothyneid noaleus.

SEQUENTIAL SERUM L E V E L S OF CALCITONIN IN THE TREATMENT OF M E D U L L A R Y CARCINOMA OF T H E THYROID BY S U R G E R Y AND 1-131. Serum levels of caleitonin (Ct) were measured by radioimmunoassay in 40 patients (10 males, age 11-75 yr, mean 42 yr, and 30 fernales, age 22-83 yr, m e a n 49 yr) with medullary carcinoma of the thyroid (MCT). before TTX (4 pats), before TTX and 1-131 -therapy (2 pats), before and after I - I 31 -ablation (2 pats), before TTX, before and after 1-131-therapy ( 14 pats), after TT X, 1-13 i -therapy and/or external irradiation (11 pats). Preoperative serum levels of Ct were 8 . 4 ± 14.6 pmol/l (n=20). They did not differ significantly in clinical groups of patients classified according to t h e size of the primary t u m o r n o r to the extent o f disease. They were significantly higher in patients w i t h hereditary MCT t h a n in patients w i t h sporadic MCT. Sequential in~a- aod postoperative measurements of serum levels of Ct in 3 patients revealed the effective half-liras of circulating Cts (initial 13-18 rain, delayed 5.5-12.0 h). To assume curative surgery, serum levels of Ct should be undeteetable or within tile normal range ( < 3 0 pmol/l) 72 h afterTTX before and after pentagastrin stimulation, Serum levels of Ct significantly decreased in g of 14 patients within B weeks after 1-131-ablatinn of the thyroid remnant. In I patient the sequential measurement revealed a destruction-induced increase of Ct within I week followed by a gradual decline within 8 weeks. Posttherapeutic serum concentrations of Ct differed significantly in clinical groups o1 patients classified according to the extent of disease. We recommend 1-131-ablation to be performed in patients w i t h sporadic and familial MCT whose serum levels o f Ct have not normalized after TTX. I n patients with hereditary MCT considered to be cured after TTX, 1-131 -ablation should be performed prophylactically to preventreeurrent C cell neoliasia in the thyroid remnant.

292 415

416

O.Testori, V.De Filippis, G,C.Manzato, F,Cottino Nuclear Medicine S e r v i c e and Division of

417

~zfgY~[9,

Endocrinology Ospeda]e Mauriz ano, Toting

E. Mcser, B. Seller, and K. Mann

Departments of Nuclear Medicine University Medical Centre Ljubljana

Depts, of RadiolosY and Medicine II, Univ, of Munich, Klinikum Grosshadern, Munich, FRG

n0sis) and 4 euthyroid controls were reinjected after labelling in vitro with appr~. 15 MBq of lil in-TFopolonate. The uptake and the distribution of cells' activity in the thyroid were evaluated w~th a c o ® p u r e r - a s s i s t e d gammac~mera 3, 2#, gB and 72 h a~ter the reinfusion, The c o n t r o l s u b j e c t s d i s p l a y e d i n the g l a n d less than ~.l% of the administered a c t i v i t y without any image Of total co~cErltratJon, Five out of t h e 8 ~ i t h the autoimmune t h y r o i d i t i s showed significantly greater values. The concentratioh in the t h y r o i d was d e t e c t a b l e 3 h sfter the r B i n j e c t i o n , re~ched peak values at 24 h and p e r s i s t e d up to 72 h. T~o of the pos i t i v e Pts had ¢.g5 and 1,2 Z of the a d m i n i s t e red a c t i v i t y in the t h y r o i d and the lease@ d i s laved focal areas of h i g h e r concentration.~oth ~ere untreated: one was borderline hypothyroid, the other transient mild hyperthyroid. The 3 o t h e r Pts were on t r e a t m e n t w i t h I-T4 since l o n g t i m e and d i s p l a y e d a ]o~er but s t i l l abnormal uptake (@.2%). Our ~tudy suggests quantitative parameters f o r the evaluation Of the thyroid trapping of the specifically sensitized lymphocytes, The d i f f e r e n t behaviour of i n d l v J d u a t p a t i e n t may be e~p ] a i n e d by d i f f e r e n c e s in ] i p i d e m i c levels, which may interphere with the i n vivo s t a b i l i t y of the label; i n blood flow, relmted to different functional status; in the degree and immunological a c t i v i t y of ceils ~ i n f i l t r a t i o n .

DIAGNOSTIC VALUE OF BASAL IRMA-TSH AS DETERMINED HY STATISTICAL EVALUATION OF LABORATORY NESULTS OF 2.~S9 INDIVIDUALS TSH concentrations as measured by a sensitive immunoradiomstric assay (IRMA-mat TSH Mallinckrodt) were statistically evaluated in order to obtain a reference interval for TSH (TSH1) for healthy subjects and for patients with pituitary deficiency. Using linea~ regression analysis, the correlation between TSE1 and TSH2 (TSH within BO min. of i.v. administration of g00/ug TRH) obtained by 903 THH tests~ was studied. A grey zone between decreased and normal TSH values was determined using a frequency distribution of 2.459 TSHI values. Since a good correlation between TSHI and TSH2 was obtained fop TSHI of O.Ol-lO mE/l(r=0.g03),as well as for lower vainns: TSHI up to 0.5 mE/l (r=0.734),TSEI up to 1.0 mE/l (r=O.7B5), for TSHI up to 2.5 mE/1 [(r=O.806), for TSHI up to 5 mE/l (r~0.B38), a normal reference interval for TSHg was read off 3.97-21.56 mE/l, which corresponds to the calculated normal reference interval For TSHI of 0.SB-g.48 mE/l (mean -l.l~ mE/l). A histogrem of TSHI frequency distribution showed the gray zone between low and normal values with the lowest frequency of data to range from O.21 to 0.536 mE/l, with the crossing point for both populations at 0.422 mE/l. The clinical value of reference intervals and gray zones was confirmed by an analysis of T4 s~d T3 in groups with decreased,borderline and normal TSHI concentrations, and thus statistically significant differences Tg and TS levels were obtained.

I

419

418 osti Balddcci M,, Lippi F., Van Middlesworth L. ° inchera A.

attedra di Endocrinologia Unfversitg di Pisa (°) University of Tennesse, Memphis, U.S.A.

RADIOACTIVE IODINE IN ANIMAL THYROID GLANDS AFTER THE CHE~NOBYL ACCIDENT The nuclear accident occurred on April 1986 at th( Chernobyl reactor released a huge quantity of radioactive iodine. 13]-I was concentrated in th rolds of grazing animals and theradioactlvicy these glands has been measured after the accideT In the present study, glands from cows and lambs bred in different parts of Tuscany (Italy) were obCained immediately after slaughtering and thell radioactivity has been evaluated thereafter. ANIM~-L BREEDING DAYS AFTER THE 131-I DOS~ AREA NUCLEAR ACCIDENT (pCi/gr) S.Tuscany

J. Faelchle, D. Engelhardt

(Italy)

Iii-ln-TROPOLONATE LABELLEDLEUCOCYTESIN AUIOIMMUNETHYROIDIIIS. Peripheral leucocytes (1-2 ./BEg) from 8 patients ~i'th autmimmune thyro~ditis (AbIQ)I/16B, AbM>I/bggg, TEH>9, thyroid swelling at the dis-

Lamb

Pavlin Eatarina, Moravec-Berger Da~a, Fidler Valentin, Prepadnik Milan

+38 38.271 +38 50.796 +38 41.400 Cattle S. Tuscany +41 3.426 N. Tuscany +46 24 +46 16 ks shown, the radioactivity registered in the ~hyroids of animals bred in southern Tuscany is ~uah higher than that measured in cattle from the lorChern parb of the same region. A possible exllanation for such a wide discrepancy could lie in I :he fact that the northern animals were bred in ~tahles where they spent most of their time and ~ere fed by forage harvested and scored before the r~dioactive fallout. On the contrary the southern :attle, because of different agricultural tradi:ions were let free to graze in the fields and kept in the stables only during nightime. Moreover.,ovin4 ire generally let free to graze the whole day and do lot receive dry fodder from t h e g n . This could ex!lain why chyrolds from lambs were more radioactive :hen the cattle ones from the very same area.

J.Datseris,p,Papapetrou,E.Hiotelis,K~S~ipsa~el~ V.Papantonio~,M.Sapr~nidou,E.TrivizBki and H. Gyftaki.

"Alexandra" Hospital Nuclear Medicine Dept.

THE VALUE OF 99m-TC-V-DIMERCAPTOSUCCINIC ACID (DMSA) SCANNING IN THE DETHCTION OF METASTASIS FROM MEDULLARY CARCINOMA OF THE THYROID AFTF~ THYROIDECrOMY. ,Whole-body scanning using lOmCi 99m-TC VDMSA and wide field of view y-Camera was per formed in eight patients with surgically confirmed medullary thyroid carcinoma. All the patients were under thyroxin medi cation, had elevated serum caicitonin levels (ranged from 194-8779 pg/ml NV <80 pg/ml) and were suspected for recurrence of the disease, THe carcinoembrionic antigen (CEA) was elevated only in two patients. THe 99m-TC-V-DMSA scanning was positive for recurrent tumor in seven patients out of the eight. The tumor in the two patients was located in the neck nodes, in one in abnominal nodule and in the remaining four at the site of thyroidectomy. The patient with the negative scanning had the lower values of calcitonin (194 pg/ml NV <80 pg/ml). According to our results a postoperative whole-body scaDning in patients with medullary carcinoma of the thyroid proved to be a valuable tool for the detection of recurrent medyllary carcinoma in cases where supportinq clinical or laboratory evidence exist.

*For the preparation of V-DMSA i) the instructions of prof. Maisey were followed and 2) an instant freeze dried kit formulation was also used (Miotelis et al, Democritus Center Greecel.

R E S U RADIOIODINE L T S - -(J31-1)-THERAPY - - O F (RIT) -IN PATIENTS WITH GRAVES' DISEASE: COMPARISON OF 60 GY AND 150 GY DOSE Graves' disease as an i~unogenic process can be treated with moderate success only, either by thyrostatic drugs or by ablation (surgery, IRIT). Using RIT, the incidence of posttherapeutic hypothyroidism is positively, that of persisting hyperthyroidism negatively correlated with the dose applied. The aim of the study was to check the efficacy of RIT using two different doses in 5g patients (pts) suffering from Graves' disease. THe diagnosis was confirmed by an endocrine ophthalmopathy stage Ill-IV (n = 32) and/or auCoantibodies against thyroid microsomes or TSH-receptors (n = 37). In 26 patients without ocular symptoms, Graves' disease was diagnosed by in-vitro-tests only. 37 pts (46%) were treated with 60 Gy by applying on the average 410 MBq 131-1. To the remainder, 150 Gy (680 ~ q ) was given. The mean follow-up I period of both groups (60 Gy, 150 Cy) was 19 months (range: 6 - 46). Using 60 Gy, only in 20 pts (54%) RIT was successful, defined as a removal of Graves l disease. In the 150 Gy group this was achieved in 18 cases (86%). The incidence of hypothyroidism after RIT was 16% in the 60 gy group, 6Z% in the 150 Gy group, however. These differences in success were significant (p 0.01). From these results it is con;eluded and recomended; A 60 Gy dose should be applied only as a first RIT in patients younge~ than 60 years without any risk factors. In all other patients 150 Gy are to be applied, as in these oases hyperthyroidism must be removed, even if postbherapeutic hypothyroidism is to be expected.

l

420 S. Ahula, H. Ernst

Department of Radiology and Nuclear Medicine, Klinikum Steglitz, F r e e University, Berlin, P.R. Germany CAN TRH REPLACE PENTAGASTRIN IN THYROID CARCINOMA(MTC)?

MEDULLARY

Calcltonin (CT) plays a central role in the diagnosis and follow-up of MTC. Stimulation tests are required for the early diagnosis of familial MTC since basal CT levels remain within the normal range at an early tumor stage, which is true especially for the precancerose condition, C-cell hyperplasia. Pentaggstrin stimulation has proved to be the most effective test, but i t is accompanied by considerable slde-effects. NAKAMUNA et el. (C1in. Endocrino1. 27: 69 (1987)) observed a higher CT production of MTC cells in monolayer culture after TRH than after pentagastrin administration. A significant increase of elevated basal CT levels was seen in 2 MTC patients after i . v . administratlon of 500 ~g TRH. In order to find out whether the pentagastrin test can be replaced by the TRH stimulation test, we performed a TRH test (400 ~g i . v . ) and a pentagastrin test (0.5 pglkg) in four patients. All four patients showed a markedly lower CT secretion after TRH than after pentagastrin: In two patients with occult metastases, a minimol or no increase occurred after T R H , whereas pentagastrin led to a twelve- or three-fold increase of CT levels as compared to the I n l t i a l values. In the two other patients with increased basal CT levels, TRH stimulation also proved less effective than pentagastrin stimulation. The results obtained in the four patients already show that TNH is a less effective CT stimulant in MTC than pentagastrin, which suggests that TRH is not adequate for the screening of subjects with normal basal CT serum levels.

293

BM Mazoyer, C Rayn~ud, N Tzourio, B Verrey, C Chiton, E Bassy, O Dulac, N Lassas, M Bo~guignon, and k Syrota. Berviee Hospltalier Fr~dSric Joliot, D@artement de Biologie, Commissariat l'Energie Atomlque, 91406, Drsay, and INSERM U29, 75 Paris, France. ERROR BLOOD

423

422

421

ANALYSIS OF REGIONAL FLOW (rCBF) M E A S U R E D

CEREBRAL IN C H I L D R E N

B Y S P E C T W I T H ~a~Xe. Reproducibility of rCBF measurements by S P E C T (Tcmomatic 564) with ~a~Xe has been studied in 87 young *atiasts. In 17 ea~es ~=Xe was administrated by a 1 minute nhalation and in 20 cases by an i.v. bolus. The study was repeated within 30 minutes using the same tracer administration mode. For each study, rCBF was computed using Lesson's method (Semin Nucl Med, 15:4, ;47-356, 1985) in 71 cortical regions o[ interest (vnil m e ..~ 4cm ~} dr~wn on the aM+gO, +40, +60 and +g0mm slices. Variance components (expressed as co..fftcients of variation) were estimated u~ing an analysis ff variance with repeated measures. A significant effect of the tracer administration mode ~,as found (p _< .0001), the injection mode leading to : C B F values 1 0 % higher than the inhalation mode. ~'owever, the between subject variance was only 12~ ]n ;he first case and 17~ in the second case. These results :ouid be related partly to the age difference between hhe two populations (lg + 4 versus 4 4- 3, mean=Esd in years), and partly to the patholo~"~ heterogenelty. r h e within subject variance was B~ and the variability with the region localization ranged [rom 3% to 8% depending on the slice level The accuracy of an rCBF measurement (the res]dua| error) wa~ 7.5%, independent o[ the region. This last result indicates that quantitative studies with rCBF measured by S P E C T with I=Xe are possible.

Raynaud~ C m Chiron, N. Tzourio, O. Diebl~r, M. Bourguignon and A. Syrota.

Dulac

[ n s e m U29 and Neuropediatrie Dept. Hospita St-Vincent-de-Paul, P~ris Serv. Hoop. F. Joliot, CEA, Orsay, France liCE REGIONAL CEREBRAL BLOOD FLOW (rCBF) MEASUREg BY SPECT IN STURGE-WEgER DISEASE S~urge-Weher (SW) disease i~ a ~euroeu~aneou~ syndrom characterized by a facial angioma: neurological signs, mainly epilepsy, and Cl scan modifies=ions. Although facial angiom~ is 9resent at birth, radiological and neurological signs develop generally in tt~ first year and SW disease is rarely recognize( in the first months of the life. However il is now accepted that antiepileptie treatmen[ should be more effective if started at birch Nine children from i to 18 years with typica] SW disease were studied in order to defin~ possible characteristic rCBF pattern o: :he disease and help =o make an early diagnosis =CBF was measuced with a brain dedicated SPEC! ~ys tom, TOMOMATIC 56h, using Xe-133 delivere~ )y IV injection. It provided five 20 mm-=hiel ~lices. The rgBF was considered decrease~ ~hen the ~ difference with the mean half-slice =CBF was at least 20%. The radiation dose ~o ~he lung was evaluated to 0~050 rad/mgi. ro prevent any head movement the childrem ~ere premedieated. ~Ii patients presented a significant rCBF decrease on an area that included the C~ ~bnormalities -contrast enhancement, ~ortical s=rophy and calcifications. The hypoperfused area was large and covering most of a~ hemisphere in ~ cases~ it was smaller in the fi others, in all patients but doe it extende~ on the frontal region. In every patient thi~ area was easily recognized. In a young chil~ ~ith a facial angioma suspected of SW, the hypoperfused a~ea was already visible at 2.~ months, These results should encourage to study th~ rCBF during the first year in patients suspecte~ of SW.

425

424 [ C
IC.

B Gu~sn.

Hospltalfor Sick Onildren, London, JK. ~CCURACY OF METAIODOBENZYLGUANADiNE IN NEUROBLASTOMA Badlo-iodlnated MIBG was introduced first for the diagnosisr and then later for the therapy of phaeochromocytoma. Its use in paediatrics has focused on neuroblastoma. Experience with MIBG has been 80 promisin~ that 1-131 MIBG therapy has been instituted in certain centres. Between 1985-86, 19 children wlth neuroblastoma were imm~ed with Tc-99m MDP~]d 1-123 MIBG within 4 weeks of diagnosis. )5 of these children had stage IV disease with a positive hone scan, yet only 13 had an abnormal skeleton on 1-123 MIBD scan. g detailed comparison of the number of skeletal sites involved showed that 76 were positive on both scans, plscordance was noted, with sites positive only on Tc-99m MDP bone scan snd also with sites positive only on 1-123 MIBG scan. These results sugEest false negatives may De seen with 1-123 MIBG at diagnosis. In January 1985, 5 children with stage IV neuroblastoma in complete remission ~ollowlng intensive chemotherapy underwent "ull restaging including Tc-99m MDP bone 3can and 1-123 M I ~ scans. Four children ~ere positive with 1-123 MIBG, mld 2 of ;hess are alive and well 36 months later ~ith no clinical evidence of recurrence. ! children relapsed ~I & 23 months folloW~ag ;he M I ~ scan. The 5th child wlth a normal m a n remmlns well. These results suggest ;hat a positive MIBG span may not reflect ~ctive malignant disease and d~monstrate :he difficulty in sssesslag the effect of 1-123 MII~ therapy in certain c~ses.

~ C l~ud f o n ~ G.Scopinaro, -B.De Bernardi L.Bertolazzi, *G,Dini, G.Villnveochia, M, San~uineti. Nuclear Medicine Service Galliera Hospital - Genoa ~*pediatrio hemato-onoology I .G.Geslini - Genoa M I B ~ S ~ J IN NEU~3BLASTOMA: A COMPARISON WITH OTHER DIAGNOSTIC TEC}~IQUES Between January "86 sad October "87 we performed 129 examination with zs~J-~IB~ on 58 PtB affected by Neuroblastoma, Studies on primitiv~ location have been compared with EGO an~/or CAT data: MI~ ECO/TAC No + + B9 -

41

+

4 15 3/4 oase~ of positive disagreement had a local relapse at Z, 4, 50 weeks, 1/4 hod a neoplastic residue as shown by surgical inspection. In 6/15 oases of negative disagreement se~n was performed few d a ~ after the surgical a b l a t i ~ of higly dlfferentiate~ tumors; in 7/15 the surgical intervention showed widely necrotic or fully differentiated tumors; in 2/15 eases scan W~ negative in sPite of the progression of disease, In the study of bone lesions seen with MIBG versus bone seen end/cr )[ray s h o w ~ good agreement in 124 eases; in 4/129 eases there was positive disagreements sad negative in 1/120 (histologically confirmed). In the assessmsat of bone marrow involvement in 6/125 cases scan was negative in sPite of the presence of 8-15% NB-monoelonal astobudy positive cells. We conclude that MIB~ scan is a hi~ly sensitive and sPecific examination in the study of primitive lo~ation and bone lesions~ of icier si~nlfiesaee in the ~ssessment of hone ~ r o w disease. -

+

426

_. Troncone, V. Rufini, C.De Laurentis °, A.Laso ~ e ~ , R ~ z z a ° , C . P i a n c a ° , R.Mastrangelo. )epartments of Nuclear Medicine and Pediatrics )f the Catholic University of the Sacred Heart, ~ome; Ontology Department of the Children Hosp~ ta] "Bambin Ges~"~ Rome, Italy

Fullbrook A.C., Moyes J.S.E., McCready V,R.

%SSESSMENTOF MIBG IMAGING IN NEUROBLASTOMA(NB) RELIABILITY OF THE METHODIN SEVERAL DIFFERENT :LINICA[ PHASES. In order to further the knowledge regarding the r e l i a b i l i t y of M[BG scintigraphy in NB, the results obtained in d i f f e r e n t c l i n i c a l phases have been analyzed and compared with other diagnostic ~odalitieg, ~hole-body scintigraphy with 1-131-MIBG was performed in 38 patients(pts.)(32 children and 6 adults)with proven NB. The patients were studied both prior to (8 studies) and after therapy (97 studles}and were divided into 7 d i s t i n c t groups, each corresponding to a respective c l i n i c a l phase during which the examination was carried out: at dlagnosis(group l),on presurgical chemotherapy{group l l ) , a f t e r surgery(group l l l ) , o n chemotherapy(group IV),on MIBG therapy(group V ) , o f f -therapy(group VI),on relapse(group V I I ) . At an overall assessment MIBG imaging proved to be effective in detecting primary tumors(gO.3%) md bone metastases(96.4%); less effective in maging salt tissue metastases{Bd.5%) and bone farrow involvement(52.9%). After a more detailec malysis MIBG scintigraphy, when compared to ot~ !r diagnostic modalities, showed a greater accu'acy in postoperative pts. (group I l l ) and in its. off-therapyCgroup VI); i t was less accurate Juring chemotherapy and substantially equal i~ :he other c l i n i c a l phases. The examination seems :o be specifically indicated in staging NBs p r i )r to therapy, in the early detection of residuiI and recurrent tumors at follow-up, to control :he progression of the disease and moniZoring :he effect of NB treatment.

EH~ DIAG~U~'II~

,epartments of Nuclear Medicine and Paediatrlcs The Royal Marsden Hospital, Sutton, Surrey, U.K.

GUANIBINE

V-~LLU~U~ ~5"/A-IUUU-~ENZYL~ (mlgG) IN NEUROBLASTOMA (NBM)

Since its introduction radiolabelled mIBG has been shown to have an affinity for neuroendocrine tumours. We have investlgated the role of MIBG as an agent for tumour loealisation in NBM. We studied 71 mlgG scans in 31 patients 22 patients with N ~ , 1 with esthesioblastoma, 3 wdth ganglioneuroma, 1 with phaeoehromocytoma and 4 non-neuroendoe~ine fumours. There were 61 mlgG scans in the 22 pat!eats with NDM. 2 isotopes labelled to mIBG have teen used 1231 and 1311. There were 41 1231-mlBG scans, 20 diagnostic 1311-mIgO scans and I0 post 1311mIBG therapy scans. Normal appearances, technique of MIBG scintlgraphy and relative merits of the 2 isotopes will be discussed. Of 20 diagnostic 1311-mlBG scans there were 14 true positives (TP), 5 t h e negatives (TN) and i false negatlve (FN). Of 41, 123ImlgC scans there were 24 TP, 13 TN and 4 FN scans. Diffuse bone marrow involvement and focal boney metastases were easily reeognised on mlBG scans. The 5 cases of f~ise negative mlBG uptake will be discussed in detail. We showed no incidence of false positive mlBG uptake. (The post therapy mlgG scans will he illustrated and discussed briefly), CONCLUSIONS i. mlDC scans have a high sp~clficity for NBM. 2. Sensitivity is highest fo~ focal tone and tone marrow sites and mlBG Imay be less reliable for small volume nodal metastases. 3. mlBG scans should be placed early in the diagnostic sequence as positive ~eans may make other staging procedures unnecessary. 4. The best results are ohtalned ~ith 123I; 131I-mIBG scans should only be used for dosimetry estimation prior to targetted radiotherapy.

294 427

428

429

Hoyes JSE, Fullbrook AC, Heiler ST, McReady VB, Q= G~b~!!~E~, J. F e r r i s , C. E s q u e m b r e , V- C a s t e l . lHospital

La Fe.

Valencia.

A. V e r d e g u e r , The Royal Marsden Hospital, Downs Road, Button, Surrey~ U.K.

Spain.

INTEREST OF T N E S C I N T I G R A P H Y W I T H MIBG (131-I.123-II IN RELATION TO OTHERS EXPLORATIONS IN T H E D I A G N O S I S OF THE NEUEOBLASTOMA. Neuroblastoma is one of the most frequent tumours in children. The success of the treatment and its prognosis d e p e n d to a l a r g e extent in the early and e x a c t d i a g n o s ~ s of the stage as well as on a r e a l i a b l e c o n t r o l Of its e v o l ~ ± i o n . We have s ± u d i e d 42 p a t i e n t s , With a h i s t o p a t b o l o g i c a l diagnosis of Neuroblastoma, distributed in a c c o r d a n c e with E v a n ' s s t a g e s as 3 s t a g e II, S s t a g e III and 34 i a s t a g e IV. In all cases, the f o l l o w i n g explorations were made: s k e l e t a l r o e n t s e n o g r a m , a b d o minal u l t r a s o u n d , caeecholamlne metabofires in 24 hour urine, bone g a m m a g r a p h y with S D m T c - N D P a n d 1 3 1 - ] - R I B G . In 20 cases CT was also c a r r i e d out. W h i l s t the other complementary examinations have shown some l i m i t a t i o n s in the d e t e c t i o n a n d a s s e s m e n t of the p r i m i t i v e ± u m o u r or some metastatic location, gammagraphy with ISI-I-HIEG has been of great importance for the diasnosis of all tumoural focciRESULTS: Primitive tumour: Rx: 88%; U l t r a s o u n d : 80~; CAT: 95~. Metastasis: Bone: RX: 75~; M D P SSmTc: 9IZ. H e p a t i c : U l t r a s o u n d : ICe%. MIBG has been p o s i t i v e in all c a s e s of ~rimitive tumours and hepatic-bone m e t a s t a s i s ( 1 C O g ) . C O N C L U S I O N : M I D G scan has high sensibility and specifity lO0~) in n e u r o b l a s t o m a s , its m u s t be the f i r s t e x p l o r a t i o n in t h e s e patients for d i a g n o s i s a n d stage.

430 ~larl%~n [PJ Tariew M~ T~lley NJ B ~

L~

Liver L~it B i r ~ (~ildre~'sH~pihal and D ~ t of Noclear Me,lathe ~udley Road Nospital Sl,m r ~ m DI-IS~ ~g~(~W~CET~CACID (DIS]DA) IN ~E DIAGNDSIS CF EXT~ H ~ I ~ C B]lJAI~CA T ~ Biliary atPesla (Bg) r~qulres s ~ c a l tre~t~-nt preferably in the fl~st e~ght ~ e ~ Of life. Sepat~bdlisw i m ~ is valuable Jn d [ f ~ i a t i r ~ BA fr~ otha~ causes ~ emk~gated hyperbilirublmemla. SL~ as neQ~sthlhepstitis (NH) oc I n t r ~ fe~ir~ ~be~ (IVF~) Excre~im or ~e mdlo~ha~u~utlml into ~ne txm~el excludesthe d:[agrc,sis of BA. but it is s ~ m e t ~ dlfTieult to ensure activityis in the bowel ~ 24 h ~ ¢ ~ q~alityi s mc¢' be,~use of" cadi~ctive decay Ho~=vemEl ~ et al beve s u ~ that those ~th BA can be ~e~ti~od by a llv~:blood ratio of <5 in the period 2} - 10 mis afpec ir6~ctlen 9~mTcDIS3DA. We have used ~sei~ te~Inlque in a group of 13 ehil~m with suspectedBA. ~ ha~ had at leash 3 days pretreat~nt ruth 5mg/k~day of phenoberbl~ to enhanc~ bilisrye~eretisn of the radlopbermaceutical The results of the ratio and eKcreti~nby gJl ~ Were as follows:-

~one

V. Castle*, B. Shulkin~, G. Coates<=, M. Audre~ = *University of Michigan, Ann Arbor, HI, USA ~McMaster University, Ontario, Canada

£(eretion ~ z4 hr

Ratio <5

31M. I IVFC

2~

~atio >5

2 ~. I ~

4

No patient with BA ah~ed D I ~ ¢(eretion by 2h hours but the ~atio was >5 in g of 5 patients with BA. geliauce ~n this ratio %D~ld have denied ~lese dlildr~n essmutisl sorcery. Reference: E1 T ~ MA, Clarke~ . Barrett JJ. Mbwat AF Arda Dis thild (1987) 62:18D-184

1231-mIBG gCINTIGRAPHY IN NEUROBLASTOMA(Nb) IARE BOTH 4 AND 24 HOUR SCAN5 NECESSARY?

THE UTILITY OF INDIUM 111 PLATELETS IN CHILDNOOD THROMBOCYTOPENIA

This prospective study compares the results 3F mIBG scans at ~hrs after i/v injection oF nIRG, with those obtained at 24hrs in children ~ith Nb. mIBG scanning is now an established method 3f staging Nb. 5-~I vie~s of the patient are taken at both 4 and 24 hours after injection of ImIBG, with each view being acquired for 10 mins To lie still whilst scanning either requires a very co-operative or sedated child. Scanning ab ~ihher 4 or 24 hrs would therefore benefit the 3atieng ( and also the nuclear medicine departnent resources). 33 sets oF 1231-mIBG scans in 18 children with neuroblastoma or other tumours were pecFormed. 75HBq mIBG was glven to children <10kg )ody weight, and 185MBq For those >10kg. For ~aeh patient in this study the same method of :hyroid blockade, soucce oF mIBG, eomera, co/1[mator and radiographer was used. All abnormal ~ites of mIBG uptake at 4 and 24 hrs in each )orient were noted. The sites were divided into groups - primary site, soft tissue, focal )one and diffuse bone marrow. The total no of ~bnormal areas o£ mIBG uptake in the 2 groups [s as Follows: Primary SoFt Focal Bone site tissue bone marrow TOTAL 4 hrs 6 15 65 5 91 124 hrs 6 15 68 5 94 These results will be discussed in detail. CONCLUSIONS I. No significant extra sites oF disease were noted by early scanning at 4 hrs. 12. Decreased background activity at 24 hrs results in scans which are essier to interpret.5. Bone morrow uptake was better visualised on 24 hr scans. 4, If nuclear medicine resources are 3imlted, scanning at 2g hrs only is recommended.

Indium lli piatelets have proven quite valuable in the classification and management of thrombocytopenic children. The relatively long half life of Indium permits in vivo survival analysis, the high labelling efficiency results in the need for only small blood samples, an~ the emitted gamma energy permits o r g a n imaging and computer analysis. We have investigated the mechanism of thrombe. cytopenia, using labeled donor platelets, in 9 children. One infant had a large hemangioma extending from the thigh to the spleen, which sequestered pla£elets (9~ recovery, normal adult g1+12), and accelerated thedr destruction (survival time 2B hours, normal adult 212±8). The scan was use~ to direct attempts at embolization. In g children with increased platelet destruction, subsequently shown secondary to immune mechanisms, recovery of platelets was low (22±15%) and survival time diminished (38± 12 hours), Imaging showed increased activity in the spleen (spleen to liver ratio, 5:1; normal 3:1). Another patient with i ~ u n e thrombocytopenia, who did not respond to splenectomy, was shown to have au accessory spleen, which was net responsible for the continued platelet destruction. Platelet survival time was 1.5 hours. g children, subsequently sheath to have bone marrow production defects, had normal recoverie~ (6g & B2%) and nearly normal survival times (95 & 136 hours) and splenic activity (spleen to liver, 3.4:1). In 4 of the patients, spleneetom] or accessory splenectomy was avoided based on the indium platelet study findings. These cases show the benefits of this technique in both identifying the mechanism responslble for thrombocytopenia and for directing clinical interventions.

431

432

D,K. Panoutsopoulog, C.£. Megreli, S.H. Pantel a k i s , H.D. Tsoka, C.G. Batsakis, J.P. Christacopoulos, ~ n t of Nuclear Medicine of Athens Hospit a l for Diseases of the Chest "SOTIRIA", I n s t i tute of Child Helth, Paediatric Unit of the "AGIA SOPHIA" Children's Hospital (Athens - GR)

TALBOT*J,N,, PrKETTY** M . L , D U R O N * ' * F., HABERT** M . O , LAFOREST* M.D., MILHAUD* G. * Service de Mddecine Nucl~aire (Pr. G. MILHAUD) * ServTce d'Endocrlnologie (Pr. P. AURERT) Nbpital SainbAntolne ** Service de M~decine Nucl~aire (P, S. ASKIENAZY) Rbpital Saints-Anne PARIS - FRANCE

A STUDY OF CONGENITAL HYPOTHYROIDISM (CH) USING 9DmTc04- AND 123[. In the Greek programme for early diagnosis of CH which has been in operation since Tg79, 831,956 newborn children were examined and the diagnosis made

in 255 cases on the basis of low T3 T4 and raised TSH levels (Incidence 1:3,262). Of these 265, 181 were subjected to thyroid scintigraphy at the age of two years, to determine whether the cause was aplasia, ectopic Bland or dyshormonogenesis. The first 159 studies were done with 99mTco4- and a rectilinear scanner (RS) or v-camera with a pinhole collimator. In the last 22 cases the scan was done with 1231 and the same y-camera. Results:

a, 9

I~shomono -genesis

09

Ectopic @land

ToAplasia t a l

10 (10.4~) 25(26,ng) 51(63,5%)

b'-~ gmTcIv-camera i2 (19.9%) 32(50.8%) 19(30.2%) 63 I c- 123I

V-camera Total

2 (9.1%) 24 (13.2¢)

16(72.7%)

4(18.2%)

~t' 181

In the case of dyshomonogenesis the 91a,d was u s u a l l y enlarged and was e a s i l y recognised by a l t methods. The ectopic glands were sma I, usual v subl i n g u a l and recognition with ggmTc was d i f f i c u l t beI cause of the p r o x i m i t y of the s a l i v a r y glands and the increased background, even though the use of the

y-camera improved detectability (26% with RS versus 50.8% with y-camera, p < 0.091), However with the use

of 123I the percentage o f ectoptc glands detected reached 7Z.7% instead of g0.B% (P <0.01). We conclude that 13,2% of CH was due to dyshormonogemesis. £ctoptc glands account fop 72.7% of cases. These however require the use of 123i and y-camera I f o r t h e i r adequate detection e s p e c i a l l y i f they are very small, Thus only 18.2% of the cases of CH are due to a p l a s i a .

LOW T H Y R O T R O P I N (TSH) L E V E L S IN G O I T R E S . R E L A T I O N S H I P WITH S C I N T I G R A P H t C F I N D I N G S AND OTHER BIOLOGICAL PARAMETERS, Low TSH levels are frequently encountered in palients presenling wilh a goilre, We assayed TSH in 588 goitrous patienls who w e r e referred for scinHgraphy and ullrasonography. When TSH was low or when a hol nodule was discovered at sc[ntigraphy (181 cases), free T3. free T4 and sex hormones binding globulin (SHBG), a marker of the peripheral effecl of thyroid hormones, were also assayed. TSH was atways low in overt hyperlhyro[d[sm, when tree T3 was elevated : 47 cases of Graves' disease, 18 cases 01 exUnclive solilary nodule, 4 cases of de Guervain's thyroidis, 2 cases of amiodarone induced thyroloxicosls, 21 cases of Ioxlc multinodular goltre. TSH was also low wil~" normal tree T3 and T4 in cireumslances leading Io a mild hyperthyroidism ; 42 % of Ihe extinctive solitary nodules and 5 patients wilh low iodine uptake due Io thyroidgis amiodarone Iroatment Surprisingly, low levels ot TSH were also encounlered 27 % of the 81 cases of multinodufar go[Ire (MNG) without a, hot area or clinical signs o1 hyperthyroidism and wgh normel {roe T3. SHBG, which was elevated in 94 % of Ihe Grave's disease patients, was normal in these cases, ]ndicagng thai the hepatic receplor was not hyperslimulated, in conlrast to the pituilary receptor. Nevertheless, TSN should be assayed Jn mulUnodular gdilre. When TSH levels are low, the patienl may be a[ high sg or over hypeithy oidism. This assurnptlon [s suppoded by the observation of 6 patients sharing the same scintlgraphlc fealures of MNG, wilhout clear thyroid hypergxaHon, who where hyperlhyroid wgh elevaled tree T3. In contrast, unexpected normal TSH levels were detected in 7 patienls with an exlinclive fhyroid nodule (17%) and in 5 palients with hol nodules in a muginodular goJlre (31%) ; Ires T3, SHBG and TSH response to TRH were normal and Ihe nodule was autonomous at Werner's lesh Therefore. normal TSH levels do not ruJe out the presence of an exfinclive nodule.

295 433

434

P.BERGMANN, J.VAN P E B O R G H , M . V A N DEI SCHUEREN Dept Clinical Chemistry, Brugmann University Hospital, 4 Sq. Van Gehuchten, 1020 Brussels.

435

VERELST, D. GLINOER.

K, IACKA, J. SOWINS~ and H. GNMBICEI Dept. of Eodecrinolegy Universi[y School of Medicine of Poz~n AI. Przybysz~oskiego 49 PL-$O 355 Poz~n Poland

~iversity Hospital Saint-Pierre, Universit4 ~ibre de Sr~xelles, Brussels, Belgium

DIAGNOSTIC VALUE MEASURED WITH IMNUNORADIOMETRIC

OF A LOW BASAL TSH AN ULTRASENSITIVE A S S A Y (IRMA).

TSH was measured with an ultrasensitive IRMA (Behring) in 288 consecutive patients who had a TRH test. In t h e 50 p a t i e n t s w i t h a b a s a l TSH l o w e r t h a n .i ~ U / m l , the increase of T S H a f t e r T R H w a s l e s s t h a n 1 ~ U / m l (specificity:iO0%). ii patients with a b l ~ n t e d r e s p o n s e to T R H h a d a b a s a l TSH between .i and .3 ~U/ml (sensitivity: 82%). 227 p a t i e n t s w i t h a basal T S H h i g h e r t h a n .i u U / m l h a d an i n c r e a s e of T S H h i g h e r t h a n 1 ~ U / m l after TRH. A m o n g 132 p a t i e n t s w i t h a low basal TSH, 42 (32%) h a d c l i n i c a l and biological hyperthyroidism, and 104 (79%) h a d a t h y r o i d i l l n e s s . M o s t of those without hyperthyroidism received thyroid hormones (n=49, 37%), either to treat hypothyroidism (n=36, 27%) or for a goiter (n=13, 10%). 18 of the patients who h a d no t h y r o i d illness were hospitalized for a severe medical disease (14%). i0 patients were apparently normal (8%). We conclude that a low basal TSH predicts that a patient will not respond to TRH, but that a TRH test is still mandatory for borderline TSH v a l u e s . A l s o , b a s a l T S H c a n b e u s e d to detect the presence of a thyroid disease, but is not ~pecific of hyperthyroidism. The additional information given by a TP~H t e s t in patients with a low basal TSH will be discussed.

436 A.Antonelli,*F. Lippi, and L.Baschieri.

~REATMENT OF COMPRESSIVE GOITER WITH RADIOIODINE [N INOPERABLE ELFfHYROID ELDERLY PATIENTS. In rare clinical instances, elderly patients 4ith benign, large and compressive goiters CaDlot be st~bmitted to thyroidectomy, mainly because of the high surgical risk related to thelr ~ge or to accompanying, medical diseases. Over ~he lash 15 years, we have treated 14 such clinically and biochemically euthyroid patients (70z5 years-old: me~nZS_D.) by large doses of cadioiodine (RI) with the aim to reduce goiter ~ize and thereby tracheal and/or esophageal compression symptoms. The patlents presented multi~odular, partly retrosternal s~d often asymmetri zal goiters, known i n m o s t of them since several ~ecades. RI therapy was justifled by goiter siz6 increase and/or by recent onset of symptoms related to compression. Thyroid volume (estimated Dy planimetry from scintiscans) was 151±67 gr; ~4 hr-uptake varied from 9% to 69% (46±19%). RI ~osimetry was calculated in order to deliver 75_ [00 ~ci/gr tissue- The doses given varied from [i to 50 ~ i (29±11 mCi). Long-term results wer~ ~valuated ~ t h clinlcally and from control scintiscans performed during the follow-up (i0 to [50 months after RI). All patients showed marker :finical improvement of compression symptoms: Ithyroid volume decreased to 71e42 gr (p < 0.001). In percentage of the initial volume, goiter re ~uction varled from 17 to 70%, reaching a mean ~f 44±16% for the grouP. Furthermore, RI effect ~as rapid, observed after less than i year and naximal after 2-3 years. Acute compllcation fro~ treatment was not observed in any of the patients; 4 patients (30%) became hypothyrold af:er 2 years, requiring hormone substitution. In summary. RI adminlstration is a safe, economic a~d effective procedure for the treatment od ~iderly euthyroid patients with inoperable lar ~e, compressive goiters.

437 P. Del Guerra,

g.gassi

Cattedra di Clinics Medics II and *Cattedra di Endocrinologia, University of Piss, Pisa,ltaly. SOMATOSTATIN (SNS) INHIBITS THYROID IODINE UPTAKE (IU) IN HYPERTHYROID PATIENTS, It has been known that SMS can reduce thyroid function by suppression of TSH. However the pr~ nonce of SNS in secretory granules of C-cells, suggests a psracrine function of SNS on follic~ lar thyroid cells. In this study we have verified the effect of SMS infusion on IU in some hyperthyroid patients. 7 patients showed toxic adenoma(l-7) and 3 showed Graves' disease(8-10). In all patients T4 and/or T3 were elevated, and 2SH resulted suppressed by ultrasensitive method ~ach patient was submitted to a basal IU (50 uCi Df 131-I per os) at theSrd and 24th hour. IU was cepeated 15 days after, previous a basal uptake 3n the neck. during SNS infusion (2.5 ug/mln for 3 hours) at the 3rd hour(h).All patients gave in formed consent to the protocol. Legend:RU-basal 3rd h IU;SMS-U 3rd h IU with SMS ~at N ° 1 2 3 4 5 6 7 g 9 i0 BU 20 21 gO 37 25 30 2g 76 80 72 SMS-U 8 6 18 17 13 17 12 63 50 43 In all subjects we observed a reduction of IU, g i t h a mean percentage 3rd hour IU reduction of ~3% during SMS infuslon with respect to BU, and in 8/10 patients the observed reduction was above 40%. Fhese results suggest that SNS, at least with this pharmacological dosage, can inhiblt IU indi 3endently from its action on TSM pituitary secretion, and seem to indicate a possible paracrine Function of C-cells.

A.N. S a v a s e r ( 1 ) , N . B o s t e n ( 2 ] , E . S c h u l z ( 2 ) L.Jorno(2),R.Felixl2) 1 Nuclear Medicine, Krankenhaus Heckesh o r n , A m g r o ~ e n W a n n s e e 80, 1 0 0 0 B e r l i n 39, F R G 2 Department of R a d i o l o g y , U K R V C h a r lottenburg, S p a n d a u e r D a m m 130, 1 0 0 0 B e r l i n 19, F R G

LABORATORY ASSESSMENT OF T H Y R O I D F U N C T I O N BY F L U O R O Z M M U N O A S S A Y VS. R A D I O I M MUNOASSAY

Diagnostic v a l u e in t h y r o i d d i s e a s e was established f o r co~unercially a v a i l a b l e europium marked DELFIA immunQassays and compared to r e s u l t s o b t a i n e d by i m m u n e assays labelled with radioactive markers. V a l u e s for t o t a l Td, t o t a l T3 a n d thyrotropin were measured in s a r a of 84 consecutive patients of o u r a m b u l a n c e . Accuracy was e s t a b l i s h e d by r e g r e s s i o n analysis and c o m p a r e d by R O C a n a l y s i s f o r a l l tests. In g d d l ~ i o n , p r e c i s i o n data and lower detection limits were obtained. The equations for t h e f i t t e d lines were y = 0 . 7 7 x + 2.47, r = 0.~6 l ~ o t a l T4), y = 1 . 0 1 x + 0.08, r 0.67 ( t o t a l T3), y = 0 . 9 0 x + 0.10, r 0.87 [TSH). Precision data and lower detection limits were comparable f o r all s i x a s s a y systems. ROC analysis showed adequate results for b o t h i m m u n o r a d i o m e t r i c and immunofluorometric a s s a y s of TSH, r e sults for radioi~L~Unoassays of t o t a l T4 a n d t o t a l T3 b e i n g s l i g h t l y b e t t e r t h a n chose for fluoroiQlmunoassays. We c o n c l u d e that europium labelled fluoroimmunoand i~unofluorometric a s s a y s are a d i a g n o s t i c alternative to assays using radioactive m a r k e r s in laboratory assessment of t h y r o i d f u n c t i o n .

T~E RISK OF THE UNCID&NCE OF H Y ~ O I D I S M AFteR R~DIOACnW IODINE TN~RAPY OF TOXIC NODULAR O01TER WITH EL~ATED ANI~T/YROID &\rrINSDIES Tne frequency ofh ypo thyroidism after radioactive iodine

131-[ therapy of hyperthyroidism varies fr~ 15 go 7~/. alter ten years. Considering that beside radiation s ~ other facsors ~ y be responsible ior theL we investigated the relation bet~en the presence of antithyroid antibodies before and alger 131 I tree,tent of toxic nodular goiter and [he incidence of hypoLhyroidi~. In 33 patients thyroid ancimieros~i/anti~dc/ and antirhy~oglohulin/anki-Tg/ antibodies were bete~ined by solid-phase radiommt~oassay 14net ancin~rane antibodies were detected by e~ymoi,~unoassay. Antioch and anti-Tg antibodies were elevated in 42 and 337~ of all cases respectively before 131-I therapy when ~he resutts of detennina£ion of ant~/nar~rane antibodies were negative. One y~r after trea~nt 15 patients (457=) ~re euthyroid, 7 (2T/=)developed hypothyroidism and ii (33%) re~ined thyrotoxic. In all 7 cases with hypothyroidism after 13l-I therapy elevated anti,Me antibodies were present before the treatment and in five ~ses its concentration incr~sed after therapy when the concentration of anti-Tg ancibodies behaved differently. Our observatio~ indlcate that slier 131-I treatment of ~oxic r~dutar goiter with the presence of anti[byroid an~ibodies the hypothyroidism ~ y occur more frequently 5hat in other cases.

438 T. Kreisi_g, C.M. Kitsch, R. Pickardt*and

E. Moser

Division of Nuclear Medicine, Department of Radiology and C/inie of Internal Medicine Innenstadt*, University of Munich, Munich, FRG

99mTHYROID UPTAKE (TcTU) IN THE NORMAL THYROID GLAND AND IN EUTHYROID AND HYPERTHYROID GOITER The visual evaluation o[ scintigraphic images alone often does not succeed in the detection of thyroid autonomy. Increased information can be derived using quantitative 99mTe-thyroid uptake (TeTU) as an analog to thyroid iodine clearance. The aim of the study was to evaluate the TeTU in the differential diagnosis between the normal thyroid gland and the goiter with and without autonomy. The study comprises 150 patients. The TcTU of 95 euthyroid patients (group 1) were compared to the one of 34 patients with incomlete or complete suppression of TSH secretion group 2). None of the patients in either group was on any thyroid specific drugs. Graves disease was excluded. 12 patients of group 1 (group 1A) had normal scJntigraphic and sonographle findings. TcTU was also assessed in 21 euthyrdid patients (group 3), who were under TSH suppression (TcTUs). TcTU of group 1 and 2 presented approximately the same distribution: group 1: median 2.4 %, range 0.8-10.9 N; group 2: median 3.0 %, range 1.2-22.6 %. Group 1A also had a similar distribution of TcTU: median 2.7 N, range 1.26.:t %. TcTU S in group 3 had g median of 1 . 1 % ~Ad a range of 0.1-4.3 %. Comparing groups 1, and 2 one can conclude that TcTU without drug-induced TSH suppression does not help to distinguish normal size thyroid, autonomously and non autonomously functiomng goiter. TeTUs-values in patients with eurhyroid goiter (group 3) presented a wide range, which overlaps considerablely with the TcTU-vaiues of hyperthyroid patients (group 2). From this data we conclude that the patients of group 3 "with a TcTU S greater than 112 % showed an insufficient TSH suppression which is consistent with asymptomatic autonomy.

~

296

M. Pillay,

441

440

439 P.H. COX and D.H.W.

gchRnfeld

M.gedda, R . P e ] l e r i t o and U.Roe~o

~P~99,

A. VATFIMO

N u t ] e a r M e d i c i n e Eervice. Otpedale Mauriziano, Torino ( I t a l y ) Dr. Daniel den Hoed Cancer Center P.O. Box 5201 3008 AE ROTTERDAM, The Netherlands ORGAN DEPTH MEASUP~MgNTg

~aclear ~edicine Lhit, Institute of Radiology, University }f Sima, Siere, Italy.

BY X-RAY ATTENUATION

OR X-RAY DXCITATION?

I

Purpose: organ depth was estimated in a dead Itissue (minced beef) phantom and with a 123i point source placed at fixed levels. Method: organ depth was measured using the X-tel to photopsak ratlo of 123I as described by Martin et al (1977) on NaI and Ge(li) detector ~ystems. The dead tissue phantom measurements el Lhe 2 inch NaI detector produced depth relation 4hich followed closely the calibrated curves )btained for a 1.5 and 2 inch NaI crystal. Now~ver, the results obtained with the Ga(li) letector proved to be less reliable although the l-ray and gamma phctopeaks were better defined. ?ypical x-ray (24.8-33.2 Key) to gamma ray (159.2 KeY) ratio for the Ge(li) detector was zhe order of 30.25 (without absorber). With i0 ~m of absorber (tissue) this ratio was reduced :o 10.7. The NaI detector produced ratios in the )rder of 72.05 without absorber and 1.83 with i0 ~m of absorber. )iscussion: This study indicates that the ~stimation of depth by "x-ray attenuation" should perhaps more appropriagely be termed "X-ray excitation". The Ge(li) detector demon;trated a relative decrease in X-ray and g~mna photopeak whereas the Nal detector has a disproportionate increase in X-rays indicating a process of iodine K shell excitation within the zrystal. Although the disproportionate increase in K shell X-rays are advantageous in performing ]epth measurements, it must be r e m e ~ e r e d that ~ach cl-ystal should be used with its o%rncaiibration curve because of the variation in iodine 3ontent related to the volume of the crystal. Reference: Martin, P.M. and Rollo, D. Estimation 3f thyroid depth and correction for 123I uptake neasurements. JNM, 18:9, 919-924 (1977).

5Lrum~ o v a r J i Js a r a r e c o n d i t i o n and very r a r e l y undergoee m a l i g n a n t =hangs with most ~requent abdeminal i n v o l v e m e n t . N,A,M.~a ~oean of 49, wa~ r e f e r r e d becaute o~ the appearance of l i v e r metastases four ymars a f t e r the removal of a struma evarii with a well d i f f e r e n t i a t e d f o l l i c u l a r aod p a p i l l a r y cancer, A f t e r surgery she had r e f u s e d the t h y r o i d a b ] a l i g n ; p e r i o d i c a l check~ were n e g a t i v e since the appearance of multiple US and T o - c o l l o i d nodular in the l i v e r , l - 5 cm.in diameter. She was tubmitted to four I ~ I I t h e r a p e u t i c courses, as f o l l o w s :

~!g e~! Iff!e~! II! 9~ £~YgBeg! IL~ ~! 6 , 5 1040 3 . 5 110 1,2 ? g.g ? $ approximate estimation

Jan8d MarS~ NovBb AprB7

150 200 170 i70

16 g.3 g.l 0.03

6,~ 7 , 0 49 5.g 5 . 4 73 1.5 b.~ 110 g,l i.B 7 of the target volume

3 single abdominal nodule appeared in the 2nd courts ad displayed the tame behavlo~r of the ] i v e r ' ~ ones. The progressive r e d u c t i o n a,d the ~inal disappearance of US, CT and sulfur colloid images were obteved, ,Serum hT6 from the f i r s t value of l ] I g r i g / e l (T~H= I ) and a maximum Of 7113 (TSH=I35) in Mar,S~ r e s u l t e d 37 ( T S H - 0 . 1 I in 3an,BB. In s p i t e of the high radiitton dose to t h e nodule~ and t h e i r d i s a p p e a r a n c e , tome t h y r o i d abnormal(?) t i H u e ~ mutt ~ t t l l murvive,

~.J. de Lange, D.A. Piers. Meijer.

W.H.J.

Groningen,

van Luijk and

The

RENAL HANDLING OF Tc-99m DMSA: EVIDENCE FOR BOTH FILTRATION AND PSRITUBULAR UPTAKE, The finding oF an enhanced excretion of To9Rm DMSA (DMSA) in pmtients with proximal tubular resbsorption disoPders prompted us to investigate the role oF FilEration in the renal handllng oF DMSA. The following experiments were emrried out; serum proteln binding studies, analysis of the tracer ~fter excretion into the urine, and continuous infusion of DMEA together with 1-131 hippu~mEe and 1-125 iothalamate for measuremenE oF ERPF and 0FR. In one normal pe~son, renal extraction oF DMgA was measured. Protein binding sEudies using ulErafiltration and TCA precipitation in human serum both indicated thag binding was about gO ~ (range 8H-94 ~). Thin layer chpomatography of human urine afte~ injection o~ DMSA gave one peak of radioactivity at the same place ~s the original DMSA solution. When u~ine of a rat after DMRA injeotlon was injected i.v. in another rat, renal uptmBe w~s seen again. Een~l extraction of DMEA in a human volunteer was 6 %. ]ontinuous infusion in 13 individuals with ~ormal renal function gave the following ~esults (mean ! sd): RRPF 558 ~ g5 ml/min, GFR L23 + 15 ml/min, plasma clearance of DMSA 34 Z mlTmin, urinary clearance of DgEA 12 + 3 nl/min. The calculated filtered load of--DMSA zlosely resembled the rate oP excretion into the urine while the plasma clearsnce was abouE B times fester. This indicates that peritubular ~ptake accounts for about 6g % and Tiltrstion for about g5 ~ oT the renal handling of DMSA. Conclusions: DMSA is excreted into the ~ i n e in mn unaltered form. Both filtration and peritubuiar uptake pl~Lv ~ role in the renal handling of DMSA.

Renal Handling of Tc99m-MeZhylene Oiphosphonate in man. The Tcg~-labeled diphosph~te~ not retained by the skeleton are rapidly excreted by the kidneys, so tJ~t ~ 24-hour ~1ole-body retention of these tracers is w~dely LL~edas inde~ oF bone ~tsboli~m. ~e pBttern of renal excretion is ~ot f u l l y unde~-stsod: some workers found boi~ glomerular f: tration and tubular secretion in rats, ~ r e a s others did not find significant differe~es in the renal handling bet ~e~ Tcg~m-la~eled PI]P and DTPA in dogs. ~ e purpose of this ~b~dy is to evaluate ~e renal h~dling of Togas-MOP in ~an. 12 patients referred for bone scan e~tered this study, each of ~nom was injected s~cce~ively wi~h 0.1 mCi oF Cr51-BTTA ~nd 20 mCi of Tcgg-M]P after pla~n~ ~olume m e a s u r ~ t by IIZR-H~. Blo~ samples ~ere done over a O-4-hour period at< ,la~ concerrLrafion (P(t)) oF each tracer ~ measured (as t concerns H~P, the dializable form was Wotalred and used Or c~l~lati~). ~ accurate urine collection was done over a 0-4 and 4-2a-hour period and ~e percent of bhe dose ~Bs measured (Qu). lhe p l a ~ time/activity curves were f i t ~d by n ~ of a sum of 3 e~pmeltial terms function. 'enal clearance (CI) of each tracer was eati~ated by the e~atlon: Cl=~/~(t)dt and ~ expressed as ml/mI , The ur1~ y excreting of ~ P was nea.sured over a 0 - 2 ~ - ~ o u period r~ U~) a~d was estimBted by the equation: UE~jEITFA(t)d~]M~P it)di~100. The CI oF Cr5%EDTAwas found B3.13tI6.D9 (M~SD) the CI oF Tcgg~-F~P~as FoundB4.~16.gR (P:r~) chowi~ I strong correleti~ (R=0.98). The LM ~es found 54.g2~13,77 ~d the UE was found 54.25~12.3g (p:ns) showinga close cor' e l a t ~ (R--0.97). In cor~lusi~n our findings show Ebat the •eral handling of Tcgg~-~I]P in man closely reflects t~ose ol ;r51-EOTA, namely the glomerular filtration rate. ]his lead~ ~s to conclude ~ a t ~he Toggm-~Do is excreted by the kidneys Aa g l ~ l a r filtrati~ ~ babular ~ l i n g .

444

443

442

liversity Hospital, Netherlands.

RAOIOMETABOLIC TREATMENT OF L~TE LIVER METASTASES FROM A MALIBNANT STRUMAOVARIII CASE REPORT.

Catefau, C. Piera, J. Pavia, E. Herrar~, A. Pavia and Setcein.

