399 2 S.R.Reske.___., F.F.Knapp*, J.Ritsch**, S.Kohlen, J.Kolkmeier
IM.Farag~l, O.Messian, P. Assayag, E. B r o c h e t , P. V a l ~ r e , B.Bok.
Dept. Nuc. Ned. RW~ AACIIEN, guc. ~ed. Group, Oak Ridge Natl. Lab. Ridge, ~, ** Dept. Cardiol. and Dept. Olin. Exp. Nuc. ~ed. Univ Bonn,
H o s p i t a l Beaujon, Cliehy,
France
ASSESSMENT OF RESPONSE TO THROMBOLYSIS IN ACUTE MYOCARDIAL USEFULNESS OF MIni SPECT
3,3-DI~THYL(p-I-123 PH~YL-)P~TADECANOIC ACID(DRIP) UPTAKE IN EXCESS~0 r~BF IN REP~FOS~D H Y ~ I ~ . Sustained C-ll palnitic acid uptake has been shown to predict'late tissue recovery of reperfused myocardiu~. ~b~s, metabolic activity of postiscbe=ic nyocardiu~ was exanined by means of I)NIP, a me~ylated,
B.Thonnart,
REPERFUSION INFARCTION
AFTER (AMI) :
The a b s e n c e of s i g n i f i c a n t r e d i s t r i b u t i o n a f t e r myoc a r d i a l uptake allows the assessment of i n i t i a l myoc a r d i a l p e r f u s i o n i n AMI u s i n g MIBI SPECT. I f MIBI i s i n j e c t e d on p a t i e n t a r r i v a l b e f o r e any t h e r a p y , d e l a y e d imaging (1 H l a t e r ) still shows p r e t r e a t m e n t u p t a k e , even a f t e r t h r o m b o l y s i s .
non-metabolizable radioiedinated free fatty acid (FFA), in a coronary occlusion/ reperf~ion Langendorffswine heart nodal. Ei~t beart~ were investigated. Utilisatien of glucose, FFA, lactate and r ~ (ml/mn * ~), determined by tracer microspberns, wererepeatedlycontrolled during a 40 nib coronary occlusion and 30 ~in reperfusion period i n control and
MIBI was injected
in 14 patients with suspected AMI of
l e s s t h a n 6 h o u r s . D i a g n o s i s was c o n f i r m e d i n 11 c a s e s (9 i n f e r i o r MI and 2 a n t e r i o r ) and 8 t h r o m b o l y s e s were r e a l i z e d (from 1 H 15 to 3 h 15 a f t e r t h e o n s e t of c h e s t p a i n ) . MIni SPECT was p e r f o r m e d l H a f t e r i n j e c t i o n , and repeated 72 H later. During this interval
reperfnsed tissue. Substrate utilisatien was deter=ined by the Fick =etl~M. DRIP was injected 5 lin before the start of reper~usien. Tissue was analyzed
for irreversible damageby WC staining and content of I~IP by radioactivity assay. Reversible injured eyocardi~m utilized glucose in preference to FFA during iscbenia and produced lactate. ~eperfusion increased F~Autilisation
the patient anglegraphy.
to a similar extent than glucosewl~reas lactate production ceased. R~BF was persistently reduced in TTC-negative tissue (5 vs 6 z,l./zin * @; n.s.),
had a 2D echocardiography and a coronary In the confirmed AMI, MIBI SPECT was
c o n s t a n t l y abnormal and p r o d u c e d h i g h q u a l i t y imaging. S l i c e s were r e a d by two i n d e p e n d a n t o b s e r v e r s and a p e r f u s i o n s c o r e was e s t a b l i s h e d after segmentation (21 s e g m e n t s , s c o r e from 0 f o r a b s e n c e of p e r f u s i o n t o 3 f o r normal segment ; maximal s c o r e = 6 3 ) . No i n t e r o b s e r v e r d i s a g r e e m e n t was n o t e d as r e g a r d s t h e l o c a t i o n of d e f e c t a r e a . For p e r f u s i o n s c o r i n g t h e c o r r e l a t i o n was r = 0.88. After thrembolysls, the mean per-
revensibly fenced in the border zone (15 ~s 32 =]/,~n * ~ ; p<.01) and generally stable in control tissue (120 vs 90 ~/mn * ~; P>.06). DI{IP
uptake was 9.3 .+2.6 t of control tissue (p < .001) in persistently isclm~ic tissue and increased to 56.4 ± 5.9 t in reversible iscbe~ic tissue (~ < .001). %us, the increase of D~IP exceededthat of r~l by about 58 t in reversible iscbe~ic tissue and clearly discriminated control fros reversible injured and irreversible d~ag~d Wocardiun. Thesefindirgs showpr~er~ed cardiac glucose and F~A utilisation as well as sustained uptake and stable retention of I~tIP in reversible iscbe~ic viable tissue in excessto r~L I)l{IP has therefore the potential for early non-ibvasive delineationof revez~ibly injured reper~usednyocardium. Supported by O~L, operated by US Department of Eser~, contract DE-A~5-840R21400 with ~artin Marietta Ener~ Systeus,Inc.
fusion score increased (40.2 ± 8.6 p
to 48.3 ± 9.2 ; although the in-
36 H i n 7 of t h e of t h r o m b o l y s i s , no s i g n i f i -
3 G. BISI, R. SCIAGRA', G.M. SANTORO*, M. LEONCINI*, P.F. FAZZINI*, U. MELDOLESI. NUCLEAR MEDICINE, DEPARTMENT OF CLINICAL PATHOPHYSIOLOGY, UNIVERSITY OF FLORENCE; * DEPARTMENT OF CARDIOLOGY, CAREGGI HOSPITAL. FLORENCE, ITALY.
T.VARETTO,M.BACCEGA,G.CACACE,G.PICCIOTTO,N.CAM~ANA, R.ROPOLO,p.G.DE SERVIZIO
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I USEFULNESS OF Tc-g9m-MIBI SPECTFORASSESSING THROMBOLYSISRESULTS IN ACUTE MYOCARDIALINFARCTIDNAND FOR PREDICTINGLATE FUNCTICHqAL RECOVERY.
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For the evaluationof the results of intravenous tbrombolysis an ~maglng methodas perfusion SPECTperformed before and after the treatment would be ideal. Tc-99m-MIBI. differently from Thallium-201. seemsto present optimal features for this kind of assessment. In order to verify this hypothesis we studied 1.3 patients affected by acute myocardial infarctionand admitted to our Coronary Care Unit within 3 hours of symptoms onset. They were immediately injected with 7d0 MBq of Tc-99m-MIBI and then intravenous thrombolysis with rt-PA was started. The images were collected at leest 2 hours later. After 5 days a second 5PECT study was performed. The tomographic images were evaluated using a semlquantitative score. According to the clinical, electrocardiographic, enzymatic and angiographic criteria 7 patients showed signs of successful reperfusion, whereas 6 did not. The per cent reduction of the SPECT defect score between admission and 5 days images was significantlydifferent in the two groups ( 66.5 ± 16.9 vs. 11.9 ~ 10.3, p < 0.002). The defect score in the 5 days images correlated well with the enzymatic infarctsize ( r = 0.79, p < 0.01 ). Finally the per cent reduction of the SPECT defect score predicted the late functional recovery evaluated by comparmg the wall motion abnormalities in the admission echocardiograms with those found in the controls performed I monthLafter the acute event (r = 0.91, p < 0.0001 ). We may conclude that pre and pastintervention SPECT with Tc-99mMIBI in acute myocardial infarction treated with intravenous thrombolysis seems to be a reliable and accurate method not only for the assessment of the ]eopardized and salvaged myacardium, but also for predicting the latefunctional outcome of the patients.
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W. H. Knapp, U. Schmidt, G. Notohamipredjo, K. Vyska, D. FaBbender.
KJ Ascab, TD Ruddy, KY Gulenchyn, WL Williams, PC Spencer, SA Kearns, .OR Ballinger, RADavies
Institute of Nuclear Medicine and *Department of Cardiology, Heart Center North Rhine-Westphalia, Bad Oeynhausen
University of Ottawa Heart Institute 1053 Carling Avenue Ottawa, Ontario, Canada
In-111 ANTIMYOSIN ANTIBODIES AND TC-99m-MIBI FOR THE ASSESSMENT OF POST-INFARCTION MYOCARDIAL VIABILITY
DETECTION OF MYOCARDI/%L S A L V ~ T H A L L I ~ IMAGING
The functional state of the myocardium is one of the determinants of therapeutic management post infarction. The purpose of this study was to distinguish viable akinotic myocardial segments from permanently damaged segments in acute infarctions (MI). In 24 patients 2 mCi In-111 antimyosin antibodies (AMAB) were injected 1-4 d after the onset of MI. Images were taken 24 and / or 48 h later using two energF ~r,,dows in at least 2 views. TP,en, 15 r~,J T(;99m-MIBI (MIBI = isonitdl derivate) provided ECG-gated perfusion and wall motion images in identical views, 45 rain p.i. The following pattems were observed: (A) accumulation of AMAB matching a deficit in MIBI uptake and segmental wall motion abnormality (N--8), (B) poor accumulation of AMAB and poor regional MIBI deficit, but extended impairment of wall motion (N=8), (C) poor accumulation of AMAB, extended concordant MIBI deficit and large wall motion abnormalities (N=6), (D) poor accumulation of AMAB, slight wall motion abnormalities and large MIBI deficit (N=2). Clinical findings and follow-up: (/%) 0/8 with manifestations of ischemia, 8/8 with persisting dysfunctions for 3-6 mo. (13) 5/8 with non-Q-infarction, 6/6 angiogr, segm. dysfunction. (C) 5/6 with manif, of ischamia. (D) 2/2 with roan'if,o! ischemia Interpretation: (A) extended acute myocardial necrosis, no significant amount of viable myocardium at dsk, (B) stunned myocardium (C) "hibernating" myocardium, DD: remote infarction (D) acute ischemia. The combined application of both tracers allows to differentiate between necrosis and viable myocardium with impaired function and thus provides useful information as for post infarction angioplasty.
Uptake of In-Ill antimyosin antibody (AM) identifies myocardial necrosis and TI-201 indicates viable myocardium. Salvaged myocardium following thrombolytic therapy for myocardial infarction is characterized by endocardial necrosis extending towards viable epicardium. We hypothesized that areas of myocardial salvage following thrombolytic therapy, would be ~dunhified m~ r~gion~ with uptdke uf both ~I ~ d TI-201 demonstrating a mixture of necrotic and viable cells. Seven patients were studied following thrombolytic therapy with 2D echocardiography (days 1 and 7) and combined AM and T!-201 imaging. AM (80 MBq) wasi injected 24 hours following thrombolytic therapy. Planar imaging was carried out 24 hours later. Then TI201 (Ii0 MBq) was injected followed i0 minutes later byJ dual isotope tomography (180 ° , 32 projections, 45 seconds), using a medium energy collimator and 20% windows. In 5 patients, AM uptake was found in regions with Ti-201 uptake (scintigraphic overlap). Wall motion corresponding to regions of scintigraphic overlap ranged from normal to akinetio on day I with significanti improvement by day 7. In the 2 patients with regions of ~ uptake without TI-201 (no scintigraphic overlap), corresponding wall motion was initially akinetic orl dyskinetic on day 1 and showed no change by day 7. Scintigraphic overlap of AM and TI-201 may identify; regions of myocardial salvage and predict subsequent improvement in wall motion.
WITH C O M B I N E D A N T I M Y O S I N
8 W Volkert, JC Lattimer, LC Corwin, AR Ketring, RA Holmes, M. Farhangi, ~J Simon and WF Goeckler
J Harvey Turner, Andrew A Martindale, Peter Sorby, Eric L Hetherington, Robert F Fleay, and Phillip G Claringbold.
HS Truman VA Hospital and University of Missouri, Columbia, MO, and ~ Dow Chemical Co, Freeport, TX, USA Fremantle Hospital, Western Australia
and
Australian Nuclear Science and Technology Organisation THE USE OF 153Sm-EDTMP FOR TREATMENT OF SKELETAL CANCER LESIONS
153Sm-ethylenedieminetetramethylenephosphonie acid (153Sm-EDTMP) is a promising new og~nt for treatment of diffuse skeletal metastases. ~J)Sm, a medium energy beta emitter, has a 46.3 hr half-life and emits a 103 keV gamma-ray convenient for scintigraphic imaging. Following completion of a variable dose radiotoxicity study in normal beagles, a 37 M B q / k g ( l mCi/kg) i.v.-administration of 153Sm-ED~P was selected as the treatment dose for 40 dogs with spontaneous bone neoplasia. Responses varied from spectacular to no response with three of the dogs cured of disease. 32/40 dogs experienced at least temporary relief of pain with many lesions exhibiting bone remodeling and tumor control on bone radiographs. The only measurable side effect was transient reduction in leukocyte and platelet counts. Both the WBC and platelet counts reached their lowest values at 2-3 weeks post-injection (p.i.) and returned to the normal range by 5-6 weeks p.i. An ascending dose safety trial in humans showed i.v. administrations of 7.4-37 MBq/kg of this agent produced palliation of pain due to skeletal metastases with only minimal and transient depression of WBC and platelets measurable at the higher doses. These results demonstrate the promising therapeutic potential of this agent.
Sm-153 EDTMP THERAPY OF DISSEMINATED SKELETAL METASTASES Samarium-153 EDTMP (ethylenediaminetetramethylene phosphonate) prepared-from a freeze-dried kit, was evaluated for therapy of painful disseminated skeletal metastases unresponsiveto all conventional treatment,in 35 patients Individual beta radiation dosimetry was based on gamma counting of a single 6 hour urine sample following administration of a tracer dose of 740MBq 153Sm-EDTMP. Retained skeletal activity varied unpredictably between 40-95% of administered dose but in all patients >98% of non-osseous activity was cleared in the urine within 6 hours. Prospective dosimetry calculation in each patient permitted administration of an accurate therapy dose schedule based upon a pre-defined radiation absorbed dos, to bone marrow to minimize myelotoxicity.Pain was relier. ed within 14 days in 18 of 24 patients (75%) evaluable a 6 weeks,when clinical response was maximal. Duration of response ranged from 4 to 35 weeks after a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment in 5 of 9 patients. No dose-response relationship was apparent. The doselimiting toxicity wa myelosuppressionmanifested particularly by thrombocytopenia. Platelet counts less than I00 x 109/1 occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered within I0 weeks of treatmen Samarium-153 EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases and in 15 o the 24 evaluable patients there was evidence of stabilis ation or regression of skeletal metastases on radiograph and follow-up Technetium-99mMDP bone scans.
401
10 A.ERMIAS I, P.BEAU 2, R . P E R D R I S O T 1, j.j. LE JEUNE 1, D . P O U L I Q U E N 1, J . L E G E R 3, A.LEPAPE 2, P.JALLET 1 1-Laboratoire de biophysique facult6 de In6decine 1 rue Haute de Recul6e 49000 ANGERS FRANCE 2-Laboratoire de Biophysiqne cellulaire , Facult6 de M6decine, 2,Bd Tonnell6 37000 Tours FRANCE 3- Oris Industrie , B.P. 21, 91190 Gif sur Yvette FRANCE
Development of micro-encapsulated B-emitting radionuclides for selective tumor radioembolization Many authors have described vectors for chemoembolization of tumors using cytotoxic compounds. To date the carrying of 13emitting isotopes has not been widely investigated. This study concerns our initial findings on the preparation, properties and use of biodegradable microcapsnles loaded with colloidal Rhenium 186.This radionuclide is characterized by a reasonably long physical half-life of 90 h and a strong 13emission ( 1Mev). A single gamma emission of 137 Kev made possible the study of capsule biodistribution, the acquisition of scintigraphic images and the evaluation of the dose delivered to the tumor. Biodegradable microcapsules , 10-15 ~tm in diameter are manufactured by interfacial-polymerization of isobutyl-cyanoacrylate encapsulating Re186 previously dispersed in an organic phase. Microcapsules are injected via the single pedicular artery o f B-16 melanoma induced in mice ( C57 BI 6/J strain) and metabolic follow-up is assessed by P31 MRS on a AM 200 WB Bruker spectrometer. The results demonstrated that more than 90% of the radio-activity injected reached the tumor.Spectra obtained showed a decrease in the ATP/Pi and PCr/Pi ratios related to the dose delivered. Furthermore, in comparison with non-treated controls, irradiation arrested tumor growth. These preliminary results seem to show that high dose radiation can be delivered to tumor areas with microencapsulated 13-emitting radionuclides. 11 P.Guerra*, L.Colombo**, G.Maira*, R.Pagliaini*, A.Terzi* C.Pizzocaro*, GC.Magri*, A.Puricelli *~, M.Bestagno*. * Servizio Medicina Nucleare - Spedali Civili - Brescia ** Servizio Medicina Nucleate - Ospedale Busto Arsizio
I31I-MIBG IN THE TREATMENT OF CARCINOID TUMOR. Seven pts affected by metastatic carcinoid were treated with 131I-MIBG. The primary was in lung in 1 pt and in small or large intestine in 5 pts; in I pt the primitive tumor was unknown. All the pts were in serious conditions with severe humoral symptoms and high levels of urinary 5-HIAA and were no longer responsive to symptomatic therapy. One or more 131I-MIBG therapeutic treatment were applied: 1 course in 3 pts, 2 in ~ pts, 3 in 1 and 4 in the last one, with 100-200 mCi for every treatment (cumulated activities 100-650 mCi). 131I-MIBG was injected i.v., with slow infusion lasting 1-4 h, depending on its specific activity (25-65 mCi/mg). In 4 pts an impressive remission of symptoms was achieved, lasting 2-20 months, despite of the fact that no reduction in size of the neoplastic deposits was observed. Three pts are still living in stationary conditions. No worsening of flushings or others symptoms was observe( during the MIBG infusion or immediately after; in 2 pts this event was observed later (1-2 weeks after); in one of these the worsening was prevented by administration oJ an antiserotoninic agent (cyproeptadine) shortly before. and after the further therapeutic course. ~o marrow depression was observed. &31I-MIBG seems to be a relatively safe and useful treatrent of the metastatic carcinoid, even if only palliatiw
B. Shapiro, J. Andrews, L. Fig, ~ndrews, J. Smith, W. Ensminger.
J.
Carey,
S.Walker-
University of Michigan, Ann Arbor, MI U.S.A. THERAPEUTIC INTRA-ARTERIAL ADMINISTRATION OF YTTRIUM-90 GLASS MICROSPHERES FOR HEPATIC TUMORS A phase I/II dose escalation study of Y-90 labeled glass microspheres administered by a selective hepatic artery Icatheter was performed to determine the maximal tolerable dose and the potential for beneficial effect. 18 patients (pts) with hepatic metastases (13 colorectal, i gastrinoma, 2 carcinoid, 2 neuroendocrine) were treated with 19 doses. Doses were calculated to deliver a nominal whole liver radiation dose of 5000 rads in 3, 7000 rads in 6, I0,000 rads in 7 and 12,500 rads in 3. Three doses were administered via implanted pumps and 16 via percutaneous hepatic artery catheters. Tc-99m-MAA studies were used to assess catheter placement and lung shunt. Posttherapy Y-90 Bremsstrahlung scans confirmed the distribution of the dose. No gastrointestinal, renal, pulmonary or hematological complications occurred. Transient (24-72 hr) fever occurred in 4 pts. In one case with a long, high resistance, implanted chemotherapy pump/catheter system the Y-90 microspheres could not be flushed past the pump. No ill effects resulted and the pt was treated successfully via a percutaneous catheter. Mean follow-up has been 5,1 months (I-Ii). 1 pt has died from factors .unrelated to therNpy. Partial responses were seen in I0 cases (in 6 only by 4 months), stable disease in 3, deterioration in 1 and 1 patient is too early for evaluation. In the patient with gastrinoma, gastrin levels fell (2044 to 242 pg/ml) within 3 weeks. We conclude Y-90 glass microsphere therapy is feasible, safe to doses of 12,500 fads, and partial responses have been encouraging.
12
!, U. S c h m i d I, H. Bihl 2
and V. Schirr-
IInstitute of Radiology and Pathophysiology, 3Institute of ImmunQ_logy and Genetics, G e r m a n Cancer R e s e a r c h Center; 2Divlsion of N u c l e a r Medicine, University; Heidelberg, FRG
MONOCLONAL A~TIBODY (MAB) T A R G E T I N G OF SMALL MET~TASES. Increasing awareness of limitations in the a c c e s s i b i l i t y of large tumor nodules for labeled MAbs is c o n t r a s t e d by the v i r t u a l absence of data regarding the situation in small metastases. This is due to inherent d i f f i c u l t i e s in i s o l a t i n g small s p o n t a n e o u s tumor lesions and to the p r o b l e m of q u a n t i t a t i n g a u t o r a d i o g r a f i c signals. To address the problem, b i o d i s t r i b u t i o n cf M A b 12-15A d i r e c t e d a g a i n s t the m e t a s t a s i z i n g mouse lymphoma ESb-Mp was r e c o r d e d on autoradiographs. These w e r e d i g i t i z e d (50 ~m r e s o l u tion) and c o n v e r t e d into a r a d i o a c t i v i t y matrix, w h i c h was c o r r e c t e d for a b s o r p t i o n phenomena. R ~ d i o i o d i n e a c c u m u l a t i o n was d e t e r m i n e d in liver metastases with diameters down to 100 ~m. H i g h e s t a n t i b o d y accumulation, i.e. up to 40 % i n j e c t e d dose per g, was found in 1 mm lesions, whereas gradually declining accumulation was noted w i t h both i n c r e a s i n g and d e c r e a s i n g diameters. In large size metastases this was obviously due to non-uniform radioactivity retention. W i t h r e s p e c t to the lower uptake in metastases
402 14
13
J.
E. Henzc, R. Lietzenmayer, R. Kunz, G. Schnur, M. Clauscn, K. Schoser, W.E. Adam
P.
* U,R.H.
[EVALUATION OF VIABILITY OF HUMAN AND EXPERIMENTAL ORGAN TRANSPLANTS BY P-31 MAGNETIC RESONANCE SPECTROSCOPY This study was undertaken to test the usefulness of a 4.7 Tesla/40 cm diameter NMR system for measuring the state of preservation of human and experimental organ transplants. First, a special cooling system was developed based on an original transplant cooling box to allow for sterile continuous cooling and, at the same time, for optimum technical conditions for NMR spectroscopy (MRS) with a surface coil. P-31 spectra in 16 experimental runs were obtained at 81 MHz !pulse frequency after optimum shimming for each individual organ. The whole measuring takes approximately 30 min. For the first time it ] could be demonstrated in 4 cases that plegic human pancreas and liver transplants contain enough ATP as viability indicator to be measured I by MRS. In plegic human pancreas the 13/7-ATP ratio declined slowly from .81 to .52 within liar and approached zero within 6 hrs. In plegic human liver lY-ATP/Pi fell from .043 at 1.5 hrs to .013 at 3 hrs to .012 at 4.5 hrs after explantation. In 6 experimental pig kidney transplants no ATP was measurable at any time, but viability could be demonstral ted by regeneration of ATP peaks during experimental reperfusion with warm blood inside the magnet; also, the ratio monophosphates/inorganic phosphate seems to indicate the state of preservation which averaged .34+-.12 at 1 hr and declined to .12+-.07 at 3 hrs and to .05+-.02 at 5 hrs after explantation. Finally, in 6 pig heart transIplants the preservation of ATP and the subsequent regeneration of depleted creatine phosphate (PC) up to a P C / ~ A T P ratio of 3.3+-1.8 could be monitored during reperfusion with blood. Thus, P-31 MRS in the set-up described offers great potential for estimating non-traumatically the metabolic preservation of human organs for routine use prior to transplantation as well as in transplantation research. 15 Philippe JEHENSON, Andr~ SYROTA.
- CHU R a n g u e i l
**Service
University of Ulm, Germany
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Durir
IH-NMR
metabolic
patways.
~terial
end method
- We used
e BrOker
ter,
imaging
with
- Examination for
:
spectra-imaging IH coil
is done
for
Magnet
of 2.35
image
and
spectra.
on leg m u s c l e
for
imsglng
Teals,
and
qO cm of diame-
locslised
on solem$
IH-speetrum.
- Exercice - Timing
is done w i t h is:
thickness
, leg
an e x e r s o m e t e r
imaging
with
a one
TR = 200 ms
kg weight.
: TE = 3q ms.
Slice
5 mm. , Selection
method
acting
: spin echo,
w i t h ~seleetion
Iocalised
pulse
at
spectrum
1,5 ppm
and
|H are done w i t h
OSIRIS
{I]
I - 3 - 3 - | water-suppres-
sion pulse, Spectrum trum tra
[|'30
Results -
at
rest
[1'30)
Leg
at
each)
at
- Spectra
show
This
results
S e a 2 is n o r m a l i s e d Volume and
let
during
that
of l a c t a t e s
since
of ~mlno
in C R D a n a e r o b i c by 02
suppressed
all.
amount
exercice
, | spec-
2nd e x e r e i c e
J.~R~
of fat w i t h i n
of p e r i p h e r i c a l
an increase
when
[I] O u t e r
important
reduction
increase
It can be seen
A. C O N N ~ L Y
during
each)
: 3 spec
:
a very
important
show
each)
[1'30
rest.
shows
8n
[I'30"
; 2 spectra
end discussion Imaging
ting w i t h
rest.
; 2 spectra
rest
fat
first acid
exercise
during
glyeolysis
muscle,
tissue
contr~
.
time and durir
exercise. is m a i n l y
used
ever
therapy.
image
related
7~= 5|g-fi25
in viva
spectroscopy
[OSIRIS]
- tgBE,
16 Paul
CANXONI,
Philippe
HANTRAIE,
Service Bospitalier Frederic Joliot, CEA, l~partement de Biologie, 91406 Orsay, Prance.
IN VIVO HEPATIC GLYCOGENMETABOLISM IN THE BABOON : A 13-ClQfll STUDY. Hepatic glycogen synthesis from glucose was studied in the baboon by '3C NMR spectroscopy at 2 Teals. Glycogen synthesis was followed for 3 hrs on natural abundance spectra during glucose infusion. (1-t3C)-glucose (3 g) was then injected. It produced a 10 times larger rate of increase of glycogen-Ct, which is much lower than expected, suggesting that glycogen synthesis mainly occurred from unlabeled gluconeogenic substrates. Signal/noise ratio was 50 for glycogen-C~ on 2-minute ~H-decoupled spectra. Labeling of C i but also C2, Cq and C~ of glycogen indicated a 35 Z contribution of indirect p~thways to its synthesis from glucose. Hepatic glycogen metabolism can thus be followed in vivo at 2 Tesla in large animals wlth enough sensitivity to alloy determination of metabolic pathways and rates.
Philippe JEHENSON Service Bospltalier l'Energie Atomique, Orsay, Prance.
Frederic 4
Joliot,
Commissariat
p l a c e du E~n~ral L e c l e r e ,
&
91406
METHOD FOR THE MEASUREMENT AND EXACT COMP~SATION OF EDDY CURRENT EFFECTS INDUCEDBY PULSED NAGNETIC FIELD GRADIENTS IN NNR SYSTEMS. Most NMR imaging and localized-spectroscopy techniques use pulsed magnetic field gradients which, however, induce multi-exponentially decaying eddy currents that distort images and spectra. This work describes a comprehensive strategy to measure and to exactly compensate for the Induced gradient and the shift in B field which are produced. The time dependence of the ~radlent, and if desired of the B shift, is measured from FID signals (or with pickup ~oils) with methods that distinguish these two components. The signals are obtained from one large or from two small samples by driving the gradient coil with a step function current pulse. A multiexponential fit through the measured temporal behavlour of the gradient determines _the amplitudes and timeconstants of the various exponential decay terms. A model allows to calculate the exact shape and parameters of the current pulse required to compensate for the eddy current effects. This also turns out to be a multiexponential (plus, of course, a constant term), however, with time-constants differing from those of the eddy currents. The pulse is easily produced electronically. After compensation of the gradient component is achieved, the AB (t) component is measured, and then corrected as for ° the gradient. The procedure is suited for automation and should avoid long and tedious manual adjustments by trial and error of the compensation, including in the case of shielded gradients.
403
18
17 AA Driedger, RT Thompson, G Marsh, D Gravelle, A Hahn.
Departments of Nuclear Medicine and Clinical Neurosciences, Victoria Hospital and University of Western Ontario, 375 South Street, London, Ontario, Canada N6A4GZ
CHARACTERIZATION OF THE MCARDLE'S DISEASE BY P-31 MR MUSCLE SPECTROSCOPY (MRS)
(MD)
DEFEC~
MD is characterized by deficiency of myophosphorylase (MP) and cramping pain with exercise (Ex) as a result 3f inability to mobilize glucose from muscle glycogen. The gold standard for the diagnosis is the absence of a positive histochemical reaction for MP in a biopsy. We present a family with MD in which the proband had a positive MP reaction but in whom the diagnosis was established by MRS and subsequently verified by both biopsy and MRS in two siblings. This case demonstrates that the MP reactivity can be positive in the presence of MD if there is a very low level of enzyme activity present. MRS during exercise demonstrated progressive alkalinization of the intracellular pH. The alkalinization in these subjects is believed to result from substrata limitation so that lactic acid does not accumulate. We devised a test to assess this possibility using a continuously incrementing work load during MRS. When log[Pi]/[PCr] was plotted vs work, normal subjects demonstrated a threshold effect corresponding to the point at which pH declined, whereas patients with MD did not. It is concluded that MD patients have an impaired phosphorylation potential which can be demonstrated by MRS and thus aid in the recognition of MD.
19 B. MAZIERE, C. LOC'H, M. BOURGUIGNON, C. RAYNAUD, P. RANTRAYE, J.L. MARTINOT, A. SYROTA and M. MAZIERE
Service Hospitalier Frederic Joliet, CEA, 91406 ORSAY, France
PET AND SPECT IMAGING OF D2 BRAIN RECEPTORS IN BABOON AND HUMAN BRAIN USING 76Br- AND 123I- LISURIDE. An ergolene derivative, lisuride, was labelled with the positron emitter 76Br or the single photon emitter 123I and used for the non invasive imaging of 02 receptor in brain using PET or SPECT. Kinetic studies in baboons displayed an accumulation of these radioligands in the striatum which reached a maximum 30 min post injection and which could be specifically displaced by haloperidol. Fost-mortem brain ligand metabolite studies of 76Br-bromolisurlde (BLIS) showed that more than 80 and 50 % of the radioactivity measured respectively in the strlatum and the cerebellum was related to unchanged ligand. In series of experiments, increasing masses of the 76Br-BLIS were injected in baboons, and in rive parameters of the striatal specific binding analysed using a saturation model. In animal models of Huntington's chorea, the results of these in-viva analysis were correlated with post-mortem histologic results. In human, a satisfactory reflection of the specific binding (i.e. a composite of affinity and receptor density) was more simply obtained by calculating the striatum to cerebellum radioactive concentration ratio. In groups of young control volunteers, the mean values of this index were 3.84 (SD=0.45) for 76Br-BLIS and 1.6 or 2.1 for 123I-iodolisuride according to the SPECT device used.
P.Y.Marie,J.M.Escanye,F.Brunotte,F.Zannad,B.Robin,P.Walker,J.Robert,J.M.G~lgenkrantz
CHU - NANCY rue Lionnois -
Laboratoire de B i o p h y s i q u e 54000 NANCY ( F r a n c e )
-
18,
SKELETAL MUSCLE MEFABOLISM OF THE LEG IN PATIENTS WIIH LOW EJECTION FRACTION. A 31 P NMR SPECTROSCOPY STUDY Patients with congestive heart failure (CHF) have demonstrated abnormal skeletal muscle metabolism. We have studied phosphocreatine (Pcr),inorganic phosphate (Pi) and pH off c a l f muscles in 9 patients (49+10 years) with low ejection fraction (29+ 15~) and i n 9 normal control subjects (44+9--years). Plantar flexion of the foot was p e r T o r m e d and t h e work level necessary to reduce the ratio Pcr/(Pcr+Pi) to about 0 . 5 was d e t e r m i n e d during a lO0 seconds aerobic (A) w o r k and an l s c h e m i c work (I). A 2 . 4 T B r u k e r m a g n e t and a s u r f a c e coil were used. Pcr/(Pcr+P'i) ratio was calculated from peak height and pH was d e r i v e d from chemical shift b e t w e e n Pi and P e r a t t h e end o f e x e r c i s e . Total work(J) Pcr/(Pcr+Pi) pH Control (A) 2.6+ 1.5 0.47+0.06 6.99+0.05 CHF ( A ) 0.9~ 0.7 0.48~0.05 6.98¥0.05 C o n t r o l (I) 0 . 9 ~ 0.25 0.47¥0.05 6.97~0.04 CHF ( 1 ) 0.29+ 0.16 0.47~0.04 6.99~0.06 Thus,despite ~imilar Per/(P~r+Pi) ratio,wor level is much lower in CHF p a t i e n t s both i a e r o b i c and a n a e r o b i c work but pH is identical. These f i n d i n g s do not support the h y p o t h e s i s tha the higher e n e r g e t i c cost in CHF p a t i e n t s coul be due either to r e d u c e d blood flow or to muscl h y p o x i a with i n c r e a s e d lactate a c c u m u l a t i o n .
20 C. LOC'H, B. MAZIERE, C. RAYNAUD, M. BOURGUIGNON, P. HANTRAYE, 0. STULZAFT, A. SYROTA and M. MAZIERE
Service France
Hospitalier Frederic Joliet, CEA, 91406 ORSAY,
SPECT IMAGING OF DOPAMINERGIC D2 RECEPTORS WITH 123-I IODOLISURIDE (123-I ILIS). Lisuride, an ergolene derivative, labeled with the 8+ emitter 76-Br, has been successfully used for PET imaging of dopaminergic D2 receptors. The iodo analogue has been produced by a 123-I electrophilic substitution on the indole moiety of the lisuride with a 90% yield and a high specific radioactivity (I GBq/nmole). In vitro and in vlvo binding and autoradiography studies in rats demonstrated that 123-I iodollsuride has a high affinity (Kd-0.27nM) and a high specificity for D2 striatal receptors. After IV injection of this radioligand in baboon, the regional brain radioactivity was measured for 3 hours by SPECT : 30 mln after injection, when a clear delineation of the basal ganglia appeared, the value of the striatum/cerebellum radioactive concentration ratio (S/C = index of specific binding), uncorrected for partial volume effect, was 1.6. In human, 250 MBq of 123-I ILIS were injected and brain was imaged for i0 min at various intervals during 7 h. This kinetic study showed that the best imaging time was 1 h after injection. At that time, the values of the S/C ratio measured using a dedicated system (TOMOMATIC 564, imaging time 15 min), or a rotating v camera (SOPHY camera, imaging time 30 min) were respectively 1.65 and 2.1. 123-I iodolisuride appears to be suitable for SPECT clinical studies of dopaminergic D2 pathologies.
404
22
21 J. Mertens. A. Bossuyt, C. Bossuyt- Piton, M.Guns, M. Gysemans
J. Mertens. C. Bossuyt- Piron
VUB-CYCLOTRON Laarbeeklaan, 103
VUB-CYCLOTRON Laarbeeklaan, 103
1090 Brussels
S E L E C T I V E S E R O T O N I N S 2 R E C E P T O R M A P P I N G IN BABOON BRAIN WITH SPECT WITH A NEW RADIOIODINATED KETANSERIN ANALOGUE Serotonin S 2 receptors can play an important role in mood disorders such as in the etiology of depression and in migraine. The role of a serotonin $2 antagonist such as Ritanserin in disthymia and neurotic depression is not yet well understood. In vivo SPECT of the involved binding aspect can help to elucidate this problem. A new 1231 Ketanserin analogue was tried for $2 receptor mapping in baboon brain with SPECT. A baboon of 15 kg was I.V. injected with 185 MBq of pure 1231 Ketanserin analogue and SPECT was performed in 1 and 2 hours post injection. The tracer shows a preferentiel uptake in the frontal cortex (FC) a brain region known to contain high concentration of S 2 receptors. After 2 hours a FC / cerebellum activity ratio >10 is observed. The activity uptake in FC is inhibited for >95 % by injecting 0.3 mg / kg Ketanserin 1 hour before the administration of the radioactive dose. This means that the tracer selectively binds to serotonin $~. ~ceptors. The binding experiments were shown to be reproducible. A b o u t 40% of the I.D. was already excreted through the liver and biliary tract within 1 hour pointing to an advantageous dosimetry. These results indicate a great optimism for SPECT mapping of serotonin $2 receptor sites in man with the new tracer.
DEVELOPMENT OF A NEW SEROTONIN S2 RECEPTOR RADIOIODINATED TRACER FOR SPECT In vivo visualisation of serotonin S 2 receptor sites with SPECT can contribute to a better understanding of mood disorders. Therefore a tracer crossing the blood brain barrier (BBB) and showing a selectivity c o m p a r a b l e to that of Ketanserin or Ritanserin is required. Until now 123 I remains the tracer for receptor studies with SPECT . Introduction of an iodine atom generally increases the lipophilicity considerably, thus increasing the aspecific binding properties. This paper proposes a new radioiodinated Ketanserin analogue which development is based on the statement of structure-activity relation by introduction of clustered compensated lipophilicity. Labelling is achieved by Cu(I) assisted nucleophilic exchange followed by appropriate purification. Saturation binding of the 125 I labelled tracer on rat frontal cortex membranes showed an apparent K D of 0.82 nM and 8-max of 37 fmoles / mg tissue, results comparable to 3H-Ketanserin. Specific binding was displaced by Ketanserin, Ritanserin and Methysergide. The lipophilicity index is comparable to that of Ketanserin. After I.V. injection, the tracer accumulates preferentially in rat frontal cortex, a region with high S 2 receptor density. The new tracer thus both shows a high selectivity for S 2 receptors and crosses the BBB readily. 24
23 A: Verhagen, W, Vaalburg
1090 Brussels
T.J. De Groot, Ph.H. Eisinqa, J.W. Pesser, A.M.J. Paans and
R. Kot~pl~, B. Shuikin, R. A]len, P. Kollros, d. Prk~, L. B#tz, T. ~ , K. Rosenspk-e,D. K~I, andB. A
Departuent of Nuclear Medicine, University Hospital, Oostersingel 59, 9713 EZ Groningen, The Netherlands. ZSF-LABELED PMOOESTINS: MOLECULhRMODELING AND ASSESSMENT OF PROOESTIN RECEPTORS WITH POSITRON EMISSION TOMOGRAPHY (PET)
Selective uptake of laP-labeled steroids in hormone responsive tumors is based on the presence of steroid receptors. In vivo assessment of steroid receptor positive tumorswith PET is potentially very useful in oncology. The presence of estrogen receptors (EN) and progestin receptors (PN) in breast cancer is correlated with the probability of responding to endocrine therapy. 21-J~F)Fluoro-16u-ethyl-19-n0rprogeeterone (];"Y)TENP) and its 16c-methyl analog [laT]FNNP are high affinity progesttns. He have found a hlgh selective uptake in the uterus of estrogen prized i.ature Wietar rats. Tissue distribution of :~F radioactivity was determined 60 and 180 zin after i,v. inieotion. After 60 alm the uterus/blood and uterus/muscle ratios for [~aP]FENP were 13 and 7. After 180 sin these ratios were46 and 19. Receptormediated uptake in the uterus was indicated by the decreased uptake iu the presence of 20 pg PEEP. In this ease the ratios were 2 and l. The preliminary results for [z*P]PMNPshowsomewhatlower ratios. PeT-imaging with (~aF]FENP of PR in a EMand PR positive mammarytuuor model is currently under investigation. The images show a high uptake of radioactivity in the hormone responsive tumor, No uptake is observed in the nonresponsive variety of this tuzor. Whether tumor uptake is NN mediated will be confirmed. Molecular modeling is evolving as an integral part of our radiopharmaceutioal design. As for progestiue we attempt to correlate the known potencies of some progesttns with electrostatic and oonfornational data derived by use of modelingtechniques. With such an approach we expect to develop a modelfor the design of mew~eF-labeledprogestl,s. Me conclude that 0ur mammary tumor model may be suitable to ensure the usefulness of[~eF]YENPwith PET in monitoring ER mud PR positive tumors, Molecular modeling contributes to a more rational radiopharuaceuticaidesign.
11C./d,IINOCYCLQHEXkI4EC/d~BQ0
earsto be i useful probefor teme~'aja~ostudiesof aminoaokl~ r ~ in tbe humanbrain.
405
26
25 F.M. Gonz~lez, M. Torres, A. Jimenez-Heffernan, M. Alvare J.M. Latre, J.M. Llamas, A. Garcfa* and A. Mateo. Nuclear Medicine and Oncology* Services. Hospital "Reina Soffa" and Radiology Department. Medical School. CORDOBA. SPAIN. CA 72.4 IN COLORECTAL CARCINOMA. COMPARISON AND ASSOCIATI( WITH CEA AND CA 19.9. We have studied 25g subjets c/sssified as follcxvs: 74 blood donors (control gra4o), 51 patients (pts) with benign diseases and l34 p t s with co.].orec't~l carcinoma: 58 with active ~ disease and 76 in oamplete remission. ~ y CA 19.9 were mesmmed in ~ram simulta-
neaus/,ywith the determi.r~tiansof CA 72.4. In a3/ cases imm.moradiar~tric assaF techniques were u ~ IiTed. In the control group CA 72.4 levels oscillated betwean 3 and 10.6 U/ml. The upper normal limit was set al 4 U/ml (95% of the control group levels). In the gro~0 of pts with beninE disease CA 72.4 levels were inferior to 3.4 U/ml in all cases. Of the 76 pts with colorectsl carcinama in ccmplete remissicn 67 (88%) were true rm~atives (~N). Of the 58 p t s with active colort~tal csrcincma 33 (57°%) h~d true positive (TP) values. However, CA 72.4 levels were supex'ifx" to 4 U/ml in ~ 2/13 pts in preoperative sitnation. If ~ e00clu~ these 13 pts 31/45 pts (C:~%)hadCA 72.4 levels higher then 4 U/ml. Comparing CA 72.4 levels with those of CEA and CA 19.9 (t~per normal limits of 5 na/ml and 37 n~ml,respectively) we observe that CEA provides 74ToofIP (T9% if cnly ~ of disease is considered) and8~%of~N. CAIg.9 provides 71% of ~P (7B% if only recurrance is o~sidered) ~ 79% of ~N. So CA 72.4 does not seem to improve t h ~ results. If we eV~Ll~ts the three together: ~A, CA 19.9 and CA 72.4 and considerir~ positive the elevation of two markers the resu3.ts improve clear36,, o b t t ~ 8U'~ of ~ (8~% if (rL~ ~ c e is considered) and ~ of ~ .
27
Institute of Nuclear Medlclne, FU Norddeutschland, Seevetal ; Department of Gynaecology and Obstetrics, St.-Josefs-Hospital Uerdlngen, Krefeld ; Federal Republic of Germany RADIOASSAY OF 6 TUMOUR MARKERS IN SERUM AND OF ESTRADIOL AND PROGESTERONE RECEPTORS IN GYNAECOLOGIC NEOPLASMS : RESULTS AND CLINICAL IMPLICATIONS When assessing their clinical value, the pretherapeutic serum concentratlon of 6 tumour markers was compared with the estradlol receptor (ER) and progesterone receptor (PR) level in the cytosol of gynaecologlc neoplasms. In 41 women (25 with breast cancer, 9 with malignant ovarian tumour, 7 with cancer of corpus uteri) CA 15-3, CA 125, TPA, CFA, CA 19- 9 and TAT I i n serum were determl ned by radl el mmunoassay, ER and PR in tumour cytosol by radioligand analysis. Sixteen patients wlth breast carcinoma had (ER+/PR+),2 (ER+/PR-), 1 (ER-/PR+) and 6 (ER-/PR-) ; before therapy TPA was elevated in 13 patients, CA 15-3 in 10, CA 125 in 5, CA 19-9 in 3, CEA in 2 and TATI in 1, with a tendency of TPA, CA 15-3 and CA 19-9 to rise especially in patients with (ER-/PR-).Three malignant ovarian tumours were (ER+/PR+), 1 (ER-/PR+) and 5 (ER-/PR-) ; before treatment CA 125 and TPA were raised in 8 women, CA 15-3 in 4, CEA, CA 19-9 and TATI in 1 patient each. Six patients wlth uterTne carcinoma presented (ER+/PR+), I'(ER÷/PR-) ; prior to therapy CA 15-3 was elevated in 3 and TPA in 2 patients with (ER+/PR+) whereas in the patient with (ER+/PR-) only TATI was raised. In conclusion, ot least in patients with breast cancer or mallgnant ovarian tumour, prior to treatment TPA, CA 15-3 and CA 125 in serum as well as ER and PR in tumour cytosol should be determined i in order to improve prognostic information.
28
F . M A R E C H A L ( 1 ) , H. L A R B R E ( 1 ) , M - G . L E G R A N D ( 2 ) , G.BERTHIOT(3),G.DELTOUR(1), A.CATTAN(1). (1) (2) (3)
D. Glaubitt, G. Crass
Institut O.H.G O.H.G
J . G O D I N O T 5 1 0 5 6 REIMS C e d e x 51000 CHALONS-SUR-MARNE 02400 CHATEAU-THIERRY
IS CA-50 SUPERIOR TO 0 A - 1 9 - 9 BENIGN DISEASES ?
IN
CANCERS AND
These two serum markers (IRMA) recognize close sialylated antigens; they have been used for the diagnosis and the follow-up of cancers of the gastrointestinal tract. C A - 5 0 ( STENA IRMA kit) and 0A-19-9 (MALLINCKRODT IRMA k i t ) have been compared in a prospective study including 323 patients with advanced carcinomas ( 56% m e t a s t a t i c ) and 1 2 0 patients with benign diseases. In cancer patients, mean, standaPd deviation, median are 88 U/ml, 488 U/ml, 13 U/ml, for CA-50 and 2 9 5 3 U/ml, 49522 U/ml, 18 U/ml, f o p CA 1 9 - 9 r e s p e c t i v e l y . Sensitivity and specificity have been studied according to the site and the extent of the disease. The threshold values w e r e 16 U/ml for C A - 5 0 and 25 U/ml for 0A-19-9. CA-50 specificity a p p e a r e d t o be lesser to CA-19-9 ( 64% vs 77%, N = 120), above all in pulmonary diseases ( ' 6 3 % vs 87%,N=60); however 0A-50 sensitivity was g r e a t e r in the GI tract diseases(62% vs 53%, N = 9 9 ) a n d e q u a l t o 0 A 19-9 in others cancers( 34% vs 3 4 % , N = 2 2 4 ) . A close correlation exists between their serum l e v e l s : in cancers, P=0,78, p <0,001; in bening diseases, r = 0,69, p < 0,001.
P. K o u t s i o u b a , Th. Akritidou,
L. I o r d a n i d o u , P . N a t s i s , A.Tsialta,G. Patsis.
METAXA CANCER HOSPITAL Nuclear Medicine Dept. STUDY OF MULTIPLE TUMOUR NAL TRACT CANCERS.
OF
PIRAEUS
MARKER
IN G A S T R O I N T E S T I
In an attempt to assess the diagnostic effectiveness of the individual and combined use of tumour markers CEA, Ca-19-9,Ca-125, A F P , 7 2 - 3 in pts with malignant a n d b e n i g n d i s e a s e of GI, w e examined 2 7 2 p t s (46 b e n i g n , 156 c o l o r e c t a l canc e r , 34 s t o m a c h c. 22 h e p a t o b i l i a r y c. 18 p a n c r e a t i c c ~ a n d 40 n o r m a l s . The diagnostic sensitivity was higher for CEA in p a n c r e a t i c and colorectal c. (57%, 4 4 . 8 % ) , fc Ca-19-9 in pancreatic, hepatobiliary and stomach 59% a n d 4 5 . 4 % ) , f o r C a - 1 2 5 i n p a n c r e a t i c cancer ( 4 2 . 8 % ) , f o r A F P in h e p a t o b i l i a r y (50%) and for 72-3 in colorectal (37.6%). The association of CEA and Ca-19-9 increased the sensitivity i n s t o m a c h c. f r o m 3 2 . 3 % t o 50%, in c o l o r e c t a l c. f r o m 4 4 . 8 % t o 58..9% i n h e p a t o b i l i a r y c. f r o m 4 0 . 9 % to 6 3 . 6 % . With the combination of the other three marke~ the sensitivity increased in stomach cancer to 57.6%, in colorectal c a n c e r t o 6 6 % , in h e p a t o b i l i a r y c a n c e r t o 9 7 . 3 % a n d in p a n c r e a t i c cancer to I00%. Conclusion. The combination of multiple tumour narkers increases the sensitivity of the diagnosis a n d f o l l o w - u p in p a t i e n t s with gastro-inte3tinal tract cancer.
406
29 H. G.
30 LARBRE, F . DELTOUR
MARECHAL,
Institut J.GODINOT 5 1 0 5 6 REIMS C e d e x
H.
M. DELTOUR,
F.
MARECHAL,
Institut J.GODINOT 5 1 0 5 6 REINS C e d e x
L.
LOEMBA, G.
DELTOUR
BP 171
BP 171
TUMOR ASSOCIATED T R Y P S I N I N H I B I T O R A NEW MARKER OF CANCER P A T I E N T S .
( TATI
):
T A T I ( FARMOS -PHARMAOIA IRMA k i t ) is a small peptide ( PM = 6 0 0 0 ) , c o n t a i n i n g no c a r b o hydrate antigen, whose origin is still unknown b u t p r o b a b l y e x t r a p a n c r e a t i c . It is s u g g e s t e d t o be a new m a r k e r of gastrointestinal and g y n a e c o l o g i c a l c a n c e r s : we have studied TATI in cancers of various sites and c o m p a r e d i t w i t h OEA, 0 A - 1 9 - 9 a n d 0 A - 1 2 5 . Out-off v a l u e i s 15 U / m l . Gastrointestinal cancers: sensitivity i s 50% in stomach cancer, 40% in colon c a n c e r and 67 % in rectum cancer. T A T I , CEA a n d 0 A - 1 9 - 9 a p p e a r e d t o be c o r r e l a t e d , but sensitivity of TATI is greater. Gynaecological cancers: sensitivity i s 70% i n metastatic ovarian carcinoma and 38% in uterin cervix cancers. Out of 20 kidney cancers, sensitivity which is most interesting since at we d o n ' t h a v e a good m a r k e r o f t h i s
i s 80%, this time cancer.
31
NUCLEAR MEDICINE DIVISIQN °, PEDIATRIC ONGOLOGY DIVISICN NATIONAL CANCER ]ZS"flqlfI~OF MIIAN, ITALY
VALUE OF LAMININ P1 FOR CANCER P A T I E N T S
Many a u t h o r s think that the laminin, a 900 KDa glycoprotein and a major component of basement cell membrane, plays a major role in tumoral invasion and m e t a s t a t i c spreading. The l a m i n i n has been studied on 157 cancer patients a n d c o m p a r e d w i t h OEA a n d CA 1 9 - 9 . The l a m i n i n P1 r a d i o i m m u n o a s s a y Behring kit was u s e d . Serum l e v e l s were found t o be 1,20--+ 0,40 U/ml in a group of 67 healthy blood donors and were 2,77 ~ 1,66 U/ml in the 157 patients. The serum levels were statistically higher in metastatic breast cancer ( p < 0,01), ovarian cancer ( p < 0,01), stomach ( p < 0 , 0 1 ) and colorectal cancer ( p < 0,01 ). However, the laminin was not elevated in the others localizations ( non m e t a s t a t i c breast, uterin cervix, l u n g , and prostate cancers ). This marker c o u l d be useful in the gastrointestinal cancers where it appeared to be positive m o r e o f t e n t h a n OEA o r CA 1 9 - 9 .
32
M.R. CASTEI/ANI u, L. ROITOLI uo, M. GASPARINI o, p. MCNfANARI o
ou
MIBG SCAN IN T ~ STAGING A~D IN T ~ F O ~ OF PAT]]9~rsA F F E ~ BY NEUROBIASqOwA. 36 pts. affected by neuroblastcma,respectively 5 adults and 31 children (median ~ge 7 years), were studied with 131 I ~ or 123 I MIBG scan, at the National Cancer Institute of Milan in the period fr~n Feb. i~°88 to Feb. 1989. 22 scans were performed during the stsgir~, 36 dining the follow-up, with a total of 58 studies. All pts. studied dlring the staging were submitted to the standard diagnostic ~ e s and were classified 8 c c o r ~ to tl~eEvans classification, as follows: 2 pts. stage I, 2 pts. stage II, 5 pts. stage III, II pts. stsge IV, 2 pts. stage IVS. Primary tumc~ was diagnosed by MIBG scan in 94% of cases. In 3 pts. the intensity of tumor t~ot~ke masked the loco-regicnal or osseus localizaticr~. In diagnosis of distant localizations MIBG scan sho~d ~nese results: bone marrow infiltration (diffuse bone t~otmke) 6/8; liver 4/4; lymph nodal 1/3; bore 10/12. In 5 cases MIBG scan r~vealed a less number of localizaticns then bone scan. Howeve~ only one case was traderstaged (from IV stage to III stage) by MIBG scan. Durin~ the follow-up MIBG scan was agreed with the clinical, i~strumm~tal f'uxltn~s in 30/36 cases (83%). It is remsnkable that in 6 studies msde to confirme the absence of the disease, one test was positive and ~nis result is not yet confirmed after 5 months. Ftrthermo~ the scan ~ s negative in 5 cases of clinical progression, which occurred, in all negative cases, Iseveral months after the onset of the disease (rathe i0 m~nths to 36 mmths).
I
LARBRE)
R.P~ Baum, A. Schwarz, K. Bosslet, E. Gussetis, A. Hertel T. Baew-Christow, F.D. Maul, D. Schwabe, B. Kornhuber, G. H~r Depts. of Radiology and Pediatrics, J.W. Goethe Universit Hospital; Radiochemical Laboratory Hoechst, Frankfurt/ Main; Behringwerke, Marburg; FRG
STAGING AND DOSIMETRY OF METASTATIC NEUROBLASTOMA USING Tc-99m AND 1-131 LABELED MONOCLONAL ANTIBODY BW 575/9 The murine IgG 1 (kappa) monoclonal antibody (MAb) BW 575/B (Behringwerke,FRG) - originally developed agains a protein epitope on small cell lung cancer cells - react in immunohistochemistry with about 80 % of neuroblastoma and other neuroectodermal tumors. The intact MAb was labeled with Tc-99m using the free thiol group method described by Schwarz with a labeling efficiency of> 95 % immunoreactivity preserved) and with 1-131 (Iodogen) and injected (20 MBq Tc-99m/kg) in 4 children (aged 2 to 8 yrs) with metastatic neuroblastomas (NB). I child was in complete remission (CR) the others were studied before and after chemotherapy (CX) by planar scintigraphy and SPECT 4-12h and 18-26h p.i. 1-123 MIBG scans were obtaine at the same time in all children. Intense MAb uptake was found in 7/8 studies except for the child in CR, correlating with the MIBG scans on a lesion-by-lesion analysis. However, about 10 % of MAb ~ositive lesions were MIBG negative and vice versa. Dosimetric data were obtained using 1 - 1 3 1 B W 575/9 i n child with only partial remission after CX and weak MIBG but strong MAb accumulation. An early (4h p.i.) and high tumor uptake (0.6 % injected dose/g; t 1/2 e f f . > 2 d ) was found resulting in a tumor dose of 8400 cGy ( We-dose 8 0 cGy ) for a therapeutic activity of 1.85 GBq (50 mCi). Combined treatment (CX, MIBG, radioimmunotherapy) might possibly improve the poor prognosis of stage IV neuroblastoma by eliminating otherwise therapy resistant ceil clones.
407
33
34
M. Tondeur, R. Denays, T. Van Pachterbeke, M. Spehl, V. Toppet, H: Ham, A. Piepsz, M. Rubinstein, P. No61.
M, Tondeur. R. Denays, M. Foulon, H.R. Ham, F.Verstraeten, A.Piepsz, M. Rubinstein, P. No~l.
St Pierre Hospital, Free University of Brussels, Belgium.
Saint-Pierre Hospital, Free University of Brussels, Belgium.
BRAIN SPECT IN NEONATES.
Tc-99m HMPAO BRAIN SPECT IN CONGENITAL DYSPHASIA.
When performed during the neonatal period, cranial echography is currently the most performant method to detect cerebral injuries; however, this test is often normal in childrenwho will later develop neurological sequelae from severe perinatal asphyxia. The clinical value of brain SPECT, well established in adults and children, is still to be evaluated in newborns. We have investigated 36 babies, all of whom presented, durina the De.rinatal p~k~,d, a~: {east one ~ ~,~ t~IIow~'lg ri~k ?a~t~,r~ : b ~ welght less than 1501 g., asphyxia at birth, respiratory difficulties, hypoglycemia, sepsis, neurological symptoms. The SPECT was performed, without premed]cation, after intravenous injection of 0.5 mCi of 123 I-IM P (n=24) or of 3 mCi of 99m Tc-HMPAO (n=12). Only regionaJ asymmetries of more than 12% were considered significant. A cranial echography was realized within a period of 1 to 3 days of SPECT study. Both tests were analysed independently. 20 patients had structural lesions echographically demonstrated, most of which were also present on SPECT studies. However, mild ventricular dilatation and bilateral porencephalic cysts were not seen on S PECT studies. In 8 of these 20 babies, SPECT showed more abnormalities than echography. 16 patients had a normal ultrasound: 8 had a normal SPECT, the 8 others presented hypoperfused areas (parasagittal: n=4; periventricutar: n=4). These results suggest that SP ECT in neonates can detect abnormalities not visualized on echographic studies. Follow-up clinical studies are however needed to assess the significance of these anomalies, i.e. its relation to subsequent neurological deficit.
35
Congenital dysphasias are developmental speech disorders not explained by deafness, phonation disorder, mental retardation, neurological lesion or psychiatric disease. The presence of brain lesions has often been postulated but conventional investigations fail to demonstrate any cerebral abnormality .We have studied by means of Tc-ggm HMPAO brain SPECT, 12 children suffedng from a global dysphasia (phonologic syntactic disorder) and 2 with only an Impaired expression (verbal dyspraxia). In these last two patients, the SPECT studydemon.~trated a hvvoneffusion in the left i~-J~tlot hovla, co~woiution, involving the Broca's area, which could explain the expression imp.~irrnentpresented by these patients. In 9 of 12 patients with global dysphasla, SPECT study showed two hypoperfused areas : a focal hypoperfusion In the left temporo-padetal region and a hypopeffusion involving the upper and middle areas of the right frontal lobe. The existence of a hypoperfusion in the left temporopadetal area could explain the difficulties in the comprehension of speech. However, as these patients also had difficulties in lhe verbal expression, the absence of lesion in the Broca's area is noteworthy. This finding suggests, in agreement with some neuropsychologJca]studies, that in congenital dysphasias the abnormal expressive speech is frequently the consequence of impaired comprehension. The relation between right frontal abnormalities and language disorder is not obvious. Different data suggest th at these anomalies are not related to the deficits in compre. hension and expression but to the reduced prosody and/or to the associated neuropsychological deficrts particularly the attention disturbances. These results suggest that congenital dysphasias could be due, like acquired aphasias, to specific impairment of the language cerebral areas and that brain SPECT studies with 9gmTc-HMPAO could be useful for a better comprehension of the physiopathology of these disorders.
36
C. RAYNAUD, C. BILLARD, N. TZOURIO, B. MAZOYER, M.C. MASURE, M. ZILBOVICIUS, C. CHIRON, O. DULAC, M. BOURGUIGNON and A. SYROTA
M. ZILBOVICIUS, B. GARREAU, B.M. MAZOYER, N. TZOURIO, C. RAYNAUD, J.L. MARTINET, C. CHIRON, G. LELORD, A. SYROTA
Service Hospitalier Frdddric Joliet ORSAY - F r a n c e Pediatric Neurosurgery Deot. Hop. Bretonneau TOURS - F r a n c e Neuropediatric Dept. Hop. St-Vincent-de-Paul PARIS - F r a n c e
Service Hospitalier Frdddric Joliet ORSAY - F r a n c e HSpital Bretonneau TOURS - F r a n c e -
REGIONAL CHANGES OF CBF OBSERVED IN DYSPHASIC CHILDREN DURING LANGUAGE STIMULATION STUDIED BY SPECT
SPECT rCBF CHANGES AND EVOKED POTENTIAL RESPONSE DURING AUDITORY STIMULATIONS IN CHILDHOOD AUTISM
In six children with developmental dyspbasia and six control children of the s a m e age without language impairement, regional cerebral blood flow (rCBF) was measured by SPECT using Xe 133 with a TOMOMATIC 564. AH subjects were right-handed; they were studied at rest, and during two verbal stimulations. Stimulation 1 consisted in a story listening, I stimulation 2 was a picture-naming test. Preliminary results showed a t r e s t no significant difference of global CBF between c o n t r o l s and dysphasics, but during both stimulations, global CBF increased significantly in dysphasics only (J. Nucl. Med. 129: 792, 1988). The rCBF was measured on 86 cortical regions of i n t e r e s t (ROD in each study, for each ROI the mean value of rCBF was calculated in both control and dysphasic groups. To prevent l against type 1 error, rCBF changes were considered significant only when p <0.01 on t test. In control children, stimulation I increased rCBF in the l e f t auditory cortex (p=g.OO7), stimulation 2 increased rCBP of the median prefrontal cortex (p=0.002). In dysphusics, stimulation 1 produced a rCBF increase in Il e f t and right associative areas and in occipital visual cortex whereas it dit not in the l e f t auditory cortex. Stimulation 2 increased rCBF in most of both hemispheres. These results suggest t h a t dyspbasics respond to verbal s t i m u l a t i o n by involving associative areas to c o m p e u s s t e their difficulty to increase rCBF on isolated language areas.
Regional Cerebral Blood Flow (rCBF) mesured by SPECT (Xenon 133 - Tomomatic 564) and Auditory Evoked Potential (AEP) were studied in 11 premedicated primary autistic children, aged from 6 to 13 years. Three rCBF m e a s u r e m e n t were perfermed - a t rest, during simple binaural auditory stimulation (80rib, 750Hz, 200 msec) and during binaural presentation of music, rCBF was computed in 86 cortical regions of interest for each examination. AEP reponse was registered during the s a m e simple 80db auditory stimulation, and permited the distinction of 2 sub groups of children, with normal (6) or abnormal (5) modulation. During the simple auditory stimulation rCBF decreased in the posterior part of the Ieft superior temporal area (p=0.O4); the children t h a t showed a abnormal AEP modulation Presented also a significant rCBF increase in the right latero-frental region (p=0.02) and in the right inferior temporal a r e a (p=0.03). During the music presentation rCBF decreased in the left temporal superior area (p=6.04). In conclusion during the simple auditory stimulation we[ observed t h a t abnormal AEP modulation and rCBF increase I were associated in a subgroup of autistic children. J The binaural music presentation showed rCBF changes but did not differentiate this subgroup.
408
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38
AM El-Shirbiny+, S Sadek, A Owunwanne, A Tagreed, L Suresh+, M Awdeh.
O.Taddei, P.Gerundini, F Zito, M Fiorenza, A.Savi, F.Fazio.
C.Messa,
M.Matarrese,
Depts. of Pathology+ & Nuclear Medicine, Faculty of Medicine, Kuwait University, Kuwait.
Istituto San Raffaele,
IS Tc-99m HEXAMETHYLENE AMINE OXIME (HM-PAO) UPTAKE IN THE TISSUES RELATED TO GLUTATHIONE (GHS) CELLULAR CONTENT?
Tc-99m ECD: A NEW TRACER FOR BRAIN SPECT STUDIES.
Previous reports mentioned Tc-99m HM-PAO uptake in tissues is proportional to GHS concentration. We planned a project to find whether this relation exists. Male sprague Dowely rats (300-350gm) were used. ii rats GHS depleted (D) by intraperitoneal injection (inj.) of 0.5 ml dimethylmaleate (Sigma) in sunflower (SF) oil (4 ~ o l ~ k ~ h ~ y weight). A ¢ontro! ~rp (C) 13 ~ats inj with equal dose of SF oil. All rats inj i.v. I hr later with 50 uCi Tc-99m HM-PAO (time of max. D). Rats sacrificed after another hr. Mean GHS content in mmol/kg was determined and showed successful depletion of liver, kidney, spleen, brain and lungs with p value of <0.001. Mean % injected dose/gm showed no sig. change between D & C except liver; there was more uptake in D (0.479Z0.030) than C (0.302!0.006) with p value of <0.01. Because of this we repeated the experiment : 5 C rats, 5 D rats and I0 D rats inj. 0.125 mg CCK one hr before HM-PAO. This table shows results: % inj. dose/gm Control Depleted Depleted + CCK Liver 0.322+0.06 0.562+0.07 0.37+0.05 Intestine 0.566~0.199 0.29+O.077 0.356+0.186 Blood 0.684+0.086 0.706+0.07 0.662+0.095 The liver showed ~ess HM-PAO uptake in D+CCK tha~ D, p value <0.0001 probably CCKrelieved cholestasis. We conclude that HM-PAO uptake in the tissues is not related to GHS cellular content.
39 G. Luci~nani, C.Rossetti, R.Blasberg, and L.Sokoloff.
University of Milan, Italy.
Tc-99m ECD (ethyl cysteinate dimer) is a new labeled compound that crosses the blood brain barrier proportionately to cerebral Blood flow. Tc-99m ECD biodistribution and SPECT imaging were studied in 2 normal volunteers after informed consent. Biodistribution of Tc-99m ECD in brain and other organs was monftored up to 5 hrs following the i.v. injection of 740 MBq of Tc-99m ECD. Whole body images were obtained at 1 and 5 hrs post i.v. injection Organ uptake was corrected fQr body attenuation. SPECT brain images at i0' and 2 hrs post i.v. injection were also performed. Within 10-60' a 7% decrease of cerebral activity and a 50% decrease of head/soft-tissue activity was observed. 45% of ~be injected dose was cleared in the urine within 4 hrs an~ 70% within 24 hrs~ The gray/white matter ratio obtained corrected for attenuation and scatter was 2.4. Vi%a~ signs, blood and urine chemistry remained normal. SPEC~ was also performed in 4 patient volunteers who have ha4 a stroke more than 4 weeks prior to the study, based c~i neurologic signs and symptoms and the subsequen~ development of an abnormal CT scan. Three patients w~%h stroke showed larger Tc-99m ECD perfusion defects than o~ the CT scans. The biodistribution results demonstra~e~ the rapid brain uptake of Tc-99m ECD. Also the chemical stability of the compound, the low dosimetry to %he patient due to the rapid wash out and the good quality of the tomographic images make Tc-99m ECD a reliable agent for cerebral perfusion studies.
40 H.Otsukl,
M. Chelliah
C.N.R. - I.T.B.A., Istituto Sclentifico H S.Raffaele Milano, Italy, Dept. Nuclear Medicine NIH and Laborator of Cerebral Metabolism, NIMH, Bethesda, MD, USA. KINETICS OF SQ32097: A NOVEL Tc-99m-LABELED TRACER FOR MEASURING rCBF. The usefulness of Tc-99m-labeled Bis 2,3-butanedlone-
dioximato(l-)-O-2,3-butanedionedioximato(2-)O-2-methyl,l -propylborato (2)-N,N',N'',N''',N'''',N''''' -chlorotechnetium (8Q32097) as a tracer for measuring regional cerebral blood flow (rCBF) with SPECT (1987, J. Nucl. Med., 28: 1081) was evaluated. The metabolic degradation of the tracer in brain and blood in vivo was examined for up to 30 min after i.v. bolus of the tracer in normal conscious rats. The unidirectional extraction fraction of the tracer from blood to brain was determined in anesthetized rats by the indicator-diffusion method with 1-125-1abeled human serum albumin as the reference tracer. The relationship between the regional distribution of this tracer in brain and the rate of rCBF measured by C-14 iodoantipyrine was also determined in rats for up 30 min after i.v. injection of the tracer. The results of this study demonstrate: I) SQ32097 is a fairly stable compound in saline for up to three hours after labeling; 2) its absolute and relatlw concentrations in blood fall rapidly after an i.v. pulse; 3) SQ32097 is metabolized in brain at a slow but significat rate; 4) its unidirectional extraction fraction is approximately 0.5 in anesthesized animals; 5) its regional distribution in brain correlates wit} the rates of rCBF only at low rates of flow and for a limited period after i.v. administration. In conclusion: the usefulness of SQ32097 may be limited by incomplete extraction and significant backflux from brain.
B a ~ g e r l I. l), R i c q s b o n a G. j), B a u e r ~ G . ¢), B o h r K. ", H a s l e r P . - ~ . ~ ' 2 ~ - ~ i g e r P.A. jJ I~ Depts. of N e u r o l o g y " and N u c l e a r M e d i c i n e ', A n i c h s t r . 35, A - 6 0 2 0 3 ~ n n s b r u c k , A u s t r i a , Dept. Radiopharmaceuticals ", P a u l - S c h e r r e r - I n s t i t u t e SH-5232 Villigen, Switzerland
123 I - I O M A Z E N I L B R A I N S P E C T IN V A R I O U S F O R M S OF E P I L E P S Y (A P R E L I M I N A R Y R E P O R T ) P r e l i m i n a r y s t u d i e s on 123 I - I o m a z e n i l - a b e n zodiazepine (BD) a n t a g o n i s t b i n d i n g to BD r e c e p t o r s - h a v e s h o w n that this t r a c e r r e g i s t e r s e a r l y c e r e b r a l c o r t i c a l p e r f u s i o n and BD r e c e p t o r s l a t e r in b r a i n . As BD d e r i v a t e s are a p p l i e d to t r e a t e p i l e p s y we s t u d i e d BD r e c e p t o r s in 14 p a t i e n t s w i t h focal e p i l e p s y (FE, n=6) and L e n nox-Gastaut-Syndrome (LGS, n:8) u s i n g S P E C T and a d d i t i o n a l p e r f u s i o n s t u d i e s w i t h 123 I - A m p h e t a mine (n:4) or 9 9 m T c - H M P A O ( n = I 0 ) ( 1 8 5 MBq 123 Ilomazenil, 185 M B q 123 I - I M P and 555 M B q 9 9 m T c HMPAO respectively, Siemens-Gammasonics Orbiter ZLC 37 c a m e r a , M i c r o v a x , i m a g e r e c o n s t r u c t i o n as d e s c r i b e d p r e v i o u s l y ) . LGS is a f o r m of e p i l e p s y s t a r t i n g in youth, f r e q u e n t l y c o m b i n e d w i t h m e n tal r e t a r d a t i o n and m y o c l o n a l s y m p t o m s w i t h an i n s u f f i c i e n t r e s p o n s e to c o n v e n t i o n a l a n t i e p i l e p tic t h e r a p y . R e s u l t s s h o w t h a t in FE ( i n t e r i c t i sally) p e r f u s i o n m a r k e r s s h o w e d a b n o r m a l i t i e s c o r r e s p o n d i n g to c l i n i c a l foci b e t t e r t h a n 123 I. I o m a z e n i l , w h i l e in LGS 123 I - I o m a z e n i l u p t a k e o a t t e r n s are c o n s i d e r a b l y m o r e a b n o r m a l than per. f u s i o n p a t t e r n s . We c o n c l u d e t h e r e f o r e that 123 I o m a z e n i l s h o u l d f u r t h e r be s t u d i e d to d i f f e r e n tiate b e t w e e n d i f f e r e n t f o r m s of e p i l e p s y a l s o concerning therapeutic approaches. Obviously s e i z u r r e s in the c o n t e x t of LGS h a v e a d i f f e r e n t n e t a b o l i c b a s i s t h a n t h o s e s e e n in FE.
409
41 K ~ n ~ ~ g ~ B ~ , H.H. Coenen 2, N. Roosen 3, P. Kling 2, O. Muzik t , H. Herzog I , T. Kuwert * , G. $t6cklin z and L.E. Feinendegen* i) Institut fur Medizin und 2) Institut fur Chemie I, KFA JUlich GmbH 5170, JUlich, FRG 3) Neurochirurgische Klinik der Universit~t DUsseldorf, 4000 DUsseldorf, FRG SPECT STUDIES OF BRAIN TUMORS WITH L-3-[Is3I]Iodo-~ METHYL TYROSINE (123IMT): FIRST CLINICAL RESULTS AND COMPARISON WITH PET AND 124IMT The purpose of this study was to investigate the intracerehral kinetics of L-3-iodo-a-methyltyrosine and to further elucidate the clinical potentials of I~3IMT-SPECT in the study of human brain tumors. The kinetic behaviour of IZ4IMT in brain and plasma was investigated in two patients with glioblastoma usin~ dynamic PET. The tracer accumulated in the brain and in the tumor tissue reaching a maximum after 15 min with a washout of 20 to 354 at 60 min p.i.. Animal experiments confirmed the accumulation of the intact tracer, although it was not incorporated into proteins. Fifty-two SPECT studies with *2SIMT were performed in 32 patients with different types of brain tumors. Tumor/cerebellum ratios (T/C) ranged from about 1 to 2.5. No significant differences in the degree of *2SIMT uptake between different types of brain tumors could be detected. The tumor extent appeared to be larger in SPECT studies than in CT scans in 12/32 patients. Repeat studies in patients with malignant gliomas before and after intra-arterial chemotherapy with the nitrosourea ACNU (iaACNU) showed no changes of T/C ratios in 5/5 patients studied 1 day after iaACNU, but changes of more than 20 % in 4/10 patients studied within 2 to 6 days after iaACNU. We conclude that *~SIMT is a promising agent for SPECT studies of cerebral amino acid uptake.
43 A.Kroiss, F.BSck, G.Perneczky, Ch.Auinger, G.Weidlich, G.Kleinpeter, A.Neumayr
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 , Ist M e d i c a l Department, Neurosurgical Department, Ludwig Boltzmann Forschungsstelle fur klin. G e r i a t r i e , KA R u d o l f s t i f t u n g , Vienna, Austria CLINICAL APPLICATION OF T c - 9 9 m L A B E L E D G R A N U L O CYTES A N T I B O D Y IN B O N E A N D J O I N T D I S E A S E S . The a i m of this s t u d y w a s to p r o o f the c l i n i c a l r e l e v a n c e of m o n o c l o n a l granulocytes antibody in c o m b i n a t i o n w i t h b o n e s c i n t i g a p h y w i t h Tc99m-diphosphonat in d i f f e r e n t b o n e and j o i n t diseases.The immunoscintigraphy (IS) was p e r performed with Tc-99m labeled antibody (BW 250/183; B e h r i n g w e r k e , FRG). The d e t e c t i o n s were d o n e 4-6 a n d 24 hrs p l a n a r a n d in p a t i e n t s with d i s e a s e s of the h i p a n d spine S P E C T p i c tures w e r e p e r f o r m e d too. In 45 pts we p e r f o r m e d the b o n e s c i n t i g r a p h y ~nd IS, 25 m a l e a n d 20 female, age f r o m 18 to 81 yrs. In 7 pts we f o u n d an o s t e o m y e l i t i s , in 5 pts a c o x i t i s a n d c o x a r t h r o s i s , in 19 pts ~e c o u l d d i f f e r e n t i a t e between septic loosening 3f h i p p r o s t h e s i s or a n o n s e p t i c , in 4 pts we found a s e p t i c p r o c e s s of the s p i n e a n d in 4 ots a d i s c i t i s . W i t h t h i s i n v e s t i g a s t i o n we Sot g o o d i n f o r m a t i o n s in pts a f t e r n e u r o s u r g i c a l spine o p e r a t i o n s a n d f e v e r a n d p a i n a t t a c k s (n=6). We f o u n d a s e n s i t i v i t y of 90% and a s p e c i f i c i t y of 86%. In c o n c l u s i o n , the m e t h o d is h e l p f u l for l o c a l i z a t i o n a n d e x t e n d of a s e p t i c p r o c e s s in b o n e ~nd j o i n t d i s e a s e s . T h e r e is no i n - v i t r o cell 3 e p a r a t i o n n e c e s s a r y a n d t h e r e f o r e e a s y to ~erform. S P E C T i m a g e s are p o s s i b l e .
42 V Ivan~evid(+), D Dodig(+), M Livakovi6(*), J Han~evi6(*), D IvanSevi6(+)
(+)Department of nuclear medicine and (*)Surgical clinic, University Hospital Rebro, Zagreb, Yugoslavia THREE-PHASE 99m-TC-HM-PAO MIXED LEUKOCYTE SCAN, THREEPHASE BONE SCAN AND 67-GA IN CHRONIC OSTEOMYELITIS There are doubts whether scintigraphy with labelled leuko cytes and with 67-Ga are sensitive methods in detecting chronic osteomyelitis.A total of 20 3-phase 99m-Tc-HM-PAO mixed leukocyte scans(MLS), 17 3-phase bone scans (3PB), and 16 67-Ga scans(GS) were performed in a group of 16 adult patients suffering from chr. osteomyelitis verified clinically, by x-ray and/or surgery.Leukocytes were labelled in plasma incubating 370MBq 99m-Tc-HM-PAO with the leukocyte suspension for 10min yielding a surprisingly io~ labelling efficiency of 34+/-11% (mean+/-SD) correlated with the leukocyte counts (r=O.70,p<0.01) and differing significantly from our own results in other patient categories with comparable leukocyte counts. 3PB consisted of a dynamic study immediately post injection(pi) and static imaging 30min and 3h pi. MLS was done I, 4 and 21h pi, GS 48h pi. Lesion to non-lesion ratios, obtained constructin mirrored symmetrical areas of interest over both extremities, were the highest with ML$ 4h pi(2.28+/-0.97,mean+/SD) but not significantly different from those in GS(2.00 +/-0.92).The sensitivity of 3PB, MLS and GS was 100%, 93% and 80%, respectively. Due to the homogeneity of our patient group there was little sense in analizing specifici ty. MLS picked up 7 inflammatory foci in soft tissue, whereas GS detected none.We conclude that mixed leukocyte scan is a sensitive method in diagnosing chr. osteomyelitis and ~referable to Ga-scan. 3-phase bone scan as a highly sensitive but non-specific method in our opinion has a place in ruling out false positive findings on mixed leukocyte scan and/or Ga-scan.
44 I. B r a n d h o r s t + ,
N.
Starker++,
D.
L. Munz*
+Institute for D i a g n o s t i c Imaging, Frankfurt; ++ D i v i s i o n of O r t h o p e d i c s , U n i v e r s i t y H o s p i t a l Frankfurt; * D i v i s i o n of N u c l e a r M e d i c i n e , University Hospital G6ttingen; F.R.G. BONE SCANNING, 99mTC-LABELED AUTOLOGOUS LEUCOCYTES, 99mTC-HSA-COLLOIDES AND 99MTC-LABELED ANTI-GRANULOCYTE-ANTIBODIES IN THE D I A G N O S I S OF INFECTIONS: FIRST INTRAINDIVIDUAL RESULTS. New procedures with 99mTc-leucocytes, inert 99mTc-colloids and 9 9 m T c - l a b e l e d a n t i - g r a n u l o cyte-antibodies (MABs) h a v e b e e n i n t r o d u c e d in o r d e r to e v a l u a t e infections. T h e a i m of o u r s t u d y w a s to p e r f o r m e an i n t r a i n d i v i d u a l comparison using these 4 methods in i n f e c t i o u s bone disorders. The 4 procedures were performed u s i n g t h e 3phase-technique (perfusion, bloodpool, late s t a t i c phase; bone -> MDP; l e u c o c y t e s -> H M P A O ; colloid -> H S A - N A N O C O L L ; M A B s -> A G - M A B s BW 250/183) in 16 pts. (8 f e m a l e s , 8 males; mean age 65 yrs.) s u f f e r i n g from s u s p e c t e d i n f e c t i o n of a r t i f i c i a l knee/hip replacements as w e l l as i n f e c t i o n s of the lower e x t r e m i t i e s . In 11 pts. we f o u n d a v e r y g o o d c o r r e l a t i o n of the 4 m e t h o d s as i n d i c a t o r of an a c t i v e infection. In 4 pts. we f o u n d an a b n o r m a l bone scan w i t h t h e o t h e r s c a n s to be n o r m a l as e x p r e s s i o n of an a s e p t i c loosening of t h e p r o t h e s e s . In I pt. a l l 4 m e t h o d s s h o w e d n o r m a l r e s u l t s due to a disk herniation w i t h p a i n in t h e h i p o p e rated. In our opinion, these r e s u l t s d e m o n s t r a t e that consecutive to a b o n e scan an additional leucocyte, or c o l l o i d or M A B s c i n t i g r a p h y is a d e c i s i v e f a c t o r in the d i a g n o s i s of infections.
410
46
45
H. Gericke*, L. Ecka~t+ , U. G6ke#, F. Kaestner*
P. Heintz, Ch. Ehrenheim, H. Hundeshagen.
University Clinic Rudolf Virchow-Wedding Free University of Berlin, * Dept.of Nuclear Medicine, ÷ Dept.of Orthopedics, # Dept.of Radiology.
Department of Nuclear Medicine, Clinic of Traumatology, Medical School of Hannover, FRG
THE SIGNIFICANCE OF N ~ I D - S E ~ - S C I N T I G R A P H Y IN THE DIA(~IS OF I ~ O N S OF A L L O ~ C S OF T ~ HIP AND ER~
The significance of bone-scintigraphy with 99"Tc-Diphosphonate in the diagnosis of bc~=-infectio~s is 1~or, because of unspecific mechanimn of osteoblastic activity. The aim of our Study was to comprehend the behavionr of Tc~gm-labelled Nanccolloids in ~ . toparat.ive changes ..agdto asses the p?tential of this method to differantiare postoperative caanges vs ostemm/eiltzs. We in~stignte 67 patients 3 wks. after i~@lantation of an artificial hip, 5 with an artificial knee. 3-Phase SS=Tc Nanocolloid-Scan were taken, add/tional radiological, clinical and laboratorical parameters were obtained. The analysis of the perfusion study of the hip implants showed two maxima. An index > 1,7 was seen as positive, an index < 1,7 as normal perfusion.Following this classification 59 % of the patients showed positive parfusion (Q > 1,7), 41% normal perfusion (Q < 1,7). The comparision of of Nanocoll-Enrichment of the blocdpool and late scans with the Nanocoll-Perfusian groups showed no difference. In cases with knee implants all showed an u n ~ y high perfueion index. In two cases with clinical signs of infection, the scan showed positive results, 2 cases without showed a false positive enrichment. In cases of clinically obvious early infection a higher penetration of Naxzx~lloids was found as well as an enlarged perfusion. After clinical healing the control scan revealed a normal study. In two cases with anclesr follow up clinic, we revealed equivocal findings. To detect late postoperative hone infection follow up scans were performed 6 months after the operation. No patients with normal early postoperative study showed any sign of late infection. In conclusion, infection scintigraphy with ""=Tc-lahelled Nanocolloids has been sho~n a r e t i e method to rule out early infections of hip-implants due to the fact that no unspecific penetration in pastoperative alterations were found. In the cases of knee-implants, the scan can't reosm~-~d yet because of false positive studies. In cases with less significant clinical signs of infection, the interpretation re~res more exparimentation with the method.
L. Reilmann,
IMAGING METHODS IN THE DIAGNOSIS OF 05TEOMYELITI$: BONE SCAN, LEUCOCYTE SCAN, AND MRS Aim of the study: Examination of patients with clinical signs of ocute or chronic esteornyelitis. P a t i e n t s : 22 patlents ( 1q adults, 8 children) wlth acute ( 1 2 ) or chronic estesmyelitis ( I O ) were examined. The preferred lacalizations of the inflammatory procass~ were the lower limb (12), the upper limb in 8 cases, and the hip (2). Methods: After x - r ~ , dynamic bone scintlgraphy using 99mTc-MDP was performed in all cases. Adults underwent a leucocyte scan after the i.v. application of 1 I1 In-oxen labell~ leucocytes. MR images were obtained using T l - , proton density-, and T2-weighted sequences. 8 patients received the paramagnetic contrast agent C~d-DTPA. Results: Bone scan showed a hyperperfusion in the acute stage, and blood pool phase r~ealed a moderate hyper~tivity in the inflammatory arm. The high activity in the late phase makes a differentiation between coteomyelitis and turnout (for example ~tamar'coma) impossible In a number of cases. Leucocyte scan is highly specific concerning the demonstration of inflammatory procaines. It usually allows a differentiation between acute and chronic "stage of osteomyelitis, as chronic processes do not show leucocyte migration, mostly. MR imaging showed Incr'ees~l signal intensity In the T2-weighted images subper'iostal, in most cases combined with an increased signal intensity in the marrow space. Corticalis may have small lesions, the edema within the soft tissue was extended in the acute inflammatory phase. In contrast to scintlgraphy the high rasolution and excellent sort tissue contrast facilitates the differentiation between inflammation and turnouts. MRI provides high ~nsitivity, and improves the specificity of im~ing techniques in the de,noses of osteomyelitis.
48
47
A.J. COAKLEY, A.G. KETTLE, R.E.C. COLLINS, Sandrock D., Merino M.J., Norton Miller D.L., and Neumann R.D. National
N. SOdkamp,
Institutes
of
Health,
J.A.,
Bethesda,
Benton
C.P. WELLS
C.S.,
Maryland,
Department of Nuclear Medicine, Kent & Canterbury Hospital, Canterbury, Kent CTI 3NG, U.K.
U.S.A.
LIGHT- AND ELECTRON-MICROSCOPIC ANALYSES OF PARATHYROID T U M O R S E X P L A I N RESULTS OF T I - 2 0 1 / T c 99m PARATHYROID SCINTIGRAPHY. The aim of this study was to determine causes for the detectability of parathyroid lesions by TI-201/Tc-g9m scintlgraphy. In our initial report (JNM 29:860,1988) only 1/3 of our surgically confirmed lesions were visualized by scintlgraphy. Specimens from 15 sclntlgrephleally true positive (TP) adenomas, 15 false negative (FN) edenomas, 15 TP hyperplaslas, 15 FN hyperplaslas, 15 true negative normal glands from patients with, and 15 normal glands from patients without hyperparathyroldlsm were studied. The g0 tissues were sectioned, HOE end antI-PTH antibody stained, and the number of oxyphll, chief, and clear cells counted In 5 randomly selected areas (103 um by 103 urn); 18,265 cells were scored In total. In 30 tissues the number of mltochondrla per cell was counted In 5 random calls of each lesion from transmission electron photo-microgrsphe (magnlnoetlon x 15,000). No correlation was found In S multivariate analysis between sclntlgraphlc detectability and the parameters of age, sex, single/multiple gland disease, anatomic Iocctlon, prior neck surgery, lesion size, serum parethormone levels prior to surgery, total cell counts, or the absolute number of chief cells. There was also no correlation between results of contrast anglography end sclntlgrephy in 19 lesions; negating enhanced perfuslon as the determining parameter. However, sclntlgraphlc TP lesions had s significantly higher number of oxyphll cells than FN or normal lesions, end • lower number of clear cells. TP lesions had a oxyphll/clear cell ratio > 1 in 23 of 30 cases, in contrast to only 1 of 30 FN lesions (p < 0.0005; average ratio TP 1,4 vs FN 0.2). Normal glands had, In all cases, ratios < 1 (ev. ratio 0.2). The number of mltochondrle per cell was higher in oxyphil cells In lesions detected by sclntlgrephy (idenomas 155 +/- 58, hyperplaslas 55 +/- 18) than In chief or clear cells In those lesions not detected or in normals (30 +/- 15, p < 0.001). In conclusion, the detectability of abnormal parathyroid lesions by Tc/TI subtraction sclntlgrsphy is primarily dependent on mitochondrla-rlch oxyphll cells, which may have • higher TI-201 uptake.
or non-detectability subtraction
Tc-99m RP30A
- A
NENAGENT
FOR PARATHYROID LMAGING
Thallium-201/Tc-99m pertechnetate subtraction scanning is the standard radionuclide method for localising abnormal parathyroid glands. Tc-99m RP30A has been introduced as an alternative to TI-201 in studying myocardial perfusion. We describe its use as an agent for parathyroid localisation. Eight patients with hyperparathyroidism have been studied with both the thallium-pertechnetate subtraction technique and also with Tc-99m RP3OA, and five of these have now undergone surgery. Three had solitary parathyroid adenomas which were correctly localised by both techniques; in two of these the adenomas were more readily demonstrated with Tc-99m RP3OA. One patient with renal hyperparathyroidism showed a similar pattern with both techniques, two of three abnormal parathyroid glands being localised and a "false" positive thyroid adenoma. The fifth patient with metastatic parathyroid carcinoma will be discussed. Examination of data showed that the improved images of Tc-99m RPBOA may be due to a longer transit time of the agent in parathyroid adenomas when compared with TI-201, as well as the intrinsically better imaging characteristics of Tc-99m. The preliminary results indicate Tc-99m RP30A may be a suitable technetium labelled alternative to TI-201 for parathyroid localisation, and is superior in some cases. Further studies are being undertaken to identify its role in parathyroid imaging.
411
49
50
Sandrock
D.. D u n h a m
R.G., a n d
Neumann
Department of Nuclear Medicine, Health, Bethesde, Maryland, U.S.A.
A.Z. Rudavsky, E.J. Fine, M. Finkelstein, L.A. Sugarman, M.I. Surks, B.A. Sachs and L.M. Freeman
R.D. Institutes
National
of
PHYSICAL AND PHYSIOLOGICAL C O N S I D E R A T I O N S IN TL-2OIITC-ggm PARATHYROID SUBTRACTION SCINTIGRAPHY USING THE SIMULTANEOUS DUAL ENERGY TECHNIQUE, TI-201/Tc-9gm duel energy eubtralctlon parathyroid sclntigrephy ial al potentially useful technique. To determine en optimum protocol, ws analyzed In detail 10 patients with primary hyperperMhyroidlem. All subjects (1 malls, 9 females, sages 45 +/- g years) had s~intlgrephlcally true-poaltlval abnormall parathyroid glalnds. Each rscelvald (i.v.) 74 Mgq (2 mCI) Tc-ggm palrtschnetete end 20 man later 74 MBq (2 mCI) TI-201 chloride. Thirty mlnutals dynamic acqulalltlone permitted creation of time-activity curves over thyroid (T), abnormal parathyroid {P), and background regions (B). Peek alctlvtty Occurred within 2 minutes post Injection, thaln linearly decreased during the next 20 mln (1.2 +/- 0.4 %/mln alnd 0.87 ÷/- 0.3 %/mln for T end P respectively). Slopes of T and P did not dlfler significantly (p ~ 0.15). Average count rates over T were 7.1 kcounts/mln (Tc-g9m) and ~.9 kcounte/mln (TI-201) Thyroid end paralthyroid phantoms (1.85 MBq (50 uCI) Tc-99m and/or TI201) walre also studied to determine Tcfrl crossover: 7.0 % of the TI counts appeared In the Tc image, while 6.5 % of the Tc counts alppeared in the TI imagal. In order to minimize the soqulsillon time, avoid patient movemalnt between Tc and TI acquisition|, equalize ell near es possible the net-count rates, and retain data for background and motion corrections, the following protocol was developed (fig. 1): 1. Inject 74 MBq (2 mCI) Tc-99m pertechnetate. 2. After 15 sin., acquire 7 frames of 4 sin. each simultaneously in the 140 ksV (To99m) and 78 key (T1-201) window. 3. Five sin. after start of the acquisition {I.e., In the second frame), Inject 111 MBq (2 mCI) T1-201 chloride. Studies were processed as follows: TI frame I wee used for it background correction o1 TI frames 3 - 7. Alter normalllzatlon of the background corrected TI frames (squall count rates In TI and Tc frames In T), T¢ frames g thru 7 alral subtracted from the corresponding background-corrected end normellzald TI frames. The five subtralctlon Images, repretentlng 20 sin. acquisition time, are aldded alnd smoothed. If the patient has moved during the acquisition, a motion correction le done before adding the subtracted frames. The protocol has been tealted successfully on ten patients end le now in routine clinical use. We find that simultaneous duel energy TiFTc acquisition minimizes the risk of patient movement for the TI.201/Tc-ggm parathyroid subtraction scintlgrephy, and provides excellent results. Vlg
t:,
ucqulsltlom rrotocol 74 Bq T¢ , , .,. do...r.... ~ ~'
~
P ~"* ~ ~
'i
i
I
i
i
I ~
75 k t Y
, .......
AMBULATORY DIVIDED DOSE 131-1 ABLATION OF FUNCTIONAL REMNANTS AFTER SURGERY FOR THYROID CANCER Ambulatory ablation of residual functional thyroid tissu, in the neck of patients operated for thyroid cancer was accomplished in 43(84%) of 51 patients using a regimen of 2 or 3 doses of radioiodine 131-I (25-30mCi) separated b2 24-96 hrs. Functional thyroid remnants in 30 of 35 patients who received 2 doses and 13 of 16 patients who received 3 doses were successfully ablated. Pathological diagnoses included papillary-follicular cancer(21), papillary cancer(!7), follicular cancer(ll), and anaplastic and medulllary cancer (i each). Operations included 'near total' thyreidectomy(23), partial thyroidectomy(12), radical thyroidectomy and node dissection(ll) and sub-total thyroidectomy(5). Criteria for successful ablation included clinical parameters (all patients), insignificant radioiodine uptake in the neck(35), negative thyroid scans(36), and TSH greater than 25mIu/ml(ll). Patients have been followed from 3 to 276 mos. Total absorbed dose at Im using this out-patient protocol is comparbale to the total absorbed dose at im from the time of discharge of an in-patient receiving a single large dose and hospitalized until the measured radiation at Im is less than 6mR/hr, as is customary in the USA. This divided dose regimen has resulted in ablation rates similar to those ~chieved by conventional protocols employing much larger single doses of 131-I, requiring hospitalization and isolation. This novel regimen is much less costly and expose~ the patient to considerably less radiation than more con7entional approaches.
52
51 ~ares, I Soossens, W ~elche, C ~'rle~berg, U Buel I
Montefiore Medical Center and North Central Bronx Hospit~ and the Albert Einstein College of Medicine, Yeshiva University, Bronx, NY and Long Beach Memorial Hospital, Lon Beach, CA
Z Klelnhans,
Dept of Nuc] Ned, Technical Univ of Aachen, FRGermany
DETECTION OF LOCAL RECURRENCIES AND LYMPH NODE METASTASES OF DIFFERENTIATED THYROID CARCINOMA BY MAGNETIC RESONANCE IMAGING (MRI): METHOD AND FIRST CLINICAL RESULTS Morphological diagnosis of recurrent tumor growth following complete thyreoidectomy is based on ultrasonography (US) and CT using contrast enhancement after infusion of iodinated contrast media preventing subsequent diagnostic or therapeutic use of 1-131. Thus, we performed MRI in 52 thyreoldectomized patients between i week and 3 years following surgery and in 7 healthy volunteers. Transversal, frontal, and occasionally sagittal MRI-sections of 6,~n thickness were obtained with a 1.5T supra-conductlng system(MAGNETOM) using 3 different coils (collar, ear/eye, experimental Helmholtz) and spin echo pulse sequences (TI, T2, proton-weighted). The results were confirmed by US, CT, 1-131 scintigraphy, hTg measurements, and surgery. In total 13 of 14 tumor lesions (93%) were detected by MRI, only 3 of them (21%) revealed uptake of 131-I. Optimal tumor contrast was gained by T2- and proton-we|ghted sequences (high signal intensity compared with surrounding soft tissue structures and scars).Signal intensity of inflammatory lesions, local edema and hematoma following surgery, however,was also high, hampering dlfferentlal diagnosis. T2-weighted transversal sections gained wlth a collar coil were most valuable for tumor diagnosls,T1- and proton-weighted images gave no further criterions to discriminate tumor and non-tumor lesions. We conclude that MRI is a promising alternative to CT in differentlating scar and tumor tissue and detecting local tumor recurrencieswhlch do not take up 1-131.
J.M. Llamas-Elvira, R. Sopena, A. Jimenez-Neffernan, M~ Martinez-Paredes, F.M. Gonzalez, M ~ D. Martinez-Piazza, J.M. Latre, A. Mateo.
Nuclear Medicine Service."Reina Sofia" Hospital. CORDOBA. Spain. MUSCARINIC CONTROL OF GALLBLADDER DYNAMICS. STUDY WITH 99mTc-HIDA AND CHOLINERGIC AGONISTS AND ANTAGONISTS. We studied 12 normal subjects (mean age 31 + 8.6 years) who underwenl four 99mTc-HIDA examinatiose. The si~dy was approved by the Honpii~'~ ethical com~itae. Each study was perfen~ed following a fasting period of 8 hours. A ii] ~Bq dose of 99mTo-HIDA was injected i.v. sad images a£quired on a 64x64yJ data matrix a i in~e/min, framing rate. Imping was initiated when lh~ gallbladder was clearly visualized and lasted 60 rain.. Gallbladdel ~nd b a c ~ d regians of interest were chonan and normalized b a c ~ ( corrected ISme-activity curves of the gallbladder were obt~ined.Gallblac~ der total ejection fraction and percentage of emptyJ_ng every 5 rain. we~ calculated. During dne first exsmination (ccnlrol), i0 minutes after th~ begining of adquisitica, one ml. of saline solution was injected subcut~ neously. The second exsmination ~ performed injecting 50 n~ of betane chol (chollnergic aganist) suboutaneously, instead of saline solutian During the third and fourlh exsminaticas i0 mg of pirenzepine (~[ ~eceptc~ blockade) and 0.15 mjlO kz of atropine (MI and M2 recepto] blockade) were injected i.v. respective/y, 5 minutes before betanecho. Lljecticn. Wilcoxcn's paired semple test was used to compare the firs 9rid second studies and die latter with the d%ird and fourth studies. The mean value of A~allbladder emptying a 60 minutes was 4Z wi~ -=aline injection and 27% wil/nbetanechol. This difference was si~ificsn~ (p < 0.05) follcwir~ the first minutes of the examination. Gallbladde~ ~nptying was observed in the study with pirenzepine, but wss si~nifican~ inferior (p<13.05) to the be%anechol value followir~ the first 35 minute~ ~tropine administratian inhibited completely gallbladder e~tyir~ in all casea, with significant differences (p
412
54
53 R.C. Stadalnik, W.L. Trudeau, D.R. Vera, R.L. Kennedy, J M~ndez: Divisions of Nuclear Medicine and Gastroenterology, University of California, Davis; Sacramento, California, USA.
R:Bent], P.Gerundini, P.Reggiani, P.Magnani, L.Cacc~mo L. Gianolli, S.Gatti, A.Bruno, D.Galmarini, F.Fazio.
Istituto San l{affaele, University di Milano, Italy. COMPUTER-BASED DIFFERENTIAL DIAGNOSIS AND PREDICTION OF PROGNOSIS VIA [ggmTc]GALACTOSYL-NEOGLYCOALBUMIN FUNCTIONA IMAGING. Functional imaging with [g~Te]galactosyl-neoglyeoalbumin (TcNGA) yields three kinetic parameters that describe the functional state of a subject's liver: Q/Vh, lhepatic plasma flow per hepatic plasma volume; [R], Ireceptor concentration; and kb, TcNOA-receptor affinity. W e have employed two quantitative methods, diacriminant lanalysls and the Cox proportional hazards model, for ~he purpose of: I) classification into one of four diagno~£i categories, and 2) prediction of prognosis. Discrlminant analysi~ using the Q/Vh, kb, and [R] paramaters to classify patients, both in terms of norn~al vs abnormal hepatic function, and membership in various !disease categories (normal, cirrhosis, hepatltls, and 'cholestasls) was also performed. In the former case, %he discrimination was successful at the 0.95 level. In t~e !latter, some classifications proved possible at the 0.95 level, while discriminations involving cirrhosis ~ere significant at the 0.90 level. Prognosis was measured as the probability of ~urvivin 2 years after the TcNGA study. Forty two patients with a variety of liver diseases (hepatitis, alcoholic cirrhosis, and sclerosing cholangltis) were studied. Cox regressions were applied to censored survival data using one of six variables: [R], serum billrubin concentration prothrombin time, albumin concentration, the amlnopyr~ne breath test, and the Ghild-Turcott Score. Receptor concentration, [R], provided the highest correlation wit survival (r=O.71, pC0.0001).
I I
SEMIQUANTITATIVE HEPATO-BILIARY SCINTIGRAPHY LIVER TRANSPLANT $UBACUTE REJECTION.
Policlinic{
IN
HUMId
Functional parameters (FP) reflecting several functiol of the liver and related organs can be defined by d~ami~ hepato-biliary scintigraphy (DHBS). A group of FP wa~ obtained from DHBS in 7 normal volunteers and i! orthotopic liver transplanted patients with subacu[~ graft rejection confirmed by liver biopsy. An early (!21 ~ec, ~ ~r/sec) and a delayed (58 m ~ , 1 fr/min) ph~$, w~re acquired after l.~. lnjec£]on o~ 290-370 MBq o Tc-99m-IODIDA in each subject. Time/activity curves w~r~ generated from ROIs positioned over right hepatic lobe spleen, duodenum and left ventricle in order to defin. the early vascular distribution, hepato-biliary uptak, and excretion of the tracer in patients and controls Blood flow FP were: I) hepatic bolus appearance %im (THA) minus time ef peak activity in !eft ventri~| (TPLV); 2) TNA minus time of splenic appearance of ~h, 5o]us (TSA). Pare~bima] lransit and e~c~liQp ~[ th ~racer were studied with: i) time of he~atic peak (TP and half peak activity (THP); 2) hepatic peak activ]t half time (TH½); 3) percent of maximum hepatic activ~t" ezcreted in one hour (HE]); 4) time of duodena appearance (TDA). Transplanted subjects presented high~ values of T}~-TSA (P
56
55 J.
of Milan,
Ortiz
Cllnica
C.h. Ehrenheirn, P. Heintz, H. Bunzend~hl, H. Hundeshagen.
Berrocal.
Puerta
de H i e r r o ,
Madrid,
Spain.
EVALUATIONOF A LIV[R TRANSPLANTBY 99mTm-DISIDASC!NTIGRAPHY. Fe~s noninvasive methods are avaiiabie to diagnose complications following !iver transpiantatisn. Hepatobi!iary sointigraphy can differentiatm rejection from primary biliary c~T:plications in patients (pts.) with nonspecifio clinical findings. We havm observsd 33 urthotopic liver transplants in 30 pts performed in our cliMc between 1986-B8,i6 maies-!4 fema!es of ages between 11 and 53 years. The post~transplant study pro~oom! included investigation with 99m-Ic Dnsoprspii-iminodiacmtico acid (DISIDA) scintigraphy and other diagnostic tecnniquem (colangio~raphy,arterimgraphy, TAC and ultrasonography). Tme investi~atzon inciudes:i~Anaiysis of hepatic perfusion measuring portal and arteria! fiow on ~hm basis of time-activity curves .2)Analysis of hepato~itarzc uptake and eiimination (dynamic sequence images warm obtained each second ~n the f i r s t minute and evsrv ~0-15 seconds for ~ hourl. Resui~s: The ~ihary ~rac= comp!ica~ons oourred more frecuently than va~ouiar complications (20%) ,99m-To DiSIDA etuo~ reveaied 5 biliary leaks (3 in thm anastomosi~ area and 2 after removal of Kher's tuoel, and on occasions showed a pattern of biJiary oostrucupn.The vaacuiar complications, notably bhrom~osis of the hepatic artery,scuffed in 9% of the pts. obsmrved. The hepatic perfus~on usiog 99mTc-DiSIDA snowed in 3 cases an absence of hepatic vieualitation during the arteriai phase, subsequently confirmed by ar~mrio~raphy,an one case of a massive stroks with absence of hepatic pmrfusion and pno~opsnic area in the deiayed images,with massive arterio-portal thrombosis. The most frequent complication was acute rejection (60Z;, 99mTcDiSIDA stu~zms showed the same pathoiogical pattern as other situahons: ischemic damage~infection, toxicity as a result of drugs and thrombosis of =he hepatio artery. in conclusion,lnvestigations wi~n 99m-T=-IDA derivatives ~iay an important role ~n t~e observation of liver tranapiant patients, a11owing improved accuracy in the diagnosis of post-operative, and particularly of biliary compiications,afford~ng maximum speed with minimum intrusion.
Department of Nuclear Medicine, Clinic of Abdominal and Transplant Surgery, Medical School of Hannover, FRG ASSESSMENT OF PANCREAS TRANSPLANTS SCINTIGRAPHIC AND MR IMAGING METHODS
BY'
Aim of the study: In order to obtain morphological end functional information of pancreastransplants dynamic contrast enhancedMR imaging was comparedto scintigrephy. Patients: 7 patients suffering from diabetes mellitus type I underwent scinttgrep~ and MR imaging soon after combinedtransplantation of kidney and pancreasand in the follow-up. Metheds: 5cintigraphy with 370 MBq 99mTc-DTPA was performed as a routine methodfor the examinationof the transplanted kidney (fast phaseof perfusion, sub~luent]y OFR assessment), likewise, an evaluation of the pancreastransplant was possible by curve generationand visual assessment. MR imagingwas performed as a dynamic study"using gradient echosequences andthe contrast agentOedolinium-DTPA. Results: The pancreas transplanter normally becomesvisible at the same time as the iliec vesseIs in the perfustan phase, a peak of 8ctJvity is measurable. During the following blood pool phase the organ appears homogeneous.In 5 casesthe scintiotaphic findings correspondedwell with the cllntcal assessment of trensplant function. This Includes the cases, that deteriorated severely within the first 9 months. MR imaging provides convincing morpholagic representation of the transplant. The dynamic study after bolus injection of Gd-DTPA me~, reveal regional disturbances of perfusion because of its exCellent soft tissue contrast and its high spatial resolution. The clinical value of this method has to be proved in further longitudinal studies.
413
57
58 M.Oondi, N.Monetti, O.Corhelli, P.Zagni, F.Marchetta*, A.Zuocala ** ,R.Baggi**, M.Mirelli***.
J.I~Anninga. C.A.Hoefnagel and L.Dewit.
Departments of Nuclear Medicine, Clinical Pharmacology*, Nephrologyam anO Vascular Surgery***, S.Orsola-Malpighi Policiinic Hospital, Bologna, Italy
Antoni van Leeuwenhoekhuis, The Netherlands Cancer Institute, Amsterdam, The Netherlands. SENSITIVITY O F S E R I A L S C I N T I G R A P H I C S T U D I E S IN T H E DETECTION AND FOLLOW-UP OF RADIATION NEPHROPATHY In a
prospective study,
renal function
(cltrdcG/. scm-
tigraphic and biochemical) was analysed In 26 patients who were irradiated over the abdomen because of Hodgkin's disease tgroup G-I,N=7), Gastric Non-Hodgkin Lymphoma (G-If, N=5), Ovarian CarcInoma (G-III,N=7) or Seminoma Testis (G-IV, N=7) with different radiotherapeutic, regimens. In G-II (40 Gy in 6 weeks: left kidney I00O~ volume), both ntitaflve 99mTc-DMSA aad 99mTc-DTPA showed a severe etional reduction (7096] after a 6-12 months latency, Creatlnine clearance (CrCI) subsequently decreased in 3 and B2-microglobulin in the urine Increased in 2 patients. In 6 patients of group I (40 Gy in 4-5 weeks;left kidney 30-50 % volume) a milder scintlgraphic functional Impairment was observed (20 %) after 18 months latency. One showed a decrease in CI"CI. In G-III (17-18 Gy in 3 weeks; both kidneys 100% volume) or IV (25-30 Gy in 2,5-3 weeks; the medial part of both kidneys 20-30% volume),revealed no significant impairment. In 6 patients a mild hypertension developed. In 4 cases, scintigraphic functional Impairment preceded the rise in bloodpressure. Conclusions. a) 99mTc-DMSA and 99mTc-DTPA are sensitive in the early detection and foUow-up of radiation nephropathy with advantages to biochemics. However its predictive value for r e n a l Insufflency and hypertension remains to be established, b) Irradiation with 25-30 Gy in 3 weeks over less t h a n 30 % of the kidney volume (medial part) or with 18 Gy in 3 weeks over both entire kidneys, do not cause a measurable deterioration of renal function.
~t~
RENALSCINTIORAPHYAFTERANBIOTENSINCONVERTINGENZYMEINHIBITIONIN THE CLINICAL EVALUATIONOF HYPERTENSIVEPATIENTSPOTENTIALLYAFFECTEDBY RENOVASCULARdiSEASE To evaluate the diagnostic capabilities of renal snintigraphy after angiotensin-converting enzyme inhibition (ACEI) in detectin~ renal arterv stenosis (RAS) 105 hypertensive patients were submitted to renal scintioraphi followed I to 2 days later by a second study performed one hour after premedication with 50 mgr of Captopril. Renal angiography, by arterial catheterization in all cases, was carried out within 30 days. 55 patients had no RAS, 29 had unilateral disease and 21 bilateral. RAS significativity was set at 50% arterial lumen reduction, which has not been taken as a proof of RVHbut rather as a limitbeyond which the renin-angiotensin system is very likelyto be activated. Thus, 68 patients (Oroup I) were considered negative (no RAS or RAS <50~), 25 had unilatera! RAS >50% (Group 2) and 12 had RA5 bilaterally ~ (Oroup 3). Of the first group significant HAS was ruled out in 66/68 cases, by meansof Captopril enhanced renal scintigraphy, Moreover 13 patients affected by nephropathies other than RAS were correctly diagnosed as having no main renal artery stenosis by the provocative test, while their baseline studies proved tc be falsely positive. In the second group, Oaptoprii administration identifieO 23/25 patients with unilateral HAS >50%. In bilateral RAS >50%the test proved to be positivein 11/12 patients. Overall specifidty was 97X and sensitivity 92%. Two patterns of positive response Were identified: markeddecrease of tracer uptake from the affected kidney (often though not always present in unilateral ~AS) and marked delay of tracer appearanceinto the pelvicalyceal system (typical of bilateral disease and frequent in older patients with unilateral HAS). Evaluation of parenchymal transit time by deconvolution analysis demonstrated a significant decrease of PTT in normal kidneys (p<.05) while stenotic kidneys showed a significant increase (p<.05). In conclusion, renal scintigraphy after ACEI proved to be highly accurate in identifying RAS >50X, which zs very often associated with renevascular ~yperteneion. This examination is thus suggested as the first approachto lypertensive patients referred for renal scintigraphy.
60
59 =_F.gmE~J, M. Cerrieri, L. Mezzasalma. D. Voltsrrani, * R. Bianchi. P. 6azzettt ind 5.6htone.
V. Koukouliou, E.. Georg±ou, A. Xvpolias, A. Kostakopouloe C. PrcRHcakis and C. Dimopoulos. Dept. of Msclical Physics and Dept. of Urology, Athens University Medical School, Athens, Greece.
~IR Institute of Clinical PhysioIoVy and * Nuclear Medicine Centre, University of }tsa, Italy, RADIONUCLIDE EV;CLUATION OF RENAL FUNCTION AFTER EXTRACORPOREAL SHOCK WAVE LITHOTP~pSY.
CAPTOPRILRADIONUCLIDETESTIN RENOVASCULARHYPERTENSION Cabtoprll RadlonuclldeTost(CRT) has beenrecently developedas a diagnostic tool ~'or renovascular hypertension, We here review its results in 58 hypertensive pts who underwent renal anolography. Patients: 25 with normal renal arteries (NRA), 5 with 150~ renal artery stenosls (RA5), 19 with ~50~ RAS, 8 with >50~ RA5 mxl a small kidney. 99mTcDl'PA dynamic sclntlgraphy: ? mCI both before and I hr after oral cabtoprll (C), concomitantly to tenth C test (Muller et el, 1986). Post< and pre-C renal curves were compared, a positive renograbhlc response being defined by elttwr a delay or an absenceof 2rid end 3rd renographlc segments after C (reflect,IN, respectively, either a decrease or a suppreaslon or glomerular filtration rate), Uptake ratios (UR) between the two kl®eys (120-180 sac) were also co.areal: a greater than -25~ UR decrement after C (as absolute value) was considered a positive response to C, CRT results In the englographlc groups were comparedwith those of baseline renograPhyand renl, C test, as shown In the table, ..........
HRA ~50~ RAG >505 HAS without small k, with small k.
basal renog, neg poe 16 9 5 1 7 0
12 8
CRT-. . . . . . . .
post< neg 25 6
renog, pos 0 0
2 7
t7 I
BURS <-25 >-25 24 I 6 0 3 7
16 1
renln C test neg poe 25 1 5 l 11 1
6 7
The results confirm the diagnostic value of" CRT for anglograpblcally relevant renal m'tery stenesls, Inspective renographtc analysis appears more accurate than the applied quantitative method, CRT Is highly specific for renal artery stenosls bet sensitivity appears lowered by the major contribution as false negaUvecases of pt~ with small poor t'unctlonlngkidneys, However, In these particular cases, baseline renogrmphya.d the renin C test appear valuable complementary tools to CRT.
It has been reported that decreased renal function and h~ pertention are side-effects of extracorporeal shock wave lithotripsy (ESWL). However, very little is known on the frequency_ and the time course of these complications. Therefore, ~1117 pati..ents who underwent ESWL, we performe a total of quantltative radionuclide renographies wit Tc-99m-diethylenetriaminepentaacetic acid (DTPA) before and 1,7,15,60,90 and 120 days post E~WLo Fran each study the following parameters were calculated for both the treated (T) and the untreated (U) kidney: Filtration fraction (FF), kidney's retention at 20 min (R20) and GFR at 2-3 min. All of those values were ccxmoared to the respective pre-ESWL values. Our results, expressed as % of the total, were classified as Improvement (I), No Change (S), or Worsening (W) of renal function, were as follows: CHAN 7days -GE T U I S W
14 57 29
8 61 31
15 d. T U
30 d. T U
60 d. T U
90 d. T U
120 d. T U
27 54 18
50 40 10
72 14 14
72 14 14
83 17 ~
20 80 0
@ 100 ~
~ 100 ~
0 100 ~
100
~%ditionaly, on each visit blood pressure and ser~n renin determinations were also perfonaed. None of the patients devel _oped statistically significant hypertention or high r.en~ levels. It is concluded that: After ESWL, a translant decrease of renal function is noted to both kidneys mainly from 1-15 days after, while no hypertention was evident.
414
62
61
W. Burchert, J. Kotzerke, 8. Heublein', J. Albes*, H. Hundeshagen
I Loutfi, JR Batchelor, dP Lavender
Department of Nuclear Medicine *Department of Heart, Thoracic and Vascular Surgery Medical School of Hannover, FRG.
Royal Postgraduate Medical School-Hammersmith Hospital Du Cane Road - London W 12 OH$ U.K. IN VIVO IMAGING AND OUANTITATION OF RENAL TRANSPLANT REJECTION USING INDIUM-I 11 LABELLED ANTI-LYMPHOCYTE, AND ANTI-MHC CLASS I AND IIMONOCLONAL ANTIBODIES IN A RAT MODEL Kidney transplantation has become a widespread procedure for management of terminal renal disease.Also, transplantation of other organs is increasingly gainig popularity (heart, liver, pancreas etc.).The common problem shared by organ transplantation technology at the present time is the rejection of donor organ by the recipient's immune system. This effect is deleterious to the procedure and necessitates early diagnosis and prompt treatment of the recipient by immunosuppression (corticosteroids, cyclosporin, etc.). However, diagnosis of re)ection, especially in kidney transplants, is based on either non-specific tests like the assessment of transplant perfusion by Tc-99m DTPA renography, or invasive procedures like renal or cardiac biopsy. Other procedures have also been tried like radiolabelled plateletor radiolabelled leucocyte imaging with littleacceptance in practice due to non-specificity and cumbersome technique, W e present our approach based on events occurring during the rejection process, It involves imaging and quantitation of the uptake of In- 1 11 labelledmonoclonal antibodies injected in vivo in aIIogeneic kidney tranplanted rats and directed to 1 ) "[cell ( Pan T McAb), 2) Activated T cells using an Anti-IL2 receptor McAb, 3) Donor Class I Major Histocompatibility Complex (MHC) and 4) Donor Class II MHC. Preliminary rasults show that this approach could be very useful in the early diagnosis of renal transplant rejection.
After transplantation a main problem is the control of organ-function and rejection. To identify a rejection non-invasively we performed 111 -In-Antimyosin scintigraphy (Myoscint, Centocor Co.) in 47 hearttransptanted patients 24 and 48 h after injection of 74 M Bq. Some patients got follow-up investigations up to three times. Analogue images were acquired in RVL and LAO 45 ° view for qualitative staging. Quantitative analysis is based on average count rates per pixel creating ROI over the right lung and the heart, No side effects, especially no allergic reactions were observed after intravenous application. In a 12 hinterval pro- or postinjection the histological classification of the rejection was done by myocardial biopsy, The qualitative results oorrelate well with the quantitative analysis. The qualitative estimation of myocardial damage was simpler after 48 than 24 hours. It was easier to classify the degree of rejection by heart-lung ratio of average counts per pixel than solely by the heart uptake. In minor histological rejections (A0-A3a) there was a mean heart-lung ratio of 1,52. More severe rejections (A3b-A4) showed elevator mea'~ heart-lung ratios of 1,71. False positive uptake was seen in 3 patients. In about a quarter of patients with bioptically proven rejection there was no uptake at all. A patient with negative results in two folio.wingbiopsies but clinical evidence for rejection had an increased heart-uptake in agreement wth the clinical symptoms. Antimyosin scintigraphy may be a new technique to diagnose noninvasively a rejection of the transplanted heart. In difficult and doubtful clinical constellations the method will be very helpful.
64
63
l. Carri6, M.Estorch, C.Martinez-Duncker.
DIAGNOSIS OF HEART T R A N S P L A N T REJECTION BY 111-IN-ANTIMYOSIN SCINTIGRAPHY
L.Berng,
M.Ballester, D.Obrador,
S. Fritsch, A. Schuetz*, C.M. Kirsch, B.M. Kemkes*, C. Kugler*, P. Knesewitsch
Hospital de Sant Pau, Barcelona.
Division of Nuclear Medicine, Departments of Radiology and Cardiac Surgery*, University of Munich, Munich, FRG
NONINVASIVE FOLLOW-UP OF HEART TRANSPLANT PATIENTS ~qF~ QUANTITATIVE ANTIMYOSIN SCINTIGRAPHY.
Ill-INDIUM ANTIMYOSIN: A RELIABLE METHOD IN THE DETECTION OF CARDIAC REJECTION
Antimyosin studies have been used to assess myocardial damage in patients in follow-up after hearttransplant (110 studies in 53 patients) from 7 days ~o 4 years after transplantation. A heart to lung ratio (HLR) derived from planar scans at 48 hrs post-injection of 0.5 mg of RII-DIO-Fab-DTPA has been used for quantitative assessment. Longitudinal follow-up showed HLR values initially high (1.89±O.3) in 30/32 patients. Repeat studies revealed a decrease in eleven with an uneventful clinical course. 4 patients with persistent high .qLR '(Zl.9) at 3 months died or reqnired retransplantat~on 19 patients studied >I year after transplantation had a HLR of 1.58±0.28 (p<0.01): 6 episodes of rejection were detected by a rise of HLR in this group. Patients who presented with a HLR ~ 1.7 at one year after transplantation had a higher probability of subsequent rejection episodes. Antimyosin scans provide a noninvasive method to detect myocardial cell damage due to allograft rejection, and to study the time course of myocF~e damage durin 8 follow-up after heart transplantation.
In the present study iii- Indium Antimyosin (IN-AM) scintigraphy was performed to investigate the clinical reliability and utility in patients with suspected cardiac transplant rejection. The results were compared to endomyocardial biopsy (EMB). In 26 patients (41 studies) studied after cardiac transplantation IN-AM (74 MBq, 0,bmg)was administered intravenously within 4 days after or before EMB. Planar and SPECT images were obtained 24 and 48 h after injection. The images were evaluated visually and the calculation of a heart to lung ratio (M/L) was performed. As control group 20 patients (n=4 myocardial infarction, n=8 unstable angina,n=8 cardiomyopathy) were examined(H/L61.6) In 18 studies a H/L ratio ~ 1.6 corresponded with a negative EMB. A H/L ratio >1.6 demonstrated various stages of rejection episodes including 8 mild forms. In 18 out of 23 pts. EMB confirmed these findings. In the 5 false negative studies 4 of 5 pts were treated with high doses of steroids before the IN-AM injection and one patient showed human antimouse antibodies. 8 pts. with mild rejection were examined in the follow up after treatment. All pts. showed a decrease in the B/L ratio to normal values and a negative EMB. Thus Antimyosin scintigraphy is an appropriate, non invasive and highly sensitive method to assess cardiac transplant rejection. False n e gative results are to be expected in patients With a high dose steroid application during rejection treatment
415
65
66
~.Jimenez-Heffernan, J.M.Latre, J.M.Arizon*, M.Torres, J.M ]Lamas, F.Gonzalez and A.Mateo.
R.P. Baum, U.F. Mondorf, A. Nertel, G. Herrmann, H.G. Olbrioh, T. Baew-Christow, H. Klepzig jr, F.D. maul, G. iKober, M. Kaltenbach, K. HObner, G. HUr Depts. of Nuclear Medicine, Cardiology, and Pathology, J.W. Goethe University Hospital, Frankfurt/Main, FRG
~uclear Medicine and Cardiology ~ Services. qospital "Reina Sofia". Cordoba 3PAIN NONINVASIVE DIAGNOSIS OF CARDIAC REJECTION The results of the protocol used in our hospital for ~iagnosis and follow-up of cardiac rejection are presented Twenty eight examinations were performed on 12 patients (IIM,IW) who underwent orthotopic cardiac transplantation. The follow-up period ranged from 15d. to 50m. The protocol comprises: Gated radionuclide ventriculography with 740MBq of 99mTc-albumin, acquired using forward-backward by thirds framing mode, 32 frames/R-R interval and i0 million total counts. Parameters of left ventricular sistolic and diastolic function were analyzed; Antimyosin antibody (AB) labelled with 74MBq of lllIn was injected and myocardium/lung uptake ratios were obtained at 48 hours, expressed in counts/pixel; Transjugular endomyocardial biopsy in the same week was performed on all patients. The results were evaluated comparing the mean values of each parameter and correlation analysis in relation to the presence or absence of histologic rejection. The following parameters showed statistical significance at p < 0.01: Peak filling rate, Average filling rate, and AB ratio. Peak emptying rate, Average emptying rate and Global ejection fraction showed statistical differences at p < 0.05. Correlation of the following parameters with the results of biopsy existed at p<0.05: AB ratio r= 0.61, PFR r= -0.49 and AVFR= -0.62. The results of AB ratios are concordant with those reported by authors, our study provides diastolic )arameters with the same degree of statistical significan(
67
THE CLINICAL ROLE OF In-111 ANTIMYOSIN SCINTIGRAPHY IN THE DIAGNOSIS OF ACUTE HEART TRANSPLANT REJECTION the purpose of this study was to evaluate quantitative In-111 antimyosin (AM) imaging as a noninvasive tool for the diagnosis of acute cardiac transplant rejection compared to right ventrieular endomyocardial biopsy (EMB). 15 cardiac transplant recipients (3f, 12 m, age 185B yrs) received O.S mg of the OTPA coupled AM Fab fragment (R11010, Centocor,Leiden) labeled with 60 MBq (mean) In-111 (labeling efficiencyA95 %). Planar imaging (ant, Lao 45) and ant "half-body" scans were performed 48h p.i and quantitation of AM heart uptake (AMU) was calculated from I)ROI analysis (heart to lung ratio, H/L-R) 2) computer based determination of % injected dose (ID/organ) 3) a visual score (0-3). Results were compared to EMB obtained within 24h before/after injection. 30 studies were performed in 15 patients (repeat studies: I pt 7x, 2 pt 4x, 3 pt 2x, 9 pt Ix ) and 6 acute rejections requiring therapy were diagnosed by EMB. An intense diffuse uptake (score 2-3, H/L-R 1.6-2.4, IO 0.20.6 %) was present in all pts suffering from rejection correlating with histopathologic rejection scores and immunohistochemical T-cell staining. No or faint activit was seen in pts with normal EMB or mild rejection. No side effects were observed and no HAMA developed even after 7 applications. We conclude that sequentially monitoring with antimyosin scintigraphy is clinically very useful for the sensitive and specific, noninvasive diagnosis of acute heart tTansplant rejection and could reduce dramatically the frequency of EM8 in patients with HTX.
68 J. M U l l e r - B r a n d ,
Q.S. Li, G. Solot, L.C. Broker.
The Johns Hopkins Medical Institutions.
M.
Pfisterer,
H.E.
Schmitt
Baltimore, MD. University
Hospital,
Basel,
Switzerland
MECHANISMS OF RP30 REDISTRIBUTION IN POSTISCHEMICMYOCARDIUM.
WHICH FACTORS DETERMINE BY T c 9 9 m - M I B I ?
The relative concentration of RP30 (Methoxy-Isobutyl Isonitrile)(RP) increases in postischemic myocardiumover time, consistent with tracer redistribution. This study was done to define the extent and mechanism of RP30 redistribution. Seven anesthetized dogs underwent occlusion (OC) of the anterior descending coronary artery(LAD) followed in 1 min by injection of RP30(10mCi), TI-201(0.bmCi) and radioactive microspheres(MS). In Group A(n=4) the LAD was released in 5 min; in Group B the LAD was stenosed to prevent hyperemia and reflow (RF) occurred after 20 min. Tomographic imaging of RP30 was performed twice, at 30 min (TMi) and 150 min (TM-2) post-injection, and the dogs were sacrificed at 210 min. Regional myocardial tracer content was expressed as a ratio of postischemic to normal region in each of 4 tomographic short axis images and corresponding tissue slices (TS). (*p<.01 vs MS-OC; +p<.01 vs TM-I) Group MS-OC MS-RF TM-I TM-2 RP-TS TL-TS A .ii 3.90* .25* .36+ .32* ,79"
To a s s e s s the i m p o r t a n c e of d u r a t i o n a n d e x t e n t of m y o c a r d i a l i s c h e m i a for its d e t e c t i o n by Tc99m-MIBI, 20 pts w i t h i s o l a t e d L A D - c o r o n a r y artery disease and reversible Ti-201-perfusion d e f e c t s w e r e s t u d i e d d u r i n g a n d a f t e r PTCA. At the s t a r t of 15, 30, 45 or 60 sec b a l l o o n occ l u s i o n , 15 m C i T c 9 9 m - M I B I w e r e i n j e c t e d i.v. and planar scintiqramms obtained two hours later as w e l l as 24 h o u r s a f t e r P T C A u s i n g a s e c o n d i n j e c t i o n of 15 m C i T c 9 9 m - M I B I . During P T C A all pts h a d c h e s t p a i n a n d / o r E C G signs of i s c h e m i a . The a n a l o g a n d d i g i t a l i z e d M I B I scans w e r e c o r r e l a t e d w i t h c o r o n a r y a n g i o g r a p h y a n d 2 0 1 - T l scan. U s i n g MIBI, d e f i n i t e i s c h e m i c d e f e c t s w e r e d e t e r m i n e d in 15 of 20 pts. T h e r e was no s i g n i f i c a n t d e p e n d e n c e on d u r a t i o n of the b a l l o o n o c c l u s i o n a n d e x t e n t of i s c h e m i a , alt h o u g h less i s c h e m i c s e g m e n t s w e r e p r e s e n t after shorter balloon occlusion (6,1 vs. 8,7). In I0 pts w i t h m i d - L A D d i l a t a t i o n (smaller i s c h e m i c area) i s c h e m i c s c o r e w a s c o m p a r a b l e to p r o x i m a l L A D d i l a t a t i o n (7,1 vs. 7,0). In 7 pts w i t h p r e s e n c e o f c o l l a t e r a l s , only 3 s h o w e d i s e h e m i a on M I B I scan, w h i l e i s c h e m i a was p r e s e n t in 12 of 13 w i t h o u t c o l l a t e r a l s . Thus, d e t e c t i o n of m y o c a r d i a l i s c h e m i a by M I B I seems to d e p e n d m o r e on the a b s e n c e of c o l l a t e r a l s a n d on the d u r a t i o n of o c c l u s i o n t h a n on the e x t e n t o f i s c h e m i c m y o c a r d i u m .
B
,15
.73*
.37*
.44+
.32*
.67*
At the time of reflow, blood RP30 activity was 6% of peak activity in Group A vs 1% in Group B. RP30 redis-tribution w a s greater in Group A than B (44% increase between TM-I and TM-2 vs 19% increase), but in both groups redistribution was much less than TI-201. These data suggest that RP30 "redistribution" is augmented by hyperemia and high blood activity at reflow, but that true redistribution still occurs when these factors are not present.
ISCHEMIA
DETECTION
416
70
69 U Buel____~l,PJ Kaiser, F Dug~t, R Uebis, E Kleinhass, SN Reske
T.H .Marwiek, R.T.Go, W.J.Maclntyre, P.J .Rehm, G.Saha, D.A .Underwood, J.King, A.Beachler. Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Depts of Nuclear Medicine and Internal Medicine I, Technical Univ of Aachen, Aachen, FRGarmany ~TS OF Tc-99m MIBI-SPEcr IN A 4 ~ ~CISEf~EST PRUEXIL USING Qt~%VrlTATI~ TO REGIC~LLY EVALaATE CG~NARY ~ DISEASE (CAD). Tne perf~sicn marker Tc-9~m MIBI ( m e t h ~ t y l i s ~ t r i l e ) was employed in a 4 hrs exercise-rest (E,R) protocol to relate quantified regic~ml myocardial uptake at E and R to state of corcma/y artery (seA;open/occluded) or to history of old myocardial infarction (CMI) or to visual reversibility (RV) or irRV (IRV) of a defect at R vs E. 150 MBK Tc-99~MIBI were injected at E. lhr later, E-SPECT was done (2 heads, 2x180 orbit). Subsequently, 850 ~ ~ r e injected and R-SPECT was performed after 2 hrs. Defects were visually searched at E- and R-slices. 33 target-like ROI evaluated short-axis cuts (2 pix) by a perfusien index (~regicmal uptake of myocardial ma:dmum) at E (PIE), R(PIR) and by the regiunal difference (PIE minus PIE: Delta PI), subsequent to correctimm for decay, dose ~ r~aining c~unts. 75 pts with CAD were examined. By coronary angio, a stenesis was found in 140 vessels, of these 30 were occluded; I01 showed RV in the supply areas; 49 had GMI. 15 pts with low prevalence served as a ccatrol. Results were (mean~SD)(§: p<.01): CMI/no OMI (~I (~I no no ccatrol SCA;RVlIRV ocolliEV o ~ I E V op~/RV occl/RV opm~RV -PIE(%) 29.8f6 38.7_+6 § 63.8_+16 60.8_+10 61.6f13 74.0i-9.9 Delta PI 4.3_+3 3.1_+3 § 16.3_+12 i0.$f8 7.,6_+5 5.0f_3.0 PIR (%) 34.1 41.8 80.1 71.7 69.2 79.0 Taere was no correlation of degree of ster~sis to PIE or DeltaPl. Frun these results We col~clude that an open vessel does neither predict the amount of MIBl-uptake nor ~ it herald positive fill i n ~ by the in~ection at rest. ~ does not govern low PIE-values or INV. MIBI-uptake at exercise see~s to predict already reversibility of a defect ! Thus, myocardial uptake and distribution of MIEI may he influenced ~ more factors than b~ ~erfusi~ alene.
BY
RB-82
Previous work has suggested the combination of dipyridamole stress with PET imaging to be able to detect coronary obstructions of 42%. The aim of this study was to analyze the sensitivity of Rb-82 PET for the identification of coronary stenoses of 40-50% assessed by subjective reading. Resting and stress cardiac PET images were acquired on a Posicam scanner (Positron Corp), after infusion of 40 to 60 mCi of Rb-82 for each image. Stress images were taken after infusion of dipyridamole (0.56 mg/kg i/v) with handgrip exercise. Scans were interpreted blindly using a quantitative color scale, and were reported as showing a normal pattern, a transient, or a fixed defect. Coronary stenoses of 40-50% were identified at angiography in 30 major coronary arteries in 89 pts. Perfusion was examined in regions of interest subtending the involved vessels - 8 zones had defects, and 22 did not, giving Rb-PET imaging a sensitivity of 27% for the detection of coronary stenoses of 40 to 50% diameter. Four pts had a 40 to 50% lesion as their only pathology, all had scans negative for isehemia. Conclusion: Coronary stenoses subjectively assessed at 50% or less diameter rarely produce impaired perfusion on Rb-PET, supporting the clinical belief that such lesions are usually not flow-limiting.
72
71 T.H .Mar wick, W.J .Maclnty re, R .T .go, D.A .Underwood, G.Saha, J .King, A.Beachler. Clinic Foundation, Cleveland, OH, USA.
PREDICTION OF "SUBCRITICAL" CORONARY STENOSIS PET USING DIPYRIDAMOLE STRESS.
P. J. Rehm, Cleveland
O. MUNDLER, Ch. GROUSSET, P. BIRKUI, M. FAUCHET.
D~partement de M@decine Nucl@aire Sce Central de B i o p h y s i q u e ( H 8 p i t a l L a r i b o i s i ~ r e PARIS FRANCE) DISPARITIES BETWEEN MYOCARDIAL PERFUSION IMAGING USING RB-82 PET AND TL-201 SPECT.
TWO YEARS FOLLOW UP OF PATIENTS WITH "FALSE POSITIVE" EXERCISE OR DIPYRIDAMOLE THALLIUM 201 MYOCARDIAL SPECT.
Defined perfusion zones were compared in pts undergoing TI SPECT and Rb PET myocardial perfusion imaging. Images were acquired on Triad (Trionix !nc) and Posicam (Positron Corporation) scanners following the same d ipyrid amole-hand grip stress, and were compared using the same quantitative color scale. Perfusion was classified as normal, or showing a reversible or fixed defect, and was compared with angiography and clinical records. Satisfactory images were available in 82 pts, and 25 perfusion zones had disparate Rb and TI results. Ischemia was detected on Rb but not TI in II pts - i had a false positive Rb result, 4 had fixed TI defects and local coronary stenoses (probably severe ischemia), 6 had false negative TI scans (reported as normal). No ischemia was detected on TI but not Rb. Scar was reported on Rb and not TI in 7 pts, 4 had local coronary stenoses (probable true-positive), and 3 were false-positives (all inferior defects). Scar appeared on TI bat not Rb in 7, 4 true positive (all had reversible RB defects), and 3 false positive, all of whom could be explained by soft tissue attenuation. Conclusion: Rb was more sensitive than TI for detection of ischemia in this study, False positive fixed defects may have related to problems with at t enuat ion c orrec t ion.
From 1986 to 1987, 346 patients (men, mean age 52 + 12 years) were referred for positive exercise (86%) or dipyridamol (14%) and redistribution TI 2 0 1 S P E C T , and because they underwent selective coronary arteriography within 48 hours after scintlgraphy exam. 36 patients (I0%), 27 exercise, 9 dipyridamole) were seen as "false positive" as their scintigraphy images presented an hypofixation or a defect with or without normal fixation 4 hours later in a myocardial teritory where there was no significant coronary stenosis (normal up to 50% of stenosis). However they had or not clinical and disease or electrical signs of coronary artery disease. After two years of clinical follow up we selected two groups : groupe I : 23 patients who had such cardiac events that they need tritherapy for 18 and underwent coronary surgery for 5 as they developed coronary stenosis 12 to 18 months after the first examination. groupe 2 : 13 patients had no cardiac events. 4 of them were patients who had left bundle block branch. However two years seems to be a short term follow up for such patients we can see that definition of "false positive" T1 2 0 1 S P E C T m u s t be re considered. Selective eoronarography cannot be the "gold standard" for TI 201 exams since myocardial scintigraphy explored as well macrocireulation than micro circulation.
417 74
73 Langen ~ , M. Hennerici z , H. Herzog ~ , L.E. Feinendegen ~ IInstitut f~r Medizin, KFA J~lich GmbH, 5170 JQlich,
T,_....g_~w~[tz, E. Hefter ~ , K.-J.
FRG SNeurologische
Klinik
der Heinrich-Heine-Universit~t
DQsseldorf, 4000 D~sseldorf, FRG
REGIONAL CEREBRAL GLUCOSE CONSUMPTION MEASURED BY PET IN PATIENTS WITH WILSON'S DISEASE The purpose of this study was to investigate the regional cerebral metabolic rate of glucose consumption (rCMRGIc) in patients with Wilson's disease (WD) and to correlate rCMRGIc with the severity of symptoms in these patients. Seven patients with WD and 23 controls were studied using a high-resolution PET (PC4096) and the ~SFdeoxyglueose method, rCMR~I~ was measured ~n 28 regions of i n t e r e s t . The s e v e r i t y of symptoms was ass e s s e d by c l i n i c a l r a t i n g s c a l e s ranging from 0 (normal) to 3 ( s e v e r e l y impaired). Data a n a l y s i s comprised the calculation of Spearman's rank correlation coefficients and t-tests. - Compared to controls, patients with WD had a significant decrease of rCMRGIe (p<0.05) in the anterior cortical regions, the striatum, and the cerebellar cortex, but not in the posterior cortical regions and in the thalamus. Significant correlations were found between the severity of speech disorder and rCMRGIc in the ventrobasal striatum, and between the severity of oeulomotor disturbances and rCMRGIc in the anterior cortical regions. This study is the first to describe a decrease of eerehellar rCMRGIc and the predominant involvement of the anterior cortical regions in patients with WD. The reported correlations underline the potential of PET to elucidate the mechanisms underlying complex neurological symptoms.
75
R. F. Ackermann & *J, L. Lear Division of Nuclear Medicine and Biophysics, UCLA School of Medicine, Los Angeles, CA ant *Division of Nuclear Medicine (A034), University of Colorado Healtt Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262 USA
QUANTIFICATION OF CEREBRAL A E R O B I C ANI~ ANAEROBIC METABOLISM USING SEQUENTIALLY A D M I N I S T E R E D R A D I O L A B E L E D FDG AND G L U C O S E We developed a method to quantify the relative amounts of cerebral aerobic (AM) and anaerobic (ANM) glucose metabolism using sequentially administered 18F-fluorodeoxyglucose (FDG) and 14C-6-glucose (GLU). Because FDG-6-phosphate (FDG-6P) accumulates in the brain in proportion to the rate of glucose phosphorylation, which occurs prior to the divergence of aerobic and anaerobic metabolism, its uptake reflects total glucose metabolism. On the other hand. cerebral GLU mctabolitc, concentration (CGLUM), reflects only aerobic metabolism, because with ANM the 14C label is lost via lactate production and diffusion out of the brain. We developed a kinetic model relating regional cerebral FDG and GLU concentrations to ANM and AM. Correction factors were developed for t4C loss through CO 2, retained lactate, and for variations in the FDG lumped constant. Using dual tracer quantitative digital autoradiography, we applied the model to normal rats, rats undergoin~ seizures, and to visually stimulated rats. In the normal rats, no areas of significant ANM were found virtually all metabolism was AM. On the other hand, in the seizing! animals specific regions of the brain had rates of ANM which were striking - reaching 200% of the value of AM. Similar discrepancies between AN and ANM occured in the visually stimulated rats. This study suggests a major reason that FDG has been found to bc more useful in PET studies of the brain than other tracers such as GLU or 150. Stimulation-induced cerebral anaerobic metabolism, which generates much less energy per glucose molecule than aerobic metabolism, results in accumulation of FDG-6-phospate out of proportion to energy production and produces more striking images. 76
M. Cordes, H. Henkes, J. Hunger, R. Felix
C. L. HAINI, F. PI6ORINI, F.H, PAU, P, NARCISO, M.A. ROSCI S. 6ALGANI, V, VOLPINI, C. LEONETTI, G. MZEI Dpt. of Nuclear Medicine, C. Forlanini Hospital, Rome Chair of Nuclear Medicine, State University, Ancona Dpt. of Infectious Disease, L. Spallanzani Hospital, Rome Dpts of Neurology and Neuroradlol., S.Camlllo Hosp., Rome 99mTc-HN-PAO BRAIN SPECT IN ACQUIRED IMMUNEDEFICIENCY SYNDRDME (AIDS) HM-PAOSPECThas been performed in 34 pts. with AIDS and neurological symproms. A semlquantltatlve analysis Including cortical and cerebellar palred regions of interest was implemented. All pts. underwent neuropsycological testing, 27 were studied by CT and 21 by NMR. The final dla gnosls was opportunistic infections in 9 pts.(group A) a~d dementia complex in 25 pts. (group B). All pts. in group A had a positive SPECTstudy; CT was positive in 5/7 and NMR in 7/7. Of group B pts. 24/25 had a positive SPECTstudy, 17/20 had a positive CT and 14/15 had a positive NMR. The patient with negative SPECThad both cortlcal and cerebellar atrophy which was the likely Cause of the false neg_a tive semlquantltatlve SPECTanalysls. The 3 pts. with nega tlve CT and the pt. with negative NMRhad clearly positive SPECT studies. In group B. pts. the fronto-parletal cortex was more often compromised (|4/24 pts.), while the tempor~ occipital cortex was relatively spared (2/24); in 7 pts. the hypoperfuslon was dlffuse and in 4 pts. basal ganglia hypoperfuslon was observed. The folIowlng conclusions are drawn: I- SPECTIs very sensitive (g7%) and i t can show hypoperfused areas also in pts, with normal CT and NMR scans, 2- The fronto-parletal cortex is more frequently compromised in dementia complex (p< 0.001 vs~ temporooccipital cortex by V2 test with a Phl2 of 0.320).
Departmen~ of Radiology, University Clinic Rudolf Virchow/Charlo~tenburg, Free University Berlin, W.-Germany HM-FAO SPECT AND CNS- MANIFESTATIONS
GD-DTPA OF AIDS
ENHANCED
MR
IMAGING
IN
Although~ ~d MR imaginghave demons~tod a highsensitiviWin denting brainlesion~,der.ermination of the etiology~usL~gthe lesionis st~ ~r. However,specllltyi~ crucialfor pro~osi~and therapyin patients~th ae~uLredimmunodetkien~s~]ndrome,suffe~g fromv~ou~ oDol'tamisticCN8 infectionsas wellas ~ernus ie~iots of the br'{in.~ions withmultipleetiolcg¢factorsthat~ur simultaneouslyin the same patient,furthercompiicat~di~g~ostkand therapeuticdecisions.The ~ of t~ep~.centst~dywa~ ~ determinethe dia~osti¢valueof ~-Pk0 SPR~ in pntien~within~craniulA]I)Smanifestations,whichhad beenconf~ed by MR. in addifio,,., the tecidenco,the loeali~ttion as wellas the degreeof alteredbrainperfasionin ~S-patientswithc~cal symptoms ofCNS diseaseand a normalMR enam~tionwas investigated. MRturial~& ~: ~ven male par.ients(age median:3T years) withl~rovodHFV-I infection,GIE ~, were examined.Clinicaland/or~tologtcdiagnoseswere t~mop/~,~Y,¢(7 patients),Y.mN~ (i patient),me~gY~(I patient),and /gV-ente~$~(2 patient~LSPiT examinationsmereperformedusinga ro~atinggemma cameraafter Lv, applicationof ~55 ~ 99mTo-HM-P^0.AXN, cor~na]and sa~ttalsliceswere generated.MR studies(o.5T M~etom) were~erform~us~ T2-weigh~ images(S~ 1800/30,70)unenhan~ as weU u GD-DTPA enhan~ TIwe~htod s~uenses(F~J~H315/14,8=90').
~ : MRi~n~g demoas~tod 20 lesi.onsin 7 patientswithcerebral,manifesmtionof tozoplamosis.~ET demonstratedfocallyul~redbrainperfusionin allpatients.Twelveo[ the 20 lesioasshowed ~peEusioa ~ lesions were $;e@n,'Y~,¢~one patientof ~ ~up had multiple~erfnsbndeficits.In o~e patient~ith 3 cerebral lympho~a~,alllesionswere hypopeffusod, In one patient~th me~i~ - as demons~ by MR - ~ffasionwas ~ucod in the adjacentbrai~uissue,in 2 patientswithfire-encephalitis and negativeMR, SPILl'detectedmultiple ~ffuulondeficits. Onto*lEntThe se~itivityof Sp~'rin detectingfocallesionsL~~eriorto MR.Atpresent,I~-P£OSPECTdoes not providedTerentmtionbetweentoxoptasmosisand ~phom~ fiowever,SPET demonstra~ alto~ brainperfus~n in arenslargerthan the corms~nd~ focaltesiondet~ by MR {,aging.SPET appem thuspotontially usefulin ~S-patientowithsymptomaticbraindise~ and a netativeMR who mW hzve alto~ brain~ffnsion. { HM-PAO SPL%T is a helpfuldi~gnosZicmethodcompLementaryto CT and MR imagingin patientswith~S-rein~ braindiseaneevaluatingthebrainpeffusionuttern.
418
78
77 K. Tatschh, A.F.. Markl,
E. Schielke*, C.M. Kitsch
K.M.
Einh~upl*,
H.
Bauer,
Division of Nuclear Medicine, Departments of Radiology and Neurology*, University of Munich, Munich, FRG ~'Tc-HMPAO-SPECT IN PATIENTS WITH HIV-INFECTION: A COMPARISON WITH NEUROLOGICAL, CT AND MRI FINDINGS
In the present study 99mTc-HHPAO-SPECT was performed tc investigate brain perfusion in patients with or at risk for HIV-encephalopathy. SPECT results were comparen [c neurological, CT and MRI findings. 30 HIV-infected patients (2 women, 28 men, age 22-71 years) ranging from Walter Reed stage I-VI were studied. 4 had opportunistic infections of the central nervous system (CNS). Neurological abnormalities were observed in 10/30. SPECT, neurological examination and CT were performed in all patients, MRI was available in 15. 5/30 had normal findings in all investigations. In 25/30 focal or patchy, multilocular decreased uptake was observed in HMPAO-SPECT. However, in 21/25 CT/MRI findinq~ were normal (16) or showed atrophy (5) only. in the 4 patients with opportunistic CNS-infections focal CT/HP: i and neurological findings well correspoaded to pathologic SPECT results, but SPECT usually revealed addi~:onal, CT/MRI negative lesions. SPECT evidently is a reliable, highly sensitive me~hei to detect a decrease of brain perfusion in patients with llIV-infection. These results may represent the func~iehal aspect of recently described (micro)vascular changes fin HIV-encephalopathy. Negative CT/MRI findings in mos= c a s e s suggest that the decrease of brain perfusion did not led to structural damage yet. The hypothesis tha~ HHPAO-SPECT may serve as valuable method for early detection of patients with or at risk for HIV-encephalopathy is promising but has to be further established ye=
P. M A O U E T , D. DIVE, E. S A L M O N , R. VON F R E N C K E L , G. F R A N C K Deparmmnt of Neurology. CHU Sart Tihnan (B 33), University of Libge, Liege, Belgium STABILITY OF CEREBRAL GLUCOSE UTILIZATION IN RESTING HEALTItY HUMAN SUBJECTS MEASURED BY POSITRON EMISSION TOMOGRAPHY AND [18F]FLUORODEOXYGLUCOSE METHOD. The reproducibility ef cerebral glucose metabolic rates was reported to be better when determined during double activation paradigms than under resting conditions(l). Using positron emission tomography and [18F]fluorodeoxyglucose method, we examined the stability of cerebral glucose utilization in nine right-handed healthy male subjects (age : 24.88 -+ 2.93) under resting conditions : in the dark, eyes closed but not patched, the ambient noise being reduced to a minimum. Each suject was studied twice at 1 to 12 week interval. Average CMRGlu was 5.40 -+ 0.71 mg/100g.min. (coefficient of variance : 13.08). The average intraindividual variation of CMRGIu w~s 7.91 _+ 15.46 % (p = 0.128). Metabolic indices (MI : regional/mean cortical CMRGlu) were used to determine tJle regional cerebral metabolic distribution. The interindividual variability (coefficient of variance : 7.13) anti intraindividual variability (avenge variation : -0.12 ± 8.76 %) of M! was smaller than tho:~cof metabolic rates. No reproducible significant asymmetry was observed. The FDG method used under resting conditions thus yields low intrai.ndividual variability of cerebral glucose utilization and of regional metabolic distribution, even at several weeks interval. Cerebral glucose utilization measured under such conditions may act as reliable reference to determine the influences of physiological or pathological processes on the cerebral metabolism. (1) Duara R et al., J Cereb Blood Flow Metabol (1987)7 : 266-271
80
79 V.B. Boshjakovic University Clinical Center, }~hclear ~t~iicine Institute, Bel-trade, Y~slavia
B.M. MAZOYER, C. SCHOUKROUN, B. VERREY, J.P. LORRE, M. JOLIOT, J. VACHERt, B. P I A G E R t , P. LEMASSONt, A. BOUVIERt. P. SCHERMESSERt, J.L. L E C O M T E t , A. SYROTA, D. COMAR.