M. Pore at I, M. Ba~i6 I, D. Batinid 2, D. Dodig I . ~ , Lj. Ni~i62, D. Milosevid 2

lluepartment of Nuclear Medicine and 2Department of Nephrology of Pediatric Clinic, University Hospital Rebro Zagreb

sits/ Clinic i Provi~cia/. Villar~], 170. 0 8 ~ - ~ar~elo~a EPPF ADD ~3(IqAM WIZH 1311-01H A ~ 9~c-MAG3 ]~ H ~ SIVE pAT]EMS.

COMPARISON OF 99Tcm-DTPA AND 99Tcm-MAG3 CHILDREN WITH VESICOURETHERAL REFLUX

Ct~ aim is the evaluation of the use of 90~Tc-MAG3 as a subs titute of 1511-OH~ in h y ~ i v e p~tients (HIP).

Dynamic renal scintigraphy was perfomed wiCh 99Tcm-DTPA and 99Tem-MAO3, respectively, in twenty children with vesicouretheral reflux of different degree. The reflux was proved in 29 kidneys by micturition cystourethrography and classifed according to International Study Group for Reflux.

A total of 30 remogrsms have bees ,rode to 15 HfP wlth 131I01H (7.1-7.4 MBq) ~nd 351.5-377.4 MBq of 9C~Tcq~AC~ (M~Jlin ckrodt Dimgnostica) by simultaneous i .v. injectinn. Padio-chemical purity cc~It~ol ~ made by }~C. Serial blood ples were ~tsken drains lh to c~c'~ate ~ . and urine collected at lh post-injection to c~calabe the ~ine ~cre ticn (t~) ~ a percentage of the deals ~4einistered. The per=meters compared were: a)Trmnait time, calculated as time-to-peak (IT). b)PerCenta~ of the ~ i m u m activity decrease at l0 mTd 20 min.(DlO', E~3'). c)percents8~ of the r~_ lative u~thke for each kidney (ca]calated ms the integral of the curve to 2/3 of the maX~)(RU). A psired Student's ttest and Paarman's correlation coefficienE were used to ans%yze the data. its:

The rsdiochemical p=ity ws~ 97.~-+ O.R

~f (see) DIO' (%) O~0' (%) I~ (%) (%) 'I~PFel/sin

0]~ ~.~:~ 28!ii 61g17 47-+13 C~ 3~9~Z33

NL~G3 3.=~Ll~ 20k10 5~7 ~6~lg ~ 191±113

Signif. ~ p
Gorrs]at. ~0.~ R=O .86 R=O.~ I~.gB R=o.97 R=0.~6

ratio (NAG3/OIH): 0.57 g 0.08 ~r~lusia%s: No aign~fin~nt stat/stinal d i f f ~ were ob e~cept for due DIO' and I~' parameters, as ~ell as for E~°F. The con~lation coefTicients ~mre very good m d x~e~ted a hi[~ significance (polo -6) for all the mrs m~alyzed. The ~alues obtained from the MAC~/OIH matio m~e similar to those a l r ~ y r~ported by edger ~xthor~. %it~x~h f l ~ investigmti~r~, are needed about rile rmdio9~mrmaceutinal kinetics, ~e believe that 9°~Wrc~MAG3 .my be m alternative to 1311-0~ in the ne~]oginal stody of ~%~ertmaive patients.

IN

The obtained data were analysed using deconvolutlon analysis of the renogram and mean transit times (MTT) for the whole kidney and kidney parenehyma, respectively, were calculated and compared 5 e t w e e n M A G 3 and DTPA. Furthermore, functional images of the mean time for each study were generated and analysed. There was no statistically significant difference between the corresponding parameters calculated from DTPA and HAG3 studies (a paired t-test, p>0.05) either for kidneys with reflux or it of them without it. Although the assessment of kidney morphology is superior using MAG3 sequential images due to lower background activity, the vissal appearance of functional images for both radlopharmaceutlcals was similar.

297 445

447

446

Z. Szab51,1 G. T o r s e l l o 2, W. S~ndmann2, ~ r g , L. E. Feinendegen

3 . L a p e l , J . H o l a n , 3. K l i m e n t % P. A l t m a n n , I . 5 v i t ~ E ~ A. Mara~ov@, J.°Buchanec

B.N~ele-WLhrle, H a h n K.

~Department of Department of

Nuc]ear Medicine, Vascular Surgery, U n i v e r s i t y DOsseldorf, F. R. Germany

Dpts. of Nucl. Medicine, grology~ Faculty Hospital 036 59 M a r t i n Czechoslovakia

Department of N u c l e a r M e d i c i n e Johannes Gutenberz-University, BED

INVESTIGATION OF THE RENAL PROTECTIVE EFFECTS OF PROSTAGLANDINEE1 (PGE1) IN EXPERIMENTAL ISCHEMIA: MEASUREMENT OF RENAL FUNCTION WITH Tc-ggm-MAGS, 1-131-0IH AND In-li3m-DTPA

P R E L I M I N A R Y R E S U L T S WITH THE RADIOPHARMACEUTICAL 99m Tc PEDIATRIC UROLDGY

E. Fennel, P. BerLelli~ , C.R,5eHina, D.Vollerrani and S.Ghione,

and

NEM

RENAL 3 IN

HAG

In dynamic renoscintigraphical studies of 5 normal volunteers and 20 children with various degree of renal i m p a i r m e n t 9Ym T c - m e r c a p t o a c e t y l t r i g l y cin /NAG 3 - M a I ] i n c k r o d t / has been compared with 13i I-OIH, 99m Tc-DTPA and 99m Tc-DMSA. It is c o n c l u d e d t h a t 99m To-MAD 3 p e r f o r m s w e l l in p a t i e n t s with impaired r e n a l f u n c t i o n s and m a y well p r o v i d e an acceptable replacement for 131 I - O I H . In r e n a l b l o o d flow s c i n t i g r a p h y it is c o m p a r a b l e to 99m Tc-DTPA w i t h t h e adv a . t a g e of more r a p i d r e n a l e l i m i n a t i o n . The i m a g e q u a l i t y of 99m T c - M A G was u n i f o r m l y s u p e r i o r . N a m e l y , it seems to be e x c e l l e n t i m a g i n g a g e n t i n some urologic disorders i.e. detection of vesico-ureteral reflux or in furosemid studies of patients with questionable obstruction and b e t t e r delineation of the ureters, where arLefacts due t o r e s piration unquietness are common. As an i m a g i n g agent of i n f l a m m a t o r y d e f e c t s of r e n a i p a r e n c h y m a it has near t h e same q u a l i t y as 99m Tc-DMSA. F i n a l l y , a t the end of t h e e x a m i n a t i o n a s t a t i c s c i n t i g r a m m zn l a t e r a l projection enables the diagnosis of renal ptosis. Thus, one c o m p l e t e e x a n i n a t i o n with 99m T c - M A G ~ g i v e s m o r e i n f o r m a t i o n s causing much l o w e r r a d i a t i o n exposure and has been f o u n d t o be a d e q u a t e i n pediatric urology.

Major s u r g i c a l i n t e r v e n t i o n s on the t h o r a coabdominal aorta and the renal a r t e r i e s may cause ischemic renal f a i l u r e . The aim of t h i s experimental study was to i n v e s t i g a t e the prot e c t i v e e f f e c t s of preoperative PGE1 i n f u s i o n in such s i t u a t i o n s . In 15 dogs (6 w i t h o u t and 9 w i t h PGE1 premed i c a t i o n ) renal lschemia was produced by tempor a r y clamping of the renal a r t e r i e s f o r three hours. At the t h i r d p o s t o p e r a t i v e day a double t r a c e r study w i t h 1-131-0IH and Tc99m-Mercaptsacetyltrig[ycine (MAG3) and subsequently a s i n g l e t r a c e r study w i t h DTPA were obtained. Tracer clearances were c a l c u l a t e d using a bicompartmenta] model. Parenchymal e x t r a c t i o n f r a c t i o n s and t r a n s p o r t times were c a l c u l a t e d from the impulse response f u n c t i o n s . Significant c o r r e l a t i o n was found between the clearance rates of a l l of the three t r a cers and the c r e a t i n i n e clearance ( r = 0.65 to 0.74). Furtherun the parenchyma] transport times showed significant c o r r e l a t i o n w i t h the dasma c r s a t i n i n e concentration ( r > 0 . 9 ) . Preischemic i n f u s i o n of PGE1 s i g n i f i c a n t l y mproved (p
448

°Podiatry

449

~

. e, A b u - R o m v h , ~, A l d a d a h .

RENAL SClNTIGRAPHIC CAPTO~RIL TEST: ANALYSIS BY FUNCTIONAL IMAGINGFOR THE DE~CTION OF GLOBAL AND SEGMENTAL HYPOPERFUSION. We and othershave recentlyreporLed[hst 99mTe-D]PA renal scinUgraphywith Capthpril(C.) test may represent a usefultoolFor the diagnosis of renovascular hypertension ainte il allows the deLsctionof the decrease of glomerular filtration raLe (6FR) in the sLenoLickidney inducedby the inhihiLionstag II. which is a known GFRregulator in the lower range ofrenal berFusionpressure, We here reporLon a ,newmethodof C. renographi¢analysiswhich, comparedLo the conventionalones.is eosier and quickerLo perform and visually more informative, due Lo the use st Functionalimaging (Gellinael el, t9~O), II consists in the calculaLionand display of a runcLlonalmap in which each pixet represents by color the Limeof peak actMly: user interaction during the analysis allows [he selecLi0n of optimal Lime ranges For the visualizaLion of the renal compartmenls (cortex, medulla, pelvisl with inter and/or intra differences in LransiL Limes.We hsve evaluated by this procedure 17 cases of paLienLs with esLab~ishaddiagnosis of pan.secular hyperlension in whom ggmTc-DTPA (BraCt) renal acinLigraphy(I frame/lOser for 15 sin) WaS performed twice, respecUveiy in basal condiLionsand 1 hr al~r C. (50ms by os). AFter C,, in 7 cases no clear dislincUon heLweencortical and medullary b-snell times was any more delectablein the sLeno[ic kidneyand a globaldelayof [hansil Limes was observed (type A response); in 6 cases the affected kidney appearedas a pure single vascular compartment, characlerized by very early [hansiL times, quite comparable to lhose of surrounding parenchymas,such as liver and spleen; in these cases,shilling [he lime scale after [he rirsl-paes range allowed no further v~sualizalion of the affected kldney [Lyre G response). This effecl indicates a completely suppressed 8FR [n spi~ of a preservedbloodflow, as slready documenLed(Fommalel ah lg85). In 4 cases funclion~l analysis afler C revealed segments) abnormaHlies, either of type A (2) or B (2), always corresponding lo the arteriopraphic findings: in these cases the response lo C. evaluaLedby convenlionalrenographic analysis was inconclusive. Theseresults show that Junctionalimagingattar C. represents a valuable adjunct technique Lo renographic analysis, which may be parlicular]y useful whensegmentalperFusiondefects are involved.

O.,Ei~ner

D.,

Heinz,

D I A G N O S I S OF R E N A L D Y S F U N C T I O N IN CHILDREN USING 99m-Tc-MERCAPTOACETYL-TRIGLYCINE (MAG~) In 7~ c h i l d r e n w i t h v a r i o u s k i d n e y diseases clearance measurements were performed using 99m-Tc-MAG3 (Mercapto-acetyl-tri~lycine). In ~6 of t h e m the v e s i c o - u r e t e r a l r e f l u x (VUH) was d e t e r m i n e d a d d i t i o nally. Due to the q u i c k e x c r e t i o n b y the k i d n e y s , the l o w r a d i a t i o n dose a n d the f a s t a v a i l a b i l i t y , this s u b s t a n c e has b e e n a c c e p t e d as a r e p l a c e m e n t of 1-131/I-123-ortho-hlppurate. The i n j e c t e d dose was 1,1 M B q / k ~ . The renal function studies were acquired d u r i n ~ a t o t a l time of 32 m i n u t e s w i t h a f r a m e r a t e of one i m a ~ e / 2 minutes. T h e r e n a l c l e a r a n c e , s e p a r a t e d for each kidney, was c a l c u l a t e d by the m e t h o d of O b e r h a u s e n . The indirect reflux-study followed after hydration in this way: S e q u e n t i a l i m a K e ~ w e r e a c q u i r e d d u r i n E five m i n u t e s w i t h a f r a m e r a t e of 4 t m a K e s per m i n u t e . VUR w a s t e s t e d f i r s t by ap m p l y i n ~ h i E h p r e s s u r e to the b l a d d e r in s u p i n e p o s i t i o n . A f t e r that the e x a m i n a t i o n was p e r f o r m e d in s i h t i n ~ p o s i t i o n d u r i n K v o i d i n ~ . The V U R w a s i n d i c a t e d b y a r i s e of a c t i v i t y w i t h in t h e [ k i d n e y s . The r e n a l f u n c t i o n s t u d i e s w i t h 99mT o - H A G 3 in c o m b i n a t i o n w i t h V U R ~ i v e s an o p t i m a l i n f o r m a t i o n , w h i c h is u s e f u l as w e l l for the f o l l o w - u p b e f o r e a n d a f t e r c o n s e r v a t i v e or surgical therapy.

450 A.

R.

and

Al-Suhaili

I

CNRInsLiLuteof ClinicolPhysiotogy.and =Nuclear MedicineCenter, UniversiLy or Piss. Italy,

Nickel

From the F a c u l t y o f M e d i c i n e and M i n l s %my of P u b l i c H e a l t h , K u w a i t .

ICAPTOPRIL MONOTItEEAPY IHYPERTENSIOE.

IN E S S E N T I A L

ll male patlents (40 + 5 years) ~ t h mild to moderate uncompllcRte~ essential hypertenslmn olo short durotlon (8 + 3 months) were studieS. IK hall medlea~ions were held for two weeks and aseline measurements of effective renal lasma flow (ERPF) utilizing Gchlegel programme d a single injection of 131-I-|lippuran, ~etients were instr'!cted to eentin,le th~i~ sual salt intake, Captoprll 50 mg twice daily as started Immediately after the baseline tudy and a second ERPF measurement %'as brained a f t e r 18-14 d a y s .

I

n 8 of the ii patients, blood pressure iesponded te Captoprll (147/105 + 8/4) to 125/86 ~ 9/6 mm~K) w i t h concomm~t~nt r i s e f EEPF from ba~ellne of 410 + 41 to 520 + effect nor ~n increment in ERPF vas d e m o n s t r a t e d i n t h e e t h e r t h r e e p a t i e n t s ~ho manifested ~ormal base llne EEPF (558 53 ml/mln/l,73m ), Sodium intLke (i00 + T5 mmol) was not restricted durins the study ~ypotensive

; c r i e d End i t did n o t seem t o c o r r e l a t e

with

~lood pressure response.

;ufb findinEs accord the previous studies ~howlng an average reductdon of 20~ of renal ~leod flow in shout two-thlrds of young Jatlents wlth essential hypertension of short duration Lnd suggested that monotherapr with aaptopril would 5e most effective and physlolaSlC in this subErou p of patieRts, gn conclusion, measuring baseline ERPF wlth 131-l-Hippuran process, could be a valuable clinical tool for more physloloslc s~tlhypertensive t r e a t m e m t ,

M.Dondi;R.Eranchi;M.Levorato;M.Mirelli* A.Stella*; A.Zuccala'**; R.Gaggi**; F . M a r c h e t t a * * * and N M o n e t t i Departments of Nuclear Medicine, Vascular Surgery* , Nephrology** and Clinical Pharmacology*** S.Orsola-Malpighi Hospital; Bologna, Italy RENAL SCINTIGRAPHY WITH CAPTOPRIL [RS+C) IN THE EVALUATION OF BENOVASCULAR HYPERTENSION (RVH) AND F O L L O W - U P OF R E V A S C U L A R I Z E D P A T I E N T S . The diagnostic advantages of R S + C in terms of sensitivity (S) and specificity (SP) as compared to conventional renal scintigraphy (Re) were investigated in 106 9 o r i e n t s , 86 moderate to severe hypertensives (Group i) a n d 20 renal r e v a s c u l a r i z e d patients (Group 2).All patients underwent Re, and 3 or 4 days later R S + C ( c a p t o p r i l 50 m g r per os one hour prior to the study),A renal a r t e r i o g r a p h i c s t u d y (RA) was carried out on all p a t i e n t s w i t h i n 30 days In g r o u p i, out of 170 r e n a l arteries, RA i d e n t i f i e d 75 s t e n o s e s (38>70%), 25 monolateral and 25 bilateral.Consldering a 70% stenosis or more as hemodinamically significant, RS+C showed 94% S and 100% SP (diagnostic accuracy 98%), while for RS values w e r e m u c h lower (50% S , 79% SP and 71% diagnostic accuracy). In g r o u p 2, w h e r e R A p r o v e d n e g a t i v e in 22 r e v a s c u l a r i z e d arteries and p o s i t i v e in 7 (i r e s t e n o s i s of the anastomosis, 2 restenoses after PTRA and 4 cases of patent graft with atrophic kidney), RS+C gave the same results. Two controlateral stenoses, not operated, were also correctly identified In c o n c l u s i o n , R S + C a l l o w s a much betterevaluation of suspected renovascu]ar h y p e r t e n s i o n and, b e c a u s e of its perfect correspondence with arteriography, was f o u n d to be a v e r y good non invasive tool in the f o l l o w - u p of r e v a s c u l a r l z e d p a t i e n t s .

298 453

452

451 Alberto Cuocolo, Kevin E. HcCarthy, Neumann,

Eonald D.

Department of Nuclear Hedicine, National Institutes of Health, Bethesda, Md, USA.

RADIONUCLIDE RENOGRAPHY PREDICTS FUNCTIONAL CHANGES IN PATIENTS WITH TAKAYASU'S DISEASE ~ND RENAL ARTERY INVCLVE~NT.

AM Peters, J Brown, D Crossman, ME Saddle, AP Beming%zay, DJ Allison.

A.M.AI-Nahhas, K.E.Britton.

Hammersmith Hospital and Royal Postgraduate Medical School, London, UK.

Dept. Nuclear Medicine, St Bartholomew's Hospital, West Smithfield, ECI, London, UK.

EFFECT OF ANGIOPLASTY ON RENAL HA~4ODYNAMICS I N RENAL ARTERY STENOSIS.

THE DETECTION OF RENAL ARTERY STENOSIS AS A CAUSE OF RENOVASCULAR DISORDER IN HYPERTENSION: A COMPARISON OF THE MEAN RENAL PAEENCHYMAL TRANSIT TIMES WITH RENAL ANGIOGSAPHY,

mood

~

to e~ch kidr~y (~F), as a 9ractien of

cardJm~ OUtlmJt (CO), cm~ £ e ~ i l l y

bem~l

fo]]owir6

A.J.Marcus,

J.Romanji,

J.E.Dacie

Renovascular hypertension is a major complication of Takayasn's arteritls (TA) contributing to the high mortality associated with the disease. Radionuclide Renography (RR) is used to detect renal artery stenosis and to study split renal function. To assess the ability of RR in TA to evaluate renal perfusion, function, and to predict changes induced by TA before and after interventions; we studied 5 pts affected by dzfferant degrees of TA. Computer-asslsted dynamic renal imaging, wfth Tc-99m DTPA and with 1-131Hippuran, and renal arteriography were concurrently performed in all pts. Two pts had hemodynamie~lly insignificant renal artery stenosls (<20% stenosis by arteriography). Both showed normal perfusion and function with Te-99m DTPA and 1-131Hippuran. Three pts had siMnlficsnt renal artery stenosis (>_90%) documented on arte~iogram and all had accompanying fuctional changes on the RR. Subsequently, 1 pt had successful interventions with bilateral renal artery by-pass grafts and improvement was documented on both arterlography and RR. Another pt was evaluated pre and post renal artery anEioplasty and demonstrated appropriate functional changes on RE. Finally, a significant relationship was found between the percent of the renal artery stenosis and the split renal function ~ssessed before and after interventlons (r=0.74; n=i8; p
bolus IV inj~-tinn of Tc-9gm [~fPA (Peters AM et al 1987,Nuci Mad C~mm 8, 8~3-37). I,~ ~ t h i S tedmique to i s ~ i ~ C e the e/Test on RBF ~ p e ~ an~lasty (FIA) i n 10 ~ddT~ys (8 patxer~s) with artery s t ~ (P~S), ~hiah in 2 ~atients was responsible for r ~ hype~icm (BVH). Indi~dus/ ~ e y ginmen~r f~/trati~ rate (~F~) was also ms~sz~d f~m tb~ diff~-~nt~l f~mcti~ m~ s~bse~ plasm d ~ of Tc-9°~ DIPA up to ~/~. Filtration f~acti(m (FF) vas t ~ o b t a ~ by ccmbinirg ~]F with h ~ R . Tne~e p m ~ h e r s were m ~ in a f ~ h e ~ 15 ~atie~cs with ~9~Itial bype~tensinn @ D ~ argic~ but not ~TA. I~F and ~ ~ highly wariable in the e~tire populatiau and n e l t ~ ~ any o a n - e l ~ i ~ n with the a~c~c f ~ , araded ~s ~ n m l , or as s h ~ m ~ miner, ~%m~ate or severe ~AS. ~ ~ ,trUly in 8 of 10 5tenable k i d r ~ (inclLxf~ 2 with R~H), following ~TA but r ~ ~ iu 2 (overs// increase: 1.1 (~D 0.71% CO ce 20 (13)% of h e s e - l J ~ ) . :~d, i n gestural, a slight ~ (mean 3.1 (3.4) ml per mdn). The d ~ r~ting t~ FFA in the 2 w i t h RVH ~ s i m i l a r to the others. FF d ~ d inconsistently, alt/~ugh d e ~ markedly in I static kich~ P e s ~ b l e f(~ ~H. A sir~le ~stimation of PaF in the w ~ " k ~ of sUSp~cb~d RVH is of l ~ h e d value, unless no~Bl, when it s~g~ests a ~ c a 3 / y irstgntfissnt lesion. Sequential studies before and a f ~ ~fA are useful to &x~mm]L the e f f e c t i v e n e s s of the proced~.

Functionally relevant Renovascular disorder, RVD, whether due to renal artery steoosis, RAS, or small vessel disease causes increased salt and water reabserption by the affected kidney, thereby prolonging the mean transit time througl the parenchyma MPTT of a non reabse~bable solution such as Tc-99m DTPA. This, in combination with a reduced relative function RE%, is used as a screening test fo~ RVD in vatients ~ith hypertension, HT. To validate this ~pproach patients who had undergone selective renal angiography, RA, for whatever reason and ~ho had also had gamma camera Tc-99m DTPA ~tudies using 400 MBq with measurement of MPTT )y deconvolution analysis were reviewed (42 ~idneys). 8 kidney donors with normal RA showed equal RF% (50t8%) and HPTT of 171±~3s (Mean±SD) 4 MT without RAS showed MPTT of 186±32s, not significantly diTferent from normal, NS. 7 patient~ ~ith significant HAS hy HA snowed prolonged NPTT (344±76s, p
454

455

456

J.

DARCOURT,

I.

MENA,

M.

KOYLE

CENTRE ANTOINE LACASSAGNE, U . E , R . DE HEDECINE

DE NICE, FR.~CE HAP~OR-UCLA MEDICAL CEh~fER, UCLA SCHOOL OF MEDICINE, USA O F R E N n L TRONL;Iq.MNT Pi£I~P'USION D U R I N G O C U T K T U B U L A R NECROSIS ~k~ r e p o r t o n z l rcLrO:~l*e~ctlvc ~ t u d y o F Sl 9 9 m T o - D T P a r o s a I f ]o ~ ~ t u d lc~ (RF) r~rforme<] o n e 6 trarlL~plan~ed ]31%tiertt° durin~ acute tubular necroois (aTN)The ~TN period ~a~ defined as stsrtin~ the day o F tr~n~plar]t~ztEon and endln[~ when the creatin~ne l~vel bad dropped ebz (average ~0.6 d !,y~. m ~ l ~ m u m ~ , ~ximum ~0), The l~V ~ t u d le~ ~re a c o u i r e d air 8 r a t e of o n e i m a ~ e l s e c o n d du~in~ one minute ot[~rtin~ from bhe bolu~ injection o f 1 5 m C i (9-55 MBq) o f 99mTc-DTPN. The camer'~t w a ~ placed ~n anterior projection over the pelvic 8reel The m lope r a t in bergen the r e s u l t in~ kidney and s o r t ~c curves K/~%) ~s computed accordin~ to Kirchner" s method. Normal vsl u e ~ ~re O . 5 5 t O . iz+ (n=~9) and acute rejection v a l u e s 0 . ~ 7 ± 0 . it (n =~0) (m±isd) . separately a n a l M secl the m t u d ies ~er f o r m e d ~ithln ~J~ hours from transplantation (D1), (luring the f i r - s t ~he Beoond and t h e t | l ~ r d q u a r t e r o f the ~TN p ~ r l o d (I/dATN, t/~ATN,Zb/~ATN)DI I/~Ih'I'N I/~h'I'N ~/~h'I'N

V. Alevizou-Terzaki,C.Zerva,D-Kyri aki-Man°la~ raki,G.Papadimitrioy,G,Zavos and J. Homatas. Department of N u c l e ~ Medicine and Transplanta. finn Unlt. Lalko General Hospital,Goudi,Athens Greece.

EVOLUTION

n p values
follo~-U M o f

these

patients.

The fate of the transplanted kidney.Changes in GFR from living donor enviror~ent to recipient. ~ne p ~ s e of the study was to determine that percentage of the fiuzction of the kidney to be donated which remains in the recipient both in the early post-tr~nsplant period and after various pericxls of stabilisation. Thirty donors were studied by Radioisotopic RenOgraphy ~rlth 99m-TC DTPA and ~-Camera to detemnine the percentage f~mction of the kidney to k~ donated. Total GFR waS also measured using the classical 4 s ~ p l e method with 51-Cr EDTA. After transplantation, the (~R of the kidney in the recipient was m e ~ u r e d at the e~d of the first ~ostoperative week and again at 3 and/or 6 months after transplantation. In transplanted patients who were not muuric prior to transplantation. The GFR was m e a s ~ e d and subtracted from post trsr~plsnt measurements. ~ e 51-Cr F/)TA method was htsed ~/~ prefere/uce to ~ r a GFR measu~E~aents to avoid difficu/ties arising from the changir~ anatomical situation of the kidney from donor to recipient. Ar~lysis of the reSLL~tS obtained shows that in the absence of serious or repeated episodes of rejection or other postoperative complicatiOD~ the f~tnction of the donated kidney in the recipient can be as good as it was in the donor and in some cases may be even better.

I.M. RIEDINGER , Y. BIDAN, T. MUNSCH, and J.L. PELLETIEB gUCLEAB ~ENTRE Rue du ~IORA

L. GOGOU

MEDICINE DEPARTMENT GEOEGES-FRANCOIS LECLSRC Professeur Marion DIJON CEDEX (FRANCE)

FC RECEPTOR FUNCTION IN PATIENTS WITH RENAL FAILURE, UNDERGOING CORTICOID OR SERIAL pLASMA EXCHANGE TREATMENT The function of the FC Receptor (Fc R) in patients with renal failure, undergoinE corticoid or serial plasma e x e h ~ g e (p.E.) treatment, has I been studied. ,Patients and methods i- Fc R activity wasexamined in 6 patients beflare and after P.E., and in S patients before and after eorticeXd treatmen t • - After injection of each patient gEM+) with Tc-SSm labeled, anti-D IgG sensitized autolo~ous erythroeytes, we calculated the clear,re %all time (T~), the spleen to liver accumulation 7atio (S/L) per pixel, and the total hepatic g o d splenic activity per mCi injected at 40 mn. ~esults - Plasma-exchange : in 5 patients, with autoimmune diseases,the beneficial effect of P.E. ,as associated with a decrease in the T~ (5 % 33 %) ~mud an increase in the g/L r~tio (g.7 % El,g %), due to a reversal of splenic blocage, (4 % - 43 %) accomp~ied in 80 % of the zases by a decrease in hepatic uptake (7 % 26 %). In one patient, the S/L ratio was the flrst parameter modified after P,E. In the last patient without autoimmune disease a clinical failure after only 5 P.E. was associated with mu increase in the T~ (25 %). 1 - Cortioold : in all 3 patients the T~ increased I (i0 % - 28 %), associated with a decrease in I ;plenic uptake (5 % - 2d %). However, we found L compensatinE increase in hepatic uptake in 2 | ,atients accompanied by a decrease in S/L ratlo.

I

I l

!his study verifies the modulation of the Fc N | "unction by P.E, and oorticold treatment and mderlines the importance of monitoring the S/L 'ati0 during P.E,

299 457 M.D. Marin, J-Coya. M.Navarro,D.Lasa,G.Riesco and g.Hernandez de Madaria~a. Nuclear Medicine Dept. Pediatric,Nephrolo~y Dept. Hospltal "La Paz".Madrid. Spain.

REFLUX NEPHROPATHY IN CHILDHOOD. We compared the renal madionuelide studies(RN) with intravenous urogram(IVU) and abdominal ultrasound(US)in children to whom vesicourete ral reflux (VUR) have been detected by mictu~a ting cystoureterogram(MCU). MATERIALS AND METHODS: We have studied 21 ehil dren (13 males ~l~d 8 females , 7 months-17 -years x=E.7 years)with VUR demonstrated by means of YOU(12 bilatera!,6 left-~ide and 3 right-side)placed on long-term antibiotic prophylaxis:with the cessation of VUR the treatment was stopped. Antirreflux Surgery w a s r e m gulfed in 5 children (8 kidneys).genal labora to~y test and the following diagnostic teehni-q,le~ were carried out:MCU,US,IVU,99mTc-DMSA,9£mTe-MAG-Furoseg}de. RESULTS:Number and VDR degrees were:grade I:l; grade II:10; g~ade III:4 and grade IV:6. On S patients the cessation of VUH was demonstrated. Normal renal cortex was visualized in 12 ohildren(~4 kidneys)by US,IVU and RN:dilated collar ring system was present in 3 out of 24 and wer~ documented by the three teshniques .Abnormal renal cortex was identified i~ 9 Children (18 kidneys): 13 out of 18 kidneys by NN,12 out of 18 by IVU and ii out of 18 by US;bilateral or unilateral dilated collecting system or/and ureter were detected in 6 patients by the three methods. CONCLUSIONS:Nuclear Medicine image has proved to be as uscfull as IVU or US in the reflux nephropathy study,The unilateral renal function euantification by Nuclear Medicine will pe~mite to compare data durin~ the follow up.

460 C.Schuemichen, R.Fischer. Th.Krause, A.Joseph, P.Sierke Department of Nuclear Medicine, University Clinic of Radiology Freiburg, FRG

PREDICTION OF OBSTRUCTIVE NEPHROPHATHY B] QUANTITATIVEDIDI~ETICRADIONUCLIDEI~NOGRAPHY ? Dlnretie r a d i o n u e l i d e r e n o g r a p h y (DRR) is t h o u g h t to distinguish patients with dilated, non obstructed systems from those with significant mechanical obstruction. In the dilated pelvis the outflow should be increased by furosemide, whereas in mechaniea obstructed systems no response or even a decreased outflow should be observed.

This widely accepted hypothsis was evaluated again. Provided t h a t the periods of disease duration were distributed randomly, a correlation between the diuretic effect of furosemide and t h e tubular clearance of the affected kidney (in absolute and relative terms was exspected. A total of 238 pts with unilateral pelvic dilation were investigated. Using a onestep protocol of DRR in 152 patients, furosemide (0.3 mg/kg) was given a t a fixed time (30 rain) after application of 15 MBq 1-123 hippuran. According to the degree of obstruction the renograms were divided into 5 subgroMps. The change iMpelvic outflow (quantitatively assessed by exponential fitting of the of the excretion phases of the renograms) was poorly correlated with the tubular clearance of the affected kidney. In 86 patients a two-step protocol was used. At first a non-diuretic radionuclide renography was performed. After complete clearance of activity from the kidneys, renography was repeated by simultaneous application of hippuran and furosemide. In 29 pts 70 MBq Tc-99mMAO3was used for this. The two~tep protocol provided a somewhat better correlation (maximumr=0.88 in patients with moderate severely delayed pelvic outflow) than the one~tep protocol (maximumr~).50). Nevertheless those results are far away from that accuracy needed in the individual case for selecting those pts who need surgical treatment to prevent obstructive nephropathy. In conclusion other criteria t h a n a simple quantification of diuretic pelvic outflow are necessary to improve the prognostic value of this test.

458

459

Budel E ; Roll K o p p e n h a g e n K,

(Department

G,;

Dieringer J , ;

o£ N u c l e a r

Medicine,

Bauer B.-R.*;

Department

o£

R.H. Bahar, M. Sabha, K. Knurls, K. E. Britton+ and H.M. Abdel-Day~. Dept. of Nuclear Medicine, Faculty of Medicine & MPH, Kuwait and +St. Bartholomew's Hospital, London, U.K.

Brology (*), Oni-Klinikum Steglitz Berlin) THE INEFFICIENCY OF THE SPACE TIME MATRIX APPROACH TO BRETERAL MOTILITY

motility o£ the ureter is used as one criterion for the effectiveness o£ surgical intervention in the renal pelvis. Conventional x-ray produces rather h i q h radiation levels in this case. The space-time-matrix approach tries to describe the peristalsis o£ the ,refer by using typical patterns or tlme-aetivitF-di£ferenees, It .as introduced i,to roatime renography .ith 1-123-hippur~ne by /I/. The method suffers from low counts and high background. To differentiate betseen true and artificial saving, the Eonte-Cavlo method .a~ used to define the 0.95~ractil o£ the number of ,aves. Renography and percutaneous fistula of the renal pelvis were compared £om examinations 0£ ureteral peristalsis. For 300 pictures, @ EDI's and a threshold equal to the means o£ the NOI's, the limit o£ significance is tO antegrade and/or 7 retrograde .ayes. In renography The

no distinction can be made between the different types o£ peristalsis. Because of background elimination peristalsis can be seen

in patients .ith fistula. Therefore. the spaoe-tims-matrix should not be part o£ routine urnlogical diagnostiQs. Example for the l a c k of the discrimination b e t ween true and a~ti£ieial ~aves: 6 ROI's an 60 p i c t u r e s & 2 see observed by generated by the reno~raphy . . . . . . Monte-Carlo-method

i:gl::l' ::~:,ii,:i':"~l,':'i"! ',',I"

, . ,',d, i " ~""" ~ '''~ ~,, ,, ,,,,, ,,, ,~,,,,, ~ , , , ,

} ':,~,~'~:,,,',~,i':C,:,~t~,:!' ~,']::,:: ,

waves marked by:~ antegrade: a retrograde: / 1 / H u e l l e r - S c h a u e n b u r g B.; Anger K,; in: UrodynamlcS 1985, Berlin-Beidelber~ pp 154-167

461

THE VALUE OF Tg-ggm [YfPA DIURETIC R}~OGRAM (RDR) IN THE ~ALUATION OF SUBGERY IN CHRONIC OBSTRUCTIVE UROPATHY (COU). A prospective study of 90 patients(pts) (95 operations) with COLT (68 chronic schistosomiasis & 22 non bilharzial COU) was done. All pts had pre & post operative Tc-99m DTPA RDR. Three obstructive renogram patterns were identified in pts who needed surgery: F3 retention of tracer & adequate response to lasix; F4 retention of tracer & no response to lasix; F5 nephropathic kidney. Non obstructed kidneys (patterns PI & F2) and completely non functioning kidneys (F6) required no operation The following operations were carried out: I. Reimplantation of ureter to bladder. 2. Lithotomy 3, Balloon dilatation of ureter 4. Catheter dilation of ureter 5. Pyeloplasty 6. Ileal conduit 7. Nephrostomy 8. Percutaneous lithotomy. For each operation and RDR pattern, the surgical outcome was as follows : F3 F4 F5 Total ] 3/9* 19/27 ]/4 23/40(58%) 2 5/10 8/10 I/2 14/22(64%) 3 2/4 8/8 0/0 10/12(83%) 4 0/I 314 0/2 3/7 (43%) 5 0/2 1/2 0/0 1/4 6 0/0 1/2 0/1 1/3 7 0/0 2/2 0/1 2/3 8 1/1 2/2 1/1 4/4 11/27(41%) 44/57(77%) 3/11(27%) 58/95(61%) * 3 out of 9 pts improved after surgery. Pts with pattern F4 benefited most f r ~ surgery, followed by pts with pattern F3; nephropathic kidneys (F5) beneflted least. We conclude that Tc-99m DTPA RDR can be used to select pts who need surgery and can predict the outcome with respect to likely improvement or otherwise.

462 Rehling M.

R.BEUSCART, D.PAgNIEZ, $.COEgtEfT, R.VERGNES

S.C.H.N. - Bopital B - F Lille C l l n l q u e N e p h r o l o g l q u e - Pr A.TACQUET - L i l l e

Departments of Clinical Phys±ology at Hvidovre Hospital and Frederiksberg Hospital, University of Copenhagen, Denmark.

CALLIUN SCAN IN ACUTE RENAL FAILURE

Gallium

scan

may

be useful In the non Invaslve management of acute renal failure (ARF) in patients without severe preexisting renal Insuffleleney. 36 gallium scans were performed early, In the first week after the onset of ARF. SUBJECTS:

METHODS: 93 MBq of galllum-67 citrate Intravenously injected. Ag hours later, posterior abdominal scans were obtained (500 000 counts). The patient, lying In the same position, was then given 111 MBq of Te99m DTPA intravenously, to determine the outline of the kidneys, and to evaluate the renal function. After quantI[Itatfon, the activity of the ROIS was analysed using the following grading: grade O - h weak activity, less than spinel grade 2:.3 close to spine, less than liver; grade . same as liver I grade 4: greater than the liver.

were

RESULTS:

16

subjects

had

intense

bllateral uptake: 2 cases of drug-induced AIN and 9 cases of septic AIN were diagnosed. In the 5 other eases, a renal biopsy was performed to establish specific diagnosis. 3

subjects

with unilateral gallium uptake~ was clinically confirmed. 16 s u b j e c t s had no g a l l i u m n p t R k e : S had a r a p i d l y f a v o u r a b l e outcome (TN). Protetnuria, renal obstructions, amphotericin toxicity and glomerulonephritis, severe preexisting Chronic Renal Failure (5 eases) were the other diagnosis. unilateral acute pyelonephritls

CONCUJSION: In heavy proteinuria, u s e d a s a marker I n f l a m m a t i o n and l e d

most c a s e s of ARF without gallium u p t a k e c o u l d be of acute interstitial to e a r l y t h e r a p y .

MEASUREMENT OF GLOMERULAR FILTRATION RATE IN ADULTS:COMPARISON OF 5INGLE-INJECTION SINGLESAMPLING PLASMA CLEARANCE TECHNIQUES. After intravenous injection of a tracer that is removed From the body solely by Filtration in the kldneys, the glomerular Filtration rate (GFR) can be determined from its plasma clearance. The method requires a great number of blood samples but collection of uric is not needed. In the present investigation the total plasma clearance of SICr-EDTA mas assessed from 15 blood samples taken 5-300 min postinjection in 44 adult patients with GFR > IS ml/min. In 54 of these patients the plasma clearance of 9gmTc-DTPA was determined simultaneously. Using these clearance values as reference the reliability of six simplified methods mere studied: five single-sample methods and one five-samples method, The standard error of estimate (SEE) of the single -sample methods ranged From 4,2 to 7.5 ml/mln using £DTA, and from 3.8 to 6.5 ml/min using DTPA. SEE of the Five-samples method ~as 5.0 ml/min (EDTA) and 3.1 ml/min (DTPA), The best single-sample methods are recommended For daily use. In patients ~ith GFR < 80 ml/ min, in whom a highly reliable determination is needed, the Five-samples method is recommended. The plasma clearance methods studied here can not be used in patients mith oedema or OFR below 1S ml/min.

300

463 A M Peters, D 8 Jones, K Evans, I Gordon.

Hospital for Sick Children, Londor~ UK.

464 p

465 ~

G. D'ERRICO and E. SALVAGGIO ~

(o), F. NAN~3VANI (0o)

) laboratoryof NuclearFedicire-ViaP.Gio~io,15-Mi/~nD i°°)Institutof UrolcE{ - Universityof ~v/32ao

RADIONUCLIDE EVALUATION OF RENAL PARENCHYMAL FUNCTION IN CHILDREN WITH "MALFORMATIVE UROPATHY" OR "PARENCHYMAL NEPHROPATY".

THE MECHANISM OF RENAL UPTAKE OF Tc-99m DMSA • DI(NJ(I/DEDI~31ESISCF VAHI[f[~C There are 2 possible routes for Tc-99m DMSA into the renal cortical cell: a) direct extraction from perltubular blood, and b) tubular reabsorption following glomerular filtration of nan-proteln baund DMSA. The relative c o n tributons of these 2 routes is not clear but will depend on 3 factors: the protein-binding in plasma, the renal extraction efficiency (E) for DMSA, and the fractlon that appears in urine. We measured these 3 parameters an~ constr~cted a model of DMSA handling. Based On HPLC and gel filtration, 74 (SE 3)% (n:9) of DMSA was proteLn-bound in plasma and ~6% was '~free". Assuming a filtration fraction of 20~, such proteln-binding would suggest a value of E for DMSA based on filtration of 0.2 x 0.26, or 5.2~. Total E, measured from gamma camera dynamic i~aging using a recently described technique (Peters AM et al 1987, Nuzl Med Cam3 8, 823-37), was 4.8 (0.5)% (n=5). Indirect estimates of E and protein-binding based on I) the time course of DMSA uptake in normal kidneys, 2) the effective volu~e of distribution of DMSA (which is dependant On the amount of protein-binding), 3) the initial rate of DMSA loss from plasma and ~) the final fraction of DMtA deposited in the kidneys were 4.9% and 63% respectively, supporting the more direct estimates. TheSe data suggest that essentially all the renal DMgA uptake is by glamerdlar filtration and tubular reabsorption Data based on the captopril test in 2 patients with renovascular hypertension generally agree( with this, although a minoriby of DMSA is take~ up directly from blood as shown by discordant changes i~ DMS~ and DTPA uptake before and after captoprll.

466 AM Peters, B Laws, RM Mialdea-Fernandez, I Gordon.

Hospital of Sick Children, London, UK.

Tc-99mDTPA RE~OGRAPHT : THE VALUE OF A POSTMICTURATION VIEW IN PUJ OBSTRUCTION Hydronephrosis may represent PUJ obstruction or result from atonic dilation withoub obstruction T e - 9 ~ DTPA renography with an I V diuretic stim -ulus is routinely used to make this distinetiQ when, in obstruction, there is no washout of activity. Our aim~ras to assess the effect of a full bladder on the response to a diuretic. 59 Penal units were studied by Tc-99m DTPA renogr-aphy in 20 children following pyeloplasty for PUJ obsruction. The function in all these renal units remained stable over a mean period of 36 months, suggesting that no obstruction was pres -ent post-operatively. The response to frusemide, given at g[~ins post DTPA injection, w-as q ~ t i f l e d as the time taken for the backgroLhnd -corrected renal curve to fall to 75~ of the 20 min value (T75). 10mine after frusemide, the child voided and a further static image w-as obtained. On bhe basis of the T75, the 59 renal units were divided into 3 groups: A) 1 ~ i n s (n=27). Obstr~ction could not, therefore, be excludedin 45 kidneys. However, 16/18 units in group B ~ d 17/27 in gToup C showed good drainage after micturition, thereby excluding obstruction in 33 of the A5 apparently obstructed kidneys. We concludethat the reliability of Tc-99mddlzetic renography in the exclusion of PUJ ohstuotion is significantly improved by the inclusion of a post-micturition i m a m , which, in this series, reduced the false positive rate, based on the r75, from 76% to 20%.

he diz~9~csisof ~asculcgenici m ~ m ~ e is o~tair~ ~sinly transcavemsm c c n t r a ~ ( c a ~ ) a ~ the ~sst~e of the ~ blood flow in hes~l ccrdition ~ e r erec~toni r ~ by vas~ti~e ~ugs. T~se met~xls /low cle~c a-~ detailed i ~ h~t are invasivea~J ~ti~es subject to importantcu~plic~ticns.To ~ v i d e dim-of v ~ o ~ a n i c i ~ e ~ - e with non invasi~ ~ethed e performed Ln 22 pts blo~ pool stu/y (inisctiane.v. of drofcsfate ar~ 15 mCi Tc 9~m)in ~ c ~ t i o n and 10 mLn intracaverna~ nniecticnof pa~verine(0.6g) and bmtol~ (0.3 g). ~ techniqueall~ the id~nt~-ic~.i~ of c~v~uo-v~rm/s leakagewich r e ~ t s an ~ t ause of er~tile d y ~ i e n . This ccnditic~s c m ~ a c t ~ F an ~hsence of w~zus b l c ~ d ~ g ere~icn sc an a ~ sl hi~n flow is n e c ~ to indme ~ed m ~ the ererich. W hen twe c~a~e of i ~ t a ~ e ~as vas~ogr/c ~e "~rd r e ~ i c n of quantitativep~nile index after vas[~cti. e drug. We think that ~ me~zd is relde~le, safe, with e~y little disc~c~t fc~ the pati~t and very usefhl in he clinical d ~ of caverno-vs~a~ lesmge as c~use ,f ~ t e r ~ e .

467

In 1960-85 112 patients (aged 2 days to 14 years) underwent Computerized Renal Radionuclide Scitigraphy or Computerized Indirect gicturating Cistoscintigraphy or both. By a retrospective survey of all data (clinical, radiological, surgical etc.) the cases could be classified: 39 normals, 73 affected by obstructive uropathy or parencbymal nephropathy. In differentiating pathological from normals the performance of the radioisotopic tests was: T.P. 60/73 (Sensitivity 82%), T.N. 33/39 (Specificity 85%), Accuracy 88%. P.V.P. R. 91%, P.V.N.R. 72%. U.S. and I.V.P. show less Sensitivity (U.S. g ~ ; I.V.P. 77%). 68 patients were referred to radioisotopic examination with suspicion of "obstructive uropathy" (54 really affected by the survey). In confirming or excluding obstructive uropathy the performance of radioisotopic test was: T.P. ~i/54 (Sensitivity 76%). F.N. 11/14 (Specificity 79~), Accuracy 76%. 44 patients were referred with suspicion of "parenchymal nephropaty" (19 really affected). In this group the results of radioisetopic test are: T.P. 19/19 (Sensitivity iOO~), T.N. 22/25 (Specificity 88%). Accuracy 93%. Conclusion: the nephrourologioal radionuclide examination is useful in the obstructive uropathy of the children (also by giving functional infermation), but particularly effective in parenchymal nephropathy.

468

R.Berberich,

H.P.gtoll,

Ii

P.Benz,

iku/a,T. and MiltunenlJ.

Abteilung f~r Nuklearmedizin Radiologische Universit~tsklinik U n i v e r s i t ~ t des S a a r l a n d e s ~ u r g / S a a r ; W. G e r m a n y

• THE

Nuclear Medicine Institute Paediatric Institute ~ Catholic University of Sacred Heart Largo F. gito - 00168 - R C M A

DIAGNOSIS OF THROMBOSIS

DEEP

echnical Research Centre of Finland Reactor Laboratory, Espoo Finland

VEIN

Tc-99m-EMPAO allows labelling of leucocytes for the diagnosis of inflammations. The substance, h o w e v e r , is w e l l s u i t a b l e for l a b e l ling platelets. We o b t a i n e d labelling yields of 40 % -50 % in patients with .normal platelet concentrations. Platelets were separated by several centrifugation s t e p s f r o m w h o l e b l o o d s a m p l e s of 45 ml m i x e d w i t h 5 m l of ACD (formula A). We incubated the platelet suspension w i t h 1.0 - 1.5 GBq TcHMPAO in 1 ml for dO min. at room temperature. Unbound activity was r e m o v e d by s i m p l e w a s h i n g steps. D u r i n g the l a s t 2 y e a r s we h a v e u s e d Tc-HMPAO labelled platelets in 50 patients f o r the d i a g n o s i s of deep vein thrombosis. 370 - 450 M E g w e r e injected into a v e i n on the foot with a congestion above the ancle thus performing a radionuclide venography. We registered dynamic scintigramms with a frame time of 0.5 seo. o v e r the l o w e r limbs, the knees, the upper limbs a n d the pelvis. Static images were acquired a f t e r 5 min., 9 a n d 20 h o u r s . The results of radionuclide veinography and of static images w e r e in c o n c l u s i o n .in m o r e than 90%. Results w e r e p o s i t i v e in 41 % and n e g a t i v e in 52 %. O u r d a t a p r o v e the p r o c e d u r e t o b e w e l l s u i t e d for the d i a g n o s i s of d e e p v e i n t h r o m b o s i s .

THE FORMATION AND STABILITY OF lllln BLEOMYCIN COMPLEX AT LOW pH m e radioactive metal-Blenmycin (BLM) complexes ~ave been extensively studied because of their =,teat potential as tt~or-seeking radiopharmaceu- ; ~ieals. However, all metal-ELM complexes have Failed to earn general acceptance because of in lira lability (In-ELM), physical half-life of [scrape (~ Co-BI/g) or lack of t ~ o r affinity etc ~ecently Hou eb al introduced a new in viva ~table and high tumor affinity In complex (BLMC) ~lich is formed when pH is ~ d e r three. We itudied the formation and stability of this (and )ther BLM) complex incubating s a b l e s varying ;onditions. Analysis were carried with TLC. We ~otmd that the presence of some metal ions remove In from BLMC, but the process is quite slow in an~+caseg+The z~effect is-~ecreasingg~_in order of Fe , Cu , Co and Fe . The molar ratio ELM/In has strong effect even above i00. Other ions and temperature have certain influence on labeling, but buffering afterwards to higher pH does not have clear effect. The formation of 81/4C is strongest at pH 2.5 and it is rapidly Jecreasing to both directions. [he formation of BLMC competes with other BI/~ z~plexes like ~ and B o . So care must be taken H e n labeling is performed. Interestingly we Found that f.ex. ionic strenhb seem to affect to relative yields of con~0eting BI~4 complexes. {eference: ~ou,D.y. ,H~ch,H., Johnston,G.S., Ts~IK. C. ,Jones, %.E. ,Farkas,R.J. and Miller,E.E., In-Bleomycin I ]on~plex for Timer Imaging: Preparation,Stability I m d Distribution in Glio~a-Bearing Mice, J.Surg. I ~coi,25:168-175 (1984) ]

301

470

469 A.D. Varvarigou~ E. Chiotellis, C. Cotsifakis

G.Ferlin*, p. Zanco*, L.Lusiani ~ , N.Borsato* A.Vison~ ° , G. Breggion§, A. Pagnan °-

"Demokri=os"l[RCPS, Radiopharmaeeutieals Lab., 133 10 A~hens, Greece

*Servizio di Medicina Nucleare e §Divisione di Chirurgia, O.C. Castelfranco Veneto, Italy. oIstituto di Medicina Clinica, Clinica Medica I, Universit~ di Padova, Italy.

A~INODITHIOLS AS INDIUM A/~D GALLIL~{ BINDING LIGANDS

iii LOWER LIMES THROMBOSIS DETECTION THROUGH INLABELLED HUMAN ANTI-FIBRIN MONOCLONAL ANTIBODY.

Recent studies demonstrated that aminodithiols labeled with Tc-99m, form lipid 'soluble complexes, capable to penetrate the B.D.B. In the present work we investiEated th~ labeling of liEands , con=aining the aminodithiol melody with In-t11 and Ga-67. Comparative biodistribution of the resulting complexes was performed in mice. The followinE compounds were studied: RS-C(CH3)2-C~2NH(CH2)-N(Rk(CH~R where R=H(1),or CHgCH2-N~

(ll)

HS-C (gH3) 2-CH2-NR ~CI[2) 2~(CII2 ) 2NH] xCH2 g (0H3) 2 S where x=l (III), or 2 (IV), Labeling was performed in alkaline pH. Analysis (ITLC, electrophoresis) revealed tagging over 98%. Biodistribution data are listed below: % Dose per organ Comp.

Brain In

Ga

Intestines In

Ga

Urine In

Ga

(I) 0.06 0.04 25.75 22.39 4.70 23.~5 (II) 0.06 0.09 37.94 14.39 13.33 3.38 (III) 0.03 0.02 57.36 43.19 16.18 28.78 (IV) 0.04 0.02 30.63 40.63 29.12 29.65 Excretion route depended both on the structure of the ligand and the metal used. No brain uptake was observed. The easy incorporation of In-lll and Ga-67 into amlnodi~hiols encourages further investigation on complexes with more specific biOloBieal properties.

472 M. Liberatore,E,Di Nocco,M.Clemente,F.Scopinarc A.Centi Colella Section o£ Nuclear Medicine, Experimental Dept University "La Sapienza" 00161 ~ome.

DIETHILDITIOCARBAMATE-201-TI(DDC-201-TI):ANI~AL BIODISTRIBUTION.PP, ELII~INARY STUDIES IN HUMANS I~ COMPARISON WITH ~-PAO-99m-Tc. The labelling oF DDC was carried out according to the tecnique described by De Bruine et al. (1985).The method used is easy ~nd o£ high labe~ .ing yield.The studies o£ biodistribution on th( mimal showed a significant accumulation of the ,adiopharmaceutical in the encephalon (about 3% )f the injected dose at 15 minutes)allowing a :lear enough scintigraphic image. According to these studies a cerebral scintig~aphy with DDC{01-TI and ~-PA0-99m-Tc was also carried out on :we healthy volunteers and two patients a£fected )y myelinopaties. In the volunteers a normal )rain pattern was obtained with both radiopharmceuticals. Scintigraphic studies showed normal ~esults in the patients afFected bymy~linopaties, whereas 201-TI-DDC d~onstrated £ocal deFects o£ brain uptake. These results are in agre ~ e n t w i t h the previous reports by Costa et ai.(1987), in which it was suggested that DDC preFerably accmuulates in the white matter, whereas }gm-Tc-HM-PAO shows a higher acctm~lation in the ~raymatter. De Bruine J.F.,Van Royen E.A.,Vyth A.,De Jong J. M.B.V. and Van der Schoot J.B.:Thallimn 201 diethilditiocarbamate: an alternative to iodine 12~ N-isopropil-p-iedoamphetamine. J.Nucl.Med.26:92[ -930 (1985). Costa D.C.,lui D.,Sinha A.Z.,Jarrit P.H.,EI! P. .:Tc-99n~d,I-~NPAO and TI-2OI-DDC show di£fe~ent intracellul~ distribution in rat brain. ~cl.Med.26:32 (1987).

471 ~..~aU¢iO, P Vainio, JT Kulkka, K Bergstr6m, M Larikka, E Lansimies. University Central Hospital, SF-70120 Kuopio, Finland.

MONOCLONAL Ill-INDIUM ANTIFIBRIN WITH BLOOD POOL SUBTRACTION COMPARED WITH CONTRAST VENOORAPHY IN DEEP VENOUS THROMBOSIS

A new monoclonal antibody specific for the beta chain of human fibmin (022A - Fab-anfifibrin, FIBRISCINT) but no fibrinogen has been produced recently for the detection of venous thrombosis lld of the lower limbs. Labelled with In. it allows to visualize thrombi in vivo. We repomt our preliminary experience, regarding iS consecutive patients (8 males, 7 females; ag~ range: B5-79 yrs), Ii with a clearcut ~vidence of acute lower limb thrombosis (B deep, 5 super~ ficial), 2 with pulmonary embolism but without evidemce of lower limb involvement, i with a history of pulmonary embolism and secondary varicose veins, 1 with a post-th~omhotie sindr~ me. A phlebographg was obtained in 9 patients. lll 7a NBq In-antifibrin were injected ~nd then the patients were scanned with a gamm~ camera at 30 mins, dbrs ,2mhrs post-injection. The lllIn-antifibrin scintigraphy was positive in all patients with superficial and deep throm hosts but two who h~d been treated with H e p ~ i n for 5 days before testing. The most consistent images were obtained at 2g hrs after injection. 2g hrs seems ±o be the most reliable time to avoid false positive results and to obtain clam zut images. No adverse effects ensued. 111 We conclude that In-labelled antifibrin is an extremely promising diagnostic tool for v~nous thrombosis of the lo~er limbs.

Monoclonal antifibrin (AF) Fab-fragmends adhere specifically to fibrin but b i n d i n g i n t e n s i t y and s p e e d v a r i e s g r e a t l y . B l o o d c l e a r a n c e is slow. W i t h 991T¢ red blood cell subtraction we t r i e d to d e t e c t thrombi earlier and more accurately. M~/2~d~: 19 pts w e r e studied. Venog r a p h y was d o n e to 25 legs and r e s u l t s were assessed individ~ally for each leg. 1 1 1 I n d o s e was 1.8 mCi and 9 9 m T e 5 - 1 0 m C i . M E - c o l l i m a t o r was used. E a r l y 3-6 and late 1 6 - 2 4 hours images of 300kc were collected. Subtraction was done w i t h a least s q u a r e s t e c h n i q u e . ¥ e n o g r a p h y was usually done between early and late studies and heparin s t a r t e d if i n d i c a t e d . R~sults: 8 true positives, 15 true negatives, 1 false positive and I false negative were found. In the e a r l y p h a s e A and in the late p h a s e 1 t h r o m b i s h o w e d as a d e f e c t in the InA~ image. T w o f a l s e u p t a k e s ( v a r i e e s ) w e r e c o r r e c t l y c l a s s i f i e d as n e g a t i v e s after subtraction. Cmn~l~sio~: I n - A F w i t h T e - R H C s u b t r a c tion visualizes deep venous thrombosis a c c u r a t e l y . A v e n o u s d e f e c t s h e u l d be classi£ied as susceptible and the diagnosis confirmed later by detecting f ~ l l i n g of the d e f e c t .

473

474

G. Demoncea<, P. Ziegels, P. Rigo, M. Brasseur, M. Steggen, L. B a l d e l l i ~ Y. Beguin, G. F i l l e t , 3.L. David, R. Leclercq, 3.C. Depresseux, P, Bourgeois,

R A Harper, W Th Goedemans, D A J Galvin, A C Meek,--C N McCollum

Cyclotron Center (Liege) and Bracops Hospital Bruxalles), Belgium.

Department of Surgery, Charing Cross Q Westminster Medical School, London, EK

METHODOLOCY OF IC-99M-HH-PAO PLATELETS LABELLING. Methodology f o r l a b e l l i n g p l a t e l e t s w i t h I c 9gm-hexa m e t h y l p r o p y l e n e amine oxime (HM-PAO) was developed. D e t e c t i o n of p l a t e l e t a g g l u t i n a t i o n is expected earlier than with platelets labelled with In-lll-oxine, as reported for leukscytes. 40 ml of blood are collected into a 50 ml polystyrene syringe containing 7 ml acid cltra te d e x t r o s e s o l u t i o n (ACD), then t r a n s f e r r e d into a 50 ml conical tube. Blood is mixed wi~ 4 ml of hydroxyethyl starch and centrifuged at 160 g for i0 minutes. Platelef rich plasma is collected and i0 ml ACD per lO0 ml are added. The p l a t e l e t s are t h e n sedimented i n t o a p e l l e l by c e n t r i f u g i n g at 6#0 g f o r 5 m i n u t e s . The s u p e r n a t a n t i s removed, c e n t r i f u g e d a t 640 g f o r 15 m i n u t e s and t h e plasma f r e e c e l l s (PFC) e t a i n e d f o r l a t e r washing of p l a t e l e t s . The b u t t o n i s l a b e l l e d w i t h 2 ml (740 MBq) of Tc99m-HM-PAO. I n c u b a t i o n t i m e i s 60 m i n u t e s at room t e m p e r a t u r e , Ten ml of PFC a r e added and c e n t r i f u g e d a t 720 g f o r 9 min, P l a t e l e t b u t t o n i s resuspended i n 5 ml of PFC and i n t r a venously injected. L a b e l l i n g e f f i c i e n c y i s ) 5 . 4 t 7 . 4 ~. P l a t e l e t t o - l e u k o c y t e r a t i o i s about 210. I n v i t r o stability studies of the complex show a 15 % degradation after 1 hour. The biological halflife in whole blood is about 43 hours. This low value is mainly due to the poor stability of the binding. ADP and collages indueed aggregation of labelled platelets are normal. In conclusion, a new .technefiate tracer for )latelet labelling is proposed, which looks useful not for the study of the plafelet survival but for clinical defection of thrombi.

ABDOMINAL SEPSIS DETECTION USING SIMPLIFIED ISOTOPE TECHNIQUES lllIn leucocytes localise abdominal abscess but cell labelling facilities are not widely available. Alternative isotope substrates have been evaluated in a large animal abscess model. Chronic abdominal abscess was induced with mixed colonic bacteria in dO pigs which were injected with either lllIn labelled tropolone, lactoferrin, fragmented platelets (FP) or mixed leucocytes. G a l a images were performed at 4, 24 and 48 hours and following sacrifice, radioactivity was measured in the explanted abscess and critical organs as a percentage of injected activity. Gamma imaging accurately localised abscess in all leucocyte and tropolone scans although radioactivity was reduced to 0.4±0.05 with tropolone compared to 1.0±0.i with leucocytes [p<0.Ol]. Neither laotoferrln (0.1±0.03) nor Fp (0.2±0.02) achieved abscess imaging [p<0.001]. Splenic uptake was lowest with tropolone (1.1±0.07) and highest with leucocytes (15.0±1.2) [p
302 476

477

K.Ozker, t.Urganclo~lu, T.Canslz, i.Uslu

K.Ozker, i.Urganclo~lu, A.Sungur, A.Erg~n, N.He@kan, N,Ardagi], A.~otuk

Department of Nuclear Medicine, Cerrahpa~a Medical Faculty, tstanbul University, istanbul, Turkey

Department of Nuclear Medicine, Cerrahpa}a Medical Faculty and Faculty of Science, istanbul University and Gekmece Nuclear Research Center, Istanbul, Turkey

E. Chiotellis*, A. Varvarigou*, C. Dassiou, S. Archimandritis*, J. Datse~is**, and E. Gyftaki** *"Demokritos" N.R.C.P.S.. 153 I0 Athens, Greece **General Hospital "Alexandra", Nucl.}[ed.Dept., Athens, Greece

LABELLING OF METHIONINEWITH Tc-99m FOR STUDYING TUMOURMETABOLISMBY SPECT

Tt-g9m-LABELLED CYSTEINE AS A POTENTIAL METABOLIC TUMOURMARKER

A FREEZE-DRIED FORM771~TION FOR THE PREPARATION OF 99mTc-(V)-DMS COMPLEX

Relatively high accumulation of methiondne in various tumours is believed to be related with the enhanced protein synthesis and/or membrane transport,Using this rationale,incorporation of mothioni~ labelled with C-11,in sam tumurs was investigated recent]y by PET. l~e purpese of this study was to investigate the synthesis of L-m~:thioninewith a single phot~ B~itting radionuclide, Ic-9~m,because of its Dranpt availability.Labelling yield of 97.9 -+ 0.9 %was achieved by a ligand substitution reaction at pHA4,~hile hydrolized-roduced Tc-BC~m(TC-FR) covered 2 %as demonstrated by paper and thin-layer chnmmtography (PC and Ill_C) and electrophoresis.Labelled and stable methionimogave a single spot on the chnmmbx3ra~s when stained, coincident with the radioactivity peak.Labelling maChndinvolvedthe transfer oF reduced Tc-BgmfrQ~ previOUsly preparedTc-BBm-citrate in physiological conditions,providing a mild e n v i r ~ t for labelling and minimizing the problmrm associated with tbe foriiBtion of Tc-FR.Labelling paramoters regarding stannons ion concentration,pH and incubation period of the anion acid with Tc-Bgm~eitrate soluUon warediscussed.PC and Ill3] results indicated an excellent in vitro stability for 24 hours while in viva s t a b i l i t y was studied by aQ~inistration of Tc-9~m-mothionine in normal rats.Organ distribution and whole-body scintigrams of rats dsnonstrated t h a t the r a d i o a c t i v i t y was selectively taken up by liver and cleared within a short period,the main route of excretion was through kidneys and there was no evidence of in viva breakthrough of label led molecule into pertechnetat~ and insoluble Tc species. The chemical and biological data revealed that Tc-g9m was firmly incorporated into the amino acid molecule suggesting a potential diagnostic use as a metabolic marker in SPECT.

Recently a number of natural and a r t i f i c i a l amino acids have been labelled with positron emitters and used for studying the metabolic rate of tissue both f o r normal and patho]ogic states. Because of the prompt a v a i l a b i l i t y of Tc-99m, synthesis of a S containing amino acid, cysteine with Tc-99m and potential diagnostic use of this agent in studying tissue metabolism were investigated. Labelling was accomplished ir two d i f f e r e n t routes, involving 1igand exchange and $1ectrolytical methods. Labelling yield of 95.8-3.9 % was achieved by exchange reaction from previously prepared Tc-ggm-citrate while hydrolized-reduced Tc-99m (Tc-HR) species covered 1.6 %, Secondly e]ectrolytie complexation using Sn electrodes was 9~.9±h9 % while enly 0.6 % Tc-HR was detected. Both exchange and electrolytic procedures provided excellent s t a b i l i t y for 24 hours as demonstrated by TLC. Validity of Tc-99n cysteine as a marker for studying the tissue metabolism was checked in an in viva mouse tumour mode]. Ehrlieh solid tumour.Concentration n the tumour was 3.5±0.6 %, go min after njectlon. The mean tumour to muscle r a t i o was . 3 / I . Scintigraphic study demonstrated a good elineation of the tumour at 10-180 min. nalytical data as well as tissue distribution ,f Tc-99m-cysteine reveals that Tc-9gm is firmly ncorporated into the amino acid molecule which as a marked uptake and retention in the in ive tumour model. This suggests that further nvestigations to j u s t i f y its usefulness in unctiona] diagnosis of tissue metabolism is feasible.

Technetium-99m(V)-~ has shown to be a promising agent for the detection of certain types of tumors. However, preparation of this radiopharmaceutical presents difficulties due tc complex instability. In the present work we describe a convenient method for preparlng 99mTc-(V)-DMS on the basis of an instant freeze dried kit. The formulation is evaluated in animals and humans. In general the kit formulation is outlined as follows: An acidic solution of DMS, tin chloride and stabilizers is mixed with alkaline DMS solution under nitrogen to give a mixture pN 7-8. One ml aliquots containing 1.36 mg DMS, 0.11 mg SnCI2, ascorhic acid. inositol and dextrose were lyophilized and stored under nitrogen atmosphere. The ingredients were reconstituted simply by adding pertechnetate in saline (20-80 mCi). Radischemlcal control by ITLC S.A. (n-butanol-acetic acid-water, 30:20:30) revealed more than 92% of activity as 99mTc(V)-DMS, BPLC reverse phase (AcCN-phosphate buffer) fractioated the complez in the void volume. Pertechnemate was retalned" more. Commercial technetiumD~S kidney agent was absorbed on HPLC c o l u ~ (80% of the total activity). The kit showed ~rolonged stability, for more than four months. Animal evaluation in rats bearing Sarcoma lalker showed good visualization of tumor 60 mir i.i. Quantitative distribution data demonstra:ed 1.08 tumor/blood ratio. Preliminary clinical trial in patients with medullary carcinoma ~f thyroid has been successful. Malignant sites lore well visualized two hrs p.i.

478

479

480

475

M. Erjavec and T.Movrin

The Institute of Oncology, Ljubljana, Yugoslavia

99m Tc (V) DMSA IN TUMORIMAGING Over 130 patients mostly with malignant tumors were imaged with ggm To (V) DMSAusing a commercial k i t with addition of I% NaHCO3 to obtain pH of about 8.B, To assess the target/nontarget ratios (T/NT) images were also printed out with symbols (0-9). High uptake (T/NT over 2.0) was found in v i r t u a l l y a l l soft tissue tumors, medullary thyroid carcinomas and in some benign conditions (e.g. neurofibromatesis) which seems to be of value in the management of such eases. Occasionally high mat mostly moderate (1.5-I.B) or no uptake was found in the rest of malignancies including those which tend to be demonstrable with 67 Ga (e.g. lymphomas). High a c t i v i t y of blood and urogenital organs is seen in 2-hour images. About half of the agent was excreted via urine the rest of i t being apparently taken up by tissue with respective half-times of about 200 and 25 minutes.

H. Matarrese, F. Colombo. J. BugaJ, D. Stepniak-Binlakiewlcz, J. Eelletlre, P. Eerundlni, F. Fazio and E. Deutsch

V.Jovanovid______________/, M.S.Jovanovid,

CNE-Istituto Tecnologie Biomedlche Avanzate, Istituto S. Raffaele, Universit~ di Milanc, Milano, Italy and Biomedical Chemistry Research Center, Univ. of Cincinnati, Cincinna tI, OH

The Boris Kidri6 Sciences, Vin~a, red, Y u g o l s a v i a

MECHANISM OF CLEARANCE OF Tc-99m RENAL AGENTS BASED ON SULFUR-DONATING CHELATES

THE E F F E C T OF H E P A R I N ON T H E R A D I O C H E M I . 3AL P U R I T Y A N D T H E B I O L O G I C A L D I S T R I B U tION o F T c - 9 9 m R E N A L P R E P A R A T E S

Several sulfur-donating chelates are used to prepare Te-99m renal imaging agents: DMSA. a bidentate-S 2 ligand, yields an agent characterized by very slow renal clearance; DABS and C0,9-DABS are tetradentate-N S llgands w ~ n i c h yield • 2 2 agents characterized by rapid tubular clearance; MAG , a tetradentate-N S ligand, also ylel2s an agent characterized ~y rapid clearance. To investigate whether it is the dentlcity of the sulfur-donatlng chelate, or the incorporation of N donors into the chelate, which predominates in determining the rate of renal clearance, we have prepared and labeled with Te-99m the bldentate-N, S chelate N-(mercaptoacetyllglyelne (MAG). The S-benzoyl protected llgand can he labeled by direct reaction with 99m-Tc-glueonate in >95% purity and >95% yield, The presumed 99m-To- (MAG) 2 product is stahle for more than 6 hours. Imaging and biodistrlbutlon studies in 200 g. female, Sprague-Dawley rats show that the blologlcal distribution of 99m-To- [MAG) 2 is characterized by slow renal clearance (25-35~ dose/g remains in kidneys over 40-|20 min post injection). Thus, 99M-To-(HAG)2 behaves much more llke 99m-Te-DMSA than llke 99re=To-DABS or 99m-Tc=MAG . This in turn implies that it iS the ~entlclty of the sulfur-donating cheIate, rather than the incorporation of N-donors into the chelate, which predominates in de~ermlnlng the. rate and mechanism of renal clearance of the Tc-Sgm labeled chelate,

The i n t e r a c t i o n of h a p a r i n a n d Tc-991 renal preparates (tc-99m Glhept i Tc-99m DTpA, T C = 9 9 m - D M S ) w a s w x a m i n e d b y the radiochromatographic method and by biol o g i c a l d i s t r i b u t i o n as the f u n c t i o n of h e p a r i n c o n c e n t r a t i o n in the r a n g e f r o m 30-300 IU/ml. In the p r e s e n c e of heparil the r a d i o c h e m i c a l c o m p o s i t i o n o f Tc-99m31hept. w a s a l t e r e d - the c o n t e n t of Tc-9~ (VII) w a s i n c e r a s e d a n d a n e w f r a c t i o n (about 12%) w a s f o u n d to a p p e a r . This f r a c t i o n c o u l d p r o b a b l y be a t t r i b u t e d t P c - 9 9 m - h e p a r i n . In the c a s e of T C - 9 9 m DMS t h e i n c r e a s e d c o n t e n t of n o n - r e n a l c o m p l e x was o b s e r v e d . No i n t e r a c t i o n between h e p a r i n and T C - 9 9 m - D T P A w a s found. It c o u l d be c o n c l u d e d t h a t t h e p r e s e n c e of h e p a r i n i n c r e a s e s the d e g r e e of p r o = tein b i n d i n g of t h e s e p r e p a r a t e s . T h i s i n c r e a s e w a s f o u n d to b e b e t w e e n 5.0 a n d Ii.8%. T h e c o n s t a n t s o f the p r o t e i n b i n ling w e r e a l s o d e t e r m i n e d . A c c o r d i n g to o i o l o g i c a l e x p e r i m e n t s on W i s t a r rats, lower l o c a l i z a t i o n of T c - 9 9 m r e n a l p r e p irates in k i d n e y s , in c o m p a r i s s o n to the 2ontrol group of animals I was observed. the d o s e of h e p a r i n of 3000 I U / k g b.w. d e c r e a s e s the l o c a l i z a t i o n in k i d n e y s : for 4 1 . 4 % in the c a s e o f T c - 9 9 m - G l h e p t , for 3 6 . 0 % in t h e c a s e of T C - 9 9 m - D T p A and for 2 2 . 4 % in the c a s e o f T C - 9 9 m - D M S , I t o u l d be s u g g e s t e d t h a t p r e v i o u s d r u g h e r a p i e s of p a t i e n t s h o u l d be c o n s i d e ed in t h e c a s e o f r a d i o d i a g n o s t i c inestigations,

I

T.Maksin

I n s t i t u t e of N u c l e a r P.O.Box 522,11001 Beog

I

J

303

F. Colombo, M. Matarrese, J, gugaj, Gerundini, F. Fazlo and E. Deutsch

P.

CNR-Istituto Tecnologie giomediche Avanzate, Istituto S. Raffaele, Universit~ dl Hllano, Milano, Italy and Biomedical Chemistry Research Center, Univ. of Cincinnati, Cincinnati, OH

Te-99m COMPLEXES OF ~,~-DISUBSTITUTED, ~-HYDROXY CARBOXYLIC ACIDS a,~-Disubstituted, ~-hydroxy carboxyllc acids are good ligands for metal centers in h i g h oxidation states, but yet are not themselves susceptible to oxidation. In order to determine if thls class of ligands could provlde a basis for the development of useful 99m-To imagln B agents, the following ligands were labeled with 99m-To: 2-hydroxyisobutyrie acid (Me2C(OR)COOH , HBA), 2-ethyl-2-hydroxybutyrle acid (Et2C(OH)COOR, ENBA), (+)and (-)-eltremallc acid, (Me(HOOCCH)C(OR)C00H 2 CMA). >95% labeling was accomplished by reduction (uslng either Sn(ll) or Fe(O)) of 99m-perteehnetate in the presence of the llgand. Imaging and biodistributlon studies in 200 g. female, Sprague-Dawley rats establish that all four agents rapidly (<5mln) accumulate in the kidney but then do not undergo any significant renal clearance in over 2 h. The extent of kidney uptake is only sllghCly dependent on the nature of reductant used in the preparation, but is markedly dependent on the nature of the llgand suhstltuents. The CMA agents accumulate to 5-6% dose/B, the HRA agent accumulates to 7-8% dose/g, and the E}~A agent accumulates to IO~ dose/g. These distributions are dramatically different from that exhibited by 99m-Te-DTPA in this animal model. ~.G-Disubstltuted, G-hydroxy earboxylic acids appear to be useful ligands about which to design potential Tc-g9m imaging agents.

I , Castanheira*, E. C h i o t e l l i s * * , C . l . Stassinopoulou**, L. P a t r i c i o * , J.,]. de Lima*** * LNETI, Sacavem, Portugal * * * URCPS "Demokritos", Athens, Greece ****Facultade de ;!edicina, Coimbra, Portugal EFFECT OF pH 021 THE FOR~ATIO~IAND BIODISTRIBUTION OF TECH~IETIUrl-cEPPA cor~PLEXES Several structures containing phosphonate groups l a b e l l e d with Technetium-99m are v a l i d bone anents. However, we have already reported kidney imaging by means of Tecbnetium-99m l a b e l l e d L-1-2-eis-eboxy-propyl-gbosphonic acid cEPPA) (1). hl the present work vle investigat~ 9mTc-cEPgA complex formation as a function of pH. Instant freeze dried k i t s of cEPPA and t i n chloride were prepared at DII ranginq from acid to neutral. Binding of ggmTc was teated by ITLC using various solvent systems; over 95% complex formation was observed. HPLC reverse 9base was applied to investigate tile technetium complex composition. The formulatigris of Tc-cEPPA were f u r t h e r evaluated in mice, at various time i n t e r v a l s . B i o d i s t r i b u tion data demonstrated t h a t the r a t i o bone/ :kidney increased from 0.39 to 6.72 one h p . i . , lwhen the nH of l a b e l l i n ~ changed from neutral to acid. At pll 2.5 99mTc-cEPPA sbowed bone a f f i n i t y , analogous to t h a t of 99mTc monophosphonates, whereas preparations carried out at neutral pll were localized mainly i n the kidneys. }IPLC analysis o-F To-cEPPA at pll 6,8 gave a single r a d i o a c t i v i t y peak, while two peaks were detected in preparations at acid pH. The d i f ferent biological behavior of Tc-cEPPA comDlexes may be a t t r i b u t e d to cbemical changes of tile ligand caused by increased a c i d i t y (2). IH NNR spectra of tile cllenical species under study support t h i s ardument.

I

1. 2.

484 G.J. Ensinq; J. Nielsen~ K. Panek

483

482

481

Mallinckrodt Diagnostics (Holland) B.V. Hesterduinweg 3 1755 ZG Petten

DEVELOPMENT OF A KIT FORMULATION FOR THE LABELLING OF MERCAPTOACETYL TRIGLYCINE (MAG3) WIIH 99mTc. Benzoyl-MAO3 (betiahide)was synthetised, using a 3-step route. The product obtained had a p u r i t y of >g9.6% (measured by HPLC), Development oF a kit formulation for the labelling of oetietide with 99mTc involved the Following steps choice oF transfer ligand amount oF tinchloride amount oF betiatide ~ing a IIRLC method for the analysis of the labelling yield, a lyophylized kit with the Following constituents was made: be tiahide l mg SnCl .2H O 47.5 pg 2 2 Na-tartrate 20 mg Using diluted eluate from Mo-Tc generators, routinely a yield oF 97-9B% oF 99mTc-MAG3 was obtained; 4 hours after reconstitution with ggmTc this yield was still >95,%. Our results do not support the observation of other investigators~ that HPLC-purified g9mTc-NAG3 is needed for routine clinical use.

T.Maksin

and

Institute for Radioisotopes, The Boris K i d r i ~ I n s t i t u t e of N u c l e a r S c i e n c e s , V i n ~ a , P . O . B o x 5 2 2 , 1 1 0 0 1 B e o g r a d , Yugosavia A COMPARATIVE PHARMACOKINETIC MAG3-Tc-99~ and PAHIDA-TC-99m

S T U D Y OF IN RATS

The c o m p a r a t i v e p h a r m a c o k i n e t i c stud~ of M A G 3 - T c - g g m ( M e r c a p t o a c e t y l t r i g l y c i n e ) and P A H I D A - T c - 9 9 m (analog of p - a m i n o h i p p u r i c a c i d ) w a s m a d e , b y the m e a s u r e m e n t E of b i o d i s t r i b u t i o n , b l o o d c l e a r a n c e , volume d i s t r i b u t i o n , h a l f - l i v e s of the di~ t r i b u t i o n a n d e l i m i n a t i o n a n d o t h e r rel e v a n t p a r a m e t e r s . The p e r c e n t a g e of pr~ t e i n b i n d i n g w a s d e t e r m i n e d too, by the m e t h o d s of d i a l y s i s and p r e c i p i t a t i o n . T h e s e r e s u l t s w e r e u s e d to c a l c u l a t e the constants and r a t e s of p r o t e i n b i n d i n g . The b i o d i s t r i b u t i o n of M A G 3 - T c - 9 9 m and P A H I D A - T c - 9 9 m w a s p e r f o r m e d on white rats. 3 m i n a f t e r i.v. i n j e c t i o n of ~ G 3 - T c - 9 9 m 2 0 - 3 0 % of the i n j e c t e d d o s e was acculnulated in t h e k i d n e y s , a n d 8.5% in the liver. W i t h P A H I D A - T C - 9 9 m , 6 - 1 0 % was a c c u m u l a t e d in the k i d n e y s and 3% in th~ ~ v e r at the same p e r i o d . A f t e r 30 min, t h e s e v a l u e s d e c r e a s e to 1.5% a n d i% f ~ M A G 3 - T C - 9 9 m a n d 2% a n d 1% for P A ~ I D A - T ~ 99m, r e s p e c t i v e l y . T h e v a l u e s of b l o o d c l e a r a n c e , v o l u m e d i s t r i b u t i o n , h a l f - l i v e s of the d i s t r i b u t i o n a n d e l i m i n a t i o n of M A G 3 - T c ~ 9 m are: C I = 3 . 5 2 m l / m i n , V d A R E A = I 9 8 . 3 4 m l I t i / 2 ~ = 2 . 3 4 m l n a n d t i / 2 ~ : 4 0 . 6 6 min. F o r I P A H I D A - T c - 9 9 m the c o r r e s p o n d i n g v a l u e s I are: C I = 0 , 9 5 m l / m i n V d A R E A = 9 7 . 8 9 ml I t i / 2 ~ = 2 45 m i n a n d t / 2 8 = 7 3 , 9 3 min.

Lima J,J,P. et a l . , Eur. J. Nucl. Med., (1985) 10:134-137. Carstenn-Licherfelde C. et a l . , J. Chem. Soe., Perkin Trans I I (1983) 7:943-947.

485 H. Panek-Finda;

B.Zmbova,M.Jovanovid, V.Jovanovi6

Roland b~ller-Suur, Ingeborg B o i s Svensson, L a s z l o M e s k o , Per-Erik Asard

Karolinska Institute Dept. Clinical Physiology and Dept. of Fbspitai Physics, Oanderyds Hospital, Stockholm, Sweden COWPARISCN CF T c - g ~ 3 - K I T WITH IO01NE-123-HIPPURATE IN CLINICAL N>JTINE PJD40~oAPHY

The aim of t h i s study was t o cc~pare k i t prepared Tcgg~-mercaptoacetyltriglycine, ~ 3, ( M a l l i n c k r o d t , Holland) w i t h our routine radiophar~ceutical for renal studies, iodine123-hippurate (123-0IH) in patients w i t h nephro-urological disorders. So far 13 p a t i e n t s f i r s t studied with 123-OIH (1 n~i) were reinvestigated with 2 rnCi MAC--3, 2-5 days later. P l a s r ~ c l e a r a n c e s of ki~G-3 (multiple samples) were lower, 61 ± 8 %, than those of 123-OIH ( s i n g l e san~ole 4 4 m i n ) but were s i g n i f i c a n t correlated (r - 0.87). Urinary excretion e x p r e s s e d as p e r c e n t of given dose 80 min a f t e r i n j e c t i o n was not s i g n i f i c a n t d i f f e r e n t . b i ~ 3 renogran~ showed identical relative kidney uptake function (r - 0.gg). Time to ~eJ(irm~n correlated less (r - 0.59) and time to fall of half maxlmum renal activity w a s longer (P < 0,O1), as compared w i t h 123-OIH, Renal M~3-3 images were almost identical w i t h those o f 123-01H e x c e p t f o r higher (P < 0.01) l i v e r t o background r a t i o , 1.75 vs 1.O4, 20 min a f t e r injection i r r e s p e c t i v e of kidney f u n c t i o n . K i d n e y t o background r a t i o , however, was t h e s a r ~ f o r both t r a c e r s . P e r i s t a l s i s in the ureters was more c l e a r l y and l o n g e r visible in the M~-3 studies,

Thus k i t prepared MAC--3 has t h e p o t e n t i a l

of replacing 123-OIH in routine renal i n ~ i n g and r e l a t i v e f u n c t i o n s t u d i e t , but i t s c l e a r a n c e i s l e s s t h a n t h a t o f OIH.

I 486

I

. BAGNI ,

L.M.

FEGGI , N. P R A N D I N I , M.

Dept. N u c l eF ae r rM NABLIATi"of 44100 r aerdai,c i n I tea, l y S t . capital ,

Anna

EVALUATION OF 99mTc-MERCAPTOACETYL6LI31NE (MAG-3) AS RENAL IMAGING AND tUBULAR FUNCTION AGENT. COMPARISON WITH 1 2 3 I AND 1311-HIPPURAN. ~enal scintigraphy with 9gmTc-mercap-toacetylglycine (HAG-3) and 1231--oi o d o h i p p u r a t e (DIN) was p e r f o r m e d i n e Jroup of 9 patients to evaluate the Jsefulness of t h e MAG--3 as an ideal renal agent. To e v a l u a t e t h e p o s s i b i l i t y t o replace 31I-OIH with 99mTc-HAG--3 f o r the : u b u l a r t r a n s p o r t (ERPF) assessment wel nave s t u d i e d a group o f 30 patients ~sing a d o u b l e t r a c e r (2 HBq o f 1311DIH) and 67 HBq o f 99mTc-MAG--S). The r e s u l t s showed a non s i g n i f i c a n t difference i n t h e k i d n e y and c o r t i c a l renograms u s i n g OIH and MAG--3. The c o r r e l a t i o n coefficient of the l i n e a r r e g r e s s i o n between t h e v a l u e s o f ERPF o b t a i n e d w i t h 131I-OIH a r ~ 99mTcMAD3 i s 0989. The c o r r e c t i o n of the spillover e f f e c t o f 131I on ggmTc was performed. The plasma c l e a r a n c e was e v a l u a t e d using a dual component model~ the r e s u l t s o b t a i n e d i n 7 p a t i e n t s shows a more r a p i d plasma c l e a r a n c e o f t h e MAG3 i n comparison t o 131I-OIH. I n c o n c l u s i o n our data i n d i c a t e s : I - The renograms a r e a l m o s t identical f o r both radiopharmaceuticals ~-- l i n e a r correlation between the v a l u e s o f ERPF i s o b t a i n e d 3 - a b e t t e r t a r g e t t o background r a t i o for MAG--3 i n comparison w i t h 131I-OIH 4-- b e t t e r image q u a l i t y o b t a i n e d H i t h MAG-3 5-- p r a c t i c a l b e n i f i t s .

304 487

489

488

P. Nelichmr,

K. Svoboda,

J. ~ o r s v e c

F.Zito, G.Taddel, C.Nessa, M.Fiorenza, P.Gerundlnl, F.Fazio

N. Moin% P. Gachon, 3.C. Maublant

H.Matarrese

INSERM U195 and Centre 3ean Perrin C l e r m o n t - F e r r a n d , France

~ucleer CSSR

Research

Institute,

Istltuto S.Raffaele, Istltuto .Tecnolog~ Biomedlche Avanzate - C.N.R.. Unlverslt~ di Milano, Milano, Italy

250 68 Re~

FACTORS A ~ E C T I N G THE E F F I C I E N C Y GEL-TYPEWWmTc GENERATOR

OF TI~

An i n c r e a s e d c a p a c i t y of the matrix (by ~ 20-30 %), r e l a t e d to Ms, is the m a i n advantage of the title generator, in c o m p a r i s o n w i t h the c ~ s s i ¢ one, based on alumina. The (n,¥) ~ M o , obtained b y i r r m d i a t i w g n a t u r a l ~o witl intensities of ~ 5xI0 ~9 n/cm~s, is use~ ss the source of the g e n e r a t o r r a d i o activity. A p r e f s b r i c s t e d title generator was developed. A m p u l e s made of materiels little activable b y n e u t r o n s (Si, A1) were p e c k e d w i t h the generatox msZrix, c o n s i s t i n g in i n s o l u b l e polymolybdates, c o n t a i n i n g p o o r l y n e u t r o n - e c t i v a b l e atoms (Zr, Ti). A f t e r irrad i a t i o n in e reactor, the ampules serv~ d i r e c t l y as e l u t i o n columns. The cons t r u c t l o n and the p r e p a r a t i o n of this g e n e r a t o r type were d e s c r i b e d previously (the ~I Congress 1987, Budapest, p o s t e r P32). A h i g h s i m p l i c i t y of the p r e p a r a t i o n end o p e r a t i o n is an advantage w h e r e a s a l i m i t e d s t a b i l i t y durin~ the r e a c t o r i r r a d i a t i o n is a d r a w b a c k of the generator. The f a l l o w i n g ~ c t o r ~ a f f e c t i n g the e f f i c i e n c y of the ~ m T c e l u t i s n were studied: d r y i u g x e r o g e l temperature, m e u t r o n flux intensity, temperature of the r e a c t o r c o o l i n g water, m o i s t u r e of p o l y m o l y b d a t e , and m p u l e - c e l u n m i r r a d i a t i o n diameter. Th~ )olymolybdate m a t r i X was e x a m i n e d b y ~he x-ray, I R s E S R s p e c t r o s c o p i c ~ethods. The i r r a d i a t i o n s t a b i l i t y was determined.

I

UPTAKE AND RELEASE OF TWO NEW Tc-99m LABELED MYOCARDIAL BLOOD FLOW IMAGING AGENTS IN CULTURED HEART CELLS

Te-99m ECD (N, N'-I, 2-ETHYLENEDIYLBIS-LCYSTEINE, DIETEYL ESTER): BIODISTRIBUTION AND TONOCRAPHIC BRAIN IMAGIN( STUDIES IN HUMANS. Tc-99m ECD is a new labeled compound proposed for the investigationof regional brail blood flow with SPECT. Tc-99m ECD hlodistrlhut/on and tomographic imaging were sBudled in ; normal volunteers following ethics co~itte( approval and written informed consent. Aftel i.v. administration of 20 mCi of Tc-99m ECD, whole body images were obtained at i, 3 and 5 hours. Table 1 shows the b~odlstTibutlon ofI Tc-99m ECD in selected organs. Organ uptake was, corrected for body attenuation according to thl "conjugate counting technique". Maximum hralt uptake ~as reached within 5 minutes. Withll 10-60 minutes a 7~ decrease of cerebral activity and a 50~ decrease of head soft-tlssue activity was observed. 45~ of the injected dose was cleared in the urine within 4 hours and 70~ within 24 ho~rs. Tomographlc brain images at 10 minutes and 2 hours post injection were obtained by a rotating gala camera and a dedicated computer. The differential uptake of the tracer between gray and white matter allowed good visuallzation of cerebral structures, similar to what is 0gserved with other brain perfuslon tracers.

Tc-99m([bis[ 1,2-cydohexanedionedioximato(l -} -0]-[ 1,2-cy¢lohexa n e dionedioximat o(2-)-0]borato (2-N,N',N",N"',N'"'~N" '"]-ch]or otechnetium) (SQ320t4) and (chloro(meZhylboron(l -)-tris[ 1,2c y c l o h e x a n e d i o n e ( - ) l - N , N ' , N " , N " ' , N ' " ' , N ' " ' '~ ](5Q30217) have recently been proposed for imyocardial blood flow imaging. Their kinetics of uptake and release, and the effects of various metabolic factors at constant e x t r a c e l l u l a r tracer concentration were studied in a model of c u l t u r e d beating myocardial cells o~ newborn Irats. l n t r a / e x t r a c e l l u l a r concentration (C) was measured at three pH levels and in the presence of l m M ouabain (OUA), 5raM cyanide ( C N ) a n d 0.1rnM iodoacetate (]AA) for the purpose of blocking the Na-K ATPase, electron transport chain and glycolysis, respectively. Results

were the following (m~sd) : 5Q3201# <2 min 30±10 ITI/2 (release) 10 min C at pH 6.6 * 102.7~2.9 C at pH g.0 * gg.7~#.6 C with CN * I07.9~19.5 C with CN+OUA* 101.7~J0.l C w i t h CN +OUA+IAA * 105.#~I 3.1 Tl/2(uptake) Cmsx uptake)

5Q30217 <2 min 539±$6 l g min 100.1{#.g

101.0~5.g /06.9~g.3 100.6±5.7

Table 1 Biodistrlhutlon of Tc-99m ECD (~ of injected dose)

g3.9~[0.3

• normalized to C values at pH 7.# It is concluded t h a t although both agents are l i t t l e sensitive to metabolic inhibition and show a rapid uptake, 5Q30217 has a definite higher i n t r a c e l l u l a r uptake and is therefore potentially a more interesting agent for myocard a bood l o w m a g n g than SQ3201q.

E. H . C h e e s m a n , M. A. Blanchette, M. V. Ganey, L. J. M a h e u , S. J. Miller, R. A. M o r g a n , R. C. W a l o v i t c h , A. D. W a t s o n a n d S. JWilliams

G. GALL I, P. ORLANDO, C. L. MAIN I, G. DELE IDE

E. I. du Pont de Nemours & Co., Medical Products Dept., Diag. Imag. Div., N Billerica, MA, USA

ISTITUTO DI MEDICINA NUCLEARE UNIVERSITA' CATTOLICA DEL S. CUORE Largo F. Vito 1 - 00168 HOMA

TECHNETIUM-99m ECD FOR BRAIN P E R F U S I O N I M A G I N G : ESTERD E R I V A T I Z E D D I A M I N E - D I T H I O L Tc COMPLEXES

99m-Tc-OROSOMUCOID: A RADIOPHARMACEUTIC A L F O R HEPATIC STUDIES

Previous studies have shown that 99mTc(V)-oxo complexes of derivatized diamlne-dithiol (DADT) ligands cross the blood-brain barrier and but are retained for times insufficinnt for optimal imaging. We report the synthesis of a number of DADT ligands incorporating potentially metabollzable ester functions as brain retention groups. 99mTc-oxo complexes of these ester-derlvatized DADT llgands have been prepared and evaluated in rats and primates as potential brain perfusinn imaging agents. The complex shown below, 99mTc-ECD, shows excellent uptake and retention characteristic~ and is now undo'going clinical evaluation. In addition to the syntheses and characterizations of these ligands and their corresponding 99mTc and 99Tc complexes, structureactivity relationships for these derivatized DADT complexes will be discussed.

/-A

L.s/\J Tc-ECD

lh

3h

5h

4 3 6 5 4.6

3.8 1.5 3 4 1.7

3.4 1 2 2 0.9

492

491

490

Organ: Brain Lungs Liver Gallbladder Blood

E~ Reich,

In a previous paper we described the procedure of labelling Asialo-Orosomucold (AOM) with 99m-To, and iEs use in hepatic studies. The aim of the present work was to study the biodistribution and catabolism of AOM injected in animals. Three experiments were performedl In the first, 12 mice were injected through the tail vein with 125-I-AOM and the biodistribution of the "AOM assessed in blood and different organs at 10', 20', 38', 40'. The liver shows the highest uptake with the maximal hepatic activity reached at 10'. In the second, rabbits were injected with 131-I labelled AOM and samples of blood examined in order to evaluate the protein-bound and free iodine radioactivity. The plasma clearance in rabbits shows a sharp decrease after inje ~ ction w followed by an increase to a maximum (10% of dose). The protein bound radioactivity is present only during the first phase, while in the second phase the radioactivity is essentially present as free iodide. In the third, rabbits were injected with 99mTc-AOM and HPLC performed on urine and Serum collected at different times (30', 60', 180'). RPLC patterns s h o w the disappearance of protein bound radioactivity in serum and the elimination of low molecular weight 99mT¢ ~ labelled compounds in urine. Ee conclude that AOM labelled with iodine or 99mTc is efficiently extracted by the liver and metabolized.

A. Hammermaier,

K.W. Bggl

Institute for Radiation Hygiene of the Federal Health Office, Neuherberg, FRO FISSION Ho-g9/Tc-99m GENERATORSA STUDY OF THEIR PERFORMANCE AND QUALITY

I

I I I I 1 I I I

Fission Mo-99/Tc-99m generators from nine different manufacturers were studied with regard to their Mo-99 content on the column, their performance and the quality of the eluates. Results concerning the Mo-99 content on the column, elution efficiencies, radionuclidic purity, Mo-99 breakthrough, radiochemical purity, pH and aluminium content of the eluates are presented. The slutish efficiency was between 80~ and 120~. Measurements and evaluations of radionuclidic purity using a HPGedetector revealed the presence of Mo-99, 1-131, Hu-103, La-140 and Be-140 in the eluates. The eluates generally exhibited a high and satisfactory radicnuclidic 'purity and good radio-chemical purity. Te separate pertechnetate and other valency states of Tc-99m we used thinlayer chromatography in aceton on silica gel immediately after elution. In all cases we found the radiochemical purity above 99%. Measurement of the dismantled column for Mo-99 content was done 1 month after calibration using a Ge(Li) detector and the Mo-99 content was calculated to the time of calibration. The measured Mo-99 values were in good agreement with the stated nominal activity of the manufacturers.Ms-99 breakthrough was also below the limit set in the European Pharmacopeia. All the eluates had pH-values between 5.0 and 6.0. The generators measured until now performed well and proved their capability of functioning as reliable sources of Tc-99m pertechnetate.

305 493 Z. Ku~ter, M. Vlatkovi6

494

495 A.J.W.Hilson P.D.Diamond, and J.E.Agnew.

Niels vinberg_I Klaus Ennow 2

Department of Nuclear Medicine University Hospital Rebro ZaEreh, Yugoslavia

the Isotope-Pharmacy, Copenhagen, Denn~rk 1 Institute of Radiation Hygiene, Denmark 2

DETERMINATION OF ELUTION PROFILE AND OPTIMIZED ELUTION OF Mo-99/Te-99m FISSION-TYPE GENERATORS A highly efficient elution and best eluate quality of Mo-99/Tc-99m fission-type generators can be attained by previous determination of elution profile. The values of kinetic parameters which determine differential (Cv,dif) and integral (ev,int) elution profile were obtained eomparln~ the experlmenr~l results (m~a~u~Tn 6 the accumulated eluate activity during the succesive elution of the generator) with the results of numerical simulation of the system solid adsorbent -99Mo/99Tem-eluent. According to the model proposed here functional dependence of these parameters is influenced h~ the chromatographic column attributes (composition and particle size of adsorbent) and eluent composition (pH, saline concentration), as has already been shown by other authors. We have found that an average volume, corresponding to the maximal activity concentration, is equal to 2.40,0.26 ml (mean±ISD), whereas the functional dependence ev,int vs. V in the region 0-15 ml can be, to a good approximation, Idescribed by the function ev,dn t = V/(a0+al+ +a2v2). Once the values of coefficients are experimentally found, it is possible to perfor= controlled elution of the generator, either by the appropriate choice of eluent volume or by the two-step fractional elution.

496 P.R. Franken 1 A Dobboieir 1, H.R. Ham 2 C. Brihoye 3, M. Guillaumo 3, F.F. Knapp 4 , J. Vandevivera 1.

1 AZ Middelheirn, Antweq)en, 2 St Peter Hospital, Bruxelles and 3 Centre Recherchas Cyclotron Liege (BELGIUM) 4 Oak Ridge National Laboratory (Oak Ridge, TN, USA).

TC-99M AEF~DSOL DELIVERY SYSTEMS ARE T ~

ACCEPTABLE?

The handling of gigabecquerel amounts of Tc-99~ labelled radiophargmceuficals under positive pressure poses special proble~. Fro~ a radiation hygiene standpoint the use of such systes~ ~re only justified if the systems are safe in use and if the radiopharmaceutical produced by the system is efficacious, e.g. c ~ l i e s with specifications for the type of radiophammaceutical and yields clinically useful results. We h~ve studied 2 different Te-99m aerosol deli very systems (Venticis II from CIS International and the lung aerosol unit manufactured by Cadema Medical Products, Inc. ). The following parameters ~ r e investigated: i. MMAD (Mean Mass Aerodynamic Diameter) d i s t r i b u t i o n of the aerosol particles, measured with a 6-stage cascade impactor. 2. Aerosol yield 3. Patient compliance and the relation between clinical and phy~ico/chemica~ results. 4. Room air contamination when patient cooperation fails. The results show: i. The fv~ syster~s yield a similar and reproducible pattern of particles. One system incorporates a "sizer" - exclusion of the "sizer" results in a non-reproducible pattern but with a higher yield of smaller particles. 2. The yield fz~m the two systems varied between 2 and 13%. 3. Both syster~ ~aere acceptable from a patients point of wiew. The physiological distribution corz~lated ~ i i with the pbys/che/~ findings.

497 A. Schwarz, A. Steinstr6Oer, M. Zimmer

HOECHST AG, D-6230 Frankfurt/Main 80, FRG

IRIDIUM-191m FROM A NEW CARBON BASED OSMIUMIRIDIUM GENERATOR SYS]~M FOR FIRST PASS LEFT VENTRICULAR EJECTION FRACTION IN MAN,

A NOVEL SUBSTANCE FOR BONE SCINTIGRAPHY WITH BETTER VISUALIZATION OF LESIONS

A new 1 Ci 1910s (15.4 days) / 191m[r generator system using an astivated carbon suppod that offers high 191mlryield (~20~742omlbolus) and consistent low lOrDs breakthrough (2x10" '/,#bolus)has been reoenlly described by O.Brihaye (J Nucl Med. 19B6). The ultrashort half life of iridiurn-191m (496 seo; 63-74 and 129 KeV photons) is potentially advantageous for first pass radionuclide angioeardiography offering Die oppodunily I0 perform rapid sequentia] studies wilh very low absorbed radiation dose to the patient. The present study reports our inlfial clinical expeiience w h 191rnlr in patients with coronary artery disease at rest, during exercise and in comparison w~th99roTe. Serial ECG gated lelf ventrloutarfirst pass studies were performed using a small field stngie oystal digital gamma camera with fhe pulse height , analyser set over Ihe x and 7 pholopaaks of I el mlr" Le/t ventricutar actMlies ranged from 10 up Io 30 Kcounie in ~he end diaslolic ROI of the representative cycle, stlowing accurate measures of LVEF. Compaitson between 191rnlrand 99mTo (20-25 rnCi) LV ueust rates indicates a 3 week useful shell-lite of this new generator system for cardiac, studies. The reproducibility of repeated LVEF determination performed in 50 patients st 2 minutes inteIval with 191mlrwas r=.97, mean diff.= 2,1 EF units, felmlr determined LVEF correlated closely with 99rnTe determined LVEF in 40 patients (r=.92; mean diff,: 2.5 EF unils). Parametric images for LV wa[I motion analysis were of high quality, indistinguishable from 99mTc images. During exercise, various patterns of LVEF response were holed. In addition. 201TI was injected at peak exemise in 32 patients providing direst comparison of myocardial peduston and function. We conclude that rapid, repeat, reproducible, high count rale first pass LVEF and wall molion studies can be ob ained with 191mlrfrom this 191Os/191mlrgenerator system.

Tc-~m-laoelled diphosphonates are currently the agents of choice for bone imaging. Different animal models have been developed previously for the investigation of new bone imaging agents with higher selectivity for bone lesions. Beside the uptake in onrma] bone, the accumulation of an osteotrabic substance in the area of increased osteoblastic conversion is of particular importance. ~ have applied an osteosarcc~ model of the rat for the evaluation of a new agent for bone scintigraphy. l~is compound, ]-Hydroxy-3-mEthylphosphinico-l,l-propane-diphosphonic acid (H~PD) exhibited after labelling with Tc-99m a rabid clearance f r ~ the blood and soft tissue and an accumulation in normal bone, comparable to Tc-gg~I4~P. lhe labelled ~omplex shoved an ~xcell~-Cc stability up to 24 hours after reconstitution. Using the osteosarc~ animal mDdel, Tc-9g~H~PD exhibited in a cmparative study with differeYc other bon~-seeking ageTts a significant higher lesion to F~n~] t~ne ratio. ~ e osteosarcoma was implanted intratibially into lO - 12 days old Spragne-Dawley rats. The investigations started a f t ~ a tuiDr growth period of about 4 weeks. Scintigrap~ic images rare made i,n~diately as ~ l l as 90 and 180,nnotes after injection by GaBm-ca~era. Tc99m~4]P was used as reFerance s u b s t ~ t ~ days prior to app?icntion of the testing sample in the sate mi~al. The ratio (Q) of the impulse-density in tu,Dr to that in contra?ateral tibia has been used as m~ure for the relative tumor uptake. Tc-ggm-HM~De~hibited a Q value of 1.28. Tnis ~ the highest ratio of all tested substances. N,N-Dibotyl~minuTethanediphosIWwmic acid, a substance with low affinity to ,onml bone, thows~only a ratio of 1.16.

D.Pavie,

Departments of Nuclear Medicine, Thoracic Medicine, and Medical Physics, Royal Free Hospital, L O N D O N N W 3 2QG, GO.

A COMPARISON OF LUNG VENTILATION SCINTIGRAPHY WITH AN ULTRA-FINE 99mTC-AEROSOL (Technegas) AND KRYPTON81m. AS part of a comparison of Technegas (TcG) with Kr-81m, we studied patients presenting with D O S s i b l e D u l m o n a r y e m b o l i s m (PE). On days when Kr-81m was evailable, the patient had the TcG study first, followed by routine v/o imaging with 99m-Tc-MAA and Kr-81m. On days when Kr-Blm was not available, the TCG s t u d y w a s f o l l o w e d b y t h e M A A study, and V/Q imaging with Kr-81m was performed on the first available opportunity. Posterior TcG and Kr8 1 m s t u d i e s w e r e d i g i t i s e d at 6 4 x 6 4 resolution for generation of Penetration Indices. The study was approved by our ethical committee. I n all c a s e s t h e T c G s t u d y g a v e a c l i n i c a l l y u s e f u l image. 5 p a t i e n t s h a d t h e full study. T h e m e a n r a t i o of Penetration Index (TcG/Kr-81m) was 1.34 (range 1.03-1.67), indicating greater peripheral penetration of the TcG. In 3 patients the same appearance was seen on images, but full q ~ a n t i t a t i o n w a s n o t a v a i l a b l e . In 2 cases the delayed Kr-81m study was not done for clinical reasons. We conclude that in this group of unselected patients with possible pulmonary embolism TcG gave greater distal penetration than Krypton-81m, and was clinically effective.

498 P.. Gfelow. I. Messerschmidt, H. Handeshagen Medizinlsche Hochschule Rannover AbtellunE Nuklearmedizin und spezielfe Biophysik Konstanty-Gutschow-Str. 8 300D Hannover 6l, F.R. Germany

PRODUCTION OF THE POSITRON EMITTER CU-64 IN A NUCLEAR MEDICINE CLINIC Copper-64. a relative short-lived positron em/tter, has been used so far primarily in the diagnosis of Wilson's desease. As it could get more importance with growing employment of positron cameras, production of this nuclide was started in our clinic with regard to preparation of radiopharmaeeuticals for PET investigations. Using our in-house nuclear reactor we perform a Szilard-Chalmers reaction on N,N'-phenylenebis(sallcylldeneimlnato)copper(II). The preparation is a modlff~ cation of an older method (DUPEIELD et al. 1946) whlch seemed to us to he inappropriate for the radiopharmaceutieal production of 6u-64. Essential steps of our procedure are an extraction (sallne/chloroform) and B chromatographic purification with two different adsorbents (alumina, reversed phase). Radiochemlcal yield of ionic Cu-6~: 10 ~, specific activity: 370 MBq / mg. The purity of the preparation was determined by Ge/Li-ga~aspeetrometry and TLC followed by autoradioEraphy or activity recording with a "TLC linear analyzer". Significant impurities could not be detected. Reactions ~ t h appropriate ligands yielded already known complexes, as Cu-64-citrate, -EDTA and -DTPA. But also a new compound, Cu-64-diethyl-HIDA, could be prepared.

306

499

500

Te{id~Mi,'~M.Ratkovid*,R.Jankov** The Boris Kidri~ Institute of Nuclear Sciences, The Institute for radioisotopes, Vinda, P.O. 3ox 522, llOOl Beograd, Yugoslavia **Dpt. of Chemistry,Faculty of Science, Beograd, (ugoslavia IIGH SRECIFIC ACITIVITY 131I-MIBG FOR THERAPY For the fact that the rata| amount of MIBG zdministred never exceeded 5mg and that typical therapeutic dose of 131]-MIBG for an adult lies )etween 5 and 7Gaq, thespecific activity of this radiopharmaceutica] foT freatment of tumours of neuroectodermal origin must be between I and 1.5 iBq/mg. The experimental conditions for the synthesh )f 1311-MIBG high specific activity by the met~od to be known as "hydrothermal melt"(HTM)method was studied. The method is based upon a heterogeneous isotopic exchange of 1271 for 1311ai

submelting temperatures. • All the experiments were carried out in sealed glass vials (7ml). The effects of the reaction time (lOU120min) ~emperature (120, 135,]50°E) and pH(1,1-2.9) on ;he labeling efficency wa~ investigated. The free iodide was removed by anion exchange chromatography (Cellex D), The purity add the labeling efficiency of 13II-HIBG were controlled

I

)y TLC (DC-Alufolien

Kieselgel

60 Merck).

The r a d i o l y t i c s t a b i l i t y of 1311-MIBG dif ~ =erent specific activity (37-1000MBq/mg~ was

investigated at two storage temperatures:4 and 30oc. I The reaction rate depends upon the tempera'ture, The highst yield(85~)is reached after 30 min at 15QOC, after log min at 135°O ant at 120°C the highst yield is only 65%after IOOmin, Based on the results obtained we determined Ithe kinetic parametars: the reaction constants, tHe order of the raction and the activation energyoF the isotepic exchange. The r a d i o l y t i c s t a b i l i t y 1311-MIBG of the Ispecific a c t i v i t y up to 37HBqlmgis 16-20 days at 4oc (free iodide less than 5~), 12-t6 days at 30oc and that one of the high specific • a c t i v i t y (740 MBqlmg) was 213 days at 4 0 0 .

MJBG UPTAKE IN AN ANIMAL MODEL OF MEDULLARY THYROID CARCINOMA (MTC). DEMONSTRATIONOF MONOAM~NE5 CARRIER ROLE We previously reported unconetant MI~G uptake in MTC (25% of cases) with a high incidence in familial disease (Cancer, 1987, 60,2189). In the present work we study what %mderlines MIBG uptake in an ani~l model of MTC . A MTC OZigimating f r ~ WAG/Rij rat was grafted into nude mice. We studied this tumor after the first transplantation into mice (Cb'T-OIH), and after the 20th transplantation (CMT-20T). Tumors were investigated as follow: plasma calcitonin levels were determined by RIA, ultcastructural and immun0histoehenical techniques were performed on tissue, MIBG uptaks studieg were performed in vivo (scintlgraphy) and in vitro usir~ cells suspension, moncanine carrier was determined in vitro using a specific ligand (H-3 tetrabenazine). Transformation of tumor occured during transplantation: CI~T-01H secreted calcitonin (>1000pg/ml) however CMT-20T did not product calcitonin.MIBG in-vivo and in-vitro uptake as well as granules with intact m0n0amines carrier (36 pm01/mg protein) were observed in CMT-01H, but not in this CMT-20T. ~ese results demonstrate that MIBG uptake in MTC ±s closely related to the presence of granules with intact mon~amines carrier. It is mandatory to look for this carrier in familial disease, first in vitro with tetrabenazine, and then in vivo with MIBG.

503

502

P Carvalbo, JP Lavender, AM Peters.

P, PELTIER.F RAFFI,0, DELAVIERRE.J.BARRIER, Ph. DEFAUCAL.B. PLANCHON,JY880LLEAU,

501

D Guilloteau. J i . Baulieu, O. Sherman, F. Fetisgor, B Arbeille, M Caillet, L Pourcelot and J C. Besnard INSERM U316, Laboratoire Biophysique Medicale Tours,IBPC Paris, France

;.Y. Wu and L.G.Colom~etti* quclear Mediclne-V.A.Medlcal Center, Long ]each, Ca. 90822, USA and U n i v e r s i t y Of ~allfornla~Imvlne- Orange,Ca. 92668 ~ I n s t l t u t e of Radiopharmacology- P.O.Box 1414, Glendale, Ca. 91209

I I ~II.M£TAIODOBENZYLGUANIDINE (MIBG) AND EXTRA VESICULAR ACCUMULATIONIN RAT BROWNADIPOSE TISSUE Brown adipose tissue (BAT) is the ma j o t s i te f o r both cold-lnduced non-shlverlng and diet-induced thermogenesls. BAT d i f f e r s from white f a t by i t s rich sympathetic fibers directly innervating the adipoayte. We Ihave r e c e n t l y demonstrated marked accumulati~'lO? M~z-~mn'~o~7~P-@Ganebhi~Fe which shares the same uptake, storage and release mechanisms as norepinepbrlne (hiE), in r a t BAT. The disappearance of MIBG from BAT was found to be slower than from heart or spleen ( O l i n . Bes. 36:167A, 1988) In thi~ r e p o r t , we examine the e f f e c t of reserpine (4 mg/Kg,IP, 4 he prior to 131-Z-MIBG adm.) --which s e l e c t i v e l y blocks the NE i n t o storage veslcles of adrenerglc nerve--on MIBG uptake in BAT. Our subjects were male rats (weight 250-350 gm) kept e i t h e r at room temperature (RT) or cold stressed.

The data obtained suggests a marked accumul a t i o n of MIBG in r a t BAT which: (1) may even exceeds in adrenal or heart, and could be used f o r imaging; (2) is inhibited 65% by reserplnebetween 3 to 24 hs, i n d i c a t i n g mainly i n t r a v e s l c u l a r uptake; and (3) is reduced in cold, but t h i s reduction is part l a l l y blocked by reserpine, suggesting the discharge of HIBG in cold-stressed animal v i a e x o c y t o l i c release of v e s i c u l a r content

504 J Muz, RHMathog, LP Davis, GA Kling. i

OBntreRen~GAUDUCHEAU.NANTESendCHRNANTES,FRANCE,

99M TO DTPA LUNGCLEARANCE IN COLLAGENVASCULAR DISCRDERS(CVD) 99m TCDTPAlungclasroase (DTPALC)studyallows lung interstiUatdi~rdars OLD) to be datast The aim of tho present preliminary WDrk Was toevaluateDTPALC results in patients with OVD. Twenty-Ode studieswore performed in 17 non-smokers with OVD. DTRALC results were tempered with the presence or abnormality of dyspnea (D). chest x re,/ interstitiallesion (RX), vital capacity (VC), diffusing capacity (De), bronehaslvaslar lava~ lymphacytasis (LY) and C,-A67 lung lupteke(ea).With patientsIn supine position,DTPALO was studiab using a plastlo nebulizer, and date acquisitionwac performed in 60 ac frames [or 20 mid, T 112 (rain) was calculated,with backgroundcorrection,over the first I0 mid of the washout curve. The 8A67 lung index was scored using the LINE method without taking medlasiinol activity into account.A C~s 50, DTPALC 145 mio, YCIBO% and DC;70% 'ofnormal value were consideredpathologic. n pathologic/n studied D RX YC DO

)TPALC 45 (n=IO) 6/10 6/I0 6/9 45(n=II)

0111

1110

2111

?/9 1110

LY 5/6

OA I/6 016

ThereW~ a relationbatwasn the pre.~n~ of interstitiallung

Jamageand DTPALCas indicated by the normality of DTPAL8 n patients with abnormal RX.YC,DC,D.Moreover, LY was )hath0logit in 5/6 patients with abnormal DTPALC,On the Ither hand. DTPALCwas abnormal in around 40% of patients vith no Dandnormal RE.YC, DCand C~. I~ met be C~noluded hat DTPALCabnormalities couldexist be[oreclinical, radioOgicel, end physiological signsof LID. However, proepastive ;tudias ore neededto demonstrate that DTPAL8rather than )thor proceduresasuldbeusedto detectLID

H ~ e r s m i t h Mospital & Royal Postgraduate Medical School, London, UK. THE INCIDENCE & AETIOLOGY OF THE REVERSE (V/O) MISMATCH DEFECT The purpose of this study was to establish I the incidence a~d causation of the reverse V/O mismatch defect (where the ventilation defect exceeds the perfusion defect). V/O scans (Kr-81m, Tc-99m MAA) performed over 1985 & 86 on 392 patients were examined. 46 (11.7~) patients demonstrated the reverse mismatch defect. Of these, 7(15%) were due to collapse/ atalectasis, 7(15~) were due to pleural effusions, 7t15~l were due to pne~onic consolidation, 11(24%) were due to chronic obstructive air,day dis=ase without any intercurrent complication, and 3(6.5%) showed chest X-ray evidence of bronchial obstruction of whom 2 proved to be due to foreign bodies ~ I w~s due to bronchial cart;dam. In the remining 11(24~), the lul~g fields were normal on the chest E-ray. This group generally presented with pleuritic chest pain but were otherwise clinically heterogeneous and included 2 with gross cardiome~aly I with graft versus host disease, 1 with pulmonary bypertension, 8no 4 otherwise well patients with pleurltic chest pain, includl~ 2 who were smokers. We postulabe that this final group had partial bronchial obstruction which was not ~ o s s enough to be detected on chest g-rays but is sufficient to cause ventilation defects on Ks-elm ventilation scanning. We conclude that there is a significant incidence of the reverse mismatch defect and that It can be caused by several diverse disease processes.