Service Hospitalier Fr~d6ric Joliet, CEA, Orsay, ~Division LETI, CEA, Grenoble, France. new head for an Anger type SC has been designed in order to meet the Qodern require~ento for ~ temporal resolution aid i~proved .~fficiency for medium energy gamm-photcns. SC head features new ;rystal (10) - light guide (12) - collimator (2) ccmplex desi@ned to [ncresse t~e crystal thickness---~thcut intoleran~ " i m ~ t of spatial "esoluticn. 2he effective crystal thickness is increased by crystal 'Zeeth" (20) designed as quadrilateral trtmcated crystal pyramids. Fheae '~eeth'! sre settled an top of a crystal plato of conventional .hidcness (22)(s). Vertical axis of the teeth is alined with vertical ~xis of a particular collimator channel. ~hus, total r~xaber of crystal pyramids equals the ~ of (preferably = _ _ squared) colimator holes. 2he space betwe~q crystal pyramids is "filled" with a light guide material (window glass). 2he crystal p~d side is angled according to the directies of highest gamma energy the SC is designed for, after penetrating through the close-to-crystal portico of the c/~llimathr septxzn for a lergth eq~lirg 2 }~ '; (~ linear absorption coefficient for in a tantalum colimator). T~ms, the J] increased crystal thickness is made effective cnly for photcns earning frc~ the '~roper" collimator channel, preventing by such eu-rsngeme~t the negative effect of Canptes I scatter on spatial resoluties in a thick [ crystal.
~
"~ ~ I
~ U.S. Patent No ~,700,074
PHYSICAL PERFOPdVIAiNCES AND FIRST CLINICAL IM A G E S OF A N E W H I G H S P A T I A L R E S O L U T I O N T I M E OF-FLIGHT POSITRON TOI~IOGRAPH. We present TTV03, a new time-of-flight positron tomograph with high spatial resolution built by the CEA-LETI. The machine consists of 4 rings (up to 6) of 7 m m wide, 18 m m high and 45 m m deep BaF~ crystals (324 per ring) individually coupled to 11 m m ¢ phototubes. Ring diameter is 89 cm, the distance between adjacent rings is 25 cm and the patient port diameter is 52 cm. Transmission data are obtained using an orbiting eSGe source (.66 rpm) made of 19 adjacent rods covering a 30 ° angular sector. The transaxia] resolution (fwhm) in the reconstructed image (8ram ¢ wobbling, Ramp filter with fc = .25 mrs -1) is 5.7 mm at center, 5.8 ram (tangential) and 6.5 m m (radial) at 10 cm. The axial resolution is 8.5 m m (direct plane) and 6.7 m m (crossplane) at center, 10.5 m m (direct) and 11.2 m m (cross) at 10 cm from center. With a 150, keV threshold, the time-of-flight resolution is 750 psec (FWHM) allowing a 4.18 nsec coincidence window which gives a sensitivity (true events) of 9800 evts/~Cqec (direct plane), 1430O evts/~Cffee (crossplane) for a total of 82100 evts/l~Ci/cc. At l#Ci/ec, the ratio of random events to true events is .20 for the total and .026 per image element. With 2.5 ~Ci/cc in a 20 cm ql phantom, the dead time losses are only 8.3%' and the tomograph is actually able to handle higher activities (over I0 I~Ci/cc) in small regions with negligible losses. Reconstruction time is 10 sec for a 1 Mevts image. FDG and RO15-1788 clinical images show a striking improvement in image quality as compared to the TTV01 prototype images. These characteristics make TTV03 particularly suitable for fast dynamic brain and heart 150 studies.
419
81
82
G Germano~ t, M Salvator¢~ Isdmto di Scicnz¢ l~Kliologich¢, Cattedra di Mcdicina Nuclcar¢, H Facolta' di Medicine, Univcrsita' di Napoli, 80100 Nepali, Italy t
Divisioa of Nuclear Medicine and Biophysics, U C L A Medicine, Los Angeles 90024
3-D I M A G I N G WITH 2-D M O D U L A R POSITRON EMISSION TOMOGRAPHY: LIMITATIONS.
QUALITY CONTROL AND CALIBRATION PROCEDURES OF A_~PECT, A SINGLE-CRYSTAL RING CAMERA FOR DEDICATED BRAIN SPECT A.P.Smith & S. Genna,DigitalScintigrophics,Inc.,Cambridge, FIA
School of
DETECTORS ADVANTAGES
IN AND
Multiplanc P E T systems employing 2-D modular detectors combine very high resolution with good sensitivity and lower cost, while multiple planes support 3-D imaging by allowing total organ axial F O V coverage with only one frame. O n the other hand, 2-D detector systems are more vulnerable to deadtime losses and event mispositioning at high count rates: if 2 annihilation photons strike 2-D detectors within the electronic integration time, the rcsulthlg "pileup" events are misposidoned. The basic resolution parameters were calculated and the effect of pilcup on them was assessed for the CTI 2-D modular detector systems for PET. L o w count measurements performed on the CTI 831/08 P E T scanner with 18-I= line sources showed in-plane resolutions of 4.7 and 5.5 m m F W H M for wobbled and stationary data collections, and axial resolutions of 5.9 and 4.8 m m F W H M for direct and cross planes. In-plane values are comparable and axial values arc superior to those obtained in comparable I-D detector systems. T o obtain high count ram information, uniform cylinder and parallel line sources of 50 m C i of 13-N were also measured as a function of time. Cylinders showed that pileup caused data loss by placing events in wrong planes, giving data losses from outcr to inner planes of the 4 by 8 2-D detector module of 6.4% and 1 2 % for 5 and I0 m C i in F O V , respectively. Line sources showed that pileup caused resohdon loss in both F W H M and F W T M : the loss was 1 0 % for 10 m C i in F O V , and deteriorated to 3 5 % at 35 m C L In conclusion, dynamic P E T studies requiring bolus injections of 30+ m C i of 82-Rb or 15-O water arc likely to require pileup corrections in 2-D detector systems. 83
ASPECT is a brain SPECT system employing a stationaryannular single-crystalNaI(TI)detector,and a rotatablecollimator The novel circulardetectorgeometry and digitalpositionanalysishas requiredthe development of new proceduresfor both routineand non-routinesystem calibrations.Routinecalibrationsincludethe correctionfor crystal non-uniformitiesand photomultipliergains,while non-routine calibrationsincludecollimatorcalibrations~indspatialIinearity correctiontables. Because the collimatorrotatesduringan acquisitionand the crystalis stationary,the uniformitycorrectionsfor the collimatorand crystalcar. be decoupledand measured independently.The crystalumformity is measured in a routine~rocedureinvolvinga uniform cylindricalphantom and the standardimagingcollimator. In contrast,the coltimatoris treated likemany othercomponents in the camera-- it is calibratedonce,not routinely,and recsIibrationis not performedexcept in the case of mechanical damage. It is shown both experimentallyand through simulationstudiesthatartifactsarisingfrom crystalnonuniformitiesare suppressedby factorsof as much as fifteenrelativeto a standardgamma camera where the crystalrotateswith the collimator.The artifactsthat do arisefrom a system driftaverageover the image, and do not appear as ring artifacts. Other calibrationproceduresfor measuringphotomultipliergain and spatialiinearitycorrectlontablesare shown. These proceduresexploit the uniquecylindricalgeometry of the camera with a specialcalibration collimatordesignedfor these determinations
I 84
S Holm, L Friberg, HK Iversen, NA Lassen Dept. of C l i n i c a l Physiology and Nuclear Medicine Bispebjerg Hospital, Copenhagen Denmark
W.A.Waddinoton, B.R.Davidson,M.D.Short. Departments of Medical Physics and Surgery, University College Hospital, London.
DUAL ENERGYBRAIN SPECT - METHODSAND APPLICATIONS new fast r o t a t i n g , 2-slice SPECT with 13 mm resolution (Tomomatic 232) has been studied with special regard to applications in research and c l i n i c a l routine of i t s dual ~nergy window f a c i l i t i e s . Energy window settings are software controlled and each event analyzed by d i s t r i b u t e d micro-processors in the gantry before transmission to the MicroVaxll. Count losses are n e g l i g i b l e at the count rates that can be obtained in studies of the human brain. The energy resolution ( < 15 % at 140 keV) is s u f f i c i e n t to separate, e f f e c t i v e l y , xenon-133 and{echnetium-99m, as demonstrated in studies of a 2-compartment brain phantom. In addition to t r a d i t i o n a l dual window scatter correction, the following applications are considered: ) Simultaneous measurement of cerebral blood flow and volume (CBFandCBV). Following i n j e c t i o n of 100 MBq Tc-99m l a b e l l e d erythrocytes repeated xenon-133 inhalation studies are performed. On 6 normal volunteers the method has proven to be reproducible and respond adequately to changes induced by h y p e r v e n t i l a t i o n o r b y vasoactive drugs (acetazolamide, indcmetacine). The method w i l l be used in the study of migraine. 2) Correlative measurements of T c / l - l a b e l l e d flowtracers and xenon-133 inhalation studies, eventually overcoming timing and positioning problems between measurements. In some cases ( e . g . , A-V malformations) specific diagnostic information can be expected. 3) Improvement of attenuation corr. from use of simultaneous transmission and emission measurements w i l l be explored. An 8 - s l i c e whole-body SPECT based on the same principles is c u r r e n t l y under construction.
PHYSICALEVALUATIONOFINTRAOPERATIVEDETECTIONOF RADIOLABELLEDMONOCLONALANTIBODIES. Radiolabelled monoclonal antibodies are used for the imaging of colorectal cancer but the visualisation of small or deeply-sited tumours is limited by physical factors. Intra-operative use of a radiation probe may, however, allow Iocalisation of small tumour deposits not normalty palpable at operation. We have investigated this technique using an 1111n labelled anti-EMA antibody ICR2 and two different detector systems; a Nal scintillation detector
(390cps/MBq 3¢nsitivity for f f I In !n .~catter, 27% energy resolution at 171keY, 16ram fwhm resolution at 2cm depth) and a new CdTe semiconductor detector (RMD Inc.,U.S.A.; 70cps/MBq sensitivity, 16% energy resolution, 12ram fwhm resolution), obtaining turnout/normal colon ratios >1,5:1 in 9/14 patients with cancer and 0.96 andt.O6:l in two patients with benign turnouts. Nodes (
420
86 $.1.1~.,
85 ~gl~L~¢i~ K.Vyska, +W. Stremmel, W.H.Knapp, U. Schmidl, D. FaSbender, U. Gleichmann, H. Meyer, H.J. Machulla, E.J.Knust, R. K0de¢
Lv.d.LOHE, g.J.SIXUI, U.~I~ff,L.
I)epts.~ucl.ited.,W~H k£C~iENand IntJed.,AcadesicTeachinqHospital DUEREN,
Heart Centre North Rhine Westphalia, Bad Oeynhausen, +Med. Klinik D, Untversit~t D0sseldorf, (FRG) IN VIVO CHARACTERIZATION OF MYOCARDIAL FATTY ACID CARRIER IN MAN The influx of free fatty acids (FFA) into human myocardium was investigated by the means of a dual-isotope technique (using 15-(p-1-123Iodophenyl)-pentadacanoic acid (IPPA) as FFA and TI-201 as flow indicator) at two different metaboY¢ states in 15 normal subjects. The FFA influx was found to be saturable with the amount of FFA being supplied to a gram of tissue in a unit of time and to obey MichaelisMenten kinetics. The Michaelis-Menten constant and maximal velecity ol FFA influx were found to be 0.47 IJmOl/g and 0.43 i.~mol/g min, respectively. These results suggest that the FFA uptake is a carrier facilitated process. In order to verify this conclusion we carded out several studies on rat heads. We found that FFA uptake, being 39_+4% ot injected dose per gram of heart in control heads, is inhibited by -bromopalmitic acid to 31_+3%. Moreover, from the endothelial cell membrane ot rat aorta we could isolate a 40-kD protein with high affinity for a variety of long chain fatty acids. The imrnunofluorescence studies with an antibody against the membrane fatty acid binding protein revealed a predominant staining of the membrane of the endothailal cell. These data indicate that the myocardial FFA uptake is mediated by a specific carder which is bound to the endothelial ceil membrane.
~rdiac free fatty acid (IIA) oxidation (0) is depressed by increasi~ ~ . r i a l plnsm concentrations ( ~ ) of 91ucose (G) or lactate (r,) in norsal i r/ocardi~ (H), vherens the influence of these s, bstrates on i s d ~ c wiocardiue (I!() is less clear. Therefore the effect of LnC of G~ Lr FFAr triglycerides (TG) and phc@holipids (PL) on cardiac FFA - O was studied in 20 patients with CADafter s ~ t o s - liaited exercise. CADwas confirmd by
coronary anqio~apby. Artorial su~trate concentrations uere noasured in arterialiled capillary blood by standard e n ~ t i c tests. Cardiac I~A-Owas assessed by leans of 1-123 phenylpentedecanoicacid (IP), a palnitic acid anoloq, and noquMtial simle photon uinsioa t o . r a C y (SPICT). The tracer was injected at peak exercise and SP~ acquisitions were pefforsed at 5-25, 35-55 and 6H5 ~dn p.i. ~e relative activity cha~nsf recorded in left vantricular seqse.te, were taken as index of cardiac I~A-O.Nyocardius in the perfueion bed of the .ost obstructed artery a~l reduced IP@take vas regarded as iscbeldc and comparedto eyocardi,m peffnsud by a non-o~tructnd vessel and hiqhnst IP-@take. ~xercise raised heart rate and scan blood pressure to 190 t and 130 | of control values ~ ± ~ , p < .001); ~ of G, I~A~ ~ and PL did not d~qe (p > .45]. AI~ of L was raised frol 1.1 .~ .2 to 3.5 _+1.~ ~ol/1 (p < .01) and van si~ificantly related to ~aximl heart rate (r = .72, p < .01). IP-release at 5-55 ale wan 29 :~ 6.7 t in H and siq~ificantly depressed in I! (20 .+ 6.2 I, p < .01). Inspective values at 35 - 85 uln were 20~6.3 and 15 .+ (;.51 (p < .05). IP-releans wan se~ttively correlated to AI~ of L in 101 (r = -.67,p <.01), ~erses no relatioe van ok~-vud in IM (r = -.19, p > .4). Ia co.cl,sio., l~reased ~ of L depressed ~IA-O, an assessed with IP and SPI~, in IB. In If, IIA-O ~an consitantly reduced but not related to L~C of exoM~s substrates, indicetlaq in~mina,t intrinsic swwe~i,~ of l~t - nstob01~m. 88
87
J.T. Kuikka, J. Mustonen, M. Uusitupa, P. Rautio, E. L~nsimies, K. PySr~l~
D. F_agEf.t*, J - E . Wolf**, F. Dubois*, J - P . M a t h i e u * , S . H a m a n t * , E. Bore!**, M. Comet*. * Laboratoire d'6tudes des radiopharmaceutiques C N R S 1287, G r e n o b l e , F r a n c e ** C l i n i q u e c a r d i o l o g i q u e , G r e n o b l e , F r a n c e .
DII~ER~TI~L I~L~RE OF L~T~/3L LACTAR ~ T I O ~ O~ C~DIAC ~TTI ACIDOII~TIO! I! ~lIt~L AM) IS~]~IC ]~OCAI~I~I/.
- URA
STUDY OF FATTY ACIDS (FAs) M Y O C A R D I A L M E T A B O L I S M IN MAN, W I T H A I O D I N E LABELED FA. INFLUENCE OF A GLUCOSE PERFUSION. To a s s e s s F A m y o c a r d i a l m e t a b o l i s m f r o m a n e x t e r n a l d e t e c t i o n c u r v e of m y o c a r d i a l r a d i o a c t i v i t y , a f t e r a n IV i n j e c t i o n of 16 i o d o h e x a d e c e n o i c a c i d l a b e l e d w i t h 1 2 3 I (IHA), w e h a v e d e v e l o p p e d a 4 c o m p a r t m e n t mathematical m o d e l : 0, 1, 2 a n d 3 r e p r e s e n t i n g p l a s m a t i c IHA, i n t r a c e l l u l a r free IHA, e s t e r i f i e d IHA a n d i o d i d e s , r e s p e c t i v e l y . T h i s m o d e l h a s b e e n v a l i d a t e d in vivo o n dog. To o r d e r to v a l i d a t e it i n m a n , 16 c o n t r o l s h a v e b e e n e x p l o r e d : e l e v e n 5 h f a s t e d p a t i e n t s a n d five glucose - insulin - potassium perfused patients. The m a t h e m a t i c a l a n a l y s i s of t h e m y o c a r d i a l a c t i v i t y c u r v e a l l o w s u s to c a l c u l a t e t h e r a t i o k21 / k21 + k 3 I, t h a t is 0 . 3 3 7 + 0 . 1 5 6 for f a s t e d p a t i e n t s a n d 0 . 7 0 6 + 0 , 1 2 2 for glucose patients (p<0.001). T h i s v a l u e i n d i c a t e s t h e p e r c e n t a g e o f t h e e x t r a c t e d F A t h a t is e s t e r i f i e d in t h e cell. T h e s i g n i f i c a n t i n c r e a s e w e o b s e r v e d w i t h a glucose perfusion demonstrate that this technique can reveal the influence of the nutritional state of the p a t i e n t o n F A m y o c a r d i a l m e t a b o l i s m . T h u s , it s e e m s p o s s i b l e to d e t e c t a n y m o d i f i c a t i o n of F A d i s t r i b u t i o n b e t w e e n o x i d a t i o n a n d s t o r a g e i n t h e m y o c a r d i a l cell, especially those induced by ischemia.
Depts. of Nuclear Medicine and Medicine, Kuopio University Central Hospital, Kuopio, Finland ASSESSMENT OF MYOCARDIAL FATTY ACID METABOLISM IN NORMAL AND DIABETIC MYOCARDIUM Free fatty acids (FFAs) and glucose are two of the major substrates for myocardial energy metabolism, but relatively little is known about myocardial metabolism in diabetic patients. The purpose of this investigation was to determine metabolic distortion of FFAs in 15 middle-aged patients with non-insulin dependent diabetes and in 6 control subjects. A dose of 4 mCi of 1-123 heptadecanoic acid was iv. injected at the end of bicycle exercise. Immediately after the exercise a SPECT-study was started. The study was repeated 25 and 50 minutes after the injection of tracer. Venous blood samples were collected at 3, 6, 10, 15, 20, 35 and 60 minutes. Exercise TI-201 SPECT was used to normalize the rate constant for I-FFA influx into myocardit~n (kl; I/rain). The other parameters evaluated were the amount of I-FFA uptake oxidized (b; 3), metabolic rate of I-FFA (MR; ~nol/min/100 g) and triglyceride rate constant (k4 ; I/rain). The results showed that there was no significant difference of kl between the diabetic (0.34 -+ 0.09 I/rain; mean _+ SD) and control (0.32 + 0.16 I/rain) groups,whereas the "true" uptake was significantly reduced in diabetes (58 + 8 and 68 + 7 %). However, MR (9.3 + 4.0 and 6.6 + 2.1 ~nol/min/100 g) and k4 (0.71 + 0.19 and 0.39 + 0.08 I/rain) were clearly increased. The findings suggest that kl = perfusion x extraction is normal in diabetic myocardit, n and FFA is not only stored and increasingly oxidized but via k4 is rapidly released.
421
89
90 K~r~BM~ x , g.P.Kaiser i , E.v.d.Lohe=, B.GeutinGt~ M.Henrich x , H.Simon a , L.E.FeinendeGen I .
M.Kann, R.Zimmermann, H.Tillmanns, M.Eisenhut, B.Bubeek, H.Achenbach, W.Saggau, G.Mall, W.Kiibler. Departments of Cardiology, Nuclear Medicine, Cardiovascular Surgery, and Pathology, University of Heidelberg, FRG.
i) Institute of Medicine, Nuclear Research Center 5170 J~lich, FRG 2) Department of Cardiology, Municipal Hospital, 5160 DQren, FRG COMPARISON OF THALLIUM-201 (TL) AND 15-(ORTHO-IODINE123-PHENYL} -PENT/LDECANOIC ACID (OPPA) IN $PECTTECHNIQUE IN 54 PATIERTS WITH CAD.
QUANTITATIVE SCINTIGRAPHY WITH IODINE- 123 PHENYLPENTADECANOIC ACID IN PATIENTS WITH CORONARY ARTERY DISEASE To investigate the diagnostic reliability of myocardial iodine-123 phenylpentadecanoic acid (IPPA) "extraction" and clearance, 22 patients with coronary artery disease were studied. During symptom limited exercise test 200 MBq IPPA and g0 MBq 1"1-201 were injected simultaneously, and planar imaging was performed with dual-channel analysis in multiple views at 5 rain, 1 hr and 4 hr after injection. Using a new computer algorithm, regional and global myocardial tracer uptake, IPPA "extraction" (count rate ratio between IPPA and TI-201 in the initial scintigrams) and IPPA clearance (calculated from IPPA scintigrams 5 min and 1 hr p.i.) were calculated after interpolative background subtraction. Myocardial uptake of both tracers revealed a high overall correlation (r=0.77; p<0.01) and was reduced in hypokinetic (TL-201: -10%; IPPA -13%) and akinetic regions (1"1-201: -18%; IPPA: -22%). IPPA "extraction" amounted to 36_+9% in the total study group and was inversely related to the maximum heart rate achieved during stress test (r=0.57; p<0.05). Global myocardial IPPA clearance revealed an inverse correlation to the Gensini score (r=0.79; p<0.01). The regional IPPA clearance was reduced in myocardial segments with impaired wall motion, most pronounced in hypokinetic areas (-30%; p<0.01). Thus quantitative IPPA scintigraphy yields sensitive parameters for evaluation of regional mycardial perfnsion and fatty acid metabolism.
91
15-(ortho-I-123-phenyl)-pentadecanoic acid (OPPA) can be used for scintiGraphies of cardiac fatty acid metabolism with SPECT, because of its long myocardial retention (T~ > 200 min) and its uptake depending on the integrity of metabolic cell functions. In this study OPPA-SPECT was compared to TI-SPECT. As T1 distribution in the myocardium mainly reflects flow, differences between OPPA and T1 should provide additional information concerning the metabolic activity of cardiac tissue. 54 patients (14 normals, 40 CAD) were examined after coronary angiography. After 12h fasting and bicycle exercise 150 MBq OPPA or 74 Mgq TI were injected. After exercise and at rest 1800-SPECTs were performed. Time between TI- and OPPA-study did not exceed one week. For the detection of CAD (stenoses > 50~) a sensitivity of 74~ for OPPA and 89~ for TI was calculated in qualitative and quantitative analyses; specificity was 79~ for OPPA and T1 as well. i0 of 25 patients with myocardial infarction showed OPPA uptake in areas with a fixed T1 defect. The results show that TI is more sensitive in the detection of CAD than OPPA. On the other hand OPPA uptake was observed in areas with fixed TI defects. The fatty acid uptake in these areas might be explained by metabolic activity of low perfused cardiac tissue. This information could be of importance when bypass surgery or anGioplaaty are considered.
92
Clorius,
~ , A. D i m i t r a k o p o u l o u , I H . Clorius, P. Schlag, E H e h s , G. Wolber
I ~ , A. D i m i t r a k o p o u l o u , J.H. Schlag, E Helus, J. Doll, G. Wolber
D e u t s c h e s K r e b s f o r s c h u n g s z e n t r u m , Heidelberg; C h i r u r g i sche Universitiitsklinik, Heidelberg;
Deutsches K r e b s f o r s c h u n g s z e n t r u m , H e i d e l b e r g ; K l i n i k f i i r Thoraxerkrankungen, Heidelberg-Rohrbach; Chirurgische Universitiitsklinik, Heidelberg; H N O - K l i n i k , K l i n i k u m M a n nh~eim, M a n n h e i m ;
POSITRON EMISSION TOMOGRAPHY (PET) USED TO ESTIMATE TUMOR GROWTH RATE IN PATIENTS WITH LIVER METASTASES. The cytostatie agent fluomuraeil (FU) has been used in clinical practice to treat colorectal carcinomas for more than two decades. The average response rate is lower than 20%. Since tumor response to FU-chemotherapy necessitates the accumulation of the cytostatic agent in the metastases, PET with F-I8 labeled FU can be used to asses~the tracer concentration in the target area. We used a two ring PET systen~ (PC2048-TWB, Scanditronix Co.) to evaluate the FU and its metabolite concentrations in patients with liver metastases prior to FU chemotherapy. The target arm corresponds to the largest tumor diameter and was determined by CT shortly before the PET study. F-I8 labeled FU was administered together with 500 mg noniabeled FU in order to obtain therapeutic concentrations. Sequential PET images were acquired for two hours beginning with the FU infusion. Normalized tracer concentrations (DAR) were calculated from~ ' i ~ . . . . . ........... ] the reconstructed PET cross sections two~ " [ - ~ • ]
POSITRON EMISSION TOMOGRAPHY (PET): A NEW METHOD FOR THE DIAGNOSIS AND FOLLOW UP 1N TUMOR PATIENTS. Several studies have appeared, reporting resuRs on brain tumor patients examined with PET. Due to the availability of whole body tornographs, these studies were able to be extended to all parts of the body. We use a two ring system (PC 2048WB, Scanditmnix Co.) for patient examinations. F-18-deoxyglucose (FDG) is injected for tumor metabolism studies, while O-15 labeled water is administered to assess the tumor perfusion. Metabolic studies in patients with recurrent colorcctal malignancies demonstrated, that PET can be used to determine the increased FDG metabolism in the masses. We were able to differentiate tumor and scar in 21 tumor patients and 8 patients with histologicadly proven sear tissue. The comparison of perfusion and FDG uptake demonstrates, that perfusion measurements in soft tissue lesions are not reliable for the differentiation between benign and malignant masses. PET studies in patients with lung tumors (n=20) showed increased metabolism in malignant lesions. Tumor recurrence after surgery and/or radiation therapy could be differentiated from scar tissue. Furthermore, the measurament of tumor matabulism with FDG or N-13-glntamatc proved to be a reliable method for therapy follow up. F-Ig-uracil (FU) was used in patients with liver metastases from colorectal malignandea in onler to evaluate the uptake of the cytostatic agent in the lesions and to assess the systemic toxieity. The distribution of the FU metabolite concentrations shows, that 76% of all metastases (34/44) have low tracer concentrations, while 24% have higher concentration values. This rate corresponds to the average response rate of colorectal metastases to chemotherapy, as reported in the literature. Furthermore,, PET studies with FU were used to compare different treatment protocols (systemic vs. regional application, pretreatment with folinic acid). Our resul~ demonstrate, that PE"T is a promising tool for both diagnostic evaluation and therapeutic follow up in tumor patients.
hoers after t~cer ~pp~on.
The tu-~ " l " ~ - :
. . . . . . . . . .
~. t
mor volume and growth rate were ealco% n~ ] leted from follow up CT studies and com-~. ~ 1 - ~ ~ I to the ~ accumulation in the me---',~, =~ ~ ~~. ~--~--~~ ~ ' ~ ~ ~ tastes prior to chemotharapy. "VaeprdiF-~ ~c~> minary evaluation includes 15 examinations. A correlation coefficient of 0.845 was obtained for the standardized FU concentrations and the growth rate of the metastases (see fig. on the right). Zero or negative growth rates necessitate FU tracer concentrations exceeding 3. Our data show, that PET can be used to estimate the tumor growth rate prior to chemotherapy and might help to predict chemotherapy outcome.
H. M a n k e , P.
422
93 M.V.gnopp. L.G.Strauss, J.H. Clorius, A.Dimitrakopoulou, U.Haberkorn, H.Manke, J.Blatter, F.Helus, G.Wolber, J.Doll German Cancer Research Center and Clinic for Thoracic Diseases, Heidelberg, West-Germany
POSITRON EMISSION TOMOGRAPHY (PET) USING F-18-DEOXYGLUCOSE IN SMAI~ CELL LUNG CARCINOMA FOR CHEMOTHERAPY OPTIMIZATION Positron emission tomography (P~I') using F-18 labeled FDG was used in patients with confirmed small cell carcinoma of the lung. Thirty patients were included in the ongoing study. Each patient was studied before and after chemotherapy. All patients were imaged by CT before the PET exam in order to locate the tumor and to select the appropriate area to be studied. Sequential as well as endpoint measurements were obtained. The tumor volume was estimated from theCT-imaqes using a three axis method. Follow up studies after therapy were performed for maximumperied of 160 days. Tracer uptake concentration forths tumor were obtained using a ROI-techniqua and standardized for the injected dose and body volume. All tumors showed a significant FDG uptake before therapy in comparison to the surrounding normal structures and were readily visualized on the PET images. We observed in our study three different uptake behavior pattern after therapy: a, decreased uptake correlating with decreased tumor size b, unchanged uptake showing also decreased tumor size, but earlier tumor reocurrence c, increased uptake correlating with no or limited response to therapy as well as increased tumor size The decrease in tracer uptake concentration correlates well with therapy response.The FDGuptake measurement showed to be a more sensitive parameter for therapyredponsethanthe volume change based on CT volume calculations. It can be concluded that PET imaging can be used to evaluate metabolic changes in the small cell carcinoma after therapy to predict tumor regression or progression even before changes in tumor volume can be measured and therefore shows to be a every important and promissing technique for optimizing chemotherapy
95
94 A. Dimitrakgpouletl, L.G. Strauss, IH. Clorius, P.Schlag, E Helus, H Oberdorfcr, I Doll Deutsches Krebsforschungszentrum, Heidelberg; Chirurgische Universitfitsk|inik, Heidelberg;
EVALUATION OF FOLINIC ACID PRETREATMENT WITH PET IN PATIENTS RECEIVING SYSTEMIC FLUOROURACIL=CHEMOTHERAPY. Since more than 80% of patients with liver metastases from celorectal malignancies fail to respond to standard intravenous fluorouracil (FU) chemotherapy, modulated treatment protocols including d,l-folinio acid have found use. Experimental studies have shown that administering d,l-fnlinic acid along with FU enhances the ability of the fluorinated nudeotide to inhibit the activity of thymidilate synthase and increase the cytotoxioity of FU. We used PET for the quantitative assessment of F-18 labeled FU and metabolite concentrations in liver metastases and normal paronchyma. All patients (nffil0) received 500 mg/m 2 d,i-folinie acid intravenously in 20-25 minutes followed immediately by a FU infusion for 12 minutes. Radiolabeled FU was administered together with 500 mg nonlabeled FU in order to obtain therapeutic concentrations. A two ring PET system (PC2048-7WB, Scanditronix Co.) was used for the PET examinations. , PET images were acquired continously ~ ~ - - - - - - - - - - - - - ~ beginning with the FU-infusion for two ~ ......i...................... .. .y:: " ] hours. W e noted a 15% increase of F-18 ~ . j . "i j : " [ tracer concentrations in the metastases~-[ .. j . i l tWO hours aft= FU-ilffusion and d,l-foli- ~'t ~ : . . . . . . !. . . . [ nic as~d appfication in six of ten patients ~o ~, i . , (see fig. on the right), while in two cases ~ ;~ ' the concentration values wero lower after wetrcatment with d,l-folinic acid. Only in one patient a 40% increase in F-18 conoentratious was noted after pretreatment. Furthermore, a significant ~cumulation of F-18 was observed in the vertebrae in thrce patients aftcr d,l-folinic acid infusion, indicating higher systemic toxi6tty. Our results show, that PET van be used to evaluate FU tracer concentrations in patients dire~tecl to modulated FU therapy.
96
R. Senekowitsch, M. Hildenbrand, G. Reidel, H.W. Pabst S. Lastorla, J.A. Carrasqulllo, R.D. Neumann, H. Pass, D. Colcher, J. Schlom, and J.C. Reynolds. Nuklearmedlzinische Klinlk und Poliklinik der Technischen Universit~t M~nchen, FRG
IN V I V 0 LOCALIZATION OF EPIDERMAL GROWTH FACTOR (EGF) RECEPTORS IN HUMAN BREAST CARCINOMA XENOGRAFTS WITH 1-131-EGF Epidermal growth factor is a peptide which stimulates cell proliferation and is known to be important in regulating the growth of breast cancer cells. In vivo assessment of EGF receptors in human breast carcinoma can be of clinical importance because of the relationship of the receptor level with the response to therapy. A method of EGF receptor identification in human breast carcinoma transplanted into nude mice was established with a radioligand assay in which 1-125-1abeled EGF was incubated with membranes prepared from tumor homogenates. Scatchard analysis indicated the presence of a single class of EGF receptors with an affinity of 31 nmol/1 and a receptor concentration of 2150 fmol/mg protein. Because of the high specific binding of EGF to the receptor 1-131-1abeled EGF appeared to be a suitable substance for in vivo localization of EGF receptors. 1-131- EGF was therefore injected into nude mice bearing human breast carcinoma xenografts. The biodistribution of the radioactivity was studied by gamma camera imaging and by dissecting animals at 1,2,3,5 and 24 hr p.i.. The substance revealed an early tumor uptake and a rapid blood clearance much faster than that of a monoclonal antibody to the EGF receptor leading to tumor-to-blood ratios of 1.8 to 2.4 at 2 hr p.i. and therefore an early tumor visualization. The early maximal uptake of radiolaheled EGF in tissue rich in EGF receptors enables visualization of tumor receptors by PET and may help to assess characteristic biological features of tumors for an individualized therapy.
Natlonal Institutes of Health, Bethesda, MD, USA.
MEASUREMENT OF 1251-B72.3 (TAG-72 RELATED) BINDING SITES IN LUNG CARCINOMA: COMPARISON TO RADIOIMMUNOSCINTIGRAPHY RESULTS. Our aim was to determine the relationship between i_~n vlvo tumor targeting and the molar concentration of B--~.3 binding sites in the tumor. Nine patients studied under an NIH approved protocol were injected with 2 mCi/ mg of lllln-B72.3 or I0 mCi/mg of 1311-B72.3 for radioimmunosclntigraphy (RIS) of non-small cell lung cancer. The lung tumors were surgically removed 8-10 days after the injections. In 4 cases, poslt~ve by RIS, the % of in jected dose (ID)/gram of tumor was 0.4 x 10-3 to 0.49 x 10-2. In 5 cases, negative by RIS, the %ID/gram was 0.28 x 10 -4 to 0.3 x I0-2. After 6-8 weeks, to allow for isotope decay, the B72.3 b~ndlng sites in the tumors were measured by in vitro quantitative autorad~ography (QAR) [as described by Del Vecchlo et al. Cancer Res 1988]. Autoradlogra~hlc images showed tumor regions with high uptake of 12~I-B72.3 surrounded by viable tumor areas of low or no uptake. This variation matched immunoperoxldase staining of the tumors. The molar concentration of maximal specific binding (Bmax) ranged from undetectable to 205 pmoles/g. Three tumors not visuallzed by RIS had undetectable levels of B72.3 binding. In 2 other tumors not visualized by RIS, B72.3 hlnd~ng was less than I00 pmols/g. RIS was positive in the four patients whose tumors showed the highest molar concentration of ~n vitro B72.3 binding (109 to 205 pmoles/g). These data support the idea that RIS targeting of tumor is greater when there is high concentration of antibody binding s~tes.
423
97 ~.F, M O R G ~ eTA NICHOLSON} J.R. THORNBACK, L. DELMON, "A. DAVISON and A.G. JONES.
Brigham and Womens Hospital and Shields Warren Radiation Laboratory, Harvard Medical School, BOSTON, MA 02115 and mDept of Chemistry, Ma~s. Institute of Technology, CAMBRIDGE, MR 02235. S E V E N @ O O R D E N A T R TECRNI~TIUM X A N T I ~ T E C O H P L E X E S : A NOVEL CLASS OF COMP(X)NDS wITH POTENTIAL IN N U C L E A R M E D I C I N E . We have synthesiaed a n u ~ r
of xanthate ligands, of general formula K+(S2COR) w h e r e R is an alkyl. The ligand synthesis is facile and easily adaptable to a large numbez of R substi~uentg~ The complexes formed with t@chnetlum have been studied using 99TC; ~he tbu~yl xantha~e has been fully oharacterised using standard techniques of nmr, mas~ spectroscopy and x-ray crystallography. In the presence of a ~ertlary erylbhu~phlne, the preferred conformation i s capped-octrahedral with a seven-coordinate techne~ium(III) centre, three bi~ntate xanthate ligands and capped in the seventh coordination po.itlon ~ the phosphine: (Tx(III)(S~OC~H,}~(PR=)} ~he V~Tch~4R spectra o£ these complexes 6 x h i ~ ~ h ~ s normally assoclated with To(V). The crystal e~,ruo~hre, resolved to ah R factor of 0.043~ shows a three fold moiecule~ symmetry. The analogous complexes formed with 99mTc have been studied and a slmple one step sy~thesls has been developed to give the same species at no car~ier added concentration levels. Several of these complexes were Investigated 'in vlvo' using CD-I male mice or ~ew zealand a~blno rabbit~ The choice1 and biolo$ical find~ng~ will b~ presented and their relevance to n~clear medicine wiil ~ediscuss@d, They are all hlghly ~Ipophillc in nature and the major route of excretion is the liver and hepatobiliary system, however some promising Indication of brain uptake was observed that makes this class of seven coordinate xanthate complex worthy of ~urther study.
99 G. Bormans, C. Van Nerom, C. De Beukelaer, M. Hoogmartens, M. De Roe and A. Verbru~gen
98 C. Van Nerom, G. Bormans, C. De Beukelaer, M. De Roo and A. Verbruggen
Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U. Leuven, Belgium METABOLISM OF 99mTc-ECD IN ORGANHOMOGENATESOF BABOON 99mTc-ethylcysteinate dimer (99mTc-ECD, I) is retained in brain of primates due to i t s rapid enzymatic hydrolysis to an ionized species (JNM 29, 747, 1988). To obtain insight in the metabolism oT-I in different organs we have studied the conversion of I to i t s mono-ester ( I I ) and diacid ( I l l ) in homogenatesof brain, cerebellum, l i v e r , kidneys, lungs and blood of a baboon. Organ homogenates were prepared at different concentrations (I/4, 1/12, 1/36, I/lOS, 1/324, 1/972) in a O.2M sucrose /O.05M trisbuffer pH 7.4 mixture, lO mCi of I (containing 0.075 mg ligand) was incubated with 2 g of the homogenates at 37°C for 20 min. The enzymatic reaction was stopped by adding 0.5 ml HCIO, 32 % V/V, followed by centrifugation and f i l t r a t i o n ~0.22 ~m) of the supernatant. The f i l t r a t e was analyzed by RP-HPLC on Rogel or PRP-I columns at 50°C, eluted with acetone O.05M NHmDAc pH 4.0 gradient mixtures. The amount of organ required to metabolise I for 50% i 20 min is about lO mg l i v e r , 15 mg kidneys, 25 m brains, 45 mg cerebellum, 215 mg lungs and 520 m blood. The mono-ester metabolite is formed in all stu I died organs, pertechnetate only in the blood and the di-acid metabolite in various degrees in each homogenate except blood. I t is clear that the brain and cerebellum possess a high a f f i n i t y to convert I to more polar metabolites unable to cross the BBB. The very fast hydrolysis of I to I I and I l l in l i v e r and kidneys explains why brain uptake has reached i t s maximum rapidly and also the rapid decrease of back-ground a c t i v i t y .
100 LGy.A.J~mloki,
E.Barbarics,
L.K6rSsi
"FJC" Natl.Res.Inst.~or Radiobiology and Radiohygiene, P.O.Box lOl H-1775 Budapest, Hungary Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U. Leuven, Belgium COMPARISON OF 99mTc-ECD METABOLISM IN ORGANHOMOGENATES OF RAT AND BABOON Prolonged brain retention of 99mTc-ECD (1) has been observed only in primates, which indicates a different biological behaviour compared to non-primates. Brain retention of I has been correlated with i t s enzymatic hydrolysis to more polar metabolites, that are unable to cross the BBB. Therefore we have now compared the nature and kinetics of metabolism of I in organ homogenates of rat and baboon, by RP-HPLC analysis on PRP-I. After incubation of lO mCi I (75 ~g ligand) with 0.5g homogenised organ at 37°C for l h, the same main metabolites are found for the respective organs of rat and baboon. Lungs and brain convert I to the mono-ester in each species, metabolism continues to the diacid in kidneys and l i v e r , but to a greater extent in rat (resp. 54% and 78%) than in baboon (resp. 18% and 20%). In blood of both animals I is decomposed gradually to )ertechnetate. In baboon the required amount of organ for 50% turnover of lO mCi I (75 ~g ligand) in 20 min is: l i v e r lO mg, kidneys 15 mg, brain 25 mg, lungs 215 mg, blood 520 mg. A different organ order is observed in rat : l i v e r lO mg, lungs 50 mg, brain 230 mg, blood 290 mg, kidneys 345 mg. I t thus appears that the metabolic a c t i v i t y of brain for I is lO times higher in baboon than in rat, but l i v e r a c t i v i t y is similar for both animals. These findings can explain the observation that in rats brain retention of I is low (< I% of I.D. at max.) and is followed by a rapid wash-out whereas in baboon brain uptake is high (> 6% of I.D. at max.) and stable.
COMPARATIVE BIODISTRIBUTIDN, PHAI~MACOKINETICSAND METABOLISM OF NEW TE~ETIUM-99m ETHER-ISDNITRILE CD~LEXES New isonitrile complexes with a high image contrast due tc better myocardial uptake and less lung and liver activity are of a clinical significance. The following three isonitrile compounds were synthesized and radiolabelled: 2-methoxy-2-methyl-propylisonitrile(A),2-methoxy-2-methvlbutylisonitrile (B), 2-methoxy-2-ethyl-butylisonitrile(C). Compounds B and C have not been reported previously. In the present study, the biodistribution, pharmacokinetics, and rates of bile and urine excretion of the compounds were determined and compared in rats. Myocardial uptake, retention and subcellular distribution were also studied. ..........................................................
Myocard.uptake Activity in Blood,Lung,Liver & retention cytosol bile Urine Comp. I.D. % % I.D. % 5' 5h % % 2h 24h at 60 min. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
A B C
1.87 1.41 1.59
1.52 1.01 1.09
89.0 4 . 2 7 3 4 . 6 0 . 1 4 0.6 3.25 7.5 0 . 3 4 1.3 6.3 1.66 0.40 2.5
4.05 21.90 39.10
In all cases we found slow myocardial clearance (TI19> 6hl and fast blood clearance. The subcellular distri~Otions bile acid and urine excretions and lung and liver activities differed. Radio-HPLC study of collected bile showed that B & C were metabolized. These preliminary data suggest that compounds B & C are promising myocardial perfusing agents. Further study is required to define the optimal imaging parameters.
424
102
101 A. LE PAPE
~ Laboratotre de Siophystque Cellulalre - C.N.R.S. - Facultd de H~declne TOURS, France and Centre d'InmJnologle et Btologte PIERREFARRE, CASTRES France. THE TARGETIN~ OF 1~3ROPHAGESWITH BACTERIAL PROTEOGLYC/~W~ : A NEW STRAIE~Y FOR THE SCINTIGRAPHICIMAGINGOF TUNGURSAND INFLAMMATORYLESIONS.
Slnce turnout growth Is characterized st its early stages by s high mcr@~ge content, we have investigated whether the targeting of this cellular popolstlon could be an efficient tool For an early sclnttgrep~lc detection. In s flrs~ s~ep, a Soluble Pepttdoglycen Derlvate lsolsted from Nocardls Ol:mcs (N~D) was purified by HPLConTSK2000 COltJ~, khan labelled w!th either Fiuorescetn or 125 Iodine, NCJPDwas found to associate electlvely to mousebaritones1 resident macro~hsgesJJ~ Vitro. For an Ym vivo targeting oP meropheges, emphiphatic molecules of NSPOcould :not be IV ~ h r ~ n l s ~ r ~ ~ ~ fotmed-mleelle lresutttn~ ~n s ~ I d @take in spleen and liver. An administration by inhalation after N~PD encapsOlatlon'into lI~o~0mes madeFrc~ hatural phosphollpld~ has allowed s selective delivery oF o l l ~ e r s In blood then an eFFicient targeting in vivo of Pz~aDI ~c¢o~ges gromn 1, OBA/2mice. AFter labelling with Technetium, the opt~J~lzedtechnique has led to visualize In C57B_/~ mlne BI6 F1 melanoma4 to 6 rm In diameter. To svold the requttemnt or llposomes encapsulstiom, a new ligang (IY25) d i r ~ t l y absorbed through the alveolo-e~plllsr heftier was deveiop~d from t~embrsne pmteoglycans of s non pathogenic Strain t~f K1ebstella pr~monta~. This fully chomlcslly chsrectbrtzed JmLcK~odUlstor was found to associate to blood mnocytes and macrophages(80 W) and to lymphocytes (15 ~). kt~n labelled with ~ TechnetJum~D2~ has allowed the scintlg~ephtc de~ectlon oF r o l l tnflmmatory lymph nodes and grsnulomas in baboonsbearing experlmentslly lndueed Beryllio~tso In s model of rsdiolnduced lung turnouts In beboons, D25 has lead Us to d~tect early lesions before any other tmeglng techmlq~es such as CT seana~ 1,5 T M~I and C~111Lmsclntlgre~hy. So, the targeting of Uerophages with highly diffusible ltgands from bacterial @tigln sppesrs ~0 be an efficient strategy for the sct~tlgraphle Imsglng Of inFlm~netory lesions end ttmours aL their early stages ' of gromth,
M.
Pap6s,
Dep. Nucl. Med. and Dep. of Pharmaceutical Szent-GyOrgyl Med. Univ. H-6720 Szeged, POB rio J o l i o t Curie National Research I n s t i t u t e
Chemlstry A.. A69.; "Fredd-
t o t Radtobiology and Radiohygiene, H-1775 BudaPest ,POB 101j Hungary EFFECTS OF LABELING CONDITIONS AND FO~IJLATIQN OF KIT IN VITRO STABILITY OF 99m-Tc-djl-HM-PAO
DIW
The aim was to c l a r i f y the influence of the l a b e l i n g cond i t i o n and klt f o r m u l a t i o n on the s t a b i l i t y of a l t p o p h t l i c complex (LC) of HM-PAO and to develoo a new. k l t f o r mulation p r o v i d i n g better zn vitro s t a b i l i t y , ine experzmental formulations were prepared from chemicals of anal a r grade and e e l f - s y n t h e t t z e d HM-PAO. The c o n t r o l fo~mula~ioo was the Ceretec kit. To analyse the c o m p i l e s ot HH-PAO, three a n a l y t i c a l methods were used: the three- s t r i p method of Netrinckx et a1.(1987), RP-HPLC and s o l vent e x t r a c t i o n methods. We i n v e s t i g a t e d s i x f a c t o r s that influence the s t a b i l i t y of the LC. The ltgand concentrat i o n (0.05-0.1 mg/ml) and pH (~-9.2) did not st=gniftcsntl y a f f e c t the s t a b i l i t y . The concentration ot Sr~(0.6-1.52 ~ g / m l ) and the presence of dissolved O= had moderate e f f e c t s , while the e l u a t e volume (1-5 ml) and a weak chelat l n g agent (~CA) ( 0 . 1 - 0 . 5 mg/ml) had s i g n i f i c a n t e f f e c t s on the s t a b i l i t Y . Tc-HM-PAO prepared with the self-me.de .~ormulation cont.~ining 0.6 mg/ml l i g a n d , 0.5 mg/ml WCh and 0.6A~g/ml 5d~ in 5 ml Nz-saturated e l u a t e has except i o n a l LC s t a b i l i t y (91.75@2~) at 120 min (Ceretec O.B~). Leukocyte l a b e l l n g ~xperiments were pertorme--d--~o ~---~'eYmine whether the high in v i t r o s t a b i l i t y of the LC influences the l t p o p h t l = h y d r o p h t l decomposition i n an in v i v o system, Using 2 x l [ P c e l l s , we found a c e i l l a b e l i n g e f f i c a c y of 65.11¢1.24~. We produced a new k i t providing hight In v i t r o LC s t a b i l i t y , which can t h e r e f o r e convent-
e~l~ ~hu~%delPn~leukocytelabelingduring
a long
period
104
103 M. Schwai~er, G.D. D.M. Wieland.
.*Barbarics, J.'~Ldzdr, Gy.A.'Jdnoki, ay
Hutchlns,
K. Roseasplre,
M.S. Hake, F_~__.~!~*, D J . E , WolP*,M. Comet* * Service de Biophysique et Medecine Nucl~aire ** Clinique Cardiologique Centre Hospitalier Universitaire - Grenoble - France.
University of Michigan Medical Center, Ann Arbor, HI TI.~.A. NON-INVASIVE EVALUATION OF THE MYOCARDIAL ADRENERGIC NERVOUS SYSTEM BY PET i Heterogeneity of the sympathetic innervatlon has been I linked to increased incidence of arrhythmta in varlousl cardiac diseases. To characterize the presynaptlc uptake and storage of noreplnephrlne (NE) in the heart, al new catecholamlne analogue FMR (F-18 metaramtnol) has been synthesized for PET imaging. FMR traces specifically NE uptake and storage as evidenced by inhlbltloni of FMR uptake after pretreatment with deslpramlne (-94%) and reserpine (-77%) in the rat model. In the regionally denervated dog heart (phenol application) myocardial FMR retention correlated closely with tissue NE content as determined by HPLC (r=0.88). PET imaging demonstrated high extractlou of FMR by the myocardlum yielding excellent image quality wlth high heart-to-lung (5/1) and heart-to-blood (4/1) ratios. Quantification of FMR uptake by serial PET imaging using a 3-compartmental tracer kinetic model demonstrated a 56% reduction of neuronal FMR uptake following deslpramine. Initial results in stunned myocardium (30 min. LAD occlusion) showed reduced FMR uptake (-26%) paralleling sustained reduction in tissue NE content. These data indicate the sensitivity of adrenergic nerve terminals to short time periods of ischemla. Thus, FMR represents a new specific NE analogue, which, in combination with PET, will allow the non-lnvaslve evaluation of the adrenergle nervous system in various heart diseases.
INFLUENCE OF DRUGS ON THE MYOCARDIALUPTAKE OF 1231-MIBG. 1231-MIBG, a nore pi ne phri ne analog, h a s b e e n recently proposed for the s t u d y of myocardial c a t e c hol a mi ne metabolism. The aim of our s t u d y w a s to evaluate t he influence of d r u g s on t he myocardial 123IMIBG uptake• 4mC i of 123I-MIBG were i n j e c t e d to 97 p a t i e n t s (10 c o n t r o l s w i t h o u t t r e a t m e n t , 10 p t s w i t h h e p a r i n . 17 p t s w ith amiodarone, 11 p t s w i t h .6 a dre nore c e pt or blocking agents, 10 p ts w i t h labetalol a n d 22 p t s w i t h c a l c i u m blockers) a n d a LAO 45 ° c a r d i a c i ma ge w a s obtained 4 h p.i.. ROIs were d r a w n a r o u n d the h e a l t h y left ventricule (LV) a n d a r o u n d a m e d i a s t i n a l area. The LV to m e d i a s t i n a l ROIs a c t i v i t y p e r pixel r a t i o w e re c a l c u l a t e d to appreciate t he myocardial u p t a k e of 1231-MIBG. The r e s u l t s were as follows : -~o~9of
...........
~-f6 ........
• H e pa ri n • LabetaIol
11=10 n=10
• Cardiac glycosides
n=l I
• .6 adrenoreceptor blocking agents • A mi oda rone
n=17
• Calcium blockers
n---22
n=17
T-7~(~ ~ ...........
1.70!O.20 NS n=2 1.49 et 1.51 n=8 no v i s u a l i z a t i o n n---5 1.32-+O.12 p<0.001 n=6 no v i s u a l i z a t i o n 1 1 = 1 3 1.57_+0.12 I)<0.01 n=4 no v i s u a l i z a t i o n n= 11 1.30~-0.10 p<0.001 n=6 no v i s u a l i z a t i o n n=20 1.51_+0.20 10<0.001 n=2 no v i s u a l i z a t i o n
especially cardiac glycosides a n d labetalol, a s t he s e d r u g s decrease, in a n i m a l , t h e u p t a k e of 3H-norepinephrine. In c o n c l u s i o n : i D r u g s influence t he myocardial u p t a k e of ]231-MIBG, also 2 - Any i n t e r p r e t a t i o n of 123I-MIBG s c l n t i g r a p h i c i ma ge s h o u l d t a k e into account the drugs t h a t have been administered to the patients.
425
106
105 M. BOURGUICRON, E. VALETTE, P. MERLET, D. ACOSTINI, B. JOUVE, J.L. D~BOIS RANDE, A.M. DUVAL, D. LELLOUCHE, A. CASTAIGNE, A. SYROTA.
R. klllnger, R.E. Coleman, w. Drane, M. Gores, R. Mendel, L. Johnson, J. Leppo, a. Reba, D. Selden, A. Wasserman, C. Williams, ~ _ ~ _ ~
S e r v i c e H o s p i t a l i e r Fr~d~ric J o l t o t , H. Nondor, C r ~ t e i l , France.
D. Grant Hosp., Duke Univ., Shands Hosp., Stanford Univ. Hosp., U. Mass. Hosp., Columbia- presb. Hosp., Geo. wash. Univ. nosp., Squibb Diagnostics.
CEA, Orsay, and CHU
1-123 HETAIODOB]DiZYI~UANIDI'I~ (MIBG) CARDIAC IMAGING AS AN INDEX OF TEE SEVERITY OF CARDIOMYOPATHIES. 1-123 MIBG imaging can assess the cardiac depletion of noreplnephrlne stores in p a t i e n t s ( p t s ) with myocardial
disease.
Myocardial
u p t a k e , q u a n t i f i e d as a c a r d i a c
to
medlastlnum ratio (R), measured 4 hours after MIBG injection, was computed in i0 pts with primary hypertrophic cardiomyopathy (PHM), in 40 pie with d i l a t e d c a r -
diomyopathy
(DCM),
in 10 normal s u b j e c t s . PHM p t s were
classified according to a previous history of congestive heart failure : 5 with (group II), 5 without (group I). LVEF, in all the PHM pts was > 55 %. DCM pts (NYHA class II-IV, LVEF < 40 %) were classified in 2 groups according to the clinical sustained improvement with therapy (digitalis, diuretics, vasodilators) : improvement (group I), no improvement (group II). PKM grI PHM grII DCM grl DCM II Normal values n = 5 n = 5 n = 23 n = 17 n = I0 R Value!l.8+.4*ll.4±,l* *-*
1.2±.i*[i+.i* *_*
LVEF %
2±.3
I
68±10 20_+7 13±g > 55 I t test *lower than the normal values, *-*lower in g r II than in gr I (p<.Ol). Cardiac MIBG uptake is decreased in pts with PHM or CMD, and inversely related to the severity of the disease. Thus, in these pts MIBG imaging can provide helpful information for their management.
Cardiology Department, Norhtwick Road, Harrow, Middx, HA1 3UJ, UK
Tc-99m Teboroxime ("TBO") (S030,217), a neutral, llpophillc complex, distributes in the m¥ocerdlum as a function of regional perfuslon end is characterized by a hlgh initial extraction fraction [>90%) followed by a rapid clearance of activity. The clinical utility of thls agent in the detection of Coronary ArteryOisease ("CAD") was studied in 194 subjects during a multicenter trial at eight institutions. Each subject was injected with 12-40 mCl (444-1480 MSq) of TBO either at rest Or during peak exercise followed by image acquleltlon. Rapid clearance of blood and pulmonary activity permitted data acquisition within 90 seconds post injection. Moderate exercise was continued for approximately 90 seconds after the stress injection. Rest injections were made 1.5 - 2.5 hours later to ensure that the subjects were in a true "rest" condition. When the rest study preceded the stress study, the second injection was initiated in lees than one hour followlng the rest study. 155/194 subjects were evaluable for efficacy. Investigatore noted the image quality as fair or good in 92% Of the cases and poor in 8%. No redistribution of the tracer was observed in any o f the subjects. The sensitivity and s p e c i f i c i t y of TBO was 83.2% and 92.1% respectively. Coronary anglogrsphy agreed with TBO in 75.4% of the cases and with TI-201 in 80.3% of the cases, a difference which is not statistically significant. Thus, the u~lque myocardial kinetics of TBO permit a complete stress and rest evsluatlon to be performed within I-2 hours. Combined with the ability to simultaneously measure global ventriculer function, the favorable washout kinetics of TBO show promlme for increasing patient throughput In camera-llmlted settings as well as for repeat evaluations following or during Interventional procedures e.g. PTCA end thrombolysle.
108
107 A Lahir$, B Higley, JD Kelly, Archer, JCW Crawley, EB Raftery
MULTICENTER TRIAL OF TC-99m-TEBOROXIME: A NEW MYOCARDIAL PERFUSION IMAGING AGENT
P Webbon,
B Edwards,
Park Hospital,
MYOCARDIAL PERFUSION IMAGING IN MAN FUNCTIONALISED DIPHOSPHINE COMPLEXES.
USING
C
Watford
NEW
99mTc
A series of novel functionalised diphosphine WmTc complexes (P53, PL37, PL46) has been synthesised and studied in several animal models and has been evaluated in 6 healthy male volunteers (age range 33 to 55 years) of whom one had previous uncomplicated myocardial infarction (MI). Following intravenous injection of 92 to 180 MBq of the 99mTc labelled agent, dynamic imaging (20 see/frame) was performed for 30 min. Subsequent planar and whole body (WB) imaging was performed for up to 24 hours post injection. Safety parameters and WB clearance were monitored for up to 48 hours. No treatment related changes were observed in any of the safety parameters. Blood clearance was rapid and allowed early visualisation of the myocardium within 3 to 4 min with P53 and PL37. Both P53 and PL37 show no significant myocardial clearance but rapid liver clearance (heart:liver=0.75 at 30 min). P L 4 6 did not exhibit such suitable characteristics for myocardial perfusion imaging. The MI scar was visualised correctly within 2 to i0 min with P53 and PL37. Both lagents have displayed excellent myocardial image quality with rapid background clearance and no evidence of toxicity. Due to favourable physical characteristics of 99mTc these agents may offer substantial improvements in image quality compared to currently available myocardial perfusion imaging agents. The potential displayed by this interesting group of compounds warrants further clinical evaluation.
H.P.Stolll,M.M~llerl,~.Sutter2~R.Berberich2 ~.~E.Oberhausen ~ , G.Brill c lInnere Medizin III, K a r d i o l o g i e 2Nuklearmedizinische Abteilung Universit~t des Saarlandes D-6650 Homburg/Sear; W.-Germany 81-RB / 81M-KRMYOCARDIAL PATIENTS WITH NIGH-GRADE DISEASE IN COMPARISON
SCINTIGRAPHY OF CORONARY-ARTERY TO 30 NORMALS
81-Rb accumulates in the myocardium a f t e r intravenous injection similar to 201-TI. It remains intracellulary fixed decaying there to its inert noble gas daughter 81m-Kr which is washed out by myocardial perfusion. The ratio Kr : Rbactivity thus reflects regional myocardial perfusion . Physical properties of both isotopes allow simultaneous scintigraphy as dual-isotope SPECT . We investigated 30 p a t i e n t s with normal coronary system who had to submit to coronary angiography in order to rule out CAD.Functional images representing the ratio Kr:Rb - activity were constructed and the ratio was determined by 8 sectoral ROI's in 4 representing short axis slices for each patient . A standard range could be established the standard deviation varying between 10 a n d 15 % o f t h e m e a n r a t i o values. A second group of 15 CAD-patients was investigated whose coronary findings varied between stenoses of at least 85% diameter reduction and complete coronary occlusion . In case of missing compensating collateralisation viable myocardial segments depending on these stenotic coronary arteries showed increased Kr : Rb values which could be clearly distinguished from the standard range.
426
110
109 ~z~iM~,S.Lazzari+,M.Agostini*,G.Sarti+, G.Moscatelli*A.Spinelli+,G.Vecchietti*, R.Sasperoni* and D.Tirindelli ° *Nuclear M e d i c i n e Department and Istituto Oncologico Romagnolo. +Health Physic Dept."M. Bufalini" Hospital Cesena. °Enea Rome I t a l y . INTRACAVITARY RADIOIMMUNOTHERAPY TRIALS IN GASTROINTESTINAL AND OVARIAN CARCINOMAS: FARMACOKINETIC BIOLOGIC AND DOSIMETRIC PROBLEMS. 13 c o l o r e c t a l 1 g a s t r i c and 12 o v a r i a n cancer patients in advanced s t a g e of disease underwent s i n g l e o r r e p e a t e d intraperitoneal terapheutical injections of specific MoAbs l a b e l l e d w i t h I131 ( m e a n dose 101 mCi). The t r e a t m e n t were r e p e a t e d , i f p o s s i b l e , o n 3 monthly b a s i s . The s y s t e m i c , h e p a t i c and r e n a l toxicity were neglegible. The h a e m a t o l o g i c toxicity resulted quite mild. The mean MoAb whole body e f f e c t i v e h a l f l i f e was 51 h r s f o r o v a r i a n and 33 h r s f o r c o l o n c a n c e r s , w h i l e t h e MoAb T/2 i n t h e tumour r e s u l t e d respectively of 39 and 33 h r s . The mean dose d e l i v e r d to t h e cancer masses r e s u l t e d 5595 cGy i n o v a r i a n cancer and 4379 cGy i n c o l o n c a n c e r . The dose t o t h e l i v e r , k i d n e y and bone marrow r e s u l t e d i n t h e s a f e t y l i m i t s . Most p a t i e n t s developed HAMA which reduced,when f u r t h e r t r e a t m e n s were performed t h e e f f e c t i v e n e s s o f t h e RIT. The c l i n i c a l and o b j e c t i v e responses recorded a r e : pain disappearance or r e d u c t i o n in most cases and ECOG s t a t u s improvement in about 50~ o f p a t i e n t s . 11 o u t o f 25 p a t i e n t s r e s u l t e d a l i v e a f t e r 12 months. I n 12 cases a stabilization of the disease was a c h i e v e d while in 4 a p a r t i a l tumour r e m i s s i o n Was i n s t r u m e n t a l l y demonstrated.
Center for Molecular Medicine aud immunology, Department of Radiology-New Jersey Medical School, UF~NJ, and Immunomedics, Inc., Varren, New Jersey. CANCER IMAGING WITH A NEW 99m-Tc-ANTIBODY METHOD. Twenty patients with carcinoembryonic antigen (CEA)producing tumors were imaged with an anti-CEA murine monoelonal antibody (IMMU-4) Fab', labeled directly with 99m-Tc. This labeling method was simple and rapid, and consistently provided almost 100% incorporation of label and retention of 98% immunoreactivity. The amount of free pertschnetate was usually less than 5%. The mean biological half-life of the labeled product in blood, measured during the elimination phase, was I0 hr. As early as 2-3 hr after injection, 85 to 90% of previously known cancer sites could be imaged by planar and SPECT methods. Based upon four regions of evaluation (chest, abdomen, liver and pelvis), an overall accuracy of about 85% was found. New lesions were disclosed, several of which have been confirmed by other diagnostic methods. The smallest detectable tumor was 0.3 cm in diameter, which was disclosed by SPECT imaging. There was no interfering background radioactivity, including the liver and bowel, at early imaging times, thus suggesting that this new imaging kit is superior to other technetium-antibody kits currently available. These findings indicate that this 99m-technetium/ antibody labeling method is particularly advantageous for the early detection of cancer by both planar and SPECT imaging. (Supported in part by NIH grant CA 39841 and NCI SBIR contract CM-87778.)
112
111 B. Shapiro. L. Hood.
D.M. Goldenberg, E.H. Ford, R.E. Lee, T.C. Hall, J.A. Horowitz, R.M. Sharkey and H.J. Hansen.
Fig,
J.
Carsyj M. Kallue,
J.
Taren, T.
M.V.KnoDD. L.G.Strauss, J.H. Clorius, A.Dimitrakopoulou H.Manke~ J.Blatter, F.Helus, F.Oberdorfer, J. Doll German Cancer Research Center and Clinic for Thoracic Diseases, Heidelberg, West-Germany
University of Michigan, Ann Arbor, MI, U.S.A, INTRACAVITARY THERAPY OF CYSTIC BRAIN TUMORS CHROMIC PHOSPHATE COLLOID
WITH P-32
P-32 chromic phosphate eoltoid (P-32 C) Was administered into c y s t i c brain tumors wlth the a l e of reducing cyst f l u l d secretion and, thus, raised Intracranlal pressure and the need for frequent a s p i r a t i o n . Patients with cyst i c brain tumors and raised Intracranlel pressure or symptoms due to f l u l d accunulation included tO ctaniopharyngiomas ( a l l f a i l e d on conventional therapy), 6 hemispheric grade I I I or IV c y s t i c gliomas (CG) i hemispheric grade II CG, 5 dtencephalie CG end 4 brainatem o r posterior loess c y s t i c l e s i o n s . P-32 C Was Introduced by s t e r e o t a e t i c i n Jection in 14, through indwelling c a t h e t e r - r e s e r v o i r system in 8 and by free hand puncture in 4~ R~dietion dosimetry was based on CT cyst volume and assUmption of uniform P-32 C suspension in cyst f l u i d . Doses delivered 20,000 rads to craniopharyngiomae (O.11-5.8 mCi), 40,000 rads to ocher l e s i o n s (0,45-10.9 ~Ci), 3 creniopharyngiomas and 7 other l e s i o n s received additional doses. Poetprocedure P-32 C l o c a t i o n was confirmed by Bremsetrahlung scanning. Of 23 p a t l e n t e w i t h follow--up, l o n s - t e r m b e s e f i t ( c y s t shrinkage, neurological improvement) occurred in 8/9 crsniopbaryngiomae, 4/5 diencephalic CC and 1/1 low grade hemispheric CG, Shorter-term benefit ( s t a b i l i z e d cyst volume, reduced freqUency of a s p i r a t i o n ) was seen in 2/6 posterior l o e s s l e s i o n s and 1/4 hemispheric high-grade CG~ but the eventual outcome was not eltnred~ No major adverse side e f f e c t s or complications were Observed. We conclude that i n t r a c a v i t a r y radiotherapy with P-32 C i s readily accomplished and r e s u l t s in long-term b e n e f i t in craniopharyngiomas and p a l l i a t i o n of some cys~tc brain, tumors.
POSITRON EMISSION TOMOGRAPHY (PET) OF LUNG TUMORS USING F-18-DEOXYGLUCOSE -Possibilities and benefits
Positron emission tomography (PET) using F-iS-deoxyglucose (FDG) was used in fourty patients with lung tumors of at least 1,5 cm in diameter. All patients had a CT scan prior PET examination. The PET studies were performed using a whole body tomograph (Scanditronix Co.) with Ii mm slice thickness. Sequential as well as endpoint measurements were obtained. For endpoint measurements a scan time of 10 min 55 min after injection was used. A total study-time of 25 min was needed for endpoint measurements. A histology was obtained in each patient studied. Follow up studies were already performed in six cases. Due to the significant FDG-uptake in neoplasms like small cell carcinoma, adene-Ca, mesothelioma etc., a high contrast to the surrounding normal structures was achieved. Those tumors were readily visualized on the images at endpoint We found no significant difference of FDG-uptake for small cell carcinoma and adenocarcinoma, while lower concentrations were obtained in mesothelioma and metastases. Positive lymph nodes showed also a significant tracer uptake. Tracer uptake was quantitated as a differential absorption ratio (DAR) using a ROI-technique and standardized for the injected dose and body volume Based on our experience, it can be concluded that PET imaging using FDG can be utilized to differentiate tumor form normal tissues. Furthermore, PET provides information for biochemical grading of tumors.
427
13
114
O.-d. Meyer, F. Orth, H.-H. Carman , O. St6ckhn ,H. Hundeshegen Abteilung Nukleermedizin und spezielle Biophysik der Medizinischen Hochschule Hannover, D-3000 Hannover 61, und *lnstitut for Chemie 1 Nukleerchemie) der KernforschungsanlagadLilich, D-5170 JOlich
JPTAKE AND PROTEIN INCORPORATION OF SOME IODINATEDAMINO ACIDS IN IRAIN TUMOR3 OF RAT8 ~ased on PET-investigations with l lc-labelled amino acids, iedinated analogueshave recently been used to evaluate the metabolic activity of brain tumors with SPECT. It is the purpose of this study to compare three different iedinated amino acids, p-l-phenylelanine (IPA), elpha-methyl3 - I - t y r = i n e (IMT), end 2-I-tyrosine (IT) in terms of their accumulation m an experimantsl rat brain tumor model. As e natural referenoB, [I 4C]_phenylalanine (pA)was used. The iodinoted amino acid derivatives were labelled with either 1251 or 1311 by electrophilic substitition or by exchange labelling. Purity and specific activities were ChecKed by chromatographic anO spactr0acoplc methods. F 1-generation rats carried brain tumors which were induced by ip- injection of nitro~ethylures to Fo-ganeration females at their 15th day of pregnancy. The brain tumor induction rate was ca 25% The tumors were graded retrospectively by histology. 0.9 MBq of either iedinated amino acid derivative were injected intravenously to tumor carrying rats. The animals were sacrificed at 15 min after the injection, brains removed end analysed for activity in tumor and non-tumor regions. Protein bound fractions of activitywere analysedby trlchloro-aceticacidpresipitation. Tumor over non-tumor ratiosreached 2.3 ," 0.3 for the reference substance phenylalonine,while IPA reached a ratio of 2.7 ±0.4. IMT exhibiteda slightlyhigheraccumulationratioof 2.9 ±0.6, while IT reached 2.3 + 0.6. All 3 investigatediodinatedamino acid derivativesare not incorporatedintobrainproteins.Analysisof the absolutuptakein %Ig gave 0.18 ±0.02 for'PA, 0.17,0.02 for IPA, 0.24,0.02 for IMT, and 0.18 *0.02 for IT
M O ' D o h e r t y , S H L Thomas, T 0 Nunan, C Page and N Bateman. St Thomas t H o s p i t a l , London SEt 7EH, UK.
THE EFFECT OF INITIAL SOLUTION VOLUME ON PULMONARY PENTAMIDINE DEPOSITION
The e f f e c t of the i n i t i a l s o l u t i o n volume on pulmonary pentamidine d e p o s i t i o n was measured in 9 p a t i e n t s w i t h AIDS. F o l l o w i n g p r e - t r e a t m e n t w i t h salbutamol each i n h a l e d 50 mg nebulised pentamidine c o n t a i n i n g a 99mTc human serum albumin marker in a s o l u t i o n volume of 3 or 6 ml. These d i l u t i o n s were a d m i n i s t e r e d using 2 nebuli s e r s , System 22 Mizer (S22M, Medic-Aid) and Respigard I I ( R I I , Marquest) d r i v e n by a 6L/min gas f l o w . Pulmonary d e p o s i t i o n was measured f o r each n e b u l i s e r and d i l u t i o n using a gamma camera. Spirometry was recorded b e f o r e and a f t e r each n e b u l i s a t i o n . For S22M and R11 r e s p e c t i v e l y (3 ml/6 ml d i l u t i o n s ) , values for total pulmonary deposition (mg) w e r e 2.63±0.35/3.71±0.41 (p
116
115
D.Popov I, R.Sreji~2, M.Zuvela 3, i.Bori~i64 Shachar Frank, Ingrid Stuermer and Paul C. Lauterbur ",+
IInstitute of Biophysics,Faculty of Medicine,Belgrade, 2Institute of General and Physical Chemistry,Belgrade
I~partments of Chemistry, Medical Information Sciences+,PhysloloByand Biophysics+, and the Biaenglneeflng Program + ; University of Illinois at Urbana-Champalgn, 1307 W. Park st., IL 61801, USA OJddc ~
IB ~
P~ltmt~tl ~,,~Jt~ In MnmrmJtl~p ~ r , nnnnn Tmmsine
Most contrast enhancing agents studied for M R I arc paramagnctic matednb. 'l'bb class of materials shortens the longitudinal relaxation time (T1) of protons in tissues In a rather limited range of frequencies for practical use in M R ! and him k:= effect 0~ the transverse relaxation time (T=.). This study comzenttat~ on iron oodde partlclca wilieh shorten longitudinal times over u wider range of frequencies and have a very mmn8 effect on transverse relaxation times. Thus, these particles can be used to enhance contrast when using T 2 weighted MR[ by substantially reducing the signal from regions which absorb them. This is a potentially useful method for imaging of the liver, spleen, bile, kidney, hone marrow and lung. Loligltudinal relaxation I:ac~.urcmcnts were perforil~ed with I1 acid cycling relaxometet (IBM) at a frequency range of 0.01 - 50 M H z and at 200MHz on a SIS 200/330 Imaging system. Solutions of particles of different sizes and different internal structUreS were studied (a total of 14 types) and on some of the solutions we studied the effect of temperature on the relaxation. Relaxation rates were found to be fairly linear in concentratlorl over the range studied (0.0065-0,19mM Fe). Mmt of the particles studied consist of Iron oxide crystab embedded in a polymeric matrix with others consisting of an iron oxide core coated with a polymer, Our studies show that relaxlvitles of the former type arc substantially tower than ~ of the latter type. At a field of 0.5T this changes the value of R t Iron1-20(s,mM)" in the former case to -100(s.mM) "1 In the latter case, At 4.7T the effect on R! is smaller but R 2 changes from "-lS0(s.mM) "l for the Iron oxide crystals embedded in a polymer to -1000(s.mM) "t for particles with an iron oxide core. Larger particles were found to have higher relaxivitles =tad tbeil" maximum value of relaxlvity was shifted to a tower frequency. At a higher temperature the felaxlvittcs are lower and the m~dmum telaxivity is shifted to a higher frequency. We conclude that high values of relaxivlty can be obtainedwhenusing larger particlesand in particularparticleswhich consist of an Iron o:ddecore coatedwith a polymerhavea relativelyveryhigh rctaxivlty(Rt and evenmoreso for RZ). Thiswill allowusage of very small doses of such materials m contrast enhancing agents In MRI.
Acknowledgements: Shachar Frank is h Howard I~rughes Medical Institute Doctoral Fellow, This work was supported In part by the Servants United Foundation.
31nstitute of Surgery Clinical Center, Belgrade 4Institute of Pathology, Faculty of Medicine,Belgrade Yugoslavia NMR EXAMINATION OF THE CELL M ~ PE~ILITY TO WATER AND PARAMAGNETIC AGF2~TS ON N O ~ L
AND NEOPLASMIC
HUMAN TISSUES The shortening of T I NMR relaxation time for water protons was followed during the penetration of paramagnetic agents (MnEDTA of GdDTPA) in normal and pathologically altered (neoplasmic) human stomach, liver and spleen tissues. The measurements were made using pulsed NMR spectrometer operating at 2,1 T (90 MHz for protons).Samples were obtained by surgical intervention on patients diseased from adenocarcinoma. It was shown that the NMR method that was introduced by Conlon and Outhred (Biochim.Biophys.Acta,1972,288: 354-361) for cell suspension can be applied to a heterogenous multicellular systems (human tissues in order to determine the average cell membrane diffusianal water permeability (~d). ~d values that was obtained o~ normal human tissues were in the range from Ix10-Jcm s-I to 3x10-3cm s -I. Average membrane permeabilities for pathologically altered tissues containing Tu-cells were substantially higher. ~d values for human stomach tissu@ sam.~es containing I ~ and 15% Tu-cells were 14x10-Jcm s- and 22x10-Jcm s- respectively. It seems also that tumor neighbouring inflan~ned cells have increased membrane permeability. Besides,the permeation rate of paramagnetic agents into neoplasmic tissues was much higher compared to the permeation rate into normal tissues, ~d measurement may have important consequences on the medical diagnostic by NMR imaging.
428
118
117
U.Sechtem, M. JurloehOIslna. P. Thelssen, K. Hungerberg, H.W. HOpp, H. Schlcha
E. Lavie, M. Bitton, S. A b r a s h k i n a n d R. A z o u r y
Institute of clinical and experimental Nuclear Medicine and Medical Clinic III University of Cologne, Cologne, FRG
Radiophrmaceuticals Department, Soreq Nuclear R e s e a r c h Center, Yavne 70600, ISRAEL. MONITORING THE FIBRINOLYTIC ACTIVITY OF TISSUE PLASMINOGEN ACTIVATOR BY NMR.
COMPARISON OF GRADIENT-ECHO AND SPIN-ECHO MAGNETIC RESONANCE IMAGING IN DETECTION OF LEFT VENTRICULAR THROMBI
TheUseof h , m a n tissue-type p l s e m i n o g e n a c t i v a t o r (t -PA) as a p o t e n t i a l t h r o m b o l y t i c a g e n t is a r e l a t i v e l y n e w a p p r o a c h to t h e t r e a t m e n t o f a c u t e m y o c a r d i a l i n f a r c t i o n a n d o t h e r thrombotic disorders. Plasminogen activators are serine p r o t e a s e s w h i c h c o n v e r t p l a s m i n o g e n i n t o active p l a s m i n t h a t i n d u c e s t h e fibrinolytic processes. T h e r e f o r e , PA ~,cts as t h e m a i n m e d i a t o r o f v a s c u l a r clot lysis. The p u r p o s e s o f t h e p r e s e n t s t u d y w e r e to develop a n e w a p p r o a c h to s t u d y t h e s t r u c t u r e o f f i b r i n clot, to explore t h e r e l a t i o n s b e t w e e n t h e clot lysis a n d possible c o m p a r t m e n t a l l z a t i o n o f w a t e r , a n d to follow t h e fibrinolysis k i n e t i c a s i n d u c e d b y t-PA u s i n g p r o t o n r e l a x a t i o n times. The a m o u n t o f t-PA in t h e a s s a y m a r k e d l y a f f e c t e d t h e ]),sis r a t e a n d level of t h e clot. The c h a n g e s i n d u c e b y t h e lytic activity of t-PA w e r e reflected i n p r o n o u n c e d p r o l o n g a t i o n of t h e t r a n s v e r s e r e l a x a t i o n times T 2. F u r t h e r m o r e , deactivationoft-PAwithdiisepropylfluorophosphate(DFP) canse o n l y nonspeeific (.10%) p r o l o n g a t i o n of T 2. T h e g r a p h i c a l a n a l y s i s o f t h e m a n g n e t l z a t i o n s i g n a l d e c a y s e e m s to b e asso c i a t c d w i t h s t r u c t u r a l f e a t u r e s of t h e clot a n d reflects t h e l i b e r a t i o n o f c o m p a r t m e n t a l i z e d w a t e r f r o m t h e clot. T2 m e a s u r m e n t s is a v e r y sensetive w a y to assess t h e p r e t e olytic effect o f t-PA a n d o t h e r p r e t e a s e s s u c h as chymot r y p s i n , t r y p s i n , etc. The p r e s e n t r e s u l t s inforee e v i d e n c e to a possible t w o - p h a s e m e c h a n i s m in t h e lysis of fibrin: t-PA a l t e r s t h e o r g a n i z a t i o n a n d t h e p r o p e r t i e s o f w a t e r t r a p p e d in t h e clot p r i o r to t h e f r a g m e n t a t i o n of fibrin. The sensitivity of t h e t e c h n i q u e is s i g n i f i c a n t l y s u p e r i o r to t h a t of o t h e r t e c h n i q u e s (such a s r a d i o a c t i v e assay) a n d p r o v i d e s i n f o r m a t i o n o n e a r l y s t a g e s of t h e fibrinolysis.
Gradient-echo (GE) magnetic resonance Imaging (MRI) a d d s Important dynamic Information to the morphologlc detail demonstrated by spin-echo (SE) MRI. To evaluate If GE MRI Improved the detection of left ventrlcular (LV) thrombl, 23 patients with LV aneurysms underwent ECG gated multlsllce dual echo SE and flow-compensated short TR (26ms) and TE (12ms) GE MRI. GE Images were reviewed In a closed movie loop. LV thrombl were Independently confirmed or ruled out by anglocardlography, echocardiography, or computed tomography. LV thrombl were correctly visualized by GE-MRI in 12/12 patients with thrombl at corroboratory studies. SE-MRI detected 11/12 thrombl. SE Image quality In the remaining patient did not permit a diagnosis due to breathing artifacts. On SE Images, thrombua was difficult to distinguish from the blood pool In 4/11 patients either due to Intraventrlcular flow signal or thrombus motion. In contrast, these thrombi were unequivocally depicted on GE-Images because even slowly moving blood had higher signal Intensity than thrombus and thrombus movement was clearly visualized on GE movies. Although SE MRI has high sensitivity and specificity In the detection of LV thrombl, GE Images Improve the differentiation of thrombl from the surrounding blood pool. Therefore, GE Images should be additionally acquired, especially In patients with prominent Intraventrlcular flow signal.
119
120
U. Sechtsm, P. Thelssen, M. JungehOlslng, H.W. HOpp, H. Schlcha
Ch. Ehrenheim, P. Heintz, H. Hundeshagen
Institute of clinical and experimental Nuclear Medicine and Medical Clinic III University of Cologne, Cologne, FRG MAGNETIC RESONANCE PROSTHETIC VALVES
IMAGING
IN
PATIENTS
WITH
Echocardlography Is sometimes difficult to perform In patients with prosthetic heart valves due to reverberations from the valve. The feasibility and diagnostic potential of magnetic resonance Imaging (MRI) was therefore evaluated In 32 patients with aortic (N=22), mltral (N=6) or replacement of both valves (N=4). All patients had a spin-echo (SE) examination and 28 patients were additionally evaluated using a gradient-echo (GE) pulse sequence. Harmful effects of the magnetic field were not observed In any of the patients. SE-Images did not show artifacts caused by the metallic Implants. In contrast, all valves caused low Intensity artifacts on GE-Images which prevented assessment of valvular motion. Incompetent artificial valves were present in 6 patients. Locallsatlon of the leak was possible by GE-MRI In all patients and was confirmed surgically In 2 patients. One patient had partial thrombosis of a mltral valve Implant which caused alteration of the normal flow profile. A paravalvular pseudoaneurysm was diagnosed In 2 patients after aortic valve replacement. The extent and relation of the aneuryms to other cardiac structures could be clearly Identified which was not possible with other Invaslve and nonlnvaslve Imaging techniques. MRI Is a safe procedure In patients after valve replacement. Indications for MRI Include technical dlftlcultles with echocardiographlc assessment and clinical suspicion of artificial valve endocardltls. Both, SE- and GE-Imaglng should be performed.
R. Harre,
M. Emter,
H. Dietz,
Department of Nuclear Medicine, Neurosurgical Clinic, Department of A n g i o l o ~ , Medical School of Hannover, FRG MR-ANGIOGRAPHY BEFORE AND AFTER SURGICAL TREATMENT OF EXTRACRANIAL CAROTID ARTERY 5TENO515 Aim of the stu~. MR-engiogrophy allows non-invssive end ropid examination of vessels. Therefore this method wee routinely applied in patients with extracreniel carotid artery stenosls before end after surgical treatment. Patients: 16 patients with a steneeisof the carotid artery were examined. All of them underwent Doppler ultrasound, cenventlonel englogroprPtand
MR-~ngiowsphy.
Methods: A method for high re~lution vascular MR imaging wee applied based on rophastng 8ncl (Bpl'~Slng 3D acquisition techniques. When a flow Suppresseddataset is subtractedfrom a flow enhanceddataset the result is a 3D doteset in whi~ stationary tissue disappearsleavingonly the signal from flow. Any projection required can be s e c ~ i l y reconstructedout of this 3D vessel dataset usingthe ray tracing technique. Results: In all casesexaminedan improvement of various ~jr'ees of the intravaeeular Flowwithin the carotid artery wee meeeurab]eafter surgical treatment. As an advantage,the method Is non-lnvssive e ~ ls therefore suitable for repeatedexaminationsand follow-up studies. The dieadventages include by the time a limited spatial resolution of MR-engtogrophyand o lack of visualization of the vesselwall.
429
121 A. K r o i s s ~ W . W e i s s , C h . A u i n g e r , G.Weidllch, T.Feich~ensChlager,
122 Ch.KOlbl, A.Neumayr B.R.Davidson. W.A.Waddington, M.D.Short, P.B.Boulos
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 , ist M e d i c a l Department, 4th Medical Department, Ludwig Boltzmann Forschungs~elle fQr klan, G e r i a t r i e ~ KA Rudolfs~ifEung# Vienna, Austria.
Department of Surgery, University College and Middlesex School of Medicine and Department of Physics and Bioengineering, University College Hospital, London, U.K.
IMMUNOSCINTIGRAPH¥ (IS) WITH 1-123 AND T~-99m LABELED GRANULOCYTES ANTIBODY (Ab) IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES.
CLINICAL EVALUATION OF AN INTRA-OPERATIVEGAMMA DETECTING PROBEFOR LOCALISINOCOLORECTALCANCERS
We wanted to proof the clinical relevance of 1-123 |Mab,47) and Tc-99m (BW 2501183) labeled Ab in patients with Crohn~ disease ( C . d . ) a n d ulceratlve coli£is (U.c.). We Used 5 mCi 1-123 and 20 mCi Tc-99m and injecEed £he labeled Ab slowly in~ravenOusiy. Images were performed 4 hrs and 24 hrs by planar scin£1graphy and by SPECT. In 30 patients with the 1-123 labeled Ab we could show £he ex£end of an ac£ive or inac£1ve bowel disease in 11 patients wi~h u.c. and in 19 paEienEs with C.d, we found a sensi~iviEy of 77 t by planar scln~Igraphy and of g l t by SPECT. In 18 paEienEs wi~h the TC-99m labeled A b w e Could show Ehe exEend of an acEiVe or inactive bowel disease in 7 pSEien~s WiEh u.c. and in 11 patients wIEh C.d. The resui~s are very similar ~o EhaE of the Mab-4?, The main advanEage o£ the BW 2~0/183 is tha~ the Ab is always available. The resul~s were concordant by t h e clinical indices~ by endoscopy, biopsy, radiography and sometimes surgical specimens, In concluslon# ~he me~hod i s helpful for localization and ex~end of active and inactive bowel diseases. SPECT images are possible.
123
The minimum size of turnout deposits which can be localised by external imaging following the administration of radiolabelled monoclonal antibodies(MAB'S) is generally 2ca in diameter. An alternative to external imaging is the use of an intra-operativ¢(IO) radiation detecting probe which has been evaluated in 16 patients with colorectal turnouts(14 cancers, I lipoma, I adcnoma) 3-6 day*~ following administration of llI!~ labelled M A B to epithelial membrane antigen(EMA)(lmg MAB/2mCi 1111n). At operation 3x20 second counts were taken over the primary turnout, normal colon, liver and suspected nodal metastases. Rescctcd specimens were also probed and biopsies of turnout and normal colon gamma counted. Turnout antigen expression of excised specimens was assessed by immunohistocbemistry. The tumour to normal colon(T/NC) ratio of counts in vivo was >1.5:1 in 9 of the 14 patients with cancer(l.83+/-0.21:l*) and 0.96:1 and 1.06:1 in the two patients with benign turnouts. The T/NC ratio was significantly higher for resected specimen probing than in vivo(4.44+/-l.37:l* vs 1.51+/-0.44:1", p=0.000) and correlated with g a m m a counting ratios (2.26+/-0.78:1" R=0.73, p<0.001). E M A expression by cancers was associated with higher T/NC ratios(2.45+~-0.65:1* vs 1.30+/-0.25:1", p=0.005). Lymph nodes(
124
d£ URBAI~,J. J~SSE~S, 6. VANTRAPP~, M. De RO0.
~2!Z~g~,
UZ. 6ASHUISSER6,LEUgEN,BELGFJ~ EFFECTOF N E R Y T ~ I N ON6ASTRICEMPTYI/~ DISCRIMINATIONBET'w'EEN SOLIDS AJtlDLI(XIIDS. Ergthromyom, a rna~olides' group anfibiotb, has reoe~t~ beenshorn to have a mofi#n-Ske effect on ~sb'oHntestk~al muscle strips. The I~rposo of this studij was to assessthe invivo effect of ErNthror~oin on patkm~ ~ i ~ delay~ gastric m~pttjmq usmq tl~ dual radionuclide tq~hnklue. Ten diab~Ucs ~tk, nts with 9ast'oparesis sgm~oms ",#erestuclied.F o ~ a basal sl~dg arid on a separate daj, end1 p ~ t ~ t r t ~ , ~ l a 15 m~rtes: IV perfusion of ! qr Erythomgcir, startmq at meal kzgest~. N~e out of lO patients yore restudied after a s~]e oral dose of 500 m~" of fie d r ~ a week later. Ten healtl~ sub~ectsv e r e used as controls. Oastr~ ernptu~n9 of solkJs (S) and ~ (L) were determk~edusk~ Tc-99rn-~ scrambled eq~s and In 11 I-DTPA m ~ater, r ~ t w e k j . S~multaneo~santerior and postedor knages vere re~orded for 2 he~rs us~n9 a dual-headed9arrena ~nera ~ ~orrected for d ~ and downso~tter. Re¢~s of interest ~¢ere rnammIl~ drawn around the stonm~hfor each anterior and 10~-~eriorT~-99rn and In-! l l irna~ and sotid a~l Ik]ukJgeometr~ rneandata ~ere ~-~-,-ated. PeroeMagesof eachboto#e retained in the stomach after 60 and 120 rain are summa~ed below (rnemi~EM) : GROUP N CONTROLS PkTENTS SOLIDS LKXJlDS SOLIDS Lg~JLIIOS 60 120 60 120 60 120 60 120 BASAL l0 ~515 913 1T~3 4±I 8517. 63+9* 54~5. 3214. NERYTHRO 10 21+5°0 4+1 .='o 2"2,,z.5°°9,~3°'=' ORALERYTHRO 9 ~ 7 ~ 25~5 ° 41±5° 19~4° * p< 0.0001 ; cop< 0.0001 IV versus basal;°p< 0.001 oral versus basal After Er~thromqoi, perfusien, solid md l k ~ ~ emptq~ncj~ r v e s vere kleMi~l. ~e oormludethat IV ~ and s-ingleoral ~rn'inistr~tion of" Erythrom~om dramafioalkj accelerates o ~ emptging of soSds and ~ m gastropares~s dtabetio~um and ~ the so~d-~ukl discrim~ion effect is abolishedbg tl~ IV Ix.rfusi~ of the drug. Ergthror~jcm appears to be i potent gastro kineU¢ ~Fhieheo~Mbe useful in dgspept~ i~-~k=ntswith de~jed ~ t r b ernl~y~ng.
R.M~llmann,
Kiiniken f~r Radiologie Universit~t Greifswald,
und DDR
S.Lifson Innere
Medizin,
ABSORBTION OF I&gYb-DTPA IN COELIAC DISEASE In d i s e a s e s t a t u s o f small i n t e s t i n e t h e r e is an increased permeability of large polar m o l e c u l e s combined w i t h m a l a b s o r b t i o n o f small molecules. So, d i f f e r e n t , mostoften chemical tests h a v e b e e n u s e d in t h e d e t e r m i n a t i o n of intestinal permeability for coeliac diseases. There are different limitation~ in the of these tests. We examined the urinary elimination rates after oral administration of mannitol (a s m a l l m o l e c u l e ) and 169Yb-DTPA (a great polar molecule) in p a t i e n t s with sprue (n=9), Crohn's disease (n=18), dysbiosis (n=26) and controls (n=30). Comparative different resorption tests (Schilling's test, xylenose, et al.) a n d m u c o s a b i o p s y w e r e per"formed. Using ROC analysis we calculated quality parameters to differentiate coeliac diseases from controls. test sensit, specifity discrimin, level 169Yb-DTPA 91% 92% 1.1% (24h u r i n e ) mannitol 98% 82% 13.5% ( 6h urine) mannitol/Yb 92% 94% 13.0 (ratio) The 24h urine recovery rate of 16?Yb-DTPA a p p e a r s t o b e an a c c u r a t e , noninvasive test to assess small bowel integrity. The ratio of mannitol and 169Yb-DTPA (different behavior of both molecules) provides the best discriminat i o n , w i t c h is h i g h e r t h a n in o t h e r r e c o g n i z e d ~reening te~t~.
430
125
126 K. Tatsch, W. Schr6ttle, C.M. Kitsch
W.G. Harttn, K. Ktrchmann, J. Adolf, H.gremer, H.W. Pabst Nuklearmedtztntsche Kltntk und Poltkltntk (Dtr. P r o f . Dr. H.~. Pabst) und Chtrurgtsche KIintk und Polikltntk rechts der Isar (Dtr. Prof.Dr. J.R. Stewert) der TU-HOnchen, FRG
Division of Nuclear Medicine, Department of University of Munich, Munich, FRG
C 14 AMINOPYRINEBREATHTEST (ABT) IN PATIENTS WITH CANCEROF THE ESOPHAGUS.
A MEN COMBINED QUANTITATIVE AND QUALITATIVE P ~ T R I C MULTIPLE SWALLOW TEST FOR ADVANCED IMAGING OF ESOPHAGEAL MOTILITY DISORDERS
In patients with cancer of the esophagus surgtcal mortality ts very htgh after esophagectomy. Surgical risk is increased in cases with associated liver diseases. The outcome of ABT is a sensitive and quantitative indicator of liver dysfunction. The aim of thts study was to assess the clinical value of ABT tn monitoring patients after esophagectomy. We used ABT tn 40 patients with cancer of the esophagus (all male, age 42 to 7I, man 55,2 years). In 10 of these attents we performed ABT before and after surgical nterventton ( l s t to 7th/lOth day post operation). In the same patients ltver function was determined by Indocyamtne Green Elimination Test (ICG) and the Galactose Eltmtnat|on Capacity (GEC). The findings were compared to the conventional liver test, the histological findings and the clinical status post operation. All of these lO patient showed a similar function of the hepatic mtcrosomal system (cytochrome P-4SO). There was an increase of the C 14 exhaled dose on the day of operation and a decrease of this particulate liver function at the third day after operation. Liver function returned to normal values up to the tenth day after operation. In contrast ICG and GEC showed different changes whtch w i l l be discussed. ABT ts a suttable test for pertoperattve evaluation of liver function tn patients wtth cancer of the esophagus and could be used to clartfy the conventional menltortng of liver function.
~
127 A. Hotze, G.S. Rao, K. Kluetsch, M. Adenacker, H.J. Biersack. Dept. Nucl. Med., Dept. Clin. Biochem., Univ. Bonn, W. Germany RADIOII~qUNOASSAT FOR PORCINE TSH (pTSHJ. S t u d i e s on TSM r e g u l a t i o n u s i n g c u l t u r e d thyrotroptc c e l l s r e q u i r e d to e s t a b l i s h an a s s a y f o r d i r e c t m e a s u r e ment of pTSH since pTSM assays are not yet commercially a v a i l a b l e . Methods: a) L a b e l i n g o f pTSH: modif, c h l o r a mine T method ~iodo beads), b) Separation of unbound 1125: PD-IO c h r o m a t o g r , column (Sephadex 25). o) E s t i m a t i o n of immunological activity of 1-125- pTSH: Binding to anti-pTSH-antibody (AE) without unlabeled antigen in PBS b u f f e r (=BO),and b i n d i n g w i t h o u t AB (=non s p e c i f i c b i n d . , NSB). d) E v a l u a t i o n o f f i n a l d i l u t i o n o f l e t and 2nd (precipitating) AB. e) D i l u t i o n o f s t a n d a r d pTSN p r e p a r a t i o n s (calibr. against A int. Stand., MRC). Results: 1. Optimal labeling time: 12 min., 2 iodo beadn. 2. Chromatogr. of the "crude" tracer revealed excellent reproducible results with 1-125-pTSM in th 14th-23th fraction, and free iodine in fractions 48-53. The best immunol. 1-125-pTSH wan found within the fraction 16-17. Protein (fraction 15) was assayed by NPLC. 3. BO binding: 35% ±2%, NSB:<5%, inter/ intra-asnay variance:<7%. 4- let AB dilution (1OO ul in assay) was found to be 1:10,000 (total assay volume: 500 ul). Assay vOlume of 2nd AB: 500 ul. 5. Standard preparations: 2.5,5,12.5,25,50,75,100uU. 6. After 18h incubation of I-i25-pTSN, let AE, unknown probe o r s t a n d a r d , 2nd AB was added; i n c u b a t i o n : 30 min., centrifugation a t 200Og f o r 15min., a s p i r a t i o n of f r e e activity, counting. C o n c l u s i o n : The a s s a y works p r e c i s e r e g a r d i n g a l l q u a l i t y c o n t r o l s p e r f o r m e d r o u t i n e l y . The e x p e r i e n c e s g a i n e d w i t h t h i s a s s a y can be e a s i l y t r a n s f e r e d to o t h e r p i t u i t a r y hormones such as LH, FSH and GH.
Radiology,
A new esophageal parametric imaging (EPI) technique is introduced, which not only permits qualitative but also quantitative evaluation of multiple swallows. EPI was performed in 30 normals and patients with different forms of esophageal dysfuntion (connective tissue diseases, diabetes, reflux). The passage of liquid (i) and solid (s) bolus were investigated by 6 consecutive swallows each. For evaluation new software was developed. Quantitative (clearance values at 10/15 sec) and qualitative (parametric images) data were calculated for each single swallow (SS) as well as for a particular created 'sum image' (SI). Clearance data for SS considerably differed from those obtained for "SI' as shown by calculation of a variation coefficient (mean: 174 (I), 234 (s); max.: 564 (i), 494 (s)). In 414 the clearance of SS differed more than + 1 SD compared to the 'SI'. In contrast to SS, parametric "SI" well and reliably characterized the predominant pathologic image pattern (cumulation, reflux, oszillation). Quantitative evaluation of multiple swallows by EPI is an appropriate method to reduce false pos./neg, results occuring in single swallow tests. In addition qualitative evaluation by parametric images evidently shows the predominant pathophysiological aspect of dysfunction. EPI combines the advantages of a multiple swallow technique with those of quantitative and qualitative single swallow tests, thus indicating a diagnostic progress.
128 ILPERDRISOT1, D.GUILLOTEAU3, J.C.BIGORGNE2 and PJALLET 1
1 Laboratoire Joliot-Curie, C.H.R.U., 1. av.HOtel-Dieu - ANGERS 2 Service de M~iccine C.- C.H.R.U.. 1, av.H6teI-Dieu - ANGERS 3 Service de M~kcine Nncl~dre, C.H.U.Bretoonenu,2 Bd Tonnell~- TOURS MONOCLONAL IMMUNORADIOMETRIC ASSAY CALCITONIN : IMPROVEMENT IN I N V E S T I G A T I O N FAMILIAL MEDULLARY THYROID CARCINOMA
O F OF
Medullary thyroid carcinoma (MTC) occurs in familial forms in 25 to 35% of the cases. Calcitonin (hCT) assay is essantial to recognize this tumor and particularly to detect occult familial MTC. Previous mdinimmunonssays (RIA) used polyclonal antibodies. In 1988 , Motte and Coll. (i) described a two site immuunradtometric assay (IRMA) for caicitonin using monoclonal antibodies. This work evaluates this new method in diagnosis, follow-up and familial greening of MTC. The two site assay (IRMA) uses a first antibody coated on u solid phase and a second antllxxly labeled with 1251. 'Ilw,se antibodies recognize re~i~cfivdy the 2432 and the 11-17 regions so only the CT-monomer is measured. The minimum detectable concentration was about 2.5 pg/ml. Patients include 83 healthy subjects of whom 18 underwent puntngastrin stimulation tests, 13 patients with renal failure, 30 subjects from families affected by MS"C. The basal values in healthy subjects were all under 10 pg/mi.Ranal fallme causes an increased basal CT (between 10 und 50 pg/ml fnc 8/13 padants). The CT peak under pentsgaslrin stimulation in healthy patients was lower than 30 pg/ml. In familial screening, basal values over i0 pghnl or peak values over 30 pg//ml correspond to subjects with histologically conrnmedCMTor mleroCMT, but subjects with micmCMT sometimes had basal values under 10 pg/ml. Polyclmul RIA performed in the same subjects failed to detect the modcoUeinereaso of CT that IRMA demonstrated taxiparticularly in cases of microCMr. In conclusion, this new method allows an earlier detection of CT increase and so, an improved diagnosis of MCT particularly in familial soreonlog. The follow-up of operated patients could also be improved by this new assay. 1. Mou~ P., Vanzelle P.. Gardnt P. et Coll. - Clin.Chim.Acta, 1988, 174, 35
431
129 M.
Martin,
130 W,
Bleys
M.J. Tabuenca, H.C. Marfn Rojas, P. Uriarte, M.J. Argueso, J. de Haro, G. ~%ra/-la, J. Ortiz Berrocal
a n d P. B l o c k x
Department of Nuclear Medicine, Antwerp University Hospltal, Edegem,
Belgium C l l n i c a P u e r t a d e Hierro, Hadrid, Spain
ANALYTICAL NON-ANALOG
AND CLINICAL EVALUATION OF A NEW, RADIOASSAY FOR SERUM FREE THYROXIN
A new FT4 assay, the Amerlex.Mab FT4 (Amersham I n t . , U K ) , c l a i m e d n o t t o h a v e t h e d r a w b a c k s of the analog tracer assays, was evaluated. This one-step assay is based upon the competit i o n b e t w e e n F T 4 a n d m a g n e t i s a b l e p a r t i c l e s foz the binding sites of a labeled monoclonal antib o d y (AB). B y t h i s p r o c e d u r e t h e m e a s u r e d F T 4 concentration becomes independent of binding protein properties. Serum FT4 was determined in 232 patients, 5 of w h o m h a d a u t o - A B a g a i n s t T4, a n d 1 h a d f a m i l i a l dysalbumlnaemia. A good correlation was found between this assay and the former Amerlex-M-FT4, after exclusion of these 6 patients and of extrapolated values (r = 0.95, new = 1.27 x former - 0 . 1 2 , n = 218, range 0.7 - 117 pmol/1). Results for patients with T4-auto-AB or with dysalbuminaemia were all in the normal range, whereas with Amerlex-M they all were very high. In our hands, better withln-assay precision was obtained with a modification of the standard protocol: separation by centrlfugation and aspiration, instead of magnetic separation and decanting. This modified procedure yielded w i t h i n - a s s a y C V ' s < 5% o n d u p l i c a t e s i n 95 % o f the cases, over the whole assay range (against 68 % CV's < 5% with the standard procedure).
F4-T SERUM LEVELS AS A METHOD FOR SCREENING THYROID FUNCTION: RIA OR FLUOROMETRIC ENZYME IMMUI4OASSAY (FIA)? Serum free T--4 concentrations more closely reflect thyroid function than does total T-4. The aim here is to study whether the determination of free T-4 in serum by RIA and FIA affords overlapping values, compare the two methods from the point of view of diagnostic reliability and cost and conclude whether they can be employed to differentiate between normal, hyper and hypothyroid function. For this, the FT-4 values have been determined by radioimmunometric and enzyme-fluorescence methods in 299 patients whose thyroid function was determined by routine measures (TT-4, TT-3, T3-U, TSH). For the entire population, the correlation index between the two methods was 0.914 (p < 0.001) with a regression curve where y=0.866; x+0.5 (Pearson correlation and least squares regression). From the point of view of its use as a screening method for the assessment of thyroid function, the determination of FT-4 alone would have been sufficient to indicate the functional situation in the following cases: Routine RIA FIA Eu Hypo Hyper
232 29 38
222 (95.7%) 27 (93.1%) 36 (94.7%)
226 (97.4%) 28 (96.5%) 38 (100%)
Total 299 285 (95.3%) 292 (100%) CONCLUSION: As a screening method, the determination of FT-4 is enough to assess thyroid function. The study of the direct cost of the expendable materials employed shows that while the direct costs are slightly higher with FIA, the cost-effectiveness ratio was greater.
132
131 Z,A, Kureishy
Th. Lyras°
M.Georgossopoulou,*
and V . G e o r g o l o p o u l o u * Department o{ Nuclear Kuwait University.
Medicine,
Faculty
of
Medicine, D e r e e C o l l e g e , Athens. A r a e t e i o n Hospital, A t h e n s U n i v e r s i t y .
A MATHEMATICAL TOOL FOR ANALYZING CORTISOL PERIODIC FUNCTION. The application o{ periodic function to describe biorhythms usually involves situations where the independent variable x represents "TIME", and the function concerned represents a cyclic or periodic process unfolding in time. The general equation of the form is in the case where the function y = a cos at; a and e are constants, and t represents time. Our intention here is to provide an equation showing a biological variable y (circulating total serum cortisol) as a function of time t. Y is observed to vary in a sinusoidal manner, oscillating between y = i and y = 2 in a 2& hour cycle. It reaches its maximum at 8.00 am, and its minimum at 8.00 pm each day. The graph of y against t has a form where time t is measured in hours starting with t = 0 at midnite, and increasing to % = 24 the following midnite. The maximum value of y occurs at t = 8.00 am. Note that y does not oscillate between two values ± a, but between I and 2; therefore we subtract the average of 1.5 from values of y. This function oscillates between values ± 0.5, hence its amplitude, a = 0.5. The time period t = 2~/e = 24, so the angular frequency e = 2K/24 = K/12. %:. = 8, the time at which the process acheives it maximum. So the equation is: y - 1.5 = s cos ~(t - to) 0.5 cos K/12(t 8). The function y = 1.5 + 0.5 K/12(t - 8). This equation ~ives the value of the function y st any time t. Thus predicted serum cortisol levels st time t can be calculated from baseline midnite values. =
-
RIA DATA MANIPULATION IMPROVEMENT BY POLYNOMIAL FUNCTION FIT One of the basic problems in improving radioassay data is that of finding the theoretical function that describes best the standard curve. Polynomial fit is a f l e x i b l e m a t h e m a t i c a l a p p r o a c h to the problem of curve fitting, by systematic analysis of e m p i r i c a l data. We a n a l y s e d d a t a of 50 s t a n d a r d c u r v e s for T3, T4, and T S H h o r m o n e d e t e r m i n a t i o n s . T h e p r o g r a m was based on a mathematical routine named POLFIT. Letting Y be the ( c o u n t s / m i n ) o b t a i n e d with a concentration X of T3, T4 or TSH, polynomial functions of 3rd up to 1 2 t h o r d e r were tested for goodness of fit to the e x p e r i m e n t a l data. R e l a t i o n of Y w i t h t h e s q u a r e r o o t of c o n c e n t r a t i o n (X) in polynomials was studied and showed good fitness. P o l y n o m i a l of 4 t h o r d e r g i v e s the b e s t fit for a simple relation between Y values and hormone c o n c e n t r a t i o n ; i n a r e l a t i o n s h i p of Y v a l u e s w i t h the s q u a r e r o o t of c o n c e n t r a t i o n , an i m p r o v e m e n t w a s n o t i c e d w i t h 8th o r d e r p o l y n o m i a l . A f t e r t r y i n g p o l y n o m i a l s in an i n c r e a s i n g order, t h i s p r o g r a m fits the d a t a on the b e s t response curve, plots graphs and finds the u n k n o w n s . Computerized data manipulation by polynomial curve f i t t i n g is a f l e x i b l e and a c c u r a t e w a y to handle radioassay determinations.
432
134
133
M.STEINLING1, D.LEYS2, Y.GAUDET2. E.OVELACQ1, M.PETITz, R.VERGNESI
~. vEa~As*, h. pJvr'r]~*, O. DIr.ME'URZ3SE", J. PAT[RNOT*, ..I.MERTJGq3* * &.~SSI~"T*" end A.CAP~" • h c u g ~ m n U ~ t v • I s i t y of h i , u n n a i l • *~ltxdeml~lw Z l o k e ~ h u l s H o s p i t a l
(Flail Univmzeity of l r U l a l i a ] (vzi~a U n i v a r s l t a 4t B~.,'ulaall)
%m~fnduct~em The C l ~ l l of th41 l h o u i d a ¢ ° l ~ l i~1~¢ome h a l boon l t t ¢ l h u t M to a h¢lchial pla~l llt~IgltiOll l l C ~ l l d e c y tO h l J l l p l e g l a t h a t i l l l t l a t e l in idZalqeZVle d ¢ • i t a t l o z e a p O n l a . H o w e ~ e ¢ , e e n ~ e l ~x0ponantl may h i v e a o m p l e x i~t t}Mi •~1~1 h tile M t ' ~ B a al~. w~ creator m¢¢tuda t h a t t h e o 4 ¢ e n e r g i e l iltlallOre gl~a~allald distuzbanc, than that expected.To neuropath~ .IONIA t a c t ~h~l h y p o t h e s i s we s t u d y t h e p ~ o ¢ 4 ~ u p t a k e of a g t ~ n a t h i d i n a enalog (NZN*XII3) b o ~ m s e t h i s g l o u d , r i c h l y 8 u p p l £ s d b y o 3 5 p a t h e t i e M r V e S a p p e a r e d to be • ~ t e s t ~ m ~ o f m~r m / ~ t h e e t e dlef~dMll~e. T ~ i a t y - t h = e o p a t i e n t s w e r e s t u d i e d 45 d a y s t - 14 e f t o ~ t h e m i t t o f h m l p l o g i e . T h e mann a ~ ~ a 62 y o e r (+- 9 . ? ) : a ~ l p a t i e n t s p r o • r a t e d w i t h a i d ~ o u i ~ J r - o l ] t ~ r O l ~ . A p l z ~ t i d s ~ l n t i g t a ~ " atud~ w~a p e r £ o m e 4 5 h o ~ s s i t a r ZV l n J e m t l ~ o~ ?4.0 MHq H ~ ZI23.T~ t e a t the ~ptigml t i J ~ to Imamtre t h e ~L~otld upthke, the b i l a t e r a l p a z = t l d a c t i v i t y of ~ l n s p a t i e n t s wall 8 t ~ e 4 It l h , ~h. $11 a n d ~ t h e f t e ¢ t h e W~l~-II23 i n J e c t l c m . P a t l e ~ t a we¢e ~o d i a b e t i c s and d i d ' o r t a k e an~ M d £ ~ : a t i o n t h a t ~ l d Integrate with t~a eympathee4c ~z~roua r ~ s t o ~ , T h a ffilco~on t e a t was u s e d f o r s t a t i s t i c a l llg~t~flca~co. l l m t t X t l The o p t ~ m l t 4 M f o r t h e ra(~¢led Of g l a n d a c t i v i t y was ~ound b e t w e e ~ 3h a n d 5h a t t a r t h e 1~ llsJo4~tlOnoAt 5 h , the dial diapsza/o~ win l e e s itt-onmme~4.&t ~lh a f t e r t h e XV l n ~ e c t l c m o~ IG~G-X133 t h e g n was • s i g n i f i c a n t i n ~ r e s J e o f p e r o t l d u p t a k e on t h e h m t l p l e g i c s i d e | 0,11 t ~ a g s l t t a t O . $ S t ZD on t h e e ~ x t t = o l a t s r s Z l i d S . T h e d l f f e z ~ m ~ a Wal h i g h l y a i g t 3 1 f l e a n t ( p ( 0 , 0 0 2 ) . g1~1 Imz~tid pstalysed lids ~LSmZ s i d e .ratio activity p4rotid activity p~¢otid a c t i v i t y (~ZD) | 0.77 0*&l (p(0,002) 0.36 1.it on .~.: 0.27 O,t5 0.13 va~.com~ (t) 0.3S 0,1S 0.1~ O~l~*ai~m ~ a~etic • a p p l y of the p l l c o t i d gland i s d e r i v e d f ¢ ~ l ~ e p l e x u s o f t h e e=vtagnal c a / o t i d a¢tez~.~ecause h Z ~ 18 On a ~ a l o g of g u I n s t h L d i r ~ l , I n I d t o n a ~ g £ g blOCking ~ o r l t and b e c a u n of t h e ~ m d s n t Ilppiy Of 83rlgathot4a swt~o Of pa¢otid, a 8 e l n t i g c a p h ~ /magin~ i S p o s s i b l e a f t e ~ XV i n ~ e c t l o n o£ t h e t ~ 5 1 o l a b o l o d m - I X - i ~ l l oz" l - [ I - 1 2 3 | H I ~ . W e tmva shown t h a t the blt t i l e f o r t h e t'O~O1*d Of t h e p l ¢ o t i d a c t i v i t y ?eta bottmeet 3~ and ~h a f t e r t ~ a HZ]lO'Z123 XV l f l J e m t i o n . H m ~ p l e g ~ l ~ l ~ a t ~ tIW~U¢ ~ 8 e t g n i Z l © a n ~ l r ~ ¢ R s e d u p t a k e {p<0.0¢2} on t h e p a c t l y z e d s i d e , T h e z N ~ ~or t h i l a l l | f u s e a 4 t e n e c g ~ c J t l m u l e t i o n o v e r t a k i n g t h e tlpl~z limb IS d i f f i c U L t t o e=pll~.Varl~l thsla~ic a~ h~thallic n u c l e i , the pra~zontal ~ o c t ~ •¢e • nmm to ~ t S t ~ l the p e ¢ l p h e t s t auto~msic n o ~ a s y s t ~ o~d c8~ b e the O ¢ I g ~ Of t h e ad=emacgic a t l l t u l a t i o n OblaL~ed.Hotmve¢, we Clralot e x c l u d e t h e p r s o m l c o , of an o x t e ~ s l v o s ~ s p a t h e t i e : a ~ i a x o r l g i n a t o d f ~ the bcachlel piegua.
S.C.M.N1 et Neurologie C 2 - C.H.U 59037 LILLE CEDEX - FRANCE ASSESSMENT OF DEMENTIA WITH TC-Hm PAO : WICH IS THE BEST REFERENCE FOR THE QUANTIFICATION? Te - Hm PAO is a useful traeer to assess brain perfusion including in Dementia (D). However several areas can be ehoosed as reference in order to quantify the SPECT tomogramms : eaudate and thalamus (CT), cerebellum (C) or hemispheric (H) values. In order to choose the most efficient criterium we have compared the results obtained with this 3 rdf~renees using the ROC curves et we have determined the "eutt of" point using the Likelihood Ratio (L.R). So we have studied 46 patients (P) : 27 P with probable Alzheimer's Disease (AD) (NINCDS - ADRDRA criteria), 10 P with MID and 11 normal patients. Te-Nm PAO tomogramms were obtained using a Tomomatie 64 and quantitative data were computed from left and right prefrontal (F) and parietal (Pa) areas, dividing their fixation values by those of the reference areas. Analysis used Mann and Whitney's U test and Kruskal Wallis' H test. Using CT as reference a decrease of both Pa areas was found in AD and MID groups versus control (P < 0.01). U~ng C
uptake as reference, significative difference were found both in F (p < 0.05) and Pa (p< 0.001) between D and normals, but not within D groups. Results were worst using the whole hemisphere value as reference. The use of ROC curves confirms these data. Computing the LR ratio and taking in account the neeessity to obtain an acceptable probability to find the critical value the best cut off value for Pa/C ratio is 0.8 leading to the following value for Sensitivity : 0.61 Specificity 1.00 and a LR =~.
135
136
D.C. Costa. M. Phllpot, A. Burns, p J Eli,R. Levy.
K. Herholz, R. Adam, J. Kessler, B. Szeltes, W.-D. Hefss
Institute of Nuclear Medicine, U C M S M and
Max-Planck-lnstttut fur neurologtsche Forschung and Untv.-Kltntk for NeuroIogte, Joseph-Stelzmann-Str. 9, D-5000 KSln 41, FRG
Institute of Psychiatry, London, UK. CLINICAL AND HMPAO/SPET ~ T I O N S
PATIENTS WITH DEMENTIA QUANTITATIVE STUDY.
IN THE FOLLOW-UP OF
OF A L ~ I M ] ~
TYPE
(DAT): A
20 DAT patients fulfilling the NINCDS-ADRDAcriteria were initially included in this ~ody of one yesr follow-up. 3 of them died before the repeat ~udy. 3 DAT patlente were too demented to cooperate sad other 3 refused to be restudied. 2 IlMPAO/SI~ studies (the "first" at the beginning, and a "repeat" at the end of the observation period) were compared with simultsaeous detailed clinicM psychometric eases•meet in the rematning 11 DATpatients S~ndard scqubitl0n sad sasfysis protocols for ID4PA0/SPET (10 MBq/kg patisat weight) were carried out with the I ~ 400AC/STARCAM system For each HMPA0/SpET study cerebrum/cerebellum ratios were cslcuJxted from coronal slices Student's t test for paired samples yes used to compare the results from the "first" sad "repeat" studies Similar s t a t i c a l analysis wss performed for the MMSEsad CAMCO0scores. The foilowin8 table shows the results (mesa) with statisUcally dgnlflcsat differences between "first" end "repeat" observations.
"first" "repeat"
CAMCOG 73.09 64.91
LANG 24.00 21.82
RFr 0.78 0.74
LPr 0.78 0.73
RPa LPa 0.77 0.76 0.71 0.71
p
-0.01
~.008
<0.001 <0.001 ~.OOZ-0.004
LANG-lsaguqe: R-rlEht; L-left; Fr-frontal; Ps-parletsl, Conclusion: HMPA0/SPET demonstrates f~rthar deterioration of brain perfusion (~dnly parietal sad frontal) in DAT patients at one year follow-up, It sdde i n important sad objective parameter to the clinical twesemsat t a d follow-up of DAT patients. It seems to reveal the progression of regional b ~ i n dsmsae in ])AT
SPECIFICITY OF FOG-PET FINDINGS IN ALZHEIMER'S DISEASE
Alterations of cerebral glucose metabolism (CMRGlu) were measured wtth positron omission tomography (PET) and 18F2-fluoro-2-deoxyglucose (FOG) in 19 patients with probable Alzhetmer's disease (AD) according to NINCDS-ARDAc r i t e ria. They were c~pared wtth 19 age,matched healthy subJects and 22 patlents wtth cognitive ]mpatment due to other diseases. Data analysis wasbased on regions of Interest drawn semiautomatically using an adjustable standard map. In comparison wtth nomals all AD patients were characterized by the following three findings: 1. reduced temporoparietal metabolism, 2. nomal cerebellar netabollm, 3. reduced CHRGIu ratio In tomporo-parletal and fronta| association areas relatlve to primary sensory areas, bralnstem, and cerebellum. These dlagnostlc criteria were fulfilled by only 4 of the other patients: I of 2 patients wlth Parklnson's disease and dementia (who might have AD also), 1 of 8 patients w t t h • l t | p l e infarcts, and 2 of 3 pattentswtth diffuse hypoxlc or hypoglycemtc brain damage. None of the other patients with ~aJor depression. vitamin-B-deficiency, alcoholism, chronic encephalitis, or various degenerative disorders f u l f i l l e d the above criteria. Thus, the overall specificity in the presents•win was 82 %.
433
137
138
J. L d v ~ i l l d , M.I.Botez, T. Botez, R. Lambert, R. T a i l l e f e r , B. Lefebvre. HOtel-Dieu de Montrdal Hospital, )840 St. U r b a i n S t r e e t , H o n t r d a l , Qudbec, CANADA H2W 1T8
E. Lavie, M. Bitte~, J. Weininger, J. Shalev, E. Verge, E. Lubin, S. Abrashkin, R. Azoury, S O R E Q N.R.C. Yavne Israel Bmhnson Hosp. Petah-Tikva, Israel.
Ic-99m HHPAO SPECT IMAGING: COMPARISONWITH NEUROPSYCHOLOGICAL FINDINGS IN PATIENTS WITH CEREBELLAR DAMMAGE. The aim o f t h i s s t u d y wee t o c o r r e l a t e the SPECT f i n d i n g s w l t h n e u r o p s y c h o l o g i c a l a s s e s s ments revealing the role of cerebellum in cognitive thought. Four g r o u p s o f p a t i e n t s were investigated: 1- t w e n t y - t w o n o r m s l s u b j e c t s as controls, 2- f o u r had an o l d u n i l a t e r a l cerebel1at infarct ( U C I ) , 3- s i x w i t h F r i e d r e i c h ' a s t s x t a ( F A ) , 4- t w e l v e w i t h o l t v o p o n t o c e r e b e l l a r a t r o p h y (OPCA). SPECT was p e r f o r m e d 20 m i n . f o l lowing t h e i n j e c t i o n o f 15-20 mCi o f Tc-99m HHPAO ( p r i m a r y c o m p l e x > 8 5 ~ ) . Images were i n t e r p r e t e d by two i n d e p e n d e n t o b s e r v e r s . Results were as f o l l o w s : 1 ) p a t i e n t s w i t h UCI had c e n t r e lateral cortical MMPAO d e c r e a s e d u p t a k e , 2) pat i e n t s w i t h FA and OPCA c o u l d have e i t h e r s m a l l (7 c a s e s ) or l a r g e r c e r e b e l l s r HMPAO r e d u c e d upt a k e (11 c a s e s ) w i t h v a r i a b l e p a t t e r n s o f c o r t i cal uptake mostly contrala£eral reduction, 3) n o r m a l c o n t r o l s showed n o r m a l c e r e b e l l e r d i s t r i b u t i o n o f HMPAO. FA and OPCA p a t i e n t s w i t h d t a e c h t s i a had l o w e r n e u r o p s y e h o l o g t c s l p e r f o r m a n c e s t h a n t h o s e w i t h s m i l d e r c e r e b e l l s r hypoeoncentration. In c o n c l u s i o n , p r i m a r y c e r e b e l l a r Inv o l v e m e n t a p p e a r s t o I n f l u e n c e i n some cases HMPAO c o n t r a l a t e r a l cortical c o n c e n t r a t i o n and c o u l d be r e l a t e d t o t h e c e r e b e l l a r - f r o n t a l and cerebellar-psrleta1 loops underlying the role of cerebellum in cognitive thought.
139 Frier, A C Perkins, D C Berridge, K C Ballantyne, M L wastie, G S Makin, B R Hopkinson
BINDING O F ACTIVE A N D INHIBITED TISSUE P L A S M I N O G E N A C T I V A T O R T O FIBRIN C L O T Recombinant tissue Plasminogen Activator (t-PA) is a drug for administration to patients with acute myocardial infarction. Its lysing properties may reduce its efficiency as a diagnostictool.This work was undertaken to develop an imaging agent for clot which would bind to it but not lyse it. The most efficientinhibition was obtained with diisopropylfluorophosphate (DFP). Enzyme activity was followed by different techniques including Nuclear Magnetic Resonance (NMR). The N M R method is sensitiveto interactionsbetween the fibrinand the compartmentalized water entrapped in the clot by even nanograrns of t-PA. t-PA was iodinated by the iodogen method. Binding of labeled enzyme to fibrin-coated plastic plates showed that deactivation by D F P did not impair the affinity of t-PA for fibrin. The binding of active t-PA to the clot was rapid and reached a max~murn in 30 minutes and then declined with time. This pattern might be explained by consecutive clot binding and lysis. The binding of DFP-t-PA was markedly differentfrom that of the native protein. Two hours post-incubation of radiclabeled t-PA with fibrin, the uptake of DFP-t-PA was found to be twice that the untreated t-PA. Parallel measurements in clots prepared from whole human blood showed a qualitatively similar trend. The biodistributiont-PA in mice was similar for the active and inhibited forms. Blood activity reached 10% of the injected dose within 10 minutes, it increased slightly during the next 20 minutes and then it dropped again to 10%. These studies suggest that radiolabeled inhibited t-PA is a potential agent for blood clot visualization.
140 P. PELTIEI~ PH. DE FAUCAL. B. PLANCHON, MD. TOUZE, B. DUPAS. J F . CHATAL.
CENTRE RENE GAUDUCHEAU - Q u a l M o n c o u s u - N a n t e s - F r a n c e Departments of Medical Physics and Vascular Surgery, University Hospital, Queen's Medical Centre, N o t t i n g h a m C H A R A C T E R I S A T I O N AND CLINICAL USE OF P256 Fab' PLATELETSPECIFIC MONOCLONAL ANTIBODY IN THE DETECTION OF ARTERIAL THROMBOSIS In-lll P256 Fab' (Amersham International) has been used in i0 patients presenting with acute lower limb ischaemia 20 MBq In-lll was injected IV and imaging performed at 20 min, 5 h and 24 h. Labelling efficiency was )97%. 85% of the indium-lll activity was shown to be associated with the platelet fraction. In 5 patients, highly positive focal uptake was seen at 5 h at sites of intraarterial thromboses. Subsequent intraarterial thrombolysis was successful in 3 of these patients with vessel occlusion confirmed by arteriography Imaging demonstrated a d d i t i o n a l patholop~y in the other 2 patients rendering thrombolysis unsuccessful or inadvisable. No focal uptake occurred in the remaining 5 patients. Thrombolysis was initially successful but in 2 of these patients immediate rethrombosis occurred. This pilot study shows In-lll P256 Fab' to have high invivo specificity for platelets. Imaging can identify sites of acute arterial thrombosis, provide additional information to arteriography, and may help to identify those patients most likely to benefit from thrombolytic therapy.
ADVANTAGE OF IMMUNOSCINTIGItAPHY {18) USING INDIUM-Ill-LABELED ANT/FIBRIN MONOCLONAL ANTIBODY IN CASES OF PULMONARY ISMBOLIMM I ndlum- 11 l-labeled antlflbrin monoclonal antibody (I 11 In AF} h a s been proposed for dlagnosls of deep venous thrombosis {DVT}. In this study, the use of I I I In AF w a s evaluated in PE suspicion. METHOD@ : The 40 patients with clinically suspected DVT h a d ventilation {99mTe radlo-aerosols}perfuslon (99mTc MAA) p u l m o n a r y s c i n t l g r a p h y 24 h before IS and phlebography. IS after Injection of 1 l l l n AF included recordings of the legs, thlgbs and pelvis at 3 h {40 times} a n d 18 h {38 times}, thoracic planar scintlgraphy WS} {anteMor view} a t 3 h {6 patients) a n d 18 h ( 1 4 patients}, a n d thoracic emission computed tomography (ECT} at 3 h (2 patients| a n d 18 h {7 patients}. IS images of the lower limbs were Interpreted blindly without reference to phlebography, a n d the Intensity of 111 In AF uptake in thrombl was rated from 0 {no uptake) to S (re W hot spot with no vascular image}. Thoracic Images {PS and ECT) were Interpreted In view of the results of ventllatlon-perfuslon p u l m o n a r y lung scan. RESULYS : P u l m o n a r y sclntlgraphy Indicated dmgnosls of PE In 17 patients WE+}. No thoracic hot spots were revealed elther by PS (3 h : 0/5. 1 8 h : 0 / 1 2 } o r E C T ( 3 h : 0 / 2 , 1 8 h : 0/7). Twenty-three patients were considered not to have PE {rE-}. The 3 thoracic PS were negative (3 h : 0 / 1 . 18 h : 0/2}. Phlebography showed thrombesls of the lower limbs in 14117 patients In the rE+ group a n d 18/23 in the r E - group. IS of the lower limbs w a s p o s l t i ~ In 1 3 / 1 4 paUents of the PE+ group and 16/18 of the PE- group with phlebitis. High I I Tin AF uptake (rating 3, 4 or S) was observed in 8 / 1 4 patients of the P E t group a n d 12/18 of the PE- group. CONCLUSION • 1) I I lln AF enables detection of thrombotic disease localized In the lower limbs. 2} 1111n AF does not enable visualization of thrombotic disease localized in pulmonary vessels either by PS or ECT. 3} The Intensity of 111in AlP uptake In thrombl of the lower limbs does not serve to predict embolic complication of DVT.
434
142
141 P. P E L ~ E ~ PH. D E FAUCAL, B. PLANCHON, MD. TOUZE, 3. DUPAS, J F . CHATAL
P Broadhurst, A Lahiri, U Raval, C James, R Wilkins, EB Raftery
CENTRE IRENE GAUDUCHEAU - Quaf M o n c o u s u - N a n t e s - F r a n c e I N D I U M - I l l ANTIFIBRIN MONOCLONAL ANTIBODY IMMUNOSCINTIGRAPHY IN DIAGNOSIS OP DEEP VENOUS THROMBOSIS : S i n ~ e or s e q u e n t i a l l~COrdl.d ? The purpose of this study was to compare the diagnostic accuracy of images recorded 3h after injection of 11 l l n AF with those of multiple sequential recordings done Immediately after injection of the antibody and 3 and 18h later. METHODS : For the 43 patients with clinically suspected DVT, recordings in anterior view of the legs, thighs and pelvis were performed 10 to 15 mtn (17 times), 3h (43 times) and 18h (39 times} after injection of 1111n AF. All patients underwent contrast phlebography within 24h. The Images at 3h were Interpreted separately and then compared with early images and images at 18h. Images at 3h (A) were considered positive ff a n area showed high uptake greater than that of blood pool and background. Pairs of early and 3h Images [B) were considered positive ff a n area showed a hot spot on the latter image not visualized on the former. Pairs of 3h and 18h images (C) were considered positive if uptake in an area had Increased in time as compared to vascular and background activity. Each side (right and left) was interpreted individually. RESULTS : The table shows the n u m b e r of correct (C) and doubtful (D) results respectively for A/B (34 comparisons) and A/C (78 comparisons). Legs A B
C 21 25
A .........
40 .......
C
60
Thigts D 6 3
C 23 28 ........
0
Pelvis D 7 4
;'; ........
i4 .......
72
2
C 28 31
D 2 2
"J ........
; ...........
74
Cardiology Department, Northwick Park Hospital, Watford Road, Narrow, Mlddx, HA1 3UJ, UK TECHNETIUM-99m LABELLED ANTIFIBRIN T2GIs FAB MONOCLONAL ANTIBODY IN PATIENTS WITH DEEP VENOUS THROMBOSIS. ISpeclfic monoclonal antibodies to fibrin have been developed which if radlolabelled with teehnetium-99m provide 'hot spot' images of vascular thrombus. We report our first experience with this technique in 7 patients suspected of havlngdeep venous thrombosis. All underwent contrast venography. The results were interpreted by blinded observers. In one subject both venogram and antlfibrin scan was normal, and in four both techniques conclusively demonstrated thrombusformation and localisation. All 4 patients had a positive antifibrin scan within 45 minutes of its injection. One obese subject with va"icose veins gave a positive scan but the venogram, although normal, was technically difficult and net all calf veins were visualised. Finally, a patient with a pnst-operative total knee replacement w l t h a peroneal vein thrombus produced an indeterminate scan, probably because of intense uptake around the prosthesis. No adverse reactions were noted. Further exploration with this promising technique is indicated in order to define its clinical utility in the diagnosis and follow up of patients with deep venous thrombosis.
0
CONCLUSION : The accuracy of 111in AF for D v r diagnosis was greater when 3h images were compared with early and 18h images. However, some thrombl had rapid AF uptake as evidenced by a hot spot on early images. It would thus appear that recording of late images (18h) is required to obtain sufficient diagnostic accuracy.
143
144
A.
JAVAID, B. SHAPIRO, AND J. J. BARRETT.
KING'S
COLLEGE
G.M.S.
HOSPITAL,
SYED,
A.P.
MOWAT R. H o w m a n - G i l e s * ,
LONDON,
SET
9RS,
U.K.
DIAGNOSTIC VALUE OF HEPATIC INDEX IN BILIARY ATRRSIA= FOUR YEAR EXPERIENCE. To provide ~n objective rapid means of excludln~ Bl!lary Atres!a , a Henatlc index was devised as reported pEevlousIF. Followinm the development of this ten minute quantitatlve test we have studied 131 infants re~erred eor billery sclntiKraphy. The hepatic index was compared with subjective assessment of abdominal sclntl~raphy performed repeatedly over 24 hours. 51 patients o~ Blllary Atresla had a hepatic index <5 (mean 2.77 +/- 1.46). None showed excretion on scintlscan. 36 patients of Neonatal Hepatitis had a hepatic index of 7.5 +/- 4~q, (excretion in 30 and no excretion in 6 on the scintiscan). 8 patients of Alpha I antltrypsin deficiency, hepatic index 8.86 ÷/- 3.67 (excretion in 7 and no excretion in I on sclntiscan). 6 patients of Arterio-Hepatlc Dysplasia, hepatic indes ~.17 ÷/- 1.57 (excretion in I and no excretion In 5 on scintlscan). 10 patients of Biliary Atresla who underwent surgery had a mean hepatic index of 2.38 ÷/- 1.24 (excretion in 6 and no excretion In 4). The hepatic index has 100~ senstlvity and a specificity of 68% as compared to a sensltlvlty and speclflclty of 100% and 73% for repeated abdominal scintl~raphy. These results indicate that a hepatic index of ~reather than 5 is much more rapid and as specific in excludln~ Billary Atresls as repeated abdominal sclntl~raphy, however, it is not useful in the follow-up of post-surKical Billary Atresla patients
R. Uren.
Department of Nuclear Medicine, Children's Hospital, Camperdown, Sydney, N.S.W. RENAL DIURETIC SCANS FOR OBSTRUCTIVE UROPATHY IN THE FIRST 12 MONTHS OF LIFE. With prenatal ultrasound, dilatation of the urinary tract in the foetus and newborn is more readily diagnosed. During the transitional period, dilatation of the urinary tract may improve spontaneously, however, obstruction must be excluded. We reviewed 38 infants with dilatation of the urinary tract in the first year of life. Average age at diagnosis was 8 weeks (7 days 12 months) and 20 patients were less than one month. All patients had an IVP, cystogram, ultrasound and a renal scan with diuretic stress from which Half Clearance Times (HCT) were calculated. Discharge diagnosis were: PUJ or obstructed ureter {17), Dilatation with no obstruction (29), Normal (22), Multicystic (3). In 51 renal units which were considered normal or had dilatation with no obstruction, the HCT were within normal range (<15 min.) and the average HCT was 3.8 mins. Sixty percent of abnormal units returned to normal by 6 months. Forty seven percent of units considered obstructed (average HCT 39.8 mins) at PUJ level or distal ureter underwent corrective surgery. Ten units either normal or dilated with no obstruction bad reflux and I gross reflux with PUJ obstruction. There are particular problems related to age and associated conditions which must be considered in the interpretation of these scans. Repeat renal scans are required if scans suggest obstruction in the first weeks of life as these may spontaneously resolve.
435
145
B.Piotrowski, R.Kalff, B.Guth-Tougelidis, St.MO11er, Chr.Reiners Department of Nuclear Medicine, C l i n i c of Neurosurgery, U n i v e r s i t y of Essen, F.R.G. PULMONARY EMBOLISM IN CARDIALLY DRAINED PUDENZ HEYER DRAINAGE Pulmonary embolism (PE) in c h i l d r e n with c a r d i a l l y shunted Pudenz Heyer drainage (PHD) has an unknown i n cidence and untreated a high l e t h a l i t y . In a prospect i v e Study we performed lung perfusions scans in a group of 94 asymptomatic c h i l d r e n with PHB and compared the r e s u l t s with c l i n i c a l and echocardiographic f i n d i n g s . We I n j e c t e d Tc-99m l a b e l l e d micropheres and acquired scintigrams in 6 views. The scans were d i r e c t l y compared t o the chest X-ray. A l l c h i l d r e n had normal lung f u n c t i o n t e s t s und normal chest X-rays. In 9/94 cases we found a p a t h o l o g i c a l scan d i a g n o s t i c f o r PE, one of these c h i l d r e n died from PE, one developed pulmonary hypertension, in 3 cases the drainage was converted t o an i n t r a p e r i t o n e a l shunt. A f t e r a mean f o l l o w up of 6 month, in 7 of the 8 s u r v i v i n g c h i l d r e n perfusion defects were resolved w i t h o u t t h r o m b o l y t i c therapy. In only 2/9 p a t i e n t s with perfusion defects and in 18 p a t i e n t s with normal lung scan a thrombus could be seen by echocardtography. This study shows a high incidence of thromboembolic c o m p l i c a t i o n s . As a consequence p e r i t o n e a l shunting is now prefered over c a r d i a l drainage, I t is not possible to estimate the r i s k of thromboembolic complications by echocardiography.
147
A. Morguet, D. Kececioglu, E. Voth, D. L. Munz Dept. of Cardiology and Pulmonology, Dept. of P e d i a t r i c Cardiology, and Dept. o f Nuclear Medicine, U n i v e r s i t y of GSttingen, F.R.G. TL-201 MYOCARDIAL SPECT AND GATED BLOOD POOL IMAGING AFTER CORONARY LIGATION IN BLAND-WHITE-GARLAND SYNDROME L i g a t i o n of the anomalous l e f t coronary a r t e r y (LCA) a r i sing from the pulmonary t r u n k i n Bland-White-Garland (BWG) syndrome i n t e r r u p t s d i r e c t blood flow from the RCA through i n t e r c o r o n a r y anastomoses. The present study r e ports long-term r e s u l t s o f t h i s procedure. In 8 c h i l d r e n w i t h BWG syndrome (7 g i r l s , 1 boy) the LCA ~ had been l i g a t e d at the age of 0.3 - 13.3 yrs. A f t e r a mean f o l l o w - u p period of 16.0 yrs, these p a t i e n t s (pts) ~underwent thorough c l i n i c a l r e - e v a l u a t i o n i n c l u d i n g ECG, b i c y c l e exercise t e s t , echocardiography, T1-201 SPECT study and gated blood pool (GBP) imaging with Tc-99ml a b e l e d e r y t h r o c y t e s . Two observers blinded t o o t h e r r e s u l t s analyzed T1-201 scans and GBP study segmentally according t o the AHA c l a s s i f i c a t i o n . A l l 8 pts denied heart r e l a t e d symptoms. The ECG showed signs o f a n t e r i o r i n f a r c t i o n in 6 pts. S i g n i f i c a n t ST segment depression during stress t e s t occurred i n 4 pts. M i t r a l r e g u r g i t a t i o n was demonstrated in 2 pts w i t h Doppl e r eohocsrdiography. T1-201 SPECT revealed at l e a s t partially r e v e r s i b l e l e s i o n s in a l l pts and p e r s i s t e n t defects in 7 eases. E x c l u s i v e l y anterobasal, a n t e r o l a t e r a l , a p i c a l and p o s t e r o l a t e r a l myocardial segments were i n v o l v e d . GBP e j e c t i o n f r a c t i o n dropped or increased i n s u f f i c i e n t l y i n 4 pts during exercise. In conclusion, a l l pts w i t h BWG syndrome demonstrated signs of myocardial ischemia a f t e r LCA l i g a t i o n . Theref o r e , the l e f t coronary system should be preserved in these pts even i f they are asymptomatic s u b j e c t i v e l y .
146
I Boca, I Pavia (t), G Moragas, J Boix-Oehoa (i), $ Aguada, FM~ouesech Turns, Nuclear Medicine Service nod Pediatric Surgery Ocpartnent (B} Boapital General and elision lufantil, Ciudad Sanitaria "roll d'Sebr6n', 6capital Cllnico Provincial ft). Barcelona. Spain, SCEENMING OF NSOPMAGEALDIENAEN IN CBILDRNM :TBN ROLN OF ESOPHAGEAL 9CINT[GRAPRT. The ain of our study was to specify the role of esopkagenl seintigruphy (ESI as the screening test in the detection of esophageal dysootility in children. Me performed ES and 24 hour_pEoetry in 50 children uith recurrent bronchitis and/or gastrointestinal syoptoos. The group was composed by l! girls and 36 boys (from 15 nontbs to II years and lO soothe old; noun 2 years II nosths). The 2t hour-pEoetry was performed using an standnrined technique, culculatisz total Line of gastroesophagenl reflux (TTIGgR) end pR global score {pB-gs). In the KS, ue studied one or tun inotnled deglutitionn constructing condensed lunges of 15 and 60 seconds. The results were classified is ( degrees depending on the voluue end the Line of retention (grade I noraa], grades 2, 3 and 4 pathological}. Considering the 24 hour-pflnetry us the reference Lest, ue calculated the paraoeters of test evaluation: 24pE-TT~GEN 24pB-GS
÷
ES
total
÷
30
5
t3
-
0
?
T
38 12
50
tot
+
Bfl
total
:
÷
]2
l
43
-
3
!
?
tot
45
5
50
Sensitivity : I.O0 Sensitivity : 0,93 Specificity : 0.50 Specificity : 0,00 Accuracy : 0,90 Accuracy : 0.92 Me have found very good accuracy, without false negatives when we conpare gS ,vith TTXGER,It .as a total coincidence of results in seven nor|al cases. KS is a harmless, easy aud rapid practice and low douinetry test, so it can be considered an the first technique in the screening of esophageal dysnotility in children with recurrent bronchitis and GE disease, 148
D.A. Goodwin. C.F. Meares, M.J. McCall, W. Chaovapong, M. McTigue, C.I. Diamanti. Nuclear Medicine Service, Veterans Administration Medical Center, Palo Alto; Stanford University School of Medicine and Department of Chemistry, University of California, Davis CA. TUMOR UPTAKE WITII I N - I l l , GA-67 AND GA-68 L A B E L E D B I V A L E N T JANUS IIAPTENS IN PRETARGETED MURINE IMMUNOSCINTIGRAPItY. We recently described a novel immunoscintigraphic method with greatly improved tumor to background ratios (Goodwin etal, 1988)1. Antibody is injected i.v., time is allowed for localization, and radio-chelate labeled hapten administered i.v. after cold circulating antibody has been sequestered in the liver by a special i.v. chase. Here we introduce an improvement with bivalent haptens having an apparent increased aff'mity for the antibody. These special haptens are named after Janus, ancient Roman god of gates and doorways with two faces looking in opposite directions. The mouse monoclona! was WC3All specific for B A B E containing a 1-4 dithiol spacer. Janus was 2 molecules of BABE linked together with 1-4 dithiol, containing Co in one end and either In or Ga in the other. The relative Ka for In Janus = 2x109 and Ga Janus = 7x108 compared to ~106 for In and Ga 1-4 DT BABE. Pretargeting mice with WC3A11 caused 35-50% retention at 24 hrs of In- I 11 & Ga67 Janus, whereas labeled Janus alone was > 98% excreted. The 24 hr mouse tumor and organ distribution of pretargeted cold MoAb was measured after a chase at 20 hrs and Janus at 21 hrs (sacrifice 3 hrs post Janus). The % doselgm and T/O ratios were calculated +-SD; n = 3 in each group. In - 111: Tu* = 7.4+-1.0, B I = 0.7+-.08; 11.1/1, Li = 1.7+-0.5; 4.6/1: similar to Ga - 67: To* = 8.4+-1.2, B1 = 0.7+- 0.3; 12.8/1, Li = 2.9+-1.9; 3.6/1 The results suggest cross-linking and increased apparent affinity improved tumor retention of activity (univalent hapten Tu* = 1.4+-0.6; *p < 0.001). T/O ratios were >3:1 in all organs except kidneys (~1/1) andgut (~1/1) producing excellent tumor images 3 hrs after Ga-67, Ga-68 & In-111Janus. 1. Goodwin DA, Meares CF, McCall MJ, McTigue M, Chaovapong W: Pre-targeted immunoscintigraphy of murine tumors with indium-111 labeled bifunctional haptens. J Nucl IVied29:226-234, 1988. IMPROVED
436
149
150
P.N. Hawkin~, J.P. Lavender and M.B. Pepys
P.N. Hawkins, R. Wootton and M.B. Pepys
Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
DIAGNOSTIC IMAGING OF AMYLOIDOSIS
PLASMA TURNOVER STUDIES OF SERUM AMYLOID P COMPONENT IN AMYLOIDOSIS - A QUANTITATIVETEST
The diagnosis of amyloidosis depends on histological confirmation, requiring potentially hazardous biopsy procedures, and it can not be excluded by negative results. We now report the in vivo diagnostic imaging of amyloid following intravenous injection of l~Sl-labelled human serum amyloid P component (SAP), This normal plasma protein is the precursor of amyloid P component, a universal constituent of amyloid deposits. In normal subjects radioactivity was confined to the blood pool in which the ~2sI-SAP had a half-time of 25 hr. In contrast, the patients with amyloidosis showed selective uptake of up to 90% of the tracer into the amyloid deposits, where it persisted throughout the 48 hr study period, producing diagnostic scintigrams of hepatic, renal, splenic, cardiac, adrenal, bone marrow and articular amyloid. We have studied the distribution of amyloid in the following patients: 25 with systemic AL (light chain type), 25 with AA (reactive systemic) and 20 with /92-microglobulin (dialysis arthropathy) amyloidosis. Serial scans, where performed, have all shown progressive amyloid deposition. This entirely novel imaging technique, based upon the specific molecular affinity of a normal plasma protein, will enhance knowledge of amyloidosis and permit objective assessment of its response to treatment. Other forms of amyloid, including the cerebral deposits in Alzheimer's disease, are under investigation. All studies were approved by the local ethical committee.
151 A W J Stuttle, J Klosok, A H Peters t J p Lavender.
Hammersmlth H o s p i t a l , London, England. IMAGING POST OPERATIVE THRONBUS WITH A PLATELET SPECIFIC MONOCLONAL ANTIBODY. Platelets labelled wlth In-111 oxlne are useful for imaging tbrombus but have not gained widespread use due to time and technical skill required. We have previously described an In-111 labelled monoclonal antibody (P256) for thrombus ~mging. Unlike the divalent forms of P256, ~he monovalent Fab' does not cause platelet aggregation. Experimental thrombus imaging with P256 Fab'in the primate gave encouraging results. Wlth have now used In-111 P256 Fab, in a prospective study of deep veln thrombus in 21 patients undergoing total hip replacement (THR). Patients received 100dg In-111 P256 Fab' ( 9 - 1 2 ~ ) intravenously 24 hr after surgery and were imaged daily for 3 days. They were then given a second injection and imaged for a further 3 days. Dynamic imaging over liver and spleen immediately after injection was conslstant wlth plateletassociated activity and showed no evidence of platelet activation. 13 patients showed focal accumulation of In-111 consistent wlth thrombus formation. I n 12 patients focal accumulation occured initially in the calf and leveloped within 48 h r after surgery. The presence of calf veln thrombus was confirmed by venography In 2 cases. 3 patients showed focal pulmonary accumulation, suggesting pulmonary embolus, which was confirmed by V/O scanning.
In-111 P256 Fab' can be used to image deep vein thrombus in the lower extremities and pulmonary vessels and provides useful information regarding the natural history of thrombus.