Harper Hospital and Wayne State University School of Medicine, Detroit, MI 48201, USA. PULMONARY ASPIRATION: ITS DETECTION AND !UANTIF!CATION WITH SCINTIGRAPHY ~piration of food or Bastric contents can be ife threatening. It usually occurs in patient~ (pts) with dysphagia due to head and neck cancer (HNCa), cerehrovascular accident (CVA) and other debilitating diseases. We have developed a stint;graphic technique allowing us to detect and quantify pulmonary aspiration (PAl. For this study, the patient (pt) swallows 2.bmCi of Tc-99m sulfur colloid solution and, at the same time, camera-computer images are obtained. The percentage of aspiration is calculated by dividing number of counts from the region of aspiration by counts of total dose given to the pt and multiplied hy 100. We have utilized this technique to detect and quantify PA in 230 pts of the following groups:

Category

No. Pts

No./PA

% of Pts/ Aspiration

~VA HNCa ~Ca/tracheostomy Others/dysphagla

i16 49 36 9

19 13 32 3

16.4% 26.5% 57.1% 33.3%

Among pts with traeheostomy, 6 pts had a removable tracheostomy ohturator. These pts were studied with the obturator in place and with the obturator removed. In 5 of 6 pts, PA ~as significantly increased with the ohturator removed. ~e consider scintigraphy a useful method for detection and quantification of pulmonary zaplration. Estimated total body radiation d o s = from this study was 43mRads.

307

506

505 R. Bauer. E. van de Flierdt, H.R. Langhammer, H,W. Pabst Nuklearmedizinisohe Klinik , TU M0nchen Ismaningerstrasse 22, D-8000 M,",nchen 80

DYNAMIC VENTILATION WITH INTRINSIC RESPIRATORY TRIGGERING Dynamic ventilation scans were performed in 12 patients with pulmonary diseases cf different degree. Based on commonly accepted procedures, single breath, equilibrium and washout of 200 MBq Xe-127 was recorded in list mode. At completion cf the investigation, the data were re-evaluated, A respiratory cycle of 1he equilibrium phase was reconstructed based on the variation in counts in the diaphragmatic region of the lungs. Be- cause intrinsic gating was used, no special hardware was necessary. The software allowed for an automatic adjustment of breathing cycles of different length and depths. Data processing was completed within 5 minutes, including operator interaction. Regional pulmonary ventilation was eva!uated by amplitude and phase analysis. In patients with normed pulmonary function, maximum regional ventilation was observed in projection onto the diaphragm. The phases (first order) of both the right and the left lungs were similar. In patients with obstructive and restrictive disorders of the lungs, the degree of regionally impaired function could be quantitated.

Conclusion: According to our preliminary results, representat[va cycles of ventilation provide new information which seems to be of relevance in differential diagnosis of lung diseases and in the follow-up ot patients.

508

D. BARON, B. PUPAS.

CentreRen~GAUDUCHEAU,NANTESandC.H,R.,NANTES, FRANCE.

INCIDENCE OF PULMONARY EMBOLISM (PE) iN PATIENTS WITH DEEP VEIN THROMBOSIS :A PROSPECTIVE STUDY Incidenceof PE was studiedby lung scan in 80 patientswith suspected deep vein thrombasis (DYT), The same day all patients had contrast vanography and ventilation-pecfusion lung scanning Ventilationscan w ~ serried out first with 99mTC-rediseerosol from a plastic nebulizer (ventieis I[) ~nhaled by the patient In supine p~itlon. With the patient remaining io (he some pomtian, the 4 ventilationimages (ant, post,lop, Pop) were recordedat 200,000 counts. Immediately after the lastventilationview, with the patient still in the same position,5 to 7 mci of 99mTC-MAA were injectedand the same 4 views were recorded at 400,000 counts, the lung scans ware in(erpretedaccordingto the followingratingscale : I no RE, 2 low probability, 3 indeterminate, 4 high probabliity. Lung scans of grade 4 or 5 were considered positivefor rE. Contrast venogram showed 8 thromboses below the knee (group A), 21 above the knee (group B) and 38 diffuse(group 0), 13 patients had no DVT (group D), The incidence of positivelung scan was 33% in grp A, 56% in grp B, 57% in grp C and ~13% in grp D. In patientswith positivelung scan, clinicalsigns of suspectedPE were present in 50% in grp A, 30% in grp B, 31% in grp C and 05% in pro 0, Overall, 49% of patientswith DVT had PE , but only 37% of these patien(s presentedoliniselsignsot suspectedrE, The incidence of PE was very high in DVT, i.e 112 DVI patients prasen(ed PE. However, 213 PE patients had no clinicalsigns of the presence of PE. Tho results of this study show the importance of the lung scan in tr~tement of the

patientswith DVT.

509

~, =rana~orst, ~. ~tas=ews~. • Bittner,

P PELTIER. PH, DE FAUCAL, B, PLANCHON, M.D. TOUZE,

F.-D.

Maul

a n d G.

:~r~ust,

Dive. Gen. Nucl. Med., Infect. Dls. and Pnetumology, University Hospital, FEankfurt/M.. FRG RADIONOKLIDE IMAGING OF SESSILE LUNG ~AKROPHAGES IN A I D S PATIENTS WITH PNEUMOCYSTIS CARINII PNEUMONIA (PCP) For s t a r t i n g t h e r a p y of o p p o r t u n i s t i c infections as P c P in AIDS pta. the e a r l y d e t e c t i o n of t h e s e c o m p l i o a t l o n s is m o s t i m p o r t a n t . The a i m of this study was to d e v e l o p e a n e w m e t h o d for Lung s c a n n i n g w i t h o u t a t l m e - s p a n of 3 ~ays in c o m p a r i s o n to 87Ga s c a n s but • ith a same h l g h s e n s i t i v i t y as well known f r o m 67Ga. In 15 pte~ with HIV antibodies (14 male, 1 female; a g e d 22-64) s u f f e r i n g ~rom d y s p n e a and c o u g h we performed ~7Ga-cltrat (2.46 M B q / k g body weight (BW)) and 9 9 m T c - A l b u m i n (5.55 MBq/kg 3W) s c i n t i g r a p h i e s . Images were taken ~0 min. (99mTc) and 3 days (67Ga) trier i n t r a v e n o u s i n j e c t i o n . In 4 pts. with PoP both scans were ~ositive (1); in 3 pts, without PoP aoth scans w e r e n e g a t i v e (II); in 5 ~ts. w i t h o u t P c P e i t h e r 6 7 G a or 9 9 m T c ~ c i n t l g r a p h i e s w e r e p e r f o r m e d and t h e y qere n e g a t i v e (III). In i pt. with liffuse malignant lymphoma of the Lungs the 99mTc scan was positive (67Ga scan negative)(IV); another 2 ~te. (i v a r l c e l l a p n e u m o n i a , i mycobacterlosis) showed positive 99mTc i m a g e s (57Ga = c a n s n o t d o n e ) ( W ) . These results demonstrate that 99mTeKlbumln lung scintiaraphy in A I D S pts. is a Eood tool f o r n o n - i n v a s l v e detectlsn of opportunistic lung diseases even in normal x-rays and negative 67Ga scans and f u r t h e r m o r e for timeshortening between injection and aol l s i % i s n in o r d e r to s t a r ~ therapy.

IM Hannah, A Sahweil, C Constant(hides, AL Mmbarak, AR M a ~ u d , M Nair, YT 0mar, HM Abdel-Day~. Dept. of Nuclear Medicine. Faculty of Medicine, Chest Hospital, Kuwait Cancer Control Center, KL~IT. Tc-99M METHOXY ISOBUTYL ISONITRILE (RP-30) UPTAKE IN B~NIGN & MALIGNANT LUNG LESIONS We evaluated the kinetics of Tc-99m RP-30 uptake in |4 patients with benign (5) or malignant (9) lesions in the lugs. Six patients with IKD and no lung lesions were used as a control. Two dynamic studies were acquired following the I.V injection of 15 mCi Tc-99m RP30. The first every second for one minute then every 30 see for 30 sin followed by static images for 5 sin at 2 and 3hrs later. Ttmour(TR)/heart(Ht), TR/contralateral normal lung (NL) NLIHt and time ts peak was calculated from 25-30 minutes images. NL/Ht TR/Ht Lesion/NL RP30+v~ IHD (6 Pts) 0.44 . . . . 0 +0.30 Untreated(6 Fts) O.43 0.64 1.6 6 sq.cell Ca +0.15 +0.29 +0.4 Untreated Poorly O.35 0.416 1.19 0* diff. sq. cell Ca (I et) Radioth. treated 0.42 0.42 I 0 sq.cell Ca(2 Pts) Benign diseases 0.46 0.55 1.2 0** (5 Pts) +0.12 +0.22 +0.3 * Pt had brain metastasis that was positive for RP-30. ** Lur~ abscess, bronchiactesis, sarcoidosis, hydatid cyst and pnet~onia. In RP-30 positive cases peak activity was reached within first minute after I.V injection. SPFLT in 3 of the 6 positive clearly delineated primary and mediastinal lesions. According to the results of this study BP-30 has ~ affinity to'concentrate in ~ l i ghent cells, it can differentiate malignant from non-malignant lesions and tumour uptake is inhibited by radiotherapy.

507 I

H. KLhn, Ch. Armbruster, N. Vetter, A. ~ s t b e c k

Dept. of Nuclear ~-=dicine and L. Boltzmann-Inst. Df Nucl. M ~ . , Wilhelm/nenspital, It. Dept. of Medicine, Puimolog. Zentrun, Vienna ~uclear medicine procedures as diagnostic adjuacts for lung infections in AIDS patients In addition to conventional ncn-invasi~ methods such as l ~ g function tests, arterial blood gases, or chest radiography, high-risk AIDS pts. m~re assessed by nuclear medicine ~ethcds. TC>gPA aerosol l ~ g clearance ~ s used to detect injuly to ~ epitheli~n, and 67 Ga imaging to detect areas of ~ctive infl~mmation and linfection. 6 pts. %~re studied after hospitaliz a t i ~ for acute P ~ e ~ s t i s cari/%ii p~etlnonia I(PCP). 3 also heal documented c y t c ~ a l o v i r ~ s infractions. I pt. had lyr~phoid interstitial pneu~nonitis (LIp) , and I pt. Kaposi's sarcoma with lung involvement, 3 A/De pts. had no evidence of pulmonary disease and 6 pts. were only Dos. for HIV antibody. Specific diagnosis was made by HAL or fiberoptic bronchosoopic biopsy. Pts. ~ith acute lung i~fections were studied during the first days of hospitalization and after spezific therapy. All other pts. were on AZT. In the 6 pts. with PCP, the average clearance was 5.46 + I .t%/min, after therapy ~ .69 _+ 0.67%/sin. In 5 of 6 pts., clearance rate improved 1-4 m~ ~fter thex~py, I pt. had accelerated clearance even after 5 ~ . 67 ~a scans were DoS. (diffuse increased uptake) in all 6 pts. with PCP and in the pt. with LIp, but not in the pt. with ~aposi's s ~ . Chest X-ray was Dos. in all these pts. 2 HIV poe. pts. without clinical evidence of lung disease had accelerated lung clearance and slightly increased localized 67 ~ uptake cn foll~w-t~ over a period of 4 no, while X-ray was neg. in both, lu~Ig function was normal in one and borderline in the other. Both pts. were chrcr/c drug abusers. Since 2 pts. with acute PCP ~ neg. with 123 I labeled anti-grandiocyte ~noclonal antibody imaging, 67 C~ se~s~ to be preferable.

510 !~ ~r_~ndhor_~, S. B i t t n e r + and G. H G r +

Staszewski~.

G.

~ H L B Inst• for Disgn. Imaging; Dive. of +Gen. Nucl. Med,, *Infect. D i s e a s e s , Univ. Bosp.; F r a n k f u r t , F R G THE DLSTRI~UTfON PATTERN OF ~ESSILE BONE MARROW MACROPHAGES IN PATIENTS W I T H LAS A N D F U L L A I D S The role of m a c r o p h a g e s and t h e m a c r o Phage d e f e c t is the m o s t interesting point in A I D S r e s e a r c h in t h e m e days. Bone m a r r o w (BH) scintigraphy using 99mTc-labelled nanocollold is a g o o d nonlnvasive t o o l to e v a l u a t e the b o n e marrow status respectively the rethiculo-endothelial p o r t l o n of B H and the d i = t r i b u t i o n ~ a t t e z n of ~ = = i l e macrophages. Further m o r e it is a simple p r o c e d u r e to f i n d out f e c a l d e f e c t s . 611 r e g i o n a l scans w e r e p e r f o r m e d in 37 pts. with positive HIV antibody titres (34 m., 3 f., mean age 36 7ears) with v a r i o u s stages of AIDS (LAS = 20(I), full A I D S = 17(II)). The pts. of g r o u p II w e r e s u f f e r i n g from Kaposl sarcoma (KS) and/or Pneumoc y s t l s c a r l n l i P n e u m o n i a (PAP). 9 9 m T o labelled nanocolloid (5.56 M B q / k a b o d y weight) s e r v e d as r a d l o p h s r m a c e u t i e a l t r a c e r for B M scanning. All o v e r in 25/37 pie. BM ecintigraphies w e r e f o u n d to be a b n o r m , l (1=11 pie., II=i4 pts.). 9 pie. w i t h LAS as well as 3 pts. w i t h full A I D S h a d a n o r m a l B N scan. iS pts. showed a BH extension up to the k n e e s a n d / o r elb o w s (I=5,11=8). 1 f e m a l e pt. w i t h KS demostrated BM e x t e n s i o n up to the a n k l e and w r i s t Joins. In 3 pts. (II) p e r i p h e r a l B M was u n v i s i b l e . In 11/25 pts, (I=4, 11=7) focal d e f e c t s of B M w e r e f o u n d (KS = 6). Obviously BM presents an intensive i n v o l v e m e n t in H I V i n f e c t i o n and s h o w s increased reaction when changing.

308 ;12

511 ~abbatmni S.,*Fini A.,*Galti A.,Raise E., Gritti F.M.

Infect.Diseases Dep. & * Nuclear Medicine Maggiore Hospital. Bologna - Italy

Serum Thymidine kinase isoenzyme gassy in infection HfV correlated. In clinical practice TK hss proved to have a very high activity particularly in haemolymph tio pathology, in brain tumours and in lung microcytomes. Lsrson and other authors point out that in cePtain viral diseases as cytomegalovirus, Epstein-Barr virus, VZV, HSV 1 e 2, Adenovirus, bighlevels of TK enzyme activity can be found:in their opinion this is maintai ned by the syntesis of genetic material of v~ ral origin. Pedersen and Inceberg have studi~ TK activity in infection from HIg and observ~ higher TK levels among AIDS patients with P . ~ rinii compared to those with toxoplasmosis or esophagitis caused by Candida and g-Sareoma.~ order to evaluate the use of TK during the course of infection by HIV ws studied 205 HIV +

p,*

Stages

pz p,

.... [nv+,g i.a.~ 24 .............

I....._ ,o,om

.......

x ~SD(n.V. 5U/l)

p,,

14.B.~8.1 ...... .....

1~5

18.e~8. •.....' ¢0.o5--~D25 :..3~=10~~.~ ~',d.~ - -

•HIV+s/c i.a.= with or without immunological alterations. • *T student test:only slgnificative diEerence~ reported.

~bbatani S., *Fini A.,*Galli A., Raise E., Gritti F.M. Infect.Diseases Dep. & ~ Nuclear Medicine Maggiore Hospital, Sologna - Italy

Thymidine kinase test in ~he following-up of ~atients AIDS affecged during the Azidovudine [AZT) therapy. During AZT treatment in patients AIDS affected clinical observation monitoring become very important in order to detect toxicity signs drug induced. In front of a possible appsaranc of symptoms as hepaticcybolisis or bone marro~ t o x i c i t y signs, therapy with AZT must be suspe~ ded. In our study we valued in a little group of patients under AZT treatment the behaviour of TK with regard to appearance of bone marrow toxicity signs. Two groups of patients are st~ died: the first (gO subje@cts) before AZT therapy. The second one (7 subjseets) after 15 days of therapy. The statistics were elaboratec by means of wilcoxon test. The serum TK walues were 30,6!15 U/l for the first group anc 60,1~21,4 U/1 for the second one (P=n.s.). Preliminary data show an increase of TK serum values during therapy with AZT. Our further purpose is to value if an increase of TK could be correlated to toxicity signs in order to stop AZT therapy and, moreover, if an eventual reduction of AZT dose takes TK level to values wieh could be correlated with the disappearance of iatrogeni6 pathology.

CONCLUSION It can be noted a progressive increase of unz) me activity co~related to the deseeme seriousness.

514 H.Herzo~L K.J.Langen~, T.Kuwert z, E.Rota Kops x, M.Hennerici ~, C.Morgenstern~, L.Felnendegen* 'I) Inst. of Medicine, Nucl.Res.Cent.J~lich 2) Dept of Neurology, U m v . of Dfisseldorf 3) Ear-Nose-Throat Dept., Univ. of Dfissel doff, FaG CORTICAL A C T I V A T I O N BY M O T O R [ C A N D A C O U STIC STIMULI R E V E A L E D BY PET A N D R E P E A T E D FDG-SCANS ~ormer PET-measurements of cortical perfuslon tnd/or glucose metabolism which were to show a mrebral activation by external stimuli were mpaired by the low spatial resolution of older PET-scanners. This paper describes a method of elucidating cor~ical reactions of local glucose .consumption (LCMRglu) by using a new high resolution PET-scanner. rwo groups of patients were investigated: group In=6) had temporo-parietal infarctions and ;roup B (n=Sl Were unilaterally deaf. 185 MBq PDG were injected into each patient and dynamic PET-scans over 50 min were acquired without ;timulation (control). Immediately afterwards ;tlmulation was started, fLIrther 185 MSq F D G ~ere i~ected, and a new serles of PET-scans ~as obtained. Group A was stimulated by writing ]umbers; group B was acoustically stimulated by ~ock music. PET-scans in 15 t r a n s v e r s a l planes ~ere done with a new S-ring pET-scanner 3C4096-15WB with a s p a t i a l resolution of 5 mm the stimulation images were corrected for :ountrates originating from the control study. 3ontrol and stimulation data as well as difference images were evaluated in t r a n s v e r s a l and ~oronal images using regions of interest. 3nly those cortical areas dedicated to the specific stimuli showed a change of LCMRglu between control and stimulation. In group writing caused a 22% increase of LCMRglu in t h e area of the praecentral gyrus c e n t r a l ] f e r a l to the hand writing. During acoustic stimulation LCMRglu in both primary auditory cortices increased by more than 20%. The method described here leads to a clear delineation of cortical areas activated by e x t e r n a l timuli and is now available for clinical studies.

515

513 J, r l ~ , A . ~OL,Ch. H I C ~ , M . COG~F~U,E. C, LATL~]~,A. M, GOFFZ ~rT. P o s i t r o n T-~ograpby L a b o r a t o r y Un~veroity of Louv~l~ 2 chopin du C y c l o t r o n B-1348 Louvaln-la-Neuve, Belgium.

~ A ~ GLUC05E I ~ T A ~ O L I ~ IN STRIAT0~IGRAL DK~TION : A PZT STUDY. C e r e b r a l glucose m e t a h e l l ~ vne ettzli~1 i n 4 p a t i e n t s ~rith S t r i a t o ~ i g r a l Degeneration (~D), a m r s dlso~der cheracterized by an L-dop~-raeieiant sgtrap ~ T m ~ l a l s1~drume, ~utono:d.c ~ a l l u r e ( S h y Drager sl~drome) ~ms p r e s e n t i n 2 c a s e s . Glucose m e t a b o l i ~ ~ s measured by p o s i t r o n e~Lsslc~ t ~ t o g r a p b y (PPr), us:L~ a n ECAT I I I t e n , g r a p h a ~ i t h e fltmrodeog~;luonse(FIX~) a u t o r a d i c q r a p h i c nethod. Patient d a t a ~ e r e co~pared t o t h o s e o b t a i ned in ten n o r m a l , age-matched v o l t m t e e r e . With the e x c e p t i o n of m~derate hypometabolism I n t h e f r o n t a l lobe ( p - 0 , 0 0 3 ) , cortical g l u c o s e utilization was g o , p a rable in patients and c o n t r o l on, loots (p-0,022). BY c o n t r a s t , all SD p a t i e n t s hod a d r a s t i c byponetabollon i n their p u t ~ i n a l (25.53 + l - 3.93 i m o l e s t 100 g. tin) caudata n u c l e i (31.30 +1-5.76; c o n t r o l valuse reepeotlvel¥ 45.58 +I- 5.53 end q G . i O + / - 6 . 0 7 ; p < O . O 0 2 ) . g e l a t l v e metabolic r a t e s , e~pregsed in p e r c e n t ot menu g r e y m e t a b o l i s m , were reduced by more tl~n 20 ~ £n t h e o t r i a t u m (> 3 S) below c o n t r o l s ; p
516

C Raynaud, B M Me~oyer, J P Soucy, G Rancurel, J C Baron, Y Samson, N Tzourio, M Bourdoiseau, S P,Jcard, M Bourguignon, N Lessen and A Syrota. Service Hospitaller Fr~ddric Joliot,D~.partement de Biologie, Commissariat l'Energie Atomlque, 91406, Orsay, Hopita] L ~ Salp6triere,75 Paris, France.

REGIONAL C E R E B R A L B L O O D FLOW (rCBF) M E A S U R E D B Y S P E C T W I T H ZSSXe: VALIDATIO~ uSING A P ~ . T / S P E C T COMPARISON. rCBF was measured in 0 patients both by S P E C T (To morn]tic 564) with t ~ X e and by P E T (ECAT II) us. ing the Cz~O~ continuous inhalation method. For east study, r C B F was computed in 14 cortical regions of in. terest (ROI) drawn on the O M + 6 0 m m slice, the RO] volumes ranging from 3.2 to 6.4 em s. Eight patient,, were in the chronic phase of a unilateral sylvian infarct and one had a transitory i s c h e ~ e ~ttxek 2 months e~r]ieri the del~y between the S P E C T ~nd P E T studie,• never exceeded 10 d~ys. S P E C T - r C B F mad P E T - r C B F were found to b, higMy line~Hy correlated, the S P E C T method givin~ larger flow v~]ues (slope = .96, intercept = 12.6, ] = .78, n=126). For all but two regions, the individual region regressions showed the same pattern wit]c slopes ranging from 1.04 to 1.19, and intercepts rang. ing from 3.5 to 10.8. T h e prefrontal and occipit~l re gions exhibited significantlydifferent regression ]in~ with lower slopes (.51 and .63) and larger intercepts (16.7 and 24.5). These two regions were not involve~ in the stroke so the range of r C B F values in these wa~ m u c h narrower than in the other regions. T h e antici. pared S P E C T overestimation in low flow areas was no~ observed in this study partly becanse the P E T value also were probably overestimated. This study validates the use of the ~ X e 5PEC'~ method for r C B F measurements in cortical regions.

~epart~ents of ~uclear Fadiciae C.H.O. k. ~ E 8 (') I.H.C. Ianlle~ Hontisny le Tilleul gruanlles BKGI~4 EOOTIHg~J/~TZflCd$IO~Of I ~ FOLU~ M~ T~ SEVERITYOF I ~ t ~ I C B~AINLESIONSIN Tc99~ H~AOaM 7L_201DCC S,P.LC.f. STUDI~. The am of this study is to validate a methodof fast routine qualification of t3e regianal cerebral blood Mood (RCEF] impairemntin stroke patiants studiedby SPECI, The ~thed is basndon a p~el-by-pixelanalysis of the t I L l slice diagru representation ( ~ } of the .hole stndy (BJils~e bagel Theonly operator i.tsrve.tion ia to outline on the 8SD izage the R0I in vMChthe calculation ~et be doneand to select the level of signilicant left-to-right difference (LE~). The pizels in the ~Oi shovir~ such a si~ficant difference with their .ymetric in the ~ ~ are co.ve~tndinto an elementary selene, ancording to a ~rsalization basedon the knowledge of the position of the pixel in the HODimage, the zool factor, the pixal si~e, ~e brain slice area, and the slice .idth. These el~entary vohema are stoned together to give the voluze of relative ischelia (VBI) for each anlect~d I,T~D lope.1. The variability of the ~antificaLion het~an Tl_201 DDC and 7c 99e ~AO ~s beentested in 10 Patients eluinnd with boTh tracers injected ancce~eivelyin the sameannditians. fie correction was lade for attsanatlon nor, in the I~A0 study, for the ne#igible activity of H_201 in the Tc_~gmvindoe. ~mulLs: In ,Lrche patients, 3 level] of relative L~D in helologotm piae]s are arbitrarily eel at nore than 7, 14 and 20 g For eacheipRficant level of u)w~Lry, results are expressed ~s: 1' the correlation coefficient betsean ~g@AOaM D~C V~I masur~ents; 2' the linear ~ i a n coefficients obtadnedsbes plctti~ the ~C V~I a~ainsLthe ~P~OP~; 3' the standarderror on the eetirated DI}CV~ frot Lhe H~AOWl calculation. 07 ~

2~3 o~ r =.956 ¥ = 0 ¢ 1.05 g 57 cc 14 ~[ 209 co r :,9~9 ~ : 4 + 1.05 X 57 cc 20] 143cc r =.959 Y=9+O,%X 48cc Conclanions: 1' The zeL~d ]lima a f ~ t and virtsally operator zndebeede~t r~tine ~ quantification of t~ain iachelio l~ior~. 2' To_gG~~PdOand ~1_201~C are bets valuable tracers for ~bis purpose, leading to co~rable results in volmmquantification. 3' 1~ane resslts suggest a possible quantification of RC~ rediatrihetio, study in van patient's viait, frm tso similar aogeisitioan separated by a pMeiologic or a pM~acolo~ic interventio~ such as the acsta~oiamdevanodilatio~ test.

309 ~17 M. Rubinalein, R. Denays, H. R. Ham, A. Piepsz and P. No~l. Depatlments of Radioisotopes and Neurology, St. Peter Hospital, Free University of Brussels, Belgium.

SPECT STUDY OF CEREBRAL BLOOD FLOW (CBF) PERTUR~J~,T1ONSINCHILDHCOD SEIZURE DISORDERS. CBF studies ere useful in adult epilepsy; interfctal focal abnormalities are indeed often found in patients when neuroradiological techniques fail to demonstrate any alrustural lesions. However childhood epilepsy is a more complex disorder, as indicated by the clinic~J pleiomerphlsm, the variety o[ etiologic factors and the unpredictable course. We have investigated whether CBF studies could provide information on diagnosis, treatment and prognosis in epileptic children. Using a CBF tracer, 123-1-1MP (0.05 mc[/kg of p,5n produced 123-1) and SPECT, we studied 14 children (age : 2 months to 13 years) with vadous seizure disorders. 9 were known and treated epileptics, and w e r e seen inleristally (3 had tanic-clonic seizures (TCS), 2 had coml:0ex partial seizures, 2 suffered from 8ravais-Jacksonian crisis, 1 from absences and 1 from a Lennox-Gastaut syndrome). 4 patients were free from anticonvulsivant therapy and were investigated from 12 hours 1o 5 days aNer their first TC.~. One child with a severe hypalonia was sPJdiep one week prior ta Ihe onset of TCS. SPECT was normal in 4 our 14 patients. All of them had normal CTscsn. The other 10 children had abnormal SPECT studies consisting in local hypoperfualon, diffuse hemispheric hypoperfualon, muitifocal and bilateral hypopeNusion, or focal hyherperfusion. In 7 cases these abnormalities were congruent eilher wTthstructural lesions demonstratep by CT or MRI or with clinical or EEG data, In the remaining 3 children, there was a SPECT abnormality not predicted by alinical, EEG or radiological data. The existence of a focal SPECT lesion in children wilh diffuse polyspike-and-wave may suggesl secondarily generalized seizures, which may have therepeulic implications. Moreover the SPECT pagern was intimately related to the severity of neurological iml~irmerd, An extensive SPECT alleral]on was associatad with a poor evolution, in lerms of irdallectual performance arld seizure frequency, Conversely all children with normal SPECT had less than 2 seizures per year and normal neurological and inlelleclual development.

520

518

i19

J, Laveill~*, G. Demonceau**, H.~. Botez *, P. Rigo**, M, De Roo***, R. Taillefer*, B,A, Morgan ***~, R.C, Wallovlgeh ~**~ l]gtel-Dieu de MonSr~al, Quebec Canada ~ University Hospitel,Li~ge~ Belgium~, U,Z, ~asthuiberg, Leuven~ Belgium W ~ ~.LDuPont de Memour & Co. (Ino.), North Blllerice HA* * % *

K.Seybold, C.Coosemans, J.Th.Locher,

k COMPARATIVESTUDY BETWEEN ggmTc ECD AND P~MPAO IN NOR~/L VOLUNTEERS AND PATIENTg. ThisprelLminary shudy was designed to compare the clinical imaging and pharmacological characteristics of Tc-99m HMPAO and Tc-99m £CD. Four normal male volunteers and two patients (IM, IF), with a story of s~roke more than weeks prior to the study were injected on separate days with 15 mid of Tc-ggm ~B~PAO an4 20-30 mCi of Tc-ggm ~CD. The patients had z CT scan within a week o{ the study. Rlght lateral dynsmic planar acquisitions over the brain region of hhe volunteers were obtained from 0 ~o 20 minuhes and SPECT study and whole-body imaging were p e r f o r m e d 3 times over the 3 h o u r ~ud~. Venous blood samples were oaken periodically. The results show both T c - 9 9 m ~ A O and T¢-99m ECD ~o have high initial exttsctlon in the brain. The time activity curves showed some initial clearance of T¢-99m HMPAO but not wleh Tc-99m EOD. At 20 minutes, the brain uptake is 3.9% and 4,6% of the injected dose (ID) Eor Tc99m ~ A O and Tc-99m ECD respeoeively, Blood cleerance of Tc-99m ~CD is more rapid and complete than that of Tc-99m ~MPAO (4.0% and i0% ID respectively at 60 min.). Facial so~e ciss~ activity and clearance rates also are more ~avo['abi~ wi~b T ~ - 9 ~ ~C~. ~y gh~ac houre ;c=~

eous brain perEusion agent and have clinical l pharmecologto charao=erisrics gha{ are superior to chat o( Tc-99m HMPAO,

M. A. MACLEOD, I. HAMILTON, P. K E ~ , M, d. FOX* and G, H. ADKISSON*

~epa~.~mt of Nuclear Hedicine 0. ~ [ / 6110 Montig~y le Iilleul, BELGI[~

~ITl~

OF ~PT-TO-OIG~~lON~l CMgRAL BLOOpFLOWIN

I)EPP~SB POII~.

This report deals with the r~olt~ of 14 depr~sed patients stedied by II.~ gIP~ PaisBien t~o~'apby ($P~I) foz ilagi]~ of their relative r ~ i o m l cerebral bleed flou (0CBFI. Iheee patie~te were referred to eaclede an underlyi~ cerebral l~ion, i l l of t h ~ ~ r e r~t-banded aM had a nomal tra~.~iesion C~lt~ted tslo~aI~Y study. tC=tho~: The 30 Idm=tes SPEC?acqu~ition static 30 mimics after an injectien of 3.7 l~q of I123 HII~M. D~ri~ injection, patients have their eyes opel i n - a dark silent room 0~e-pixel reconstructioo slices are recoastructhdin the orbital-~atal planeand ~ rearrangedinto 3 grousedslic~ representing the uppzL the lediL aM the loverleve]sof the brain. 5 leftand ri0ht s~mmtricaIROle are autslaticallydefinedby the comI~t~ in these3 ~-oupedslices, exthnd~ngPromthe frontalref~on to the occipital re~ion, teft-ts-ri~t activity ratios are calculated in a l l 10 pairs of OOIs. Oes~its: R~ions gpoor lave/ ~iddle level Lo~-r level RI 1.00@ p(.001 1.171p(.OOl 1330 p( .O01 R2 1.047 n s 1.@17 n s .052 n S R~ 1.019 n s 1.011 n S .g67 n S ~4 1 100 n s 1.010 n s 1.074 pc.01 R5 i . I ~ p(.00l 1.172 p(.00l 1.164p(.001 ~ t r i ~ l ~0Is extend truethe foRhead -01 to the o~iput -~. lhe m~n aM the standarderroron the estmathd lean are COlF~ted far all 15 ratios, and are co,payed for significance with the expected value of U~ty, according to Lhe T test. Conclusions: ~ r ~ t ~CB@ ratios~ si~dficantly increased in the anterior and the postsrior r~i0ns of the brain. These results are in ag~me~t with a BCI~ study ['1 ~sing Xe130 in depressed patients, reporting increased values in the left frontalregion and ~ecrea~ed v~lue~ in the right occipital re~ion; thus leadir~ to increased left-th-right ratios in both re,ions. [*] P ~ t d e ~ e f , J lacquy & J ~ndle~icz, in "Hew~ a ~ ~ z n g techniques and peychophanmacolog~",n' 9, Oxford Bnivexsity Press Trimble 19~6.

Department of Nuclear Medicine and ENT-Department*, Kantonsspital Aarau, Switzerland RESULTS OF TC-99M-HMPAOPERFUSIDNSPECT IN PATIENTS WITH VESTIBULARDISORDERS. Although dizziness due to central vestibular disfunctien (CVD) is a frequent complaint in pa tients (pts) undergoing neurootological (n.o.) examinations, the objective n.o. findings may be discreet. The aim of this study was to eveluate the brain perfosion pattern in those pts. [n order to demonsLrate disturbances oF blood perfusion of the brain, 12 pts with n.o. symptoms of CVD had undergone perfusion SPECT studies after injection of 600 MBq Tc-99m-MMPAO. Transverse and frontal sections were reconstruc ted and evaluated visually by two observers. Additionally, all pts had CT and extensive n,o. examinations. AIm data were compared: from 12 pts, ~I were found to have circumscript zones of impaired brain perfusion. In 8 from 11 cases CT findings were normal. 5 of these 8 pts were already treated for psychosomatic disorders or depression, as objective symptoms of their disorders were discreet. In view of our findings w( conclude that Tc-ggm-HMPAO SPECT can reveal brain perfusion disorders in case where the pts complaints are important and in discrepancy wit~ discreet n.o. findings, where other radiologieel methods cannot confirm pathological finding~ in the brain and where pathological perfusion iI considered to be a probable etiological factor. In order to evaluate the specifity and sensitiv i t y of Tc-ggm-HMPAO SPECT in this clinical )roblem more extended studies will be done.

I 521

c.g.B.

M.PodvineO

Departments of Nuclear Medicine~ RN Hospital, KaslaP, Gosport and *Underwater Medicine, Institute of Naval Medicine, Gosport, Hones, U.K.

Tc-99-E94PAO SPHT IMAGING IN THE DIAGNOSIS OF CEREBRAL BAROTRAUMA Cerebral barotauma, or the neurological m~nifestatisn of the 'bends', is a relatively common disease of divers and aviators. To dace, however, no-one has succeeded in demonstrating a cerebral or spinal cord lesion in rive, following a decompression incident, despite the presence of definitive clinical signs and symptoms of iNS involvement. This paper describes the use of Tc-99m labelled hexamethylpropyleneamine oxime (To-ggm-HMPAO) with single photon emission tomography (SPET) in a study Of three individuals involved in diving accidents. ALl three suffered cerebral barotrauma during decompression and all exhibited clinical signs and symptoms of dysbarism to a varying degree. Imaging was performed , following the incidents, at time intervals ranging From 2 hours to several days. The results showed well defined cerebral ischaemic lesions ibn all three subjects. We conclude that Tc-ggm-HMPAO imaging provides a significant advance in locating and demonstrating cerebral lesions following barotrauma and will contribute greatly to our understanding of the pathophysiological )rocesses involved.

522 A. Ahonen, A. Laihinen, H. Aronen, J. Kuikka, N. Lindblom, M. Komu, K. Katevuo and U. Rinne Departments of Nuclear Medicine, Neurology and Clinical Radiology, University Central Hospital Turku, Finland HEMODYNAMIC CHANGES IN THE INFARCTION AND REMOTE BRAIN AREAS EVALUATED BY Tc-9gm HM-PAO AND MRI

A new l i p o p h i l i c tracer, TC-ggm HM-PAOhas been shown to be a useful regional cerebral blood flow (rCBF) marker. MRI is a very sensitive method for detection of cerebral ischemic lesions; but both the infarcted area and the surrounding edema are visualized in spin echo (SE) images. The aim of this study was to evaluate how well the true infarction area and the remote effects of infarction could be assessted by those methods. An intravenous bolus injection of 700 MBq of Tc-9gm HM-PAO was given for 18 patients with supratentorial infarction. Immediately after the dynamic study for determination of regional cerebral circulation time and first-pass extraction (E) a SPECT-studywas undertaken. SE-images using an ultra low f i e l d (0.02 T) magnetic resonance imager were produced. In some cases also the relaxation time (T1) in brain infarct and in corresponding contralateral area w e r e determined. CT examination was u s e d for to confirm the infarcted area. Abnormal SPECT findings were found in 17 out of 18 patients, correspondingly abnormal SE-images in 16/18 patients. On some patients these HM-PAD rCBF/hypometabolic abnormalities were found outside the infarcted region, probably reflecting remote effects of infarction. Those areas could not be detected in SE-images of MRI studies, although abnormally long TI-values were also found in contraleteral brain area in a few patients studied so far. Thus, a HM-PAO study may give valuable hemodynamic information in future management and treatment of patients.

310 523 M. STEINLING I ; Y. YONEKURA 2 ; PH. KASSIOTIS 1 ; NA. LASSEN 3 i. Service Central de Mddecine Nucldaire ; CHR Lille ; FRANCE 2. Dept. Of Nuclear Medicine ; Unlv School Medicine ; Kyoto ; dAPAN 3. Dept. Of Clinical Physiology Nucl. Med : Bispebjerg Hospital ; COPENHAGUEN HE "FILLING OUT" PMENOMENON WITH HmPAO 99"~c= : WHEN ? WHY ? RmPAO labelled with 99mTc is a very pratictable tracer of the cerebral perfusion with a stable uptake in the brain after the initial back diffusion from brain to blood with a feed back rate lower than O.5 %/H (Costa et al 1996). However, a case of leakage of the HmPAO from the brain has been described by Holmes et al (1987). We have observed 5 others cases, always in "high flow" ("high uptake") situation. These eases were corresponding to a meningioma, an arterial vascspasm when it was just lifting, and 3 luxurary perfusion after embolic is chemic stroke. All these patients had had repeted measurements, at least, at 5 min and 5 hours after administration of 200 uCi/kg of HmPAO To. In four cases, the Relative Uptake Ratio (R.U.R. %) was computed dividing the counts obtained at delayed time in several RDIs (high uptake area, centrelateral cerebellum, visual cortex) by the initial values. When the average R.N.H % values for 20 normal areas was 99 % (sd : B.O3), the R.U.R % for the high flow area was significaterely lower : g4 % (sd : 0.02). From the Neirdnckx's four compartimental model (1987) several hypothesis to explain this leakage can be discussed : a meoanieal passage through a dammaged blood brain barrier (as proved by CT scan with contrast enhancement in fear of our cases)~ May the value of the high flow be evocated ? Or a modification of thespeed of convertion from the lipophilie to the hydrophilic forms ? More informations have to be collected to answer. It remains that MmPAO is usually very stable in the brain, but in several circumstances (when "high uptake") occurs but not in all the cases it ca~ be however observed a moderate delayed leakage (3 %/H) the "filling out" phenomenon.

;26

524

525

Roosen s, J.C.W. Felnendegen ~

Kiwlt~,

G,

StEckltn~,

L,E.

1)Instltut f~r Medlzln und 2)Instltut ftlr Chemic 1, K F A JGlich GmbH, 5170 Jflllch, F N G 3)Neurochirurgische Klinik der UnlversitRt D~sseldorf, 4000 DSsseldorf, FRG 8PECT-IMAGING OF BRAIN TUMORS WITH L - S [*z~I]IODO- S - METHYLTYBOSINE L-S- [*~I]lodo-a-methyltyrosine (*Z~IMT) h a s been used for pancreas imaging (Tis~ar et el., J Nucl Med 20:973, 1979) a n d detection of melanomas (Bockslaff et eL, Nuklearmedlzln 17:179. 19B0) and recently for brain tumor imaglng with SPECT (Biersack et al., J Nucl Med. in press). The purpose of this study was to confirm the value of *~IMT-SPECT in the study of brain tumors. - 8 patients with brain tumors (4 malignant gliomas, 1 metastasis, I neurinoma) were studied with x~"IMT-SPECT, One patient with a m a l i g n a n t glloma w a s r e e x a m i n e d o n e w e e k a f ter intravenous chemotherapy with the nltrosurea ACNU. The BPECT studies were started 15 mln after intravenous injection of 200 M B q ~IMT. E4 images of 36 sec. each were acquired using a Philips Diagnost Tomo Ganuna Camera wlth a 30" slant hole collimator. After prefilterinE of the projection data transversal slices were reconstructed by rampfiltered back projection and converted Into orhltomeatal parallel slices. - DurinM t h e a q u i s l t l o n time (35 mln) a 30 loss of whole brain activity was measured. Still, excellent images with clear delineation of the tumors were obtained. The tumor to normal b r a i n r a t i o (T/B) was g.o for t h e m e t a s t a s i s , 2.4 for t h e n e u r l n o m a a n d r a n g e d from 1.g to 2.4 for m a l i E n a n t gliomas. T h e tumor s t u d i e d before and after c h e m o t h e r a p y with ACNU s h o w e d a n i n c r e a s e of T/B from 1.E to B.4. - The results confirm t h a t ~ I M T is a p r o m i s i n g agent for brain t u m o r imaging with SPECT. Further investigation is needed to understand the role of aZSIMT in tumor metabolism and therapy control.

527

Radiological Clinic, University Clinic Rudolf Virchow/Charlottenburg, West Berlin

CEREBRAL INFARCTS: SPECT EX~MIMATION OF REGIONAL CEREERAL BLOOD FLOW (rCBF) AND -VOLUME (rCBV) COMPARED WITB GD-ENRANCED NRI Purpose of the present study was to compare the findings of rCBFand tOBYmeasurements by SPECT with those of Gd-enhanced MRI in patients with cerebral infarcts at various stages. SPECT examinations were performed in 30 patients with cerebral infarcts, proved by clinical data, using 99m Tc-HM-PAB (rCBF} and 99m To-labelled red blood cells (rCBV). I All patients had a Gd-DTPA-enhanced M R L Time range for SPECT and MRI was within three days or less. gemiquantitative evaluation of the SPECT images was performed by calculating regional indices. Group i: In patients with acute or subacute infarcts (n = 21, within 21 days after clinical onset), MRI reveale~ Gd-DTPAenhancing lesions in 19 out of 21 cases. While tbe rCBV was elevated in all eases, tbe rCBF was either reduced or increased. group 2: in the chronic stage (n = 9, more than Ig0 days after clinical onset), Gd-DTFAenhancement was missed on HRI. rCBF and tOBY both were reduced. In conclusion, combined rCBF and rCBV studies using SBECT demonstrate hemodMnamic changes in acute and subacute infarcts corresponding to vasoparalysis and luxury perfusion as well as reduced hemodynamic support in chronic infarcts wehereas the use of Gd-DTPA-enhanced ~RI can depict a disrupted blood-brain-barrier in acute or subacute cerebral i~farction.

528 Et~rus,

M. Guyot, B. Lambert, J.P. Maire, J. Caix, E. Jeandot, A.J. Brendel.

J Villanueva-~er, K ~rrett, R G i c ~ t t i , and I . G _ ~ n a _

J

Hepital Univ. Pellegrin, Bordeaux, France.

Division of Nuclear M ~ c i n e , FL~dical Center, Torrance, CA, USA

Harhor-UCLA

IMP-I-123 BRAIN SPECT AFTER CEREBRAL RADIATION THERAPY (CBT) ORT may cause late neurological damage as shown by intellectual troubles ocouring usually between 18 and E0 months after irradiation for brain tumors. We evaluated cerebral perfu sioD several months after CaT fop brain tumors in gB patients (pts) (age 17-B5:mean 39). CBT had been performed By using high energy beams (obtained by linear accelerators ~ d Cobalt-BO units). The total delivered dose was 51 to B8 Gy, over a ~eriod of 4 to N weeks with individual daily doses being no greater than 2 Gy. After a mean delay of 35 months following CaT, brain SPECT was performed 20 min after IV injec$ion of B mCi of I~-I-iBB, using a singlehead rotating g~ma-camers. In ~0 pts there was a focal IMP decreased uptake matched with the tumoral location, and in T of these pZs a controlateral decreased uptake was also noted. In 5 pts. we found cortical defects in the field of the CAT which mismatched the ttnnoral locmtion (4 axial and i left frontal tumors). In 3 patients with axial tumors, the BPECT images were normsl. There w~s no correlation between the extent of the observed areas of decreased uptake and the tumoral histological type a n d grade. On transve2se slices there ~as a similar distribution between the iso¢on~ours of IMP uptake and the delivered iso~os~s. All the areas with decreased uptake lad received at least 50 Gy. No abnormality ~as seen for an irradiated volume lag cm3 •nd for a total delivered dose 58 G F, We ¢on:lude that IMP brain SFECT shows that radiation-induced cerebral perfusicn impairaents e r e frequently observed several months )r years after CRT for brain tumors. This ?isk could probably be reduced by a hatter ~elimitation of the irradiated volume and by ~elivering more appropriate doses.

M. Cordes, 8. Renkes, A. Scholz, R. Felix.

SIZE OF P]~qB~SI(]N DEFECT IN ~ STI~KE STUDIED WITH T c P ~ , (KI~EL~R'ION WITH CT.

report on the use of Tc99m-ethilene cysteine d ~ r (ECD) SpECT in patients with chronic brain stroke. Tc99m-ECD is a l i ~ l i l i c agent that crosses the blood brain harrier and is a c o m ~ m l a ~ in the brain as a function of perfusion. 5-8~ o ~ t h e d o ~ retained by the brain. 30 mCi of ~ 9 9 m - E f D were injected intravea~ously and 2 hours later I 64, 6 degrees angle images of the brain were gathered. Transaxial. coronal and perasagittal i ~ s were obtained. Ahmormal t~otake was defined as a d ~ below 60% of the m a x ~ a l eP~ephalic activity. Non contrast brain CTs ~ r e done within 48 hottrs. studied 5 ~ t i e n t a (ages 40-78 years} with c/ironic brain inf~urotion, 0 aLreas of infarction were id~_ntified. The strokes were more than 2 ~ old ar~ there was no ne,/rolegical c h a ~ within the last two t~=e~. size of the stroke was N~asured in three di~nsiorLs, in both R ~ 9 ~ - F ~ erECT ~ CT, and the voltage estimated (ml). ~ne volume of the infarct was estimated in ral: CT

Tc99m-ECD

mean 34.5 nd 50.5 ml SO 31.5 43 The correlation between g r o ~ is r=.81. 1.1 x --+12.6.

Y =

concl1~e t-bat perfusion defe~rts d e t ~ with T c 9 ~ E C D in strt~e B a t i s t e are 32% larger than the ~r~lo~ical defects with cr.

K Rootwelt, T Bogsrud, D Russell, R NybergHanson

Departments of Clinical Chemistry and Neurology, Rikshospitalet, University of Oslo, Norway

C~%EBELIAR BLOOD ~ RESPONSE TO ACETAZOLAMIDE IN PATINffS w n R G~OSSED C~%EBROC~%EBEILAR DIAS(~ISIS I.v. injection of acetazolmnide (AAA) increase.~ cerebral and cerehellar blood flow (CBF) in normal subjects. In patients with severe cerebrovaseular disease the response to AAA is attenuated or abolished in the affected perfusion territories. Nothing is known about the AAA response in regions that have reduced base: CBF despite intact arterial supply and normal morphology. In order to elucidate this we have studied the effect of AAA on cerebellar CBF in patieDts with hmmiparesis and crossed cerebrocerebellar diaschisis of CBF. Eleven heniparetic stroke victims %~re studied. F~an age 55 years; range 39-70. CBF was determined with 133Xe inhalation and dyrmqmic SPECT. Measurements ~ r e done at rest and 20 rain. after i,v. injection of 1.0 g AAA. Resting ~ a n regional CBF in the affected cerebral territories was 35.6% lower than on the non-affected sides. (40.0 and 62.1 mi/100 g/rain) and showed aztenuated AAA response (5.1 and 15.4 ml/100 g/min respectively). In cereb e l l ~ the ~ a n side difference in basal flow w-as 12.6% (57.3 and 50.1 ml/100 g/rain). After AAA the mean increase in flow wag not significantly different in the tWD hemispheres (12.0 and Ii.i ml/100 g/rain). Thus the asymmetry persisted at the sa~e level (11.7%). The absolute increase in cerebellar CBF was of the same magnitude as in 12 healthy controls (10.4 ml/lO0 g/rain). It is concluded that eerebollar vasoreactiviny is intact in h~niparetin stroke. This supports the concept that the asymmetry in basal cerehellar CBF is secondary to functional deactivation ipsilateral to the hemiparesil

311 529 D.H.W. Sch~nfeld, Ch.J. Vecht, P.H. Cox, M. Pillay

Dr. Daniel den Hoed Cancer Center P.O. Box 5201 3008 AE ROTTERDAM, The Netherlands

SPECT A~A~YSIS IN DEX~24ETHASON~ TREATMENT OF BRAIN METASTASES Purpose: TO evaluate the effectiveness of 99mTc- HM-PAD in monitoring of dex~ethasone treatment in patients with brain metastases. Method: Nineteen patients with histologically docuunented solid cancer were studied by neurological ex~ination, CT scan and SPECT and reevaluated one week after treatment with dexamethasone. SPECT zmaginq was performed ten minutes after injection of 350 MBq 9SmTc- HMPAO. Regions of interest were studied by integration of the pixel activity in affected areas and comparing tJ]e~ with contra-laterR1 n o d a l areas. Discussion: Eighteen patients showed marked ROI abnormalities with a mean decreased CBF of 19% +/- 7.3% in the initial SPECT ex~ination. All of these lesions were sho~m by CT as characteristic for brain metastases. Following dexamethasone treatanent CBF was significantly improved in all eighteen patients. There was no relation with the dosage used (random 16 & g mg qd). Conclusion: These results demonstrate that ~ s c a n ' - - n i n g with RM-PAO is a sensitive indicator of CBF changes in brain metastases during dex~methasone treatment prior to radiation therapy.

532 O. Nickel, g. N~gele-W6hrle, $. Fischer, D. EiSner, E. Mahn.

Dept. of Nuclear Medicine, Klinikum d. Joh.Gutenberg University, Mainz, FaG.

QUANTIFICATION OF REGIONAL CEREBRAL BLOOD FLOW AND BLOOD VOLUME WITH SPECT: THEORY AND FIRST RESULTS The method for guantitalive estimation of CHF with 99m-Tc-RMPAO, which has been developed previously, has been improved including a measurement of CBV using Tc-99mlabelled red cells. In 70 patients brainSPECT-studies were performed with a dual head rotating camera after injection of Tc99m-Pertechnetate for labelling red cells and a subsequent injection of Tc-99m-HMPA0. The brain activity concentration of the red cells as well as that of Tc-99m-HMPAO was measured from the countrates within the attenuation-corrected reconstructed tomograms. During the first pass of Tc-99m the cardiac output of the patients was measured by a cardiac study. First-pass extraction and washout of Tc-99m-HMPA0 were estimated from time-activity curves over the brain hemispheres. The mean hemisphere CBF was calculated from the activity uptake, extraction and washout of HMPAO and from cardiac output. The mean hemisphere CBV was calculated from the activity concentration of the labelled red cells a n d f h e activity of a bloo~ sample. The resulting CBF and CBV values were in the same range as those from PET-measurements. CBF/CBV was significantly reduced in patients with carotid artery occlusions. These results indicate that the method gives valuable quantitative information about cerebral perfusion.

i30 Shyh-Jen Wang, Shin-Hwa Yeh, Joung-Liang Lan and Min-Shan Lin

Veterans General Hospital, Taichung, Taiwan EVALUATION OF SYSTEMIC LUPUS ERYTHE~[ATOSUS INVOLVING CENTRAL NERVOUS SYSTEM: TC-99M }iMPA0 BRAIN SPECT VERSUS TCT Kushner et al demonstrated alteration in cerebral perfusion in lupus patients using xenon-133 inhalation method. (Neurology 37: 1596,1987) T c - 9 9 m H M P A 0 displays considerable promise for imaging cerebral blood flow. Transmission computed tomography (TCT) has been reported to be useful in indentifyin~ lupus patiemts with central nervous system (CNS) involvement. This led us to compare the relative value of TCT and HMPA0 brain SPECT in evaluating the brain affected by systemic lupus erythematosus (SLE). Over a 6 month period, a total of 18 (CNSSLE) patients had both a SPECT and a TCT study performed within a week of each other. The patients (3 male and 15 female) ranged in age from [6 to 66 years. The manifestations of CNS-SLE included organic brain syndrome, seizures, headache, TIA and focal neurologic deficit. The YCT scan was performed with a SOMATON DR3 SIMENS total body scanner. Elscint APEX ECT system was utilized for data acquisition and reconstruction of }~PA0 brain SPECF. The TCT and SPECT studies were reviewed blindly by three nuclear physicians. As a results, i0 (55%) were deteoted by TCT in contrast to 9 (50%) by ~MPA0 brain SPECT, which demonstrates that HMPA0 brain SPECT imaging is comparable to TCT scanning in detecging CNS-SLE.

533

531 R.T. Co, A. 5algado, P.K. Rel'm, A . J . F u r l a n , W.J. M a c l n t y r e , J.R. L i t t l e , G.B. $aha, C. Sila, J.K. O ' D o n n e l l , H.K. Kung, J . L . King. Cleveland C l i n i c Foundation Department of r ~ c l e a r Medicine 9500 E u c l i d Avenue Cleveland, Ohio U.S.A. qgl06 1-123 HIPDM BRAIN SPECT CAROTID ARTERYOCCLUSION.

IN PATIENTS WITH

[-123 HII~]VI b r a i n SPECT was conpared to CT a l x l l o r MR w i t h respect to i d e n t i f i c a t i o n of al~norrrelities in 22 patients with a t h e r o s c l e r o f i c c a r o t i d a r t e r y o c c l u s i o n by angiography w i t h c l i n i c a l diagnoses of stroke (15), TIA (5) or asymptorretic o c c l u s i o n (2). Studies were performed with institutional approval of the research protocol, and each patient p r o v i d e d infon~ed consent. SPECT imaging was performed immediately and 2 hours post injection. Time inte;=val between 5PECT and CT/IVR was 0-9 mo. w i t h 15122 being done within 1 month. There was no change in clinical s t a t u s between the CT/MR and SPELT exams. SPECT showed i p s i l a t e r a l hypoperfusion in 15/15 cases w i t h i n f a r c t i o n , i n q/5 w i t h T I A ' s and 1/2 w i t h asMtptonetic o c c l u s i o n . The a b e o r m a l i t y on SPELT ~ras equal to (q cases) or more extensive than (16 cases) the lesion seen on CT/MR, except in 1 case w i t h lacunar i n f a r c t s end 1 case w i t h normal studies. There was no d i f f e r e n c e in detectability of abnormalities between the early and delayed SPECT s t u d i e s . Delayed SPECT scan was unchanged in 11/22, improved in 9/22 and worse i n 2/22 cases. In a 10 month mean f o l l o w ~ u d , I p t . had 2 r e c u r r e n t strokes ipsilateral to occlusion and SPECT a b e o r m a l i t y ; I p t . had 2 p o s t e r i o r c i r c u l a t i o n T I A ' s ; there were 2 deaths due to cardiac disease. The r o l e of HIPD~4 SPELT i n the evaluation of patients with carotid o c c l u s i o n warranfs f u r t h e r investigation.

534

J.L. MORETT%, G. DEFER, L. CINOTTI, P. CES~RO, N. VIGNERON, C. PETHE.

RH Reid, KY Gulenchyn, JR Ballinger, ECG Ventureyra, j Bradford and M Krelina.

Bobigny, Creteil, Du Pont de Nemours France

O t t a ~ Civic Hospital, Children's Hospital of Eastern Ontario and the Royal Ottawa Hospital, Ottawa, Canada.

COMPARATIVE TOMOSCINTIGRAPHIC STUNy OF STRORES USING ECD Tc99m, H~PAO Tc99m and IM? I123. PRELIMINARY ~REU~TS. T~0scintigraphy was perfo~ed on 4 patients suffering from left hamiplegia with positive CT scans more than one month after the onset. Patients were 2 males and 2 females. Their mean age was 72 yearn. Exploration was achieved with a rotRtlng y Camera. Tee 3 studies were carried out over an 8 day period. All 3 tomo~elntigraphies were compared after reo~ientatlon at the same level of slices. Each slice ~as q~ntitatlvely assessed after applying an alienation correction method (CHANG). All the snrokes were clearly delineated With the 3 techniques~ bur ischemic areas w e r e better visualized by a higher contrast with ECD To99m due to ~ better t~ssue to blood activity ratio. Thus ECD Tc99m seems to be a promising agent to assess reversible and irreversible ischemic lesions in the brain.

CLINICAL USE OF Tc-99m }~4PAO FOLLOWING ACIrfE AND NON-ACUTE CEREBRAL TRAUMA. In OUr clinical use of Tc-99m }~iPAO for cerebral perfusion imaging, w~ have studied t ~ groups of patients following cerebral trauma. The acute group were studied within one week of injury and were followed for up to six months. The non-acute group were studied more than one year post injury and many of these were referred to us by the Forensic Psychiatry Service due to aggressive behaviour. All patients had complete clinical ~ r k - u p , CT scan and in some cases MRI scan. The acute traL~nas included gunshot wound and blunt or sharp traL~a with or without skull fracture. All patients showed an equivalent or greater extent and degree of alteration in perfusion than would be expected from CT scanning. ~4PAO also showed abnormalities earlier than CT scans. Patients who showed incomplete short-term resolution of parfusion deficits all suffered past-traumatic headaches. Patients with residual crossed cerebellar diaschisis showed persistent motor deficits. The non-acute patients Were free of motor deficits but exhibited headaches or aggressive behavior. All had unilateral perfusion deficits despite normal or only mildly abnormal CT scans. Aggressive behavior was asscciated with temporal lobe abnormalities.

312 535

536

D.Perani*, V . D i Plato °, C.Messa*, O.Vallar+ S.Cappa+, G.Eottdni+, A,Eerti+, G.Scarlato+ P.Gerundlni*, G.L.Lenzi °, F.Fazio* * Dipartlmento di Scienze e Tecnologi~ Biomedlehe, Istituto S. Raffaele; ° Dipartlmeats dl Neuroscienze, Universit~ di Rome + Ospedale Maggiore Policlinico, Dndverslt~ d Milans, Italy. 99m-Tc ~ - P A O - S P E C T STUDY OF REGIONAL CEREBRA/ PERFUSION IN EARLy A L Z H E I M E R DISEASE. Sixteen out-patients w i t h clinical d%agnosi~ of Alzheimer's disease (AD) in the earl clinical phase and sixteen healthy elderl controls were studied using single photo emission computerized tomography (ERECT) an( Technetium-99m hex~etylprspyleneamlne oximE (99m-Tc HM-FAD) to evaluate regional cerebra: perfusion. Focal brain abnormalities wer( excluded by transmissio~ computed tomograph] (TCT) and/or magnetic resonance (M~). t eortical-eerehellar activity ratio was obtaine( for both patients and controls. Cortical perfusion was significantly reduced in patientsl wlth A~ compared with the sixteen normal elderly subjects as revealed hy analysis of variance (F = 998.51; df = i; p<. 001). Significant differences between regions w e r e also found w i t h i n each group (F = 6.06; df = 3;I p<.O01): the most marked reductions of perfusion w e r e found in the frontal (p<.005) and posterior temporo-parletal (p<.O05) cortlcal regions bilaterally whereas smaller reductions w e r e found in the ironic-parietal (p<.O2) and occipital (p<.05) areas. In addition, relative perfusion indexes were calculated as left to right counts ratios in order to assess perfusion differences between cerebral hemispheres. Asy=F~etrdes of relative perfusion w e r e detected in eight out of sixteen patients. In these patients a correspondence of the cognitive de:delta and the hemispheric side of major perfuslon impairment was sbo~n~. In eoneluslon, the 99mTe N M - P A O SPECT technique provides functional i n f o ~ a t i o n that parallels clinical and psychometric d a t a in patients w i t h early AD.

538

537

R V~/kema. R van den Berg, JAK Blokland, JAJ Camps, SE Papapoulos, OLM Bijvoet, EKI Pauwels. Department of Diagnostic Radiology, division of Nuclea~ Medicine and Clinical Investigation Unit, department of Endocrinology, University Hospital, Leiden, Netherlands. IMPROVED PRECISION IN DUAL PHOTON ABSORPTIOMETRY WITH A RECTANGULAR REGION OF INTEREST. Fur the application of dual photon absorptiometry (DPA) of the spine in follow-up measurements high reproducibility is very important. Especially in osteoporosis, where vertebra] demarcations are often unclear, precision is affected by differences in region of interest (ROD used for calculation of bon~ ni,~t'al coatant (BMC)~ We have investigated the precision and interobserver variability in calculations of BMC (expressed in gilA) in duplicate DPA measurements of 11 healthy subjects using a simple rectangular ROL The rectangular RO1 was determined to contain the projected area of L2 - 1.4 of the fLrstDPA measurement as closely as possible in each individual, while a ROI of the same dimensions was used to calculate BMC oJ the second measurement BMC vaines were also calculamd using the standard software (NOVO version I) and an adapted version of this, allowing the operator to draw an irregular ROI. Precision of the 3 methods, each by 2 operators was compared. Overall precision (duplicate measurements in 11 norrnals) Method STANDARD IRREG. ROI RECT. ROI Observer I 2 1 2 I 2 Precision 2.2% 1.7% 3.0% 2.0% 1.6% 1,6%

M.W, Eustace, P.J. Eli.

I.D. Cullum, R.D, Speller,

INSTITUTE OF NUCLEAR MEDICINE, UNIVERSITY COLLEGE & MIDDLESEX SCHOOL OF MEDICINE, LONDON, D.K. ASSESSMENT OF A NEW DUAL PHOTON BONE DENSITOMETER. A dual photon bone densitometer (scan detectronic BMC lab 23), utilizing a Igadslinium 153 source. Measurements have been made to investigate:1. Short and long term reproducibility of bone mineral content (RMC) measurement on a marble calibration phantom, 2. Short term reproducibility of BMC measurement on ten human volunteers. 3. The effect of variations in:a. The thickness of soft tissue; b. The vertical position of bone; c. The amount of bone fat. 4. The relationship between measured BMC and true bone density. Short term reproducibility was 0.15% (ISD) for the phantom and 1.0% ~o 2.3% for the human volunteers. Long term reproducibility for the marble phantom was 0.49%. Variation in the total depth of soft tissue (water) from 16cm to 30cm produced a decrease in measured BMC of 8.0%. Varying the position of bone in 15cm of soft tissue (water) produced a variation of 11.8% in measured BME.

i

Interobserver variations in the difference between thp 1st and 2nd BMC value, expressed as % of the 1st value, were 1.3% Or the s tandard method, 2.1% for the irregular ROI and 0.3 % Or the rectangular ROI method. ~onclusion: Precision and interobserver variability of umbar DPA measurements are improved if a simple recangle is used for demarcation of the region of interest.

Equivalent results will be presented for a n e w dual energy x-ray system (Hologlc QDE 10g0),

539

540

t

d. Spitz *, H. Becker, *, N. Clemenz *, K. TitLe] **, F. Schauwecker **, H. Weigand *** *Dptm. of Nuclear Medicine, ** C)inic of Accidental Surgery, *** Central X-Ray-Dtpm.

J. Spitz * , N. Clemenz *, N. Lauer *. K. Tittel **, F. Schauwecker **, H. Weigand ***

B.BRUNOT, J.L.DEMANGEAT,

* Dptm. of Nuclear Medicine, ** Clinic of Accidental Surgery, *** Central X-Ray-Dtpm.

Municipal Hospital, D-6200 Wiesbaden, FRG

Municipa] Hospital, D-6200 Wiesbaden, FRG

Nuclear Medicine Department 3HEU Hautepierre, Avenue Molidre $7098 STRASBOURG CEDEX - France

INACTIVITY INDUCED OSTEOPOROSIS AND ITS INFLUENCE ON THE SCINTIGRAPHIC PATTERN OF BONE REMODELLING IN THE FOLLOW-UP CONTROL OF TRAUMATIC BONE LESIONS Introduction : scintigraphic evaluation of benigne b o n e lesions Is gaining growing importance. Especially for the limbs secundary b o n e remodelling processe~ ( l.e. d u e to inactivity) have to be r e g a r d e d . Material and Method : The

122

patients with

a plaster cast of the upper limbs due to a fracture of the distal radius or the us seaphold w e r e investigated b y m e a n s of Tc-99m-HMDP s k e l e t a l scintlgraphy u p to 12 w e e k s a f t e r t h e a c c i d e n t . The bone r e m o d e l l i n N

process was measured by scintimetric evaluation, comparlnE the injured bone to the conira-lateral s i d e . Results : Approximately 4 weeks after the accident w e f o u n d a general intensivation o f t h e b o n e r~modelling within a l l t h e c a r p a l bones. 7 - e

weeks

after

the

trauma this remodelling be-

comes so strong, that often the clrcumscript accumulation within the b o n e lesion can no longer b e distinguished from t h e remodelling due to the Inactivity. Similar results w e r e found within the tarsal bone.s,

After

taking

away the plaster cast and star-

tJng a gymnastic training, the scintigraphy shows a reactive high p e r f u s i o n and accumulation in the involved wrist, mimicking pseudarthrosls or a Morbus S u d e c k for some time.

Conclusion : The correct

I n t e r p r e t a t i o n of t r a u m a t i c b o n e l e s i o n s In l i m b is o n l y possible w i t h t h e knowledge of the secundary remodelling processes d u e to inactivity 0 s t e o p o r o s l s .

SC1NTIMETRIC INVESTIGATIONS Of TRAUMATIC B O N E LESIONS Introduction : As far as now there exist only few systematic investigations of traumatic bone lesions. T h e aim

in

of

bone

this study Is to s h o w the differences remodelling of the spine and carpal

bones after fracture.

Material and Method : i90 patients with traumatic l e s l o n s of the bones or fractures o f the spine. T h e time interval b e t w e e n the trauma and the scan w a s 24 hours up to 12 weeks. All acquired data w e r e stored digitally to c o m p a r e the b o n e lesion semiquantltatively to a r e f e r e n c e area (sclntlmetry). Results : B o n e leslons of the forearm s h o w up within 24 hears ~ f t e r t h e i n j u r y w i t h a n lntermlve accu-

carpal

mulation (mean Q = 2,5), mureaslng to a maximum after 10 days (mean Q = 5,4). Lesions o f t h e spine react slowUer a n d weaker ( m e a n Q = l,g after 24 - 4g hours), reaching a less maximal accumulation after 2 - 3 weeks (mean - l , g ) . So w i t h i n the first days after the the lesion of t h e s p i n e m a y b e missed in t h e b o n e s c a n . Similar results w e r e f o u n d f o r p e l v i s , r i b s a n d d i a v l c u l a w h e r e a s tarsal Q

injury

bones behave like carpal bones. ConclUSion : The scJnttgraphic detection of traumatic induc e d b o n e lesions Is d e p e n d i n g o n t h e t i m e Int e r v u l between t h e t r a u m a a n d t h e s c a n and the l o c a l i z a t i o n o f the lesion. So the Interpretation o f b o n e s c . m ~ h ~ t o t ~ k e r e g a r d to t h e i n d i v i d u a l r e a c ¢ l o n o f the different s k e l e t a l parts of t h e b o d y to a v o i d m i s s - i n t e r p r e t a tion.

A.CONSTANTINESCO

ARTERIAL M E A N BLOOD VELOCITIES IN THE HANDS MEASURED BY ANGIOHCENTIGRAPHY IN REFLEX SYMPATHETIC D I S T H O P H Y (RED). Mean blood velocities in the arterial network of hands were measured during the first phase of a classical three phase bone seintigraphy. A low resolution collimator was used to record band palmer views, after I.V. bolus injection of 99mTe-MDP via a catheter (10[~q/kg), sixty l-set, 128xlE8 pixsl frames were acquired. The dynamic series was filtered over time and space prior a fdrst order derivative filtering is made in order to determine the arrival time histograms in selected regions of interest. Three regions of 5 pixels height i were ehoosen : ths wrist, the palmar vessel arches and the digital pulps. Two mean velocities, proximal Vp and distal Vd, were measured in each expressed in c m / s , = ~ x / At, where A x is hand according to V the calibrated distance between two regions and d t the difference bstween the corresponding arrival tlmes. Until now 105 patients were investigated and data analysis is still in p~ogress. Preliminary results for a group of Sl patients (9 normal, 16 RED and O Hemip~egia) ape the following. In normal hands Vp - 3.3±0.6 and Vd - 5.8±3.6. In E8tien~s with NSD (dvolution lower than 20 wk). Vp = e.~±2.7 (p - 0.02) and ~d = 8.9±5.7 (p = 0.I0) for the affected side,, whereas normal values were found foe the healthy side. In patients with Hemiplegia Vp = 3.1±l.g (N.S.I and Vd = g,ez4.g (N.S.) in the affected limb ; in the healthy hand Vp=4.8±4.0 (N.S.) but Vd = 2.3±1.6 cms -I (p = O.05). Such quantitative results are important for understanding circulation phenomena and pathophysiolcgic prosssses in NED.

313 541

542

F.D.Maul.

A.H. El~azzar, A.A. Malki, A. Sahweil, H.M. Abdel-Dayem, S.A. Razzak, H. Kubasic. S. Jahan. A . M ~ o u d , M. E1-Sayed, E. Higazi.

Divisions of General Nuclear Medicine and Dermatology I

Dept. of Nucl. Med. & Surgery, Fac. of Medicine & KCCC and Ai-Razi Hospital, MPH, Kuwait,

G,N~r, O . B i t t n e r , U . N i e s e , l. Brandhorst, S . S o l l b m r g

O.w.@~ethm-Onivareigy

Frankfurt,

FRG ROLE OF THALLIUM~201 IN DIAGNOSIS OF SOLITARY SONE LESIONS(SBL) .

CLINICAL ACCEPTANCE OF BONE SCINTIGRAPEY: ANALYBIS OF 301 CONSECUTIVE CASES There arm few publloations dealing w i t h the acceptance and response of c l i n i - I clone monmarninE nuclear me@imal re- I ports o n bone scln~itraphy, Nuclear medloina reports and .final clinical, outcome of 301 consecutive bone ecintiSrJphlas (B$) were anulyeed with ghej lalm to investigate relevance and c l i n g - I cal acceptance of BS. 8 c e n t i g r a m s ware 1 ~arriad out 2-4 hours after i n J a c t l o n I of 550 ~'~q T o - 9 8 m - H M D P . Ag l.ast aI ventral whble body ~nd regional spine! scans were done. ~n 2 6 , 9 g parfuslon and hloodpool wmmm studied additionally as a 3-phase-scint~raphy. 7~.0~ of %he patients were inves%iEated for a m a l e s man% or suspicious malignant disease. 48,1~ w~re females, 66,0~ o~ all pa%imnts were between 31 and 60 years old. In 5 3 , 0 ~ B S was done before X-ray, CT, or hle%oloET. In [email protected]~ the f i n a l dlalnosis or indication of final diagnosis was emta~lished hy Be, Diagnosis of BS was confir~md in 5 9 . I ~ a n d p a m t l a l l y c o n f i r m e d in 11,0~. In cases of a clinical and radiological mls~atch BS was 'ignored in the f i n a l c l i n i c a l report. In c o n c l u s i o n ~ S is w e l l accepted as a zelevang c l i n i c a l t o o l at % h e b e g l n n i n g of the clinical dia~noetic procedure mainly

~o

Imsse~

for confirmation Of diagnosis.

mllnlcal

gag ~ gulc~

indication

the

but

final

544

545

De H a r o , J ; L o p e z L a c o m b a , D ; T a b u e n c a , M J ; Cabrera,R;Chamorro,JL;Lanchas,I;Ortiz Berrocal,J.

Clinica

Puerta

in m a l i g n a n t

The p u r p o s e of t h i s s t u d y w a s to m a k e a c o m p a r i s o n of b o n e (BS) a n d b o n e m a r r o w (BMS) s c i n t i g r a p h y in p a t i e n t s w i t h systemic malignancies. 31 p a t s w i t h ~ y s t e m i e m a l i g n a n c i e s ( p l a s mocitoma~non-Hodgkin linfoma~Hodgkin Disense) w e r e s t u d i e d . B M S w e r e p e r f o r m e d 30 m i n u t e s a f t e r I.V. a d m i n i s t r a t i o n of 3 7 0 - 7 4 0 M B q of 9 9 m T c N a n o c o l l o i d . The s c a n s w e r e e v a l u a t e d a c c o r d i n g to:a) P r e s e n c e / a b s e n c e of c o l d l e s i o n s and b) M a r r o w e x t e n s i o n . B S w e r e p e r f o r m e d t w o h o u r s a f t e r IV. i~ j e c t i o n of 740 M B q of 9 9 m T c - D P D . B o n e M a r r o w b i o p s y w a s u s e d as ~ e f e r e n c e Results: B.M.Biopsy B o n e M a r r o w So. B o n e So. c o l d les. M.Expansion

(-)

14 p.

17 p.

P, Bourgeois, C. Gassavelis, M. Malarme, W, Feremans and J. Fr~hling. CHJ Bracops, 79 rue Dr. Huet, 1070 Brussels, Belgium.

de H i e r r o , M a d r i d . S p a i n

Bone marrow scintigraphy systemic diseases.

(+)

Determining the etiology of SBL in patients with extraosseous malignancy may be difficult and needs biopsy before instituting or changing trea~ent. The aim of this prospecbive study is to evaluate TI-201 in differentiates benign from malignant SBL. Twenty eight patients(9 with extrasseous malignancy) with SBL on bone scans were studied. Each was I.V injected with 2 mCi of TI-201. - Dynanic and static images were acquired using a g~mma camera interfaced to a computer. The uptake ratio of the lesion (L) to the adjacent or contralateral normal bone (BKG) was m ~ s u r e d in all cases and correlated with biopsy (21 cases) or definite elinico-radlographic evidence (7 oases). Lesions in 8 cases proved to be malignant (3 primary and 5 metastatic), 7 showed intense TI uptake visually and a L/BKG ratio ranging from 3 to 7,2. The Bbh case (Hedgkin's Disease) showed moderate uptake visually with L/BKG ratio of 2.3 and was examined following completion of cheno therapy. Twenty cases had flnal diagnosis of benign lesions (il osteumyelitis, 2 T.B. 2 benign bone tumors, 2 tra~a, 3 bone cyst). Only l case of T.B. shewed significant TI uptake with a L/KeG ratio of 2.35. The other 19 ca~es showed minimal to absent uptake at the site of the SBL, L/KBG ratio ranged from 0.8 to 1 .B. We conclude that T1-201 is a useful non invasive procedure to differentiate benign from malignant SBL.

(+)

12p.

(+) 4 p.

(+)

(-)

2p.

(-)lOp.

(-) 6p.

Bp.

(+) 2p. ( - ) 15p.

(+) 2p. (-)lSp.

(+) 5p. (-)12p.

Conclusions:l)The BEg identifies a high p e r c e n t of s y s t e m i c m a l i g n a n c i e s c a s e s w i t h bone m a r r o w i n f i l t r a t i o n and is u s e f u l fo~ t h e d e t e c t i o n of l o c a l b o n e ma--rrow destruction~2)The p a t t e r n of b o n e m a r r o w e x p a n s i o n w a s f o u n d to be an ins e n s i t i v e m a ~ k e r for t h e p ~ e s e n c e of m a r r o w i n v o l v e m e n t and 3 ) T h e BS d o e s n o t detect lymphomatous bone marrow involvement

BONE MARROWSCINTIGRAPHY (BMSc) IN CANCEROUS DISEASES. BMsc obtained in case of cancerous diseases (breast : 101; digestive t r a c t : 43; Lung : 4B; prostatic : 45) at the same time as l i v e r spect i n v e s t i g a t i o n and using the same product have been reviewed and classified as - , + (abnormal bone marrow extent) or ++ (cold defect), They lhave been compared to conventional bone s c i n t i gram (CBSc) results (said - , ? : i f not pathognemanic for metastasis , or + i f c l e a r l y metastat i c ) and to fellow-up data of the patients, Liver CBSc? CBSc+ BMSc+ BMSc++ mete Breast n=IOl 31% 21% 36 % 34 % 12 % Prost n= 45 13 % 49 % 5 % 6g % TD n= 43 9 % 14 % 27 % 28 % 30 % Lung n= 45 22 % B % 20 % 16 % 11% Only 4 BMSc were falsely classified as -. Bone Marrow defects are observed before or without corresponding CBSc abnormalities. Patients with abnormal BMScextension (BMSc +) seem te have a worse prognosis tha~ patients with BMSc -. Under treatment, responses of BMSc and CBSc may be different. I t is concluded that BMSc performed at the same time as l i v e r spect investigation and using the same product represent a rational adjunct to cancerous diseases management.

543 A. Ahmed, R. Glynne-dones,

P.J. Ell

Institute of Nuclear Medicine and Meyerstetn Institute of Radiotherapy, University College and Middlesex School of Medicine, London, UK. BONE METASTASES IN CARCINOMA OF THE BREAST - A LONG TERM RETROSPECTIVE STUDY Bone scans from 387 women (age range 24-85 years) with histologically proven primary carcinoma of the breast were retrospectively analysed to assess outceme and prognosis. The patients were referred through a radiotherapy unit over a period of lU years (Jan. 1978 - Dec. 1987). Patients were followed up to date or until death with a mean follow up Lime e£ 41 months (range 3 - 121 months). They were classified in clinical stages (UICC criteria) at the time of first presentation. Patients in stage IV were excluded due to advanced disease. An initial hone scan was always carried out in the immediate postoperative period (within 6 weeks), 132 patients had follow up bone scans according to their clinical status, mainly due to bony pain. 23 patients had positive initial bone scan, Repeat bone scans in 45 of the 132 patients who had follow up studies became positive. The following table shows th~ results of the initial bone scans and clinical staging:

Initial scan +re Initial scan -re

Clinical stage I II III 2 8 13 78 216 70

Total 23 364

The mortality rata in the 23 patients who presented with a +re initial bone scan was 52%. The mortality rate was higher for patients in stage eli (69%) than for the ones in stage I and el together (40%). Only 27% of patients with -re initial bone scan died. 37 of the 45 patients with +re follow up scan died (mortality rate = B2%), against 17 with -re follow up scan (mortality rate : 20%). In conclusion, a +re bone scan seems to be a good indicator of the prognostic outcome of patients with carcinoma of the breast.

546 I.Szilv~si, M . S z e ~ d r g i + , G.Papp, L . J ~ ~o~k~uTT~-].Borsay , K . K g l I 6 + 3rd M e d i c a l C l i n i c and O r t h o p a e d i c Surgery, SerTnelwels M e d i c a l U n i v e r s i t y B u d a p e s t , H-q121 E g t v g s 12, HUNGARY CLINICAL VALUE OF BONE MARROW SCINTIGRAPHY IN ORTHOPAEDY O i a g n o s i s of o r t h o p a e d i c d i s e a s e s is sometimes e q u i v o c a l a f t e r c l i n i c a l eval u a t i o n , X - r a y and h i s t o l o g i c a l examinations (differentiation between E w i n g ' s sarcom and o s t e o m y e l i t i s ; l o o s e n i n g and i n f l a m m a t i o n in p a t i e n t s a f t e r a r t h r o q l a s t y , a c c u r a t e s i z i n g of m e d u l l a r y involvement etc.). In a t o t a l of 2&q p a t i e n t s w i t h v a r i o u s o r t h o p a e d i c d i s o r d e r s (128 w i t h suspected p r i m a r y bone t u m o u r s , 26 a f t e r arthroplasty, 24 w i t h c h r o n i c osteomyelitls, 63 o t h e r s ) bone s c T n t i g r a p h y (BS) bone marrow s c i n i i g r a p h y (BMS) w i t h Tc- g g m - n a n o c o l i o i d , X - r a y and h i s t o l o g i ¢ (122 p t s ) e x a m i n a t i o n s were p e r f o r m e d . BMS p r o v e d to be u s e f u l i n d i f f e r e n t i a t i n g between o s i e e m y e l i t i s and m a l i g nant bone tumours ( e s p e c i a l l y E w i n g ' s sarcom and m a l i g n a n t lymphom of the extremities), evaluating medullary e x t e n s i o n of bone m a l i g n a n c i e s and detecting medullary (skipping) metastasis. No f a l s e p o s i t i v e BMS was found i n p a t i e n t s w i t h d e g e n e r a t i v e changes. Loosenimg and i n f l e r r r n a t i o n can be d i f f e rentiated in p a t i e n t s a f t e r a r t h r o p l a s t y [n c o n c l u s i o n : BMS is a c l i n i c a l l y u s e f u l method in s e l e c t e d o r t h o p a e d i c p a t i e n t s w i t h e q u i v o c a l r a d i o l o g i c and histologic findings.

314 547

548

L.Faggioli, L.Catozzi, G.Giovannini, M.Giganti, D.Pelizzola, A.Piffanelli.

Istituto di Radiologia dell'Universit~ di Ferrara.

ASSESSMENTOF A RADIOLIGANDBINDING ASSAY FOR EGF RECEPTORMEASUREMENT. One of the major advances in breast canceF managment has been the use of hormone receptor characterization (ER,PgR). There is s t i l l a need for a more detailed biochemical study of individual breast tumors to face challenge imposed by the biological heterogeneity of the disease, f t has been focused the interest on the Epidermal Growth Factor (EGF) Receptor whose level in breast cancer biopsies might be considered ss a new predictive test. The present work was undertaken to provide a rapid and reproducible method foF EGPR assay, by means of radlollgand binding assay. By performing repeated experiments on a bulk quantity of placenta membranes, we have optimized the main parameters oF the method assaying l i t s accuracy as follows: 1)adequate cell membrane preparation, 21optimal incubation time: r2 h at 26°C, g)bindlng competition curve: optimal concentration of unlabeled ligand ~O0 nM, 4 ) t i t r a t i o n curve of 1251-EGF binding saturation between 0.8 and 1 nM, 5)Scatehard analysis: Kd 5 nM, 6)"precision p r o f i l e " : RV< B% in the range 8-150 fmol/mg of membrane protein. Testing the p r a t i c a b i l i t y of the method 70 breast cancer biopsies were assayed for EGFR. Approximately 40% were EGFR+ (> 5 fmol/mg of membrane protein). The greatest advantage of the protocol is that i t can be applied.to minimal b~opsies assayed concomfttently for estrogen and progesterone receptors.

550

A. Cuartero, ~ .

549 G, moragas, G. Encabo. ~enoll~ a n d 2l monn~,

Nuclea~ medicine S e r v i c e . H o s p i t a l V a i l d'Hebr6n, P. ~ e l l d~Heb~6n.s.n. 0 8 ~ 5 . BARCELONA ( S p a i n ) .

e Inst. of Radiology, Lhiversity of Ferrara - Italy ~* Dept. of Animal Biology and ~ Dept. of Obetetrics and Gynecology, University of Turin Italy

5TITUS DISEASE It~ HAE~ATOLOGICAL MALIGNANI 3]SORD£R5, PRELIMINARY RC50LT5. The ~im of t~e present study was to invest! gat@ if the seric levels of deoxythymldine kl ~ a s e ( s T K ) c o r r e l e t e to the disease status(OS) of patients with haemetologic malignant disoz Sere, A total of 237 Plood samples were colec ted from patients with several haematologic nalignant diseases and aTE was determined usl g a radioenzyme assay(TK-REA.Prollfigen).The atients were classified accordlnD to the D5 complete remission(CR),st~tionaryCS),pertiel remission(PB)and progZsssion(P))and also if they were off all treatment a t least i month (group A)or receiving chemotherapy in the last SOzdpyslgroup B)before sample collection The mean age was 56 y e a r s ( r a n g a : 1 5 - D 5 ) . The data were analysed by the chi-square and Man~ Whitney tests. The median values and ranges of sTK levele(b/L)in each disease status subgroups were:group A ( C R 1 3 . g ( 1 . g ~ l g ) S : 5 . B ( 1 . g 25)PR:7.4(2.3-dli)P:16.1(2.9-1619))~Group B (ER:6.6(3.2-1B.2)St?.B(2.7-54)PRtIi.3(2.6-237 )P:21.3(3,9-2068)).There usre slgnlficent di X ffe~ences between CR-P(pBOU/L:P(ib/Sl)ana-PR(g/65)). ~e conclude that sTK correlates well with the status disease of haematologlc malignant disorders, specially in those having a high r a t e or cell division, end that chemotherapy cause short-ter~ perturbations in sTR ualues

M. Gion, R. Mione, R. Dietadi, A. Leon, G. Bruscagnln. Divisione di Radioterapia e Medicina Nucleate, Fisica Sanitaria, Centro Oncologico. Ospedale Civile, Venezia, italy.

RADIOENZYMATIC DETERMINATION OF CYTOS O L I C T H Y M I D I N E KINASE A C T I V I T Y IN H U M A N B R E A S T CANCER. 'Fn?midine labellingindex as an indicator of cell proliferation is not easily evaluated in clinical rou dne. We have developped a simple radioenzymatique technique for the m~asorement of thymidine kinase (TIC) activity. This enzyme is necessary for thymidine phosphorylation for DNA synthesis. This technique is performed with the TK-REA kit (Sangtec Medical - Sweden) on cytasul prepared for the assay of hormone receptors fflR) ; it can be used with very sinai1 m o u n t s of material. Result can be obtained within 6 h and is expressed as mU/mg proteins. Our study was done on a total of 192 samples from primary breast tumors (128 mastectomy specimens and 64 biopsies. The TIC levels ranged be tween < 5 and 800 mU/mg ptot. With a mean of 92.1 for m~tectomy samples and 119.6 for biopsies (p=NS). These results were compazexl to histologicalexamination ( W H O type and SBR grade) and to HR; a stadsdcal analysis was restricted to invasive duetal carcinomas. No correlation was observed batwecn T K level and FIR level or presence. A significant cormlatinn was observed between T K level and histological grad~ (p = 0.005 for mastectomy specimens, p = 0.03 for biopsies). Among the criteria used for the determinadon of grading, the number of mitoses was the most related to TIC level (p<0.001 for mastectomy specimeas). Radincnzymafic determinadon of TK activity, on the same material as that u filized forHR determination, providerapidly a parameter strongly related tu thymidine labelling index, which is known as an important prognosde factor in breast cancer.

552 ~ G . G { ..... ~n[,C.Bozz~tt~,N.~ Ialdi,A.Ri~eobon~W.Zo~f~R.Ditt%di M.Gion 1-Quereloll,G~Messerl[L.~abozzi,L.Faggio i,D.Pel±zzola,M.Giganti. 'isb.Radiologia l ~ c n

m

~ST0~0~[C 0EIEWR~T1GN00 p21ras E)~a5510N IN M~M MARY CARBINES5 Increasi~ evidence indicates that the product of cellular ras proto-oncogene are involved in the regulation of cell growth in both norml and pa~ologlcal tissue. In breast ~ e r , ras p r o t ~ are not affected by s t ~ r a l altar~iors or mutations but they have ~ reported to be ~mxpr~ in breast ba,*~rsas compared to mrlal tissue. ~ measured the relative levels of the pZ1 r ~ product in a range of h ~ breast ~11e~. iml~ir 0 primary carcino,as, node and cutaneous metastases, benign lesions and nomal tissues, by SOS-page inntnoblotting followed by comF~ter-assisted image analysis of autoradicgraphs, in an attenlotto explain the significance of r ~ overe×pression in breast cancer. We observed that in 5g% of primary carcinomas as well as in all me,ase2ses, p~1 levels were significantly higher than in normal tissue, whereas in fibrocystic disease the overexpression occurred only in 15%= of the cases. Moreover, a correlation b e t ~ p21 levels with both linph node in~Iveme~t and T gra~ f ~ i ~ e relationship beh~en estrogen receptors ~ed expression of ras proto-oncogene ~ s investigated in breast cancer: the predominant class consisted of tumors w~th a high p21 level and positive estrogen receptors; in fibro cystic disease, instead, the prevalent class Was constituted by biogsies Which were negative for both p21 and zstro gen receptors. No statistically significant correlation ~ s found batten estrogen receptor levels and ras protooncogene overexpre~sion, even if the cases were divided ac cording to mnopa~l status. A cooperative action bet~e~ hormones and proto -oncogene rather than a co-regulation, in ~m~ary neopl~ia, may be hypothesized. Our resul~ aug gest that p21ras e~pre~sion identify different tumor popo_ lations in human breast cancer. Follow-up data will define the possible prognostic significance of p~l in huwan cancer.

Fondafion Bergoni~, 180, me de Saint-Gen~s F-33076 Bordeaux.

SERUM THYf'IIDI~E KINASE AS AN INDICATOROf

551

Cat'ozzi L.*, OeBortoli M.~*, Oati C.~*, Sismondi P.~, Faggloli L.*, Giovamini g.*, GigBnti M.*, Piffanelli A.*

J. Wafflart, M. Trojani, R.M. An#beau, F. Bonichon, L de Mascarel, B, Parsi.

RADIOIMMUNODETECTION O F TUMOR MARKERS IN BREAST CANCER TISSUE Since 1982 40S patiants with primary breast :ancet have been evaluated. Concentrations of :areinoembryonic antigen (CEA), ferrkin, tissue ~oly-peptide antigen (TPA) CAiS-] and M C A ~ere determined in the cy~osol from 403 breast :ameer and 97 normal breast tissue samples. rumor markets were measured using immunometric methods whose performance characteristics were lalidated in a cytosol matrix. Relationships with :lin/eal and biochemical parameters. CA15-3 and ~tCA cyznsal levels were higher in smaller tumors and in cases with less tlma 10 positive lymphnodes, respectively. Levels of EEA, TPA and C A l S - 3 were higher in receptor positive caSes. Ferritin showed higher levels in beth larger rumors and in receptor negative cases. Relationships between carcinoma and normal breast tissue. In each patient tumor markers evaluated were significantly higher in the careinoma than in normal breast tissue; however it was impcssible to establish a cue-off level between cancer and normal breast tissue due t o the wide overlapping of iedividual values. Relationships between c ~ o s o l and serum levels. For each tumor marker e y r ~ o l concentrations were many alines higher than in serum. A significant direct correlation was found between serum end c ~ o s u l levels in the case of C E A and ferritin. From these findings we conclude that cytosol levels of tumor markers evaluated (a) s e e m paFzly related to tumor spread and [dlf[erentiation, (b) are expzassed in both [carcirmma and normal breast tissue, and (e) are tnoorlv relayed to serum levels.

Univ. F E B R A ~ A ; O S e r v . O n c o o ol ~g a F O R L I , ; * Me

R A D I O L I G A N D B I N D I N G ASSAY V E R S U S IMMUNOE N Z I M A T I C T E C H N I Q U E FOR S T E R O I D RECEPTOR E T E R M I N A T I O N IN M A M M A R Y CANCER.

I

The most importanrt use for r e c e p t o r analysis in patients with primary and advanced brea st cancer w~s in the selection of patients for endocrine therapy(JAMA, 1985).The irmunoasaay(EBEIA,PR-EIA) produced by Abbott with monoclonal ~ntibody have been compared in this trial with bhe standardized dextran coated charcoal assay (Eur.J.Cancer.Olin.Oncol .,1986) on 211 breast mrcinomaSmeasured in 5 Laboratories over the ~ame period.The statistical analysis of the resuits are summarized as follcw:1)the 2 immunome~ric assay(ER-EIA,PR-EIA) showed a good intrala~ratory precision indexes compared to DCC(Impre ]ision Profile of the 3 methods was carried out) ~)quality assurance evaluation demonstrated good Lntralaboratory precislon(11.8%fbr DCC;12.efor ~A) and acceptable interlaboratory variation ~oefficients(24.~ for DCC; 37.7~ for EIA) 3) a rery high correlation(r=O.87 for ER;r=0.86 for ~R) was demonstrated between both ER and PgR e~ti~ted with EIA and DCC 4)with regard to posi;ivy/negative estimation the concordance rates in the total of the cases was 92% for ER-DCC/ER~IA and 86~ for PgR-DCC/PR-EIA.An Inbra and iht~ aboratory eontrol have been carried out. In oor ~lu~ion, measuring immunoreaetive E R a n d PgR by mmunoenzimatic asSay has certain advantages o'er and above the current DCC method(Jensen et 1,]986), but further correlations are needed or ~linical trial bases.

315

G,Ugolotti ° , D.Franchini°~

P.gonelli°~

V,Delisi + . Medicine PArma. + Se~vizio Maggiore

555

554

553 Nucleate

0spedale

di 0 n e o l o g i a Parma.

Maggiore

0spedele

P R O G N O S T I C V A L U E OF I M M U N O R A D I O M E T R I C A S S A Y OF B R E A S T C A N C E R A S S O C I A T E D ANTIGEN S e r u m l e v e l s o f CA I5-3 a n t i g e n hag b e e n h y p o t h e s i z e d to be s t r i c t l y r e l a t e d to t h e p ~ e s e n e e of b r e a s t t u m o u r s , t h i s r a t i o n a d e led us to s t u d y CA 15-3 l e v e l s in 13q c o n s e c u t i v e p a t i e n t s unde~elng s~e~ b e c a u s e of b r e a s t t u ~ mours, 7q O u t of I3q w e r e f o u n d to h i ve c a n c e r , but h i c h l e v e l s ( > q 0 ~ U / m l ) w e r e o b s e r v e d in a s i n g l e p a t i e n t ~ the~efo#e we b e l i v e t h a t this m a r k e r does not a l l o w to i d e n t i f y e a # l y b r e a s t o a ~

sets. To o b t a i n f u r t h e r i n s i g h t s into its r e a l s i g n i f l e a n c e we e x a m i n e d I07 patients from ~Doh'/npto A u g u s t 1986 who a l r e a d y u n d e r w e n t s u r g i c a l o p e m a finn. A m o n g t h e s e ~ 63 a p p a r e n t l y h a d no b o n y or p a r e n o h i m a l m e t a s t a s e s ~ b u t six p a t i e n t s a l m e a d y h a d h i g h CA I5-3 levels, Of t h e s e ~ f i v e h a d r e c u r r e n c e s fin the f o l l o w i n g ~ o n t h s , A s e c o n d g r o u p o f 98 p a t i e n t s w i t h b r e a s t tLLmOU~S w e r e s a m p l e d s e v e r a l t ~ m e s up to S u n s I987~ a m o n g the 50 p a tients without apparent metastases 9 h a d h i g h l e v e l s o f C A I5-3. E i g h t of these nine patients developed reeur~en ces in t h e n e x t f e w m o n t h s , ~herefoPe-t h e CA [5-3 l e v e l s e e m to be a g o o d p~e d i e t e r of # e c u r r e n e e s o f t h e d i s e a s e t h u s a l l o w i n g a b e t t e r u n d e r s t a n d i n g in the e v a l u a t i o n of s e i n t i g r a p h i c p a t t e r n s u s p i c i o u s for b o n y m e t a s t a s e s .

556

MI ~ - t i n I, P. Biockx I, D. B e c ~ A. Vrancken l-

2 end

Departments of Nuclear Medicine (1) and

Clinique d'oncologie et

C ~ P ~ d ~ S C ~ OF CA 15.3 ~ BREAST C A B C I N ~ .

~

CA 15,3 is a h t ~ bre~ tq~aor associated antigen, reoognized by two m~oclonal anti[*3die-~: c ~ (115 D 8) ~ s ~ against antigen of htanan milkfet globule n ~ e ~ a r ~ , the ~ (D~ 3) ~ s J ~ a me~srane e r ~ i c / ~ f r e e m e n of a huwan breast carcinama. These monoclanal antibodies were used in a solid phase two site I F ~ te d e t ~ i r ~ the o o n c ~ a t i ( ~ n of the glyooprotein CA 15.3 /n ~ sema of b r e ~ c ~ 9atiez~ts. In a r e ~ L 3 e ~ v e study, we c o r ~ ser~ levels of CA 15.3 a ~ ~ in 80 patients ~ / % ~uis~3ol~ic~Elly p ~ breast c ~ / / ~ . A fi&~st ~ E u p (xx~sistc~ of 65 patients ~ ~ d neve~ h~ tl-eat~ befog: 55 without ~ met~s t ~ e ~ (Me) , iO ~ / n raet~a~te~ (M+). A s e ~ z ~ ~ E u p i ~ l u d ~ 15 i~atients, unto-eared since at leaSt ~ ye~Er and presenting for the first time with met&stsses ( r ~ ~ ) I In ~ Me ~ E u p , i ~ e d values for CA 15.3 (Gn/t off level = 35 U/ml) ~ f ~ in 9% of 3he c ~ , a g ~ 16% for CT~A (cut off l e ~ l = 5 £~/ml ). In c~tras~, the M+ fizz)ups h c ~ 9[~% ~levated CA 15.3 values, aga//ts% c~ly ~ % for ~EA. ~his correlated rather well ~rlth ~ r&ew 4, g~aup, ~fnere CA 15.3 was /r~zreased in 93% of hhe case-s, a g a / ~ t 7 ~ for CFA. BEe~se re~l~;s suggest CA 15.3 %o be more ~e/~s±ti~a~ ~ mor~ specific for [ ~ e ~ a t ~ c 3feast c ~ , then is C~A. I ~ , ~ overall ~ e ~ i t i ~ t y for metastatic disease observed in this st~d~ was 92% for CA 15.3, agsinst o~ly 59% for C~A, while t/he specificity a ~ t e d ~3 _~-~-#cively 91% (CA 15.3) an~ 84% ((~A). It sbo~id he r~ted that of the 5 Mo patients eith i ~ c r e a s ~ CA 15.3 value-s, S had a v e ~ Large ~ (T4) end could in fact t ~ e b~d m/hcl//lical metastases at %he tJ/ne of d i a g ~ i s

557 Department of Gynaecology and Obstetrics* and Department of Urology**, St,-Josefs-Hospital Uerdingen, Krefeld; Institute of Nuclear Medicine, FU Norddeutschland. Seevetal; Federal RepubUc of Germany

HUMAN EPITheLIAL 0VARIAN CARCINOMAS ; OUR EXPERIENCE 0F MONITORING WITH CA 125, CA 19-9 AND CARCINOEMBRYONIC ANTIGEN.

TUMOUR ASSOCIATED TRYPSIN INHIBITOR ( T A T I ) IN SERUM AS TUMOUR MARKER IN GY NAECOLOOY AND UROLOGY

This present study was undertaken to debermine the Pole of CA 125, CA 19-9 and CEA as tumormarkers in human epithelial ovarian carcinomas. Patients amd methods 294 serum samples were obtained from 21 patient~ before cytoreductive operation and from 33 patients with persistent or recurcent disease. Assays were respectively made with CIS-ELSA 125, CI5-ELSA 19-9 and CEA-ENZELSA kits from 0RIE INDUSTRIE.

Theclinical efficacy of the turnout-associated trypsin inhibitor ( T A T I ) in serum as a turnout marker was investigated in 107 gynaecologic and urologic patients with different types and stages of malignant turnouts. The study comprised 85 patients aged 28 to 97 years with malignant ovarian tumour (18 women), breast cancer (55 women) or uterine carcinoma (12 women) as well as 22 patients aged 19 to 78 years with malignant tumour of the testis {12 men), prostatic cancer (7 men) or renal carcinoma (3 patients). The tumour stages varied and were classified according to the TNM classification. Blood samples were taken before the patients were treated (by surgery, chemotherapy or radiotherapy) and during follow-up. The se rum concentration of T A T I , TPA, CEA, CA 125, CA 15-3 and CA 19-9 was measu?ed by radioimmunoassay using 1-125 labelled antigens or antibodies. In healthy persons the serum level of T A T I ranged between 3,0 and 21,0 Ug/I. Serum T A T I was raised in 9 of 18 women with malignant ovarian tumour, 1B of 55 with breast carcinoma and 4 of 12 with uterine cancer, in 1 patient each among 12 men with malignant testicutar tumour, 7 with prostatic cancer and 3 patients with renal carcinoma. In ~ women solely T A T I in serum detected growth, metastazisation or recurrence of a tumour. T A T I enhanced the sensitivity achieved by the turnout markers used previously. in conclusion, monitoring the serum concentration of T A T I as an additiqnal turnout markerappears to be valuable in patients with malignant ovarian tumour and breast cancer, probably also uterine carcinoma.

Concomitant measurement oF CA 123, CA 19-9, Lnd CEA did not prove to be superior to measurement of CA t2e alone.

CHU

IN i ~ D

CRNTNE GEORGES-FRANCOIS LECLERC Unit@s de Biophysique-M4decine Nucl@aire et d'Immunologie Rue du p#ofesseur Marion 21034 DIJON CEDEX (FRAMCE)

-

Radiotherapie,

TOUR5, FRANCE.

Crass, G.*, W. Wagner** and D. Glaubitt

pre0~tive levels of CA lEE and tumor stage. Serous tumors, and levels of CA 125, CA 19-9 and CEA before surge?y : elevated levels of CA 125, CA 19-9 and CEA were found ~espectively in 93,3 %, 20 % and 0 % of cases. - Cytoreductive surgery and level of CA 125 : on average we Pound a 73 % decrease from the pPetreatment level. - Predictive value of CA 125 antigen levels in second look procedures : She predictive value of a pos£tive CA 125 titer (~35 U/ml) is i00 % and the predictive value of a negative CA 125 .evel is 53 %. Alteration of CA 125, CA 19-9 and CEA serum levels with clinical course ; ser£almeasu~ment of CA 125 levels correlated respectivelE ~ith disease progression and dlsease regression 90,5 % and 1O0 % of cases- CA 1£-9 c o P r a lazed only in 40 % and 50 % and CEA levels in .E,5 % and EO % of caSeS.

B O U G N O U X ~-~ Laboratoire de Medecine Nucl~aire in Vitro,

B-2520 Edegem, Belg&u~n

J.M. RIEDINGER, P.NOIGNOT, F. COLLIN P. FARGEOT, J.L. PELLETIER and M. BONDER

Results - Tumour staces and preoperative tumor-markers levels : a relation was found between median

VALAT*. 0. LE FLOCI-I*~, 6. CALAIS~4., A. REYNAUD-BOUCNOUX~ , J.-C. BESNARD* ~ ,

CLINICAL VALUE OF PLASHA T A - 4 LEVEL IN MONITORIN6 UTERINE CERVIX CARCINOMA. In order t0 assess the clinical value of the new marker TA~4 in cervix carcinoma, samples were obtained for one year from all patients w i t h stage Ib to IVb (FICO) cervix carcinoma undertaking Initial treatment or examined for systematic follow-up. Plasma TA-4 determinations were performed with a radiotmmunoassay k i t (Abbott SCC-RIA); the marker was considered as positive above the threshold of 2 ng/m). The data obtained showed that: 1)- In untreated patients, the frequency of the p o s i t i v i t y of the marker was increased as a function of tumor size Mean levels clearly increased when clinical extension was greater than the stage 2)-During the therapy, there for t w o weeks

lib five weeks of initial radiation was an increase in the T A - 4 level in many patients; thereafter level came back to normal 3)-During the post-therapy follow-up period, evaluation of T A - 4 in relation to relapse was: s e n s i t i v i t y 65 ~ and s p e c i f i c i t y 79 ~ 4)-During the relapse, the T A - 4 mean level was higher when the disease was in progression than when i t was stable or in regression. These data confer to T A - 4 the value of a usefull marker in the initial evaluation of stage lib to IV c o . - i × ccrclno,,-,z, and in the follow-up period.

558 Han R.,

Radovid

N.,

Micid

D.,

Manojlovid

D.,

MJ~id J.V., MButinovid P,S. Institute of Nuclear Medicine, Belgrade, Medical School, Belgrade

University

of

EVAbUATION OF 99mTc-Dll~A RETINOGRAPHY IN NON-INSULIN DEPENDENT DIABETICS WITh INCIPIENT RETINOPATHY The use of radionucllde retinography (R~,) In patients with insulin dependent diabetes meIlitus (]DDf4) and var}ous grades of reLinopathy wa~ previously shown (Freeman et ai.,]984). The alrr

of this study was to evaluate the RR in patients with incipient retinopatby and non - insulir dependent diabetes mellitus (NIDDk4). The study was performed in t0 healthy volunteers and in 40 patients with NIDDM and "background" retinopathy proved by ftuoresoein angiography. Known duration of the disease ranged from 7 to 26 years. Planar scinUgraphy of both orb/tat regions and

cerebral

hemispheres

was

performed

by

gamma camera in A P Waters projection, two hours after intravenous administration of 550 iViBq of 99mTe-DTPA. Regions of interest were placed over each orbit and both hemispheres. Orbital counts were divided by mean cerebral counts on a per plxel basis and eye-to-brain (e/b) ratio was obtained. Mean values (+-SEM) of the e/b ratio in controls and in patients with NIDD~4 were 1.67+-0.23 and 1.92+-0.3, respectively, )he difference between the means was significant (p < 0.0l). Significant positive correlation was found between known duration of the diabetes and the e/b ratio (r=0.6,p < 0.05). No corre]aUon was found between the age of subjects in controJ group and e/b ratio. It could be concluded that RR is relaibte diagnostic parameter in patients

with NIDDM and incipient retinopathy, particularly in those with non-transparent anterior segment of the eye. If vitreous fluorophotometry is not ava-

ilable HI& could act as an acceptable alternative. Ereemen ~4h~ Barnes EW, Eastman G, Evens h, Gergans G. Kelertas A, EmenueIe N, Kaplan E.: Radionuclide Detection of Blood-Retinal Disruption in Diabetes MeHitus Sea Nuc] Med, VoLXIV,No.], 16-20~ (1984, ..

316 561

560

559 A.VerrJllo ,A.de T e r e s a , L .Verrillo, G .~Aar tino, G. di Chiara.

A. Verrillo, A. de T e r e s a, C. Martino, L. V e r ri_l to ,G .di Chiara.

Institute of Internal Medicine,ll School of M e dicine, University of Naples, Italy

Institute of Internal Medicine,ll School of M e dicine ,University of Naples ,Italy.

M. D'BERgOMEZ I, p. FIALDES I, S. COEQUYT I, ~ J . ARNAUD 2 . i. SCMN (Professeur R, VERGNES) 2, Endocrinolosie (Professeur P. FOSBATI)

SERUM BETIC

SOMATOMEDIN - C IN T Y P E I D I A PATIENTS WITHN E P H R O P A T H Y

SUBJECTS LERANCE

WITH

IE4PAIRED

GLUCOSE

TO-

S erum somatomedin-c (Sm-C) was measured from single non-fasting samples in 70 n o r m a l subjects ( m e a n age 35 + IO y e a r s , m e a n + S D ) and 7 ~ type I diabetic {atients ( m e a n a{e 37.6 + 9 years ) with varying degrees of n e p h r o p a {by from incipient t o advanced. S m - C levels w e re similar in normal and diabetic subjects ( i. ~ + 0 . 3 U / m l vs i . $ ~ + 0 . 2 U / m I , N S ).Multiple regression analysis-of data from the normal subjects revealed a significant correlation with age only ( r = -0.61 ,P < 0 . 0 0 2 ). A m o n g s t the diabetic patients ,the correlation with age w a s w e a k e r (r = - 0 . 2 3 , P < 0 . 0 5 ) , b u t w a s stro_n get for severity of nephropathy (r = O. 38 ,P < 0 . 0 0 1 ) and glycemic control m e a s u r e d by gl3 cosylated H b A I (r= ~ 0 . 2 6 ~ P < 0 . O l ) . D e s p t t e s miler age and HbAl,patients with a d v a n c e d ne phropathy (n = 22 ) h a d higher S m - C values than those with ineipient nephropathy (n = 52 ) ( 1 . 9 L + 0 .~ vs 1.07 + 0 , 1 8 U / m l , P < O .002) and also h a d higher levels than the n o r m a l control! ( P < O .005 ).Patients w i t h incipient n e p h r o p a thy h a d S m - C levels similar to those of conItrols.These results suggest that p o o r glyce 'mic control leads to impaired S m - C generatio~ while S m - C levels are high in type I diabetic *atients with clinical nephropathy.

B e c a u s e of con~hcting reports with regard t o plasma levels of total immunoreactive glucagon ( ] R G ) i n subjects with impaired glucose to lerance (IGT), w e investigated ~by gel filtra- " tion,the individual I R G fractions in 30 I G T patients and 32 subjects with n o r m a l glucose tolerance ( 16 of normal body weight and 16 obese ) . M e a n total I R G w a s 1 2 ~ + 12 pg/ml in nono. bese controls, 136 + 13 pS/ml- in obese subjects and 178 + 15 pg/ml in I G T group ( P < 0 . 0 1 ). In n o n o b e s e controls ,the 3500 molecular weight fraction of I R G averaged 2 2 + 2 pg/ml.ln the group of obese subjects, big-plasma glucagon and 9000 m o l . w t . c o m p o n e n t s w e r e slightly higher ,not reaching statistical significance, whj teas the 3500 mol.wt.fraction w a s significantly elevated ( P < 0.005). T h e subjects with I G T exhibited the highest level of the 3500 mol.wt. fraction ( ~ 5 + 5 pg/ml, P < 0 . 0 0 2 vs nonobes e and obese cO-ntrols ).A wide variability of big d a s m a glucagon levels w a s found in all three ~roups , m e a n levels not being significantly diferent.No correlation w a s found comparing go. dy weight and total I R G . O n the other hand,the ~500 mol.wt, component and iota] [ R G correla. ted significantly only in the n o n o h e s e controls (r=O.56,P<0.O2),whereas no such relation~hip w a s found in the obese and I G T subjects. T h e s e data suggest that ~he 3500 mol.wt, c o m ponent of p l a s m a I R G is elevaled in I G T patients a finding that m a y be m a s k e d by m e r e m ~ a s u r e m e n t s of total I R G alone.

562

563

R, Ja,~s, J. Zawa~ki, J. Tretten P. Janu~zewiuz, and A. Jelonek.

II

Hospital - Sassati - I t a l y

Dept~ of Nuclear Medicine, Nephroloffy, and Dialysis and Transplantation, Child Health Cenmr, Warsaw 04-736, Poland. PROCESSING OF Or.--ATRIAL NATRIURETIC PEPTIDE ( c ~ - A N P ) BY THE RAT GASTROINTESTINAL MUCOSA AND OTHER TISSUES. The exact catabolic fate of ~/- -ANP in different mammalian tissues is poorly understood at present In this study we have investigated the ~ - A N P catabolic activity of the rat gastrointestinal mucosal cells, liver, kidney, heart and blood, Preparation of cellular membranes and cytosol were obtained as previously described (Gastroenterology. 92, 1451, 1987). 10 20,ug of protein of each preparation was inoJbated at 37°C with 1~ 15 pg of 1251 .eL-hANP , (Amersham) in lOO,ul of the buffer (Tris-Hepes 25 raM, Ca++, Mg++ 10 raM, BSA 0,1%, pH = 7.4). In the incubation media the inactne~ of 1251 - ~ - hANP was monitored using; 9% TCA preciplfitabgity test, adsorptivlty test with 8% talc, Sephadex G25 column chromatography, and o~ - hANP C=terminal ]mmunoreactivity assay (Amersham). Homogenates, membranes and cytosol of mucosal cells of fundus, antrum, duodenum, small intestine, colon, and liver, kidney, henri and blood cellsall degraded t 251 -~.- hANP with ff~e half.time = 4.5 +~ 1.5 min. X :" SEM. Blood plasma was about 60% as acgve as serum, while urine and peritoneal dlaiysate (human) did not degrade 1251 -~-- hANP even after 3-6 hrs at 37o0. In all cases s~died, eprotinin, PMSF. EDTA, heparin, sodium azide and merthiolate did not inhibit ~ - ANP degradatton.~ but the effective inhibitor was bacitracin, EO50 = O.¢5_+ 0.25%, X +SEM, except of the duodenal mucosal calls where ~t was uneffecRve. Decrease of c¢, -hANP C-terminal immunoreact[vity was paraJell to tbe decrease of 1251 - ,4 . hANP TCA precip~titability or talc adsorpdvity. ~n the elution profile an accumulation of short ¢~- ANP fragments, containing f251-Wrosin, was obserVed. Michaelis constant of the enzyme present in the heart and small intestine was of this same range; Km = 45 .%.15 nM, X ¢ SEM, insulin, ACTH, somatos~atin and gastrin had considerably lower affinity. Since hormones do not react specificaJly with non-target tissues, Jt is po=ible that ~astrointestinal mucosal cells, like as other cells, are involved inthe ~t,-ANPphysiology. Biologica/ activity of =L-ANP is associated with its tyrosin containing C-terminal end, therefore simple methods like TOA and talc tests can be used for tbe control of the stability of labelled ~ - ANP during its interaction with different target tissues.