Serum amyloid P component (SAP) is a normal plasma protein which is incorporated into amyloid deposits via a specific binding mechanism to all types of amyloid fibril. We have performed 7 day turnover studies of 12Sl.labelled pure isologous SAP in 10 normal volunteers, 40 patients with systemic amyloidosis and 15 patients with diseases predisposing to amyloid. These studies were approved by the local ethical committee. In normal controls SAP was synthesized at around 2 mg/hr and remained predominantly intravascular with a plasma half-time of 25 hr; over 80% of injected radioactivity was excreted into the urine in 7 days. Values for "disease controls" were the same. In patients with amyloidosis there was rapid early plasma clearance of the tracer coupled with decreased urinary excretion of radioactivity. The observed expansion of the extravascular compartment was diagnostic, and represents SAP associated with the amyloid deposits, serial quantitation of which permits monitoring of amyloid deposition. These metabolic studies of labelled SAP provide the first direct evidence for slow turnover of amyloid deposits in vivo and yield an objective, diagnostic and quantitative assessment of systemic amyloidosis.
152 P.Goethalsl,M.Coenel,D.Vogelaers2,3,j.Ev~raert G .Heyndrickx 2 ,F.Colardyn 3 and I.Lemahieu 4 .
3
i L a b o r a t o r y of A n a l y t i c a l C h e m l s t r y , I n s t i t u t e for N u c l e a r S c i e n c e s , R i J k s u n l v e r s l t e i t Gent,Belg i u m ; 2 L a b o r a t o r y of Normal and Pathological Physiology and 3Intensive Care U n i t , U n i v e r s i t y Hosp i t a l ; 4 L a b o r a t o r y for E l e c t r o n i c s and Metrology. Ga-66 ACUTE
PRODUCTION MYOCARDIAL
AND LABELING OF A N T I M Y O S I N FOR I N F A R C T I O N STUDIES USING PET.
In-lll labeled a n t i m y o s i n a n t i b o d y (AM Ab)is an effective agent for the d e t e c t i o n and localisation of acute myocardial i n f a r c t i o n (MI).However q u a n t i f i c a t i o n is d l f f l c u l t . P E T opened a new dim e n s i o n for biomedical i n v e s t i g a t i o n s in vlvo.We designed a p r o c e d u r e to prepare carrier free Ga66,a p o s i t r o n emitter w i t h a h a l f llfe of 9.4h. It is p r o d u c e d by the 63Cu (4He,n)66Ga reaction on copper and separated from the matrix by extraction w i t h dllsopropyl ether. The ether is evaporated and AM Ab is labeled w i t h Ga-66 at a high yield (99%) by t r a n s c o m p l e x a t l o n from an acetate b u f f e r w i t h the D T P A labeled antibody. Imaging of HI was p e r f o r m e d in a n a e s t h e t l s e d dogs after i n t r a v e n o u s l y i n j e c t i o n of 1.5 mCi 6 6 G a - D T P A - A M A b . C a r d i a c imaging by PET was obtained at 1,2,4,6 and 8 h after i n j e c t i o n . C l e a r imaging of p o s t e r i o ~ wall necrosis was already obtained 2h after i n j e c t l o n . T h e dogs were sacrificed and transmural n e c r o s i s was d o c u m e n t e d by macroscopic examinatlon;Myocardlal samples from both normal and i n f a r c t e d zones were analysed for Ga-66 activity (count r a t i o : l / 3 ) . I n conclusion 6 6 G a - D T P A - A M Ab can be used as a tracer for m y o c a r d i a l n e c r o s i s , w l t h the advantage of a long half life and a high s p e c i f i c i t y for necrotic my°cardium'Three-dlmensi°nal r e c o n s t r u c t i o n and q u a n t i f i c a t i o n of the infarct is thus possible.
437
154
153
Keske U*, Cordes M i, Wilfling Felix R I
M 2, Hunger Ji, Gahl G =,
R. A.M.J. Claessens and F.H.M. Corstens.
i
Departments of Radiology* and Nephrology 2 , Universit~tsklinikum Rudolf Virehow, Free Berlin, F.R.Germany
Department of Nuclear Medicine, University Hospital, Nijmegen, The Netherlands. Tc-99m-MAG3 CLEARANCE DETERMINED IN PATIENTS BY SIMPLIFIED METHODS Knowledge of the individual kidney's ERPF is most helpful In the interpretation of HIppuran (OIH) renograms, especially in the follow-up of unilateral renal disease. To be of practical use, a simple, yet accurate method for determination of the global ERPF is required. Recent studies have shown, that Tc-99mMAG3 Is a good replacement of 1-131-OIH. A linear relation was reported between the clearance of OIH and MAG3 (range for MAG3:58-550 ml/min). In this ~tudy two well known m~thods for esti,,"nation of thc- renal clearance (Blaufox's and Tauxe's methods) were applied to data obtained using Tc-99mMAG3. In 132 patients the Tc-99m-MAG3 clearance (range: 35-428 ml/min), calculated from the whole plasma curve by means of Sapirsteln's two compartment model, was plotted against the distribution volume (dose divided by plasma concentration) at various times after injection. Parabolic and exponential regression curves were calculated. The best correlation between clearance and distribution volume was found at 39-41 min after injection. Results, with an error of _+16 ml/min, were slightly in favour of the exponential regression curve. The reproducibility wastested In 11 patients by repeating the study within 24 hr. The difference was 15 -+8 ml/mln (mean __. SD). In 93 patients the clearance (range: 35-405 ml/min), calculated from the plasma curve according to Sapirstaln, was compared to the clearance calculated from a curve, obtained with a probe above the heart, calibrating with plasma samples taken at 5 and 30 min after injection. The correlation was good (r = .96). The errorwas +_ 18 ml/min. Because Tauxe's method Is slightly more accurate and Blaufox's method provides compartmental data, we used both methods with Tc-99m-MAG3 in more than 1000 patient studies. Clinical results will be discussed.
155
99mTc-MAG3 AND 131J-OIH IN PATIENTS AND IMPAIRED RENAL FUNCTION
WITH NORMAL
The aim of this study was to test the applicability of the new radic~0harmaceutical 99mTc-MAG3 as a substitute for 131J-OIH in patients with normal and i m ~ renal function (creatinine > 2 mg/dl, creatinine clearance > 50 ml/min). Patients received i00 MBq 99mTc-D~G3 and 18 DSq 131J-O]]{. The effective renal p l ~ flow (~PF) calculated from the ratio applied dose/45 rain plamml concentration was compared in a simultaneous measurm~mt for both r a d i ~ c e n t i c a l s in 30 patients with normal and 20 with impaired renal fumction. In another 20 patients (7 of those with i m ~ renal function), the images, time-activity-curves and the relative fenction of right and left kidney were ccmpared in two ~ i v e investigations. Linear regression analysis with calculatien of the correlation coefficient (r) and the slope (q) was performed. Results: ~PF: n r q all patients 50 0.95 0.62 normal renal function 30 0.89 0.63 impaired renal functiun 20 0.79 0.58 tim~ctivit~: ma~ 4O 0.98 1.01 decrease from m a x ~ after 12.5 + 25 rain 40 0.92 1.07 relative renal function: 20 0.94 0.97 images: much better differentiation of pelvis, caliculas and perenchyma with MAG3. Cxmclusicns: - MAG3 is suitable to measure ~ and renal time-activity curves in patients with normal and impaired renal function; - MAG3-~PF averages 62% of OIH-~PF, in renal impairment 58%.
156 KE B r i t t o n ,
J. L. Lear & A. J. Feyerabend. Division of Nuclear Medicine (A034 I University of Colorado Health Sciences Center, 4200 E. 9th Avenu~ Denver, CO 80262
S M i c e v a , F F i o r e , MJ C a r r o l l ,
St B a r t h o l o m e w ' s H o s p i t a l ,
A RATIONAL A P P R O A C H T O
A NEW TWO SAMPLE TECHNIQUE FOR ACCURATE ESTIMATION OF EFFECTIVE RENAL PLASMA FLOW The reference method (RM) for determination of effective renal plasma flow (ERPF) with iodohippuran requires many plasma samples over 60 minutes. Simplified methods have been proposed requiting only one (single sample technique, SS) or two (slope-intercept technique, SI) plasma samples, but both techniques have potential sources of error. Variations in distribution volume (Vd) cause errors with the SS method and systematic overestimation of V d causes systematic overestimation of ERPF with the St technique. Wt- develnped a new two ~ample (TS) technique ba~ed on the observation that, while variations in Vd occur from paticnt to patient, the relationship between intra- (VI) and extravascular (V2) components of V d and the rate of exchange between the components (k) are stable throughout a wide range of physiological and pathological conditions. dC l / d t = - { E R P F / V l x C t } - {kx (C l - C2) } d C 2 / d t = k x (V 1 / Vg.) x (CI - C2) V I = V 2, k = 0.05 Where C 1 and C 2 = intra- and extravaseular hippuran concentrations. We applied the new TS technique to a series of 30 transplant patients by fitting the model to plasma samples obtained at 44 and 60 minutes and compared the results with the RM, SS, and SI techniques. The new two sample, two compartment technique is significantly more accurate than either the single sample or slope-intercept techniques. M E A N E R P F (ml / rain) ERROR (S.E. versus RM)
University
RM 171
TS 160 24
SS 185 53
SI 199 41
CC Nirrmon.
London EC1A 7BE, UK.
INTERPRETING
FRUS]~MIDE DIURESIS.
The m e a s u r e d change i n t h e r e n a l a c t i v i t y time c u r v e , RATC, i s t h e b a s i s of d e t e r m i n i n g t h e r e s p o n s e to F r u s e m i d e , F, d u r i n g a r e n a l r a d i o n u c l i d e s t u d y , RRS. The r a t e of f a l l of t h e RATC due to F i s d e p e n d e n t on and c o n s t r a i n e d by i t s p r e v i o u s r a t e o f r i s e d u r i n g t h e u p t a k e p h a s e . E x c r e t o r y i n d i c e s r e l a t e o n l y to t h e r a t e of f a l l of t h e RATC due to F and may l e a d to e r r o n e o u s interpretation when r e n a l f u n c t i o n , RF, i s i m p a i r e d . One h a s to j u d g e w h e t h e r t h e RATC r a t e of f a l l is a p p r o p r i a t e to t h e p r e v i o u s r a t e of r i s e . T h i s may be achieved quantitatively by c o m p a r i n g t h e c u m u l a t i v e u p t a k e , CU, by a k i d n e y w i t h t h e c u m u l a t i v e o u t p u t , CO, by p l o t t i n g CO as a p e r c e n t a g e of CU f o r e a c h time i n t e r v a l - t h e o u t p u t e f f i c i e n c y , OE%. CU i s g i v e n as the integral of t h e b l o o d c l e a r a n c e c u r v e f i t t e d by l e a s t s q u a r e s to t h e u p t a k e p h a s e of t h e b a c k g r o u n d c o r r e c t e d RATC and CO i s g i v e n by t h e s u b t r a c t i o n from CU of t h e a c t u a l RATC b o t h b e f o r e and a f t e r F. Using 370 ~ q Tc-99m DTPA o r 100 ~3q Tc-99m MAG3 i n j e c t e d i v f o r a RRS and 40 mg F i v at 18 min, OE% was compared with conventional interpretation and t h e p a r e n c h y m a ] t r a n s i t t i m e i n d e x , PTTI, i n 88 k i d n e y u n i t s from normal to o b s t r u c t e d . OE% c o r r e l a t e d w e l l w i t h PTFI ( r - 0 . 9 7 P<0.001) and c o r r e c t l y identified t h e p r e s e n c e or a b s e n c e of o b s t r u c t i v e n e p h r o p a t h y in t h e one t h i r d of the kidneys with relative RF 15% - 40%, i n c o r r e c t l y classified by a c o n v e n t i o n a l a s s e s s m e n t , Use of OE% improves the objective a s s e s s m e n t of t h e f r u s e m i d e response by correcting for renal function.
438
158
157 I C Dormehl*, W P Pilloy**, M Maree*, R de Winter*~ L Jacobe*, N Hugo*
Beatrix
*University of Pretoria, Box 2034, PRETORIA 0001 **Medical University of Southern Africa, PO MEDUNSA THE "INTEGRAL SPLEEN" METHOD OF RADIORENOGRAPHIC ANALYSIS ASSESSED FROM PARAMETER CHANGES AFTER PHARMACOLOGICAL AND SURGICAL INTERVENTION
The "integral spleen" method calculates parameters of total renal function (T~), relative renal perfueion (P), clearance (C~), filtration fraction (FF) and mean urine transit time (MTT). The relevance of these parameters were investigated after surgery or certain drugs with well known effec~B~ on six baboons (i~7~ozzvai~7~). 8eeeline radiorenographic studies (77~Tc-DTPA) were followed by renography after various drug interventions (furosemide, mannitol and captopril) and eventually after unilateral renal vein 11gation, at 30 min, 2 days, one month and lastly at 8 weeks postoperatively. The parameters were evaluated from the renal, splenic and cardiac timeactivity curves. The blood compartment of the tracer in the kidney is simulated by the spleen perfusion curve normalised to the kidney perfusion curve. From the nett kidney curve (renogram minus normalised spleen curve) i.e. the tracer filtered in urine and from the time integral of the normalised spleen curve (bloodflow)~ the average FF for each kidney is calculated. The cumulative urine input into the urine compartment (i.e. average FF x integrated normalised spleen curve) minus the nett kidney curve is the cumulative output to the bladder. The average delay between this in- and output is the MTT of the tracer in this compartment. Relative clearances and perfusion for each kidney are obtained respectively from areas under the nett kidney curves and from the maximum height of the kidney perfusion curves. T~ comes from the cardiac time activity curve. These parameters did change on pharmacological and surgical intervention in accordance with pathophysiologioal knowledge. Non-invasive estimation of relatlvo renal perfusion and calculation of individual FF without blood and urine sampling became possible, and our algorithm for MTT calculation was experimentally validated.
K6nig,
R.
R6hle,
H.
K6hn,
A. M o s t b e c k
Dept. of N u c l e a r M e d i c i n e a n d L. B o l t z m a n n i n s t i t u t of N u c l e a r M e d i c i n e , Wilhelminenspital Vienna
QUANTITATIVE MEASUREMENT OF SPECIFIC CEAA N T I B O D Y U P T A K E IN I N T E S T I N A L TUMORS. In a p r o s p e c t i v e clinical study, radioimmunoscintigraphy was performed in 17 p a t i e n t s (6 colon, 7 rectum and 2 carcinomas of t h e s t o m a c h ) t h e d a y b e f o r e a n d o n t h e d a y of s u r g e r y u s i n g the monoclonal anti-CEA-antibody BW 431/26. Patients underwent surgery 24-28 hours after the i.v. injection of 25 m C i 9 9 m T c - l a b e l l e d antibody. A few grams of t u m o r and peritumorous [tissue obtained at s u r g e r y were counted in a gamma-counter and both the specific tumor uptake [and t h e u p t a k e r a t i o tumor/peritumorous t i s s u e w e r e c a l c u l a t e d u s i n g a s t a n d a r d o b t a i n e d at the t i m e of i n j e c t i o n for calibration. The median v a l u e of t h e t u m o r u p t a k e (n=lS) w a s 0 . 0 0 6 3 D%/g, of t h e p e r i t u m o r o u s tissue 0.0014 D%/g. The uptake ratio tumor/peritumorous tissue had a m e d i a n v a l u e of 4.8, r a n g i n g f r o m 1 . 0 6 - 21.5. No significant differences were found between tumor uptake, uptake ratios and tumor site (stomach, colon, rectum). Uptake ratios as m e a s u r e d in tissue correlated significantly with ratios o b t a i n e d f r o m R O I ' s in p l a n a r o r S P E C T i m a g e s . ~he lowest ratios were found in t h e p l a n a r images. These ratios differed significantly from the r a t i o s o b t a i n e d b y S P E C T (p < 0.005) or m e a s u r e d in t h e t i s s u e (p < 0 . 0 5 ) . T h e r e w a s no significant difference b e t w e e n t h e l a t t e r two.
160
159 A Chetanneau*.R Bares'*,RP Baum**,JF Chatal*,JY Herry*,PA Lehur*, JC Llehn*,AC Perkins***,JC Saccavini .... .
Lind P., Langsteger W., K01tringer P., ~ h n e r Eber O.
* ** *** ....
Barmherzige Brtider Eggenberg Hospital, Internal Department, Bergstrasse 27, 8020 Graz *II.Department of Surgery, University of Graz **Institute of Pathology, University of Graz, Austria
Cancer Institutes of Nantes, Reims and Rennes - FRANCE University Hospital of Aachen and Frankfurt-FR GERMANY University Hospital of Nottingham - ENGLAND CIS Bioindustrle - FRANCE
P.*, Beham A.**,
RESULTS OF A EUROPEAN MULTICENTRIC STUDY OF 92 IMMUNOSCINTIGRAPHIES USING 111-INDIUM -LABELED ANTI-CEA OR 19-9 IN COLORECTAL RECURRENCES
Tc-99m LABELED MONOCLONAL ANTI-CEA ANTIBODY (BW 431/26): CLINICAL RESULTS IN THE DETECTION OF COLORECTAL CARCINOMAS AND RECURRENCES
Thirty-four patients of a retrospective study and fifty-eight other patients, with suspected recurrence In previously operated and histologically confirmed colorectal adenocamlnomas, were examined by Immunoscintigraphy (IS). The final diagnosis of recurrence and (or) metastasis was determined In 24 cases by second-look surgery, in 28 cases by a clin¢cal follow-Up period of at least 6 months, and in 6 cases by other examinations. The results of IS in visualizing suspected recurrences of colorectal cancer were compared blindly with those of computed tomography ( CT ) and ultrasonography ( US ) in pelvis and extrahepatic abdominal tumor sites .If the results of retrospective study are considered on the basis of the number of anatomical sites In pelvis and extrahepatlc abdomen the sensitivity of IS was 84 % , and the specificity 94 % .With the same analysis for prospective patients the sensitivity was 79 % the specificity 96 %. The results were better in pelvis,with excellent sensitivity 9 1 % and specificity 97 %. The difficulty of CT or US In distinguishing a possible pelvic recurrence from postoperative fibrosis led to lower sensitivity rates In extrehepaflc abdomen and pelvis than for IS respectively 41% ( i T ) , 35% (US). The specificity of CT was 95% ,'and 10[:)% for US. The conclusion was that IS using 11 l-Indium-labeled antiCEA or 19-9 should be carried out prospectively in patients at high risk of recurrence of colorectal cancer.
With the introduction of Tc-99m labeled monoclonal antibodies against CEA a clinically relevant extension can be expected in the diagnosis of colorectal tumors by immunoscintigraphy (IS). This study comprises a total of 49 patients (primary colorectal tumors, occult neoplasms and suspicious recurrences), in whom immunoscintigraphy (IS) with Tc-99m MAb BW 431/26 was performed. After injection of 1100 MBq Tc-99m MAb BW 431/26 a whole body scan was performed in anterior and posterior projection 5 1/2 hours p.i., SPECT of the abdominal region was done 6 and 24 hours pi. In the course of primary rumor identification (n=20), all coloscopieally diagnosed and operatively verified carcinomas were confn'med and correctly localised by IS (n=l 1). In 3 patients with positive IS and suspicious coloscopic findings surgery was declined by patients and relatives. In 5 cases IS was true negative, in one case false positive. In the diagnosis of recurrences (n=29) IS revealed an uptake in computer tomographicaUy and coloscopically suspicious areas in 17 cases. In 12 cases IS was rated negative (11 true negative findings in scar and granulation tissue, 1 "false" negative finding in paraaortal lymph nodes). Elevated serum CEA-levels were found only in 12 of 28 patients with true positive IS. In postoperative cancer care IS with Tc-99m labeled anti-CEA antibody plays a preeminent role in the exclusion or identification of colorectal recurrences.
439
161
W. BECKER.J. ~ ,
162 M Granowska, SJ Mather, KE B r i t t o n , SJ B e n t l e y , I S z i l v a s i , D E l l i s o n , P Richman, R Sobnack, RKS P h i l l i p s , JMANorthover.
H. FEISTEL. G. PLATSCH.
W. KARPOWICZ. F. WOLF e
Clinic and pollcllnlc of nuclear medicine and clinic of surgery of
I m p e r i a l Cancer R e s e a r c h Fund, N u c l e a r Medicine U n i t , St M a r k ' s H o s p i t a l , London EC1, UK
~he unlverslty of Erlangen-NUrnberg. FRG A NEW Tc-99m LABELLED MONOCLONALANTIBODY FOR COLORECTAL CANCER RADIOIMVIUNOSCINTIGRAPHY
SENSITIVITY OF TC-99m-ANTI-CEA-MoAB SCANS IN I~CURRENCE AND METASTASES OF COLOFECTAL CANCER ~ I N G ON IMAGING TECFINIQUEAND C F _ . A - ~ PURPOSE AND METHODS: For the purpqse of Iqcreaslng the d!agnostlc accurasy of Imm,uno-, scmtigrapny the results of 31 examinations with a /c-vvm-moe.eo anti-CEA IgGl-lsotype(BW431/26}Mo.ab were reviewed. All the patients were suspected of having a ioca! recurrence or liver metastases. 740-9,00MBq Tc-99m labelled antlbodles(20Ou~l protein) were Injected. Planartn=37) and SPECT(n=30) studies from !!ver/spleen and the pelvis were performed 18h p:l.. The results were compared with the results oT surgery, sonograpny, computed and magnetic resonance tomography and the CEA levels at the time of examination. RESULTS: In 20 of 37 patients(55g} planar Images and In 21 of 30 patients (70%) SPECT Images iocallsed all the tumor manifestations as positive antibody accumulations. In patients with CEA levels higher than 40ug/ml only some tumor manifestations or no positive tracer accumulations could be detected, Excludlncl patients with CEA levels hlQher than 40 ua/ml in our series of p~tlents( advanced tumor stage ) andperforr~ing only SPECT studies In 21 of 23 patients { 93g) the complete tumor manifestations could be Iocallsed. In 2 of 37 patients(6Z) clinically relevant additional ioformatiors could be achieved. CONCLUSIONS: The diagnostic accuracy was best In SPECT studies and in patients with CEA levels lower than 40ug/ml. This was not due to CEA complex formations, So we believe that in advanced tumor masses the target-to-non-target ratio is reduced due to a lower tocav anuoooy concentrations at the different tumor sites.
163 A . K r o i s s , J . S c h U l l e r , A . T u c h m a n n , W.Weiss, M.Wirth, C h . A u i n g e r , K.Dinstl, A . N e u m a y r .
The r o u t i n e w i d e s p r e a d a p p l i c a t i o n of r a d i o l a b e l l e d monoclonal a n t i b o d i e s f o r c a n c e r management r e q u i r e s t h e Tc-99m l a b e l and an a n t i b o d y k i t . I n the r e v o l u t i o n a r y t e c h n i q u e of Schwarz, a n t i b o d y S-S bonds a r e opened w i t h 2-mercapto e t h a n o l and s t o r e d . P r i o r to u s e , a bone s c a n n i n g k i t to p r o v i d e the t i n r e d u c i n g agent and Tc99m e l u a t e are added. This a p p r o a c h has been t r a n s f e r r e d s u c c e s s f u l l y to a d i f f e r e n t d e p a r t m e n t and antibody, PRIA3, against a columnar c e l l surface antigen. C o l o r e c t a l ca took up I n - l l l PR1A3 x3 more than a n t i CEA in our p r e v i o u s s t u d y . 250-500I~Bq Tc-99m PRIA3 was g i v e n to 20 p a t i e n t s w i t h c o l o r e c t a l d i s e a s e , imaging at 10 min, 2-4, 6 and 24 h w i t h tomography at 5 h w i t h a Siemans D i g i t r a c 75. High q u a l i t y images w i t h p o s i t i v e tumour i d e n t i f i c a t i o n as e a r l y as 4 h o u r s were a c h i e v e d . No unblocked t h y r o i d u p t a k e was s e e n at 24 h c o n f i r m i n g i n v i v o s t a b i l i t y . There were 18 p o s i t i v e images: 12/12 p r i m a r y c o l o r e c t a l c a n c e r , 2/2 l i v e r m e t a s t a s e s , 2/2 p e l v i c r e c u r r e n c e s , 1 r e c u r r e n t and 1 p r i m a r y v i l l o u s adenoma; and 2 normal images, one : i n m i l d i n f l a r r m a t o r y bowel d i s e a s e and one s u s p e c t e d r e c u r r e n c e c o n f i r m e d n e g a t i v e by b i o p s y . The a d v a n t a g e s of Tc-99m o v e r In-111 monoclonai a n t i b o d y i n c l u d e : the a b i l i t y to image on the day of r e q u e s t and o b t a i n a provisional result the same day; r a p i d h i g h count images, reduced c o s t s and a 1 / 2 0 t h r a d i a t i o n dose per mCi. These a r e c o u p l e d w i t h a h i g h d i a g n o s t i c a c c u r a c y in t h i s p i l o t s t u d y .
164 A. Cuocolo, S.L. Bacharach, R.O. Bonow, E.F. Unger, R.E. Carson, M.V. Green, R. Finn, P. Herscovitch.
I n s t i t u t e of N u c l e a r Medicine, ist M e d i c a l D e p a r t m e n t , ist S u r g i c a l D e p a r t m e n t , L u d w i g B o l t z m a n n F o r s c h u n g s s t e l l e fur klin. Geriatrie, KA R u d o l f s t i f t u n g , Vienna, Austria.
Department of Nuclear Medicine and Cardiology Branch, National Institutes of Health, Bethesda, Maryland, U.S.A.
I M M U N O S C I N T I G R A P H Y (IS) IN P A T I E N T S W I T H COLORECTAL CANCER RECURRENCES.
POSITRON EMISSION TOMOGRAPHY (PET) MYOCARDIAL BLOOD FLOW WITH OXYGEN-15 WATER WITHOUT BLOODPOOL SUBTRACTION SCAN.
The aim of this study was to proof the diagn o s t i c a c c u r a c y of IS in p a t i e n t s (pts) w i t h c o l o r e c t a l c a n c e r and r e c u r r e n c e s , e s p e c i a l l y in pts w i t h r e g i o n a l h e p a t i c therapy. IS was p e r f o r m e d w i t h T c - 9 9 m l a b e l e d antibody (Ab; a n t i - C E A antibody; BW 431/26; B e h r i n g werke FRG). The images w e r e done 4 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. IS was done in 13 pts w i t h c o l o r e c t a l cancer, in 21 pts w i t h c o l o r e c t a l r e c u r r e n c e s , in 2 pts w i t h b r e a s t cancer, 2 pts w i t h c a n c e r of the lung, 2 pts w i t h e l e v a t e d CEA levels. We found a s e n s i t i v i t y of 88 % and a s p e c i f i c i t y of 9 1 % . The levels of CEA were found b e t w e e n 3.1 and 1400 ng/ml. B e c a u s e of these good r e s u l t s we p e r f o r m e d IS in 14 pts with regional c h e m o t h e r a p y in pts w i t h s u r g i c a l l y i m p l a n t e d h e p a t i c a r t e r y catheter. In 14 pts w i t h m e t a s tasis of the liver we found ii "cold" lesions and 3 "hot" lesions, in 8 pts we found local r e c u r r e n c e s , in 5 pts we found c a r c i n o s i s p e r i t o n e i , 1 pat w i t h m e t a s t a s i s of the b r a i n and the lung. The r e s u l t s were c o n c o r d a n t by c l i n i c a l indices, by endoscopy, biopsy, r a d i o g r a p h y and s o m e t i m e s s u r g i c a l specimens. In c o n c l u s i o n , the Ab l a b e l e d w i t h T c - 9 9 m seems to be a v e r y h e l p f u l d i a g n o s t i c tool in f o l l o w - u p s t u d i e s of c o l o r e c t a l cancer.
H2 150 i s f r e e l y d i f f u s i b l e a c ros s myocardial membrane s and t s a p p l i c a b l e f o r assessment of myocardial blood flow (MBF). However, spillover of counts from the left ventricular (LV) cavity into the myocardlum requires a CO blood pool scan, limiting the applicability of the technique for intervention studies. We investigated using dynamic PET to eliminate the need for CO bloodpool subtraction by i n c l u d i n g LV s p i l l o v e r in the c o n v o l u t i o n e q u a t i o n f o r MBF. The measured myocardial time activity curve (TAC) Is assumed to equal the true (no spillover) myocardial TAC plus a splllover fraction (SF) constant times the measured LV TAC. For known partition coefficient (p) one fits the measured myocardial TAC to f.LV(t) X exp (-ft/p) + SF.LV(t), where LV(t) is the LV TAC, X represents convolution and f Is the flow/volume. Least squares fltting yelds SF and f, thus f is measured Independently from SF, and bloodpool substractl~ scan is not required. We tested the technique in 24 H2"JO studies in 4 dogs at different MBF values. The measurements were compared to those by radlolabeled mlcrospheres and the arterial sampiing technique. SF in i0 ROls (2 freewall, I apical, 2 septal in 2 sllees) were compared to the values from a CO study. SF from the modified convolutlon equation correlated wlth those from the CO study (Fit= 0.92.C0-0.05; SEE=O.05, rffi0.85, p<0.001) independent of the MBF value. In concluslon, wlth a PET scanner wlth sufficient sensitivity and count rate ability, MBF can be measured using bolus H2150 without a bloodpool subtraction scan.
440
165
Y. Oda, M. Yamashita, S. Otsuka, Y. Kira, M. Kondo, H. Horii, H. Yamagishi, R. Fajii, K. Wakita, H. Nakahashi.
166 Stewart RE, Kalus ME,Gacioch GM, Mollna E, Squlcciarinl SA, Hutchins GD, Kuhl DE, Schwaiger M.
The First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Nishijin Hospital, Kyoto, Japan, 602
University of Michigan A N E W MYOCARDIAL IMAGING M E T H O D USING FACTOR ANALYSIS WITH H21SO AND DYNAMIC POSITRON EMISSION TOMOGRAPHY. Conventional myocardial perfusion phase images with H~ lsO require subtraction of the blood pool activity obtained from separate ClSO scans. There are various problems involved in obtaining real myocardial blood flow images; i. e . , corrections for the partial volume effect, accurate measurements of the input function, and estimation of the tissue/blood partition coefficient. We applied factor analysis ( F A ) to Ha 150 dynamic PET studies to extract the myocardial physiological components and factor images, and also evaluated the validity of the factor images as a new myocardial perfusion imaging method compared with the subtraction method. PET studies were performed after bolus injection of 10 - 15 mCi of Ha 1sO with a scanning protocolof 125 sac and 8 - 30 see scans. The acquisition data was reconstructed with a pixel size of 2x2 mm~ and transferred to a Simis 3 computer(Sopha Medical). The FA parameters were : a) 4 or 5 factors, b) Dixel dimension of 8x8 pixels, c) Analyzing 50 dixels with the highest count number, d) Positive constraint. 60 consecutive patients (8 normal, 45 coronary artery disease (CAD), ? cardiomyopathy) were analyzed. The results showed that myocardial factor images clearly separated from both cardiac cavitieS were obtained from all of the subjects. Particularly in CAD patients, it was possible to qualitatively estimate the lesions of coronary arteries based on the factor images which agreed well with those obtained by the subtraction method. These results indicate that this FA myocardial imaging method using H2~SO dynamic PET is viable as a new myocardial perfusion imaging method.
167 U Buell, E KleiILhans, R Uebis, S Kohlen, M Henrlch, HJ Kalser, H Herzog, LE Feinendegen, SN Reske
Medical
Center,
Ann Arbor,
MI.
DETECTION OF CORONARY DISEASE WITH Rb-82 PET: TECHNICAL CONSIDERATIONS AND COMPARISON WITH TI-201 SPECT. To evaluate the diagnostic performance of Rubidium-82 (Rb) PET, 42 pts (17F,25M) selected from a population with high prevalence of CAD were studied with both Rb PET and TI-201SPECT (31 exercise, Ii dipyrldamole (D)) within a 3 week period. 21 pts had prior MI; 37 had undergone coronary anglo; 5 pts without anglo were included for their low likelihood for CAD. Basal Rb PET imaging was performed following infusion of 60 mCi Rb-82. "'Stress" Rb PET followed infusion of D (0.56 mg/kg), isometric handgrip and 60 mCi Rb-82. Average mean counts/study (15 transaxlal planes) was 7.7+3.0 million. Mean true counts/plane were 350,000+150,~00. Quality of Rb PET studies was judged good (4~%), fair (48%) or poor (12%) by 2 observers. Both Rb PET and TI SPECT studies were graded visually for perfusion defects in 126 vascular territories; sensitivity (SENS), specificity (SPEC), predictive value (PV) and accuracy (ACC) of studies in detecting significant CAD (_>50% stenosls) were determined:
Rb PET TI SPECT
SENS 74% 67%
SPEC 92% 87%
(+)PV 87% 80%
(-)PV 82% 78%
ACC 84% 79%
In these initial results, the overall diagnostic accuracy of Rb PET and TI SPECT was comparable. The relatively low count statistics found in many studies, however, represents a limitation and may affect the specificity of Rb PET in detecting CAD.
168 U. Sechtem, P. Thelssen. S. Langkamp, M. JungehQIslng, H.W. H6pp, H. Schlcha
Depts of Nuclear Medicine, Internal Medicine I, Technical U~iv of Aachen, Aachen and Inst of Medicine, KfA Juelich, F R a y
Institute of clinical and experimental Nuclear Medicine and Medical Clinic III University of Cologne, Cologne, FRG
MYOCARDIAL I ~ AND P ~ S I O N IN CORONARY HEART DIS~SE (C~D): CCMPARATIVE STUDY WITH MAGRETIC R E ~ IMAGING (~RI: SPIN-ECHO (SE), P E ~ T I C ~ ) AND SPECT (TI-201), ASSIST~ BY PET (F-18 DOG).
CORONARY ARTERY BYPASS GRAFTS: ASSESSMENT BY MAGNETIC RESONANCE IMAGING AND ANGIOGRAPHY
A
Changes of wall thickness (CWT) from enddiustole (~) to end~tole (ES), gained from gated NRI, may reflect myocardial p e r f - - . Exercise/rest TI-201 SPECT illustrates state of perfusien; a persistent defect may herald a scar: no CWT is expected. We determined how (at rest) ~T performed in such defects. In selected cases (n=8), findings from PEr with F-18 DOgluccse were added. 51 pts (mean age 52 yrs; 47 m, 4 fro) with C~D and 6 normals were ex~ed. All pts (36 with old MI) had corenary anglo, cineventriculography, MRI (to avoid maturation in SE-technique, slices have to be changed cyclically during TR intervals (permutatien)) and e/r SPECT within 4 wks. Of these, 48 had technically sufficient sequences (1.5 T, ECC~ted, TE 22 ~ec, slice-thickness 7 ram, 4 myocardial slices/pt, SPECT-defect orisntated angulaticrm; ~ I, ES 3 (ES +/- 50 msec) sets of representative slices; WT determined visually). In 35 pts, C~T was additic~ally measurable in ram. Irrversible Tl-defects (n= 36; 5896anterior, 30% lateral wall) were cc~firmed by low TI-201 uptake (%). In 75%, irreversible defects visually revealed no CWT. Control areas showed increase of ~T in 85%. Such increases ranged from 1-9 ram, depending cll t o ~ a p h y (lateral wall > sept,). Regional TI-201 uptake(%) ccrrelated to C~r(mm) with r= 0.66. CWT, in the comparable selected cases, matched findings with FDOG precisely. We cenclude that regular increase of WT from ~ to ES heralds om~tractile, viable myocardilm~. CWT is significantly reduced in myocardium with persistent low ~erfusien and/or low FDG-uptake. MRI may help i n describing myocardial viability by determining CWT. However, inherent probl~ led to same insufficient results in visual (16%) or erit~tical (39%) evaluatiors.
To evaluate the patency of coronary artery bypass grafts (CABG) 22 patients (20 male, 2 female) with 45 CABGs were examined by anglography and magnetic resonance Imaging
(MRI). The entire heart and the ascending aorta were covered with transversal 8-mm-sectlons using the s p i n - e c h o technique (SE-MR) (repetition time (TR) depending on heart rate, echo time (TE) = 30 ms) and the gradient echo technique (GE-MR) (flip angle 40 ° , TR = 28 ms, TE = 16 ms). The bypasses were assessed In three seperate groups: bypasses were grouped according to their vessel of Insertion. Anglography RIVA (N=23) RCX (N=17) RCA (N=5)
19 patent/4 occluded 5 patent/12 occluded 2 patent/3 occluded
MR-GE 20/23* 11/17" 5/5*
MR-SE 19/23" 12/17" 4/5*
*correct as patent or occluded assessed CABGs from the total number
Using GE-MRI and SE-MRI 36145 and 35•45 CABGs, respectively, were correctly assessed. The sensitivity of both techniques was 68% and 59%, the epeclfity was 85% and 92%, respecUvely. Positive and negative predictive values for GE-MRI and SE-MRI were 82% end 78%, respectively and 75% and 85%, respectively. These results indicate that MRI can be useful to nonlnvaslvely assess the patency of CABGs. Patent CABGs can be more re,ably Identified by both pulse sequences than occluded grafts. SE-MRI was limited by low signal Intensity artifacts from clips whereas breathing and fat-water shift artifacts lead to ;a;~e ~;a~;;o~e~ wtth GE.MRI.
441
169
170
~ , U. Sechtem, M. Jungeh01sing, A. Linden, H.W. H6pp, H. Schicha Institute of clinical and experimental Medical Clinic III University of Cologne, Cologne, FRG
S.Danilov, V.Muzykantov, A.Klibanov, E.Atochina, E.Puchnina, Yu.Arkhapchev, V.Serglenko
Nuclear Medicine and
VENTRICULAR SEPTAL DEFECT: EVALUATION OF ANATOMY AND SHUNT FLOW BY MAGNETIC RESONANCE IMAGING To assess the capabilities of magnetic resonance imaging (MRI) in the diagnosis of ventricular septal defects (VSD) 21 patients (age 3 month to 67 years) were examined. MRI findings were compared with findings at cardiac catheterization (CC). Fourteen patients had a perimembranous VSD, 6 a muscular and 1 a supracristal VSD. In 4 patients a re.VSD following surgery with patch.occlusion of the defect was fOund. All patients had transverse spin echo (SE) sectiona with a slice thickness between 5 and 10 mm. Additional transverse gradient echo (GE) imaging (flip angle 40 °, repetition time = 28 ms, and echo time = 16 ms) was performed in 18 patients. GEMRI permits visualization of cardiac motion and assessment of abnormal blood flow. In 13 patients the entire heart was covered with transverse GE sections. Shuntfraction was calculated from the stroke volumes of the right and left ventricle and compared to CC values. Localization and type of the VSD was correctly identified by the SE technique in 14 patients. In 7 patients the defect could not or not clearly be demonstrated. In all 18 patients who had additional GE images, turbulent shunt flow and its direction through the defect was depicted and the VSD correctly identified. Calculation of shunt size in 13 patients showed a correlation coefficient of 0.85 compared to CC. MRI is able to identify noninvasively localization and type of a VSD. GE-MRI is essential for following the motion of small defects through the cardiac cycle and demonstrating turbulent flow through the defect. Assessment of complications after surgical correction is possible. The relative merits of the technique in comparison to echocardiography need further definition.
171 P. DIOT*, E. LEMARIE*, J.L. 8AULIEU*, M.S. DELASSAN**, G. NORMIER**, H. BINZ**, A.M. PINEL**, L. DUSSOURO D'HINTERLAND** and A. LE PAPE*. * Laboratoire de Biophysique Cellulaire - CNRS-Universit@ de TOURS, France. ** Centre d'Immunologie et Biologic Pierre Fabre, CASTRES, France.
EVALUATION OF LUNG SARCOIOOSIS IMAGING VIA THE TARGETING OF MACROPHAGES WITH RADIOLABELLED D25. D25, a glycopeptidic immunomodulator isolated from membrane proteoglycans of a non pathogenic strain of Klebsiella pneumoni~ was demonstrated to target electively macrophages /n vivo and so, to allow the scintigraphic imaging of inflammatory lymph nodes in the experimental berylliosis in baboon. Due to its amphiphatic properties, this molecule cannot be I.V. administered because it forms micella that are trapped by the R.E.S. in spleen and live~. Ho~ever~ Administration by aerosol of 025 labelled with 99m technetium results in a selective delivery of oligomers in blood then a rapid clearance allowing sointigraphic imaging from 5 to 4 hours after inhalation. The aim of this study was to determine whether the D25 scintigraphy could be efficient to image lung granulomas and hilar lymph nodes in human sarcoidosis, a granulomatous disorder clinically and immunologically very similar to berylliosis. 8 patients gave informed consent and were explored by both 99m Ic D25 aerosol scintigraphy and 67 Gallium lung scan. In 2 patients with a L~fgren's syndrome, an intense fixation of D25 was noticed in mediastinum. 3 patients presented lymph node enlargement and reticulonodular pattern ; positive imaging of the hilar lymph nodes was observed with both D25 and Gallium scintigraphy. In 3 patients with diffuse pulmonary disease without lymph node enlargement, D25 showed an intense and diffuse activity in lungs whereas Gallium scans were subnormal in the same regions of interest. The preliminary results on D25 scintigraphy are in accordance with the findings obtained in experimental berylliosis in baboons and indicate that the targeting of macrophages could constitute an index of the activity of the disease, even at the early stage of alveolitis.
USSR Cardiology Research Center, Moscow, USSR PULVDNARY UPTAKE OF RADIOLABELED MONOCLONAL ANTIBODY TO ANGIOT~qSIN-CONVERrING ENZYME FOR THE EVALUATION OF LUNG MICROVASCUIAR ~NDOTHELIUM Previously in was shown that mouse monoclonal antibody (i~) to angiotensin-converting enzyme (ACE), named 9B9, radiolabeled with 1-125 and In-lll, v~ry efficiently ar~ specifically a c c t ~ a t e s in the rat lung (up to 40% of injected dose vs 0.5% for control IgG). Moreover, intravP_n~11s injection of In-lll Y ~ 9B9 allows to obtain ima- I ges of the rat and monkey lungs b y g ~ - s c i n t i g r a p h y . 1 S i n c e ACE localizes on the surface of the endothelial 1 cells, we propose that damage of the lung microvascular endothelit~n faight change the value of the lung acct~nula- i tion of MzDAb 9B9. Rat p u ~ n a r y edema induced b y naphtyl- I thiourea was a c c o n ~ e d by significant decrease of M ~ I 9B9 lung a c ~ l a t i o n (up to 60% frown the control an//nals despite evident increase of non-specific IgG accL!mulation ~%ich was sindlar to accurm/lation of ~ and achieved 5CX31 from the control. In contrast, injection of E.coli endotox/_n O127:B8 s e r o t y ~ did not induce edema T ~ a c c t ~ n u lation of ~ add IgG reran/ned unchanged). However, ~bAb 9B9 lung accn/nulation drastically decreased 15h after en- I dotoxin injection (radioactivity per g of lung to that of the blood was 3.95+0.08 ws 7.09+0.42 in control). So, we conclude that evaluation of specific lung acc~m~ulation of Y~ 9B9 can sez've as a very sensitive marker of the lung microvascular endotheli1~n status. A t present, we try to estimate %~nether the changes of pulinonary uptake of In-ll 9B9 during lung injury model are sufficient for the changes of irm~ges of that a c c u s a t i o n .
172 M. Cordesl, D. RollI, M. Langer*, M. Ruhnk~, N. Hostm~, H. Eichst~dt2, K. J. Grif2 , R. Felix* Department of Radiol~JYI and Department FU Berlin, UKRV/C, FRG
M. T r a u ~ ,
DIAGNOSTIC (4 h p.i.)
SCANS PCP
VALUE OF EARLY GALLIUM-67 IN PATIENTS WITH AIDS AND
of
Mslicin~
Patients with acquired immunodeficiency syndrom (AIDS) have a high risk for opportunistic infections such as Pneumocystis carinii pneumonia (PCP). Since chest radiographs may he negative in the early stage of PCP, gallium scans are of high importance in the early diagnosis. Aim of the study was to evaluate the significance and validation of early performed gallium scans (4 h p.i.). We examined 25 patients (3 women and 22 men, age 22 to 54 years) with clinically and/or radiologically suspected PCP. Scans were performed 4, 24, 48 and 72 h after intravenous administration of ii0 MBq gallium-67 citrate. Visual and quantitative evaluation with regions of interest and calculation of counts per pixel ratios lung/liver (q) was performed. Diagnosis of PCP was confirmed in 9 patients by bronchial lavage and in 4 patients by clinical and radiological outcome. Statistical significance (p) was computed by the MannWhiteny test. Results: K!o secured (n=13) I K ~ emcluded (n=12) l meanq I meanq ~__~ 4 h i 1,05 I 0,70 I <0,001 24 h I 0,98 I 0,63 I <0,0005 48 h ~ 1,09 I 0,60 I <0,002 72 h ~ 1,08 I 0,53 I <0,001 Conclusion: Gallium scans are of high clinical importance in the diagnosis of PCP and may show positive results as early as 4 h p.i.
442
173 H.K6hn,
174 Ch.Armbruster*, B.K6nig, A.Mostbeck
N.Vetter*,
of Nuclear M e d i c i n e and L. BoltzmannInstitute of N u c l e a r Medicine, Wilhelminenspital, II. Med. Dept. Pulmol. Zentrum*, Vienna
M. Lemb,
T.H.
Oei,
U. Sander
Dept.
VALUE OF N U C L E A R MEDICINE PROCEDURES FOR DIAGNOSIS AND M O N I T O R I N G OF O P P O R T U N I S T I C LUNG INFECTIONS IN AIDS PATIENTS AIDS patients are at risk of life t h r e a t e n i n g o p p o r t u n i s t i c lung infections. 57 HIV-pos. patients (28 AIDS, 3 ARC, 26 a s y m p t o m a t i c according to DCD criteria) were studied by 67 Ga scanning and 99m TC-DTPA lung clearance in addition to chest X-ray, lung function tests and blood gas analysis. Diagnosis was performed by BAL, culture or tissue biopsy. Pts. with acute Pneumocystis infection had both pathological Ga-scans and X-ray. Tc-DTPA clearance was s i g n i f i c a n t l y (p<0.001) h i g h e r at h o s p i t a l i z a t i o n (5.46 ± I.i %/min) than after 3 wks of specific therapy (1.69 ± 0.67 %/min). 3 Kaposi's sarcoma had neg. Ga-scans but increased lung clearance. In follow-up (17 mo), epithelial lung c l e a r a n c e had a similar time course as lung function tests as compared to X-ray, blood gases or Gascans. In 3 pts., PCP d e v e l o p e d during the observation period. Lung c l e a r a n c e became pathological up to 4 mo before p a t h o g e n s were detected in BAL and X-ray became p a t h o l o g i cal. Due to its high sensitivity, an increased lung clearance together with p a t h o l o g i c a l lung function tests should be an indication for a diagnostic BAL even if X-ray is neg.
175 F. De Geeter, A. Bossuyt, M Jonckheer.
RSntgeninstitut Dras. and Nedizin. Klinik Bremerhsven
Oei/Lemb, Bremerhaven Krankenhaus am B5rgerpark
VENTILATION-PERFUSION LUNG SPECT IN THE DIAGNOSIS OF PULMONARY THROMBOEMBOLISM (PTE) USING TECHNEGAS. Combined vent/perf acintigraphy has been shown to have high sensitivity and specifity in the diagnosis of PTE. Using a radioaerosol with big alveolar deposition SPECT data acquisition is possible. In 50 pat. with suspected PTE we used the following technique: after inhalation of 37MBq Technegas in supine position SPECT data acquisition was performed. Immediately after the ventilation study perfusion SPECT scans wer~ obtained after injection of 385 MBq 99m Tc-MAA in the same position. By comparing the transversal, coronal and sagittal vent and perf SPECT slices, diagnosis was made. In some special cases the V/P-quotient was calculated slice by _ slice. Outing SPECT-acquisition conventional planar scans were performed. Results: 32 of the 50 examined pat. showes pathologic results, 15 of them were embolic and 17 embolic and partially obstructive. All planar findings could also be represented by SPECT. In 72% of all pathologic findings SPECT showed a better spatial resoiution. In 2 cases smail PTE couid only be documented by SPECT. No centrai deposition was seen in the vent scan in any case In summary Technegas is an excelient tool for SPECT studies. Vent/perf iung SPECT is the better procedure to screen patients suspected of having PTE.
176 P. PELTIER, Y. ZAIR, A. CHETANNEAU, JF. CHATAL
Department of Nuclear Medicine, University Hospital, Vrije Universiteit, Brussels, Belgium CENTRE RENE GAUDUCHEAU - Quai Moncousu Nantes - France COMPARISON OF TECHNEGAS T M TO 81mKR AS VENTILATION AGENT. To investigate the clinical utility of the new Tc-based ventilation (V) agent Technegas we studied 24 consecutive patients. A Tc-V study was obtained first, followed by the alternative acquisition of perfusion (P) and Kr-V images. Threehundred kcotmt anterior, posterior, left and right lateral and left and right posterior oblique views were obtained with a large field of view gamma camera. Technegas was inhaled during 5 consecutive deep inspirations. If the count rate in the anterior view was less than 2000 counts/minute Technegas was re-administered up to 3 times Kr obtained, gxorn a gb/Kr genexato; was administered dur~ag the acquisition by means of a face mask. For the P study, 185 MBq 99mTc-MAA were administered I.V.The studies were read by 3 independent experienced observers. Image quality of the V studies was assessed visually. In 7 patients aged from 66 to 93 year sufficient count rates could not be obtained after Technegas administration, mostly because of insufficient breathing amplitude. In 2 out of the other 17 patients V studies with Technegas were rendered uninterpretable by heavy tracer deposition in the bronchial tree. Eleven of the 17 patients had Tc images that were of at least equal quality, when compared to the Kr images. Differences between Kr and Tc images included: deposition of the Tc tracer in the bronchial tree (10 patients), in the buccal or cervical region (10 patients) or in the stomach (4 patients); a better delineation of the lungs with To; and the presence of activity in the tubing and the face mask with Kr. The decision wether perfusion defects are matched or not was always the same with Tc and Kr images. The quality of the P images was not degraded by the previous administration of Technegas. We conclude that Technegas may be a valuable adjunct to perfusion imaging. The high failure rate, if confirmed in a more extended series, is a major problem in eider patients. On the other hand, the instantaneous availability as well as the often better image quality are assets of this new ventilation agent.
"TECHNEGAS" VENTILATION STUDY
Isotopes (133Xe, 127Xe, 81mKr) and radloaerosuls have been proposed for ventilation study In diagnosis of pulmonary embolism {PE). In this respect, nebulization of submicronlc particles of 99mTc using "rechncgas" would seem to be an Improvement over the radloaerosols ordinarily used. Method : 42 paUents (21 men, 21 women)with suspected PE were explored, Including 5 smokers and 10 presenting COPD. The 99mTc aerosol was generated on average from 10.1 mCI of~9mTc by "Technegas". Four views {anterior, posterior, LPO, RPO) were recorded using a precount of 200 k-counts. Image quality was assessed (1) semlquantitatlvely by scoring bronchial and gastric actMty from O to 4 (0 = no hyperactivity : 4 = intense hyperaeUvityrendering documents unlnterpretable), and peripheral 99roTe penetration from 1 to 4 (1 ffi good ; 4 ffi very poor, making Images unlnterpretable) : and (21 quantitatively by computing the peripheral penetration index for the lelt lung (LI), r~ght lung (RIJand mean (MI) : L! and RI were equal to PA/IA. where PA mean activity per pLxelof peripheral lung and IA - mean activity per pixcl of central lung, M1 being equivalent to (LI + RII/2. Results : Tolerance was perfect 40 times, and 2 patients had respiratory dlmcultles of no consequence. The mean time for obtaining 200 k-counts In posterior view was 181 + 14 s. Table 1 indicates the frequency of bronchial and gastric uptake : peripheral penetration was good 32 times, moderate 8 times, bad 1 time and very bad with unlnterpretable images 1 time : L1 was .75, R1.80 and M1.78. Table 1
Activity Level Bronchial Gastric
0
35 35
I
4 6
2
3 1
3
4
Conclusion: "rechnegas" gives very good quality images without interfering bronchial or gastric hyperacUvRy, which exists when there Is COPD. The examination is well tolerated and requires only a minimum of patient cooperation which, if absent, can make Images difficult or Impossible to interpret (2 cases).
443
178
177 M. Schwaiger, G.
Hutchins,
K.
Rosenspire,
D.
Kuhl.
I):iujie Liu, M.D., Xuebin Wang, Ph.D.* Cardiovascular Institute & Fu Wai Hospital, C A M S & }~,~C, B e i j i n g , C h i n a Beijing Normal University, Beijing, China
University of Michigan Medical Center, Ann Arbor, MI U.S.A. NON-INVASIVE QUANTIFICATION OF MYOCARDIAL BLOOD FLOW BY PET. Conventional sclntlgraphlc techniques such as TI-201 imaging allow only qualitative evaluation of regional myocardial blood flow (MBF). Dynamic PET imaging in combination with N-13 amouia (NH 3) permits temporal definition of blood and myocardial tissue tracer concentration. A 3-compartmental model has been employed to describe the exchange of NH 3 between vascular and extravascular space (K l and k2) as well as the myocardial trapping of NH 3 in the form of glutamine (k3). K 1 refleets MBF assuming high extraction of NH 3 and is expressed in ml/mln/lO0g. Since N H 3 is rapidly metabolized in blood, N-13 labeled metabolltes in blood were determined at different tlme-polnts. The contribution of metabolites to the input function has been incorporated into the flow model together with correction for activity spillover. Coronary reserve (CR) determined by this technique in normal volunteers averaged 4.4~I.0 and was homogeneous throughout the left ventricle. MBF averaged 68+12 ml/mln/lOOg at rest and increased to 264+24 ml/m~n/lOOg following i.v. dipyrldamole and handgri~. These results indicate that non-invaslve quantification of MBF by PET is possible. CR measurements were in good agreement with invaslve results. Thus, PET in combination with NH 3 may permit non-invaslve quantification of myocardial blood flow and allow improved characterization of extent and severity of coronary artery disease.
179
The Developments Imaging
Agents
of Myocardial Perfusion
in China
Because TZ-201 is not ideal myocardial perfusion a g e n t d u e to i t s p h y s i c a l a n d b i o l o gical characteristics, particularly it i s n o t available i n C h i n a . S o far, a n u m b e r o f h e x a k i s technetium analogues labeled with Tc-99m have been developed in China, including Tc-99m-TBI
(1985), Tc-99m-CPI
(1987),
Tc-99m-MIBI
(1988).
10 patients with normal coronary arteriography a n d 2 5 p a t i e n t s w i t h C A D confirmed b y c o r o n a r y arteriography h ~ v e b e e n s t u d i e d w i t h T c - 9 9 m CPI, the sensitivity (sen) and specificity ( spec) of Tc-9qm-CPI planar imaging was 92~, 80% respectively and the sen. and spec. of S P E C T w a s 9 0 % , 9~YZ r e s p e c t i v e l y . Tc-99m-MIBl myocardial p<=rfusion imaging was performed i~ 204 patients with planar imaging and 104 patients with SPECT. The results showed Tc-99mZ I B I i m a g i n g is e q u a l to T ! - 2 0 1 f o r d e t e c t i n g myocardial infarction end ischemia, SPECT imaging improves the localization of defects. The gated Te-99m-MIBI myocardial tomographic imaging which shows the ventricular wall motion has a good correlation with Echo and contrast ventriculography permitting simultaneous evalua%ion of myocardial perfusion and ventricular function.
180
A W J startle, A M Peters, J G J~ckson, R J Bm~dson, J P L ~ , D J All/son.
P MARTIN (If, B PEPERSTRAETE (2], J PATERNOT (I) and M. VERHAS (1)
Departments of Nuclear Medicine (I) and Cardiology (2), Brugmann University Hospltal, 4, place A Van Gehuchten, I020 Brussels.
HJ~dERSMITH HOSPITAL, LONDON, ENGLAND. IMAGING PU[/4ONARY THROMBUS WITH IN-Ill LABELLED ANTIPLATELETNONOCLONAL ANTIBODY. Thrombo-embolic disease comprises two components, venous thromhus in the legs (identified by peripheral venography) and pulmonary arterial thrombus (identified by ventilatlon perfuslon scanning or pulmonary anglography). We recently described and In-111 labelled antibody, P256, with high affinity for the lib IIIa flbrlnogen receptor on p l a t e l e t s , which could be used to identify venous thrombus. In a series of 21, non-antlcoagulated, postoperative patients receiving In-111 P256 Fab', 13 patients had focal uptake in the legs indicating venous thrombus. In 3 of these, there was also focal accumulation in the pulmonary artery, confirmed in 2 as embollc on Y/O scanning. A further patient showed venous thrombus and an abnormal V/O scan, but no accumulation of P256 in the lungs. In order to explore the ability of this tracer to identify thrombus in the pulmonary bed, we have ex~mined 3 patients undergoing therapeutic embollsatlon of pulmonary arterlo-venous malformations using planar imaging following injection of In-111 P2561 lesions were readily seen in all 3 patients. In 2, all lesions emboliaed were s e , a d n , major lesions were seen out of
a total o~ ~
em~£se&two
We conclude that In-111 P256 is able to detect thrombus in the pulmonary arteries in a high proportion of patients.
INTEREST OF III IN ANTIMYOSIN MONOCLONAL ANTIBODIES (MoAB) IN MYOCARDIAL INFARCTION AND IN CASE OF ANGINA PECTORIS WITHOUT NECROSIS. 9 patients with a myocardial infarction and 22 patlents with a coronary bypass, presentingl~Ith chest pain were selected to investigate the uptake of In antimyosin MoAB in case of ~rosl@ or #sqhema. They received an LV injection of 74 MB~of an In laSelle~ anT|myosln -MdA~: ~ planar- sclnTigrap~y t~ incidences 0 °, 45° and 90°) was recorded at 24 H and 48 N and analyzed by 2 Independent observers. Results were compared to ECG findings In case of Infarction and to coronary angiography In case Of chest pain. The lesser background at 48 H resulted In an improvementof the Interpretation. At that times the 2 observers were in agreement In 87% of the scans. These were concordant wlth ECG in 8 cases (89%) of necrosis. In one case, the sclntlgraphy was unable to locate correctly the infarction. 12 patients (54,5 %) wlth one or several stenosls/obllteratlon of bypass or coronary artery had an increase of MoAB uptake in the same correspondent territory at the scintigraphy (true positlve). In 4 cases (IB %), the scan showed an uptake of the MoA8 in a region whom the vessels were normal (false positive). 6 patients (27.3 %) with a normal anglography, also had a normal scan (true negative). In some of them, a mild diffuse uptake ~f the tracer was observed. There was no false negative scan. llin antimyosin MoAB is useful in the detection and localization of infarction, by binding of the AB to myosin of damaged cells. The good correlation between uptake of the AB and ECG findings in the cases of necrosis eonflrme the Interest of the test in that athology. We also Investigated the ability of AB uptake In schemla. We showed that the presence or absence of e significant vessel stenosls was correctly predlcted In 82 % of the cases. The mechanism of uptake could be due to hypoxemla of the ceil, resulting In an increased permeabillty of the wall wlth as consequence an Increased ability of fixation of the A8. The mild diffuse uptake of the tracer by the myocardlum of subjects with normal angiography was surprising. It would be of Interest to investlgate the ability of uptake of the AB In a normal population.
~
444
182
181
_E_D~LC~RT, JP BINON, R C~AY P,Reuland,B.K~veker~U.Feine Department of Nuclear F~icine C.H.U.A. V~ZALE 6110 Monti~ny le Tillesl, BELGIbld Abtlg.Nukl.Med.,Radiol.Klinlk,Unlv.THbingen § Chirurg.Klinik,Universit~t T d b i n g e n FRG
FRG !.4AC.~_?ACY OF s_Awivm~nIST~I~ION IK~GES I0 ~;ALUATE IHE D ~ I
OF ISEI~IA
~TER INITIALMYOCARDIALINFAI~3TION R E D U C T I O N OF T H R O M B O C Y T E S ' INTERACTION C U L A R G R A F T S BY F I B R O B L A S T S , D E T E R M I N E D LABELED THROMBOCYTES
W I T H VASBY I l l - I N
The s u c c e s s of v a s c u l a r g r a f t s in p a t i e n t s w i t h arterio-venous-occlusion d i s e a s e d e p e n d s on the thrombocytes a g g r e g a t i n g on the g r a f t ' s w a l l . T o o v e r c o m e this p r o b l e m we c o v e r e d the w a l l s w i t h a m o n o l a y e r of f l b r o b l a s t s . The e f f e c t was c o n t r o l l e d by the p a t i e n t s ' thrombocytes labeled with lll-In-oxine in the usual m a n n e r . T h e a p p l i e d d o s e w a s 5 to io MBq. The m e a n l i f e - s p a n was d e t e r m i n e d p r e o p e r a t i v e , 3 and 6 m o n t h s a f t e r s u r g e r y . O n e week, 3 and 6 m o n t h s a f t e r the g r a f t ' s i m p l a n t a t i o n its intera c t i o n w i t h the t h r o m b o c y t e s w a s d e t e r m i n e d as follows:A double-isotope scan of p e l v i s and t h i g h was p e r f o r m e d a f t e r an a d d i t i o n a l l a b e l i n g of e r y t h r o c y t e s (99m-Tc,in-vivo).The w a l l adhesive t h r o m b o c y t e s then w e r e c a l c u l a t e d by subt r a c t i o n of the b l o o d - a c t i v i t y . Patients with flbroblasts-seeded grafts showed no s i g n i f i c a n t a g g r e g a t i o n , in c o n t r a s t to t h o s e w i t h u s u a l g r a f t s , i n w h i c h the w a l l a t t a c h e d thrombocytes r e a c h e d up to 3o~ of the b l o o d contents of the g r a f t . T h e m e a n l i f e - s p a n of the thrombocytes d i d not d e p e n d on the i m p l a n t e d type of graft. The p r e s e n t e d m e t h o d d i m i n i s h e s the r i s k of reo c c l u s i o n as c o u l d be d e m o n s t r a t e d by the t e c h n i q u e of l a b e l e d t h r o m b o c y t e s .
183
184
P. K o u t s i o u b a ,
L.Iordanidou,M.Fatsis,A.Hatzinis
P.Natsis,G.Antypas.
METAXA Chest
Cancer Surgery
COMPARISON TYPE
The aim of the study was to evaluate the accuracyof the one-daystress / rest t~11itm study for assessi~ a reversible i s c ~ i a heyo~ the extent of a p~vious myocardial infarct. 30 patients recovering from a proved myocardial infarct were included in the study. The first SPR~ study was performed after a bicycle or a dipyridamole stress test. An early redistribution study was perform@ 4 hours l~ter aM.a rest study was next performed at 24 hours, after a. n~. injection o,t a nal~ thallium dose. A mappin~ of the ischemic zones was nbtalneo ~rem each s tuoy comparing the short arts "bullseye" representation with a data base cl nor,~l subjects (male or female). The extent of significant myocardial ischemia w~s calculated according to the statistical threshold of 3 standard deviatigT~ from the normal distribution. Final data were expressed as the percentageof the total left ventricular myocardial mass. Patients werecor~ider~4 to have a significant early redistribution i f the at~olute difference in the extent iscl~stia betweenstress and redistribution images was more than 5 percent a~ to have a delayed redistributionif isc~ia decreased more than 5 pe.rc~,nt hetween 4 hours and 24 hours post injection. Among t~ 30 patients included, 12 had no early redistribution, 16 had partlal redistrimtion, and 2, hao a sh~bt inv~se,r~istribution at.4 hours..~ _ In two patients resioua~ iscnemza was siign~ty wore severe at Z4 hours ~r~h at 4 hours; both bad a clear direct redistribution at 4 or 24 hours as com~m& with the stress images. In 17 patients, there was no difference between e~r~y aed delayed ~istrzbution images', 9 patients in this group had no redistribution and the other 8 had partial redistribution at 4 hours with no fur~hez change at 24 hours. In g patients, iscbe~iaextent was clearly decrease~ i, the 9.4 hours images as compared ~ith the 4 hours images, and in 3 of them difference was more than ten percent. the part of the reversible ischemia estimated from initial and early r~li~r= ibutzon images was misdingnosedin 5 out of the 14 patients with no earty redistribution {3) or slight reverse redistribution (2), and underestimated t, 6 out of the 16 patients with significant direct early redistribution. ?bus, the accuracy of the early redistribution as compared with the rest s t ~ was only 50% : the reversible iechemia extent was correctlyestimated in ml) 10 out of the 21 patients with significantdifference between stress ano ,eat images. These results suggest that the early redistributionimage is i,a~. curate to differentiate between reversible ischemia and non viable ~ocardi~m.
Hospital Dept.
OF L U N G
of P i r a e u s ,
Nuclear
OF C E A A N D CARCINOMA
N.Mylonakis,D.Papagrigoriou,L.Iordanidou,N.Papanikolaou,P.Kosmidis,P.Koutsiouba
CA-125
Medicine WITH
THE
M E T A X A C a n c e r H o s p i t a l of P i r a e u s Oncology BDept and N u c l e a r M e d i c i n e
Dept. STAGE
AND
PREOPERATIVELY.
E i g h t y five pts (81 men, 4 women) 35-81 years, w i t h p r o v e n lung c a n c e r (35 s q u a m o u s , 39 adeno, 8 m i c r o , 3 l a r g e cell) w e r e c l a s s i f i e d a c c o r d i n g to the N e w Inter. Syst. (Mountain 1986) in stage I-II (21 pts), I I I a ( 3 4 pts) , IIIb (25 pts), IV (5 pts). T h e s e r u m s a m p l e s w e r e o b t a i n e d b e f o r e surgical exploratioh of t u m o u r or m e d i a s t i n o s c o p > We u s e d C E A - S o r i n a n d CIS E L S A C a - 1 2 5 a s s a y s respectivelly. R e s u l t s . I. A r e l a t i o n was f o u n d b e t w e e n level of CEA-~ C a - 1 2 5 a n d t u m o u r stage. I n c r e a s e d v a l u e s I of C E A a n d C a - 1 2 5 w a s f o u n d r e s p e c t i v e l y in stag~ I i-If 33.3%, 25%, in stage IIIa 39%, 43.5%, in sta ge I!!b 41.1%, 58.8% a n d in stage IV 66.6% for both. 2. A r e l a t i o n w a s f o u n d b e t w e e n level of C E A and C a - 1 2 5 and the h i s t o l o g i c a l type. In a d e nocarcinoma 52%, 56% a n d in s q u a m o u s c e l l s 27.2% a n d 36.3% r e s p e c t i v e l y . Conclusion. In lung c a n c e r C a - 1 2 5 is f o u n d m o r e s e n s i t i v e as t u m o u r m a r k e r p r i n c i p a l l y in a d e n o c a r c i n o m a t h a n CEA. T h e r e is a c o r r e l a t i o n b e t w e e n the v a l u e s of ~ E A a n d C a - 1 2 5 w i t h the stage of the d i s e a s e .
Dept.
C E A , C a - 1 2 5 S E R U M L E V E L S IN N O N - S M A L L C E L L LUNG CANCER AND CORRELATION W I T H T H E R E S P O N S E TO CHEMOTHERAPY. S e r u m s a m p l e s of s e v e n t y four pts 35-75 years m e a n 56.3 w i t h lung c a n c e r (21 in stage III and 53 in s t a g e IV) w e r e e x a m i n e d for d e t e r m i n a t i o n of C E A and C a - 1 2 5 b e f o r e and a f t e r c h e m o t h e r a p y . The histological type was, 44 a d e n o c a r c i n o m a , 23 s q u a m o u s cell c a r c i n o m a , 3 l a r g e cell carcin. and ~ ~ n d e f f e r e n t i a t e d . I n c r e a s e d v a l u e s of C E A and C a - 1 2 5 w e r e found 59.5% and 70.3% r e s p e c t i v e l y . T h e s e n s i t i v i t y of the c o n t r i b u t i o n of b o t h m a r k e r s was 89.2%. S e r u m C a - 1 2 5 f o u n d to be m o r e s e n s i t i ~ e in s t a g e IV a n d in a d e n o c a r c i n o m a s . T h i r t y t h r e e of the p a t i e n t s w e r e e s t i m a t e d for the r e s p o n s e to the c h e m o t h e r a p y . S e r u m Ca125 i n c r e a s e d in 1 0 / 1 4 ( 7 1 . 4 % ) in pts w i t h pro~ r e s s i o n of the d i s e a s e w h i l e C E A i n c r e a s e d in 6/14(42.9%). In 11 pts w i t h r e g r e s s i o n of the d i s e a s e s e r u m C a - 1 2 5 d e c r e a s e d in 7/11(63.6%) a n d C E A in 4 / 1 1 ( 3 6 . 3 % ) . Conclusions. C a - 1 2 5 as t u m o u r m a r k e r is m o r e S e n s i t i v e t h a n CEA, p r o p e r l y in a d e n o c a r c i n o m a ~ n d in a d v a n c e stage a n d it seems to f o l l o w the clinical course.
445
185
186
A Hertel, RP Baum, B Auerbach*, A Herrmenn, G HSr
Division of Nuclear Medicine, University Hospital Frankfurt/Main, *Research Laboratories Behringwerke Marburg,FRG
A SIMPLE PROCEDDRE TO uETbCTANTI-IDIOT~ RUMAMAN/fMOUSEANTIBODIES (HAMA) AFTER IMMUNOSCINTIGBAPHY Repeated immunoscintigrephy (IS) with murine monoclonal antibodies is followed by e HAMAresponse which can be ent i - i s o t y p i c , anti- idietypic or both. A strong snti-idiotypic reaction most probebly prevents tumor targeting by blocking the antigen binding site of the antibody (Meb). Aim of the study was to develop e simple procedure for mes~ s-~ing enti-idiotypic HAMA. Methods: In 15B studies with 6 different Mab we found 29% H A l ~ i t i v e pstients(pt). 9 serum samplesof B p t with high HAMAtiters(C-4 epplicetions/lh-154d pi/HAMA factor(to value before application): 5.7-15.2) were tested for s n t i - i s e - / e n t i - i d i o t y p i c HAMA. All samples were tested f i r s t with Enzygnost(R) HAMAmicro sssay(Behringwerke) designed for using the specific Meb applied before in vivo. The fine specifity was evaluated with e slight modification of the BssBy:HAMA sere were preincubated for 30 min with Meb of the same or different iso~ type as the IgGi MBb(BW 431/28 e-CEA) used for IS which wee else bound on the solid phase. After performance of the original test procedure the strength of the inhibition of the HAMAbinding to the solid phase antigen was evelusted by different immunoglobulins: No inhibition wee found using polyclonsl sheep or rabbit antibodies or an IgM Meb. In most cases, other Mab of the IgG1,IgG2a,IgG2b,IgG3 leotype were about 50 to IO0 times weaker in their efficiency to biock the HAMA solld phase binding. A significant antiidiotypic HAMA response couid be demonstrated in 8 out of 9 serum samples. These data cieerly show that the measurement of enti-idiotypic HAMA is very important before repeated immunoscintigraphy to avoid faise negativ resuIts caused by anti-idiotypic biocked Meb.
187 M. Martin,
I.Vir~olini, G.Lupattelli*, P.Angelberger, J.Pidlich, H.Sinzinger. Atherosclerosis Research Group (ATK) of the Austrian Academy of Sciences, 2nd Dept. of Nuclear Medicine, University of Vienna, Austria; * 2nd Dept. of Internal Medicine, University of Perugia, Italy. IN VITRO LOW-DENSITY LIPOPROTEIN (LDL) APe B,ERECEPTOR BINDING TO HUMAN LIVER: COMPARISON OF DIFFERENT METHODS FOR LDL ISOLATION AND RADIOIODINE LABELING. LDL were isolated from the same donors'blood either by immunoaffinity chromatography (LDL, VLDL) or ultracentrifugation (LDL). Purified LDL (3 mg) were labeled with 123I (0.1 mCi/ml) using either Iodogen or Iodine Monochloride (ICL) each followed by purification with gel chromatography or dialysis. An aliquot was used for direct binding assays investigating the specific binding of labeled LDL to human liver ape B,Ereceptors. In separate experiments displacements of bound 123I-LDL by unlabeled ones (1000 fold excess) was studied. In all the preparations high affinity binding was found in the range of 0.1 to 5 Mg 123I-LDL/200~I assay volume (100 ~g liver membrane protein/200~l) amounting to approximately 95% of specificity. The binding capacities estimated by Scatchard analysis were similar to each other being independent from the method used for their isolation and labeling. The affinity constants were in the range of I to 5 nM, thus being very similar. It is concluded that the Iodogen or ICL method of radiolabeling for clinical investigation can be recommended to be equally good since no significant difference was found at the LDL-receptor level between these methods.
188 P. B l o c k x
M. Martin,
D e p a r t m e n t of N u c l e a r Medicine, A n t w e r p U n i v e r s i t y Hospital, Edegem,
E V A L U A T I O N OF A M O D I F I E D P R O T O C O L P R O G E S T E R O N E RIA KIT
Belgium
FOR A N E W
We e v a l u a t e d a P r o g e s t e r o n e Ria kit, the A m e r l e x - M P r o g e s t e r o n e (new) Ria kit, u n d e r m o d i f i e d conditions. M o d i f i c a t i o n s in the p r o c e d u r e w e r e m a d e at two levels. F i r s t l y we u s e d a c e n t r i f u g a t i o n and a s p i r a t i o n step i n s t e a d of the p r e s c r i b e d m a g n e t i c separat i o n in o r d e r to o b t a i n b e t t e r w i t h i n - a s s a y p r e c i s i o n and to e l i m i n a t e rack c o n t a m i n a t i o n in the g a m m a counter. S e c o n d l y the i n c u b a t i o n time at room t e m p e r a ture was s h o r t e n e d from 2 hrs to 1 hr. W h e n u s i n g the m o d i f i e d s e p a r a t i o n step (cent r i f u g a t i o n and aspiration) the w i t h i n - a s s a y p r e c i s i o n b e c o m e s s l i g h t l y b e t t e r (CV < 3,7% for all control levels, a g a i n s t CV < 5,1% in the o r i g i n a l protocol), the d e t e c t i o n limit is s o m e w h a t lower (0,05 ng/ml vs 0,08 ng/ml in the o r i g i n a l p r o t o c o l ) and t h e r e is no a s s a y drift. The use of a short protocol (i hour i n s t e a d of 2 hours) does not i n f l u e n c e the r e l a t i v e binding (B/Be) of the d i f f e r e n t standards, nor the w i t h i n - a s s a y precision. A h i g h level of linear c o r r e l a t i o n was o b t a i n e d b e t w e e n these two p r o t o c o l s (r = 0.99) w i t h s l i g h t l y h i g h e r conc e n t r a t i o n s for the 1 hour i n c u b a t i o n protocol. These d i f f e r e n c e s , however, have no c l i n i c a l implications.
P. Blockx
Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium COMPARISON OF DIFFERENT METHODS FOR THE DETERMINATION OF HORMONES IN FERTILITY SCHEMES.
We compared different methods for the assay of LHsp, Estradlol(E2) and Progesterone(Prog). For LHsp the standard and the short protocol were evaluated wlth the Medgenlx(M)IRMA, the BiomBrieux(Bm)Coatria and the Behring Riagnost (BE) kits. wlthln-assay CV's < 5% were found in 71% (M), in 73% (am) and in 84% (BR). Assay drift after 100 tubes towards lower values was present for M (-6%) and Bm (-11%), but did not exist for BR. In the short protocol the wlthlnassay CV's for all kits were worse, but BR remained most precise. Determination of E2 was evaluated with %he EIR Direct, the Medgenix(M) Ria and the BiomBrieux (Bm) Coatria kits. CV's for all kits were comparable, between 71 and 79% < 5% CV. A very big assay drift towards higher values existed with Bm (+30% after 100 tubes). Bm is the only kit with an extended range (20-5000 pg/ml). For Prog the Amersham(Am)Amerlex-M (new) His, the BiomBrieux(Bm)Coetria and the Behrlng Riagnost(BR) kits were compared. Excellent wlthin-assay CV's (89% with CV < 5%) and no assay drift were obtained with Am when a modified protocol (centrifug. and asp. instead of magn. sep°) was used. For Bm and BR the CV's were worse and an assay drift of resp. +7% and -9% was found after 100 tubes.
446
189
190
Y. Oda, M. Yamashita, K. Tashiro, S. Otsuka, Y. Kira, M. Kondo, H. Horii, K. Wakita, R. Fujii, H. Yamagishi, T. Kakiuchi, H. Nakahashi. Kyoto Prefectural University Hospital, Kyoto, Japan.
of
Medicine,
Nishijin
EVALUATION OF RESIDUAL MYOCARDIAL BLOOD FLOW AND GLUCOSE UTILIZATION IN PATIENTS WITH MYOCARDIAL INFARCTION USING DYNAMIC POSITRON EMISSION TOMOGRAPHY. To assess residual myocardial blood flow (MBF) and 91u cose utilization in pathological Q wave infarcted areas with abnormal wall motion, we studied 10 normal subjects and 26 patients with prior myocardial infarction (MI) using dynamic PET with 0-15 water and FDG under resting and fasting conditions. Myocardial activities were determined from serial PET images and corrected for spillover of blood volume radioactivity. Regional MBF was calculated by fitting the time activity curve with a modified single compartment model. A total of 52 regions with abnormal wall motion were selected for assessment. The residual MBF values in MI regions demonstrated a significant decrease compared with the normal MBF values (0.60fO.18 ml/min/g vs. O.97~O.09, p<.001) and also demonstrated a significant decrease in accordance with the severity of wall motion abnormalitles (A: mild hypokinetic, 0.8OfO.17; B: severe hypokinetic, O.61±0.O8; C: akinetic, 0.46±0.06; D: dyskinetic, 0.4010.09). 34 regions (97%) in groups A and B showed residual MBF values greater than 50% of those of normal regions, whereas only 4 regions (24%) in groups C and D showed values greater than 50%. Furthermore, increased FDG uptake was observed in 33 regions (94%) in groups A and B. On the other hand, 5 regions (29%) showed increased FDG uptake in groups C and D. This data suggests that residual MBF values of more than 50% of those in normal regions may be required to preserve myocardial contractility and reversibility after the onset of MI.
191 C. De Landsheere, D. Raets,L. Pi~rard, C. Degueldre, V. Legrand, C. Lemaire, M. Guillaums, D. Lamotte, H.E. Kulbertus, P. Riga. Cyclotron Research Center, University of Liege, Belgium.
REGIONAL MYOCARDIAL PERFUSION AND GLUCOSE UPTAKE : CLINICAL EXPERIENCE IN 92 CASES STUDIED WITH POSITRON TOMOGRAPHY.
Patients with ischemic heart disease are usually characterized by perfusion studies of limited value for the assessment of regional myocardial viability, particularly after a myocardial infarction (MI). This work simes to evaluate regional glucose uptake (GU) in addition to perfusion (P) in 75 poet Ml patients and in 7 cases of severe angina pectoris compared to I0 normal subjects. Positron emission tomogra~hy was performed at rest, using petassium-38 and [iBF]-deoxyglucose. Data were normalized to the intrascan peak activity and a circumferential profile analysis was used. Results were expressed in percent of P and GU; we calculated also a ratio (R) of GU over P providing an index of glucose extraction. Coronary anatomy is known in 78 out of 82 patients. In angina pectoris, P decreased to 54.7~i0.5% whereas GU and R respectively increased to 128.1±45.0% and 2.47+ 1.36. In patients with chronic anterior MI and complete coronary occlusion, P decreased to 39.1±Ii.5%; GU was similarly a l t e r e d and R : 1.02±0.27. In c a s e s s t u d i e d w i t h i n one month a f t e r MI, results were dependent on treatment and severity of residual stenosis (S). After thrombolysis, P was decreased to 58.2±19.6% in cases without significant S. Perfusion was 37.3±7.9% in cases with high grsde S (>90%), GU : 68.6±27.5% and R : 1.84±0.96, demonstrating persistence of flow deficit and severe ischemla. In conclusion, combined assessment of perfusion and glucose uptake allows identification of ischemic but still viable myocardium and objective evaluation of the results of therapy in individual patients.
M~ ~ g ~ g h I, K.P. Kaiser i, H. Herzog x, E. Vester 2, H. LSsse z, E. v.d. Lohe s, H. Simon s, L.E. Feinendegen I i) Institute of Medicine, KFA d6lich, 2) Dept. of Cardiology, Univ. D~sseldorf, 3) Dept. of Cardiology, Municipal Hospital D~ren, FRG
IeF-2-DEOXYGLUCOSE (FDG), 15-(ORTHO-i=3I-PHENYL)-PENTADECANOIC ACID (OPPA) AND THALLIUM-201 (TI) UPTAKE IN PATIENTS AFTER MYOCARDIAL INFARCTION: A COMPARATIVE STUDY WITH SPECT AND PET.
Uptake of FDG and I=3I-fatty acids reflects myocardial metabolism. FDG has been used for delineating viable myocardium in infarcted areas. The purpose of this comparative study was to clarify whether OPPA may be a potential indicator of viability. 25 patients were investigated with TI-SPECT and FDGPET. TI-SPECT was performed after symptom limited exercise and 3 h later at rest. FDG-PET was carried out at rest after injection of 185-370 MBq FDG. About 45 min before injection patients were loaded orally with 40 g glucose. PET data were acquired from 45-75 min after injection. Three days later 14/25 patients underwent a SPECT study with 150 MHq OPPA at rest. In 12/25 patients FDG uptake in fixed thallium defects was detected. In the group investigated with TI, FDG and OPPA, 6/14 patients exhibited FDG uptake in fixed thallium defects. In two patients OPPA uptake in T1 defects was observed as well. These two patients had the highest FDG uptake in T1 defects within the group. These results suggest that OPPA-SPECT may be able to delineate viable myocardium in fixed thallium defects, the sensitivity, however, appears less than with FDGPET. Further evaluation of the clincal outcome after revascularisation compared to the degree of FDG and OPPA uptake is necessary.
192 A.Buck*, R.Haldemann*, H.Reist***, K.Leenders***, R.Weinreich***,F.Amann***, I.Turina**, G.Westera*, G.von Schulthess* *Nuklearmedizinische Klinik, **Med. Poliklinik, ***Med Klinik, Universit~itsspital Zfirich, ****Paul Scherrer Institut. Wiarenlingen
HIBERNATING MYOCARDIUM DETECTED WITH FDG-PET AND TL-SPECT The aim of this study was to identify hibernating m y o c a r d i u m , that is: myocardium which has been ischemic for a prolonged period and is in jeopardy but is still vital. Such myocardium could be saved by a r e v a s e u l a r i s a t i o n procedure. The typical finding is normal or increased glucose metabolism and decreased perfusion. Patients and m e t h o d s : I n 14 patients with myocardial infarction, glucose metabolism was examined with 18FDG and PET. In 9 of these patients perfusion was studied with Thallium-SPECT at rest. Thallium was used because a PET perfusion tracer was not available. All patients had a coronary angiogram. Seven were treated with streptokinase. R e s u l t s : 4 patients showed larger areas with mismatch between PET and SPECT. Three of these patients were treated with streptokinase. All other patients with both studies showed a complete match between PET and SPECT. Conclusions: Our preliminary results indicate that a combined PET/SPECT study can identify regions with m e t a b o l i s m / p e r f u s i o n mismatch which are thought to present hibernating myocardium. Such regions appear to be more c o m m o n in patients with streptokinase treatment.
447
93
194
~
A. Ahonen, L-M. Voipio-Pulkki, U. Ruotsalainen, S. Parviainen, M. Haaparanta-Solin,P. Korkeila, R. Virkki, U. Wegelius
M.HopP, H.Ledermann, U.Noelpp, H.R6sler,
W . emrelc"-"'
" h**.
Departments for Nuclear Medicine a n d *Cardiology, Iuselspital, University of Bern, **Paul Scherrer Institute, Villigen, CH
Turku University Central Hospital and Medical Cyclotron Project, Turku, Finland
~OUTINE DETECTION OF NONPERFUSED BUT VIABLE (HIBERNATING 3R STUNNED) MYOCARDIUM AFTER RECENT INFARCTION WITH 18F.FLUORO-DEOXY-GLUCOSE USING A GAMMA CAMERA. =IRST RESULTS OF THE SUBSEQUENT CORONARY ANGIOPLASTY, rhere is need for an appropriate selection of patients (pts), who would benefit most from myocardial revascularization procedures. 18 F-_Fluoro-_Deoxy-_Gincose 18F-FDG) is known to be taken up in ischemic _M_yo__Cardium(MC), even in ~rsisteat perfusion defects with 201 Thallium (201 T1), i.e. in "hibernating or tunedMC". Eapcrience.,swith P_ositronEmission Tomography (PET) imaging can b e
reproduced with the use of a modified Anger-type Camera, i.e. the most common NueMed tool. The camera was shielded with a lead reinforced table and fitted i ~th special lead protected S_even_P~ole (SPH) Collimator. The patient was )ositioned prone above the camera. System sensitivity and resolution for 18 F was found comparable to 201 ~I and 99m To, ,~ing a phantom. Routinely static SPH images with 99m Tc-Cardiolite were compared with 18FFDG images done during the same session and in identical position in pts. 3-8 weeks after acute M___yocardialInfarction (MI). 201 T] stress/redistribution studies had shown "scars" in all, confirmed by X-ray coronaro/angiography, and 99m Tcfirst pass- angiography. More than half of these "scars" showed increased circumscript FDG uptake in the lesions. After subsequent successhd coronary angioplasty, regional 201 T1 uptake was found improved and wall motion recovered with these pts only. Ire- and post-treatment results with the first t e n consecutive pts. will be presented. We conclude that SPH-Tomoscintigraphy with 201 T1, 99m Tc-Cardiolite and 18F-FDG is a widely available method for the detection of ischemic but viable myocardium after/VII. This technique can be used much easier than PET in daily practice. 18F-FDG exams are made available for NucMed Dept.'s wathin 1 hour transportation distance from a cyclotron.
ASSESSMZNTIF MY~DIa_ vI#aILITY IN PATIENTSWITH SEVEREANGINA. A CO~PARATIVESTUDYUSINGTc-99mMIBI ~D TI-201 SPECT~ (F-18)FDG PET The aim of this study is to evaluate the role of Tc-99m MIBI SPECT in assessmentof myocardial viability in patients with severe angina. We have studied 15 patients with severe angina pectoris with resting FDG-PET, Tc-ggmMIBI and Tl-201 SPECTexercise test and coronary angiography. Patients were given a 50 g oral glucose load I hour before the administration of FDG. This servedto enhancemyocardial glucose utilization. Myocardiumwas devided into 11 anat~ic ventrlcular segrents. FDG uptake wa~ mxi:rately decreased in 15 oUt of the 20 segments with a fixed MIBI defect, in 3 segmentsFDG uptake was normal, and in 2 seg,ents a total FDGdefect could be found. Two segrents out of the 5 ~nts with a total FDG defect showednormal MIBI distribution, whereas in one segTent ischemic MIBI uptakewas obtained. FDG uptake was moderatelydecreased in 7 segments out of the 25 segments with a completely reversible MIBI defect, and a normal FDG uptake was documented in 18 segnents. Correspondingly, FDG uptake was moderately decreased in 3 out of the 13 segnents with a partially reversible MIBI defect, W~ereas in 10 seqrents FDG distribution was non,al. The size of a fixed MIBI defect corresponded the size of a fixed thallium defect in 3 patients, ~aereas MIBI defect was snaller in 4 patients and larger than a fixed thallium defect in one patient. Correspondingly, the size of a ccmpletely reversible MIBI defect oorresponded a thallium defect area in 6 patients, MIBI defect was larger in 4 patients, and smaller in ore patient. k~ conclude that in patients with severe angina pectoris s3~Iptoms, myocardial viability (documented by FDG uptake) is largely preserved in segrents classified as infarcted by fixed MIBI defects. Fixed thallium defects were larger than fixed MIBI defects, v~ereas ischenic MIBI defects were larger than thallium defects.
196
195 O. L. Munz, A. Morguet, A. Conrady, H. H. Klein, S. Pich, E. Voth, W. Eschner, H. Kreuzer, D. Emrich Dept. of Nuclear Medicine and Dept. of Cardiology Pulmomology, University of GSttingen, F.R.G.
and
DOUBLE-TRACER MYOCARDIALSCINTIGRAPHY USING I N - I l l ANTIMYOSIN (AM) Fab AND TC-99m METHOXY-ISOBUTYL-ISONITRILE (MIBI) IN SUBACUTEEXPERIMENTALINFARCTION This study was performed to find out whether i t i s possible to discriminate normally perfused (I), reversibly damaged ( I I ) and necrotic (III) myocardium as it will result from early thrombolytic therapy or PTCA in acute myocardial infarction. In 14 pigs, the LAD was occluded for 45 min and then reperfused. Forty-eight and 72 hrs after removal of the occlusive clamp, 74 MBq In-lll AM
Fab and 740 MBq Tc-99m MIBI, resp., were injected i . v. One hr after MIBI i n j e c t i o n , the LAD was occluded again at the same location, and the normally perfused myocsrdium labeled with flourescein. Thereupon, the heart was excised. Double-nuclide planar and SPECT scanning of the whole heart and planar scanning of 2 - 4 heart slices cut p a r a l l e l to the a t r i o v e n t r i c u l a r groove Was performed. On the heart slices, previously ischemic zones were d e l i neated by using uv l i g h t i n g and necrotic areas by count e r s t a i n i n g with tetrazolium. Using scans and macrohistochemical pictures, tissue samples were obtained from myocardial areas I - I I I . Based on % injected dose/g tissue, the following r e l a t i v e tracer d i s t r i b u t i o n was found: I
II
III
Tc-99m MIBI 1 0.83 + 0.28 0.30 + 0.20 In-111 AM Fab I 2.79 ~ 1.29 3.96 ~ 2.48 In conclusion, uptake of I n - l l - f AM Fab not o ~ y occurred in necrotic but also in mscrohistochemically reversibly damaged myocardium. Thus, i n f a r c t size may be overestimated by using In-f11 AM Fab.
J.M.Latre, A.Jimenez-Heffernan, M.Pan*, M.Torres, J.M.LLamas, F.M.Gonzalez y A.Mateo.
Nuclear Medicine and Cardiology* Services Hospital "Reins Sofia" Cordoba SPAIN RESIDUAL MYOCARDIAL NECROSIS ASSESSMENT AFTER EFFECTIVE THROMBOLYSIS The reliability of various infarct-dellneatlng radiopharmaceuticals in the assessment of residual necrosis extent after effective thrombolysis are evaluated in this paper. Twenty patients who underwent intravenous thrombolysis (i0 STK,IO rTPA) in theacute phase of trsnsmural infarction (i0 AS,9 INF,I LAT) were studied using a prospective protocol. The study comprises: 99mTc-PYP scintigraphy 48 hours post-MI, antimyosin antibody -lllIn (AS) injected after PYP exploration and imaged 48 hours later, and myocardial perfusion scintigraphy with 99mTc-MIBI or 201TI, at rest 7-10 days after the acute episode. All examinations were acquired using SPECT and 4 projection planar scintigraphy (PS). Arterial recanalization was assessed by coronary angiography immediately after TIV completion in all patients. The number of pixels occupied by the areas of abnormal uptake and uptake defect were calculated and compared using the paired T test, establishing significance levels for each one. Our results support the affirmation that PYP and AB overestimate the size of residual necrosis measured with MIBI ( p ~ 0.001) when reperfusion of the infarcted area is achieved. Overestimation of necrosis size is higher with PS in both cases. AB overestimates necrosis size more than PYP (p
448
197
T W ItENNIGAN(I~, R CARPENTER(I), R BEGENT(2) AND T G ALLEN-MERSH(1). (1) Department of Surgery and (2) Department of Medial Oncology, Chafing Cross Hospital, Fulham Palace Road, London W6 8RF, United Kingdom. PHARMACOLOGICAL MANIPULATION OF VASCULAR PERMEABILITY INCREASES TUMOUR ANTIBODY UPTAKE Treatment of colorectal hepatic metastases with antibody-isotope conjugate (AIC) depends on achieving a high tumour:liver dose advantage.Tumour AIC uptake is influenced by intravascular dose, tumour blood flow and capillary permeability. We have attempted to increase tumour uptake by regional delivery and pharmacological manipulation of capillary permeability using histamine. LS 174T, CEA-expressing, human colon carcinoma xenografts were ~own in the'fiind limb 0f athymlc ra~ co derive tll~BtOO~ s'oppty ream ~t~e femoral artery. Four weeks after innoculation, a lumbar vein and the contralateral iliac artery were cannulated with the tips at the inferior vena cava and aortic bifurcation. In 12 animals, A5B7 anti-CEA antibody conjugated with 15uCi of iodine 131 was infused into the right lumbar vein (systemic infusion) whilst saline was infused into the iliac artery(regional infusion). In 15 animals, AIC was infused regionally whilst saline was infused systemically. Finally in 12 animals, AIC was administered regionally with histamine (10mg/kg). After 48 hours the tumour and liver were removed and gamma activity measured in a well counter. Mean tumour:liver ratio of activity after regional administration (mean=l.69, SD=0.56) was greater than after systemic administration (mean=l.17, SD=0.40) but the difference did not reach statistical significance. However there was a significant (10<0.05, Mann-Whitney Test) increase in the mean tumour:liver uptake when AIC with histamine were administered regionally (mean=3.21, SD=0.89). Regional delivery of AIC and histamine increased turnout:liver antibody uptake approximately three-fold compared with systemic administration.
199
198 L,_~, W. v.d. Broek, O. Boerman, W. Buijs, R. Claassens, R. Verheijen, L Poels, Ch. SchlJf, Q. van Hoesel, P. Kenemans, and F. Corstens Departments of Obstetrics and Gynaecology, Nuclear Medicine, Cell Biology and Histology, and Medical Oncology, University of Nijmegen and University Hospital, Nljmegen, The Netherlands PHARMACOKINETICS AND BIODISTRIBUTION OF IN-t11-OV-TL 3 F(AB')2 MONOCLONAL ANTIBODY IN PATIENTS WITH OVARIAN CANCER This study was performed to obtain information about the biological behaviour In patients of a new murlne monoclonal antibody (OV-TL 3). After written informed consent, fifteen patients were injected I.v. with 140 MBq In-111-OV-TL 3 F(ab')2. Blood samples were taken regularly upto 96 hrs after injection. Furthermore urine, faeces, ascites, and cyst fluid samples were obtained. During the operation, 6 clays post injection, tumour deposits and fragmer~ of'nOrmal tissttae ~btood, liveF,r~scle, bowel, lymph node, skin, ovary, and uterus) were removed by the surgeon. Disappearance of activity from blood was similar for all patlens studied and could be represented by a bi-exponential curve with T~/2-values of 6 and 32 hr. In patients with ascites an increase of ascites activity was seen from 0.2% of the dose per liter at 24 hr to 1.5% of the dose per liter at 5 days post Injection (p.L). Total urinary excretion (urine collection up to 96 hr p.L) amounted to approximately 17% of the dose, white total stool activity reached 2% of the dose over the same period. Tissue uptake values, expressed as % of the Injected dose per gram tissue (mean + SD x 103)were 3.8 _+0.8 for tumour, 11.5 + 6.5 for liver, 3.0 ± 0.7 for omentum and 0.5 ± 0.4 for skin. Tumour to normal tissue ratios did not exceed 10.4. To assess the homogeneityof activity distribution within in a tumour mass, multiple samples were taken from a large ovarian tumour and the activity uptake of each sample was measured. Uptake expressed as % of dose per gram tissue (x 10°) ranged from 0.3 to 5.8 with a mean of 2.4 and was in accordance with the macroscoplcal inhomogeneityof the tumour mass. Based on biodistribution data, the radiation burden was estimated tn one patient. Liver: 1.8 mSv/MBq and kidneys: 1.3 mSv/MBq; somatic affective dose equivalent: 0.5 mSv/MBq.
200
R. Claessens. L Masauger, R. Verheyen, L. Pools, Ch. Schljf, Q. v. Hoesel, S. Strljk, C. Yedema, W. BulJs,A. Meauwis, P. Kenemans, and F. Corstens.
G. L e l n s i n g e r , J. S c h e i d l e r , W. Eiermann, W. Meier and C.M. Kirsch
Departments of Nuclear Medicine, Obstetrics and Gynaecology, Cell Biology and Histology, Medical Oncology, and Radiology, University of NiJmegenand University Hospital, Nljmegen, The Netherlands.
Depts. of Nuclear Medicine and Gynecology, University of Munich, Munich, FRG
SCINTIGRAPHY OF OVARIAN CARCINOMAS WITH A NEW In-11 I-LABELED MONOCLONAL ANTIBODY (OV-TL 3)
VALIDATION OF IMMUNOSCINTIGRAPHY(IS) USING SPECT IN EPITHELIAL OVARIANCANCER(OC)
The objective of this study was the assessment of the saf~y of OV-TL 3 in patients and the preliminary evaluation of its diagnostic accuracy. So far, 20 patients underwent sclntigraphy (planar and SPECT) after I.v. injection of 140 MBq In 111_OV.TL3-F(ab')2. Written informed consent was obtained from each patient. This study was approved by the local ethical committee. Patients with an allergic diathesis or a diagnosis of a second malignancy were excluded. Scintl%1aphywas performed {laily between 4 and 96 hr after injec. tlon. Each patient underwent CT-scannlng and uftrasonography of abdomen and pelvis. In one patient a definite dlagnosls of ovarian carcinoma could not be made so far. Seven patients, suspected of primary ovarian carcinoma, were scheduled for surgical treatment. One patient was scheduled for second look evaluation. Eleven other patients had been treated for ovarian carcinoma; ten of these showed either clinical or radiological signs of recurrence. A total number of 13 patients underwent surgery within 5-7 days following scintlgraphy. Agreement between sclntlgraphlcal, radiological, and surgical results was found In 12 patients (12/13; 1 neg. and 11 pos.). In one patient at scintigraphy no discrimination could be made between Intestinal and tumour activity. The clinical or radlologlcal signs of recurrence in five other patients could be confirmed by sclntlgraphy. One patient was positive on sclntigraphy, but did not show any sign of recurrence (except for an elevated CA-125 level in plasma) sofar (6 mnths after scintlgraphy). Except for a transient rash, observed In two patients until 72 hr after administration of OV-TL 3-F(ab')2, no furhtar side-effects were noted. In conclusion: the first results of sclntigraphy with OV-TL 3-F(ab')2 are most promising. Intestinal and ascites activity hampered Image interpretation. SPECT appeared indispensable for correct localization of tumour deposits.
In the follow-up of patients (pts) with epithelial OC clinical status, tumormarker levels and explorative laparotomy are used to detect tumorrelapse. Aim of the present study was to validate IS in visualizing local recurrencies or metastases of OC. The study includes 45 pts.ln 8 pts IS was performed before primary surgery and in 37 pts in the follow-up of OC. In 8 pts IS-controls were performed. SPECT-imageswere acquired 4 to 7 days after i.v. application of 131-I labelled MAB to CA 125 (I mg F(ab')2; 70-140 MBq). I of 8 IS-controls was not evaluable because of human antimouse antibodies. True positiv IS-results were found in 4 pts with primary OC. IS was true negativ in 2 benign ovarian tumors and in I lymphoma I false positiv finding was caused by an abscess. In the follow-up of OC tumorrelapse was confirmed by explorative surgery in 40/44 cases. In 2 pts tumorprogression was observed in the clinical course inspite of normal surgical findings. Tumorrelapsewas visualized by IS in 40/42 pts (sensitivity 95~). No differene between sensitivity in detecting local recurrencies and diffuse peritoneal carcl' nosis was found. Meantarget-to-non-target ratio of circumscript tumors was 4. In 29/30 pts (97~) with elevated CA 125 levels (>65 U/l) IS was true positiv. In addition, t r u e p o s i t i v I S - r e s u l t s were found in 11/14 pts (79~) w i t h normal tumormarker l e v e l s . In c o n c l u s i o n , IS using 1131-I MAB and SPECT is a s e n s i t i v e method t o d e t e c t even I s m a l l - s i z e d d i f f u s e metastases o f OC. In pts w i t h e l e v a Ited CA 125 l e v e l s IS could be used instead o f d i a g n o s t i c llaparotomy.
449
201 J. Scheidler, G. Leinsinger, K. O.E. Scheiffarth*, K.G. Riedel*
202 Scheidhauer,
C.M.
S.M.Reske, J.H. Karstens *, W.Gl6ckner **, U.Buell
Kirsch,
Dept. Mucl. Ned., * Radiotherapy and ** Internal Medicine If, RWT~ Aachen, FRG
Department of Radiology, Division of Nuclear Medicine and Department of Ophthalmology*, University of Munich, FRG
IMMUNOSCINTIGRAPHY O F O C U L A R
MELANOMA
BONEMAEROWSCINTIGRAPHYBY ME~5 OF Tc-99m LABELED MCA-A~'rIBODIES (TcMCAA) In BREASTCARCI~OI~ (MC) AND MALIGNANTLYMPBOI~ (ML)
Although ocular melanoma can be diagnosed by ophthalmoscopy and ultrasound, up to 20% of lesions remain questionable. The aim of this study was to validate immunoscintigraphy (IS) in planar and SPECT technique for early diagnosis of ocular melanoma. 76 patients (pts) with lesions ranging from 1.4 to 23 mm in size (mean 6.3 a m ) were examined using the 225.28S antibody (Sorin) against the high weight molecular antigen. 6-16h after I.e. administration of 350 lag 99aTe labelled monoclonal antibody (F(ab)2-fragments, 450-1000 MBq) planar and SPECT Images of the head were obtained. Results: 52/65 melanoma were detected by IS (sensitivity 80%). 21 (40%) were excusively visualized by SPECT. Two pts were suffering from metastases, 8 from naevi and one from an old posttraumatic haemorrhagia. The haemorrhagia and a binocular naevi were false positive. In the other naevi and in the metastases no pathologic antibody accumulation was found (specificity 82%). Detectibility varied depending on lesion's size: g4 mm 63%, ~6 mm 80%, :g8 mm 78% and >8 mm 100% of melanoma were visualized. In contrast, there is no correlation between detectibility and location o~ lesions (nasal/temporal). No extraorbital metastases were seen by IS or have been diagnosed clinically. In three enucleated melanoma immunohistoehemistry was performed to demonstrata antibody binding. In conclusion, IS substantially contributes to the diagnosis of ocular melanoma. SPECT is essentially required to detect even lesions of small size with a high sensitivity.
TcMCAAare murine nonoclonal IgG1 antibodies directed against CEAand non specific cross reacting antigen (NCA), exposed at tile cellular meKbrane Of peripheral qranulocytes and myelocytes in bone marrow. About 80 %of these cells are located in bone ~--cow. ~us, T~CJh~provide a new approach for non-invasive scintiqraphic evaluation of bone aerrow in man. Bonemarrow biopsies abundantly deaonstrate incipient bone Jarrow netantases in MCand ~ . Wetherefore examined 15 patients (P) with MC and knownskeletal metastases, 10 P with ~ stage I - IV and 15 controls (C) without suspected laliqnant disease by Reans of TcNCAA. ~ole body qa~-caNera scans were
porforaed 3 hrs after injection of 300 ± 15 ~ t TcNC~ i.e.. Bonemarrow biopsies were obtained in 4 P with ~ and all P with ~. Skeletal scintiqraphy, plane radioclcapbsand CT of selected skeletal regions were used as reference for confiraation of skeletal lesioun. TcMCAA scans showed boaoqenous uptake in axial and proxiBal appsndicular skeleton of C. Liver and spleen bad noderate antibody uptake, not significantly obscuring vertebral bone marrow uptake. Scintiqrapbic quality of TchTA~ scans was essentially conparable to that of bone scans and clearly superior to the conventional colloid scan. 15/15 P with MC and 5/10 P with ~ had uni- or mfltifocal ~-defects on T c ~ scans. In ali these P, results of BM-biopsies, radio1~ical and clinical findings indicated skeletal mtastases as underlying patholow of ~-defects. ?he ~cMC/~k-scandetected significantly more lesions than the bone scan in He (p < .027) and ~ (p < .036). In sole P, ~-defects were the first findings indicating skeletal Jetantases. In conclusion, excellent ~-scans can be obtained by neans of T e ~ . First clinical results indicate the potsntial for sensitive and conceivably early detection of skeletal involvement in MC and ~ by this new approach.
203 P. 01OT*, S. ZAFFREYA*, E. LEMARIE*, J.L. BAULIEU **, H. BINZ***, G. NORMIER***, A.M. PINEL***, L. DUSSOURDd'HINTERLAND***, L. POURCELOT*~ and A. LE pAVE*. * Laboratolre de Biophyslque Cellulaire, Facult~ de Mddeclne - C.N.R.S.,
TOURS, France. ** Serv. de M~declne Nucldalre- INSERH U 316, CHU Bretonneau, TOURS ,
France.
*** Centre d'Immunologle et Biologle PIERRE FABRE, CASTRES, France. SCINTIGRAPHIC IMAGING OF LUNG CANCERS USING D25, A GLYCOPEPTIDIC IMMln40MODULATOR ISOLATED FROM KLEBSIELLA. The recruitment of macrophages is a host reaction occuring at the very early stages of growth in a wlde variety of primary tumours and metastases. Using experimental models of lung granulomatosls and radio-induced carcinogenesis In baboons, we have demonstrated that the /n vivo targeting of macrophages should offer a new strategy for the sclntlgraphie detection of lung cancers and metastases, mainly invaded lymph nodes wlth slze less than I cm in diameter. In a first step, NSPD (Nocardla Soluble Peptldoglycan Derivate) that electlvely concentrated into activated macrophages was successfully used as a sclntlgraphlc agent after 99m TC labelllng. Due to its physlcochemlcal properties, NSPDwas relatively heterogenous and It had to be administered as an aerosol after encapsulation into llposomes to facilitate Its absorption through the alveolo-capillar barrier. So, a fully chemically characterized molecule (D2S) was developped from membrane proteoglycans of a non pathogenic strain of K1ebslella pneumonim. This amphiphatic agent that is absorbed by the lungs without the requirement of any encapsulatlon into llposemes was demonstrated to image in baboons inflammatory lymph nodes in experimental berylllosls and submacroscoplc lung radlo-lnduced tumours. 15 patients with lung cancers gave informed consent and were explored after inhalation of I mg D2S labelled wlth 555 MBq 99m Tc in the presence of stannous chlorlde. In ? patients, medlastinal lymph nodes and hllar tumours were imaged. A milllmetrlc cutaneous metastase and a metastatic proved axlllary lymph node were discovered in 2 patients. Images were difficult to Interpretate In 6 patients wlth serious ventilation defects but no falsely positive image was found out of tumoral areas. We conclude that the targeting of macrophages with D25 could be a potent strategy for imaging lung cancers and their lymphatic involvements.
204
r ~I,Babich. B.Davidson, H.Young, W.Waddington, G Clarke, M.Short, P.Boulos, J Styles, C. Dean. Department of Nuclear Medicine, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey and Departments of Surgery and Nuclear Medicine, University College and Middlesex School of Medicine, London, U.K. IMMUNE COMPLEX FORMATION AND THE BIODISTRIBUTION OF 111In LABELLED MONOCLONAL ANTIBODY(MAB) FOLLOWING COLD MAB ADMINISTRATION Circulating immune complexes may affect the results of radiolabclled MAB imaging. Wc have investigated the effect on biodistribution of administering uniabelled MAB to Epithelial Membrane Antigen (EMA)(5mg in 1130mls normal s,-dineintravenously over one hour) prior to administering 1 mg of the same antibody labelled with 1111n.(MAB ICR2. 100MBq 11 fin/rag MAB) in 12 patients with colurectal cancer. Circulating antigen was assessed by a competitive binding assay and immune complex by HPLC. Blood, urinary and tumour activity was assessed by gamma well counting of samples. Liver uptake was assessed using an anthropomorphic phantom and region of interest analysis for the spleen, bone marrow and kidneys. Patient serum analysis prior to lllIn-MAB administration showed [EMA] of 544+/- 340* ng/ml. On I-IPLC of serum prior to cold antibody administration using 125I labelled ICR2 34.2+/-4.66*% of activity formed high molecular weight (mol. wt.) complex. Cold MAB administration in 6 of the 12 patients reduced this by a mean of¢% to 30.2+/-1.92*%. Following 1111n-ICR2 administration the % high mol .wt. complex decreased with time, the rate unaffected by cold MAB administration. Liver uptake at 48 hours was significantly less and spleen uptake at 45rains, 24 and 48 hours significandy greater (all p<0.05) in the cold MAB group. No significant differences were found with cold MAB administration regarding the tumour, marrow or kidney uptake nor the blood clearance or urinary excretion of activity. Large amounts of unlabelled MAB would be required to inhibit circulating immune complex formation. * mean +/- standard deviation.
450
205
J.Spltz*,
206
M.Stoecker*, M . F i s c h e r * *
* D p t . o f Nucl. Med., Municipal Hospital, Wiesbaden, F R G ** D p t . o f N u c l . Med., M u n i c i p a l H o s p i t a l , K a s s e l , F R G
COMPARATIVE MEASUREMENT OF BONE MINERAL C O N T E N T WITH D P A A N D D E X A This s t u d y c o m p a r e s t h e e f f e c t i v e n e s s o f t h e e s t a b l i s h e d d u a l p h o t o n e b s o r p t t o m e t r y (DPA) w i t h t h e n e w l y d e v e l o p e d d u a l e n e r g y x - r a y a b s o r p t l o m e t r y (DEXA). Material and Method: 120 p a t i e n t s w e r e m e a s u r e d w i t h t h e L u n a r D P A a n d L u n a r D E X A s y s t e m on t h e s a m e d a y . T h e BMD o f t h e l u m b a r spine and the proximal femur was estimated. The reproducibility w a s e v a l u a t e d b y t h e 10 f o l d i n v e s t i g a t i o n o f a s p i n a l phantom a n d t h e l u m b a r s p i n e of e v o l u n t e e r . Results : 1) B o t h t e c h n i q u e s a r e a p p l i c a b l e to t h e p a t i e n t w t t h o u t p r o b l e m s 2) T h e g o o d p r e c i s i o n o f t h e D P A i n s t r u m e n t is s t i l l s u r p a s s e d b y t h e D P X v a l u e s (1,5 % to 0 , 3 5 % ) f o r a s p i n a l phantom. 3) S m a l l e r r a d i a t i o n e x p o s u r e b y D P X (2 m r e m v e r s u s 5 m r e m in DPA). 4) T h e I n v e s t i g a t i o n t i m e is r e d u c e d f o r D P X ( f a c t o r 3). 5) T h e r e s o l u t i o n o f t h e D P X s c a n s is much b e t t e r t h a n t h e D P A t e c h n i q u e . 6) T h e t n d t v l u a l v a l u e s of b o t h t e c h n i q u e s a r e c o m p a r a b l e (r = 0,96). T h e l i n e a r r e g r e s s i o n e q u a t i o n f o r t h e l u m b a r s p i n e Is D P X = 0 , 8 9 D P A + 0 , I 6 . 7) T h e D P X t e c h n i q u e a l l o w s t h e BMD e s t i m a t i o n of more different skeletal sites and the whole body. 8) T h e D P X s y s t e m s n e e d no c h a n g e of t h e G d - 1 5 3 s o u r c e . Conclusion : T h e n e w D E X A t e c h n i q u e f o r t h e e v a l u a t i o n of t h e BMD s u r passes the established DPA technique by better precision, higher resolution, shorter scanning times and lesser radiat i o n e x p o s u r e f o r c o m p a r a b l e r e s u l t s o f t h e BMD in l u m b a r spine and femur.
207
R. Valkema, L.F. Vcrheij, J.A.K. Blokland, S.E. Papapoulos, O.L.M. Bijvoet, E.K.J. Pauwels. Division of Nuclear Medicine, department of Diagnostic Radiology and Clinical Investigation Unit, department of Endocrinology, University Hospital, Leiden, The Netherlands. PREC~ION OF DPA IS ~ BY VARIATIONS IN SOFFTISSUE To calculate the bone mineral content (BMC) of lumbar vertebrae from dual photon absorptiometry (DPA) measurements, the subtraction of a soft tissue (ST) baseline is necessary. The paravertebralST is assumed to be homogenous and representative for the ST inside the region of interest (ROI). The extent to which ST non-homogeneity contributes to errors in calculation of BMC is not clear. Therefore, we have investigated the variations in the ST baseline in patients and normal volunteers, and calculated the estimation error in the final BMC result caused by these variations. DPA of the lumbar spine (L2 - L4) was performed with a Novo BMCLAB 22a densitometer. The weighted mean and standard deviation of the ST layer were estimated, thereby automatically excluding falsely low (e.g. perirenal fat) and high values (e.g. ribs). Results with this method were compared with the random error (Poisson distribution), calculated using the countrates in the 44keV and 100keV channels, and straightforward measurement of the variations in water layers of different height. The estimated error with the new method matched very closely (r = 0.98) to the calculated and measured errors. In all of 57 patients with osteoporosis, the ST variations were larger than the expected random error, typically twice as large. This reveals a source of error related to the non-homogeneity of the soft tissue in humans. Variations in ST of normals were slightly less than in patients. However, the error of estimation in BMC caused by ST variations was 1.5% in patients (mean BMC = 26 gilA) and 0.7% in normals (mean BMC = 43 gilA). The CV derived from duplicate measurements in normals was 0.7% - 1.4% (2 observers) and in patients 2.6%. Our results indicate that ST related errors are an important limit to the precision of DPA measurements. Other sources of error, such as ROI selection, repositioning and longer term fluctuations in performance of the densitometer will add to this.
208
P. Theissen, A. Hoffmann, M. Jungeh~ilsing, A. Linden, K.F.R. Neufang, J. Wollenhaupt, M. Kr~imer, H. Zeidler, H. Schicha.
rc_Y~[LcLqL~J:¢[~, St v Gumppenberg**, B AIIgayer***, R Bauer*, HR Langhammer*, HW Pabst*
Institute of clinical and experimental Nuclear Medicine and Medical Clinic II University of Cologne, Cologne, FRG
*Nuklearmedizinische Klinik, **Chirurglsche Klinik, ***lnstitut for RSntgendiagnostik Technische Universit~lt, Klinikum rechts der Isar, Munich, FRG
SACROILIITIS: EVALUATION BY MAGNETIC RESONANCE IMAGING, RADIOGRAPHY, AND BONE SCINTIGRAPHY Conventional diagnostic of the sacroiliac joints often shows equivocal results, especially in early stages of sacroiliitis (SI). Fiftysix patients with clinical signs of SI and normal or equivocal findings by radiography and bone ecintigraphy (BSc) underwent magnetic resonance (MR) examination. Transverse magnetic resonance images of both sacroiliac joints (SCJ) were acquired on a 1.5 Tesla magnet. T1, "i"2, and protondensity weighted spin echo images with a slice thickness of 6 mm were performed. In 45 patients T2 weighted gradient echo images were acquired. Conventional lumbar spine, and pelvic radiographies were performed in all patients additionally. Planar MDP-BSc was performed in the early and the late phase All patients ' underwent SPECT imaging of the lumbar and pelvtc region. For comparison, MR imag ng was performed in 10 healthy volunteers. Radiographies, BSc and MRI were evaluated without knowledge of the results of the comparative studies. I The Sl Ioatients were classified in two groups (I,II). Group I included 381 )atients with clinical signs of SI and radiological grade 0 or t of SI according to the Benett-classification. The 18 patients of group II had the definite radiological diagnosis SI (grade 2 to 4 of the Benett-classification). The MR| changes in signal intensity at the SCJ and the surrounding bone marrow (BM) were interpreted as destruction of the cartilage, increased intraarticular fluid and signs of inflammation of the periarticular BM. All group II patients had two or more of these findings but also 29/38 (76%) of the patients in group 1. None of the controls showed these findings. In group I 22/38 patients (57%) and 14/18 patients (80%) of group II showed an increased radionuclide uptake at one or both SCJ by SPECT imaging. Only 4/38 group I patients and 2/18 group II patients showed an increased radionuelid uptake in the planar BSc in the eady phase. This study frequently showed pathological MRI findings indicating SI in patients with clinical symptoms but normal or equivocal radiography of the sacroiliac joints. MRI also seems to be more sensitive than BSc detecting signs of inftammtion in early stages of SI. Therefore, MRI is expected to allow an earlier diagnosis of SI.
COMPARISON OF BONE SCAN AND MR IMAGING IN TRAUMATIC VERTEBRAL FRACTURES Bone scan (BS) has proven to be a useful diagnostic procedure in detecting primary and metastatic bone disease as well as in evaluating skeletal trauma. MR imaging (MRI) seems to be more sensitive In vertebral metastasis. The aim of the study was to compare the diagnostic value of both BS and MRI In traumatic vertebral fractures (n=56) of different age (age of fracture from 0-2 too: 11, from 3-6 too: 5, from 7-24 mo: 34, from 2448 too: 6). The age of the patients ranged from 18 to 35y. All fractures were classified by BS according to radlonuclide uptake in 4 groups: normal (GO), weak (G1), moderate (G2) and marked Increased (G3). These results were compared with findings in MRI, especially increased signal In T2 images but also abnormal signal in T1 images. 016 GO-, 2/28 Gt-, 10/15 G2- and 717 G3-fractures showed signal enhancement of different degree In T2 Images. Decreased signal in T1 Images correlated either with marked Increase In T2 (edema) or with loss of signal In all modes (sclerosis). Increased signal In T1 was only found In G1 representing fatty degeneration of marrow in fractures older than 12 mo. t. According to pathophysiology, BS Is more sensitive than MRI in detecting and follow up of traumatic InJudes of the vertebra. 2. MRI may be useful as primary investigation in patients with neurological deficits and before surgical Intervention.
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210
P. Heintz,
Ch. Ehrenheim,
E. Peters,
M. Hammer,
H. Hundeshagen. Department of Nuclear Medicine, Centre of Internal Medicine and Dermatology, Medical School of Hannover, FRG MR
IMAGING:
A
NEW
METHOD
IN
THE
DIAGNOSIS
OF
SACROILEITIS?
Aim of the study: Examinationof patients with clinical signs of sacroileitis in the acute stageand in the follow-up.
Patients: The patients examined were suffering from various diseases:M. Bechterow (15), polyarthritis (8), unspecific arthritis (6), and reactive arthritis (6). Furthermore a control group consisting of 15 narmals was examined.
Methods: Basic diagnostic means included clinical end serological examinations. In all patients conventional x-ray, and in some cases conventional tomagraphy was performed. Dynamic bonescanning was done in the elder patients, additionally. All patients underwent magnetic resonance imaging. In order to reduce MR imaging time (30 min) - because the examination in supine position was very painful in the most cases - coronal views in T I - , proton density-, and T2-weighted sequenceswere done, only. Thereafter, calculated T I - and T2-images were made. Results: The MR images provided the following informations: I. A diffuse increase of T 1 and T2 in the bone marrow beside the sacroiliac joint was observed in the acute stage, only, without signal changes in the area of the joint itself. 2. 3ubsequently, T2-weighted high signal intensity within the sacroiliac joint (meaning increasedintraarticular fluid) without any changes (inflammatory) in the bone marrow was observed. 3. No inflammatory intrsertioulor or periorticu]ar changes were found, i.e. no signal changes persisted, whereas the area of the joint appearedblurred, now (sclerosis). The acute stage as described ( 1) was found in 6 patients, the intermediate stage (2) was seen in 5 patients, and the stageof sclerosis (3) in 7 patients. All other MR examinations did not reveal pathologicalchanges. MR imaging seemsto be a highly sensitive imaging method in the diagnosisof secroilettts, as an advantageit does burden the almost young patients with ionizingradiation.
211 P. Antonacci*, M. Bellb*, G.L. Canata °, G.C. Castellano*,
G. Ceppi*, G. Comaglia*, C.L. Maini^, V. Podio*, A. Sargiotto*, (~.L. Turco*
J. L u m b r o s o * , O. Oberlin**, Ph. Terrier***, 0 Hartmann**, Z. Chouffai**, V. Edeline* D Valteau**, L. Brugieres**, J. L e m e r l e * * and C. Parmentier*. Departments of N u c l e a r M e d i c i n e (*), Pediatrics (**) and H i s t o p a t h o l o g y (***) of Institut G u s t a v e Roussy, and I N S E R M U66 (*), Villejuif, France. MAY 123-1 m I B G C O N T R I B U T E TO I M A G I N G EW1NG SARCOMA OF BONE? The role of radiolabelled meta-iodobenzylguanidine (mlBG) is established in the detection and staging of neuroblastoma. We designed a study of mlBG scanning for patients with Ewing's sarcoma, a tumour for which a neuroectodermic origin has been proposed. We studied 15 children with round cell sarcoma of bone analysed by histology and immunochemistry. The site of the primary was pelvis (5 cases), vertebra (1), sternum (1), ribs (2), femur (2), tibia (3) and fibula (1). Four patients had metastatic spread in the 1,m~ (1 case), m the lung and bones tl), an me bones and me bone man'ow (l) and only in the bone marrow (1). All the patients were explored by conventional imaging techniques, including CT, MRI and technetium-99m hydroxy-methylene diphosphonate (HMDP) bone scans. In addition, a whole body scan was carried out 24 hours after injection of 3.7 MBq/kg of 123-I mIBG. All these tumors showed histological uniformity of small round cells without rosettes. Glycogen was absent in 2 patients as defined by PAS negative staining. Detection of neuron specific enolase was performed in 12 cases and was positive in 6 cases. HMDP scans were all positive at the level of the primary and of the bone metastases ; however, this technique did only demonstrate the reaction of normal bone to the tumor without direct tumor visualization. No patient demonstrated significant mIBG uprake neither at the level of the primary tumor nor of the metastases. These negative results may be linked with the already described expression of only cholinergic transmitter enzymes, acquisition of adrenergic neurotransmitter enzymes being typical of more differenciated neural tumors such as neuroblastoma. Although HMDP scan is a non-specific imaging technique, it remains the only isotopic modality for explorin~ Ewin~'s sarcoma patients.
212 G.Panoutsopoulos I, P.Megas 2, K.Dafermou I, • I • N.Papathanasiou 2, E.Lambiris Z, J.Christa.
I
*Cattedra di Medicina Nucleate - Universitd di Torino (Italy) °Centre Traumatologico Ortopoedico - Torino (Italy) ACattedra di Medicina Nucleate - Universit~ di Ancona (Italy)
I. Nuclear Hedicine Department of the Athens hospital for diseases of the chest, "SOTIRIA" 2. Orthopaedic Department off General Hospital of Athens
Three-Phase Bone Scintigraphy in Athletes
BONE SCAN (BS) AND BONE MARROW SCAN (BMS) IN POSTRAUNATIC AND AVASCULAR FEMORAL HEAD NECROSIS (FHN).
Dynamic and static bone studies were performed in 18 athletes with dynamic acquisition at injection and static imaging at 5 minutes and four hours with 99mTc-MDP. In 14 among them, x-rays were not able to show alterations; in the remaining four, radiographs, although positive, were considered unsatisfactory and insufficient to explain symptoms.
Aim of the study was to evaluate the contriuution uf scintigraphy in the diagnosis of postraumatic and avascutar FIIN. We studied 66 pts. Forty eight of them (group I) had femoral neck fracture (32 pts) or dislocation of the hip (16 pts). The remaining 18 pts (group if) without a history of trauma had hip pain and their radiological finoings were suggestive of FHN or unremarkaule.Aii pts were submitted to 3 pilase BS and only 27 of them to 3 phase ahS. The scintigraphic findings were compared to the clinical, radiologieal and surgical ones during the fallow-u 9 period that ranged from 9mo to 5yrs (means 24 mo). T~eitty two oF the pts, 11 of each group had abnormal pacterns, in the metabolic phase of BS.In 9 of them of group I the accumulation of radioactivity in the FH was reduced or completely absent, while in the remaining 2 of the same group as well as in the 11 pts of group If,the accumulation of radioactivity in the FH was diffusely or focally increased. Confirmation of FHN was made in 18 of these 22 cases while in the other 4 remains improven. The BHS was helpfull in only 13 out of 27 cases (7/11 with necrosis and 6/16 without). The remaining 14 BHS were unhelpful3 mainly because of lack of UN activity even in the healthy head. The arterial and blood-pool phase of fiS as weli as of BMS were unhelpfull. Conclusion: The BS is a very sensitive (100%) and specific me{hod in the early diagnosis of FhN. The pattern of postraumatic necrosis is reduced activity in contrast to the avaseular necrosis pattern which comprises diffusely or focally increased activity. The 81.15 sensitivity !is 63% while its specificity is only 37,5Z.
Dynamic and static bone scans showed no alteration in six patients among the 14 with negative x-rays: subsequently a diagnosis was established in all these patients and was consistent with negative scintigraphy. In the remaining 8 patients with negative radiographs, scintigraphy was abnormal and showed one periosteal injury, one tibial stress fracture and one covert fracture; five patients had joint abnormalities and connective tissue injuries. In the four patients with positive x-rays, two had bone scanning consistent with radiological diagnosis, in one scintigraphy revealed a tibial stress fracture not detected on radiographs and the last showed knee joint abnormality not evident on x-rays film. All final diagnosis were established on the basis of subsequent x-rays imaging, arthroscopy or clinical evolution. In our athletes population, three-phase bone scintigraphy proved to be able to detect soft tissue abnormalities non showed by x-rays imaging; it was also abnormal in bone injuries not evident in radiographs. Final diagnosis, as established according to standard criteria and without scintigraphy contribution, was in all ways consistent with bone scan results.
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213
~,
M.Clausen,E.Henze,E.Sigmund ,W.E.Adam
*,
Div. of Nuclear Medicine, University of Ulm, (FRG) * Bundeswehrkrankenhaus Ulm, (FRG)
J. Vanreaemorter 1, A. Bossuyt 1, F. De Geeter 1, A. B6ttger3, F. Canters 2 Departments of Nuclear Medicine 1 and Geography2 Vrije Universiteit Brussel, Brussels, Belgium and University of Technology 3 , Delft, The Netherlands.
A GENERAL PROCESSING METHOD FOR SPECT AND PET-STUDIES
OF THE BRAIN USING REFERENCE-CIRCLE-METHOD Quantification of regipnal findings of PET and SPECT-studies of the Drain is dilfieult and is mainly done by comparing left and right side_count rate differences of drawn regions in selected slices. To overcome these shortcomings a method was developed, that allows quantificatxpn of findings in tomographic brain studies oy aigital comparison to the distribution of normals, including the dedicated standard deviations . This new REFERENCE-CIRCLE-METHOD involves the following steps: The tomographie brain slices were transformed t9 their standard circles. The radiant orofiles o~ varying l@ngth from the original . slices were transrormeo Dy Linear interpolation Znto the radii of the standard circles using 360 sample angles. thereby_ transferring the variation in shape and size ot the indivxdual human brain slices into standard sized circles. Retransformation of original shade and form of the data is feasable with an error ol 1%±0.3%. As a first application, 1 5 studies of patients with normal TC-HHPAO uptake were transformed and superimposed to form mean normal standard matrices including standard deviations of normal. Individual brain scan examples were compared against the normal reference matrices, documenting areas of significantly depressed Tc-HMPAO uptake. The results of this REFERENCE-CIRCLE-METHOD proved to be highly reproduceable. The m e t h o d may be applied to all brain scans to firstly create normal reference pattern and secondly, to quantify abnormal regional distTibution of activity uptake automatically and without the need of controversial ROI-techniques.
215 B.M W Tsui, D.R G~lland, X.D. Zhao, J.G. Ballard, E.C. Frey, G'.T. Gullberg ~, J.R. Perry, W.H. MeCartney and T. Bernstein 2 .
APPLICATION OF CONFORMAL AND EQUIVALENT TWODIMENSIONAL REPRESENTATIONS TO SPECT BRAIN DATA The method of two-dimensional representation allows an observer to compare equal regions of the left and right hemisphere of the brain rather than stepping through the subsequent transversal slices of a reconstructed brain SPECT. We have applied various two-dimensional representations of three-dimensional data and evaluated the results on HMPAOSPECT studies. After total volume reconstruction, the three-dimensional data are reoriented to a plane parallel to the orbito-meatal line and rescaled using the cerebellar activity as a reference. Interactive thresholding is applied to mask background and inner white matter activity. The data are recentered to the center of the slice below the frontal lobes and above the cerebellum. From this point, the data are integrated in all radial directions and projected to a sphere inscribed in the 64x64x64 data cube. To represent these data we have applied both stereographic and conical projections which yield conformal (with retention of angles) or equivalent (with retention of areas) two dimensional representations of the three dimensional data. The resulting 'brain maps' can be compared easily with the maps of a normal individual or with previous examinations of the same patient. To evaluate various projections we have applied them to repeated HMPAO-SPECT studies performed in stroke patients with and without visual stimulation and compared with the results obtained with the use of three dimensional ROIs. 216 Bailey DL, Hutton BF, Meikle SR, Fulton R R and Jackson CB. Department of Nuclear Medicine, Royal Prince Alfred Hospital, Sydney, Australia.
Univ. of North Carolina at Chapel Hill, Chapel Hill, NC, USA, Iuniv. of Utah, Salt Lake City, UT, USA, 2CE Medical Systems Group, Milwaukee, WI, USA.
IMAGE RECONSTRUCTION AND PROCESSING TECHNIQUES FOR IMPROVED QUANTITATION IN CARDIAC SPECT IMAGING Quantitative information in cardiac SPECT imaging is affected by photon attenuation, detector response and scatter. The problem is compounded by different tissues with highly non-uniform attenuation coefficients in the chest region. We applied and evaluated image reconstruction and processing methods which compensate for these effects for improved quantitation in cardiac SPECT. These methods utilize iterative reconstruction algorithms which accurately model the non-uniform attenuation in the chest region and the response function of the detector system. Scatter radiation is compensated by subtraction using a dual energy acquisition method. In the evaluation study, a realistic cardiac-chest ~hantom was generated based on patient x-ray CT scans. Projection data were generated from the phantom with the effects of attenuation, detector response and scatter. The corrective reconstruction methods were compared with conventional methods in terms of the accuracy in reconstructing the known activity distribution in the computer-generated phantom. An experimental phantom which simulates the cardiac-chest region was also constructed. The quantitative accuracy of the reeonstruetion methods was determined based on the known radioactivity distribution placed in the phantom. The results demonstrate the greater quantitative accuracy obtained from the correction methods using the iterative algorithms.
ITERATIVE SCA'ITER CORRECTION INCORPORATING ATTENUATION DATA Scatter correction methods in SPECT and PET generally assume that scatter is an additive component of the measured data. Based on this model, we have further developed this approach to incorporate an .iterative estimation of scatter which incorporates attenuation (/~) data in the spatial distribution of scatter. This iterative scatter correction (ISC) provides estimates of scatter frcc projection data given by: gn=g0-k(g~.,*s) where go is the original projection data, go.1 and g, are the previous and current estimates of the scatter flee data g, k is the scatter fraction, s is the mono-exponential scatter function, and * indicates 2-dimensional convolution. The scatter fraction k can either be a scalar or a 2dimensional function estimated from sactter build-up which based on the measured/~ data. SPECT studies were conducted on phantoms which incorporated a high or low attenuation object containing no radioactivity (100% contrast) and a 'hot' cylindrical flask in a low activity background. All studies were 2nd order attenuation corrected with a modified Chang algorithm incorporating measured/~ values. Results for contrast and quantitative accuracy are shown below. Correction Applied %Contrast %Accuracy High /~ Low/.~ High/.* Low No scatter correction 76 78 103 104 ISC(k=f(/.0) 99 89 97 104 ISC(k=constant) 99 97 94 99 Axelsson's method 100 95 81 77 ISC generally exhibits excellent contrast while maintaining quantitative accuracy. Incorporation of ~ values derived from simultaneous emissiontransmission acquisitions may have particular relevance for both attenuation and scatter correction in thoracic tomography.
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J. DELFORGE, M. JANIER, J.M. VALLOIS*, C. CROUZEL, J. CAYLI D. FOURNIER, M. CROUZEL, B.M. MAZOYER, A. SYROTA.
O. Muzik I, H. Herzog i, R. Fulton 1,2, Kuwert: and L.E. Feinendegen I
K.-J. hangen I, T.
Service Hospitalier Frdddric Jolio 6 CEA, 91406 Orsay, France. *Inserm U13, H~pltal Claude Bernard, 75108 Paris, France
i)Institut ffir Medizin, KFA Jfilich 5170, J61ich, FRG 2~Department of Nuclear Medicine, Royal Prince Alfred Hospital, Sydney, AUS
IDENTIFIABILITY ANALYSIS AND PARAMETER I D E N T I F I C A T I O N OF A N IN VIVO L I G A N D - R E C E P T O R MODEL. We have investigated the possibility of identifying from positron emission tomography data the parameters of a ligand-receptor model including three compartments (arterial concentration, free ligand and specifically bound ligand) and six parameters. This non-linear model i allows to identify separately the receptor density (Bma=) and the association and dissociation constants (k+l and k-l). Last year (Syrota 1988), we have shown that a complete identification was possible from data obtained in the case of C-11 labelled MQNB binding to myocardial aeetycholine receptors, provided that a displacement experiment (injection of an excess of unlabelled ligand) is performed 20 rain after the tracer injection. Actually this protocol led to two very different identified parameter sets with acceptable standard deviations and corresponding to two satisfying and very similar fits. This result shows that a good fit and acceptable standard deviation estimates are not sufficient to prove the biological validity of the identified parameters. In order to discriminate between these two solutions, we have used a protocol including three injections by adding a co-injection ( injection of both labelled and unlabeUed ligand) at 40 min. With this new protocol, which led to a unique solution, we have obtained a quantification i of the model parameters. In dog, Bma z is found to be equal to about 25+ 5 nM, k+l to 3 i 0.3 ml/(pmol rain) and k-1 to 0.3 4-0.02 rain -1. Thus the dissociation constant Kd, defined by the ratio k-l/k+1, is estimated to 0.1 nM. Reference: Syrota A., Delforge J., Mazoyer B.M., Ear. J. Nucl. Med. vol. 14, p. 232, (1988).
NODELLING OF A DOUBLE-INJECTION TECHNIQUE FOR CONBINED CONTROL-STIMULATION STUDIES OF CEREBRAL ACTIVATION USING PET AND 18FDG. Changes of cerebral glucose consumption (LCNRglu) caused by external stimuli have recently been examined by our group using two combined PET studies with ISFDG. LCMRglu for control and stimulation was calculated by a simplified approach. The aim of this study was the derivation of an exact mathematical formulation of this technique, so that individual changes of LCZRglu between control and stimulation could be measured using fitted rate constants. After a first injection of FDG the control state was examined by a dynamic PET scan for 50 minutes. Immediately after the stimulation was started, a second injection of FDG was given and another sequence of PET images was obtained for 50 minutes. Curves of tissue activity uncorrected for decay were obtained for various cortical areas. A general solution for the second FDG scan sequence was derived with respect to the different decay corrections for both injections as well as the remaining tracer from first injection. The analysis shows that this solution can be expressed by the usual FDG equation with two additional exponential terms representing residual tracer from the first injection. Thus the time course of activity in the free and metabolic compartments could be determined throughout the whole procedure, yielding LCMRglu in both states. We have applied our model formulation to a number of test-retest studies, and it appears to be well suited to the determination of changes in LCMRglu.
220
219 A.M.J. Paans, B.J.G. Daemen, Ph.H. Elsinga, W. Vaalburg
Department of Nuclear Medicine University Hospital Groningen The Netherlands DETERMINATION OF THE IN-VIVO PROTEIN SYNTHESIS RATE USING DYNAMIC PET DATA FROM L-[I-IIC]TYROSINE IN AN ANIMAL MODEL. A four compartment model is used to describe the protein synthesis rate (PSR) using L-[l-11C]tyroslne (llC-tyr) in an animal model. The four compartments are the plasma, the intercellular free pool, the protein bound compartment and the metabolites formed from 11C-tyr. llC-tyr was selected because its very low metabolite fraction. By injecting the llC-tyr into the femural vein of a rat positioned inside the positron camera, dynamic tissue data are obtained. The plasma data, obtained from blood samples, are fitted by a multi-exponential function. Special attention is paid to the onset of the input profile since this part of the input function determines the value of the rate constant describing the outflux of amino acid from the plasma into the tissue. The tissue data are than fitted by adjusting the kinetic parameters of the model. Incorporated into the model is the fact that 11C02, being the main metabolite of 11C-tyr, is exhaled immediately. After the fitting procedure the PSR is calculated from the model parameters and the cold plasma concentration of tyrosine. The use of such a model in the field of oncology not only yields an important functional parameter but is also valuable in the evaluation of the efficacy of therapeutic interventions llke radiotherapy and/or hyperthermia. The model and the extraction of metabolic parameters from dynamic PET data are tested using two experimental tumor models, Walker 256 carcinosarcoma and rhabdomyosarcoma in rats. In both tumor models also the effect of therapeutic interventions was studied.
P. HANNEQUIN, J.C. LIEHN, J. VALEYRE
Department of Nuclear Reims, France.
Medicine,
AUTOMATIC SEGMENTATION OF DYNAMIC CLUSTER ANALYSIS.
Institut
J.
Godinot,
SCINTIGRAPHIES
USING
An original fully automatic algorithm is proposed to select Regions of Interests (ROls) on dynamic series of scintigraphie images. This algorithm is based on the joint us~ of Factor Analysis and Cluster analysis. It consists of extracting the orthogonal factor images of the series using Factor Analysis of Correspondence. These factor images are then automatically divided in ROIs using a Hierarchical Ascendant Classification procedure. The distance used for the classification is the "minimum added intra-class variance" distance. This algorithm has been implemented on a SUN based Nuclear Medicine System (Nodecrest Micas V system). The time of calculation is less than 5 min for a dynamic series consisting of 40 images when the search for the ROls is limited to an area of i000 pixels and when S factor images are used. This algorithm has been validated using a numerical phantom and has been illustrated using renal (99m Tc DTPA) and cardiac (equilibrium gated angiography) dynamic scintigraphies. The results show that the algorithm is able to automatically recognize the bladder, the renal cavities and the renal parenchyma on the renal series and the ventricules and the atria on the cardiac series.
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P. DIOT*, E. LEMARIE*, N. VERNEUIL*, C. JUBAULT*, 3.L. BAULIEU**, P. CHOUTET***, F. BASTIDES***, J.C. BESNARD**, L. POURCELOT** and A. LE PAPE*.
A. M e r c i e r , B. D e l a l o y e
* : Laboratoire de Blsphysique Cellulaire - C.N.R.S. - Facultd de H~decine, TOURS, trance. ** : Service de M4declne Nucl~aire, CHU Bretonneau, TOURS, France. *** : Service de M4decine Interne, CH~3 Bretonneau, TOURS France.
Centre
INTEREST OF THE SCINTIORAPHIC QUANTITATION OF PENTAMIDINE DELIVERY TO TH£ DEEP LUNGS FOR THE OPTIMIZATION OF AEROSOLTREATHENTS IN AIDS PATIENTS Aerosollzed Pentamldine is extensively used for the treatment of Pneu-~ mocystls csrlnll pneumonia in AIDS patients. However, to-date, protocols of treatment suffer from a lack of standardization for the use of nebullsors, and the delivery of Pentamldlne to the deep lungs should bealte~ ed by bronchopulmonary lesions and adverse reactions of the drug. So, we have developped a sclntigraphic method to assess the deep lung accessibility of the drug when administered in the conditloms of the treatment. Two hundred mg of Pentsmldlne (LomldlneR) was labelled wlth 370 MBq 99m terhnmtJt~ ~f~er redHnttnn with stannous chloride. The ~erosol was administered using two types of nebulisors : an Ultrasonic TV 6000SIEMENS (Germany) and a compressed a i r Ventieis IIORIS (France) device. The tecN nique was formerly assessed in four unanesthetized baboons receiving the ;radioaerosol for 15 min and submitted to a dynamic seintlgraphy or the thorax. In a second step, four AIDS patients submitted to s preventive treatment gave informed consent and participated in the study. A f i v e minutes static acquisition was performed immediately after the inhalation and the Pentamidtne lung burden was assessed based on the comparison of the lung a c t i v i t y to the counts obtained in a thorax-like phantom containing 37 HBq 99m Tc. Using the TV6000 nebulisor, only 0.4 ~ of the i n i t i a l dose, i . e . 0.8 mg deposited into the lungs whereas the oesogastric tract was dramatically contaminated (3.1 ~). With the Ventteis I I device, 2.1 ~, i.e. 4.2 mg reached the deep lungs contrasting with the negligible gastric contamination. These results rule out the crucial role of the aerosolization procedures end the requirement for a quantitation of the dose effectively delivered to the deep lungs. The scintigraphic quantitatton of aerosolized Pentamidine should provide a potent tool for the optimization of curative and preventive treatments of Pneumocystis c a r i n i i pneumonia in AIDS patients
223
A. B i s c h o f - D e l a l o y e ,
Hospitalier
Universitaire
M. D u t o i t ,
Vaudois,
CL-H.
Blanc,
1011 L a u s a n n e
DETECTION OF SUBACUTE AND CHRONIC OSTEITIS WITH TC 99M LABELED ~TIGRANULOCYTE M O N O C L O N A L A N T I B O D I E S (MAb)
The a i m o f t h i s s t u d y w a s to d e t e r m i n e if i m m u n o s c i n t i g r a p h y w i t h T c - 9 9 m a n t i g r a n u l o c y t e s M A b was h e l p f u l in the d i a g n o s i s of s u b a c u t e a n d c h r o n i c o s t e i t i s w h e r e o t h e r n o n i n v a s i v e p r o c e d u r e s m a y n o t be c o n c l u d i n g . 40 p a t i e n t s , 27 m a l e s , 13 f e m a l e s , a g e d f r o m 20 to 92 y e a r s h a v e b e e n s t u d i e d a f t e r i n f o r m e d c o n s e n t a c c o r d i n g to the p r o t o c o l s a c c e p t e d b y the l o c a l e t h i c a l c o m m i t t e e . M e a n i n j e c t e d a c t i v i t y w a s 25 mCi. P l a n a r i m a g e s w e r e a c q u i r e d 1 , 4 - 6 a n d 2 0 - 2 4 h a f t e r i n f u s i o n (30 ~ ) of the T c - 9 9 m ~Ab. 28 p a t i e n t s p r e s e n t e d w i t h p a i n f u l t o t a l h i p a r t h r o p l a s t y (THA) (26) o r knee p r o s t h e s i s (2), in 12 o t h e r p a t i e n t s o s t e i t i s o f i n f e r i o r (ii) or s u p e r i o r (i) l i m b s w a s suspected. Final diagnosis was made by microbiological e x a m i n a t i o n in 34 cases, 20 p o s i t i v e , 14 n e g a t i v e . O n l y t h e s e 34 p a t i e n t s w e r e t a k e n i n t o c o n s i d e r a t i o n . T h e r e w e r e 1 6 / 2 0 (80%) t r u e p o s i t i v e , 1 3 / 1 4 (93%) true n e g a t i v e 1 false positive (sympathetic reflex dystrophy) and 4 f a r s e n e g a t i v e r e s u l t s (4 i n f e c t e d THA). M o s t o f the p o s i t i v e c a s e s w e r e a l r e a d y s h o w n on the 4-6 h images. The t i m e c o u r s e Of p a t h o l o g i c a l u p t a k e v e r s u s n o r m a l b o n e marrow visualization was often helpful whereas ECT a l l o w e d to c l a r i f y d i a g n o s i s in a s m a l l n u m b e r of ~atients only. These data indicate that immunoscintigraphy is u s e f u l in the d i a g n o s i s of s u b a c u t e a n d c h r o n i c o s t e i t i s a n d t h a t it h e l p s to d i f f e r e n t i a t e s e p t i c f r o m m e c h a n i c a l l o o s e n i n g o f THA.
224
K.H. Winker, P. Reuland, U. Feine, S. WeilBr
R.A.M.J. Claessens. W.J.G. Oyen, W.J.M van den Broek, F.H.M. Corstens and J.W.M. van der Meer Trauma Center and Department of Nuclear Medicine, University of TObingen, FRG INFECTIOUS COMPLICATIONS IN ORTHOPEDIC SURGERY: IMAGING WITH THE NONOCLONAL ANTI-GRANULOCYTES ANTIBODY 8W 250/183
Successful detection of inflammatory lesions with Tc-££m-labelled monoclcnsl antibodies (MAbs) against granulocytes has been reported recently. The aim of the present study was to determine the clinical value of this new scintigraphic procedure in orthopedic surgery. 80 ~atients (24 women, 56 men, age range 1B-82, mean age 46) from the Trauma Center, Univ. of TSbingen, FRG, with suspected (50 pts) or known (30 pts) bacterial infection in the musculoskeletal system following orthopedic surgery were investigated using the Tc-9£m-labelled MAb BW 250/183. Administration of the MAb BW 250/183 was performed accordin to the recommandations of the producer Behring-Uerke, FRG. Planar and occasionally SPECT images were obtained with gamma cameras at 5-6 h after MAb administration. Infection could be visualized correctly in 43 pts (TP) while 30 pts had negative scans (TN) corresponding to the clinical course. Two FP anf five FN scans were observed. The diagnosis of an infection has been confirmed by surgery in all 43 TP-pts. In conclusion, leukocytss scanning with the Tc-£gm-lsbelled MAb BW 250/183 appears suitable for the detection of infection in the musculoskeletal system. This may contribute to a better management of this homogeneous patient group. The few FN and FP scans need a further definition in terms of etiology and clinical significance.
Departments of Nuclear Medicine and Medicine, University Hospital, Nijmegen, The Netherlands. SCINTIGRAPHIC DETECTION OF INFLAMMATION SITES WITH In-111 LABELED POLYCLONAL HUMAN GAMMAGLOBULIN (IgG) Radiolabeled nonspecific polyclonal IgG has shown to accumulate in inflammation sites as well as specific monoclonal antibodies (1). Based on these findings, in groups of 4 Wistar rats with a Staph. aureus infection of the left calf muscle a comparative pilot-study was performed after i.v. injection of either 150 ~Ci mln-lgG or 100 i~Ci 1311odinated human serum albumin (HSA). Indium labeling was performed according to the bicyclic anhydride method. The labeling yield was always better than 95%. Two brands of IgG were corr+pared: CLB and S-~ndoz. Rats underwent scintigr.,phy at either 2 and 24 or at 6 and 48 hr after injection. Groups of rats were sacrificed at 24 hr and others at 48 hr after Injection. At 2 hr after injection a clearly higher uptake of IgG than of HSA is noted in the infection focus and as early as 6 hr after injection the difference is significant (p<.01). The infection focus can easily be identified by scintigraphy. No significant difference is observed between the uptake in the infection focus of either brand of IgG. However, the CLB-IgG reveals a significantly higher uptake in liver, spleen, and kidney, when compared to the Sandoz IgG (p < .01). At 24 and 48 hr p.i. the target to background ratio for IgG is higher than 10 and for HSA approx. 4. These data show, that in addition to hyperaemia and increased permeability of the vessel walls, other factors are involved in the accumulation of IgG in the inflammation site. Interaction between IgG and Fc-receptors on inflammation cells might provide an explanation for the results obtained (1). We conclude, that scintigraphy with radiolabeled IgG Is a promising technique for rapid detection of Inflammation sites, considering the fact that IgG Is permanently available and that, in contrast to white blood cell labeling, no complicated and time consuming isolation techniques are required. First patient studies show promising results. (1) Fishman et al. - Detection of Acute Inflammation With 111in.Labeled Nonspecific Polyclonal IgG. Sem. in Nucl. Med.,Vol XVIII, pp 335-344 (1988).