The insulin like growth factors or somatomedim a r e growth hormone-dependent polypeptides. Righ levels of SMC/IGFI are found in acrome~aly. Durin S recent years radioi~unoassays (RIA) have been developed. This report describes the application to sere of acromeEaly and hypophysectomized patients. Two RIA for SMC were purchased from Nichols Institute Diagnostics (kit i) and from INCl ~ u n o Nuclear Corporation (kit 2). INC assay measured IGFI after separation of SMC from its binding proteins by gel filtration and acid ethanol extraction. Nichols assay use a dilution of unextracted serum. Serum GH were determined in duplicate by specific RIA. 7 patients with acromegaly (3 men, 4 women) were studied during long term SMS-201-995 therapy (one year] The intra assay variability, expressed as the coefficient of variation was 4,68% in kit 1 (37 u/ml), 4,40% in kit 2 (30 u/ml) a~d 4% in GH assay (5 ng/ml). The interassay variability was 5,6g% in kit i, 5=40% in kit 2 and 6.2% in GH assay. The mean plasma IGFI (n = 40) was 2,31 i 1,07 uUl/ml (kit i) ; 3,12 ± 2,02 (kit 2) ; means are not different in kit 1 and kit ( p
564

G.M~eddu ,Fr.Dote,G.B.Cucc~/,A.R.Csm/,G.Sed~i.Fa.lk~r~,A .At_ ru.G.Marr~ ,M.piga,V.Lorig~,A.Stsng~ni.M.longer. De~nts of Nuclear Medicine, Ha6mmtolc~y~ d interr~ni Medicine. Universitiesof ~ i , Cagliari and Milan. Transfusic~ Unite - ~

Measurement of Insulin Like Growth Factor I during therapy of acromegalic patients (SMS 201-995) : Comparaison Radioi~unoassays.

)ARATHYRO/D~ I C N ~ P A T I ~ WIrd HCMOZYGOUS8ETA-THAL~ MAJOR (TM) A~D ~ I A ( T I ) . Pama%~Wro~f~mcticn is still debated in TM and TI. In our ~tudy we m e ~ PTd, os+~2dcin (bone specific GLA pl~orein), cslci%onin (CT) and ferritinby E/A. Ca and Pbyst~n( m~d co]c~imetry, bone mirersd densi~ [B~D; m~/~) by d~a/: photon adscrptiomei~ in distal ~adius ( o s ~ s c a n ~ ) . The ~atients were 85 thmnsfusi(md e ~ t TM (43 M. dl F) di~J~ in 3 ~ s : ~ I for an s~e r ~ e 9 %o 14. ~ II15 to 18, group Ill 19 TO 30 ye=~r.s; i n ~dditicnwe studied 12 never tr-=nfusedTI patients {7 M. 5 F) aged 20 to 42 yrs and sged matched ccn~mols. ~rmee pati~s of gr~u~ III had ] ~ Ca, high P ~nd low PTH levels with clinics] evidenceof bypopaI~%Troidism. In the oi~er ~atientsPTH levels ~ithin the normg/ r~=mge;hoover ~ ~a]ues were s]i~tly higher hh=~nccn~R-olspar,ticuia~lyin ~coup III (20,4 +_ 8.E4 vm 1R.7 _+4.8 pg/m/) and in TI (21 + 8.3 vs 18.04 + 5 p~/m/ : a v ~ siaDificant/ylo~e~ and P higher O~n nor.m~ in all oatients ~nd even in TI if c ~ r e d to group III patients. '~eanCt levels wsre norton/in rollpatients. 0steoc~cin levels in I / ~ d ~ a were lomem than in m~Iz~hedccntro]s; the difference ~ s significant (p
J. ~ N ~gIRI2~F***, L. B U C ~ * * * and J. CCRVTIAIN*.

Dept~ of Internal ~Wi~ne*, Nuclear Medicine** a m Soz~erg***, H~itsl Univ~-sitaire ~ , 4, pl. V ~ Gehudgc~ I020 Brummlles.

PRm~m~--CIVE L~mLI~ZlCN OF A p A ~ I T £ n ~ 9 ADEml~; CC~mARIglV ~ 201 TI-99 TO SCmVPIG~k~TZ A ~ T m 2 ~

30 parathyroid smlntlgrams in o ~ t i ~ patients wig prima~ h ~ ~ ~re a n ~ ~ t i y by two observe. 19 of t h m ~ patters a l ~ bad a catboterism of the th~3i~ ~ with ~ t of ~ (N-teEninal a~ay] . sc~tigra~ was ~ u ~ i ~ in 16 out of 60 ohservaticr~. S~itlvit~ and ~Jecificit9 Of ~in~igra~,calculatsd ~ the basis of aTl observations (120 glands o h ~ r ~ d twi~) ~ 35~ and 86~ repecti~l9 (56~ and 7 ~ for lateralizati~ only). When an ~as visualized by o n e Of the observers (7~), it ~ms ice,trod correctig in 34~ of the c~se2. Both oh~rvers omr~orded to visualize the edewa¢,aat the ~ a plaoe in ll case~ out of 30 (3~), and t h ~ the d ~ ; 1 ~ i c n ~as corc~t in 5 patients (46~). In these case~ w~th u n i w ~ l scan interpretstin~ lateralimt~n was ~ z e m t in i0 out of 14 pati~f~s (71~). ~thetexi~

otwarvatia~

~

and

~u.~ive

in

~itivity

20

out

=m~d . ~ f i c l t ~

of

38

for

locallza~i~ were 26~ and 92~ r ~ - t i v ~ l y (42~ and 76~ for laterali~tinn only). In cases ~ sclntigra~y mas ino~clu~i~ or the inte~retstion discordant =ath~t~ri~ To omrlude, 201 TI-99 To parathNmmid (PT) gland ~nti~y ~it~ ~9~i~ m~ra~d=n ~form~ s~p~ntiallw 9 a ~ a p~ar i n f ~ t i n n om FI ad~w~a lo-~l~;tic~, thou~ it s ~ a t better than t~groid catheter~-~. ~ s c o m ~ m ~ o n is ~ ~ to a t ~

.small

~

of

the

a6enu~as

in

our .patler~ts

(ma~J~n

~_ight:500 roT, mean ~erum i P ~ level: 1112 ; g ~ l (N.320~20) a~d ~ s m ~ m calcium le~l : ~ , 5 mT/dl), it w~s ~ pre~i~dsl~ t~at ~ ~mT~i~ wms h=tter Tor larpa ed~nomas.

317 567

566

565

L.B. Arkles, G.D. G i l l , T. Jones, T.J. Martin, M.A. DeLuise.

W B Tindale, N A T Hamdy, J A Kanis. S. Amico, J,C, Liehn, M.J, Delisle, J.B. Flament, J. Valeyre.

C. gibold,

Institut Jean Godinot and CHR, Reims,

France.

IS PARATHYROID Ti-To SCINTIGBAPHY STILL USEFUL IN THE PRESENCE OF THYROID ABNORMALITIES ? The aim of this study is to assess the value of parathyroid scintigraphy in patients with hyperplasia or adenoma in the presence or in the absence of thyroid abnormalities. Forty-five scans were performed after sequential injection of Tl-g01 and Tc-99m. According to surgery, the prevalence of parathyroid abnormalities was 42/45: 36 adenomas in 35 pts, 16 hyperplastic glands in 7 pts. The prevalence of thyroid ~bnormalities was 17/~5 (38 %). The ~ethod of image subtraction which performs the geometric and gray-level registrations and generates the image of the significant differences. The superiority of this method over visual analysis and over cl~ssieal image subtraction was previously assessed {i). The patients were classified in 4 groups: Bdenomas (l), hyperplasias (II), adenomas and hyperplasias with (III) and without thyroid abnormalities (IV). The results expressed by the Sensibility (Se) and the Specificity (Sp) are as follows: Observer 1 Observer 2 Obse~er g Groups Se Sp Se Sp Se Sp I 76% 92% 76% 87% 87% 82% II 31% 92% 35% 91% 56% 92%

III IV

62% 64%

92% 95%

24% 72%

87% 78% 95% 81%

83% 96%

In conclusion~ the sensitivity and specificity are higher when the hyperplasias are excluded. The specificity is higher when there is no thyroid disease hut the sensitivity remains nearly the same (obs.l and 3), yielding parathyroid scintigraphy useful even with underlying thyroid disease. i) AMice S, LIEHN JC, DELIELE MJ, VALEYRE J: Parathyroid scintigraphy ; does imaBe subtraGtien helm9 J'NIICI. MED.PS 5RP-RR~ (Iq~7]

568

Depts. of Medical Physics and Hu~m~n Metabolism Royal Hallamshire Hospital SHEFFIELD $I0 2JF England PARATHYROID SCANNING IN CHRONIC - AN UNDERVALUED TEST?

RENAL

FAILURE

The use of TI-Tc subtraction scanning for the localisation of hyperplastic glands in the secondary hyperpara£hyroldlsm of chronic renal failure (CRF) is controversial. Whilst doubts have been expressed concerning its value prior co surgical intervention, a hitherto unexplored role of the technique is in the staging and management of patients. In view of the complex biochemical interactions in CRF, the degree of osteitis fibrosa (OF) is accepted as the most reliable indfeator of parathyroid activity. We evaluated the use of Ti-Te scanning as a ~on-invasive indicator of OF grade in 49 patients with renal failure. Each patient also ~ad a bone biopsy and serum calcium and PTE ~eterminations. Scanning was performed using a modified thallium first technique, with least ~quares image sub~raetion. All subtraction images were classified hy a single observer as positive or negative. The scan outcome showed significant correlation wiah 0F grade (p < 0.01), As a predictor of OF, scan positivity has a sensitivity of 82% and a ~pecific~ty of 63%. The presence of •ypercalcaemia was not related to OF grade (p > 0.I). PTE levels above and below a ~tatistically determined threshold of 6000 pmol/l showed a significant correlation with OF ~rade (p <0.025), sensitivity 41%, specificity 91%. Ti-Tc scanning is more sensitive than zonventional biochemical indices for predicting 3F grade in patients with CRF. A negative scan is a reliable indicator of mild OF. A positive ~ean and a FTH value of > 6000 pmol/l is a reliable indicator of severe 0F. The small percentage of pacfents not falling into these categories require further clinical znvestigation,

Departments of Nuclear Medicine, Endocrinology and Surgery, Repatriation General Hospital, Melbourne, Australia. PRE-DPERATIVE PARATHYROIDSCINTIGRAPHY - DOES IT INFLUENCE SURGICAL MANAGEMENT? Parathyroid subtraction scintigrephy (PSS) has been shown to be helpful in the pre-operative I o e a i i s a t i e n of parathyroid adenoma. The impact of these findings on the subsequent surgical approach i s not well documented, General experience indicates that preoperative l o e a l i s a t i o n does not a l t e r the operative procedure in most centres. We therefore reviewed PSS studies performed in our department over the past 4 years (76 ~atients). No patients were excluded from these studies. Our technique was to give 74MBg Tl 201 I.V. and complete the Tl acquisition prior to performing the Tc study. A delay line gamma camera interfaced to a computer system was used. Processing allowed for assessment of movement in the 4 Tl frames as well as the summed TI (800K) and Tc (400K) frames. The subtraction study was performed following normalisation of both right and l e f t lobes. 34 patients (37 studies) had surgical confirmation of parathyroid disease, 5 having had previous thyroid surgery, 2 for secondary ihyperparathyroidism. The r e l i a b i l i t y of PSS in our i n s t i t u t i o n was s e n s i t i v i t y 81.9%, s p e c i f i c i t y 91.6% and accuracy 89.9%, The surgical approach was modified in 12 of the 37 operations (32.4%) as a consequence of the PSS. II patients had lateral or local exploration only of the neck and one sternal s p l i t t i n g . Reoperatlon on the 3 patients with i n i t i a l f u l l neck exploration was more d i f f i c u l t and time consuming than the 2 patients who had limited surgery only in the f i r s t instance. These findings suggest that the surgical approach may be influenced by pre-operative PSS

57O

569

V. Ruflni, L. Troncone, Zarka Zemva,

Djuro Shelb

G.DABASI,

Departments of Nuclear Medicine and Gin. Clinic University Medical Centre Ljubljana INFLUENCE OF STRESS ON PRL AND E ENDORPHIN VALUES AT PATIENTS 1N IVF-ET PROGRAMME The authors wanted to find out the correlation of physical and psychical stress and values of PRL in serum and g endorphin in plasma (by RIA method) at patients in I~ Vitro Fertilization Smbrio transfer programme.They are operated wit] two groups. In the first one (30 women),there we~'e neurotic patients and in the second one (30 women) there were psychical healthy patients. The authors also wanted to find out if the values of ERL and ~ endorphin are elevated in the first group and if these values are in correlation with the unsuccessful pregnancies. The psychotests of neurotical patients indicats the significant greaber rate of unsuccessful pregnancies in the first group of patients.eRL in serum was determinated in 4 stage at ultraso nic ovarium puncture:l -iO m~nutes after intra venous introduction of cantle, ~nd-lo minutes rd after premedication, ~ painful stage - g minutes after ultrasonic punction of the first fold cle, 4th_ d hour after ultrasonic punetion. Afte )remedication the values of PRL in serum are e.evated over the normal range in both groups of latients. The highest values of FRL (ea,B~ug/l) ~n vere observed in the srdstage, and in the/~ stage it was observed the fall of PRL values (S4,8/ug/l).At ET the patients in both groups were mentaly tranquilized withought drugs and PRL values in serum were same in both aroups (20,0 ~ a,R/ug/l).The same correlation was foun out w~th ~ endorphin determination in the grd ~ d a th stage in both groups (11,3 p~ol/1- 3rd ~rqups and 5,3 pmol/i in the ath group),

s t

.

.

Radlological Clinic: Sz~melweis Medical School~ Budapest/Hungary

" F I R E F L Y S I G N " IN A D R E N A L IN P R I M A R Y A L D O S T E R O N I S M

Univ.

SCINTIGRAPHY

54 d e x ~ m e t h a s o n e - s u p p r e s s i o n seintigrap h i e s in P A weme c o m p a r e d w i m h the suPgical results. Three groups were found: : true positive 22 a d e n o m a s , .: f a l s e n e g a t i v e D a d e n o m a s , III.;true negative 26 b i l a t e m a l h y p e m plasias. - In 17 c a s e s of the ~ m o u p I. o n l y a l i t t l e , ~ o u n d ~ h o t s p o t w a s seez on t h e e a r l y s c i n t i g r a ~ m , reflecting tc The e a m l y c h o l e s t e r o l u p t a k e of the adenoma. The surrounding ipsilateral a n d the c o n % T a l a t e r a l ~lands became later visible. We c a l l e d t h i s p h e n o m e n o n " f i r e f l y s i g n " . In a l l of t h e s e patients s u r g e r y and h i s t o l o g y f o u n d T h e a t r o p h y of the i p s i - a n d c o n t P a l a f e r a l g l a n d s . In The o t h e r 5 t r u e p o s i t i v e c a s e s t h e tissue ~ P o u n d i n g the a d e n o m a and the c o n i ~ a l a t e r a l gland w e r e n o r m a l or d i f f u s e h y p e r p l a s t i c . Ir g r o u p IS. a m i c r o - or m a c r o n o d u l a r hyp e r p l a s i a was v e r i f i e d . "Fire~y sign" w a s n o t s e e n in g r o u p II. ar~ III. We measured a significant diffemenee in serum aldosteronej 18-0N-oortleosTe~on l e v e l s and T h e p e r c e n t a l u p t a k e of Scintadren between the firefly group a n d t h e f a l s e n e g a t i v e aden(z:a c a s e s . In t h e f i r e f l y g r o u p a l l p a t i e n t s b e came c~plaintless after su~gemy 5 while p a t i e n t s w i t h f a l s e n e g a t i v e scans, needed even afte~ The mesectlon of adenQma antialdost~mone therapy. 'Fimefly s i g n " s e e m s to h a v e a p r o g n o stic v a l u e in t h e t h e r a p y of a l d o e t e ~ o nomas.

~i

F.M. Danza°, A.L. Va-

T~n~

L.Duffek

Departments of Nuclear Medicine and Radiology ° of the Catholic University of the Sacred Heart, Rome, I t a y ASSESSMENT OF THE ROLES OF MIBG IMAGINGAND CT IN THE LOCATION OF PMEOCHROMOCYTOMAS(PHEOS). The respective diagnostic roles in the detectiol of pheos of MIBG imaging and CT have s t i l l to be defined. In order to contribute f u r t h e r on this matter, records of pts. strongly suspected of bearing pheos and studied with both modalities, were reviewed end the results compared. F o r t y - f i v e pts. were selected, 23 females and 22 males, age range 17-70 years; in 22 the presence Df pheos (3 b i l a t e r a l ) was h i s t o l o g i c a l l y e o n f i r ned. Scintigraphy was performed by I.V. i n j e c - tion of 37 MBq of 1-131-MIBG (120 MBq of 1-123~IBG) a f t e r thyroid blockade with Lugol's solution and imaging carried out over 2-3 days consecutively. CT scans were performed with a IV ~eneration machine. Scintigraphy was c o r r e c t l y negative in 22/23 cases, c o r r e c t l y p o s i t i v e in i i / 1 2 adrenal and 5/5 axtraadrenal phees, and in 4/5 malignant phees (metastases were also i d e n t i f i e d ) . CT was negat i v e in 20/23 oases(a mass other than a pheo was ~etected in 3 p t s . ) ; i t c o r r e c t l y i d e n t i f i e d 12/ 12 adrenal and 5/5 extraadrenel pheos and 5/5 ma lignant phees (only principal lesions were i n v ~ tigated). S e n s i t i v i t y , s p e c i f i c i t y and accuracyDf scintigraphy and CT were respectively 90.5% and I00%, g5.6% and 87%, 93.2 % and 93.2%, The overall data indicate the complementary role ~f MIBG imaging and CT. A flow-chart is proposed in which scintigraphy is a f i r s t choice method, ST is reccomended f o r surgical p]anning in MIBG oosftive cases and in those with negative or equivocal outcomes but with a biochemical eviden:e of pheo.

318 i71

573

;72

d,Bomanji, A.d,Sinclair, G.M.Sesser, K.E,Britton.

P.Harris, G.Ross, O.

57

CaSe!lore,

J.

E;~ue=~;? V.

Hospital

La re.

Petrie,

A.

VerdeEuer,

caste~.

Valencia.

1-123 meta-lodobenzylguanidlne (MIBG) localizes in adrenergic neurones. A comparison of the clearance rates lexpressed as percentage decrease per hour) from various organs was carried out in seven normal volunteers (NV) and fourteen patients (PAl with phaeochromoeytoma and/or paragangliema pPe- and post-treatment usinE I-i23 MIBG. Clearance rates oT 1-125 MIBG during the time intervals of 50 man to ~ h were as follows: heart~ NV, 7.~6±I.E9 vs PA~ 15.1O±2.EI (p<0,O01), lungs, NE, ~3±1.52 vs PA, 13.89±1.52~ (p~o,05), liver~ NV, 7.56±1.65 vs PA, ~5.55±5.55 (p<0,Ol). There was no slgnificant correlation of plasma catecholamines (PCA) levels, and 1-125 NIBG clearance rates. Pollowing treatment the clearance rates oF 1-125 MEBG from these tissues between 30 man to h were similar in both groups of subjects. This observation coincided with the normalisation of PCA levels in most of the treatment group. Tn conclusion there were significant differences from normal in clearance of 1-125 MIBG in patients, but no direct correlation with high PCA, suggesting that this is not purely due to competition oF PCA for the tramspert pump, but other mechanisms such as passive diffusion and secondary haemodynamic effects of circulating PCA are also contributing factors.

L. Vannucchi, A.M. Vannucchi, A. Grossi, D. Nafanelli,P. Rossi Ferrini DopE.

A

DOT

Ospedale !!C.S,S." IS THE UPTAKE NEUROBLASTONA MALIGNANCY?

OF NIBG ALWAYS

(131-I,123-I) INDICATION

IN OF

The u p t a k e of E I B G in n e u r o b ] a s t o m a is 0ormally l i n k e d to the d e g r e e of mall E0ancy a n d to t h e s e c r e t o r y c a p a c i t y of these tumours. Tbe histopathologic ~ i a g n o s i s of ~ o pagben~s in o u r s e r i e s , ' ~ith a p o s i ± i v e u p ± a l e of NIBG, shows the affinity of ±he radionuclide tO •d r e n e r e i c l e s i o n s , b u t not n e c e s a r i l y a tumouTal malignancy. ~ase I: 3 year old boy with abdominal ~ass and i n c r e a s e of homovanilic and ~anilmandeldc acid excretion. MIBG scintigraphy: g r e a t a r e a of h y p e r u p t a k e in the t O m B O y , with m a x i m u m intensiYy ~fter 24 h o u r s . S u r g i c a l t r e a t m e n t . Hishology: E a n B l i o n e ~ r o m a . ~ase 2: Boy with medias±anal leuro~]astoma, 2 0 ~ e x @ r e s i s of t u m e u r a l nasa ag 13 m o n t h s . R a d i o a n d c h e m o t h e r a py. ~ a v o u r a b t e evolution during S years: ~o s y m p ± o m s , n o r m a l r e p e a t e d c o n g r o l s o~ :atecholamines. MIBG: f i r s t s t u d y a f t e r ~urgical e x e r e s i s : h y p e r u p t a k e of t u m o u :al mass, persistin~ in all la±er :ontrol e x p l o r a t i o n s . Pine-needle aspiration b i o p s y : ganglioneuroma, gt is a :ase of neurohlas±oma ui±h evolution ;owards ganglione~roma, lost in the secretory capaci±y and a positive upgake )f EIBG. T h e s e t w o c l i n i c a l o b s e r v a t i o n s ;uggest t h a t the u p t a k e of H I B G in neu:oblastoma is n o t a l w a y s i n d i e s ± i r e of ~alignancy, so ghe evaluation of that Lptake m u s t be m a d e b e a r i n g in m i n d the ;finical aspec± a~d evolution of the )arlenE.

575

574

of

Hematology, University and USL IO/D, 5013& Florence, Italy

ASSAY

FOR E B Y ~ O P O I E T I N WITH I-rEp

RECEPTOR(S)

The recent cloning of the human Erythropoietir (Ep) gone and the expression of the cDNA ham made available a recombinantla~ure prepare±icy ~hieh has been labeled with I with recover 3 of the biological activity and which has beer used to study the binding to membrane receptors. In order to 'study the expression of the E; receptor and for the purification, a sensitiv~ and specific assay is required. We hav~ developed a dot assay to this purpose, which ie based on the protein bindir~ principle od nitrocellulose. Membrane extraxts obtained from the spleen of phenylhydrazine-induced anemic mice (which is a good source of cells bearin receptor(s) for Ep) were applied to microdishe (0.5 cm diameter) of i~tr°cellul°se'=u an( incubated overnight with I-rEp in the well~ of a microtiber tray, A si~ificant correlatlor between bound radioactivity and the amount oI membrane prot@ins applied to the nitrocellulose dishes was found (r=0.99), with s variatior coefficient 6~. gmon E a panel of hemopoieti( growth factors, either recombinant or in crud~ conditioned media, only unlabeled rEp was abl~ to compete with the iodinated tracer in th~ bindin~ to nitrocellulose dishes, The procedure, althouEh developed primarlly foi the assay of Ep receptor(s), is potentiall 3 applicable to the quantitation of any recepto~ in comple~2~embrane preparations, given that th~ specific I-labeled ligand is available,

~.Petracca Ciavarella, AmBonazze, M.Greco, VmFrusciante, F,Dicembrino, F.Barbano.

Spain.

St Bartholomew's Hospital, West Smithfield London, ECI UK. PRE- AND POST-TREATMENT CLEARANCE RATE OF 1-123 MIBG IN PATIENTS WITH PHAEOCHROMOCYTOMAS AND PARAGANGLIOMAS.

[

Re±cede (ITALY)

Y%Tc-HANDCOLLAND HIIH-CI DONEHARAOUSCIN~t6RAPHYIN EARLYgTAh[ aYELOFIDR~IS AN~ ~aNEI~gROg ~CAOSlh.

T~ radiopharm~ceutJca}slRP) are currently available in bane marre~ ~vatuatipn:ggmTc ~anpco]toidl~),~hich portraits the reticu]oendotheliat component,and llltn-Cl ~hich J| cmnsidered to repreant~at Least in Smilecases,the hmtopoietJc component though ~ot as ~ l ] as iron,There are remarkable differences between the ~ in terms of :ost,nvaJ]abilily~eaaminatJnn ties,radial/De hazard.]t is useful to NIDU if ~'~iTC can replace Illtn in clJaJcal app]lcaltons. EJeven lalie~ts ~ith not advanced myetofibromis and 3 ilith abuts bone |arrmw ne~rosis due to an occult cancer have been studied by both tF.555 I~q of ~mTc-NC were inje(tnd, starting ezaminakien 90'inter, ~si"~ a total body vie~ ~Jth e ~end ~f S ca/sin, Ill-in-tilTh I@q) ins injected at the end of the Lest z ~ visualization obtained 46hr. labor,by the same technique.]n patients ruth bone uarrem rmcresis ;tandard bone scan I~lS performed I ~k,after indium ezaminztion. The distribution pattern Of hone marrnm~as altered in at] iyelmfibr(~sis salients with moderate reduction of activity in the central iarrDw and a variable grade uf peripheral expansion,ranging from moderate ~o advanced,even in catcar~al bnnes. Splenoeega]y mas present Jn ~ariable extent and soeetimes hepatoee-ga]y was also fnund.A]though superior Tc physical characteristics yielded better images,both ~howed the san howe marrow patternsu with liver and ~]een m]mays zero evident on Tc eaaminations.Dn In scans spleen had a large variability of appearance, sometiees being only faintly visibtelin spite ef the nerila] 1c pattern. Me den'l knem if this findin~ is related to possible entramedutlery hemato-poiesis. ]n bone marrow lecrnsis the dialributimn pattern varied from an a l l o t complete absence of marrom representation (1 case of generalized necrosis]to I patchy aspect in facet necrosls.Bone scintigrmphy shamed multiple syperaclivity spots in 2 cases and ~as completely normal in one Focal case. Re~artabte differences bet~en the t,o ~ mere present in I case of focal involveeent (hone scan negative) ~ith a partial :oabIementarity pattern of cold Tc Lesions #are on Indium scan and iceversa.]n sum, we think that i f lllIn-CI scintigraphy can't be performed aton~ ~itb a ferrokinetk study there is no real advantag in using tflJ| RF instead of 99mk-NC in ilyeIofibrosls.Ho~everdn bone marrom necrosis 99mYc"HCand Ill[n-C] ~ay provide substantial] ifferent inforiatiens about marrom distribution.

Id i76

A. Sagripanti, M. Ferdeghini~ F. Papineschi, M, Petrini, E. Pinori~ S. Grassi Servizio di Ematologia e Servizio di Medicina Nucleare~ Universit~ degli Studi di Plea, Spedali S.Chiara, Piss, Italy.

~ O L E C U I , A R M ~ E R S OF HEMOSTASIS ACTIVATION IN ~YELOPROLIFEPaATIVE DISORDERS (MPD) ~o investigate hemostasis activation in chronic MPD, we measured in platelet-free plasma by radio immunoassays fibrinopeptide A(FPA), 8 throu~oogl~ bulin(~TG) and platelet factor 4 (PF4) in 54 adult patients (26 n~ales and 2B femalesh 15 had chronic myelogenous leukemia in phronie phase(CML), 8 were in blastic phase(Be), 13 had agnogenic myeloid m~ taplasia(~[F), 18 had essential thrcmbocytemia(ET). No subject studied had clinical evidence of throm boe~olism. FPA,eTGandPF4 were expressed in ng/ /ml; 8TG was corrected for platelet count(ratio). ResuItSc~±SDI:

S. Giovanni

BP

ET

MP

No~L~

FPA 1.6±0.6 6.2±5,8 1.3±0.4 2,4±I,5 l.l±O.E 3TG 80±63 I13t76 100±64 132±85 25±7 Ratio 22e11 67±58 12±7 83±68 16±6 ~F4 12~6 I0~6 10±6 11±9 5±2 FPA was normal in ET, elevated in CML (T-test p< <0.Of vs normals) and in M~ (p<0,001 vs nor~als), very high in BP (p<0.0l vs CML); procoagulants from blast cells may accountforFPA increase in BP patients. The elevated 8TG levels we found ir HI1 the MPD (p
P.Kostamis, N.Vassilopoulos, G.Theodorakis, S.Gerali, D.Tsigourakos, D.Tsinikas, C.Constantinides and D,Kremastinos. Department oF Nuclear Medicine, Alexandra University Hospital. Department oF Cardiology, General Hospital of Athens, Athens-Greece. IRON OVERLOAD AND LEFT V£NTHICULAR DYSFUNCTION I N B[TA TNALASSEHIA STUDIED BY RADIONUCLIDE V£NTRICULBGRAPHY Gated Radionuclide Ventriculography (GRV) is an atraumatlc and highly sensitive method for the early detection of preclinical myocardial dysfunction. Sixty two (62) patients with tramsfusion depended beta thalassemia aged 6-55 years (mean±s.d., 19.7±6.5) were sLudied aL rust ~nd during exercise by GRV in order to assess the role or Iron Overload (IO) and Serum Ferritin (SF) in the development oF Heart Failure (HF). Patients had received 23-985 blood units (413±198) end their 5F was 300-8800 ~g/1 (3740 ±2235) to examination time. Changes in Ejection Fraction (CEF) and Systolic Time (CST) from rest to peak exercise were measured as heart dysfunction ±ndices. Rest EF was 42-83~ (63±8). Exercise EF was 48-B4~ (68±9). CEF varied between -54~ and 53~ (8.7+11.7%). Rest ST was 284.6-415.5 (363.5± 27.2) ms. Exercise ST was 295.8-412.4 (553.2± 27.4) ms. CST varied between -20.3~ and 25.6% (2.5±9.7). There Was no statistically significant correlation between IO and CEF (r=0.068, p=NS) and CST (r=0.041, p=NS) indices. Similarly between 5E and CEF (r=0.112, p=NS) and CST (r=0.194, p=NS). Conclusion: Our results suggest that although IO and SF are predisposing factors, they are not critical in the development of HF in patients with Beta Thalassemia.

319 577

578

J. A. Cardarelll, D. W, Slingerland, A. Miller, B. A. Burrows

579

FXBRINOPEPTID-A P~DX0~[0NO ASSAY ~ Z A T I O N IN ~H~ C~INIOAL PP~CTI~ AND P~SEARC~

A. Sagripan±i, A. Carpi;E. Pinori~M. Ferdeghini

M.Horv~th,~.Pszota,Zs.Kugler,G~,Szlgeti Nuclear Medicine Service, Boston, Massachusetts

V.A. Medical Center,

Hun@~.~2

W.AI~oht Mallinok~odt-Dia@nostie~, SPECIALLY SHIELDED GAMMA C A M R R A F O R MEASUREMRNT OF Bl2 ABSORgTION We have reported the advantages of body coun~ ing in an iron room for the direct measurement of the absorption of 57Co-labelled vitamin Bl2, Similar results have been obtained without an iron room with a gamma emnera shielded with a inch thick lead cone with a small-end diameter equal to that of the crystal (10 inches), a distal end diameter of 16 inches, and a height of 6 inches. A flat field analysis with an extended source (liver phantom) with or without the cone showed no difference. The cone, in zonjunction with an underlying lead shield, reduced background 4 folg. The spectrm~ of the ~ackground was flat with no significant peaks ~nd is presumably largely Compton in origin. ]omparative backgrounds in other intra-hospltal locales are virtually identical. The use of thE :one permitted a statistical error of only 9% [or gl2 absorption measurements as low as 3% ~ith a 10 minute counting time. Without the con ~0 minutes was required to get similar accuracy. This simple body eo~mting technique has ~llowed us to I) discriminate the normal from the i~trinsic f actor deficient patient, and 2) ~elineate a dichotomy between food and crystalLine El2 absorption in an occasional intrinsic [actor deficient pati~t. For those using the :lassic ghilling test~ bogy counting will ]istingulsh the patient with low El2 absorption [rom one with a low urlnary 57C0 gl2 excretion ]ue to incomplete urine collection.

Servizie di Ematelogia, Clinica Medica 2* e Servizio di Medicine Nucleare o, Universith degli Studi di Plea, Spedali S.Chiara, Plea, Italy.

Sgate Hospital for ~ardiolo@~,Balato~i~ir~ Wien

The FPA is the firSt spllt~J~g V r ¢ ~ o % of fibrlno~en and @0 sensitive'marker of the

~HE MEASUREMENT OF P L A S ~ [N CANCER PATIENTS

scot-/fallen 8enerati~ prooesso Detemminatio~ b~i "been o a g T i e d ou~ with Malllnokro~%

~lt!

saturation

afialysis,

"

do~le ~uti~o~y'rea~tiom.T-ter asSa~ V C < l o % in our practice,Normal plasma l e v o l < l , 2 ~ g / m ~ I~ p u l m ~ n a ~ embolie~n an~ a~uto ~ o o e ~ d . infarction the level w~s in@reasin~ up %0 long/ml and b o i n ~ pr~m~% norBalizod e B ~

~ e ~ p y , o u % ~Azhout a n ~ e o ~ l a t l o ~ sever~l days, Af%e~ l,bMioU s%rSp%okinase-SH rapid elevation into the x ~ loo~5oon~/ml, fast deo1~ase still on the ls% day.ThiS e ~ oessive Jet was the ~e~ul% of wash out. The elevated PPA level of remote m ~ oax~ial Infa~o%ion patients was moreover i n c r e a s i n g on ergome%l~lo stress,mostly ahd s ~ on hyperlipaemi@s from 3°5 %0 4.bng/ml. On io 3-vessel c o r o n ~ h e a ~ disesae patients,the PPA pla~za level being w o ~ n e d in % h e ~ r u n s t a b l e angina p e r i o d fr~z= I ~ Z I . 3 to 3,6-1.6ng/ml,

The normolipaemNo heav~ ~ o k e ~ s h ~ ] ~IBc e l e v a t e d FPA up %0 4a~/ml era,4 a t ~ l l ~ @ ~ h e h e hyperli~aemios,en~oe~ platelet p r o m i n e n t % aotlvi%~,measu/~d by the~ratN~ of t h 1 ~ m b o x _ ~ and 6-keto-pmos%agland~u-la kit of the H ~ g . R~ioisotope Institute. SiRm.elevation of PPA of 20 diabetic " ~asoulopa%hiss ~p %0 6ng/ml wa~ in ac6or~L~oe of ~ u p ' t o 6opg/ml end o f the ratio from 1*0 tO 2 , 0 * On acute lard end olotted fatty cream lozf %he ohsmges of FPA,TxB~,6-k,PGF-Ia re~ t e d %he bypercoagulabil tendeno~ of normo h~perlipaemics as well:lbo6-57.Sng/ml, The observed PPA elevation duming u n s ~ ~ g l n a p e o t o r i s is in a c c o r d a n c e wlth the ~ o l i o pattern observeA hy Nerl Sernerl ~rou n%he unstable pe~od.

~dd

580 Fortunate J.S., Pinheiro M J , Rodrigues M A, Amaral i. Centre de Fisiologia da Hemostase (INIC) Depts of Physiology and Nuclear Medicine Oporto Medical School 4200 PORTO PORTUGAL

PLATELET KINETICS DUPING BODY HYPOTHERMIA. COMPARATIVE STUDY BETWEEN INFERIOR VENA CAVA AND UPPER ABDOMINAL AORTA INJECTION OF lllln-LABELED PLATELET5 IN DOG Splenic and portal (intra and extrahepatic) sequestration of lllin-labeled platelets (Plt) has been ~eported as the justification for brao slant thrombocytope~ia during hypothecmla (Fort u n a t o et a l (19B7)E.N.M. Cong. Budapest,), Autologous lllln-Pl~ w~re injected in the lower vena cava (group I) or in the upper abdominal aorta (group II) in groups o~ ll normal dogs. The animals were cooled to 22sC in iced water and alter rewarmed to ~6~ C. Radioactivity in blood aliquots was counted in vitro and changes of fractional distribuhinn o~ lllIn-Pll were evaluated by dynamic study in a Gamma Camera Computer-assisted. In vitro illIn-Plt counts decreased less during cooling in the group II (32 vs 53%) but during rewarming they recovered t o ~ 5 % of initial value in both groups. In group I Pit circulating pool decrease was twofold the sequestrated pool during cooling, and its increase during rewarming was twice the size of Plt m o b g h z e d from bepatx and e×trahepatic portal circulation, suggesting that in vena cava injected dogs 50% of Pll are reversibly sequestrated out of gOI during cooling. In the group II circulating and sequestrated pools changes in the abdominal organs were twice the size of group I.lhese data suggest that upper abdominal aorta injection is more suitable for assessing Plt kinetics during body hypothermia. Liver was responsible for 50~; oF total sequeshrstion in both groups and was the only site where it was wholly reversible, suggesting s specific mechanism for Plt sequestration at hepatic level.

581 V. Ivangevi6,

FIBRINOPEPTIDE

A (FPA)

~o investigate activation of blood coagulation in 0alignancy, we measured by radioirmmunoassay (Mal Linckrodt) plasma FPA, a specific indicator of in ~ivo thrombin activity,in 70 healthy subjects and Ln 98 cancer patients(ps)~ 49 ps had breast cancer, 21 renal adenocarcinoma, iB bladder cancer and 10 miscellanea; 47 had distant metastases "MI'I FPA (ng/ml) was 2.7~±I.90(X±BD) in cancer ps and 1.12± :0.55 in normals(T-test p
582 Z. Ma~trovid,

D. IvanEevid

Department of Nuclear Medicine, University Hospital Rebro Zagreb,

Yugoslavia

PARAVENOUS ACTIVITY AT THE SITE OF INTRAVENOUS RADIONUCLIDE APPLICATION ~ND A CORRECTION METHOD Paravenous activity (PA) is a source of error in examinations in which the quantitative relation between administered and e.g. blood sample activity is important. We quantified the activity portion of ~he applied radionuclide compound that remains at the injection site on 59 examinees. All activities were measured on a shelf above a NaJ(Tl)-scintillation counter for liquid samples. We measured the activities of radionuclide doses before injection and, according to a predefined procedure, the activi~es of the examlnee~' forearms at the injection and a corresponding contralateral site. PA averaged 1.80 +/- 4.65% of the administered dose, the highest value reaching 28.8%. Clinical estimation of the PAs proved unreliable. This procedure allows mathematical dose corrections for PA, Evaluation of the method by repeated measurements was carried out on patients referred to our department for blood volume determination in whom significant PA was found during ~he first determination. We found a close correlation between co~recced and repeated results. We suggest that application sites of radionuclide compunds be routinely measured for acitivi~y in examinations in which exac¢ knowledge of actually intravenously administered acitivity is relevant.

g Forssell gronsson ~, I M LO g a f s t r ~ ~, S B Hol~ber~ =, L Lindholm ~

Grgtarsd6ttir~ L lacobsson I ,

Departments of Radiation Physics', Surgery ~ and Mlcrobiology z , Sahlbrenska Hospital, University of Gotebor~, S-41g 45 Gbteborg, Sweden,

T~

IBPLHEICE

OF

N.ODULATI ON

ON KINETIC IN RATS,

TU~E3UR-BEARIJ6

AND

RES

MONOCLONAL ANTIBODY (I~Ab)

KAb kineti~ is influenced by many factors, i e type of antibody, fragmentation, labelling and also by host factors such as function of RBS (reticuloendothelial system), RES is influenced by i e tumour burden, This study examines the influence of stimulation or depression of RES on MAh kinetic in non-tumour (lEg) and tumcur-bearin 5 (IS) rats, The tumeur model is chosen for studies af the unspecific aspects of MAh kinetic, ]daterial and Kethod: 26 Wistar rats without and HH with experimental adenocarcinom~s Srcwln5 in muscle and subcutaneous tissue, Some of them were RHS stimulated with Zymosan (3 m~/100 g i v) or depressed with methylpalmitate (100 mg/100 g i v), The a£1m~is were i v 5ivan i0 ~g MAb '~JI-C241 IbGI ~g MBq) raised against SiLe" ~anglioside antigen. which was not expressed by the tumour, Wh~le body '=II activity was registered immediately and after @ days, just before the animals were sacrificed. Liver (L), blood (B) and tumsur (T) activity was measured, MAb whole body retention (WB) was calculated as per cent of given activity and organ content as per cent per gram tissue, Results: Vntre~ed

WB L NR TB

B

RES ~%imul~ted

7

350,31,0 240,10,40,2

WB L

B

T

290,20,7 380,20,70,4

RE~ depressed

~B L

9

7

420,30,9 330,I0,20,1

C~clusfon: MAb kinetic is altered by tumour burden, In tumour-bearing rats MAb kinetic is influenced by RHS-modul~tlon.

320 584

583 B.A. Rhodes, lew

K.D. Pant, G.H. Hinkle,

RhoMed Inc.-Albuquerque, bus, Ohio, U.S.A.

I

J. Bucke-

New Mexico and Colum-

0UALITY CONTROL TEST FOR IMMUNOREACTIVITY RADIOLABELED ANTIBODY

OF

585

J.C. Liehn, P. Eennequin, D. Lebrun, J. Valeyre.

Institut Jean God;not,

S. Nasca, A. Valoni, P.Oehr ~, U.Wuddel*, U.Rumbach*,F.Werner* A.Bockisch*.J.Huhlmannn*,H,J.Biersack* B.Bj~rklund**, V.Bjgrklund**

Reims, France. * Nuklearmedizin, ~* SBL, Stockholm,

NON SPECIFIC ACTIVITY HOW TO DEAL WITH IT ?

ON IMMUNOSCINTIGRAPNY

Most of the labelled monoclonal antibodies (MoAB) still suffer from the presence of non specific activity (NEA). We describe here our experience with different attempts to deal with NEA. This study is based on 70 immttnosointigraphies (IS) performed with ill In labelled MoAb For the diagnosis of recurrences o~ secondary lesions of cold-rectal (explored with anti-CEA) or ovarian (explored with OC-ig5) cancer. The attempts made in order to reduce the disturbances introduced by NSA are : i) Optimization of the color scmle by using an algorithm based on the number of counts in the iliac crests, instead of the intrinsic color scale, ii) Definition of the normal pattern of IS (i.e. the normal NSA) ; ill) Using tomographic images ; iiii) Using blood pool and liver images and a new image subtraction method. The comparison of the standard with optimized display made on pelvic images obtained in Ea patients who were subsequently operated on shows an increase of sensitivity (.Bl vs .79) for the same specificity (.65) (BOO analysis is used). The improvement of IS by image subtraction is particularly high in the liver (sensitivity = 12/13, specificity = 7/9) while unprocessed images are not interpretable in the liver. Outside the liver, image subtraction also increases the value of IS, but the interpretation of the subtraction image must take into account the fact that blood pool and liver NSA subtraction does not correct for other components of NSA (i.e. bone, kidney colon...). lln conclusion using one or some of the described methods increases the value of immunoscinti graphy.

586

587 ~. ~eilJer,

~. Nagener,

J. Fass, U.

BeAts. Nuclear Medicine, Olinical Chemistry, and Surgery, Technical University of Aachen, FB Germany EFFECTS OF HUMAN ANTI-HOUSE ANTIBODIES (HANAs) ON REPEATED RADIDINMUNOSBINTIGRAPHY (RIg) WITH

MURINE MOHUCLBNALANTIBODIES (MARs) During the past i0 years murine polyclona] and monoclonal antibodies became commonfor diagnostic and therapeutic purposes. The aim mf our s t u d y w a s tO a n a l y z e the influence of pre-existing HAMASon SIS imaging, Measurement of HAMA r~sdonse~ in s~rum I formin~ oF immunohomplexes between 2 different murine antibodies and HAMAN ) was achieved by a i n - v i t r o tes~ developed and practised by C.W.. A total of 27 blood samples from 22 patients was examined, In SI% (22/27) significant HAMA responses could be detected though HAMH Jevei~ measured by an enzyme immunoas~ay were low or n.s.. Repeated Rig-studies wer~ performed in 12 of these patients 2 days t i l l 19 month9 ( average 204d ) following the f i r s t MAB appJicmtion. Diagnostic scinttgrams could be obtained in 10 patients, in the remaining 2, who revealed thm hiohest HHMA responses, a dramatic change of NAB distribution was apparent: rapid b l o o d clearance leading to highly increased uptake within BEN indicating phagocytosis of immunmcomplexes (MAB-HAMA). In addition ~linicaI symptoms including uneasi~ nasa, tachycardia, and hypoten~ion occured about 24 hours following MAR injection ~uggestin~ mild anaphylaxie. Our results indicate t h a t the existence of HAMAs is a commonresult of previous MAR injections and may lead to c l i n i c a l symptoms and altered MAB distribubion~ i f a second MAR injection is given, Thu~, i n - v i t r o tssts ehe~Id be employed to recognize patients at risi~. Measurement of MAMA serum levels seems not be sufficient becauss of the heterogeneity of HANGS.

Bonn, FRG

:

IA method and test kit has been developed For the measurement of the percentage of the total radioactivity in a radiolabeled antibody prepsration which is associated with immunoreactive antibody. Crude tumor antigens sre prepared from human tumor xenografts grown in nude rats. The tumor tissue is homogenized and the proteinl bound to plastic particles. Excess binding sites are blocked with an inert protein. A negative control Consists of only the inert protei~ bound to the plastic particles. A radiomegrit assay is carried out under conditions of antigen excess. Percentage binding of the radio a c t i v i t y is measured at two diliutions of the radlolabeled antibody as a way of assuring that the test is conducted under conditions of antigen excess. This assay is being used to test rS diolabeled antibody reactivity with TAG-7G, CEA and other colorectal tumor markers. As much as a two fold variation in percentage of bound i.~. immuNoreactive) raddoactivity has been ob served between different preparetions using the seme antibody and radiolabeling procedure. The assay results are being correlated with the ta~ get-to-non-target ratios of radiolabeled uptake measured during radioimmunoguided surgery. This method is recommended for use with radiolabeled antibodies intended for imaging or therapy of ~atients.

R. ~ r e ~ , Buell

Universi~t Sweden

OPTIMIZED REDUCTION OF PRIMARY CIRCULATING RADIOACTIVE ANTIBODIES IN VIVO BY TITRATION WITH "COLD" SECUNDARY ANTIBODY One of the problems of im~unoscintigrsphy is radioactive background induced by circulating antibodies. This background can be reduced either by electronic suhtractic., or i. vivo, e.g. by injection of a second "cold" antibody directed against the specific radiolaheled primary antibody. We wented to find o0t whether there was a relation between the optimal precipitation ratio of first and second antibody in vitro and in vivo. ~efdelher~er curves were established to find the optimal in vitro concentratio, for precipitation of two different primary monoclonal antiTPA antibodies, (21E4 and MS). The optimal ratio of anti-TPA/antimouse antibodies was 2,5/1 8nd I0/I respectively. In later experiments, rats bearing small solid HeLa cell tumors~ were injected with monoclonal anti-TPA antibodies (either 21E4 or M3). After 5 days, the remaining quantity of circulating radioactive primary antibodies was estimated and anti-mouse a~tibody was injected into different animals using concentrations below, above and at the optimal antiTPA/anti-mouse ratio. A follow up of background reduction was made by immunoscintigraphie imaRing and the results were calculated hy counting the epm/g blood and cpm/g tissue. We found that the optimal in vitro precipitation ratio corresponded to the optimal background reduction in vivo.

588

R Caroagnter, T Hennigan, Joyce Matthews, Ruth Harper, Barbara Pedley, R gegent, T Alien-Marsh.

K.J.A.

Departments of Surgery and Medical Oneology, Chafing Cross and Westminster Medical School, London

Division of Nuclear Medicine and II Dpt. of Gynecology and Obstetrics, Helsinki University Central Hospital, Melsinki, Finland

REGIONAL PERFUSION 0F ANTIBODY/ISOTOPE CONJUGATE CAN INCREASE TUMOUB UPTAKE.

ILIOFELVIC AND DORSOPEDAL IMMUNOLYMPHOSCINTIGRAPHY (ILS) AND IF~4UNOSEINTIGRAPHT (IS) IN GYNECOLOGIC CANCER

T h e value of antibody/isotope conjugate (AIC) in deliverin B a lethal radiation dose to solid tumours is limited by poor differential tumour uptake. We have assessed whether regional perfusion of AIC increases tumour uptake in a novel animal model. LSI74T CEA-produclng colon cancer cells were injected subcutaneously to produce thigh tumours in nude rats. Three weeks after inoculation, once solid tumours (mean weight g.BB) were evident, the femoral artery was casnulated and anti-CEA1~noclonal antibody labelled with 70-100uC ~ I was infused over 1½ hours. In Further anlmal~, AIC was administered intravenously into the tail vein. Animals were sacrificed at 48 hours and the tumours were removed and counted.

I

Mean uptake of reglonally administered AIC (8.~XIO-B uc./M tumour) was significantly grea~r Ithan that of systemically adminlstered AIC I(5.9xi0 2 uC/g tumour, Mann ~ i t n e y test. p
Kairemo, P. Lehtovirta,

K. Liewendahl

19 patients with gynecological cancer (17 ovarian, 2 cervical) were imaged with 131I-labelled monoelonal antibodies [anti-CA 125 (15 pt) or anti-CEA/CA 19-9 (4 pt)] before second look laparotomy. In 7 cases an ILS approach was used: in two cases dorsopedal subcutaneous interdigital injections (id) and intravenous in ;action (iv), in two cases iliopelvic (ip) in;actions and in three cases only (so) ;d-injections. ILS-patients were immged 3-4 times (2130 h) and IS-patlents 2-4 times (I-7 d) after the injections. The patients had raised serum CA 125 or ERA levels and/or a suspicion of recurrency. The results were compared with the results of CT or US. In order to improve the interpretation of g a m a images subtraction methods using gemTc-tracers were employed in 8 cases: DTPA (kidneys); Sn-eollolds (liverspleen); RBC (blood pool). There were true positive findings in 11 cases and true negative findings in 7 cases; preoperative CT and US findings and operation results (histology) were used for verification. In one case there was a false positive result, probably because of lymphatic sisals. In three cases the IS or ILS findings were truly positive, whereas US a n d CT were negative. According to our preliminary results ILR is more sensitive than IS in detecting lymphatic ~tastases, especially in the para-aortle and )ara-iliacic region. The ip-injeetion is also :elevant but the activity at the injection site can overshadow pathological findings in the ischiorectal fossa. IS, and ILS in particular, appears a highly promising method for Iocalizlng recurrencies and metastases in gymecological cancer.

321

D.L. M u n z , M,J. and D. E m r i c h .

591

590

589 Sessler,

H. K H h n l e ,

Department of Nuclear Medicine and D e p a r t m e n t of G y n e c o l o g y and O b s t e trics, U n i v e r s i t y o f G o e t t i n g e n , F.R.G. IMMUNOSCINTIGRAPHIC " S T A G I N G " IN PATIENTS WITH OVARIAN CARCINOMA This p r o s p e c t i v e i n v e s t i g a t i o n was u n d e r t a k e n to e l u c i d a t e the v a l u e of immunoscintigraphy (IS) u s i n g m o n o c l o n a l ant i b o d i e s (~IAbs) in " s t a g i n g " of o v a r i a n c a r c i n o m a (ON). In 44 p a t i e n t s (pts), 5[ IS s t u d i e s w e r e p e r f o r m e d a t l e a s t 5 w e e k s a f t e r f i n i s h i n g c h e m o t h e r a p y before s e c o n d or t h i r d l o o k s u r g e r y . Pts w e r e g i v e n i n t r a v e n o u s l y e i t h e r a mixture of 1 - 1 3 1 F ( a b ' ) ~ f r a g m e n t s of the M A b s a n t i - C E A 35, a n t i - C A 19-9, a n d ant i - C A 125 (n=32), or f r a g m e n t s of a n t i C A 125 a l o n e (n=19). P l a n a r s c a n s w e r e f a b r i c a t e d 1 to 6 d a y s p.i. IN " s t a g i n g ' w a s d o n e i n d e p e n d e n t of g y n e c o l o g i c a l e x a m i n a t i o n , C T s c a n n i n g , a n d ultrasono. g r a p h y . S e r u m l e v e l s of the t u m o u r - a s s o . c i a t e d a n t i g e n s (TAgs) CEA, C A 19-9, anl C A 125 w e r e d e t e r m i n e d b e f o r e M A b a d m i nistration. T h e r e was n o e v i d e n c e o f t u m o u r deposit= o n the IS s c a n s in 21 of the 51 s t u d i e s L o c a l r e c u r r e n c e s c o u l d be r e v e a l e d b y IS in 30 s t u d i e s , a m o n g t h o s e b e i n g 4 l o c a l a n d 14 d i s t a n t m e t a s t a s e s . S e n s i t i v i t y of IS u s i n g the ~iAb m i x t u r e w a s 92% for l o c a l r e c u r r e n c e s a n d 78% for m e t a s t a s e s as c o m p a r e d to 88% resp. 73% b y use of a n t i - C A 125 alone. T h e c o r r e s p o n d i n g s p e c i f i c i t i e s r a n g e d b e t w e e n 70 and 76%. T h e r e w a s no c o r r e l a t i o n b e t w e e n T A g s and t h e IS r e s u l t s . In c o n c l u s i o n , IS is a v a l u a b l e approach in " s ~ a g i n g " o f OC. T h e r e is no sign i f i c a n t a d v a n t a g e o f the M A b m i x t u r e over a n t i - C A 125 alone. T A g s in s e r u m d( not c o r r e l a t e w i t h the TS r e s u l t s .

592

D. M e s t a s , 3. B o n a f o u s , P. F e r r i 6 r e , 3. O a u p l a t ,

C e n t r e 3ean P e r r i n , C l e r m o n t - F e r r a n d , F r a n c e

I M M U N O S C I N T I G R A P H Y IN THE D E T E C T I O N OF RECURRENT CARCINOMA : INITIAL E X P E R I E N C E WITH 1-131-OC125 F(ah')2 AND 1-131-19-9 F(ab')2,anti-ACE P(ab')2 MONO C L O N A L ANTIBODIES The value of t w o m o n o c l o n a l a n t i b o d i e s (MAb), i.e., I-l]l-OCl2J F(ab')2 (OC i2~) and 1-131-19-9 F ( a b ' ) 2 , a n t i - A C E F{ab')2 (19-9) in t h e d e t e c t i o n of c a r c i n o m a r e c u r r e n c e by i m m u n o s c i n t i g r a p h y (IS) was s t u d i e d in a series of i9 p a t i e n t s (pts). F i f t e e n pts w i t h a h i s t o r y of o v a r i a n c a r c i n o m a and i n c r e a s e d CA 12~ blood level r e c e i v e d OC 12J a n d four pts w i t h n o n o v a r i a n c a r c i n o m a a n d i n c r e a s e d ACE r e c e i v e d 19-9. In all pts MAb was a d m i n i s t e r e d by slow i n t r a v e n o u s infusion a t a dose of 92.51 2 9 J MBq (2.5-3.~ mCl) a f t e r t h y r o i d blockade. I m a g i n g w a s p e r f o r m e d f o r up to 6 days. All pls u n d e r w e n t an e c h o g r a p h l c (19pts) or a c o m p u t e d t o m o g r a p h y (CT) e x a m i n a t i o n (14pts). Diagnosis of r e c u r r e n c e was c o n f i r m e d at s u r g e r y in 9 pts. R e s u l t s w e r e t h e following: n(pts) true+ falset r u e - false+ 0C125 15 g ~ 2 l [99 # 2 2 0 0 in three pts of the OC 125 series, recurrence was confirmed retrospectively by ultrasound and CT t h a t could be more specifically oriented at the site of recurrence shown by IS. False negative results occured in pts w i t h either small r e c u r r e n t nodes (#pts) or ascites (2pts). The only false posihve case was in a pt of the OC 125 series showing an area of increased uptake located just over the bradder. Although surgical exploration was negative, t h e CA 125 blood level still r e m a i n s e l e v a t e d in this pt. It is concluded t h a t IS (a) is a sensitive m e t h o d f o r t h e diagnosis of o v a r i a n c a r c i n o m a r e c u r r e n c e , (b) is specially useful w h e n t h e t ~ " e "

Division of Nuclear Medicine and Dpt. of Radiotherapy and Oncology, Helsinki Universit] Central Hospital, Helsinki, Finland

Department of Nuclear Medicine, Guy's Hospital ICRF Unit, Guy's Hospital, London, SEt 9RT.

maTmnary cancer patients were imaged using In-11 l-labelled anti-CEA-antibody F (ab ')2fragments (BW 431/31), All patients had known metastatic disease; the aim of this study was to localize metastases and compare i~unoseintigraphy findings with those obtained using other radiological (US, BT, MRI) methods. All patients were imaged at least twice (I d and 2-3 d). For imaEe enhancement subtraction techniques and 9SmTc-labelled substances were employed: MAA (lungs), tin-colloid (liverspleen), DTPA (kidneys), nanocolloid (bone marrow), citrate (blood pool), pertechnetate (thyroid). Liver-spleen subtraction was done iu all cases because of the relatively strong accumulation of l~lln-lahelled antibody in REg. A total of 336 lesions were detected. Of these lesions 267 (79%) were also detected by clinical or radiological investigation. Of known lesions 11 (3,3%) were not detected by i[m~unoscint far aphy. The serum CEA-level did net correlate with irm~unoscintigraphy findings. This study shows that in m a ~ a r y cancer i~unoscintigraphy is a aseful method for assessing the extension of metastatic disease and in many cases it provides information not obtainable with other methods.