455
226
225
W. BECKER, J. MARIENHAC~N, D. ORDNUNG, F. WOLF B. Briele, A. Hotze, A. Bockisch, W. Ruether, F. Moeller, J. Ruhlmann, H.J. Biersack. Dept. Nucl. Med., Dept. 0rthop., Univ. Bonn, W. Germany
Clinic and policlinic of nuclear medicine of the university of Erlangen - NUrnberg, FRG
HMPAO-LABELED LEUKOCYTES, Tc-ANTI-GRANULOCXTE-ANTIBODY I (AGAB),AND NANOCOLLOID IN SUSPECTED BONE IHFECTION. 54 patients (pts) were studied with Hl~PA0-1eukocytes and AGAB: suspected osteomyelitis of lower extremity n=41 pts./47 localizations, susp.spondylitis n=13 pts. In addition, in 15 pts. a Tc-nanocolloid scan was performed. In all pts. studied a final diagnosis had been established (surgery, biopsy, microbiol., x-ray, clin.course) Methods: Separation and labeling of leukocytes with HEPA0 and AGAB with Tc were performed accord, to stand, protocol. In all 3 methods scans were carried out 4 and 24h p.i.. Results: I n 39 localizations scintigr, findings and final diagnoses were in agreement (true +: n=19, true -: n=20). In 12 cases inflammation scans (both HMPA0-1eukocytes, AGAB) were false pos.: accumul, of labeled cells in aseptic lesions of lower extremity. False neg. scans were found in 9 cases: failed pos. visualization in 8 spondylitis, and I coxitis (instead of expected increased cell accumul, we found "cold lesions"). The false pos. and false neg. findings were independent of the respective method used (HMPA0, AGAB, nanocolloid). Sens. and spec. were calculated to be 67.8% and 62.5%, respectively, and are thus much lower than previously published data, which is most likely due to the selected pts. of former studies. Conclusion: Inflammation imaging (both in vitro and in vivo labeled leukocytes) does not enable an appropriate differentiation between septic and aseptic lesions of the lower extremity. A negative scan, however, does exclude a bone infection with a high likelihood (N.P.V.: 95%).
KINETIC OF IN-111-OXIN LABELLED. TC-99rn ANTI-NCA-95-MoAB IN-VIVO AND ~N-VITRO LABELLED GRANULOCYTES PURPOSE: The kinetic of the. NCA-95-antibody-granulocyte reaction after after antibody injection is still uncertain. So we measured the activity disappearance rate in the peripheral blood after injection of a Tc-99m-NCA-95 antibody(BW250/183)(n=5), in-vitro-antibody labelled autologous qranulocytes(n=5) and In-111-oxin-tabelled 'pure'granulocytes (n=5). METHODS: All 15 patients were admitted to our clinic with suspected infectious diseases. The Tc-99m-NCA-95 antibody was labelled in our laboratory. The granulocytes were prepared as 'mixed' leukocytes or as 'pure' granutocytes after density-gradient centrifugation on a d.iscontinuous METR ZAM DE/PLASMA-gradient as previously described. Blood samples were taken 5',15',30',45' and 60'p.i of the antibody or the labelled cells for calculation of the recovery rate of the circulating activity(cells). Dynamic gamma camera images (1frame/rain) were taken from lungs,liver,spleen and bone marrow. RESULTS: The blood disappearance curves in patients examined with In-111 cells and Tc-99m-anti-NCA in-vitro labelled cells were nearly identical (t-1/2:140 and 167 min).The disappearance of theinjected antibody was significantly faster(t-I/2: 50rain). The infectious lesions could be correctly diagnosed in all three qroups. The organ kinetic curves were comparable but could notDe quantified because of the urge of a slow injection of murine antibodies. CONCLUSIONS: 1.)The early behaviour(6Omin.p.i.)of anti-NCA-95 labelled granulotes is not impaired in comparison to the tn-111-oxin labelled ceils ) The significantly higher Tc-g9-Moab clearance of in-vivotabelled granulocytes demonstrates that the injected antibody binds not only to circulating but also directly with bone-marrow and spleen cells
~.
228
227 S.N.Reske, *K.M.Zillkens, **W.Gl6ckner, U.Buell
A. Hotze, B. Briele, A. Bockisch, J. Ruhlmann, F. Moeller, W. Ruether, H.J. Biersack Dept. Nucl. Med., Dept. Orthop., Univ. Bonn, W. Germany
Depts Nucl.Med., Orthopedics and Internal Medicine If, RWTH Aachen, FRG
LOCALIZATION OF S~ACUTE AN])CHRONIC INFLAMMATORY LESIONS BY MEANS OF Tc-99m LABELED ~RENE NONOCLONAL ANTI-NCA-ANTIBODIES (TcNCAA)
TcNCAA label selectively granulocytes in peripheral blood and maturated myelocytes in bone marrow (BM). Labeling is accomplished by stable binding to non specific cross reacting antigen (NCA), exposed at the cellular membrane of these cell types. Whereas recent evidence suggests sensitive detection of acute inflammatory soft tissue lesions by means of TcNCAA, the diagnostic potential of this approach in s~acute to chronic infections is not known. We thus examined 45 patients (P) with following potential inflammatory pathologies: fever of unknown origin (15 P), osteomyelitis (4 P), spondylodiscitis (5 P), sacroileitis (i P), periprnsthetic hip or knee joint infections (4 P each), aseptic TEP loosening (3 P), encapsulated abscess of the thyroid (i P) and 9 P with soft tissue infections of the extremltles.~ After i.v. injection of 300 ± 15 NBg TcNCAA, whole body scans were performed by means of a LFOV gamma-camera eqipped with a LEAP collimator. Scans were recorded 4 and 24 hrs p.i. Localized antibody uptake in soft tissue comparable to that of BM or a circumscribed defect in BM were regarded as positive findings, indicative of an inflammatory lesion. In 30 P, inflammatory lesions were localized by other imaging methods and confirmed by histology, bacterioloqical tests or therapeutic response during clinical follow up. TcNCAA demonstrated 20 concordant positive,15 concordant negative, 2 false positive and 8 false negative findings. Thus, in a study population with a prevalence of 67 %, sensitivity of the TcNC~ scan was 67 %, specificity 88 %, positive predictive value 9 1 % and negative predictive value 65 %. In comclusion, these results indicate a moderate sensitivity and high specificity in difficult diagnostic cases of chronic soft tlssue and bone infections. In axial skeleton, the latter were invariably characterized by reduced TcMCJ~ uptake compared to BH and presented as cold spots. TcNC/u~ offer a rather specific, rapid and easy to perform new approach for delineating inflammatory lesions at a highly reduced radiation exposure. ,
,
I
TC-99m-ANTI-GRANULOCYTE-ANTIBODY (AGAB) IN ORTHOPEDIC PATIENTS. 22 orthopedic patients were studied with Tc-AGAB, 16 pts. with susp. septic bone infection of lower extremity (hist. of fract., prosth, impl.), and 6 pts. with susp. infect, of axial skeleton. A final diagnosis was established prior to AGAB scan by surgery, biopsy, microbiol, and clin.course. The AGAB scans were then evaluated independently by two physicians without knowledge of diagnosis. AGAB (epitope BW 250/183) was labeled with 300 MBq Tc-99m immediately prior to the study. Scans were then performed 4 and 24h p.i.. Results: In 16 pts. scintigr, findings and the final diagnosis were in agreement. True pos.: 10, true neg.: 6. False ~os. 2 pts. (=unspecific accumul, in non infected bone lesions.). False neg.: 4 pts. with proven spondylitis (unspec.:n=2, tuberculous:n=2). In these pts. cold lesions were found instead of increased AGAB accumulation, and were therefore not diagnosed as true pos.. The foll. values were then calculated: a) total pts.: Sens.: 71%, Spec.: 75%, Acc.: 54%, P.P.V.: 83%, N.P.V.: 60%. b) excluding pts. with vertebral column lesions: Sens.: 100%, Spec.: 75%, Acc.: 88%, P.P.V.: 85%, N.P.V.: 100%. Conclusions: I. AGAB is not as promising in differentiation of septic/non-septic bone infections due to the moderate spec.. 2. Excl. vertebral column lesions AGAB provides excellent clinical information regarding of either sept. or nonsept, bone infect.. 3. AGAB offers considerable practical advantages compared with conventional HMPAO in vitro leukocytes. 4. Appearance of "cold lesions" in infected vertebrae remains still unclear.
456
230
229
B.Erbas,T.Ozdemir,M.Calg(ineri,S.Kes,C.F.Bekdik.G.Erbengi. A Cuocolo, RO Bonow.
FL Sax, JE Brush, BJ Maron, SL Bacharach,
ant
Department of Nuclear Medicine and Cardiology Branch, National Institutes of Health, Bethesda, Maryland, U.S.A. DIASTOLIC FUNCTION INHYPERTENSIVE PATIENTS WITHOUT LEFt VENTRICULAR HYPERTROPHY: A RADIONUCLIDE STUDY. Impaired left ventricular (LV) diastolic filling at rest is a common finding in patients (pts) with hypertension (HTN), even in the absence of decreased systolic performance. Reduced peak filling rate (PFR) in such pts correlates with increased LV mass. However, whethel impaired diastolic function may occur before the development of LV hypertrophy remains controversial. We therefore studied 35 HTN pts with normal echocardiographic L~ mass and 35 normal volunteers by radionuclide angiograph> at rest and during exercise. Sex, age and LV ejectio~ fraction (EF) at rest were similar in HTN and normals. In contrast, each index of diastolic filling differed significantly. PFR at rest, normalized to end-diastolic volume (EDV) or stroke volume (SV), or expressed as the ratio of PFR to peak ejection rate (PER) was reduced and time to PFR (TPFR) (ms) was prolonged in the HTN pts. EDV/s SV/s PFR/PER TPFR Normals 3.3+0.7 5.9+1.1 1.2+0.3 147+25 Hypertensives 2.8~0.6 5.0~0.6 1.0~0.2 165~26 P value <0701 <0701 <0701 <0.O5 Diastolic indexes were not related to pts age, heart rate or blood pressure. However, pts with reduced systolic reserve (EF response to exercise <5%) had greater diastolic impairment at rest, and PFR correlated significantly with the EF response to exercise (r=0.58, p
ALTERATIONS IN MYOCARDIAL DIASTOLIC FUNCTION IN PATIENTS WITH
COLLAGENTISSUEDISEASESUSINGRADIGNUCLIDEVENTRICULODRAPHY, Csrdiovascular abnormalities are frequently found in patients with co!la~n tissue disease(CTD) without clinicalfindings, This study was undertaken to investigate the status of left ventricular ~stolic and diastolic function using radionuclide angiography(RA), radionuolide ventriculography (RV) and Doppler- echocardiography. 51 patients wera studied (mean age:38.4+12)After administnation of 15mCi 99mTc-labelled red blood cell, RA and RY were performed at rest. Cardiac output (CO), cardiac index (el), stroke volume (SY), stroke index (SI), ejection fraction (EF), peak ejection rate (PEP,), peak filling rate (PFR),time to endsystol (TES),time to peak ejection (TPE) and time to oeak filling(TP F) parameters were calculate& In comparison with angiographically normal group,EF( mean: 57. I+ 8.7%) PER ( mean: 2.91 +0.71sea), TPE( 132+42.4 sec ), TPF(mean: 135.7+50 sac), CO (mean:5260±1208 ml), el(mean: 3305+694 ml/m2), SY (mean: 72.385+I 7.42 mllmin),SI( mean.. 41.231+8.55 mllmin Ira2) were not significantly different. TES (mean :312.4±55) was lower than control group(mean:330.56±45) but not statistically significant. Only TFR ( mean: 2.63±0.77) was significantlydecreased ( p
232
231 A.Facello ~ , A.Constantinesco ~, J.L.Demangeat ~, P.Bareiss ~
Nuclear Medicine and Internal Medicine Department, Medical Faculty,Hacettepe University. Ankara,Turkey.
J.R.Kieny ~ ,
B.Brunot ~ ZAGNI P,,
DONDI M., FRANCUI F., CDRBELLI C., BELLANOVA 8., *TARTAGNI F.,
*ANTONIOLI F., MDNETTI N.
Nuclear Medicine (~) and Cardiology (~) Departments C.H.R.U. Hautepierre ; F-67098 STRASBOURG.
Oepartlent of Nuclear Medicine , S.Orsola-MalpighiPal(clinicHosoital; *Institute of Cardiovascular Deseaee,Universityof Bologna. Bologna - Italy
TIE
RAO]ONUCL[SEANGIOGRnPHIC EVALUATION OF CRRO]OVRSCULRRPERFORMANCEIN ATHLETES PRACTICINGPOWERAND ENDURRRCESPORTS It is well known that a prolongedphysical training, mainlyin professional athletes, modifies cardiovascular performance (left ventricle diastolic as well as
TO P E A K F I L L I N G F U N C T I O N A L I M A G E S F R O M R A D I O N U C L I D E ANGIOCARDIOGRAPHY : A N E W W A Y TO L O C A L I Z E A C C E S S O R Y P A T H W A Y S IN W O L F F - P A R K I N S O N - W H I T E SYNDRO~.
The treatment of Wolff-Parkinson-White syndrome (WPW) occasionally requieres accessory pathway (AP) ablation. With new percutaneous techniques, non-invasive diagnostic methods for AP localization are desirable. In 25 patients (pts) with WPW, radionuelide angiocardiography acquisitions were made in S projections : left anterior oblique, anterior and left posterior oblique with 32 images/cycle and a forward-backward rejection window of ±5% of the mean cardiac cycle. Functional images of time to peak! filling rate (with onset at R wave) were obtained to assess the ventricular relaxation sequence (Rel). From these images, a topographic localization was assigned using a dynamic visualization of Rel. The eleetrophysiological (EPh) analysis, carried by an independent observer showed that 15 pts had free wall AP (8 left, 7 right sided), 4 anterior and 6 posterior paraseptal AP. Rel was in agreement with EPh localizations in 21/25 (84 %) of pts for this four topographic categories. The 4 discrepancies were : 1 pt with intermittent WPW, 2 p t s with mechanical function abnormalities (dilated cardiomyopathy and Ebstein's disease) and in 1 pt the locali-i zation was assigned to near sites (left anterior and left anterior para- septal). Strikingly, time to peak filling sequence is in close agreement with ventricular activation in patients with normal ventrieular function a n d constitutes a simple, promising method for non-invasive localization of AP in WPW pts.
systolic function)and increasesmyocardialmass and wall thickness. Cardiac performance at rest Js well assessed by echocardiography
(EC) which
unfortunatelycannot be easily carried out during stress, so that exercise-induced variations of left
ventricle performance are not accurately
detected. To
overcome stress EC shortcomings radiunuclJdeangiography (RRA) has been proposed as noninvasivediagnostictool Eighteen professional athletes, B practicing wrestling and weight-lifting (Group A, 'powerexercise")and I0 practicingcycling and marathonrace (GroupS, "endurance exercise'),
were submitted
to RNA at rest
(Rt, during isometric
handgrip (HGI and during maximal isotonicstress (C) with cycloergoeeter. Heart rate (HRI, systolic blood pressure (SBP), diastolic blood pressure (OBP) left ventricle diasto)ic (EDV) and systolic volume (ESV), ejection fraction (EFI~ cardiac output (CO), peak ejection rate (PER), peak filling rate (PFR), stroke voluae (SV), systemic vascular resistance (SVR} have been evaluated both at rest and during stress. Of group A athletes I 3/e presented with high OBP values (>=lO0 aIHg) at rest; during HS GSP increased in 7/B. This DBP changes during HS never occurred in group B athletes. EF decreased by more than 5X during HG in l/S athletes in gruop R and 5/10 in group B. In all IS athletes (group R÷B) EF increased by aore than 5%
during C stress though EF increase was due to a reductionof ESV in group A athletes, while in group 9 it was due to an increase of EOV associated with a reduction of ESV. This behaviour is re}ated to an isovolumetric increase of CO in group A, while it depends on the Frank-Starling mechanism in group B athletes. Notwithstanding the increase of ventricular wall thickness which affects ventricular f i l l i n g in group A athletes, changes of dyastolic function (PFR within normal limits) mere not observed, even in athletes treated with anabolizing drugs.
457 233
234
M.P. LAROCK, R. CANTINEAU, J . L . VAN CUTSEM,
C h r i s t i a a n WJ Schiepers, Carl K Hoh, Tahlr Tak, Lynn Jacobs, Michael E Siegel, Shahbudin H Rahimtoola, and P Anthony Chandraratna
P. RIGO
U n i v e r s i t y of Southern C a l i f o r n i a School of Medicine C . H . U . LIEGE, UNIVERSITY OF LIEGE, BELGIUM. 99mTc-MI81 TO ASSESS GLOBAL AND REGIONAL V E N ' [ R I CULAR FUNCTION IN THE ACUTE PHASE OF MYOCARDIAL INFARCTION. We have attempted to evaluate the diagnostic performance o f 99mTc-mibi (MIBI) to assess global v e n t r i c u l a r fun ct i on with f i r s t pass measurement o f the ejection fraction (EF) and regional wall motion and wall t h i c k e n i n g with gated t o mography (G-tomo). In this s t u d y , we have analysed 25 patients { p t s ) at rest within 15 days a f t e r acute myocardial i n f a r c t i o n . A n g i o g r a p h t c c o n t r o l was available in 11 pts. All pts also had a comparative p l a n a r thallium scan and an .. , iequilibrium radlonucllde v e n t r l c u l o g r a p h y . ( E R V ) . The c o r relation between f i r s t pass LV EF obtained with MIBI iand equUibrlum LV EF obtained with 99mTc red cells was e x c e l lent ( r = 0.96). In G-tomo, the comparison between s y s t o lic and diastolic frames revealed abnormal wall motion, lack o f t h i c k e n i n g as well as abnormal p e r f u s l o n . The segmental correspondence between MIBI G-tomo and a n g i o g r a p h y f o r detecting abnormal wall motion was 87% while the c o r r e s p o n dence between G-tomo and ERV was 93%. Rare d i s c r e p a n - i cies occured In pts with multiple necroses, in presence o f large p e r f u s i o n defects and large abnormalities o f myocardial wall motion on MIBI tomograms. Abnormal wall motion and lack o f t h i c k e n i n g can also be visualized on functional images obtained by s u b s t r a c t i o n o f systole from diastole (D - S Image], o f diastole from systole {S - D Image} o r by their addition. 99mTc-MIBI appears v e r y promi~iir~g to document myocardial Infarction as well as to p r o v i d e functional information on global and regional v e n t r i c u l a r f u n c t i o n ,
Los Angeles, C a l i f o r n i a , USA CCMPARISON OF SCINTIGRAPHIC AND SONOGRAPHIC FRACTIONAL SHORTE~IINGANDMYOCAROIALTHICKENING Tc-g9m MIBI has the p o t e n t i a l for simultaneous e v a l uation of myocardial p e r f u s i o n and f u n c t i o n . Adequate count s t a t i s t i c s a t l e w g a t i n g , and thus information on wall motion and thickening. A method was developed to q u a n t i f y these wall changes. 900 MBq Tc-ggm MIBI was administered on separate days at peak e x e r c i s e and at r e s t . Cardiac images were acquired in a 6 4 x 6 4 m a t r i x w i t h 24 frames/cycle f o r 5M counts. A best septal I_AO v l e w w l t h cephalad t i l t was used in order to o b t a i n a " s h o r t a x i s " planar view. A r e s t i n g M-mode sonogramwas obtained w i t h i n two weeks. In t o t a l , 160 myocardial segments were analyzed in 5 patients. Myocardial borders at end d i a s t o l e and end s y s t o l e were determined w i t h edge d e t e c t i o n programs. Average f r a c t i o n a l shortening (FS) and myocardial t h l c k enlng (MT) was computed from these edges. At r e s t , FS was 27±8% f o r inner and 10±4% f o r outer borders; corresponding sonographlc r e s u l t s were 22_.+4%and 9_+1%. FS a f t e r e x e r c i s e increased to 41±12% f o r inner and 10_+3% f o r o u t e r . MTwas underestimated by s c i n t l g r a p h y : 17_+3% vs 33_+2% by echo. This may be r e l a t e d to the use of geometric edge d e t e c t i o n , o m i t t i n g count r a t e changes. Findings of l i t t l e motion of the outer myocardial border, and c o n t r a c t i o n by inner border motion, mimlc dynamics in the o p e r a t i v e s u i t e . Conclusion: semi-automatic programs have been developed to assess FS and Mr on gated Tc-ggmMIBI scans. Inner and outer FS appear as accurate as sonography. Thus, a s i n g l e n o n - i n v a s i v e test provides m u l t i p l e parameters of cardiac f u n c t i o n and myocardial p e r f u s l o n .
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~. Reiche, H.-J. Kaiser, C. Weiller, U. Buell, A. Kersting, R. Schneider, E.B. Ringelstein
W.H. Knapj;), U. Schmidt, G. Notohamiprodjo, K. Vyska, *K. Minami
Departments of Nuclear Medicine and Neurology, University of Aachen, FRGermany
Institute of Nuclear Medicine and *Department of Thoracic and Cardiovascular Surgery, Heart Center NRW, Bad Oeynhausen, FRG
Technical
COMPARISON OF MRI- AND SPECT-FINDINGS IN SUBCORTICAL BRAIN LESIONS: RESULTS OF A ROI-OVERSAY METHOD Subcortical lesions may appear as infarction of basal ganglia, terminal supply area or subcortical hemorrhage. This investigation was undertaken to detect with brain-SPECT imaging (regional cerebral blood flow (rCBF), volume (rCBV), perfusion reserve (rCPR)) functional changes in correlation to neuropsycholog/cal (NPS) tindinga and morphological alterations (~RI) in the lesions and adjacent cortex. 24 patients - 8 with }~S, 9 without NPS and 7 controls - were invPscigated <30 days after ictus with ~ (1.5 T, spln-echo-technique), F/VSPECT with 99"Tc-HMPAO and 99=Tc labelled red blood cells (rCPR calculated as rCBF/rCBV). Results were compared to clinical presentation. l~I- and SPECT-slices were matched together in a Micro Vax II computer, compared in am overlay-techn/que and quantified with free selected ROI by interh~mispherical ratios and by reference to a cerebellar ROI. Results of Flow/Volume-SPECT and NRI were interhem, ratio ((path/norm) minus 1.00) SPELT vs ~ X lesions rCBF rCBV rCPR size with NPS* (n=7) -0.23 +0.33 -0.32 same size adjacent cortex -0.19 +0.20 -0.18 ~RI normal %ithout NPS~ (n--9) -0.13 +0.65 -0.22 same size adjacent cortex -0.04 -0.07 -0.02 both normal controls (n=7) +0.01 0.00 0.DO normal -+0.05 -+0.10 _+0.06 adjacent cortex -0.02 0.00 +0.03 normal -+0.03 -+0.24 _+0.07 *)aphasia, dysathria, neglect We conclude, that the combination of subcortical lesions and NPS is accompanied by exhaustion of the rCPR in the adjacent cortex without respective morphological alterations.
GLOBAL AND REGIONAL RESPONSE OF CEREBRAL PERFUSION TO CO2-STIMULATION IN CEREBROVASCULAR DESEASE (CVD) Decreased cerebral perfusion pressure is widely compensated by mobilisation of the perfusion reserve mediated by local CO2 balance. The question is posed whether an increase in arterial CO2 enhances Tc-99mHMPAO uptake so that this increment could be regarded a measure of perfusion reserve. 50 investigations (based on two consecutive injections of 8mCi Tc99m-HMPAO) were carried out in 44 individuals; the first injection was made during normo- or hypocapnia (mean CO2 = 3.7 vol%), the second one during hypercapnia (mean CO2 = 6.0 vol%) with a delay of 40 min. SPECT imaging (1800 orbit) was begun 5-10 min after each respective injection. The first data set (A) (with correction factor for tl/2) was substracted from the second one (B). A.100/B - 100 was thus the % increment of activity uptake (dU). In 31 asymptomatic patients (pts) dU averaged 35.8%. Reproducibility testing tor U resulted in a mean deviation of 3.8 _+2.0% (N=5). dU was linearly related to dCO2. Therefore the following data were normalized to dCO2 = 1%. In 5 normal subjects dU averaged 15 + 2%, in 11 pts with CVD (stenoses <75%, asymptomatic) 12.2 +_3%, in 15pts with stenoses >75% (asymptomatic) 10.5 _+ 4.8% and in symptomatic pts with CVD 7.0 + 4.5%. 6/16 pts with unilateral ACI occlusion showed regional or hemispheric decrease >10% in dU. All of them were symptomatic. 11 pts (8 with stroke) had regional decrease in U, but normal dU. Transcranial Doppler ultrasonography (TCDU) was additionally performed in 9 pts. Flow response to CO2-stimulation, exceeded clU by a factor of 1.8 on average. Though absolute flow response is underestimated, the clinical data and typical regional patterns suggest that Tc-99m-HMPAO uptake at different end-tidal CO2-1evels is a measure of regional perfusion reserve which is compromised in symptomaI~ CVD.
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G. Leinsinger, H. Fflrst, P. Schmiedek, K. Einh/iupl, T. Kreisig and C.-M. Kirsch
I.G. Bottqer**H.-P. Schli~ke , I.W. Hu,sstedt , K.H. Grotemeyer , B. Vollet , O. Schober
•.
~
.
**
**
Departements of Nuclear Medicine, Surgery, Neurosurgery and Neurology, University of Munich, Munich, FRG
Nuclear Med~c=neand **Neurology Clinics, University of MOnster, MOnster, F. R. G. EVALUATION OF CEREBROVASCULAR RESERVE CAPACITY (CVRC) IN PATIENTS WITH STENOTIC CAROTID ARTERY DISEASE
CEREBRAL BLOOD FLOW IMAGING BY 99mTc-HMPAO AND SPECT IN VASCULAR HEADACHE SYNDROMES
cerebral blood flow, serial rCBF-measurements were performed in 78 patients with carotid attery disease. The indication for surgery was based on doppletsonographic findings of high grade stenosis of the internal carotid artery. rCBF was measured by 133-Xe DSPECT at rest end after i.v.-appticatlon of 1 g acetazolamide, in previous studies normative data of rCBF-increase were established and ranges of slight, moderate or severe reduction of CVRC were defined. Results: Preoperative mean resting flow over the operated hemispheres was 47 + 9 ml/100g/mln (normal: 56 + 8 ml/100g/mtn). In 31 of 83 operated hemispheres (37%) CVRC was reduced preoperatively. Follow-up studies 6 days (n=29) and 3 months (n=45) after surglcal treatment showed no significant change of resting flow. However, an improvement of CVRC was found in all patients who had a reduction of CVRC preoperatively. The extent ot this improvement was inversely related to the degree of preoperative CVRCreduction. Conclusion: The present study indicates that measurement of rCBF under resting and stimulated conditions provides information to identify patients at risk from hemodynamic insufficiency of cerebral blood flow, who may have a benefit from carotid endartereetomy.
Based upon earlier~231-BIMP(amphetamine)-SPECT results we now extended our rCBF studies in various forms of migraine (M) by use of a second flow tracer,99mTc-HMPAO, and SPECT (documentation by x-ray film plus colour print; evaluation: qualitative). Patients: n = 34, 19 females, 15 males, mean age 30 y, range 17-61 y : classic M (CM): 19 16 thereof with migraine accompagn6e (MA), Common M (CoM): 9, and cluster headache (CH): 5 (classification: "Ad Hoc Committee on Classification of Headache"). CT and/or MR were performed in 21 and 6 patients, respectively, yielding normal findings, rCBF was =maged in the pain-free interval. The following results were obtained: focal reduction of rCBF could be observed in 9/19 patients with CM. 0/9 with CoM and 0/5 with CH. Normal rCBF findings were present in 4/19 patients with CM, 6/9 with CoM and 5/5 with CH. Focal rCBF findings could be related to the topography of accompanying neurologic symptoms during M attack in 10/16 patients with MA, in 2 of them additionally using~ZI-BIMP. In conclusion, especially MA - in the paid-free interval - reveals focal reduction of rCBF, also by use of ~:~JmTc-HMPAO, altered rCBF frequently corresponding to the focal neurologic symptoms occurring during M attack. This again shows solitary rCBF alteration by ~mTc-HMPAO/SPECT in a functional neurologic disorder, even in the symptom-free interval.
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In order to study the effect of carotid endarterectomy on
~. DEHONCEAU, J. LEVEILLE, J.L. NORETTI, N. DE ROO, P. BIGO, R. ~qALOVITCH
W.-H. Dingler~ W. Lindheimor,
H.-K. Deininger
Dept. Radiology & Nuclear H~dicine Municipal & Teaching HospiLal D-61OO Darmstadt, Fed. Re;~. Germany ~niverslty of Liege, Nontr~al, Paris and Leuven. Du Pont de Nemcurs ~ . CHRONIC STROKE : COHPARISON OF ECD, HH-PAO, AI~D CT-SCA?: ~:c evaluated thepotential of detection of the Tc-99~eethylcysteinate dimer (ECD), comparing the resu]tln? itches with another technetate CBF's tracer, the ~c-99m he:~amathylpropyleneamine oxime (}D~-PAO) and with the ET-sca:~net. Nine patients, sufferin F from stable hemiplegia since =t least 4 weeks, were studied by the 3 methods in a 7 days interval. Tomographlc acquisition and reconstruction Were realized using similar parameters for both tracers. The contrast of the imaFe as well as the size of the lesions were evaluated from visual examination by 4 inde~endant observers in a double blind study. Noreover, ccrrazhion for effective half-llfe during tomographic aoqulsi~ion was made in 3 patients, assuming similar monoexponintial decay for all the parts of the brain (as observed in healthy man) : each tomographic view was thus multiplied by a correction factor, than the reconstruction was a~ain performed. No significant difference in the contrast w ~ observed between the 2 tracers. A similar size of the 6~[ect, systematically larger then with CT-scan, was observed. A mean clearance of li.8% for ECD, 10% for HM-PAQ was calculated during the acquisition, but no slgn~ficant variation of the measured size of the lesion was observed before and after correction, for both tracers. In cencluslon, no significantly different results were observed between the qualities of the images obtained with ECD anf HM-PAO in this limited number of chronic strokes.
99M-TC-HMPAO-SPECT IN PATH~NTS WITH REVERSIBLE CEREBROVASCULAR DISEASE (CVD): COMPARISON OF THE SENSITIVITY WITHOUT AND WITH ACETAZOLAMID (DIAMOX) SPECT imaging of the brain was performed in 66 patients with reversible CVD utili=ing 99m-TC-HMPAO i 35 patients were studied after intravenous administration of Ig Acetazolamid, 31 patients got none. Sensitivity of these two methods were compared differently in reversible hemispheric (TIA) and ver:,~brobasilar insufficiency (VBI). Cerebral infarcticu was excluded by TCT. Sensitivity in TIA withou= provocation was 55 %, in VBI 36 %. Aeetazolamid improved sensitivity to 90 % and 64 %. In reference to tot~l CVD sensitivity increased from 48 % to 80 %. II pat~onts who were investigated with both methods within a few days, showed an increase of sensitivity from 45 % ~,~ 8 1 % , 3 patients with amaurosis fugax and severe stenosis of the internal carotid artery were norma~ with Acetazolamid. However, in 8 patients with asympt~matic severe carotid stenosis the ipsilateral hemispheric blood flow was reduced by the provocationtest, Conclusions: SPECT imagin~ with 99m-Tc-HMPAO shows in patients with reversib~o CVD in provocation with Acetazolamid a distinct hi~her sensitivity.
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W.J. Maclntyre, R.T. Go, T.H. Marwick, P.K. Rehm, D.A. Underwood, G.B. Saha, and C.C. Simpfendorfer. Cleveland Clinic Foundation Departments of Nuclear Medicine and Cardiology 9500 Euclid Avenue Cleveland, Ohio 44106 U.S.A.
G. DEMONCEAU, A. RICHEL, D. HEBBELINCKX , J.P. DRION, P. RENOY, P. BOURGEOIS
Bracops hospital, Brussels (BELGIUM) COMPARISON OF RUBIDIUM-82 AND THALLIWJM-201 SINGLE-STRESS MYOCARDIAL PERFUSION IMAGING IN DIAGNOSIS OF CAD Comparison of different modalities of myocardial imaging has often been complicated by the need for separate stress procedures as well as by the use of different display systems that could give one modality an advantage. It is the purpose of the present study to compare myocardial perfusion imaging of Rubidium-82 (Rb-82) by positron emission tomography (PET) with SPECT imaging of Thallium-201 (TI-201) by recording both ~asurements with a single dipyridamole stress and reading both images with the same display. Rest and stress Rb-82 perfusion studies were obtained on a Posicam system (Positron Corporation) following injections of 40-60 mCi Rb-82 (Squibb Diagnostic Inc.). Stress was achieved by a combined dipyridamole infusion and hand-grip protocol. Two mCi TI-201 were injected four minutes after the beginning of the stress Rb-82 acquisition and TI-201 images obtained from a Triad system (Trionix Inc.). Data from both systems were transferred to a VAX 750 for identical reformatting and three axis display. Critical CAD was identified by recent angiography demonstrating -->50% stenosis. From the results of 95 of the first 99 patients, the Rb-82 results showed a sensitivity of 88% and specificity of 76% while the TI-201 results exhibited a sensitivity of 75% and specificity of 80%. Although the increased sensitivity and specificity results with Rb-82 were only moderate, the improved contrast resolution of the PET technique resulted in markedly superior images and a more confident identification of defects.
243 P. Thelssen. U. Sachtem, H. Kaemmarer, U. K0nlg, H.W. HSpp, H. Schlcha Institute of clinical and experimental Nuclear Medicine and Madlcal Clinic III University of Cologne, Cologne, FRG NONINVASIVE FOLLOW-UP IN pATIENTS WITH SURGICALLY CORRECTED AORTIC COARCTATION Functlonal Impalrmant and local pathologlcal changes of the aorta especlally at the slte of corractlon are wall known compllcatlons after surgery for coarctatlon of the aorta. To evaluate the longterm results after thls operatlon, 23 patlents were assessed by physlcal examlnatlon, ergometry, and magnetlc resonance Imaglng. The postsurglcal Interval ranged from 1 to 28 years. The most frequent postoparatlva symptoms were vertlgo, headache, dyspnea on exertion, cardiac arrhythmlas, and left thoracic pain. Elevation of the left shoulder was found In 19 of the patients due to left lateral thoracotomy. Fourteen patients suffered from arterial hypertension. Five patients additionally had hypertension on exertion. Magnetic resonance Imaging showed pathological changes of the aorta and the aortic branches In all patients. The origin of the left subclavian artery was displaced distally In 8 patients. The proximal part of the left subclavian artery was dilated In 11 patients. Fourteen patients had a hypoplastlc aortic arch. An aneurysm of the ascen-dlng aorta was found In 5 patients. Anaurysmal dilatation of the descending aorta In the region of the anastomosis was present In 3 patients. Restenosls of the descending aorta occurred In 2 patients. In conclusion, after corrective surgery for coarctatlon of the aorta many patients continua to have symptoms which require a regular follow-up. Magnetic resonance Imaging provides a complete and nonlnvaslva examination of the heart and the great vessels and Is therefore Ideally suited for this purpose.
COMPARAISON OF SCINTIGRAPHY WITH TC-HM-PAO LABELED PLATELETS TO RADIOLOGICAL PHLEBOGRAPHY To evaluate the clinical interest of Tc-99m-NM-PAO labeled platelets scintigraphy (Tc-PLT), we have compared it with radlological phlebography in case of deep vein thrombosis (DVT). 38 patients were studied, which were clinically suspected from DVT of the le~ or suffering from pulmonary embolism demonstrated by lung seintlgraphy (V/P). Each one underwent a radiological phlebography (Rx) and, in 36 cases, a V/P in the same week as the Tc-PLT. About 250 HBq of Tc-PLT were injected 4 days (mean value) after the onset of symptoms. Planar acquisitions were performed in anterior and posterior views, on the lower llmbs, abdomen and chest, 20h after injection. In 18 of these patients, an additional study was realized 4h after injection. Visual comparalson with Rx was made, dividing the lower limb into 4 segments. Signal on noise ratio was measurdd to evaluate the potential value of the early study. Finally, the ability to detect pulmonary embolism by Tc-PLT was evaluated. Comparing to the floating clots demonstrated at Rx, the overall sensitivity a~ 20h was 74%, the specificity was g3% and the accuracy was 90%. No uptake but one, was observed in the case of organized thrombUs demonstrated by Rx. Earlier imaging decreased the sensitivity and the specificity. Only one in 14 pulmonary embolisms demonstrated by V/P could be demonstrated by Te-PLT. These results demQnstrated the clinical interest of the method for the detection of fresh clot, able to create pulmonary embolism,but not of the pulmonary embolism itself~
244 D Jain, A Lahiri, U Raval, C James, EB Raftery
Cardiology Department, Northwick Road, Harrow, Middx, HA1 3UJ, UK EVIDENCE OF MYOCARDIAL DIAGNOSTIC ECG CHANGES.
NECROSIS
Park Hospital,
IN
THE
Watford
ABSENCE
OF
Cardiac imaging with 1111n labelled antimyosin antibody (In-AM) is a sensitive and specific scintigraphie method for the detection of acute myocardial necrosis. In a prospective study, 119 patients (pts) with suspected acute myocardial infarction (AMI) or unstable angina underwent cardiac imaging with In-AM. The diagnosis o f A M l was made independent of the results of I n A M , based upon the serial electrocardiograms (ECG), cardiac enzymes and clinical course Seventy five pts had AMI of whom 7 showed no diagnostic changes of AMI on serial ECG but had positive In-AM uptake. Out of these 7 pts, 5 had no previous documented infarction, the ECGs were technically adequate and normal conduction was present in all. Two pts underwent DC cardioversion prier to In-AM imaging Coronary angiography revealed significant coronary artery disease in 6 out of 7. The In-AM uptake was located in the apical and lateral myocardial segments in all hut one and this was confined to the territory supplied by the affected coronary arteries. One pt had discrete uptake at two different sites. These results show that a significant number of patients (7/75, i.e. 10%) may not show any diagnostic electrocardiographic changes of AMI even in the absence of a conduction disorder. In-AM imaging may be helpful in confirming the diagnosis and in localising the site of infarction in these patients.
460
245 A.H. Elgazzar, M.T. Jaradah, M. EI-Sayed, S. Mahmoud, J° Hashimi, S. Bhatnagar, A.M. All, A. Ai-Yousof, H.M. Abdel-Dayem.
Depts. of Nuclear Medicine & Cardiology, Faculty of Medicine and Mubarak Hospital, MPH, Kuwait. USE OF Tc-99m METHOXY ISOBUTYL ISONITRILE (MIBI) IN THE DIFFERENTIAL DIAGNOSIS OF ACUTE CHEST PAIN IN EMERGENCY ROOM PATIENTS. Twenty four patients (pts) with first time chest pain of more than 30 min duration were studied. Each pt. was injected i.v. with 15-20 mCi Tc-99m MIBI before receiving any medication. I-4 hours later, after pts. were stabilized, static and multigated images were acquired in the ant. and 40 deg. LAO projections using mobile gamma ~re inte~face~IWith ~ni~OmFUter. ReSH~tS ~f MIBI compared with ECG changes, enz!ane levels on day of admission and for 3 consecutive days and with wall motion abnormalities from biplane echocardiography are showen in the following table : ECG Enzymes Echo MIBI Static No. True positive 13 15 12 13" No. True negative 7 8 I 8 No. False positive 2** -i -No. False negative 2 1 -3*** Total 24 24 14 24 * wall motion abnormality on multigated images was detected only in 7 ** ischemic change and unstable angina *** apical defect in LAO in 3 cases. We conclude that Tc-99m MIBI is suitable for 24 hrs service for assessing status of myocardial perfusion at the time of admission and for localizing site of ischemia or AMI. MIBI-multigated images are less sensitive than static images.
247 R. Taillefer, R. Lambert, D.C. Phaneuf, J. L6veill6, B. Lefebvre. H6tel-Dieu de Montr6al Hospital, 3840 St. Ur bain Street, Hontr6al,Qu6bec, CANADA H2W IT8
MYOCARDIAL PERFUSION IMAGING WITH Tc-99m METHOXY ISOBUTYL ISONITRILE ( M I B I ) : COMPARATIVESTUDY BETWEEN TREADMILL STRESS TEST AND INTRAVENOUS DIPYRIDAHOLE IN DETECTION OF CORONARY ARTERY DISEASE. The purpose of this study was to compare treadmill stress test (STRESS) to dipyridamole (DIP) myocardial MIBI imaging in patients with coronary artery disease. Seventeen patients (12H, 5F) referred for coronary anglogram were submitted to three MIBI injections (20mCi/7Okg) separated by an interval of 24-48 hours: at rest, after STRESS (Bruce protocol) and after intravenous DiP (0.142 mg/kg/min during 4 minutes). Planar images (3 standard views, 10 min/view) were obtained 90-120 minutes following the injection. Studies were analyzed by 5 independent observers. The left ventricle was divided into three segments in each image (total of 155 segmenks). Myocardial uptake (cpm/pixel/mCi), heart/lung ratio and ischemie/normal wall ratio (excluding partially reversible !" defects) were determined for both STRESS and DIP studies. Seven patients had a prior myocardial infarction while 6, 8 and 5 patients had single, double and triple vessel disease respectively. STRESS and DIP detected 51 and 54 ischemic segments respectively while both studies showed 15 fixed defects. Other results are as follows. STRESS DIP myocardial uptake 15.2 ±5.2 11.9 ±5.5 n.s. heart/lung 2.9 ±0.5 5.4 ±0.5 p < 0.05 ischemic/normal wall 0.86±0.04 0.79±0.7 p < 0.01 In conclusion, although the number of patients is Limited, sensitivity of both STRESS and DIP MIBI imaging is similar. DIP showed more favorable imaging parameters.
246 M.N. HaLsey, Q. Majeed, Y.C. Nsjm, P. Holt, A.D. Timmis, E. Sowton.
Division of Radiologieal Sciences, UMDS, (Guy's Hospital) London SEI 9RT. A COMPARISON OF GATED AND UNBATED MYOCARDIAL IMAGES USIN8 Tc-99m HEXAMIB 2-METHOXYISOBUTYL I-ISONITRILE. The purpose of this study was to evaluate the potential for improved diagnostic accuracy of routine cardiac gating for the detection of localised myocardial ischaemia. 46 consecutive Tc~99m 2-methoxyisobutyl 1-isonitrile (MIBI) gated myocardial perfusion studies were performed in 24 pts with coronary artery disease (CAD)._ Images were obtained in 3 views (Ant, LAO 45 ° and 70u). End-diastolic (ED) images were compared to ungated images and to angiographic findings. The LV myocardial image was divided into 5 segments in each view and myocardial perfusion graded on a scale of certainty from 0 to 4 (O=Definitely normal, 4=Definitely abnormal. The images were reviewed without sngiographic data. End diastolic images alone had a lower number of normal (Grade O) segments (17.5 vs 21.5), segments which were obtained on both images had a higher mean level of diagnostic certainty. The sensitivity of detection of segmental abnormality (using 50% angiographic lesions was higher (87%) for the end diastolic image. The total number of patients with a b n o r m a l studies was the same. In conclusion these ifindings mhow that without increased data collection time the performance of the planar myocardial imaging perfusion study with Tc-99m hexa MIBI may be enhanced by the use of end diastolic gated images.
248 M.OnlO, H.Durak, N.
Ulutuncel, i.Bernay,A.Kllln.c,C.F.Bekdik
Department of Nuclear Medicine, Hacettepe University Medical Faculty, Ankara, Turkey EXERCISE INDUCEDASYHETRICALCORTICOHEDULLARYRENALUPTAKE INDEX OF 201T1 CORRELATEDWITH PLASHA RENIN ACTIVITY IN CAD Patients(pts) vith CAD have increased incidence of hyperteneion(HT) and so renal uptake (RU) of 201T1 meu reNect renal perfusion. The relationship between renal T1 uptake, HT and plasma renin activity (PRA)was searched in 29 pts( 15 M,14 F,meon ege:4?.3+B.9)vha vere undergoing routine 2OlTl stress myocardial SPECTstudy. Blood semp|es for PRA were taken at rest in supine position on the same day before the stress test. PRA vas measured by RIA. PooteMor views of the kidneys vere obtained for 5' after the administration of 201T1( 1 O0 MBq) at Peek exercise,before (at 39 end immediately following (at 20') $PECT acquisition. Total (TU), cortical (CU) and medullary (MU)~ uptake of 2°iT1 andoortical/medullary uptake index (CMI) vere quantified for both kidneys. Considering that 201T1 primarily concentrates in the medulla soon after its administration, a 24 h viev was a|so obtained in all pts to determine the size eftha medullary ROl's. Nine of 29 pts (31%) had elevated PRA (mean:4.95+1.95 ng/ml/h) whim the others were in the ncrmel range (mean:O.94+O.?Sr~/ml/h). TU,CU and HU for both kidneys in HT pts vere slightly lover but this was not statistically siyrrlficant from the normal PRA group.Thare was no statistically significant asgmetry in TU,CU,HU in normal and elevated PRA group but CHI was significantly asymetricol in 5' post-exercise in PRA elevated group (left CH1=0.952+0.071, right CM1=0397+0.123, 0.0005
461
250
249 Sialer G., von Segesser L.*, R a f f W., Pfeiffer A., von Schulthess G., Klinik fiir Nuklearmedizin und *Klinik liar Herzgefiisschirurgie, Universit~itsspital Ziirich
P. FLORENTZ,
J. CHAMBRON, D. GRUCKER.
Institut de Physique Biologique. Facultg de M4decine. 4, rue Kirschl4ger. F- 67085 STRASBOURG Cedex
PERIOPERATIVE COMPLICATIONS AFTER ACB- SURGERY DETECTED BY 99m-Tc-MIBI-SPECT The phyical properties, the availability of 99m-Tc and the lack of significant redistribution of 99m-Tc-MIBI are advantageous for the SPECT evaluation of the heart of patients undergoing coronary bypass surgery. Onehundredandfourteen myocardial segments of 20 patients (19 male, 1 female) were examined 1 day prior (planar and SPECT), one day after (planar: in intensive care unit) and one week after (planar and SPECT) coronary bypass surgery with 99m-TeMIBI. The examinations were done 2 to 4 h post injection of 5 0 0 - 8 0 0 MBq of the substance into the resting patient. In 11 patients, infarcts were known to have occured in 17 myocardial segments (13 years - 3 months prior to scintigraphy). Preoperatively, 35 (planar) and 45 (SPECT) segments showed a significantly decreased uptake. One day postoperatively there were 33 (planar) and one week postoperatively there were 32 planar and 43 SPECT defects. Of the 17 clinically diagnosed infarcted segments, 4 could not be demonstrated. No significant differences were seen in the n u m b e r o f hypoperfused segments pre- and postoperatively, except in one case who had a severe postoperative infarction, which was clearly demonstrated. Six s e g m e n t s showed improvement. The planar technique disclosed only 78% (35/45) preand 74% (32/43) postoperatively of the SPECT lesions. Myocardial scintigraphy at rest with 99m-Tc-MIBI-SPECT is a promising method to evaluate perioperative perfusion of the heart of patients undergoing ACBP-operations and m a y be able to identify therapeutic success early on.
I. Kdsa, T. GBQI, N. Gruber, M. CsanQdy, L. Csernay
J. L~ng,
Oepartment of Nuclear Medicine, Department of Cardiac Surgery, 2nd Department of Medicine; Albert Szent-Gy~rgyJ Medical University, Szeged, Hungary
(DIP) STRESS CARDIOLITE SPECT FOLLOW-UP OF PATIENTS AFTER CORONARY BYPAS5 SURGERY (CBS)
DIPYRIDAMOLE
20 patients were investigated i week before and 3 weeks after CBS with a two-day stress, rest protocol. 99m-Te CAROIOLITE dose: 600 Maq~ infused amount o£ Dip: 0.56 mg/kg. The SPECT study was begun at least 1 hour after CARDIOLITE injection. Three representative transversal slices were evaluated, with a 5 grade score system. Before CBS, overall sensitivity was 20/20; that of detection of LAD narrowings (AN and AS) was 17/20 under stress, but 19(!)/20 at rest. The RCA/CX sensitivity (INF and IS segments) was i0/i0 under stress and 9/10 at rest, with a specificity of 6/10 and 7/10, respectively.
number of hypoperfused segments under stress at rest before CBS a f t e r CBS
D!MENSIO~
New myocardial perfusion agents like 99mTc hexakis (2 methoxy-isobutyl-isonitrile)(M.I.B.l) allow myocardial gated tomoscintigraphy without decreasing the signal to noise ratio, in comparison with 201 TI. Dynamical 3D reconstruction shows clearly the decrease of the defect size during the systole compared to the diastolic size. Patients with anterior or inferior infarction confirmed by coronarography underwent rest 99mTe MIBI gated tomography. Tomographic acquisition was performed 90 minutes after intravenous injection of 20 mCi of 99mTc MIBI. Collection of 30 views consisting of 8 gated image gives after normalization and filtered back projection reconstruction 16 slices at 8 times of the cardiac cycle. 3D reconstruction at each time displays the myocardium activity during the cardiac cycle. A cine mode display show clearly in all the patients studied a decrease of the size of the activity defect in systole compared to the diastolic size. The difference between diastolic and systolic size of the defect is very dependent on the myocardiumkinetics. In conclusion the dynamical 3D reconstruction of myocardial gated tomoscintigraphy underlines the dependence of the size of activity defects on myocardium kinetics. This study shows that gated tomography which take in account the motion of cardiac walls enhances much ~ore the resolution of the tomoscintigraphy than zorreotions for patient movements.
252
251 J. Nester, G. Kov~cs,
iMYOCARDIAL GATED TOMOSOINTIGRAPHY DYNAMICAL 3 RECONSTRUCTION.
110/280 66/280
69/280 41/280
After RDA bypass an AS or AN perfusion improvement was detected under stress in 15/20, and a t r e s t i n 17/20 c a s e s . A f t e r RCA/CX b y p a s s , an INF or IS i m p r o v e m e n t was d e t e c t e d i n 7/B c a s e s under s t r e s s , and i n 6/8 c a s e s a t r e s t . I t i s c o n c l u d e d t h a t Dip 99m-Tc CAROIOLITE SPECT i s u s e f u l i n t h e management o f C8S p a t i e n t s .
A.Vattimo,R Bertelli,C.Gennari,R.Nami
Nuclear Medicine Unit and Inst.of Med.Semeiotics, University of Siena, I t a l y ASSESSMENT OF POSITIVE INOTROPIC EFFECTS OF HUMANCALCITONINE GENE-RELATEDPEPTIDE (hCGRP) IN MAN BY MEANSOF RADIONUCLIDE ANGIOGRAPHY. Human CGRPis a potent vasodiIator with documented p o s i t i ve inotropic and chronotropic effects in man.However,it is s t i l l unknown i f the cardiovascular effects of hCGRPare direct or mediated by the adrenergic system.Therefore we evaluated the acute cardiovascular effects of 25 ug hCGRP i . v . in 6 healthy normolensive subjects before and after a B-blocade with 800 ug pindolol i . v . by means of gated blood pool radionuclide angiography.Human CGRPalone caused a transient but significant increase in heart rate, hypotension and facial flushing.Moreover, a positive inotropic effect of hCGRPwas documented by a significant increase in cardiac performance indices.Pindolol did not affected these hCGRPinduced effects (Tab.l).Therefore,it seems that the adrenergig system does not partecipate as mediator in the cardiovascular action of hCGRP. Tab. l (EDV:count based method) mean values hCGRP hCGRP+PindoIol T~ T3~ T6~ T~ T3~ T6~ EF EDV ESV SV
HR
62.6 100 36.4 63.6 65.5
?2.9 105 29.3 66.4 78.3
62.7 79.2 28.7 50.6
60.7 98.6 41.2 57.4
77.8
66
71.3 105.4 30 75 78.5
66 118.? 39 80 68.2
462
253 J.L. Beret, S. Benkirane, L. Bordenave, Isidore, M. Dalloehio, D. D u c a s s o u
254 E. Jullien,
Services de M & d e c i n e N u c l ~ a i r e et de Cardiologie, du Haut L~v@que, 33600 B o r d e a u x - P e s s a e (France)
M.P. A.IND[IVINA,
E.LiEATA.
HSpital
EFFECTS OF DILTIAZEM ON LEFT VENTRICULAR DIASTOLIC F U N C T I O N AT REST AND DURING EXERCISE IN H Y P E R T E N S I V E PATIENTS WITH M Y O C A R D I A L HYPERTROPHY. Calcium channel b l o c k i n g agents are effective in improving left v e n t r i c u l a r (LV) diastolic filling and symptoms in p a t i e n t s with myocardial hypertrophy. H o w e v e r the diastolic effects of these drugs have been rarely m e a s u r e d during exercise. ii h y p e r t e n s i v e p a t i e n t s with m y o c a r d i a l h y p e r t r o p h y (septal thickness > ii mm) were studied by e q u i l i b r i u m gated r a d i e n u c l i d e a n g i o c a r d i e g r a p h y at rest and during supine exercise. After a 30 mn r e c o v e r y period, a second study was p e r f o r m e d after a d m i n i s t r a t i o n of 0.5 mg/kg intravenous D i l t i a z e m (DZ), a calcium channel b l o c k i n g agent with no n e g a t i v e inotropic effect. Peak filling rate n o r m a l i z e d to ejection fraction (PFR), time to PFR from end systole n o r m a l i z e d to diastole d u r a t i o n (TTPFR), filling fraction at the first third of diastole n o r m a l i z e d to the cycle length (FF) and their changes during exercise have been measured. Results showed that DZ increases impaired FF (p < 0.02) and normal PFR (p < 0.05) at rest, without reducing abnormally long TTPFR (NS). No significant change in each variable with exercise was observed after DZ. Thus DZ improves at rest the early LV active filling, but atrial c o n t r i b u t i o n to LV filling remains p r e d o m i n a n t in h y p e r t e n s i v e patients w i t h m y o c a r d i a l hypertrophy. No additional i m p r o v e m e n t to exercise in diastolic variables after DZ can be detected.
255
CHAIR OF MECIEAL
THERaPY, PALERMO UNIVERSITY
QUANTITATIVE THALLiLM-201EPECT.COMPA~;ISON PLOTS AND 3D SUSFPEE DISPLAY.
OF BULLSEYE
Bullseye protocol (BP) makes a q u a n t i t a t i v e analysis of short axis Thallium-201 m i o c a r d i u m SPEE:T slicea End it does a con parative analysis with files of patients with low probability of coronary heart disease (less then5%). Bullseye plots have two dimension, shape and perfusion defects have a surface and a shape not es they ~ave in reality.We evaluated if T h a l l i u m - Z 0 1 S P E E : T 3 din ersion surface display (SD) gi~es e better estimation of dimension, shapes and placee of perfusion defects in coronary heart disease. In 5B p a t i e n t s , 5 with normal BP end 25 with net roznel BP, ED was reconstructed from transaxial slices with fixed distance arid variyng angle and treshold,64 views,everyone at 360/64 d e g r e e , w e r e reconstructed sets of ~iews were made,one with 40% treshol~,cne Lith 511% treshold and one with 60% t r e s h o l d . S D ga~e a Eetter picture of d i m e n s i o n , s h a p e and place of perfusian defsct~ Perfusion defects surface varied with tzeshcld.Normsl BP patients were normal at BD with all tresPald.At 40% treshold only 22 of 25 not normal BP patients had r~ct normal SD.At 50% treshold as et 60% treshald all 25 patient~ with not normal BP hac not normal BD.In conclusion a treshcld of' at least 50% ahoLld be u a e d ; S D offers a new and p~omising way cf qusr,titative analysis of Thallium-201 SPECT slices end it car be done the same ms BP.
256
MARTIN P (I), PEPERSTRAETE B (2), PATERNOT J (I) and VERHAS M (I) Departments of Nuclear Medicine (I) and Cardiology (2). Brugmann University Hospital, 4 pl A Van Gehuchten I020 Brussels, Belgium
A. I. Santos., G. Oantinho, A. P. Hachado, J Robrega e Silva. J. A. Baavedra, F. Godinhc, R. Ferreira e O. Ribeir.o Instituto de Hedicina ArsEnic Cordeiro, NSH.
Interest of a single intra-venous injection of 99mTc MIBI In the evaluation of myocardial wall perfusion and left ventrlcular ejection fraction. Comparison wlth equilibrlum radlonucllde ventrlculogrephy and echogrephy. 15 patients (mean age + SO: 64.4 + 6 years) with myocardial infarction or angina pec--#oriswho we-Fe admitted to the coronary unit received an Intra-venous injection of 550 MBq of 99mTe-2-methoxylsobutyl Isonltrlle (MIBI). Immediately after Injection, a left anterior oblique gated acquisition of left ventricle actlvlty was performed for 30 seconds. One hour later, a planar scintignaphy (3 incidences: 0 ~, 45 ~ and 90 °) was recorded. A left ventrlcular ejection fraction was calculated using the formula: Left ventricle end-dlastolic activity - Left ventricle end-systollc activity / Left ventricle end-diastolic activity. The results were compared to those of the gated radlonuclide ventriculography performed at equilibrium with in viva 99mTc labelled red blood cells and with those o f echographic ejection fraction measurements. The scintigraphic images were compared to electrographic findings. There was an excellent correlation between the ejection fraction calculated with 99mTc MIBI and the ejection fraction found with red blood cells at equilibrium: EF (MIBI) = - 1.65 + 1.02 x EF (RBC) (n=15, r=0.96, p(O.O01). A very good correlation was also found between 99mTc MIBI ejection fraction and echography ejection fraction: EF (MIBI) = - 1.97 + 1.025 x EF (eehography) (n = 15, r = 0.86, p(O.O01). In 6 cases with electrocardiogrephically proven myocardial infarction, a defect was found In the same territory at the scintigraphy performed one hour after injection. None of the patients with angina pectorls without myocardial infarction had an abnormal scintigraphy. We conclude that 99mTc MIBI is a promising myocardial agent: the good energy of 99mTc end the high count rate allow quallty images of myocardial wall ebnormaIltias. Moreover, at rest, a single intravenous injection permits the calculation of the left ventricular ejection fraction, providing more functional information on the effects of Ischeemic disease or myocardial infarction.
Nuclear,
FML
e
UTIC
T t ~ T t~ T T % ~ STUDY OF LEFT VENTRIC'JLAR FU~ICTIO~I WITH 1. .0. .? , r i.~NU-~.L~.~ ANGIOGP~%PHY IN HYPERTENSIVE SUBJECTS. EFFECTS OF A ~;E~; BETA-BLOCKER (~EBIVOLOL) PRELIHINARY RESULTS.
Nebivclol (N) is a ne~, selective beta'adrenoreceptoz blocking drug which has been granted improvement in cardiac performance. In the setting of a randomized, double-blind pr.otcccl of camper ison k.et%,een N .. in monotherap!.,, versus placebo (P) in hypertension, a group of patients (pts) ,.,as studied by radionuolide angiography (.RNA) at. rest (R) and after mazimal ei:ercise test ,,,,it.}] cyoloer.gomet.er (E). All DiS ~ez-e essential hypertensives vitheut complications end gave written consent to enter. the ~tudy, After 4 week~ o~ P they warm eligible t o the trial if blood pre~suz.e ,;as > 9~ mmHq. They then proceeded to the H period I[2.5 rag/day) for' 4 ~eeke and finally to the do:~ble-blind phase N/P during 4 more weeks. ENA was perforated at the end of each period. In 8 pt.e. (6 o and 2 o) {age> 47, the left ventricular Ejection Fraction (EF) , Time to Peak Ejection Rate (TPER), Peak Ejection Rate (PER), Time to Peak Filling Rate (TFFR) and Peak Filling Rate (PFR) were determined, I~;~.~:% ~ml~l~ndt~.t~t~rof 4 aweeks c~f P ¢.h~.z'e~ult..m a t R -normal pobula~ion-t(EF}=~l,°4, =64%, < TPER> =i15 ms, =&5 ms: =6EDV/a). After 4 reeks of N simil~r result~ %,ere found. Only 1 Dt O, aged ~l, sho%,ed lou values of the studied parametezs on P, which changed to ncr-mal after H. Analysing these first results we cbeerved that, in a popul~tion of hypertensive pte withot~t complications, the left ventzicular f~nction (.....~i ~ ano dlas~ollc) s.zudlsd with R~A didn' % change after week-= of H on a fixed dose. We have not analysed the res~!lts of the double-blind n h ~ m ~,m tn thin ~mml] ~nmh=T
463
257
258
M. Axelrod, Ao Porcari, K. Holmstrand, E. Lopez, M.L. Maayan. Nuclear Medicine Service, Veterans Administration Medica Center and State University of New York, Brooklyn, N.Y. U.S.A.
VALUE OF 201-THALLIUM CHLORIDE STUDY (TIC1). SPECTIVE STUDY IN AN ALL MALE POPULATION.
A RETRO-
The sensitivity and specificity of 1800 TIC1 studies performed between 1979 and 1899 were assessed matching where available with coronary angiography as the "golden standard". Of 1800 patients who were submitted to Stres~ Thallium studies, 335 were followed up by coronary angiography. Of these, 272 presented abnormal TICI and abnormal angiogram (True Positives); 17 had normal angiograms, and normal TIC1 (True Negatives); i0 had normal TIC1 but abnormal angiograms (False Negatives); 20 presented abnormal TIC1 studies indicating eardiomyopathy, with normal angiograms; and 47 had abnormal Thallium studies with normal angiograms (False Positives). Applying the Bayes' Theorem, the overall performance presented a 96% sensitivity, but only a 37% specificity. However, due to the high prevalence of disease in the population studied, the positive predictive value was 80%, the efficiency was 81% and the post test predictive value was 84.7%. It is concluded that TIC1 stress studies is a valuable non-invasive tool in diagnosing and monitoring myocardial disease.
E. G.
inglese, Favre'tto,
R. S a r a , I1. G. P i , : l : a ] . b
Mi:l. e l l a ,
M. Melloul, E. $egenreich E*, R. Singer**, E. Lubin, C. Servadio**, Dept. of Nuclear Medicine, and Dept. of Urology*, Fertility Laboratory**, Beilinson Medical Center, Petah Tiqva, Tel Aviv University Sackler School of Medicine, Israel
Pessa
Depa, r t m e n t o£ N u c l e a r M e d i c i n e []st::,sdale N ~ g u a r d a CA G r a n d a .... M i l a n o
-
Italy
SIMUL.TANEOL~S I'EBT OF V[
With the (R/E) in.jection o-P the new myocardial agent T e c h n e t i u m . I s o n i t r i l e it is possible to test simultaneously {'irst pass ventr'icular .F'unc..... tion
(FPVF)
and m y o c : a r d i a ] ,
per'fusion
(MP).
~5
l:,ost-in'~arction pts, mean age 50.6 (8 ,~J.tl-, 'IVD, 8 with ~VD, 3 with 3VD and "I with NVD) were studied on d:i.~£eren't days durin 9 an R/E test. ]l,e aim o~ this study was to validate a multipararhe .... trio approach £sr the dete,:tion e~ residual mye .... cardial ischemia in the 'functional evaluation o£ CAD. Only a reduction o£ more than 5% in LVEF durin:~ eY.ercise and/or a transient de~ect o.F MP (3 views gated planar AC(~) were assumed 't~i be espressions o~ stress ischemia. When both MP and FPVF result,~ were either positive or" negative, the nuclear markers o.~ ischemia were considered concordant (C).l~' the e;.:ercise s'tress tes't (ES'I) was a l s o i n a g r e e m e n t , the 'final conclusions wer e considered ~ u l ] , y c o n c o r d a n t (F-'C). When MP and FF'-'VF: ~ i n d i n , ] s ~,;ere c o n { l i c t i n , ~ , the t'esult!- were
classi¢ied
as discordant
(D).
FPVF ,;.,ere C; i n t h i s group i n 40% o.F t h e C , ] r o u p t h i s to i n v a l i d a ' t e EST r e s u l t e . O'~' ~o],low--Lip is needed to
~indings in the remaining authors will suggest some
259
M.
In 15 pts, MP and
o n l y 9 w e r e FC. T h u s , new a p p r o a c h was a b l e An extended period
evaluate ~'ully the D 10 pts. Meanwhile, the possible eY.plana%ions.
260 N. H. 0~_a~/essian,
Instibube
S. 7. G 1 ~ g e n i a n ,
of C a r d i o l o g y ,
R.S. ~iekaelian,
Yerevan
NI/~ QUAI~FITAIIWI!EVALUATION OF "SUB-CLINICAL" VAEICOCELE
RADIOhrUCLIDE E S T I m a T I O N OF L E F T ~fENTRICULAR I~fOCARDIU}~ STATE OF I T S H Y P E R T R O P H Y IN P A T I E N T S W I T H A R T E R I A L HYIOERTENSION
Detection and grading of varicocele is usually based on physical examination. The palpation can be questionable in small varicocele. Several diagnostic methods for the detection of varicocele have been suggested. Radionuclide scotal blood pool imaging is done routinely in our department. The technique was modified allowing us to give a qualitative as well as a quantitative evaluation of the varieocele expressed as "scrotal blood pool index" - SBPI. The SBPI contributes to the detection and grading of left, right and bilateral varicocele. The main contribution of the study is for the detection of subclinical varicocele and postoperative recurrences. 784 studies on 540 patients with infertility problems were reviewed, among whom 194 patients (36%) were sent as "subclinical" varicocele where the palpation was questionable or normal. 159 patients (82%) were found to have abnormal studies, 99 patients (60%) were operated upon. Postoperative results with a 2-year follow-up showed a marked improvement of the spermatic counts in 77.8% of the patients, pregnancies and childbirth in 44.4%. These promising results lead to believe that scrotal blood pool imaging is the best non invasive study for the detection of "subclinical" varicocele.
Correlabion betweeu myocardium hypertrophy and ibs p e r f u s e d m e t a b o l i c sbabe is s b u d i e d insufficienbly;bhe a v a i l a b l e d a t a is b a s e d on E C G e v a l u a t i o n . The g i v e n w o r k d e a l s w i t h h y p e r t r o p h i c m y o c a r d i u m suabe i n v e s t i g a t i o n in 57 p a t i ents w i t h a r t e r i a l h y p e r ~ e n s i o n ( A H ) by polypos i t i o n a l s c i n t i g r a p h y w i t h 9 9 m - T c - p y p w i t h rad i o a c t i v i t y c a l c u l a t i o n over the c a r d i a c a r e a and c 0 n t r a l a ~ e r a l z o n e ( b a c k g r o u n d area). Left Left v e n t r i c l e h y p e r b r o p h y ( L V H ) was c h a r a c t e r i zed b y e c h o g r a p h i c v a l u e of left v e n t r i c ~ l a r m y o c a r d i u m mass(LW,~I). A c c o r d l u g be the L V H the p a t i e n t s were d i v i d e d into 2 groups: I - w i ~ h LNf~,[ f r o m 151 to 2OOg., II-LNf~[ 2OOg. In the I g r o u p in 18 p a t i e n t s of 30 d i f f u s e acctumala~ion of 9 9 m - T c - p y p w a s o b s e r v e d in c a r d i a c a r e a w i ~ h b a c k g r o u n d c o u n t i n g r a t e over b a c k g r m m d from 53 be 69To. In the s e c o n d group in 16 out of 18 p a t i e n t s p o s i t i v e s c i n t i g r a m s were r e c o r d e d , while in 12 - a c c u m u l a t i o n had d i f f u s e c h a r a c t e r w i t h b a c k g r o u n d a c t i v i t y e x c e s s till 4 ~ ,f- i n ~had an i n t e n s i v e o n e , w i t h t e n d e n c y to f o c u s s i n g ° Thus, in p a t i e n t s w i t h AH, w i b h L V A scinO i g r a m s m a y be b o t h negabive(2)/~) and p o s i t i v e (77%). S c i n b i g r a p h l c i n d i c a t i o n s of p e r f u s e - m e ~ tabolie violations coincided with ECG indications of isehemic m y o c a r d i u m lession.
464
262
261 J.C.Maublant,
N.Moins,
P.Gachon.
R.Zimmermann, M.Kapp, G.MalI, H.Achenbach, G.Zimmer, B.Bubeck, S.Hagl, P.Georgi, H.Tillmanns.
Centre Jean Perrin and INSERM U195 Clermont-Ferrand France
Departments of Cardiology, Pathology, Cardiovascular Surgery, and Nuclear Medicine, Ruprecht-Karls-University, Heidelberg, FRG.
DIFFERENCES BETWEEN TL-201 AND MIBI IN CULTURES OF MYOCARDIAL CELLS AT RECOVERY AFTER METABOLIC INHIBITION. This study was designed to assess the effect on the cellular uptake of TI-201 and MIBI of recovery (REC) after complete metabolic inhibition. Cultured beating myocardial cells of newborn rats were incubated with a mixture of 5 mM cyanide and 0.i mM iodoacetate in order to block the respiratory chain and glycolysis. The duration of incubation was 20, 40, 60, 120 or 2~0 min. Three durations of REC were assessed: (a) no REC (b) one hour and (c) 24 hours REC~ At the end of each REC period, a series of cultures were incubated for 20 min with 37 kBq of TI-201 or MIBI, then the cellular uptake of the tracer was measured. In a parallel experiment, the cellular viability was assessed by a trypan blue dye coloration. Results demonstrate that (a) without REC cellular uptake starts to be strongly inhibited after 20 min for TI-201 and after one hour for MIBI, (b) after one hour of REC there is a rebound phenomenon for TI201, but not for MIBI, (c) after 24 hours of REC uptake is very low for both tracers, even for a 20 min inhibition, (d) tracers uptake is always more decreased than cellular viability when expressed relatively to the controls. It is concluded that the cellular uptake of TI-201 and MIBI are significantly different in the early phase of metabolic inhibition and REC.
Departments Cardiology,
To investigate the structural correlates of reversible and fixed TI-201 uptake defects, 18 patients with coronary artery disease and ~75% stenoses of the left anterior descending coronary artery underwent quantitative stress TI-201 scintigraphy prior to coronary artery bypass grafting. During surgery, transmural biopsies were obtained in each patient from the a n t e r i o r wall of the left ventricle. W h e r e a s r e g i o n a l T I - 2 0 1 u p t a k e in initial scintigrams failed to show significant relations to morphometric parameters, poststenotic TI-201 uptake in the delayed scintigrams was inversely related to volume density (VD) of interstitial tissue (p<.05), and d i r e c t l y r e l a t e d to the VD of m y o f i b r i l s (p<.05). Patients with severe fixed TI-201 uptake defects revealed increased VD of interstitial tissue, but diminished VD of myofibrils and capillary surface density; subgroups of patients showing normal tracer uptake, redistribution or moderate fixed defects, however, failed to reveal significant intergroup differences. Thus, the presence of moderate fixed TI-201 defects does not necessarily mean myocardial scar tissue.
264
263 M.Clausen, A.Schmidt,
MYOCARDIAL STRUCTURAL ALTERATIONS AND REGIONAL THALLIUM-201 UPTAKE IN PATIENTS WITH CORONARY ARTERY DISEASE
E.Henze, W.Ost, R.Weller, W.E.Adam
R.Lietzenmayer,
ITh. Krause, A.Debertin, S.Renkert, C.Sch~michen, E.Moser University Hospital Freiburg, Dep. of Nuclear Medicine, Freiburg, FRG
of Nuclear Medicine and University of Ulm, West-Germany
TYPICAL ARTEFACT PATTERNS IN COLOR-CODED DISPLAYS OF MYOCARDIAL SPECT.
POLAR
The presentation of myocardial SPECT studies in polar coordinates implies compression of a huge amount of data into one functional image and offers thereby easy reading. The purpose of this study is to list some drawbacks of hhJs al~orithm in order to p~e~en% cl~n[cal misjudgments. 65 p~tie~ts underwent a~qio~raphy and Thallium-201 myocardial SPECT. The quantification procedure in polar coordinates included calculation of the area of significantly reduced tracer uptake. Taking these numbers alone resulted in a high rate of false positive findings, which could be traced down to the following list of artefacts~lesions: cresent-shaped at the periphery; small apical; sectorial at 2 hour; high septal; increased uptake depression inferiorly. numbers only: numbers+slices sensitivity: 83 % 83 % specificity: 43 % 87 % In conclusion, any analysis of myocardial emission tomography should be based on a critical evaluation of the short and long axis slices by the experienced investigator. The role of the color-coded polar quantification should be reduced to a decision assistance.
THE VALUE OF ADDITIONAL 6 HOUR TOMOGRAPHIC TI-201 MYOCARDIAL PERFUSION STUDIES The usefulness of a 2-4 hour redistribution study for differentiation of viable myocardium from scar is still a point of discussion. To assess the frequency, significance and intensity of delayed RD (6 hours p.i.) 287 consecutive patients (pts) with perfusion abnormalities at 3 hour study were additionally imaged at 6 lhours. 43/287 pts had no previous myocardial infarction. Quantitative analysis revealed late redistribution (RD) (3-6h) in 213/287 pts with a 32% decrease of the 3 hour defect size. In 28/244 (11%) pts with prior infarct, ischemic reaction was evident only at 6 hours. 23/43 pts )(53%) without prior infarction and with partial RD at 3 hours showed complete RD at 6 hours. Delayed RD was more pronounced in pts with nonQ-wave than in Q-wave infarction (p<0,05). No further correlation was seen concerning the presence or intensity of delayed RD (number of diseased vessels, percent stenosis, wall motion, ergome-try, presence or intensity of early RD). In conclusion, late RD study is recommended in: i. pts without prior infarct but with defect at 3 hours and 2. in pts with infarct in whom evidence of myocardial viability is a presupposition in deciding wether invasive therapy is opportune. Pts without Q-wave infarction may benefit most by 6 hour delayed imaging.
465
266
265 P.Kress*, M. Clausen**, R. Weller**, F. Bitter**, W.E. Adam**, V. Hombach*
Division of Cardiology*, Department of Internal Medicine Department of Nuclear Medicine** University of UIm, UIm, FRG
R.Weller,M.Clausen,E.Henze,F.Bitter,W.E.Adam Division of Nuclear Medicine University of Ulm (FRG)
PIXEL-BY-PIXEL QUANTIFICATION OF LV WALL MOTION ABNORMALITES BY REFERENCE-CIRCLE-METHOD
DIFFERENCES IN EXERCISE HEMODYNAMICS BETWEEN PATIENTS WITH CHRONIC AORTIC (AR) AND MITRAL VALVE REGURGITATION (MR) AS DEMONSTRATED BY RADIONUCLIDE VENTRICULOGRAPHY (RNV) RNV is the only practical technique to determine regurgitation fraction (RF) also during physiological exercise. The decrease in RF during exercise in AR is a well-known phenomenon (Corrigan 1832). In contrast, the exerciseinduced change of RF in MR is still debated controversely (Rigo et al. 1987). To study this issue, 31 patients with AR and 9 patients with MR underwent RNV at rest and during supine exercise (mean 94_+29 watt, and 67+22 watt resp.). RF was measured according to the formula RF = 100 X (1-1.43/regurgitant index), 1.43 being the normal value for the regurgitant index in our laboratory. At rest there was no significant difference in RF between the two groups. 22 out of 31 pts with AR (71%) had a decrease in RF during exercise, while this was the case in only 3 out of 9 pts with MR (33%). Hence, mean RF decreased during exercise in pts with AR (49.9+13.0% vs. 46.0_+10.1% p
Quantification of myocardial wall motion abnormalities by Fourier amplitude analysis is difficult, because of the individual size and shape of LV-Fourier-Amplitude images. It is usually accomplished by dividlng the LV-ROI in sectorial regions and comparing reglonal values to normal ranges. To overcome these shortcomings a REFERENCE-CIRCLE-METHOD was developed, that allows inter-individual comparison and definitlon of normal LV Fourier amplitude pattern on a pixel base. For this purpose the original LV Fourier amplitude scan was transformed into a standard sized circle. The radiant profiles of varying- length from the oriEinal LV-ROI were linearly interpolated into the radii ol the standard c i r c l e using 360 sampling angles. Retransfo[mat±on ol the individual left ventricular amplitude from the standard circle is feasible with an error of only 1%±0.3%. This method was applied first to 20 normal LV amplitude studies in order to establish a normal reference circle matrix. All 20 studies were composed to form a normal mean circle and a standard deviation circle image. In a second step, the Fourier amplitude scans of nine patients were compared against this normal matrix circle, Kevealing significant differences in all pixels of signilicantly depressed amplitudes. T h e s e are summarized, related to normal and aefined as hypokinesia fraction. This fraction correlated well with the size of infarction as quantified in the same nine patients by TC-99m Isonitril-SPECT with r = 0.92. We conclude that this method is able to quantify regional wall motion abnormalities with data won b~ a radionuclide ventriculography. The clinical significance is proved by the correlation to the size of the scar as a result from TC-99m Isonitril-SPECT perfusion study.
268
267
CAPILLARY FILTRATION TEST BY 99mTc-ALBUMIN M.Estorch,
l.Carri6,
L.Berng,
C.Martinez-Duncker,
BEHAR A., ALBAGLI B., COHEN-BOULAKIA F., LEVY M., LAGRUE
C.Alonso, B.Ojeda. D~partement de BIOPHYSIQUE Facult~ DIEU - 15, Rue de l'Ecole de M~decine 75270 PARIS CEDEX 06 - France
BROUSSAIS-HOTEL-
Hospital de Sant Pau, Barcelona. III-IN-ANTIMYOSIN MYOCARDIAL
UPTAKE
IN
PATIENTS UNDER
ADRIAMYCIN THERAPY FOR ADVANCED BREAST CANCER. Ten post-menopausal patients presenting with advanced breast cancer were studied with radionuclide ventriculography before and after Chemotherapy (I0 cycles mg/m2,
of Cyclophosphamide 600 mg/m2, Adriamycin 50 5-Fluorouracil 600 mg/m2), and after treatment
Ant±myosin (AM) scans. AM planar scans were obtained 48 hrs post-injection and graded visually as: O, no uptake; I, mild uptake; 2, moderate uptake; 3, intense uptake. A heart to lung ratio (HLR) on the anterior view of AM scans was calculated for quantitative analysis. Ejection Fraction (EF) was calculated prior and after chemotherapy. FE prior
FE after
AM(visual)
HLR
n=5
56%±7.2
46%±11.5
2
2.04±0.I
n=5
58%±1.9
59%±1.7
1
1.69±0.06
In conclusion,
myocardial Ant±myosin
uptake is very
prevalent in patients under Adriamycin therapy. Patients with a decrease in EF after treatment show more intense Ant±myosin uptake.
i- The 99mTe-albumin test can be used to confirm idiopathic cyclic oedema syndrom (ICO), or microangiopathy in diabetes, by pathological retention of albumin following the release of the tourniquet, in upper limbs. Retention is more than 8% of the maximum level when the tourniquet is in place. These results are obtained in 500 patients compared with i00 healthy women. 2- In a second experiment, the test was completed in a study involving double labelling using 131I-albumin and 99m Tc-red cells. In ICO, we found irregular oscillations after tourniquet removal only in the albumin test. The study of these oscillations by fast Fourier transform (FFT) revealed reproductible abnormalities in the low frequency zone (from 17 to 32 harmonics). All the tests with red cells, and all the 131I-albumin tests on healthy subjects have, in the low frequency zone, less than 2 oscillations, with amplitude << i% (compared with the fundamental amplitude). 3- Finally the 99mTc-albumin test with FFT study was carried out : In iO0 patients with ICO disease, all of them having an abnormal test, and in the low frequency zone, more numerous oscillations (from 3 to 5), and high relative amplitude > 1% In diabetes, the same test was carried out in 87 patients, 45 have abnormal oscillations, in the FFT and i0 also having an abnormal test. We proposed a model, according to Taylor's hypothesis, to e x p l a i ~ these ~esults,
466
269 M.Kapp, R.Zimmermann, H.Tillmanns, K.Schlumpp, B.Bubeck, M.Eisenhut, P.Georgi, W.Ki~bler. Departments of Cardiology, Nuclear Medicine and Pathology, University of Heidelb'erg, FRG.
EFFECT OF GALLOPAMIL ON REGIONAL MYOCARDIAL PERFUSION AND FATTY ACID METABOLISM IN PATIENTS WITH CORONARY ARTERY DISEASE. Purpose of the present study was to investigate the effect of chronic treatment with the calcium antagonist gallopamil (G) on global and regional myocardial TI-201 and iodine-123 phenylpentadecanoic acid (IPPA) uptake and clearance. Eighteen double-tracer studies were performed in 6 patients with stable angina pectoris and angiographically documented coronary artery disease: 80 MBq Tl-201 and 200 MBq IPPA were injected simultaneously after symptom limited exercise one week after placebo treatment (baseline investigation), 4 weeks after oral treatment with G (3x50 mg/die), and again one week after double-blind treatment with G or placebo. Planar images were performed in different views at 5 rain, 1 hr and 4 hr after injection using a Siemens Micro Delta system. Data were then transformed to an IBM PC (AT03) and converted to PC DOS format. In predefined regions of interest, regional tracer uptake, IPPA "extraction" (count rate ratio IPPA/T1-201 in the initial scintigrams), and IPPA clearance (calculated from the scintigrams 5 min and l hr p.i.) were determined using a recently developed computer algorithm. G caused a decrease of maximum heart rate from 148_+24 bpm to 128_+25 bpm (p<0.05). Despite reduced global uptake of both tracers under G treatment (T1-201:9%,ns.; IPPA:-21%,p<0.05), in poststenotic regions TI-201 and IPPA uptake was even slightly increased (both +4%). IPPA clearance, however, was markedly enhanced after G treatment (+26%, p<0.05). Thus, in addition to globally reduced tracer uptake due to decreased myocardial oxygen demand, G provokes an improvement of poststenotic myocardial perfusion and fatty acid metabolism.
270 P.F. Hoilund-Carlsen N. GadsbOll, J.H. Badsberg, J. Marving, B. Hjort Jensen, H. L~nborg-Jensen. Department of Clinical Physiology and Nuclear Medicine and Department of Cardiology, Glostrup University Hospital; Statistical Research Unit, University of Copenhagen, Denmark. LEFT VENTRICULAR VOLUMES AND EJECTION FRACTIONAS INDICATORS OF PROGNOSIS AND OF CHANGES IN V E N T R I ~ FUNCTION ACUTE MYOCARDIAL INFARCTION Purpose. (I) To detemine the relative prognostic significance of left ventricular end-diastolic volt~e index (EDVI), end-systolic volume index (ESVI), stroke volt,he index (SVI), and ejection fraction (EF) measured shortly after acute myocardial infarction (MI). (2) To compare changes in EDVI and EF one year later as indicators of ventricular functional status. Protocol. Absolute ventricular volumes and EF were determined by the count-based equilibrit~n radionuclide technique in the second week after MI in 189 patients. Re-examination was carried out after one year in 57 patients. Results. (i) Two weeks after MI there was an increase in EDVI in 53% of the patients and in ESVI in 72%, a decreas( in SVI in 19%, and a decrease in EF in 67%. Death from cardiac causes occurred in 29 patients within the first year. The combination of clinical heart failure and measured EF was superior to other possible groupings, considering also EDVI, ESVI, and SVI, with regard to prediction of one-year survival. (2) After one year there was in the re-examined patients a 22% increase in median EDVI an 27% increase in median ESVI, and a 21% increase in median SVI, whereas median EF had not changed. Conclusion. (i) Increased EDVI early after MI carried a bad prognosis, but ventricular volumes did not supply additional prognostic information to that obtained by measurement of EF. (2) Progression of ventricular dilatation late after MI was not paralleled by further reduction of EF.
272
271 Troch M, Versee L, Claeys R, Hollander G and J Huys'. Departments of Nuclear Medicine and Cardiology Algemene Kliniek Heilige Familie, Gent, Belgium. "Department of Radiotherapy and Nuclear Medicine,University Hospital, Gent, Belgium.
S,t,.~N~C.O,J.C, LIEHN, A. BOUCHARD. J,L. CHANPAGNE, J. VALEYRE.
Oeperteent of Nuclear Nedicine. Inatitut JEAN GODINOT. REINS, FRANCE. USE OF THE EARLY INAGES FOR BACKGROUND SUBTRACTION IN LABELED CELL SDINTIGRAPHY
Value of 111 Indium-antimyosin imaging in doubtfull acute myocardial infarct: routine experience in private practice. The aim of our study was to assess on a routine base in a mediumsized private cardiologic department the value of 111 Indium- antimyosin imaging for the detection of doubtfull AMI. 36patients were examined either in case there wa~ no correlation between the clinic, the enzymatic and the ECG changes or when it was impossible to differentiate an old from a new lesion. Two to three mCi of 11 l-Indiumantimyosin were given intravenously and planar scans were performed after 24 and 48 hours. Without the result of the scan the cardiologist presumed AMI occurred in 21: the scan was positive for 17, for 2 not convincing and 2 were considered a bad tag. For the 15 patients where AMI was not retained by the clinician the scan was positive in 4. In 3 the diagnosis of AMI was afterwards confirmed ( one had no further examinations) .We actually consider antimyosin imaging a usefull examination in clinical practice, especially for patients where AMI is a possibility but the routine diagnostic methods remain inconclusive. The result of the scan is defining further diagnostic examinations which can have more morbidity and which are not always easily avai lahie.
Background lleIn radioactivity in the circulating blood pool decreases the sensitivity of labeled-cell studies and imposes the recording of late (up to 4 days) images. Me have shown that a new subtraction image technique which automatically performs geometric registration and normalization, increases the sensitivity of parathyroid scintigraphyand immunoscintJgraphy.This technique makes it possih]s to subtract images recorded at differenttimes, The aim of this pre]iminarystudy is to determinethe benefitsof using early images for blood background subtraction in labeled-ce]]scintigraphy. Patients and method: 20 patients presenting with suspicion of intra-cardiac thrombosis were referred for llIIn plate]eLscintigraphy, 23 patients were referred for llIIn leucocyte scintigraphy (most with suspicion of hip prosthesis infection). 30 min after the injection of labeled cells, early images were recorded with a 9ammacsmera. De]eyed images were then recorded (at 4 and 24 h for ]eucocyte scans and at day I to 4 for p]atelet scans). The early image was then subtracted from the latter imagesusing the new subtraction image technique.
Results: A]] positive scans (5 plstelet and 12 leucocyte scans) were better. visualized and more precisely ]ocelized after subtraction. This procedure avoids the use of mm'Tc labeled red cells giving lesser irradiation, no subtraction artifacts (same isotope for subtraction image) and shortens .the duration of examination. Moreover, in some cases, an aar]ier diaBnostic was possible, Conclusion: The use of early image for blood-pool backgraund subtraction simplifies ]abeled-cell scintigraphy and can provide earlier results.
467
274
273 J-Y
DEVAUX,
M. VRILLON,
D.
DUBOC,
F. GUERIN,
O. G A U D I C H E ,
J-F EGU,
J-C R O U C A Y R O L
Cochin U n i v e r s i t y Hospital, Saint Ja cq ue s 75674 PARIS
S.HOLTMEIER,
M.CLAUSEN,
F.BITTERp
R.VELLER, E.HENZE,
H.J.BAIR, W.E.ADAM
27 rue du F a u b o u r g Cedex FRANCE
Division of Nuclear Medicine University of Ulm (FRG)
RADIONUCLIDE EVALUATION OF LEFT V E N T R I C U L A R PERFORMANCE AT REST AND WITH ISOPROTERENOL IN M U S C U L A R D I S T R O P H Y D U C H E N N E DE B O U L O G N E The left v e n t r i c u l a r p e r f o r m a n c e of thirty two patients, w i t h d o c u m e n t e d D u c h e n n e de B o u l o g n e myopathy (DDB), has been e v a l u a t e d by 99mTc gated blood pool technique, in order to detect and evaluate the cardiac failure risk during spine o s t e o s y n t h e s i s surgery. Global ejection fraction (GEF) and regional wall motion (RWM) a n a l y s i s were p e r f o r m e d at rest, after intravenous administration of i s o p r o t e r e n o l and after recovery. 20 ! At rest, 13 pts had a GEF b e l o w 60% and pts had ab no r m a l RWM in more than one myocardial segment. After isoproterenol, 20 ! pts i n c r e a s e d their GEF by more than 10% while 12 remained unchanged or s l i g h t l y worsened. Among these 12 pts, 8 showed an increase in the number of RWM a b n o r m a l segments. D uring the re co ve ry p e r i o d seven p a t i e n t s p r e s e n t e d a significant drop in GEF as c o m p a r e d with the value recorded at rest. No a d v e r s e effect on cardiac rhythm was noted. We c on cl ud e that the i s o p r o t e r e n o l test is a well t o l e r a t e d p r o c e d u r e in DDB and a v a l u a b l e tool for the evaluation of the m y o c a r d i a l contractility reserve in p a t i e n t s with DDB, u n ab le to p e r f o r m e x e r c i c e tests.
CENTRAL DEPRESSION OF THE RNV AMPLITUDEA COMPUTER SIMULATION STUDY
In radionucllde ventrieulography (RNV), a left ventricular (LV) central depression of the Fourier-amplitude image has been observed in patients without any regional wall motion abnormalities. However, this phenomenon appears to be correlated with a dilatation of the LV with a high ejection fraction (EF), as observed in patients with aortic valve insuffiency. In order to reveal a physiologically relevant explanation of this phenomenon, a computer-simulation model has been developed. The ventricles and the atrial chambers are approximated by contractive ellipsoids. The end-diastolic volume (EDV) can be varied as well as the EF, the contractive kinetics, the distances between the cardiac chambers and their centers of gravity. It is found, that an enhanced EDV of one of the ventricles modifies the movement of the chambers and the center of gravity in such a way, that the central depression can be observed provided the EF exceeeds a value of about 40%. These results agree well with the LV-dilatation of our patients. Thus it can be concluded, that the central depression may occur in enlarged ventricles with relatively well preserved global function, such as in volume overloading, as a misleading observation in amplitude imaging.
276
275 P.Kostamis, 3.Lekakis, N.Vassilopoulos, S.Rokas, N.Sifakis~ Th.Athanasoulis, Chr.Kalliontzi, D.Tsinikas, Sp.Moulopoulos.
R. SCIAaRA', G. BISI, O.M. ,.SANTORO*, F. C)IUSTI, M. LEONCINI*, P.F. FAZZINI*,U. MELDOLESI. NUCLEAR MEDICINE,DEPARTMENT OF CLINICAL PATHOPHYSIOLOBY, UNIVERSITY OF FLORENCE; * DEPARTMENT OF CARDIOLOGY,OAREGGI HOSPITAL. FLORENCE, ITALY.
Dpt of Therapeutics and Dpt of Nuclear Medicine "Alexsndra"University Hospital, Athens Greece SPECT vs PLANAR IMAGING DURING DIPYRIDAMOLE-Tc99m RP-30 TESTING: SIGNIFICANCE OF ANATOMIC LOCATION AND SEVERITY OF CORONARY ARTERY DISEASE. SPECT imaging during dipyridamole
Tc99m-RP-3Oseintig~aphy seems tobesuperior to planar 3 view imaging (PL). To investigate the significance of severity and anatomic location of CAD to differences in sensitivity between SPEC~ and Planar imaging (PL) we analyzed data from 39 patients (pts) who underwent coronary arteriogrsphy and Dipyridamole-Tc99m RP-30 testing. Data were analyzed according to extent of CAD (1,2 or 3 vessel disease), degree of stenosis (50-70%, >70% and vessel diseased (LAD, LCX, RCA). Results ere (*p<0.05). Sensitivity (%)
SPECT PL
Vessels I 2 3 93 100 100 79 83 90
Stenosis 50-70% >70% 50. 87 19 62
LAD 86 62
Vessel LCX RCA 56. 88 22 69
Stenosis >70% was comparable among LAD (71%), LCX (67%)! and RCA (81%). Specificity was similar for SPECT snd PL in LAD (9~% vs 81%),LCX (95% vs 100%) and RCA (67% vs 63%). In conclusion: SPECT during Dipyridamole-Tc99m RP-30 is superior to PL imaging especially in LCX disease and moderate stenosis.
TC-99m-MIBI STUDIES USING DIPYRIDAMOLE INFUSION:USEFULNESS OF COFIBINING FIRST-PASS ANGIOCARDIOGRAPHY AND MYOCARDIAL PERFUSION SCINTIGRAPHY. Until now dipyridamole infusion (DI) has been usually employed as stress test for coronary artery disease detectionby studying eithermyeeardial perfusionwith Tl-201 scintigraphyor wall motion and leftventricular functionwith echocardiography. The features of Tc-99m-MIBI, however, allow to evaluate both global and regional ventricular function with first-passradionuclideangiocardiography (FRA) and perfusion with myocardial seintigraphy(MS). We estimatedthe value of thiscombined assessment by comparing its results with those of echocardiographyperformed during DI and thoseof exerciseMS, using coronary angiography as referencestandard. Twenty patientswith suspecteffortangina were studied.Of them 19 had angiographic evidence of coronary artery disease (7 one-vessel, 7 twovess~l and 5 three-vesseldisease).With three separate injectionsof 740 MBq of Tc-99m-MIBI in differentdays, they underwent baseline FRA and MS, exercise M$, DI FRA and MS. In the last occasion two-dimensional echocardiographywas alsoperformed. The sensitivityin identifyingcoronary artery disease patientswas 95% with exercise MS, 90% with DI MS and only 47.4 % with DI echocordiography. When the resultsof DI FRA and DI MS were combined, 95% sensitivitywas achieved.ExerciseMS and DI MS were also compared with regard to the recognitionof the individualaffectedterritories:sensitivitywas 75% with exercise MS and 69.4% with DI MS', specificitywas respectively 87.5% and 83.3%. We may concludethat the combined evaluationof function and perfusion with lc-99m-MIBI using DI isan effectivediagnasticmethod, which offers good resultsas compared to other establishedapproaches.
468
278
277
A.Notghi, C. F. Bekdik D~oartment of Nuclear Medicine, Hacettepe U n i v e r s i t y Faculty of.Medicine, Ankara, Turkey.
P.Kress*, M. Clausen**, E. Henze**, R. Weller**, F. Bitter**, W.E. Adam**, V. Hombach*
NEW APPROACHES IN QUANTITATIVE ANALYSIS OF 20iTI MYOCARDIAL PERFUSION PLANAR SCINTIGRAPHY
PRE- AND POSTOPERATIVEEVALUATION OF LEFT VENTRICULAR EJECTION PERFORMANCE IN PATIENTS WITH MITRAL VALVE STENOSIS (MS) ALS DETERMINED BY RADIONUCLIDE VENTRICULOGRAPHY(RNV) Depression of left ventricular ejection fraction (EF) in MS has been reported by many authors and was primarily attributed to myocardial damage due to rheumatic heart disease (Hildner et al. 1972), regional wall motion abnormalities adjacent to the mitral valve apparatus (He er eta. 1970) and mpa red eft ventricular (LV) filling through the stenotic mifral valve (Gash et al. 1983). The postoperative course of EF might give insight into the underly ng pathophysiological process. However, evaluation of postoperative LV ejection performance by echocardiography may be misleading due to common paradoxical septal motion following mitral valve surgery (OP). Therefore, we studied 12 pts with pure or predominant MS before and 6-18 months following, OP by RNV. Preoperatively, there was a slight depression of EF (_<50%)in 6 of these pts. All these 6 pts had an increase in EF following OP with a postoperative EF exceeding 50% in 4 cases. An increase in EF could be observed in another 3 out of the 6 pts with normal preoperative EF. The increase in EF for the total group (50.8 -+ 12.3% vs 59.8 -+ 10.3%) is statistically significant, (p
.i
i
In 22 normal subjects (2F,2OM,mean age: 44.9±89) in addition to myocardial 201]'1 wesh-out(WO%),uptake(UT%) and common maximal uptake % (CMUT%) rates we investigated the wash-out difference (WO%D), wash-out difference %(WO%D%) and uptake difference %(UT%D%) rates of myocardial sectionsa~ording to the maximal point value in each scintigram taken from anterior, 45OLAOand LL positions.The mean~2$D normal values of these parameters'were compared with those values obtained from 20 CAD patients (P): I OP(4F,6M,mean oge:53.1+ 10.7) with reversible ischemia and lOP, (all M,mean oge:51.2±8.7)who had myocardial infarct(MI) respectively. Among the parameters mentionedabove the WO%D% rates were found more accurate in detectionof myocardial perfusion defects than WO% rates in CAD (with accuracies of 83.5% enct 75.5% respectively) and ISC P (wtth accuracies of 83.5% and 76.0%). In P with MI delayed CMUT% rates were more accurate (with 96% accuracy) than other parameters mentioned above. While UT%D% rates were not more valuable than other conventional parameters. In conclusion we found that more standard parameters such as WO%D% rates, were of more vane than the individual WO% rates in P with CAD and ISO. Furthermore, we suggestthat new quantitative ecinUgraphy programs sh0u]d be written, Programs that include norrtra] range values and/or curves (with desirable standard deviations), statistically obtained from individualized normal groups, automatically transfered and over-displayed on the oMgina] values and/or curves of the patient, wll] be helpful In quanUtatNe analysis of mu]tifactoria] sointigrophic tests such as 201T] myocardial perfusion sclntigraphy.
Division of Cardiology*, Department of Internal Medicine Department of Nuclear Medicine** University of UIm, UIm, FRG
References: Gash AK, Carabello BA, Cepin D, Spann JF: Left ventricularejection performance and systolic muscle function in patientswith mitral stenosis.Circulation67:148-154 (1983) Heller SJ, Carleton RA: Abnormal left ventricular contraction in patients with mitral stenosis. I Circulation42:1099-1110 (1970) Hildner FJ, 3avier RP, Cohen LS, Samet P, Nathan MJ, Yahr WZ, Graenberg JJ: Myocardial i dysfunctionassociatedwith valvular heart disease. Arn J Cardio130:319-326 (1972) I I
279
280
J.KIUDELIS,
L. N y i t r a i , L. Zsonda, M.Ruszn~k and Zs. Nagy
Z.SATKEVICIUS,
R.NAVICKAS
Radioisotope Laboratory, l e t and 3rd Department of I n t e r n a l Medicine INSTITUTE
Jdsa AndrOs Hospital, Nyiregyh~za, Hungary H44~1Nyiregyh~za, P.O.Box: 159. EVALUATION OF REGURGITATION FRACTION (RF) AND LEFT VENTRICULAR FUNCTION USINg A PORTABLE, NON-IMAGING, MULTICHANNEL NUCLEAR DEVICE (MG Z87). Combining the functional parameters (EF,EDV,CI) of the MG Z87 /l~xl~xSmm CdTe detectors/ with the parameters of M-,2D-, and Doppler US, our aim i s to suggest the optimal time of surgical i n t e r v e n t i o n , and to £ollow up the patients a f t e r valve replecament. We use two independent methods for RF evaluation in HG ZS? measurements. ~:The difference of the f i r s t - p a s s " e f f e c t i v e " EF(EF f-p) and e q u i l i b r i u m EF(EF eq) can evaluate RF in percent of EDV, 2:A tw0-c0mpartment model in equilibrium investigation. Our results show, that the severiety of regurgitation can be evaluated and compared with the regurgitation index (2+,3+,4+) obtained in cardiac catheterization. Myocardial dysfunction can be detected too before irreversible symptoms develop. The 2nd method can not be used if the left ventricle function is severely damaged ( E F ~ t , EOV>I8~ ml/m2). Using the Ist method left-to-right shunts(L-R S) influence EF f-p the same way as regurgitation, on the other hand L-R S is obviously seen on the lung curve. After elimination of input and right ventricle dispersion effects using model-free transfer function, EF f-p is absolute value. We can conclude, that our noninvasive, low-cost, nonimaging radioisotope method could be very important in management of patients with aortic and mitral valve disease
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469
28,2
281 A.Facello, J.R.Kieny, B.Brunot, P.Bareiss.
A.Constantinesco,
J.L.Demangeat,
F. Corstens*, P. Smits, W. Aengevaeren ~ and Th. Thien. St Radboudhospital, *department of nuclear medicine, #department of cardiology and department of interns] medicine, Nijmegen, The Netherlands.
C.H.U Hautepierre,
67098 STRASBOURG, France.
PHASE ANALYSIS OF BLOOD POOL GATED SPECT FOR THE DIAGNOSIS OF BYPASS TRACTS LOCALIZATION IN WOLFF-PARKINSONWHITE SYNDROME.
Non-invasive methods for the localization of accessory pathways (AP) in Wolff-Parkinson-White syndrome (WPW) are needed specially since new percutaneous techniques for AP ablation a r e under development. We studied 23 pts with WPW : iS pts had free wall AP (7 left sided and 6 right sided),"6 posterior paraseptal and 4 anterior paraseptal AP. In each pt, gated SPECT was made in 18 projections (one minute each) over 180 ° after 30mCi Tc-99m red blood cells labelling. 16 up to 20 images/cycle were obtained at a fixed time/image of 40 msee. Images reconstruction was carried keeping same limits and same axis to obtain two-pixels slices in the three planes : short axis, long axis and four chambers. Fourier analysis was applied on these images and a dynamic display of the sequence of ventricular activation was observed. Results were compared with electrophysiological (EPh) localization obtained in maximal pre-excitation during atrial pacing by an independent observer. SPECT localizations were in agreement with EPh in 19/23 pts (83 %). In 3/4 discrepancies, side of AP was correct but judged to a near region. In the pt with total disagreement, an associated dilated cardiomyopathy was present. In conclusion : gated-SPECT is a sensitive method to diagnose the localization of AP in WPW pts and a wider clinical utilization is forseeable with the faster processors which are coming.
CAFFEINE REDUCES DIPYRIDAMOLE-INDUCED MYOCARDI~ ISCHEMIA. Dipyridamole induces coronary vasodilation by increasinc endogenous adenosine levels. Since caffeine shows I adenosine-antagonism in-vitro, we hypothesize that caffeine inhibits the vasodilation after dipyridamole. I After a caffeine abstinence of 36 hr, Z°iTl-myocardial imaging was started 6 min (initial) and 3 hr (delayed) after dipyridamole (0.56 mg/kg i.v.). In 6 patients re~r~ib]e Derfus~on detects were observed~ and thi~ group underwent a 2=d test, but now 20 min after caffeim (4 mg/kg i.v.). These defects were quantified by calculating the ratios between the averaged counts/ plxei in the defects vs normally perfused myocardium. Without caffeine, dipyridamole induced chest pain and STdepressions on the ECG in 3 patients, whereas no problems occurred after caffeine. The fall in mean arterial pressure averaged -14.7±3.6% after caffeine abstinence vs -3.9±0.7 after caffeine (P<0.05), and the rise in heart rate numbered respectively 33.2±7.8 vs 9.2±3.2% (P<0.01). Visually, all perfusion defects were disappeared or reduced in the 2n= test. The calculated ratios in the inital images from the anterior, LAO-40 and LA0-70 view numbered respectively 0.76±0.05, 0.79±0.02 and 0.77±0.04 after caffeine abstinence. These ratios were higher after caffeine: 0.88±0.06 (P<0.025), 0.88±0.03 (P<0.02) and 0.87+0.05 (P<0.001). The delayed images were similar in b o t h - tests. These findings support our hypothesis, suggesting that an abstinence of caffeinated beverages (coffee, tea) of at least 24 hr should be recommended jPrior to dipyridamole ZO~Tl-tests.
284
283 TD Rudd[, M White, KY Gulenchyn, PC Spencer, EJ Cooper, MG Baird, JF Marquis, J Ballinger, RA Davies,
P.Kress*, T. Hermann-Grassl*, M. Clausen**, E. Henze**, R. Weller**, F. Bitter**, W.E. Adam**, V. Hombach*
University of Ottawa Heart Institute 1053 Carling Avenue Ottawa, Ontario, Canada
Division of Cardiology*, Department of Internal Medicine Department of Nuclear Medicine** University of UIm, UIm, FRG
DETECTION OF CORONARY ARTERY DISEASE WIT]{ METABOLIC SCINTIGRAPHY USING IODINE-123-PHENYLPENTADECANOIC ACID AND INDUCED HYPEREMIA
DETECTION AND QUANTIFICATION OF PREMATURE LEFT VENTRICULAR (LV) EJECTION IN MITRAL REGURGITATION (MR) BY RADIONUCLIDE VENTRICULOGRAPHY (RNV) LV time-activity curve (TAC) yields information concerning the enddiastolicendsystolic count rate difference being essential for the calculation of LV ejection fraction (EF) and the regurgitant index. However, the shape of the TAC rarely was the sub ect of investigation. In MR premature LV ejection due to favorable oading cond tions s suspected but has not yet been documented by RNV. Therefore, we studied 40 pts with MR (30 with severe MR (angiographic degree Ill or IV), 10 with mild MR) and 32 normals by high time resolution RNV (32 frames per cardiac cycle). Fourier transformation was applied to the TAC's. Duration of systole (SD) and enddiastoUc-endsystolic count rate difference (2 stroke volume (SV)) were normalized and expressed in % for comparison. The mode of ejection was quantified by two methods: First, sequential analysis of the TAC was performed, measuring the percental of SD to eject the first 10, 20 etc. % of the SV. Second, the mode of ejection was quantified by the area underneath the systolic part of TAC in percent of the theoretical maximum. We found a premature ejection in severe and mild MR as compared to norreals which was statistically significant (p < 0.01) for the first 10-70% of ejected SV. For example, in severe MR 29.3+_5.9% of SD is needed to eject the first 20% of SV, while in mild MR 31.8+_2.7% and in normals 36.3+7%. There is also a significant difference in the area underneath the systolic part of the TAC between the 3 groups (severe MR 45.0±4.3%, mild MR 47.2+_1.9%, normals 49.3+_3.1%; p
Myocardial uptake of iodine-123-phenylpentadecanoic acid (IPPA), a synthetic fatty acid, is directly related to blood flow and aerobic metabolism. Dipyridamole results in flow differences and often ischemia (anaerobic metabolism) in pts with coronary artery disease (CAD). Thus, myocardial uptake of IPPA after dipyridamole should be reduced in myocardial regions ~ u ~ i ± e d ~2 ~t6[~o~d c o ~ o n a ~ a~teY-±es. T~he diagnostic accuracy of dipyridamole IPPA imaging for the detection of CAD was evaluated in 55 pts with chest pain (35 with and 20 without CAD defined as >70% diameter stenosis by quantitative coronary angiography). Pts were imaged tomographically (3 serial 16 minute studies) after dipyridamole and IPPA injection. Rapid IPPA clearance permits redistribution imaging immediately after initial imaging. Results for detection of CAD by decreased uptake of IPPA are below. SENSITIVITY
CAD LAD LCX RCA
SPECIFICITY
DIAGNOSTIC ACCURACY
0.94 0.80 0.89 0.82 0.82 0.82 0.60 0.94 0.82 0.87 0.70 0.75 Dipyrida~1ole IPPA tomographic imaging has high sensitivity, specificity and diagnostic accuracy for detection of CAD. Redistribution imaging immediately after initial imaging results in greater patient and laboratory convenience. Dipyridamole IPPA imaging may be a superior alternative to stress thallium imaging.
470
285 M.M.J. Mohammed, I.M. Hassan, C. Constantinides, M. Nair, N. Bellani, N. Khan, Y. Kewan, H.M. AbdelDayem.
Depts. of Nuclear Medicine and Cardiology, Kuwait University, Ministy of Public Health, Kuwait. ASSESSMENT OF THE DELAYED SPECT THALLIUM-201 (TL) IMAGES FOR DIFFERENTIATION OF VIABLE FROM SCARRED MYOCARDIUM. Recently, 24 hrs delayed stress (St) T1 images has been proposed to differentiate myocardial (M) scar from severe ischaemia. Because it has several problems, we planned a prospective study to compare early, 3, 6, 24 hrs SPECT images for St T1 studies. 19 patients included were injected 3 mCi TI-201 at max tolerable Ex. (14 M & 5 F~ age (45+8.5, yrs). Slices of 0.6 cm thlck~s~ for short, vertical and horizontal axes were normalized and displayed together with bullseye. Activity in 4 M segments (S) was blindly interpreted by a consensus of 2 experienced observers and graded 0 = normal, 1 = complete reversible ischaemia (CRI), 2 = partial reversible ischaemia (PRI) & 3 = scar. CA within 2 weeks showed 6 had 3 vessel diseas~ (VD), 7 (2VD), 6 (IVD). Considering early & only 3 hrs images for reporting : 22 S had CRI, 14 PRI and 7 scars. At 6 hrs 8 segments of the 14 PRI, became CRI and 3 from scar moved to PRI. At 24 hrs the ii S from 14 PRI at 3 hr became CRI and only one from scar group moved to PRI. However, at 24 hrs, areas of the normal or CRI segments at 3 hrs became patchy and difficult to differentiate from reverse redistribution pattern. This problem was not faced at 6 hrs. We conclude that 24 hours delayed images for St. T1 studies has problems due to insufficient counts and T1 kinetics. The 6 hrs images has better information regarding M viability with better physical characteristics.
287 Th.Krause, C . S c h u e m i c h e n , W . K a s p e r , ~ h . M e i n e r t z E.Moser U n i v e r s i t y H o s p i t a l Freiburg, Dep. of N u c l e a r Medicine, Freiburg, FRG
NONINVASIVE IDENTIFICATION OF THE CULPRIT VESSEL IN A C U T E M Y O C A R D I A L I N F A R C T I O N BY S I M U L T A N E O U S Ti-201/Tc-99m PYROHOSPHATE TOMOGRAPHY The i n f a r c t r e l a t e d v e s s e l a f t e r a c u t e m y o c a r d i a l i n f a r c t i o n (AMI) is i d e n t i f i e d by a n g i o g r a p h y only. T h i s 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 a s s e s s the d i a g n o s t i c u s e f u l n e s s of T I - 2 0 1 t o m o g r a p h y (tomo) and s i m u l t a n e o u s T i - 2 0 I / T c - 9 9 m P y r o p h o s p h a t e (PPi)-tomo (3 h o u r s later) for det e c t i o n of the "culprit" v e s s e l in 122 c o n s e c u t i v e p a t i e n t s w i t h AMI. All e x a m i n a t i o n s were p e r f o r m e d w i t h i n 7 days a f t e r AMI. T h e r e s u l t s of the s e c t o r i a l a n a l y s i s w e r e c o m p a r e d to c o r o n a r y a n g i o g r a p h y (gold standard). The s e n s i t i v i t y and s p e c i f i c i t y for i d e n t i f i c a t i o n of the left a n t e r i o r d e s c e n d i n g (LAD:n=51), c i r c u m f l e x (LCX:n=44) and r i g h t c o r o n a r y (RCA:n=27) a r t e r i e s were: TI-201 Tomo Ti-2Ol/Tc-99m Tomo LAD LCX RCA LAD LCX RCA S E N S . : 82% 81% 50% 92% 96% 86% S P E C . : 94% 83% 94% 98% 91% 97% In c o n c l u s i o n T I - 2 0 1 / T c - 9 9 m PPi t o m o is a v e r y s e n s i t i v e and specific, n o n - i n v a s i v e m e t h o d to i d e n t i f y the i n f a r c t r e l a t e d v e s s e l in AMI. The m e t h o d p r o v i d e s s u p e r i o r r e s u l t s c o m p a r e d to TI201 tomo. The c r u c i a l p r o b l e m ot d i f f e r e n t i a t i o n b e t w e e n LCX and R C A by T I - 2 0 1 t o m o a l o n e is s o l v e d by a p o s i t i v e v i s u a l i s a t i o n of M y o c a r d i a l n e c r o s i s in both, the left and right v e n t r i c l e as it is p o s s i b l e by T i - 2 0 1 / T c - 9 9 m PPi tomo.
286 TD Ruddy, KY Gulenchyn, KJ Ascah, WL Williams, PC Spencer, SA Kearns, JR Ballinger, RA Davies University of Ottawa Heart Institute 1053 Carling Avenue Ottawa, Ontario, Canada
COMPARISON OF IN-ill ANTIMYOSIN ANTIBODY PYROPHOSPHATE IMAGING OF MYOCARDIAL NECROSIS
AND TC-99H
In-ill antimyosin antibody (AM) and Tc-99m pyrophosphate (PYP) imaging detect myocardial necrosis. Although AM has high specificity for necrosis, experimental studies have shown PYP accumulation in necrotic and adjacent viable ischemic regions. To determine the relationship between AM and PYP uptake in acute myocardial infarction in man, we evaluated 5 p~ti~nts fuilowiii~ UhiD~olvtio therapy with simultaneous AM and PYP scintigraphy. Coronary angiography showed reperfusion in 4 and failure in i. The infarct-related vessel was LAD in 3 and RCA in 2. AM (80 MBq) was injected at 24 and PYP (740 MBq) at 72 hours following thrombolysis. Dual isotope imaging was carried out 3 hours after PYP injection using a medium energy collimator and tomography (360 ° rotation, 64 projections, 35 seconds per projection) and 20% windows. Transverse image slices were reconstructed after scatter correction (estimated at 11%) and the patterns of AM and PYP uptake were compared. In 4 patients with reperfusion, the extent of PYP uptake was significantly greeter than AM (p<0.05). Excess PYP localized to adjacent regions supplied by the infarct-related coronary artery. In the 1 patient with faile( reperfusion, extent of PYP and AM uptake was similar. Thus, AM and PYP localization differ in patient~ receiving thrombolytic therapy for myocardial infarction. Excess PYP uptake most likely identifies severely ischemic myocardium that may recover.
288 G. Neumann, A. K~gler, S. Wei~brodt, L. Otto, A. Wffusche Karl-Marx-University Leipzig, Dep. of Radiol. Div. of Nuclear Medicine, Liebigstr. 20, 7010 Leipzig, GDR
SPECT-I'~STIGATIONSWITH THALLIDM-201ANDMYOSPECT (Tc-99m-DIMETHYLPHOSPHINOETHAN) The aim of this paper was to compare the new substance Myospect with Thallium-20S chloride in patients with a chronic ischemic heart disease. 28 patients have been selected for this comparative study at random. Myocardial scintigraphy using TI-201 was performed after bicycle ergometer and after redistribution. Myocardial scintigraphy with Myospect was carried out I week after the TI-201 investigation. Data were acquired from 45 LPO to 45 RAO arc, 64 x 64 matrix, 32 projections, at 30 seconds stop. Visual analysis was performed in short axis, long axis and horizontal axis projections. SPECT imaging with T1-201 and Myospect showed the same findings in 82% for the patients. A discrepancy between both methods was found in 5 cases: all scans with TI-201 were normal whereas Myospect scans showed defects. The defects were localized in 4 of the 5 cases in the posterior wall. The positive interspecific coefficient of ~ssociation (Cole) is I, therefore a strong similarity exists between both methods. Statistical certainty with chi-square test yields a probability level lower than
I%. SPECT imaging with Myospect is an alternative to TI~201 in the detecting of ischemic heart disease.
471
289
290
Manntin9 F., Morgan M.G. J-Y DEVAUX, G. BERGER,
Dept. Clin. Phys., University Hospital Uppsala, Sweden NEW QUANTITATIVEMETHODSFOR ASSESSMENTOF PULMONARYTL UPTAKE IN MYOCARDIALSPECTSTUDIES. The aim of this study was to evaluate new methods u t i l i z i n g raw SPECTdata, to assess pulmonary T1 uptake, and to test the methods'discriminative function in patients with CAD vs normals. Stress T1 SPECT studies were performed in 24 normals and 35 consecutive patients with CAD. Pulmonary/ myocardial (PM) ratios, pulmonary/mediastinial ratios (PMED), and absolute pulmonary T1 uptake (P) were computed from composite raw SPECT data using standardized pulmonary regions: upper l e f t lung ( u l l ) , and right lung ( r l ) . 30 of the subjects underwent additional evaluation of pulmonary T1 uptake with a standard planar method. P showed a strong inverse correlation to BSA (r=-0.67, p
291 J, L. Lear, U. Raft, R. Jain. Division of Nuclear Medicine (A034), University of Colorado Health Sciences Center, 4200 E. 9th Avenu, Denver, CO 80262 USA
E R R O R S IN M Y O C A R D I A L T H A L L I U M W A S H O U ' I D E T E R M I N A T I O N AND D I A G N O S I S OF CORONARY A R T E R Y D I S E A S E C A U S E D BY I N T E R P O L A T I V ] ~ BACKGROUND SUBTRACTION While the interpolative background subtraction frequently used ir quantitative planar thallium scanning has been shown to overestimate the background overlying the heart, the effects of the backgrounc oversubtraction on quantitative analysis have not been well defined. We therefore developed a mathematical model which relates measured myocardial washout determined using interpolative background subtracfio.-,, W~,~, tc~ tr.e myocardia! washout, W t Solution of the model's equations yielded: 1- [ (Cd/B i - Bdm/Bi) / (Ci/B i - Bim/Bi) ] Wm/W t ................................................... 1 - [ (Cd/Bi - Bdm]Bim) / (Ci/Bi - 1) ] Where: Ci = initial cardiac activity, C d = delayed cardiac activity, B i = initial true background activity, Bim = initial measured background activity, and Bdm = delayed measured background activity. The model was tested using phantoms and applied to cardiac and pulmonary thallium kinetic data from 100 patients. Measured washout in normal myocardium was found to be accurately defined using interpolative background subtraction, but depending on the relationship' between cardiac and pulmonary thallium kinetics, myocardial washout in ischemic regions and areas of infarction could be substantially over-' or underestimated. Such errors in washout measurements were shown at times to cause infarcts to be misdiagnosed as ischemic areas and ischemic areas to be misdiagnosed as normally perfused areas using generally accepted quantitative criteria. The model also explained the observed occurrence of "reverse redistribution" in infarction and "negative washout" in ischemia in the absence of a physiological basis.
D. DUBOC, F GUERIN,
R. CALDERA, B. RICHARD,
O. GAUDICHE, J-C ROUCAYROL
Cochin University Hospital, 27 rue du Faubourg Saint Jacques 75674 PARIS Cedex FRANCE
DIPYRIDAMOLE AND THALLIUM-201 TOMOGRAPHY IN MUSCULAR DISTROPHY
MYOCARDIAL
Rest and Dipyridamole (DPD) thallium-201 myocardial tomograms were compared in fourty seven patients with various muscular dystrophy diseases (37 Duchenne de Boulogne 6 Steinert, 3 Becker and 1 Proximal Myopathyl. This study was made to estimate the part of the coronary microcirculation in myocardial impairement as previously evoked by positron imaging. Thallium scans with and without DPD were performed at one week intervals on an alternate basis. Care was taken to inject a similar activity (2 mCi) for the two studies. As the myocardium was divided into 9 segments for each patient, 423 segments were studied. 45 patients (96%) had perfusion defects on resting scans, representing 284 segmental defects and the mean number of segments with defects was 6.0. These results are in good agreement with current literature. After DPD, the total number of defects was 173, with a mean number of 3.7 (p<0.0001). The results show that DPD can produce a significant improve in myocardial perfusion defect in muscular diseases, suggesting a potential benefit of vasodilators in these patients.
292
S. BERTI. D. NEGLIA,D. LEVORATO, O. PARODI, M.T. BARATTO, M.G. BONGIORNI, C. ARLOTTA, M. PIACENTI, L. PAPERINI, A. POZZOLINI, G. KRAFT, C. CONTINI Institute of Clinical Physiology, C.N.R., Pisa
Role of radionuclide angiography of early myocardial damage
in
diagnosis
Complex ventricular arrhythmias (CVA) may be an early manifestation of dilated cardiomyopathy. To recognize early ventricular dysfunction in these patients (Pts) we studied by radionuclide angiography (RNA) 27 Pts, class I NHYA (21 males, 6 females, mean age 39 years) (group I) that showed CVA in 24-hour Holter monitoring. All Pts were submitted to complete cardiological evaluation, inclusive of: physical examination, chest-x-ray, standard and stress ECG, 2D-ECHO. Hypertensive, valvular, ischemic, congenital heart desease or other sistemic pathology were excluded. The hemodinamic study, performed in all Pts showed no coronary arteries abnormalities. RNA data obtained in group I were compared with those of a control population of 20 normal subjects matched for age and sex (group II). Regional wall motion abnormalities were detected in 24/27 Pts (89%) in group I, involving the right (33%), the left (30%) or both ventricles (26%), and in no patient in group II. In group I, 16/27 patients (59%) showed pathologic right (RV) and/or left (LV) ventricular ejection fraction (EF) values. Moreover mean EF values were significantly lower in group I (RV EF= 41+12; LV EF= 53+9) than in group II (RV EF= 50-+-5; LV EF= 61+5) (p< 0.01). In conclusion: 1) Pts with CVA show frequent regional ventricular dysfunction and less frequent but significant global systolic impairment; 2) both ventricles may be involved; 3) RNA allows early diagnosis of myocardial impairment in patients "at risk" to develop dilated cardiomyopathy.
472
294
293 G.ROUL, A.FACELLO, A.CONSTANTINESCO.
P.BAREISS,
JL.DEMANGEAT,
B.BRUNOT,
f
CHU HAUTEPIERRE - S T R A S B O U R G .
F.Brt~, S.B0rziaoi, G.(h~cco, G.P.B~zante, P . ~ o , C.Psstorini, M.A~ Y~s~ernrm,A. ~tillo, C . F ~ , G.~aro, M.BalDi, S . C ~ t t o , *P. Bisssaui. Cat-tedra di Cardiologia, CatteG~ di F~dic~ Nmleare, thiversitAdi Cenzv~
FRANCE
DIASTOLIC FUNCTION ABNORMALITIES IN MILD HYPERTENSION : RELATION WITH ASYNCHEONY OF FILLING AND EFFECT OF LEFT
VENTRICULAR MASS. Asynchrony of filling (AF) was related to diastolic abnormalities in ischemic heart disease and hypertrophic cardiomyopathy. To assess the influence of AF on diastolic parameters and the effects of left ventricular (LV) mass in mild hypertension (HT) we studied by radionuclide angiography at rest 56 hypertensive patients (pts). Filling parameters were obtained by first and second derivative of time-activity curve. AF was quantified at FWHM of histograms of functional images representing the time to PFR in the LV region of interest. We found a good linear correlation between AF and time to pFR (r:.58) isovolumic relaxation time (r=.60) mean velocity of rapid filling (MVRF r=-.50) and atrial contribution to total filling (AC:r=.48) (all p<.08). AF and PFR correlate only weakly (r=.34 p(.05). In 39 pts, eehocardiographic LV mass index could be appreciated : 21 pts (GI) had normal mass (,130 gr/m2) and 18 pts (G2) had LV hypertrophy. There was no statistical differences between the groups regarding age, heart rate and systolic parameters. AF was higher in G2:68+35 vs 118+81 msee (p~.O05). O t h e r parameters of filling were significantly different : PFR=2.79+55 vs 2.24+62 EDV s ; PFR/PER index : 85+14 vs 7 2 + 1 8 ; MVRF = .17+.0~ vs .13+.04 (all pK.05).
In conclusion, AF is one of the determinants of diastolic filling abnormalities in patients with mild HT, and is more pronounced when abnormal LV mass is present.
DIATIOLIC YdkUTlgNAT ~JfK A~D I M V E D ~ AFIER ATRIAL P~CLN~: FT_FST PASS A h r ~ AND EG=EER [£HrAEOlC~C SILDY. Aim of cur study ~ to evaluate diestolicfunction at peak auisl pa~ng (TAo) a ~ ~mmdiately aft~ TAD in patiante (pt~) with con:rmry ar'te~ di~sse (CAD). 15 pte ~ t cc~ a'~i~ (CA);allpts u~brwmt first pass P~ at rest, at peeck T~P (PACE l) a~d i~mediatlyafter TAP (P~E 2) m m ~ t a ~ m s first ~ r~cnnn~ a ~ g ~ (m) pAlsed wave chppler ~ o g r a [ 9 ~ (P~ Eq~oler). All pts ~ a ~cs/tive TAP test (a-gi~ a--d/~ ecg amGrrm/t~es). 9-e gld::al r ~ of sisuificants ~ t i c vesselswas 29. Glctaldiestolic fu~tiau with ~W Doppler at PACE 2 ~z~ed the followingpattexrs: 6pts with ~ p e s c k e a r l y m i t r a l flcwvelccity (MFf) but zorm~ o r i r n ~ V a t a U ~ c ~ n t r a c t i a n (NZ), a r e d ~ ratio of peackearly~VtotfatatAC; 9 p t e w i t h fontal or" pe~k YFf in early disstole,a~ or g~cresssd at AC, an ircreasein tt~ ratio of early ~4~/to that at ~3. About regis-el disstolic~tiauassessedby~irstp~ssPA we fcLnfl at P~CE i 28 tercitorieswith d i ~ regicrsl moticn ~ozmalities (F~), at P ~ 2 21 territories with diastolic ~ . We c~r~io~e that im~diatly after TAP all pt~ glct~l and regianal diesUalic~mTalities; evak~ticn of diastolic F ~ at pe~k i s ~ c event aee~s to be more a:nL~ate to detect the real exba~t and site of j ~ n ~ .
296
295 M. A b d e l - K a z z a k
and
M, Y o u s r i
H.Wieler* , B.Henkel**,A.Ebert* and H . F a l i e n * * A.C. M e d i c a l
Center,
Cairo
,
Egypt.
Depts.of Nuclear Medicine* and C a r d i o l o g y * * , Bundeswehrzentralkrankenhaus Koblenz,F.R.of Germany
S C I N T I G R A P H I C E V I D E N C E OF L E F T V E N T R I O U L A R I N V O L V E M E N T IN S C H I S T O S O M A L ( B I L } D ~ Z I A L ) C01{ PULMONALE.
SPECT USING MIBI: DIAGNOSTIC ACCURACY IN CORONARY ARTERY DISEASE
C a r d i o p u l m o n a r y s c h i s t o s o m i a s i s is c h a r a c t e r ized b y w i d e s p r e a d n a r r o w i n g a n d / o r o b l i t e r a t ion of the p r e e a p i l l a r y p u l m o n a r y v e s s e l s l e a d ing to progressive, r i s e in. p u l m o n a r y a r t e r i a l p r e s s u r e and r l g h t v e n t r l c u l a r s y s t o l l c o v e r load. O r i g i n a l l y , the left v e n t r i c l e w a s b e l e i r e d to be u n a f f e c t e d . This b e l e i f w ~ s r e c e n t l y q u e s t i o n e d b y some w o r k e r s . I To s o l v e this p r o b l e m , the size and c o n t r a c t i l i t y of b o t h v e n t r i c l e s w e r e e v a l u a t e d b y r a d i o n u c l i d e g a t e d e q u i l i b r i u m b l o o d p o o l study, as w e l l as b y e c h o c a r d i o g r a p h y i n 35 b i l h a r z i a l p a t i e n t s ( 20 w i t h o u t c a r d i a c a f f e c t i o n , and 15 h a v i n g b i l h a r s i a l cor p u l m o n a l e ). In p a t i e n t s w i t h o u t c a r d i a c a f f e c t i o n , r i g h t v e n t r i c l e w a s e n l a r g e d in 40%, w h e r e a s the left w a s e n l a r g e d in 2 0 % of cases. M y o c a r d i a l c o n t r actility was normal, with normal left ventric u l a r e j e c t i o n f r a c t i o n ( L V E F ) . In c o n t r a s t , in p a t i e n t s h a v i n g b i l h a r z i a l cor p u l m o n a l e , r i g h t v e n t r i c u l a r e n l a r g e m e n t w a s o b s e r v e d in 8 7 % of cases. L e f t v e n t r i c u l a r e n l a r g e m e n t w a s s e e n in 7/15 p a t i e n t s (47%), w i t h d i m i n i s h e d c o n t r a c t i l ity in 6 c a s e s (40%). T h e s e l a t t e r h a d d i m i n i s h ed L V E F . The o b t a i n e d r e s u l t s d o c u m e n t the p r e s e n c e of left v e n t r i c u l a r i n v o l v e m e n t in b i l h a r z i a s i s .
In a prospective study, we i n v e s t i g a t e d the diagnostic accuracy of s i n g l e photon emission computed tomogrsphy (SPECT) usin 9 Technetium-ggm-hexakie-2-methoxy-2-methyl= p r o p y l i s o n i t r i l e (MIBI) f o r detecting coronary a r t e r y disease(CAD) in 47 p a t i e n t s ( p t s ) undergoing coronary angiography 24 hrs a f t e r the r a d i o n u c l i d e study. MIBI(259 MBq) was i n j e c t e d during symptom-limited exercise t e s t and tomographic imaging began 60' l a t e r . To assess ischemic areas,the pte received a second MIBIi n j e c t i o n ( 8 5 0 MBq)after f i r s t tomographic a c q u i s i t i o n (at r e s t ) and 2-3 hrs l a t e r , r e s t images were performed. In the 22 pts with CAD (>50% luminal diameter s t e n o s i s ) , o v e r a l l SPECT s e n s i t i v i t y ( S ) was 95.5%(100% in pts with myocardial i n f a r c t i o n and 90% in those w i t h o u t ) . S p e c i f i c i t y ( S p ) , p o s i t i v e ( + ) and n e g a t i v e ( - ) p r e d i c t i v e vatue(PV) and o v e r a l l p r e d i c t i v e accuracy(PA) f o r detecting of stenoses in the l e f t a n t e r i o r descending (LAD),right (RCA) and circumflex(LCX) coronary a r t e r i e s were:Sp=56%,+=65.6%,-=93.3%,PA=74.5%. The r e s p e c t i v e values f o r the i n d i v i d u a l d e t e c t i o n of stenosis in LAD,RCA and LCX are discussed s e p a r a t e l y . In addition,SPECT with MIBI i d e n t i f i e d 21 of 22 pts with c o n s t r i c t i n g CAD.Thus,MIBI-SPECT has medium t o good accuracy in diagnosing the existence of CAD but there i s a need f o r q u a n t i f i c a t i o n to ameliorate the s p e c i f i c i t y and the p o s i t i v e p r e d i c t i v e values.
473
298
297 t. URGANCIOGLU, O. N. ULUT!N, G. ONSEL, A. AKBULUT,
E. VARDARELi
B.
VALBTTE,
P.
BRIANDET,
H. BOURGITIGNON, D. AGOSTINI, H-C GRBGOII~, P, MERLBT, D. LE GULUDRC, P. VEINI~ENN, C.
BERT, C. RAYNAOD, A. SYROTA. NUCLEAR MEDICINE DEPARTMENT and DIVISION OF HAEMATOLOGY, CERRAHPA~A MEDICAL FACULTY, iSTANBUL UNIVERSITY, TURKEY QUANTITATIVE EVALUATION OF THE PERFUSION IN PATIENTS WITH PERIPHERIC ARTERIAL DISORDERS This study deals with the i n v e s t i g a t i o n of the perfusion in lower e x t r e m i t i e s of p a t i e n t s having a r t e r i a l disorders. The subjects had atherosclerosis or Buerger's disease. Some patients with atherosclerosis were also d i a b e t i c s . The lower e x t r e m i t i e s of the subjects were placed on the p a r a l l e l hole c o l l i m a t o r . A r t e r i a l flow was interrupted by the use of a sphyngomanometer in order to obtain a r e a c t i v e hyperemia. ~0 MBq/kg 99mTc-DTPA was ac~inistered by an intravenous bolus as soon as the pressure was released. Serial gamma camera images were acquired every 3 sec f o r 78 sec. T i m e - a c t i v i t y curves were obtained by the ROIs generated over the both e x t r e m i t i e s . Perfusion index (Pl) was calculated by the use of time period ( t ) , peak count (p) and area under curve (~A) to reach the maximum. Mean PI f o r normal controls 4.482±0.740, while i t was between 0.178 to 2.336 f o r atherosclerosis and 0.996 to 2.536 Buerger's disease r e s p e c t i v e l y . The patients with atherosclerosis and Buerger's disease were treated with d e f i b r o t i d e (the compound of a natural polydeoxyr i b o n u c l e o t i d e extracted from mammalian lungs bycontrolled depolymerization has a p r o f i b r i n o l y t i c and ant±thrombotic a c t i v i t y ) . A f t e r the treatment the patients showed PI values rangingfrcm 0.210 to 4.533 and 1.328 to 3.704 respectively. Diabetic patients with atheroscleresis had no significantchanges in Pl following the defibrotide theraPy. In conclusion, quantification of peripheric arterial perfusion allows useful indices for the evaluation of arterial disorders in addition to visual information of the he~odynamicsbythedescribed imagingprocedure.
HULTIBARHONIC FOURIER STUDIES : GLOBAL OR ANALYSIS ?
ANALYSIS OF GATED BLOOD POOL PIXEL TO PIXEL LEFT VENTRICULAR
In i0 normal patients, LV peak ejection-filling rates (PER-PFR) were computed : I) from the global LV time activity curve (GLVTAC), 2) from each single pixel TAC (SPTAC) and averaged over the LV R01. Normalized PER-PFR (rate/end diastolic counts/see) were calculated from the analytical formula as the Ist derivatives of the Fourier series taking in account 3 harmonics (H) for GLVTAC, 2 or 3 H for SPTAC. Baseline (B) values were compared to those measured after IV dobutamine (DO: 2 gmmm~/kg/min)= PER B
PER DO
GLVTAC 3.6±.8 4.45±.7 SPTAC 2H 3.8±.4 5.03±.9 SPTAC 3H 4.4±.4 5.8±.I PER-PFR (SPTAC 3H) values were the other values (ANOVA).
p values
PRR B vs DO
PFR B
PFR DO
3.1±.6 3.5±.5 3.1±.5 4.2±.7 3.9±.5 4.8±.6 significantly higher than
P ~ B vs DO
GLVTAC 0.02 , 0.15 . SPTAC 2H 7.10-? 2.10-~ SPTAC 3H 2.10-q I.i0-~ GLVTAC analysis failed to demonstrate the well known effect of DO on diastolic function. SPTAC clearly demonstrated these effects on both PER and PFR. Thus SPTAC is more accurate to assess the hemodynamlc effects of drugs.
300
299
M.Horv4.t.h,g.Pszota,M.Kdrmdm, E.S~sz~rmg~y t + F,Raki~se.M.Bodor p. T . P ~ I ++ + S t a t e Hospital for c a r d i o l o g y , B a l a t o n f ~ r e d ++National I n s t i t u t e of pharmacy,Badapest Hmmgary III-INMYOSCINT /Centocor E u r o p e / S T ~ ON ALCOHOLIC CAEDIOMYOPATHIC /ACY~/ PATIENTS The labellng y i e l d of Msc. w i t h Amersham I l l - I n p r o d u c t was a~mays o v e r ~ o p c . The Rf v a 1 ~ e s of I n - ~ s c . , I n - D T P A and tnCl$ agreed w i t h the l i t e r a t ~ c r e data. The_cr~terla
Service Hospitalier Frederic Joliot, CRA, Orsay, France.
of M s c . p o s l t t v l t y
were: hot
acclmmtation on VLanar s c a n trom = . d l r e c t i o ~ s and in the 24-48hrs.pictHres, in the case o a t y p i c a l p o s l t i v i t y one of t h e s e was l a c k i w . 18 male v o l ~ t e e r s have been a s s e s s e d , p a r a l l e l wtt~ I control s ~ j e c t , l ~ t I a~d 2 post-r~Jocardtal i n f a r c t i o n patieHtSo 7 p a t . - s were typiaat~5 a t y p i c a l p o s i t i v e s t d n~gatives The hsart/l~Lo~g Qat|y~ty q= typ.+ t.75~o.45, atyp.+ 1 . 6 8 - o . 4 4 , ¢ o n t r o l l . I5p AH! 1 . 0 l . Heart d i l a t a t t c n : t y p . + 5/7,atYP.+ 2/5,neg. Z/O Low EF / < 4 5 ~ 4 / 7 , ~ / 5 , l / d , e l e v a t e d PCP as w~L , Pathol.ECG 5 / 7 e l / 5 , l / 6 . S e r ~ garra~ gLu~amyL I t r a ~ s f e r a s s + a c t i v i t y in the g r o u p s l 155-155w I 2 5 0 - 1 4 8 , l T a - I # l u / t , / n o r m a l Less than 4 o u / l . / I being in each case enhanced, there wasn't, how-I e v e r , e v i d e n t coIFelation between the a c t i v i t y a~d Msc.hot i n t e n s i t y . 4 t y p i c a l aPtd s a t y p i c a l p o s i t i v e pat.-S were in progr.stage ot ACPtwith d i l a t a t i o n , . rhythm d l s t a r b a a c e . The p o s i t l v i t y doesn't seem to be s p e c i f i c , /aat~/tmaa~ c a r d i t i s may perhaps play some r o l e t h e r e i n .
H u i y a n g ZHAO and Aina YUAN Department of Nuclear Medicine Zhong Shah Hospital Shanghai Medical University Shanghai, China
PHASE ANALYSIS USING CARDIAC PHANTOM AND A P P L I C A T I O N S OF PHASE ANALYSIS IN CORONARY AND N O N - C O R O N A R Y DISEASE The accuracy, r e l i a b i l i t y and reproducibility of phase analysis were assessed by the studies of the cardiac phantom. The results showed that the peak of histogram c o r r e s p o n d i n g to the value of unsymmetrical curve is consistent with that of the sine curve. The overall spread in phase from the base to the apex is reasonable. The reproducibility of data was very s a t i s f a c t o r y , e s p e c i a l l y the phase angle width and the ratio of phase angle width to height. This paper also reported the results of 349 cases r a d i o n u c l i d e phase image analysis, including coronary and n o n - c o r o n a r y disease. The results showed that the ventricle phase angle was an important parameter which consisted with the pattern of contraction and conduction of ventricle.
474
302
301 N.Oondi, R.Franchi, N.Honetti, P.Zagni, C.Corbelli, F.Tartagni*, L,Naiello*, P.Lieonetti*
B. P.
Beparteent of Nuclear Medicine, S.Orsola-BaIpighi Policlinic Hospital, Bologna SInstitute of Cardiovascular ~isease, University of Bologna, Bologna, Italy
D e p t s . of C a r d i o l o g y a n d N u c l e a r M e d i c i n , Academic Medical Center, Amsterdam and Dept. of C a r d i o l o g y ~ T h o r a x c e n t e r , Rotterdam, The Netherlands.
SAMEBAY STUDYNITH SPECTAND ~ SPLIT DOSE OF Tog?cHIDe AFTERDIPYNIDANOLE: CONPARISSNNITH TI2O] FOR LOCALIZINGCORNARYARTERYDISEASE The ale of this study was to evaluate the use of GPECTand a split dose of lcgge-eethoxy-isobutyl-ieonitrile (TC-MIBI), after injection of Oypiridamole as pharmacological stress, in the diagnosis of CAD. Results have been compared mith those of TI-201 and coronary angiography. 30 patients mere studied, 26 males and 4 females, lean age 59 years, all submitted to coronary angiography mithin 1 aenth: stenoeis >70%mas found in 26 patients (B had a one vessel, 12 had a two vessel and 6 a throe vessel disease). Altogether, 16 diseased left anterior descending [LAD), ]9 right coronary (RCA) and ]5 cJrcui{]ex arteries (LCX) uere found. Patients sere i.v. injected mith Oypiridaeole lOPS) in a dose of O.lg2 egr/kglzin, uithin 4 minutes. Three to four minutes later 250 NGq of Tg~n-NIBI mere injected as a bolus, foliomed by 240 agr of aeinophilline after tiFteefl to twenty ainutee. One hour later a first GPECT study mac performed, Fdlo,ed by i .cond injection of 7~0 BJQ of TC-HIB], #ithin one wlZk the lien paHonts und,ruent l]2O] 8PECT. Hyocardia!, rogionl ~ero correlated ~o coronary vessels: the anterior and septal sills sere re~erred to Lh~, the in~erior call to GC~ and the lateral halt to LCL lhe overall sensitivity and specificity obtained with exercise and pharmacological tests for identifying significant lesions on LAB and on RCAILCX territories nero as {olloms~ GPECT-TI20I SPECT-TCNIS[ LAO RCAICX LAG RCAICX SENGITIVITY ~ 7~ 92 7b 85 SPECIFICITY % 82 90 B7 93 Identification of patients ,ith eultiveseel disease mas similar for the two methods (20/2b=7~%). Glfferences in myocardial uptake hetmoen early and late examinations, for differentiating acute from chronic ischemia, nero also similar (20126 TI vs ]9126 NIBl). In conclusion the examination can be accomplished in fem hours and the diagnostic inforiation obtained is similar to that derived from T]-SPECL
303 D Jain, P Broadhurst, A Lahiri
v a n V l i e s , P. F i o r e t t i , E. v a n R o y e n , A d e m a , J. R e i b e r a n d J. v a n d e r S c h o o t .
P R O G N O S T I C V A L U E OF I N D I U M - I l l A N T I M Y O S I N U P T A K E FOR T H E I N C I D E N C E OF N E W I S C H E M I C EVENTS AFTER MYOCARDIAL INFARCTION. To a s s e s s the r e l a t i o n b e t w e e n the u@~i~ied ~nrlll Monoclonal ~nti~yosin n ~ i n Q u y o u p ~ a K e ~s ~ m e a s u r e r o t ~ @ @ m Q u n ~ Or n e c ~ o ~ s ~n ~ Q u ~ e m y Q c a r u ~ a l i n r a r e t l o n a n a ~ne i n c l a e n e e or p o s ~ infaret ischemie events (proven ischemia, n e e d for c o r o n a r y b y p a s s s u r g e r y or angioplasty, re-infarction) during follow up, 53 p a t i e n t s w i t h a f i r s t m y o c a r d i a l infarctlon were investigated. W i t h i n 48 h o u r s a f t e r a d m i s s i o n 8 0 m B q I n - l l l A n t i m y o s i n was i n j e c t e d a n d p l a n a r i m a g e s w e r e m a d e a f t e r 2 4 - 4 8 hours. I n - l l l A n t i m y o s i n u p t a k e was e v a l u a t e d for C o u n t D e n s i t y I n d e x ( C D I = c o u n t d e n s i t y of i n f a r c t z o n e / l e f t lun~ c o u n t d e n s i t y ) in the l e f t a n t e r i o r o b l l q u e p r o j e c t i o n . w h i c h d i s p l a y e d the i n f a r c t z o n e w e l l in all p a t i e n t s . In 2 0 / 5 3 p a t i e n t s i s c h e m i c e v e n t s w e r e p r e s e n t d u r i n g f o l l o w up ( 4 6 + 2 3 w e e k s ) . The m e a n CDI was 2 . 2 1 + 0 . 5 1 in p a t i e n t s w i t h o u t i s c h e m i c e v e n [ s a n d 1 . 8 1 + 0 . 2 8 in patients with ischemic events, p~0.005; r e f l e c t i n g less n e c r o s i s a n d s t l l l m o r e m y o c a r d i u m at r i s k in the i n v o l v e d area. 18/28 p a t i e n t s w i t h a CDI <2.05 h a d i s c h e m l c e v e n t s in c o n t r a s ~ to 2/23 p a t i e n t s w i t h a CDI >2.05, p < 0 . 0 0 1 (chis q u a r e test). Thus: e a r l y CDI is c a p a b l e to r e c o E n i z e p a t i e n t s at r i s k for n e w i s c h e m i c e v e n t s after myocardial infarction.
~
304 U Raval,
T Smith,
EB Raftery,
D. LE GULUDEC, B. VALETTE, M. BOURGUIGNON, FRANK, G. FONTAINE, B. JOUVE, J.L. MOBETTI, SYROTA.
SHFJ,
D~partement
de
Biologic
M. SLAMA, R. G. MOTTE, A.
du CEA, Orsay ; H6p. A.
B~cl~re, Clamart ; H6p. J. Rostand, Ivry, France. Cardiology Department, Northwick Park Hospital, Road, Harrow, Middx, HA1 3UJ, UK
Watford
LATE IMAGING OF MYOCARDIAL INFARCTION WITH 1111N-ANTIMYOSIN ANTIBODIES. 1111n-antimyosin antibody (In-AM) imaging is a highly sensitive and specific technique for imaging the extent of acute myocardial infarction (AMI). In-AMprovides good quality and easily interpretable images without interference from overlying structures. However, it is not yet known as to how long after AMI does this antibody bind to myosin in the infarct region. Fourtee~ p a t ~ e n ~ ~:Titb Qwave AMI (6 anterior, 8 inferior) underwent late imaging with In-AM. Seven were studied within one week post AMI and 7 were studied between 7-12 (9±3) weeks after AMI. Positive In-AM localisation was noted in all and the InAM uptake was confined to the ECG location of AMI. Intensity of In-AM uptake was comparable to that seen in previous studies where imaging was carried out within 4 days of AMI. Thus unlike WgmTc pyrophosphate, In-AM can provide diagnostic images up to 12 weeks post AMI. Further studies at different intervals are required. This interesting finding may also help us to gain important insight into the process of infarct healing and remodelling.
MULTIEARMONIC ~BHOGENIC
FOURIER ANALYSIS IN T H E DETECTION RIGET VENTRICULAR DYSPLASIA (ARVD).
OF
Gated blood pool studies were performed for the detection of RV wall motion abnormalities (WMA) in twelve pts w i t h ARVD proven by X-ray angiographic and e l e c t r o p h y siological studies. Data were acquired over 5 min during sinus rythm in a 64x64 matrix format, 16 images per cycle, in LA0-30 °, RA0-20 ° and left lateral views. After a 3D filtering (l.7,1), RV and LV NOra were determined a,tomatJcally. Foutie~ analysis was performed using one (HI) and three ([13) harmonics. The parametric image choosen for the ~MA analysis was the time of systole (TS). TS images (Hi) demonstrated a clear delayed phase area in LA0-30 ° in 9 pts (Group I) ; the diagnosis was !established in the remaining 3 pts (Group II) with the additional RA0-20 ° view. TS images (H3) demonstrated a clear delayed phase area in all the 12 pts in LA0-30 °. Quantitative phase shift analysis (t-test) compared the mean RV TS to the mean LV TS, knowing that these HI and H3 values are not significantly different from each other in normal pts. In the Group I, mean RV and LV TS were significantly different (p<0.05), with both HI and H3 analysis ; in group II, they were different (p<0.05) with H3 analysis only. Conclusion : The diagnosis of ARVD can be made accurately with GBP studies i) either with HI analysis b,t require 2 incidences 2) or with H3 analysis on a single standard LA0 view.
475
305
M.P. LAROCK, V. LEGRAND, H. KULBERTUS, P. RIGO
C.H.U. LIEGE - UNIVERSITY OF LIEGE - BELGIUM EVALUATION OF THE EXTENTOF MYOCARIDAL ISCHMIA, OF THE RISK AREAAND OF THE RESULTS OF PTCAWITH 99mTc-MIBI TOMOGRAPHY. We have injected during PTCA, a perfusion agent (MIBI), presenting a stable myocardial uptake with no redistribution, to evaluate with MIBI tomography (MIBI SPECT) the extent of myocardial area at risk. MIBI SPECT performed within 2 hours allows then to define the extent of the risk area. We have comparedat stress, in patients (pts) with single vessel disease, the relation between the extent of myocardial ischemia (IS) during exercise and of the area at risk, to determine the factors responsible for differences and the predictive value of the exercise IS. This preliminary study includes 5 pts without previous myocardial infarction and with angiegraphic control. MIBI SPECT control was performed both at rest end at stress before and after PTCA in all pts to evaluate the results of myocardial reperfusion. Ventriculography performed during PTCA demonstrates the extent of abnormal wall motion during occlusion. In all pts, the extent of the risk area appears to be significantly larger than the extent of myocardial IS before PTCA. MIBI SPECT control performed at stress after PTCA, confirms regional myocardial reperfusion in the corresponding vessel t e r r i t o r y , after successfull angioplasty. The injection of a perfusion agent such as MIBI, with stable myocardial uptake, during PTCA, provides, the opportunity to document short myocardial ischemic events as well as information about the location and the extent of the myocardial area at risk.
307 J.L. Barat, S. Benkirane, L. Bordenave, E. Jullien, M.P. Isidore, M. Dallochio, D. Ducassou
306 P.Kress*, M. Clausen**, E. Henze**, R. Weller**, F. Bitter**, W.E. Adam**, V. Hombach*
Division of Cardiology*, Department of Internal Medicine Department of Nuclear Medicine** University of UIm, UIm, FRG
EVALUATION OF PATIENTSWITH ATRIAL SEPTAL DEFECT (ASD) AT REST AND DURING EXERCISEBY RADIONUCUDEVENTRICULOGRAPHY(RNV) RNV is a reliable technique to measure left-to-right shunts (LRS) from ASD and is applicable also during exercise. There was a good correlation (r=0.66; n=35) between the LRS as determined by oxymetry and the LRS derived from the radionuclide regurgitant index (RI) according to the formula LRS (%) = 100 X (1 - RI/1.43), 1.43 being the normal value for the RI in our laboratory. To study the changes of RI and LRS during exercise, 15 pts with ASD and a LRS - as determined by oxymetry - exceeding 31% underwent RNV at rest and during supine exercise (mean 88+_49watt). All cases had a RI at rest between 0.79 and 0.40 (mean 0.61 +-0.11) corresponding to a LRS by RNV between 45 and 72% (mean 57.1 ±7.9%). In 12 out of these 15 pts (80%) there was an increase in RI during exercise. The increase in RI for the total group was statistically significant (0.61 + 0.11 vs. 0.79 +-0.24; p <0.001). In 3 pts the RI during exercise exceeded 0.89 and was then within the normal range. This normalization of the RI (1.54 and 0.98, resp.) was found in the only 210ts with significant pulmonary hypertension from ASD and tendency to a balanced shunt: In one patient a LRS of 26% and a dght-to-left shunt (RLS) of 21% was calculated by oxymetry, in the other neither a significant LRS nor a significant RLS could be measured in the presence of a large ASD which subsequently was verified during cardiac surgery. The third pt had the smallest LRS as determined by oxymetry and the RI during exercise only slightly exceeded the lower limit of normal (RI=O.90). By contrast, all pts without normalization of the LRS during exercise had pure LRS without significant pulmonary hypertension during catheterization. In conclusion, in pts with ASD a significant increase in RI and decrease in LRS during exercise could be demonstrated by RNV. However, in cases with normalization of a depressed RI during exercise pulmonary hypertension and shunt balance must be suspected. Similar results were reported by Flamm et al. in 1970 using dye dilution techniques. Thus, evaluation of LRS from ASD by RNV is not only useful at rest but also during exercise. Reference: Flamm MD, Cohn KE, Hancock EW: Ventricularfunction in atrial septal defect. Am J Med 48:286-294(1970) 308
J.M ROCCHISANI*, N. GALEZOWSKI°, C.CHAPELON°°,P.GODEAU°°, G.HERREMAN°. Cochin*, St Joseph°, Piti6-Salp~ti~re °° Hospitals. PARIS. FRANCE.
Services de M~decine Nucl~aire et de Cardiologie, H6pital du Haut L~v~que, 33600 Bordeaux-Pessac (France). LEFT VENTRICULAR DIASTOLIC BEHAVIOR AT REST AND DURING EXERCISE IN HYPERTENSIVE PATIENTS WITH MYOCARDIAL HYPERTROPHY. Detecting early cardiac changes in hypertensive patients remains an important diagnostic goal. Impaired diastolic filling at rest is known to be associated with abnormal left ventricular (LV) hypertrophy. However few data are available on the measure of these abnormalities during exercise. ii Hypertensive patients with myocardial hypertrophy (septal thickness > ii mm) and 15 normal subjects underwent rest and supine exercise equilibrium gated nuclide ventriculography. After analysis of LV activity time curves, peak filling rate normalized to ejection fraction (PFR), time to PFR from end systole normalized to diastole duration (TTPFR), filling fraction at the first third of diastole normalized to the cycle length (FF), and changes of these parameters during exercise have been measured. Results showed that impaired LV active filling is associated with predominant left atrial contraction in patients at rest : reduced FF (p < 0.02), increased TTPFR (p < 0.001), normal PFR (NS). During exercise, FF increases in both group (difference : NS), TPFR increases only in normsl controls (difference : NS) and PFR increases more in patients (p < 0.01). In conclusion, the LV rapid filling phase is mainly due in patients with LV hypertrophy to atrial contraction and is more marked during exercise. This augmented atrial contribution during exercise could result from a compensatory machanism far paor LV distensibility.
Indium Bacterial
111
Neutrophil
Imaging
in
Subacute
Endocarditis.
Subacute bacterial endocarditis (BE) is a frequent but difficult to diagnose disease. Using In-111 Neutrophils, we have search for a cardiac and a possible extra-cardiac localization of the infection that could help for the diagnostic. Twenty patients under treatement for retrospectively proven BE were studied. Fourteen other patients without thoracic infection were used as normals. Neutrophils from 100 ml of autologous blood were labelled with 20 MBq of In-111 oxinate. Anterior, posterior and LAO images of the chest were obtained 24 hours following injection. Images of on the head and abdomen were also realized. Normal chest images showed a faint background and cardiac activity and a moderate bone uptake. Five patients with a significant diffuse cardiac uptake were considered as positive by three observers. In one patient, this uptake disappeared after one month of treatement. Three patients (1 positive) had a dental or intestinal uptake. Positive patients (respectively negative) had 4 (respect. 9) cases of positive hemoculture, were treated since 7 days (respect. 10 days) for an estimated disease evolution of 8 weeks (respect. 13 weeks). The patients had only a slight elevation of WBC. This results indicate that In-111 Neutrophil scintigraphy appear to be specific but not sensible and is of little value for diagnosing subacute BE.
476
309
310
J. Castell, M. Fraile, F. Worner, J. Candell, r,========
J. Verd6, D.Ortega
Hospital General Vail d'Hebron.
MJ E e n i g e van, FC V i s s e r , C-MB Duwef, JP Roos. Barcelona. Spain
We~lerLooh s pros]t,ctive study i~ 3l paticeLe (30 male) aged 30 Lo ?l (mesa 54.3 tears) in orderto comparefourdiffer~t eetheds of obLainiagleft ve,tricelar volume (I,W) ,eusurcoenZsby .eausof equilibrium~i0,.clide ~iocardi0(nk~y(~WA).1~erewere27 patients with OAO, 18 pts with myocardial lsfarctiou, 3 pts with e~est pain sad oonml coronary arteries, and one ease eaek of myoperieaeditis sad usrtie regurgiLatico. Within 72 hours ~ and eontrsst vcetieulogr~y (~} were perforled in every case. I,W was deterlioed by bipluse C'/using the urce-leegth approach. @eyingprocessed the ~ through a eeuiautelated edge deLcettco prugrua, the following methodswere applied in each paLient to obtain absolute LW: trigonometric-ba~'~d deLemiuatice of LW after Links ~ eL a). (198Z) and Verusi ~ eL al. (1985) end individual meusaremeetof the Lrusuaitioo factor of s radiacLive mtree i,side the esophagus,14surer ~ eL ul. (1983) or the gusLrie f~dus. 8sterehH eL ul. ({98?),gegression usalysis between CV LW us({~A LW was usedfor sLstisLicol purposes. 9~$9~T~: I(AI~R~ ~II)R(] I,IWI~ V~.AWI C'V ~v al (Neus~D) 144.8+78 83.1+52 118.8!41 108.4+.43 103.T+.4! ~rrelatico coefficicet 0.7483 0,5~09 0.{985 0,8119 Standard error (S~K) ~8.8 36.9 34.4 33.9 We conclude that, is our e~erienco, there are differences bebece trilo,metrie ~nd internal source traauaiusico methods for determining abuslute LI/V~ce comparedto ~. Althou~ it overestiMLes absolute ]~V values, Lke method after llaurer seems to be the be~t uL predicLiag CVLW ~es regression analysis is employed, -~sterch II, Carrio J, krtigae k, eL u]. Bey ~p lied W~I~ $:49-54, 198T. -Links Jlq, Becier LC, Shindledeoler JO, eL al, CiroelaLioe 85:8X-90, 1982, -Wusrer AB,8hegel Jk, DeoeobergBS, eL al. ~ J Cardio] 5h853-858, 1983. -Ve~Mi I~ ~ &, he~llao ~ , eL el, J I~c1 IL~ 28:1394-1401, 1985.
311 D Jain, A Lahiri, U Raval, JCW Crawley,
AJP
Karreman,
Dept. of C a r d i o l o g y , Free U n i v e r s i t y , A m s t e r d a m , The N e t h e r l a n d s .
D E T E C T I O N OF A B N O R M A L 1-123-HEPTADECANOIC ACID METABOLISM IN P A T I E N T S W I T H A N G I N A P E C T O R I S The aim of the study was to relate the results of coronary angiography with the presence or absence of abnormal 1-123-heptadecanoic acid metabolism in patients with proven coronary artery disease, but without previous myocardial infarction. The time-activity curves of 42 pts were analyzed on a p i x e l by pixel b a s i s a f t e r 5x5 smoothing. Time-activity curves were fitted with a monoexponential plus constant (parameters: halftime value Tl/2 and amplitude/ a m p l i t u d e + c o n s t a n t ratio A / A + C ) . Ten p a t i e n t s with normal coronary arteries were used to d e f i n e the n o r m a l r a n g e in the TI/2-A/A+C matrix. Abnormal metabolism was defined if more than I0% of all p i x e l s w e r e o u t s i d e the n o r m a l range. T a k i n g the results of c o r o n a r y a n g i o g r a p h ~ as the g o l d e n s t a n d a r d thd s p e c i f i c i t y was 89% and the sensitivity 72%. In patients w i t h one v e s s e l d i s e a s e a s e n s i t i v i t y of 64% was found and in patients w i t h m u l t i v e s s e l d i s e a s e 78%. It is c o n c l u d e d that i) a r e l a t i o n e x i s t b e t w e e n the presence of s i g n i f i c a n t c o r o n a r y a r t e r y s t e n o s i s and an a b n o r m a l I - H D A m e t a b o l i s m and 2) in a m a j o r i t y of the pts with coronary artery disease m e t a b o l i s m of h e p t a d e c a n o i c acid is d i s t u r b e d .
312 EB Raftery A.Vattimo,P.Bertelli,L.Burroni,R.FavilIi°,R.Gaddi L.Baldi°,A.Ferretti °
Cardiology Department, Northwick Park Hospital, Watford Road, Harrow, Middx, HA1 3UJ, UK COMPARISON OF ELECTROCARDIOGRAPHY AND 1111N-ANTIMYOSIN IMAGING IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION. Standard electrocardiograms (ECG) were compared with 1111n-antimyosin (In-AM) uptake from planar images in 73 patients (pts) with acute myocardial infarction (AMI). Group (Gp) I consisted of 53 pts with Q-wave AMI and 20 pts had non Q-wave AMI (Gp II). When the extent of ECC changes presenting with Q-waves were compared with In-AM uptake, a complete match was noted in 14(269), In-AM > in 36 (689) and EGG changes > in 3 (69). However, when leads showing either new Q-waves or ST-T changes were compared, a complete match was noted in 24 (454), In-AM > in 22 (424), ECG changes > in 7(134). In Gp II, 7/20(354) pts showed no diagnostic ECG changes despite chest pain and a typical rise and fall in cardiac enzymes, but all 7 had positive In-Am images. When the ECG changes were compared with In-AM, a complete match was noted in 4(204), In-AM> in 9(45~) and ECG changes > in 7(35~). These results indicate that in AMI, necrosis is more extensive than the extent of ECG changes and a significant proportion (i0~) of pts may not show any diagnostic ECG changes. In-AM can identify the entire extent of myocardial necrosis and may be used to confirm and localise myocardial necrosis in the absence of ECG changes.
Nuclear Medicine Unit Siena U n i v e r s i t y , I t a l y
and D i v i s i o n
of Cardiology
o,
° of
ASSESSMENT OF THROMBOLYSIS IN ACUTEMYOCARDIAL INFARCTION (AMI) BY MEANSOF Tcg?m-MIBI MYOCARDIALIMAGING Tc99m-MIBI accumulates in the myocardium in proportion to the coronary f l o w , i t s distribution is costant for several hours and i t is not affected by therapeutic procedures. In order to detect myocardial perfusion changes after thrombolysis in AMI,we injected 6 pts.admitted to the coronary unit care for AMI prior to the l,V.infusion with streptokinase. Three hours later the pts.were imaged in 3 standard views by means of an ECG-gated acquisition. The study was repeated 48 hours later. Images were visually scored by consensus of 3 blinded observers. The perfusion defect was considered consistent with AMI i f the dyastot i c defect persisted in the systolic frame(absence of residual systolic thlckening-RST).Reperfusion was considered successfu11 if,on the repeated study,RST was present at least in a previously abnormal segment.All the pts. presented 3 to 4 non perfused segments in the baseline study. The repeated study showed a significant reperfusion in 3 pts.,whereas no changes were observed in the other cases. These data,well correlating with c l i n i c a l evolution and follow-up studies,suggest the usefulness of MIBI myocardial imaging in the assessment of reperfuslon procedures in pts. with AMI,requiring a baseline study to compare the post-treatment one,without delaying the thrombolytic agent administration.
477
313
314
D Jain, A Lahiri, U Raval, C James, EB Raftery
J.L. Barat, H. Douard, D. Commenges, L. Bordenave, P. Rondoyani, J.B. Lamouliatte, M.P. Isodore, J.P. Broustet, D. Ducassou.
Cardiology Department, Northwick Park Hospital, Road, Harrow, Middx, HA1 3UJ, UK DO R E C I P R O C O L
EGG CHANGES
IN A C U T E
MYOCARDIAL
Watford
Services de M6decine Nucl@aire et de Cardiologie HSpital du Naut L@v@que, S3600 Bordeaux-Pessac (France)
INFARCTION
PREOPERATIVE DETERMINANTS OF CONTRACTILITY RECOVERY AFTER CORRECTION OF CHRONIC AORTIC REGURGITATION. In patients with aortic regurgitation (AR), valve replacement results in various outcome depending on merpholegic and functional preoperative alterations of the left ventricle (LV). In order to evaluate the predictive value of non invasive measurements for contractility recovery after operation, 29 AR patients were studied immediately before and 6-12 months after surgery by 2D echocardiography and equilibrium gated blood pool scintigraphy at rest and during supine exercise. LV ejection fraction (EF) at rest, and changes in LV EF, end diastolic volume (EDV), end systolic volume (ESV), systolic blood pressure/ESV index ratio (P/V) with exercise were measured. Results showed that the postoperative improvement in P/V change with exercise was related to i) the preoperative LV end diastolic diameter (r : - 0.48), ii) the preoperative EDV change with exercise (r = 0.41) and iii) the preoperative P/V change with exercise (r = - 0.51), but unrelated to preoperative resting EF and EF and ESV changes with exercise. Thus in these AR patients, recovery of contractility reserve after operation is predicted by preoperative values of LV cavity dimension, LV dilatation and contractility reserve during exercise. This study confirms that preoperative rest and exercise EF are not ~redictors of postoperative LV systolic function.
REPRESENT ADDITIONAL ISCHAEMIA OR NECROSIS? The underlying pathophysiology of reciprocal electrocardiographic (EGG) changes in acute myocardial infarction (AMI) is unclear. 1111n antimyosin (In-AM), resting 2°ITI (TI) and gated blood pool imaging were performed in 37 consecutive patients (pts) with first Q-wave AMI. In 27 pts, reciprocal ECG changes were present (Group i) and in I0 pts reciprocal changes were absent (Group 2). The myocardial segments representing the reciprocal ECG leads were compared in the two groups for In-AM uptake, TI defects and wall motion abnormalities (WMA). No significant differences were detected between the segments with or without reciprocal changes. Incidence of abnormalities in the myocardial segments representing reciprocal leads in the Groups I and 2 were as follows: WMA were present in 8 (33%) vs 3 (30%); I n - A M u p t a k e in I0 (37%) vs 3 (30%); TI defects in 2 (7%) vs 2 (20%); WMA alone in 4 (15%) vs i (10%); no abnormalities in the reciprocal segment in 12 (44%) vs 6 (60%). Multivessel coronary disease and ejection fraction values were similar in both Groups. Thus, in pts with AMI the presence of reciprocal EGG changes do not necessarily imply myocardial necrosis or ischaemia in the myocardial segments associated with these ECG changes.
315 G.Medolago,G.Virotts,C.Bertocchi,A.Piti~,M.Tespili*,F.D'Adda*,E.Gotti*,A.Casari*. Dept. of Nuclear Medicine ~Dept. of Cardiolog~ OSPEDALI EIUNITI DI BERGAMO ITALY
ACUTE MYOCARDIAL INFARCTION (AMI) AND THROMBOLISIS:SCINTIGRAPHY WITH DOUBLE TRACER (ANTIMIOSIN IN111 AND TC99M MIBI). To evaluate the diagnostic and prognostic role of new nuclear tracers, 28 consecutive pts+ admitted within the 6 ^ h of AMI underwent, after Thrombolysis i.v., scintigraphy with AM-IN111 followed soon after by a perfusion study with Tc99m-MIBI. We have done a semiquantitative evaluation of the uptake of AZ-!NIII (grO=absent;l=mild;2=discrete;S=intense) and defect of Tc99m-MIBI (grO=transmural;l=severe;2=partial;S=normal). We divided 2 groups: A)Peak C K ~ I 2 ^ h (iSpts);B)Peak CK ~12 ^ h (15pts).In A 8pts (62%)and in B llpts ('73%) showed transmural perfus~on defects (PDs). The PD was larger than uptake of AMA-INIII in 3pts in A (29%) and 2 in B (19%). In the short period follow-up 19pts (73%)-10 (A) and 9-(B) had coronary events or reversible PDs on further perfusion stress study. CONCLUSIONS:Tc99m-MIBI showed lesser incidence of transmural PDs in pts with early Peak CK (A);A PD larger than the uptake of AMA-INIII is more frequent ~n A;in our population the discrepancy between the 2 tracers, could not mark off pts with higher incidence of coronary events or residual ischemia in the short period follow-up.
316 R.Dudczak, T.Lai~ha, K.Kletter, R.Sehmoliner
l.Med.Univ.Klinik, Abteilung fur Nuklearmedizin 1090 Vienna, Lazarettgasse 14 PLANAR Tc99m-MIBI SCINTIGRAPHY: FEASIBILITYOF QUANTITATIVE ANALYSIS FOR DIAGNOSING CORONARY ARTERY DISEASE (CAD) IN DIPYRIDAMOLE
STRESS
(DPM) ~ REST STUDIES.
56 patients who underwent coronary angiography (0 VD: 10; I VD: 12, MI/5; 2 VD: 8, MI/5; 3 VD: 26, MI/18) because of chest pain had DPM stress (0.7 mg/kg/5 min) - rest scintigraphy after iv. injection of 10-15 mCi Tc99m-MIBI, with both studies done on separate days. Planar images were obtained 3 h after tracer injection utilizing the 3 standard views (APEX 215M0. Images were collected for 10 min and stored in a 128~128 matrix format. For quantitative analysis images were normalized in regard to the injected activity and circumferential profiles were generated. The % activity difference (AD) between stress and rest studies was calculated. The correlation eoeff, for tAD determination was 0.98 and the VC for individual segments < 2 0 % . Based on findings in patients with 0 VD a tAD of < 10% and or a regional difference in tAD of ~ 2 5 % was regarded as abnormal. By visual interpretation of images these were abnormal in 9/18 and 25/18 of patients without or with Hl, thus CAD was diagnosed with a sensitivity of 74% and a specificity of 90%. Sensitivity and specificity for assessing the number of diseased vessels was 45% and 98%, rasp.. However, By quantitative analysis sensitivity for diagnosing CAD increased (96%) and specificity decreased slightly (80%); fo~ assessing the number of diseased vessels these numbers were 90% and 81%, respectively. Our data show, that the diagnostic value of planar Tc99m~IBI scintigraphy can be improved by quantitative analysis,
478
317
318
S.R. MORRIS, G.M.S. SYED, G. BERGMAN AND B. SHAPIRO.
P.Kostamis, J.Lekakis, N.Vassilopoulos, D.Maintas, A.Theocharis, Ch.Kalliontzi, N.Sifakis, Sp.Moulopoulos,
N.Kokolakis, Th. Athanasoulis,
Dpt of Therapeutics and Dpt of Nuclear Medicine "Alexandra" University Hospital, Athens Greece
KING'S COLLEGE HOSPITAL, LONDON, SE5 9RS, U.K. COMPARISON OF RP30 AND TL-201 IN MYOCARDIAL PERFUSION IMAGING USING CORONARY ANGIOGRAPHY AS THE GOLD STANDARD. Prior to its possible routine application, the new myocardial perfusicn agent RP30 (Du Pent) was compared with TL-201 using coronary angicgraphy as a final arbiter. Twenty-eight patients suspected of coronary artery disease were studied. Myccardial perfusion imaging was performed within twc weeks of coronary angicgraphy using either RF30 (13 patients) or TL-201 chloride (15 patients). 500MBq RP30 (Tc99mHexamibi) was given i.v. on two separate days for stress and rest imaglng. A single dose of 74MBq TL-201 was administered at peak exercise. Images were recorded in the anterior, LAo40Cand LAO70 ° projections following stress and at rest. Each image was divided intc 5 radial segments for comparison between exercise and rest scans. RP30 studies revealed 17 Infarcted segments, 47 Reversible Isbaemia (RI) segments and 131 Normal segments. All were confirmed angiegrapbically except for 6 RI segments supplied by blood vessels with insignificant stenoses. There was complete agreement in 11 patients(84.6~ Thallium studies revealed 30 Infarcted segments, 45 RI segments and 150 Normal segments. All but 5 RI segments were confirmed by angiography. Complete agreement was reached in 12 patients (80%).Sensltivity&Specificity were: RP30 TL-201 RP30 TL-201 Infarct-Sensitivity ~ ~ Specificity ~ RI-Sensitivity 100% 100% Specificity 95.6% 96.8% We conclude that RP30 is of equal diagnostic value with TL-201 in myocardial planar imaging. Its future use in SPECT and Multigated studies may render it preferable.Its daily availability, however, must be set against the disadvantage to the Datlent of double attendance.
SILENT vs SYMPTOMATIC ISCHEMIA DURING DIPYRIDAMOLE-Tc99~ RP-50 TESTING: SCINTIGRAPHIE AND ANGIDGRAPHIC CONSIDERATIDN
To evaluate the significance of ischemic perfusion defects (PD) without chest pain during Dipyridamole (D7 infusion we examined 52 consecutive patients (pts7 with proven (>50%7 CAD and transient PD during D-Tc99m RP-50 testing. 20 pts had silent isehemic PD (SI) and 12 pts presented angina (A). There were not significant differences in age (SI 52±18, A 54±17),male/female ratio (SI 18/2, A 10/2), maximal heart rate after D-infusion (SI 98±17, A I01±207~ double product after D-infusion (SI 12100±1200, A 12500±21007 and previous myocardial infarction (SI 4/20, A 5/12) and non reversible PD. Pts with SI had less segments with reversible PD (SI 1.6±1.5, A 3.8±2.2, p < 0.0017 a lower ratio of reversible to total Idefects (SI 0.44±0.57, A 0.78±0.55, p < 0.01), a lower i number of vessel diseased (5I 1.45±0.6, A 2.2±0.86, p < I 0.01) and lower Gensini score (SI 17.9±11.6, A 45.2±19.7 !p < 0.001). Ejection fraction was comparable between two I groups. In conclusion: Pts with silent PD during D-Tc99m RP-5( !testing have less reversible ischemia snd less extended CAD.
320
319 J. Soares Jr.; R. Snitcowsky; J.C.Meneguetti; F. H. Hironaka; R.V.C. Assls; M.C.P. Giorgi;M.Ebaid; F. Pileggi; E.E. Camargo.
M. Sorribes, M. Fraile, J. Castell, J. Cortadellas,
The Heart Institute, Paulo, Brazil.
Barcelona. Sgain
J. Candell, F.M. Domenech-Torn~ Hospital General Vall d'Hebron
GALLIUM-67 CARDITIS.
IMAGING
Sao Paulo University, IN THE DIAGNOSIS
Sao
OF RHEUMATIC
Routine tests for m o n i t o r i n g patients(pts) with rheumatic disease usually show low sensitivity in the detection of earditis. To evaluate the u s e f u l n e s s of gallium-67 imaging inthe diagnosis of rheumatic carditis, 11 pts (6 male; 6-17 yrs) with active rheumatic disease were studied. All pts had acute phase positive serology. Cardiac imaging w i t h gallium-67 was p e r f o r m e d 48 hrs after tracer injection and the scintigrams compared to endomycardial biopsy. Time interval between imaging and biopsy ranged from 0 to 12 days (mean 6.3 days). Scintlgrams were positive in 8 pts and negative in 3. E n d o m y o c a r d i a l biopsies were also positive in the same 8 pts and negative in the remaining 3 pts. These results show that cardiac imaging with gallium-67 i n p t s withactive rheumatic disease can be u s e d t o determine the presence or absence of cardiac involvement. A positive study may have implication in the therapeutic management and prognosis of these pts.
FlONOCLOHALHTOSIN AHTIHODT HJIHIOFs5 IN AC•S WTOCAHDIA5IJPARCTZOgDIAOIOSl8 Ye are reportimg oar preliminar! reeultueitk tke use or this HAm in u group or AHI patients, Our stud! group consisted of |l pan (36 male) aged 3l to T5 (mean 5S,5) wink eoorirued ARk tZ Q-wave ANt, gO non Q-wave AHI, and ! peropermtire AWL Three other ptu bad to be ezcluded because HH[ dimgoouin could not be confirmed. 99z-Te PTP ueistigrapk! was perroroed in the tirst place (one to seven days after AH[ syaptouu onset, seam = ! dmye}, laoedietel! after, In-Ill HNABwan odninlutered i.v. (l.g2 to 2.1S |Ci, lean : 1.58~ and anterlor sod left anterior oblique I0 sin. images were taken 48 bourn later with m 5FOY camera. Data mere also stored in an on-line computer to derive uptake within the cardiac region (ms u percentage ot the administered radiactime done), as well as ditreremt uctivit! ration, huge Kemn g Z uptake of dose in Agl 0.45-2.83Z I.ZTZ 21 Heart-to-lung ratio 1.37-3,10 1.83 24 Heart-to-liver ratio 0.23-0.81 0.41 24 geort-to-sternuo ratio 0.82-1.Sl 1.03 IS CPK-HB pick (U/5) 17-244 63 41 go correlation ass lamed between AH[ else estimate 5y CP|-Im pick ud 8HHBuptake (Z of dose or an! activity ratio), 3cintigropkic images evaluation by two independent observers yielded the tolJoeind reeu]ku: Q-AH[ non @-AHI Perop ARI Totals 8~gB ~ PTP ~ IT 6 1 34 HHAB - PTP 2 l 3 6 NNAB ~ PTP 2 2 5 9 H~AB - PTP ~ I I O Z ?cLaim ZZ 10 9 41 Although nor series is too ,emil to reach definlte conclusions, It seems that HHAB results are very sililar to PTP scJotigrapb! results ia q-Jmve ggl patients. Hosever, HHADuse in non q-wave and peroperative Afli patients is probabi! o better choice as infarct avid agent,
479
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322
T. Jarada, A.H. Elgazzar, M. Elsayed, S. Mahmoud, S. Bhatnagar, A.R. Ai-Yusuf, H.M. Abdel-Dayem. Departments of Medicine and Nuclear Medicine, Ministry of Public Health and Faculty of Medicine, Kuwait University, Kuwait.
F. Portaluppi,*B.
Bagni, E. degli Uberti,
L. Montanari,
G. Trasforini, A. Margutti Clinica Medica, University of Ferrara *Nuclear Medicine, S. Anna Hospital i-44100 Ferrara, Italy CIRCADIAN RHYTHMS OF ATRIAL NATRIURETIC PEPTIDE, RENIN,
ROLE OF IN-ill ANTIMYOSIN (AM) IN THE DIAGNOSIS OF NON-Q WAVE MYOCARDIAL INFARCTION (MI) IN PATIENTS WITH UNSTABLI ANGINA
ALDOSTERONE, AND CORTISOL IN ESSENTIAL HYPERTENSION. The aim of our study was to assess the circadian rhythm of atrial natriuretic peptide
The diagnosis of HI in the absence of Q wave on 12 lead ECG is a difficult diagnostic problem. 22 patients admitted to coronary care unit with cardiac pain at rest of more than 30 minutes duration and no Q wave on E C G were studied with In-ill AM. Each patient was injected with 74 MBq of. In-lll AM intravenously. Ten minute views in the anterior, 40 and 70 degrees LAO projections were acquired 24 and 48 hours post injection. Scans were interpreted blindly by two nuclear medicine physicians and results were correlated with clinical, ECG and serial CPK-MB changes measured by the sensitive immunoradiometric assay (IRMA) every 8 hours for 40 hours. Twelve out of 13 patients (92%) with final diagnosis of MI showed positive In-lll AM scan and 8 out of 9 (89%) patients with no evidence of MI had negative scans. The case of positive In-ill AM and normal CPK-MB was in a female diabetic and can be explained by the fact that the infarction was of more than 24 hour duration and that the peak of enzyme elevation was missed. The case of negative In-Ill AM scan and elevated CPK-MB could be due to a small MI not resolved on the planer images and probably SPECT would have given a better resolution. We conclude that In-ill AM scan is a useful marker of myocardial necrosis and can be used for early diagnosis of MI in patients with cardiac pain when other diagnostic criteria particularly the 12 lead ECG are not diagnostic.
For this purpose, the RIA method was used to determine the plasma levels of each hormone, and the data were analyzed with the standard,
chronobiological,
inferen-
tial statistical method of the single and mean cosinor. ANP,
plasma renin activity
(PRA), aldosterone
cortisol (C) were assayed in ten hospitalized with essential hypertension at the end of a
(A)
and
patients synchro-
nizing period of one week. The day of the study, blood samples were obtained every four hours. A significant mean circadian rhythm was demonstrated for each hormone with the following characteristics: Mesor Amplitude Acrophase ANP (pg/ml) ............ PRA (ng/ml/h) .......... A (pg/ml) ............
26 ......
4:10 a.m.
1.3 ....... 0.4 ...... 12 ....... 5 ......
79 .......
6:58 a.m. 7:51 a.m.
C (~g/dl) ............ 12 ....... 5 ...... 8:42 a.m. Previous studies demonstrate the existence of a circadian rhythm of ANP in normal subjects. In hypertension, we found a similar rhythm at higher levels. Based upon acrophase asynchronism, no causal relation may be hypothesized between ANP and the other hormones.
324
323 J. DARCOURT*, O. MIGNECO', J.t. LAGRANGE**, J. BENOLIEL*, R.J. BENSADOUN**, F. LAPALUS* * Department of Biophysics and Nuclear Medicine ** Department of Radiation Therapy Centre Antoine Lacassagno - NICE - FRANCE ASSESSMENT VENTRICULAR
(ANP) in essential hyper-
tension, and its relations with the circadian patterns of other hormones affecting the cardiovascular system.
OF ACUTE DYSFUNCTION
Richard Bauer, UIIrich Gebhardt, Everhard van de Flierdt, Regine Truckenbrodt, Hans Werner Pabst Nuklearmedizinische Klinik Technische Universit&t M0nchen, FRG
TEMPORARY ASYMPTOMATIC DURING THORACIC IRRADIATION
Following preliminary data presented last year at the EANM meeting, we report on the completed results of a prospective study on the acute cardiad effect of thoracic Irradiation (TIR). Each patient underwent 3 successive gated radionuclide angiographles at rest : before starting TIR (GRA1) ,during or within one month following the end of TIR (GRA2) and more than 2 months alter (GRA3). Left ventricular ejection fraction (LVEF) was calculated by a semi-automatic single region of interest method (interobserver correlation 0,96; std error 2.4 %).Right ventdcular ejection fraction (RVEF) was determined by a manual 2 region of interest method (interobserver correlation 0.95 ; std error 3.4 %). For each patient the differences between the successive EF measurements were calculated (D1 = GRA2 - GRA1 and D2 = GRA3 - GRA2) and the mean values of theses differences were tested for each group. Out of 102 patients studied, 11 in whom TIR did not include the heart served as controls and did not show any significant LVEF variations. In the other 91 patients whose myocardium was irradiated there was a highly significant drop and then recovery of LVEF (D1 = - 3.4 +_6.8 % ; D2 = 3.6 +- 5.6 % ; p < 10 -4 tot both). Among them, the same evolution was found in the 45 who underwent TIR of the entire mediastinum (p<10 -4) and in the 21 patients who received irradiation to the right internal mammary chain ( p < 0.05 ) but was not significard for the 25 patients who received irradiation to the left internal mammary chain. There was no significant difference between the 36 patients receiving Addamycine (D1 = - 4.1 + 7.2 ; D2 = 3.6 +_ 5.9) and the 29 drug-free patients (D1 = - 3.3 +_ 7.6 ; D2 = 3.6 + 6.3) both showing a singificant drop and recovery. RVEF was measured In a subgroup of 20 patients irradiated on the mediastinum and showed the same evolution (D1 = - 4,2 + 7.3, p < 0.02 ; D2 = 10 + 8.6, p < 10-4). These results demonstrate for the first time in humans an acute asymptomatic tall of LVEF and RVEF due to cardiac irradiation with recovery after 2 months.
PLANAR SCINTIGRAPHY (PS), SPECT AND NUCLEAR MAGNETIC RESONANCE IMAGING (MRI) IN THE DETERMINATION OF MYOCARDIAL UPTAKE OF MIBI We investigated the absolute myocardial uptake of MIBI in the whole heart and per gram myocardium. 17 patients with various diseases were studied, 6 at rest, 11 both at rest and after exercise. PS of the region of the heart were recorded 0.5, 2, 4 and 6 hrs p.i. in ventral and dorsal view, ECT was performed 2 and 4 hrs p.i. Anatomy of the heart and of the thorax and myocardial mass (MM) was assessed by MRI. Absorption was measured by PS and calculated from MRI. MM was 269+52 g, myocardial uptake was 3.5+1.0 % and 4.1+1,6 % of injected activity at rest and following exercise, respectively. Specific uptake per g myocardium was 0.012 and 0.015 % (rest and exercise), the quotient between myocardial and pulmonary uptake was 3.2 and 4.0 with SPECT and MRI evaluation, respectively. The uptake, which is 20% higher than quoted by the distributor (NEN), is in good agreement with the coronary perfusion at rest of 5-6 % of the total cardiac output and a myocardial extraction of MIBI of 6070 % as found in animal studies.
480
326
325
Ph. PEZARO. A. FURBER, J.J, LEJE~E, Ph. GESLIN, A, TADEI, P, JALLET
D. Neotla, C. Palombo,O. Psrodl, 6.M. SarnbucsU,C. Msrebottl, A. 6enovesI-Ebert, F. Nudi. S. Bhlone. A. L'Abbste. C.N.R. Institute or Clinical Physiology, and IsUtuto dl PatologieMedico, University or Piss, Piss. Italy. NONINVASIVE DETECTIONOF EARLYMYOCARDIALDYSFUNCTIONIN PATIENTS WITH LEFTVENTRICULARHYPERTROPHYSECONDARYTO HIGHBLO00PRESSURE. Whether left ventrlculor (LV) function ts Impaired In patients with high blood pressure (HBP) and LV hypertrophy Is still questioned. Aim of" this study was to assess tn this setting e possible early LV dysfunction by means of redlonucltds onglogrsphy (RNA) combined with handgrlp test (HG). Eight hypertensive patients (HT) (I-II W.H.O. stags) with LV hypertrophy (septal diastolic thickness -1.5±0.2 crn) and 8 norrnotanslves(NT) underwent RNA In basal conditions and during HG, with nonlnvsslve 5P msnRorlng. LV ejection traction (EF), endsyetollc and enddlestollc volumes (ESV, EOV}end volume indexes (PER, PFP.)were computed from RNA. The ratio betweensystolic BP and ESV was usedmsan additional Indexof contractility. In bssal condiUons, HT and NT differed only for BP (mean BP: 131,19 ve 87±0) and porlphersl restst~ce (TPR: 2B.6,11.7 vs 15.7±3.2) (p(.O5). During H6, similar increments in mean BP were round In the 2 groups (HT: +25~, NT: +22~), while heart rats end TPR showed higher Increments tn HI then In NT (+32X vs 20X end +59~ vs +23~), I~NAdata at rest end during H6 ore reported in table (" - pc.05): LVEF EDV ESV PER PFR SPIESV CO HTBasal 60,I0 143±49 74±35 2.4±6 1.4±.3 2.4,I.! 55,I.9 Stress 53±15" 127±52" 79,43 19,9 14±5 2B±14 45±18. NTBasal 52,5 134±47 75,30 2.3,.4 1.6,.4 1.g*.7 5,4,1~4 Stress 63+7 122,51 69±33 2.3±.9 1.6±5 2.7±1.6" 5.5±1.3 During He, In NT the Increment in TPR wee compensated by an Increase in controcUItty, ss assessedby SP/ESV, while the other Indexeso£ LV function dtd not changeslgnlrlcantly and COwas preserved. In HT, the higher IncreaseIn TPR wss not parallelled by a significant Increment In contractility end wss associated with e decreaseIn LVEFand CO. Furthermore, HT showed, at variance wtth NT, s significant decreaseIn EDV (Increasedstiffness?) and e trend towards an Incresse In ESV end e decreaseIn PER. In conclusion: paUentswith hypertension end LV hypertrophy show a reducedsystolic functional reserve during Isometric stress. RNA cornblnndwith HG ts s useful tool to detect early LV dysfunction In hypertensive heart disease.
327
CHU ~GERS - 49000 - FP.~VCE,
GLOBAL ~D REGIOFk~LASSES~EN-I OF DIASTOLIC O¥SFLtNCTIONIN COROt~R¥ ARTERY DISEASE WITH NOI~'IALSYSTOLIC F~CTION BY RAOI~UCLIOEANGIOGBAPHY (l~i~). To assess the ability of ~ to detect clinically relevant abnormalitiesof left ventricular (LV) diastolic function at rest in coronary artery disease (CAD) without systolic impairment,we compared the global and sectorial indices of early and late LV filling observed in 22 strictly selected one-vessel diseased patients (pts) and in 15 age-matchednormal subjects. Population: CAO pts were selected on normal X-ray and ~ global and regional ejection fractions, normal X-ray LV mass and lack of hypertension. The artery involved was left anterior descending artery (LAD) in 15 pts, circumflex artery (Cx) in 5 pts and right coronary artery (RCA) in 2 pts, Methods: From gated ~ w i t h ]6 frames/cycle, one global and 12 sectorial volume curves were expanded to 44 points/cTcle after Fourier transform. One-third (I/3FF), mid-diastolic (I/2FF) and atrial (AFF) filling fractions and time necessary to reach one third of the total iV filling volume (TFI/3) were calculated on each curve. Time of peak riding rate (TPFR), normalizedPFR and atrial filling rate (AFR) were calculated on the first derivatives. Results: Despite a normal systolic function, a significant impairment of some global diastolic indiceswas noticeable in more than 5~ of CAD pts, index I/2FF TFI/3 TPFR PFR ~FPJPFR
all CAO (n=22) /controls sensitivity p <0,001 64 % p <0,001 64 % p <0,01 59 % p <0301 82 % p <0.05 50 %
LAD (n=I5) Cx or RCA (n=7) /controls sens. /controls sens. p <0.001 67 % p <0,01 57 % p <0,001 67 % N.S p
The sectorial analysis sh~ed that this dysfunction was related partly to an increased diastolic temporal usynchronim (significantfor TFI/3 and TPFR) and affected quite specifically the sectors depending on the involved artery,
328
G.Lucignani, G.Fragasso, M.C.Gilardl, A.Savl A.Conversano, F.Colombo, A.Compierchio, G.Rizzo M.Matarrese, S.Chierchia, P.Gerundini and F.Fazio. C.N.R., Istituto Scientifico of Milano, Italy.
Services de Medecine Nucl~aire et de Cardiologie
H S. Raffaele,
EVALUATION OF MYOCARDIAL PERFUSION COMBINED USE OF SPECT AND PET.
AND
H. VALETTE, M. BOURGUIGNON, P. M E P ~ T , D. LE GULUDEC, WEINMANN, B. JOEv'E, C. RAYNAUD, A. SI'ROTA.
P.
Service H o s p i t a l i e r Fr~d4ric J o l i o t , CEA, Orsay, France.
Universit,
METABOLISM
B
Seven patients with the clinical history of coronary artery disease underwent myocardial rest perfusiom studies with both SPECT and PET using 99m-Technetiumlabeled methoxyisobutyl isonitrile (MIBI) and N-13-1abeled ammonia, respectively, and myocardial metabolism studies with PET and I8-F-labeled-2-fluoro2-deoxyglucose (FDG). SPECT scans were performed following the i.v. administration of approximatively 74G MBq of MIBI by a rotating gamma camera. Transaxial resolution was 1.5 cm FWHM, slice thickness was 0.48 cm. PET scans were performed following the i.v. administration of approximately 370 MBq of N-13-1abeled ammonia and after the administration of 200 MBq of FDG. I Transaxial resolution was 0.6 cm FWHM, slice thicknessJ was 1.35 cm. To obtain SPECT and PET slices of 1 comparable thickness, three SPECT slices were summed. I SPECT and PET cardiac transaxial images were divided I into four anatomical regions: anterior, septal, lateral 1 and infero-posterior. An index of perfusion, ranging from I to 4, was assigned to each area; the analysis based on circumferential profile techniques is in] progress. We observed a good overall correlation between I the semiquantitative assessment of myocardial perfusion] with ammonia/PET and MIBI/SPECT. Thus, viable tissue[ within ischemic regions could be identified by the I combined use of MIBI/SPECT and FDG/PET. Combined use of I SPECT perfusion studies and PET metabolic studies may constitute a powerful technique for clinical purposes.
BREAST ATTENUATION AND LEFT ANTERIOR DESCENDING CORONARY ARTERY DISEASE : CHARACTERISTICS IN ~OMEN ON T1 201 TOMOGRAPHIC IMAGES.
The breast attenuation pattern (BAP) was studied in 27 women with normal coronary angiograms (NCA), in i0 with LAD stenosis and i0 with anterior myocardial infarction (AMI). Tomographic imaging was performed in a standard manner : 2 mCi of T1 201 injected at peak exercise, acquisitions 5 and 180 min later, 32 steps over 180 ° starting from LPO, 30 s per step, standard reconstruction including baekprojeetion and 3D fJlterJ,g. S ~ NCA had a normal T1 dJsttib,~io,. 2 1 N C A presented an abnormal (BAP) pattern : a defect strictly limited to the anterior myocardium in 19 of them, also involving the septum in the remaining two. In women with LAD stenosis or AMI the defect always included the septal wall. Redistribution (R) and wash-out (WO) were assessed (sectorial analysis) in the most abnormal slices : Defect (X) R (%) WO (~) BAP (n=21) 81±7 3±1 48±8 LAD stenosis (n=lO) 79±8 9±2 43±9 AMI (n=lO) 73±8 4±4 45±14 The above analysis does not help to differentiate gAP from LAD diseases. Conclusion : a gAP is frequently observed in women. Because it is identical to the defect induced by LAD diseases, except a subtle difference : the septal involvement, the BAP should be interpreted cautiously.
481
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330
J.Lekakis, A.Arka, N.Vassilopoulos, S.Gerali, D.Tsinikas, D.Maintas, P.Kostamis, Sp.Houlopoulos
.I. Szilv~si, I. Balogh, R Kiss, E. 8erentey
A.
" '+ Harsanyl,
L.
MaJor,
Dept. of Radiology and Coronary Care Unit + Postgradual Medical School, Budapest, Hungary Dpt of Therapeutics and Dept of Nuclear Medicine. Alexsndra University Hospital, Athens Greece DIPYRIDAMOLE Tc 99m RP-3O SPECTvs DIPYRIDAMDLE GATED RADIONUCLIDE VENTRICULOGRAPHY IN DETECTING CORONARYARTER DISEASE Intravenous administration of dipyridamole (D) is an a] ternative to exercise stress during perfusion scintigraph~ for detecting coronary artery disease (CAD), but its diagnostic value in conjunction with gated rsdionuclide ventriculography (GRV) is not yet documented. To investigate the value of GRV after D-infusion and to compare with Diperfusion scintigrsphy we evaluated 19 patients (pts) who underwent GRV before and after D-infusion(0.56 mg/Kg) as iwell as D-Tc Rp-50 scanning. CAD by coronary arteriography was present in 14 pts (>50% stenssis). Failure to increase global ejection fraction ( G E O l 5 units after D~infusion or a decrease in regional ejection fraction(REF) was considered abnormal responses for D-GRV.9/14 (64%) of p t s with CAD presented abnormal GEF responses after Dinfusion. REF abnormal response was present in 11/14 pts with CAD (79%). All subjects without CAD increased GEF >5 i units (specificity 100%). In pts with CAD concordance between D-GRY and D-Tc99 m Rp-30 was observed in 12 pts while in 2 pts with positive D-Tc99 m Rp-50, D-GRV was negative. In one pt with positive D-GRV, perfusion defect was not detected. Sensitivity of D-Tc 99 m Rp-50 was 12/14 (86%) and specificity 80%. Of 32 normal vessels 31/32 were detected as normal by D-GRV (regional specificity
97%) and 28/32 by D-Tc99m Rp-30 (88%). 15/24 (63%) abnormal vessels were detected by REF response while 17/24 (71%) by Tc99m Rp-30. In conclusion D-ERr a) i s a r e l i a b l e non-invasive method f o r d e t e c t i n g CAD. b) i s comparable with dipyridamole perfusion s c i n t i g r a p h y .
TC-99M-ISONITRILES FOR EVALUATING THROMBOLYTIC THERAPY OF ACUTE MYOCARDIAL INFARCTION Tc-99m-isonitriles are a new group of myocardial perfusion radiopharmaceuticals without significant redistribution. One of advantages of Tc-99m-labelling is: they can be used in emergency situations. In our study Tc-99mmethoxy-isobutyl-isonitrile /MIBI/ scintigraphy was used to evaluate therapeutic effect of intravenous thrombolysis with streptokinase inifusion in 12 patients with acute myocardial infarction. 57o MBq Tc-99m-MIBI were in~ected immediately upon admission and streptokinase infusion was started. Scin±igraphy was performed at convenient time up to 24 hours later. Resting Tc-99m-NIBI study was repeated after one week. Circumferential activity profiles of pre- and post-therapy planar myocardial perfusion images w e r e compared to each other. Results were correlated to serial enzym determinations and ECG find3ngs. In 9 of 12 patients marked reduction of resting perfusion defect was observed corresponding to clinical signs of successful myocardial reperfusion. In conclusion: emergency myocardial perfusion scintigraphy with Tc-99misonitriles is a reliable noninvasive method to evaluate clinical usefulness of reperfusion interventions in patients with acute myocardial infarction.
332
331 J.R. KIENY, A. FACELLO, P. BAREISS, G. ROUL, J.L. DEMANGEAT, B. BRUNET, A. SACREZ, A. CONSTANTINESCO
G.Fragasso , R.Benti, M.Scian~narella, E.Rossetti, A.Savi, D.Cianflone, A.Dolci, F.Fazio, P.Gerundini, S.L.Chierchia.
C.H.U. Hautepierre, Strasbourg, FRANCE
Istituto (Italy). NORMALIZATION OF RADIONUCLIDE LEFT VENTRICULAR EJECTION FRACTION AFTER CARDIOVERSION OF CHRONIC ATRIAL ARRHYTHMIA IN IDIOPATHIC DILATED CARDIOMYOPATHY. To assess potential improvement of left ventricular ejection fraction (LVEF) after cardioversion of chronic atrial arrhythmias in dilated eardiomyopathy, we studied prospectively 17 patients (pts), aged 58,6 years, by r a dionuclide angioeardiography at rest. Atrial fibrillation was present in 16 pts and atrial flutter in 1 pt. LVEF was determined before treatment (LVEFI) and at a mean delay of 4.7 months after eardioversion was attempted (LVEF2). Return to sinus rhythm was obtained in 12 pts (GI), with amiodarone in 5 pts and after electrical eardioversion in 7 pts ; 5 pts remained in atrial fibrillation (GII). No factors could predict success of cardioversion. Results LVEFI (%) LVEF2 (%) GI 32.1,5.3 52.9,9.7 p < 0,001
(24-41) GII
30.0,9.1
(19--44)
(37-71) 29.5,8.3 (22-41)
NS
When sinus rhythm was restored, LVEF increased of 20.6 ,11.3 % (-i to +37 %) and was normal ( ~ 55 %) in 50 % (6/12) of the pts. After a mean delay of 16,10 months, 2 pts in GI returned in atrial fibrillation and LVEF decreased again in both pts. We conclude that LVEF increases substantially and normalizes in half of the patients after suceessfull eardioversion of chronic atrial errhythmias in idiopathic dilated eardiomyopathy.
Scientifico
0spedale
San
Raffaele,
Milanc
LEFT VENTRICULAR STUNNING INDUCED BY SYMPTOM-LIMITE: EXERCISE TESTING: A RADIOVENTRICULOGRAPHIC ASSESSMENT. To investigate the possibility that maximal exercis testing (ET) could induce prolonged impairment of lef ventricular function (LVF), we studied 14 patients (pts 1 with coronary artery disease (CAD) and 9 agematche6 controls with atypical chest pain and no CAD Radionuclide ventriculography was performed at rest, at peak ET (semisupine, symptom-limited), during recovery and 2 and 7 days after ET. Ejection fraction, peak filling (PFR) and peak emptying rate (PER) were analyzed. All controls had negative ET at maximal workloads and improved LVF with ET. In CAD pts, although ET was discontinued when angina or equivalents occurred diagnostic ST~ (~ir0m) developed much earlier than symptoms. Eight pts rapidly developed 1 n~n ST$ (2.4 ~ 1.5 min) for low workloads (34 ~ 12 W) (group A): 6 (group B) tolerated longer exercise times (time to 1 n~n ST$ 6.5 1.8 mm min) and higher workloads (58 ~ 12 W). Predictably, all pts showed, at peak ET, a decrease of both PER and PFR which, in group B, normalized within the recovery period. However, in group A, PFR remained depressed throughout recovery (p<0.0009) and was still reduced 2 (p<0.0007) and 7 days (p<0.04) after ET. In pts with very low ET tolerance, prolonged exercise may cause sustained impairment of diastolic function. In these pts, ET should be performed with caution and a more conservative approach based on the development of diagnostic ST changes, rather than occurrence of symptoms, should be used.
482 334
333 A.Constantinesco, P.Bareiss
A.Facello,
C.H.U. Hautepierre,
B.Brunot,
J.Demangeat,
STRASBOURG - FRANCE.
REST / DIPYRIDAMOLE RADIONUCLIDE ANGIOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE. Intravenous infusion of dipyridamole (dip) wa~ reported to induce abnormal wall motion in coronar~ artery disease (CAD). We studied changes ~ EF) ir global ejection fraction (EF) for diagnosis of CA[ using radionuclide angiography at rest and after 4 minutes dip infusion (.44 mg/kg) in 60 patients i (pts) witho~t myocardial infarction who underwent coronary arteriography. They were divided in normal arteriograms (NA), single vessel (SVD) and multiple vessel disease (MVD). NA(n=27) SVD(n=IS) MVD(n=I8) rest EF(%) 60 ~ 7 56 ± 7 60 ± 6 AEF(%) 7.8 ± 5.8 5.8 ± 4.9 1.2 ± 5.0 AEF values baaing significantly different (p ~ 0.01) between the three groups when rest EF is used as a oovariate. The sensitivity (Se), specificity (Sp) and accuracy (Ac) of the EF dip test for the diagnosis of CAD was assessed using different thresholds of absolute increase in EF. Se (%) Sp (%) Ac (%) (S+MVD) (MVD) (S+MVD) (MVD) (S+MVD) (MVD) EFt4% 52 67 89 85 68 77 A EFt5% 55 67 74 72 63 68 A EFt6% 70 89 63 70 67 55 A EFt7% 73 94 56 67 65 53 The EF d i p t e s t , able to detect CAD p t s , is a simple alternative test to exercise radionuclide angiography.
Department of Cardiology and Nuclear Medicine; St. Antonius Hospital, Nieuwegein. *University Hospital, Le~den; the Netherlands. COMPUTER-ASSISTED DIAGNOSIS IN THE NON-INVASIVE ASSESSMENT OF CORONARY ARTERY DISEASE: A MULTIVARIATE ANALYSIS MODEL. The purpose of this study was to derive a multivariate logistic regression model (MLR) from independent clinical, exercise and scintigraphic variables of 106 patients(pts) to calculate posttest probabilities in coronary artery disease (CAD)()50% stenosis). We considered 13 variables: age; sex; history of typical angina (TA); rest electrocardiogram; multiple exercise parameters, including exercise heartrate-blood pressure product, angina during the test (AT),ischemic ST response; visual analysis of planar Thallium-201 scintigraphy; quantitative analysis (QA) of uptake and washout(QAUW);QA of uptake alone(QUA). A stepwise logistic regression analysis was used to provide a probability estimate of the presence and severity of CAD. The incremental value of each test was assessed by adding it sequentially into the logistic model. MLR showed 5 variables to reach the maximal accuracy in predicting CAD: (I) QUA,(2) TA,(3) QUAW,(4) sex, (5) AT. Using the MLR in a second group of 221 pts, 73% of the pts with a low likelihood (<20%)and 85% of the pts with e high likelihood(>90%) of CAD could be identified. In case of TA and a positive QUA a 91% likelihood of CAD was predicted. Other variables added little extra information. We conclude that: (I) Using a multivariate analysis model the probability of CAD can be derived more accurately, (2) Quantitative analysis of the initial uptake of planar Thallium-201 myocardial scintigraphy was selected as the most powerful variable separating normal patients from those with coronary artery disease.
336
335 A. Giordano, R. Manni, R. Mastrodonato,
MtG.NiemeYer, M.J.Cramer, J.F.Verzijlbergen, S.Lelbach, E.E. van der Wall ~, A.H.Zwinderman*, E.K.J.Pauwels*, C.A.P.L.Ascoop.
G. Galli.
Istituti di Medicina Nucleare e Chirurgia Geriatrica, Universit~ Cattoliea del Saero Cuore, Largo A. Gemelli 8, 00168 Roma - Italy
Tc99m-MIBI(MIBI) AND TL2OI(TL) IN LOWER LIMBS MUSCLES SCINTIGRAPH¥: EVIDENCE OF DIFFERENCES In this report we present the results obtained in 7 nor mal subjects (with approval of UCSC Bioethioal Committee) and in 7 patients with Lower Limbs Arterial Occlusive Dis ease (LLAOD) who underwent stress/rest muscle scintigraphy with TL and MIEI in order to compare the scintigraphic patterns. Rest TL images were obtained 18 ~ours after the stress study (2 mCi); rest MIBI images web's obbained by re injection (25 mCi) performed at the end of the stress exa, (5 mCi). For each subject 2 blinded observers comparatively examined thighs, calves and feet images (84 pairs of images). Results in normals: no side differenceswere detected with either tracer (0/42 images). Results in LLAOD pts.: perfusion side differences at rest were detected in 14/21 images (7 were definite mismatches) mainly due to absent or milder MIBI ischaemic pattern. Perfusion side differences at rest were detected in 11/21 images, mainly due to more evident MIBI reperfusion. On the basis of clinical, doppler and arteriographic data we conclude that TL has higher sensitivity than MIBI to detect muscle effort isehaemia; conversely at rest the possibility of a 2nd MIBI injection seems to allow a more reliable assessment of rest perfusion than TL 18 hours redistribution which tend to reflect, at least in part, the early scintigraphic pattern.
IM Hassan, MMJ Mohammed, G Cherian, C Constantinides, M Nair, N Bellani, N Khan, N Hayat, HM Abdel-Dayem.
Fac of Medicine & Ministry of Public Health, Kuwait.
SEGMENTAL DIAGNOSTIC DAMOL Tc-99m METHOXY MYOCARDIAL PERFUSION WITH CORONARY ARTERY
ACCURACY (SDA) OF SPECT DIPYRIISOBUTYL ISONITRILE (DP MIBI) IMAGING (MPI) IN PATIENTS (PTS) DISEASE (CAD).
The aim of this study was to determine the SDA of SPECT DP MIBI for the detection of CAD. 21 pts were studied prospectively (16 M, 5 F, age 52~7.7 year). All had first-pass (FPRA) immediately after first MIBI dose (lOmCi) given after DP infusion 0.568 mg/kg over 4 min). The rest dose of MIBI (15 mCi) given 4 hrs Later SPECT acquired one hour after each MIBI injection. DP infusion resulted in significant changes in HR, syst & diast BP. 3 pts developed headache & vertigo and only 6 had cardiac symptoms; 4 required aminophylline. Considering CAD with more than 50% stenosis CA done within 2 weeks showed 9 pts with (3 VD), 7 (2VD), 4 (IVD) and one normal. The FPRA EF for RV = 52~8; for LV = 58+14 compared to 51+9 by CA (r=0.84). The LV was divided ~nto 4 segments. MPI was assessed visually and by bullseye by 2 observers and scored 0 normal, i reversible ischaemia, 2 scar and 3 reverse redistribution. The sea. sens.(SE), spec.(SP) and accuracy (AC) are : Ant sept LaSt Inf Global SE 83 89 77 92 85.5 SP i00 100 100 88 95.5 AC 86 90 86 90 88.1 We conclude that DP infusion is relatively safe, its use in a protocol such as presented here with Tc-99m MIBI is useful for MPI in detecting CAD.
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338
A M Peters C.A. Buchpiguel; S. Roizenblatt; J. S c a r e s Jr.; J.C. Meneguettl; F.H. Hironaka; W. Cossermelli; S. Santos; E.E. Camargo. Hammersmith Hospital, London, England. MICROVASCULAR PERMEABILITY TO SMALL SOLUTES Although the leakage of proteins across capillaries has been well studied, the transfer of small hydrophilic solutes has received little clinical attention. By applying techniques for measuring individual kidney GFR from the Tc-99m DTPA renogram to a non-renal region of interest, the regional clearance rate (PSr) of DTPA from intravascular (IV) to extravascular (EV) spaces can be derived. This is analogous to the permeability-surface area product a classical parameter of capillary permeability which also has units of clearance. Although the EV DTPA clearance represents the net transfer rate, and consequently decreases with time after DTPA injection, the unidirectional transfer into the EV space can be estimated from the initial 2.5 min after injection. The plasma volume (tPV) of the tissue within the region of interest is also obtained In the lumbar region below the kidneys normal PSr and tPV were 1.0 (SD 0.2) ml/min/100ml and 5.0 (2.0) ml/1OOml tissue respectively, with a ratio of 0.23 (0.05) min-1. In order to address the problem of back diffusion of DTPA, a small dose of Tc-99m HSA was given 5 min before DTPA in 8 patients. This gave a tPV similar to that derived from DTPA with a mean Patio of 0.96 (0.09), while the PSr was about 12 times less (and possibly the result of free pertechnetate). As an illustration of its potential clinical value, we measured PSr for DTPA in 6 patients with myeloid leukaemia before and after bone marrow transplantation. It increased, in all of them from a mean value of 1.1 (0.3) to 2.0 (0.4) ml/min/100ml, with no change in tPV. This technique deserves further clinical investigation.
C e n t e r of N u c l e a r Medicine and The Heart Institute, Sac Paulo U n i v e r s i t y , Sac Paulo, Brazil. R a d i o i s o t o p i c A s s e s s m e n t of Cardiac and Peripheral Muscle I m p a i r m e n t in P o l y m y o s i t i s / D e r m a t o m y o s l t i s (PM/DM). Cardiac i n v o l v e m e n t in P M / D M is a s s o c i a t e d w i t h a poor prognosis, w h i c h justifies the search for non-invasive diagnostic procedures to evaluate these p a t i e n t s (pts). To determine the f r e q u e n c y of cardiac i n v o l v e m e n t in pts w i t h o u t c a r d i o v a s cular symptoms, iO pts (6 female; 5-50 yrs) w i t h cllnicaLenzymatic and h i s t o l o g l c d i a g n o s i s of PM/DM were studied. M y o c a r d i a l and p e r i p h e r a l muscle imaging was o b t a i n e d 6 hr after intravenous injection of ggmTe-PYP. C a r d i a c f u n c t i o n at rest was e v a l u a t e d by gated blood pool (GBP) imaging. Two pts (20%) had normal enzymes and seintigrams. Both enzymes and imaging of p e r i p h e r a l m u s c l e s were abnormal in 8 pts (80%). C a r d i a c involvement
by EKG and PYP was found in 5 pts, 2 of them with m a r k e d m y o c a r d i a l uptake, abnormal GBP and abnormal e n d o m y o e a r d l a l biopsy. The r e m a i n i n g 3 pts showed mild PYP uptake and normal GBP. All pts w i t h m y o c a r d i a l PYP uptake had clinical, enzymatic and s c l n t i g r a p h i c evidence of p e r i p h e r a l muscle involvement. R a d i o i s o t o p i c e v a l u a t i o n is important for the early d i a g n o s i s of cardiac involvement in P M / D M and to follow response of these pts to therapy.
339
340
R.Picozzi,S.Boceolari,R.Baroffio,P.Verga,B.Palagi
P. Thelsseq, U. Sechtem, S. Delder, K.F.R. Neufang, H.W. H0pp, H. Schlcha.
Servizio di Medieina Nueleare e di Cardiologia con U.C.C Ospedale di Saronno-Italy.
COMPARISON BETWEEN INTRAVENOUS RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR AND STREPTOKINASE FOR TREATMENT OF ACUTE MYOCARDIAL INFARCTION. To compare the effectiveness of intravenous recombinant tissue plasminogen activator (rt-PA) with that of intrave nous streptokinase (SK) for treatment of acute myocardial infarction,we studied 47 consecutive patients treated at random (SK group:23 patients; rt-PA group:24 patients) with equilibrium gated radionuclide angiography performed between the 2nd and 8th day and with dipyridamole thallium myocardial perfusion scintigraphy performed between the 15th and 20th day of the onset of symptoms. The incidence of major in-hospital complications was not
aignifleantly different in the two group~, Furthermore,we did not observe any significant difference of left and right ventricular ejection fraction both in the global comparison of the two groups and when we consi~ dered anterior and inferior infarctions apart. Moreover,neither the incidence of left ventricular dyskine tie segments nor that of residual isehemia showed any significant difference. In conclusion our preliminary results show that intravenous rt-PA is not superior to intravenous SK for treatment of acute myocardial infarction.
Institute of clinical and experimental Nuclear Medicine and Medical Clinic III University of Cologne, Cologne, FRG DEMONSTRATION OF INTIMAL TEARS IN PATIENTS WITH ACUTE AND CHRONIC AORTIC DISSECTION Gradient-echo magnetic resonance Imaging (GE-MRI) provides additional blood flow Information which may be diagnostically useful In aortic dissection. Therefore, 23 patients with surgically (N=18) or anglographlcally (N=5) verified aortic dissection underwent transverse GE-MRI. Two sections were scanned simultaneously. Images were displayed In an electronic movie loop to assess Intravascular blood flow. All patients had spinecho (SE) MRI end computed tomography (CT) for comparison. GE-MRI provided the correct diagnosis In all patients. One dissection was not be detected by SE-MRI and two were not detected by CT. Dynamic MRI facilitated the differentiation between true and false lumen In ell cases by demonstrating earlier blood flow In the true than In the false lumen. It also Improved visualization of the Intlmal flap which moved considerably In patients with acute dissection end was therefore at times difficult to visualize with SE-MRI or CT. The additional flow Information facilitated differentiation between slow blood flow and Intravasculer thrombus. In 15 patients an Intlmal tear with turbulent blood flow between true and false lumen reflecting the site of an entry was Identified. Associated aortic regurgitation (N=6) and aortic stenosls (N=I) could also be diagnosed by GE-MRI In contrast to CT and SE-MRL GE-MRI Is a useful technique for nonlnvaslve assessment of aortic rupture and aortic dissection. It may provide the correct diagnosis when CT Is difficult to Interpret and determine the site of an Intlmal tear.
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141 K. Kouris, H.M. Abdel-Dayem, B. Taha, N. Bellani, I.M. Hassan, "C. Constantinides, M. Nair, M.M.J. Mohammed.
Faculty of Medicine and Ministry of Health, Kuwait.
EJECTION FRACTION (EF) CALCULATED FROM Tc-99m MIBI DUAL GATED (DG) SPECT PROCEDURE AND COMPARISON WITH CONTRAST VENTRICULOGRAPHY (CV). DG SPECT studies at ED & ES were acquired in 24 IHD patients one hour after the IV injection of 20-25 mCi Tc99m MIBI. The ES study started at peak ECG R-wave for 80 ms and the ED one for the same time period at the descending slope of the T-wave. Acquisition was: 180 deg. fron LPO to RAO, 32. projections, 64x64, 75 cardiac beats per projecelon. ~nort axis slices were reconstructed using a 3-D non-linear filter followed by a linear filter with parameters chosen to suppress noise. A program was developed to display corresponding pairs of ED & ES short axis slices with or without a selected threshold level. Circles are defined around the outer and inner LV margins of the reconstructed slices at each cut from apex to base. The LV cavity is searched for within these two circles. The program calculates all )ixels 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 LV ED & ES volumes (vol.) and EF and the myocardial (myo.) volume, are then calculated. Histograms of no. of Myo. pixels against counts are presented for ED & ES. The program will encounter problems when there is a major defect in the Myo. wall of more than 25% of the whole Myo. circle. The LV EF and LV ED & ES vols. have been correlated with those from CV. The mean calculated EF was 52.7+14.0 versus 54.6+13.3% for CV (NS). The EF correlation coefficient was r=0.96 with linear slope 1.011.
I N D I U M iii LABELLED ANTIFIBRIN ANTIBODIES ( A F I } , 99MTC HMPAO LABELLED PLATELETS, CONTRAST VENOGRAPHY (CV) AND VENTILATION-PERFUSION SCAN (VP) IN THE MANAGEMENT OF PATIENTS WITH SUSPECTED DEEP VEIN THROMBOSIS (DVT) AND/OR LUNG EMBOLS (LE} ; PROSPECTIVE STUDY,
Alms o f the study ; o) to prospectively assess the s e n s l t l v l t Y and s p e c i f i c i t y of A F I {n~25+29) and PLT (n=19+29) scans in the diagnosis of DVT wlth reference to CV results (n=73) in patients (n:101) wlth suspected DVT and/or LE (28 CV not done;AFI=18,PLT=IO) b) to compare in the same patients (n=29) t h e i r results and clot/normal veln a c t i v i t i e s ratios (R:AFI and R:PLT) c) to evaluate the interest of the systematic reallsatlon of VP in pstlents wlth c l i n l c a l symptoms of DVT only (CSODVT) and the r e l a t l v e importance of AFI and/or PLT scans Hlth regard to CV problems or contralndlcatlons met in our hospital Results ;
o) - sensitivity and specificity were for AFI, 95% and 82% and for PLT, 90% and 88% - when compared to CV Pictures, AFI and PLT accumulate malnly in fresh " f l o a t t l n g " thrombl b) - for each patlent, correlatlon betHeen R:AFI and R:PLT Has observed, slope varying from one patient to another - no clear r e l a t l o n betHeen R:AFI and LE was found but well between R:PLT and LE c) - VP demonstrated LE in ~l% of patients with CSODVT - CV not done, unsuccessful1 or contralndlcoted : 28 (DVT diagnosed by AFI and/or PLT in 18, LE found in 17) - q patients wlth LE had po~Itlve AFI and/or PLT studies but normal CV, l case was revleHed as unconcluslve for site of sclntlgFoPhlc p o s l t l v l t Y , one Positive scan Has obtained a f t e r a normal CV Conclusions - systematic VP r e a l l s o t l o n is recommended in patients wlth CSODVT - AFI and PLT hove c11nical Interest and appear as valuable tools in order to diagnose DVT but wlth respective draHbacksl
344
343 E Voth I, U Tebbe 2 , D Emrich I
P. BOURGEOI.S, J.P. VANGYSEL, W. FEREMANS AND G. DEMONCEAUX. C.H.J.BRACOPS, FREE UNIVERSITY OF BRUSSELS~ SERVICES OF NUCLEAR MEDICINE, SURGERY AND INTERNAL MEDICINE 79, RUE DR HUET ,1070, BRUSSELS , BELGIUM.
H Schicha I,
Div. of 1Nuclear Medicine 2Cardiology, University FR G e r m a n y
KL N e u h a u s 2 , HW Strauss, T Yasuda, M Ishibashi, Rocco, A Suzuki*, and
of
Div. of Gdttingen,
INTRAVENOUS STREPTOKINASE IN A C U T E MYOCARDIAL INFARCTION (ISAM): FOLLOW-UP BY RADIONUCLIDE VENTRICULOGRAPHY UP T O T H R E E Y E A R S F r o m M a r c h 1 9 8 2 to M a r c h 1985, 1741 patients with acute myocardial infarction (AMI) and d u r a t i o n of s y m p t o m s S 6 h w e r e t r e a t e d w i t h 1.5 'million IU of s t r e p t o k i n a s e (STK) or p l a c e b o (PL) in a double-blind multicenter trial (ISAM). In p a t i e n t s t r e a t e d at o u r i n s t i t u t i o n (60 STK, 60 PL) determination of left ventricular ejection fraction (LVEF) by the g a t e d b l o o d p o o l m e t h o d w a s p e r f o r m e d at r e s t 3 d a y s a f t e r AMI, a n d at r e s t a n d d u r i n g e x e r c i s e i, 7, 18 a n d 36 m o n t h s a f t e r AMI. inferior AMI Results: anterior AMI at rest: STK PL p STK PL p n LVEF n LVEF n LVEF n LVEF 26 58 30 56 NS 3 days 20 49 25 40 0.02 28 57 29 53 NS 1 month 19 52 24 40 0.01 29 60 29 56 NS 7 m o n t h s 21 52 26 42 0.03 18 m o n t h s 22 50 24 41 0.04 29 59 28 57 NS 36 m o n t h s 21 51 24 40 0.01 25 57 26 57 NS D u r i n g e x e r c i s e L V E F i n c r e a s e d s l i g h t l y in b o t h t r e a t m e n t g r o u p s . In p a t i e n t s w i t h i n f e r i o r A M I i n c r e a s e of L V E F w a s h i g h e r in the S T K group. Conclusions: In a n t e r i o r AMI intravenous STK im~proves l e f t v e n t r i c u l a r f u n c t i o n . B e n e f i t is preserved up to 3 years. In inferior AMI i n t r a v e n o u s S T K d o e s n o t i m p r o v e L V E F at r e s t but contractile reserve during exercise.
J Taki, N Tamaki, T.
Massachusetts General Hospital, Boston, MA and *Capintec Co, Ramsey, NJ
The VEST - Characterization and applications The cardiovascular responses to a variety of daily activities have been elucidate using the ambulatory ventricular function monitor. Validation studies (VEST EF vs. EF by GBPS) revealed a correlation coefficient >0.89. Re-positioning the detector resulted in <.03 change in ejection fraction. In normal subjects, ejection fraction increases 3-5% during walking, standing, or eating: conversely, EF decreases with exposure to cold or micturition by 3-5%. In contrast to normal subjects, patients with coronary disease may demonstrate asymptomatic episodes of ischemia accompanied by a fall in ejection fraction: in the periinfarct period, this finding has been associated with a poor prognosis (Kayden/DS, et al J. Am Coil Cardiology 1988;12:669-679). The instrument can also define left ventricular filling rates and filling fractions. Functional reserve has been investigated by quantifying changes in filling rates and systolic function during passive leg raising: patients with normal systolic function tolerate the modest volume load, but patients with impaired systolic function may have a fall in EF and subnormal filling rates. These data suggest that ambulatory monitoring of ventricular function will be useful in the assessment of mechanistic, therapeutic and prognostic issues in cardiac patients.
485
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345 P Broadhurst,
Richard Bauer, Everhard van de Flierdt, Ulrich Busch, Inge Sackmann, Hans Werner Pabst
P Cashman, A Lahiri, EB Raftery
Nuklearmedizinische and I. Medizinische Klinik Technische Universit&t M0nchen, FRG Cardiology Department, Northwick Park Hospital, Road, Harrow, Middx, HA1 3UJ, UK
Watford
EARLY DETECTION OF LEFT VENTRIGULAR DYSFUNCTION ATRIAL PACING USING A MINIATURE NUCLEAR PROBE.
DURING
We have developed a miniature, non-imaging Csl/ photodiode nuclear probe (Oardioscint), enabling the continuous monitoring of left ventricular (LV) function. Validation was performed in 43 patients undergoing routine gamma camera radionuclide ventriculography. This produced a mean difference in LV ejection fraction (EF) between camera and probe of 1.2% (r=0.82), utilizing a ~an~_~e!!y selected background. Atrial pacing was performed in 7 patients with obstructive coronary artery disease, with concomitant measurement of pulmonary capillary wedge pressure (PCWP), the ST-segment and EF and LV volumes, the latter continuously assessed with the nuclear probe. EF fell significantly in 6 out of 7 patients prior to angina, significant ST or PCWP changes. Following the administration of 5mg buccal nitroglycerin, the test was repeated resulting in delaying the onset of the various indices of ischaemia but nitrates did not change their temporal relationship. Thus the Cardioscint measures EF with reasonable accuracy and may provide earlier means of detecting myocardial ischaemia than traditional methods. It may prove useful in the early detection of spontaneous myocardial ischaemia in patients with unstable coronary syndromes.
The change of thickness of the myocardium c3M of the left ventricle (LV) was investigated by means of nuclear magnetic resonance imaging. EDV, ESV, and myocardial volume (MV) of LV were determined integrally by means of serial parallel tomograms perpendicular to the long axis of the LV. Determination of MV was very precise, the correlation between data ol~tained during diastole and systole was r=0.98 in 122 patients. Assuming a spherical geometry of the LV, a mean overall o~Mwas computed. Correlation between 3M and EDV or ESV was poor (r=0.44 and r=0.65~ but high between 3M and EF (r=0.93). ~gM was 4.2 mm in normals (n=10) and 4.0 mm in coronary artery disease without infarction (n=27), elevated in LV hypertrophy to 6.5 mm (hypertrophic CM, n=9), 5.9 mm (stenosis of the aortic valve, n=9), and 5.2 mm (hypertension, n=33), decreased in myocardial infarction to 3.4 mm (n=14), and very low in dilative of ischemic CM 1.8 and 1.5 mm (n=8 and n=4). Wall tension was comparably high in normals and various diseases without reduction of cardiac function but elevated in patients with low ejection fraction. Simultaneous analysis of LV pressure, volume, mass and 3M may render new information concerning pathophysiology and prognosis.
348
347 H. H~ffken I, M. Leschke 2, K. Joseph I
F. Pa¥cha*, M.C Aumont°, Ph. Tellier*, L. Philippe*, G. Russ*, PG Steg°,
Dept. Radiol.Div.Nucl.Med. I, Univ. Marburg, Dept.Med.Div.Card. 2, Univ. D~sseldorf,
CHANGE OF THICKNESS OF THE LEFT VENTRICULAR MYOCARDIUM IN NORMALS AND IN CARDIAC DISEASES
D-3550,
D-4000,
F.R.G.,
JM Juliard°.
F.R.G.
INFLUENCE OF BLOOD VISKOSITY ON MYOKARDIAL TL-2OIUPTAKE AND WASH-OUT
*Medecine nucl6aire, ° Cardiolegie, H6pital Bichat 75018 Paris, France
Elevated fibrinogen levels induce an impairment of myocardial microcirculation in coronary artery disease due to increased plasma viscosity and erythrocyte aggregation We studied 23 patients suffering from coronary artery disease who underwent fibrinolytic therapy by urokinase (n=10) and fenofibrate (n=13). Myocardial perfusion was tested before and during therapy by quantified exercise/ rest thallium-201SPECT. Vitality index and wash-out were calculated in 29 sectorial regions of polar myocardial plots reconstructed from short axis ~lices. The range of vitality index and wash-out for normal myocardium, ischemia and scar was derived from a total of 382 investigations: VI WO 65 % - 100 % >35 % : normal 65 % - 100 % <35 % : ischemia (slow wash-out) 50 % - 65 % <30 % : ischemia (redistribution) <50 % <30 % : scar
DOES BETA-BLOCKADE LESSEN THE SENSITIVITY OF EXERCISE THALLIUM-201 MYOCARDIAL PERFUSION IMAGING IN CORONARY ARTERY DISEASE ? The aim of this prospective study was to assess the influence of 13 blockers on the sensitivity of exercise thallium O"1)-201 myocardial perfusion imaging (Ex MPI) on upright bicycle in the detection of myocardial ischemla (isch) in patients (pts) with high prevalence (p (D) > 75 %) of coronary artery disease (CAD). Exclusion criteria were : unstable angina, myocardial infarction (MI) < 3 wks, and absolute conWaindication to stress test. At peak exercise (Ex) 74 MBq of TI-201 was injected intravenously and the pt encouraged ~o exerelse addifionaiiy for 30 ~ 60 seconds. Inifiai (5 rain -,d'ter Ex) and delayed (3 hrs later) 10 rain-images were acquired in the anterior, 45 ° and 70 ° left anterior oblique projections. Each view was acquired by means of a standard gamma-camera with a medinm-resolution low-energy collimator and interfaced with a minicomputer, which collected every image in a matrix of 64 x 64 pixels (600,000 to 700,000 counts per view). T1-201 images were interpreted after nine-point weight smoothing and uniform background substraedon. A segmental peffusion abnormality was judged significant when its counting rate was < 65 % in the inferior segment and < 75 % otherwise. Images were lead by two blinded observers. Ex MPI and coronary artedography were obtained in 26 consecutive pts (age 43-74 yrs, average 57 yrs ; 3 females) without withdrawal of their usual treatment. The clinical and ECG status of all the patients was stable during the study period (1 me). CAD was defined as > 50 % stenosis in at least one artery. One pt had CAD, 14 had single-, 6 had double-, 5 had triple- vessel disease. Seventeen pts had a history of previous MI (5 anterior, 12 posterior) ; 5 of them had no residual isch. At the time of Ex MPI, 9/20 pts were on 13blockers, and 3 without any medication. Global sensitivity of Ex MPI was 70 % (14/20 pts). The main result of this study is that in our patient population, when assessed by Yates-corrected chi-square tests, neither E-blockade (Chi2 = .01 NS) nor failure to reach 85 % of the maximal predicted heart rate (Chi2 =1.67 NS) influenced the outcome of Ex MPI as assessed by the prevalence of reversible initial defects.
Under urokinase 55,2 %, under fenofibrate 32,8 % of the evaluated sectors showed improved scintigraphic findings. Plasmaviscosity as the most relvant rheological determinant of microcirculatory flow decreased from 1.42 ~ 0.08 to 1.33 ~ 0.09 mPas (Urokinase) and from 1.43 ~ 0.09 to 1.37 ~ 0.07 mPas (fenofibrate). Vitality index and wash-out are influenced by changes in blood viscosity. T1-201-myocardial SPECT turned out to be usefull in testing the efficacy of rheologic therapy.
486
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349
CASSET-SENON, L. PHILIPPE, P. COSNAY, JP. FAUCHIER,
D[ITTI
J . L . D e m a n g e a t ~, A . C o n s t a n t i n e s c o ~, H . B r u n o t ~ A.Facello ~, P.Bareiss ~, J.M.Mossard ~
Nuclear C . H . R.U.
Medicine (~) a n d C a r d i o l o g y (~) Hautepierre ; F-67098 STRASBOURG.
Departments
NORMALIZED INDEX OF TI-2OI MYOCARDIAL UPTAKE AFTER EXERCISE OR DIPYRIDAMOLE : A CRITERION RELATED TO THE CORONARY STATUS.
Coronary a r t e r y d i s e a s e (CAD) is u s u a l l y a s s e s s e d from 201Tl-scans by h y p o f i x i n g areas relatively to a r e a s of maximal activity (presumed normal). Qusntitation assessm e n t of myocardial u p t a k e s h o u l d be u s e f u l to d e t e c t und e r p e r f u s e d r e g i o n s a p p e a r i n g as r e l a t i v e l y n o r m a l . Planar 201TI scans w e r e performed in 239 p a t i e n t s (30-80 yrs) a f t e r c o n v e n t i o n a l exercise (EX = 147 pts) or D i p y r i d a m o l e infusion (DIP = 92 pts). A n o r m a l i z e d i n d e x of m y o c a r d i a l uptake (MU Index) was d e f i n e d fro~ the o v e r a l l LV m y o c a r d i a l a r e a in the 40 ° LAO p r o j e c t i o n a n d e x p r e s s e d in counts, c m ' 2 . m i n - l . m C i -I. This q u a n t i t a t i o n w a s d o n e at 7 m i n in 74 pts, at 15 m i n in 89 pts a n d at 23 m i n in 76 pts. All p t s u n d e r w e n t c o r o n a r y a r t e riography and were divided into 4 groups : N (75 pts without significant stenosis), MI (87 pts w i t h p r e v i o u s myocardial infarct), C (44 c o r o n a r y pts w i t h o u t MI) g r a f t - C (33 g r a f t e d c o r o n a r y pts). The m a i n r e s u l t s w e r e the f o l l o w i n g : I) MU I n d e x was s i g n i f i c a n t l y higher a f t e r D I P t h a n a f t e r EX for all g r o u p s (p
351 M.M. L a M a n n a , J.M. T e i x e i r a , F.J. Lumia, S.D. Cha, S.B. Amini, a n d V. M a r a n h a o . Deborah Heart andLung C e n t e r , B r o w n s M i l l s , NJ., UMDNJ, P i s c a t a w a y , NJ.
Departments of Nuclear Medicine and Cardiology Trousseau University Hospital TOURS, France EQUILIBRIUM GATED NUCLEAR ANGIOGRAPHY (EGNA) ASSESMENT OF LEFT VENTRICULAR DIASTOLIC FUNCTION BEFORE AND AFTER THERAPY IN PATIENTS WITH HYPERTROPHIC CARD1OMYOPATHY WITH (HOCM) OR WITHOUT (HCM) OBSTRUCTION. Left ventricular (LV) diastolic function has been assessed by EGNA in 10 patients (5M, 5F, aged 22-71) with HCM (n=2) or HOCM (n=8, mean LV gradient = 93_+46mmHg). Hemodynamic and echocardiographic findings were : LVED pressure = 18_+SmmHg, septum thickness = 16-+6mm and posterior wall thickness =12_+2mm. All patients were investigated before and after verapamll V (480mg daily for 2 months) and propranolol P (320mg daily for 2 months) in a cross-over, double blind study. EGNA was recorded in the LAO projection, using list-mode data acquisition (framing 30ms/image for each study). LV time-activity curve was generated from this sequence and was fitted with Fourier transform (4 harmonics). The first and second curve derivatives were evaluated at each point. Several parameters were computed: ejection fraction, peak ejection rate, time to peak ejection rate, isovolumic relaxation period (IRP), peak filling rate (PFR), time to peak filling rate (TPFR) and the ratio between percent of LV filling during rapid filling and percent of LV filling during atrial systole. Curves before and after V and P were superimposed. LV diastolic function parameters were slightly better after V than after P: TPFR decreased from 210-+55ms to 197+48ms (ns) during V , vs 195+42ms (ns) during P ; PFR increased from 2.9+0.SEDV/s to 3.2+1.1 (ns) during V, vs 3-+0.9 (ns) during P. V decreased the isovolumic relaxation period in 7 patients with prolonged IRP in the baseline study. In this study, LV diastolic function is difficult to be characterized only by parameters. EGNA was highly suitable to compare the effects of treatments, considering the same framing rate.
352 M. Sciammarella, P. Gerundini, G. Fragasso, A. C a p p e l l e t t i , L. M a f f i o l i , S.L. C h i e r e h i a
Istituto (Italy) RADIONUCLIDE VENTRICULOGRAPHY IN P E R C U T A N E O U S A O R T I C BALLOON VALVULOPLASTY. Percutaneous aortic balloon valvuloplasty (ABV) w a s p e r f o r m e d in 60 c o n s e c u t i v e p a t i e n t s (pts.) m e a n a g e 74 w i t h v a l v u l a r a o r t i c s t e n o s i s . A o r t i c v a l v e (AV) g r a d i e n t s w e r e r e d u c e d f r o m 64-+3.4mm Hg ( M e a n ± S E M ) to 30± 3 .2mm H g ( p = O . O 0 0 1 ) . A V a r e a i n c r e a s e d f r o m 0.4 to 0 . 7 c m ±0.04 (p=O.0001). AV patients underwent resting radionuelide ventriculography (RNV) w l t h TC p e r t e c h n e t a t e w i t h i n 24 h o u r s p r e a n d p o s t A B V w i t h f o l l o w - u p at 3 m o n t h s (25pts.) a n d 5 m o n t h s (20 p t s . ) . R e s u l t s w e r e as f o l l ows: (Mean±SEM) Pre ABV Post ABV 3 Months 6 Months $I 31±2.1 31±1.9 28±2.8 34± 4.4 LVEDV 139±9.0 146±8.7 101±11.4" 118± 18.2 LVEF 41±2.8 39±2.4 49± 4 . 6 55± 2.2* RVEF 40±2.2 39±2.0 44± 2.6 38± 4.5 ( S V = S t r o k e V o l u m e , S l = S t r o k e V o l u m e Index, L V E D V = L e f t Ventricular End-Diastolic Volume, LVEF=Left Ventricular Ejection Fraction, RVEF=Right Ventricular Ejection Fraction, * p = O . 0 5 ) . S u c c e s s f u l A B V is a s s o c i a t e d w i t h s i g n i f i c a n t r e d u c t i o n in A V g r a d i e n t . There was a significant i n c r e a s e in the L V E F b e t w e e n t h e 1 a n d 6 m o n t h f o l l o w - u p ~nd a s i g n i f i c a n t d e c r e a s e in L V E D V a n d L V E D V I b e t w e e n the 1 a n d 3 m o n t h f o l l o w - u p d e m o n s t r a t e d b y RNV. There ~ere no s t a t i s t i c a l c h a n g e s in the R V E F or p r e s e n c e of r R at f o l l o w - u p i n t e r v a l s . A B V is a s s o c i a t e d w i t h o v e r ~ii i m p r o v e m e n t in l e f t v e n t r i c u l a r f u n c t i o n p a r a m e t e r s i~t 3 a n d 6 m o n t h s w h i c h w e r e n o t a p p a r e n t at the i n i t i a l Dost-valvuloplasty study. R N V is a u s e f u l t o o l in t h e ~ o l l e w - u p of A B V p a t i e n t s .
Scientifico,
Ospedals
San R a f f a e l e ,
A.R. Savi,
Milano
HIGH SENSITIVITY OF TC 99m MIBI SPECT ]~ DETECTING MYOCARDIAL ISCHA~MIA END NECROSIS ]~ PATIENTS WITH CORONARY ~RTERy DISFASE. In 56 patients (pth, 45 males, mean age 55 + 5 years), with a clinical diagnosis of ischaemic heart disease (IHD), we assessed the ability of TC 99m-2-methoxyisobutylisonitrile (MIni) GPECT to detect myocardial ischaemis and necrosis. All pts were studied at rest, 90 rain after IV injection of TC 99m MIBI and, 48 hrs later, at peak exercise (modified Brace protocol). Images were collected hy a rotating gamma camera on 32 angular projections from 45° R~O (Right ~mterior Obllq~e) to 45D LPO (Left Posterior 0bli~e), over 30 miD. Daia were reconstructed without correction for attenuation with a 64 x 64 matrix. T~,ograms were correlated to diialcal,and ECG findings and to the results of coronary arteriogcaphy (CA), end left vantriculography (LV), performed within two weeks of radionuclide studies. Scintigraphic data ware analyzed for the presence of persistent (PPD) and transient perfesinn defects (TPD) end LV was evaluated for presence of regional akinesia, indicative of m~ocardial necrosis; coronary artery disease was assessed by quantitative angiogrephy and a )60% reduction in coronary diameter was considered significanl. Of the 46 pts exhibiting PPD, 42 also showed significant Q waves and regional akinesia, indicative of t r ~ myocardial infarction, whilst 3 only had akinetic segments; and i pts showed neither Q wawen or regional wall motinn abnormalities. On exercise, ECG evidence of traDsient myocardial ischae~ia (ST ~ >/0,1mV) was observed in 28 pts, of whom 24 showed transient perfusion defects; of the remaiDing 4, 2 had persistent perfuaion defects end 2 had a normal perfusion scan. Of the 6 pta, who experienced angina in the absence of diagnostic ST depression, 5 had TPD. In 43 pts, the area exhibiting transiset or persistent perfusion defects was supplied by a significantly atenotic vessel. In conclusion, in pts with IHD, TC 99m MIBI SPECT affords a high sensitivity and specificity for detecting both myocardial iachae~ia and necrosis,that in ~st ca ass (95%) are aasnsiated with sigdificat coronary arter~ disease.
487
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354
I C Dormehl, N Hugo, M Mare% R de Winter, L Jaeobs. R Raulio, P Vainio, M Helin, L~nsimies. Kuopio University Finland
J Kuikka and Hospital,
E
AEC Institute for Life Sciences, University of Pretoria, Box 2034~ PRETORIA 000% FOURIER PHASE PARAMETERSFROMRNV WITH POSSIBLE DIAGNOSTIC SIGNIFICANCE AS ILLUSTRATED BY A CASE OF ABNORMALA-V CONDUCTION IN A BABOON. The possible diagnostic importance of parameters defined from radionuclide ventriculograms and Fourier phase analysis was investigated for data from normal baboons ( E ~ z ~ ) under prolonged anaesthesia (? hours). Seven animals were studied using indwelling cardiac catheters for haemodynamic monitoring. Phase angle differences across the l e f t ventricle between the electro-mechanical activation of the septum and the l e f t lateral wall (LLW) and again between the activation of the septum and the apex indicated no significant differences (p > 0.05) for the consecutive hourly values. Mean normal values and their ranges (mean * %SD) were subsequently obtained for these parameters (table 3). ~he activation delays between the septum and the LLW, and the septum end the apex differed with the latter being significantly longer. The phase angle histogram parameters of atrial peak width, left ventricular plus right ventricufar peak width (LV and RV), LV-to-RV peak separation and LV-to-atrial peak separation were similarly analysed and found not to change significantly between hourly measurements. Meannormal values and ranges were thus also obtained for these parameters possibly to serve as baselines for the diagnosis of conduction pathology. This was duly i11ustrated in a case of abnormal A-V conduction monitored hourly in a baboon model for 5 hours (table 3) where the corresponding parameters were markedly prolonged. Table 1: Delay at each hour in degrees. A-V block baboon Normal Parameters Oh lh 2h 5h Meen ± %SD Septum to LLW -51 -l& -20 -51 1.2 1.? Septum to apex -25 - ? - ? -14 5.5 2.1 The negative values indicate that the septum was activated after the LLW and the apex for the baboon with the A-V block.
355 D. Yang, Do Patel, Lo Gould, P. Maghazeh, 0. Zavala, S. Sherbell, J. Giovanniello.
The Methodist Hospital, 506 Sixth Street, Brooklyn, New York, 11215 USING RADIONUCLIDE IV TOTAL BODY ARTERIOGRAPHY TO EVALUATE ABDOMINAL AORTIC ANEURYSM - A NEW NON-INVASIVE SCREENING METHOD Radionuclide IV Total Body Arteriography (TBA) introduced by our group is useful to evaluate occlusive arterial disease and patency of arterial bypass grafts. It is also useful to evaluate abdominal aortic aneurysm (AAA). We reviewed 30 cases of AAA (2 false and 28 true aneurysms) studied with TBA. All were verified by either sonogram, CT scan, contrast arteriography or combination of the tests. 29 of the 30 AAA were detected by TBA. One small thrombosed AAA was not visualized. With a single injection of Tc-99m labeled RBC (less than 1 cc) into antecubital vein, first-pass total body arterial images, multiple projections of high resolution total body blood-pool images as well as MUGA studies can be obtained. The imaging time for firstpass arterial image is 70 sec., for each total body blood-pool image 2 to 3 min. TBA provides not only information regarding the size, location of AAA and its relationship to renal arteries and kidneys, but also coexisting abnormalities in the remaining aorta and ilio-femoral arteries and cardiac function (when MUGA is done). Calcified aortic walls and thrombosed portion of aneurysm can be seen as photon-deficient areas. Post operatively TBA can be used to evaluate the status of aortic reconstruction such as patency of bypass grafts. We concluded that TBA is a useful non-invasive screening imaging procedure to evaluate AAA and a useful modality for post operative assessment.
99mTc-meihoxy-isobutyl-isonitrile (MIBI) SPECT in the diagnosis of coronary heart disease (CHD). 99mTc-MIBI was evaluated for the diagnosis of CHD, 51 pts with suspected CHD were studied. 400 MBq 99mTcMIBI was injected 1 1/2 min before the end of a maximal symptom limited ergometer exercise test. Rest injection was given two days later in sitting position. A standard 180o SPECT imaging was applied. Coronary angiography was accomplished on the day between the SPECT studies. A program for the quantification of myocardial short axis slices was developed. LAD, LCX and RCA areas were evaluated separately from exercise, rest and subtracted b~ll's-eye maps. Perfusion index was calculated for each vessel and the change of perfusion between rest and exercise was used in combination with ordinary long and short axis slices to judge the results. Perfusion images with 99mTc-MIBI correlated well with angiography and sensitivity and specificity for the diagnosis of CHD was 0.98 and 0.83. For different vessels the results were: LAD 0.89/0.92, LCX 0.83/100 and RCA 0.94/0.88. The main advantage of the quantitative approach was in patients with multiple vessel disease. In normals the perfusion in exercise was at least 2.1 times rest perfusion. A few patients showed areas with diminishing flow in exercise. 99mTcMIBI detects CHD with great accuracy. Quantitative evaluation helps in estimating disease severity.
356 J.A.S~nchez Mart~n~ J.A.Jorge Herrero~ A.Navarro Izquierdo~" C.Pardo Pardo~ T. Caparr6s~" and J.Vicente~"" Servicios de Medicina Nuclear 11 Mediclna Intensive "", and Oncolog~a.- FUNDACION J I ~ N E Z DIAZ. Facultad de Medicine, Universidad Aut6noma de Madrid. Espa~a. USEFULNESS OF MYOSIN I R ~ IN THE EXTENSION AND PROGNOSIS OF ACUTE MYOCARDIAL INFARCTION (AMI). IP~ with two monoclonal antibodies of hioh affinity for heavy chains of human ventricular myosin of the cardiac wall, was used for the determination of myosin in serum. Our healthy control group showed circulating values lower than 250 nU/ml, on the contrary increase level appears in M y o c a r d i o p ~ i ~ s caused by oncological treatment and in AHI. The follow up of these I was perfor~ m e d taking samples from the ~ r ~ from the Ist t O the 12 th day. The kinetic of release of myosin, start at ~ 6 hours after the infarct , showing the maximal level 4-7 days later, with complete normalization in the cases with good response to treatment about the IOth day. Delay in the maximal p e ~ , lack of normalization after the IOyh da D and great surface of the area of the curve indicated bad evolution. The degree of release of myosin, seemed to be proper, tionally related to the ~.xtension and intensity of the necrosis of the ventricular wall, correlated with 2OfThallium myocardium images. Fibrinol[tic treatment in 16 cases of AMI, decrease significantly the levels of m~,es~n in serum, with normalization in IOth days~ correlated wlth coronary artery recanalimation. We can sug0est that in the AWl the myosin in serum evaluate the mass of necrosis and the effectiveness of fibrinolytic therapy.
488
358
357 Xiujie
Liu,
V..D., Zuo3:iang He, ~.D.
R.L. Nicholson, B. Manglal-lan, U. Barnes, Department of Diagnostic Radiology and Nuclear Medicine, University of Western Ontario, St. Joseph's Health Centre, London, Canada.
C ~ r d i o w ~ s c u l a r I n s t i t u t e & Fu Wai IIospital, Chine.~e A c a d e m y of ~.!eOica! Sciences & P e k i n g Union r']edJcsl Coi!ege, Beijing, C h i n s Nuclear
C~rOiology
in China
Sirce !979 th~ n u c l e a r stethoscop~ .hmc first been used for evs!uL~tion of cardimc function, n u c l e a r c a r d i o l o g y in China has developed rapidly, so far, mere thsn 50 S P ~ C T s -~nd 55 Caroms camera system have been used for m y o c a r d i a l p e r f u s i o n imaging, 80 nttclesr probe, ~. for cardiac function studies. ~?he ~nsjor d e v e l o p m e n t s of n u c l e a r cardJo!ogy in China include: I). d e s i g n i n g n u c l e a r c a r d i o l o g y data p r o c e s s i n g s y s t e m (hard/soft ware). 2). d e v e l o p m e n t of m y o c a r d i a l p~rfusion i m a g i n g agents, such as Tc-9~m-TBI, Tc-99m-CPI, Te-99m-HIBI. Over 400 patients have been studied with T c - 9 9 m - C P I and 'i~c-9~m-HIBI, i n c l u d i n g planar and t o m o g r a p h i c imaging. 3). interventional n u c l e a r cardiology: a lot of Chinese t r a d i t i o n a l herb m e d i c i n e have been investigated with n u c l e a r techniques. H i g e n a m i n e and C i n s e n g which have been used for ages for treatment of heart disease have been studied with n u c l e a r technique. Data shows that both drugs can improve the cardiac function ~nd increase the cardiac reserve.
SPECT FOR SPINE SCINTIGRAPHY: LOW SENSITIVITY AS AN INDEPENDENT MODALITY. In view of advances in camera/computer technology over the past 5 years, SPECT 99mTc-phosphonate imaging of the spine was evaluated as a 'stand alone' modality independent of planar imaging. Thirty patients with undiagnosed back pain had anterior and posterior planar images, plus SPECT usin§ an LFOV camera (G.E. Starcam) in elliptical orbit, 360 stop and shoot with 128 stops of i0 secs; data was reconstructed in 64x64 matrix in 3 planes. SPECT and planar studies were separated, randomly sorted, and interpreted independently by two physicians blind to all clinical and radiologic patient data. Then, SPECT and planar studies for each patient were recombined and interpreted as a pair by one physician blind to clinical and radiographic data and to the previous interpretations. True diagnosis was established by the referring physician for each patient on the basis of clinical course and response to treatment, radiographs and/or CT.
PLANAR COMB.
TP
TN
FP
FN
IND
SENS
SPEC
__
31 17
3 2
Ii 2
3 0
0.52 0.82
0.914 0.891
Sensitivity of SPECT (0.62) was higher than planar (0.52) but at the cost of reduced specificity (SPECT 0.84, planar 0.91). Combined interpretation achieved a much higher sensitivity than either (0.82) with equivalent specificity (0.89). Clearly, SPECT and planar imaging must be used together for optimum results.
359
360
R. Campini, M. Galante, R. Giubbini
M..Erklllc, B.Karayal .cln, A.T.Aydm, A.Y11dlz
Nuclear Medicine and Physical Therapy Rehabilitation Dpts. Clinics del Lavoro Foundation, Institute of Care and Research, Medical Center of Rehabilitation VERUNO (NO) - Italy
Depts. of Nuclear Medicine and Orthopedics, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
99mTc NANOCOLLOID SCINTIGRAPHY IN THE MANAGEMENT OF RHEUMATOID ARTRITHIS 16 female patients (pt) with rheumatoid artrithis (RA) (aging 58+ 12) were studied. 62 joint scans were classified as positive or negative by two blind observers. Each pt was studied twice, before (TO) and after (T1) local treatment with ~ stream f r e e iiq~d ~itrogen (3 times ~ac'~ day f ~ 10 days) and without modifying the standard medical therapy. The scans were performed 30 rain. after i.v. administration of 500-600 MBq of 99mTc albumine nanocelloid. Elbows, wrists, knee s = and feet were considered. All the patological joints except one (control group) were treated. The joint/BKG ratio values were respectively 1.91+0.7 and 1.76+0.6 (p
QUANTITATIVEBONE5CANNINGIN EYAL~TION OF PATELLAR PAIN IN YOUNGPATIENTS 28 patients (mean age: 29+6.73) who have patellar pain without any Xray findings were studied bV quantitative bone scintigraphy. As an index patella~femoral ratio (PFI) was used to evaluate both symptomatic and noneymptomatic knees. Each patient received 15 taCt (555 l'lBq) Hgdroxy-Hethylen PiPhosphanete (HHDP) i.v. and bone scanning performed two hours later because of high targetlnenterget ratio with HMI)P. The count information of both lateral views of kneeswere recorded on disc for further procesaing of PFI. 4×4 pixel area as a region of interest (ROI) were chosenon patella and one third distal region of femur.Two different ROI were used for patallar region, one yea as]acted just at the center the other one at subchondrel region of patella. PFI was calculated after backgroundsubstraction by formula patellar counts/(patellar+femarai cnts). PFI va]ue i n nonsymptomaticgroup mean value was calculated as 54.6±3.2. But in sgmptornetic group PFI mean value was found 71.6:~9.5. PFI waa observed significantly increased value (p
489
361
362
D.Brecht-Erauss, C.T.Trepte, B.Bitter, F,Bltter, W.E.Adam, W.Puhl, S.Glatz L. Eckart +, M. Gericke *, U. G6ke # U n i v e r s i t y of Ulm ; D i v i s i o n of N u c l e a r M e d i c i n e a n d C l i n i c of O r t h o p e d i c s 7900 Ulm/Do. FRG O U A N T I T A T I V E - S T A N D A R D I Z E D COMPUTERSCINTIGRAPHY B Y G R A D I E N T I M A G I N G IN P A T I E N T S W I T H L O O S E N I N G OP HIP ENDOPROSTHESIS. T h e main p r o b l e m in c e m e n t l e s s i m p l a n t a t i o n of h i p p r o s t h e s i s is i n s t a b i l i t y . T h e r e a r e 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 X - r a y a n d c l i n i cal symptoms. The aim of t h i s s t u d y is to detect i n s t a b i l i t y or n o n - i n s t a b i l i t y of h l p p r o s t h e s i s in p a t i e n t s w i t h u n c l e a r c l l n l c a l a n d / o r r a d i o l o g l c a l signs. 75 p a t i e n t s are stud i e d by q u a n t l t a t l v e - s t a n d a r d l z e d computerscintlgraphy, 12-15 months postop. Using computera i d e d g r a d i e n t i m a g i n g ( = f i r s t d e r i v a t i o n of t h e s c l n t l g r , image) six s t a n d a r d R O I ' s are d e f i n e d p l a c i n g t h e m on m e t a p h y s i s (M), d i a p h y s i s (D) a n d soft t l s s u e s ( T ) of femur. Q u a n t i t a t i v e eval u a t l o n is 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 dens i t y r a t i o of M / S and D/S. By this q u a n t i t a t i v e m e t h o d f o l l o w i n g v a l u e s are o b t a i n e d : I) M/Si n d e x = 4 . 4 6 +/- 0 . 2 7 ; 2) D / S - I n d e x = 4 . 4 2 +/0.23 V a l u e s , d i f f e r i n g s i g n i f i c a n t l y from t h e s e m e a n v a l u e s , i n d i c a t e i n s t a b i l i t y or beg i n n i n g l o o s e n i n g of the hip. In 55 pat. (=73%) w i t h o u t c l i n i c a l and r a d i o l o g l c a l s i g n s n o r m a l v a l u e s are d e m o n s t r a t e d . In 20 pat. (=27~) a d e v i a t i o n is o b s e r v e d , I0 of t h e s e w e r e f o l l o w ed by r e i m p l a n t a t i o n of the hip. We c o n c l u d e quantltatlve-standardlzed computerscintigraphy is a s u r e and o b j e c t i v e m e t h o d in d i a g n o s i s and t r e a t m e n t of h i p i n s t a b i l i t y , w h i c h o f f e r s various facilities.
363 N.N. Sy, l.S. See & K.G. Tal
Department o f Nuclear Medicine The Brooklyn H o s p i t a l / C a l e d o n i a n H o s p i t a l , B r o o k l y n , New York, U.S.A. REGIONAL FLOW STUDIES (IIFS) OF LUMBO-PELVIC AREA IN SELECTED PATI~'rs ON ROUTINE BORE SCINTICRAPHY (BS)~Between 1987-1988, 221 adults with low back/hlp paln or suspicion of renal disease had supplementary RFS of the back A pelvis and hips prior to BS using IV injected 20 mCi of 9~mTcMDP. This was to assess the role, if any, of the RFS in the interpretation of BS. The abnormal RFS showed as hypervascular (47.1% or 104) or hypovascular focl or areas (3.2% or 7) and 49.7% (II0) were negative. The hypervaseular abnormalities were related to bone/jolnt (59/104) or extraosseous (37/104) pathology and 8/104 were indeterminate. All 7 hypovaseufar abnormalities were extraosseous. Table I (Addendum) outlines a wide-range pathology as discerned on combined RFS and BS. The abnormal RFS were rated as to whether:a) causes of abnormal features on RFS were unsuspected clinleally, b) abnormal features supported clinical impression or augmented static image findings, c) noncontributory. In 43 studies (19.5%) the causes of abnormal RFS features were clinically unsuspected. A majority of these, 29/43 were extraosseous. In 60 studies (27.1%) the RFS findings supported the clinical impression or enforced the significance of the BS findings. A majority or 45/60 studies were bone/joint in origin while 15/60 were extraosseous. The rest, 53.4% or 118 were non-contributory. In selected patients, it is felt that RFS before BS is recommended, since it contributes significantly not only to the BS diagnosis but also uncovers clinically unsuspected pathology, thereby fine-focuslng the work-up.
University Clinic Rudolf Virchow-Wedding Free University of Berlin , * Dept. of Nuclear Medicine, + Dept.of Orthopedics, # Dept.of Radiology.
EFFICACY OF NANOCOLLOID-SEQUENCE-SCINTIGRAPHY IN DIFFERENTIALDIAGNOSIS OF BONE AND JOINT INFECTIONS AND ITS VALIDITY AS FOLLOW-UP METHOD. A simple, always available method in detection and evaluation of inflammation is especially important in orthopedic surgery. Scintigraphy with 99"Tc Diphosphohate agents aren't helpful in dlfferentiation against posttraumatic, tumorous and degenerative alterations. The aim of our study was to evaluate the diagnostic potential of 9S-To-labelled Nanocolloids in detecting and differentiating infectious lesions in bone and joint diseases and its behavio~r in malignant and systemic diseases. The study included 71 patients with chronic and acute osteomyelitis, septic arthroplasty loosening, bone tumors, non-unions, arthrosis, Paget disease, myositis etc. In 36 patients additional bone scans with 99"Tc Diphosphonate were performed. There were no false negative or false positive results in any case with a definitive diagnosis. In 8 cases final evaluation was not yet possible . The differentiation between chronic and acute osteomyelitic processes seem to be discernable due to different perfusion rates and uptake intensity measured by ROI technique. Nanocolloid-scintigraphy was helpful to differentiate positive bone scans in cases with arthrosis, non-unions and bone tumors from infectious processes. The additional results of the conventional bone scan were useful in recording bone involvement in soft tissue infections. Follow-up studies showed the high value of the nanocolloid-scintigraphy in confirming the therapeutic management and showed excellent correlation with clinical status.
364 J.Spitz*,
H.Beeker*,
N.Ctemenz*,
K.Tittel**,
H.Weigand***
* D p t . o f N u c l e a r M e d i c i n e , ** C l i n i c f o r A c c i d e n t a l S u r g e r y , ***Central X-Ray-Department, Municipal Hospital, Wiesbaden, FRG SENSITIVITY OF THREE-PHASE-SZINTIGRAPHY WITH TC-99m-HMDP AFTER TRAUMA OF THE WRIST D u e to t h e c o m p l e x b o n e s t r u c t u r e s t h e d i a g n o s t i c e f f i c i e n c y o f x - r a y a f t e r t r a u m a o f t h e w r i s t is k n o w n to b e o f l i m i t e d v a l u e . T h i s s t u d y w a s d o n e to e s t a b l i s h t h e d i a g n o s t i c v a l u e o f b o n e s c i n t i g r a p h y in t h i s c o n t e x t . Material and Method: 147 p a t i e n t s b e t w e e n 10 a n d 80 y e a r s , 1 to 90 d a y s a f t e r trauma of the wrist. The diagnostic procedure contained x - r a y in 2 or 4 p l a n e s a n d t h r e e - p h a s e - b o n e - s c i n t i g r a p h y w i t h T c 9 9 r n - H M D P ( I D - C i s ) w i t h i n s o m e d a y s as w e l l as i follow-up-control of x-ray and bone scintigraphy, depending on t h e c l i n i c a l n e e d s on a l a r g e - f i e l d g a m m a - c a m e r a (Apex 415). T h e d a t a w e r e c o m p a r e d to a g r o u p o f 30 n o r m a l s . In addition to the visual interpretation a seintimetric evaluation of the bone lesions w a s c a r r i e d out. Results: B e g i n n i n g w i t h t h e 3. d a y a f t e r t r a u m a b o n e s c i n t i g r a p h y s h o w s a s e n s i t i v i t y o f 100 %. 53 % o f t h e f r a c t u r e s a l r e a d y s h o w up w i t h i n 24 h o u r s . T h e r e l a t i v e l y l o w s p e c i f i c i t y o f 81% f o r t h e f i r s t e x a m i n a t i o n is i m p r o v e d to t 0 0 % b y r e peating the bone scan within i week. Initial x-ray resulted in a s e n s i t i v i t y o f 58 %. T h e s p e c i f i c i t y o f x - r a y w a s i m p r o v e d f r o m 5 7 % to 79 % d u r i n g f o l l o w up c o n t r o l . Conclusion : Seintimetrie investigations with Te-99m-labeled HMPD have a high importance for the diagnosis and differentiation of t r a u m a t i c l e s i o n s o f t h e w r i s t . In c a s e s o f d o u g h t f u l x - r a y b o n e s c i n t i g r a p h y is m a n d a t o r y .
490
366
365 B.
N~Nele-Whhrlg,
0.
Nickel,
S.
Fischer,
K.Hahn
!R.Valkema. J.A.K. Blokland, L.F. Verheij, S.E. Papapoulos, O.LM. Bijvoet, E.K.J. Pauwels. Division of Nuclear Medicine, department of Diagnostic Radiology and Clinical Investigation Unit, department of Endocrinology, University Hospital, Leiden, The Netherlands.
Dept. of Nuclear Medicine Johannes G u t e n b e r g - U n i v e r s i t y , M a i n z , FaG B E N I G N AND M A L I G N A N T L E S I O N S OF THE SPINE SPECT BONE S C I N T I G R A P H Y
-
In a p r o s p e c t i v e study 121 p a t i e n t s with traumatic, i n f l a m m a t o r y or m a l i g n a n t bone lesion were e x a m i n e d w i t h planar and SPECT bone s c i n t i g r a p h y . On c o n v e n t i o n a l bone scans hot spots can be p r e c i s e l y d e l i n e a t e d in the d o r s a l p r o j e c t i o n in the lateral and v e n t r a l p o s i t i o n it can be d i f f i c u l t to i d e n t i f y the a n a t o m i c a l s t r u c t u res. SPECT p r o v i d e s 3 - d i m e n s i o n a l i n f o r m a t i o n (sagittal, coronal, transverse) and t h e r e f o r e the exact l o c a t i o n and e x t e n s i o n of the lesions can be v i s u a l i z e d b e t t e r than with planar bone s c i n t i g r a p h y . The p r e d o m i n a n t l o c a t i o n of the lesions, w h i c h were m i s s e d or not c l e a r l y seen by p l a n a r t e c h n i q u e was in the v e r t e b r a l b o d y or arch structures. Furthermore SPECT d e p i c t e d the e x t e n s i o n of the e x t e n s i o n b e t t e r than c o n v e n t i o n a l technique. I n 85 cases the r e s u l t s w i t h p l a n a r t e c h n i q u e ~and SPECt i m a g i n g were identical. In 35 cases SPECT a c q u i r e d s u p e r i o r d i a g n o s t i c i n f o r m a t i o n Icompared to the p l a n a r technique. The 3d i m e n s i o n a l bone scan acquires c o m p l e m e n t a r y diagnostic information, w h i c h often facilitates the d e c i s i o n for an a d e q u a t e t h e r a p y )rotocol.
367 B. Ba_As_Ei, * V . V a l p o n d i , *F. Pansini Nuclear Medicine, St. Anna Hospital *Istituto di C l i n i c a O s t e t r i c a e G i n e c o l o g i c a , U n i v e r s i t y of F e r r a r a 1-44100 Ferrara, Italy
SINGLE PHOTON ABSORBIOMETRY, DUAL PHOTON ABSORBIOMETRY (X-RAYS), QUANTITATIVE C O M P U T E R I Z E D T O M O G R A P H Y AND D I G I T A L R A D I O G R A P H Y IN POSTMENOPAUSAL OSTEOPOROSIS: NORMAL RANGES AND PROGNOSTIC VALUE. In a g r o u p of 80 p o s t m e n o p a u s a l w o m e n (mean age 50 y e a r s , range 40-65, without pharmacological treatment and radiological signes of spine fractures), the n o r m a l r a n g e of Quantitative Computerized Tomography (O,C.T,) in our population a g r e e s w i t h t h a t o f UCLA ( U S A ) . Thei fracture trheshold is d e f i n e d as the value differing two standard deviations from thei normal r a n g e at the age of p e a k b o n e m a s s (30 years). A s e c o n d g r o u p was e x a m ± R a t e d by S i n g l e Pothonl Absorbiometry (SPA), Dual Photon Absorbiometry (DPA)(X-RAYS), OCT a n d D i g i t a l Radiography of the spine: the r e s u l t s o b t a i n e d e m p h a s i z e the low s e n s i t i v i t y of SPA , the h i g h sensitivityi of DPA a n d OCT and the low r e p r o d u c i b i l i t y of OCT in comparison with the DPA(X-RAYS). In conclusion, each m e t h o d for the b o n e minerall mass e v a l u a t i o n s h o u l d be u t i l i z e d in s p e c i f i c situations: DTPA is the m e t h o d of c h o i c e for longitudinal studies and therapy follow-up, w h i l e OCT r e m a i n s the m o s t s e n s i t i v e m e t h o d for d i a g n o s i s of o s t e o p o r o s i s : t h i s is c o n f i r m e d by the h i g h i n c i d e n c e of s p i n e f r a c t u r e in p a t i e n t w i t h low Q C T v a l u e .
IT-IEINFLUENCE OFINTESTINAL CONTENTS ONPRECISION OF DUAL PHOTON ABSORPTIOMETRY OF THE LUMBAR SPINE In follow-up measurements of spinal bone mineral content (BMC) using dual photon absorptiometry (DPA), the intestinal contents is one of the factors that definitely will have changed. Since it is not known to which ~xtent this contributes to the overall error in BMC, we have investigated this in duplicate measurements of lumbar BMC in normal subjects. Eleven normal volunteers (6 men and 5 women, age 23 - 49 yrs, mean BMC 44 gilA) underwent on the same day two lumbar (L2 - L4) DPA measurements with a Novo BMC-LAB 22a bone densitometer. The first measurement was performed in the morning, after a very light breakfast. The second one took place two hours after a standardized meal, containing 800 mg calcium and 750 mg phosphate from dairy products. The results were analyzed, by two independent observers. Rectangular regions of interest (ROI) were used to ensure that the size of the ROI was exactly the same in both measurements of the same subject. The variations in the soft tissue (ST) baseline were also investigated. The observed mean (+SD) change in BMC was 0.4% +2.1% (NS) for both observers, with an inter observer error of 0.6%. The mean variation in the ST baseline (SD per pixel) increased from 0.011 g i l a to 0.012 gilA (P < 0.05), inducing an extra error (CV) in the final BMC ranging from -0.07% to 0.16%. The overall reproducibility was 1.6% for both observDrs.
These results show, that although a slight increase in variation of the ST basehne is observed after a meal, there is no substantial systematic error nor a major contribution to the overall error due to altered intestinal contents.
368 B.Brunot, J.L.Demangeat, A.Constantinesco, G.Foucher
Nuclear Medicine Department C.H.R.U. Hautepierre, F-67098 STRASBOURG
THREE PHASE BONE SCINTIGRAPHY IN THE REFLEX SYMPATHETIC DISTROPHY (RSD) OF THE HAND : DETERMINATION OF ARTERIAL MEAN BLOOD VELOCITIES. Three phase bone scintigraphy (740MBq 99mTc-MDP) was performed in 154 patients : 93 with and 61 without RSD. At angioscintigraphic time, sixty 1-see 128x128 frames were acquired. Generation of NIN-MAX images was used in order to determine tracer arrival times in the arterial network. Data were analysed by choosing 3 regions of interest : wrist, palmar arch and digital pulp. Mean blood velocities were calculated according to V=~x/At (cm/sec), whereA x=Ap.f=pixel difference multiplied by calibration factor and At=arrival time difference between 2 regions. Proximal Vp (wrist/palmar arch) and distal Vd (palmar arch/digital pulp) mean velocities for affected CA) and healthy (H) side were studied as a function of evolution time and etiologic factors : Vp(cm/s) ~ Vd(cm/s) A H A H RSD (n=93) 4 . 2 ± 2 . 6 3.3±2.0 5.5±4.7 4 . 8 ± 4 . 5 non-RSD ( n = 6 1 ) 3.2±1.9 3.3±1.9 3.8±3.5 3.6±1.9 RSD EVOLUTION (weeks) 0-20 (n=61) 4.6±2.7 3.6±2.2 6.5±5.5 5.2±4.9 20-60 (n=20) 3.2±2.0 2.6±1.1 4.3±3.3 3.9±3.0 60-100 (n=6) 2.9±2.1 2.2±1.2 3.6~2.9 2.5±2.5 RSD FACTORS (0-20 weeks evolution) Wounds (n=lO) 4.6±2.1 4.0±1.7 9.9±8.3 7.6±7.4 F r a c t u r e s (n=14) 6.2±3.9 4 . 3 ± 2 . 4 8 . 0 ± 4 . 7 6.3±4.8 Dupuytren (n=14) 4.5±2.1 3.2±2.0 5.2±2.7 4 . 9 ± 3 . 9 Hemiplegia ( n = l l ) 3,4±2.3 3.9±3,4 4.3±3.0 3.3±3.3 The overall significant differences in these results will be discussed on a pathophysiological basis.
491
370
369 S.T. ZWAS,
M. SADAN,
I. KRONENBERG
B.Brunot, J.L.Demangeat, A.Constantinesco
Chaim Sheba Medical Center, Tel-Hashomer and Sackler School of Medicine, Tel-Aviv University, Israel. THE ROLE OF SKULL SCINTIGRAPHY IN FRONTAL SINUSITIS.
Frontal sinusitis (FS) is a disease which poses a great hazard if left uodiagnosed or inadequately treated. Clinical presentations vary and radiological findings are often non-spocific. Forty-four in-patients with acute or ~ c recurrent FS with positive skull x-rays underwent bone and g~dli~ scintigral~hiesin order to detect and assess hone infections. Fifty-three Tc-99m-MDP skull scintigral~hies (aS) including 9 follow-ups); and 21 Ca-67 studies (GS) post-surgery and during treatment including 8 follow-aps were performed. ~hirty-four (including 9 post-operative (PO) ahaormsl scintigraphies demonstrated mild to markedly increased radionuclide acctmm/ations distributed either in the regions of frontal sinus walls (9/34); diffusely-within the sinuses silhouette (ZJ34); or in a mixed pattern-in walls and silhouettes (21/34). Nine concurrent GS ware positive inclt~Ling I/6 P0 sites, and negative in others; including 3 treated cases who had moderate reactive bone uptake. However, 7/8 follow-up GS showed residugl or newly increased activity compared to initial GS, mostly in asymptematic cases. Except for 10 complicated FS cases, there was no clinical indication of bone involvement as visualized scintigra~%cally. Combined Ca and bone scintigra~hies localized the extent of active bone infection and clearly distinguished between early mucosal involvement (10/44) with negative hone scans; and advanced disease with osteitis/osteo~yelitis.
S~DA x-r%ys signs (excludingPO changes) of muco~l hyperthre~hy, air fluid level and/or opacifications, were encountered in both disease stages. Dual radionuslide studies in FS have an important role in increasing the efficiency of detecting and indicating hone infections, monitoring resolution, and guiding further patient management.
A.Boilletot,
S.Babin,
Nuclear Medicine Department C.H.R.U. Hautepierre, F-67098 STRASBOURG. REPEATED QUANTITATIVE BONE SCINTIGRAPHY (QBS) A YOUNG PATIENT WITH A FEMORAL OSTEOSARCOMA TREATED BY CHEMOTHERAPY AND ALLOGRAFT. Absolute quantitation of bone tracer uptake (counts/ pixel-sec.) allows to compare activity variations in own bone (healthy side : H) and in transplanted bone (affected side : A). The results of 15 QBS (99mTc-MDP 7.4 MBq/kg) performed during the follow-up (42 months) of a femoral osteosarcoma in a 12 years old patient, who underwent a combination chemotherapy and an allograft, are discussed according to 3 possible direct applications in clinical osteolog~v : i. PEDIATRICS. Involution of epiphyseal cartilages and bone maturation during the growth cause a diminution of bone uptake of the order of 20 % per year (between 12 and i£ years). 2. CANCEROLOGY. Bone uptake variations consecutive to c y c l i c a l chemotherapy were analyzed. Results of QBS in H and A side showed a two-phase response on treatment: first the uptake moderately increased (15 % over 3 months) and then much more significantly decreased (40% over the same time). A new increase was observed when the treatment was stopped. 3. BONE GRAFT. Measurement of bone uptake in a diaphysoepiphyseal graft (28 cm long ; 880 days implantation) showed : a) the existence of a diaphyso-epiphyseal bone activity gradient, which remained constant with time, b) an extensive neo-osteogenesis in the whole allograft. After 880 days the uptake in diaphyseal segment was as high as that in own bone (A/H = 1.0), whereas in epiphyseal segment the uptake was much higher (A/H = 1.5).
372
371 ~l.W. Arndt. A.H.M Taminiau, J.H.v Bockel, E.K.J. Pauwels.
PREDIC P., VENGUST V.
University Hospital, Division of Nuclear Medicine, Building 1, C4q, Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands
Hospital Celje, Nuclear Medicine Dept., Ortopedic Medicine Dept. Kersnikova i 63000 CelJe ~Yugoslavia
m
LYMPHSCINTIGRAPHY IN PATIENTS AFTER ROTATION PLASTY. Rotation plasty is accepted treatment of primary malignant bonetumors in the distal femur. Vascular resection and reconsu'uction have proven reliable in this procedure. The only remaining connection between body and lower leg during surgery is the ischiadic nerve. No lymphedema of the lower leg and foot in these patients with good functional results is found. Having no explanation for this clinical finding we started a lymphscintigraphic investigation (LSc). Investigated are 10 patients (pts), all osteosarcoma liB, mean age 17 (range 14-26)years. One pt was investigated twice. Only I pt had no vascular resection. LSc was performed from 11days-51months after surgery. 20MBq of Tc99m-nanometerslzed albumin-colloid (Nanocoll) is injected interdigital in the subcutaneous tissue avoiding i.v. injection. After 0,5, 2 and 4 hours scintigrams are obtained from foot to liver. Visualization of inguinal and higher lymphnodes(IN) proximal of the anastomosis is considered functional repair of lymphchannels(LCh). Early appearance of the liver is considered a sign of an alternative venous drainage for the inhibited lymphdrainage (LD). In 9 LSc IN were seen at 30rnin, although with normal intensity in only 3 cases. In lpt ( 11 days post surg) even 7h pi no IN were seen. In 1 pt (19 days post surgery) IN were observed at 2h. In 2pts"dermal backflow" was found, although there was some activity present in IN at 30rain. In the lpt examined at ] 9 days and 8.2 months post surgery LD changed from delayed to normal. In 5pts we found signs of venous drainage of the colloids, including 2 with delayed LD. Conclusions: 1)Spontaneous functionalrepair of LCh has been shown to take place within 19 days, which is less than reported in earlier studies using lymphscintigraphy in humans. 2)Scintigraphic signs of pathologic LD even a long time after surgery can be found without clinical lymphe5ema, probably because of the alternative drainage by the venous system. .
.
.
EARLY DIAGNOSTIC OF ASEPTIC HIP NECROSIS Aseptic necrosis of the femur head is a great diagnostical problem in the orthopedics. A correct early diagnosis is, therefore, very important for the therapy. Etiologically it is assumed that aseptic necrosis {idiopathic) is the result of absence of blood supply to the head, which causes avascular aseptic necrosis. Therefore, we have introduced in our work besides the static scintigraphy also a dynamic scintigraphy with the quantification of relative perfusion in the artery phase (3T) for the quantitative estimation of psrfusion. We inject bolus of 5gO-740 MBq Tc-99m-DPDand take 40 photographs in 60 secutlds by a computer. Then we set symmetrical regular regions of interest over the areas including heads and partly necks, and we generate symmetrical curves and calculate the 3T of the affected hip in comparison with the normal one. The examination has included 16 patients (ll males and 5 females) with aseptic necrosis aged between 26 and 76 years. The 3T valuehas been calculated in all patients and compared with the normal 3T. Nsrmal 3T is from 0.92 to 1.08 (i t 0.08). In the examinees with aseptic hip necrosis lower perfusiOn of the affected hip has been established so that 3T ranged from 0.39 to 0.99. (~=O.71). Some of the patients were Subjected to the surgical correction with implantation of the bone-vascular graft. The quantitative control of perfusion after the surgical treatment showed normalization of perflusion (3T-normal). Introduction of the dynamic scintigraphy of hips including calculation of 3T shows lowered perfuslon of the affected head in the patients with aseptic necrosis. At the same tlms it enables an early detection of hypoperfusion changes and selection of the correct treatment.
492
374
373 K. Knurls+, N.M.Ai-Ghussain+, E.Higazi+, R.S. Affana+, H.M. Abdel-Dayem+ B.D. Collier*.
Babi6 Lj.,B.Segedi,Lj.Djilas,N.6uri6 Institute of Pathophysiology Medical Faculty Novi Sad,Yugoslavia
+Fac of Med, Kuwait, *Medical College of Wisconsin, USA.
CORRECTION AND EVALUATION OF THE BLADDER ARTIFACT IN HIP SPECT.
PARAMETERS OF BONE METABOLISM IN THYROID DISEASES
The bladder artifact (BA) in Tc-99m MDP SPECT studies prevents proper visualization of the femoral heads which are obscured in the transaxial slices by broad shadows projecting beyond the bladder and in the coronal slices by photon deficient areas. A multi-slice computational correction method for the removal of the BA operates on the pro~e~tion ~ t e prior to image reconstruction by modifying only those segments of the projections that contain contributions from the bladder. By using the corrected tomographic dataset for reconstruction, the contributions of the increasing bladder radioactivity and volume and/or large activity levels in the bladder are removed and the pelvic bones including femoral heads are better visualized. The correction method was evaluated in 23 patients both b y visual assessment and by comparing profiles and left/right ratios through the femoral heads from raw data in projection i and uncorrected & corrected coronal slices. The left/right ratios did not change significantly but visual interpretation showed major improvement in 13 patients, minor in 4 and no improvement in 6. Out of the 13, the major improvement involved the region of the femoral heads in 3 and additional regions adjacent to the bladder in i0. Out of the 6 patients in whom no improvement was evident, there had been no artifact in 3 and only a minor artifact in 3. Hence the BA correction method is clinically useful.
The interrelationship between thyroid hormone and bone metabolism has been known for decade. Nowdays method for more precise measurement pa rameters of bone metabolism and bone mineral content has made possible to recognize slight changes of these paramewers. To investigate the pathogenesis of bone disorde in thyroid diseases we determined values of PTH,25(OH)D vit.,bone GLA-p(BGP),alkaline phos phatase(AP),hydroxyprolin(Hy-p),Ca,P in serum and urine in 21 hyperthyroid,in hypothyroid, lo treated hypothyroid and 14 patients with euthyroid struma.Serum levels of BGP,FTH,thyroid hormone were measured by RIA~TSH by IRMA method using commercial kit,25(OH)D vit.by com petitive binding assay,other biochemical parameters were measured by standard procedures. Lumbar BMD(L2-I~)was determined with bone mine ral analyser BMC-Lab 23.Hyperthyroid patients had lower level of PTH(l17+56 ng/1)and higher level of BGF(13,6+6,2 ng/mI)and AP(141+74IU/1) Hy-p(2o9+lo7umol/m2/d)compared with th~se ones in eu-an~ treated hypothyroid(14o+5ong/1;5,o7+ 2,25 ng/ml;45,6+27,8 IU/l;8o+2oum~i/m2/D,res-pectively.BMD w~s slightly d~creased in hyperthyroid compared with same one in eu-thyroid. We conclude that in hyperthyroidism increased bone resorptiQn and formation exist. 376
375 M" Rajt@r, P. Nilassin
, O. Esik , L. Csernay
Dodig D., S.Popovid, l.~imonovid, M.Poropat
DEPARTMENT OF NUCLEAR MEDICINE UNIVERSITY HOSPITAL, ZAGREB, YUGOSLAVIA
Department of N u c l e a r M e d i c i n e , Radiology , A l b e r t Szent-GySrgyi v e r s i t y , Szeged, Hungary
Department of Medical Uni-
PINHOLE-COLLIMATOR SCINTIGRAPHY (PCS) IN DEGENERATIVE INVOLVEMENT OF THE SPINE In 1987, Yong et al. described scintigraphic signs of vertebral metastasis, compression fracture, and tuberculous end pyogenic spondyli%is by PCS. The aim of our study was to obtain specific scintigraphic signs of spondylarthrosis (causing a major problem in the interpretation of early metastatic loci) by means of PCS. One hundred end twenly-four vertebrae of 53 patients were studied by multihole collimator scintigraphy (MCS), PCS and X-ray. The specific diagnoses verified by X-ray and/or tomogrephy were as follows: 42 metastases, 70 spondylarthroses, 5 compression fractures, 2 pyogenic spondylitis. In 8 patients, no pathology could be shown on X-ray or tomography. The diffusely increased (metastasis-like) vertebral uptake revealed by MCS was shown to be restricted to spondylophytes by PCS in 76% of the spondylarthrotic cases (53 vertebrae), connecting the neighbouring vertebrae with or without narrowing of the intervertebral spaces. On ventral localization of the spondylophytes, no convincing unique scintigraphic sign could be found. In our opinion, PCS is an easy, inexpensive and efficient method of differentiating solitary vertebral foci without extra radiation exposure.
DETECTION OF DIFFUSE SKELETAL LESIONS BY MONITORING THE KINETICS OF LABELED PHOSPHONATES A method for detection of diffuse skeletal involvment by monitoring the kinetics of labeled phosphonates has been studied. The accumulation of labeled dlphosphonates was determined indirectly by measuring plasma and urine concentration of the radiopharmaceutical.The study involved 31 persons without bone changes and 26 patients with diffuse skeletal involvment. The urine was collected at each hour until hour 5 after administration of the radiopharmaceutical and activity was calculated as percentage of injected dose.Blood samples were taken at the same intervals and activity in 1 ml of plasma was calculated as percentage of administred dose in 1 litre of plasma. The results indicate that measuring of the quantity of the radfopharmaeeutical excreted in urine allows a reliable separation of the patients with diffuse skeletal involvment from normals.The test is performed simultaneously with hone sclntigraphy. It provides at the same time the bone scintigram and quantitative data about radlopharmaeeutical accumulation In the skeleton. It was not possible to differentiate the group of patients without skeletal involvment from the group of patients with diffuse skeletal involvment by determination percentage of administered activity in plasma. Our results of dfphosphonate retention in skeleton by measuring the amount of radiopharmaceutieal excreted in urine are in agreement with the results of the authors who calculated 24h excretion, but our results show that the method is realible even at 3 hours after application.
493
377 S..~...._6.M.I..QQ~ , J , P . VALEYRE 1 ,
378 ESCHARDz , J . C .
LIEHN~ , J ,
I Dpt o f Nuclear Medicine. I n s t i t u t J.GODINOT. 2 Dpt o f Rheumatology, H o p i t a l SEBASTOPOL. REIMS, FRANCE DOES CHEMONUCLEOLYSIS INDUCE BONE SCAN ABNORMALITIES ? Chemonucleolysis (CN) i s a m e d i c a l a l t e r native treatment of herniated lumbardiscs. This method aims t o o b t a i n the enzymatic d i s s o l u t i o n o f the nucleus pulposus by the i n t e r v e r t e b r a l i n j e c t i o n o f chymopapaYne, a p r o t e o l y r i c enzyme which h y d r o l y z e the p r o t e o g l y c a n s o f the nucleus. The aim o f the study i s t o determine i f t h i s enzyme induce e a r l y o r l a t e bone l e s i o n s o f the a d j a c e n t v e r t e b r a e , E~.t.J..@.~.qs......a.n.d...........~.e.~.h.Q.~: 2 groups o f 10 p a t i e n t s ( p t s ) each were s t u d i e d . Group I was s t u d i e d by 2 b o n e scans performed I day before and 4 t o 6 days (median: 5 days) a f t e r CN. Group 2 was s t u d i e d by 2 b o n e s c a n s performed 1 day b e f o r e and 13 t o 21 d a y s ( m e d i a n : 20 d a y s ) a f t e r CN. Bone scans were performed w i t h S~mTcHMDP; images were recorded w i t h a gammacamera, Re.s.u]...ts: 19 p t s had no c o m p l i c a t i o n and no d i f f e r e n c e was seen beetween the pre-CN and post-ON bone scans. One pt develloped a 'chemical discitis which induced the u p t a k e of the tracer by a vertebral plate only
(pattern different from the infectious discitis where the 2 v e r t e b r a l p l a t e are a b n o r m a l ) s e e n on t h e l a t e bone s c a n . QQ.n.c.]...usj..qn.: CN g e n e r a l l y d o e s n o t i n d u c e bone lesions. If a discitis is develtoped, the late b o n e s c a n show the v e r t e b r a l p l a t e u p t a ] < e .
379 C. Alexander, E. Oberhausen, R. Berberich (Homburg) A. Steinstr~Ber, A, Schwarz, M. Zimmer ( F r a n k f u r t ) Abt. f. Nuklearmedizin der Radiologischen K l i n i k ; U n i v e r s i t ~ t s k l i n i k e n im LKH; D-6650 Homburg and Radiochemisches Laboratorium der Hoechst AG; D-6230 F r a n k f u r t (M) 80
M., Bra~i6 ~kugor M.,, Poropat ~imonovid I.
I., Ga§parovid Z.*,
Clinical Hospital Center Zagreb, Department of Nuclear Medicine, Yugoslavia Clinical Hospital Center Zagreb, Department of Urgent Internal Medicine, Yugoslavia DETERMINATION VALUE OF 99mTc-MDP BLOOD CLEARANCE IN DIALYZED PATIENTS Bone scintigraphy is used in detecting metabolic bone diseases. Sometimes, it is very difficult to detect early bone changes by some other diagnostic methods, as well as by scintigraphy. We examined a group of 33 dialyzed azotemic patients. Apart from the semiquantitative analysis of scintigrams, we followed up Tc99m-MDP blood clearance. On the basis of the clearance courve we determined t/2 of its second component which is assumed to represent the incorporation of the radiopharmaceutical into the bone. We divided the scintigraphic findings into five groups: l. normal findings (6 pts); 2. focal uptake of radiopharmaceutical (6 pts); 3. diffuse increased uptake of radiopharmaceutical (8 pts); 4. diffuse + focal pathologic uptake of activity (5 pts); 5. diffuse + focal + + extraosseous uptake of radiopharmaceutical (8 pts).The second component clearance courve (SCCC) t/2 (mean value) was 82,5 min for the first group, 68 min for the second, 36 min for the third, 50 min for the fourth and 43 min for the fifth group. We compared the scintigraphic findings and SCCC t/2 value with RTG and laboratory tests and we found a high degree of concordance. Our results exhibit a significant difference in Tc99m-MDP SCCC t/2 value in the group without scintigraphic bone changes in comparison with the group with bone changes. We think that this method, although technically complicated, can he performed in those cases where other methods are insufficient and in which the clinical signs of a disease are present.
380 D-Brecht-Krauss
I R.Wetzel, W.E.Adam,
U n i v e r s i t y of Ulm, D i v i s i o n a n d C l i n i c of O r t h o p e d i c s 7 9 0 0 Ulm, F R G
R.Weller, W.Puhl
of N u c l e a r
Medicin(
SKELETAL SCINTIGRAPHY WITH IMPROVED BONE LESION DETECTABILITY: A CLINICAL COMPARISON OF MDP AND HMPD
BONE S P E C T IN O S T E O C H O N D R O S I S K N E E JOINT.
D I S S E C A N S OF
For better identification of osseous lesions a maximal uptake of the radiopharmaceutical in the normal bony tissue mustn't be favorable in any case. Substances that are uptaken l i t t l e in normal bones but quite well in osseous lesions can be helpful for the detectability of skeletal metastases. The subject of the present study is l~ydroxy-3-~ethyl phosphinico-l, l propanediphosphoneacid (FIVPD), a new skeletal imaging agent. Ten patients participated in the clinical cen%Darisonof MI)P and F~IPD. Each person had a clinically proved metastatic carcinoma. In each case f i r s t a MDP bone scintigraphy then after 2 to 4 days a FMDD-study was performed. The evaluation of both studies was performed by ROl-technique: One region of interest coincided with the lesion, the second one, that was of the same size, with the normal bone of the opposite side and the last one with an adequate soft tissue area. The contents of the f i r s t two ROl's were corrected by those of the soft tissue-ROl and the lesion/normal bone-ratio was calculated. Furthermore for each patient the bone/soft tissue-ratio was determined in the femoral region. The evaluation of 29 lesions showedthe following results: In the FMDD-studies the lesion/normal bone-ratio showed a mean increase of 63.3 % (MDP:5.48 +_6. 50/FIVPD:9. 06 +_ 12.66), and the bone/soft tissue ratio a mean decrease of 42.6 %(NDP:2.77+ O,94/FNPD:I.59 + 0.35). The size of the skeletal metastases was nearly equal (FDP:77.45 pix/FMPD: 71.52 pix). 33 lesions were detectable by both substances, but five additional metastases were visible only by means of FI~DD. Towards these results llV]PDsee~ to be a premising radiopharmaceutical for skeletal imaging. A better and earlier bone lesion detectability should be possible by this substance.
B o n e s c i n t i g r a p h y is a r e l i a b l e m e t h o d d i a g n o sing osteochondrosis d i s s e c a n s of k n e e joint, e s p e c i a l l y w h e n c o n v e n t i o n a l r a d i o g r a p h y is negative. As for localizing suspected internal d e r a n g e m e n t s of the k n e e as for a n s w e r i n g the q u e s t i o n if t h e d i s s e c a t is d i s s e c a t e d or n o t arthroscopic knee evaluation before orthopedic o p e r a t i o n is n e c e s s a r y . T h e a i m of t h i s s t u d y is to c o m p a r e p l a n a r b o n e i m a g i n g w i t h b o n e S P E C T detecting and localizing internal derangements o f t h e k n e e p r e o p e r a t i o n a n d e v a l u a t i n g a succ e s s f u l l o r t h o p e d i c i n t e r v e n t i o n . 15 p a t i e n t s are e x a m i n e d b y p l a n a r and SPECT b o n e i m a g i n g .
A r t h r o s c o p i c e v a l u a t i o n is used as the standard of c o m p a r i s o n b e f o r e and 3 m o n t h s after o r t h o p e d i c o p e r a t i o n . D i a g n o s i n g o s t e o c h o n d r o s i s dis secans a n d e v a l u a t i n g s u c c e s s f u l l o r t h o p e d i c i n t e r v e n t i o n w e h a v e a 100% s e n s i t i v i t y b y S P E C T b o n e i m a g i n g a n d a 75% s e n s i t i v i t y for planar bone scintigraphy, Based on our initial r e s u l t s w e c o n c l u d e t h a t S P E C T b o n e is a u s e f u l n o n - i n v a s i v e p r o c e d u r e to e v a l u a t e k n e e joint pre and post operation in osteochondrosis dissecans. W e are a b l e to o f f e r o u r o r t h o p e dists a non-invasive method evaluating knee joint and we are sure that the invasive method of a r t h r o s c o p y m a y b e r e d u c e d s i g n i f i c a n t l y .
494
381
382
Matovic ~ilojevie B,Kostie K University 1University
Lj,Zivkovie
Clinical-Hospital Clinioal
~CI NTI GRAPHI C FRACTURES OF
M,Stanisavljevic
Centre,Kragujevac
Centre,Beograd
VI SIIALI S A T I ON OF FACIAL BONES-COMPARI
TRAUMATI C SON WITH
RADIOGRAPHIC AND SURGICAL F I N D I N G S Using a c o , ~ u t e r - s u p p o r t e d gammla s c i n t i l l a t i o n camera, and OOmTc-DPD(dicarboxy-propane-diphospho~ a t e ) , s c l n t l g r a p h l c v l s u a l l s a t i o n of facial bones Was p e r f o r m e d on 11 p a t i e n t s w i t h c l i n i c a l and radiographic findings of post-traumatic fractures ~even of the patients had fracture of the
a n f ~ r t e r ~m*li e4" &h~m~s~4Ll]al-y s i n ~ ) ~ four
also
had fracture
of
the
~
~ch
Upper
wall of the m a x i l l a r y slnus, and three fractm-e o f the ethmold
bone. Two p a t i e n t s had f r a c t u r e of the a n t e r i o r wall o f the f r o n t a l slnus, and the remaining t w o p a t i e n t s had f r a c t u r e of the ethmold bone. The g r o u p c o n s i s t e d of s e v e n m n and four women, the age r a n g e b e i n g f r o m ~0 to 50 years. The control g r o u p c o n s i s t e d of f i v e patients, w i t h o u t either i n j u r i e s or d i s e a s e s of facial bones, l n c r e a s e d ~ p t a k e o f O O m T c - D P D was fotmnd in all patients, in Lhe f r a c t u r e areas that w e r e p r e v i o u s l y d i a g n o s e d c l i n i c a l l y and r a d l o g r a p h l c a l l y . However, ln f o u r patients the scintlgrams indicated additional f r a c t u r e s of facial bones, w h i c h w e r e not o b s e r v e d on r o u t i n e radlographs, bu£ w h i c h w e r e clinically S u s p e c t . I n these patients surgical exploration conflrmd the regions of increased uptake to correspond t o fracttn'es of the appropriate bone struct~res. Ou~- m o d e s t e x p e r i e n c e s indicate that sclntigraphic i~ging ~ a y play a significant role |nf~dJ_agru~.~tlr-~of facialbonelnj~ries.
383 Strau~ ~., Meyer L., R i c c a b o n a G., O b e r l a d s t ~ t ter M, U n i v . - K l i n i k f0r N u c l e a r m e d i z i n , Anichstr. 35, 6020 Innsbruck, A u s t r i a
M. LItHH~24Sq~IN. C. I~DK44ICA. N. SAL~{I, D. BINNS, J. A~<~)RS~S. J. wAPX, L. FLICKER. Dept. of Nuclear Medicir~e. Royal Melbourne Hospital Dept. uf Medicine. U,dversity of Melb0urlle.
CoNV}~%glON OF AN O17) GAMMA CAMERA TO A HONE MIN~ERAL DE~SITOMEFRY (BMD) UNIT A 15 year" old ~qearle Pho Gamma camera no longer acceptable for clinical use was converted to a bone derlsitometer. A Conve~gir~ collimator' focal ler~th 5ca with an attached C arm housing a 250mci Gd ~.'~:;I'~ source at the collimator's focal point was mounted on the Ga~m~a camera. Flc<
384
Kostadinove I., M.Donchev, 5t.Milanov, 5t.Kovacheve, E.Baltov, M.Ganchev, T.Petrev Section "Radioisotope Diagnosis and Radiolmmunology"Sofia, Oepertment of Reentgenelogy and Radiology, Pieven, Bulgarian Medical Academy, Bulgaria
FROBLEMS FOR D I F F E R E N T T A L D I A G N O S I S OF C H R O N I C IBACK p~IN BY DUAL PHOTON D E N S I T O M E T R Y (DPD) AND !BONE SCANS (BS) D P D has gained c o n s i d e r a b l e i m p o r t a n c e to assess o s t e o p o r o s i s in p o s t - m e n o p a u s a l women, patients with chronic renal failure, under l o n g t e r m cortisone therapy and a v a r i e t y of other m e t a b o l i c diseases. Cost e f f i c i e n c y ratios of the method are still a m a t t e r of discussion. Using a Lunar DP 3 - s c a n n e r - s y s t e m for DPD and a Siemens Gamm a s o n i c s ZLC 37 gamma camera with image regist r a t i o n on x-ray film we did 212 DPD studies and 5227 BS with 555 MBq 99m Tc-DP in 1988. Normal bone m i n e r a l content (BMC) was studied in a control group of 29 persons of d i f f e r e n t age and sex groups. It seemed i m p o r t a n t to compare DPD With BS in 14 p a t i e n t s above 47 yrs. of age (13 fem., I male), admitted to our service because of c h r o n i c back pain, e q u i v o c a l x - r a y - s t u d i e s and a s u s p i c i o n of malignancy. Results show that 2 p a t i e n t s had g e n e r a l o s t e o p o r o s i s , 2 metastases and 10 patchy o s t e o p o r o s i s with i r r e g u l a r spots of i n c r e a s e d bone d e n s i t y and o s t e o c h o n drosis. The c o m p a r i s o n of BS with DPD helped to f o r m u l a t e a correct d i a g n o s i s in all cases. We Conclude therefore that in elderly people with chronic back pain DPD is helpful to assess the 5one p a t h o l o g y but only when D P D - s c a n s are int e r p r e t e d c o n s i d e r i n g not only "BMC-mean values" but also local a l t e r a t i o n s of BMC in c o r r e l a t i o n with BS and clinical picture.
OETECTION OF PROSTHETIC HIP INFEC]ION, USING
99mTc
BONE 5CINTIGRAPH¥ AND LABELED LEUCOCYTES WITH 99mTc-COLLOID AND I:111n-OXINE An assessment was made of the roles of bone scintigraphy enO labeled leucocytes / Le / in identifin 9 infected hip prostheses. Thirty pts uith single or
double side i ~ a n t a t i o n ) being in p a ~ were investigated with Tc-diphospbonat~1~n d Tc-sulfurcolioiO-Le. In 14 of the cases In-Le-scan use also performed. The correlation beteen clinical or surgical results and scintigraphic finding revealed: bone scintigraphy detected infection with sensitivity of 90%, specificity-?2~ anO accuracy-88%. Le-scsn / as a whole / had sensitivity of 62~, specificityg4~ and accuracy-UO%. There weren'tg~ig Discrepancy between t ~ I r e s u l t s , obtained with mle-Le/accuracy78~/ and In-Le/accuracy-86~/, uhich made the first method preferable, because of convenience, low cost end radiation dose. It was concluded, that in these pts, bone scan should be performed first and thenLe-scan) which was more specific, but less sensitive.
495
385
ph~l~ S y A~,
386
Sowiflskl
K.Dafermou, G.Panoutsepoulos, J.Christakopoulou
J.