(°9

~ u n o s c i n t i g r a p h y in breast cancer with ~I labelled monoclonal antibodies (MoAbs) The presence of tumour involved nodes in patients with breast cancer can at present only be demonstrated following surgical re~ection. We have assessed the uptake of two IL~I labelled MoAbs, EMFSI and SM3 in patients undergoing mastectomy with axillary clearance. 14 patients have been studied, 4 with HMFOI injected subcutaneously (SC) into the finger webs of both hands, 4 with SM3 injected SC, and 6 with SM3 injected intravenously (IV). Patients were imaged at I, 4 and 20 hours post injection and blood and urine samples collec~d The resected specimen was imaged, the nodes and tumour then dissected, counted individually and examined histologically. Imaging showed sy~etriea I uptake in both ~xillae following subcutaneous injection, and n¢ t ~ o u r uptake was observed after IV injection of aM3. Determinations of amount of antibody in nodes and tumour showed no significant uptake ir tumour or tumour bearing nodes following SC or iV administration of either antibody. The Following ~ l e shows the mean percentage injected ~I MoAb/g of tissue.

{MFNI (SC) ~M3 (SC) ]M3 (IV)

(°) Labzstc~y of ~Inlesre~edicire -Via P iGiovio,15-Milsno (0=)i~t of ObstetricsUniversityof Milan.

I/NICAL DLPERIE~KECF ~ G ~ P H Y ~S [EIN] OC IB5 M]qO]iNAL ANTIEDY

CF 0VARIAN CAR'G~

Cithicsl u s e f t ~ of i ~ t i g ~ (/5)withCE 125 (ab'~ for detectionof pr~r~ry,r~currentovarian adercc c/na~ Was assessed. 73N~q of 131 i lakeled F(ab,,2 fPagments (specificactivity 111 F~q~g) ~ere alninisteredi.v. to 22 wraen aged b e t ~ n 46 and 72 years with histolcgicall~ ca~ein~d ovarian ~ . Planar scintigrsphyin 3 jectims ~ s ~erformed 3 to 5 days after injectianof the ~mcr/crsl antib~y usirg Selo ~ - - ~ m ~ a hsvirg a 40 ~ , field of v i ~ fitted with a ~ ere2g~ calli~storand deta ~ ' e s t c r ~ t y cnnput~. 99m Tc-la~ed ~ aed free ~ t a t e were bled to sin,/ate the distrSb~ticn of ~he ~ e d antibtdy in d / c u l a t i n n . After aG:~uiniticn of the second zmge and thre~qoldtngof the 1311%4e~ hack~rcmd mbtracticn was carried oat. 19/PP pts s ~ e d positive ~ t h t i g ~ N V ~ p/ear t~d'niq~e, g ~ muld dsmnstrate a retravescical~ ~ clearly seen by p ~ IS. ~ r assxn~ted antigen CA 125 i n serum was in alZ pts. Dla~x~s ~as ca%Firmad by CT, ~ h y , ~~ery o~ biopsy. IS c~uld localize relapse seve~=lmmths b~ fore any other ~ i c ~ ~as cooclusive. Immn3scin~y with 0C 125 is sensitive and of cli~/cal value for dete_rmirmtirgthe exT~nt of ovaman ~ and i n the d i a ~ c s i s of relapse.

594

593 S. Clarke, C. Twelves, C. Lazarus, A. Girling S. Allen, S. Mather, J. Taylor and I. Fentiman

22

(°), G. MAmEHI (°°), C. ~

The divisions ol N u c l e a r M e d i c i n e a n d O n c o l o g y ,

K.J.A. Kairemo, H. Aronen, K. Liewendahl, A-L. Brownell, S-L. Karonen, M. M~ntyl§

IMAGIN G WITH IIIIu-LABELLED MONOCLONAL ANTI-CEA-ANTIBODY IN PATIENTS WIT~ BREAST CANCER

I ~ G 3 I ~

A. Veyre

Normal nodes

Tumour nodes Tumour

O.Ol 0.007

O.O07 0.005

Normal Breast

-

0.0037

0.005

summary we have demonstrated a valuable model for evaluating the uptake oT MoAbs in patients with breast cancer and have also shown that preliminary data s u ~ e s t s no specific uptake of either H ~ G I or NM3 in patients with breast cancer.

A.ATHANASIOU,D.PECTASIDIS,K.PATENIOTISL TZIMIS~P.NATSISA-LAFI,I-TAYLOH -PAPAl DIMI~R!OU,A.EPENSTOS,P.KOUTSIOU/~A. D e p t , o f N u c l e a r Med. and Ist Dept of P& t h o l o g y M E T A X A C a n c e r Hosp. P i r a e u s . I m p e r i a l C a n c e r Nes. Found. g a m m e r s m i t h Hospital. THE P H E - O P E R A T I V E D E F E C T I O N OF C L I N I C A L AND S U B C L I N I C A L L Y M P H NODE M E T A S T A S E S I B R E A S T C A N C E R P A T I E N T S U S I N G 131-1 LABE LLED M o A b H M F G S AND H M F G I ( F a b ' ) 2 . In a ~ : a t t e m p t to p r e - o p e g a t i v e l l y detec c l i n i c a l and s ~ b c l i n i c a l a x i l l a r y l y m p h nodeb m e t a s t a s e s in b r e a s t c a n c e r p t s , w e u s e d the 131-1 l a b e q l e d M o A b H M F G 2 and H M F G I ( F a b ' ) 2 . W e s t u d i e d 1Opts w i t h clin i c a l l v o b v i o u s a x i l l a r y l y m p h node di sease (group A ) , 1 O p t s w i t h c l i n i c a l l y I n e K a t i v e a x i l l a ( g r o u p B ) , u s i n g MeAb HMFG 2 , 5pts w i t h c l i n i c a l l y n e g a t i v e aI x i i l a ( g r o u p C), u s i n z M o A b H M F O I ( F a b ' ) 2 ~nd 6pts w S t h c l i n i c a l l y p o s i t i v e a x i l l & g r o u p D) u s i n g n o n - s p e c i f i c MoAb 11.4.I nd 4C4. All pts h a d c l i n i c a l d i a g n o s i s f b r e a s t c a n c e r , Each pt r e c e i v e d I-1.5 Ci as a s u b c u t a n e o u s i n j e c t i o n into the ebs b e t w e e n the 2nd &3rd f i n g e r s of bot h a n d s . T h e pts were s c a n n e d at 2 h - 9 6 h p o s t - i n j e c t i o n . In g r o u p A 7pts h a d posi tire scan and 3ots n e g a t i v e due to prob le.ms of i m p r o p e r i o d i n a t i o n . T h e h i s t o l o EY & i m m u n o p e r o x i d a s e staining confirme the p r e s e n c e of t u m o u r in the l y m p h nodes in all p t s . I n g r o u p B t h e r e were 4 true positive scans,4 true negatlve~Ifa ise p o s i t i v e & I false n e g a t i v e . L T m p h ~ 0 d i n v o l v e m e n t c o n f i r m e d h i s t o l o g i c a l l y in 5 p t s . l n g r o u p C t h e r e were 4 t r u e n e g a tive s c a n s . I n Ipt the MoAt s t o p p e d ~ i n the m i d d l e of the r i g h t arm, dKe to the l y m p h a t i c o b s t r u c t i o n . T h e h i s t o l o g y conf i r m e d the a b s e n c e of t u m o u r in tde lym Dh n o d e s . I n g r o u p D, t h e r e were 3 true n e g a t i v e scans w i t h MoAb 11.h.I & 3 tru n e N a t i v e scans w i t h MoAb hch. Th~ presense of t u m o u r c o n f i r m e d h i s t o l o g i c a l l y in all pts.

322

_R~__OS_J.,CALVO CASTEJON

C.,G;FONT

I.,R.ALVAKEZ

O.BERROCAL

CLINICA

597

596

595 M..DE

HARO

JL.,G.DURAN

J.,

BD BLAIR, M Salmon, S Riggs, P Southall, G Boxer, R BegenP, P Gregory, NA Theodorou

J.C. Liehn, P. Hannequin, D. Lebrun, J. Valeyre.

S. Nasca,

A. Veloni,

J.,

J.

PUERTA

DE

HIERRO.-MADRID.-SPAIN

CORRELATIONBETWEENiNRUNO~!NTIORARHY AN~ I,MMUNOHIPTOB~,%OTRY FINDINGS[N DIRGN~IBGFCOLON-RECTALCARCINOMA, the purpose &i ~his ~or~~ £a present Ohmcorr~lationshig ~tN~en ~ur pres~Q~ry~indings with Anti-OEA-a~ocion~lantlb~ IN-HI /maunoscintiqr~phy (lSS) perior~d in 27 ~atients with colo-rectaJ ~arcinoma and p~stsurB~cy ~ounts in epeci~ns Bnalyzeb hlstologlc~]ly, basically rei~Ling thm m~tivity p~ ~r~ body ~aight o( de t u ~ I

i~estin~I, ~ i s ~ [TIT} with tt,az healthy

intesdnaI tissue (~T]; ~CT~ODI.~Y: I,- D~termlnBtion tf tEA by RIA. 2.- Intravenous

inj~ctlon of f~ti-CC~ I~-ill, 3,- Reaiizmti66 3-4 oay~ after

injection wil~ R~tI-CE~In-lll iamuno~cintigr~hy el;plora~io~. 4.~rgical removal,of tumor before the eighth day aft~F ~njection, 5.- Det~inatiod of th~ upt~e attlvitY in the different ~peci~ens surgically obtai~ in rel~tion wlt~ the a~tivity of HIT. &.- !uunohistoch~iBtry {IHC} study obtained by ~ur~ery.

of th~ specimens

RESULTS: In 59 of thm'27patient~ ~t~died, the ISG image w~ oositive with or m!hout sub~ration, In 2 paHen~ mz!i~ry liver meta~taBeB were observedin surgery~iuh Here not ~ezeczed ~ith ~ny diagnostic techniques :SG, US1 CT,...L Only,2: ~f the J~ positive .patienb had CEAle,,~ls a6ove5 ngr/ml. The TIT/HiT motivity ratio r~nge~between1,9 and ~,5~ beinB all ~he p~sitive patients in the ICE st'.dr Ebc'¢e2.5, Theb patie:,t~ i~Itn the ~!phe~t "HT/HZT ~:hvityr'~:ic c9:-re~pond~pto gig ~:c ~SZl-O~e~ ~mor~ and wererelated ~i:h high positive !~G. Health, G~nglicn tis~ue/~iT azziviiyratio rented ¢ro~o.5 ~ 50.6 ano aiwmys above the T]TI~!~ activity rauo in all trim patience. ~t~s~atic ~n~!ia/liIT a~tiv~t~ rat o rangeobebwe~z,,,l zo 5.L: mlwmys consideri~giocal Q~giia. Th~ IHCde~onetrm~e¢tnet bi@hl macrophagi; capture ;f A~ti tEA In--i:i as an strar,%ea~÷n: ; aOdy~qd S~=Ond&yyC'aESpOFZ tO the ganglia. I C~CL~S!ORE: Thereis a ccrrela~ionship between a ri;n posi£ivity in the I~G stud)' and a eievateb TIT/H!T activzty razio.The ma~rophmgic activity ~ppears'tohe responsible of ~ome pcdtive ISB due eitHer~be pos~ib!e =rest/on of anti~odims against anti~ERmon~lonal an~i~d? In%I! or the b~ilt-upof immun:co~piexee betwee;i local tumo:-~! ~ti~ens aria the antibod~ u~edin 155,

598 IA. Steinstr~Ser, L. Kuhlmann, A. Schwarz, M.Zimmer and K. Bosslet

IOECHST AG, D-62BO Frankfurt/Main, FRG; 3EHRINGWERKEAG, D-3550 Marburg/Lahn, FRG THE ROLE OF LIVER IN IMMUNOSZINTIGRAPHY In contrast to theory on an immunoscintigraphic image is to be seen not only the tumor but also )rgans of the RES and the kidneys. This paper restricts to the l i v e r . I t is shown that uptake into the l i v e r is not :aused by colloids or by transchelation e f ~ muclide. Using antibodies labelled biosynthetically ~ith Se-75 methionine, i t is demonstrated that uptake by the l i v e r is part o f the physiological distribution of monoclonal antibodies. We compared studies of antibodies labelled with 1-131, I n - I l l and Tc-ggm with these results, in order to determine the effect of labelling method reap. of nuclide. All these preparations showed i n i t i a l l y the same high l i v e r uptake. But later on in case of iodine and special versions of Tc-MAB, a rapid decrease of a c t i v i ty occurs. Using cytological and chromatographical methods local/sat/on, klnetics and metabolism of monoclonal antibodies labelled with 1-131, I n - I l l and Tc-g9m are investigated on cellular evel in the l i v e r , in order to find the reason ~or this observation. The primary accumulation and metabolism is :he same for all the three preparations. But ihe behawour of the small metabolites is very lifferent. Whereas in case of iodine the Lctivity is excreted out of the cytosol and :leered from the extracellular space, indium is mcumulated in cytosol of l i v e r cells. In case of a technetium labelled antibody where a modification of the MAB is necessary ~or labelling) i t depends on the degree of this led/f/cation whether the a c t i v i t y is accumulared or excreted by l i v e r cells.

Department of Surgery and cancer Research Campain Labs, Chafing Cross Hospital, London UK

Institut Jean God/not,

Reims, France.

D E T E C T I O N OF THE EXTENT OF COLO~CT~-L C A R C I N O M A USING 1125 LABELLED ASS7 ANTI-tEA ~ N O C L O N A L AMTIBODY

DIAGNOSIS OF LIVER LABELLED MONBCLONAL IMAGE SUBTRACTION.

METASTASIS WITH iIl In ANTIBODIES (MOAB) AND

Peroperative clinical assessment of colerectal carcinoma spread may be difficult. We h a v e stuaied whether complete excision can be improved by peroperative intraabdominal scanning of lesions with a hand held g a l a d e t e c t i n g probe. Twelve patients w i t h colerectal carcinoma were injected w i t h 1125 labelled anti-CEA monoclonal antibody [aSbT) 4-8 days preoperativelyAt laparotomy, the probe was placed directly onto tumour, surrounding tissues and background areas and gamm~ emissions counted. Counting was repeate( on the resorted specimen and resulms were correlated with histology. In 19 patients, there was increased radioactivity over the aumour compared to normal colon w i t h a m e a n ~sem of 3.2Z0.4 times. Scanning of the resorted specimen showed lower counts hut still w i t h a m e a n ratio of 3.5 times backgroundThe uptake of antibody was independent of the serum tEA level. There were e Dukes C carcinomas o~ which 5 showed high counts over lymph nodes. High counts were also obtained over 2 invaded distal resection margins and one active duodenal u l c e n L o w counts were recorded over histologically normal small bowel adherent to a Pumour. Peroperative anti-CEA scanning helps to aefine the extent of colorectal carcinoma and zhere is scope to improve results by reducing backgroun~

It is a generally thought that high liver non specific activity on immunoscintigraphy (IS) )erformed with In labelled moAb precludes the use of this technique for the diagnosis of liver metastases. Preliminary results have indicated that a proper image subtraction method mmy overcome this problem. The purpose of this study is i) to validate the subtraction method on 22 patients; ii) to extend the subtraction method to tomographie image~. Twenty-two patients with cole-rectal or ovarian cancer were explored with anti-CEA or 0C-IE5. At day 2 or 3. liver images are recorded. Then, a liver morphologic image is performed after injection of In colloid phytaCe. The image subtraction is only performed between images obtained with the same radionuclide. In some patients tomogfaphio images are also recorded. The im~e of the significant di fferences is generated after proper normalization and geometric registration (3 D rOE/seDation in the case of tomographic data). The gold standard is CT and/or US. Thirteen of the 22 patients had proven liver metastases (7 of them < 3 cm) ; 12 of them were seen on the subtraction image. Seven of the 9 normal liver imbues were true negative. These surprising good results suggest that image subtraction performed between images recorded with the same isotope is very helpful for immunoscinti~raphy of the liver. Nevertheless this study which takes US mld CT as the gold standard was not intended to C dem°nstrateT the superiority of IS over US and .

599

600

P.H. Cox, M. Pillay, A. Planting, J. Verweij ind e. Booter

A. K r o t s s , ~ ,

Dr. Daniel den Hoed Cancer center P.O. Box 5201 ]00a AE ROTTERDAM, The Netherlands

I n s t i t u t e of Nuclear M e d i c i n e , KA R u d o l f s t i f t u n g , Vienna

III-INDIUM~/~TI~fosIN SF M Y O S ~ C O M A

CLINICAL APPLICATION OF 1-12B LABELED ANTIGRANULOCYTES ANTIBODY.

FOR THE IN VZVO DETECTION

Introduction: The aim of the study was to th~ potential of lll-In-l~belled anti~yosin for the in vivo detection of rhabdo- and leiomyosarcomas. Method: A series of patients w i t h known tumour localisatiens, which had been verified b y X-ray, 3T and/or ultrasound, received 74 M B q Of mndium labelled ant/myosin (R1tDiO Fob fragment) intravenously. So/nO/grams were p e r f o r m e d &t 4, 24 ana 4E hours p o s t injection. ~sults and conclusion: Four rhabdomyosarcoma patients showed positive uptake at 24 and 48 hours at all known tomour sites. Two others were considereg to be true negative so/nO,grams. Of 4 patients with leiomyosarcoma 8 t z ~ ~ositives Lnd 5 false negatives were observed. ~ o u r to )ackground ratios of i0:i were Eound% ~ .ncidence of false negative leiomyosarcoma may be related to reactions to therapy.

W. Weiss, CN. K ~ I b l . K. D i n s t l , A. Neumayr

The aim of t h i s study was to p r o o f the clinical r e l e v a n c e of monoclonal a n t i r r a n u l o c y t e s a n t i b o d y (Mab-47), r a d i o a b e l e d w i t h 1123 in d i f e r r m n t i n f e c t i o u s l e s i o n s . The d e t e c t i o n s were done 4-6 hrs and 24 hrs by p l a n a r s c i n t i g r a p h y and by SPECT. In 6 p a t i e n t s w i t h Crohn~ disease we found an i n c r e a s e d uptake of the abscess and o n l y in I p a t i e n t t h e r e was no h i g h e r uptake. In 4 p a t i e n t s w i t h ulcerative colitis we found a h i g h e r uptake in the colon s i g n a l i z i n g a recent colitis w i t h abscesses and in 2 p a t i e n t s we found no h i g h e r uptake. This r e s u l t s were concordan.t w i t h clinical, endoscopic, X - r a y and o p e r a t i o n r e s u l t s . In I p a t i e n t s w i t h Crohn~ disease w i t h i l e o s t o m i e and ~tatus p o r t M i l e s o p . the d i a g n o s i s of ~nal f i s t u l a was o n l y p o s s i b l e w i t h ~his method. A v e r y i m p o r t a n t i n d i c a t i o n l f o r t h i s method ls the d e m o n s t r a t i o n of i n f e c t e d hip g r a f t s as we found in 6 ) a t i e n t s and acuteand c h r o n i c o s t e o n y e I i t i s as we found in 7 p a t i e n t s . . o r a l / z i n g abdominal abscesses w i t h t h i s method is v e r y i m p o r t a n t and we :ould f i n d 4 p a t i e n t s w i t h h i g h e r ibdominal uptake and found in s u r g i c a l i n t e r v e n t i o n s t h a t we had made up a :orrect diagnosis. In c o n c l u s i o n , the method / s t h e l p f u l For l o c a l i z a t i o n and extend o f abscess ~r f i s t u l a and i t is p o s s i b l e to do t h i s i n v e s t i g a t i o n p l a n a r and by SPECT.

323

D.BAFALOUKOS, D.PECTASIDIS, M.DIMITRIADIS ~,-TJ~, A.LAFI, P.KOUTSIOUBA, A.ATHAZASTOU. Dept of N u c l e a r M e d i c i n e a n d ist D e p t o~ Pathology, METAXAS Cancer Hospital, Piraeus.

3 O R R E L A T I O N OF C E A A N D C A - 1 2 5 S E R U M L E VELS W I T H T H E P R E S E N C E O R A B S E N C E O F DISEASE,I R E S P O N S E TO C H E M O T H E R A P Y A N D T H E 2ND L O D K F I N D I N G S IN O V A R I A N C A N C E R P A -

rIEN}S. W e h ~ t u d i e d the c o r r e l a t i o n of C E A a n d C a - A 2 5 s e r u m l e v e l s w i t h the p r e s e n c e o~ t u m o u r in 60 pts w i t h e p i t h e l i a l o v a r i a l c a n c e r . We a l s o s t u d i e d the c o r r e l a t i o n of t h e s e m a r k e r s w i t h the c o u r s e of the d i s e a s e and the h i s t o l o g i c a l f i n d i n g s a~ the 2nd look l a p a r o t o m y ~ 1-9 b l o o d samples w e r e c o l l e c t e d f r o m e a c h p a t i e n t . A b d o m i n a l s e r u m l e v e l s of C a - 1 2 5 f o u n d in 4 6 ( 8 0 , 5 % ) pts w i t h c l i n i c a l o b v i o u s d i s e a s e . On the o t h e r h a n d 9(19,5%) pts with positive clinical examination gave f a l s e n e g a t i v e r e s u l t s . N o r m a l s e r u m le,els of C a - 1 2 5 f o u n d in 14(100%) p t s w i t b legative c l i n i c a l e x a m i n a t i o n . In 1 2 / 1 6 ~ho h a d c h e m o t h e r a p y , the C a - 1 2 5 s e r u m .ovals f o l l o w e d p r e c i s e l y the c o u r s e of disease. S e c o n d l a p a r o t o m y w a s p e r f o r m e ( .n 13 pts. F i v e pts w h o h a d p a t h o l o g i c a l .y n e g a t i v e 2rid look l a p a r o t o m y , h a d norlal s e r u m l e v e l s of C a - 1 2 5 , O n the o t h e r land the 8 pts w i t h p o s i t i v e 2 n d look . a p a r o t o m y h a d a b n o r m a l C a - 1 2 5 s e r u m levels. T h e C E A s e r u m l e v e l s w e r e a b n o r m a l m l y is 5/46 (10,8%) pts w i t h c l i n i c a l )by(pus d i s e a s e . : o n c l u s i o ~ : C a - 1 2 5 is a p r e c i s e m a r k e r [or the f o l l o w - u p of pts w i t h o v a r i a n :ancer.

?.H. Cox 2 , A.J.G. Swank I , M. Pillay 2 and K,H. {an I H. Y F, P e k i n , M. T, Ercan, Z. Hasoelik, C.F. Bekdik

Departments0[ Nuclear Medicine,and PhysicalMedicineend Rehabilitation,Hec~ItepeUniversityMedical School,Ankara, Turk~

¥13UALIZA[ION OF INFLAMMATORY LESIONS WIIH 99mlc-NANOCOLLOI D 99mTo nanocolloid (99mTc-NC) was ~aluo(ed for the scintigraphic visualization of inflammatory lesions and compared to 99mTc-MDP 25 women (~e range;17-65, mean: 47.5) with derlnilive rneumatoid arthritis in egtremi(l~, b~ed on ARA diegnoeticcriterle, gave thelr informed ooeean((o be includedin ~his studY. Naneaollklts were obialnedFrom So!coNuclear,Switzerland,and labelled wi!h 9geTs eaearding~ekitdireations 8- ]0 rnCi99mTc-NC wee IV edminlstered to edcb patient. $cinUgrems were obtained30-45 rain posi~ini~tlenby the use of a gamma camera (ZLC 75 with Scmtlview, Siemens) 3-5 days later bone 5cinUgrame were obtainedin the some patients3 h cite? odminlstratlon O( ]5-20 mCi 99mTc-bIOF, The poHeete were medically treated and salled For repeal sears with g9mTc-NC ) and 3 months later ROI was drewrl ever the sitesend (he ratiosel mflemn,atety lesion[o normal Ueeues (InflN) were calculatedbath !n 99"ITe-NCand -MDP scans. $cirUgrephlo images dehnleted (he m[lammotory lesions very well Before medical treatment InUN ratios ef 233t0.94 end 495t3 56 were ob~alned m 65 altea (or 99mTc-NC and in 54 sites[or 99mTc-MDP, respeatlvelyAt I and 3 monlhs after U'eo~men~2.15 -+ 0 91 (45 oilea)and 2.23_+0.63 (28 sites) were obtained, reapea~ively The differences between the initial values of the two radiophermaceutioals, end the mii:ai values aod thOs~ obleined after ! and 3 months wild 99mTc-NC were all ~ignificent(o
Bohdan Huszno,

D e p a r t m e n t of E n d o c r i n o l o g y of In&t~tnt( o f I n t e r n a l M e d i c i n e and D e p o r t m e n t of O r t h o p a e d i c s , ~ e d i c a l A c a d e m y in E r s k 6 w Ioland THE SCINTIGRA2HIC ~%ALUATION OF THE HIP JOlh~ STATE AFTER ALLO}LASTY BY THE US~ OF S O L C O - N A h 0 C O L L 2 R E I A R A T I O N T h e e v a l u a t i o n of e f f i c i e n c y of t h e end o p r o t h e s i s i m p l a n t a t i o n into the h i p joint and t h e d i a g n o s i s of its c o m p l i c a t i o n s , m a i n l y in the f o r m of t h e i n f l s mm~ry p r o c e s s , a r o u n d the p r o t h e s i s r e presents ssrioas difficulties.The stud i e s has b e e n p ~ r f o r m e d in 20 p a t i e n t s in v a r y i n g t i m e a f t e r i m p l a n t a t i o n of h i p ~oint e n d o p r 0 t h e s i s . The p a t i e n t s vere given 3olco-~snocoll labelled with 8 - I 0 inCi ( 2 9 6 - 3 7 0 MBq) 9 9 m T c and s e i n E ( g r a b b y of h i p joint was o b t a i n e d b y the use o f S i e m e n s gsmm~-cs/~era ZLC D i g ( t r a p " 7 5 ~ C , A m o n ~ t h a t p a t i e n t s in ~0 c a s e s the p r e s e n c e of c o m p l i c a t i o n corresponding to the l o o s i n g of the ors. t h e s i s or inflem.matory p r o c e s s a r o R n d the t r a n s p l a n t has b e e n s u s p e c t e d and in ~O o t h e r c a s e s the e x a m i n a t i o n h a s ea o n l y b e e n a r o u t i n e one. In t h r e e c a s e s the f o c a l a c c u m u l a t i o n of i s o t o p i c label at s i t e of o p e r a t i o n has b e e n s t a t e d cor r e s p o n d i n g to i n f l ~ m a t o r y lesions, w h i c h the s e c o n d operation confirmed. In one case, d e s p i t e the a d v a n c e d inflammat o r y p r o c e s s s t a t e d d u r i n g the operatic: the s p i n % ( g r a p h i c e x a m i n a t i o ~ was n e g a tive. In o t h e r s c i n t i g r e p h y - n e g e f i v e c a s e s the r e p e a t e r ( o n s h o w e d o n l y l o o s ing of e n d o p r o t h e s i s . E n c o n c l u s i o n N s n o c o l l 3 c a m s to be a v a l u c ~ l e ~ g a n t in e a r l y d e t e c t i o n of inflammatory l e s i o n s a f t e r h i p joint a l l o ~ l a s t y .

~ B~rs~+9., M, Starker*, c h r i j v e r ' , P. W o l f ~ a n d G, H ~ r #

I ELB

Ins%,

f o r Diagn.

Imaging;

f Orthopedics and #Gee.

N~cl,

M, D e

[ntroduction: In patients with polyarthralgia ind no clinical evidence of synovitis the ~ressure of a positive skel~tal stint(gram has %0 predictive value with respect to the eventu~ development of synovitis. Nanocolloid has been ~hown to accumulate in inflan~nato~y lesions in pints and therefore may be a more sensitive adios%or than skeletal scintigraphy. de%hods: A group of Ii patients with polyirthralgia and no synovitis were subjected to ~keletal (~P) and nanocolloid scintigrams and zompared with 7 patients who had clinically ~vident synovitis. For the nanocolloid study 170 MBq was injected intravenously and scinti[r~ms were made at ± 30 min. post injection. {esults and conclusions: In the ii polyarthral[ia patients without synovitis all X-rays were legative and aid skeletal scintigrs/ns positive. Nanocolloid sointigr~s were positive in the e~sence of evidence of inflames%ion. In the 7 ~atients with evident synovitis 6 X-rays and ill skeletal scintigr~s were positive whilst n~ocolleid scans were positive and 2 (falsel ~egative. No explanation for the false negative ~cintigrams is evident and the incidence of ~sitive colloid scintigr~s in the group ~ithout synovitis does not agree with the 5 rear follow up incidence of the development of nov(tie (2%).

en osteomyelitis is suspected after artificial joint replacement 3-Phase-bone-scintigrephy

M.A.AI-Jsnabd, A.K.P.Jones, K.E.Eritton, K.Selanki, R.Sobnack, J.Bomanji, A.M.AI-Nahhas~ E.C.Huskisson.

Mad.,

Hoop.; F r a n k f u r t , FRG; " S o l c o asle LEd, Div. R a d l e p h e r m . , B i r s f e l ~n. ~wlt~API .~d -PHASE-BONE-SCANNING, 99mTo-COLLOIDS ND 99mTe-HMPAO-LABELLED AUTOLOGOUS E U C O C Y T E S IN T H E D I A G N O S I S O F INFECD ARTIFICIAL KNEE R E P L A C E M E N T S

(3PEa)

~S performed usually. Today ~he dlffe~entlel diagnosis (DD) of u n s t a b l e psteosynthesis and septic ioosen£n~ is ompletsd by new methods of r s d i o n ~ fide imaging with in-vitro labelled eucocytes (ILL) end nanometer-sized olleidal tracers (NCT). The purpose f this study was to compare these 3 rocedures and to point out advanages. ~n I0 pts. (8 m., 4 f., m,a. 68 years) ~ith TAR of one knee (operation up to

i

130

~ECHNETIUM NANOCOLLOXD SCINTIGP~MS AS AN hNCILLARY TO SKELETAL SCINTIGRAPHY IN THE ,]VALUATION OF JOINT DISEASE

*Dive.

niv.

tel I[TA~)

aepts.of RheLunatology I and Nuclear Medicine a ?.O. BOX 520] ~008 AE ROTTEP~DA~I, The Netherlands

606

605

i04 Zbigniew 3zybi£ski, Japusz Otfinowski

603

602

601

mmr~th ago) ar=d a pain,Ful lo~ 04 mobility 3PBSp ILL a n d ~CT w e r ~ [perfurmed a t i n t e r v a l s of ~ days. AL" this t i m e ~ - r a y s and laboratory data Nere n o t e v i d e n t . In 7 / 1 0 pt~, all 3 s c a n s s h o w e d hypep-~er f u s i ~ n (HF) ~ enhanced b l oodpoQi : o n t r a s t (EBC) ~rld arl i n t s n s e a c t i v i t y ~Lptakm (IAU) in t h e l a t e p h a s e cor r e ~ monding t o t h e a c t i v e inlet%ice, In 3 / 1 0 pt~. the 3 P B S show~Q a~ well I'IP, ~.~.1 ESC and also an I n t e n m Q late up-'. hake. But a g a i n s t t h i ~ ILL and N C T .ere q u i t e normal c o r r q s p o n d i , l g t o an ~ s e p t i c loosenirl@ o$ t h e p r o s t h e s i s . These results sho~ t h a t in c a ~ e of ~uspectod i~tf oct i on and/or aseptic i o~Jsening o~ TAR an additional ILl_ a n d / o r N~T iS g r e a t l y u!~e~ttl @or c l ~ a r 00. F u r t h e r more, NC'T" take-~ less t i m e and Shows t h e r e s u l t e ~ r l i ~ r .

St Bartholomew's Hospital, West Smithfield, London, ECI UK. QUANTITATIVE UPTAKE OF Te-99m HEXAMETHYL PROPYLENE ANINE OXIEE, HMPAO, LABELLED LEUCOCYTES IN RHEUMATOID ARTHRITIS. Objective methods for assessing the activity, progression and response to treatment off rheumatoid arthritis, SA, are lacking. With this aim the technique of Te-99m HMPAO, white cell labelling has been simplified and applied to imagin e the knees of RA patients before and after intra articular triameinolone injection, Our modified approach to white cell labelling requires only 20 ml blood, allows 400 MBq Tc HMPAO to be added and takes only one hour. Efficiency of labelling, leucocyte migration in vitro, low lung and high spleen uptake in vivo are similar to the technique requiring I00 ml blood. Radioleucoseintigraphy was performed in 8 patients, not on second line therapy, with one severe and one less affected RA knee at ~ and 22 hours, using a special mould for positioning the knees. Quantitatdon of uptake was by a geometric mean method applied to regions of interest on anterior and posterior gamma camera views after interpolative background correction. Uptake ranged from 1.25xI0-~ to 8.39x10-3% injected dose (mean 3.15±1.86xI0-3%) before therapy. After in%re articular steroid injection, restudy 5-10 days later showed a reduction of uptake by 50-80% in 7 whose pain and swelling scores decreased ~O.01) and increased by 8% in one with increased pain. This Quantitative approach should help to evaluate the activity of RA knee joints and their responses to therapy.

324

O.

Caballero

Car~ena,

a n d J.

Pardo

idon-

tenet.

Hospital

609

608

607

"La Fe".

Valencia.

M©Cullough, RickyW. and Mlkolich. Dennis Brown Unk,ersdy, Program-in-Medicine. The Miriam and Veterans Adminis~'a[ion Hospitals. Providence, Rhode Island,

SPAIN.

To-99m-MDP A N D GALL17/M-67 CE'P~&TE I M A L GING FOR TH~ DIAGNOSIS OF I N F E C T I O N A N D LOOSENING OF PAINFUL TOT&L HiP PROSTHESIS. While total hip replacement hes been liEly sucoessfsl in O r t h o p e d i c , complications do occur, m a i n l y l o o s e n i n ~ a n d i n ~ection. T h i s study, w a s p e r f o m e d in o r der to d e t e r m i n e h o w u s e f u l , M D P a n d G a [ m a x i m E a r e in the e a r l y d e t e c t i o n of these c o m p l i c a t i o n s , Forty patients with total hip prosthesis h o v e b e e n s t u d i e d , 8 of t h e m w i t h im31antefion-scan i n t e r v a l l e s s t h a n 12 nonths, a n d the o t h e r s ~2 w i t h the i n t e r ~el ~ r e a t e ~ t h ~ n 12 m. u n t i l 5 y e a r s . T h e distribution after surgical t~eatment, ind b a c t e r i o l o g i c a l t e s t s was: 18 i n f e c tion, 17 l o o s e n i n ~ , and 5 normal. In a l l cases, tWD S C a n S with: 9 g m T c - M D P (555MBq) ind 6 7 - G a (185 MBq) w e r e p e r £ o m e d . Pelvls a n d f e m u r i m a g e s w e r e o b t a i n e d ~ f t e r 3h. ( ~ n p ) , ~nd ~8h - 7 2 h . (~a), with a ~ m ~ a camera.

T h e r e s u l t s o b t a i n e d w i t h the H D P - s e a m h o v e been: p o s i t i v e ~ in the ~5 p a t h o l o g i c a l c a s e s s t u d i e d (IO0~), w i t h two p a t & terns;diffuse, showin~ acefabular-femoral L c f i v i t y (17 cases, 1~ o f t h e m p r e s e n t .nfection) a n d focal, s h o w i n £ f e m o r a l die "isis a c t i v i t y (18 cases~ I~ o f t h e m p r e ~ent l o o s e n i n g ) . T h e G a l l i u m - s c a n , has *een p o s i t i v e in the 18 c a s e s o f i n f e c tion (]OO%), a n d n e g a t i v e in the r e m a i n let oases: l o o s e n i n g a n d nozlnal. In c o n c l u s i o n : i m a ~ i n @ w i t h T o - M D P an~ ~a-67, are u s e f u l f o r d i f f e r e n t i a t i o n be. ~ween mechanical loosenin~ and infection )f t h e p r o s t h e s i s b e f o r e d e f i n i t i v e radi3 1 o ~ i c a l sirens a p p e a r .

DIAGNOSIS OF INFECTION IN ORTHOPAEOI( lAND TRAUMA ~R~R~ ~ - ~D-~CANN~NG~ ,To--99--HM-pAO

INEEC'FION FOLLOWING SURGERY IN THH ~USCULOSKELEfAL SYSTEM STILL IS A ~ R O B L E M OF TOP P R I O R I T Y A N D SOMETIMES flARD TO DIAGNOSE. THE EARLIER INFECTION IS D E T E C T E D T H E ~ E T T E R THE C H A N C E F O R THE P A T I E N T TO BE CURED. AE FIRST INVESTIGATED A CONTROLLED 3ROUP OF 15 P A T I E N T S WITH INFECTION 30NEIRMED ~Y SUBSEDUEN'I O P E R A T I O N TO !VALUATE THE M E T H O D OF W B C - S C A N WITH Tc-99m-HM-PAO. LATERON BO MORE =ATIENTS WITH SUSPECTED INFECTION WERE EXAMINED, ~ACFERIAL INFECTION WAS ASSUMED IN =OCAL UPTAKE OF THE NUCLID, DIFFUSE ACCUMULATION WAS CONSIDERED N O T TO BE bACTERIAL INFECTION. TRUE POSITIVES WERE FOUND IN 32/&S, =ALSE POSITIVES IN 2/&~, TRUE ~ E G A T I V E S IN 1 1 / & 5 AND F A L S E N E G A T I V E S IN 0/~5 PATIENTS. INEECI'ION WAS DETECTED IN S O E T TISSUE, JOINTS AND 5ONES. EASELLED GRANULOCYTE SCINTIGRAPHY WITH To-99m-HM-PAO SEEMS ]'0 BE A VERY ISEFUL AND RELIABLE METHOD IN ~ETECTION OF INPECTION IN THE ;KELETON. W E C - S C A N C A N BE S U P E R I O R TO : L I N I C A L ASSESSMENT. THERE IS A CHANCE • TO A V O I D UNNESSESARY O P E R A T I O N S AND ~. TO ACCELERATE TNE I N D I C A T I O N FOR ~N I N T E R V E N T I O N AS ~ E A L BENEFIT FOR "HE P A T I E N T . z

611

610 A.Abbati, ~ P . L ~ o ,

F P ~ u m m C e r l t I-e ~ t - u f s g e n o s s e n s c h a ~t i ich~ U ~ f a l i k i i n i k z ~ i v i ~ i o ~ of Nucle~P Medicine, D~p~tme~t of R a d i o l o g y , UnivePsity ot rUbingen, West Gepmatqy

R.Benti, F.Zlto, N.Ciancagllni, A.Del Maschio, M.Giancrlstofaro, P.Panlzza, P.Gerundlnl, F.Fazio.

*N.Oliv~io, *D.Dall'Olio.

Diagnosing Oeleomyelllle by using Time Activity Cur,/ee In Dynamic Bone Imeglng. This study was conducted to ascertain the scintigraph~c signifeancs of time aclivily cuP,,s~ (TAC's) in the diagnosis of osleomye[itis. Pal[enls were given a bolus inJeclion of 9gmTc diphosphonate (MDP) at time, I=0, Regions of interesls (ROI) were placed above, below and al the level of disease iovoivement in both the a~fecled and nonaffected limbs. Counts were collected in fhese ROl's from O to 60 seconds producing curved segmenls called TAC I & TAC II ar
For the affeck~l limb in OSlsomyelitis, the time of arrival forthe bolus, i[srateofentryandiisg0 second accumulalion is quantil]ab~e and is o . average 4-13 times gmaler than the unaffected limb. By oontrasl for the affected limb in cellulitus the bolus's arriwJ time, rate of enlPl and the 60 sac accumulation was observed lo never exceed 1.1,51imesgrealerthaJllheunaffectedlimb. Thus TAC in dynamic bone imaging renders a quantitaliv~ dis~ioetion of osteomy~lilis from similarly apbear[ng clinical disorders such as c~llulitus Them am several illuslrative cases which are inst~ctive in 1his rega,'d, The physiologic significance of 1hose curves have bee~ discussed tc[ioicml Nuclear Medicine. July 1988).

612 D.Bracht-Krau~, C.Trepte, A.Reinhardt, D.Hellwig, B.Bitter, W.E.Adam, W.Puhl

OSPEDALE MAGGI0f~, BOLOGNA (Italy) Nuclear Medicine Service and ~Nose and Tbl~t D e p a r ~ t

Istltuto San Raffaele, San Paolo Hospital. Universit& di Milano, Milan, Italy.

University of U l m D i v i s i o n of N u c l e a r M e d i c i n e C l i n i c of O r t h o p e d i c s , 7900 Ulm, F R G

~"Tc MDP ~nd 6Ga7 sc~n in ~ e diagnosis end f o l l o ~ Ext~ NaliEnant Otitis (E.M.O.)

NONINVASIVE ASSESSMENT OF BONE DAMAGE WITH CT AND SPECT IN TEMPORO-MANDISOLAR-JOINT (TMJ) OSTE0~THRO$IS.

Computerassisted quantitative bone scintigraphy in p a t i e n t s w i t h c e m e n t less endoprosthesls of the hip.

Patients with clinical suspicion of TMM osteoarthrosis of recent (< 1 year, 8 patients, Ii joints) or late (> 1 year, 17 patients, 20 Joints) onset with local symptoms underwent noninvaslve imaging assessment of TMJ bone damade with CT and semlquantltative bone SPECT performed two hours after the injection of 555 M3q of Tc-99m-DPD. TM3 structural alterations in ET transaxial and coronal slices were scored by independent observers. Box and 30~ isocontour thresholded ROIs were defined in tPECT transaxlal slices of TMJ structures (2.54 cm thick) and mlddle cervical spine (as bone reference) respectively. From TMJ and bone reference counts in the ROIs were obtained TMJ-TMJ-Ratios (TTR) and TMJ-Reference-Ratlos (THE). Each TMJ was scored comparing TTR and T~R values with a "normal" distribution p~ttern obtained in a control group (9 subjects) without clinical and anamnestlc evidence for TMJ disease. SFECT detected abnormal hone activity in all but one symptomatic j Dints with advanced bone involvement established by CT (8 of 9 THIs). CT detected bone damase only in 4 of t[ TMJs wlth recent TMJ pain while the SPECT score was abnormal in all. These results suggest the utility of SPECT bone scintigraphy for assassin d both early and advanced hone i~volvement in symptomatic patlents with suspected TMJ osteoarthrosls.

Since several years cementless h i p replacement has been prefered. But there are many problems in i n t e r p r e t a t i o n of X-ray and clinical symptoms. The aim of t h i s s t u d y w a s to d e m o n s t r a t e a normal scintigraphic follow-up after cementless hip-replacement using a computerassisted quantitative bone evaluation. By a g t a d i e n t - i m a g l n g met h o d (a h i g h v a l u e in g r a d l e n t - i m a g i n g is a h i g h u p t a k e in the o r i g i n a l i m a g i n g ) its p o s s i b l e to d e f i n e ROIS investigator-undependently. 32 p a t i e n t s w e r e s t u d i e d in r e g u l a r t i m e s t e p s u n t i l 2 y e a r s p,o. Q u a n t i t a t i v e evaluation w a s b a s e d on d e t e r m i n a t i o n of c o u n t - d e n 6 i t y r a t i o of a c e t a b u l a r regio/soft tissue and shaft regio/ soft tissue. By quantitative evaluat i o n we o b s e r v e d an i d e n t i c f o l l o w up c u r v e to an i n d e x - l e v e l of 4.9 (+ 1.3) for a c e t a b u l a r / s o f t tissue r a t l o a n d 3 . 3 5 {± 0.6) for s h a f t / s o f t tissue ratio (after about nine months) In 22 p a t i e n t s w i t h o u t c l i n i c a l a n d radiological s i g n s this f o l l o w - u p c u r v e c o u l d be d e m o n s t r a t e d . In 8 p a tients a deviation was observed. 2 of these were followed by reimplantation b y l o o s e n i n g of the hip. 6 p a t i e n t s showed clinical and/or radiological symptoms indicating the p o s s i b i l i t y of instability/beginning l o o s e n i n g of the hip. W e c o n c l u d e d c o m p u t e r a s s i s t e d quantitative bcn scintigraphy can be a h e l p f u l tool in d i a g n o s i n g loosening of the hip.

of

9~ 67 Two cases of E.M.O. in ~atoh Tc ~DP and Ga scan si~_ fica]tly cmntributed to die.sis ~ follow-up ~ proven ted. As known, E.M.O. is a p r o ~ i v e P s e u d ~ in~ec_ tim of the e~ternal ~uditory canal and adjacent structo r~s whida occurs in elderly disbetic patiente. If the in fe~ticn is not controlled, m
and

325 613 G, P ~

614 L G ~ t ~ b ~ I (°), F. B01ELLI (oo), G, N ~

(oo)

(o) Lab~atary of Nuclear Medicine -Via P Gisvia,154~dlanc (°°)~.$yisinn of .~th~edic ~edicire H~spital of S. Donato M~laf~se (M//ano) )I/~C UTILITY g: P L ~ B ~ /~D SINGLE PHOT~ ~gqS[T/3N C ~ T ~ (SOECT) ~1 SP~YL0578 /&D ~:U~DYLB/SESIS examired fou~ healthy volunteers and 18 pts. (&2 males and G ~omen) aged between 31 and 68 yore-s, with lumbar pain land radiological signs of spaedylolysis cm spaedylolischesis and EO otndr coqcs~ltant lumb~ peteloey. After i . v . inj. OF 20 mCi OF 9£m Tc ~ , t~ee ours later plansr ~c~z3raphy ~ s doe in the crtogonal planes, and axial, :c~onal and lateral t~,,~j~.phic sections, 1.3 cm. thick, #ere obtained usin9 SiLO digital wide hea~ g a r m ~ - ~ , ~ith high-resolution ~ , interfaoed with a om#utm _INK rood. M ~ 5000. In r~m~al subjects, examiPedwith stat i c scan and ~ECT, the trao~ was distributed sym~=trical[y into the right and left sid~ of the postaris~ lumbar E_ wich w~re clearly disting~Eshable. In the 18 pts. dth sy~Btams, the increased uptake of ~-a~er was detecta)le i n 13 both by planar s ~ ar~ S°ECT, ~nile in ~ the ~igh uptake of tracer v~s preset only in the SPECTexamine : ~ ; S~ECTis ~ sensitive than static be~e scars (88~ b%~ceedof 7~/~) Froviding clearer, t~m-eedimensi0~al ~ f i n i :ioq of altorat~s~s due to better ~3~Zrsst of the ~ g e . ~ l ~-esent findings indicate that wheq back pain is caLsed by ~3oedylolysis ~ spaedylelisthesis, the redislcgically denotable lesions of the istmus ~ frequently ass~cisted ~th ]seal o s t ~ c hyperactivity wish is detectable ~th SPECT, ~nile when the back pain is not due to such ra Jlol0gi~lly visible altoratiors, both SPECTand bone scin--/zj~aphy give a normal pict~e.

616

A. van Dalen x, J. Favier xx and I . S ,

615 Marion XXX ,

Depts of XNuclear Medicine and XXGynaecology, Bleuland hospital, Gouda, The Netherlands and XXXDept, of Gynaecology, MAY hospital, Budapest HunKary, SLOPE ANALYSIS OF CA 125 LEVELS DURING THERAPY, The aim of our study was to prove that the slop, of the disappearance curve of CA 125 during therapy would be a better parameter of the disease state than low CA 125 levels at the time of the second look operation. CA 125 was determined using the IRMA of Centoool (Malvern, USA). From our series 54 patients witl zystadenocarcinoma's of the ovary could be ana[yzed in the past 5 years (stagin E I:4" ll:5; llI:39 and IV:U). All histological types were included. After the primary debulkin E operation 3abSents were treated with a variety of chemotherapeutic drugs. Slope analyis was performed using monthly CA 125 values in serum samples taken just prior to chemotherapy. %8 out of 54 patients did show an apparent half Life (T~) during treatment of ~6 days. in 24 patients (50%) the minimal CA 125 value was above the reference level (35 U/ml) at the time of thl ~econd lock operation. This was always accompatied by residual disease. In the other 24 patients the minimal CA 125 value was (35 N/ml. Ir L9 out of these 24 patients there was at least ~tnimal residual disease. The other 5 patients ~ere false positlve according to the T~ crite"Sum. All these 5 patients had initially stage [ or II disease with pro-operative levels of CA 25 <210 U/ml. 6 out of 54 patients showed a T~ <6 days. Still in 3 patients (58%) minimal residual disease or microscopic disease was estallished at the second look opeyabion. in conclusion, T~ ~ S days is a better parameter )f the actual disease state than the upper roTe"once level of 95 U/ml, especially if patients ~ith low pre-operative levels (i.e. stage I a~d i) are excluded. T~ < S days does net guarantee disease free condition.

617

V.VALENZA, M.L.MAUSSIEE, G.9.DOGLIETTO o , I.SALETNICH, D.FRONTERA o , R.BENEVENTI ~o , L.TRONCONE.

I.Kambas2,V,Thecdoropoulos2,A,Tavernara ~i 2, T h . C ~ a b z i p a n a g i o t o u ~ , N,Eaziotls I and A.Pspad~Itricul,

iIstituti di: Medicine Nucleate e Patologia Chirurgica o Universit~ Cattolica Sacra Cuore [Roma); Lab. Patologia Clinics ~ H 9.Carlo (Pz)

N u c l e a r M e d i c i ~ e b e p t I a n ~ D e n t of C o m ~ u ted T o m o g r a p h y , Saint Savas'Bospita!~ 3reek Anticancec Institute, Athens.

THE USE OF FIVE DIFFERENT TUMOR MARKERS IN DIF[I RENTIATING BENIGN AND MALIGNANT PANCREATIC DISBJ 5E In an attempt to assess a better approach for early diagnosis of pancreatic cancer the diagnc stic effectiveness of the individual and combS ned use of tumor markers (CEA,TPA,CA 19-9,CA 50 and AFP) in patients with proven malignant and benign pancreatic disease was evaluated. Eighty-eight patients, 50 males-39 females, age( 20-85 years (13 cronic and 5 acute pancreatitis, B cysts and 68 carcinomas) were tested. All pts. were given clinical and histological (tumors) confirmation of the disease. The diagnostic sensitivity in identifyin E pan_ creatic cancer was greater for TPA (90.4%), CA 19-9 (76.9%) and CA 50 (88.8%) when c o m p ~ e d to that of CEA (57.5%) ~ d AFP (2.9%). The false positive results for CEA and AFP were 0%, for TPA 14.0%, for CA 5O A.7% and for CA 19-9 1.6%. The TPA has a hish incidence of positive outcomes in non-malignant pancreatic patholo~ieE (42.1%) compared to CA 19-9 (10%) and CA 50 (37.5%). Neither the association of CEA/CA 19-9 (84.6%~ nor that of CA 19-9/CA 50 (91.6%) and not even that of all the markers combined (87%) showed a significant increase in sensitivity when compared with the individual sensitivity oi CEA, CA 50 and CA 19-9. The overall results in dicate that CA 19-9 alone, or eventually associ ted with CA 50, assUre a high diagnostic effect veness in dia~osing pancreatic" cancer compara_ ble to that of a multiple association of markers

:A 1 9 - 9 S E R ~ M ! C O N C E N T B A T I O N S AND CT F!N)I~GS IN PATIENTS W~TH PANCREATIC CARCI~arbohydrate antigen ( C A ) 1 9 - 9 is a n e w :~or asscsiated a n t i , o n w h i c h c a n be ~ e t e o t e d by a m c n o c l c n a l antibody. ~hls p a p e r d e s c r i b e s the clinical useful Lness of =he m e a s u r e m e n t of C A 1 9 - 9 tuner m a r k e r c u n c e n t r a t i o n s in t h e diagno. sis o f p a n c r e a t i c carcinoma and discusses i t s r e l a t i o n w i t h t h e f i n d i n g s of CT axaminatlon~0 23 of 35 p a t i e n t s S u s p e c t e d ~for p a n o r a m i c : a r c i n ~ m A h a d ta p O ~ & t i v e hlstological examinaton. Al~ patients underwent CT examination a n d t h e s e r u m l e v e l of t h e 2A 1 9 - 9 a n t i g e n w a s m e a s u r e d b v t h e radlc ~&mu£oassay method (ZLSA C A 1 9 Z P , C I S ) . T h E u p p e r o u t o f f v a l u e of n o r m a l r a n g e w a s determined at 370/mi, 119 of 2 3 ( 8 3 % ) p a t i e n t s w i t h p a n c r e a t i c . c a r c i n o m a h a d a p o s i t i v e CE e x a m i n a t i o n and in 20/23(87%) t h e s e r u m .CA 1 9 - 9 l e v g W a s 3 7 0 / m i . T h r e e of t h e f o u r p a t i e n t s with negative CT examination had eleva~ tumor marker levels end all the three =atients with normal antigen values had positive C T s c a n n i n g . T h u s 22 of 23(96%1 atlents with pamcraatic carcinoma had i i t h e r t h e t w o (CT a n d t u m o r m a r k e r ) o r ane of t h e s e e x a m i n a t i o n s positive, [n c o n c l u s i o n the results indicate that 1)as a t ~ o r marker for pancreatic car = :inoma, the CA 19-9 has a quite hlghse~ sltivity (87%) c o m p a r a b l e to t h o s e b y C~ (83%) 2 } T h e c o m b i n a t i o n of t h e b w o e x a minations increases the diagnostic ac:uracy for the pancreatic carcinoma to )St,

~.Pilo,G,C.Zuech, elli,M.R.Chiesa, S.Mesini

CNR I n s t i t u t e of Clinical Physiology v i a S a u l 8~ 5 6 1 0 0 P I S A , I t a l y IMPROVEMENT OF THE B E T H E E N - L A B O R A T O R Y AGREEMENT OF C E A A S S A Y O B S E R V E D D U R I N G A C0LLABORATIVE STUDY.

S t a r t i n 9 From 1984~a natic, n a l i n t e r l a b o r a t o r y q u a l i t y c o n t r o l has been c a r r i e d o u t for CEA i m m u n o e s s a y ; 15-20 c o D t r o 1 s a m p l e s h a v e b e e n s e n t t o ca. iO0 p a r t i c i p a n t ~ in each control cycle (of approximately 6 months).The betweenlab a g r e e m e n t (total variability> estim a t e d as mean CV f r o m r e s u l t s of all QC s a m p l e s a s s a y e d in e a c h c ~ e l e w a s e x t r e mely high(54-i58%)at the begtnning(1984) decreased to 3 8 . 1 % a n d 3 5 , 6 % i n 1 9 8 5 and in 1 9 8 6 ; Jn the l a s t year a marked improvement(23,8%) has been observed, A N O V A a n a l y s i s of the t o t a l variability indicated that the b e t w e e n - k i t a n d the within-kit =omponents were 16.8% and 16.8% respeetiuel~ in 1 9 8 7 in c o m p a r i s o n to 30.5% and 10.4% in 1986;thus it is concluded that a better between-kit agreement is m a i n l y r e s p o n s i b l e for the d e c r e a s e of the total v a r i a b i l i t y . T h e same c o n c l u s i o n s c a n be d r o w n f r o m t h e kit biases(average % deviations from consensu~ mean)reported in the table: ............... 1987 .... 1 9 8 6 -n Blast n Bias% Satin IRMA 2~,2° + 1 9 , 0 287 +28.2 Abbott IRMA 65 + 9,7 79 +27.2 Behertnger EIA 118 + 8,5 . . . . Abbott EIA 159 + 4.7 87 +24,0 C i s IRMA 138 - g.4 60 - 5.8 Serono IRMA 238 -12.1 . . . . Radim RIA 60 -15.7 ~6 -23.3 8e~or, o R I A 184 -19.4 348 -18.7 E t k e n RIA 9 -70.8 68 -71.8

618 R.Novakovi£, Lj.Gli~id, J.hemberger, O.Frim, V.Katid. haboratory of Radioactive Isotopes in Medicine of Medica] Faculty in Belgrade Clinic of Gastroenterology and hepateiogy of Clinical Centre University of Belgrade THE SIMOUI!TANEOUS DETERMINATION OF SERUM PEPS~IO(3EN l, GAS]WIN A N D TUMOR MARKER CA 19-9 IN PRECANCEROUS lESIONS OF; THE STOMACH The aim." With the determination of the level serum Pepsinogen I and GastrJn the authors wanted b investigated the JocaHzation and stage of various types of chronic gastritis, but increased concentrations of tumor m a r k e r CA 19-9 should be useful for discovering of precancerous lesions of the stomach. Methods: In 560 patients with d i f f e r e n t types of chronic gastritis and gastric adenomas if was examined simultaneously ( R I A ) the level of serum Pepslnogen l (Sodn-Biomedica) Gastrin and CA 19-g ( O S X Summary of the ~ l t s : The mean values( + SD) of Pepsinogen I, Gastrin and CA ] 9 - g in control group were: log qg/m[, 80 pg/m[, 20 [J/ml,(No.6O). In Chronic superficia} gastritis: Pepsinogen 1, Gastric, CA 19-9 Fundus (No.165) 80 + ]2 140 + 20 36 + 4 Antrum(No.7O) 110 +- 15 120 + 16 54 + 8 In chronic atrofic gastritis: Fundus (No.75) 50 +- 5 220 + 25 40 + lO Antrum(No.45) 60 + lg 40 +- ]0 28 + In gastric adenoma Fundus(No,lO5) 50 + 6 IBO +- 20 ]45+- 15 Antrum(No.nO) 120+- ]4 36 + 6 190 -+ 20 In Pernicious anaemia (No.35) 20 + 5 520+-50 40-96va]. Conc]usisn:The comparative examination of Pepsihogan [ and Gastric is very useful test for d i f ferentiation of severe forms of chronic gastritis. Tumor m a r k e r CA 19-9 is of value in gastric adenomas and pernicious anaemia as a precancerous lesion.