C l i n i c of E n d o c r i n o l o g y University S c h o o l of M e d i c i n e ,
Pozna~i,
Poland
SERUM OSTEOCALCIN CONCENTRATION, SCINTIGRAPHIC AND ROENTGENOGRAPHIC STUDIES FOR DIAGNOSING OSTEOPOIIOSIS OF ENDOCRINOLOGIOAL ORIGIN T h e s t u d y w a s a i m e d at e v a l u a t i n g the a p p l i c a b i l i t y of s e r u m o s t e o c a l c i n determii~tion, bone roentgenography and sceletal sclntigraphy for diagnosing osteoporosls a n d its c o m p l i c a t i o n s . The studied group ineludled 37 n o r m a l a n d 167 patients with osteoporosis s u b j e c t s : ~9 of the lathes'had pri~my ~8teep~>ro~is and ~18petlents secondary osteoporosis d u e to e n d o o r l n o l o g i c a l d l s e a s . "[T~e p a t i e n t s studied were divided into two groups: group A-56 patients with vertebral compression fracture and group B-111 patients without vertebral compression fracture.We found that the d e t e r m i n a t i o n s of s e r ~ n o s t e o o a l c l n , |~easurements on roentgenograms of the v e r t e b r a l body and the second metacarpal bone and calculat i o n of t h e e o r r e s p o n d l n g i n d e x v a l u e s w e r e useful for differentiation of t h e s e two t y p e s of osteoporosls. T h e s t u d y a l s o s h o w e d t h a t i n oateoporotic patients the m o s t f r e q u e n t l y involved sites of f r a c t u r e the v e r t e b r a l b o d i e s a n d the ribs. These observations suggest that seeletal solntlgraphy is h e l p f u l i n d i a g n o s i n g o s t e o p o r e sis and its complications. Total body isotopic i m a g i n g m a k e s of p o s s i b l e to d e t e c t all fresh f r a c t u r e s d u e to o s t e o p o r o s i s a n d it m a y a l s o be u s e f u l in measurii~ the c h a n g e s in height and other anthropologic dimensions of a patient.
387 M Alexander, A M Peters, J Cleland, J M B Hughes, J P Lavender.
J.Pantalos,
C.Batsakis,
Nuclear Medicine Department of the Athens Hospital for diseases of the chest "SOIiRIA" PANOIID UPIAK£ OF 61Ga-CIIRAIE IN SARCOIDOSIS MEANS gLAND INVOLVEMENI? Aim of the study was to evaluate if selective accumulation of 67Ga by the parotid glands (P), the rhinopharynx (R) and the lacrimal glands ( L ) i s a normal finding or is disease related. One hundred fifty seven pts divided in 3 groups were studiet: Goup I: 36 pts with proveo sarcoidosis (S).Group If: 56 pts with Diffuse Pulmonary Fibrosis (UPF) or possible S. Group If!: 65 pts used as controls (C) since their67Ga scan was made to rule out osteomyelitis.Ai! pts were suDmitteu to 67 Oa scan, 48h after IV administration of 2-5 mCi of 67Ga-citrate. The P, R and L 67Ga uptake was considered as s3gnific a n t when it was more i n t e n s e than t h a t ~t" the s t e r r , um. RESULTS
P
R
L
S (No 36) 33.3% 36.0% 45.0% DPF (No 56) 10.7% 39.3% 33.3% C (No 65) 8.3% 43.1% 29.u% Analysis with the chi square Lest gave no difference (P>0.05) in the L and R 67Ga uptake between any of the groups. On the contrary, there was statistically very sinificant increased activity in the P, in the 5 group p < 0.01) as compared to the C group, and statistically significant (p<0.05) between the S anf DPF group, probably because some cases of 5 were included in this group. We conclude that increased accumulation of 67Ga in L and R constitutes a non significant finding, in contrast to that of P in the S group that seems to be disease related, indicating the gland involvement by the disease.
388 W.M. $7, I.S. Seo, A. Quevedo, K.G. Tai and J. Desai. The Brooklyn Hospital, 121 DeKalb Ave., Brooklyn, NY, USA
Hammersmith Hospital, London, England. LEFT LOWER HYPOVENTILATION IN CARDIOMEGALY We have previously observed a decrease in ventilation to the left lower lobe, measured by continous inhalation o£ Kr-81m, in 27 of 49 patients with csrdiomegaly on changing from the prone position to supine, hut in only 4 of 41 patients with normal cardiac size. The purpose of the current study was to elucidate the mechanism of this change in those patients with cardiomegaly in whom it occurs. The regional clearance o£ Xe-133 from the lungs was sequentially recorded following i.v. injection first in the supine and then in the prone position. Following Xe-133 wash-out, ventilation images were recorded during Kr-81m inhalation in both positions. After these ventilation studies a perfusiOn image was acquired with Tc-99m MAA in the supine position. Two days later MAA was given in the prone position. The positional changes in ventilation (Kr-81m), ventilatory turnover (Xe-133) and perfusion (MAA and initial Xe-133 counts) were expressed as changes in the ratio of counts over R0I of equal size placed over the left and right lower lobes respectively (L/R ratio). The L/R ratio for Kr-81m fell in 6 patients When moving to the supine position from 0.73 (SD 0.16) to 0.32 (0.11). However, the L/R ratio for Xe-133 clearance, ~AA and the initial Xe-133 counts did not change significantly. We conclude firstly that the predominant mechanism for the decrease in left lower lobe ventilation is alveolar compression rather than air trapping, and secondly that it is not accompanied by significant hypoxi~ vasconstrictlon.
THE INCIDENCE AND CLINICAL INPLICATIONS OF REVERSED V/Q NISNATCH (rV/Q)
The occurrence of multiple segmental and/or subsegmental perfusion defects and normal ventilation images is highly indicative of pulmonary embolism. The reverse, combined abnormal ventilation and normal perfusion images5 (rV/Q), although infrequent also occurs. The clinical implications and incidence of rV/Q are assessed from an eight-year data experience. Twenty-nine hundred eighty six adults had 3610 perfusion and 3465 ventilation scintigraphs (1979 using Xe-133, 702 with Kr-81m and 392 had both gases.) Reversed V/Q was noted in 12 with underlying Alzheimer's, asthma, seizure disorders, TB and COPD. Five showed more than one segmental ry/Q, of which two who had collapsed lung responded dramatically to emergency bronchoscopy, two with ateleetasis responded to either intuba~ tion and suction (I&S) or hydration and physiotherapy (HAP) while one with no therapy worsened. In seven whose rV/Q was subsegmental, four responded to lag or HaP, while in three untreated ones, one worsened and in two the symptoms were unchanged. Repeat scans showed reversal of rV/Q in all who improved. Mucus plugs at various levels caused the rV/Q in all clinically improved cases. The incidence of rV/Q is low, but the urgency for immediate and proper interventlonal therapy is imperative once the diagnosis is suspected. Not infrequently a V/Q mismatch is the clinical rule out diagnosis, but rV/Q is equally critical and its recognition is pivotal for appropriate intervention.
496
389 Evan de Flierdt. R Bauer, C Wagner-Manslau, HR Langhammer, HW Pabst Nuklearmedizinische Kiinik und Poliklinik, Klinikum rechts der Isar Technische Universit~it M0nchen, FRG VALIDATION OF A NEW METHOD OF AEROSOL INHALATION IN OBSTRUCTIVE LUNG DISEASE AND F O R INVESTIGATIONS OF M U C O C I L I A R ¥ CLEARANCE A new ultrasonic nebulizer operating with a frequency of 2.5 MHz was used to produce a liquid/solid aerosol. The diameter of the solid part ranges from 0.2 - 1.0 I~m. Droplet size distribution has been determined by nebulizing a salt solution of known concentration: After evaporation of the droplets in a drying path, size distribution of the solid residuals was measured by means of different spectrometric methods. Droplet size (mass median aerodynamic diameters, MMAD) was 2.0 pm (geometric standard deviation 1.2) with and 2.8 pm (GSD 1.35) without a preselecting system, respectively. First investigations in patients without obvious lung disease (n=6) showed high peripheral activity. Mucociliary clearance of the central deposited activity was 30% per 1 hr (range 1835%). Patients with obstructive lung disease of different degree (n=8) showed higher central deposition of activity. Primary deposition and mucociliary clearance showed high interindividual differences. The most important factors for primary deposition were the degree of obstruction and the breathing pattern. On the other hand, evaluation of intraindividual changes due to therapy were possible without difficulties. During investigation up to 4hrs after inhalation, there was no significant resorption of activity.
391 N. Cho, M. Suzuki and K. Nagase
390
D.
D.
P a t t o n 1, L.
A. Garcia 1, d.
I,t.
Woolfenden 1, W.
H,
Williams t and P, L. E b e r s t a d t R, tUniversity o f Arizona, Tucson, Arizona, and 2University Mexico, Mexico City.
of
SMOKER'S LUNG: h NEW SIGN IN PERFLISION LUNG SCINTIGRAPHY.
Perfusion lung scintigrams (PLS) in heavy s m o k e r s w e r e o f t e n noted t o exhibit a c h a r a c t e r i s t i c g r a n u l a r p a t t e r n : numerous uniformly d i s t r i b u t e d fine round d e f e c t s suggesting a "Swiss cheese" appearance, t h e " s m o k e r ' s lung p a t t e r n " (SLP). To determine the relationship between this s u g g e s t e d p a t t e r n and smoking h i s t o r y we reviewed t h e PLS o f 114 p a t i e n t s with no Known pulmonary disease. All PLS w e r e o t h e r w i s e normal, i.e. . . . . . i showed no evidence o f pulmonary embohsm o r o t h e r smgnmflcant pulmonary disease. PLS w e r e reviewed blindly by :~ nuclear p h y s i c i a n s with r e f e r e n c e t o a "training s e t " o f t h r e e PLS showing t h e SLP in heavy s m o k e r s . Images w e r e r a t e d on a s i x - p o i n t scale: [absolutely certain/relatively certain/just g u e s s i n g ] [SLP is p r e s e n t / a b s e n t ] . SLP c o r r e l a t e d m o d e r a t e l y well with smoking ( r = .31, n = 114, P < .Of). A r e a under the ROC curve was 0.654. The d e g r e e o f image abnormality c o r r e l a t e d marginally with t h e number o f p a c k - y e a r s ( r = .R3, P < .O5). T h e r e was good i n t e r o b s e r v e r agreement (P < .OO1 f o r all pairs). For f o r m e r smokers who had quit, t h e d e g r e e o f image abnormality c o r r e l a t e d negatively with time since quitting ( r = -.32, n = 17, P < .Ot). We concluded: (1) Smokers o f t e n exhibit a c h a r a c t e r i s t i c p a t t e r n in p e r f u s i o n lung scans; (-~) its d e g r e e c o r r e l a t e s with p a c k - y e a r s o f smoking h i s t o r y ; and (3) i t s d e g r e e d e c r e a s e s with time in t h o s e who have quit smoking. While t h e scintigraphic p a t t e r n is s u b t l e and n o t likely t o i n t e r f e r e with t h e o r d i n a r y i n t e r p r e t a t i o n Of PLS, t h e p a t t e r n may be useful in demonstrating o r assessing lung damage f r o m smoking.
392 A Giordano, L Aulisa, B Santucci, M Galii, R Piste]li, L Fuso, G Galli. Istituti di Medicina Nuc]eare, Ortopedia e Clinica Medica; Universit& Cattoliea del Sacro Cuore. Largo A. Gemelli 8, 00168 Roma - Italy
Department of Radiology, School of Medicine, Junteado University EVALUATION OF VENTILATION AND DIAPHRAGM MOVEMENT (DM) IN PULMONARY SCINTIGRAPflY WITB I 123 IMP IN VARIOUS LUNG DISEASES ESPECIALLY EVALUATION ON DIAGNOSIS OF RADIATION PNEUMONIA -
It is known that 1 123 IMP accumulates in the lung and liver when the radioactive isotope (RI) is used for diagnosis of cerebral blood flow. Availing that c h a r a c t e r i s t i c of the RI, i . e . , l~I accumulation in the lung, we investigated the a p p l i c a b i l i t y of examination with 1-123 IMP to determination of damaged s i t e s in lung t i s s u e s and differential diagnosis of diseases. A detector was placed on the chest of a patient in a supine position on a bed, and RI was injected into the cubital vein. Accumulation of the R1 recorded with a computer immediately a f t e r injection. Twenty nine patients received the examination, and a few p a t i e n t s were examined several times. Therefore the examination was performed 34 times. The normal subjects consisted of volunteers and subjects undergoing cerebral blood flow scintigraphy. The p a t i e n t s with lung diseases consisted of 11 with lung cancer (10 of them had undergone radiation therapy), 5 with bronchopneumonia, 5 with i n t e r s t i t i a l pneumonia, ] with f i b r o s i s of the lung, 2 with pulmonary embolism, and others. The level of R] accumulated in the normal lungs reached a maximum immediately a f t e r intravenous injection of the RI, and thereafter i t decreased wi th time. The lung cancer patients showed almost no aocumulation in the tumors: and many of t h e s e p a t i e n t s on r a d i a t i o n t h e r a p y showed R] accumulation at the i r r a d i a t e d s i t e a f t e r radiation. Some of the p a t i e n t s that had been ceased oral medication already given for prophylactic purposes in p r o t e c t i o n a g a i n s t r a d i a t i o n f i b r o s i s caused a complication of radiation fibrosis of the lung. It was found that I 123 IMP accumulated well in inflammatory lesions in pulmonary inflammatory diseases, particularly pneumonia.
'IDIOPATHIC SCOLIOSIS (ISCOL) BY RADIOAEROSOL LUNG SCINTIGRAPHY (RL8). Neither regional ventilation nor DM have ever been investigated by RLS in ISCOL. Therefore we submitted 22 pts with various angles of ISCOL curves to a RLS which has been complemented with: i) a dynamic acquisition which all.owed a qualitative evaluation of DM by eine-display anaiysis and by time/act, curves; 2) two pairs of static scans acquired in ant and post views during max. inspiration and expiration. An originai method implying the normalization/ subtraction of images and few ROI based computations a]lowed a quantitative assessment of DM:by a DM-Index. Results: I) a good correlation (p (.Ol) was obtained between the angle of the scoliotie curve and the ventilation abnormalities (scored in 5 classes) detectable in all pts with >45"angle; 2) in a]i p t s o n ] y the lung on the concave side showed ventilation abnormalities; S) a reduction of DM of the hemidiaphragm of the concave side was qualit 9 tive]y and quantitatively detected: convex DM-Index= 35±6, concave DM-Index= 28~5 (p <.0001 vs values obtained in 7 norma]s). Also DM impairment significantiy correlated with the scoliotie angle (p (.05). In conclusion ISCOL produces an impairment of ventilation and DM on the concave side in pts with >45"curves; RLS can be usefully complemented with the evaluation of DM.
497
393 M.K. Nawaz, A.H. Elgazzar, H.K. Walia, H.M. Abdel-Dayem, A.R. Sulaiman, A.O. Farag and S.A. Baig.
394 !~, Oantinho, F. Godinho, L. Oiiveira, J. P. d~ Lima ~.]. Baztar.do, I. Santo.-_-.,A Omuto, ~{. Freits.=~ e ,0o.~ta INSTITUTO DE ~ D I O I N A NUOLEAR, FHL and FHO. SERVI00 DE PNEU~-~ONOLOGIA.HSM L I ~ O A
Dept. of Nuclear Medicine, Amiri Hospital and Faculty of Medicine, Kuwait University. EVALUATION OF DELAYED Tc-99m PYROPHOSPHATE AEROSOL (PYP) POST PERFUSION VENTILATION STUDIES (PPVS). The diagnosis of pulmonary embolism (P.E) has several problems with all pre- and post perfusion vent±latter studies using Xe-133, Xe-127, Kr-81m and Tc-99m DTPA aerosols. We evaluated delayed PPVS using Tc-99m PYP performed 3 hours following a small dose (37-34 MBq) Te99m MAA perfusion studies. Counts/second from residual Tc-99m MAA activity were increased atleast 2-3 folds after Tc-99m PYP aerosol inhalation. This protocol is designed to avoid unnecessary ventilation studies. Tc-99~ PYP has slower clearance than DTPA allowing better quality images and possibly SPECT imaging. 35 patients had Tc-99m PYP PPVS. 18 had normal perf. or a small subsegmental defect matching with chest x-ray finding; no PPVS was necessary. The remaining 17 patients had Tc-99m PYP PPVS, 9/17 had matching defects and were considered low probability and pulmonary angiography (PA) was not recommended. 3/17 had high probability because of mismatching defects. Only 5/17 had moderate probability because of mismatching defects, and therefore had PA, in all 5 the diagnosis of P.E was confirmed. Only one patient from the low probability group had a perfusion defect compatible with an opacity on the chest x-ray ventilation study was not done and P.; on basis of clinical suspicion confirmed P.E. We conclude that delayed Tc-99m PYP PPVS has the advantages of slower clearance from the lungs, better images, tomography is possible and avoids unnecessary ventilation studies.
395 B.Brunot, P.Budor, J.L.Demangeat, J.J.Braun, A.Constantinesco Nuclear Medicine Department C.H.R.U. Hautepierre - F-67098 STRASBOURG.
el J! MF)klAD VI~klTI/ATI£%~.|/ PERFUS!QN ....... T . . . . . . . . . -,'~
T~
AND BUmTcMAA. Several method; h~ve been described Io quantify regional tung ventilntion (LY}. We have developed a new approach which enable us to quanti~ simultaneously LV and lung pedusion (LP). The results obtained where compared with the study o! ventilation mechanic~ performed with body plethismographF (BP). We ~tudied 22 sub)ec~s, 12 e and 4 o, with =51, 10 olthem with chronic obstructive lung disease (CFJLD). 6 w~h chronic red,dive lung disease (ORLD) and 6 normats volunteers. Thex where ~ubmited to LV study with 133Xe (10 me_,i),followed bF LP study with 99mTc,MAA (2 mC~}. In the 10 patient~ with C~)LD the LV study was pedormed twice, before and after bronchediln~ion (BD - tenoterol in aerosol, 0.4 mg). The LV dn~a acquis~ion was dilmmic. 10s/frame. 90 trames. The LP acquisition was.static, 120s. We used a 64x64 mMvi~in both ~tudies. We developed software to be able to qu;mtify the global and regional lung 133Xe trnnsit time (FT) and clenrance (C'), at the same time obtaining two fun~onal images in which the different celour map corresponds to dRerent -i-r aridC. Finally we regresented in a 4 gaJ'nmeter disgl~ the combined r~uff~ ot LV and LP.In the normal subje~s we |ound TT=28-48s and C=O.00~t-O.0O3/s.Ot the 10 ¢__,T_~LDpatients we found prolonged TI- (5~t-753;) with slewed O (0_001-0.019/s): in 7 of them there was signifi~.nt -improvement a~terBD. due to reaionai changes o! various degree. In the 6 CRLD patient-~the 13- and C values where ~Jightlv changed in ~mpari~on with normais (TT=50-g0s, O=0_O0B-0.018/s). By comparing the patients LV ~nd BP stuctie; we found they matched well, the LV with 133Xe being mere sensitive and a!;m~ng a ;egiona! quantification of |he pathological clm~ges a s well a s the response to the !armacologica!intewentiom
396 M. CANPANA, M. BACCEGA, G. PICCIOTTO, R. ROPOLO, T. VARETTO, P.G. DE FILIPPI
S e r v i z i o di M e d i c ± h a N u c l e a t e . Ospedale Molinette. Tot±no. R O L E O F GA-67 CHEST SCANNING IN A I D S PATIENTS
MEASUREMENT OF NASAL MUCOCILIARY FUNCTION IN MAN WITH DIFFERENT RADIONUCLIDE LABELLED PARTICLES.
Mean transit velocities of a radioactive droplet (SDI; 3mCi/ml of lO-lOOum 99mTc-HSA macroaggregates) were calculated in 15 healthy volunteers (38.7±13.9 years ; range i~-62). The site of deposition was i cm behind the head of the inferior left turbinate. Serial acquisition with a gammacamera (twenty 80-sec. 64x64 frames) allowed to follow up the course of the labelled particles and to determined mean velocities (mm/min.) owing to several regions of interest (3 to 6) according to the formul a v =AI/At, where AI = Ap.f = pixel difference multiplied by calibration factor and At = transit time difference between two regions. Especially at the beginning and at the end of the course, inhomogeneities in the translation velocities were observed. Mean velocities determined in the middle horizontal part of the droplet course were : 7.0±1.2 mm/min. It was verified that this result was indeDendent of age : r = 0.17, N.S. (one subject with v = 15.i mm/ min was excluded from the study). In 4 subjects a double labelling was used (99mTc-HSA macroaggregates 3mCi/ml + 1Sl-I HSA 0.08 mCi/ml). No significant difference in transit velocities were found: 7.6±0.9 mm/min.
The role of G a - 6 7 chest s c a n n i n g in AIDS patients suspected of p u l m o n a r y o p p o r t u n i s t i c infections or n e o plasms may be discussed, concerning d e l a y e d or n e g a t i ve g a l l i u m accumulation caused by leucopenia. 37 G a - 6 7 scans of the chest were p e r f o r m e d in 28 AIDS p a t i e n t s (mean age 34: range 18-46) with fever and/or r e s p i r a t o r y symptoms. 3 p a t i e n t s h a d Kaposi sarcoma(KB] G a l l i u m scans were p e r f o r m e d at 24 and ~ S h after i n t r ~ venous a d m i n i s t r a t i o n of 5mCi (185 ~Bq) of Ga-67 citrate. W h e n e v e r possible, v i e w s of a b d o m e n and pelvis were also obtained. G a l l i u m s c a n s were compared retros p e c t i v e l y with chest radiographs. 17 out of 37 scans were abnormal. Only in 5 oases r a d ~ g a l l i u m d i s t r i b u t i o n was correspondent to chest r a d i o graphy. In the three KS p a t i e n t s chest radiography was negative; two patients showed positive g a l l i u m scan. 20 p a t i e n t s were negative b o t h at scanning and radiography. ~hus, g a l l i u m scanning seems to be more sensitive than radiography for initial d i a g n o s i s of pulmonary infections or neoplasms in AIDS patients. D e l a y e d or n e g a tive g a l l i u m a c c u m u l a t i o n seems to have a poor p r o g n o stic value.
498
397
398
S. Solfane]li, P. Fozzi, A.M. Singer*, A. Ionni * * ,
I'I. Frediani.
B.Karanfilski,O.Vaskova,V~Bogdanova,V.Cvetanov
C.N.R. Institute of Clinical Physiology of Piso, * Service of Morbid Anatomy $.Chiaro Hospital of Pisa, * * Section of Thoracic Surgery, University of Pisa. Pisa - Italy
Dept.of Pathophysiology and Nuclear Medicine,Medical faculty,Skopje,Yugoslavia
67-0A IN PULMONARY ,.~RCOIDOSI5. A METHOD FOR HEASUREt'IENTOF 67-BA ACTIVITY IN PERIPHERAL LYMPH NODE
EVALUATION OF PULMONARYEPITHELIAL PERMEABILITY IN PATIENTS WITH ASBESTOSIS
A 26 years old woman (bedy-weight=53 Kg) wlth erythema nodosumand chest x-ray showingenlargementof hiiar and mediestinumlymph nodeswas injectedby 5 mOl of 67-0a citrate.Totalbody scan performed at 48 hrs. and 96 hrs. with a large fieldcamera (photopeak=93 KeY,W=20% collimator =ME, counts registredfor imegec=4OOK on NMB Kodak film) pointed-out a thoracic abnormal' uptake corresponding to mediastinum and both hila. Moreover a furter uptakewas revealedin leftsupraclavicularregion.In this regionIO0 hrs.after injectionof 67-0a a biopsywas performed and a lymph node was removed. A lymph node scan was immediately performed by the same camera collecting1200K counts for 1000 seo. on film. To assess the absence of 67-GB uptake in supreclavicularleftregiona thoracicscan at 148 hrs. was performed. The photodensitometricanalysisof the images (thoracic scan beforeand afterbiopsy- lymph node scan)and the histologicalresponse produced these results:a) lymph node size :1.2 x 0.8 x 0.5 ore.b) lymph node weight: 64 rag.,c) 67-0a activity in lymph node at 100 hrs. = 1.2 microCi, d)histolegicalresponse = pulmonary sarcoidosis. These results. confirms the utilityof 67-Ga for the study of the pulmonary sarcoidosis 'because it is possibleto find peripheral region For easy biopsy and control the activityof the disease,moreover we have estimate the 67-0a specific !activity(microCilg) containedin a lymph node (20 microCilg) is 200 times the activity injected (0,I microCilg) to confirm the 67-Ga uptake in inflammatory tissue with ]ong-lasteningpersistence.
399 F.Rogowski, L.Malinowska, A.Citko, E .3 ar os ze w i c z
The rate of absorption of dietylene triamide pentaacetate labeled with technetium(99m-Tc-DTPA)from lung to blood was measured a f t e r i n h a l a t i o n of aerosol using Mallinckrodt Ultra-Vent-system.For c a l c u l a t i o n of the clearance of 99m-Tc-DTPA,the lungs were imaged using the gamma camera. The h a l f time clearence was measured in 17 asbestos exposed subjects(from 3 to 14 years)and 21 normal c o n t r o Is. The results are sumarised in the f o l l o w i n g t a b l e : n Asbestos exposed subjects 17 Control subjects 21
Clearance of 99m-Tc-DTPA(T I / 2 ) Mean value From-to
56,0 min.
23-95 min.
81,7 min.
p 0,05 55-105 min.
Presented results indicated increased pulmonary epithelial permeability in asbestos exposedsubjects. In 10 cases there was not clinical and radiological evidence of asbestosis.
400 A.Siemi~tkowski,
Department of Nuclear Medicine and Department of Anaesthesiology, Medical Academy, Bialystok, Poland
SOME BIOCHEMICAL MARKERS OF ADULT RESPIRATORY DISTRESS SYNDROME (ARDS)
The aim of the study was i n v e s t i g a t i o n of the choosen metabolites of arschidonic acid and serotonin which play r o l e in pathegenesis of ARDS. Using RIA k i t s , the levels of leukotrien B4-LTB4 (Amersham,England), C4-LTC4 (NEN, USA), thromboxane B2-TXB2 - as a metabolite of TXA2, prostaglandine 6-keto-PGFl~- as a metebolite of prostacycline ( I . I . , H u n g a r y ) a n d serotonin-SHT (DRG,USA) were measured. The concentrations of studied substances were determined in p l a t e l e t - r i c h plasma of four patients with ARDS during the period from the onset ( a f t e r the m u l t i p l e trauma) to the 6th day of h o s p i t a l i s a t i o n ( i n 24h i n t e r vals); of two patients with r i s k of ARDS ( a f t e r oesephagectomy) and 1Z healthy persons serving as controls. The obtained r e s u l t s showed no s i g n i f i c a n t changes of leukotrienes'concentrations in a l l studied groups. The T×B2 and 6-ke±o-POFl~concentrations in both groups were 2 - f o l d higher than in controls and did not show time-dependent changes. The decreasing tendency of 5HT level, f o l l o w i n g i t s increase on the f i r s t day, lasted t i l l p a t i e n t ' s death. But during the recovery in both groups we observed the increase of 5HT concentrations from low to normal. The increased levels of 5HT and TXB2 ere probably the result of platelets'activation but augmented level of 6-keto-PGFl~may indicate the slight injury of endothelium, characteristic of ARDS.
S.J.Oldenbur~1,R.A.de Vries2,M.de Bruin3,Th.Thelosen ] F.W.J.Huijgen'and A. van de Wiel 2. I) Dept.of Radionuclide Techniques,University of Utrecht, Utrecht,The Netherlands. 2) "De Lichtenberg" Hospital,dept of Internal Medicine, Amersfoort,The Netherlands. 3) Interfaculty Reactor Institute,Technical Univ.of Delft Delft,The Netherlands. A NEW METHOD TO STUDY TWO RED CELL POPULATIONS WITHIN ONE INDIVIDUAL BY DOUBLE LABELLING AND USE OF A GE-DETECTOR. Until now no reliable technique was at h&ud to study survival times of two different populations of red cells, e.g. autologous and homologous,within one individual.For this purpose a double labelling technique was developed, using radioisotopes with identical chemical characteristics and behavieur.Application of a semiconductor detector with high energy resolution and detection efficiency enabled us to meastu~e more than one radionuclide at once, down to low activity levels(0,O09 Bq/ml).In vitro investi gations led to a labelling procedure with Co-57,Co-58 and tropolone as a mediator.Stable and neutral Co-complexes could be prepared,which have been incorporated in the erythrccytes up to 80 %.In order to optimize the labellin efficiency various parameters like incubation temperature and time and composition of the incubation medium have been investigated.The method was also tested in vivo by studying,within one individual,the survival of two identical samples of red cells,labelled with C0-57 and Ce-58 respectively.No difference in lifetime between both label could be observed,which indicates the identity of both labels.The low activities injected caused the radiation dose to be less than 10 ~Sv.A comparative study,carried out simultaneously with Co-57 and Cr-51 ery's,showed a good agreement of the survival behaviour.It can be concluded thai this method may be well applied to study the survival of two red cell populations simultaneously within one individual.
499
401
402
B.Jsnsson,
B.Berg,
A.Shanwell,
Pharmacy Department, Blood and D e p a r t m e n t of H o s p i t a l Huddioge Sweden.
University
EVALUATION AND S T O R E D
L.Svensson
Transfusion Physics.
Hospital,
S-141
Service
86 H u d d i n g e
OF P L A T E L E T S P R E P A R E D BY A P H E R E S I S FOR FIVE DAYS: IN VIVO S T U D I E S .
At p r e s e n t p l a t e l e t s are i n d i s p e n s a b l e blood c o m p o n e n t s w i t h i n most blood t r a n s f u s i o n services. P l a t e l e t s a p h e r e s i s (PA) u n i t s p r o c e s s e d with an open s y s t e m c a n n o t be s t o r e d for more than 24 hours. However, using a blood cell sep a r a t o r with a " c l o s e d s y s t e m " the s t o r a g e time is five days. The aim of the p r e s e n t study was to make a comp a r i s o n of the q u a l i t y of fresh PA and units stored for five days. In viva s t u d i e s were c a r r i e d out with In-111 l a b e l l e d s u t o l o g o u s p l a t e l e t s in e i g h t v o l u n teers. We used p a i r e d c o m p a r i s o n s between fresh and stored PA from the same blood donor to study in viva s u r v i v a l of a u t o l o g o u s l y t r a n s f u s e d platelets. PA with 100 ml plasma a d d e d were s t o r e d in two 1000 ml c a p a c i t y c o n t a i n e r s (PL 732) at 22°C d u r i n g a g i t a t i o n . P l a t e l e t s from one of the con. tainers were l a b e l l e d with In-flfll and r e i n f u s e d into the v o l u n t e e r w i t h i n 24 h. P l a t e l e t s from the other c o n t a i n e r were l a b e l l e d a f t e r five days of s t o r a g e and r e i n f u s e d into the same donor. There were no s i g n i f i c a n t d i f f e r e n c e s between PA s t o r e d for one day c o m p a r e d to five day~ Mean p e r c e n t a g e r e c o v e r y was 58.4 % and 57.6 %, T½ 69 h and 67 h, s u r v i v a l time 5.5 days and 5.6 days,
S. Savolainen, M.T. Syrj~1~, K. Liewendahl, J. Grlpenberg and U. Nieminen
respectively.
403 Z. Ma§trovi6, N. Topuzovic , V, Ivan~evid, B. Ugarkovid, D. Ivan~evi6 Clinical Hospital Center Zagreb, Department of Nuclear Medicine Ceneral Hospital Osijek, Department of Nuclear Medicine* Yugoslavia EVALUATION OF THE SCINTIGRAPHIC DYNAMICS OF HEPATIC HEM~ANGIOMAS BY PERFUSION, PLANAR SCINTIGRAMS AND ECT The aim of our study was to investigate the hemodynamic behaviour pattern of hepatic hemangiomas and to evaluate the scintigraphic diagnosis in order to rationalize the scintigraphic procedure. Scintigraphy was performed with 740 MBq of 99mTc-labeled red blood cells. The dynamic perfusion study (90 sec), early planar scintigrams (EPS) (up to 30 min) and emission computed tomography (ECT) (at least 2 hours post injection) were performed. All of the 13 patients were examined by ultrasound, 8 of them had CT finding, 9 of them colloid scintigraphy and 3 angiography. Not a single lesion in our series exhibited hyperperfusion. Hypoperfusion was observed in 4 patients with lesion size 7-12 cm. Smaller lesiond could not be distinguished from the surrounding hepatic tissue. On EPS 8 lesions (2,5-8 cm) in 7 patients were "hot". Four lesions could not be identified. Three lesions (7-12cm) exhibited mixed pattern - with "hot" and "cold" areas. Thirteen lesions (2,5-8 cm) in i0 patients were "hot" on ECT, while 3 lesions (7-12 cm) exhibited mixed pattern. Our results seem to confirm that scintigraphy is the method of choice for hepatic hemangioma diagnosis. Unlike most authors, we could not confirm the miss-match pattern of the EPS and delayed scintigrams, since we found ii out of 16 lesions to be "hot" already on EPS. This allows a substantial reducing of imaging time.
Department of Clinical Chemistry, Division of Nuclear Medicine, Helsinki University Central Hospital Haartmaninkatu 4, SF-00290 Helsinki, Finland COMPARTMENTAL ANALYSIS OF PLATELET KINETICS In-111-1abelled platelets were used for studying platelet kinetics in patients with idiopathic thrombocytopenic purpura (ITP). Dynamic gamma camera imaging was performed in 43 ITP patients and time-activity curves were analysed by three methods: two-compartmental model (1), three-compartmental model (II) and two-exponential curve fitting of the inverted splenic curve (Ill). Method I could be applied on data from 39 cases: the mean rate constant from blood to spleen (Kbs) was 0.184 (i 0.014) I/min and from spleen to blood (Ksb) 0.075 (± 0.007); there was no significant difference between rate constants from patients With a positive or negative test for platelet-associated autoantibodies (PSIFT = platelet suspension immunofluorescence test). Method II could be applied on ~8 cases only: mean Kbs 0.141 (± 0.010), Ks b 0.059 (± 0.007), Kbl (blood to liver) 0.218 (± 0.054) and Klb 0.255 (± 0.088); there was no significant difference between rate constants from patient with positive or negative PSIFT. Method Ill could be ap~lied on 35 cases: the half-life for the fast component ~f the splenic curve was 2.5 (± 0.2) min and for the slow component 16 (± 2) mln; in patients with a positive PSIFT the half-life for the slow component was significantly longer than in patients with a negative test 11 ~ 2 min vs. 25 ~ 4 min, p < 0.01). Conclusion: fitting a two-exponential function to the inverted splenic time-activity curve provides a more useful approach to the analysis of pathological platelet kinetics than the compartmental models.
404 A.Tarkowska,
J.Zaorska-RaJca,
J.Roli6ski,
Z.Rupniewska. D e p a r t m e n t of N u c l e a r M e d i c i n e , A c a d e m y in Lublin, P c l a n d
Medical
B O N E SfilNTIGRAPHY AND BONE M A R R O W IN M A L I G N A N T LYMPHOMA.
SCINTIGRAPHY
The aim of the study was to c o m p a r e the value of bone s c i n t i g r a p h y and bone m a r r o w s c i n t i g r a p h y in e v a l u a t i n g o r g a n i n v o l v e m e n t in m a l i g n a n t lymphoma. The study was p e r f o r m e d in 29 adult p a t i e n t s w i t h g e n e r a l i z e d m a l i g n a n t lymphema, i n c l u d i n g 7 s u b j e c t s w i t h H o d g k i n , s d i s e a s e /LGR/, stage IV, 8 s u b j e c t s w i t h n e n H o d g k i n , s l y m p h o m a /Ly/, stage IV, and 14 subJects w i t h chronic l y m p h a t i c l e u k e m i a /LLC/. Bone i m a g i n g was c a r r i e d out w i t h ~ D P 99mTc. B&ne m a r r o w s c i n t l g r a p h y was p e r f o r m e d 7 - 14 days later, u s i n g n a n o c e l l 99mTc. N o r m a l bone s c l n t i g r a p h y was s t a t e d in 12 patients, i n c l u ding 5 p a t i e n t s w i t h Ly and 7 p a t i e n t s w i t h LLC F i f t e e n subjects h a d m u l t i p l e a r e a s of i n c r e a s e d ~DP 99mTc a c c u m u l a t i o n . Cold l e s i o n s were found in 2 patients. Five p a t i e n t s showed a d i f f u s e i n c r e a s e of M D P a c c u m u l a t i o n in the b o n e s w i t h very low s o f t - t l s s u e a c t i v i t y and a l m o s t invisible kidneys / " s u p e r s c a n " / . B o n e m a r r o w s c i n t l g r a p h y was n o r m a l in I patient. Hot spots were s t a t e d in 14 subjects. Cold l e s i o n s were found in 9 patients. T w e n t y - t w o subjects had s c i n t l g r a p h i c features of p e r i p h e r a l bone m a r r o w expansion. R e d u c t i o n of c e n t r a l bone m a r r o w was d e t e c t e d in 21 patients. The r e s u l t s o b t a i n e d suggest that bone m a r r o w i m a g i n g is s u p e r i o r to bone s c i n t i g r a p h y in e v a l u a t i o n of organ inv o l v e m e n t in m a l i g n a n t lymphoma.
500
406
405 CI. de LABRIOLLE-VAYLET x, A. PETIET, N. COLAS-LINHART, T. PHAM HUU and B. BOK. XService de M6decine Nucl6aire. CHU Saint-Antoine 75012 PARIS. Facult6 X. Bichat, Biophysique et H6matologie 75018 PARIS. FUNCTIONAL AND MORPHOLOGICAL LABELLED WHITE BLOOD CELLS.
STUDIES
OF
HMPAO-99mTc
The ability of labelled white cells to detect infectious foci is strongly related to their functional status. Therefore we compared in vitro mobility, adherence and oxidative burst of leukocytes labelled with Tc-99m HMPAO (140 MBq) and control cells. Spontaneous and attractant oriented locomotions were tested by the under agarose technique. A~herence assays were performed on plastic culture chamber slides. Oxidative burst was measured by the walue of the induced chemiluminescence. Labelling homogeneity was assessed using a microaudiographic method (MAR). Morphologic appearance was observed by electron microscopy (EM). Our results show no difference in chemotaxis and chemokinesis between labelled and control cells. Plastic adherence slightly decreases after labelling (average 80% of control). Stimulated chemiluminescence is slightly but not significantly decreased (average 83% of control). Heterogeneity of labelling was shown by MAR. No significant morphologic change was observed on EM. We conclude that the labelled leukocytes is functional activity is in vitro.
appearance of Tc-99m HMPAO not modified and that their not significantly impaired
407
Fortunate J S, Pinheiro M J, Rodrigues M A, Monteiro M C, Amaral I Centre de Fisiologia de Hemostase (INIC) and Dpts of Physiology and Nuclear Medicine, Oporto Medical School 4200 Porto-Portugal ACUTE EFFECTS OF A O R ~ I N E ON 11 IINDIUM PLATE-LET KINETIC AND BEHAVIOUR ON ANESTHETHIZED DOGS. REVERSION OF THFSE EFFECIS WITH A I H R O M B O X ~ - SYNTHESIS INHIBITOR.
Thrombotic-ischemic events can be triggered by adrenergic discharges during stress. Plt Kinetics and behaviour after repeated Adrenaline CAd) bolus injection in the upper abdominal aorta ( 80 and 40z~g/kg) were studied in anesthethized dogs previously injected with 1111n-labeled autologous Plt. Other groups of animals were injecIted with 20 mg/Kg of Indobufen (IBF) before (group 2) or after (group 3) the priming of Ad. I Dynamic studies were performed in a Gamma-Camera com puter-assisted. Arterial blood was collected before and {1,5,10 and 15 min after 111In-Pit or Ad Injections. 1111n activity wa~ counted in a Gamma-scintillation counter and formalin treated or untreated unlabeled Plt were counted in an automatic counter in order to evaluate Plt aggregation ratio (PAR). In IBF treated animals (groups 2 and 3) Ad effects on Plt in vivo aggregation and sequestration on portal intra an--dextrahepatic and splenic microcirculations were only partially inhibited after the priming Ad injection and reversed after further injections. Plt mobilization from sequestrating sites is blunted when cardiovascular effects of Ad are depressed by Phentolamine or loss of myocardial contractility, suggesting that reversion of Plt sequestration in IBF-treated animals depends on homodynamic factors also.
408 Kostadineva
A.Verrillo, A.de Teresa, C.Martino, G.di Chiara,A. Gattoni.
I n s t i t u t e of I n t e r n a l M e d i c i n e , II S c h o o l of M e d i c i n e , U n i v e r s i t y of N a p l e s , I t a l y .
I., Ts.Tsanev, St.Rilanov
Section "Radioisotope immunology",
Diagnosis and Radio-
Bulgarian Medical Academy
Sofia - Bulgaria IMAGING OF INFLAMMATION WITH 1111n-LEUCOCYTES AND
E F F E C T O F M E T F O R M I N ON T H R O t ~ 4 B O X A N E , B E T A T H R O M B O G L O B U L I N AND P L A T E L E T FUNCTION IN TYPE 2 DIABETES M E L L I T U S . Abnormalities of platelet aggregation and increased synthesis of the proaggregant and vasoconstrictor thromboxane A 2 ( T X A 2 ) have been implicated in the pathogenesis of diabetic microangiopathy. In 22 newly-detected type 2 (non-insulin-dependent) diabetic patients whose fasting s e r u m g l u c o s e l e v e l a f t e r 6 w e e k s of d i e t a r y t r e a t m e n t w a s not r e d u c e d to l e s s t h a n 8 . 0 m m o l / 1 , we s t u d i e d the r e s p o n s e of T X A 2 , b e t a - t h r o m b o g l o b u l i n ( B - T G L ) and p l a t e l e t a g g r e g a t i o n to m e t f o r m i n t r e a t m e n t . S e r u m d e t e r m i n a t i o n s w e r e done p r i o r to the t r i a l , a f t e r 6 w e e k s of d i e t a r y t r e a t m e n t , and a f t e r 6 and 12 w e e k s of c o m b i n e d d i e t a r y and m e t f o r m i n t r e a t m e n t . T X B 2 , the s t a ble m e t a b o l i t e of T X A 2 , and B - T G L w e r e m e a s u r e d by r a d i o i m m u n o a s s a y . W i t h n o r m a l i z a t i o n of blood g l u c o s e , TXB2 and B - T G L d e c r e a s e d s i g n i f i c a n t l y ( T X B 2 : 5 6 2 + 198 ng/1 at 0 w e e k s v s 289 + 166 at the end of the t r i a l ,P < 0 . 0 1 ; B - T G L : 1 6 5 + / ~ n g / m l v s 39+ 14, P < 0 . 0 2 ) . P l a telet aggregation responses did not improve during metformin treatment. Thus, a period of combined dietary and metformin treatment reduced T X B 2 and B - T G L ;however, the effects on platelet aggregation appear to be complex and other extraplatelet factors also seem to influence the aggregation response.
APPLICATION Of SUBTRACTION TECHNIQUE
Because of the normal biodistribution of Iabeied leucocytes in bone marrow, spleen and liver, sometimes it is difficuIt to interpret Ieucocyte scan /LS/, especially in cases of low grade activity infection, since images could superimposed. The aim of the study web, by the u ~ 1 o f routine method of imaging inflammation with In-oxine leucocytes, to apply subtraction technique after injecting ~VmTcsulfurcolloid, allowing simultaneous subtraction of the images of the organs of RES, depending of the localization of the suspicious area. lhe method consisted in two stages: the first included searching of inflammation in the body and LS end second O epenoing of the localization of the suspicious areaa ate D subtraction of the different organs of RES, to obtain an image, suitable for interpretation. Twenty pts were investigated, in 7 of whom it was difficult or impossible to interpret the rasult~ without appiing the subtraction technique. We concluded, that with the proposed method, the physician was facilitated in diagnosing of the inflammation.
501
410
409 Kostadin~va
I., S t . M i l a n o v ,
Ts.Teraieva,
Section "Radioisotope Diagnosis
l.Kurtev
and R a d i o i m m u n o l o g y '
Bulgarian Medical Academy, Sofia - Bulgaria
RAOIOISOTOPE
METHODS
SYNDROME
For
IN THE A S S E S S M E N T
IN P A T I E N T S
the a s s e s s m e n t
erythrokinstic labeling
of e r y t h r o p o i e s i s ,
marrow sointigraphy
in 17 patient~
d i f f e r e n t f e r r o - anO using oual
with 59Fe ann 51Cr. Bone
was c a r r i e d
out and s e r u m level~
of vit.B12 , folio acid and ferritin were d e t e r m i n e d blightly
Oecreasso
reO call's
volume ann iron turn-
over w e r e e s t i m a t e d and r e d u c e d u p t a k e of bgFe and 1111nC13
from bone marrow,
v i t . B 1 2 , as a whole, patients,
findings
as well. S e r u m level of
tenoeO to be dacreaseO.
The p o s a i O l e m e c h a n i s m s
were discussed.
oecreaseO
erythropoiesis,
of these
It was c o n c l u O e d ,
a n a e m i c s y n d r o m e in this kinO of patients
patients
In soma
the main d e s e a s e was c o m p l i c a t e o w i t h
iron o e f i c i e n c y .
complicated
with iron and v i t . U 1 2
of
Milano,
Istitutc
OF A N A E M I C
p a r a m e t e r s were followed,
of a r y t h r o o y t e s
I. T . B. A. - C. N. R . , University H. S. R a f f a e l e , Milano, I t a l y .
WITH MYXEDEMA
w i t h m y x e d e m a and 10 c o n t r o l s ,
C .Messa, F. Zito, C. Rossetti, F. Colombo, M. M a t a r r e s e , G. T a d d e i , E. D e u t s c h , G. L u c i g n a n i , a n d F. Fazio.
that was due to
in some
deffioiency.
411 P.O. KOTZKI I, E. DUVAL 2, J. VALMIER 2, F. BARNAY I,
Tc-99m d , I - C B - P A O : A NEW TRACER FOR CEREBRAl PERFUSION STUDIES : PRELIMINARY RESULTS IN HUMANS. Tc-99m c y c l o b u t y l p r o p y l e n e amine oxime (Tc-99m d , I - C B - P A O ) is a new h p o p h i l i c t r a c e r e a s i l y p r e p a r e d from a n i n s t a n t k i t in g r e a t e r t h a n 95% radiochemica] p u r i t y a n d which is s t a b l e in v i t r o f o r more t h a n h o u r s . T h e whole b o d y b i o d i s t r i b u t i o n of t h i s new t r a c e I was s t u d i e d in 3 normal v o l u J l t e e r s at 15 miu, 2 h alld h a f t e r a n i . v . b o l u s injection of a b o u t 13 mCi of Tc-99rc d , I - C B - P A O . V e n o u s blood s a m p l e s a n d u r i n e sample~ were collected. O r g a n u p t a k e s w e r e c o r r e c t e d f o r bod~ a t t e n u a t i o n b y t h e c o n j u g a t e c o u n t i n g t e c h n i q u e . In th~ same s u b j e c t s a p l a n a r d y n a m i c s t u d y u p to 10 rain p o s injection a n d a tomographic study at 1 h post a d m i n i s t r a t i o n were p e r f o r m e d . B r a i n u p t a k e is 4% of the i n j e c t e d d o s e w i t h i n 5 rain p o s t - i n j e c t i o n ; a b o u t 5~ d e c r e a s e in c e r e b r a l a c t i v i t y is o b s e r v e d b e t w e e n 15 rnin a n d 2 h p o s t i n j e c t i o n . T h e t r a c e r is r a p i d l y c l e a r e d from blood. A p p r o x i m a t e l y 30% of t h e i n j e c t e d d o s e is cleare( t h r o u g h t h e r e n a l s y s t e m w i t h i n 5 h , a n d 40% is clearec within 24 h . Tomogrraphic b r a i n images show a good definition of cortical a n d s u b c o r t i c a i c e r e b r a l s t r u c t u r e s . In c o n c l u s i o n , Tc-99m d , I - C B - P A O h a s a good b r a i n u p t a k e a n d i t s c e r e b r a l d i s t r i b u t i o n is s u f f i c i e n t l y stable to allow SPECT s t u d i e s . T h i s new t r a c e r m a y p~ovide u s e f u l r e p l a c e m e n t f o r Tc-99m d , I - H M - P A O .
412 B. L. PHILIPPON, R. CHACORNAC, M. MONTARRY, R. KAYAYAN
M. ROBSI I, M. BALDY-MOULINIER 2 . 1 - M6decine Nucl6aire, HSpital Lapeyronie, Montpellier, FRANCE. 2 - Exploration du Byet~me Nerveux, HSpital GuideChauliac Montpellier, FRANCE.
Neurological Hospital and Nuclear Medicine Center 53 Bd PINEL, 69003 LYON - FRANCE -
THE INTEREST OF SEMIQUANTIZED SPECT-HmPAO APPLIED TO THE ASSESSI~NT OF PARTIAL EPILEPSY
EFFECTS ON CEREBRAL BLOOD FLOW OF TWO CALCIUM BLOCKERS DURING SUBARACHNOID HEMORRAGE
The interpretation of the cerebral blood flow imaging in the field of partial epilepsy can be made easier by fits association to morphological data using a 3D craniostatic referential system (Kotzki and al, 1988) but also, iby a relative quantization which allows to define a norma lity threshold. We have developped an automatic and semiquantitative methodology to analyze relatlve flows. Once ~econs~rueted 5 slices of 18 mm thickness are generated from a frontooccipital plane of reference. Except for the cerebellum, each of these slices is automatically divided into 7 symetrieal right/left regions of interest. A normality threshold for each ROI, always below or equal to 5 % of asymetry, was evaluated from 25 control subjects, without previous history. A second population of 16 epileptic subjects was analyzed. 15/16 showed at least one hemodynamic abnormality (low blood flow and/or abnormal asymetry index), whereas only 8 patients had shown abnormalities with CT. No subject is showing an HMPAO hyperfixation during the intercritic period. For ii of them the low flow is correlated to the EEG localization epileptic focus. In conclusion, semiquantized SPECT-HmPAO appears to be usefull to the assessment of partial epilepsy. Kotzki P.O. and al (1988), Confronting of morphological (MRI) cerebral images with functionnal ones (CBF with HMPAO seintigraphy : methodological aspects. Eur J Nucl Ned 14:254.
36 measurements of rCBF were made on patients with subarachnoid hemorrage, before and after i.v injection o f O.l mg/kg of Nicardipine (n = 18), or 0.03 mg/kg of Nimodipine (n = 18). Action on CBF of Nicardipine is studied lO mn after injection, and lO and 30 mn after i.v, for Nimodipine. CBF variations were compared with results of a reproducibility test, performed on 19 PR!ND !or CS patients in the same conditions. CBF measurements were conducted by the 133 Xe inhalation method (IBI), with a double-headed gamma camera and high efficiency collimators. No variations are enregistred for pC02, and only for Nicsrdipine, a significant decrease for arterial ~ressure (- ll %). Mean hemispheric CBF were in all cases ~ithout variations (i.e 38.4 sd 9.6 before, and 39.0 sd 8.5 after Nicardipine). We can observe a significant increase (Bonferroni test) on the most oligaemic area of the 2 hemispheres, after Nieardipine or Nimodipine : mean percentage of variation of these areas is + 28.7 % (sd 25.8 %) with Nicardipine, and + 18.2 % (sd 19.3 %) with Nimodipine (only 30 mn after injection), variations highly significant by comparison with variation of most oligaemic area in reproducibility test (- 1 . 1 % sd 9.5 %). The hemodynamical effect of these two calcium blockers is of type "inverse cerebral steal", and a likely confirmation of anti-vasospasm action.
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J. L. Lear* & R. F. Ackerrnann *Division of Nuclear Medicine (A034), University of Colorado Health Sciences Center, 4200 E. 9th, Avenue, Denver, CO 80262 USA and Division of Nuclear Medicine and Biophysics, UCLA School of Medicine, Los Angeles, CA
EVALUATION OF RADIOLABELED ACETATE AND F L U O R O A C E T A T E AS T R A C E R S OF CEREBRAL KREB'S CYCLE M E T A B O L I S M Radiolabeled fluoroacetate (FACE) and acetate (ACE) have been I suggested as tracers of Kreb's cycle metabolism in manners analogous to the use of deoxyglucose (DG) and glucose as tracers of glucose metabolism (LCMRglu). FACE is metabolized to fluorocitrate in the ftrst step of the Kreb's cycle, but because fluorocitrate is not a substrate fo~ aconitase, further metabolism is negligible. Radiolabeled ACE is i metabolized through the Kreb's cycle to CO 2, but the radiolabel is temporarily trapped in intermediate pools. We compared the rates of cerebra) accumulation of i4C-labeled FACE and ACE with LCMRglu measured simultaneously with ISF-FDG in awake rats using dual tracer quantitative autoradiography. Both FACE i and ACE crossed the blood-brain barrier. Metabolic uptake of FACE by the brain, however, was found to be undetectable, even through 2, hours. Metabolic uptake of ACE by the brain was significant by 10 minutes, but its rate of accumulation was less than 10% that of FDG. I Metabolic images of ACE, corrected for CO 2 loss, were qualitatively similar to FDG, but different patterns were found in some structures, i The very slow rate of ACE uptake probably results from low activity of acetyl thiokinase (the enzyme which converts acetate, to acetyl CoA) I relative to pyruvate decarboxylase (the enzyme which converts the natural substrate, pyruvate, to acetyl CoA). This observation, that the rate of acetate uptake may be more closely related to regional acetyl thiokinase activity than LCMR~Iu, has profound implications in the use I of radiolabeled acetate to trace Kreb's cycle metabolic rate. While ACE I uptake has been shown to reflect oxidative matabolism in the heart, it] does not appear to be useful in the brain. |
J 415
FJ M e n a , YC Chou, J Kuperus, Thompson, K Garrett and I Mena.
S Read,
B Miller,
C
Division of Nuclear Medicine and Department of Neurology, Harbor-UCLA Medical Center and John Douglas French Center for Alzheimer's Disease, Torrance and Los Alamitos, CA. Tc99m-I~4PAO IN A L Z H E I M E R ' S D I S E A S E (AD): Sm~IQE~NTITATIVE P~%FUSICN WITH BE~EVICR.
CCRRELATIGN
OF
Behavioral pathology in (AD) was correlated with brain SPECT perfusion imaging. 22 AD patients (pts), 8 m a l e s and 14 females (45 to 87 years), were compared to 4 controls (65 to 78 years). Two hours after IV injection of 20r~i of HMPAO, SPECT 1 cm. thick brain images were gathered in the sagittal, coronal and transaxial views. A modified circtm~ferential profile of the average counts/pixel (c/p) determined at 6 degree intervals was examined in the six medial sagittal cuts. Data were normalized to cerebellar c/p. Extension of Hypoperfusion (Hp) (abnormal cuts/normal cuts) and severity of Hp (standard deviation (SD) of mean c/p /SD normal c/p) were determined. HP of Inferior Frontal (IF) occurred in 19/22 pts, Superior Frontal, 4/22 pts, Parietal, 20/22 pts and Temporal (TP) 14/22 pts, with correlation of extension versus severity of .82, .93, .93 and .63 respectively, denoting a high degree of internal consistency of the data. 4 psychological tests were correlated with Hp. At low dementia severity (Mini-Mental State (MMS) =24--+3, N= 7), TP correlated with MMS r .61 and IF with Behavior scale of aggression .49. In the total population: (MMS 28-0), Parietal lobe showed correlation of HP with MMS and behavior aggression scale at .60 and .61 respectively. Tc99m-HMPAO quantitative brain SPECT provides high resolution images with modest correlation to clinical behavioral scales.
416 . .... , • ** ** ** BAYHAN,H. ,0ZGUVEN,M.A. ,NADERI, S., ERDO~AN,A., EGI~M~, N.
E. SALMON, B. SADZOT, G. FRANCK
• G.M.M.A. Department of Nuclear Medicine • * A.U. Avi Cenna Hosp. Department of Neurosurgery
University of Li%ge EVALUATION OF VASOSPASM IN PATII~qTS WITH SAH USING SPECT,CT, DSA AND SEP. HAEMODYNAM/C AND METABOLIC VARIATIONS OBSERVED WITH POSITRON EMISSION TOMOGRAPHY DURING PARTIAL STATUS EPILEPTICUS IN ALZHEIMER'S DISEASE. Ahheimer's disease is a degenerative dementia whose anatomopathological lesions have first been described in cortical areas, mainly in the associative cortices, but are also observed in a lot of subcortical structures. Numerous studies pointed to a decrease of cerebral blood flow and metabolism in those cortical regions where histological lesions are found. Clinically, different associations of symptoms exist in Ahheimefs disease, and epileptic seizures are not unfrequent. We report the case of a patient with moderate to severe dementia of the Alzheimer's type whose clinical status suddenly worsened with the apparition of epileptic Grand Mal seizures. They were followed by a prolonged obnubilation and electroencephalographic recordings demonstrated a diffuse slowing of background rythms, with generalized slow spikes and intermittently, bilateral anterior discharges of slow spikes predominant on the ;ight side. The CT scanner showed a slight generalized atrophy. With positron emission tomography and the steady-state 15-oxygen method, a decrease of the regional distribution of cerebral blood flow and metabolism was demonstrated in the temporo-parietal associative cortices. But there was a relative increase of the perfusion and oxygen consumption in the internal frontal and right fronto-central areas, corresponding to the EEG abnormalities. The regional blood flow and metabolism remained coupled, oxygen extraction ratio beeing unchanged. This observation demonstrated that neurons in Alzheimer's disease are still able to increase their oxygen utilization. It remains to be determined if the cellular metabolic abnormalities in Ahheimer's disease can be responsible per se of the advent of epileptic discharges.
Before SAH (Sub-Arachnoid Hae~orrhage) surgery,it is important to evaluate the cerebral tissue having a borderline perfusion.Vasospasm naturally occurs as a defensive mechanism to limit the haemorrhage. But if surgery is applied to such poorly perfused regions,paralysis arise post-operatively as a result of surgical trauma. 60 % of cerebral vasospasm,secondary to SAH, can be detected angiographieally. But 30 % can only be determined clinically and they have normal ranged angiographic findings. To improve the vasospasm detection percentage in SAH patients, Tc 99m HM PAO Brain Perfusion SPECT (Single Photon Emission ComJputurised Tomography) is applied to 12 patients ( 6 male, 6 female) with SAH at ages from 9 to 60,pre-operatively. CT (Computurised Tomography), DSA (Digital Substraction Angiography) and SEP (Somato-sensorial Evoked Potentials),are also performed with in one to two days and all the results are correlated in terms of vasospasm detection. SAH is diagnosed in all patients with CT,but only one patient had ischemic findings that could be related to vasospasm.Nine out of twelve patients had vasospasm in their DSA findings which were i00 % correlated with their SPECT results.However,the remaining three patients had also perfusion defects in their SPECT findings, well-confirmed with their clinics,although their DSA's are nega tire. SEP tests were well correlated in five of twelve patients but were negative in seven. CT, should only be used for the diagnosis of SAH and is not valuable to screen the perfusion changes especially in acute phase. Perfusion defects were found in the SPECT of three patients hay ing normal DSA's.Vasospasm was clinically confirmed in these patients.The value of SEP in diagnosing vasospasm is doubtfull unless supported by some other tests. Brain Perfusion S P ~ seems to be the favorable method in diagnosing and following cerebral vasospasm as being non-traumatic,non-invasive,non-allergic,cheap, practical,reproducible and more sensitive.
503
417
418 F. GrOnwald, H. SchrOck, H. Theilen, and W. Kuschinsky
B.L. PHILIPPON, R. KAYAYAN, N. NIGHOGHOSSIAN, C. HOUZARD
Neurological Hospital and Nuclear Medicine Center 53 Bd Pinel, 69003 LYON - FRANCE -
Department of Physiology and I n s t i t u t e f o r C l i n i c a l and Experimental Nuclear Medicine, University of Bonn, Fed. Rep. Germany
A SIMPLE METHOD OF QUANTIFICATION OF CBF HMPAO TOMOGRAPH' USING 133 Xe AND A GAMMACAMERA
CHRONIC NICOTINE ADMINISTRATION ALTERS LOCAL CEREBRAL GLUCOSE UTILIZATION.
A simple (but approximate) solution in quantification of cerebral blood flow (CBF) SPECT realized with 99m Toq~P# has been tested, using a double-headed rotating gamma camera (Siemens). Two consecutive acquisitions are made l- a non-tomographical CBF measurements of the two profils, by 133 Xe inhalation, with 2 high efficiency collimators, and calculation of the initial slope index (ISI-ml/mn/lO0 g). 2- a SPECT/HMPAO acquisition with standard collimators. Sagittal slices are regrouped in two pseudo~profils, a ~ correction of the attenuation difference between 80 and 140 Key. These profils are compared with 133 Xe profils, for calculation of the conversion factor between the activity/pixel (HMPAO) and CBF-ISI (133 Xe). The factor is utilised for the "quantification" of regional activit in HMPAO slices. For obtention of realistic values of regional CBF on HMPAO slices, a post-reconstruction deconvolution (with effective FWHM correction) is necessary. Thus for a normal subject~ ~he HMPAO-measured values in grey matter were 75-100 ml/mn/ lO0 g, and 25-30, in white matter, as visible on the figure.
419
LCGU was measured in 45 regions of the r a t brain during chronic n i c o t i n e infusion using the 2-deoxy-D(1-C-14)glucose method. Osmotic minipumps, f i l l e d with i - n i c o t i n e , were implanted 14 days before the measurement of LCGU. The infused dose of 12.5 pg/kg/min resulted in a plasma nicotine concentration of 77+17 ng/ml. One day before the LCGU experiment spontan~us locomotor a c t i v i t y was reduced s i g n i f i c a n t l y . LCGU showed a s i g n i f i c a n t increase in 6 structures: brain structure: LCGU increase: globus p a l l i d u s I0 % septal nucleus 20 % l a t e r a l geniculate body 9 % superior c o l i i c u l u s 33 % interpeduncular nucleus 30 % optic chiasm 19 % These results are p a r t l y congruent with previous data of our group obtained during acute n i c o t i n e infusion. C6nclusion: Chronic nicotine infusion has d i s t i n c t effects on the functional a c t i v i t y of several brain structures which are p a r t l y congruent with those affected during acute nicotine infusion and p a r t l y d i v e r ging from them. These findings may contribute to understand more detailed mechanisms of chronic nicotine abuse in man.
420 K. Herholz, U. Pietrzyk, K. Wienhard, I. Neubauer, R. Wagner, W.-D. Heiss
U. Gebhardt. F. Sclmlau~, R. Zimmer *, G. Buttermann
Nuklearmedizinische Klinik und Psychiatrische K1inik (*), Technische Universit@t M(inchen, FRG ALZHEIMER'S DISEASE (AD): RELATION OF REGIONAL PERFUSION (rCBF) OF T c 9 9 m - H M P A O AND CLINICAL GRADING 18 AD-patients, classified by Mini-Mer,tal State Examination (MMSE) in mild (6), moderate (8) and severe (4) cases, were investigated by SPECT to evaluate the rCBF in these 3 stages. TI~e AD-patients were imaged 20-30 min. p. i. of 550 MBq Tc99m-HMPAO. Transversal slices reorientated in parallel to the orbito-meatal line were used for image analysis. Count ratios of cortical areas relative to the cerebe!lum (CR) were computed as rCBF- equivalent. All patients had complete psychiatric examination including CT. In control patients who had no signs of cerebral disease, the normal CR range was 1.00 _+0.12. In patients with AD, CR was reduced to 0.82-0,87 (mild), 0.80-0.85 (moderate) and to 0.68-0.80 (severe). These CR deficits were found in following regions; mild AD: I16 pts. only temporal, 2!6 pts. only parietal,216 pts. temp. and par, 0/6 pts frontal, 216 symmetrical deficits,but 116 pts. with normal CR; moderate AD: 818 pts. temp. and par-.,5/8 pts. frontal 418 pts. with symmetrical deficits; severe AD: 4/4 pts. temp. and par., 314 pts. occipital, 4/4 pts. frontal, all with symmetrical deficits.Reduced CR's were in good relation to the clinical grading of AD. Symmetrical reduction of CR temporo-parietal and the reduction in the frontal lobe were found more frequently in patients with severe AD.
Max-Planck-lnstitut fur neurologische Forschung and Univ.-Klinik fur Neurologie, Joseph-Stelzmann-Str. 9, D-5000 K~In 41, FRG EFFECTS OF INCOMPLETE TRACEREXTRACTION ON FOREBRAIN TO CEREBELLUM RATIOS IN MEASUREMENTSOF CEREBRALBLOODFLOW Cerebral blood flow (CBF) measurements with the diffusionlimited tracers O-15-water (H20) and PET or Tc-99m-HM-PAO (HM-PAO) and SPECT were comparedwith PET measurements using the freely diffusible inert gaseous tracer 18Ffluoromethane (FM). 20 patients with cerebrovascular disease, migraine or angiomas were studied in each series of paired measurements (H20 vs. FM and HM-PAO vs. FM). Absolute CBF values were on average 23.9 % lower with H20 than with FM and underestimation was most pronounced in high-flow areas (basal ganglia and areas with pathological hyperperfusion), as to be expected as a result of the incomplete first-pass extraction of H20. However, CBF underestimation was significantly less severe in cerebellum than in forebrain, in spite of comparable CBF levels: the forebrain to cerebellar CBF r a t i o was 1.01+0.14 (SD) with FM vs. 0.88+0.13 with H20. The ratio was even lower with HM-PAO (0.8~0.11). The findings can be explained by the high cerebeITar capillary surface area described in anatomical studies (Lierse, 1963) which tends to f a c i l i t a t e first-pass extraction of diffusion-limited tracers. In conclusion, forebrain to cerebellar CBF ratios, which are in commonuse for data normalization, must be regarded as method-dependent. Reference W.: Acta anatomica 54:1-31 (1963)
504
421 ..
422 *
*
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** ....
*
..
*
ZGLrfEN,M.A.,BAYHAN,H.,TANRIDA~,O. ,ONGEL,Q. ,OZTURK,E. ,GUNALP,B. • G.M.M.A. Department of Nuclear Medicine, •* G.M.M.A. Department of Neurology.
E SALMON*, B. SADZOT*, P. MAQLTET*, A. CAPON °, G. FRANCK* University of Liege* and University of Brussels°
EVALUATION OF THE VALUE OF SPECT IN APHASIA Pd~RIBILITATION, COMPARED WI~{ CT. Aphasic patients,secondary to a CVA (Cerebro Vascular Accident) were taken into therapy programs end their improvements were followed by CAT (G~MA Aphasia Test).The patients included in the therapy group were selected according to the size end the localization of the lesion seen with CT (Computurised Tomography).As the lesion was small end away from the related centers,the patients were expected to recover. However,some patients,although selected accor ding to the same parameters,did not respond and showed no clinical improvement. To find out the reason of this clinical situation,Tc 99m HM PAO Brain SPECT was applied to twelve patients ( 8 male,4 female ) being aphasic since 8 months to 2 years end had no improvement at aII.CT was also performed with in one to two days.The areas of CT and SPECT lesions are calculated by using computer analysis end planimetrie methods.SPECT (Single Photon Emission Computurised Tomography) results ware also quantified by comparing the total co unts of the lesion to the total counts of the eontrlateral,normally perfused cerebral tissue. SPECT lesions were found to be two to five times larger than CT lesions and by the way ~overing some related centers,which were thought to be outside the CT lesion.The localization of the lesions were I00 % correlatd in both procedures. SPECT seems to be at least complementary to CT,in choosing and following the patients to undergo aphasia therapy.In addition to the CT detectable,well-demarcated structural changes;there is also a borderline perfused cerebral tissue surrounding this area that can only be detected by brain perfnsion SHECT studies.
423 C.Wikkels~, L.Jacobsson, AC.Bergh, S.Lindberg. Departments of Neurology, Radiophysics and Clinical Physiology, section of nuclear Medicine.
SUBCORTICO-CORTICAL DEAFFERENTATION IN DEMENTIA FOLLOWING BILATERAL THALAMIC ISCHEMIA DEMONSTRATED BY POSITRONEMISSIONTOMOGRAPHY Thalamic ischemic lesions can produce mnesic, phasic or left-sided hemiattentional troubles and a homolateral cortical hypoperfusion or hypometabolism has been observed which is thought to correspond to subcortico-corticaldeaffemntafion. We report the case of a 66 year old patient who, after a brief episode of coma, evolved in 9 months to a dementia characterized by memory troubles with confabulation, unmotivation and excessive diurnal somnolence, attentional deficit, apathy or more frequently a manic appearance. There was an anosognosia. Several features suggested a frontal syndrome and were reminiscent of a "subcorticaldementia". The CT scan demonstrated isolated bilateral thalamic lesions in the territory of the paramedian thalamie artery, the midline nuclei and the dorso-medial thalamus, comprisingthe mamillo-thalamic tract and probably extending to the internal medullary lamina. Positron emission tomography with the [18F]fluorodeoxyglucose method showed a decrease of glucose consumption in both thalami, but it also revealed a hypometabolism in bilateral cortical frontal and anterior temporal areas when values were compared to those of age-matched volunteers (n=ll). The hypometabolism corresponded to the preferential cortical connections of the dorso-medialand midline nuclei respectively. This observation demonstrated the cortical metabolic repercussion of subcortical focal bithalamic lesions and suggested that the dementia syndrome of the patient resulted from bilateral interruption of the many connections existing between thalami and f~onmllobes.
424
Tampere
E-mail:
Regional distribution 9~ CBF in patients with dementia evaluated by 99mTc-Hexamethylpropyleneamine oxime (HM-PAO}. To e v a l u a t e t h e d i a g n o s t i c v a l u e of r e l a t i v e quantitation of C B F u s i n g S P E C T a n d H M - P A O in dementia 3 well characterized groups were selected; 7 patients with Alzheimers Disease (AD), a g e d 63±7 y e a r s (mean+SD), 7 w i t h multi-infarct dementia (MID~, a g e d 73±3 a n d 7 with normal pressure hydrocephalus (NPH), a ~ e d 68±14 years. T h e d e g r e e of d e m e n t i a w a s e s t l mated by mini-mental-state (MMS) score, ii v o l u n t e e r s w e r e u s e d as r e f e r e n c e . SPECT data collection was c~ried out following i.v. i n j e c t i o n of i000 M B q 9 ~ m T c - H M - P A O u s i n 9 a r o t a t i n g g a m m a c a m e r a (GE 400 A/T). A c q u i s i t l o n s w e r e m a d e d u r i n g 30 m i n r e c o r d i n g 64 a n ~ u l a r views using a 128x128 matrix. For quantltative Inalysis 5 t r a n s v e r s a l (in I O M plane) s l i c e s (5 )ixel each) w e r e c o n s t r u c t e d a n d s e m i - a u t o m a t i cally d i v i d e d i n t o 6 - o r 8 r e g i o n s . A c t i v i t y ratios b e t w e e n t h e r e g i o n s w e r e c a l c u l a t e d a n d n o r m a l i z e d to m a x i m a l c e r e b e l l a r a c t i v i t y . CBF in p a t i e n t s w i t h A D w e r e c h a r a c t e r i z e d by a high ratio between frontal and poster÷or reglons in I O M + b c m ( t h r o u g h t h e b a s a l g a n g l i a s) a n d io% ratios between posterior regions and the cereb e l l a r a c t i v i t y . M I D a n d N P H p a t i e n t s h a d in the 3 u p p e r s l i c e s l o w e r a c t i v i t y in t h e f r o n t a l anf c e n t r a l r e g i o n s c o m p a r e d to c e r e b e l l a r a c t i v i t y than v o l u n t e e r s a n d A D p a t i e n t s . T h e d e g r e e of ~ e m e n t i a e s t i m a t e d b y M M S c o r r e l a t e d to r e d u c e d ratio b e t w e e n f r o n t a l a n d c e n t r a l f l o w in t h e h e m p o r a l l o b s (IOM+2) a n d c e r e b e l l a r a c t i v i t y .
M.Koskinen, J . L a u n e s and
P.Nikkinen,
BULL'S
K.Liewendahl
University Central Hospital SF-33520 Tampere Finland [email protected]
EYE
DISPLAY
IN S P E C T
OF r C B F
A n e w c o m p u t e r p r o g r a m was w r i t t e n to e v a l u a t e the shape of H M - P A O d i s t r i b u t i o n in t r a n s a x i a l brain slices using so called bull's eye presentation. The environment of the p r o g r a m is a G a m m a 1 1 - 1 i k e s y s t e m w i t h V S V 0 2 - d i s p l a y . Brain was d i v i d e d into 9 s l i c e s and 12 s e c t o r s in the a n a l y s i s . A l o w e r t h r e s h o l d of 50 % was used to c h o o s e pure b r a i n t i s s u e for a n a l y s i s . Program displays 4 i m a g e s as a final result: segmental relative count image, an image of count ratios between symmetrical segments and then images where the discrepancy between actual values and the m e a n reference images w e r e shown in SD units. Reference material: 25 p a t i e n t s studied because of headache but interpreted sufficiently healthy.
mainly to be
Reference values: Relative c o u n t s v a r i e d from 48 to I 0 0 - - ~ SD of 6 - 18 % in different s e g m e n t s . Ratio v a l u e s r a n g e d from 0.97 to 1.07 w i t h SD from 0.05 to 0.27. C o n c l u s i o n : The r a t i o image u s e f u l in e v e r y d a y r o u t i n e .
has
proved
to be
505
425
426
L. P~vics,M.
Albert
Bodosi,T.
Szent-Gy~rgyi
DSczi,G.
Medical Hungary
BlahG,L.
Cserna
University,
Szeged
C O M B I N E D SPECT STUDIES OF R E G I O N A L C E R E B R A L BLOOD FLOW ( r C B F ) ( 9 9 m T c HM-PAO) ANO BLOOD VOLUM ( r C B V ) ( 9 9 m T e RBC) SPECT IN P A T I E N T S WITH ARTERIOVENOUS M A L F O R M A T I O N (AVM) The m a n a g e m e n t of 7 p a t i e n t s with c e r e b r a l AVM is reported. In 5 o n e - s t a g e and in 2 t w o - s t a g e e x t i r p a t i o n of the AVR was p e r f o r m e d s u r g i c a l l y 15 c o m b i n e d rCBF and rCBV SPECT examinations were p e r f o r m e d before and after the s u r g i c a l int e r v e n t i o n to detect the haemodynamic alterations. In all cases the AVH was r e c o g n i s e d on the rCBV images, in good a g r e e m e n t with the results of the X-ray a n g i o g r a p h y . In the region of AVM, the rCBF SPECT studies revealed a large area with decreased activity in 2, a less Jronounced defect in 4, and no a b n o r m a l i t y in i )atient. On the p o s t o p e r a t i v e c o n t r o l images no ~athological s t r u c t u r e s , with i n - c r e a s e d blood volume were detected. With the e x c e p t i o n o~ one patient, the a c t i v i t y defects were g r e a t e r than p r e o p e r a t i v e on the rCBF SPECT. The findings were c o r r e l a t e d well with the c l i n i c a l s y m p t o m s and signs of the patients. C o n c l u s i o n s : The AVM ~ere clearly visualised on the rCBV SPECT zmages, and with this non-ivasiv method it is ~feasible to check the e f f i c a c y of the s u r g i c a l treatment. On the rCBF images, the AVM and the surrounding ischaemic zone with decreased activity were to be seen. The post-operative studies showed the d a m a g e d areas, due to the : o n s e q u e n c e s o£ the s u r g i c a l p r o c e d u r e .
427 ~k.~u~Q~,~, GOFFINET.
2arik Ai-Ba~hdadi, Hussein Malibary, Asma AI-Dabbagh Department of Medicine, King Abdulaziz University Hospital, P.O. Box 6615, Jeddah - 21452 Kingdom of Saudi Arabia
METABOLIC BRAIN SCAN IN EPILEPSY The new technology of Single Photon ~nission Tomography (SPET) and the technetium labelled Hexamethyl Propylene Amine Oxine (Tc99mHM-PA0) has been applied in brain scanning. This technique has proved valuable imaging modal~ty in different types of brain diseases. It has been shown that its sensitivity in detecting some lesions of the brain is in the range of 100%(e.g., dementia and extrapyramidal disorders). Also, it was observed that this method has a significant role in visualization of epileptic lesions. We have applied this technique which could be called the "Metabolic Brain Scan" (MBS) in evaluating epileptic patients who have been diagnosed clinically or by Electro encephalography (EEG). In addition to that, Computerized Tomography (C.T.) scan for the brain was also performed. The results of these studies showed that EEG has a limited role in specifying the location of the epileptic lesion although it showed variable abnormal changes in nearly all patients. C.T. scan showed only significant structural abnormality in low percentage of the eases. The MBS was positive in almost all patients studied. It was able to localize the site of the lesions and their extent. In conclusion, we suggest that Metabolic Brain Scan can be the imaging method of choice in assessing epileptic patients and will be of value in lateralization of the epileptic focus in those patients who may need surgery.
428 C. LATERRE, A. BOL, CH. MICHEL, A.M.
G.-J. Meyer, K. W]ldhagen , P. Heintz, (~. Steppe + , H. Hundeshagen
Positron Tomography Laboratory University of Louvain 2 chemin du Cyclotron B-1348 Louvain-la-Neuve, Belgium.
AbteilungNuklearmedizinund spezielleBiophysik Abteilung Immunologleund Transfuslonsmedlz]n +Abteilung Neurelogie MedizinischeHochschuleHennover,D-3000 Hennover 61
BRAIN GLUCOSE UTILIZATION IN POST ANOXIC SYNDROME.
ANALYSIS OF NEUROPSYCHATRIC SYMPTOMS IN SYSTEMIC LUPUS ERYTHEMATOSUS BY PET AND CO['IPARI,SONWITH MRI FINDING6
In order to understand better the consequences of anoxia on global as well as local brain metabolism, regional brain glucose utilization was measured in 11 patients with post anoxic syndrome due to cardiac arrest (9 subjects) or carbon monoxide intoxication (2 cases). i Twelve studies were carried out with positron emission tomography (PET), using an ECAT III tomograph and the fluorodeoxyglucose (FDG) autoradiographic method, at least one month after ~rain anoxia. Six subjects were comatose (stage 2 to 3); the others had regained n o r m a l consciousness b u t disclosed various focal neurological signs. Patient data were compared to those obtained in i sixteen . normal, age-matched volunteers. The protoco l bad been approved by the Medical Ethics Committee of the University of Louvain. Mean gray metabolism averaged 31.1 + 9.3 (SD) p.mols / (100g brain, rain) in patients vs. 50.5 -+ 6.1 in control subjects (p=0.0001), but this difference was due to the inclusion of comatose subjects. The [regional pattern of glucose utilization displayed drastic alterations, with large individual variations corresponding to clinical status. The [most significant finding was a relative hypometabolism in parietooccipital cortex (10 cases), the frontier between posterior and anterior cerebral circulations (t-test, Bonferroni correction, 0.05 level). Less systematic alterations were found in other areas such as cerebellar hemispheres (2 cases), striatum (3 cases with axial dystonia), ifrontomesial junction (3 cases) and visual cortex (2 cases with cortical Ibtindness). This study suggests that brain anoxia results in a global brain Ihypometabolism, which appears related to the vigilance state as well as [in more selective hypometabolism in areas located at the frontier between vascular territories.
Neuropsychetric symptoms in systemic lupus erythematosus (NP-SLE) occur in 30- 75% of all cases. Clinical manifestations are focal deficits like cerebral infarctions, cranial nerve palsies, and movement disorders, or so-called global dysfunctions like organic mental syndrome and psychosis. Up to now there is a lack of reliable markers for disease severity and activity. In this study we present 18FDG-PET as a highly specific indicator for reduced glucose metabolism in NP-SLE. We examined 18 patientswith clinicalsignsof NP-SLE. PET data were analyzedusingmultlplerelatlveparameterslikerightover lefthemisphere region ratiosand carebeIlum over corticalgray matter and corticalwhite matter regionratios.All patientswere investigatedby MRI and X-ray CT as additionalimagingmethco~.All patientswith neurologicalsignsof cerebral involvement showed glucoseutilizationdeficits.MRI detectedall focaland spinal lesions.In about halfof the caseswith more globaldysfunction,MRI showed multiplesmall regionsof slightlyelevatedsignal intensityin the periventricularwhite matter.CT could not detectcorrelatesfor any of the more globalimpairments. FDG-PET seems to be a highly sensitive method showing cereb~'al involvement with and without morphological changes. Furthermore, FDG-PET has been found to be normal in our study, when there are no neuropsychatricsignsof cerebral involvement,despiteclinicalevidenceof SLE.
506
429 G.-J. Meyer, R. Harre , F. Orth, M.R. Gaab*, H. D etz , H. Hundeshagen,
430 B.Erbas.H.Kumbasar,Y.Do~an,S.Aytaq,C.F.Bekdik,G.Erbengi.
Abteilung Nukleermedizin und spesielle Biophysik, Abteilung Neurochirurgle, Medizinische HechschuleHannover, D-3000 Hannover 61
Nuclear Medicine Department,Hacettepe University, Pschiatry Department,Ankara University. Ankara,Turkey
IN VIVIO PROTEIN ,SYNTHESISIN HUMAN BRAIN TUMORSMEASURED WITH I IC_L_METHIONINE"
REGIONAL BLOOD FLOW CHANGES ON ALCOHOL ABUSE USING 99mTc-HMPAO . EVALUATION OF SPECT AND CT PARAMETERS. In this study ,we investigated regional cerebral blood flow(reeF) changes in i chronic alcoholism associatedwith cerebral atropy using 99rnTc-HMPAO as a criteria of cerebral dysfunction during abstinence. 28 alcoholics,all male/mean age:38.5+11.8 ) were examined. After the administration of 600 MBq 9gmTo-HMPAO,using a single head rotating gamma camera(TOSHIBA GCA-601 E)(360°,6°,30 see) tomographic slices were determinated. Slices were analyzied quantitatively. Eight region It hemisphere were drawn on transaxial section end tracer redistribution was calculated for each region.Frontal/occipital ratio(F/O) and frontal/ whole(F/W) slices were determinated for each patients.Patients were scanned also using x-CT(Picker 1200$x) and following parameters were calculated: $ulcal widening(SW),lateral ventricul diameter(LV),3.ventricul diameter( 3.V),frontal horn diameter( FH),bicaudate diameter (CC), distance b~tween the ou{er tabulae (OTcc)in the level of CC ,CClOTcc and CC+ FH. Patients had significantly decreased F/O(mean:O.99+O.051) and F/W(1.01.-0.028) reties in comparison with controll group(p
I IC-L-methionine is used for localization, functional, and differential diagnosis of brain tumors with PET. Clinical data show a strong correlation between tumor grade and the amino acid uptake, It is unclear, however, whether this correlation of the intensity of the PET signal with the tumor type and metabolic activity can also be expressed by a measure of protein synthesis, By animal experiments we have established that the increased uptake of amino acids in brain tumors is mainly governedby transport phenomenaand that the metabolic activity ls only Inadequatelydescribed by mere protein synthesis. Since there is a lack of data in human brain tissue, we have measuredthe 1 I C_L_methionine incorporation into protein of human brain tumors. -t patients undergoingsurgery on diversified glioblastomas received I - 3 mCi of I IC_L_methionine intravenously at 5 to 15 rain before the explantation of tumor tissue. In each case 2-3 samples of 0.2-0.3 g were taken and analyzedfor free and protein boundactivity.
The free and.bound fractions were plotted against the time span between injection of 1 IC_L_methionine and sampling of the tumor tissue. Despite varying malignancY of the tumors, the free and bound fractions follow a simple exponential regression line. The data suggest that the incorporation rate of amino acid into protein does not correlate strongly with the tumor grade, corroborating our conclusion from anlmal tumor expeMments that increased transport is the driving force for amino acid uptake in brain tumors.
431 M. De Rag, L. Mortelmans, P. Devos, E. Carton, R. Dam, J. Cootjans, H. Hauman, P. Denef.
U.Z. Gasthuisberg (Leuven), U n i v e r s i t y P s y c h i a t r i c Centre (Bierbeek), Psych. Dept. A.Z. St. Norbertus C l i n i c (Duff e l ) , A,Z. H. Hart (Tienen), Belgium DIFFERENTIATION OF DEMENTIA SUB-GROUPS BY USING Tc-99m HM-PAO CEREBRALBLOODFLOW SPECT In c o n t r a s t to X-Ray CT and MRI, more s p e c i f i c informat i o n can be obtained in demented p a t i e n t s by high r e s o l u t i o n SPECT with Tc-99m HM-PAO, which reveals f r e quently a p a r t i c u l a r pattern of abnormal c o r t i c a l blood flow. The p a t t e r n of these a b n o r m a l i t i e s can be d e s c r i bed by using i n t r a h e m i s p h e r i c region to region r a t i o ' s . In AD p a t i e n t s (22 cases), t r a c e r d i s t r i b u t i o n abnormalit i e s appear more d i v e r s i f i e d in comparison to the l i t e r a ture and can be c o r r e l a t e d to the grading of the pat i e n t s according to the general d e t e r i o r a t i o n scale (GDS) and age, p r e s e n i l e cases presenting with more abnormal SPECT images than s e n i l e cases. The s t a t i s t i cal and m u l t i v a r i a t e analysis of the variance of the region to region r a t i o ' s of AD p a t i e n t s versus young and age matched c o n t r o l s and age matched a s p e c i f i c dementia p a t i e n t s , show t h a t only the p r e s e n i l e cases can be separated from the other groups, w h i l e there i s a gradual change of the regional uptake p a t t e r n from e l d e r l y c o n t r o l s to s e n i l e AD p a t i e n t s . The pattern of d i s t r i b u t i o n in f r o n t a l dementia cases (Pick's disease, f r o n t a l lobe dementia and supranuclear palsy) ( I I cases) is characterized by a reversal of the uptake r a t i o ' s versus AD cases. The data about f l o w d i s t r i b u t i o n pattern are also import a n t f o r the d i f f e r e n t i a l diagnosis dementia v e r s u s psychosis. More careful study of the pattern of t r a c e r d i s t r i b u t i o n using blood f l o w SPECT in dementia p a t i e n t s can be useful f o r the d i f f e r e n t i a t i o n of the subgroups.
432 H ~ilves+r} N. Mo!eg. G. ~oni, G. !ervs~i, A. C~s~ni*, PL. Ohil~rdi*, O. II.~riani,F. C~rmassi and R. Bianchi. Istitutodi FisiologiaClinica del CNR, l~titutodi Clinica Medico It, Servizio df I"ledicinaNucleate. *Istituto di Clinica Otorinolarinooiatric~, Universib:I of Piss,561 O0 rise, Itah.I BRAIN SPECT WITH 99rnTo-HPl-PAO FOR THE DIAGNOSIS OF CEREBRAL PERFUSlON DEFECTS IN PATIENTS AFFECTED BY VESTIBULAR DISEASE. Permanent or transient blood flow reduction to the central and/or peripheral ,.estfb,Jlar~'tructuresrepre.~entsthe most import~r,tc.auseof labyrinthicdisease. CerebralSPECTcanestimatethe regionalcerebralbloodflow (rCBF.}.The aim of this study is to evaluateinpatientsaffectedbg vestibulardisea.~eif cerebralSPECT m~y be of diagnostic.andclinicalutilityin comparison with other nen-invasive tests like computerized tomography (CT) and d~plers,)nography(DS) for the rnorphofunctional study of cerebralcirculation.Westudied13 patients,11 male.and2 fernale,aqed5377 yrs, affected by vertiginous sgndrome, in ~
(95-I ~.5 mCO 99mTo-HH-PAO (Ceretec,Amershem International),with the patient lyingsupine and employing a head restraintdevice, using a tomooamera G.E.Staroam 400a equiI:,pedwith a low energy, high resolutioncollimator.Images w'ere acquired using .)E=4x64 by~'.ematrix for a totalof 64 projectionsv.'hilethe camera covered in 20 minutes a full 360 ° rotation. Transaxial, coronal and sagittal tornoqrarns ".#ere reconstructed; the presence of cerebral blood Flew asymmetries ,~.~a~evaluated by eompariny sgrnrnetricROls, selectedover transaxial frarnes.
I t of ~3 studiedsubjects had a cerebral SPECT positive fcr rCBF reduction. The follov;in(Itablere~,ortsfor 9 patients the comparison belween the results obtained ~.~,ithSPECT, DS and CT, respectiveh.i: SPECT SF'ECT÷ SPECT+ l SPECT+ SPECTDS DS + DS I CT CT 2 2 5 7 2 These data suggest: ~hat cerebral SPECThas a good sensitivttg and specificit,_.I for the detection of cerebral perfusion defeats in the_capatients. Thus 99mTo-HH-PAO SPECT seems to be one of the most u.ceful tests to evaluate if a vestfbulepathy is associated -
with an alteredoerebralbloodflow, and get informationsfor prognosisandtherapy. We think that cerebral SPECTcould be useful even for the follow up of these patients
underther~py.
507
433 A.
434
LOBOGUERRERO
-T. H E R R M A N N HEALY
- E.
- D.
G R E M I L L E T * - M. G R A N J O N - D. M I C H E L
DECOUSUS + - J.C.
S.de Medecine Nucleaire,H.Bellevue,St Etienne * C.d'Imagerie Nucleaire,PC.Baulieu St E t i e n n e + S.de Neurologie,H.Bellevue,St Etienne NORMALISATION AND POLAR PLOTTING HMPAO BRAIN CORTEX UPTAKE
OF
99mTc-
In o r d e r to i m p r o v e a s s e s s m e n t of 9 9 m T c - H M P A O brain cortex uptake,we have developed a p o l a r p l o t t i n g m e t h o d , d e r i v e d f r o m the c l a s s i c a l m y o c a r d i a l b u l l ' s eye (BE). B r a i n S P E C T d a t a are a c q u i r e d a n d p r o c e s s e d in a usual way (60*30sec/projection over 360°,Hanning-Hann backprojection).If necessary o b l i q u e r e o r i e n t a t i o n is D e r f o r ~ e d tc a l ~ g n the t r a n s v e r s a l s l i c e s w z t h the a x i a l p l a n e . E a c h s l i c e is m a s k e d w i t h an a n n u l u s ROI e x c l u d i n g b a s a l g a n g l i a a n d a BE r o u t i n e is a p p l i e d to 14 s l i c e s s t a r t i n g f r o m a b o u t 2 5 m m b e l o w v e r t e x : p o l a r p l o t t i n g of t h e s u m of the 3 h o t t e s t p i x e l s a l o n g e a c h of 60 r a d i i at 6 ° i n t e r v a l s . Thus, c e r e b e l l u m u p t a k e is n o t s a m p l e d . T h e BE is n o r m a l i s e d b y s e t t i n g to i00 the m e a n v a l u e of its 25% h o t t e s t p o i n t s . A n o r m a l d a t a b a s e has b e e n o b t a i n e d f r o m 17 normal volunteers (21-76 y r s , m = 5 1 yrs), c o n s i s t i n g in a BE of m e a n ( M B E ) a n d a BE of s t a n d a r d d e v i a t i o n (SDBE). A p a t i e n t ' s BE (PBE) is c o m p a r e d to n o r m a l b y c o m p u t i n g his defect's significance BE:DSBE=I00(MBEPBE)/SDBE. In c o n c l u s i o n , t h i s m e t h o d is e a s i l y i m p l e m e n t e d a n d p r o v i d e an o b j e t i v e a s s e s s m e n t and a v i s u a l s i g n i f i c a n c e t e s t i n g of l o w c o r t i c a l u p t a k e of 9 9 m T c - H M P A O .
435 C.C.Nimmon, K.E.Britton, M.R.Newton, ~i.Charlesworth, >LJ.Carroll~ k. Solanki, G. Dolke and k.J. Greenwood. St. Bartholomew's Hospital, London ~egional 8ehabilitation Unit, Homerton, London, U.K.
tHE USE OF Tc-99m HM-PAO SPECT IN "[HE EVALUAIION OF CLOSED }lEAN INJURIES DURING EEHABILITATION. fo evaiuate the extent of brain damage due to closed head injury, regional cerebral blood flow (rCBF) using Tc-99m HM-PAO SP~ICT imaging was compared to standard C[' and lqRl scans in 19 patients between 3 and 36 months after closed head injury. Quantitative values of global CBF ml/min were also obtained using a non-invasive first pass method lhe clinical status of the patients which was assessed using the Glasgow Outcome Scale varied from severely disabled and dependent on nursing care to fully independent with only mild neurological impairment. A total of 43 perfusion defects were detected in the 19 patients by SPECI as compared to 21 abnormal areas by NRI and 3.3 by Cf. A linear regression between the number of lesions per patient (NL) detected by SPECf and the clinical grade showed that the most severely disabled patients had the highest number of lesions (NL=4) and the lowest global gBF values as compared to the least disabled (NL=2), with an r valse of 0.82~ p<0.05, ihe relative contribution to disability from single lesions at different sites was examined by a multiple regression technique. The results indicate a lesion in the basal ganglion region to be most significant followed by a lesion in the parietal~frontal and temporal areas respectively, r value of 0.58,p~0.05. 11~ese preliminary results show that the H~IPAO SPECT study yields additional information complementary to ti~e clinical assessment of closed head injury at the rehabili ration stage.
A. Sehweil, S. Ei-Hilu, S. Jahan, E. Higazi, M. Salhat, S. Ai-Mohannadi and H.M. Abdel-Dayem.
Dept. of Nuclear Medicine, Kuwait Cancer Control Center and Faculty of Medicine & Dept. of Psychiatry, Ministry of Public Health, Kuwait. CEREBRAL PERFUSION CHANGES IN SCHIZOPHRENIA PATIENTS USING Te-99M HEXAMETHYLPROPYLENE AMINE OXIME (HM-PAO). Schizophrenia is known to be associated with brain atrophy. We studied cerebral perfusion changes in 20 patients with clinically documented diagnosis of Schizophrenia. Mean age was 29.6+4.2 years. All patients were on medication. The aim of the study was to detect the extent of cerebral perfusion abnormalities in such group of patients. Single photon emission computerized tomography (SPECT) was performed 15 min after i.v. inj of 555-740 MBq Tc-99m HM-PAO. The results showed a spectrum of abnormalities as follows: diffuse decreased perfusion involving the majority of one side or both sides of the brain in 6 pts. 37 focal areas of perfusion changes less than one lobe was seen in the remaining 14 pts: 28 foci (78%) were decreased perfusion and 9 foci (24%) foci of increased perfusion. The incidence of the focal lesions were: parietal 12(32%), occipital 8(22%), temporal 7(19%), frontal 5(14%), basal ganglia 3(8%) and cerebellum 2(5%). This study confirms that Tc-99m HM-PAO SPECT study is a sensitive method for detecting the extent of cerebral perfusion abnormalities in Schizophrenia patients.
436 J. L. Lear, R. Kasliwal, V. Meury, A. Feyerabend. Division of Nuclear Medicine (A034), University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262 USA
MAPPING R E G I O N A L C A P I L L A R Y T R A N S I T T I M E S WITH SIMULTANEOUSLY DETERMINED CEREBRAL BLOOD FLOW AND BLOOD V O L U M E We developed an autoradiographic technique for mapping regional cerebral capillary transit times by simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral capillary blood volume (LCBV) in rats. Rats were given intravenous injections of 30 mCi of Tc-99m DTPA under light anesthesia. Two minutes later, a 20 - 30 second ramp infusion of 50 gCi of C-14 iodoantipyrine (IAP) was administered. Arterial blood samples were obtained at 3 second intervals during the lAP infusion and the rats were killed by decapitation. The brains were rapidly frozen, sectioned into 30 micron slices, mounted on cover slips, and dried on a hot plate. Two sets of autoradiograms were produced, each predominantly representing exposure from one of the tracers. The images were digitized and C-14 cross-contamination in the Tc-99m images was subtracted. Based on arterial tracer concentrations, LCBV images were generated from the DTPA exposures and LCBF images were generated from the IAP exposures. Capillary transit time images, LCBV / LCBF, were then created on a pixel by pixel basis. LCBV was found to average 0.5%, with a range of 0.2% in white matter to 0.7% in gray matter. While LCBV generally correlated with LCBF, it was more homogeneous. Specific regions in the midbrain and cerebellum had relatively high ratios of LCBV / LCBF. Thus, even assuming that the brain preparation probably caused systematic underestimation of LCBV, this study suggests that variations of capillary transit times occur in certain structures. Such variations could affect the regional kinetics of substrate transport.
508
4.38
437 C. POZZILLI, E. ZANETTE, F. GIUBILEI, C. ROBERTI,GL.LENZI C. FIESCHI.
• . 1 Department of Nuclear Medlclne, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, Canada T6G IZ2 and Department of Psychiatry, University of Alberta Hospitals, Edmonton, AB, Canada T6G 2B7
Department of Neurological Science, University of Rome "La Sapienza" TIME COURSE OF CEREBRAL PERFUSION AFTER ISCHEMIC STROKE: SPECT VS TRANSCRANIAL DOPPLERSONOGRAPHY (TCD). Twenty-two patients were investigated within 6 hours and after 7 days from the onset of stroke by means of CT scan TCD and SPECT with TC-99 HM PAO. An index of asymmetry (I.A.) was calculated from the SPEC2 maps by taking the difference of values from two symmetrical ROIs placed respectively on the affected and contralateral middle cerebral artery (MCA) territory. Diagnostic criteria for TCD were mainly the presence or the absence of MCA. When this artery was found, an I.A. between the mean MCA velocities of the two hemispheres was also obtained. Early SPECT study showed a significant I.A. in 18 out of 22 cases examined. Early TCD showed a significant I.A.in 8 cases, MCA was not found in 5 cases whether the remaining 9 cases showed no significant I.A. At the control examination, a significant I.A. and/or an absence of arte rial detection was found by both the techniques only in few cases (3/22). These data suggest that spontaneous cerebral reperfusion is a common finding at one week after stroke. Both TCD and SPECT could be employed to monitor the potential effect of thrombolytic agents to induce pha[ macological reperfusion in acute stroke.
QUANTIFICATION OF HEXAMETHYLPROPYLENEAMINE OXIME (H~AO) DISTRIBUTION IN PEDIATRIC PSYOIIATRIC PATIENTS. We have developed a 3-D brain fitting program to analyze semi quantitatively SPECT studies performed with H~AO, In a series of 12 normal volunteers, normal ranges have been established for 14 regions. Values are expressed as a percentage of total counts, and as a ratio of regional to cerebellar counts. We have applied this analysis program to H ~ A O studies in 28 patients referred from the department of pediatric psychiatry with the following diagnoses (some patients have more than 1 diagnosis): schizophrenia (9), borderline or manic (6), mental retardation (3), conduct or social disorder (6), substance abuse (4), normal (2), unknown (2). SPECT imaging was obtained after the injection of 500 MBq 99m-Tc HMPAO using a GE 400 AT camera interfaced to a Picker PCS-512 computer• The images were reconstructed with a filtered back projection algorithm using an image dependent Hetz filter and analyzed using the 3-D fitting program• Regional activity > 2 standard deviations from the mean was defined as abnormal. Clearly defined patterns of abnormal perfusion have been seen. Schizophrenia appears to be associated with frontal lobe hypoperfusien . (7/9), manic and substance abuse with generalized hyperperfusien (7/10), mental retardation with generalized hypoperfusion was seen in patients with learning disorders (314). We believe quantitative analysis of HMPAO tomography will have an important role in the management of patients with psychiatric disorders.
440
439 M.STEINLII~G1 ; E. OVEIsACQ1 ; PH. I~ASSIOTIS2 ; MAZINGUE'; F. AMEGASSI~ ; R. VERGNES%
A.
CT
and
EEG
O. N i c k e l , B. Nfigele-W6hrle, F i s c h e r , K. H a h n
P. U l r i c h ,
S.
Depts. of N u c l e a r M e d i c i n e and N e u r o s u r g e r y , Klinikum der Johannes Gutenberg-Universitaet, Mainz, FRG
1 - Service Central de Mddecine Nucldaire 2 - Service de Neurologie C ; CHRU ; F Lille 59037 Cedex Te-Hm PAO-SPECT, MRI, Temporal Epilepsy.(LE.)
A.J.B. McEwan1, M. Blackman2, W. Paterson 2, H,R. Hooper 1
in
Intractable
The exact localization of the cerebral lesion is often very difficult in Intractable Temporal Epilepsy. The measurement of cerebral blood flow (CBF) has been proposed as a nice solution to solve this problem, showing a decrease of CBF values in the pathological area at the interictal phasis (I.I.P.). New technics are now available as MRI or Tc-HmPAO tomography. The aim of our work was to compare the results obtained with Tc - Hm PAO with two ~/Cameras and MRI. So we studied 21 patients (P) : 11 W, 19 M ; age : 24,5 years ; (r : 15 - 66y) with IE criteria at I.I.P. Superfical EEG and SPECT tomogramms(Tomomatic 64) were performed in all the P. ; 18 (P) were also studied with a rotating camera, 19 by MRI using fast images, T2 and T1 images (Magniscan CGR), 19 by CT scan. Surgical proof of the lesion was obtained in 4 cases. The final diagnosis was : Tumor (4) ; neonatal encephalopathy (6) ; Rasmussen's encephalitis (I) and unknown origin (10).EEG abnormalities were found in all cases but one. Sensitivity was 26 96 for CT, 47 % for MRI, 28 % for dedicated SPECT and 11% with rotating Camera. When the lesion was a tumor, CT scan and MRI w e r e positive if performed. Hm PAO SPECT was always normal. A decrease of Hm PAO uptake was observed only in transaxial slides in cases of neonatal encephalopathy (3)and in unexplained I.E.(2). Coronal slides wieh theoritecally allows a best appreciation of temporal lobe appears unuseful from our results. This can be linked to the difficulty to obtain a magnificient positionnement w i t h conventionnal rotating camera. Our work shows that MRI is the best method to investigate IE.
EVALUATION INDEX WITH
O F A REGION~fL C E R E B R A L B L O O D SPECT: PRELIMINARY RESULTS.
VOLUPXE
In this s t u d y the r e l e v a n c e of a r e g i o n a l c e r e b r a l b l o o d v o l u m e i n d e x (RCBVI), m e a s u r e d w i t h SPECT, for d e t e r m i n i n g the c e r e b r a l p e r f u s i o n r e s e r v e h a d to be p r o v e n . In 150 p a t i e n t s i n - v i v o l a b e l l i n g of red c e l l s w i t h 9 9 m - T c and a s u b s e q u e n t S P E C T - s t u d y of the brain with a dual-head rotating gamma camera was p e r f o r m e d . A f t e r this s t u d y 9 9 m - T c - H M P A O was i n j e c t e d and a s e c o n d S P E C T s t u d y was a c q u i r e d . T h e a c t i v i t y of the red c e l l s of 48 s e c t o r a l r e g i o n s of the b r a i n ( d e f i n e d on the H M P A O images) was c a l c u l a t e d f r o m the r e g i o n a l c o u n t r a t e s w i t h i n the a b s o r p t i o n c o r r e c t e d t o m o g r a m s . The b l o o d v o l u m e i n d e x was c a l c u l a ted by a f o r m u l a , w h i c h t a k e s i n t o a c c o u n t the t o t a l b l o o d v o l u m e , the a c t i v i t y c o n c e n t r a t i o n in b r a i n and the i n j e c t e d a c t i v i t y . In 32 c a s e s w i t h I C A - o c c l u s i o n COz s t i m u l a t i o n tests with 133-Xe inhalation were performed b e f o r e the S P E C T s t u d i e s . R e s u l t s : T h e m e a n v a l u e s of the R C B V I w e r e in the s a m e r a n g e as R C B V v a l u e s f r o m P E T m e a s u r e m e n t s . The r e s u l t s of the CO2 s t i m u l a t i o n m e a s u r e m e n t s c o r r e l a t e d w e l l to the R C B V I e v a l u a t i o n . C o n c l u s i o n : The R C B V I g i v e s a v a l u a b l e a d d i t i o n a l i n f o r m a t i o n c o n c e r n i n g the c e r e b r a l perfusion reserve.
509
441 W _ . . ~ W .
4~,2 Lindheimer, H.-K. Deininger
iC. Sawas-Dimopoulou, C. Soulpi "Demokritos" National Research Center 153 10 Ag. Paraskevi Attikis, Athens, Greece
Dept. Radiology & Nuclear Medicine Municipal & Teaching Hospital D-6100 Darmstadt, Fed. Rep. Germany
AGE-RELATED CHANGESOF BRAIN-59Fe UPTAKE IN THE RAT DIFFERENTIAL TYPOLOGY OF ISCHAEMIC BRAIN INFARCTIONS WITH 99M-TC-HMPAO-SPECT AND CLINICAL VALUE IN COMPARISON WITH TCT 41 patients with strokes were investigated with 99m-Tc-NMPAO-Single-photon-emission-CT (SPECT) and Transemission-CT (TCT) in order to compare both methods in differentiation according to cerebral microand macroangiopathy. 80 % of early and 83 % of late territorial infarctions appeared as larger defects on SPECT than TCT, positive diaschisis cerebellaris only in early infarctions. Evidence of infarctions in the basal ganglia (2-3 cm ~) was seen on SPECT in all cases including reduced perfusion of the ipsilateral cortex with different dimension, depending on severe stenosis or occlusion of the ipsilateral carotid artery. Solitar lacunar infarctions were not seen in SPECT, but terminal supply area infarctions could be excluded. Multilaeunar infarctions showed flow deficits in the bilateral cortex in all cases. Conclusions: Stroke can be differentiated sufficiently by SPECT according to cerebral micro- and macroangiopathy. Clinical application of interest of SPECT is to estimate prognosis and development of stroke and to define indication for endarterectomy or bypass surgery, in better correlation than TCT.
Iron concentration in brain has been found to be closely related to the functional a c t i v i t y of dopaminel sites. The purpo§R of our study was not only to document alterations in ~:Fe-uptakein the rat brain during development upper normal conditions, but also to examine the effect on ~:Fe-uptake of a transient depletion of iron-stores, occuring early in the postnatal period of l i f e . The rat is p a r t i c u l a r l y appropriate for such a study, as a s i m i l a r i t y between i t and humans has been shown concerning brain iron biodistributien. 59Fe ( f e r r i c citrate) was injected i.p. in Wistar new born rats 9 days old, in young mature rats 60±2d old, and in newborn rats treated at 5d a f t e r ~ r t h by desferrioxamine (0.6 mg/g b.w.)+pyrophosphate (0.2 mg/g b.w.) i.p. The biodistribution of r a d i o a c t i v i t y was studied by direct tissue measurementsand brain autoradiographies. The mean value of byFe-uptake for the brain, as a whole was 2.02±0.31% of injected dose for the newborn rats compared to 0.24±0.02% for the mature rats. The values for the treated newborn rats were decreased to 0.57±0.14% <0.01). The mean values of the % injected dose of :Fe/1% b. w. for the brain of the treated newborn rat were reduced by 46% (P
~
In conclusion a significant reduction of brain iron has been shown during normal development and i t is suggested that these changes could s i g n i f i c a n t l y influence brain function.
443 Tarik Ai-Baghdadi, Asma Ai-Dabbagh, Malibary, Mohammad Ai-Hadramy D e p a r t m e n t of M e d i c i n e King Abdulaziz University Hospital P.O. Box 6615 J e d d a h - 21452 K i n g d o m of Saudi A r a b i a
444 Hussein
FUNCTIONAL IMAGING IN Z~ALUATING BRAIN LESIONS
The application of regional cerebral blood flow scanning with single photon emission computerized tomography (ECBF-SPECT) has been used in the last few years in the diagnosis of certain brain diseases. The recent introduction of technetium labelled Hexamethyl Propylene Amine Oxine (Tc99mHM-PAO) made this technique available to a large number of nuclear medicine centers. It has proved to be of value in the early detection of stroke and other ischemic lesions of the brain. In our institution, we have used Tc99mHM-PA0-SPET recently in patients who presented with neurological manifestations of different illnesses. These patients have been also examined by x-ray computerized tomography. Comparing the results of these two techniques with the clinical data, it was found that all lesions observed by x-ray C.T. images were also visualized by the Te99m HM-PAO-SPET images. The extent of the lesion is better assessed by Tc99mHM-PAO-SPET and correlated well with clinical manifestations. We can conclude that early detection of lesions in certain brain diseases by Tc99mHM-PAO-SPET is better than x-ray computerized tomography.
J.
Lepej,
V.
Horfik,
J.
•
+
Klzment,
J.
8 u c h a n e c ++
Departments of N u c l e a r Medicine, Urology and P e d i a t r i c s (++) Comenius University Faculty Hospital 036 59 M A R T I N CZECHDSLDVAKIA
(+)
EVALUATION OF THE URETERAL MOTILITY IH PATIENTS WITH URINARY TRACT INFECTION (UTI) BY MEANS OF 99mTc-MAG 3 P a t i e n t s and methods: 53 p a t i e n t s (pts) with d i f f e r e n t types of UTI were i n v e s t i g a t e d by c o n v e n t i o n a l s c i n t i g r a p h i c technique using 99mTc-MAG 3 (Mallinckrodt). The s p a c e - t i m e m a t r i x a p p r o a c h and t i m e - a c t i v i ity c u r v e s ever the u r e t e r area were c r e a t e d simultaneously. Both a p p r o a c h e s were used for Ivisual e v a l u a t i o n of u r e t e r a l f u n c t i o n . According to the c h a r a c t e r i s t i c c h a n g e s in the space ~-time m a t r i x p a t t e r n s (STMP) the f i n d i n g e s were d i v i d e d into 6 g r a d e s (0, I-V) and c o m p a r e d with the c o n t r o l group (30 pts: normal, h y p e r t e n s i o n nephritis without infection) and with IVU, US results. Results: __
No IVU
renogram (s) T max. T 1/2
STMP 0
(%) I-V
C o n t r o l group UTI UTI, VUR
30 26 27 +
225~ 51 3 9 1 ± 1 8 4 216± 54 3 6 2 ± 1 4 2 291±131 540±289
95 ii 4
5 89 96
The r e s u l t s demonstrate that STMP is v a l u a b l e to assess the u r e t e r a l disorders in pts with UTI even in the cases when r e n o g r a m s were normal. MAG 3 with more o p t i m a l target to background ratio in c o m p a r i s o n with OIH and OTPA (26 pts) i m p r o v e s the s e n s i t i v i t y of this method.
510
446
445 KE B r i t t o n , S Miceva, K S o l a n k i , A A A1-Nahhas, F F i o r e , R A J a f r i , J Bomanji, MJ C a r r o l l , CC Nilrmon.
RH Bahar, M Sabha, F Abu-Ziadan, KE Britton, K Kouris, C Nimmon, HM Abdel-Dayem
Department of Nuclear Medicine, H o s p i t a l , London ECIA 7BE, UK.
Depts. of Nucl Med & Surg, Fac of Med, Mubarak A1-Kabeer Hosp, Kuwait & St. Bart. Hosp., London, UK.
T~
St
Bartholomew's
ROUTINE USE OF T c - 9 9 m M A G 3 FOR RENAL STUDIES. THE VALUE OF PARENCHYMAL TRANSIT TIME INDEX (PTTI) IN EVALUATION OF SURGERY IN OBSTRUCTIVE UROPATHY (OU).
If 1-123 o r t h o i o d o h i p p u r a t e , OIH, were w i d e l y and c h e a p l y a v a i l a b l e , i t would be used r o u t i n e l y . Tc-99m MAG3 i s a l s o t u b u l a r l y s e c r e t e d and we have shown a clearance linearly related: OIH = 1.5 MAG3 + 40 ml/min (S/~E + 8%). I t s t r i a l u s i n g 100 ~ q in r o u t i n e RRS in place--of Tc-99m DTPA was u n d e r t a k e n i n 600 p a t i e n t s , 40% hypertensives, 33% outflow disorder, 20% renal t r a n s p l a n t , 7% o t h e r s . Normally the i n s t a b i l i t y of Tc99m MAG3 r e q u i r e s i t s use w i t h i n 60 min to r e t a i n 95% purity. Using the e x p o n e n t i a l dependance of r e a c t i o n r a t e on t e m p e r a t u r e t h r o u g h the A r r h e n i u s e q u a t i o n , we showed t h a t s u b s e q u e n t to the b o i l i n 8 s t e p , f r e e z i n 8 4 a l i q u o t s of the p r e p a r a t i o n p e r v i a l e n a b l e d m a i n t e n a n c e of over 95% p u r i t y f o r o v e r 8 h o u r s , r e t h a w i n g j u s t b e f o r e u s e . The l i p o p h i l i c i m p u r i t i e s c o n t r i b u t e to the 3% l i v e r u p t a k e which i s independent of r e n a l f u n c t i o n . Image q u a l i t y w i t h Tc-99m MAG3 e q u a l l e d t h a t of 1-123 OIH and exceeded t h a t of Tc-99mDTPA e s p e c i a l l y in r e n a l t r a n s p l a n t s and i n r e n a l f u n c t i o n impairment. R e l a t i v e f u n c t i o n s were h i g h l y c o r r e l a t e d : MAG3:OIH r=0.97 P<0.001: MAG3:DTPA r=0.94 P<0.001. Parenchymal t r a n s i t times were w e l l c o r r e l a t e d : MAG3:OIH r=0.81 P < 0 . 0 5 : MAG3:DTPA r=0.83 P < 0 . 0 5 . Frusemide r e s p o n s e s were similar. The a d v a n t a g e s of Tc-99m MAG3 combining the availability of Tc-99m w i t h the b e n e f i t s of t u b u l a r s e c r e t i o n and low background, make i t s s l i g h t l y h i g h e r cost over Tc-99m DTPA w o r t h w h i l e where RRS a r e f r e q u e n t l y performed in a n e p b r o - u r o l o g i c a l environment.
Time activity curve (TAC) patterns of radionuclide diuretic renogram (RDR) is frequently used to evaluate surgery in CB. Recently PTTI have been introduced as a more accurate parameter of RDR. We described six TAC patterns and used them efficiently to identify obstruction in CU. A prospective study of forty patients (46 operated urinary units) with CU was conducted. All had Tc-99m DTPA RDR initially and at variable intervals up to 12 months after surgery. The PTTI was more sensitive than TAC pattern (96%, 92% respectively) but it was less specific (86%, 97% respectively) in identifying obstruction. The detection accuracies were comparable (90%, 95%). PTTI/ being independent of renal uptake function, could not predict the outcome of surgery whereas TAC pattern, being dependent on renal function, was able to. We conclude that PTTI can be used as efficiently as TAC in identifying obstruction preoperatively, but not for predicting the outcome of surgery. Postoperatively PTTI could be used to identify patients with residual nephropathy better than TAC. TAC would be more useful in predicting the outcome of surgery and monitoring improvement in drainage function.
447
•
I
Keske U, Hosten N, Roll D, Cordes M, Felix R.
Department of Radiology, Universit~tsklinikum Virchow, Berlin, F.R.Germany
448
MM[ Sabha, A.H. Elgazzar, R.H. Bahar, F. Abu Ziadan, Awdeh, H.M. Abdel-Dayem.
Rudolf
Depts. of Nuclear Medicine & Surgery, Faculty of Medicine, Kuwait.
COMPARISON TECHNIQUES
OF DIFFERENT ERPF CALCULATION WITH MAG3 AND OIH
Three different calculation techniques for the effective renal plasma flow (ERPF) that were adjusted for 0IH were first verified with OIH and then tested with the new radiopharmaceutical MAG3. Patients received i00 MBq 99mTc-MAG3 or 18/24 MB( 131/123J-OIH. Sequential gamma camera images were obtained for 25 min, blood samples were taken after 1224 and 45 min. The following ERPF calculation techniques were used: ratio of applied dose and plasma concentration (modified Tauxe), gamma camera partial body clearance (Winkler), and ratio of camera partial body clearance and plasma concentration (modified Oberhausen). Linear regression analysis with calculation of the correlation coefficient (r) and the mean ratio of i the obtained ERPF-values (q) was performed. Results: HAG3 (n=150) OI_~H (n=66) r
q
r
q
Tauxe/Oberhausen 0,90 1,23 0,90 0,94 Tauxe/Winkler 0,77 0,81 0,66 1,06 Oberhausen/Winkler 0,76 0,67 0,68 1,05 Conclusions: - linear correlation of all ERPF calculation techniques was found - for MAG3, Tauxe-ERPF averages 123% of Oberhausen-ERPF and 81% of Winkler-ERPF - for OIH, values of 94% and 106% were found - as a consequence of this, slight modification of the calculation techniques is necessary in order to adapt them for MAG3.
PREDICTIVE VALUE OF DIURETIC RENOGRAPHY BEFORE RELEASE OF COMPLETE URETIC OCCLUSION IN SHEEP. Radionuclide diuretic renography (RDR) is used to diagnose obstructive uropathy. Being a functional study which reflects renal function and urodynamic changes, it could have a role to predict the functional recovery of kidney after the release of occlusion. In 9 sheep, 58 serial Tc-99m DTPA renographic studlies were performed before and after release of complete un&ia~erai ure[eric occlusion for a maximum perlod o~ 7 weeks. The renal flow, individual kidney uptake, time activity curve (TAC) patterns and parenchymal transit time index (PTTI) were correlated with the duration of the occlusion and with their respective findings after release of the occlusion. The renal flow, individual kidney uptake and uprising slope of TAC shQwed progressive deterioration with increasing duration of occlusion, while the PTTI did not show correlation with duration of occlusion. The PTTI was prolonged during early weeks of occlusion and fell down to normal after the 5th week. The cause for this is histologically documented by severe tubular damage, which consequently caused very low statistics on renography. We conclude that the individual renal uptake and uprising slope of TAC of RDR which reflect renal uptake can be used to predict the outcome of surgery while PTTI being independent of renal uptake cannot be used.
l
L
511
450
449 A.H. Elgazzar, R.H. Bahar, M. Sabha, F. Abu Ziadan, M. Awdeh, H.M. Abdel-Dayem.
F.J.LomeSa, J.M.Campistol,* A.Catafau, M.Moragas, A. Muxi, F.Pons, A.Garcia, R.Herranz y J.Setoain
Dept. of Nuclear Medicine, Faculty of Medicine, Kuwait. EXPERIMENTAL STUDY OF THE RENAL RECOVERY AFTER RELIEF OF COMPLETE URETERIC OCCLUSION USING RADIONUCLIDE DIURETERIC RENOGRAPHY. Complete ureteric occlusion leads to increased resistance to flow of urine which leads to increased intraluminal tubular pressure. This later causes parenchymal damage which can be evaluated by radionuclide diuretic renography (RDR). In 9 sheep with complete unilateral ureteric occlusion 58 RDR were performed before and after release of the occlusion for a maximum period of 7 weeks. The aim of study is to use RDR to study the functional changes during occlusion and functional recovery after release of occlusion in correlation with duration. In each study parenchymal transit time index (PTTI), time activity curve (TAC) and relative uptake function were correlated with the histological changes. Kidneys obstructed for less than 3 weeks showed good and rapid recovery after release of obstruction. This was reflected on kidney TAC pattern and PTTI. Renal uptake took longer time to recover. Kidneys obstructed for more than 6 weeks showed severe deterioration in renal function on RDR which was documented histologically. The PTTI fell down to normal because of the low statistics provided by such kidneys. These kidney showed minimal recovery after relief of occlusion. We conclude that sheep's kidneys completely obstructed for 3 weeks has good chance of recovery while kidney completely obstructed for 6 or more weeks has no chance to recover.
Servicio de Nefrolog~a Servicio de Medicina Nuclear Hospital Clinic . Barcelona (Spain) IND1724-III PLATELET SCINTIGRAPHY IN THE FOLIf~-UP O F RENAL BIOPSY q~e aimof otr s t u ~ is to dsiEI~Lc~Le the valL~ c~ In-Ill Plabeof t=~=,~,m,~3~after ~ R~q~--
l e t Szi.ntig_c~J~, (PS) m th~ ~ i ~ (~).
T~F~ti~fcs (p), 15 hales an~ 5 fsra]es, aged 18 to 25 M~rs (~ = 47) ~ sb_~i~ ~ All of thsn ~ d n=mal ~ d c n b~ts. ~S~BS j;~ic~d du~ to a rs%~l disease. Six p hsd n~m~l renal D_ncticn a ~ 14 had a s~n/n crpatlnine>1,5 mg/dl.
p]pi-~l~cS ~ ]=Ibe.ledwt_ih Ii~-1]_l n e . L L ~ of In-l]1 p1~l~ts ~ reinjecb~. ~fu~ty m i - ~
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add 150
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and z ~ l e ~ ~ ~ ~ i a e l y after ~, at 24 an~48 h~xs later PS didn't shcw any d ~ after ~ in 12 p. I n 5 ~ a ~ u p t ~ in i~e bk~s~d k ~ e y ~BS rhP~r~ed. In one p th~ t ~ wgs ~ a~d 2 p h~d ami~sd ~LL~u, ( fccsl + diffuse Lpta~). All chax/s of PS ~ r e s ~ n in t ~ fizst s~n. Fooal upta~s ~nm~d sate ~ t y , ~hile diffuse LIXa~S 4 e c ~ s s d at 24 a~d 48 h ~ s s~ns. p ~ h ~ (drop of 5 p~in~s in ~ L o c r i t ~Dd ~ h ~ ) , 2 with 13mmifi~ PS (i fcr~l, 1 fo~l + diffuse). Oneof ti~, ~"£~d a ~L~u~.~itcreal s ~ at 24 and48 hcL~s scars. Only this p h~d a Ir~iti~ eo~9~Jhy at 24 h~urs. Six p~_ients had rn~i~i~ PS (5 diffuse, 1 focal + diffuse)
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p~tb~n oould he du~ to h~xiiPaTdc c ~
in ren~l ~
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452
451 E.Jak~id, S.Midid, P..Han and K.Kostid Institute of Urology and Nephrology, Institute of Nuclear Medicine, University School of Medicine and Clinical Centre, Belgrade, Yugoslavia
El@azzar AH, Mahmoud AH*, E1-Sayed M, Nilson* TE, Abdel-Dayem HM, Ai-Mohannadi S.
Depts. of Urology* and Nuclear Medicine, Faculty of Medicine and Mubarak Ai-Kabeer Hospital, Kuwait.
SCROTAL BLOOD POOL SCINTIGRAPHY(SBPS) IN DETECTION OF VARICOCELE Varicocele is a common cause of testicuIar disfunction. Surgical removal of varicocele significantely improves the possibility of conception. The purpose of this study was to evaluate the use of two-phase SBPS in detection of varicoceIe. SBPS using erythrocytes labeled in vivo with ]75 M~q 99mTc was performed in 98 infertite patients with proved varicocele and in six controls, i-irst, dynamic phase (consists of 2~';. frames, 4 seconds per frame) was used for detection of retrograde blood How in ]eft testicular vein, while on static image(500 KC) focal accumulation of labeled erythrocytes in dilated parnplniform plexus was searched. ScJntigraphic results were compared with clinical and surgical findings. Results obtained with SBPS were in accord in 84~ with clinical findings in patients with verified varicocele(VV), o w in 80~/o in patients controled after surge~y(SC), in 71,~ in patients with right-sided varicocele(RV), while in patients r o! with subclinical varicoceIe(~V) only in 52% The presence of retrograde blood flow in 72~ studied subjects was noted. In at] patients studied final diagnosis was confirmud surgicaly. Sensitivity and specificity of SBPS in detection of varicoce]e was 9~C and 83~, respectively (in patients with VV 95~ and 91°/o, in SV 90~ and 807~, in P,V 94% and 50~, in SC ]00~o and t00~). In conclusion-SBPS allows simple, reliable and accurate' detection of varicocele and postoperative follow up.
EVALUATION OF FUNCTIONAL CHANGES AFTER EXTRACORPOREAL PIEZOELECTRIC LITHOTRIPSY (EPL) BY RADIONUCLIDE STUDIES. Thirty seven patients (pts) treated with EPL were evaluated for changes in renal function using Tc-99m DTPA (pre-, I and 7 days post EPL) and Tc-99m DMSA (pre and one day post EPL). The following parameters were evaluated: parenchymal transit time index (PTTI) 3~ p ~ . ~elative up%~k~ ~un~t~o~ (RUF) 36 pts; GFR 13 pts and time activity curve (TAC) all pts. PTTI was prolonged at 1 day in 26 pts on treated side and in 23 pts on untreated side. Values returned to normal in 15 and 17 pts respectively by 7 days. At 1 day RUF of treated side decreased in i0 pts and increased in 5. At 7 days RUF of 7 and 4 pts returned to pre EPL value respectively. GFR on treated side increased at 1 day in I0 pts, 7 returned to baseline at 7 days. Obstruction was detected on TAC in 5 pts at 1 day and in 2 pts at 7 days only. Significant increase in size of treated kidneys was seen in 7 pts of whom 4 returned to normal at 1 week: Conclusions: I. Sequential radionuelide studies should be considered after EPL for early detection of functional changes and of obstruction which sometimes is unnoticed clinically. 2. Majority of post EPL changes return towards baseline by 1 week, and spacing of repeated EPL sessions by a week is proposed. 3. PTTI could be a useful parameter reflecting return of kidneys to baseline condition.
512
453
454
A M Peters, J Brown, M E Roddle, D Crossman, D J Allison.
HAMMERSMITH HOSPITAL, LONDON, ENGLAND. RENAL BLOOD FLOW CHANGES INDUCED BY CAPTOPRIL There is controversy regarding the value of angioplasty (PTA) in renal artery stenosis {RAS) in terms of improvement in blood pressure. We previously described a g~mma camera technique for measuring renal blood flow (RBF) with Tc-99m DTPA which may be useful in the evaluation of these patients. In 14 hypertensive patients with RAS confirmed by angiography, a single oral dose of captopril (50mg) I hr before DTPA induced a significant increase in RBF to stenesed kidneys: 17 (SD 27)% of base-line (n=16, p ~ 0.05) and a similar increase to non-stenosed contralaterals: 15 (24)% (n=10, p ~ 0.05). In 10 hypertensive patients with normal angio~raphy, captopril increased RBF by 24(21)% (n=20, p~0.001), greater, but !not significantly so, compared with kidneys with EAS. 10 kidneys (8 patients) were subjected to PTA 2 weeks after which RBF had increased by 24(41)% {p(0.001). However, it also increased in 4 of 5 non-operated contralaterals Coverall 11~ p ) 0.05). In 6 kidneys studied 2 weeks after PTA, captopril increased RBF by a further 19 (20)% (p) 0.05). Only 3 patients gained benefit from PTA in terms of blood pressure control 6 months following PTA but their RBF responses either to captopril or PTA were unremarkable compared to the others. The RBF response to captopril is similar to that induced by PTA, and additive Although it does not predict the outcome of PTA, RBF measurement should be useful in the overall assessment of RAS, such as monitoring the haemo-dynamic benefits of PTA.
455 p.J.Vassilakos. Ch. Pierrakeas,A.Ragavas,N.Pallikarakis, M.Profanti,D.pagonis,J.Dunis,Th.Gorilas,G.Metakides, G.Barbalias
N. Karatzas * I. Sotiriou**, Ph Papachristou**, Z. PapadopoulouKouloupmi**, I. Makridis*. • Departments of Nuclear Medicine, ** Pediatrics and Podiatric Nephrology of Aristotelian University, and ttippokratio llospital of Thessaloniki GREECE KIDNEYLENGTHANDWIDTHCORRELATEDWITHAGEIN CHILDREN'S KIDNEYSWITHORWITHOUTVESICOURETERALREFLUX(VUR). The purpose of this study was to determine kidney growth rate in 66 children aged 3 months to II years with a history of urinary tract infections with or without vesico-ureteric reflux (VUR). Lenght (I,) and width (W) were measured in 132 kidneys imaged with ~9~Te-DMSA or GHA and VUR was confirmed in eact~ case through Micturating Cystography (MC) and Direct Manometric Radionuclide Cystography (DMRC). The patients were divided into three groups (A,B and C) according to the type of renal lesion detected. Group A included the kindneys without morphological lesions and no VUR ~59 kidneys, wiCh average age 4.5-+3 years. L=8.3±l.3 cm, W.-4.Z_~0.6 era, i:-+S.D./. Group B included the kidneys without morphological lesions and VUR (45 kidneys, with average age 4.7_+2.7 years, L=7.7_+1.1 cm, W=3.9-+0.6 cm, :i~S.D.). Group C included the kidneys with scars and VUR (28 kidneys, with average children age: 4.9_+2.7 years, L=7.7± 1.5 era, W=3,8_+0.7 em, x-+-S.l).). Data was proccessed using ANOVA and ttest analysis. Regarding age, there is no statisticaly significant difference between all groups. There was also no difference between groups B and C regarding L and W. There was a difference in 1, between A and B (p<0.02), and between A and C (p= 0.05). There was also a difference in W (for A, B p<0.05 and A, C p<0.02). In Group A regression line was fitted on the data correlating age (X) and L (r=0.73, p<0.001, slope=0.31) and X - W (r=0.66, p<0.001, slope=0.14). In group B, the results were: X and L (r=0.78 p<0.001, slope=0.32), X and W (r:= 0.32 p<0.05, slope=0.08). In group C the results were: X and I, (r=0.45 p<0.05, slope=0.26) and without correlation between X and W (slope--0.007). '['he anual rate (slope) of kidney growth (L and W) was lower in group C while in group B only W was affected. The amount of reflux in group B was of small intrapelvic volume (<3 ml) and of high intravesieal pressure ( > 15 cm H20) and in C was of high volume ( < 3 ml) and low intravesical pressure ( < 15 em H20).
456
J. L. Lear, A. J. Feyerabend, C. Gregory. Division of Nuclear Medicine (A034), University of Colorado Health Sciences Center, 420C E. 9th Avenue, Denver, CO 80262
Depts of Nuclear Medicine. Medical Physics, Mathematics and Urology, University of Patras, Patras Greece. DIAGNOSIS OF RENAL FUNCTIONAL ABNORMALITIES USING RADIONUCLIDE RENOGRAM (RR) CURVE AND AN EXPERT SYSTEM An expert system was developed for diagnosis of renal functional abnormalities which is using a combination of parametric quantitative analysis of RR curve and diagnostic rules based both in Nuclear and Clinical Medicine experts. : RR 9emTc-DTPA was performed under a special i ~ clinical protocol.A Microcomputer 1.2 MB RAM with math co-processor ann very nlgn resolution graphics was used. : Our electronic archive consisted of 340 [127 of those were normals (clinically and laboratory tested)]. Method : The created software program was a coope~ion of two software p~p~rams in Turbo PascalT M 4.0 and in Turbo Prolog =~. Inls prograln acquires the examination data directly from t h e ~-camera using a prototy£e interface which was ueveloped in our uepartmerit. Then the progr@m leads the user to the proc~ssi~ section WhiCh conslsts or : i. NK curve creation.lne ~ curve is divided in two sections (a.for a duration of 64 sec. and b.for a ~eriod of 26 min.),2. Parameter calculation. Six (6) different parameters were calculated for the first section (renal blood flow) and eleven (11) [or filtration and excretion phase (renogram). 3. ~arameter values storage. 4. Classification of the stored values. The Turbo Prolog program is activated and fits the calculated values to out data base of normals and abnormals and characterises them respectively. The results of the characterisation are displayed and in a continuous dialogue with the user physician a . diagnosis ot a renat runctaonal aDnorma~ity Is evaluates. Conclusion : Our system is considered capable to diagnose abnormalities of the renal function a~d provide new more efficient values for the used parameters, Furthermore our system is able to guide the under specialisation physician user by pointing out the way of thinkin@ of the Nuc. Medicine experts in the interpretation %,f the RR and to suggest the final diagnosis .
ERRORS IN SINGLE PLASMA SAMPLE-BASEl) VALUES OF EFFECTIVE RENAL PLASMA FLOW C A U S E D BY V A R I A T I O N S IN D I S T R I B U T I O N V O L U M E We have observed discordance in effective renal plasma flow (ERPF) measurements between techniques which use single versus multiple samples of plasma I-131 hippuran concentration to determine ERPF. To investigate possible causes of these discrepancies, we evaluated the influence of time of samples (T), volume of distribution of hippuran (Vd), and effective renal plasma flow (ERPF) on plasma hippuran concentration (C), the measured parameter. In particular, we investigated whether the contribution of V d in determination of C was negligible compared to that of ERPF, an assumption implicit in the single plasma sample method. A model which compared the partial derivatives of the the expression defining C with respect to V d and ERPF as a function of T was developed and applied prospectively to a series of 20 patients.
O(C/I) / O(ERPF) a(C/I) / a(Vc0
=
3(ERPF) / 8(Vd)
=
(.T/V2) e-(ERPF x T / Vd)
(1/Vd3) {(ERPF x T) - V d ] e-(ERPF x T / Vd) =
{Vd- (ERPF x T)] / (Vd x T)
Results of the mathematical analysis and patient studies showed that the influence of distribution volume on plasma hippuran concentration can be significant, indicating an important and previously unappreciated ~ource of error in the single sample technique for ERPF determination. Similar errors will occur in single sample-based techniques for lomemlar filtration rate (GFR) estimation.
513
457
458 F~a!le M± Castell
J.G HFALY
Domenech-Torn~
J, Martinez
P, Buxeda M, Gonzalez
Ser~ce A ~ : ~ de k~bc~e Nud~e. Hop~ j%~. £F~U de St m~me Averue Albert ~ 42277 St Priest en Jarez
Nuclear Medicine Hospital General
V ~
SIMPLIFIED METHODTO DERIVE ABSDLUIE RENALFUNCTIONUSING ggm-To-MAG3.
OF 99nTc-YTTPA B I ~ P ~ A l ~ ~ ~ I ~ IN OF Rt~OVAgC~AR H Y P ~ A ~tive st~fy of 20 patients wo~d be aI~e to aR;reciate the real c m b ~ m of renal sc~gml~y coiffed w~h capto~r~ test, ~ diagnsis of rmovascular h ~ t ~ s i m . Only patients crswerk~g the fdbwhg selecticn criteria~s are cansidered: h~ertmsim and o ~ t r y of renal size, renal fa~re c~d hM~e~m, rra~igr~i h,~ertemim s ~ , and c~satisfactory respmse of a n ~ r t~sive therapy. Basal, and after captapnl simulation (one hg~ after a s~le dose of 50 rag) n e p ~ are performed for each patient : A c~ssical method is used (a 30 r~nutes d ~ c recor~ after 370 MBq 99mTc-DTPA rinse). The re~tive r~ml f~ctLm is calculated as the pe~ent cmtrilr~on of each Mdney to the s~n of the acti~ty of the renal c~eas (lot to &d rm).
An ar~eno~y s~dy is perfo.ned to eye,ate me n e ~ n re~i~ An asymtric relative glamemlar f~tmtim rate (CIR) is observed at b~sal n e ~ in 60~,~of the case~ T~refore, a decrmse of I0 po~ts, of the lowest relative CIR, or in the case of sym~rical f~cti~ a dect~e of 10 pokers of me of the k ~ is considered as a positive ~ . Result : h all the ~se2, rosen a ~dateral tight ~ of r ~ l artery is vet~fi~ ( • 7~/4 the mp~op~ test is po~t~ve, h the ~ov~_rtight ste~L% mptop~ test cc~ be nega~v~. the o t ~ r p~thobc~es (u]flateral cmg~tal ~ chronic ~elonei~ritis, ne~m~mgiasclerosis, renal tunor) no nndificatim of the re~tive GFR, t~der captopril ~ i m is noticed. Oonclusim : 7h~s sady canfim~ the i~erest of the ne~hrog,~ with captoIril test for the detection of the re~%~salar ~ i c ~ in a target poplatic~ It also suggests that c~ly the h e r o i c a l l y sig~ificative s t e r r ~ g~ve a pc~itive effect to the test
459
Service Vail d'Hebron.
Barcelona.
Spain
99m-lc-MAg3 (MAG3] zs bole9 used as a replacement for i31-1-Ortho1odohlppurate IOIH). We are Feportlnm a slmpllfled method to derlve Effectlve Renal Plasma Flow (ERP~I mslnq MAG3 and regresslon analvsls in a group of Datlents wlth renal c}Iseasm. 20 patients were studled: 8 female, 12 male, aqed 24 to 64 (mean 44 years}. There were I0 m11ograft remlp]ents with stable renal functlon at least one year after Xransplantatlon Iserum mreatlnlne under 1,6ng/100 ml), 4 patients in the post-transplant perlod NIth lnpmlred renal function (creat 2,4 to B.2), one >atÂenD with chrofllc qlomermlonephrltlS and mlld renal failure (creat 2.4), one utlent w)th chronlc renal failure from insterstitlal nepbrltls (oread LD), ano our patients mlth urologloal disorders and normal renal funotlon. Simultaneous DIH and NAG5 clearance rates were determlned after s1nmle-shot 1elect)on by ~}eansof the memoand blexpoeential analysis of bJooO disappearance
curves (BDC - mu~hple samples,dramn at 5 min intervals up to one hour) plotted for both tracers. The follom~ng parameters mere derlved: ERPF, IER IIubuJar Extraction Rate, MAG,~clearance rate), TER-2 (TER by monoexponentlal analysis of the slow component of t4AG5BDC), and V40-c (distrlbutlon volume at 40 minutes, corrected for body surface). Regression .qna]ys~.s r Equatlon SEE (ml/mln/mZ) TER vs ERPF D.9528 ERPF--22+ I,45TER TER-2 vs ERPF 0.g323 ERPF:66+O.74TER-2 44 V40-o vs ERPF 0.g270 ERPF:56+7.27V40-o 45 Althouqh wltb some error, both TER-2 and V40-e are able to predlct ERPF on regression analvs~s, and th~s property makes them useful in general nuclear nepbrourologv. V40-c is more convenient because only one plasma sample is needed to derlve ERPF, Neither V40-c nor TER-2 Should be used if flne measurement of absolute renal function is desired.
460
C h r i s t i a a n WJ Schiepers, Anne M Glaser, Michael E Siegel
Lynn Jacobs, and B. Ba@ni, L. Feggi.
U n i v e r s i t y of Southern C a l i f o r n i a School of Medicine
*F. Portaluppi,
Nuclear Medicine,
Los Angeles, C a l i f o r n i a ,
USA
*Clinica Medica, 1-44100 Ferrara,
ALTERATION OF RENAL THALLIUM KINETICS AFTER TREADMILL EXERt I SE: REL.,%TIONSHI P TO EXERt I SE LEVEL The perfusion tracer TI-201 has been proposed f o r d e t e c t ion of reno-vascular disorders. Renal thallium k i n e t i c s were i n v e s t i g a t e d in patients undergoing e x e r c i s e testing
for myocardial ischemia. 25 patients with normal renal function ( c r e a t i n i n e < 1.1 m g / d l ) were e v a l u a t e d . Kidney uptake was determined at 10, 30 and approx. 200 min a f t e r i n j e c t i o n of 111MBq T I - 2 0 1 at peak e x e r c i s e . Posterior 5 min images were a c q u i r e d in a 128x128 matrix with LVOF camera, LEAP c o l l i m a t o r and 2 energy windows. Correction for decay and background was applied. Renal u p t a k e decreased, by an average of 3% from 10 to 30min,
JM,
FM
and by 10% from 30 to 2 0 0 m i n post i n ~ e c t l o n .
This
finding contrasts strongly with reported data of decreased splanchnic perfusion a f t e r e x e r c i s e . The expected pattern: i n i t i a l t y decreased u p t a k e , subsequent increase and then decrease to resting levels, was seen o n l y in patients achieving >g0% of age p r e d i c t e d max heart rate; t h i s group i n i t i a l l y showed a mean uptake increase of 3% (10 to 30 min) and then a decrease of 11% from30 to 200 m i n u t e s . No s i g n i f i c a n t d i f f e r e n c e s were found in p a t i e n t s 1) with or without hypertension, and 2) on or off medical t h e r a p y . Conclusion:
we
found
2
different
pharmaco-kinetic
patterns
of renal TI-201 d i s t r i b u t i o n post e x e r c i s e . Kidneys maintain or increase perfusion at moderate e x e r c i s e l e v e l s , w i t h i n i t i a l decreases seen only at high l e v e l s . Tt-201 p e r f u s i o n may reveal unexpected renal d i s o r d e r s and prove a v a l u a b l e imaging tool for reno-vascular d i s e a s e . E x e r c i s e l e v e l appears to be an important v a r i a b l e .
N. Prandini,
*L. Montanari,
S. A n n a Hospital University Italy
of Ferrara
T E C H N E T I U M - 9 9 m MAG3 VS. IODINE-131 ROUTINE D E T E R M I N A T I O N OF EFFECTIVE
H I P P U R A N IN THE RENAL P L A S M A FLOW.
T e c h n e t i u m - 9 9 m Dt~G3 has been p r o p o s e d as a useful alternative to Iodine-131 Hippuran for the scintigraphic determination of effective renal p l a s m a flow (ERPF). The aim of our study was to compare the consistency of ERPF values o b t a i n e d with the two radiopharmaceuticals. For this purpose,
a simultaneous
i.v.
injection
of 74 MBq
of 99mTc-MAG3 and 0°74 MBq of 131I-Hippuran was routinely a d m i n i s t e r e d to the patients who u n d e r w e n t a renal scintigraphic study. Plasma clearance and ERPF were calculated with the two methods in 107 subjects, either normal (n=20), or with a clinical diagnosis of essential hypertension (n=60) or renal insufficiency (n=27). Lower clearance rates were found w i t h MAG3 than with Hippuran, but the experimental values of p l a s m a activity fitted in the same b i e x p o n e n t i a l curve. The linear fit of the values o b t a i n e d with the two methods was h i g h l y significant (r=0.B9; p<0.0001) and is e x p r e s s e d by the equation: ERPF(MAG3) = 0.464 ERPF(Hippuran) + 21 The time-activity curve for kidney and b l o o d were quite similar. In conclusion, it appears that no significant difference results from using either of the two radio)harmaceuticals that we compared.
514
461
462
C. Z e r v a , D. K y r i a k i - M a n o l a r a k i , E. K i t s o u , G. P a p a d i m i t r i o u , A. G e o r g i o u , I. H o m a t a s , A. K o s t a k i s a n d V. A l e v i z o u - T e r z a k i . Dept. of Nuclear Medicine and Transplant Unit.
A M Peters, J Heckmatt.
F W Ballardie,
General GREECE.
Hammersmith
Hospital,
Laiko
Hospital,
Goudi,
Athens,
11527,
PRACTICAL PROBLEMS IN THE REPLACEMENT OFTcDTPA BY 99mTc MAG-3 IN RENAL TRANSPLANT EVALUATION. 99 mTc DTPA has been used in the evaluation of renal transplants in our department. In the hope that 99 mTc MAG-3 would prove a more valuable agent, 50 patients were studied with both DTPA and MAG-3 within 4 days and under stable clinical conditions. The DTPA study preceded the MAG-3 study. Normal transplants, acute and chronic rejection, ATN and obstruction were included in the material studied. Cost, ease of preparation, useful life once prepared, Perfusion Index, Renogram curve shape image clarity and diagnostic value of study were the paramet e r s c o m p a r e d . Tc M A G - 3 w a s m o r e e x p e n s i v e , m o r e difficult to prepare with a significantly shorter life once prepared than 99 mTc DTPA. The smaller dose and more rapid excretion of MAG-3 favourably affects the radiation dose. The perfusion indexes were comparable. The shape of the renogram caused difficulty in interpretation. In poor renal function accumulation of MAG-3 was better than DTPA but continued to increase. This was only observed in obstruction with DTPA. Image quality was considerably better with MAG-3. Considerable experience is required in interpreting MAG-3 renograms before they can, at some cost and little diagnostic g a i n r e p l a c e 99 m T e D T P A .
463
J M Rows,
London,
N Hassan,
England.
PATHOPH¥SIOLOGY OF CYCLOSPORIN NEPHROTOXICITY. What is the renal pathophysiology of cyclosporin (CyA) nephrotoxicity in man ? We addressed this question by measuring renal haemodynamic parameters in 6 adult bone marrow recipients before and after high dose CyA for graf versus host disease, and in 14 children treated with CyA for dermatomyositis. Renal blood flow (RBF) and filtratio fraction (FF) were measured from Tc-99m DTPA renography, and total GFR from the DTPA plasma clearance. Individual kidney GFR was calculated from GFR and differential function determined from the renogram. The 6 adults showe a consistant fall in GFR from 106(SD 12) to 49(7) ml/min 73(SD 40) days after initiation of treatment. RBF changed with less consistency. It was essentially unchanged in 3 and fell in 3, although not as much as the GFR. ConseQuently FF,.measured both directly from the renogram and indirectly from RBF and GFR, fell in all 6 adults by 22 and 35% of baseline respectively {p < 0.01). 3 were followed up for 6-13 months. GFR and RBF remained subnormal in one and recovered in another, while in the third, RBF partially recovered but GFR remained sub-norma In 3, CyA nephrotoxicity was associated with significant changes in differential function. In one this change was not accompanied by a corresponding change in differential RBF. There was no clear evidence of any nephrotoxic effects of CyA in the children except in one who showed a minimal deterioration in renal function, which was also asymmetric. CyA nephrotoxicity occurs at oral dose levels greater than 7.5mg/kg/d, by apparently complex mechanisms
464
D.G. Pavel, P. Orellana, E. Olea,.
J.M. Llamas-Elvira, A. Jimenez-Heffernan, M ~ Martinez-Paredes, M ~ J. Requena, F.M. Gonzalez, M. Tortes, R. Sopena, A. Marco.
University of Illinois Hospital, Chicago, IL; Catholic Universit~ Hospital, Santiago, Chile.
Nuclear Medicine Service and Urology Service. "Reina Sofia" HnsDital. CORDOBA. Spain. DIFFERENTIAL RENAL FUNCTION: 99mTe-DMSA versus 99mTc-MAG3.
FACTOR ANALYSIS OF Tc-DTPA AND I-HIPPURAb R A D I O N U C L I D E R E N A L STUDIES IN NEPHRO-UROLOGY. Functional images obtained by factor analysis (FA) of dynamic DTPA and H i p p u r a n sequences were used in over 100 patients, in parallel with a standard sequential display. In addition calculation of GFR and L e f t / R i g h t kidney ratios was obtained by the percent uptake method. Useful information by FA has been found in the following areas: 1) Evaluation of global and differential function: the method enables identification of cases where global function and L / R ratios are inaccurate due to significant organ superimposition (most frequently liver and occasionally spleen); this was found in 19% of the cases; 2) Separation of cortical f r o m pelvocalyceal kinetics: this is done in a fully automatic mode without any operator intervention and works in the presence of dilated pelvis and calyces; 3) Longitudinal follow-up: FA can indic.;:., qualitatively, a progressive deterioration/improvement in time, often better than standard images; 4) Evaluation of poor renal function: in some cases the method elicits unequivocally evidence of tubular kinetics, which was not clearly defined otherwise; 5) Identification of two cortical kinetics in some renovascular hypertensions; 6) Identification of two renal pelvis kinetics in cases with distended pelvis; 7) Improved evaluation of ectopic kidneys, g) Patient Motion detection. Conclusion: FA images are usually well defined and are obtained automatically. Overall the method contributes to a refinement of the functional analysis, but most importantly avoids reporting of erroneous interpretation of quantification results, due to organ overlap or motion artifacts.
We studied the comparative results of two different methodsin the evaluationof differentialrenal ft~qetionin a group of I00 patients with various kidney disorderswhose effectiverenal plasra flow (/~) bad been calculatedpreviouslyby sir~le 125-I-0IHir0ectienend multiple blood sampling. The two methods used to assess differentialrerml fanctios were: a) relative 9 9 , f f ~ uptake calculatedby normalized background and attenuation corrected cumulativecctaqtsin each kidney twenty four hr postinjectien,and b) relative99mTo-MAG3uptake within minutes one and t~o postinjectien calculated by norn~lized backgra~d and
attenuatiencorrectedcctaatsen each renal area. Patients were divided into three groups 8ccord/r~to daeir right kidney ERPF obtainedfrom ~]e total ~PF usirg the differentialrenal functionobtainedwith 9~TcD~A as a reference test: I) ERPF>250 ml/min., 2) 1 ~ < 2 5 0 ml/minand > i00 ml/min, 3) ERPF~
515
465
466
M. CASTELL; J. MARTIN-COMIN; R. PUCHAL; O. GRINO * ; Y. RICART; A.M. CASTELAO *; E. URIBE; J. DAUMAL; M. ROCA
Poropat I M., D. Batini6 2, M. Ba~i6 I, D. Dodig I, I. BraSi6 I, M. ~kugor I, D. Milo~evid 2.
Serveis de Medicina Nuclear i de Nefrologia ( * ) . Hospital de B e l l v i t g e . Hospitalet de Llobregat. Barcelona. SPAIN.
1 DEPARTMENT OF NUCLEAR MEDICINE AND 2 DEPARTMENT OF NEPHROLOGY OF PEDIATRIC CLINIC, UNIVERSITY HOSPITAL REBRO ZAGREB
99m-Tc-MERCAPTO-ACETYL-TRIGLYCINE KIDNEY EXTRACTION INDEX IN KIDNEY GRAFTS. We have studied 25 kidney g r a f t r e c i p i e n t s (15 males, mean age 41.7 + 13 years). In them 42 kidney g r a f t examinations were-performed with 2.5-4 mCi of 99m-Tc-MAG-3 (MAG). 22 examinations were performed in functioning g r a f t s (FG) and 20 in non-immunological acute g r a f t f a i l u r e (ATN). MAG extractiQn index was calculated in two d i f f e r e n t s ways. I) g r a f t a c t i v i t y / r e f e r e n c e area a c t i v i t y ( E l i ) , and 2) g r a f t a c t i v i t y / ( r e f e r e n c e a r e a - g r a f t a c t i v i t i e s ) (EI2). The time to maximal (TM) a c t i v i t y and the visual i z a t i o n of ureter and bladder a c t i v i t i e s as well as the g r a f t image at 3 and 30 min were also evaluated. In FG r e s u l t s were: E l i : 30.9 + 14.8; E l 2 : 5 7 . 7 + 40.7; TM: 19.3 + 11.1 min. The bladder was seen in 1 6 p a t i e n t s (70%) and-the ureter in 10 (40%). The g r a f t was c l e a r l y v i s i b l e at 3 and 30 min p . i . in a l l p a t i e n t s . The El was s i g n i f i c a n t l y (p<0.01) lower in ATN: E11:17.~ + 6.0; E l 2 : 2 4 . 1 + 10.9; TM: 29.8 + 1.7 min. Bladder act i v i t y was seen i n 6 p (30%) and t~e ureter in 4 (20%). The g r a f t was f a i n t l y seen at 3 min p . i . and c l e a r l y at 30 min p . i . - Comparison of MAG-3 Eli with previous experimented El of 131-I-hippuran (HIP) did not show sign i f i c a n t differences in FG but i t did in ATN (p
467
99mTc-DTPA RENAL SCINTIGRAPHY WITH FUNCTIONAL IMAGES OF MEAN TIME IN EVALUATION OF VESICOURETERAL REFLUX IN CHILDREN In 21 children (33 kidneys) with vesicoureteral reflux of various degrees dynamic renal scintigraphy with 99mTc-DTFA in zoom mode was performed. From each study 6 functional images of mean time were generated. Kidney contuor was defined on the summed image obtained between first and second minutes of study and was superimposed on each functional image. Focal areas of increased mean time were observed in 20 kidneys, in the area corresponding to renal cortex in 10 of them and in 10 in the area of renal medulla and/or adjacent calices. Over these areas the regions of interest were defined and time activity curves (TAC) generated. TACs generated in the regions corresponding to renal cortex show a sharp increase of activity on descending part of the curve. We propose it mihgt be caused by return of urine from collecting system to the kidney cortex (intrarenal reflux). TACs generated in the regions corresponding to renal medulla and/or calices show delayed elimination of activity probably due to obstruction in refluxing urinary system. In our opinion analysis of functional images of mean time might be a method for more accurate detection of intrarenal reflux i.e. of children with high risk of acquiring renal scars.
468
I. Szilv@si, E. Berentey, Zs. Kopcs@nyi, L. Major Dept. of Radiology Postgradual Medical School, Budapest, Hungary
J.Ch. ABBE, A. STAMPFLER, J.P. MEYER, M.FISCHBACH Service du R@acteur Nuql6aire Universitaire, BP 20, 67037 Strasbourg Cedex, CHU Hautepierre, P6diatrie 3, 67200 Strasbourg
TO DILATE OR NOT TO DILATE? Captopril-renography in decision making
MULTI TRACE ELEMENTS ANALYSIS IN BLOOD FROM PATIENTS USING NEUTRON ACTIVATION ANALYSIS
'Percutaneous transluminal angioplasty /PTA/ is an effective interventional technique in treatment of renovascular hypertension but not without risks. Morphologic abnormalities of renal arteries in patients with hypertension are sometimes of questionable haemodynamic significance and challangin9 many "interventionalists" to perform balloon dilation. Captopril-renography proved to be a reliable method in diagnosing renovascular hypertension. In our study 15 hypertonic patients with borderline angiographic findings were examined. Tc-99m-DTPA or -MAG5 renography were performed after captopril. Differential renal function was analysed by deconvolution technique. Blood pressure returned to normal after balloon dilation in all of nine patients with prolonged mean transit time of the affected kidney. No therapeutic effect was observed in patients with normal /n=4/ or bilaterally prolonged /n=2/ post-captopril mean transit time values. In conclusion: captoprilrenography is a useful method to assess haemodynamic significance of aequivocal angiographic abnormalities found in patients with hypertension of possible renovascular origin. It should be performed to make clinical decision to dilate or not to dilate.
DIALYSIS
Neutron activation yields to a most powerful multi element analysis technique. Basically, an element can absorp a neutron to generate a new isotope ; most generally, this later is radioactive which allows its identification (qualitative analysis) on one hand and its measurement (quantitative analysis) on the other hand, the activity induced being proportional to the concentration. Apart from its generally very high sensitvity (down to some ppb in most favourable cases), this technique allows simultaneous multi element analysis in plain liquid or solid samples. Results obtained at the nuclear reactor in Strasbourg will be reported on the blood levels of Zn, Fe, Se, Br in patients with chronic hemodialysis, before and after the dialytic procedure.
516
469
470
SARAH W. NEWTON, G.M.S. SYED, C. NICHOLL AND B. SHAPIRO. J. Datseris, B. Papantoniou, J.Tselfes, P.Ziroyiannis, Chr. Palaistidis, M. Christoforaki and H. Gyftaki.
King's College Hospital,
" Alexandra " University Hospital Nuclear Medicine Department.
London, SE5 9RS, U.K.
IS IT WORTHWHILE PERFORMING SEPARATE Cr51 EDTA CLEARANCE TEST? In certain clinical situations such as diabetes, chemotherapy and immunosuppressive therapy when repetetive assessment of renal function becomes necessary, the patient would~ normally, be referred for combined Tcqqm DTPA r e n o ~ r a p h y / C r 5 1 E D T A e]earance investigation whereby both radioisotope procedures will usually be carried out on the same day. Thirty-seven patients were studied with an aim of replacing the single shot multiple blood sample GFR measurement with Cr51 EDTA by Tcggm DTPA renal uptake measurement. Five hourly blood samples were collected following the i.v. administration of C r 5 1 E D T A (3 MBq), whereby quantitation was carried out aceordinR te well established routine method. Concurrently, a second i.v. dose of Tc99m DTPA (200 MBa) was applied to enable dynamic kidney ima~in~ as well as Scan GFR estimation applyin~ the previously reported technique. T h e GFR values obtained ranged between 48 and 145 mls/min the scan GFR range was 44-160 mls/min, and a very ~ood linear correlation (r=0.91) was found between the two sets of results. In conclusion, the Scan GFR provides e viable alternative to the clearance test across the whole spectrum of renal pathology, obviatin~ the need for m u l t i p l e blood sampling, spares additional radiation dose and waiting time for the patient and, finally, eliminates the need for separate radiophermaceutical preparation with consequent laborous protocol execution.
Renogram was performed in 30 outpatients.15 of them,who ha~ all the parameters of renogram and biochemical tests in normal range constituted the control group.15 of them had polycystic renal disease.Renogram was performed by a y-Camera connected to a computer.370-555 MBQ of 99m TCDTPA was given bolus i.v. and the following parameters were investigated:Renogram of each kidney,histograms from selected,regions of renal parencyma and renal cysts (at least 3) perfusions index of each kidney and the difference in time between maximal concentration in abdominal aorta and in kidneys (A.Peak~.Results:Renegramwas abnormal in 12 patients and it concerned either to perfusion or to excretion or both.Some of the regional histograms of the parencyma have showed a significant improvement compared with renegram of the corresponding kidney:and some of the histograms of the cystic regions have showed accumulation of the 99m Tc - DTPA or were indicative of renal function, Tested at the 0,05 significance level, the A.Peak difference observed is statistically significant for both kidneys.For the perfusion index the difference approach to be statistically signficant at the above level (tRK=2,O32 , t r w=2.O54).Conclusions: l.The abnormal perfusion zndex ah~ the signficant difference of times of maximal concentration indicate a disturbance in intrarenal blood flow. 2,The participation of different parts of polycystic kidneys in renal function is not equal.
472
471 D.G. Pavel, P. Orellana, E. Olea, E. Michaels.
U n i v of Illinois Santiago, Chile.
RENAL PERFUSION INDEX AND CORTEX HISTOGRAMS AS MORE ACCURATE METHOD OF ESTIMATING RENAL SUFFICIENCY IN POLYCYSTIC RENAL DISEASE.
Hospital,
USE OF F U N C T I O N A L L Y T H O T R I P S Y (ESWL)
M.R. CASTEL[ANI °, A. RODARI o, E. SEF~GNI o, G. ZAFFARONI oo O.A DELL'AGNOLA °°, M. GASPARLNI o, p. MONTANARI o F. CRIPPA "
Chicago, I1.; Catholic
RENAL
IMAGING
University,
(FRI)
POST
The patterns of abnormality and indications for FRI in relation to ESWL are not yct fully established. Method: Te-99m DTPA and 1-131 Hippuran were used with a protocol set-up to encompass a m a x i m u m of functional imaging and parametric evaluation for a minimum amount of time. DTPA: early I0 sec. frames sequence, 500K early image; 1 minute image (between 56 min.); L / R D T P A ratio; Hippuran 30 sec images for 21 rain. (followed by Lasix if needed), renogram curves, and factor analysis (FA) of both. Material: 40 pt/54' ESWL/77 FRI. All had F R I done more than 2-3 weeks post ESWL. In addition some had pre-ESWL studies, or early studies and/or multiple studies. Results: Can be grouped in the following categories (same patient can be in several): 1) Normal: after 2 weeks; 2) Minor pelvo-calyceal (P-C) h a n g - u p w i t h o u t s i g n i f i c a n t excretory delay (Ex-Del): 3) P-C hang-up with Ex-Del and without significant loss of function: had normal response to Lasix; 4) same as (3) but with significant loss of function: 10/11 had abnormal Lasix response; 5) Acute changes post ESWL: with or without pseudoparenchymal stasis; 6) Improvement and/or impairment (including total loss of function) on longitudinal follow-up: up to 8 mo.; 7) Preexisting major pathologic changes: FRI is most useful in this group as well as in (6) and is the only type of study with enough sensitivity to enable evaluation of even subtle functional improvement/impairment post ESWL. In most cases, in all categories, FA results c o n f i r m e d or a d d e d to the information given by standard methods. Conclusion: a wide spectrum of functional imaging provides a better understanding of the indications, consequences and strategy for ESWL.
MEDICI~ DIVISION, NATICNAL CANCER INSTITOTE o_ P~)IATEIC SURGICAL D M S I O N , ISTITuTICLINICI DI PERFEZION/~f[O o o _ MILAN, ITALy MAG3 SCANS ~T C H I L D ~ WITH OBSTRUCTIVE ~ T Y . From Oct 1987 to Feb 1989 we investigated with MAG3 302 children affected by several twological diseases. In this study ~e e x a ~ n ~ 143 pts. with obstructive ur~pat~y, in order to point out the dis~nostic value of MAG3 in t40per (99 pts.) 8nd in lower (44 pts.) obstructior~ of dle urinary tract. A total of 169 examinations wex~ done; 25 pts. were studied with or more scsr~, 21 children were t~er 1 mot2]tho!d. After i.v. inj. of 9O~c .-NAG3, a dinamic acquisition of 20 rain.was made, utilizing a cc~outerized &~ma camera. Analogues images ware a]so obtained at 2-3 rain. intervals. When an upper (and sometime lower) severe obstruction was observed, we carried out a diLretic test wit}] fL~3semide, after voidir~ the bladder, and prolcr~ed the investigationof 15 rain.The ha/f-li. fe of excretion time was then calculated. For each examination we evalu~ ted: l)the parenchg~l inte~rity;2)thetype and the a,~t~ntof the obst~u ction;3)the response to diuretic test (when it was needed). The renal d~ mage was evaluated morphologically and by the calculus of the ripartitio of radioactivity between ~le kidneys, two m ~ t e s after the in~. of the tracer. It "~as considered significant when it was above to 10%. Tse diuretic test was pathological when it was more then 15 rain. MAG3 is very effective in the eval~tion of the renal d ~ e and of the de~ree of the obstructive pictta-e.For the reproducibility of the test, also in very you[~ children, it is very Usefull in the mc~toring of pts. u a ~ o n e surgery or not. In all eases t~]der 1 mot~]thold, this ~ethod confirmed the ante natal u l t r ~ h y c dia&nasis of hydrcnephrosis and in 5 cases showed a ic~r obstructive pattern. So in ~ experience ~ G 3 is very USefull to pediatric surgeon in the monitorin~ of pts. before er after surgery.
517
473
474
M.A. Antar, A.P. Grimond, A.U. Buatti, R.A. Rembish.
M.E Girelli,D.Casar~,D.Rubello,M.Piccolo,B.Busnardo Istituto di Semeiotica Medica, UniversitA di Padova, 9ivisione di Radioterapia e Medic±ha Nucleare Ospedale
V.A. Medical Center, Newington, CT and Univ. of Conn. Health Center, Farmington, CT. U.S.A.
di Padova, ITALY
RENAL GALLIUM-67 CITRATE U P T A K E I N
ROLE OF THYROGLOBULIN (Tg) AND ANTI-Tg ANTIBODIES (TgAb) IN THE FOLLOW-UP OF THYROID CANCER
INTERSTITIAL NEPHRITIS
Radiogallium imaging has been advocated for detection of both interstitial nephritis and infectious renal disease. Therefore, we reviewed 115 consecutive radiogallium studies among our patients. Of these, 20 patients had been referred because of abnormal renal function tests or suspected kidney disease (20/115, 17.4% The ages range between 38 and 65 years. Organ radiogallium uptake was assessed both qualitatively and quantitatively by use of a standardized densitometer (with correction for film background). For images at 48 hours and later, the qualitative interpretation of normal renal uptake was rated as zero, normal bone as (2), and normal liver as (3). There was good correlation (r = + 0.80) between the qualitative assessment and the densitometric measurements. Patient analysis was performed in each of 3 groups. Group 1 consisted of 7 patients with documented interstitial nephritis. Their mean renal densitometric measurement was 0.46 ± 0.14. Group ii consisted of 6 patients with renal infections. Their mean value of 0.34 ± 0.17 was less than group i. Group iii (6 cases) consisted of other varied renal disorders; densitometric readings were 0.34 ± 0.09. The twentieth patient had AIDS, with renal radiogallium values of 0.56 at 48 hours and 1.16 at 72 hours. From the viewpoint of detecting renal disease, the radiogallium study evaluated in this manner showed one false positive (5%) and one false negative (5%). Although radiogallium uptake is nonspecific, it appears to be useful in assessing interstitial neDhritis.
475 A. CATAFAU, F.J. I f ~ ,
The importance of serum Tg assay in the follow-up of patients with differentiated thyroid cancer is well known as well as the possible interference in Tg IRMA assay of circulating TgAb,which results in understimated Tg values. The aim of the present study was to evaluate the usefulness of Tg as tumoral marker,assayed on and off TSH-suppressive therapy by thyroxine,in 193 patients with metastases. Tg serum levels were assayed by IRMA,(values above 3 ng/ml were considered pathological),TgAb were assayed by RIA method. Sites of metastas~s were located by total body scan X-ray,echography.The following table su[marizes the percentage of patients with Tg>3 ng/ml: lymph nodes lung bone others n=95 n=43 n=47 n=8 on off on off on off on off TgAb- % 69 96 92 99 97 100 1OO 1OO TgAb+ % 27 45 50 75 1OO 1OO Tg serum levels were significantly increased in TgAb negative vs TgAB positive patients (p
476 M.J. RICART~, M. MORAGAS, A. MUXI, C. PIERA
V. RUFINI, L. TRONCONE, A. GIORDANO, M.S. DAIDONE
and J. SETOAIN. Department of Nuclear Medicine of Catholic University of the Sacred Heart, Rome - ~taly Nuclear Medicine and ~Transplant Unit Services. Huspi%al Clinic i Provincial-.Barcelona (SPAIN) lllIn LABELED PLATEiEI~ IN MONITORING HUMAN PANCREATIC TRANSPIANTS. iii i In order to evaluat~ the utility of In-labeled plate]eis (In-~) scintigraphy in monitoring human pancreatic trsnsplsn%s, we have r e v i ~ 68 ~ sc~]s performed in 13 patients with pancreas txgDsplant, and we have compared retrospectively the In-p uptske with the graft ~logical situation. I Autologous platelets were labeled with lllIn-Oxine (first 8 studies) and lllIn~lercaptcDiridine (remaining labelings). 100-200 uCi of In-p were reinject~°d and scintigraphic images were obtained with a Dyne 4/15 Picker ga~macsmera an line with a PDPII Dig±tad cc~uter. Quantitative analysis (Allograft/Ad~acenttissues ratio (A/AT)) was performed in i0 studies. S ~ t i c r ~ of panc.~atic rejection or ~nntmological tolerance were retrospectively established by evalUatian of clini~al data and co,p]emenTar~ tests (g]ycemia,urine ~ m y l a s e , C - P e p t i d e , u l a ~ h y ) available during The In-p study for each patient., and in msr~ cases by the later graft evolution. Results: A diffuse q0take was seen in 5 of 6 patients with pancreas rejection. The secretsbecame positive before chan~es in biochemical tes~ were detected. No In-p uptake was seen in 6 of 8 norma/ly 1~ctioning grafts. Two cases of venous thrcmbosis, 3 per±grafts baematcmas and a haematoma in the surgic~l ~o~nd appeared like focal 7n-p accumulation. A/AT ratios were (~c~.&):1.58-*0.20 for diffuse uptake; 1.53-+0.14 for focal uptake and 1.0~- 0.09 for negative scans. Conclusion: ~ scintigraphy is S useful method for the early detection of Ddncreatic rejection, and it is helpful in the differentia] diagnosis between this and other complications such as ~ i s or haematomas.
EVALUATION OF DIAGNOSTIC EFFECTIVENESS OF NEW SCINTIGRAPHIC TECHNIQUES IN MEDULLARY THYROID CARCINOMA (MTC) Some recently introduced radiopharmaceuticals provide new possibilities for an early diagnosis of MTC which is essential for treatment. The Authors ~ o r t the r e s u l ~ obtained using radioiodinated MIBG, Tc(V)DMSA Ti131 131 ' chloride and l-F(ab')2antiCEA. I-MIBG imaging (37 IMBq given i.v.) showed in 20 proven MTC a high specificity (no false positive results), but less satisfactory sensitivity, which was only just acceptable in detecting primary/recurrent tumors (sensitivity = 64.4%). 99mTc(V)DMSA (370 MBq given i.v.) imaged most of the tumor sites in i0 cases (sensitivity = 85.6%) but showed a relatively low specificity L~I fals~ positives). Four out of S cases were imaged with Tl-chloride (iii MBq given i.v.) and 2 out of 3 cases with i311-F(ab')2 antiCEA (iii MBq given i.v.). From these preliminary favourable data a new diagnostic approach in detecting and following up MTC seems to emerge I t is based O~o[he use of the highly sensitive 99mTc(V) IDMSA (and/or Tl-chloride~ as first choice examination, 123/131 and the highly s p e c i f i c l 3 1 I-MIBG (and/or F(ab') 2 antiCEA labelled with I) as the test to confirm the previous results. MIBG imaging may also indicate a possible metabolic treatment.
518
478
477 L. Lieberman,
D. Chamovitz, A. Fogelfeld, A. Steinmetz
"Sheba" Medical Center, Tel-Hashomer, "Wolfson" Medical Center, Holon, Israel
LOW DOSE ABLATION OF THYROID REMNANT TISSUE APTER SUBTOTAL R~4YROIDECTOMY We studied 17 patients, who had near-total thyroidectomies for well-differentiated carcinoma of the thyroid, with low dose 1-131 ablation of remnant
tissue. Thyroxine medication was stopped 3-6 weeks before treatment and resumed 72 h. t h e r e a f t e r . Patients were on no s p e c i a l d i e t and d i d n o t r e c e i v e diuretics o r TSH s t i m u l a t i o n . There were 14 f e m a l e s and 3 males ( a g e 1 5 - 8 2 ) who r e c e i v e d 1 d o s e o f 30 mCi of 1-131. P a t i e n t s were s c a n n e d (2 mCi) p r i o r t o and a t l e a s t 3 months a f t e r t r e a t m e n t . Post-therapy scans were c l a s s i f i e d v i s u a l l y as p a r t i a l (<50%), n e a r t o t a l (50-90%) and total ablation. According to these c r i t e r i a 2 p a t i e n t s from t h e ~Toup o f 17 had t o t a l , 3 had n e a r t o t a l and 12 had p a r t i a l a b l a t i o n . Seven o f t h e 17 p a t i e n t s who r e c e i v e d 1 d o s e were g i v e n a second d o s e o f 30 mCi. Two p a t i e n t s a c h i e v e d t o t a l , 2 near total and 3 remained w i t h p a r t i a l ablation. Our r e s u l t s a g r e e w i t h p r e v i o u s r e p o r t s o f poor r e s p o n s e to a single low dose ablation. However, after two low dose ablations 66% o£ our patients responded favorably, which is comparable to the reported success rate of 5068~ frem a single large dose of 1-131 (6G-188 mCi). Low dose ablation may be desirable in patients under age 40 because of lower radiation absorbed dose and because it requires no hospitalisation. The disadvantages are extended period required fop satisfactory ablation and the necesslty to interrupt thyroxine treatment several times.
479 Erik 0ster-JCrgensen, Karen Pedersen,
M.Pioe-E.Martino-F.Velluzzi-L.Bartalene~-A.Loviselli-L.Grasso~-L.Petrini-M.Falcone~-A.Pinchera~ Istituto di Ned. l n t e r n a - C a t t e d r a di E n d o c r i n o l o 9 i a - , O e n t r o di Med. N u c l e a r e - U n i v e r s i t ~ di C a g l l a r i ~lstituto di E n d o c r i n o l o g l a e Med. C o s t i t u z i o n a l e U n i v e r s ; t & di P;sa - I t a l y -
LACK OF NOCTURNAL SERUM TSH SURGE AS EARLY INDEX :OF THYROTOXICOSIS IN PATIENTS WITH "PRE-TOXIC" NODULAR GOITER. C i r c a d i a n v a r i a t i o n o f serum TSH c o n c e n t r a t i o n s h e ve been r e p o r t e d w i t h h i g h e r v a l u e s o c c u r r i n g i n t h e e a r l y m o r n i n g . R e c e n t l y we r e p o r t e d t h a t t h e la ck O£ n o c t u r n a l serum TSH surge is a s s o c i a t e d with s u p p r e s s i o n of TSH s e c r e t i o n in t h e morning and no response t o TRH in h y p e r t h y r o i d an~ in L-T4 sup p r e s s i v e t r e a t e d p a t i e n t s . In t h i s s t u d y t h e noctu~ nal TSH surge and TSH response t o TRH have been eve l u a t e d in p a t i e n t s w.ith F u n c t i o n i n g thyroid adenoma (FA),nontoxic goiter(NTG)and untreated hyperthyroidism
(H). Subjects Normals H
N ~ct.surge -
20 39
39
TRHbtes ~
~orn;n9 20
2~ 39
39
FA NTG
6 6 6 1 5 27 18 9 18 9 1 5 3 (+):present;(-):absent;n:normal~b:bland,a:absent response This study i n d i c a t e t h a t in p a t i e n t s with nontoxic g o i t e r or Functioning adenoma the lack of nocturnal TSH surge r e p r e s e n t s the e a r l y index of a c t u a l ~ly r o t o x i c o s i s and can be c o n s i d e r e d a p h y s i o l o g l c e ] t e s t more s e n s i t i v e t h a t t h e p h a r m a c o l o g i c a l TRH stimulation test.
480
Kjmr Pedersen and Svend Arne
Departments of Nuclear Medicine, Medical Endocrinology and Surgical Gastroenterology, University Hospital, DK5000 Odense, Denmark
THE INFLUENCE OF INTRAVENOUS GLUCOSE ON GASTRIC EMPTYING RATE IN NON DIABETICS AND DIABETICS The gastric emptying rate of a 1400 kJ omelette tagged with 40 MBq 99m-Te-Sulphur colloid and 150 ml water mixed with 8 MBq III-In-DTPA was measured with a gamma camera equipped with high resolution, parallel hole collimator. Anterior and posterior uptakes each of 30 seconds were recorded every 10th minute during I hour. Retention curves were drawn based on geometric means and expressed in percent of the first value in the relevant phase. The emptying rate of solids was expressed as a relation to the slope of the curve 30-60 min after ingestion. The emptying of liquids was expressed by the half emptying time of the exponential decreasing curve. After approval of the scientific-ethical committee eight non diabetics and 8 insulin treated diabetics in good metabolic controle were examined without and with intravenous infusion of 555 mosmol glucose, the half infused in the hour before and the remaining half in the hour of measuring the gastric emptying. The emptying rates of both phases were lowered in all 8 subjects in the non diabetic group, a result which is highly significant (p < 0.01). The emptying rate of solids decreased in 6 and the emptying rate of liquids decreased in only 2 diabetics. These results were not significant. Any relation to the actual plasma glucose, glycated hemoglobin, duration of disease, presence of retinopathia or presence of a from the outset lowered emptying rate could not be demonstrated. CONCLUSION: Intravenous administered glucose lowers gastric emptying rates of solids and liquids in non diabetics but the same effect could not be demonstrated in diabetics.
M. Odavid, R. Lazi~, R. Bjelovuk, N. Bojanid, and R. Spaid
Institute of Nuclear Medicine M.M.A., Crnotravska Str. 17. 11 000 B E 0 G R A D (Yugoslavia) DIAGNOSTIC RELIABILITY OF RADIONUCLIDE SCINTIGRAPHY (RNS) IN ADRENOCORTICAL DISEASE - EXPERIENCE IN 350 CASES The aim of the study was to evaluate RNS using 75-Se Scintadren (AmershamInternational), in patients suspected to hormonaly induced hypertension (47), Conn's syndrome (109) Cushing's syndrome (91), Addison's disease (15), hirsutism (28), "silent" adrenal tumors (43), and other diseases (17). Clinical and/or operative (126 pts) findings were compared to RNS and TCT results. In pts with suspected Conn's syndrome we found 38 adenomas, 25 l e f t adrenal microadenomas, and 22 bilateral hyperplasia (20 normal) were discovered. In the remainding pts, 8 adenomas, 19 microadenomas, and 25 hyperplasia were found. Incidentaly have been discovered 43 (12,3%) "incidentaloma", where RNS revealed 12 adrenal tumors, 9 cortical adenomas, 7 microadenomas, 6 nodular cortical hyperplasia, 4 cysts, 3 carcinomas, and two pheochromocytomas. Using "descision matrix" system, the following diagnostic r e l i a b i l i t y have been achieved: total sensitivity 77,03% (in Conn's syndrome 72,73%, in Cushing's syndrome 74,07%), specificity 94,74%, accuracy 93,95%, and for TCT 51,09%, 78,95%, and 54,49%, respectively. Our results suggest that RNS provides a reliable, nonrisky, functional, and anatomic localization of adrenal tumors and hormonal disfunction, particularly after dexamethasone-suppression scintigraphy.
519
481 A. SIGNORE, V. FIORE, S. BOEMI and F. SCOPINARO Endocrinologia (I), Cliniea Medics (n) and Dept. Medicina Sperimentale, Sezione Medicina Nucleare, University "La Sapienza", Roma, Italy.
482 Chr.Reiners, B.Grothe, St.M]ller, B.Odth-Tougelidis, B.Piotrowski, G.Benker, M.Scheulen
Departmentsof NuclearMedicine, Internal Medicineand Oncology, University of Essen, F.R.G. INSULIN KINETICS IN PATIENTS WITH TYPE 1 AND TYPE 2 DIABETES MELLITUS: INFLUENCEOF METABOLICCONTROL, It has been suggested that hyperglycaemia in diabetes mellitus may induce a functional defect of insulin receptors. We developed a technique for studying in vivo insulin (INS) biokinetics and we demonstrated in both Type I and Type 2 diabetics an altered INS kinetics respect to normal subjects (Sinclair A,J. et al. Nucl. Med. Cornm. 8:779;1987). The aim of this study was to evaluate the influence of metabolic control on INS kinetics. We studied 8 patients with Type 1 and 8 patients with Type 2 diabetes before and after achievement of good metabolic control. For kinetics study, p~tients were injected i.v. with 37 MBq of 123Iodinelabelled INS and gamma camera images were acquired for 40 mins at a frame rate of 4 frames/min. Time-activity curves (TAC) were then generated over the heart, }iver and kidney, Blood sampJes were also collected at min 2 and 5 and then every five rains and plasma radioactivity was counted. On the liver TAC the following parameters were evaluated: time of maximum uptake (T-Max) and time of 50% reduction of maximum uptake (T1/2). Results showed no significant differences between Type 1 and Type 2 diabetics before achievement of a good metabolic control (T-Max=7.O+l.2 and 7.6+_2.3; Tl/2=23.1+_6.3 and 25.2±3.8, respectively). After treatment, in good metabolic control, Type I diabetics showed a significant reduction of T-Max (6.0±0.4; p<0,O2, paired t test) and T1/2 (20.3±3.2; p<0.05). Type 2 diabetics also showed a reduction of T-Max (24.3±4.4) and T1/2 (6.4±0.8) but not statistically significant. However. in these patients, we observed that plasma radioactivity at rain 5 was 54.0±21.7% of radioactivity counted" at min 2. before therapy, and 39.7±12.6% after therapy (p<0.05) indicating a melioration of INS utilization also by extrahepatic tissues. In conclusion, our data show that INS kinetics is altered in both Type 1 and Type 2 diabetes and the defect consists in both liver uptake and metabolism, secondary to poor metabolic control. After achievement of good metabolic control these defects can be partially restored.
4-83 G a h b a u e r G.I!, Obendorf L . l ) , ^ Z e c h m a n n W. I), R i c c a b o n a G. I~, Wawschinek. O. m! ~ e p t . of Nuclear M e d i c i n e ~ A-6020 Innsbruck and Institute of B i o c h e m i s t r y ~ A-8010 Graz, A u s t r i a
TISSUETHYROTOXICOSISONTSH-SUPPRESSIVETREATMENTWITHLEVOTHYROXlNE IN CANCERPATIENTSAFTERTHYROIDABLATION? In differentiated thyroid cancer receptors for TSHwhich may promote tu~or growth havebeendescribed by several authors. Therefore, i t is generally acceptedthat substitution with levothyroxine (LT4) in cancer patients has to be TSH suppressive. The amountof LT4 necessaryhas to be discussed in the light of recently developedsensitive TSHassays. The crucial question is possible tissue thyretoxicosis with negative impact on bone, heart or liver whichmay occur on high doses of LT4 according to recently published studies in goiter patients. studied 52 cancer patients (31 wcmen,21 men,meanage 51.5 years) after ablation of the thyroid by surgery and 1-131. Patients were on long term LT4 replacementwith 175-300~g of LT4 daily. Blood samples were drawn 24 h after the last LT4 ingestion. M~asurementsof thyroid hormonesFT4, FT3 and TSHas well as of parametersof thyroid hormone action at the "tissue level as osteocalcin (OC), sex-hormonebinding globulin (SFBG)and procollagen-lll-peptide (PIIIP) wereperformedby
RIA. The study shows a significant correlation of serun FT3, which is better suited than FT4 for follow-up in patients on LT4, with OCand PIIIP. Abovethat, SFBG(5,02 +0,67 versus 3,43 ±0,50 ~ / I ) and PIIIP (8,36 + 0,31 versus 7,78 ± 0,36 rag/l) levels are significantly higher in patients with totally suppressedunmeasurablebasal and TRHstimulated TSH (n--36) as comparedwith patients with measurablebasal TSH < 0.1 mU/l and stimalated TSH< 0.5 mU/l (n=16). According to our results "oversuppression"with LT4 should be avoided in thyroid cancer patients becauseof possible tissue thyrotoxicosis.
484 K. F. Gratz, E. Koch, H. Dralle, and H. Hundeshagen
Abt. Nuklearmedizin und spezielle Biophysik and Klinik for Abdominal- und Transplantationschirurgie, Hedizinische Hochschule Hannover, FRG C O N C E R N I N G F A M I L I A L ALBUMIN A S S O C I A T E D HYPERT H Y R O X I N E M I A (AAHT): A REPORT ON 22 CASES AAHT has been r e c o g n i z e d 10 years ago, especially as RIA's for T4 and FT4 were p r a c t i c e d (I). This m e t a b o l i c a b n o r m a l i t y can lead to a w r o n g d i a g n o s i s of h y p e r t h y r o i d i s m and inadequate therapy if e x a m i n e r s are not aware of the syndrome. We studied 49 prepositi b e l o n g i n g to a family clan and found that 22 had AAHT and were mostly e u t h y r o i d by c o m p a r i n g TT4, FT4 (analog tracer), TSH, T3, TBG and clinical results as well as agarose gel e l e c t r o p h o r e t i c studies. The results show that o b v i o u s l y AAHT has a dominant autosomal genetic transmission, that a d i s c r e p a n c y of TT4 and/or FT4 with TSH r a d i o a s s a y results can show the way to an a d e q u a t e d i a g n o s i s which then has to be proven s c i e n t i f i c a l l y by a p p r o p r i a t e e l e c t r o p h o r e s i s . In positive cases familiar s c r e e n i n g should be p e r f o r m e d to avoid u n n e c e s sary thyroid therapy and families should be informed accordingly. (I) H e n n e m a n n G., Docter R., K r e n n i n g E. et al.: "Raised total thyroxine and free thyroxine index but normal free thyroxine (a serum a b n o r m a l i t y due to i n h e r i t e d i n c r e a s e s affinity of iodothyronines for serum b i n d i n g protein"; Lancet I: 639, 1979.
Mt2~I-Benzylguanidine Single Photon Emission Computed Tomography(SPECT) in Clinical Routine Diagnostics HtzSI-BG is considered to be representing the more favorable radiation dosimetry than mt3~I-BG. This permits SPECT-imaging. We proved this more expensive diagnostic procedure in clinical routine all over the year 1988. 72 studies in 67 patients have been performed. Indications for ecintigraphy were: differential diagnosis of adrenal tumor (16 studies), hypertension and/or increased catecholamines (32), search for metastases (2), diagnostics pre-t3*I-therapy (4), ]fEN II syndrome (15) and postoperative control (3). Planar scans and SPECT of the adrenal region have been performed simultaneously in 61 studies. Both procedures have been judged as negative in 48, as positive in i0 cases. In 1 case only SPECT x~as positive (verified histologically). Increased adrenal cland uptake seen in planar scans has been identified as intestinal activity by SPECT in two cases (confirmed clinically). In cases with multiple tumor locali~ations survey was obtained best by whole body scans. Hence 8PECT-imacing in m123I-BG-seintigraphy ~las superior to planar scans in only 3 out of 61 cases, a routine use of SPECT seems not to be necessary. Equivocal positive planar scans should be confirmed by $PECT, ~henever it is possible. For locating tumor or adrenal glands in SPECT images orientation on liver activity was very helpful. Thus SPECT done 24h p.i. is recommandabl~. The whole body scan is indicated for excluding multiple paragangliomas or metastases of pheochromocytoma or neuroblastoma, only if there is any anamnestic hint.
520
485 A. Ramann, K. F. Gratz, B. Soudah, S. Fritsch, A. Georgii and H. Hundeshagen
486 J.L.BAULIEU~ J.C.BESNARD
D.GUILLOTEAU,
F.BAULIEU,
L.POUKCELOT~
Zentrum Radioloqie, Abt. Nuklearmedizin und spezielle Biophysik und Zentrum Patholoqie und Rechtsmedizin, Abt. Zytopatholoqie, Medizinische Hochschule Hannover, FRG
Unit6 INSERM 316. Laboratoire de Biophysique M6dicale. Facult6 de M@decine 37032 TOURS C@dex France
Clinical and patholoqzcal behaviour of oxyphilic thyroid carcinoma
MIBG QUANTITATIVE IMAGING OF ADRENOMEDULLAR GLANDS MIBG uptake reflects the function of amine carrier of chromaffin granules in APUD tissues and tumors. In order to p r o v i d e a simple p a r a m e t e r to evaluate adrenomedullar function, b a s e d on MIBG uptake, the s c i n t i g r a p h i c contrast of adrenal image (SC) was evaluated 24 hours after 131I MIBG 37MBq injection. MIBG uptake was calculated after calibration of the injected dose, from counting in ROI corresponding to adrenomedullary gland, using background and deepness corrections. SC was calculated from posterior view as the ratio between counting in the pixel of maximum activity in the adrenal image, and the mean counting in a background ROI around the adrenal area. The image was acquired during i0 minutes and was smoothed one time (9 points weighted) A linear correlation (r = .95) was found between MIBG uptake and SC. SC values were : 1.0 - 1.5 in five normal glands, 1.5 - 2 in five suspected hyperplasic adrenomedullar glands and was higher than 2 in four pheoc5romocytoma. These preliminary results indicate than the determination of SC could be useful in differentiating normal, hyperplasic glands and pheochromocytoma. This simple m e t h o d m a y be standardized in v i e w of cooperative studies of familial or multiple endocrine neoplasia.
On revieving 50 oxyphilic thyroid neoplasms, 41 follicular and 9 papillary lesions were found to be carcinomas. All tumors were divided into two groups according to the degree of invaslveness. The female:male ratio was 1.6:1. The m~an age a[ time of diagnosis was 55 years ranging from 13 to 75 {widely invasive: 65, minimally invas[ve: 52; no significance). A h s o h t e tumor size (mean: 4.2 cm, range: 1.2-10) and predominant histological ~umor type (follicular vs. trabecular/solid) showed no positive correlation vith the degree of invasiveness or the number of metastases. The incidence of metastases in both groups }~are significantly different as well as if extension into extraglandular structures was compaired with intrsglandular crovth. After total thyroideetomy all patients were followed up for a period of maximal 18 years (mean; 5.5)~ I . ; ~ a erases or local recurrences could be demonstrated in ii patients. Of these, 3 accumulated ~3JIodine in cervical iymphnodes and lung and stayed for therapy. Concerning the patients without initial metastases, a positive tumermarker thyrogiobulin was evaluated in each case. According to our results, a dlstinction between minlmaiiy and widely i~vasive oxyphilic carcinoma see~s to he meaningful, in contrast to several authors ~e did see radioiodine uptake of metastases and would recommend to use IS~iodine scintigraphy for follow-up as w~l! as thyroqlobulin measurement.
487 A" Hotze, A. Boekisch, J. Ruhlmann, F. Gr~nwald, H.J. Biersack. Dept. Nuclo Med., Univ. Bonn, W. Germany
488 IL. TRONCONE, V. RUFINI, M,S. DAIDONE, A.L. VALENTINI, F.M. DANZA Departments of Nuclear Medicine and Radiology of Catholi( University of the Sacred Heart, Rome - Italy
SERUM THYROGLOBULIN IN NON TOXIC GOITER The determination of human serum thyroglobulin (hTg) is currently important in the follow up of thyroid carcinoma patients after surgery. Recent reports, however, have described the signigficanee of hTg in non malignant thyroid diseases. We therefore studied whether serum hTg levels are correlated with goiter size, thyroid nodules, or 1-thyroxine therapy. Patients/methods: retrospectively, 520 euthyroid patients with diffuse or nodular goiter (age: 18-43a) were analyzed with respect to serum T4,fT4, T3, hTg, thyroid scans, sonography and intake of 1-thyroxine. According to these criteria 8 groups of patients were established. Results: Diffuse {oiter Nodular goiter Size: I II I II III hTg(ng/ml) 17t2 2]~3 27±I 36!4 69~I L-thyroxine treatment Dose: no treatment 10Oug >100ug hTg(ng/ml) 31±3 16±I 14~3 It is evident that there exists a strong correlation between serum hTg, goiter size and nodular goiter. There is further evidence that serum hTg concentration decreases when 1-thyroxine is given for goiter size reduction. Conclusion: From these data it seems to be clear that measurement of serum hTg might become an important parameter in follow up of treatment of non toxic goiter. This is, in particular, of interest since a new sensitive assay system (IRMA) is being developed which makes it possible to measure hTg with higher precision than the RIA system which is currently used.
INCIDENTALLY DISCOVERED ADRENAL MASSES:FUNCTIONING OR NON FUNCTIONING? A NEW FIELD OF APPLICATION FOR ADRENAL IMAGING The wider application of sensitive diagnostic modalities ~has led to the detection of a high percentage of inciden~tally discovered adrenal masses.They do not elaborate any ~recognizable hormone in excess and their management is not unanimous. This paper reports our experience in this field Iduring 1988. Twenty-three adrena] masses were investlg~ted by adrenal 75 scintigranhy using Se-selenocholesterol (ii.i MBq i.v.) ~, 131 ana/or I-MIBG (37 MBq i.v. after thyroid blockade). Eleven out of 12 cases (91.6 %) examined on the basis of clinical and biochemical suspicion were correctly diagnosed a s s eortisol- and 2 aldosterone-secreting adenomas, 14 pheos and 2 neuroblastomas; one small aldosteronoma (< I0.5 cm) was missed. Eleven adrenal masses were fortuitous ly detected by CT (2 in extraadrenal tumor staging): 3 of them were not imaged (one adrenal cyst); 8 showed an elec rive radiocholesterol uptake in the unilateral mass (suppressed with dexamethasone, when given). Five masses removed were histologically cortical adenomas; 3 are in r e ! low up, and unchanged so far. This preliminary survey confirms the high incidence of fortuitously discovered adrenal masses and stresses the potential of seintigraphy in characterizing them and gai~ ning further knowledge on their natural history.
521
490
489 M. STEINLING1 ; J=L WEMEAU2 ; ~). FIALDES1 ;.E. GrL~ILLE z ; M. DECOULX-; R. VERGNESi
B. Huszno and Z. Bzybi~ski Endocrinology Denartment of Itedical Aea(lem~ in Cracow, Poland.
1-Service Central de M4decine Nucl4aire 2- U.S.N.A. C.H.U.R. F 59037 Lille Cedex HYPOTHYROIDISM INDUCED BY AMIODARONE IMMUNOLOGICAL AND ISOTOPIC STATUS.
:
In order to try to elucidate the meehanisms of the Amiodarone Treatment Indueed Hypothyroi'dism (A.I.H) we stud!ed the immunological (anti mierosomials, antithyrgtp,p,~lins ano fl~tireeeptors antibooies) and the i s o t o p i l ~ = ~ I ( 6 h ) and ~-Ga(24h) Thyroid uptake) status. When -z~I was higher than 10 % a perchlorate test was also perfdt'med. This study was carried on 10 Patients (9W ; 1M ; a g e :60-89 y) t r e a t e d for cardiac troubles by A (700-1000 mg/week)for a long time : 45 months (range : 9-84 m). T.S.H. was increased in all the subjects,free T 4 was decreased in 8 a ~ 3 f r e e T3in 6. Only 3 P had a hypertrophic thyroid. I uptake was very low (< 5 %) in 3 P, low (<20 %) in 5 and normal in 2. The perehlorate test was positive in 2/4 eases indicating an hormonosynthesis trouble. The 72 h after injection 67 Ga uptake was slightly increased in one ease ( > 0,2 %) and normal in 2. An increase of the a n t i t h y r o f d antibodies was observed in 6 eases. A treatment by perchlorate (1 g/day during a week) was uneffieient in 2 observations but led to normal in two one. These results suggest that functionnal abnormalities in A.I.H. may be linked to several meeanisms as iodine organification failure or thyroi'ditis lesions with or without immunological troubles. So it appears that complete immunological and isotopic investigations can be useful to manage correctly these patients with A.I.H.
491 C GIBOLD, H GRULET, H LARBRE, MJ DELISLE, G DELTOUR Institut Jean Godinot 1, rue du G~n~ral Koenig BP 171 51 056 REIMS
APPLICATIOH OF T ~ RADIOISOTOPE 131 Cs I~ EARLY DIAGNOSIS OF THYROID CANCER. ~eareh for the sensitive ;~!arl=erof thyroid e~neer constantly lasts. The examination of thvro~lobuli~e in early stages of the thyrgii neoplasm is sometime3 dsceptive~ Fe~ a long time it has been observed that 131 Cs 2an actual!ate in t h e ebld neGules of t h e t|1~roid gland. The studies cotnprised durin~ five @e~rS 8398 patients with nodules of tip-reid and the isoto~ie e~aminntion revealed in 5687 c~ses the cold nodules of that glnnd. In this group 1103 p~tients were treated surgicaly, and among them 131 ~atie~ts were diagnosed as thyroid malignant neoplasm. Each eperated patie.~ underwen~ additional scintigraphy of radiocesium. Results of selective scan with 1 3 1 C s were true ~ositive in 113 eaSes, true negative in S~6, false positive in 78 and false negative in 26 eases. Then the sensitivity of e~mmin~tion was calculated. It was shawn t ~ t the semsitivity of the identification of the pathological focus by radiocesium ~s equal t~ 0,812. It means that additional scintigraphy b~ use 131 Os e~ab!ed the pre-surgicnl d i ~ ~osi~ of thNyoid cancer in 81,2~ eases.
492 F. OZ, t . URGANCIOGLU, i . USLU, B. KANMAZ, B. OZ
DEPARTMENTS OF PATHOLOGY AND NUCLEAR MEDICINE, CERRAHPA~A MEDICAL FACULTY, iSTANBUL UNIVERSITY, TURKEY
ANTI-TSH RECEPTOR ANTIBODIES ASSAY ' CLINICAL USEFULNESS FOR THE MANAGEMENT OF HYPERTHYROIDISM IN GRAVES' DISEASE ? The aim of this study is the evaluation of the diagnostic and prognostic value of Anti-Thyreostimuline Hormone (TSH) Receptor
Antibodies (ARTSH) in patients with Graves' disease (GD). Method : The diagnosis of GD is based on clinical, biochemical and selntigraphic features. ARTSH are mesured by TRAK-Assay (Henning). Normal range is < 10 %. : In orde~ to nsses~ the diagtmatic "~alue ~f ARTS[{ J,t~ GD ARTSH were mesured in 103 patients with GD, 66 patients with an other thyroid disease than GD and 30 normal sub jets. In order to assess the pronostic value of ARTSH, 51 patients with GD treated medically with Carbimazole have been followed for up to 38 months after cessation of the drug. And 43 others patients with GD had repeted ARTSH 'measurements : before treatment (33 with Carbimazole and 10 with radioiodine), and after 2, 6 and 12 months. Results : The sensibility is 81%, better in ophtalmupathic patients (88 %) than in non ophtalmopathic patients (61%). The specificity is 97 %, with 2 false positives in a toxic multinodular goiter and in a Hashimoto's thyroiditis. The relapse is more frequent (78 % vs 41% with p < 0.05) when the initial value of ARTSH is > l0 %. An initial "value > 40 % indicates always a relapse. However, an initial value under 10 % can't exclude a relapse. In the 33 patients received rapidly degressive treatment of carbimazule, ARTSH progressively decrease (p < 0.05 at 6 months and p < 0.01 at 12 months). In the J,0 patients treated with radioiodine, ARTSH increase at 2 months, then decrease at 6 and 12 months (p < 0.05). Among these 43 patients, the response 1[o the treatment is favnurable in 90 % of the cases when the ARTSH nre < l0 %. These results suggest that ARTSH are useful in the managementef-tmtl~nts with GD.
EARLYCYTOLOGICALCHANGESTHYROCYTESIN PATIENTSWITH HYPERITIYROIDI~ AFTERRADIOIODINE(I-131) THERAPY. Acute effects of radioiodine treatment on the thyroid ceils of 80 patients (22 male and 58 female) with hyperthyroidism who had received a total dose of 6-25 mci 1-131 were investigated. Fine needle aspiration biopsy (FNAB) had been performed in 207 cases during the past 5 years with 96,14 % accuracy as ccnDared with surgery. The patients were devided into four groups each consisting 20 cases. FNABof 50 patients with hyperthyroidismwho were not treated with 1-131 were used as a control. Thyrocytes of 50 patients with hyperthyroidism had densely but finely reticular chromatin structure and nucleeli were slightly enlarged. Moreover, the cells showed slight to moderate anisonucleosis. First week: The thyrocytes had finely distributed chranatin sturucture but SQTehad granular pattern in certain regions of the nuclei. No nuclei were seen. There were vacuole in cy[oplasm of s(ine thyrocytes. Second week: Instead of finely reticular pattern, roughly granular or thick linear chromatin sturucture was observed in scmethyrocytes. Third and fourth weeks: Moderate anisonucleosis was seen. The chrcmatin of most thyrocytes had thick linear structure in the center of the nucleeus which was cluTI~ in a ci~ular pattern. The nuclei and cytoplasm were enlanged and cytoplasm had sate vacuoles. Conclusion: The early microscopic changes of thyroid cells of the patients with hyperthyroidism after 1-131 treatment has the granular pattern of the chramatin in somecells. After twD weeks chrcmatin became roughly linear in sameregions. After third and fourth weeks i t was observed that the chrcmatin got clLmmed and thickened in circular pattern in the center of the nuclei. All these findings were considered as early therapeutic radiation effects. They were regressive, but not carcincmatous changes.
522
4.93
494 K. Gratz, H. Dralle, S. Schr6der, K. Neumann, R. Besch
Z.Kusi6, ~ ,
D.V.Becker, E.L.Saenger, P.Paras, H.Prpi6, N.Djakovi6, ~.Spaventi
"Dr.M.Stojanovid" Hospital,Zagreb,Yugoslavia; The N Y H o s p l t a l - C o r n e l l M e d . C t r . , NY; U n i v . o f C i n c i n n a t i M e d . C t r . , O h i o ; N C D R E , FDA, S i l v e r S p r i n g , M a r y l a n d , USA. DISCREPANCY BETWEEN SCINTIGRAPHY
T c - 9 9 m A N D I'123 T H Y R O I D
The p u r p o s e of t h e s t u d y w a s to i n v e s t i g a t e d i f ferences between 1-123 and Tc-99m pertechnetate as i m a g i n g a g e n t s f o r n o d u l a r g o i t e r u s i n g c y t o logic or histologic follow-up. Cytological or histological examination was perf o r m e d o n 32 t h y r o i d n o d u l e s w i t h d i s c r e p a n t s c a n f i n d i n g s u s i n g T c - 9 9 m a n d 1-123. Examinations of nodules with a positive (normal o r i n c r e a s e d ) u p t a k e o f T c - 9 9 m a n d n e g a t i v e (decreased or normal) uptake of radioiodine revealed a variety of lesions: colloid goiter in 9 c a s e s , c o l l o i d g o i t e r w i t h c y s t in 2 c a s e s , h e m o r r h a g i c c y s t in 2 c a s e s , l y m p h o c y t i c t h y r o i d i tis in 2 c a s e s , f o l l i c u l a r a d e n o m a in 1 c a s e , n o r m a l t h y r o i d in 1 c a s e a n d s e v e r e a c u t e inflamm a t i o n i n 1 case. 'I N o d u l e s w i t h a n o t h e r t y p e of d i s c r e p a n c y : negative (normal or decreased) Tc-99m uptake and positive ( i n c r e a s e d o r n o r m a l ) r a d l o i o d i n e uptake were: follicular adenoma in 5 cases, colloid g o i t e r in 5 c a s e s a n d h e m o r r h a g i c c y s t in 4 c a ses. T w o c a n c e r s w e r e f o u n d i n the g l a n d s w i t h discrepant images but did not correlate with scintlgraphic discrepancy. There w a s n o c o r r e l a t i o n b e t w e e n t h e o b s e r v e d t y p e of d i s c r e p a n c y a n d c y t o l o g y o r h i s t o l o g y of the n o d u l e .
Abt. Nuklearmedizin und spezielle Biophysik, Klinik f~r Abdominal- und Transplantationschirurgie und Abt. Klinische Endokrinolo0ie, Med. Hochschule Hannover; Institut f~r Pathologie dsr Universithtskliniken Hamburg, FRG BENZYLGUANIDINE-SClNTIGRAPHY IN PATIENTS WITH SPORADIC ADRENAL MEDULLARY HYPERPLASIA BEFORE AND AFTER THERAPY Adrenal medulla hyperplasia with hypercatecholaminemia is regarded as the earliest adrenal manifestation in HEN type 2. Hov~ver, morphogenesis, pathogenic and pathnphys~ological mechanisms involved in the developement of non-familial pheochromocytoma as well as pre- and postoperative diagnostic has not been elucidated until now. We report three cases which are the first documentation of adrenal hypertension due to sporadic unilateral adrenal hyperplasia successfully treated by unilateral adrenalectomy. We used mJslI - and m12SI-benzylguanidine (BG) for pianar and SPECT scintigraphy. Scintigraphy as well as transmission computed tomography (TCT) and ultrasound (US) failed to demonstrate an enlargement of the adrenal aland vith diffuse hyperplasia. The weight of th~ adrenal gland was 3.8 g. In both cases with focal hyperplasia scintigraphy localized correctly, whereas TCT and US ~ailed in one case respectively. Planar scintigraphy was ~ble to demonstrate the correct side already in a 8 g ~eighted gland. In the other case (5.3 g) SPECT was necessary and correct. IIormal gland uptake could be demonstrated vith SPECT postoperatively. To localize focal forms of hyperplasia BG SPECT seems to be the best non-invasive p[ocedure. Lateral~sation of the adrenal gland uptake is diagnostic. After Rdrsnalectomy a distinction between normal and abnormal gland could not be made. Quantification of the uptake provides a possibility for further differentiation.
496
495 M. Rodrimms, M. R. Vieira, R. Santos and E. I/robert.
LI. Berne, I. Carri6, M. Estorch, C. Martfnez-Duncker, A. Garc~a, R. Cabezas, C. Alonso.
Hospital de Sent Pau, Barcelona. Servi~o de Medicine Nuclear end Servigo de Endocrinologia,InstitutoPortaguEs de Oncologia, Lisbon, Portugal. 03~CAL
OF o~irc(v)-D~','n~A~o~ c
EV~CN
-[P OF P A T I ~
W~
M ~
~OID
AC~TT~A) ~
CA~.
Medullary thyroid carcinoma (MIU) has a high incidence of recurrence.In 1984, the group of Kyoto University reported successful imaging of MIll using 9O~Tc(V) - roSA. (roSA),
evaluste the role of I~A imaging in 20 patients (pts) (12 female and 8 male) with histologically proven MR], mmely in the diagnosis of recurirence end metastases. Age at diagnosis range ]4-81 (mean 47.47)yeers.Two ~pts were imsged prior end after total thyroidectc*ny(TF) (4 studies) and Z18 pts (27 studies) only after Tr.Tbirteen pts (19 studies) had biochemical and/or clinical evidence of recurrent disease. Pts were injected with lOmCi 99~c(V) - I~A IV and images ~e_reacquired on a gamma camera at 2 end 4 h postinjectien.Anteriorand posterior head, neck, thorax and abdomen images ~ere obtained. The 2 pts imaged prior and after Tr showed positive uptake of IIVSAin th_y roid prior RT and no uptake after T L Positive uptake of ~ in metastases and/or in residual thyroid ~ere observed in 14 studies;at time of ires ging only iI pts had elevated calcitonin levels,9 pta elevated CEA level~ and 12 pta clinical evidence of disease. No abnormal uptake of 1 ~ was observed in 4 pts with elevated calcitenin levels,3 pts with aleveted (YA levels end 2 pts with clinical evidence of disease.Two pts with positive uptake of I ~ in metastases had negative CAT scans;two other pts had me~ tastases ~sualised on CAT scans and no abnormal uptake of II~A.Three pts without evidence of disease after Tr showed no abnormal uptake of I~A. We concluded that I]V~Ais a useful imaging agent for follow - up of MrC, with a sensitivity of lesion detection of 63%=in pts with proves recarren ce and/or metastases;posiriveuptake of I]¢BAcan be the only positive fi~ ding, even before elevated csicitonin and flealevels.
131-I-ANTICEA SCANS IN PATIENTS WITH RESECTED MEDULLARY THYROID CARCINOMA AND HIGH LEVELS OF TUMOR MARKERS. It is often difficult to localize recidive or metastases sites in patients with resented me~111ary thyroid carcinoma (MTC) presenting with elevation of calcitonin (CT) and carcinoemhrionary antigen (CEA). To assess the ability of 1311-AntiCEA to detect recurrency, 9 patients with resented MTC and high levels of CT and CEA were studied with 1311-AntiCEA, Computed Axial Tomography (CAT) and ~mII-MIBG scans. Planar scans were performed 5-7 days post-injection of i mg of F(ab')2 antiCEA. Confirmation of recurrency was obtained by biopsy, ulterior imaging techniques and/or surgery. l J AntiCEA
I t + t 8 1 l I L
I J
I
MIBG
CAT
2
3
7
6
AntiCEA scans detected more MTC sites than MIBG or CAT scans. When surgery was performed, findings were congruent with AntiCEA scans. Immunohistochemical analysis revealed presence of CEA in rigors. AntiCEA scans seem more sensitive to localize recurrency in patients with high levels of tumor markers.
523
497
498
F.Corstens. C.Ticheler, H . d e Boer, P . K l o p p e n b o r g and W.Buijs.
Departments of Nuclear Medicine, Surgery and Endocrinology University Hospital, Nijmegen, The Netherlands. LOW SENSITIVITY OF PARATHYROID SCINTIGRAPHY FOR UPPER POLE ADENOMATA AND A NEW SUBTRACTION METHOD TO IMPROVE THEIR DETECTABILITY.
In a retrospective study of 35 parathyroid scans preoperatively performed in 35 patients with a peroperatively proven parathyroid adenoma we found sensitivity to be remarkably influenced by tumour localization. Lower pole parathyroid tumours were correctly detected in 72% (13/18), upper pole adenomata only in 12% (2/17). This outcome may be explained by the fact that upper pole parathyroid tumours usuallylay behindthe thyroid while lower pole adenomata often are localized partly beneath the thyroid,
A phantom study in which neck-, thyroid- and parathyroid compartments anatomicallyand radiochemicallywere simulateddemonstrateda"parathyroid turnout" next to the '~hyroid"to be easily detected whereas the subtraction , imagefailed to show the same "parathyroidtumour" if put behind the '~hyroid". To improve the detection of (retrothyroidal) parathyroid adenomata we designed a method of subtraction which comprises a new formula for calculating a multiplication factor (MF) whereby the Technetium-99m (Tc)-image is multiplied before being subtracted from the Thallium-201 (TO-image.We drew two regions of interest in the Tc-image, one within a thyroid lobe (R1) and another region in the neck area (R2). We recorded the average number of counts per pixel (N) in these regions in the Tc-image (NR1,Tcand NR2,Tc)as well as the TI-image (NR1,TIand NR2,TI).Then: MF = (NRI,TI - NR2,'rl) / (NR1,TcNR2,Tc).
This method applied to the phantom studies resulted in a subtraction image which clearly showed the "retrothyroidalturnout". In practice MF turned out to be smallerthan an in a customaryway calculated normalizationfactor, so there is less noise in the subtraction image. Our method produced a subtraction image in which thyroid and neck area have nearly equal count densities consequentlyresulting in a higher contrast in the displayed image. In three out of four patient studies which were falsely negativeif analyzed in a customaryway, our subtraction method correctly demonstrated the parathyroid tumour site. Patient studies are going on to clinically verify this new and simply feasible subtraction method. 499 F. Corstens, D. H u y s m a n s , P. K l o p p e n b o r g .
Departments of Nuclear medicine and Endocrinology University Hospital, Nijmegen, The Netherlands.
L O N G - T E R M F O L L O W UP IN S O L I T A R Y A U T O N O M O U S T H Y R O I D N O D U L E S T R E A T E D W I T H 131-1.
In this study the long-term effects of radio-iodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty patients with thyrotoxic symptoms and a single hot nodule on the preliminary thyroid scan with visualization of the extranodular tissue on scan,-,ing after TSH, received a therapeuLic dose of 20 mCi of iodine-131. Follow up data after 3 to 17,5 years (mean 9 years) included a medical interview, physical examination and a biochemical evaluation of thyroid function. Clinical euthyroidism was present in 47 patients, one of whom had received a second dose 1,5 years after the first because of recurring hyperthyroidism. Two of these patients had slightly ' elevated T4 levels and may need further therapy in future. Five of them had TSH levels of 5 to 8 mU/I together with normal T4 levels, for several years. The stability of this situation over several years argues gainst developing hypothyroidism. Overt hypothyroidism had occurred in three patients 3, 7 and 15 years after radio-iodine therapy. This development was not related to the calculated radiation dose. In conclusion: with a standard dose of 20 mCi of radio-iodine most ~atients with a toxic solitary autonomous thyroid nodule can be cured. With the proviso of complete suppression of the extranodular tissue at the time of 131-I-treatment, the incidence of hypothyroidism is low at long-term follow up.
A. Hotze, A. Bockisch, J. Ruhlmann, F. GrUnwald, M. Horst, H.J. Biersack. Dept. Nucl. Ned., Univ. Bonn, W. Germany
• B~A~ OF NOr TOXIC GOITE~ W I ~ L-'±%Um0XI~E AH~ IODIDE OR P0~E L - ~ m n ~ 0 x I ~ ( L - ~ 4 ) . 80 euthyroid patients (pts.) (age:18-3Oa) with non toxic diffuse goiter were treated either with 100ug L-T4 (group I,n=40) or 100 ug L-T4+1OOug iodide (group II, n=30). Both groups were of comparable age, body weight and height , as well as initial thyroid volume (th-vol.) (estimated by ultrasound). Methods: In addition to serum T4, fT4, TS, delta-TSH, th.-vol., and human thyroglobulin (hTg) with recovery tests and hTg antibodies (TAB) were determined before treatment, and 10 weeks and 6 month~ later. Results: All laboratory parameters with exception of delta-TSH, hT~ and thyroid volume did not show significant changes in either group, hTg recovery was found to be normal in each pt., and no TABs were detectable. The pts. treated with the compound prep. showed a higher reduction in percentage of delta-TSH, hTg and thyroid volume compared to those treated with pure L-T4: delta TSH: 10 weeks 87%vs85%, 6 months: 94vs86% hTg (ng/ml): 10 weeks 78~vs73%, 6 months: 75vs84% Th-vol. 10 weeks 34%vs19%, 6 months: 37vs25% Conclusion: These results clearly show that the efficacy of the compound preparation which contains a physiol, dosage of iodine is superior to the pure L-T4 in th.-vol. reduction and decrease of delta-TSH and hTg. This effect must be definitely attributed to the iodine since both preparations contained the identical amount of L-T4.
500 K.reisig T., C.R. Pickardt*, Knesewitsch
C. Vaitl,
C.M. Kirsch and P.
D e p a r t m e n t of Radiology, Division of Nuclear Medicine and D e p a r t m e n t of Internal Medicine Innenstad*, University of Munich, Munich, FRG
GLOBAL 99mTC THYROID UPTAKE (TCTU): A USEFUL PARAMETER IN THE DIFFERENTIAL DIAGNOSIS OF IMMUNOGENIC (IH) AND NON IMMUNOGENIC HYPERTHYROIDISM (NIH) ? Besides t h e visual i n t e r p r e t a t i o n of thyroid s c i n t i s c a n s more objective i n f o r m a t i o n can be derived from t h e q u a n t i tative evaluation of t h e TcTU of t h e whole gland. The aim of t h e s t u d y was to evaluate t h e u s e f u l n e s s of t h e TcTU in t h e differential diagnosis of IH and NIH. Out of 85 p a t i e n t s (p) with overt h y p e r t h y r o i d i s m - c o n s e cutively diagnosed - and without any thyroid specific drug 28 p (30%) had IH. IH was diagnosed by eye signs and/or TSH receptor antibodies. Hyperthyroidism with an h o m o g e neous s c i n t i s c a n was found in 27 p (96%) of IH and in 11 p (19%) with NIH. 15 p out of t h e s e 38 p had TcTU values above 10% 1 p with NIH and 14 p with IH. H o m o g e n e o u s s c i n t i s c a n s and a TcTU above 10% were diagnostic for IH with a sensitivity of 48% but a s p e c i f i c i t y of 93%, w h e r e a s a TcTU below 10% could not d i s c r i m i n a t e b e t w e e n IH and NIH. If two of t h e following t h r e e criteria, "TcTU > 10%% "thyroid volume < 30 ml", "low e c h o g e n i c i t y by u l t r a s o u n d " , were positive, IH could be diagnosed with a sensitivity of 63% and a s p e c i f i c i t i y of 100%. Conclusion: To d i s c r i m i n a t e b e t w e e n IH and NIH in p a t i e n t s with h o m o g e n e o u s s c i n t i s c a n s (96% of all IH) TcTU is ~. useful additional p a r a m e t e r . The s p e c i f i c i t y is 93% for IH when TcTU is above 10%. In c o m b i n a t i o n with thyroid volume and e c h o g e n i c i t y a sensitivity of 63% with a s p e c i ficitiy of 100% for IH could be reached.
524.
501 D.Casar~,D.Rubello,H.E.Girelli,A.Perin,B.Busnardo °Divlsione di Radio~erapia e Medic~na Nucleate, Ospedale di Padova; Istituto dl Semexiotlca Medica, Universit~ di Padova, Padova ITALY
502 N. P A U N K O V I O ,
J.~ILADINOVIO,
Medicel
Centre
Nuclear
Medicine,
ZsjeSsr,
O. P A V L O V I O
Yugoslavia
ROLE OF RADIOIODINE THERAPY IN 256 PATIENTS WITH DISTAXT METASTASES OF THYROID CANCER
E V A L U A T I O N OF A U T O I M M U N E S T I M U L A T I O N OF THYROID BY 99m-Tc PERTECH~TATE UPTAKE TEST
~he importance of radioiodine therapy (RIT) in differentia ted thyroid cancer (DCT) is well known.To evaluate RIT usefulness in the different sites of metastases,we studie a group of 256 patients with distant metastases (122 papilary-P,|43 follicular-F)before and after RIT.AII underwent total thyroldeetomy and RIT.F/H=5/I,age 18-77,mean 47. Vollow-up ranged 18-96 months.Remission/progression of disease was ascertained by clinical findings,X-ray,total body scan and serum thyroglobulin.Patients with lung (33'% of P,28 of F)or mediastinie (24% of P,~8% of F) or brain llv~r (23% of P,20%of F)metastases had the greatest % of remission,while response in cases with bone metastases wag very poor (0% of P,4% of F).Patients in remission were younger than those who had died of disease (respeotivel 2 mean age was 30 vs 57 yrs for P and 44 vs 57 for F). Conclusions:in distant metastases of DCT,RIT seems to give the best results in lung,and then in mediastinic,brain, liver metastases. The worse results were obtained in bone metastases. Probably,in the latter site radiotherapy and chemotherapy may play a role.Age appears to have an important prognostic value in distant metastases treated by RIT.
Physiological (TSH) a n d p a t h o l o g i c a l (TSI) s t i m u l a t o r s of t h y r o i d f u n c t i o n h e r e i n f l u e n c e on m o n c v 8 l e n t e i o n s t h y r o i d u p t a k e . We h a v e sdspted 99m-Tc pertechnetate uptake test for t e s t i n g of T S I a c t i o n on t h y r o i d gland. Tc-9~m pgrtechnetstewss 8ppligd intr~venou s ± y 8 n ~ r a z e of t h y r o i a 8 c c u m u l s ~ l o n o e ~ w e e n 1 to 5 m i n u t e s w s s m e s s u r e d , R e s u l t s w e r e c o m pared with clinicsl diagnosis and evaluation, thyroid hormones concentrations and 8ntireceptor TSH antibodies findings. F o l l o w i n g d a t a w e r e o b t a i n e d : t e s t is n e g e t i r e i n e u t h y r o i d s u b j e c t s (30). In p a t i e n t s w i t h G r e v e s " d i s e s s e t e s t v e l u e s ere e l e v a t e d , in u n t r e a t e d p a t i e n t s (21) es well 8s in p e t i e n t s w i t h r e l s p s (l#). In u n t r e a t e d p a t i e n t s w i t h d i f f u s e t h y r o i d a u t o n o m y (9) t e s t is n e g a t i v e . In r e m i s s i o n of G r a v e s " d i s e a s e , v a l u es of t e s t are e l e v a t e d m o s t l y in p s t i e n t s w i t h p o s i t i v e f i n d i n g s of a n t i r e c e p t o r T S H a n t i b o d i e s (8 of ll), w h i l e in p s t i e n t s w i t h o u t sntireceptor e n t i b o d i e s v a l u e s of p e r t e c h n e t s t e u p t a k e t e s t sre f r e q u e n t l y n e g a t i v e (18 of 22 p a t i e n t s ) . We c o n s i d e r t h e t u s e d t e s t e s t i m e t e s a u t o i m m u n e t h y r o i d s t i m u l e t i o n r e t h e r t h e n its hyperfunction.
503
504 George
A. Lie
M. B~hre
Said Zubi M.D. Vernice Ccwell
Institute of Nuclear Medicine, Medical University of L[ibeck, D-2400 L[ibeck, F R G
B ~ v s t a t e M e d i c a l Center D~pt. of N u c l e a r M e d i c i n e 759 C h e s t n u t S t r e e t S p r i n g f i e l d , MA 01107 U.S.A.
T H Y R O I D A U T O N O M Y INVESTIGATED BY HIGH-RESOLUTION SUPPRESSION SCINTIGRAPHY: ITS P R E V A L E N C E IN D E P E N D E N C E O F PATIENT A G E A N D PALPATION FINDINGS The study aimed at evaluating predictive parameters for the existence of functional thyroid autonomy in endemic goitres. In 426 individuals from an area of iodine deficiency, quantified high resolution suppression scintigraphy with pertechnetate was used to reveal the existence of autonomous tissue in vivo. The prevalence of autonomy was determined in dependence of the following features: presence of a goitre, thyroid mass, goitre type (diffuse or nodular) and patient age. A relevant extent of autonomy causing an increased risk of hyperthyroidism was found in 2 % of individuals without goitre but in 23 % of all goitrous patients. Relevant autonomy was also present in 47 % of goitrous individuals aged over 35 and in 67 % of those with a thyroid mass above 50 g. Since the patients were unselected respecting the combination of the features investigated, these frequencies represent the range of prevalence of autonomy in the collective. In the cases with abnormal suppression, the frequency of enhanced TT3-concentratlons under suppression with thyroxine increased with the equivalent for the nonsuppressible iodide clearance confirming a continuum of different extents of autonomy. Conclusion: Clinical criteria allow to estimate the prevalence of thyroid autonomy and the risk of hyperthyroidism in iodine deficient goitres, thus providing criteria for efficient diagnostic and therapeutic decisions.
METHOD IMPROVES P A R A T H Y R O I D A D E N O M A DETECTION A new method Of d o u b l e tracer thyroid image subtraction for parathyroid adenomas is described. The corona of thallium scatter activity, that is present in current subtraction techniques, is eliminated by a new subtraction program. An injection of 32 MBg Tc-99m is given. At twenty minvtes , a t e c h n e t i u m thyroid image and scatter image are obtained on T C - 9 9 m and TI-201 energy w i n d o w settings respectively. Then 32 MBg TI-201 are injected and fige t h a l l i u m thyroid images are obtained on TI-201 energy windows. All images are of five minutes duration and are motion corrected. Regions of interest (ROI) are drawn on the thyroid and background proximal to the thyroid. From the ROI's, the computer determines the ratio of t h a l l i u m thyroid signal to back ground noise. For each thallium thyroid image, the computer makes a t e c h n e t i u m mixture image by adding scatter images to the technetium thyroid image in such a way that the signal to noise ratio in the mixture image will be equal to that seen in the t h a l l i u m thyroid image. The t e c h n e t i u m mixture images are normalized and subtracted from the t h a l l i u m thyroid images. The resultant images are scatter free and have enhanced parathyroid adenoma visualiztion. Surgical reports from fifty patients were evaluated. Accurate parathyroid adenoma visualization was achieved in 94% of cases with our method as compared to 82% with current methods.
525
506
505
G . L u p a t t e l l i * , I . V i r g o l i n i , F.Rauscha, J.H@bert, H.Sinzinger. A t h e r o s c l e r o s i s R e s e a r c h G r o u p (ATK) of the A u s t r i a n A c a d e m y of Sciences, 2nd Dept. of N u c l e a r Medicine, U n i v e r s i t y of V i e n n a , Austria; * 2nd Dept. of I n t e r n a l Medicine, U n i v e r s i t y of Perugia, Italy.
B. Huszno, Z. Szybi~ski Endocrinology Department of Medical Academy in Cracow, Poland
APPLICATION OF THE RADIOISOTOPE 131 Cs IN EARLY DIAGNOSIS OF THYROID cANCER Search for the sensitive marker of thyroid cancer constantly lasts. The examination of thyroglobuline in the early stages of the thyroid neoplasm is sometimes deceptive. For a long time it has been observed that 131 Cs can accumulate in the cold nodules of the thyroid gland. The studies comprised during five years 8398 patients with nodules of the thyroid and the isotopic examination revealed in 5687 cases the cold nodules of that gland. In this group 1103 patients were treated surgicaly, and among them 131 patients were diagnosed as thyroid malignant neoplasm. Each operated patisnt underwent additional scintigraphy of radiocesium. Results of selective scan with 131 Cs were true positive in 113 cases, true negative in 886, false positive in 78 and false negative in 26 cases. Then the sensitivity of examination was calculated. It was shown that the sensitivity of the identification of the pathological focus by radiocesium is equal to 0,812. It means that additional scintigraphy by use of 151 Cs enabled the pre-surgical diagnosis of thyroid cancer in 81.2% cases. The highest specificity of the accumulation of 131 Os was shown in relation to papillary carcinoma and then to folliculary
R A D I O I O D I N A T E D LDL FOR IN V l V O S T U D Y I N G OF L I V E R APO B , E - R E C E P T O R ACTIVITY. The role of liver LDL r e c e p t o r s for c h o l e s t e r o l h o m e o s t a s i s is known since m a n y years. The aim of this study was to i n v e s t i g a t e ape B,Er e c e p t o r a c t i v i t y in the liver in rive in p a t i e n t s w i t h and w i t h o u t h y p e r c h o l e s t e r o l e m i a . A u t o l o g o u s LDL w e r e l a b e l e d w i t h 123I (4 mCi) by the m o n o c h l o r i d e m e t h o d or by Iodogen. In each p a t i e n t d y n a m i c i m a g i n g over the liver and p r e c o r d i u m using a L V O F - g a m m a c a m e r a was p e r f o r m e d for 20 m i n u t e s (Iframe/30 s). Thereafter S . P . E . C . T . - s c i n t i g r a p h y was done with a d o u b l e h e a d e d gamma camera (30 s/angle). Before r e i n j e c t i o n of a u t o l o g o u s LDL b l o o d was taken for l y m p h o c y t e i s o l a t i o n and in vitro LDL b i n d i n g studies. The tracer u p t a k e m e a s u r e d over the liver r e a c h e d e q u i l i b r i u m after 15 minutes. In some p a t i e n t s a s i g n i f i c a n t l y lower tracer uptake was o b s e r v e d (related to their liver v o l u m e w h i c h was d e t e r m i n e d by a s p e c i f i c c o m p u t e r program). In these p a t i e n t s also the n u m b e r of LDL r e c e p t o r s / c e l l at intact l y m p h o c y t e was signif i c a n t l y lower. This study shows that the m e t h o d p r e s e n t e d could be a new a p p r o a c h for the d e t e r m i n a t i o n of r e c e p t o r a c t i v i t y in the liver and could be c l i n i c a l l y used for s t u d y i n g it after diet or d r u g therapy.
o~rc~nom~.
508
507
t . URGANCIO~LU, G. ONSEL, t. USLU, E. VARDARELI S.K.
IMAM
D e p a r t m e n t of N u c l e a r M e d i c i n e Golestan Medical Centre A h w a z U n i v e r s i t y of M e d i c a l S c i e n c e s Ahwaz Iran OUTBREAK
OF
'FRIGHT'
G01TRES
IN W A R A R E A S
A s u d d e n a p p e a r a n c e of g o i t r e has b e e n e n c o u n t e r e d in a p o p u l a t i o n l i v i n g in a s e r i o u s l y a g i t a t e d w a r r e g i o n s 5-15 days following severe missile attacks, heavy b o m b a r d m e n t s and c a s u a l t i e s in f a m i l i e s . The p u r p o s e of this s t u d y is to f i n d s a l i e n t f e a t u r e s and c a u s a t i v e f a c t o r s l e a d i n g tc s u d d e n a p p e a r a n c e of s u c h g o i t r e s . M E T H O D S : T h i r t y f i v e s u c h c a s e s are d i v u l g e d b l a m i n g the w a r to be the c a u s a t i v e f a c t o r for t h e i r t h y r o m e g a l y . T c 9 9 m t h y r o i d i m a g i n g , TS, T4, FTI, and TSH e s t i m a t i o n s w e r e p e r f o r m e d . In some cases, TS u p t a k e w a s also included. R E S U L T S : As a w h o l e , 5 - 1 5 % i n c r e a s e in i n c i d e n t s of g o i t r e s has b e e n p e r c e i v e d w i t h v a r y i n g p a t t e r n of h o r m o n a l levels. H a e m o r r h a g i c c y s t s w e r e also f o u n d in some cases. C O N C L U S I O N : The d a t a has b e e n a c c u m u l a t e d to f i n d a c l u e for the exact c a u s a t i v e f a c t o r a n d its r e g u l a t i o n to the c a t a s t r o p h i c situation. A possible underlying mechanism h a s b e e n p r o p o s e d in t e r m s of h o r m o n a l p a t t e r n in the a f f e c t e d cases.
ISTANBUL UNIVERSITY, CERRAHPA~AMEDICAL FACULTY, NUCLEAR MEDICINE DEPARTMENT, TURKEY GALLBLADDER FUNCTION IN HYPERTHYROIDPATIENTS The purpose of t h i s study was to investigate the hepatob i l i a r y system in normal subjects and in hyperthyroid patients by using Tc-99m iminodiacetic acid (disofenin) and to r e i n v e s t i g a t e the same patients at 3 and 6 months a f t e r they became euthyroid e i t h e r by 1-131 and MMI combination, or MMI alone. In a l l patients, in addition to physical examination, serum T4, T3 values and routine l i v e r function tests were performed I n i t i a l l y and at 3 and 6 months a f t e r therapy. Gallbladder function was investigated 10 normal and in 10 hyperthyroid patients. All of these hyperthyroid Datients were restudied a f t e r the treatment. Nonral controls had no evidenceof gallstone by cholecystographyor by ultrasound. In hyperthyroid patients, cholecystography was not donepurposelybut they had no evidenceof galls-tonoby ultrasonographicexamination.After overnight fasting 0.5-I mCi (18-37 F~q) Tc-ggm labelled disofenin were injected intravenously. ParelIel hole collimator was placed on the right upper quadrant and the cotnts were registered for one minute in every 3 minutes for the first 15 minutes and then every 5 minutes for 120 minutes. Activity in the liver was surveyedthrough the whole study. At 60 minutes "Boydenmeal" was given orally. Latent period (LP), ejection period (EP), ejection fraction (EF) and ejection rate (ER) weremeasured.Time period to reach ma~im~nin gallbladder in the beginningof gallbladder B11Dtyingand hB1f period of this activity were also measured.Peakliver activity and half period of this activity were also measured.As a conclusion, after six monthsof t r e a i ~ t , gallbladder function becamenonral through LP, EP and ERwere in!provedafter three monthsof treatment. The liver dynamicsshowedthe sameimprovenent.
526
509
510
[ ROCA, I PAVIA, ~ AGUADB,0 NORAGAS,J BOTE~ F PORTA. Bervicio de Redieiea Nuclear y de Alergis Pediatrie~ Hospital General and Cliuica l~taoti]. Ciudad Sanitaria "Vail d'Bebron' Servicio de Nedlcina Nuclear. Hospital Cllnico Provincial. Barcelona. 8pain.
~OPHAGBALSCINTIGRAPBTIN CS[LDBEN¥ITB ABTHMA During the last decade multiple publications have related asthea and recurrent bronchitis (gB) with gaotroeoopbagea] reflux (~BB}, Eoophagic scintigraphy (KS) is an easy, los dooieetry and eel] tolerated technique. It detects alterations in gastroenophagic transit in children with bronchopolsonnry symptoms. We have studied 2t! children with recurrent bronchitis by means of ana]itica] results, ioaunoallergy,cutaneousand challengetesta, lung functional test, roengcntnological gastroesophsgic transit and RS. They were classified n three groups : [gg dependent asthma (IgKA), spasmodic cough (KCg) and no lgg dependent asthma (B[ggg}. KS studied two dcglntitions of liquid labelled with 99|Te-sulphur colloid. A computer programconstructs the condensed image of deglutition. The results were coantified in four grades (1, normal; 2, 3 and 4 abnormalesophageal retention). NIgRA IgKg BOO ÷ gO
39
51
3t
fZ
0!
]7
Z ÷ 0,48 O.gl 0,00 We have seen a percentage significantly higher of pathologic RB in patients with atopic asthma {Bt~, o=B3, =(0,04) and in patients with spasmodic cough ti51, n:48, l(0,03) in relation with patients with no [gE dependent anthna ( | S t n:8]}. liken me compared KS nith radioiogical transit, ee round a relatively lo. aceurac (o.sg}. The results of this study shov s high percentage of esophageal aboornlitie in children with EB, mitt sigoiffieaotly higher results in children with atopic criteria, [gB dependent asthma and with spasmodic cough.
A.Z. MIDDELHEIM and ALGEMEEN KINDERZIEKENHUIS ANTWERPEN,BELGIUM.
A comparat ve evaluation of the separate kidney function in children by means of Tc-99m MAG3 and Tc-99m DTPA. Tc-99m DTPA is a good marker of the glomerular filtration and allows an evaluation of the separate kidney function by means of a gamma camera. In young infants the results are less reliable, due to dosimetric considerations and immature renal function. It is tempting to substitute Tc-99m DTPA by Tc-99m MAG3 because of the higher extraction rate. We compared the separate renal clearance of both tracers, with an interval of 2 days, in 8 children, age 1-15 years, suffering from various pathologies (pelviureteric junction stenosis, kidney displasy, vesicouretheral reflux...). The calculation of the clearance is based on a sequential acquisition during 20 minutes and a blood sample at the 20-th minute. The correlation coefficient between the clearance data of both agents is .81 and the regression line y= 14.7+3.83 x. The perirenal area is used for background subtraction and the clearance is calculated by 3 methods simultaneously: surface ratio correction and slope method; 80-140 sec fit and integral method and linear fit with double correction. The mean difference between integral and slope method obtained with Tc-99m DTPA and Mug3 is respectively 9.1%(c.v. t 1.9%) and 2.8%(c.v. 5.7 %). The mean difference between integral and the linear fit is 13.6%(c.v. 7.3%) for DTPA and 7,7%(c.v. 8,2%) for Mag3. The transit time is not significantly different. The results of Tc-99m Mag3 are more reliable and less influenced by the background. Tc-99m Mag3 is better adapted for young infants to estimate the separate renal function. 512
511
J.Fettich, R.Kenda, T.Kenig, Z. Pleterskl Depts. of Nuclear Meaicine,
J, VANDEVIVERE, A. DOBBELEIR, H. CAPPIAU, K. MELIS, A. JESPERS,J. VANDAMME.
Paediatrics and
Radiology - University ~eaical Centre
J.J.Fettich,
R.Kenda,
T.Kenig,
Z.Zupancic
Departments of Nuclear Medicine, Paediatrics, and Radiology University Medical Centre Ljubljana, Yugoslavia
Ljubljana, Slovenia,Yugoslavi a
RADIONUCLIDE C Y S T O G R A P H Y (RCG) A N D RENOGRAPHY (RNG) IN C O M P A R I S O N W I T H U L T R A S O U N D (US). EXC R E T O R Y U R O G R A P H Y (EU) A N D C O N T R A S T C Y S T O G R A P H Y (CG) IN C H I L D R E N W I T H U R I N A R Y T R A C T I N F E C T I O N Children with proven UTI should undergo evaluation to detect any underlying structural anomaly after their first UTI. As there is disagreement as t o w h i c h d i a g n o s t i c procedure s h o u l d be p e r f o r m e d f i r s t , we compared results of direct RCG, CG, US, RNG and EU in 77 patients (35 infants 3 weeks to i year old 46% male, a n d 42 c h i l d r e n 1 - 6 y e a r s of a g e 10% male). Vesicoureteric reflux was discovered in 5 7 % in the younger g r o u p bz C G a n d in o n l y 1 5 % by R C G , w h i l e in t h e e l d e r g r o u p it w a s f o u n d in 3 0 % by C G a n d in 3 4 % b y R C G . 9 upper UT abnormalities were detected by RNG (4 +ve on EU, 3 +ve on US), and 2 additional o n e s by U S ( b o t h - v e o n R N G a n d E U ) . There were no abnormalities detected by EU being -ve on RNG or US. In c o n c l u s i o n we recommend CG, US and RNG for the initial diagnostic workup after the first UTI in i n f a n t s y o u n g e r than i year, while RCG c a n be u s e d i n s t e a d o f C G in e l d e r c h i l d r e n . EU and cystoscopy s h o u l d be u s e d in +ve cases only, i.e. in o n l y approximately 1 5 % o f our population.
RADIONUCLIDE CYSTOGRAPHY (RCG) AND RENOGRAPHY (RNG) IN COMPARISON WITH ULTRASOUND (US), EXCRETORY UROGRAPHY (EU) AND CONTRAST CYSTOGRAPHY (CG) IN CHILDREN WITH URINARY TRACT INFECTION (UTI). Children with proven UTI should undergo evaluation to detect any underlying structural anomaly after their first UTI. As there is disagreement as to which diagnostic procedure should be performed first we com~:ared th: r ~ u l t : of d i r ~ t RCG, CG~ UP, RNG, and EU in 77 patients (35 infants 3 weeks to 1 year old 46% male, and 42 children 1 to 6 years of age -10% male). Vesicoureteric reflux was discovered in 57% in the younger group by CG and only in 15% by RCG, while in the older group it was found in 30% by CG and in 34% by RCG. Nine upper urinary tract anomalies were found by RNG (4 +ve on EU, 3 +ve on US), and 2 additional ones by US (both -re on EU and RNG). There were no abnormalities detected by EU being -re on RNG or US. In conclusion, we recommend CG, US, and RNG for the initial diagnostic workup after the first UTI in infants younger than 1 year, while RCG can be used instead of CG in older children. EU and cystoscopy should be used in +re cases only, i.e. in only approximately 15% of cases in our population,
527
514
513
l Rocn, g Iqorngns, I Pavinz, S l`i6An=, II Cnbosm, tt Legnisazou', FMDoaenech-Torne. Servieio de Mediciua lluelenr y Secci6n de Neunologin PediAtrics* llospitnl general y ClinicsInfantil Ciudnd Sanitaria "Vall d'Bebr6n' ~ervicio de i~edicins Nucleari flonpitnl Cliuico y Provincial Barcelona
Fran¢oise TISON, Pascal LECOUFFE, Jean ROUSSEAU, Hubert YTHIER, Xavier MARCHANDISE Service Assoei4 de Mddeeine Nueldaire CHU DE LILLE - 59037 LILLE CEDEX - FRANCE Service de Pddiatrie CH de ROUBAIX - 59200 ROUBAIX - FRANCE
E~OPgAGEAI`SCINTIGRAPHYII ~llgLl` 8BILDR]~NMITII SEVEBEI~gcuRRIIIT8tONOBIT[S ASSESSMENT
The association of gastroesophsgenl reflux (GBR) and recurrent bronchitis is uidel! described is liternture. We have estudied 15 children lounger than 30 nnnths (hens lg,8 uonthsl, uitb clinical nriterin of severity {nnro than sheening crisis during the last S aonthu}, All children sere studied by means or 2! hours pllietry and esophageal scintigraphy (ES), Both tests sere performed in u seek interval, with 48 hour of previous uithdra.nl of drug therapy, gS studies two liquid deglutitions of 99=Tc-colloid sulphur, t couputed programnonstruct,~ the condensed innge, and the results were quantified in four grades, The 2! hours pHsetry uas performed, calculating total time of GER (TTOKR)and pfl global score (pHOS}. I clinical score (Ca} was calculated, based on the numberof uheesin~ episodes and emergency room admissions in the last months.
I"l
"'°"
,s÷ I I 1 6 I 3 I ! I
-Izl
sis
I01
I"
TTORR+I I
-is
5
z
"l""'l I 11 0 /|
Considering the 24 hour phetry an the reference tent, we calculated the pnraaeters of KS evaluation. We have found a good accuracy betueen ?TGKR amd KS, eitkout false negative results in the KS, Me obtained nore pathologic results in children uitb severe disease in both techniques, Comparing results from both techniques uith the clinical score (Spearuau's rank tent correlation}, ue have found los correlation coeficients, probnbly due to the snnll si~e of the group, TTGER I
" ÷1
÷
" ITOTAL Sennitivity
: 1.00
in 2 [lZ3 Specificity :0.60 0 3 Accuracy : 0.87 TOTAl, 10 5 [ 15 Ye bays found a relationnbip betueen clinical severity, p§uetry and E~ in this specific group of children younger than 30 months, although due to snnll number of eases ue could not find statistical signification.
BONE
MINERAL
CONTENT
IN C H I L D R E N
Dual photon absorptiometric examination in children is quite similar to examination in adults. But, beyond usual troubles owing to younger (little size of the target areas, untimely motions), definition of normal range is a point all the[ more critical because of the connection with growth. Moreover, ithere are no published data. ! i Our results have been obtained in 43 children, 24 boys and 19 girls, without any suspicion of current pathology. Ages were 2-16 and at least 2 children were present in each year of age. Measurements were performed over lumbar spine (L2-L4) and over femoral neck using a 153Gd Novo Lab 22a. As a standard, peak bone mass was obtained from 50 healthy male, age 25-~5 ; over L2-L4 it was 44.0 +/- 6.7 gila or 0.89 +/- 0.12 gHA/cmMeasurements in children were correlated with age, weight and height. We did not observe any significant difference between boys and girls. Correlations with the height alone were the m o s t satisfactory. Until 10 years old (20 children), a linear regression was the best for spine site as for femoral site : BMCv (g) = 20.2 * Height (m) - 13.1 (r = 0,874) BMCf (g/ca) = 1.89 * Height (m) - 1.03 (r = 0.870) but exponential regressions accounted for the whole sample : BMCv = 0.792 * EXP(Height * 2.18) (r = 0.942) BMCf = 0.170 * EXP(Height * 1.64) (r = 0.938). In older children, vertebral data are 15 % below than of adults although heights were in adult range. In children with renal failure, bone mineral content musl be compared to controls of same height. 516
515
G.Dabasi,
OF
L.Duffek
B.Karanfilski,V.Bogdanova,CoPisevska,M.Zdraveva
R a d i o l o g i c a l Clinic, Semmelweis U n i v e r s i t y M e d i c a l School, B u d a p e s t / H u n g a r y
I n s t i t u t e of Pathophysiology and Nuclear Medicine, Medical Faculty,Skopje,Yugoslavia
SHE P R O G N O S T I C ROLE OF THE D I F F E R E N T SCINTIG R A P H I C PATTERNS IN N E U R O B L A S T ~ A U S I N G 131-I-MIBG
COMPARATIVE STUDIES WITH RADIONUCLIDE ANGIOGRAPHYAND ECHOCARDIOGRAPHY IN DETECTION AND QUANTIFICATION OF LEFT-TO-RIGHT SHUNT Using standard diagnostic methods(clinical examinatior ECG,RTG)and echocardiography(2D and M-mode)250 children fron I month to 16 years o l d , w i t h l e f t - t o - r i g h t shunt were c l a s i f i e d according generaly accepted haemodynamic c l a s s i f i c a t i o n in four grups:87 with v e n t r i c u l a r septal defect I-M.Roger(VSD I),57 with v e n t r i c u l a r septal defect (VSD 11),64 with a t r i a l septal defect(ASD),and 42 with canalis a t r i o ventricularis(CAV)oDiagnosis was confirmed in 54 c a t e t e r i z e d and 49 s u r g i c a l l y operated children from a l l three groups,of wich 13 were operated without previous cardiac cateterizationoGroup of 50 children with an innoucent heart murmur was studied by the same methodology as a controls° Using Malts and Traves technique f o r radionuclide angi ography we obtain results sumarised in the f o l l o w i n g table: Group n Index QP/QS SD VSD I 87 1,1-1,9 1,35±0,18 VSD I I 57 1,3-3,7 2,34±1,47 ASD 64 1,35-4,5 2,23±0,67 CAV 42 1,5-2,8 2,1530,42 Controls 50 1,0-1,2 1,12±0,04 Presented results indicated the good c o r r e l a t i o n between radionuclide angiography and echocardiography in 88,8 percent of patients.Only in 11,2% there was no c o r r e l a t i on between the two methods as a consequence of the pulmonary hypertension and r i g h t - t o - l e f t shunt.
We studied 96 MIBG scans in 42 patients and compared with other d i a g n o s t i c m o d a l i t i e s . In the iO /!/ false negative cases the children were older, the p r l m a r y tumor was m o s t l y extraabdominal, only the d o p a m i n e level was elevated no m e t a s t a s e s were p r e s e n t at the time of the diagnosis. In 26 of the 32 true p o s i t i v e cases m e t a s t a s e s were also detected. Different s c i n t i g r a p h i c patterns of the m e t a s t a s e s were observed. Patients w i t h d i f f u s e intensive uptake of the skeleton had bone m a r r o w involvement h i s t o l o g i c ally d e s p i t e of normal or subtly abnormal bone scan. F o c a l MIBG uptake with e q u i v a l e n t bone scan was c h a r a c t e r i s t i c of cortical bone destruction. The focal uptake of the skull base was the early sign of m e n i n g e a l m e t a s t a s i s . The d i f f u s e and focal uptake of the liver and soft tissues was rarely seen. During the follow up s t u d i e s the activity of th p r i m a r y tumor often decreased, the diffuse uptake of the skeleton and liver disappeared, but t-~focal activity remained u n c h a n g e d . V i s u a l i z a t i o n of focal m e t a s t a t i c u p t a k @ during the clinical f o l l o w up has a poor prognosis.
528
517
518
C.Apri!e , L.Avolio,
M.Carena,
G.Chiari,
R.Saponaro.
~z_~99~Z~,
Fond. Clinics Lavoro IRCCS, Nuclear Ned. Serv. S.Matteo H IRCCS, Dept of Surgery-Pediatric Surgery
M. Guyot, R.Jeandot,
J. Gu~rin, A.J. Brendel.
Sect.
27100 Pavia - Italy Hapital Universitaire 99m Tc-APROTININ
UPTAKE
TEST IN CHILDREN
WITH VESICO
Pellegrin,
Bordeaux,
France.
IMP-I-123 BRAIN SPECT IN CRANIOSYNOSTOSIS
URETERIC REFLUX The aim of this work was to assess of the 99m Tc-Aprotinin(TcA) with vesieoureterie
uptake
reflux(VUR).
the clinical
utilit
test in children
Fortyseven
children(age
range 45d-llyrs) with VUR were investigated 90min after iv a d m i n i s t r a t i o n of 40-120 M B q of TeA,as we previously reported(Eur
J Nucl Med 1 2 : 3 7 , 1 9 8 6 ) ; i n
VUR was bilateral
and 19 underwent
31 of them the
surgery.
The mean fol-
low-up time was 23 months(range 7-52m,i12 studies). Results: i- There is no correlation between Xray grading and parenchymal
damage
at the time of the diagnosis.
2- The presence of cortical scarring or diffuse parenohy-J mal disease represents a poor prognostic factor in about half the cases with this pattern,while
dilatation
of the
collecting system does not seen to correlate with the clinical outcome. 3- The rate of renal growth is independent from Xray c l a s s i f i c a t i o n , t y p e Of therapy and amount of renal damage at the time of the diagnosis. 4- In eomp~ rison w i t h urography the detection of cortical scarring. is 15:1. In conclusion,the TeA uptake test is useful in childrer with VUR to quantify the degree of renal damage,to assess recovery and/or residual growth after therapy.
damage and the rate of renal
519
Krolicki L.,Klislewicz R.,No~ok M.t Skibi6~ki L,,Grsbsn W. !.!~I:sr~ment of N u c l e a r Medicine,Count,7 IIc~l~:i~!
Surgical treatment of Craniosynostosis (Cs) can prevent ocular and neurological damages due to an increased intracranial pressure (ICP). In order to evaluate brain perfusion in Cs, we performed SPECT images 20 mn after IV injection of IMP-I-123 (0.05 mCi/Eg) in 17 children (ages:l month to 4.6 years; mean:ll months). We identified 2 groups of patients (pts): Group I (n=ll) : "simple Cs" : sagittal synostosis (scaphocephaly) or coronal synostosis (acrobrachicephaly) or trigonocephaly ; Group II (n=6) : "complex Cs" : oxycephaly or severe craniofacial malformations. The ICP was increased in 8 pts (4 in Group I and 4 in Group II), was normal in 6 pts (4'in Group I and 2 in Group II), and was not measured in the 3 remaining pts. Different SPECT imaging patterns were observed : Type 1 : normal or subnormal cerebral uptake: n=S (29%): 4 in Group I, 1 in Group II. Type 2 : focal cortical decreased uptake : n=3 (18%) : 2 in Group I, 1 in Group II. Type 3 : diffuse cortical patchy uptake : n=8 (47°/o) : 5 in Group I, 3 in Group II. Type 4 : extensive photopenic areas with ventricular dilatation: n=l (6%) : 1 in Group II. There was an increased ICP in 7 of 13 pts with abnormal SPECT images (2 types 2, 4 types 3, 1 type 4). These preliminary findings show that IMP-I-123 brain SPECT may be helpful in the pre-surgical evaluation of Cs. Further studies are being done on post-surgical follow-up of Cs to assess cerebral perfusion benefits.
520 M. Ingels, M. Verboven, M. Delree and A. Piepsz.
~on~r~tow~cz~ 8,~or:)sw,!'olend.
Akademisch Ziekenhuis, Vrije Universiteit Brussel. INTERMITTENT RHINORRHEA IN CHILDREN:OVERPR~SS~ RE RADIONUCLIDE CISTERNOGRAPHY/ORNC/ VERSUS METRIZAMIDE COMPUTED TOMOGRAPHIC CISTERNOGRAPHY
IMCTC/
The~diasmesls of cerebrospinal fluid fistulas seems to be difficult in cases of so-called intermittent liquorrheas.We present the clinie cal observations on 25 children.ORNC wss employed combined with the placement of nasal pledgers in 19 cases.ln 16 cases MCTC was performed Both types of investigations were done in 11 casea.OBNC technique:after itLmbsr puncture 99mTo-DTPA/tmI,O.5-3mCi/waa injected end the infusion of artificial CSF followed.CSF pressure wee continuously measured/it increased no more as 400mmH20/.MCTC techniqua:CT was performed lh after intrathecally instillation of 5ml of metrizamide.The rhinorrhea was diagnosed in 14 cases/all cases were verified through operation/.In the group of MCTC,4 results were true positive,7 true negative and 5 false negative /sensitiv&ty 40%/.In the group of ORNC,9 results were true positive,8 true negative and 2 false negative/in both cases rhinorrhe8 was observed I-2 weeks thereafter-after additional head trauma/.Sensitivity was 82%.Concerning the gr. of MCTC and ORNC-4 cases were false negative with MCTC,but true positive in OR-NC.Conclusion: ORNC seems to be more sensitive in comparison to ~CTC.MCTC however may be useful precisely locating the CSF fistulas.
99mTc-DMSA SCINTIGRAPHY IN ACUTE URINARY TRACT INFECTION IN CHILDREN 24 children with symptomatic urinary tract infection (UTI) underwent systematically ultrasound studies (US) and 99mTc-DMSA renal scans. Among the 15 patients considered as acute pye onephr t s (APN) on c nical grounds, the scan was abnormal in 12 cases, in contrast with only 1 abnormal scan in the clinical subgroup of the lower UTI. Among the 10 abnormal scans that were repeated later on, 6 did completely normalize. US showed only once a parenchymal appearance suggestive for APN. Our findings suggest that the DMSA scan has to be considered at present as the most sensitive imaging technique for the detection of APN.
529
522
521 H.WIOLAND, CI. deLABRIOLLE-VAYLET Service de H6decine Nuc16aire, Hopilal Saint-Antoine 184, rue du Faubourg Saint-Antoine 75012 Paris (France)
INTERVENTIONAL NUCLEAR HEDICINE IN PEDIATRIC ORTHOPAEDICS
K. Kervinen, Y.A. Kesgniemi
M.J.
Savolainen,
J.I.
Department of Internal Medicine and of Clinical Chemistry, University Finland.
Heikkil~,
Department of Oulu,
IN VIVO VISUALIZATION OF THE HEPATIC UPTAKE LOW DENSITY LIPOPROTEIN IN MAN
OF
Some surgical interventions are simplified if the lesion can be located at surgical sites by virtue of the uptake of radioaclivity, For some years, this procedure has been used in pediatric othopaedics to locate at surgical sites the osteoid osteomas. For this purpose, a s t e r i l i s a b l e radiation probe wfth a collimated opening of 2 mm in diameter was designed. The associated portable counler of" r a d i o a c t i v i t y converts the disinlegraUon r a l e s i n l o an acoustic signal lhat increases steeply wilh the increasing disintegration rate, the acoustic signal enabling the surgeons and isotope specialists to monitor readily the radioaclivily of the region of interest without having to look away from the surgical site. D i m e t h y l a m i n o d i p h o s p h o n a t e was the osteotropic radiopharmaceutical chosen for carrying out the intraoperative bone scinUgraphy, since the available data show that this chemical increases by 25 % the pathological to normal bone uptake ratio of the lesion compared to the usual disphosphonates. T h i r t y interventions on osleold osleomas were carried out according to the procedure of" the intraoperative bone scinligraphy. They showed that this procedure allowed the rapid location of the lesion at surgical sites, the reduction of"the dimensions of the excized areas, the objective termination of the operation and in some cases, the simpllficalion of the surgical technique.
Low density lipoprotein (LDL) particles are cleared from the circulation mainly by specific hepatic receptors. To investigate how alterations in the number of LDL receptors affect cholesterol levels in man, 13 hypercholesterolemic patients (6 with familial hypercholesterolemla) were studied off and on treatment with a hypocholesherolemic drug (lovastatin). LDL particles were isolated, divided into two aliquots, one labeled with 99=Tc and one with IslI and both preparations reinjeched simultaneously. The distribution of labeled LDL was visualized 4 and 24 hours later by scanning the thorax and abdomen with a digital gamma camera, and the liver/heart (L/H) and liver/lungs (L/L) ratios were calculated. Overall, the fractional catabolic rage for LDL was correlated positively with the L/H ratio (r=0.785, p<0.001) and with the L/L ratio (r=0.620, p<0.001) calculated from the 24 h images. Lovastatin treatment increased the L/H ratio by 12 % (p<0.01). The liver imaging using 9g=Tc-LDL provides a useful new noninvasive method to visualize the hepatic uptake of LDL in vivo in man. Lovastatin enhances the hepatic removal of LDL suggesting that the number of LDL receptors is increased.
523
524
J. ROLAND, A. DOBBELEIR.
P. Thouvenot, P. Maincent, X. Pelletier, G. Ansellem. G. Debry, A. Bertrand.
A.Z.Middelheim, Antwerp, Belgium.
Department of Nuclear Medicine, CHU Brabois, University oi Nancy, France. INFLUENCE OF STRESS ON GASTRIC EMPTYING. Gastric emtying (GE) by means of radionuclide studies is routinely performed. Althought some external stress factors may influence the results, they are never taken into account. The aim of the study was to evaluate the effect of stress on gastric emtying in male healthy volunteers. We studied solid phase GE using a continuous acquisition in 6 normal non smoking volunteers (mean age 25 years) with no history of gastro-intsstinat diseas~ and witbo,,t any meclicatJon.After an overnight t~st .a pancake (500kJ) marked with 10 MBq Tc-99m colloid, cut in pieces of 1 cm2, was ingested without additional liquid. Simultaneous dynamic acquisitions of gastric activity in anterior and posterior incidence were taken during 90 min starting from the onset of the meal. The GE was, within a 3 week period, evaluated 3 times in basal conditions and once under mental stress. This stress was induced by means of an acoustic stimulus and started at the end of the meal lasting for 30 minutes. The attenuation correction was performed by means of the geometric mean. The lag phase and GE rate in basal and in stress conditions were compared. Lag phase GE rate mean ( + sd ) mean ( +_sd ) Basal Stress
11 (_+3;5) min 35 (_+10) min
77 ( + 22 ) %/h 100 ( + 37 ) %/h
In conclusion we can say that, studying GE during induced stress, the lag phase is significantly prolonged. This is in contrast with the GE rate which is not significantly influenced.
GASTRO-INTESTINAL TRANSIT OF DIETARY FIBERS: EFFECTS ON MEAL TRANSIT, GLUCOSE LEVEL AND LIPIDS ABSORPTION. The gastro-intestinal transit of a meal (1000 cal.) and of nona b s o r b a b l e dietary fibers (fibers of A m o r p h o p h a l l u s Konjac) in twelve 13 h-fasting healthy volunteers was studied. The meal was labeled by incorporation of cellulose acetophtalate microcapsules (0.2 to 1 mm size) resistant to gastric iuice and containing 99mTc-DTPA-labe~ed potato starch. The fibers were labeled with 111 In-DTPA. In vivo studies, both in a n i m a l s and humans, h a v e s h o w n that o v e r 9 6 % of the radioactivity (99mTc and 111 In) was found in feces. The gastric emptying w a s m e a s u r e d e v e r y 10 mn for 3 h. The intestinal transit w a s controlled for 7 h and measurec through the mouth-to-caecum transit time. The blood glucose and the total lipids were measured every 30 mn for 6 h. Three series of the a b o v e m e a s u r e m e n t s were performec on set days: DO, only labeled meal; D15, labeled meal plus 1.5 g of 1111n-DTPA-fibers; D45, labeled meal plus 1.5 g ol 11 l l n - D T P A - f i b e r s , the v o l u n t e e r s having ingested 1.5 g ol non-radioactive fibers every morning and evening during the month preceding the experiment. The ingestion of fibers slows d o w n the meal's gastricemptying process and accelerates its intestinal transit. The fibers m o u t h - t o - c a e c u m transit w a s faster than the meal m o u t h - t o - c a e c u m transit. Glucose levels w e r e significantly lowered. These effects d i s a p p e a r e d after a chronic ingestion of fibers. Finally there was no change in serum lipids level.
530
525
526
E, Henze. P. Malfertheiner, M. Clausen, H. Ditschuneit, W.E. Adam. LECOUFFE P., MEURIOT S., ADENIS A., COLOMBEL J.F., VENEL H., DEVEAUX M., CORTOT A., MARCHANDISE X. Service Assoei~ de M&leeine Nucl4aire Clinique des Maladies de l'Appareil Digestif
University of Ulm, Germany
CHU ~ HLLE- FRANCE
VALIDATION OF THE C-14 UREA BREATH TEST AS A SINGLE SAMPLE TEST FOR ROUTINE USE IN DETECTING CAMPYLOBACTER PYLORI NON-INVASIVELY. Campylobacter pylori is involved in the pathogenesis of gastritis and deer. As this germ produces urease enzyme which degrades urea into CO2 and NH3, CO2-exhalation tests after oral application of labeled urea have been suggested. In this study, a rather sophisticated C-14 urea breath test with extended breath sampling was developed in the f'wst instance with the intention for later valid simplification. The test was validated in 14 normals and 61 patients who also underwent gastroscopy with urease quick-testing. 110 kBq of C-14 urea were administered orally with a 400 ml fluid meal and the exhaled C-14 CO2 was trapped in 10 rain intervals for 90 rain in lmMol duplicate samples and measured. C- 14 activity exhaled over 90 rain was integrated and expressed in % activity of the total dose given. In 14 normals, a mean of 0.59+-0.22 % was measured resulting in an upper limit of normal of 1.03 % (mean+2SD). A sensitivity of 91% (31/34 true positive) and a specificity of 81% (22/27 true negative) for detecting Campylobacter was found. Subsequently, the test's single parameters were analyzed to determine the optimum and most simple variant of this test for practical use. Correlating the individual probes at each time interval with the integrated result revealed optimum correlation of the 40 to 60 rain breath specimens ranging from r = 0.986 to 0.996. The test's diagnostic accuracy did not change at all when reevaluated with the 40, 50 or 60 rain sample data alone. Thus, the C- 14 urea breath test can be applied routinely as a non-invasive, low-cost and one-sample test which allows to perform the test in many peripheral clinics and mail the sample to a central unit for B-scintillation counting. This test may become a routine tool with high diagnostic accuracy both in primary diagnostics and treatment follow-up.
527 Erik Oester-Joergensen, Niels Qvist, Claus Hovendal, Lars Rasmussen and Svend Arne Pederseno
Departments of Nuclear Medicine and of Surgical Gastroenterology, University Hospital, DK-5000 Odense, Denmark.
BILIARY KINETICS EVALUATED BY CONTINUOUS INFUSION OF 99mrc-HIDA: THE RELATION TO DUODENAL MIGRATING MOTOR COMPLEXES IN INDUCED HYPERGLYCEMIA IN HEALTHY MALES. After approval of the scientific-ethical committee the influence of hyperglycemia on duodenal motility and biliary kinetics was studied in healthy males (n=8) and compared to a control group (n=9). They were examined fasted in supine position. A combined technique of dynamic hepatobiliary gamma camera scintigraphy using 99m-Tc-HIDA with a continuous infusion rate of 40 MBq per hour and motility recordings by a naso-gastroduodenal tube (continuous flow, high pressure, low compliance system) was used. When phase III (regular contractions of 10-12 per min) of the migrating motor complexes (MMC) appeared the hyperglycemia group received an intravenous bolus injection of 50 ml 50% glucose followed by infusion of 20% glucose at a rate of 75 ml per hour. Plasma glucose attained values of 12 to 17 mmol]l, fairly constant during the examination period. In the hyperglycemia group the median duration of the MMC cyclus was significantly shorter than in the control group (89 versus 135 min) conditioned by shortening of phase II (irregular contractions) (58 versus 94 min). In the hyperglycemia group a continuous rise in gallbladder radioactivity throughout the entire MMC eyclus was seen in all but one subject, who had a short pause ill gallbladder filling 40 min after the onset of phase II. In the control group extended or repeated pauses began from 7 to 32 min after the onset of phase II. CONCLUSIONS: Induced hyperglycemia in fasted subjects shortens phase II of MMC and the related pause in gallbladder filling is abolished or delayed.
LUNG AND INTESTINAL PERMZABILITIES IN CROHN'S DISEASE. A preliminary study. A latent involvement of the lung is frequently described in patients with Crohn's disease (CD). Moreover intestinal permeability (IP) is known to be increased in CD. The aim of this study was to evaluate both lung permeability (LP) and IP in CD. We studied 12 patients (age 18-50) with CD. 9 patients with active CD were studied again as CD was quiescent. Healthy volunteers (age 21-45) acted as controls. LP was [assessed using a DTPA-99mTc aerosol (0.8p). After 2 rain breathing in supine position, 60 s frames were acquired for 30 Imin. T½ (rain) was obtained from exponential fitting on pulmonary clearance curve after vascular background correction. IP was concurrently evaluated from 24 h urinary excretion !of 51Cr-EDTA expressed as a percentage of the total oral dose. Compa~'ed with controls (49.3 +/- 20.8 rain), T½ was not significantly different in CD (39.0 +/- 27.6 rain). But LP increased significantly (p,=.05) in quiescent CD (30.2 +/- 13.1 rain). IP was higher in CD (8.8 +/- 6.6 %, p .01) than in controls (2.0 +/- 1.3 %), especially in active CD (8.1 +/- 7.2 %, p~.01). The difference between 51Cr-EDTA excretions in active and quiescent CD was significant (p ~.05). No correlation was found between IP and LP. Our results confirm increased IP in CD with influence of disease activity but they failed to clearly show a common mucosal permeability. The wide range of normal T½ values suggests strong influence of methodology especially in vascular background correction. Increased LP found in quiescent CD has to be concurrently investigated with others lung parameters, because it would be of high interest in CD physiopathology.
528
T. Aro$, B. Erba$, M. Bayraktar, G. Tatar, C. F. Bekdik Departments of Nuclear Medicine, Endocrinology and Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
HEPATOBILIARY FUNCTIONS IN HEREDITARY HYPERBILIRUBINEMIA AND TYPE II DIABETICS COMPARED WITH NORMALS USING 99mTC-DISOFENIN Hepatic blood flow, Tmax, T1/2, to time of gall bladder (tl) and duodenal filling (t2) were calculated after the administration of 185 MBq 99mTcdisofenin (Hepatolite, Dupont) in 9 hereditary hyperbilirubinemia (HH), 15 type II diabetic patients and 9 normal volunteers. Hepatic blood flow was obtained by division of hepatic artery to portal vein area under curves. In normal volunteers, the hepatic perfusion index was 72.51±29.55%, "[max 13.30.6.28 rain, Tl/2 54.47±30.56 min, tl 11.53±7.55 min,. t2 12.80±6.89 min. In patients with HH, hepatic perfusion index was 58.77±31.76%, Tmax 12.23±4.54 rain, TI/2 54.98±22.88 rain, t 1 17.23+9.07 rain, t2 I0.86±4.06 rain. When compared with normal volunteers, there was no difference In these parameters in patients with HH. While in type II diabetic patients, the hepatic perfusion index was 44.13±29.84%, Tmax 18.12±5.91 mln, Tj/2 106.74±56.47 rain, tl 16.88±7.78 rain, t2 19.55±7.16 rain. When the results of diabetic group were statistically compared (Mann Whitney-U test) with normal volunteers, there was a significantdifferencein hepaticperfusion index ( with 71% sens., 60% spee.),Tmax (with 77% eens., 6 4 % spee.),tIl2 (with 77% sens.,64% spe¢.)and t2 (with 88% sens.,73% spec.). In the diagnosis of hepatic complications and the follow up of the type II diabetic patients, it will be useful to investigate these parameters with 99mTc-disefenin, becauseconventionalhepaticfunctiontestsare normal in such patients.
531
530
529 G±_RUSS,F.
PAYCHA,L.
PHILIPPE,G.
BENHAMOU,M.
WLPILLAT.
Nuclear Medicine and Surgery Departments Bichat University Hospital. COMPARISON BETWEEN PER-RECTAL AND FIRST PASSAGE INTRAfENOUS SCINTICRAPHIC TECHNIQUES FOR THE STUDY OF PORTAL CIRCULATION. Per-rectal scintigr.aphy is supposed to be better than intravenous administration to study portal flow because thallium directly goes into the portal system without prior arterial passage of the radionuc]ide.We compare the ]two methods in a prospective study. Administration of thallium 201 (2 mCi) per rectum is first performed.We measure the heart to liver (H/L) uptake at 25 min.Then,10 mCi of Tc99m pertechnetate are rapidly intravenously injected and 30 images (2 sec. each) are taken: An index of portal flow (IPF) is calculated by dividing the areas under the liver and spleen curves after the spleen peek has occurred. The two methods are compared against each other and with clinical data,echo~raphy,computerized tomography and angiography in 15 patients: Control sub~ects(n=2),liver cirrhosis(n=6),metastatic liver cancer(n:4),primary hepatic carcinoma (n=3) . Correlation between H/L and IPF is quite good (r=0.82). Sensitivity of both tests is I00~ for portal hypertension (Ii eases) and portal vein thrombosis (4 cases).Finally~ intraobserver reproducibility is very high for both indices: 98.7g (IPF) and 99-7% (H/L). We conclude that both methods give similar results in the study of portal circulation.However~intravenous pertechnotate is more comfortable for the paticn%cheaper and 30 times shorter to perform.Therefore,per-rectal technique should be given up.
531 K.Kosti6, O.Popovi6, V.Artiko, S.Jano~evi6, M.Djordjevi6 Institute of Nuclear Medicine, University School of Medicine end Clinical Center, Bel~ade, Yugoslavia
OF BILE ACID ABSORPTION BY 75Se HCAT IN ILEAL DISEASE AND OTHER INTESTINAL DISORDERS Abdominal 75Se HCAT retention (ASR) was used to reveal bile acid malabsorption (BAM) in patients with different intestinal diseases. It was estimated 7 days after peroral administration of 370 kBq taurc-23 (75 Se) selena-25 hctaocholic acid (Amersham) using an uscoli~ted gamn~ camera. Mean ASR was 36,73+11,06% (SD) in 9 controls. This value did not differ (p> 0,05) in patients with irritable bowel (n=5, 33,55+17,48%) and blind loop syndrcme (n=3, 20,07+7,67%). ASH rattle ~ icier (p~ O.01 ) in patients with prh~ary bile acid malabsorption~(n=19, 5,5-3,34%), 8+ in ileal (n=4, 7,05-+3,44%) @ohn's • h ea disease, as well as in patients with postcholecystectomy d~r+r (n=7, 5,11Z4,26%), in 4 of 7 patients with giardiasis (9,7327,73%) and in 4 of 5 patients with terminal ileal resection where it was lower than I%. Individual ASR values were censiderably lower in ~tients with postcholecystectcmy diarrhea (n=7, 0,57-12,84%) than in cholecystectcmized without diarrhea (n=4, 16,40-22,20%) as well as in those suffering fr~ the ileal Crohn's disease (n=4, 1,41-9,91%) in ccmparison to patients with Crohn's disease affecting the colon (n=2, 14,09 end 19,56%). BAM was confirmed in patients with PBAM and PCD by an unequivocal response of diarrhea to cholestaramine treatment. In ~tients with giardiasis, erradicatien of the parasite did not improve ASR in all the cases. 175Se HCAT is an useful test for ~easurement of ileal capacity of bile acid absorption and reco~nitien of some specific intestinal disorders (as PBAM) as well as a qu_ideline for the treatment. PBAM PCD
J. Kotzerke, O. Krischek, R. Schwarzrock, H. Wiese, B. Ringe*, H. Hundeshagen Department of Nuclear Medicine Department of Abdominal- and Transplant-Surgery* Medical School of Hannover, FRG FOCAL NODULAR HYPERPLASIA (FNH) AND HEPATOCELLULAR CARCINOMA (HCC) - HOW RELIABLE IS THEIR DIFFERENTIATION BY CHOLESCINTIGRAPHY? In a retrospective study the cholescintigraphic patterns of FNH (n=72 pts.) and HCC (n=67 pts.) were examined in order to obtain criteria for the differentiation of these lesions. Using 370 MBq 99mTc-DISIDA, cholesCintigraphy was performed as a three-phase scintigraphy with at least four views in the early phase (up to 10' pi) and in the late phase (>120' pi). Five different patterns of perfusion, uptake and tracer-retention were found. The combination of hyperperfusion, increased or normal uptake in the early phase and retention in'the late phase ("trapping") was identified in 62 FNHs (86%), but only in one HCC. However, a decreased or missing uptake in the early phase was seen in only 2 FNHs, but in 64 HOes. Minimal (n=l 1) or moderate (n=18) uptake was detected in 40% of all HCCs, in 16 HCCs the uptake was markedly inhomogeneous. With this technique the differentiation of FNH and HCC by cholescintigraphy is possible in almost all cases, so unnecessary invasive procedures can be avoided in clear cases of FNHs. The most important feature is the liver-like-uptake of the lesion in the early phase.
532
B.Erbas.T.Aras,H.Kumbasar,S.Ayta¢,Y.DoOan,C.F.Bekdik. Department of Nuclear Medicine,HacettepeUniversity. Department of Psychiatry,AnkaraUniversity. Ankara,Turkey. HEPATIC PERFUSION INDICES FOR THE EVALUATING OF PARANCHIMAL DYSFUNCTION IN ALCOHOLICPATIENTSUSING99mTc-DISOFENIN. In paranchimal liver diseasetotal hepatic perfusionmay not be significantly altered, but the arterial-venous ratio may be considerablydisturbed. The aim of this studywas to determinethe ability of the several perfusionindices to assess the gravity of alcoholicliver disease. 23 patients with alcohol abuse (mean aga:37:~8.5 ranga:21-51) were studied. Hepatobilier scintigraphy, liver ultrasoundand liver function tests were performed. After the edm n strat on of 5mCi 99mTc-disofenin ( Dupont)(2,6 diisopropylphenylcarbamoylmethylimino-diacetic asid)120 kinetic frames for 2 rain. and 30 frames for 30 rain were recorded. The indiceswere obtainedfrom analysisof the time variation in liver activity on the first pass study. Hepatic slope(HS) ,portal slope(PS),hepatic slope/portal slope(H/P), left/right lobe count/pixel/min(L/R) and hepatic perfusion index (HPl)(comparing the integral of the arterial and portovenous part of hepatic perfusion curves) were determinated. These indices were compared in enzyme analysis and parameters which calculated using ultresound.HPl (mesn:30+4) showed high correlation with gamma OT(r=O.997), L/R(r=0.865) and hepatic uptake betwenn first and second min.(r=O.862).HIP (mean:O.691+O.295)had a good correlation with LIR (r=0.845), gamma OT(r=0.75), SOOT(r=0.779) and HPI(r=0.76). PS(mean: 11.21±7.09) was in correlation with SGPT(r=-O,89S)and HS(mean:6.91+3.3) with SGPT(r=-811 ), caudal lobe
enlargement(r=-713). In conclusion,this methodis very simple and could be applied to evaluatethe changesof liver hemodynamicsand degreeof hepaticdysfunctions in any kind of hepaticdisorders ,including alcohol abuse.
532
534
533 J£ URgAIN,L. HORTELHANSV. VANDENMAEGDENBERGH,A. VANDECRUYS, E. VANCUTSEH & M. DE RO0.
M.R. CASTELLANI ", F, CRIPPA o, R.A. ALDISIO ~o, E. SERE&NI °, P. b~.~ANAKI o
US. GASTHUISSER6, LEUVEN,BELGIUM. ! THE DUAL PHASE GASTRIC EMPTYING. IS LkBELINGOF LIOUIDSUSEFUL? la this stodg we have evaluated the contribotien of the laheled liq~ddphase of a p~siological test meal m the assessment of gastr~ emptying of different t~pes of gastric dgsrnotilitg.Foortgpatientswere investigated" l 0 idiupathicdgspepsia (ID), tO diabeti~ (I)), 10 patients with proximal gastr~ vagetomg (PV) and 10 ! patients with a Bfl]roth II procedure (BII). Ten heafflN sub~=cts (C) rn~tchedfor age were used to define the normal range of emptging. After an overnkJht f ~ t each patient and C w a s given the same test meal cons~ting of 1 scrambled egg labeled with 500 IkCi of Tc-99m-SC, 2 slices of bread and i 50 ml of water with 1O0 pCi of k,diurr,-111-DTPA. Sirf,ultanoous anterior and posterior ~'.agc-swere tee
NUCLEAR MEDICI~ D M S I O N o, SURGICAL CNCOLOGY A D M S I C ~ °° NATIO~a£ CANCER I]ISTITOTEOF MILAN, IT.A£y f~PATOBILIARY SCINTI(~RAPHY IN T ~ M A N A ( ~
OF FISTULAS OF T ~ BILIARY
TRACT. In order to identify and to localize a fistula of biliary tract after injury due to surgical resection or to the removal of a biliary-enteric drainage, we studied with IDA-scsn 18 pte. who were £reated for liver cancer between Dec. 1984 to Jan. IS@9 at the National Cancer Institute of Milan. IDA-scan was performed 1 wask-3 months after liver reSection (13 pts.), or bili&~y-enteric a n a s ~ e s
(5 pts.). A pts., who t~Ider-
went to multiple surgical procedures, had ~ or more scans. After i.v. inj. of 5 mCi of 99mTc-Trimeihyl-IDA a dinsmie acquisition of 60 rain. was made utilizing a cemputerized g-dn~acsmera. Analogues images were also obtained at i0 rain. intervals during the same time and after 2-3-6-24 hrs. The scan was considered positive when the pathological finding (hot area) persisted in the late controls. There are 3 ~F~tdos of pts.: l)Sy~otcmatic, in whom the sc/m~was made to localize the site and the m~ant of fistula (9 scans); 2)Contre]s recovered fr¢~ an known fistula (8 scans); 3)Asymptc~atic controls, 8-10 days after surgical resection (6 sce~s). In the first ~ the scan always positive; in the second and in the third group it was positive in 3 cases and in 1 case. The time of visualization of the hot ares was the diserim/nation between sirc~g fistulas that should had been ctmed and mild or recovering fistulas. In the first case the time ,*as 15-[90rain., in the second case the time was 50-60 rain. and the hot area was more evident at 2-3 hrs. Conclusion: this e x ~ t i e n was effective in i) detecting the presence of fistulas of the biliary tract 2) establishing the anoint of the leakmge 3) followird~the clinical cOU~e.
536
535 S.M.HUSSEIN ELAZRAK, AND J.J. BARRETT,
B.
SHAPIRO,
G.M.S.
SYED
t. URGANCIO~LU, K. OZKER, I. USLU, M. RAZAVI and O. F. $ENYOZ 'NUCLEAR MEDICINE and PEDIATRIC SURGERY DEPARTMENTS,
KING'S
COLLEGE
HOSPITAL,
LONDON,
SE5
9RS,
U.K.
DIAGNOSTIC POTENTIAL OF QUANTITATIVE HEPATOBILIARY SCINTIGRAPHY IN CHRONIC LIVER DISEASE. TO date there is still no well-established clinical test to enable objective quantitative assessment and follow-up of chronic liver pathology. To evaluate the diagnostic potential of dynamic hepatobiliary imaging twelve patients with a variety of chronic liver disease were investigated both scintlgraphieally as well as biocbemically. Hepatobiliary scintigraphy was carried eut using a 15OMBq bolus of Tc99m Tribromomethyl Iminodiacetic Acid (TMB-IDA),Rapid first pass framed followed by a slower dynamic sequence were recorded for 20 minutes. Subsequently, the fractional contribution of venous blood supply to the liver, i.e. the Portal Fraction (PF), as well as the relative liver uptake i.e. the Hepatic Index (HI), were quantified by methods applied in colloid liver scintigrapby and paediatric hepatobiliary imaging. Static liver imaging was performed within 48 hours and the quality of Tc99m colloid (80 MBq) uptake was assessed by subjective scan grading(l-4 scale). Biochemical tests included serum bilirubin, aspartate aminotransferase, prothrombin time and the serum albumin levels. The HI values were found to correlate significantly with the portal fraction(r:O.66), the serum albumin level (r=0.70) and the colIoid scan grading (r=-0.86). First results suggest that Tc99m TMB-IDA hepato r biliary imaging followed by PF and HI derivation can provide rapid, simple and objective quantification of the extent of chronic liver pathology in adults. The value of combined PF and HI measurement in management of chronic liver disease deserves a full clinical evaulation on a large series of patients.
CERRAHPASA MEDICAL FACULTY, iSTANBUL UNIVERSITY, TURKEY NONINVASIVE EVALUATION OF PORTAL CIRCULATION USING 9-gmTcPERTECHNETATE Portasystemic shunts in p a t i e n t s with various d i f f u s e liver diseases were evaluated by r e c t a l a d m i n i s t r a t i o n of 370 MBq 99mTc through a thin polyethylene tube. Serial scintigrans of the abdomen were acquired using a gammacamera interfaced to a computer with a frame rate of 5 sec/image for 7.5 min and a static image was obtained with 7.4 MBq 99mTc-Sn colloid to locate the l i v e r in patients showingan insufficient l i v e r radioactivity. Portal shunt indices (St) were calculated using the areas under time-activity curves generated by heart (H) and l i v e r (L) regions of interest (ROts), expressed as percent H r a d i o a c t i v i t y over the sum of H and L radioactivities for a period of 25 sec. In patients without l i v e r diseases the l i v e r was clearly visualized in a short period while the heart was demonstrated in the late images. Healthy subjects had a mean St of 2%. In patients with diffuse l i v e r diseases visualization of liver parenchyma was prolonged due to minor or major diversion of portal flow through the collateral channels to H and subsequent flow via the hepatic artery. The influence of back diffusion and recirculation in the calculation of St wasminimized by early sampling. St weremarkedlyhigher in patients with diffuse liver diseases than in nonnals, ranging fron 28.5% to 82.3%.In cirrhosis SI rangedwidely (34%to 82.3%) but the meanwas higher than in nonnals and in chronic hepatitis. The St was higher in patients wi~h esophageal varices than in thosewithout, these results suggestthat ~Tc-pertechnetate transrectal portal scintigraphyprovides,easilyand safely with less ex~nse,infonnation about the flow patterns and the functional state of portal circulation.
533
537
538
H.SENCKE-GONCALVES,R.GNELDOF,J.PATSRNOT. L.VA~
TSICHT
P.BERGMANN
and M . V E R H A S
Bru~mann university hospital (Universit~ Libre de Eruxelles) and u n i v e r s i t y h o s p i t a l ([~niversit~ Rederale de Rio de Janeiro)
V I T A M I N E BI2 A B S O R P T I O N ; C O R R E C T I O N OF I N T E S T I N A L R E T E N T I O N BY W ~ O L E - B O D Y P R O F I L E A C T I V I T y OF V E T A M I N E B 1 2 - 5 8 C O B A L T A ~ D BY DOUBLE TI~ACER T S C H N I Q U E Intestinal retention could give false negative results in determining the whole-body retention of vitamine Bit absorption (WBC B 1 2 - 5 8 C o ) . A f t e r h a v i n g validate the WBC B12-58Co, taking the Schilling test as re~erence, we have studied the feasibility to e v a l u a t e the i n t e s t i n a l c o n t a m i n a t i o n by m e a s u r e m e n t of the p r o f i l e 8 c t i v i t y d i s t r i b u t i o n of v i t a m i n e B I E - L B C o and b y a d o u b l e t r a c e r technique (WBC B12-58co/ W B C 51CrCI3). M B t h o d o l o a v T w e n t y - f i v e p a t i e n t s w e r e s t u d i e d . F o r eleven of them the W e E B1258Co r e t e n t i o n w a s m e a s u r e d at the 7th day after the oral a d m i n i s t r a t i o n of 37 KBq of B 1 2 - 5 8 C o u s i n g a four d e t e c t o r ~ w h o l e b o d y c o u n t e r . O n e w e e k later, a S c h i l l i n g test was p e r f o r m e d after the o r a l a b s o r p t i o ~ of 18.5 KBq B12-57Co. Results were expre~ed as % I ~ . I n these patients, one m i n g l e peak of h e p a t i c a c t i v i t y was o b s e r v e d o n the w h o l e - b o d y p r o f i l e and thus no further intestinal c o r r e c t i o n w a s needed. In o r d e r to e v a l u a t e the i n t e s t i n a l c o n t r i b u t i o n , w e m a k e d in n i n e o t h e r p a t i e n t s the p r o f i l of the w h o l e - b o d y d i s t r i b u t i o n of a c t i v i t y at i hour, 1 w e e k and two w e e k s a f t e r the oral adm~nistratlon o f B l Z - 5 8 C o . F o r f i v e o t h e r p a t i e n t s a d o u b l e t r a c e r t e c h n i q u e w a s u s e d for i n t e s t i n a l C o r r e c t i o n a f t e r the s i m u l t a n e o u s oral a d m i n i s t r a t i o n of 37 KBq of B 1 2 - 5 8 C o and 1,85 MBq of 5 1 C r C l 3 . T h e B 1 2 - 5 8 C o a b s m r p t i o n was e v a l u a t e d after i n t e s t i n a l c o r r e c t i o n b a s e d on s u b t r a c t i o n of the 5 1 C r C l 3 contribution after the formula: S l 2 - 5 E C o (%ID)=WBC B 1 2 - 5 8 C o - W B C 51CrCI3/I - WBC 51CrCl3 R e s u l t~ The c o r r e l a t i o n w i t h the S c h i l l i n g test was f o ~ d excellent:r=0.94 ( n = l l ) . T h e n o r m a l i t y for W B C r e t e n t i o n (n=7] w a s d e f i n e as 5 3 . 2 + - 1 2 , 4 % ID (SD).For nine p a t i e n t s s t u d i e d at the 7th day, the p r e s e n c e of a d o u b l e p e a k (hepatic and intestinal peaks) allowed the s u b t r a c t i o n by exponential e x t r a p o l a t i o n ; t h e c o r r e c t i o n r a n g e w ~ s 4.4% to 3 7 . 2 % . W i t h the e x c e p t i o n of one o b s e r v a t i o n there was no d i f f e r e n c e in the m e a s u r ~ of vii el2 a b s o r p t i o n b e t w e e n the 7th (after correction) a n d the 14th day of o b s e r v a t i o n . F i v e p a t i e n t s w e r e studied b y d o u b l e tracer t e c h n i q u e for intestinal correction. For one p a t i e n t there was an intestinal c o n t a m i n a t i o n a c c o u n t i n g for 65,3% of the total b o d y activity; two p a t i e n t s were studied at the 2nd and the 4th day.N0 significant d i f f e r e n c e , a f t e r correction, was noted. Discussion The W B C B 1 2 - C o 5 8 r e t e n t i o n has the d i s a v a n t a g e of a p o s s i b l e intestinal retention of the tracer that could give false results.We have shown that, in the m a j o r i t y of cases, the p r o f i l e s u b t r a c t i o n w a s s u f f i c i e n t for this p a r t i c u l a r a r t e f ~ c t . l f we assume that 51CrCI3 is not a b s o r b e d from the gut. that the tracers f o l l o w the same i n t e s t i n a l t r a n m i t and finally that no i n t e s t i n a l e x c r e t i o n of B 1 2 - 5 8 C o a b s o r b e d o c c u r s w i t h i n the o b s e r v a t i o n time, we can c o n c l u d e that the d o u b l e t~ace~ t e c h n i q u e allows a correct m e a s u r e m e n t of vitamine-Sl2 a b s o r p t i o n . as soon as 48 hours and without stool collection.
539
O.L.Oumitra@cu, O.Oumitra@cu, S.Tamas, S.Cotul and O.Pascu, Dept. of Nuclear Medicine, Third Medical Clinic, Institute of Hygiene and Public Health, 3400 CluJ-Napoca, Romania
GASTRIC EMPTYING OF AN ISOTONIC LIQUID MEAL MARKED WITH In-DTPA IN ENDOSCOPIC NEGATIVE DYSPEPSIA A i m : The a i m o f t h i s s t u d y was t h e r a d i o i s o t o p i o q--6~ntitative a s s e s s m e n t of the g a s t r i c emptying
(GE) of an i s o t o n i c l i q u i d meal in subjects with endoscopic negative dyspepsia (END). M a t e [ ! a l and metho.ds: 26 p a t i e n t s with END and i0 healthy c o n t r o l s were i n v e s t i g a t e d comparatively, In all the subjects, C~ o f 500 ml s a l i n e a t room t e m p e r a t u r e , m a r k e d w i t h 37 MBq I n - D T P A i was assessed redioisotopically with a gamma camera. The half-time (T/2) of the GE curve was measured and correlated with the maximal acid output (MAO) in each case. Results; 16 patients (61.5~I presented prolonged T-'fT~-TType I curve), 4 (15.2%) normal T/2 (type 2 curve), and 6 (23.3~) shorter T/2 (type 3 curve), GE c o r r e l a ted negatively w i t h HAG ( s e e T a b l e ) : T/2 x csec) SEM ~ MAO ~
~
8.4
~
5.2
~8.9 4.9
6.8
20.7
44.8
Co'nt'rois15,:O, 4.4 22.4
SEM(mEq/h) 3.9 9.9 10.2 9.5 The d i f f e r e n c e s between groups are significant (p< 0.05). Conclusion= In patients with END, an isotonic liqui~ meal marked with In-DTPA may have different types of GE speed, depending on the acid secretory status of the stomach.
540
K. QZKER, ~. URGANCIOQLU, i . USLU, M. RAZAVI, T. TURO~LU ~. ONSEL, H. EMIR and O. F. ~ENYOZ
B.Davidson. H.Young, J. Babich, W.Waddington, G. Clarke, M. Short, P.Boulos, J.Styles, C. Dean, P. Ell
NUCLEAR MEDICINE and PEDIATRIC SURGERYDEPARTMENTS,
Departments of Surgery and Nuclear Medicine, University College and Middlesex School of Medicine, London ar.d the Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, U.K.
CERRAHPA~A MEDICAL FACULTY, tSTANBUL UNIVERSITY, TURKEY EVALUATION OF TRANSRECTALPORTAL SCINTIGRAPHY USING 99mTc-FIvPAOFORQU/V~TITATIVEASSES~ OF PORTALHEMODY~ICS Transrectal portal scintigraphy (PS) using 99mTc-pertechnetate(Tc04) allows excellent visual information of portal circulation. But a second radionuclide study is usually needed for quantification of the shunting due to rapid liver wash-out and recirculatien of TcO4.The cell viability and distribution of 99mTc-HePAOin organs, according to the local blood flow directed us to investigate the validity of this agent jnintransrectal PS, in comparisonwith Tc04. 0.1 ml, 3.7 M3q/100 g ~'~fc-(d,l)FFPAO(Amersham)was instilled into the t~Der recttrn of rats with and without partial portal vein ligature. Serial scintigrams were acquired every 5 sec for 360 sec using a gammacamera interfaced to a ccmputer. In normals 99mTc-I~AO was almost ccmoletely removedby the liver during the initial passage. In portal hypertensive rats, the heart was visualized at an early phase due to the diversion of portal flow through the collateral channels. Time-activity curves of heart (H) and liver (L) were studied to obtain useful indices. Meanshunt index (SI) was 2.1 ~ 0.12 % expressed as percent radioactivity under the curve of H, divided by the s~ of H and L curves, whil_eTc04 gave an SI of 4.7-+1.2 %in normals. In portal hypertensiverats 9t~Tc-FFPAOand Tc04 SI were 59.5±6.5 %and 58,2-+5.5 %respectively Both H and L curves increased rapidly with time reaching to a plateau, whereasthe Tc04 curves showed a continuous rise due to the rapid liver wash-out and recirculation. H to L uptake ratio curve of 9gmTc-F~PAOwas also levelled off after lOO-+13 sec giving a fairly constant H/L values of O.M-+O.01 and t32-+0 25 in normal and in portal hypertensiverats respectively, unlike the Tc04H/L values which were too variable from one point to another The results encouragethe use of transrectal 99mTc-FFPbOstudy both for visual and quantitative evaluation of portal circulation, in a single procedure.
THE LOCALISATION OF COLORECTAL CANCERS AND THEIR METASTASES WITH A MONOCLONAL ANTIBODY (MAb) TO EP~IAL MEMBRANE ANTIGEN(EMA) EMA is expressed by the majority of eolorectal cancers but has not been investigated as a target antigen for imaging with radiolabelled MAb's. The rat IgG2a MAb ICR2 raised to EMA was labelled with 111In (100MBq/mg MAb) via ecDTPA and administered intravenously to 22 patients with known or suspected colorectal cancer. Dailyplanar imaging was carried out for 72 hours between administration of IlIIn-ICR2 and tumour excision. At surgery, cancers and normal colon were biopsied for gamma well counting. Immunohistochemistry for EMA expression was earned out on the resecteu specimens. Independent subjective and objective(blind) reporting was carried outon a l1s c an s. Th e snm~vlt e "t' ' y o f l l l I n -ICR2 for detecting cancers was respectively 80% and 60% on subjective and objective assessment and the specificity 20% and 60%. The low subjective specificity was due to false positive localisations in severely dysplastic benign tumours(n=2)and in inflammatory tissue(n=2). Liver metastases present in 3 patients were cold relative to normal liver. Lymph node metastases were localised in 1 of 6 patients pre-operatively. Mean absolute uptake of 11 lln-MAb in tumour tissue was 7.75+/-3.77* x 10-3 % I.D./g and ratio to normal colon 2.1+/0.92* : 1. On immunohistochemistry EMA was expressed by both dysplastic adenomas, 16 of 17 primary cancers and all nodal metastatic deposits. EMA -re turnouts (1 cancer + 1 colonic lipoma) had -ve MAb scans and those -re or showing only focal EMA expression had lower tumour/normal colon ratios (1.3+/-0.26" : 1 vs 2.46+/-0.68 *: 1, p=0.006). These results suggest a role for 1111n-ICR2 in detecting colorectal cancers and metastases but not liver deposits. * mean +/- standard deviation
534
542
541 G. V i l I a v e c c h i a , F. C l a u d i a n i , M. S a n g u i n e t i .
G. Coccia*., O. S c o p i n a r o ,
L. B e r t o l a z z i , C. G e n o v e s i * ,
Servizio di Medicina Nucleate * Divisione di Gastroenterologia Ospedale Gal'liera - G E N O V ~ - IT/~LY
P. Thouvenot, J-C. Ray, M-H. Laurens, J-M. Antoine, L-J. Anghileri, A. Bertrand. Nuclear Medicine Department, CHU Brabois, University ol Nancy, France.
The study was designed to evaluate the usefuln e s s of e s o p h a g e a l scinti~rap]oy (E.S.) in patients affected by non-cardiac che~t pain and apparently normal esophagus. In i0 p t s ( m e a n a g e 50.7 yrs, NCP ~roup) in which esophageal X-rays, endoscopy, 2~h pHmetric monitoring, basal manometry and Bernstein test were normal or negative, esophageal function was further tested by manometry after Bethanechol (B) a n d E . S . . F i ve normals were examinated as controls (C group). E.S. was performed in t h e s u p i n e p o s i tion administratins a 15 m l l i q u i d b o l u s c o n t a i ning 0.5 mCi of 99mTc-DTP~. ~etivity was recorded at the rate of ~ frames/see f o r 30 sec. In NCP Eroup LESp, wave duration and wave amplitude increased s~gnificantly ( p < 0 . 0 0 1 ) a f t e r B. In C group no significant difference, a f t e r B, was observed, In N C P g r o u p t o t a l e s o p h a g e a l transit time (TTT), expressed as i n t e r v a l b e t w e e n t h e initial esophageal activity and its final clearance, was 15.6 see+-8.8 (m+-SD); in C group TTT wa~ 7.2 see+-0.8; the difference was significant (p<0.05). In N C P p t s , with normal basal manome- try, b u t wit.]] q u a l i t a t i v e and quantitative esophageal motor alterations r e v e l e d b y B, E. S. showed a significantly prolonged TTT. Consequently, in pts wit]] non cardiac chest pain, E.S. can be used as first diagnostic approach.
EFFECTS OF PHYSICAL EFFORT ON GASTRIC EMPTYING. In order to know if: 1) gastric emptying (GE) is the same for sedentary individuals than for sportive subjects at rest, 2) GE is modified by physical effort during digestion, and 3) the nature of the physical effort has an influence on GE, the following protocol was performed. A meal of pasta (50 g of starch), labeled with 99mTcalbumin, was ingested with 250 ml of water. Corrected acquisitions (1 mn), on the stomach area, were carried out every 15 mn dunng a 3 h perioO. Population: A) 24 sedentary volunteers, B) 12 sportive subjects trained for competitive sports, either kept at rest or making a physical effort (60% of max VO2)for 3 h on ergocycles just after the meal ingestion, C) 12 sportive subjects making the same physical effort, either on ergocycies or a 2 hour run, with a 1 h delay between the ingestion of pasta and the start of the physical effort. Necessary time (mn) for 10, 50 and 80% of the food bolus to leave the stomach (mean + SEM): A B at rest B+ergo- C+ergo C+footcycle cycle race t 10% 28(1.6) 14(1.0) 29 (3.8) 17(3.1) 13(2.8) t50% 91(6.1) 62(4.8) 74(8.1) 75(5.3) 56(3.3) t80% 175(5.6) 126(6.4) 131(7.3) 137(9.2) 110(6.3) The trained subjects at rest had a faster GE and a shorter lac phase than the sedentary ones; the physical effort prolongec the lag phase without changing the total time for GE; thG kinetic of GE is affected by the nature of the physical effort.
543
544
ESOPHaGEaL SCINTIGRAPHY IN NON CARDIAC CHEST P~IN P~TIENTS WITH APPARENTLY N O R M A L ESOPHAGUS
F.SPIgELLI, M.MILELLA, F.BA~FI, L.C4ILLITELLI,R.VIGONELLI, R.SARA
C.CorbeIli, P.Zagni, B.Dondi, M.Levorato, R.Frennhi, 8.Bsilanova, N.Monetti C.Brignola*,P.lannono*,M.Campieri*
Departmentof NuclearMedicineand I^ Medical Clinic* S,Drsola-MalpighiPolinlioicaIHospital,Bologna, Italy D E P A R I ~ OF NUCLEAR ~3ICI~E,O~EDALE NIGUARDA--CA'G~A, MILANO,ITALY. T~E STUDY OF LOCATION AND ACTIVITY CF ~@'IAM~ATORYBOWEL DISEASE WITH 99mTc-HNPAO IABELIZD lEUCOCYTES. Seventy-two patiants,51 with ~ disease and 21 with ulcerative colitis, have been studied after reinjeetion of autolqgons leucocytes labelled with 99mTc-~AO,in order to assess the reiisbilit~ of the exanination i~ evaluatin~ the location and activity of the disease.The gcanulocytes int ~ i t y was assessed by a 20 sin initial dynsmic study evaluating the iN wash-out,rasultingin a t h r e ~ a s e clearance curve with. a first fast cc~nponant(~/~:mean82 ssc),a second slower co,ponest (~/~:masn353 sec) and a dlird c o u n t with a pratically irrelevant slope.The static planar im~as were performed at 1,2,4 and 24 h(xms.With 99mTc-H~AO only the early images ar~ dia~eestic in bowel disease.As far as the Iccation of inflsmmatJon is concerned,a high correlation (r=0.978) was found bet~leen ~adiolop=icaland endoscopic findings,performedwithin 2 weeks from the scan,and gr~nu]ocyte scan in the dis~nosis of the bowel segments involved.The disease activity by scan was evaluated by compaFir~ the activity in the bowel with txmqemsrrow activity at 2 hours.The results were exp]:~ssed by ,gradir~ the uptake from 0 to 3 and as bewel/bone marrsw uptake index.In the positive bowel scans the index was co,prised between 0.17 and 29.7.The difficulty to exactly assess clinically disease activity is a drawback in the correlation w~th scan resulte.Howevem,dividir~the activity into fouP levels (no actual disease,low,moderateand hi~n activity)we found a very high ccrre]atieqbetweenthe classical para1~tsrs and scan findir~s.In conclusion,we believe d~at ~ranulocEte scan with 99mTc-h'~A0 could be the test fo choice in the follow-up of Crohn disease and ulcerative colitis.