6

326

621

620

619

D e ~ t s of Nuclear ~ d i c i n e (i) and O : ~ l O ~ , / " (2), ~ t ~ L~dvE£-sity F~3spital, B-2520 E d e ~ , Belgit~n

M~dical Centre at Subotica and Medical Faculty, University of Belgrade~Belgrade,Yu~slavia

A~%LYTIC~L C ~ A R I S ~ N OF TWO IMMUNORADIOF~-TR/C ASSA~/S FOR THE DEq~2~MLNATION OF CA 15.3 We investigated the analytical perfcyrmance of twodifferent kits for assay of (1% 15.3, based on an l~V~% m e t ~ l o g y : Ce~tocor C~ 15.3 l-adioinm~a~oassay and Else CA 15 3 CIS The two producers use the same two mcrnclcnal antib ~ e . s . The f i ! ~ ( ~ (115 D 8) W-as rB.ised Rgains% ant/gen of hun%gn milk,at globule r~rar~ and the s e c c ~ one (DF3) a g a / ~ a n e ~ e~iriched fraction of a h~nan breast -,~ir~. T ~ t-~ kits diffe~r Jn solid phase, standard range, sa~ling, /ncubaticn time, incubatic~ temperstu2e and washing

p=cedu~ Binding capacity was about two times higher ~Tith the CZS kit (lazger coated s u r f a c e , h i g h e z incubatlcn telloeratu~e ). This (~uld partly be the reasc~ of a sensit/vlty six times better than with the Cen%cccr kit. The WithnLn assay ~recision 9r~s oon~3arable for both kits. ~ay dr~ft towards lower oonce/%~-a~c~is, as dete~ed with c o n ~ I s at different places ir the r~n, was observed with the Centcc~r kit. ! The differences, seen with the CIS kit, axe most likely due to i~precision only.

~max. Stand./Total

detectic~ lim/t: mean S O + 2SD assay drift: after i00 tutus after 150 tubes after 200 tubes

GUILLET,

J .Lemher~er, S.Skenderovi6, T .T~r~k,E .Libman, B.Marton,S.Vo~ni6 snd R.Novakovi6

M. b~-tln I, P. Blockx I, D. Becquart 2 and A. ~ a n c ~ e n I

Centooor 5.2%

CIS i0.6%

0.59 U/el

0,09 U/nll

- 11% - 10% - 6%

+

-

9% 2% - 11%

M.

C. ROLE,

Biophysique, M4decine Nucldaire, UrologieCentre Hospitalier d'AGEN 47023 A O E N C 4 d e x F R A N C E PSA R A D I O I M M U N O A S S A Y . P R O S T A T I C C A N C E R ?.

C0~A2TSON OF DIAGNOSTIC USEFULP~SS OF CA-~o m CA 19-9 AND CEA IN EFFUSIONS I t is known that the determination of CA-5o, CA 19-9 and CEA in serum are of significance in detecting of malignant tumors s especially of ] d i ~ s t i w system~ This study wa~ carried out to Itest,whether this tumor markers in effusions could predict the primaz7 source of malignancy. l~ ~ b n ~-r~ - s ~ u l ~ - a r ~ - u - s - ~ = u ~ o ~ a - ~ m = e % ~ i c ~ssay of CA-~O,CA 19-9 a n d CEA in effusions of %3 patients with non-malignant diseases and in 52 patients with cancer of d i ~ s t i ~ system, ~vary,lung,breast and lymphoma. The upper range of normal values in the control Group were for CA-5o 16 U/ml(mean+2 SD), for CA 19-9 43 U/ml and for CEA 14 ng/ml. Pathological level of ~A-5o and CEA ~m~ registered in ~o%~ but CA 199 in 9~% of patients with malignancy. By simultaneous determination of CA 19-9 and C~A the diagnostic ser~itivity c~n be increased Eo 73%. The achieved results sho~;, that all 5 markers are produced by tumors within and vithcut the dig~stlve system, too. Through the e~-aluation cf results by sensitivity~speoificity diagram it .has been established that CA 19-9 has some favourable characteristics in relation to CEA ~ud CA-5o. In conclusion, CA 19-9 in effusions is a useful pam~meter in diagnosis of malignancy. IIo~v~r~ this marker is not characteristic for ~astrointestinal malignancy because is frequently produced by ovarian and in lesser extent by pu~nonary tumors, too.

FRANCOIS

SCREENING

FOR

PSA a high s e n s i t i v e p r o s t a t e t u m o r ass< c i a t e d m a r k e r , s e e m s to b e s u f f i c i e n t l y r e l i a b l e as a s c r e e n i n g test. M a t e r i a l and M e t h o d . 3 O O O p a t i e n t s w i t h c l i n i c a l p r o s t a t i c s y m p t o m s , a n d i o o o not u r o l o g i c a l i n p a t i e n t s o l d e r than 5 5 y r s w e r e t e s t e d w i t h Pros C h e c k PSA Yang?ravenol EIA kits. D i a g n o s i s was o b t a i ned from h i s t o l o g i c a l d a t a d i r e c t e d by ~SA results and o t h e r i n v e s t i g a t i o n s . lesults. All the s a m p l e s from the 387 ) r o s t a t i c c a n c e r patients b u t one h a d ~SA s e r u m l e v e l s > 2 , 5 n g / m l at d i a g n o s i s . ~he s p e c i f i c i t y and the p o s i t i v e prediclive v a l u e are b e t t e r , w i t h P S A > l O n g / m l Ln the 3000 p r o s t a t i c p a t i e n t s r e s p e c t i zely 98% and 7 7 % . I n the i c o n impatients, ~4 c a n c e r s w e r e d i s c o v e r e d . D i g i t a l rec:al e x a m i n a t i o n was not c o n s i s t a n t w i t h ~ r o s t a t i c c a n c e r in 7 of these p a t i e n t s . )iscussion. W h e n PSA i n c r e a s e s a b o v e LOng/ml c a n c e r risk has to be c o n s i d e r e d Ln p r o s t a t i c p a t i e n t s even if d i g i t a l rectal e x a m i n a t i o n e v o k e s b e n i g n prostatic h y p e r t r o p h y (3% of our p a t i e n t s ) , qhen PSA i n c r e a s e s a b o v e ~ O n g / m l , i n m e n 91der than 5 5 y r s of a g e , w e think that a zarefull m a n a g e m e n t w i t h at l e a s t d i g i tal r e c t a l and u l t r a s o n o g r a p h i c e x a m i n a tion m u s t be done. In all cases, h i s t o l o ~y does g i v e d i a g n o s i s . C o n c l u s i o n . PSA nay be c o n s i d e r e d as a s c r e e n i n g w a r n i n g test for p r o s t a t i c c a n c e r in m e n o l d e r than 55 y e a r s Of age, and in p r o s t a t i c patients.

These results suggest that on analytical ~nd practical g r ~ , the Else CA 15.3 kit is slightly superior to the C~_ntoo3r kit (especially fo~ sensitivity and ~ssay drift).

622 ~!l~-~"

MATRIEU E.

;23

624

C. de L~ F~ts. JmJ.L. Cordovil]a, J.l. ~ n z ~ , V. L l o z ~

IF~ F a l c o n s ,

C. Arnal and J.M. Carril.

p.

Lagarta

Centre Hospl~elier de C o r b e i l E s s o n n e s - 91108 CORBEIL ES$0NNES - S e r v i c e de MSdecine N u c l ~ a i re.

SERUM dONE GLA

PROTEIN ( S B G P ) AND PHILlC TUMORS'S METASTASES.

OSTEO

SBGP or o s t e o c a l c i n is a v l t a m i n e K depen* den~ protein, synthetized by osteoblasts and mesured I n serum by RIA ( O r l s Industry). All metastatic process i n bone w i l l result in o s t e o ¢ l a s t J c resorption f o r with hypercalcemia is the more Irequent signal, 'sire examined 145 patients coming lfn or bone s c i n t l g r a p h y even i s o l a t e d for metasatic evaluation o f p r i m a r y tumor o r s e v e r a l times repeated In view t o evaluate the respon= i v e n e s s of m e t a s t a s e s after chimio e n d / o r radiotherapy. We've compared this group (60 females underdolng breast cancer, 62 males undergoing prostatic cancer) with an o t h e r group coming in f o r a bone's s c i n t i graphic exgloration in view to evaluete metastatic evolution of lung cancer (11 bronchial c a r c i n o m a and ]2 small cell e p i t h e lioma). Results are p r e s e n t e d slmultsneous = l y with o t h e r tumor markers (CA l d . 3 , CA 125, CA 1 9 . g . TPA ; PdA, PAP, TPA ; $CO, MSE, N e e p t e r i n and TPA r e s p e c t i v e l y ) . This study allows te conclude that : I) petlents undergoing arthrosi¢ lesions ave normal SBGP. with regards to t h e age h 2) patients undergoing a ~etesta¢lc process in hone have a l o v e r SBGP (inversely :orrelated . t t h TPA in b r e a s t c a n c e r } ; 31 patients who present smaller and/or less dense metastatic image after chimio end/or radiotherapy have h i g h e r SgGP ( i n v e r sely correlated w i t h TPA in b r e a s t cancer)

4)

patients

with

metastases elsewhere (cerebral or h e p a t i c } lJka

than in bona wlth patients undergoing lung cancer have • normal SBGP. Thus SBGP seems to be a h i g h p e r f o r m a n c e B a r k e r of bone m e t a s t a t i c process end a l s o o f m e t a s t a s e ' s recovery,

S~"v~cin de M e d t ~ Nut/mr. }bspir~lN~.IS.~IValdec:L!.l~ Catedra de R ~ o l o ~ y ~ i c J ~ Fislca. bhisersidadde Can tabr~. S A ~ . ~PA~.

Pneumological Division, Palagl 9, 1 - 4 0 1 3 8

Bologna,

P,Y (GS) A ~ X ray ~ SA~Dinu~IS. It Pes bee~ woved tlmt S ~ are i n c r ~ in thee8 I~U~in ~licJ~ e~ist callula~ ir~mn~ityalterat£oa. On basis, ~ have s t ~ its m]e as activity marker ir Sarc~idesis(~a) by correlanmg its levels with two i q ~ techniques: on~ mmj~,otosi~, ~ ~ ( ~ ) and t.~ other mm-ker of activity, GS. ham hem mmsm-ed by RIA,in 22 p~tientswith Se,ag~ frun ~9 to 60(m~n 42),and in a o ~ i u ~ l g r o ~ of 21 h~ith~ eople.ln tota~,~e have Eat 26 ~ from 20 patients in d i f f e r ~ c ~ and wir~ d ~ f f ~ t GS f/ndinBs.(~

THE CEA CRITERION

IN PLEURAL EFFUSIONS

26 cases.9 ~

~

t o he i n ~

0.6 c.~ses i n l ; ~

1.2 in ~ 2 and 9 in RS 3. IL=pa~hn~ on GS d ~ f ~ ~ere dls~rlbubsd:lO with normal ~ m m ~ ( h ~ ) , with

~

4 with ~

uptake(~),6

vlth

a~d ~

~pt~e(~:'J).

pulmo~zy uptakeO°[l)

arz

~ ~ coatz'ol group ~ 2.3 4 - 1.2 rmml/l, a~ i n group of ~ t i s n t s with Sa ~ e 7 + - 3.5 nmol/L (I

0.C01). D e p ~ on ~S, mere ~ ~ere: RS O: 5.3 + 2.1 mmi/L. RS I: 6.7 + - 3.5 mml/L. RS 2:7.5 + nmol/L. RS 3:9.3 + - 4.5 nmol/L. D e ~ cm GS flndings msm ~ ~ere: N~: 6.3 + - 3.7 nmol/L. ~ : 8 + - 3.1 nmol/L. Pal: 8 + - 4 mmml/L. ~d: 5.8 + - 3.5 nr~l/L. I f all with ~ t h e l o ~ GS f i ~ ~ere co,sldered, m ~ ~ ~ 7.5 + - 3.6 .m~i/L. ~ s ~ remlts shaw a ~ro~ssi~ i.m-mse of ~ ~ wi~ ~-e ~S, ~/theugh the ~nly sign~fi~ differare fo~ is betws~ RS 0 and RS 3. If m~n ~ is ~roups with diffs re~t GS findings are cuagsred, no S i ~ i c ~ t dlferem~ is found, neither b e r n d/ffmmmt scinti~raphlcgroups ,or ,meal ~ pa~loglcal GS f l r ~ groups. Fru, ~ e results we canclude: - ~ e r e i s a s r ~ : i s t i c ~ / y si~d~icant ~ ~ in patient vi~h Sa ~hea c o m p ~ ~o hml~hy people. - ~ is cucrelar/un ~ S% ~.- ~ is not ~ - ] a t i ~ p betwsm~ S~L end GS f ~ . This could be d~e to the different a c t i v i t y m c h a d ~ s that they repmsmt. Altheush few ca~s m-e studied, thee faults desm-~ ~=p~= m ~ fmT/*~ evalua~len.

In neoplastic

pleural

Halpighi H o s p i t a l , Italy.

effusion=

of

lung cancer

we observed generally that pleural level of CEA (PL) was >7.5 nglml (Kit Abbott) and the ratio between pleural and blood level (PLIpl) was d2Aim o f

o u r s t u d y was t h e c o m p a r i s o n b e t w e e n t h e o f t h i s CEA c r i t e r i o n (C-CEA: P L > 7 . 5 and PLIp1)2) in pleural effusion of untreated lung cancer and in effusions observed in the follow up of brest cancer after surgical =reatment. RATBRIAL AND METHODS - B o t h cytological examin~ t i o n and C-CEA were i n v e s t i g a t e d in 65 pleural exudative effusions : 22 occurred i n untreated lung cancer. 2O occurred after surgical treatm e n t o f b r e s t c a n o e r (mean t 1 + / - 6 m o n t h s ) ; 2 3 non neoplastic effusions ~ere control subjects. The diagnosis o f e f f u s i o n s was carried out by Cytology, ~horacosvopy o r surglcal e x a m i n a t i o n . RESULTS - All effusions during lung cancer were recurrencles and 12120 had neoplastic oFtology; 20•22 effusions in brest cancer were neoplastic result

with 14/20 neoplastic cytology; all benign e£f~ s t o n e had normal c y t o l o g y ~ h i l e one c a s e o f TBC had C-CEA p o s i t i v e (PL 1 B . 6 , p l 3 , P L / p I 6 , 2 ) , T a b l e I ~hows d i a g n o s t i c accuracy of cytology,

IC-CEA and combined results of both examination. ~ ~ E ~ cytology C-CEA ¢ombined

65 c a s e s 78.5~ 73.8B 86,1~

22 l u n g c . 45.5~ 45.5S 72.7~

20 b r e s t c . EO.O~ 70.ON 90.01

C-CEA in non neoplastic 76.9~ cytology CONCLUSIONS - C-CEA a p p e a r

40.0~ useful

66.7~

in diagnostic bhase of neoplastic pleural effusions both i n ~resence o f primary l u n g c a n c e r and i n case o f •e c u r r e n c i e s during follow up in subjects after surgical remora] of b r e s t c a n c e r .

327 627

626

625 Kanitz r W., M~ller, R., Heiaenreich, P.

~+ P.BARI~STEIN, U.TABORSKI, I . B ~ ,

*

+ N.MULLER

* KLINIK u, POLIKLINIK f. NUKLKABMEDIZIN, Institute of Nuclear M~icine Zentralklin/Jr~nAugsburg, FRG IS THE DETERMINATION OF HTG BY I R Y ~ % - ~ I Q U E SUP~IOR TO R I A - ~ I Q U E ?

The determination of circulating HTG is of high clinical value in the follow-up of patients with differentiated thyroid carcinoma. We cat,pared the values of Ser~-HTG measured by a double-antibody RIA (Menning) to those of an IP~A (Sorin-Bic~ica), expecting higher sensitivity with the IRMA. The study includes 134 HTG determinations out of 48 patients with differentiated thyroid carcinoma. The results were correlated to the actual clinical findings. Endogenous TGantibodies were determined by RIA and/or Hoyden-test. 26 athyroidpatients without metastases showed no HTG elevation both by IRMA andRIA. 13 patients with proven metestases were all correctly determined by IRMA, whereas in 2 of these patients the RIA failed. The other Ii patients showed IP4~-values 3 to 5 times higher than RIA-values. The IR~Aalso showed significantly higher values in 6 patients with residual thyroid tissue before ablative J-13l-therapy. In 3 patients (all without m~tasteses] with proven endogenous TG-antibodies the IRMA was not affected. In contrary the RIA in 2 cases showed falsely elevated HTG-values; the recovery however was poor only in one case. The clinical value of 2 "falsely" elevated IRF~-determinations has yet to be proved. In concluszon, the HTG-determinationby IP~4A-technzque is of higher sensitivity and specifity cca~aredtoRIA-technique and seems not t o b e affected by endogenous TGantibodies.

J.

NIKOLA

IBDICAL CENTRE "DR T R I F U N PANOSKI" DEPARTM'~T FOR N U C L E A R M E D I C I N E WITH CLINICAL PHYSIOLOGY BITOLA, MACEDONIA, S.F.R. Y U G O S L A V I A

Department of Nuclear Medielne and i) Department of Endocrinology, University Hospital Rebro, Zagre5, Yugoslavia

UNIVERS IT~TSKLIN Ig MONSTE~ BEI~R QUALITY OFWHITE BLOOD CELL SCAN IN PROBI~ CASES BY SEPARATING THE GRANI~yTES WII~CELLSEPARATOR IN patients with severe anemia or granulocytopanda eonventional preparation techniques are not able to extract a sufficient n~mber of granulocytes, to ensure a satisfying sensitivity of the method. We helieve that the application of heterologous labeled granulocyt@sis not justifiable because of the relevant infection risk. In severe anemia the extraction o~ granulocytes from whole blood will increase the current anemia. All methods working with density gradient centrifugation have the risk of sensibilisation against the necessarely needed substances. An alternative method is the gaining of granulo cytes with the cellseparator. The advantages of this method are: little loss of erythrocytes, higher yield of granuloeytes~ higher sensitivity of this technique because of highly purified granulccyte-preparation (>90% granulocytes), with the ability to migrate and chemotaxis unal toted. With this technique (granulocytes labelled with indium-lll-oxine) we examined 12 patients, subdivided in 3 diagnostical groups: localisation of diseased bowel segments and grading of activity in Crohns disease (n=5), proof or exclusion of osteomyelitis in cases of positive findings in skeleton scintigraphy (n=3), search of a focus in unclarified inflammatory disease (n=4) Results: 7 true positive, 4 true negative, I case false negative. Our present experiences reveal that the cellseparation, which was well tolerated by all patients, is a suitable technique for the im)rove~ent of scan-quality in problem cases.

629

628 KOSTURSKI

+ INSTITUT f. TRANSFUSIONSMEDIZIN~

V.lvan£evid, E. Kora~ Z. Ma~trovi6, Z. Ku§ter, D. IvanEevid

].Th. Locher and K. Seybo]d

Department of Nuclear Medicine ~antonsspital Aarau (Switzerland)

L A B E L L I N G OF L E U K O C Y T E S ~ T H DTPA-Tc99 A CO[KBINED IN V I V O - I N VITRO T ~ C H N I Q U ~

EFFORTS FOR OPTIMIZING IMMUNOSCINTIGRAPHYWITH LABELED MONOCLONALANTIGRANULOCYTEANTIBODIES.

It is the aim of the p a p e r to show the t e c h n i q u e for l a b e l l i n g of leukocy tes with D T P A - T c 9 9 m , w h i c h we used for v i s u a l i s a t i o n of abscesses in men. The p a t i e n t is given DTPA 0,5ml i.v. and 30 m i n u t e s after that 16ml of blest with ~ml ACD is taken from the vein and ft is put in a s~rile p I a s t i c test-tabs. The b l o o d is added 5ml H e m a c e l and the t e s t = t u b e is put in a v e r t i c a l pos i t i o n for one h o u r on a r o o m t e m p e r a ture for i s o l a t i o n of p l a s m a rich with l e u k o c y t e s and trombocites. The leukocytas were i s o l a t e d from the f r o m % c o y tea by c e n t r i f u g i n g 15OG, l0 minutes while the s u p e r n a t a n t is i s o l a t e d and the d e p o s i t e d l e u k o c y t e s is added 570 MBq T c 9 9 m and it is i n c u b a t e d 50 minutes on a r o o m temperature. The u n b o u n d T c 9 9 m is i s o l a t e d by on~ w a s h i n g of the leukoeytes w i t h 20 ml H e m a c e l by c e n t r i f u g i n g of 15OG, lO minutes. The l a b e l l e d l e u k o c y t e s are res u s p e n s e d in 1 ml H e m a c e l and are rein e c t i o n e d on the patient intra venous. The u p t a k e of the T c 9 9 m in the leuk o a y t e s is 15% or 55 MBq. S c i n t i g r a m of abscess of a knee is done 50-60 minutes after r e i n e e t i o n of the labelled l e u k o c y t e s and a good v i s u a l i s a t i o n of the abscess is registred. The m e t e d for l a b e l l i n g the leukocytes is very fast. We. w o r k e d c o m b i n e d in vivo and in vitro with a small v o l u me of blood. The uptake of the T c 9 9 m in the l e u k o c y t e s is good and stable and good r e s u l t s for v i s u a l i s a t i o n can he obtained.

During the past two years we have reported our experiences with 1-123 anti-CEA monoclonal antibody (Mab) and have recently published the l a test results of physiological and c l i n i c a l testings (Eur J Nucl Med 13, 1988). We hBve demonstrated that the method obviates Lhe need for cell i s o l a t i o n by d i r e c t i n t r a venous i n j e c t i o n of the tracer and allows the detection of infectious lesions by planar scintigraphy and/or by SPECT, We have also shown, that the agent does not influence the v i a b i l i t y and the physiological properties of the in vivo labeled leucocytes, which is also true f o r new preparations including Tc-g9m labeling, that is reported in this study. Our experiences include more than 100 studies and many examinations wit~ double isotope techniques (In-111). Compared with other scanning methods the diagnostical s u p e r i o r i t y of Mob scanning was obvious, espec i a l l y f o r the detection of low grade infection. In addition to the e f f o r t s made f o r improving the diagnostical techniques we studied the long. term inmunoreaetion of the patients (pts) having undergone single or repeated immunoscintignaphy. IgG and IgM serum levels remained eitheT negative or unchanged when tested with human antimouse antibodies (HAMA) in 30 pts. In 3 pts with p o s i t i v e HAMAfactors prescan Mob's were found together with very high levels of rheumatoid immunoglobulins. We, therefore, conclude that the Mob-amount injected is not e f f e c t i v e enough f o r a c l i n i c a l l y relevant immunisation of pts.

ECT AND 99m-Tc-HM-PAO LABELLED LEUCOCYTES IN EVALUATION OF CROHN'S DISEASE Since its introduction as a leucocyte labelling agent several authors evaluated 99m-Tchexamethylpropylene amine oxime (HM-PAO) in imaging abdominal inflammatory disease, mostly using planar scintigraphy. In our study we prospectively investigated the possible role of ECT in an imaging protocol to assess actdvlty and localization of Crohn's disease. In ii patients.with k n o ~ Crohn's disease we performed 99m-Tc-HM-PA0 labelling of a mixed leucocyte suspension obtained after gravity sedimentation of 45 ml of venous blood in 6% dextrane (1:6) and ACD (!:io). Static imaging was performed 3o-6o min, 3-4 h and 2o-23 h after injection of the labelled cells. Rotational tomography of the abdomen was done 2-4 h after injection with a twoheaded Siemens Rote camera. In some patients dynamic imaging of chest, liver and spleen was carried out i[maediately after injection. In most of the patients inflammatory lesions already showed after 3o-6o min, being more clearly visible after 3-4 h. ECT proved valuable in delimitating pathologlcal food from transported gut activity and from superpositioT of intestinal loops over each other and other tissues. We agree with some authors that late scanning after 20-23 h is hampered by unspecific intestinal activity and long recording times. ECT is superior to planar scintigraphy in distinguishing pathological from non pathological activities in the abdomen. Static planar imaging, however, offers the possibility of a short term follow-up of abdominal activity. In conclusion, ECT in addition to planar scintigraphy represents an optimized protocol for the detection of inflammatory loci in Crohn's disease.

630 C. Palestro, L. Needle, D. F ~ S. Vallahhajosula, S. J. Goldmuith Mz~mnt sinai School of Medicine New York, NY, USA

INDIUM WBC IMAGING: EFFECT OF ANTIBIOTIC TH~APY AND DURATION OF SYMPTC~IS 90 patients (pts) not suspected of AIDS, with rJO (boO7 ~ 3~ c, wBc >2000/~m) und~t In-lll oxine labeled autolcgc~s let~ocyte scintigralgny (In-WBC) 24 hours after the injection of labeled cells. Final diagnosis were confirmed surgically (7 pts) , histologically (20 pts), C&S (17 pts), and positive blood culture plus other imaging modalities (4 pts). 52 infectious foci were identified by all methods in 49 pts. In-WBC identified 39 of the 52; there were 13 false negatives; overall sensitivity (by site) was 75%; specificity 70%. Rx and duration of fever in daN (d) influenced results as follows: ~x (-) ~X (+] 0-20 d >21 d 0-20 d >2ld True (+) 9 2 17 ii F a l ~ (-) 2 0 g g True (-) 7 8 8 7 False (+] 1 2 5 3 sensitivity 82% 100% 85% 50% Specificity 88% 80% 62% 70% Ehe specificity in pts on Nx is lower, regardless of durmtion of s y ~ , suggesting that s~me false positives are antibiotic r~lat~i. Sensitivity is,,especially diminished in pts c~ Rx with symptoms >, 21 days alTmhough In-WEC is a valuable diagnostic tool, its utility is dependent upon duration of s y ~ and Rx and neqative results in this population should be interpreted with this caveat.

328 131 8.D.AksiJI.$.A.Ram, LA. Trembeth,B.D.Collier,C.F.Bekdik

Departments of Nuclear Medicine at H~ttepe University, Medical School, Ankara,Turkey and Me:Iical College OF Wisconsin Milwaukee, Wl, USA.

EVALUATIONOF LEUKOCYTELABELIN@WITH ggmTc-HMPAOFOR DETECTIONOF AB,SCE,~E$

Reqtonuclide imping For detection and lecaIlzDtion of abe~eeses developed in the Ig7Os. Recently,it has been rePOrtedthat new brain ~gent,99mTo-Hexemethyl propylene ,amine oxime (d,l HMPAO) has the potentialto Su~fully labelleukocytee. IR this study, we triedto rim,elope RSmToHMPAO labeledlegkocyteefor detectionof abeceeees.A canine meqel was cbesen to stu~ the labeling parameters. Leukasytee were berveeted by sedimentation of red blood ~lls (RBC), low speed ~ntrifugation,short time hemolysis techniqueto remove RBCs from leukocytefr~tion. The kits containing 0.5ms HMPAO, 7.6ms ef $n812. 2H20 were reconstituted with 30 mCi in 5 ml of ggrnTcOA purged with nitrogen. ITLC analysis shewed that kits contained 85 to 92% Iipophiltofrestion. Leuk~/tes (2-5x10 B calls) were incubated with tO -12 mCi of freshly prepared ggmTeHMPAOin 2 ml volume for 15 rain.The labeling efficiency of 1 I samples was 06.2 ± 3.7% and the viability of the labeled cells wee about 90% using the trypen blue test. The b]ecd radicactivity over 24 h petted end analysisof these eatableS showed two componenIs with half ]1gee 1 and 6-8 h respectively. The 20 h wbelebeqy Image was Found to be similar in biedistrlbutton to Illln-Oxine labeled leukecylee visualizing spleen, liver, bode marrow end bladder.No siginlficantastiviti~were Found in lung~and G-I tract.The time requiredfor lhe whole procedure in each c~se was lessthan two hours.

634 Heusegger K., F. FlOckiger and G.F. Fueger

)iv. of Nuclear Medicine, Dept. of Radiology, University Hospital, Braz, Austria

THE SIGNIFICANCE OF 99m-Tc-HSA-NANOCOLLOID SCINTIGRAPHY IN THE EVALUATION OF CHRONIC OSTEOMYELITIS Our study examined the relationsship of SBm-Tc Nanoeolloid (NNC) Scintigraphy'to MOP scintigraphy i n the evaluation of the activity of chronic osheomyelitis (CO) in 38 patients with that proven clinical diagnosis. The findings of dynamic and static (30 min) NNC scintigrephy were related to those of 3-phase 99m-Tc MOP bone scans and, if available, those of In-liiWBC scintigraphy. In the diagnosis of CO O-phase MOP bone scans displayed a sensitivity of 92 % and specificity of 50 %, whereas NNC scintigraphy reached a sensitivity of 83 % and a specificity of 85 %. The highest sensitivity in the diagnosis of active CO was accomplished by In-III-WBC scinhigraphy (i00 %), albeit at much greater technical difficulty and time consumption. Both, MOP scintigraphy and NNC scintigraphy, showed pathologic focal tracer accumulation and hyperperfusion in the location of active flare-up in 86 % of the cases. These cases were considered typical of florida CO, in which NNC scintigraphy added no further information. On the other hand, NNC scintigraphy was definitely needed in the differentiation between reactively increased bone turn-over (e.g. adjacent to soft tissue infections) and manifest bone infection; the lack of osseous NNC deposition ruled out bone infection. In some cases it was difficult tO differentiate between pathological osseous NNC deposition and normal bone marrow activity especially in long bones. 3-phase MOP bone scans remained the basic examination in the evaluation of chronic osteomyelitis, in cases of questionable focal flareup, NNC scinti9raphy (inclusive of radionuclide angiography ) was needed to establish the diaQnosis of active C0.

632

633 N.Ariano~ L.L~mberti, F.Dutto, and F,Cottino

Fortunate J S, Pinheiro M J, Nodrigues M A., Faria R A, Amaral I.

§z~f@~9, P.Bigatti

Centre de Fisiologia da Hemostase (INIC) Dpts of Phys±ology and Nuclear Medielne. Oporto Medical School. 4200 Porto Portugal

Nuclear Medicine Service Ospedale Maurizlano di Torino Animal Biology Dept,, Ue|verslty of Turin Torino ( I t a l y )

LEUCOKINETICS IN DOG HIPOTHERMIA. SPLENIC POOLING AND PARTIAL RECOVERY OF CIRCULATING LEUCOCYTES AFTER REWARMING. Autoloqous lllIn-labaled NBC were injected in the upper abdominal aorta in lO normal dogs (group I). The animals were cooled to 22~0 i n iced water and a f t e r rewarmed to 36~ C. In a second group lilIn-WBC were injected again at 22 ° C of esophggeal temperature and then rawarmad to 36~C. Radioactivity and WBC in blood samples were counted in vitro and changes oF lli-wBC fracti, hal distribution ware evaluated by dynamic study in a computer-assisted Gamma-camera. During cooling WBC decreased 77% and reeovere( Sl% during; lllIn-WBC decreased 4S~6 and recovered 3A~ in the same periods. Liver was responsible for 54~ oF WBC sequestration an for B7% oF hotel mobillzation in group I, whereas in the group IT 51~ were sequestrated and 96% of the total were mobilized by the liver. Seventy percent of mobilized WBC accounted for the circulating pool increase in both groups; in group IT no significant pulmonary sequestration occured and splenic accumulation was sixfold than that observed in group I.

CHROMOSOME RBERRATION FREUUENEY, CELLULAR IKINETICS AND SISTER CHRONATID EXCHANOED IN HUMAN LYMPHOCYTE CULTURES TREATED WITH 131 I .

The present study i n v e s t i g a t e s the in v i t r o e f f e c t Df i r r a d i a t i o n by I 3 1 1 ( l . e By) on humin lymphocyte c u l t u r e s and discusse~ the resu/tm in the l i g h t Qf previou~ work, Our data show e significant increase either in total chtomosom~ aberratimn~ and in the number of c e l l s with chromosome aberrations (From I.DX to b.l% and ~r~m I.D% to 5,2% respectively). Thi~ increase is mainly due to isochromatid break~ and a c e n t r i c fragments. No dicentric chromosome ~ere found in the c o n t r o l s ~ h i l e three samples mho~ed one d i c e n l r i c chromosome a f t e r the ISl irradiatibn. A Two Way Anova o~ s~eter chrmmatid e~chanqe frequency

showed that there was no effect to i~dine expomure, Finally, after the treatment an increase of Cells which have undergone three or ~ore cyc~e~ of division Was

linked

observed even though this increase was not 6.6;

statieticalIy ~iqnificant ( chi-sq, = d , f , = 2; p 0 . 0 5 level = b,~},

We ~ c o n e l u d e that in spite of the reversion of hepatic sequestration a secondary splenic pooling avoids a complete recovery of WBC eounb after rewarming.

635 I. Zanzi, L. Attas, S. Kroop, V. Vinciguerra, J. Marlno, W. Robeson, and D. Margouleff. Depts. of Medicine and Radiology, North Shore University Hospital and Cornell University Medical College, Manhasset, New York, USA.

GALGIUM-67 SPECT A~D PLANAR IM~_~S OF THE IN PATIenTS WITH LYMPHOMA. A s p art of a prospective trial, 17 consecutive patients (pts) with Hodgkin's Disease (~) (26 scans) and 11 pts with non-Hodg~in's lymphama (NHL) (12 scans) were studied. Of these pts, scintigraphies were obtained pre-therapy in 13 PD and in B NKL pts. Most of the pts received a dose of 10 mCi of Ga-67 citrate followed by both early and delayed planar v i e ~ and SPHCT images at 48 to 72 hours. The tomographic studies were acquired every 6 ° over 360 ° . Both planar and SPELT images were graded I-5 (low to high probability) and compared independently of each other. Site to site comparisons of Ga-67 ald CT chest abnormalities were made using CT as a standard. Results revealed that differentiation of sites of abnormalities between hila and m e d i a s t i n ~ w a s difficult by Ga-67 even using SPECr. In pre-therapyHD pts, overall SPECT sensitivity was O .71 and specificity O .29. H e n differentiation between mediastinal and hilar localization was not attempted, SPECT revealed a sensitivity of 0.79 and a sl~ificity of 0.67 (corresponding values for planar l~c-~es, 0.71 and 0.33; 0.69 and 1.0). Of 36 abnormalities detected by SPECT, 9 w~re not evident in the planar views. A S P E C T also resulted in the upstaging of I pt with NHL f r ~ IA to IIA. Statistical analysis was only performed in pre-therapypatients because extended follow-up is needed to ascertaln if regions positive by CT criteria but negative by Ga-67 SPECr correspond to disease, infection, or fibrosis in post-therapy patients. Overall, our ex~rieece suggests that SPECT oompl~ents and moderately improves the evaluation of pts with lymph~ma as compared to planar images alone.

636 M.A. Antar, R.A. Rembish, R. Engelman, H. 0tani, R, Clement, S. Hoory, D. Bandyopadhyay and D.K. Das. V.A. Medical Center, Newington, CT and Univ. of Conn. Health Center, Earmington, CT, U.S,A,

SCINTIGRAPHIC EVA~UATION OF EFFECT OF MYOCARDIA$ INFARCTION ~LND REPEKFUSION ON REGIONAL MYOCARDIAL INFLUE OF In-IlI-NEUTROPHfLS. Oxygen free radical production is postulated to be a major mechanism of reperfusion myocardial injury and neutrophils have been implicated in this free radical production due to lysosomal activation. We used an isolated, in-vivo pig heart model to evaluate ln-lll labeled neutrophils influx after myocardial infarction (MI) and reperfusion. This was performed with or without pretreatment with ibuprofen, a non-steroidal anti-inflamatory agent. Eleven hearts (D control, E ibuprofen) were subjected to 60 min normothermic reperfusion after LAD occlusion (60 min), (to imitate surgical revascularization post MI.) The experimental group received 50 pMibuprofen prior to LAD occlusion, 120-130 ~Ci of In-ill labeled polymorphonuelear leukocytes (PMNs) were injected into the circulation at the start of the reperfusion. Galena camera scintigraphs and analyses of regions of interest were performed. Experimental hearts showed higher concentration of In-Ill labeled neutrophils in the regions supplied by LAD compared to the well perfused areas (2-4 times those normal areas). In contrast, after ibuprofen, there was global inhibition of PMNs influx in the LAD regions. Ratio of mean activity of control to ibuprofen treated plgs was 100:31; P < 0.001. Thus, the scintigraphs showed relatively homogeneous distribution of activity. But, there was no reduction of reperfusion injury as detectedby biochemical analyses. The findings suggest that this noninvasive modality can be useful in evaluating in-vivo changes in neutrophils influx and monitoring the effect of drug therapy (ibuprofen) on their influx after Ml.

329 639

638

637 I C OONMEHL, J P Pretorbus, N Burow~ M Maree, D Hugo, C Hordijk and g Beverley.

AEC Institute of Life Sciences, Universlty of Pretoria, PRETORIA, South Africa.

A.C. Tweddel, W, Martin, E. Winslow, E. Barton, R. Mason, I. McGhie, R. Marshall, I. Hutton

University Department of Medical Cardiology, Royal Infirmary, and Organon Laboratories, Glasgow, Scotland

CARDIACFDNCTIONCHANGESMONITOREDBY RADIONUCLIOEVENTBICULOGBkPHYIN THE BABOONMODELDUOIMON~TIC gNOCK. Nen-invasive radionuclidB techniques with ~mTc-labelled red blood cells were used t0 establish the nature and extent of changes in cardiac volumes, cardiac output (COr) end left ventricular ejection fraction (LVEF) occurring with the b~boen mode~ in septic shock after an i,v. infusion of E.co11. End-diastolic and end-systollc volumes (EDV, ESV) and stroke volume (SV) were measured hourly for 10 hours with the baboons (n=8) in septic shock and under pentobarbitone anaesthesia, fho changes with time in these parameters were compared between the group of B baboons in shock and another group of 6 baboons (controls) similarly anaesthetisad but not in shock. The time of onset, the duration and the extent of the shockinduced changes with respect to the control v~lues were noted. From the table i t is clear that large changes occurred for the average cardiac volumes, and cardiac outpots by radlonuclldeand thermodilutlon techniques (CO and COth). Heart rates (HR) and LVEF increased dramatitally. These changes were all slonifioantly larger than any which occurred for the control baboons. All the parameters except HR and SV had returned to normal values by the end of the study. The investigation continues to explore reasons for the volume losses and subsequentreturn to what seems to he normal. Table Time interval of signifiE~tent (%) Parameter cant changes sLarblng at of maximum hour k to hour B. changes A(hr) B(hr) HR 3 10 ---> +45 Egg 2 9 -5? ESV 2 8 -75 SV 5 HO ---~ -33 COr 2 6 +~7 COth 2 3 *29 LVEF 3 6 +64 Arrow (--'>) indicates HH and SV values had not returned ~p normal by the lOth hour.

MYOCARDIAL PERFUSION PATTEP~NS FOLLOWING INFARCTION IN RATS

640

641

Ligation of the left anterior descending (LAD) artery in the rat is commonly used as a model for human myocardial infarction. This produces reproducible infarcts and these are thought not to be supplied by a substantial collateral flow. In 20 rats, the LAD was ligated and Cobalt 57 microspheres were injected via the carotid artery prior ha sacrifice at 6-36 hours. The hearts were extracted and immediately infused with triphenyl-tetrazolium chloride, then fixed in formalin. In sham operated rats (n - 2) the left ventricular myocardium was divided into two and the flow was fairly equal (1.3 ± 0.15% anterior/post wall). Flow distribution was imaged by opening the heart and laying the ventricle flat on a Gamma camera. This allows quantitation of regional flow by regions of interest techniques. In addition, samples were counted in a standard Gamma counter and result~ from the two techniques correlated well. The ratio of flow in infarcted to non-infarcted myocardium, from the Cobalt 57 microspheres was similar at each time point - at 6 hou~s 0.38 ± 0.04%, n = 4; at 12 hours 0.33 ± 0.07%, n = 5; at 24 hours 0.22 ± 0.05%, n = 4; and at 36 hours 0.34 ± 0.09%, n = 5. These results suggest that there continues to be significant blood flow to infarcted myocardium, presumably either from collaterals within the myocardium or from extra-myocardial sources and this is established by six hours post infarct.

K. Scheidhauer, G. Leinsinger, C.M. Kitsch, and E. Maser

Departments of Radiology hadern) and Dermatology University of Munich, FRG

De H a r o , J ~ G a . S u a r e z , M ; A . A l h a m b r a j C ; R a mos3J~Calvo,C;Encinas,JL~Ortiz Berrocal

Nuclear Medicine Dept.A~d Istituto logico Romagnolo"N.Bufalini"Hospital

(Elinikum

Gross-

DETECTION OF INTEANSIT- AND LYMPMNODEMETASTASES IN MALIGNANT MELANOMA USING 99M-TOLABELED FIAB')2-ANTI MELANOMA ANTIBODY 225.285

Since the prognosis of malignant melanoma (MY) is stage-depesdent, early diagnosls of MM is essential. The alm of this study was to evaluate immunoscintigraphy (IS) as a diagnostic tool using 99m-To labeled F(ab')2 fragments of the monoclonal antibody 225.28S directed against the high-molecular weight, melanoma associated antigen. 75 patients with history of ~M, and suspected to suffer from lymph~odeor subcutaneous in-tramsit- metastases were studied (lesions' size: 0.5 to 10 cm, mean: 2.9 cm). IS was performed 6 to 24 hours after i.v. injectio~ Of 0.3 mg protein of the IgG-ga monoclonal antibody 225,285 labeled with 400 to 1O0O MBg 99m-To. The a~tihody was availahle as a ready-to-use kit. Scans were taken in planar mode and/or by SPECT using a rotating single head gamma camera, and evaluated by two unbiased observers. IS results were correlated to the histological diagnosis after surgical removement: In 59/75 lesions, ~ was histologically confirmed. IS detected 45 lesions (16 %)- Axillary lymphnodes and in-transit lesions (n=34) were detected hy both, planar IS and SPECT (26/34); in the area of the groin, SPECT detected 19/25 lesions (76 ~), planar scans only 14/25 lesions (56 %). In the 16 non-MY lesions, IS gave 1 false positive result, In contrary to the axillary lesions, SPECT improves the sensitivity of IS in the groin (76 % vs. 56 %). With a sensitivity o~ 76 ~, IS can Be recommended as a follow-up tool in MM patients after primary therapy and with suspicion off lymphnodeor intransit- metastases.

Clinica

M.I.F~zy, r~si,

Puerta

de H i e r r o . M a d r i d . S p a i n

for

Radioimmunodetection

of

eye melanomas.

Radioimmunoscintigraphy(RIS)with intact nonoclonal antibodles or f r a g m e n t s m a y b~ ~dvantageus for localization of m a l i g n a n tumours. Phe a i m of t h i s s t u d y w a s to a s s e s t h e v~ lue o f R I S in t h e p r i m a r y o c u l a r melanom~ using a radiolabelled monoclonal antibod' 225.2as,reacting againstHMW-MAA. 27 p a t i e n t s w e r e s t u d i e d ( 2 4 p a t s . w i t h melanoma and 3 with otherslesions),Size of lesion,measured by u l t r a s o u n d , r a n g e d fro~ 5 to 1B ~Lm. An a m o u n t s of 1 0 0 - 1 2 5 ug, e a c h of F ( a b ' ) f r a g m e n t s l a b e l l e d w i t h 9 9 m T c w a s I.V. injected. Scintigrams w e r e a c h i e v e d in t h e p l a n a r m o d e 4-6 h o u r s a f t e r a d m i n i s t r a t i o n of 4 B 0 - 6 0 0 M B q 9 9 m T c M o a b . Ganunacamera c o n n e ¢ t e d o n - l i n e w i t h a c o m p u t e r w a s used. In 15 p a t s . w i t h m e l a n o m a R I S s h o w e d in viva accumulation(+ in 9 c a s e s , + + in 6 c s e s ) . I n 9 pats. w i t h m e l a n o m a , R I S was ne g a t i v e . In 3 p a t s . w i t h o u t m e l a n o m a , R I B was true negative. NO r e l a t i o n s h i p b e t w e e n R I S a n d s i z e of lesions was observed. In c o n c l u s i o n , l ) R I S has a role with othez diagnostic t e s t s in d e t e c t i o n of e y e m e l a noma,2)RIS h a s a r o l e in d i f f e r e n t i a t i n g l eye melsnomas from others lesions and 3) T h e s e d a t a c o n f i r m t h e p o t e n t i a l u s e ~ulness of R I B to d e t e c t s m a l l l e s i o n s .

Ont.

Gy.A.J~noki,

and

Radiobiology

Budapest,

Italy.

B.Spett,

L.K~-

Zs.Karika

N a t l . Inst. Oncc

IMMUNOSCINTIGRApHY APPLICATION IN THE FOLLOW-UP OF M E L A N O M A P A T I E N T S A T H I G H RISK OF RELAPSE:A pERSPECTIVE STUDY. 37 p a t i e n t s , a l r e a d y o p e r a t e d f o r m a l i g n a n t s k i n m e l a n o m a w e r e s t u d i e d b y me a ~ of i m m u n o s e i n t i g r a p h y a i m i n g to an earlN detection Of metastatic lesions. The patients were apparently free,of d i s e a s e a n d w e r e s e l e c t e d o n the b a s i s of ~stolc_ gieal examination ( C l a r k e l e v e l II or higher) Or of the a n a t o m i c a l s i t e Of prJ mary tumour(back): these distinctive f~ tures being associated to h i g h p r o b a b i l t y Of tLnnour r e l a p s e . T h e a n t i m e ~ a n o m a F(ab')g 2g5.~Bg(Sorin Biomedica-Italy)l b e l l e d w i t h 9 ~ m T c w a s u s e d . In 25 p a t tients(67.5%) the i n v e s t i g a t i o n resulte negative. All these patients are s t i l l completely free of d i s e a s e d u r i n g a foll o w up time of 1 2 - 1 8 m o n t h s . In r e m a i n i n g lg p a t i e n t s the i m m u n o s c i n t i g r a p h y gave us positive outcomes. I n 6 of %hes~ c a s e s the p r e s e n c e of u n a s ~ e c t e d metastases was confirmed by radiological Or surgical examinations w i t h i n 3 -9 month~ T h e re/Aaining g p a t i e n t s resulted false ~ositive. This study points out the h i g h a c c u r a c y Of this t e c h n i q u e in c o n firming the absence of neoplastic dise~ so. M o r e o v e r the a b i l i t y o f the m e t h o d in d e t e c t i n g , e a r l i e r t h a n o t h e r tools. O c c u l t l e s i o n s is f u r t h e r c o n f i r m e d .

Landthaler,

642

LMoscatelli, L. R a s c i t i , M . A g o s f i n i , A. Spi nelli,R. Tassini,S.Severi and p.Riva.

Cesena

N.

and

"FJC"

Natl.Res.Insi

Radiohygiene,

Hungary

Im~unoscintigraphy antimelanoma F

with 99Tcm labelled lab,/2 f r a g m e n t s

Immunoscintigraphy was performed with Technemab-K-I /Satin Biomedi~/ in 25 pts w i t h m e l a n o m a malignL~n. ~ W T c TM l a b e l ed a n t i m e l a n o m a fragments were injected in 20 p t s iv a n d in 5 p t s so. In e a c h case the primary tumour had been operat ed b u t o n e b e f o r e s c i n t i g r a p h y . 23 p t s had metastases o r l o c a l recurrences.Two pts w e r e d i s e a s e free. B l o o d s a m p l e s were taken after 5-15-3o-6o min and 4l o - 2 4 h r s a n d w h o l e b o d y s c a n s w e r e performed i-4-io-24 hrs after administration of antimelanoma f ~ a g ~ e n t s , L y m p h node s c a n s w e r e d o n e in 5 p t s / L y m p h o s c i n t Solco/. Elimination of radioactivity from the b l o o d is b i p h a s i c . T h e h a l f t i m e of t h e t w o p h a s e s is 4 7 . 7 m i n a n d 14 h r s r e s pectively. Sc f n j e c t e d r a d l o a c h i v i t ~ 1~ach~ at 4 h r s a p e a k , m a x . 1 2 % in t h e b l o o d . A f t e r 24 h r s 3-6% of a c t i v i t y w a s retair ed in t h e b l o o d . In a l l p t s l y m p h n o d e m e t a s t a s e s larg, er t h a n 20 ~un r in o n e p a t i e n t s u s p e c t e d local recurrence, in one patient the p r i m a r y t u m o u r , b r a i n metastasis w e r e visualized. NO l i v e r m e t a s t a s e s were detected. In o n e d i s e a s e f r e e p a t i e n t occult lymph node metastasis w a s revealed. Sc i n j e c t e d a n t i m e l a n o n a fragments we~1 delineated t h e n o r m a l l y m p n o d e s a! c o m p a r e d to l y ~ p h o g r a p h y but slightly t h e t u m o r o u s one. S i d n e y w a s v i s u a l i z e d in a l l c a s e s , l i v e r w a s s e e n o n l y if antimelanoma f r a g m e n t s w e r e i n j e c t e d iv. In c o n c l u s i o n b o t h iv a n d sc a d m i n i s t r a t i o n o ~ a n t i m e l a n o i ~ a fragY~ents I n o ~ h s ~ c :he s p e b l f i t y o f diagnosis.

330

643 S. Clarke, C. Lazarus, P. Harper

~44

645

A. SteinstrEBer, F. Lappe, A. Schwarz and L. Kuhlmann

Departments of Nuclear Medicine and Medical Oncology, Guy's Hospital, London, gel 9RT

HOECHST AG, D-6230 Frankfurt/Main, FRG

Immunosclntigraphy in patients with metastatic melanoma using XMME-OOI-DTPA-111 In

RADIOIMMUNOTHERAPY SELECTION OF NUCLIDES

Although malignant melanoma ( ~ ) i s a tumour resistant to most forms of treatment, many therapy trials are in progress at present. An imaging technique that will accurately detect and localise disease would be of great bebefit in assessing the efficacy of various treatment regimen. XMME-001-DTPA-IIIIn is an antimelanoma antibody that we have used to study patients with proven recurrence following surgery for primary MM. 9 patients were studied, 2 female, 7 male age range 24 - 68 years (mean 43 years) with skin, node, liver and lung metastases from ~ . All metastases were documented by CT scanning or visually. Patients w ~ e injected with 3mCi (IIOMBq) X ~ E 001-DTPA-''In intravenously and whole body scans performed at 24 and 72 hours. Protein dose ranged from 0.2 - 5 mg. X~E-O01-DTPA-111In successfully identlfied IH of the 13 metastases present. It failed to identify a large recurrent tumour mass in a patient with an amelanotic melanoma. In one patient, axillary nodes were visualised but not a hepatic metastasis and in a further patient no uptake was seen in axillary nodes which were assumed although not his~dogically proven to be involved. Overall sensitivity for lesion detection was 77%. X~E-001-DTPA-111In has yielded promising results in this preliminary study, and detection o f ~ recurrence was possible with low doses of antibody.

646

-

tosimetric aspects determine the selection of nuclides both for immnoseintigraphy and i,munotherapy. Due to microdesimetric considerations and since no appropriate nuclides regarding helflive are available, we excluded the use of~-s~itters for the therapy of solid tumors. The tumor uptake found in man (in contrary to animal models) is about O.Ol % inj. activity per grame. For the study this value was used. With 1-131 and Y-90, we compared tma classes of B-s~itting nuclides. In case of a stable labelling (Y-90) doses in spleen and kidneys exceed clearly the radiation dose in tU,Dr (ratio of doses twnor/splean: O.21, tb,or/kidney: 0.15). But due to ~W~laleganation effects this is not the case for iodine: the maximumof dose distributlon is found in the tumDr ratio of doses t~r/spleon: 3.5, tumDr/kideey: 3.6). lhe possible ths)retical uptake of MABain a solid tumor s estimated on two ways: • by assessing blood flow passing the tumor. Here is the xtraction fraction the limitating factor. Assuming an Jptake of 0.gl %, the extraction results lover than 1%. _P. by detennination the mass of antibodies which saturate the epitopes of I grmme tumDr cells. Here we found 1 pg ~B per g tumor. But animalatudies on cellular level show, that antibodies (at least anti CEA M~Bs) are not only Fixed on the cell,s.brano but also at a bigger extant in ~he extr~ellular space. The nuclide with the best feasibility .for imnmotherapy is 1-131 in combination with a complete Mab. Using other ~eglications in preference to the i.v. route, modified mtibedies with higher extraction rates and using a s~all mount of protein with high specific activity, then immmotherapymay obtain clinical relevance.

647

~va C.Orbdn, 3.gurucz, A.Kerekes, L.T.Kocs~r

Y,Antonucci*, M.Cost~tlni*~A.Testa*~ g.Berto-

"Fr~d6ric 3olio±-Curie" National Research Institute for Radiobiology and Radiohygiene, Budaqest, P.O.Box lO1. 1775, Hungary

lone***, E.gn~laro **.

DETERMINATION OF BILE ACIDS IN SERUM. A COMPARISON OF A RAOIOIHHUNOASSAY (RIA) WITH ENZYMATIC AND ENZYME IHHUNOASSAY (EIA) METHODS. Concentration of bile acibs in 25 serum samples was determined in parallel by "Enzadile-7-alpha" enzymatic method (Nyegaard and Co. AS, Oslo), "ENDAB Cholylglyclne Enzyme Immunoassay Test Kit" (Immuno±ech. New 3emaey, USA) and by "I-125-Conjugated Cholic Acid RIA Kit" (IZINTA Isotope Trading Enterprfse, Budapest, Hungary)• The enzymalic method is a £ela±ively quick test with easy performance. However, there are some disadvantages: required volume of serum is one milliliter (af the RIA it is only 20/ul), and is not sensitive enough to analyze ~erum bile acid ef normal subjects. EIA method is favoured because it requires only 50 /ul of serum samples and the sensitivity of the'fes± is adequate (O.lO/umol/1). However,the specificity of its antiserum is not satisfacfory. Unfortunately the measured bile acid values are influenced occasionally by elevated levels of alkallne phosphatase. The EIA method is in our opinion, rather labour and time consuming. In spite of the afore mentioned disadvan±ages, our results obtained by EIA and RIA showed a good correlation (r-0.9930) in a wide concentration range• Our studles suggest that~due to the alternaling advantages and shortcomings of enzymatic and EIA methods, on balance, RIA seems,for lls easy performance, high sensitivity (O.03/umol/1) and specifity, to be more promising in routine laboratory work.

*Ist. Nefrologia O.C. Udine ** Ist. Medicina Nucleate O.C. Udine *** Ist. Nefrologia O.C. Treviso

OSTEOCALCIN (BOP) IN AORTIC ATHEROSCLEROTIC CALCIFICATIONS BGP was measured in calcified aortic fragments intraoperstively taken in fifteen male patient: subjected to aortic surgery for aneurismectomy and/or revaseularization, not diabetics, aged 50-75 years. We used as control group fragments of abdominal aorta taken in B mult~ orga~ donors. Fragments were pulverized in a miorodismembr~ tot, homogenized in physiological solution ans centrifuges to yieald a ~zssue extract. HGP was measured in the cytosol hy RIA method. Serum BOP was also measured in the atheroscl£ retie patients. Statistical analysis showed that mean value of aortic BGP was significantly higher than serum BOP (p
A. R.NOGUEIRA, G. DENARDO

Lab.Med.Nuclear,IPOFG Lisbon Radiodia~nosis Therapy Section University of California, Davis THYROID RADIATIOWDOSIMETRY IN PATIENTS UNDER THERAFEWITHMONOCLONAL ANTIBODIES (LYM I) LABELLED WITH 1-131 In the treatment of cancer patients with monoclsnal antibodies (MeAd)labelled with a radionuclide is important to know the absorbed dose delivered by the therapeutic activities to the organs of the patient. Regarding the thyroid, all the protocols prescrlbe the administration of a blocking agent like the Lugol's solution some days before and during the treatment until the 8 or lOth day. But, sometimes, we can visualize the thyroid of those patients on the scintigraphic images after treatment. Our report presents the results of the measurements of the absorbed dose received by the thyroids of 8 cancer patients ( 13 treatments) under treatment with MeAd specific to B-cell lynfoma (LYM i) labelled with I lJl. Some assumptions had to be made but always based on experimental data, so we can accept our results as a reasonable approximation. Results- I) The values of the absorbed dose per mCi of administered activity dont't show any relationship with the absolute values of the activity. 2) All the values determined are low, ranging from 0.08 to 3.6 tad per mCi of administered activity.