Comparison between Tc-gge lobe]led BAR BW2501183 leucocites scanning (LS) in Crnhn's disease (CD),
and In-Ill mixed
In-111 LS provedeffectivein eva]uatingCO activity, but it is a time consumingprocedure. Recently Tc-g?m granulocyteslabelled 'in vivo'by means of a specificMAR have been proposedfor detectionof inflammatory processes (J Nucl Med 1987:28:271). The aim of this work was to compareresultsof thesetwo methods in 18 potions with proved CO, The distributionof Tc-ggm labelledHAR~ which binds to the antigenNCA-95 presentin almost all humangranulocytes,was studied 4 and 24 hours after i.v. injection.EverypatientunderwentIn-lll LS 4 days later. In both studies,extensionof diseasehas been quantified by calculatingthe number of pixels (EXT) in the lesionoccupiedarea, both for TcMABand In-lll tS scans, The activitydegreeof studiedlesionshave been expressedas the ratio (CR) betweenthe uptake in the regionof interest and the uptake in the iliaccrest. Tc~AB gave imagesof similarqualityand same EXT Ir=O.g7Jas In-ill.CR of TcMA8 was lower than that of In-ll! Ir=O.67L In this preliminarystudh TcffABresultswere found to be similarto those obtained with mixedleucocytes Inlll scan,howeverTcMAR scintigraphyis easier to performand time sparingand showspromisingapplications in thm detectionof chronicinflammatorybowml disease.
535
545
546
J.DAUMAL; M.ROCA; C.BALIELLAS; M.A.GASULL; C.BADOSA; L.PRAT; J.MORA; E. CABRE and J.MARTIN-COMIN
Servei de Medecina Nuclear. Hospital U n i v e r s i t a r i de B e l l v i t g e . H o s p i t a l e t Barcelona.Spain
de LLob.
INFLAMMATOTY BOWEL DISEASE EXAMINATION WITH 99mTc-HMPAOiLEUKOCYTES. We have performed 45 exams in 41 p a t i e n t s ( 2 5 males,mean age 32+17 years) with suspicion of inflammatory bowel diseas~ (IBD), 23 of Crohn's disease (CD) and 18 of u l c e r a t i v e c o l i t i s (UC). In a l l cases autologous leukocytes were l a b e l l e d in plasma : s a l i n e ( I t 1 ) medium with 2.5-5 mCi of 99mTc-HMPAO and r e i n j e c t e d to the p a t i e n t . Mean l a b e l l i n g e f f i c i e n c y was 37+10% Usually two images of the abdomen(one i n c l u d i n g ITver and spleen) were o b t a i ned at 30 min. and 4 hours p o s t - r e i n j e c t i o n . Barium enema and/or endoscopy was obtained as soon as the p a t i e n t ~condition p e r m i t t e d i t . Labelled leukocytes l o c a l i z e d mainly in spleen and l i v e r . The g a l l b l a d d e r was seen in 2 p a t i e n t s .Urinary bladder a c t i v i t y was high at 30 min p . i . Bone marrow was c l e a r ly seen in a l l scans. The s e n s i t i v i t y , s p e c i f i t y and accuracy were r e s p e c t i v e l y 91%,75% and 88% f o r CD and 100%, 75% and 95% f o r UC. Two f a l s e p o s i t i v e r e s u l t s were due to a y e r s i n i a i n f e c t i o n and a colocarcinoma. Two f a l s e negatives were found. In CD as w e l l as in UC the number of a f f e c t e d areas was g r e a t e r in the scan than in the barium enema.The p o s t - v o i d i n g caudo-craneal view was of help to make out u r i n a r y bladder from r e c t a l a c t i vities. In summary: The use of 99mTc-HMPAO-Leukocyte scan permits a quick and accurate e v a l u a t i o n of the l o c a l i z a t i o n , extension and a c t i v i t y of IBD.
547
VALUE OF ggmTc-HmPAOGRANULOCYTESSClNTIGRAPHYIN THE INTESTINALBOWEL OISEASE. *S. Modoni, *V. ~[~s£~an~e, ^A. ~angia, ^A. Gabbrieili, ~L, Gabbriel!i, *P,G. Paieani-Vetteri. * Dept. of Nuclear Medicine, ^ Dept. of Gastroenterology General Hospital "CASASOLLIEVOdella SOFFERENZA", S. Giovanni Rotondo (Fg), Italia
The recent improvements in granulocytes labelling by 9gmTc-HmPAO proposed by Peters and coworkers (The Lancet, October 25, 1985) allow nowaday a significant progress in diagnosis of inflammatory diseases. Ne applied this method to the study of bowel diseases as Crohn's enteritis and ulcerative colitis and, therefore, we have examined 33 patients (16 affected by Orohn's enteritis and 11 by ulcerative colitis). 27 patients were studied also by endoscopy, while in the others it was not feasible for fear of intestinal wall perforation. For granul£ cyte labelling we employed the method proposed by Peters. Imaging was performed at 30 min. and 3 hrs., after the labelled cells administration, by acquiring a two million counts images, matrix
255x256. Latter images are not useful because of biliary radiophamaceutical excretion and mucosal granuloeytes exudation into the bowel lumen. Mean labelling efficiency was Of 43~, with no significant in vitro cells modifications and in vivo lasting pulmonary retention. Positive results were obtained in all the patients in both earlier and latter images. Better images were obtained if the examination was performed in the acute phase of disease, without influence of cortieostereid therapy. In all the patients checked also by the endoscopy we found a good co£ relation with scintigraphic results regard to disease extention, In conclusion, we think that ggmTc-HmPAO-Granulocytesscintigraphy allows a great advantage because of its ready availability, lower radiation dose, non-invasivity and better image quality,
548 d,l~anzo,M.D.Abes, E.Prats, J.L.Hortells, d.LopezZaborras and
J.M ROCCHISANI, Cochin Hospital.PARIS. FRANCE.
R,garciaRe/ Nuclear Medicine Division.Universitary Hospital.Zaragoza.Spain.
Comparison of SPECT and Planar Gastrointestinal Bleedinds.
imaging
in
Abdominal scintigraphy using Tc99m tagged Red cells is a useful examination for the detection and localization of gastrointestinal bleeding. We have search if SPECT could improve this method. Eleven patients referred for a recent melena were evaluated in the present study. Bleeding site was localized by endoscopy, angiography or surgery in the upper (5 cases), middle (2cases) and lower (4 cases) abdomen. Images, both planar (PS)and SPECT, were acquired several times: 15 minutes, 3 , 6 and sometimes 20 hours following the injection of 600 MBq of labelled red cells. The study consisted of attenuation corrected transverse, coronal and saggital slices (3x64 matrices 64x64) computed from a 15 minutes acquisition ,in addition to anterior, posterior and oblique planar views (128x128 matrix). A correct detection was obtained by SPECT for all patients and for 7 of them by PS. It was uncertain in 3 cases and negative once in PS. In 5 cases it was obtained one time earlier by SPECT than by PS. A segmental localization was determined in 8 patients by SPECT at the upper (4), middle (1) and lower(3) abdomen, and in 3 patients by PS in the middle(I) and lower(2) abdomen. the site of 2 active bleedings has thus been found by SPECT. This study indicate that SPECT can be recommended for the evaluation of gastrointestinal bleeding.
"EFFICACY OF CHOLEGCINTIBRAPHY IN COMBINATION WITH THE ADMINISTRATION OF MORPHINE IN THE DIABNOGh5OF ACUTE CHOLECYSTITI$" Introduction, The morphine augments the tone of Oddi's sphincter, increasing intraductal pressure and thus increases the flow of the radiopharmaceutical into the gallbladder, provided that the cystic duct is permeable. I'loth~ls an materials. We have evaluated prospectively the hepatobiliary scanscarried out on ,t0 patients under the following crlteria:l. The administration of 185-222 MBq of 99mTc-Disedenin (30 patients) or of 99mTc-Trimetil-IDA(lO patients). 2. A radionuclide angiography (33 patients). 3, A sequential basal hepato-biliary study: statics imagesat 5' ,20', 40'and 60',4. The i.v. administration of 2 mgrs of morphine chloride (2 minutes). 5. A post-morphine hepatobiliary study: imaging at 5',10' ,20' and 30'. All the patients presented the following symptons and background: 1. A clinical examination wich suggested acute cho]ecystitis. 2 Non-visualization of the gallbladder in the basal hepatobiliary study. 3. No acintigraphic eviderico of an obstruction in the comon bile duct. 4, Normal plasmatic levels of amylase. 5. The non-administration of analgesics durlng the previous 3-4 hours 6. Non-previous Oddl's sphincterotomia and 7. A diagnosis confirmed by ultrasound and/or surgery and/or by clinical ecolution. Results. After the administration of morphine 23 patients presented non-visualization of the gallbladder; in 16 patients the gallbladder was visualized and in one patient a cholecystocolic fistula was detected.We obtained a sensitivity of 0.87 and a specifity of 0.87. Conclusions, The low dosesof morphine are well tolerated and can be regarded as a valid alternative to the current practice of delayed imaging (4 hours) in establishing cystic duct patency.
536
550
549
L.PRAT; J.MARTIN-COMIN;J. FI GUERAS*; R.RAFECAS*; R. PUCHAL; E. J A U R R I ~ n d M. RAMOS.
H A Ziessma__nn, CE A r o o f f ,
NW Barton
Georgetown University Hospital, Washington, DC N a t i o n a l I n s t i t u t e s of Health, B e t h e s d a , MD
Servei de Medicina Nuclear ,Unitat de trasplantament*. Hospital universitari de Bellvitge. Barcelona.Spain. DELAYED
MICROCOLLOID AND IDA SCANNINGIN LIVER GRAFTRECIPIENTS. We have studied 23 liver graft recipients with two different methods. In 10 patients 30 g9mTc-EHIDAscanning (IDA) were performed. The portal contribution to hepat i c (PC) blood flow was calculated 40 times in the remaining 13 p. with 99mTc-microcolloid. Overall 70 examinations were performed. 30 of ~hem in patients with functioning graft(FG), 17 in acutely rejecting patients(AR), 11 after succesful treatment of a rejection episode(PRR), 9 in patients suffering from hepatitis (HEP) and 3 during a cholangitis episode (CHOL Diagnosis was based on usual clinical and biochemical criteria as well as on histological data. PC differentiated AR from FG, PRR and HEP, but did not differentiate between AR and CHOL. Results with IDA showed a normal tracer uptake in FG and PRR while elimination was slowed in 7 out of the 18 cases.A sharp decrease in tracer uptake was seen in all AR episodes. In one case of HEP a slight decrease of tracer uptake was seen while the remaining two showed only a slowed elimination. The CHOLpatient showed a normal scan. In summary both methods are useful to l i v e r g r a f t pat i e n t management. Both evaluate d i f f e r e n t l i v e r funct i o n s and should be used according to the pathology we are looking f o r .
GASTRIC EMPTYING
IN F A B R Y ' S D I S E A S E
F a b r y ' s d i s e a s e (FD) is an x - l i n k e d d i s o r d e r due to a d e f i c i e n c y of t h e l y s o s o m a l e n z y m e alphag a l a c t o s i d a s e A a n d r e s u l t s in t h e p r o g r e s s i v e m u l t i - s y s t e m d e p o s i t i o n of a g l y c o s p h i n g o l i p i d , ceramide trihexoside. Tissues involved include v a s c u l a r e n d o t h e l i u m , n e u r o n s of t h e p e r i p h e r a l , c e n t r a l and a u t o n o m i c n e r v o u s s y s t e m and kidney. Gastrointestinal complaints of p o s t - p r a n d i a l bloating, early satiety, diarrhea, constipation, n a u s e a a n d e m e s i s a r e c o m m o n . T h e p u r p o s e of t h i s s t u d y w a s t o d e t e r m i n e if d e l a y e d g a s t r i c emptying (GE) m i g h t b e c o n t r i b u t i n g to t h e s e patients symptoms. Seven patients with Fabry's h a d s o l i d and l i q u i d G E s t u d i e s a n d c o m p a r e d to n o r m a l c o n t r o l s . T h e m e a l c o n s i s t e d of a T c - 9 9 m l a b e l e d ~ g g - w h i t e s a n d w i c h (i mCi) and 200 cc of I n d i u m ~ l l l l a b e l e d w a t e r (200 uCi) . P a t i e n t s w e r e imaged continuously in t h e L A O v i e w for 90 minutes with large field-of-view gamma camera and medium energy collimator. Follow-up studies w e r e p e r f o r m e d a f t e r 1 w e e k of o r a l t h e r a p y w i t h m e t o c l o p r a m i d e , T h e r e was s t a t i s t i c a l l y s i g n i f i c a n ~ d i f f e r e n c e in the r a t e of s o l i d GE b e t w e e n p a t i e n t s a n d n o r m a l c o n t r o l s 67 ± 13% vs. 41 ± 15% (p < .005) . Of 5 s y m p t o m a t i c p a t i e n t s , 4 had d e l a y e d GE. O n e a s y m p t o m a t i c p a t i e n t h a d n o r m a l e m p t y i n g . A l l s y m p t o m a t i c p a t i e n t s r e s p o n d e d to o r a l t h e r a p y . GE s t u d i e s s h o u l d b e p e r f o r m e d in all s y m p t o m a t i c p a t i e n t s w i t h F a b r y ' s d i s e a s e .
552
551
A.D.H3/~, P . L I ~ , S~%[L~N,R.MASCN,S.(IANKE
A. J A V A I D , BARRETT.
KING'S
_s~u~
cest~ic ~ptytng ~n the ~ t - a ~
To date, the only reliable method of measuring rat gastric emptying involves sacrifice of the animal at various times after intragastric instillation of radioisotope. This study describes a technique by v~ich solid and liquid gastric emptying may be assessed repeatedly over a long period of time using the ganma camera, and without sacrifice of the animal. Intragastric instillation of either lml of 99m Tc-labelIed tin co|1oid or 99m Tc-labelled Dowex resin in B r a n ~ s performed under a short general anaesthetic using a rat endoscope. Rats of 200 grams weight or above were then place(]over a garnna camera in a purpose-built rat holder, Sequential images over 2 hours showed a linear pattern of solid
e~ptylng and liquid e~ptylng of mmncexponential pattern with half-life of t0 minutes. The technique correlated well with that of intragastric instillation followed by sacrifice ( r=0.9l, p 0.0001). This study demonstrates that it is possible to assess gastric emptying in the rat in a sequential manner and without the need for animal sacrifice, This method is enabling further studies on the pathology and manipulation of gastric emptying disorders and the effect of surgical procedures on gastric ~mptying.
B.
COLLEGE
SHAPIRO,
G.M.S.
HOSPITAL,
STEP,
LONDON,
SE5
AND J.J.
9RS,
U.K.
SCINTIGRAPHIC QUANTITATION OF HEPATIC PERFUSION: COMPARATIVE CLINICAL EVALUATION OF TWO METHODS. Quantitative assessment of liver perfusion can be incorporated into the static liver ima~in~ with Tc99m labelled colloid. Two previously reported methods were considered with respect to their applicability as added diagnostic value. Thirty-three patients with Chronic Liver Disease were studied. A rapid i.v. dose administration (BO MBq) was followed by first-pass data acquisition of 90 0.5 second frames. Beth methods were used to quantitate portal venous fraction PFI and PF2 whereby the second method was adjusted to first-pass protocol. All scans were subjectively ~raded (I-4 scale), ~rade I indicating nearly nermal scan appearance. The average PFI and PF2 values were calculated for each scan ~rade. Very Rood correlaticn (r 0.95) was found between the mean flow fractions and the scan ~rade. Significant correlation (r=0.71) was obtained between the PFI and the PF2 results. The ~rade I means of PFI and PF2 were 0.78 +/- 0.08 and 0.52 +/- 0.11 as compared to previously reported normal values of 0.64 and 0.64. The mean flow fractions for 5 patients with Alcoholic Liver Disease and 8 patients with Primary Biliary Cirrhosis did not differ significantly by either method. Both methods were found easy to apply and produce similar results that are in line with prevJou~ work. Altheu~h the fractional flow values can predict th~ severity of liver involvement and may be used for patient follow-up,their value in differential diaRnosis of Chreni~ Liver Disease however, remains to be demonstrated. SimilaH approach for quantitatin~ hepatic perfusion and hepatoeyte function with a biliary agent may prove more useful.
537
553
554 HA Ziessman, RA Vigersky.
M.R. CASTELIANI ~, M. BELLON~ ~, G. COZZl oo, E. SERE(~I °
Georgetown
FH
Fahey,
University
WK
Desehner,
Hospital,
MJ
Washington,
Collen
DC.
NtLZEAR ~DICINE DMSICN o, GASTROINTESTINALRADIOLOGY DEPT.°U NATIONAL CANCER INSTITLfIEOF MILAN, ITALY IDA SCAN IN T ~ FOLLOW4JP OF PATI]~I% TRFATE~ BY SURGICAL OR PEROJTANEOt~ BILIARY DERIVATION. This study was p e r £ o ~ to evaluate the bilisry flow in patients with cholestssis due to b e , ~ (3 pte.) Or to neoplsstic (i0 pts.) stricture of the bile duct, after either surgical (biliary-entericanastomosis] (4 pte.) or radiological (percutaneousbiliary drain~zes) (9 DiS.) biliar~ derivation. After i.v. inj. of 5 mCi of 99mTc-Trimethyl-IDA, each patients was sb~died with a ~ c acquisition of 60 rain.,utilizir~ a co~outerized game csmera; analogue images at i0 man. intervals were also obtained. The data collected were plotted to generate time activity craves and th4 half life of hepatic wash-out, which was considered an inde~:oflb~]iavy flow. The normal T 1/2 of the hepatic wash-out was calculated utilizing, as controls, i0 patients without choleatasis. The patients with biliacy derivation were studied with a total of 21 sc2n~. No scan were made wi~J bi]irubine values more then i0 m~/lO0 ml. In the patients with percut~neeas drainage, biliary flow was always decressed. The T 1/2 of the ep~ tic wash-out rsn~ed between 68 to 233 rain. In the patients with sporadi~ cholsr~it/s after biJiary-ente~ic armstxmmsis d~e T 1/2 of the hepatic wash-<~t was only moderately prol~ed (50 rain.),even in one case with stasis at the level of the bi]iary ducts. In one case with do6nm~nted biliary stasis at the level of an enteric efferent loop, the flow i~proved dramatically after i.v. inj. of me~gcl~pFanide. All patients slowed a good correlation between clinical and scinti~raphie f i n d s . Thus this examination is very effective in monitorir~ patients with biliary, surzical or per£utaneous, derivation.
AND LIQUID GASTRIC EMPTYING CONTINUOUS ACQUISITION IN THE
iN DIABETIC: LAO VIEW.
Gastric emptying (GE) in 19 d i a b e t i c s with symptoms of g a s t r o p a r e s i s are compared t o I0 norma!s using continuous acquisition. After ingestion of a T c - 9 9 m S C egg sandwich and In-lll DTPA labeled water, studies were acquired on computer f o r 90 m i n i n t h e L A O v i e w . The LAO gives results similar to the geometric mean ( F a h e y et al. J N M 1 9 8 9 ; 3 0 : 2 3 3 - 2 3 9 ) . S o l i d GE was linear and had a lag phase in all diabetics and normals. Diabetics had reduced 90 m i n % G E (mean 4 2 % vs. 6 7 % GE) ( p < . 0 1 ) and delayed lag phase(36 vs. 16 min) c o m p a r e d to n o r m a l s . Solid GE w a s d e l a y e d i n 9, n o r m a l i n 8 a n d r a p i d i n 2 diabeZics. The lag phase was delayed in 5/9 diabetics and the tl/2 emptying rate delayed in 8/9 w i t h r e d u c e d 90 m i n % G E ( p < . 0 5 ) , b u t in n o n e w i t h n o r m a l o r r a p i d GE. L i q u i d G E w a s e x p o n e n tial with no lag phase. Curve stripping showed 2 components, an early fast one (6 m i n tl/2) in 6/10 nls and 13/19 diabetics followed by a 2nd slower one. The slow component of liquid GE correlaned with the solid GE rate (r:.826 in normals, .885 in d i a b e t i c s ) and was delayed in 7/9 diabetics with delayed s o l i d %GE. C o n t i n u ous acquisition provides data from the early p h a s e of GE, a l l o w i n g a better understanding of the pathphysiology of d i a b e t i c g a s t r o p a r e s i s .
556
555 V. ANDREICA, D. DUMITRASCU, S. COTUL, S.TAI1AS, G. FREISLER 3rd Medical C l i n i c , I n s t i t u t e o f Medicine and Pharmacy, 19-21 C r o t t o r i l o r S t . , 3400 CluJNapoca, Romania
ACTION OF PGE/(MISOPROSTOL ) ON GASTRIC EMPTYING OF LIQUIDS: o~INTIGRAPHIC ASSESSItENT P r o s t a g l a n d i n s a r e used i n t h e t h e r a p y o f u l c e r . M i s o p r o s t o l (M) is a s y n t h e t i c a n a l o g u e o f PGE1. The a c t i o n o f H on the g a s t r i c e m p t y i n g of p h y s i o l o g i c a l salt s o l u t i o n is investigated. Material and method: In 18 s u b j e c t s
(i0 m e n
and 8 women) w i t h o u t g a s t r o i n t e s t i n a l diseases the g a s t r i c e m p t y i n g ~ f physiological salt solut i o n l a b e l l e d wi~h W~mTe was a s s e s s e d . By t h e stfnti~rsphi¢ t e m h n i q u e we d e t e C m l n s d r t / 2 ( m i n ) f o r the w h o l e stomach (W) and f o r two s e g m e n t s : p r o x i m a l ( P ) ( a p p r o x i m a t e l y the u p p e r 2 / 3 ) and distal ( O ) ( a p p r o x i m a t e l y the l o w e r I / 3 ) . t4eas u r e m e n t s w e r e dens b e f o r e t r e a t m e n t and a t 2 - 3 days i n t e r v a l , 1 . 5 hours from t h e M ( C y t o t e c Searle) administration 8o0~, Results: t4 t e n d s t o reduce the g a s t r i c emptyi n g t i m e (T 1 / 2 ) f o r the p h y s i o l o g i c a l salt solution (Table): Before W 'l'~'.li$'x
SOLID USING
T 1/2 treatment
P 13,83'+
O 18,2"8+
T 1/2 After W l O . 1 7 + 'x
--
treatment P D 9.61+ 12.78+
7.51-7.05-- 10.41-5.76-6.02-7.40-X) p ~ O . 0 5 . M s l o w e d the e m p t y i n g o f the w h o l e stomach by ZS~, and o f P and D segments by 31~. Conclusions: M s h o r t e n s t h e tim~ of g a s t r i c e m p t y i n g of p ~ y s i o l o g i c a l s a l t s o l u t i o n , an e f f e c t which may be used to r e l i e v e g a s t r i c stasis in the patients with qastric ulcer.
Mz_Abd~zRa~ak,
S. A n w a r
a n d R. A w a d e i n
A.C. Medical Center Cairo , Egypt.
SCINTIGRAPHIC P A T T E R N O F T H E L I V E R IN P U R E SCHISTOSO~IL ( BILH&RZIAL ) INFECTION. In t h i s c o n n e c t i o n , p r e v i o u s r e p o r t s d e l t w i t h p a t i e n t s d i a g n o s e d on c l i n i c a l g r o u n d s , w i t h o u t h i s t o l o g i c a l p r o o f . In c o n t r a d i s t i n c t i o n , the nresent work studied iO oatients having heDatosplenic bilharziasis. Liver biopsy showed that 28 h a d p u r e b i l h a r z i a s i s . The r e m a i n i n g 12 p a t iente had bilharziasis a n d c h r o n i c h e p a t i t i s cr cirrhosis. The o b t a i n e d r e s u l t s s h o w e d t h a t d e l a y in r a d i o e o l l o i d c l e a r a n c e f r o m the c i r c u l a t i o n , as w e l l as s h i f t of c o l l o i d to the s p l e e n w e r e m o r e m a r k e d w i t h i n c r e a s i n g s e v e r i t y of the d i s e a s e . Heterogeneity in distribution of r a d i o a c t i v i t y w a s m o r e e v i d e n t w i t h i n c r e a s i n g s e v e r i t y of the d i s e a s e as w e l l as i n the o r e s e n c e of m i x e d a e t iology. In a d d i t i o n , the s c i n t i g r a p h i c p a t t e r n o b t a i n e d i n b i l h a r z i a s i s w a s s i m i l a r to t h a t s e e n in c i r r h o s i s . H o w e v e r , the size of the s p l e e n t e n d e d to be l a r g e r .
538
557
558
O . d . P e g r o s s i , T . Watanabe, H.Garcia del Rio, C.Devoto , P.Oliveri and E.B.Degrossi.Teo.Ass. M.O. de ~ncalves.
German Hospital and Institute Roffo, Buenos Aires, Arqentina DIAGNOSIS AND FOLLOWUP OF BONECHONDROSARCOMAWITH Tc-99m CHONDROITIN SULPHURICACID (CSA) CSA-Tc-99m was labelled by means of an electro]yticaI method using 15 mg CSA, 925-18b0 MBq Tc-99m in 2-2.5 ml volume and 315 ~g CI Sn++ .Quality control showed less than 2% free Tc. In 10 patients with chondrosarcoma, 10 with osteosarcoma, 25 patientes with bone metastases of breast and prostate primitive tumors and 5 normal volunteers~ 740-925 MBq of CSA-Tc-99m were administered i . v . and bone scans were carried out 2 to 5 hours afterwards; 48-72 hours after the CSA study a MDP-Tc-99m scintigraphy was carried out. All patientes with bone metastases and 9 ot the osteosarcoma patientes did not show significant increased CSA act i v i t y in positive MDP areas. All patientes w i t , chondrosarcoma and one patiente with primitive osteosarcoma of chondral rece showed increased CSA a c t i v i t y in positive MDP areas with the same or bigger size and similar shape. One patient with a primitive chondrosarcoma of the t i b i a presented in the CSA study ,and extension of positive area to the femur bone marrow of the same leg (correlated at surgery with extension of the i l l n e s s ) ; another patient with chondrosarcoma of the femur showed in the CSA study post surgery treatment, uptake in lung metastases. These two cases were negative in bone marrow and lungs in MDP scintigraphy. These results indicate that CSA allows a better determination for surgycal resection and follow up of chondrosarcoma; appears as a pormising image agent in tumors of chon dral rece.
559
Departments of Obstetrics and Gynaecology, Nuclear Medicine, Cell Biology and Histology, and Medical Oncology, University of Nijmegen and University Hospital, Nijmegen, The Netherlands
PHARMACOKINETICS AND BIODISTRIBUTION OF IN-111-OV-TL 3 F(AB')2 MONOCLONAL ANTIBODY IN PATIENTS WITH OVARIAN CANCER This study was performed to obtain information about the biologcal behavlour in patients of a new routine monoclonal antibody (OV-TL 3). After wdtten Informed consent, fifteen patients were Injected i.v. with 140 MBq In-111-OV-TL 3 F(ab')2. Blood samples were taken regulady upto 96 hrs after injection. Furthermore urine, faeces, ascites, and cyst fluid samples were obtained. During the operation, 6 days post Injection, tumour deposits and fragments of normal tissues (blood. liver, muscle, bowel, lymph node, skin, ovary, and uterus) were removed by the surgeon. Disappearance of activity from blood was similar for all patiens studied and could be represented by a bl-exponential curve with halflifes of 6 and 32 hr. In patients with ascites an increase of ascites activity was seen from 0.2% of the dose per liter at 24 hr to 1.5% of the dose per liter at 5 days post injection. Total urinary excretion (urine collection up to 96 hr p.i.) amounted to approximately 17% of the dose, while total stool activity reached 2% of the dose over the same period. Tissue uptake values, expressed as % of the injected dose per gram tissue (mean -+ SD x 10~) were 3.8 + 0.8 for tumour, 11.5 -+6.5 for liver, 3.0 + 0.7 for omentum and 0.5 _+ 0.4 for skin. Tumour to normal tissue ratios did not exceed 10.4. To assess the homogeneity of activity distribution within in a tumour mass, multiple samples were taken from a large ovarian tumour and the activity uptake of each sample was measured. Uptake expressed as % of dose per gram tissue (x 103) ranged from 0.3 to 5.8 with a mean of 2.4 and was in accordance with the macroscoplcal inhomogeneity of the tumour mass. Based on biodistdbution data, the radiation burden was estimated in one patient. Liver: 1.8 mSv/MBq and kidneys: 1.3 mSv/MBq; somatic effective dose equivalent: 0,5 mSv/MBq.
560
A. D i m i t r a k o p o u l o u , L.G. S t r a u s s , J.H. C l o r i u s , P. S e h l a g , F. H e l u s , F. O b e r d o r f e r , Jo D o l l Deutsches Krebsforsehungszentrum, sehe Universitiitsklinik, Heidelberg;
L. Massuger, W. v.d. Brock, O. Boerman, W. Buijs, R. Claessens, R. Verheijen, L. Poels, Ch. $chljf, Q. van Hoesel, P. Kenemans, and F. Corstens
Heidelberg; Chirurgi-
M. Tortes, A. Jim6nez-Heffernan, C. Baamonde ~, J.M.Latre, F.M. Oonz~]ez, Mo Martinez, F . L o p e z - R u b i o ~* and A. Mateo. N u c l e a r Medicine, Thoracic Surgery~ and Pathology** Services. Hospital "Reina Sofia" and Radiology Department. Medical School. CORDOBA.
PET STUDIES WITH F-18-URACIL IN PATIENTS WITH LIVE1; METASTASES RECEIVING INTRAARTERIAL CHEMOTHERAPY. Fluomuracil (FU) is the most important eytostatie agent for the intravenous ehemotherapy of liver metastases from eoloreetal cancer. We used PET and 'F- 18 labeled FU to investigate the distribution pattern of FU and its metabolites in metastases and normal liver parenehyma after intravenous and intraarterial infusion of the eytostatie substance. Furthermore, we administered O-15 labeled water to determine the perfusion in the different tissues and we compared the O-15 labeled water concentrations with the FU accumulation. A positron emission tomograph (PC2048-7WB, Seanditronix Co.) with two ring detectors was used for the PET examinations. The system )rovides for the acquisition of three slices simultaneously. Double examinations were performed in 10 patients using the i.v. and i.a. approach. All patients had a surgically implanted catheter in the gastroduodenal artery and a subcutaneous port system. Five one-minute images were acquired after bolus injection of O-15 labeled water, while ima- ,f ........ .................. ges were acquired continuously for two ~. ] hours after infusion of FU Higher FU$ ./ . . . . . . t--. . . . "1 coneentratmns 2 h p.L were obtained m 7< .. • , ~ - ~ / / of 13 metastases (see fig. on the righ0,~jl. ~ ' ~ i f ~ while lower tracer concentrations were ~'S". noted in 3 metastases after i.a. FU infu . . . . . . . . F,, ~.~. ,~, sion. An increased systemic toxicity was observed in 6 of I0 patients. Generally a high O-15 accumulation in the metastases did not correlate with increased FU uptake. Our results demonstrate, that perfusion examinations are insnffieient to estimate the FU distribution pattern and studies with FU are required to optimize the regional chemotherapy and to select those patients who do profit from the intraarterial approach.
SPAIN.
LUNG CARCINOMA
IMMUNOSCINTIGRAPHY
WITH MoAb ANTICEA-IIIIn.
F(ab')2 fr~rents of MoAb FO23CS-fllIn were utilized to study 41 patients with a diagnosis or clinical suspicion of lung carcinoma. Nonspecifie antibody uptake was evaluated in 5 patients using f(ab')2 frs~ments of MoAb 4CA-IIIIn (anti-hepatitis) and in one patient with lung neuroblastoma using antiCEA. The tt~nor was visualized in the six patients although t u ~ D r / b a c k ~ d (T/B) ration were never higher than 1.51. Therefore, immunoseintigrephy was considered positive when the T/B ratio was higher than 1.60. Usir~ this criteria and evalustir~ planar and SPECT im~es, the results obtained for pa]monsry tumors were 26/34 true positives (TP)and 6/7 true negatives (TN) with a false positive case in one of ~ree abscesses studied. In the detection of local recurrences the results were 6/7
TP and 3/3 TN. 9/13 metastasis were detected with bao FP. /~stochendstry was p e r f o r ~ in ii patients and ~ e results were in agreement wida i n r n u o s c i n t ~ in 8 cases. The findir~ of positive CEA stainig in glandu/ar aress of the center of an indifferentiated carcinana and in metaplasic cells in the periphery of an epidermoid carcincrm~are of special interest. Serum CEA levels were concordant with immunoncintigraphic results in crdy 12 of 35 patients. We conclude that antiCFA i ~ i n t ~ may be useful in stagir~ lur~ tumors and in the early dis~osis of recurrence, although the positive result obtained in a patient with an abscess reduces its utility in m e differential dis~nosis of p u ] ~ n~gsses.
539
561 L. Pools1, O. Boerman1, C. Thomas2, L Massuger2, R. Claessens3, and P. Kenemans. Departmentsof C~I Biology and Histology~, Obstetrics and Gynaecology2, and ~uclear Medicine°, University of Nijmegen and University Hospital, Nijmegen, i The Netherlands.
IMMUNOCYTOCHEMICAL AND BIOLOCALIZATION CHARACTERISTICS OF OV-TL 3, AN ANTI-OVARIAN CARCINOMA MONOCLONAL ANTIBODY A cloned hybridoma cell line producing a mouse monoclonal antibody (OVTL 3; IgG1), was developed after immunization with a tumour cell suspension prepared from an endometdoid ovarian carcinoma specimen, tmmunocytochemical studies on frozen sections showed intensive staining in 93 % (62/67) of the ovarian carcinomas (primary as well as metastasized)of different histological types. Immunoelectronmicroscopyshowed that the OV-TL 3 defined antigen (OA 3) was associated with the membrane of the turnout ceils. No immune reacti';,,itywas found In breast carcinomas or other non-gynaecologic turnouts. Slight staining was found on some endometrial carcinomas (8/12) and oviductal carcinomas (3/3), being in line with weak expression of the OA 3 antigen in the epithelial lining of the oviduct and |ocally on endocervicel epithelial cells. Hardly any reactivity was found on other normal cell types such as mesothelial cells (expressing CA 125), Cross inhibition experiments showed that the OV-TL 3 antibody recognizes an epitope different from the anti-ovarian carcinoma antibodies OC 125 and MOv 18. The binding of the OV-TL 3 antibody on NIH:OVCAR-3tumour cells in vitro was relatively fast, while the dissociation was slow. The affinity constant as determined by 8catchard analysis as well as by displacement studies was high (1.3-1.6 x 10~ M"). Based on a sandwich immunoradiometdc assay the OA 3 determinant could be quantified in ovarian carcinoma extracts as well as in cyst fluids and ascites from ovarian carcinoma patients. The antigen, however was not detectable in serum of ovarian carcinoma patents. Biodlstnbubon studms w~th 1~25-1abelledanbbodles in athymtc mice beanng NIH:OVCAR-3 xenografts subcutaneously, showed that high tumour localization was found (48 hr p.i.) with OV-TL 3 (8.8 % ID/g) compared to 5.1% ! ID/g for OC 125 antibodies. Tumour/non-tumour label uptake ratios of greater than 10 were found for most organs, while turnout/liver and kidney ratios reached about 2.5. The data suggest that OV-TL 3 might be a potent antibody for radioimmunolocalization of ovarian carcinomas.
563
562
L.G. Strauss, A. Dimitrakopoulou, J.H. Clorius, A. Schadel. F. Helus, G. Wolber Deutsches Krebsforschungszentrurn, Heidelberg; HNO-Kli nik, Klinikum Mannheim, Mannheim;
POSITRON EMISSION TOMOGRAPHY (PET) WITH F-18-DEOXYGLUCOSE USED IN PATIENTS WITH HYPOPHARYNX CARCINOMA. Metabolic studies with PET had found use in oncology for the diagnosis of tumor recurrence. We used PET in patients with hypopharynx carcinoma in order to evaluate the metabolism of the tumors prior and after therapy. Furthermore, studies prior and after chemotherapy were performed to assess changes in tumor metabolism. F-18-deoxyglueose (FDG) was administered intravenously (8-12 mCi) and three PET images were acquired 60 min post injection. We use a two ring PET system (PC2048- 7WB, Scanditmnix Co.) which provides the simultaneously acquisition of three slices (two primary sections, one cross section). CT examinations were performed shortly before the PET study in order to obtain morphologic information about the tumor and the involved lymph nodes. The target area for PET was also determined by CT. All patients were directed to chemotherapy shortly after the first PET examination. A second PET examination followed after the first chemotherapeutic cycle. The quantitative evaluation was performed using a region-of-interest technique and standardized concentration values were calculated from the PET data. The preliminary evaluation includes seven patients. We noted an increased FDG uptake in all tumors prior to treatment. The tumor-to-soft-tissue ratio exceeded 2.2 prior to chemotherapy. A 20-50% decrease of the FDG accumulation in the tumor was observed after the first chemotherapeutic cycle in three of seven patients. The decrease of tumor metabolism was correlated with decreasing tumor volume in these patients.
564
K. OZKER, i . URGANCIO~LU, F. OZUM, t. YILDIZ J.C. Reynolds, C. Farrington, M.E. Lora, J.A. Carrasquillo
NUCLEAR MEDICINE and PEDIATRICS DEPARTMENTS, CERRAHPASA MEDICAL FACULTY, tSTANBUL UNIVERSITY, TURKEY National Institutes of Health, Bethesda, MD, 20892.
99mTc(V)-DMSAAS A TUMOURIMAGINGAGENT:DETECTIONOFMALI(~CIES Ol}ER llIhN FEDULLARYIIIYROIDCARCINCMA 99Tqc(V)-Dimercaptosuccinicacid, (Tc V-DV6A)has beenused for the detection of various tumeurs including medullary thyroid carcinova (MTC) in the recent years. This study deals with the evaluation of ~a~nTc(V)I]MSAfor the detection of bone and soft tissue tunours. Whole-bodyand spot imagesof all patients with suspectedprimary and secondarybone and / or soft tissue ttrnours were acquired at various time intervals for 2 hours using 370 NBq ~JnTc(V)-[VSAand a large field of view gamna c~nera interfaced to a ccmputer. Regionsof interest (ROIs) were generated over the areas of high uptake and contralateral sides, when ~ossible, or over a similar tissue. Time-activity curves and tb~eur to nontarget ratios (T/NT) were ~b,tained on the selected ROls. The nature of ttrnours were identified by umErFc-M3Pand CT scanning, clinical and histopathological examinations. Secondarybone conditions with relation to various 15rimarymalignancies including MTC, selectively concentrated the 99mTc(V)-CMSA,demonstratedvisually as areas of high uptake and elevated T/NT ratios probably due to its P04 like biological properties. A markeduotake of 99mTc(V)-I]MSAwas reached in all bone and soft tissue sarcamas. Time-activity curves of the tunours increased rapidly reaching to a maxintrnbetween45 to 60 min while the NT curves persistantly decreased. The uptake in Ewing's sarcomawas 3 to 4.5 times of the NT at 15 and 60 min post injection respectively. The thyroid tLmours other than MTC showedno significant uptake. Accunulation in carcinomas was to variable. In conclusion, the preferential uptake of 99mTc(V)-DMSAin primary and secondarybone malignancies and in sarccmas, involving bore and soft tissue, may provide a diagnostic potential inaddition to its unique characteristics to detect the primary and recurrent MTC.
MEASUREMENT OF HUMAN ANTI-MURINEANTIBODY IN BASELINE PREINJECTION SERA FROM PATIENTS UNDERGOING RADIOIMMUNOSCINTIGRAPHY. We tested for human antl-murine antibody (HAMA) in baseline pre-injeetion sera from patients undergoing radiolmmunoseintigraphy (RIS). H A M A i n these patients could cause changes in antibody biodistributien or lead to very high anti-antibody levels. HAMA levels were measured by an RIA using 1251- B72.3 tracer and protein A separation and also by size exclusion (SEC) HPLC where levels were calculated as the % of counts found as high MW complex when 50 ng of 12Sl-labeled antibody (B72.3 or TI01) was incubated with 0.09 ml of patient sera. In the SEC HPLC assay inhibition of complex formation by non-speciflc antibodies 2-135 or BL3 confirmed the presence of HAMA. All baseline sera were HAMA negative by RIA except one which was trace positive. Pre-injeetlon sera in I0 of 44 patients studied with B72.3 RIS (epithelial tumors) had HAMA by SEC HPLG (range 4-100% complex). 9 of those positive developed HAMA by RIA following RIS compared to 12 of 34 (35%) who were pre-lnJeetionPJdiAnegative (p < 0.005). The mean TI/2 beta of patients with pre-lnJeetion HAMA was 61 hours and for the negative group was 84 hours (p ~.40). Pre-inJeetlon sera from 2 of 14 patients studied with TI01 RIS (CTCI or CLL patients) had HAMA by SEC HPLC. I of 2 positive patients later developed positive levels by RIA compared to 4/12 who were pre-inJection negative. Thus low levels of H A M A m a y be found in up to 22 % of pre-injeetion sera. Although these low levels may not relate to changes in TI/2 beta, positive patients are more likely to have an immunologic response to injected murine a n t i b o d y .
540
565 i.
566
URGANCIO~LU, F. OZOM, K.OZKER J:Spitz*, N . C l e m e n z * , J . M . G r a f * , O . G a m s t f i t t e r * * , D . M a u r e r * * *
NUCLEAR MEDICINE DEPARTMENT, CERRAHPA~A MEDICAL FACULTY iSTANBUL UNIVERSITY, TURKEY
99r"Tc(V)-DMSA- SCANNINGOF THE FOLLOW-UP PATIENTSWITH MEDULLARYTHYROIDCARCINOMA Planar neck and whole-body images of 15 patients with s u r g i c a l l y confirmed medullary thyroid c~Ginana (ME) were obtained a t various time i n t e r v a l s using 370 FBq ~ T c ( V ) - [ I ~ and large f i e l d of view ga#na camera interfaced to a ccmputer. A c a m e r c i a l kit treated with
a sterile solution of NaHC03to reach pH 8-8.5 prior to the addition of pertechnetate was used for i.v. injection. ITLC and invivo distribution of the final solution in rats were regularly carried out in order to eliminate the poor results due to insufficient formation of 99mTc(V)-I:MSAas indicated by an increased renal accumulation. Time-activity curves of the persistent tunours showed a maximJmat 30 to 45 min post injection giving a ~ to background ratio ranging from 3 to 5. Conventional radiology or CT and 99mTc-M]Pscanning were used to evaluate the areas of increased uptake. All patients with persistantly elevated calcitonin levels showedan increased accunulation of 99mTc(V)-DMSAin the thyroid and/or soft tissue and bone metastases. Metastatic bone and liver conditions were also detected by 99mTc-M]pand 99mTc-Sncolloid scans as areas of increased and decrased uptake respectively. In 3 patients with surgical ly proven MTC no abnormal uptake was shown. Plasmacalcitonin levels and the results of other imagin9 procedures were also normal verifying a true negative conclusion of 99mTc(V)-I]MSAscan. The thyroid tumours other than MTC showed no significant uptake. Results of this study reveal that 9gmTc(V)-I]MSAscanning is valuable post operative follow-up method for detecting the persistance or recurrence of MTC. I t provides the visualization of both bone and soft tissue metastases with relation to MTC in a single procedure.
C L I N I C A L BENEFIT OF T H E T U M O R A S S O C I A T E D A N T I G E N C A - 7 2 - 4 IN T H E DIAGNOSIS OF M A L I G N A N T TUMORS OF T H E S T O M A C A N D T H E OVARIES T h e a i m of this not y e t c o m p l e t e d study is to show t h e clinical r e l e v a n c e of t h e t u m o r a s s o c i a t e d a n t i g e n C a - 7 2 - 4 in p a t i e n t s w i t h known m a l i g n a n c y of t h e s t o m a c h or t h e o v a r i e s . M a t e r i a l and Method : 168 s p e c i m e n s : 82 s m o k i n g and non s m o k i n g n o r m a l s , 38 malign o m a of the s t o m a c h , 48 c a n c e r of the o v a r i e s . In addition CEA and C a - 1 9 - 9 w e r e m e a s u r e d m a l i g n a n c i e s of the s t o m a c h , CEA and C a - 1 2 5 in p a t i e n t s w i t h o v a r i a n c a n c e r . Results: Non s m o k i n g n o r m a l s : S C a - 7 2 - 4 - v a l u e s a b o v e 3,5; non s m o king n o r m a l s : 1; g a s t r i c m a l i g n a n c y : 26 % e l e v a t i o n of CEA and 34 % of C a - 1 9 - 9 and 52,6 % (I) e l e v a t e d C a - 7 2 - 4 levels. I0 p a t i e n t s }25 %) s h o w e d e x c l u s i v e l y an e l e v a t i o n of Ca 72-4. T h e c o m b i n e d e s t i m a t i o n of CEA and C a - 7 2 - 4 r e s u l t e d in a s e n s i t i v i t y of 60 96, c o m b i n e d w i t h C a - 1 9 - 9 of 7 1 % . O v a r i a n c a n c e r : 50 % e l e v a t e d Ca-125, 42 % e l e v a t e d Ca72-4, 27 % e l e v a t e d C a - 1 9 - 9 and only 16 % e l e v a t e d CEA levels. 12 % only in Ca-12S, 10 % only in C a - 7 2 - 4 . The c o m b i n a t i o n of C a - 1 2 5 and C a - 7 2 - 4 r e s u l t e d in 73 % sensitivity. Conclusion : The p r e l i m i n a r y d a t a of C a - 7 2 - 4 show a t w i c e as high sensit i v i t y for g a s t r i c c a n c e r c o m p a r e d to CEA. In p a t i e n t s w i t h o v a r i a n c a r c i n o m a the c o m b i n a t i o n of C a - 1 2 5 and C a - 7 2 - 4 imp r o v e s the s e n s i t i v i t y to 73 %. C a - 7 2 - 4 s e e m s to be a valuable c o m p l e m e n t a r y I n f o r m a t i o n to the e s t a b l i s h e d t u m o r m a r k e r s In p a t i e n t s with g a s t r i c or o v a r i a n c a r c i n o m a .
568
567 J. F r o h n , R.P. Baum, J. Happ, G. HGr Division of Nuclear Medicine, Department of Radiology, University Hospital, Frankfurt~Main, Federal Republic of Germany
INTRAINDIVIDUAL COMPARISON OF SPECT AND PLANAR IMMUNOSCINTIGRAPHY WITH Ill-IN LABELED ANTI-CEA MONOCLONAL ANTIBODY BW431/31 F(AB')2 The purpose of the present study was to compare intraindividually planar and SPECT imaging with In-Ill-DTPA labeled anti-CEA F(ab')2 monoclonal antibody (MAB) fragments. 17 patients with different carcinomas (eoloreckal (n=12); lung (n=2); malignant pheochromocytoma, stomach carcinoma, unknowm primary tumor, n=l, each) were studied 24-144 h after injection of up to 185 MBq In-III-BW 431/31 (Behringwerke Marburg, FRG) anti-tEA MAB.The results were confirmed by histology, CT scan, and sonography. Results: SPECT-IS
Sensitivity Specifity Pos. predictive value Neg. predictive value Diagnostic Accuracy
* D p t . o f Nucl. Med., ** Clinic of S u r g e r y , *** Clinic of G y n a e c o l o g y , Municipal Hospital, D 6200 Wiesbaden, F R G
P l a n a r IS
83% 60% 83% 60%
60% 60Z 80Z 43%
76%
65Z
P l a n a r s c i n t i g r a p h y h a s t h e a d v a n t a g e o f whole body examination and easy performance.Our results demonstrate, however, a higher sensitivity of SPECT-IS, especially for the detection of lung and pelvic lesions, enabeling a much better topographic orientation and the estimation of tumor size.
DR P. BOURGEOIS, M. M A L A R M E AND W. F E R E M A N S C . H . J . B R A C O P S , FREE U N I V E R S I T Y OF B R U S S E L S S E R V I C E S OF I N T E R N A L AND N U C L E A R M E D I C I N E 79 RUE DR HUET, 1070 BRUSSELS, BELGIUM.
BONE MARROW SCINTIGRAPHY (BMS) AND/OR CONVE~TIONAL BONE SCINTZGRAPHY FOR THE DiAGNOSiS AND MANAGEMENT OF SKELETTAL METASTASIS FROM PROSTATIC CARCINOMAS ? Aim of the study; To evaluate the contribution of BMS respective ~o CBS in prostatic ca. hearing patients Material and methods; Performed in 73 prostatic ca. bearing men (mean age=74 years, range=51-88,33 cases with skeletal metastasis rodiologically or histologically proven at the time of the first BMS), BMS obtained at least 2Q minutes after injection of i0 mi!liCuries of 99mTc labelled nanacollaids and classified ~MS- if normal, BMS+ if with abnormal extension, BMS,+ if focal defect, have been compared to CBS results obtained in the same patient and classified as CBS- if normal, CBS? if exhiairing abnormalities that could be related to other nanmetastatic situations and CBS+ if clearly metastatic (CBS-+ if super scan). Results; Sensitivity Specificity ~MS+I~MS~+ 94% 84% BMS++ 83Z 87% CBS?/CBS+/CBS++ 100% 73% CBS~/CBS++ 88% 97% - no skeletal metos in 8 patienls With CBS? and BMS- 5 CBS? out of 6 with abnormal BMS confirmed to be metastasis - evolution under treatment of metastatic pictures (wilh respect to predictive value, to the outcome of the disease) ; BMS>CBS in B (for instance, CBS return to ni with BMS+~ unchanged and disease evolution thereafter] • BMS=CBS in 8 and CBS>BMS in l Conclusions; it is thus recommended to perform BMS systematically after C~S in cases of prostatic co.bearing patients when dubious CBS are found and as a way to evaluate the response to treatments of skeletal metastasis
541
569 A.NICOLINI, *L.GIULIANI, C.COLOMBINI,*L.LUCIANI,*G.MEUCCI, A.CARPI, C.TIBALDI.
570 A. CARPI,A. NICOLINI,S. TOSCANO. Nuclear Medicine Service and 2nd Medical Clinic of Pisa U n i v e r s J t y . S p e d a i l S. Chlara.561OO P i s a , l t a t y .
lind Medical Clinic and *Institute of Surgical Clinic, University of Pisa - Pisa, Italy. MEASUREMENT OF CA 15-3 IN THE POST-OPERATIVE FOLLOW-UP OF BREAST CANCER PATIENTS WITH TUMOR MARKERS. The purpose of the study was to evaluate the usefulness of CA 15-3 in 314 breast cancer patients (pts) submitted to post-operative follow-up with CEA and TPA. So far 39 (12%) pts withdrew the study and in 53 (19%) of the remai ning 275 ones distant metastases occurred. In the "early" diagnosis of relapse sensitivity of CA 15-3,CEA and TPA were 36%, 41% and 72% respectively. Association of CEA and TPA increased the sensitivity to 83% which was higher than that of TPA and CA 15-3 and of all three tumor markers con temporaneously measured. Nevertheless in 3 (43%) of 7 pts in whom CA 15-3 with CEA and/or TPA preceded the clinical and radiologic signs of relapse, serum CA 15-3 levels increased some months before those of CEA and TPA. In the relapses pts the sensitivity of CA 15-3, CEA and TPA to monitor the response to therapy was 59%, 95% and 55% respectively. Association of CEA and/or CA 15-3 with TPA did not increase the sensitivity. High values of CA 15-3, CEA and TPA occurred in 25 (11%), 17 (7%) and 75 (34%) respec tively of the 222 pts without distant metastases. All 25 pts but 9 with CA 15-3 elevated levels were affected by liver disease and/or diabetes. In conclusion these data suggest:a)Determination of serum CA 15-3 levels is useful to "early" diagnose breast cancer relapses; b)it does not increase the TPA sensitivity to monitor the response to therapy of relapsed pts; c) CA 15-3 has specificity similar to CEA and higher than TPA.
571 J. Ruhlmann, P. Oehr, N. Schafer, A. Bockisch, B. Briele, F. Gr~nwald, A. Hotze, H.J. Biersack Dept. Nucl. Med., Dept. Urol., Univ. Bonn, W. Germany
BONE SCAN IN METASTATIC BREAST CANCER CONFINED TO SKELETAL SYSTEM.
Recent r e p o r t s show that breast cancer p a t i e n t s ( p t s ) w i t h d i s t a n t met ast ases( D. M. ) l i ml t ed to bone have a b e t t e r prognosis than those with relapses in other sites.We report t h e main f e a t u r e s of bone s c a n ( B . S . ) i n these p t s . From 1977 t o 1988 230 p t s w e r e f o l l o w e d up by clinical,laboratory and i n s t r u m e n t a l exams.Up to t o - d a y 46 women showed D . M . ; 1 8 ( 3 9 % ) h a d D.M. l i m i t e d t o bone d u r i n g
all
the
dJseas~ or t ! [ l
staKe. In the remalnin~
572 M.FUzy,
B.Spett,
Nail.Institute Institute of FIRST RESULTS OF RADIOIMMUNODETECTION (RID) WITH ANTIPSA-ANTIBODIES. For t h e first time in a clinical trial RID using antiPSA-antibodies was performed in 9 patients with metastatic prostate carcinoma. I mg of the complete monoclonal anti-PSA-antibody, labeled with 70 MBq 1-131 and dissolved in 100ml HSA solution was infused within 30 min. i.v.. Whole body scans were then recorded at 3, 4, 5, and 6 days after injection on a LFOV gamma camera. In case of suspected pelvic or abdominal metastases bloodpool scans and in case of suspected skeletal metastases bone marro scans were performed and subtracted from immunoscans Results: Bone metastases: true positive: 2 ; true negative: 2 false positive: 0 ; false negative: 2 Lymphnode : true positive: 2 ; true negative: I metastases false positive: 0 ; false negative: I Our first results demonstrate that conventional radionuclide bone scans are superior to RID in detecting bone metastases since RID failed to visualize proven bone metastases in 2 cases (false neg.). However, the detection of hitherto unknown lymphnode metastases, in particular abdominal lesions, might be improved by using this new antibody for RID. Nevertheless, the scintigraphic technique has to become more sophisticated by reduction of unspecific activity and increased blood pool clearance. 1 In conclusion, anti-PSA RID seems to be a promising me- 1 ~ m~nitoring patients with prostate cancer subse- I quent to surgery and chemotherapy.
the f l n a l
28(61%)D.M. w e r e In t u n g , l i v e r or b r a i n w i t h or w i t h o u t bone involvement.Age and a x i l l a r y lymphnode s t a t u s was not d i f f e r e n t in the 2 gloups.Oead pts w e r e 7(39%)in the former and 19(68%)in the l a t t e r group.ln a l l t h e ' p t s of the 1st group B.S. was the Ist sign,alone or concomitantly with other ~igns,of r e l a p s e ; t o t a l number of B.S. was 52,of which 19 w e r e performed before the Ist true p o s i t i v e r e s u l t . l n the following controls multiple(>3)hyperfixing areas occurred in 40% of the B.S. in the s t i l l a l i v e pts and in 76% of the B.S. in dead pts.Only 5% and 6% of the true p o s i t i v e B.S. were observed in the i s t and in the 2nd postoperative year respectlvely.The time i n t e r v a l between the i s t sign of relapse(B.S, in the pts with bone recurrence)and death was longer in those pts with D.M. confined to skeleton than in those with D.M. in other sltes(m=25 vs. 8 months,p
L.K6r~si,
of Oncology Radiobiology,
J.A.J~noki,Zs. Karika
and "FJC" Budapest,
N a t l . Res. Hungary
RADIOIMMUNOSCINTIGRAPHY WITH Tc-99m AND I n - l l l LABELLED ANTIMELANOMA F ( a b ' ) 2 FRAGMENI. Radioimmunoscintigraphy was p e r f o r m e d w i t h Tc-99m labelled monoclonal fragment (TechnemabK-l) in 46 p a t i e n t s and w i t h I n - i l l l a b e l l e d one ( I n d o m a b - K - l ) in lO p a t i e n t s s u f f e r i n g f r o m mal i g n a n t m e l a n o m a . T c - 9 9 m l a b e l l e d p h a r m a c o n was i n j e c t e d in 30 p a t i e n t s i.v. and 16 p a t i e n t s s.c. In-l]l l a h e I ] e d p h a r m a c n n was a d m i n i s t e r e d i.v. E l i m i n a t i o n of r a d i o a c t i v i t y f r o m the b l o o d was d e t e r m i n e d and the r a d i o a c t i v i t y was c o u n t e d in urine. S c i n t i g r a m s w e r e p a r t l y c o m p a r e d w i t h s c a n s m a d e by G a - 6 7 and T c - 9 9 m l a b e l l e d S o l c o L y m p h o s c i n t r e s p e c t i v e l y . In all p a t i e n t s p r i m a r y s k i n t u m o u r s , c u t a n e o u s and l y m p h n o d e m e t a s t a s e s l a r g e r t h a n 1 5 - 2 B mm w e r e w e l l v i s u a l i z e d . B r a i n m e t a s t a s e s a l s o w e r e i m a g e d . L i v e r and lung met a s t a s e s w e r e not or s l i g h t l y d e m o n s t r a t e d . S.c. a d m i n i s t r a t i o n of r a d i o p h a r m a c o n did not o f f e r any a d v a n t a g e o v e r i.v. i n j e c t i o n . C u t a n e o u s tum o u r s w e r e b e t t e r i m a g e d by a n t i m e l a n o m a f r a g m e n t t h a n by Ga-67. In c o n c l u s i o n T c - 9 9 m and In-lll labelled antimelanoma fragment increased the s p e c i f i c i t y of d i a g n o s i s and it is a v e r y u s e f u l a d 3 u n c t m e t h o d in the d i a g n o s i s of mal i g n a n t m e l a n o m a . No side e f f e c t was seen.
542
573
574
M. I]nlO,H. AlanyaIL O. Akhan, M. T. Ercan, C. F. Bekdik
F~THERAIN,
Departments of Nuclear Medicine, Radiotherapy and Radiology, Hacettepe university Medical School, Ankara, Turkey
Service de M~decine Nucl4aire Zentre Hospitalier R4gional d'Orl4ans
INTERNAL MAMMARY LYMPHOSCINTIGRAPHY WITH SPECT AFTER US-GUIDED INJECTION OF SSmTC-DEXTRAN
16 e ~ 3 1 I } i o d o ii 8 Methoxy - 17 8 E s t r a d i o l : synthesis in vivo distribution and preliminary clinical results.
12 Women (mean age: 44, range: 30-53), Stoge III breast cancer patients were evsiusted bg SPECT to determine the number, size, three dimensional localiz~ion, and depths from s~n surface of the internal rnemrrrarg lymph In=Ms for accur~e rafiotheraphy porte1 plannin¢ The SPECTrasulte were alse compared to placar imaging (PI). I Two-step injection~ of 99mTc-dextran (20 MBq in 0.2-0.4 ml for each) was done under Us-guidenca with 22 G biopsy needs for US use, into the =posterior sheat of the m. rectus abdominis first at the operation side accard| ng to Eye's technique. 1.5 h after the first injection an anterior planer 'view ~dth anatondcal markers was obtained to evaluate cross-drainage (16.6~ was observed). Then, the secondinjection was done at the opposite side in the same manner. Planer and tomographic (9 o, 150", 180 o) images were obtained 1.5 h after the second injection with single-hend rotating gamma camera (Toshiba GC~-6OIE). A lend belt was used to avoid sc~ter effects of radioactivity at the injection sites. 5PECT images were reconstructed with uniformity correction for 99mTc, ~Mthout attenuation correction and filtered bzj a modified Shepp-Logan filter. We obtained for the depth of lymph nodes 15.2,7.6 and 14.9±6.0 m m and for the ~ameter of the lymph nodes9.5±4.5 and 9.2±5.7 mm for 5PECT and PI, raspactivelg (p~O.40 for b~h). The tote1 number of nodes in 12 patients detected bg $PECT was more (65) compared to PI (62) which was ! ~atistica11 g significant (0.025
575
J. GROS,
D. D E B R U N ,
G. P I C A P E R
16~ {131I} iodo 118 Methoxy-17 8Estradiol (ME 2) a compound with a good binding affinity to t h e astrogen receptors ( R . B . A = 50 % ) a n d a h i g h specificity has been prepared by a halogen exchange procedure starting f r o m 178 B r o m o ii 8 M e t h o x y 178 E s t r a d i o l . U p t o 60 % o v e r a l l r e c o v e r y of t h e i o d o d e r i v a t i v e (95 % r a d i o chemical purity) can be obtained (basal over I o d i n e ion) a f t e r s e p a r a t i o n on a short Diol HPLC column eluted with diehoromethane. The s p e c i f i c activity evaluated by scatchard analysis ~sing Estrogen receptors ranges from 300 t o 5 0 0 Ci/mmole. 2 h o u r s a f t e r i n j e c t i o n a tissue uptake study of this compound to immatur~ r a t s s h o w e d a u t e r u s t o b l o o d r a t i o C f 87 ~ 12 (n = 5)(andn- u t e r u s t o n o n t a r g e t t i s s u e of 94 2 2 2 - 5). T h e s e r a t i o s w e r e r e d u c e d t o respectively 2.2 ~ 0 . 5 a n d 6.0 ~ 1 . 5 w h e n t h e animals were treated simultaneously with excess unlabeled estradiol. The preliminary results obtained in primary human breast cancer imaging underline the i n t e r e s t of M E 2 in i d e n t i f y i n g the presence of estrogen binding sites in vivo.
576 ~'FE
1,
CHR.EILLES I , R.MARTIN 2, R.DUMMER3, W.BECKER4
~K l i n i k
u . P o l i k l i n i k f o r Nuklearmedizin ~Neurologische U n i v e r s i t ~ t s k l i n i k ~Universit~ts H a u t k l i n i k
Universit~t
WOrzburg, D-8700 WOrzburg
4Nuklearmedizinische K l i n i k u . P o l i k l i n i k d.Univ.Erlangen
PRELIMENAR¥ RESULTS WITH LYMPHOKINE AKTIVATED KILLER (LAK) CELLS LABELED WITH IN-111-OXINE IN MELANOMA PATIENTS LAK c e l l s were generated by c u l t u r i n g of peripheral blood lymphocytss (PBL), i s o l a t e d from s i x p a t i e n t s with melanoma, in complete medium containing 1000 U/ml native I n t e r l e u k i n - 2 (IL-2) and labeled with In-111 before i n j e c t i o n . Intravenously i n j e c t e d I n - I l l - l a b e l e d LAK c e l l s d i s t r i b u t e d primary to lungs, l i v e r and spleen with minimal uptake in bone. We obtained 8 scans from 6 p a t i e n t s at 4, 24 and 48 h p . i which showed an enrichment of labeled c e l l s in bone and lymph node metastases in 3 cases, whereas the e x t e r n a l detection f a i l e d in one p a t i e n t with a s o l i t a r y lung metastasis. In two out of 4 p a t i e n t s with primary negative scans, p o s i t i v e lymph node images were found in repeated scans 5 and 6 month l a t e r , according to the ~ l i n i c 8 1 signs of tumor progression.
We conclude t h a t PBL seems to r e t a i n t h e i r a b i l i t y to migrate a f t e r (IL-2) s t i m u l a t i o n and I n - i l l - l a b e l i n g . This technique may be h e l p f u l f o r an e x t e r n a l detection of metastases in p a t i e n t s with melanoma.
M ~ Martinez-Paredes, F. Valverde, A. Jimenez-Heffernan, J.M. Llamas-Elvira, M. Tortes, F.M. Gonzalez, J.M. Latre, A. Mates.
Nuclear Medicine Service and Dermatology Service. "Reina Sofia" Hospital. CORDOBA. Spain. DETECTION OF MALI~iNT MELANOMA BY INMUNOSCINTIGRAPHY AFTER INJECTION OF 99mTc-LABELED F(ab,)2 FRAGMENT FROM MONOCLONAL 225.28S ANTIBODY. Seventy two ~ e s c i n t i ~ c examinaticrswere performed on 57 patients (mean age 47.7 years) with malignsntmelanama in various C/ark levels (I-V) and clirdosl stage (I-IV). The study was retrospective in ii patients (15 exam/z~tions) and prospective in 46 patients (57 examinations). MDnoclonsl entibedies 225.285 (mean 293.05 ug)labeled with 99,~c performed 8 and I0 hours pos~in,eolian. Average in~ec~ed antivity was 925.74 MBq. Cases with clinical stls]0icianor difficult planar images underwent SPECT imaging. Twen~ seven patients v~me ~ s t c c h e m i c a l stl~f usir~ the avidJ_nbiotin-per~qd~se technique. The following parameters were evaluated: imprevemant in lesion detection using SPECT, earlier detection of lesions with ~ i n t i ~ 6 . M e n ocmpared to radiological techniques, Ix~oc/bac~d ratios~at 8 and I0 hours, size of visualized lesions, con~e/aticn between histochenical and i n m L a i D s c i n ~ c results, specificity of MoAb in non-melanoma skin lesiczls, and diagnostic perfonmnce indexes.
were infected intcavenous~y and ~
Lesions were detected 3 a 6 months before they became evident widl standard radiolop=icproced/res. TL~or/h~ ratios oscillated between 1.5 and 3.35, the mean value was 2.11 at 8 hours and 2.43 at 10 hours. The size of visualized lesions oscillated between 0.7 and I0 cm, mean 2.4 cm (12 lesions were lar~er than 1.5 cm). Histochemistry was positive in 24 patients and i n m u n o s c / n ~ in 23 patients, both techniques agreed in 20 of 27 patients in whom histocheminal stsdy was perfccm~d. Diagnostic indexes were Sansitivity=96.2~4,Specificit~=79.~%,Accuracy= 91.~,positive predictive value=91.6, end negative predictive value=gEP%.
543
577
578
K. Herholz, W.-D. Heiss, J. Rudolf, J. Jeske 1 M. R. Quastel , A.M. Richter 2 and J.G. Levy 2
Max-Planck-lnstitut f~r neurologische Forscilung and Univ.-Klinik fur Neurologie, Joseph-Stelzmann-Str. 9, D-500O KSln 41, FRG
MEASUREMENT OF BLOODVOLUME, HEXOSETRANSPORT AND METABOLISM IN HUMANBRAIN TUMORSWITH DYNAMIC FOG PET Fifty patients with histologically classified brain tumors were examined with dynamic PET and 18F-2-fluoro-2-deoxyglucose (FDG). Parametric images of blood volume (BV), tracer transport across the blood-brain barrier (KI) and metabolic rate (MR) were generated using a recently developed techniaue (Herholz, 1988). Grade I I gliomas were characterized by low BV, KI, and MR, all similar to normal white matter. Most anaplastic gliomas showedlarge alterations (high and low) of MR, but BV and K1 was in the range of normal gray and white matter. Glioblastomas were very heterogeneous in all three parameters, and in most cases foci of increased metabolic a c t i v i t y were identified as well as necrotic areas with very low K1 and MR. Reactive postoperative tissue alterations were characterized by high KI but low MR. Meningiomas showed quite variable K1 and MR and were often characterized by a higher blood volume than observed in normal brain and gliomas. In conclusion, dynamic FDG PET proved to be useful in the classification of humanbrain tumors. Reference ~ K . :
Eur. J. Nucl. Med. 14:477-484 (1988)
iInst. Nuclear Medicine, Soroka Medical Ctr. and Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel, and 2Dept. of Microbiology, Univ. of British Columbia, Vancouver, Canada IMAGING OF TUMORS WITH IN-Ill DIHEMATOPORPHYRIN ETHER Dihematoporphyrin ether (DHE), the tumor localizing fraction of hematoporphyrin derivative (HPD), was labeled with In-lll(1) to assess its potential use for measuring tumor uptake of DHE by scintiscanning for photodynamic therapy, In-III(*)DHE was infused into DBA/2J mice hosting transplanted rhabdomyosarcomas, with In*Cl 3 for comparison. Within 1-2 hrs, both agents appeared prominently in the tumor, liver, spleen and kidneys. After a day, the liver had taken up most of the In*DHE, whereas the uptake of In*Cl 3 was mainly renal. Tissue distribution of In*DHE was the same as for 14C- and 3H-HPD and DHE (2,3). Unlike In*Cl3, 2/3 of the In*DHE cleared from the tissues after 24 hrs, though not from the tumor. Region of interest(ROI) in vivo measurements of tumor In*DHE uptake agreed well with direct counting of dissected tumor tissue. This was not true for In*Cl 3 which was detected in vivo by ROI in high amounts compared to dissected tumor, probably due to binding to non-tumor tissue. Excess unlabeled DHE given with In*DHE did not suppress tumor uptake of the latter. In* dissociation from DHE in rive wasmeasured by acetic acid/ethylacetate extraction. About 80% of extractable tumor In* remained bound to DHE after a day and about 74% after 4 days. It is concluded that the uptake and distribution of In*DHE in vivo is the same as that of the unmetallated DHE, that it remains largely undissociated in vivo and" that it may thus be useful to trace quantitatively the tumor uptake of DHE. (i) Lavallee, D.K. and Fawwaz,R.(1986) Nuc.Med.Bio] 45,879 (2 (3)) Gomer{C.J. and Dougherty,T.J.(1979)Cancer Res.39,146.
Bellnle~
579 PRE-THERAPEUTIC EVAI_UATION OF ANTI-CEA MAbB LABELED WITH i 3 i I IN HEPATIC METASTASES FROMCOLO-RECIAL CANCER M. Ychou, J. Lumbroso, M. Ricard, P. Rougier, B. Aubert, M. Prade, P. Lasser, 3.C. Saccavini (I), F. Bucbegger (2), J.P. Mach (2) and C. Parmentiec. Institut Gustave Roussy et INSERM U66, Villejuif; (1) CEA ORIS, Gif-sur-Yvette; FRANCE. (2) Institut de Biochimie, Lausanne, SUISSE. Immunoscintigraphy using anti-carcinoembryonic antigen (CEA) monoclonal antibodies (NAbs) has demonstrated a selective tumoral uptake especially in cole-rectal cancers and their metastases. Anti-CEA Nabs radiolabeled with therapeutic activities of z311 gave objective responses in nude mice bearing human colon cancer xenografts. We therefore designed a study for clinical protherapeutic evaluation of these agents. 13 patients having hepatic metastases from eolo-rectal cancers and for whom surgery was scheduled, entered the study with informed consent. We used an anti-CEA Mab, whole IgG in 7 cases and F(ab')2 in 6 cases. 15 to 40 mg of NAbs were labelled with 0.55 to 1.48 GBq (15 to 40 mCi) of 13lI. We chose these relatively low activities in order to be able to carry out early surgery (day 4 to 8 after injection) and to avoid any adverse effect to the bone marrow. We assessed the biodistribution of the NAbs by daily scintigraphy (whole body gamma-camera and tomsscintigraphy). The effective period in blood was 0.75 to 2 days; external detection allowed a very clear visualization of the metastases. The estimation of the tumoral uptake on surgical samples varied from 5.7 to 74 kBq (0.1 to 2 pCi) /g in the IgG group and from 3.7 to 37 kBq (0.1 to IpCi) /g in the F(ab')2 group. The contrast (tumour to normal liver) range was 2.8 - 35 and 2 - 16 in respectively each group. In one patient receiving 1.48 MBq ( 4 0 m C i ) of 1311 - NAbs, the radiation dose was estimated to be 5.5 Gy to the liver metastasis and 0.26 Gy to the normal liver; the effective half life in the liver of the radioactivity was 1.5 day.
D.A. et al (ig89) in~ press
580 Sandro~:k D., Taraboletti G., Rotman M.H., Green S.L., Liotta L.A., and Neumann R.D.
Lora M . E . ,
Department of Nuclear Medicine and Laboratory of Pathology, National Institutes of Health, Bethesda, Maryland, U.S.A.
IN VITRO STABILITY AND BIODISTRIBUTION OF 1-131-LABELED LAMININ-C1-FRAGMENT IN NORMAL AND TUMOR-BEARING MICE. The purpose of this study was to investigate the In vitro stability and kinetics of the rsdioiodlnsted Isminin.Cl.frsgment (molecular weight 50 k D ) a f t e r injection in normal and tumor xenograft-bearlng nude mice. This fragment, containing regions of the B1, B2, and A chain, has previously been shown to bind to tumor cells and Inhibit experimental metastases (Barsky st el., J Clln Invest 74:843). The I s m l n i n - C l - f r s g m e n t was labeled with 1-131 ( i o d o g e n . m e t h o d ) to a specific activity of about 370 MBq/mg (10 mCl/mg). After incubation of the labeled fragment st 37 ° for 1, 2, and 8 hours with serum-free medium, pooled mouse serum, blood, And homogenstes from mouse liver, spleen, and kidney, HPLCs were performed. Twenty-four adult nude mice (12 normals, 12 with an A 2058 human melanoma xenograft, diameter 0.5 cm, 2 weeks after 106 cells s.c. dorsal neck) were injected I.v. with 0.74 and 1.48 MBq (20 - 40 uCi) 1-131-1abeled C f - f r s g m e n t . Blood samples, scintigraphic studies, tissue counting, and quantitative autoradiogrephy were performed at various time points up to 48 hrs. post injection (p.i.). 1-131 was re~eased from the Cl-frsgment after 8 hrs. incubation at the following percentages of the Initial activity: in serum 6 %, blood 9 %, liver homogenate 14 %, spleen homog. 18 %, and kidney homog. 13 %, The in vivo whole body clearance followed first order kinetics with a half.life of 5 hrs. in normal and tumor-bearing mice. The serum half-life was 4 hrs. for the first 10 hrs. and 8 hrs. over the next 38 hrs.. Radioactivity cleared from the tumors with e half-life of 10 hrs.. HPLC of serum and urine at 60 mln. p. i. showed 36% and 62 % free iodine indicating rapid deiodlnstlon of the protein. The organ distribution s h o w e d no significant difference between normal and tumor-bearing mice with accumulation of labeled fragment In liver (1.6 % InJ. dose/g, 8 hrs. pJ.), spleen (1.7 %, 8 hrs.), kidneys (5,4 %, 4-8 hrs.) and stomach (11.4 %, 4-8 hrs.). The tumor uptake ranged from 2.0 % dose/g tumor (< 2 hrs. p.i.) to 0.09 % (48 hrs.). Quantitative autorsdiogrspby and sctntigrsphlc analysis matched the results of the tissue counting. In conclusion, with improved radiolabellng laminin-Cl-fragment h a s potential for tumor sclntigraphy.
544
582
581
P. Antonacci*, G. Avataneo*, M. Bell6*, G.C. Castellano*, G. Ceppi*, A. Comandone*, C.L. Maini°, V. Podio*, E. Seccamani ^, G.L. Turco*
B Guth-Tougelidis, 5P MUller, M Mehdorn", HJ Machulla "*,
*Cattedra di Medicina Nucleare - Universitd di Torino (Italy) °Cattedra di Medicina Nucleare - Universit~ di Ancona (Italy) ASORIN Biomedica S.p.A. - Saluggia (Italy)
Dept. Nuclear Medicine, Neurosurgery", Radiation Physics ~*
Successful Imaging of Pancreatic Cancer by anti-CEA F023C5
I - i 2 3 ¢-HETHYL TYRO51N AND T c - g 9 m - H H P A O ACCUHULATION IN BRAIN TUHOR5
Chr Reiners
University Essen, Hufelandstr. 55, 4300 Essen 1, FRG
During a study on the clinical applicationof immunoscintigraphywith anti-CEA F(ab')2 labelled with 1311(F023C5, SORIN Biomedica, Italy) in gastrointestinal adenocarcinomas, the same antibody was used in 5 cases of pancreatic tumor (case 1, 2 and 3 were primary carcinomas and 4, 5 secondary pancreatic neoplasm from gastric cancer after total gastrectomy). All patients had normal CEA levels and 4 had high CA 19-9 levels. Planar imaging was performed at 48, 72, 120 and 168 hours after administration, with best results obtained between 5 and 7 days. Results are reported in the following table: cases 1 2 3 4 5
CEA [ng/ml] 14 39 3.9 6.6 13,5
CA 19-9[ng/ml] >120 >120 5 >240 >240
immunoscintigraphy +++ +++ +++ ++ ++
CT-scan was positivein cases 3 and 5, negativein case 1 and 4, not performed in case 2. US was negative in cases 1 and 5, doubtful in cases 3 and 4, not performed in case 2. Though the group of patient is extremelysmall, they present normal or low CEA levels and high CA 19-9 levels, it is therefore intriguing that immunoscintigraphy with an anti-CEA antibody were always strongly positivewith a sensitivity higher than those of CT and US.
Our results show a T/NT of less than one in 26/34 patients studied with HHPAO, whereas all tumors in the aHT group had a higher uptake than the normal brain. Three patients with recurrences were positive on the ~MT scan, 2 patients without evidence of tumor recurrence had T/NT < 1. In 10/28 tumors we found a T/NT < 1.5 on the ~¢1Tscan: in 7/8 tumors with substantial necrosis on CT/MRI, T/NT was <1.5, wheras only 1/8 tumors, an astrocytoma I I without evidence for necrosis, had aT/NT <1.5. In the remaining cases the presence of necrosis could not be determined. Our results with HMPAOare in agreement with PET findings of reduced tumor blood flow compared to the normal brain. This property makes HMPAOunsuitable for discrimination of tumor recurrences from gliosis, or abscess. The presence of necrosis yields an apparently decreased T/NT due to partial volume effects for both, HMPAOand cMT. The higher tumor uptake of oJ'lT, however, s t i l l gives a sufficient T/NT to be useful, Unlike HMPAO,e~'lT promises to be helpful in the manaqement of Patients with brain tumors. 584
583 B. Briele, A. Bockisch, J. Br6kelmann +, A. Hotze, P. Oehr, D. Krebs +, H.J.Biersack. Dept. N u c l . Med., Dept. G y n e c o l . (+), Univ. B o n n , Germany
We compared a group of 34 patients with primary and secondary brain tumors studied with Tc-99m HMPAO with a second group of 30 patients studied with I-123 a-methyltyrosin(~MT). We acquired SPECT studies after injection of 550 MBq Tc-99m or 240MBq aMT respectively,and calculated tumor/non-tumor ratios (T/NT) from ROI's placed over the tumor and the normal brain in the slice of largest tumor extent according to the CT/MRI images.
A. Chetanneau*, N. Tournemaine*, G. Ricolleau*, P. Peltier*, and J.F. Chatal* W.
ANTI-CA 12.5 RADIOIMMg~0DETECTION (RID) IN THE FOLI~W-UP OF 0VARIAN CARCINOMA - A PROSPECTIVE STUDY. In this prospective study the significance of RID as a diagnostic tool in the detection of metastases was evaluated in 40 patients with metastatic ovarian carcinoma !during or subsequent chemotherapy. 1-131-1abelled (74 MBq) whole anti-CA 12.5 antibody (ZMACIS II, Isotcpen Diagnostik CIS) diluted in 100 ml of physiological NaCI solution was injected as an infusion within 30 min. Planar images (ventral and dorsal views) of the pelvis, abdomen, thorax, and head were obtained at 72 and 120 h p.i.. In each study blood pool scans (Tc-99m-labelled red blood cells) were performed and subtracted from the antibody scan. Results: Zn 16 out of 18 cases with suspected (clinical investigation, ultrasonography, and X-ray CT) abdominal metastases RID was true positive and even the only imaging modality to detect an iliac lymph node metastasis in I case. In another case a histologically proven metastasis of the vagina (2cm) was clearly demonstrated. Yet it failed to mark a supraclavicular metastasis in a patient who had intraabdominal metastases proven by RID a s well as X-ray CT. In 17 of the remaining 22 cases RID was true negative a n d false negative in 5 cases. Conclusion: RZD was found to be valuable for the detection of intraabdominal metastases. A negative finding is helpful in avoiding second look surgery.
* Centre Rene Gauducheau, Nantes, France
COMPARISON OF IMMUNOSCINTIGRAPHY (IS) USING ANTI-CEA LABELED WITH 99mTc AND THEN 111In IN THE SAME PATIENTS The same anti-CEA monoclonal antibody labeled with 99mTc and then 111in was used in 8 patients presenting gastrointestinal adenocarcinemas (5 colon, 3 rectum). All patients were injected with 99mTc-labeled anti-CEA monoclonal antibody (mean activity 1110 MBq). Planar scintigraphy and SPECT were done 6 and 24 h after injection. At day 1, 7 patients were injected with i l 1in_ labeled anti-CEA fragments (mean activity 111 MBq). Surgery on the eighth patient after 99mTc-anti-CEA IS prevented comparison with 111 In-anti-CEA IS. In 1 of 2 retrospective cases, comparison 2 days later with surgical results alone showed that IS was falsenegative (FN) , The other case was true-positive (TP) with 99mTc-anti-CEA as of the sixth hour after injection, whereas 1111n-anti-CEA was FN at day 2. Only 3 of the 6 prospective cases were concordant with both labeling methods: 1 FN and 2 true-negatives (TN). Two other patients rated TN with 111 In-anti-CEA were FP with 99mTc, due to stasis artifacts of the colon. The sixth patient was TP in ECT with 111in at the level of a left lateroaortic node whereas 99mTc was FN. Colic elimination artifacts with 99mTc-anti-CEA hindered the search for and localization of colorectal tumors. The more immunogenic nature of the intact antibody required for 99mTc labeling also remains a major problem.
545
586
585 D.M. Goldenber$, J.A. Horowitz, E.J. Pawlak-Byczkowska, H.J. Hansen, R.M. Sharkey, E.H. Belisle, R. Stephens, and T.C. Hall. Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, and Imr,unomedics, Inc., Warren, New Jersey.
M. Ferde@hini, A. Gadducci, C. Prontera, T. Ceccarini, R. Cristofani, V. Faochini, P. Fioretti, R. Bianchi. Serviz]o di Medicina Nucleare, Istituto di Clinica Ostetrica e Ginecologica, Dipartimento di Sanita' Pubblica e Biostatistica dell' Universita' di Pisa, Istituto di Fisiologia Clinioa del CNR, Pisa, Italia.
TUMOR MARKERS IN UTERINECARCINOMA.
EPB-2: A NEW MURINE MONOCLONAL ANTIBODY (MAb) FOR IMAGING AND THERAPY OF LYMPHOMA. EPB-2 is a MAb developed against Raji cells. It is an IgG2a that was selected for clinical evaluation because it is a pan-B-cell MAb that, by immunohistology on normal tissues, only reacts with the germinal centers of tonsils and lymph nodes. By flow cytometry, EPB-2 does not react with circulating B-cells or with tumor cell lines of non-B-cell origin. In contrast, EPB-2 shows a high percentage of immunore ctivity with lymphoma tissue sections and with lymphoma cells in culture. Due to the radiosensitivity of human lymphomas 1.0 mg of EPB-2 labeled with 1-131 has been studied in a pilot clinical trial of lymphoma imaging. This MAb has been found to image known sites of disseminated lymphoma, including lung lesions, which were previously undiagnosed, spleen and liver, tumor, and intraabdominal, supraclavicular and inguinal lymphadenopathy. Normal organs have not shown non-specific targeting. Minimal complexation (<20%) was seen in the plasma 1 hr after injection. These initial results indicate that EPB-2 may be useful for antibody-mediated isotopic or drug therapy of B-cell lymphoma. (Supported in part by NIH grant CA39841.)
Recently many serum tumor markers have been detected in patients (pts) with epithelial ovarian carcinoma(EOC). Otherwise, few data are actually available about
antigens useful in uterine carcinoma(UC). CA 125, a glycoprotein antigen, which represents the most reliable marker for EOC, has been also found in pts with endometrial carcinoma(EC) or cervical carcinoma(CC). CA 50 is a ganglioside antigen detected in a spectrum of carcinomas of different organs included EC and CC. CA 72.4 is an antigenic determinant on high molecular weight mucin-like glycoprotein, TAG-72, recognised by the monoclonal antibody (MAb) B72,3, which is able to react with a large series of carcinomas, including EC and EOC. SCC antigen is a peptide consisting of 18 aminoacidic residues recently isolated and purified in tissue specimens of cervical squamous cell carcinomas (CSCC). In the present work CA 125, CA 50, CA 72.4 and SCC were assayed in blood samples Obtained at diagnosis from 45 pts with CC, 42 pts with EC and 68 with benign uterine diseases as controls. CA 125 was measured with solid phase sandwich IRMA utilising MAb OC125 (ELSA-CIS,I), CA 50 with solid phase sandwich IRMA using MAb C50 (Stena, S). CA 72.4 was assayed with a sandwich type IRMA using two MAbs: and cc49 as catcher and B72j3 as tracer (ELSA-CIS,I). SCC was measured with a RIA using a polyclonal antiserum (Abbott, USA). Table: >36 Ut~=
>66 U/ml
>20 u ~ l
CA ;'2.4 >s.s U ~ l
S¢¢ >3.6 rig/m1
21/87 24,1 11142 26,2
13/87 14,11 9/42 2t,4
19168 27,@ t 1/32 34,4
9/68 13,2 7•32 21,8
~6/66 24,2 5/30 16,7
24//36
CA 126
UTERINE CARCINOMA SENStTIVITY ~ ENDOMETRIAL CARCtNOMA SENSITIVITY %
..................
. . . . . . . . . . . . . . . . . . . CERVICAL, CARCINOMA SENSITIVITY *¢
~OC*~NOM~ I-Ila F,I.G.O. STA•E Hb-W F.I.G.O, STAGE S Q U ~ L ~ CELLCARClNOM~ I-Ila F I,G,O. STAGE lib-IV F,I,G,O, STAGtE BHNIGN UTERINE PATHOLOGY SPECIFICITY ~
CA SO
'2,'
%',V
10/45 22,7
4145 g,1
8/36 22,2
115 2/4
115 0/4
3/19 4/f7 I 7/68 75,0
1/tS 2/17 6•68 gl,2
........ 5,6
1/6 1 t I36 30,6
2/4 113
0/4 1/3
0/3 113
3/15 2114 11/63 82,5
1/15 0/14 0/62 100,0
2/16 8114 12158 79,3
As shown in Table, SCC is the most reliable tumor associated antigen among pts with CSCC, while CA 125 and CA 50 are the most sensitive tumor marker in cervical adenocarcinoma and EC. CA 72.4 showed the lowest sensitivity and the best specificity among the examined tumor markers in UC.
588
587 D. Vrbanec,
D. Cvrtila,
and A. B o l a n ~ a
N u c l e a r M e d i c i n e and Oncology Clinic, "Dr. M l a d e n Stojanovid" U n i v e r s i t y Hospital, Zagreb, Croatia, Y u g o s l a v i a C I R C U L A T I N G CA 15-3 AND C E A VALUES PATIENTS WITH B R E A S T C A N C E R
IN M O N I T O R I N G
Serum c o n c e n t r a t i o n s of CA 15-3 and carcinoembryonic antigen (CEA) were m e a s u r e d in 241 patients w i t h b r e a s t cancer. M e t a s t a t i c disease was d e t e c t e d in 65 of them. Two h u n d r e d and t w e n t y - s e v e n healthy subjects p r o v i d e d our normal CA 15-3 reference value. Upper limit of the normal range for CA 15-3 and C E A were found to be 26.4 U/ml and 2.5 ng/ml, respectively. Both CA 15-3 and C E A values were higher in patients w i t h metastases. S i g n i f i c a n t l y more patients had e l e v a t e d levels of CA 15-3 than C E A (62.5 % versus 48 %, p<0.05) as m e a s u r e d at various stages of the disease. Even one increased tumor m a r k e r value was c o n s i d e r e d as a positive finding thus increasing d i a g n o s t i c accuracy to 70.8 %. CA 15-3 and CEA values w e r e raised in 37/176 ( 2 1 % ) and 23/176 ( 1 3 . 1 % ) of patients, respectively. C o n c e n t r a t i o n s of CA 15-3 and C E A varied s i g n i f i c a n t l y w i t h the stage of the disease but also in the relation to the t r e a t m e n t response. However, CA 15-3 is more closely associated to the clinical status a s s e s s e d in the f o l l o w - u p period. CA 15-3 levels vary in accordance w i t h the obvious disease status changes and m i g h t precede clinical r e c o g n i t i o n of tumor progression. These tumor markers are accordingly of p r o g n o s t i c value r e g a r d i n g survival period.
B.Kiersnowska-Rogowska, E.Jaroszewicz
F.Rogowski,
D e p a r t m e n t of H a e m a t o l o g y N u c l e a r Medicine, M e d i c a l Poland
A.Citko,
and D e p a r t m e n t of Academy, B i a l y s t o k ,
RADIOIMMUNDLOGICAL ESTIMATION OF LEUKOTRIENE B4 (LTB4) AND C4 (LTC4) PRODUCTION BY LEUKAEMIC CELLS
The purpose of this study was the investigation of the alterations of LTB4 and LTC4 production by leukaemic cells in comparison to the normal leukocytes, measuring their concentration in supernatants of 4-day PHA stimulated culture and in plasma of leukaemia myelogenes patients. Leukocytes and plasma were collected from 18 untreated patients with acute myeloblastic leukaemia (AML), 16-with chronic granulocytic leukaemia (CGL) and 12 healthy persons. The measurments of LTB4 were made with Amersham (England) and LTC4 by NEN (USA) RIA kits. The obtained results showed decreased concentration of LTB4 in supernatants of AWL and CGL but increase of LTC4 level comparying to the control. However, plasma LTB4 concentrations were significantly elevated in leukaemia patients (especially in AML) but LTC4 increased in AML only. Decreased LTB4 concentration in supernatant and high level of LTB4 in plasma may be the evidence for extraleukocytic (probably tissue) source of this leukotriene production. The chemotaotic properties of LTB4 may explain the formation of leukaemic infiltrations in tissues. The elevated level of LTC4 both in leukaemic cells culture and in plasma may suggest the intensification of this leukotriene biosynthesis in leukaemic cells.
546
589
590
J.M. RIEDINGER, M. BORDES, C. TOUZERY, J. CUISENIER J.M. NABHOLTZ, J.L. PELLETIER
ELF~TA N. PIP,~-~qCOVA
Service d'Immunologie et Unit~ de M~deeine Nucl~aire CENTRE Georges-Franqois LECLERC Rue du Professeur Mar~on 21034 DIJON CEDEX
NATIONAL
USEFULNESS OF PREOPERATIVh SEaUM LEVELS OF CA 15-3, COMPARATIVELY WITH CEA IN BREAST CANCER The purpose of this study was to determine the possible relationship between preoperative serum levels of CA 15-3 or CEA and clinical, surgical or analytical parameters. Patients and methods : serum samples were obtained from 225 patients with untreated breast carcinoma before surgery. Assays were made with CIS-ELSA CA 15-3 ( N ~ 3 0 U/ml) and CEA-ENZELSA (N4 5 ng/ml) kits from ORIS Industrie. Results : a positive correlation was found between the frequency of positivity of CA 15-3 or CEA levels and the extend of tumour stage (p
591 S. Lastoria, R.D. Neumann, J.A. Carrasquillo, D. Colcher J. Schlom, and J.C. Reynolds. National Institutes of Health, Bethesda, MD, USA.
MEASUREMENT OF REGIONAL CONCENTRATION OF B72.3 BINDIN( SITES IN EPITHELIAL TUMORS. The distribution and molar concentration of binding of 125I monoclonal antibody B72.3 IgG was measured in 30 hu man epithelial tumors by in vitro quantitative autoradio graphy (QAR). 8 um frozen sections were incubated with i~ creasing amounts of 125I-B72.3 to determine the total bin ding and with labeled plus unlabeled B72.3 to determine the non-saturable binding. QAR images of the tumor and 125I standards were digitized by microdensitometry and the regional concentration of B72.3 was calculated. In 19 tumors the maximal specific B72.3 binding ranged from 35 to 430 pmoles/gram; in ii tumors the binding of B72.3 was undetectable. The B72.3 distribution was uniform in only 5 (26%) of the positive lesions. In the other 14, there were foci of B72.3 uptake. To further evaluate the hetero geneity of B72.3 binding, the QAR images were compared to tumor histology by H&E, mucicarmine and immunoperoxidase (IP) stainings. In discrete tumor nodules B72.3 binding was generally uniform. When tumor was infiltrative or interspersed with normal tissue, B72.3 binding was loca! ized or scattered. Scattered tumor cells were associated with scattered activity, but in 2 cases focal areas of binding were associated with mucin. The areas with the highest B72.3 binding included tumor and/or mucin. In all cases the p a t t e r n of IP staining was similar to the auto radiographic activity. In conclusion: i) specific B72.3 binding sites (BS) can be detected and quatified by using QAR, 2) these BS can be uniformly or heterogeneously distributed in tumors, 3) the high concentrations of the se BS favor the B72.3 uptake in radioimmunodetection.
CANC~
CENTRE
-SOFIA.BUY,G~IA
ESOPHAGOSCINTIGRAPHY TRACING THE EFFECT OF SURGICA~ TREATMENT OF ESOP}L~G~AL CANC~. On a gamma-csmmera an esophageal transit (ET)
traced with lisuid and original solid meal ~ as olus,labeled with 99m-Tc-~zton (55 ~Bo) or
II~m-In-coinol (I¢8 MBq)performed in 43 p~tients ~zi ~h Esophageal cancer.In order to determin the 'effect of surgical treatment and functional ccn~ dition of anastomoses,tracing was held in different times after radical operation.The obtaihed ouantative results of ~TT(esophageal transit times) in sec.,the degree of esophageal clearence for ETT was normal Co~ and the appreximal speed of ET-also normal-V(~s) was jaxtaposed with the determined normal finding. In wich ETT for liguid is 5,9+0,3s for solide meal 7,5+0,4s, C~resoectively - ~0,2÷I,2% and 90,~+I,4% w~ile V '°- 75,0+0,5~s and I$,5+0,7W/s. In-esophageal resectio~ combined with ~astroeetomy or proxima] stomach resecctia,all indexes for solid meal was abnormal. In the anastomoses site a reflux proved in 85,7% for all cases showing typical scintigraphy immage.This method has the adva%age to detect minimal early and late postoperative complications (esophagitis, Beflux-esonhagitis~ or strictures). Wich needs a different therapeutic tactics after radical treatment of oncological disease.
592 G. M A R I A N I I'2,
C. R O S A 2, A.G.
Siccardi 3
(i) D e p t . of R a d i o l o g y , B r i g h a m a n d W o m e n ' s H o s p i t a l . H a r v a r d M e d i c a l S c h o o l ; B o s t o n , M A (USA). (2) C N R I n s t i t u t e of C l i n i c a l P h y s i o l o g y ; P i s a . (3) D e p t . of B i o l o g y a n d G e n e t i c s , U n i v e r s i t y o f M i l a n ; M i l a n (Italy) SIZE-RELATED DIAGNOSTIC SENSITIVITY OF RADIOIMMUNOSCINTIGRAPHY VERSUS SOFT-TISSUE X-RAY IN PATIENTS WITH OCULAR MELANOMA
A g r o u p of 26 p a t i e n t s w i t h choroidal melanoma was s e l e c t e d o u t f r o m a t o t a l of o v e r 300 patients included in a multicenter clinical t r i a l o n the d i a g n o s t i c a c c u r a c y o f t u m o r r a d i o immunoscintigraphy (RISG) w i t h m o n o c l o n a l 2 2 5 . 2 8 S - F ( a b ' ) 2 in p a t i e n t s w i t h m e l a n o m a f r o m v a r i o u s s i t e o r i g i n s . P a t i e n t s w i t h all m e l a n o m a l e s i o n s e i t h e r s m a l l e r / e q u a l o r l a r g e r t h a n 1 c m in d i a m e t e r , a n d all p r o v e n i n d e p e n d e n t l y f r o m R I S G or x-ray were selected for this study. Given these selection criteria, statistical analysis could o n l y b e p e r f o r m e d in t e r m s of s e n s i t i v i t y of t h e t e s t s as to p a t i e n t s ' c l a s s i f i c a t i o n ; c h i - s q u a r e a n a l y s i s w a s u s e d t o c o m p a r e the d i a g n o s t i c s e n s i t i v i t y of R I S G w i t h t h a t of x - r a y . The results of t h e a n a l y s i s s h o w e d t h a t the diagnostic sensitivity of RISG was much higher t h a n t h a t of x - r a y in t h e ii p a t i e n t s w i t h c h o r oidal melanomas smaller than 1 cm (63.3% versus 9.1%, P < 0 . 0 5 ) . Conversely, even though sensitiv i t y of R I S G w a s h i g h e r t h a n t h a t of x - r a y (93% v e r s u s 80%), the d i f f e r e n c e d i d n o t reach statistical significance in t h e 15 p a t i e n t s with m e l a n o m a l e s i o n s l a r g e r t h a n 1 cm. The results of t h e p r e s e n t a n a l y s i s confirm the remarkably good d i a g n o s t i c p e r f o r m a n c e s of t u m o r R I S G in p a t i e n t s w i t h c h o r o i d a l m e l a n o m a .
547
594
593 R Bares, G Weiller, J Fass, M Lichtenstein, U Buell
P.Oehr*, U.Germer*, B.Bj6rklund**, V.Bj6rklund**, J.Westermann*, H.J.Biersack*
Depts of Nuc] Med, Surgery, and Unlv of Aachen, FRGermany
Dermatology, Technlcal
IMMUNO-SPECT WITH Tc-99m LABELLED MONOCLONAL ANTIBODIES (MAB), INTACT (IAB) AND FRAGMENTS (FAB): METHOD, BIOKINETIC ASPECTS, CLINICAL RESULTS The significance of Immuno-SPECT for Tc-99m labelled IABs (anti-CEA, BW 431/26) or FABs (F(ab')2, anti-melanoma, 225.28S) was analyzed in 66 patients with malignant tumors (35 colorectal, 8 pancreatic, 23 melanoma). Planar scintigraphy (5 and 24 hpi of I.IGBq, 1000/500 kcts/view) and SPECT (6 hpi, 10-20 mill cts/360 rot) were performed using a double-head rotating gamma camera. The results were validated by CT and surgical findings. To document biokinetics, we measured Tc-99m whole body and blood retention.Results (except liver foci): Neg. Sensitiv.(%) Acquisition True pos. Equiv. I.IAB : 43 patients, 43 lesions 19/40 30 planar 5hpi 13/43 7/43 8/43 74§ n.s. 24 32/43 3/43 11/43 60§ SPECT 6hpi 26/43 6/43 2.FAB : 23 patients, 25 lesions 8/25 52 planar 5hpl 13/25 4/25 8/25 52,p<0.05 24 13/25 4/25 5/25 76* SPECT 6hpl 19/25 1/25 3 of 17 liver lesions were positive, 11 appeared as cold lesions(3 only visualized by SPECT). Halflife of EABs in blood compared to IABs was shorter(5h vs 21h, p<.O01) as was 50%-whole-body-retention-time (40 vs 11Oh, p<.O01). We conclude that with 99m-Tc labelled FABs SPECT does increase sensitivity of IS significantly and should thus be applied to gain optimal results. With IABs, however, diagnostic profit of SPECT is small, since tumor contrast often occurs too late to perform adeauate SPECT.
R A D I O I M M U N O T H E R A P Y OF CANCER WITH A N T I - T P A M3 Most of the human c a r c i n o m a cells are positive for Tissue P o l y p e p t i d e A n t i g e n (TPA). The p u r p o s e of this study was to find out w h e t h e r t r e a t m e n t of T P A - p o s i t i v e tumor cells with antiTPA could inhibit the s p r e a d i n g of tumor cells. 5x106 c e l l s / a n i m a l were t r a n s p l a n t e d intrap e r i t o n e a l l y into rats (n=40). In seperate experiments, a n t i b o d i e s (140 ~g/animal) were I. i n j e c t e d w i t h o u t label, 2. c o n j u g a t e d to c a d m i u m or 3. labelled with a p p r o x i m a t e l y 200 ~Ci IsII/ animal. In the control group, antibody treatment was omitted. R a d i o i m m u n o s c i n t i g r a p h y showed selective uptake of the a n t i b o d i e s in the tumor. The highest uptake was found when labelled a n t i b o d i e s were i n j e c t e d on day 0, 4 and 8 after HeLa c e l l i m p l a n t a t i o n leading to a t u m o r / t i s s u e ratio of 20. D e t e r m i n a t i o n of the tumor weight 22 days after Hela cell i n j e c t i o n showed a 17fold r e d u c e d tumor g r o w t h in the case of treatment w i t h r a d i o l a b e l l e d antibodies, w h e r e a s the t r e a t m e n t with n o n - l a b e l l e d a n t i b o d i e s r e s u l t e d only in a 1 . 3 - f o l d d e c r e a s e of tumor weight. Our results allow the a s s u m p t i o n that treatment of p a t i e n t s with r a d i o l a b e l l e d a n t i - T P A might be of interest d u r i n g surgery of cancer in order to reduce cancer cells and metastases. Since e f f e c t i v e i r r a d i a t i o n of tumor cells might take 3 months, it can be assumed that our results could be i m p r o v e d when the t r e a t m e n t is c o n t i n u e d for more than 22 days.
596
595
A E Southee, AF McLaughlin, D E Joshua, GJ Bautovich, BF Hutton, BR Wylie, J Gibson, H Kronenberg, JG Morris.
M. CHOt
* Departement
Immunolagie et Immunopharmacologie ULP ILLKIRCH GRAFFENSTADEN 67400 o Exploration par les moyens physiques at laboratoire Centre Paul STRAUSS STRASBOURG 67000 BIODISTRIBUTION
* I n s t i t u t e for clin. and exp. N u c l e a r Medicine, U n i v e r s i t y of Bonn, FRG; **SBL N a t i o n a l B a c t e r i o l o g i c a l Laboratory, Stockholm, Sweden
OF
INDIUM-111
LABELLED
UER
Pharmacie
Departments of Nuclear Medicine and Haematology. Royal Prince Alfred Hospital, Sydney Australia.
des radioisotopes
MACROPHAGES
IN
MICE
BEARING SOLID TUMORS Murine macrophages expa:nded and activated in culture are cytotoxic for tumor cells and caused regression of solid carcinoma in C57BL/6] after intravenous or peritumoral iniection. We have studied the biodistribution of these macrophages and of bone marrow derived activated macrophages (0,1 ~tg LPS + O,1 ~tg TNF) after adoptive transfer to mice. Labelling was done with 111-1n oxine (international CIS ) and biodistribution followed by scintigraphy and organ counting after dissection in healthy animals and in mice bearing 15-20 days old carcinoma in the hind muscle of the left leg. Following IV injection macrophages are filtrated in the lungs with a longer retention time far animals bearing solid tumors and lung metastasis. Thereafter maerephages distributed mainly in the liver and in the spleen during the first 6 hours. A slow but specific accumulation was observed in the primary tumor reaching its maximum after 48 hours. In case of peritumera] iniection macrophages remained confined for several days in the tumor area with very limited redistribution to the liver. Similar experiments have been performed on labelled human macrophages differentiated from blood monocytes and activated by rHu IFN-2( .These biodistribution data confirm that activated macrophages infiltrate the tumor tissue causing locally necrosis and tumor regression. Phase I experiments are undertaken actually in cancer patients affected with peritoneal carcinomatosis to follow the fate Qf autologous macrophages adaptively transfered. ]n addition to their therapeutic use labelled 111-In-macrophages have been proposed as a new imaging agent for the detection of recurrence of malignancy. An important objection is the fact that they are involved in inflammation.
GALLIUM SCANNING AS A PREDICTOR OF OUTCOME IN MEDIASTINAL HODGKIN'S DISEASE A mediastinal mass (MM) occurs in at least 60% of patients with Hodgkin's Disease (HD) and if bulky is associated with increased relapse. A residual MM after treatment is a difficult management problem. Biopsy may be used to determine active disease but a reliable non-invasive method would be preferable. 10 mCi gallium (Ga) scanning was performed on 39 patients with biopsy proven HD. There were 20 males and 19 females; average age 36; mean follow-up 35 months. All had Ga avid MM prior to treatment. Post treatment results and disease status at last follow-up: Ga Positive Ga Negative All 14 deaths or PD 17 CR patients 1 CR 7 PD, relapse or death
MM
NO MM
4 deaths 4 PD
7 CR 2 relapse, 2PD*
3 deaths 3 PD 1 CR
10 CR 1 relapse (now CR) 1 PD* (now CR), 1 death*
* 4 patients scanned within 5 weeks of chemotherapy. PD = progressive disease CR = complete clinical remission. Ga scanning provided excellent differentiation of patients with active disease after treatment (p< .001, n=39). Prognosis was equally good in Ga negative patients with or without a MM. Ga had a high predictive value (93%) in Ga positive patients. The predictive value of a Ga negative result was 71% but 4 of the false negative studies were performed early after chemotherapy. In treated mediastinal HD a Ga positive scan accurately predicts outcome. If Ga scanning is performed too soon after therapy false negative results may occur. Outcome is independent of the presence of residual MM.
548
597 P.Guerra ~, G.Maira ~, C.Pizzocaro ~, A.Terzi~,GC.Magri ~, R.Pagliaini ~, A . G a r a v e n t a *~, F.Claudiani °, M.Sanguineti B.De Bernardi **, M.Bestagno ~. Med.Nucleare - Spedali Civili - Brescia ~ Clin.Pediatrica Istituto Gaslini - Genova o Med.Nucleare Ospedale Galliera - Genova
1311~MIBG TREATMENT OF NEUROBLASTOMA We report here the cumulated experience of MIBG treatmen~ for neuroblastoma, as attained in two italian institution Of 24 pts treated since 1985, aged 18 months - 12 years, 9 had initially St. III and 15 St. IV disease. All pts had been previously treated with chemotherapy; some of them also underwent surgery. In 16 children the disease was in progression, in 4 in partial remission and 4 stationary or non longer responsive to therapy. i0 pts received 1 course of 131I-MIBG, 5 pts 2 courses, 7 pts 3 and 2 pts 4, respectively. The mean activity for course was 4-9 m C i / K g (148-333 MBq/Kg). Intervals between cycles varied from 4 to 8 weeks. The mean follow-up ranged from 1 to 24 months (median 8 months). 2 children achieved very good partial remission sustained for 6 months, and 3 partial remission. Stabilization of disease occurred in 4 children; no response was observed in 4 pts and progression in ii. Complete remissions were not obser red. All children with pain before treatment experienced good relief w i t h i n a few days. Side effects of MIBG treat ments were confined to bone marrow depression with predominant thrombocytopenia. The nadir of platelets occurred at 3rd-4th week and its value decreased with number of cycles and/or bone marrow infiltration. 0nly in one case blood trasfusion was given; autologous marrow transplant was never needed.
599 P Galofr~-Mora, S Mmfi~-Herrero, A Cuartero-Plasa,FM Domenech-Torn4, R SimdCanonge~, M Boada-Eovira'~, A Capdevilm-Cirera ~'',
8ervcis de Bedieina Nuclear, Endocrinologia'and Neurologia**BG Val! d'Hebron, Centre de Resson6nciaMagnetismde Barcelona*". P. Vall d'Hebron s/n 08035 BARCELONA. Spain,
MAORRTIC RRHONARgR IMAOINO (RRI) IN THE 8PIRAL MRTABTAHRB OF DPFFRR~NTIATBD THYROID CADOIROMA (DTO) DTC is a 1ow incidenceneoplasticdisease with a good general prognosisbut the spinal involvement may cause neurologicallesions resultingin poor quality of life and even early death for the patient. We used MRI to make an early diagnosis in order to establish therapeuti0alstrategies. From a total of 197 patientsdiagnosedend treated for DTC, IZ showed evidence of b0ne metastases, and of these, ? presentedvertebrallesions and/0r paraspinal masses f5 with and Z without neurologicalsigns]. We performed 9 MR1 explorations 0n these pmtlents. ~e observed 6 vertebral lesions and 4 paraspinal masses with 4 cases of medullary involvement and i case with multiple radicular lesions.We als0 observed metastases in other 10calizati0ns (s0ft-tissue masses, pulmonary metastases, etc.) Pathological sites coincidedwith 1311 uptake in the whole body scan IWDS) in all caee~ but two who presentedparaspinaJmasses in MR1 explorationwithout Jail uptake. One patient had positive HBS in lumbar spine with inconspicuousMR1
changes. COMMENTS I MRI is the 0nly diagnostictechnique able to show the spinalcord. vertebral b0se and surroundingtissues together in sagittal and o0r0nsi slices and in early
stages, This technique is especially useful in patients without neurological signs hut with radioiodlneuptake in the spinal region, He used MRI is therapeuticaldecision making (radioiodinsor even surgery) and in evaluatingtreatment efficacy in order to avoid or preventneurological complications,
598 J. M.
Mueller-Brand, Rist
University
A.
Hospital,
Miserez,
Basel,
H.
Maecke,
Switzerland
V~LUE OF A MUCIN-LIKE CARCINOMA ANTIGEN (MCA) I N P A T I E N T S WITH CARCINOMA
ASSOCIATED PROSTATIC
M C A is a h i g h m o l e c u l a r glycoproteine with !mucin-like characteristics and can be detected immunohistologically in various carcinoma. A two step solid phase sandwich EIA has been 'developed (Roche Ltd.) to detect MCA in serum. In this study, the MCA concentration in blood of 170 patients with prostatic carcinoma was measured and compared with the clinical course and bone scintigraphy. Results: In 200 Healthy persons the MCA mean value (± 1 SD) w a s 6 , 3 ± 3 , 2 U/ml a n d ii U/ml was considered as upper normal limit. O f 90 patients with tumor but without evidence of distant metastases 78 h a d M C A v a l u e s of less t h a n ii U / m l a n d i n 12 M C A v a l u e s were elevat e d . I n 72 p a t i e n t s with bone metastases, statistical evaluation showed sensitivity 56%, specificity 85%, pos. pred. value 75%, neg. pred. value 7 2 % . I n 24 p a t i e n t s with follow up under hormone treatment, MCA has an excellent correlation with clinical course. Conclusion: In over 55% of patients with metastatic prostatic carcinoma, M C A is s e c r e ted and can be detected in serum. In these patients, serial MCA determinations are valuable parameters for monitoring of response to treatment.
600 S E Clarke,*S J Allen~ C J Twelves,*S Mathert C Lazarus,* A Girling,*J Taylor,+M Rlchards.* *Department of Nuclear Medicine and ICRF Breast Unit, Guys Hospital,London SEI. + I C R F Laboratories,Lincoln Inn's Fleld,London SEt iMMUNOSCINTIGRAPHY IN BREAST CANCER WITH 1-123 AND 1-125 LABELLED SM3. A murine antibody, SM3, was evaluated in breast cancer patients under-going mastectomy with axlllary clearance. SM3 was label!ed with 1-123 to assess early (24 hours) or 1-125 to assess late (72 hours) uptake. Labelled SM3 was injected either subcutaneously (sc) into the finger web spaces or intravenously (iv). With 1-123 SM3, patients were imaged before surgery. The resected specimen was imaged at 24 hours, the nodes dissected out and counted in a gamma counter together with a sample of tumour and normal breast tissue. With 1-125, the surgical specimen was resected at 72 hours and t h e dissected nodes and breast tissue counted. All samples were examined histologically. 223 nodes from 19 patients were studied. Imaging showed symmetrical axillary uptake, and uptake in resected lymph nodes. Uptake dld not correspond to histologically proven metastases, and the primary tumour was not visuallsed. The quantity of isotope in the specimens is shown below as mean % injected 1-123 or 1-125/g tissue. normal metastatic normal primary SM3 n nooes nodes tissue tumour 1231sc 4 0.0051 0.0068 12311v 6 0.0037 0.0036 0.O021 0.O020 1251sc 3 0.0085 0.0360 0.0015 1251iv 6 0.00075 0.0061 0.00085 0.0021 Although the uptake at 24 hours was disappointing, there is specific uptake at 72 hours in tumour wlth iv injection and nodes wlth sc.
549
602
601 A.C. Prost 1,2, p. Langlois 3 , F. Menegaux 3 , J.L. Jost 3 M. Koulibaly 4 J.M. Vidal 4 , j.p. Chigot 3 , P. Vayre 3 ' A. Aurengo 1 , 'J.C. Legrand 2 and G. Rosselin 5 Services de Biophysique 1, Biochimie 2, Chirurgie gdndrale et digestive 3, Anatomie pathologique 4, C.H.U. La Pitid-Sal5P~tri~re 91 Bd de I'HSpital, 75634 Pars Cedex 13, et INSERM U.55 , H6'pital St Antoine, 184 rue du Fg St Antoine, 75571 Paris Cedex 12, France.
LABELED MARKER
TRANSFERRIN FOR HUMAN
IS A NON-SPECIFIC BUT COLORECTAL CANCER.
IRE-CELLTARG,
B-6220 FLEURUS. BELGIUM
POTENT Antitumor Activity of the 1123 Z Ii beta Chloremethyl 17 alpha iodovinyl estradiol on ER containing tumors.
The transferrin receptor number of a cell is closely related to its growth and maturation. In this regard, tumoral cells generally express more transferrin receptors than normal cells from the same tissue. With intent to know about human colorectal cancer as compared to normal colorectal mucosa, we used 1251 radiolabeled transferrin as a marker for transferrin receptors. The maximal binding of transferrin to crude membranes prepared from surgical pieces and its dissociation constant were determined according to Scatchard analysis. The ratio T/N , i.e. maximal transferrin binding to the tumor divided by maximal transferrin binding to the normal mucosa, are indicated in the table. Number of cases
M. Zeicher, M. Deblaton, P. Henrot, Y. Karaman, R. Pirotte~ J. Quivy.
T/N (range values)
Polyadenoma
1
0.486
Adenocarcinoma
6
1.437
10.119
Villous tumor + Adenocaroinoma
2
1.082
1.159
As opposed to polyadenoma, cotorectal adenocarcinoma or transformed villous tumors had a higher transferrin binding capacity than the normal mucosa. Therefore, labeled transferrin appeared as a non-specific but potent marker for human colorectal cancer with future prospects in gammascintigraphy or nuclear magnetic resonance.
In the process of their decay by electron capture, some radioisotopes release cascades of low energy Auger electrons possessing a subcellular range of action (a few nanometers). If the decay occurs in the vicinity of the DNA it will induce double strand breaks and less than I00 disintegrations are sufficient to kill a cell. On the contrary if this occurs at the cell surface or within the cytoplasm it has a negligeable effect on the cell survival. One way to bring these radioisotopes near the DNA is to attach them to steroids with high affinity to the nuclear associated steroid receptor. These steroids with selective biodistribution and appropriate radietoxic potential are suitable agents to achieve an efficient and safe estrogen receptor mediated radiotherapy of hormone-dependent cancers. We have synthesized an estrogen derivative with very high affinity for the estrogen receptor (ER), the Z isomer of the II beta chloromethyl 17 alpha lodovinyl estradiol (11 beta CMIVE). It was labelled with an lodine 123 Auger electron emitting radionuclide of short half-life (13.21 hours). This agent demonstrates a very selective biodistribution in ER containing tissues. We will present the results of our studies describing the selective cytotoxicity of the Iodine 123 labelled II beta CMIVE. In vitro cytotoxieity was assessed using a modified MTT assay on ER positive and negative human cell lines. In rive experiments were performed on BDFI mice bearing the syngeneic breast carcinoma MXT.
604
603
I. CASANS, A. LLUCH, J. JIMENO,
J.. CIUDAD, V. BELLOCH.
J.l. Quivy, M. Deblaton, P, Henrot, Y. Karaman, R. Pirotte and M. Zeicher. NUCLEAR MEDICINE AND ONCOLOGY DEPARTMENTS. HOSPITAL CLINICO UNIVERSITARIO. IRE-CELLTARG,
VALENCIA. SPAIN.
B-6220 FLEURUS. BELGIUM
Synthesis of Z-ll~.chloromethyl-170~-iodovinyl estradiol a very high affinity estrogen with high in vivo accumulation in estrogen receptor containing tissues. In order to prepare high specific estrogen bearing iodine 123 for imaging and therapy of estrogen receptor (ER) containing tumoral tissues, we have substituted the steroidal skeleton with chemical groups confering: - high affinity and low dissociation for ER - low non-specific binding (e.g.to plasma steroid-binding proteins). I I ~ - chloromethyl and 1 7 ~ - iodovinyl substitutions can fulfill these conditions . The challenge was to prepare a steroidal molecule bearing two different halogens which one radiolabell~d. An original chemical synthetic route starting from /< -adrenosterone after 13 steps produced E or Z-11~-ehloromethyl-17~-iodovinyl estradiol. Binding studies on human MCF-7 and calf uterus ER showed very high affinity ("superaffinity") of these two isomers E and Z with either cold or iodine 125 labelled, respectively by indirect competitive assay with 3H estradiol and direct binding (Scatchard plot). In animal studies (ovariectomized mice), we have demonstrated specific high accumulation of iodine 125 or 123 labelled Z isomer after 6 hours in ER containing tissue like uterus. More striking, experiments with mature mice show that this preferential accumulation in ER positive tissues (uterus, ovaries, breast tumors) are not greatly affected by the endogenous estradiol secretion.
ISOTOPIC VENTRICULOGRAPHY IN SERIAL ASSESSNENT OF CARDIOTOXICITY INDUCED BY EPIRUBICIN (E) IN BREAST CANCER. W e have studied prospectively 42 patients with advanced breast cancer treated with two different chemotherapy FEC combinations, receiving E doses of 50mg/m2 (Group I (G-I) 25 patients) and 75 mg/m2 (Group II (G-II): 17 patients) every 3 weeks until progression or to an E cumulative dos (ECD) of 750mg/m2(G-I) and 900mg/m2(G-II). By serial equilibrium isotopic ventriculography at rest, we determined the left ventricular ejection fraction (EF) in baseline state, on reaching E doses of I:50-250, II:300-400, III: 450-550, IV:600-700 and V(only G-II):8OO-9OOmg/m2, and 318 months after finishing therapy(total EF determinations: 147). The mean ECD was 590±214mg/m2(G-I) and 750~131mg/m2 (G-II). An EF fall) 15% from the baseline value was considered as laboratory eardiotoxicity, detecting in 8 patient (32%) of G-I and 6(35%) of G-II. In these cardiotoxic patients, mean basal EF and mean final EF were respectively 83.8+6.6% and 52.5+12% in G-I (p:O.91) and 65.1+9.1% and 41.5~7.9% in G-II T p < O . O l ) . The mean EF % fall-was in G-I 2 3 . 0 + I S . 8 % and in G-II 37.0+19.S% (p
550
605
606 M. Rait~r , O. Esil<, I_. Cse~nay
A.J.B. McEwan I, P.M. Venner 2, A.T. Porter 3
Department of Nuclear Medicine I and Medicine 2, Cross Cancer Institute, 11560 University Avenue, Edmonton. AB, Canada T6G IZ2 and Department of Radiation Oncology ~, UWO, London, Ontario, Canada N6A 4L6 STRONTIUM 89: A SAFE AND EFFECTIVE PALLIATION IN PATIENTS PREVIOUSLY TREATED WITH WIDE FIELD RADIOTHERAPY. Strontium-89 (Sr-89) has previously been shown to be an effective therapy in the palliation of patients with prostate cancer metastatic to bone. We have assessed the safety and efficacy of this form of treatment in patients previously treated with half body or whole body external beam radiation. Thirty-five patients have been treated with Sr-89 with a dose of 1.5 MBq/kg (18 with previous local radiotherapy and 17 with prior wide field radiotherapy). Prior to therapy all patients were assessed for hematological status and with respect to pain and analgesic requirements. Follow-up of these parameters was monitored for 3 months, and at 1 and 3 months formal evaluations were made. response
wide field local
not evaluable
pain free
significant
failed
1/}2 3
1/12 3
1/12 8
i/~2 2
1
3/12 5 3
3
3/12 3 3
7
3/12. 7 9
2
3/12 2 3
At 3 months response rates in the two groups are equal (80%) and comparable to those in the literature. We believe that Sr-89 is safe and effective palliative therapy in patients who have failed wide field radiotherapy.
607
Oepartmen% of Nuclear Medicine, Departmen% of Radiology , Albert Szent-GySrgyi Medicai University, Szeged, Hungary VALUE OF
BONE MARROW
SCANNING (BMS) IN BREAST
CANCER The interpretation of early metastatic loci (EMF) revealed by bone scanning (BS) Js a ma~or prob]em because of the lack of specificity. In this study we posed the following questions: 1. Wha± role can the 8MS play in different~atin~ [MF revealed by BS Jn breast cancer? ?. Can the diagnostic sensitivity be increased by means of BMS? One hundred and sixty-nine consecutive breast cancer patients were studied by BS, BMS and X-ray/tomography simultaneously. All 40 patients with d~sseminated bone metastas~s~ and 35 of 68 patients (5].5%) with EMF had focal defects CFD) and/or d~minished radiocol]oid uptake (ORU) by BMS. FD were detected in 8 of 61
p a t i e n t s "(13.1%) w i t h n e g a t i v e BS and X-ray w i t h or w i t h o u t DRU, 3 of whom developed BS and/or radio]ogic evidence of metastasis ~n a 4-year follow-up, In our experience: I. 8MS Js of limited value Jn differentiatino EMF revealed by 8S in breast cancer because the predilection sites of the foci are often covered by the liver and spleen radioactivity, and the extent of bone marrow involvement detected by 8MS is generally less than that of bone metastasis by 8S. 2. BMS has no prioritv as opposed to BS in screening skeletal involvement.
608
Ankov V.K., Romanova A.M., Metchkov G.M., Galabova I.K., Milanov St.Chr., Tcanov Tc.I., Tcanev Tc.St. Higher Medical Institute, Medical Academy, Sofia, Bulgaria
IMMUNOSCINTIGRAPHY AND RADIOIMMUNOMETRY IN PATIENTS WITH GASTROINTESTINAL CARCINOMA AND MALIGNANT MELANOMA Immanoscintigraphy and radioimmunometry were performed in 40 patients with gastrointestinal carcinoma and [mmunoscintigraphy only in 10 p~tients with malignant melanoma. A 131 I - labelled F/ab I/2 anti-CEA antibody and a cocktail of 131 I - labelled monoclonal antibodies - 19.9 F/ab I/2 and anti-CEA F/ab I/2 were used for immunoscintigraphy in gastrointestinal carcinomas. A 99mTc labelled - F/ab I/2 anti-melanoma antibody was used in cases with malignant melanoma. Gamma-camera images were obtained by subtraction technique. An uptake of radiolabelled antibodies was found in 31 p~tients with gastrointestinal carcinoma and in 6 patients with malignant melanoma. The diagnosis was confirmed by ultrasonography, computed tomography, surgery and biopsy. Radioimmunometry of CEA, CA-19.9, AFP, TPA and 8 -microglobulin in serum was carried out. An2evaluation of the role of immunoscintigraphy and radioimmunometry for diagnosis of local recurrences and metastases was accomplished.
C.NISTOR(L) ;Z.UHAY(1),K.MAKKAY(2),N.MIHAIL(3):)(3 "--M.UJ~-A-~T~,C C.NIS~OR(3),V.NISTOR(1),V.TRICA M.HEB~D~AN(3);M;ONISOR(1),M.BALAN(1),S.SZABO(3) ~.FAUIR(3),T.HARKO(1),I.BR~S(~),Z.SIMU(3),M.UAN (1),M.CARASTOIAN(3),C.STANCULEA(3),D.SOAR~ (3) (l.Oncolog. lnst. ;2.Fec.Chem,;3.Interdisc.lab. Univ.;Oluj Napoca ; ROMANIA ) RADIOCAPTATION OF RADIOIRON IN WISTAR RATS INTOXICATED WITH CZCLOPHOSPHAMIDE,AND PROTECTED W I T M CHOLINE LACTATE. We studied the effect of 0holine laetate(CL)on Wister rats intoxicated with Oyclophosphami~e (C),in the following lots of io animals;Lot I (control lot);Lot II(The C L control lot); Lot III(The 0 intoxicated lot);Lot IV (the C intoxicated and protected with CL lot).The CL were used in cone.of 20 m~/kg b.w/day,and 0 in concoof 40 mg C/kg b.w./daX.After 5 days of restoring period,the animals were sacrified.5 ho~u-s before the sacrification, they wer~ injec ted w i t h IJL Ci 59-Fe citrate,and the medLLllsr~ eplaenic radiocaptatlon of radioiron was measured and exprimed in impulees/min. The experimental data in the incorporation of 59-Fe citrate in haemstopoietic system were;Lot I(964+6o);Lot II(978+.41);Lot III(535Z48);Lot IV(972Zb~).Our experimental results show the favorable effect of the ~ L in the rsdioeaptation of the radisiron,respeetivelly the medulloproteetive effect of CL,in the medullodepreseion indQced in rats by C.Our results recommended the use of C L for
prevent and treatment of medullodepression induced with eitostatics in cancer chemotherapy and as 8djuvans in chemotherapy of cancer.
551
610
609
P. Bartenstein, J. Sciuk, R. Erlemann*, and O. Schober.
J.L.Chamorro, Argueso,
Klinik und Poliklinik for Nuklearmedizin,* Institut fQr Klinische Radiologie. Westf&lische Wilhelms-Universit&t, D-4400 MQnster West-Germany.
COMPARISION OF WHITE BLOOD CELL SCAN (WBC) AND MAGNETIC RESONANCE IMAGING (MRI) IN INFECTION OF THE LOWER EXTREMITY The present study compares the usefullness of white blood cell scans (WBC) and magnetic resonance imaging (MR1) for differentiation of the healed from the active state in chronic bone infection (OM). The study involves 23 patients (10f, 13m), ages 19-75, with clinical suspicion of infection of the lower extremity (no metal =mplants), history of disease for 6 weeks to 5 years. All patients underwent previous radiographic and bone scan (3- phase). The following methods were used: MRI: T1 weighted sequences (500-600/15-22 Tr/Te), T2 weighted sequences (1800-2500/70-90 Tr/Te); WBC: 111-185 MBq 1-123 labelled monoclonal antigranulocyte antibody, planar images at 4-6 and 20-24 h p.i, SPECT in 2 cases. Results: MRI: true pos.: 15, false neg.: 2, true neg.: 6, false pos.: 0; WBC: true pos.: 14, false neg.: 3, true neg.: 6, false pos.: 0. The final diagnosis was established in 17 pts. by needle biopsy or open surgery, in 2 true neg pts. on follow-up. The false neg. MRI were an acute recurrence of chronic OM, and chronic OM interpreted as malignoma; the false neg. with the WBC being an Brodieabscess and 2 patients with chronic,low active OM. Conclusion: MRI and WBC indicate an active bone infection with high accuracy. The advantages of both methods should be used dependent on clinical question.
L.A.Pulp6n,
C.A.Alhambra,
C l i n i c a Puerta de Hierro,
J.Ortiz
Madrid,
POSTER WITHDRAWN
EVALUATION OF 4HR Tc-99m HMPAO LEUCOCYTE LOCALISING INTRA-ABDOMINAL SEPSIS
IMAGES
FOR
Physiological uptake in Tc-99m HMPA0 labelled leucocyte scans (TLLS) occurs in bowel, kidneys, bladder and gall bladder which increases with time after injection, and it is reported to be generally present by 24hrs after injection. It is not seen normally in 24hr In-lll leucocyte scans (ILLS). Therefore the ability of TLLS to replace 24hr ILLS for detecting intra-abdeminal sepsis (IAS) will depend in part on the degree of this false positive uptake in earlier abdominal images (e.g. 4hr). 35 patients were investigated with simultaneous TLLS and ILLS. (Table I)
IAS excluded (n=24) IAS confirmed (n=ll)
TLLS (4hr) +re -re
ILLS (24hr) +re -ve
8 ii
i ii
16 0
23 0
8 of the abnormal ILLS were also abnormal at 4hr. The sensitivities of the 4hr TLLS and the 24hr ILLS were both 100%, but the specificity of" the former (67%) was less than for the latter (96%). It was concluded that despite its high sensitivity, the significant number of false positive 4hr TLLS would hinder an accurate interpretation. Imaging earlier than 4hr warrants further investigation. Therefore, even though 4hr TLLS offers a more convenient technique than ILLS, and yields a lower radiation dose, the latter should remain the method for routine detection of IAS.
Berrocal.
Spain
The p u r p o s e of this p a p e r is to e v a l u a t e lllIna n t i m y o s i n - F a b imaging for the d i a g n o s i s of rej e c t i o n after c a r d i a c t r a n s p l a n t a t i o n (CT). M A T E R I A L A N D METHOD~: W e h a v e s t u d i e d 21 pat i e n t s d i v i d e d into t h r e e groups: I, 7 patients with m y o c a r d i a l scans (MS) e v e r y 15 days for 2 months; II, 7 p a t i e n t s w i t h a single MS one y e a r after CT; III, control group. Antimyosin scan and e n d o m y o c a r d i a l b i o p s y were performed in a p e r i o d of less than 24 h. MS were ob~$ned 24 and 48 h after i n j e c t i o n of 2 mCi of --In-antimyosin-Fab. H e a r t u p t a k e was quantified by c o m p a r i s o n w i t h lung, liver and skeletal activity. RESULTS: The normal h e a r t / l u n g (H/L) activity ratio in control p a t i e n t s was <1.2±0.2 at 48 h. This v a l u e was 1.65±0.23 in p a t i e n t s w i t h CT w i t h o u t s u s p i c i o n of acute r e j e c t i o n and 1.9± 0.32 in p a t i e n t s with acute rejection. After follow-up of 9-12 months, the normal v a l u e s in CT p a t i e n t s were 1.43±0.18. CONCLUSIONS: The m e t h o d is useful for the det e c t i o n of c a r d i a c r e j e c t i o n after CT. Its real v a l u e is not an i s o l a t e d h i g h measurement, but its e v o l u t i v e comparison. In only 1 pat i e n t w i t h a high H / L ratio, endomyocardial b i o p s y showed no sign of a c u t e rejection.
P.J. MOUNTFORD, A.G. KETTLE AND A.J. COAKLEY
Department of Nuclear Medicine, Kent & Canterbury Hospital, Canterbury,Kent CT1 3NG, U.K.
M.J.
I I I I N - A N T I M Y O S I N - F a b IMAGING. D I A G N O S I S OF REJECTION AFTER CARDIAC TRANSPLANT
612
611
l.Castej6n,
552
614
613 G.Petrscoa ~ o ,
A.Bcr~o, L.V:igLiarn]i, S.M:xk~ °
Ol~clear ~ Dept. S. GIOVANNI ROT(~KD (E})
Oa~c~irnlar.D~0t. ITALY
RAD]II~JG~I~ E V ~ OF A[DIIC~ Td~ MLUGXETA~ ~ tried to evaluate the dmirsge Rmcti~ of the a~itory tube using a radioactive tmoer released in the midile ear ~ n t ~ c me~brane w~s dimaJpted in c ~ t ~ e r o s i s . ( ~ 1974).About 0.05 ml of 99mTc E~g-M~A(1850 EBq)~ze released in the ,~M1e ear via a smut1 m ~ ' t e r cmr'~-,ted ~ a miczoi~,~x~m otcscqaic eautrol a m ckCmctiea e q u i ~ included an electronically z0mmd ~mma with a ~ p~pose ~allel hole m]]~m~r. Om~mr~m assisted acquisitim ~ perfb~ed by stoMrg IN' frm~s for 30 ~.20
~atiauts Dave beau ~ i e d , 11 male and 9 f~male, agirg 14 to 65. I~ t~o ~ m t i ~ the test ~es repeated in the smme ear, to assess r e ~ i l i t y . Patiauts wa~ lyirg supine ~ith thair heed in a p~oec mould. A r i ~ ¢r left lateral view ~ s cbtairmd, in c ~ to bare the tubarie ~ p e ~ e u l a r to the cmm~afield. view provides the best viaa]i~tica of the p h a r ~ a n i e t~be. ~ ~s m ~o~lar ~ proomsirg o U ~ ~ visual one.A transit time f~m middle ear to ~ d ~ c t ~ ~han 10 ~ms dmerved in all ~atiants with maintained active ~l~y ~ . In 3 ~atie~ts the~ w a ~ no c ~ in activity ~mitiea drirg the test. In the~ ~atiauts t~me ~as an acute inflsmmarian of the midile ear.~ ~ave ~ n ~ that tubsric clearance is an
active lxeoess (a ci-ange in head position does not atTect t r a n s i t time). ~hen acute f l o ~ s is present the med-snical abstacle may cause the om~lete irhibitien of the clearance. ~ think that radicsotopic evaluation could provid~ a rel~shle tool in a s s e s ~ ~ilim~y ftmction of the l i ~ t ) m p m ~ i c tube to p ~ c t I ~ ftmction ~ovemaut after middle ear r e s t i v e ar~.
615 A. Bockisch, A. Hotze, W. RNther*, F. M~ller*, B. Briele, H.-J Biersack, Dept. Nucl. Med., Dept. Orthop., Univ. Bonn, W. Germany
IDENTIFICATION OF ACTIVE I ~ T O R Y DISEASES OF ThE VERTEBRAL COLUMN BY SCIRTIGRAPHIC SUBTRACTION TECHBIQUE~.
In leukocyte scans spondylitis, usually appears cold since the destructed bone marrow does not accumulate leukocytes. The differentiation between active inflammatory disease and residual state is in many cases thus not possible. The RES seeking nanocolloid, however, is also known to accumulate in inflammation. Assuming that leukocytes are specific for inflammation and the nanocolloid ms a Specific RES marker, we performed subtraction studies using both agents. The leukocyte study was initially performed 24h after i.v. administration of 550 MBq Tc99m-labelled anti-granuloeyte-antibody. The nanocolloid study was added 30 min after the leucocyte study without moving the patient in between. The normalized nanocolloid scan was subtracted from the leukocyte scan by means of a computer program. Computer assisted subtraction scans were considered positive for inflammation when an increased activitY was found at the site of the cold lesion on the original leukocyte study. In studies with 11 patients with questionable active spondylitis, 5 subtraction scans were true positive, 4 true negative, and 2 case false negative. The scintigraphic findings were substantiated by surgery, biopsy, microbiological studies or clinical course. Conclusion: These preliminary data illustrate that this new technique might be helpful to overcome the well known ~roblem in diagosing infection of the vertebral column.
C.Martinez-Duncker, I.Carri6, Ll. BernA, J.Verg4, M.Gurgui, J.L.Barrio, V.Ortega.
M.Estorch,
Hospital de Sant Pau, Barcelona. ~9~'TC-ANTIGRANULOCYTE MONOCLONAL ANTIBODY (BW 250/183) TO DETECT INFECTION SITES. Twenty-four patients with suspected infectious disease were studied with Antigranulocyte antibody (AGMoAb). Labeling efficiency of the preparation at 4 and 24 hrs was >95% and >85%. Planar images were obtained 4 and 24 hrs after i.v. inj. of 0.i-0.5 mg of AGMoAb. Confirmation was obtained on 23 sites by surgery, bacteriological studies and clinical outcome. Bone Vascular Abscesses l
Scan:
FD
+ :
+ 66*)
1
0
5(*)[
I
+
+
l [
1 •
0
2
2(~)
0
3
0
3
I FD: Final Diagnosis. (*): in 3/11 additional information regarding bone marrow viability was obtained. (&): Cold images corresponding to encapsulated abscesses were seen. The method allowed detection of 1 unsuspected pneumonia. All positive studies showed increased local uptake at 4 hrs; images at 24 hrs improved contrast in all cases due to reduction in blood pool activity. In conclusion, AGMoAb scintigraphy provides a suitable method to detect infection sites.
616 M. A. Antar, D.M. Douglas, R.A. Rembish, J.C. Russell, D. Bandyopandyay, S. Hoory, and D.K. Das.
V.A. Medical Center, Newington, CT; Univ. of Conn. Health Center, Farmington, CT. U.S.A. ~-SCINTIGRAPHY OF In-lll POLYMORPHONUCLEAR LEEIKOCYTES INFLUX DURING WOUND HEALING: INHIBITORY EFFECT OF IBUPROFEN AND ALCIDE. During wound healing, there is a massive influx of polymorphonuclear leukocytes (PMNs) which produce superoxide radicals as part of the phagocytic response. The influx of In-lll labeled PMNs was studied in an in vivo rabbit model. Three pair of parallel wounds were created surgically in each rabbit. Each pair of wounds was topically treated in a different manner: Alcide, an antimicrobial and antiflammatory compound, was applied to the first pair of wounds (Group i); ibuprofen, a nonsteroidal anti-inflammatory agent, was used to treat the second pair of wounds (Group ii); and the third pair of wounds lwas treated with saline and served as a control group (Group iii). ~'-scintigraphy using In-lll labeled PMNs, tissue radioactivity counting, and biochemical and morphologic examinations were performed at day i, 3 and 6. }~ximum PMN influx was demonstrated scintigraphically and by tissue counting at day 1 and the least influx at day 6 (7.165 + 1.21 and 0.007 + 0.00?% of injected dose/gm Itissue respectively. Both alcide and ibuprofen markedly inhibited In-lll PMNs influx from 7.165 + 1.12% (control at day i) to 0.011 + 0.005 and 0.020 -+ 0.010% respectively. These results correlated well with the concentration of malondialdehyde and conjugated diene formation in the wound. The findings suggest that max/nnmn influx of PMNs and in turn free radical production occurs during the early period of wound healing process and that inhibition lof PMN influx and generation of lipid peroxide can be [achieved by alcide and ibuDrofen.
553
618
617 M. Liberatore*, E. Di Rocco*,M. Clemente*,F. L. Rizzo**, A. Centi Colella*
Speziale**,
S.ZaboriI, R.BerberichI, C.Blum2, E.OberhausenI I
*Dept.Experimental Medicine,Sect. Nuclear Medicine; ** Chair of Vascular Surgery; University "La Sapienza", Rome, Italy A COMPARISON BEq34EEN lll-ln-Tropolone AND 99m-Tc-HMPAO LABELED LEUKOCYTES SCANS IN THE STUDY OF ARTERLAi PROSTHETIC GRAFT INFECTIONS. Prosthetic vascular graft infection is a severe complication of vascular surgery. Because of the insidious onset and clinical course an early and accurate diagnosis of graft infections .may be difficult, lll-In and, more recently, 99m-T¢-HMPAO labeled leukocytes seem to be the most sensitive diagnostic methods. Aim of this work is to co_~mpare the clincal usefulness of these tracers. 36 patients with suspected graft infection were studied with labeled white cell scan: 20 (14 aortofemoral, 4 iliacofemoral, 2J axillofemoral grafts) using 99m-Tc-HMPAO and 16 (7 ~ aortofemoral, 1 axillopepliteal, 2 axillofemoral, 1 aorto-iliac grafts) using lll-In-Tropolone. Each patient underwent surgery: the removed prosthetic graft were submitted to bacteriological and coltural examinations. The diagnostic accuracy of the procedures is sho~m in the following table: lll-In-Tropolone TP 8
TN 3
FP 2
99~-Tc-HMPAO FN 3
TP I0
TN 8
FP 1
FN 1
pAbtezlung for Nuklearmedizin -Nephrologische Abteilung, Innere Medizin UniversitAt dee Saarlandes D-6650 Homburg/Saar; W.-Germany IMMUNOSCINTIGRAPHY IN THE DIAGNOSISOF ACUTE AND CHRONIC RENAL INFLAMMATORYPROCESSES D i a g n o s i s o f a c u t e and c h r o n i c p y e l o n e p h r i t i s by means of clinical, radiological and chemical methods often is considerably difficult. The aim of this study was to investigate the diagnostic value of immunoscintigraphy in detection of renal inflammatory processes. We investigated 10 patients with acute and chronic pyelonephritis using Tc-99m labelled anti-granulocyte MAB BW 250/183 (Behr±ng-WerkelMarburg, W.-Germany). 0,74 GBq Tc-g9m labelled MAR were injected intravenously. Immediately after injection, after 5 h and 20 h planar scintigrams as well as dual channel SPECT studies including weighted scatter co~ection were performed. All 10 patients were scintigraphically positive. In 8 of these patients, scintigraphic results were in good conclusion with clinical, biochemical and radinlogical findings. In 2 cases radioiogical and biochemical methods failed in indicating an inflammatory renal process. Clinical course, however, proved the presence of chronic pyelonephritis. Actual results of the study indicate immunoscintigraphy using anti-granulocyte MAB to be a valuable tool in the diagnosis of acute and chronic inflammatory renal processes.
In conclusion 99m-Tc-HMPAO leukocytes appear to be more useful than lll-In-Tropelone leukocytes in the diagnosis iof vascular graft infection.
I n some cases i m m u n o s c i n t i g r a p h y was t h e onZy method which could r e v e a l a chronic p y e l o n e p h r i t i s .
620
619 I BANZO,
CARNAL,
JM C A R R I L
N.V.Budihna*, M.Milcinski*, J.Hebede** University Clinical Center, Zaloska 7, 61000 Ljubljana, YUGOSLAVIA
Medicina Nuclear. Hospital Nacional Valdecilla. Radiologla y Medicina Fisica. Facultad Medicina Santander. Espa~a ~ 7
~
OF ~
* Dept. Nucl. Med., ** Traumatol. Dept.
CHE~T IN I]~E EVAII]ATION OF I{[V (+) P A ~
Patients with acquired inmmodeficiency syndrome (AIDS) are predisposed to a wide variety of opportunistic infections. Several reports ,have been made on the utility of Ga67 scan in the evaluation of patients with AIDS or AIDS-related complex (AgC). Wereviewed our experience with Ga67 scan of the chest in the diagnostic of lung cemplications in ,r~-V(+) patients presenting with fever end respiratory sympt~ns. The study includes 22 HIV(+) patients, 9 ARC and 13 ~ (20 males and 2 females, mean age 28 years). Of the ~ patients, 18 weredrug addicts, 2 b~nsexnals end 2 .he~philics. Anterior and posterior ~lews of the chest were obtained 48-72 hours after IV injection of 185 ~ q of Ga67-citr~ate. Information density of 1000 counts/era2 was obtained in liver. Four patterns of Ga67 uptake were identified: diffuse lung uptake, lymph nodes and ]ung uptake, acc~nulation of C~67 in lymph nodes groups (axillary, cervical, mediestinal), and nornml. ~ese patterns were compared to chest rddiographs (PO0 end final diagnoses. 11 scans showed diffuse lung uptake. In I0 of ii patients, pnem~cystis carinii pneumonia (FCP) was diagnosed, 4 of them bad negative RX. The other patient had a Gram(-) pnelmmuia. L~nph nodes and lung acctmmlation was shooed in 2 patients with pulmonary mycobacteriom tuberculosis (3~B). Both patients had negative ZX. Abnor~l uptake in lymph nodes was found in 6 ~ , 2 of th~n with negative ~X. The normal Ga67 pattern was seen in 3 patients (1 ~TB and 1 herpex sJ~nple pneumonia with P~X positive, end I salmonellosis with ~X aegative). In conclusian, Ga67 lung scan was useful in the management of T{IV(+) patients. The extension and severity of puimnary involvement was better detected by Ga67 scan than by RX. Several Ga67 patterns were observed. Diffuse lung uptake was detected most cormonly in PfP,, but also in others pulmonary entities. Uptake in ]ymph nodes ~ ¢ a s associated to MIB in all cases.
HETEROTOPIC SPLENIC AUTOTRANSPLANT. LONG-TERM FOLLOWUP Heterotopic splenic autotransplant (HSA), usually to greater omentum, is used to preserve splenic function after splenic rupture. The long-term survival of HSA was not extensively studied. The aim of our study was to evaluate the long-term survival rate of HSA and its possible uncontroled growth. ~n 13 poiyLrauma~.ised pa(ients with spieen rup~u,-e, HSA to g,ea~.eJ"oli~uF,turn was implanted. Patients were 5 to 38 years old (mean 21,3). Splenic function in early (1 to 7 months) and late (3 to 4.5 years) stage after operation was tested by selective splenic scintigraphy using heat damaged 99m Tc labeled autologous erytrocytes. Scanning was performed on both occasions. The splenic surface area was calculated in anterior projection using a standard reference area. The shapes of ectopic transplants were compared on both scans. The uptake of spherocytes in HSA was graded regarding the liver uptake. The average size of HSA was 28.2 +-14.7 cm2 in eady and 44.1 +- 14.3 cm2 in late examination. The difference is significant ( 0.5 < p < t % ). The shape of HSA was similar on both scans. Only three pts had some small additional splenic tissue on later scans maybe not large enough to be detected on first examination. The fun(:ion of HSA in terms of intensity of tracer accumulation was better on long-term followup scans. No patient had any serious infection, what probably signifies good function of preserved splenic tissue. We conclude that HSAto greater omentum is a reliable method to preserve splenic function after traumatic splenic rupture. Long-term follow-up proved survival of all autotransplants. Increase of surface area and improvement of HSA function without important additional splenosis was observed.
554
621 Y. RICART, D. PODZAMCZER, J. MARTIN-COMIN, D. BONNIN, F. BOLAO, E. URIBE and M. RAMOS. Servei de Medicina Nuclear. Hospita] U n i v e r s i t a r i de B e l l v i t g e . Barcelona. SPAIN,
USEFULNESS OF 67 Ga-CITRATE SCINTIGRAPHY IN THE DIAGNOSIS OF LYMPHADENOPATHY HIV-INFECTED PATIENTS. The aim of the work is to evaluate the usefulness of 67-Ga citrate scintigraphy (Ga scan) ~n the differential diagnosis of enlarged lymph nodes in HIV-infected symptomatic patients. We have studied 19 HIV-postive patients (15 drug addicts and 4 homosexuals) with fever and/or weight loss and loca]ized or ge~era]ized lymphadenopathy.ThB Ga-scan was performed 72 hours a f t e r the intravenous i n j e c t i o n of 3-4 mCi of 67 Ga-citrate, The following regions were scanned in each patient: lungs, a x i l I a r y , supraclavicular and cervical node areas. Subsequently a lymph node biopsy was done in a l l patients. Resu]ts: In 9 out of 10 patients with normal Ga scan the biopsy showed f o l l i c u l a r hyperplasia, in the remainder i t showed a Kaposi's sarcoma. The Ga-scan showed increased uptake in one or more lymph node areas in 9 patients (5of them showed also mediastinal uptake). The biopsies demonstrated ganglionar micobacteriosis in 8 cases (7 M.tuberculosis and I non-specificied atypical micobacteria) and in the remaining patient showed f o l l i c u l a r hyperplasia. In summary the Ga-scan may be usefu]l to c l a s s i f y HIVinfected patients with c o n s t i t u t i o n a l symptons and ]ymphadenopathy. A p o s i t i v e scan strongly suggest mycobacter i a I infection while a negative scan probably represents follycular hyperplasia.
623 K.H. Winker, P. Reuland, U. Felon, S. Weller
Trauma Center and Department of Nuclear Medicine~ University of T0bingen, FRG PATHOLOGIC LEUCOCYTE SCANS WITH THE MONOCLONAL ANTIBODY (MAb) BW 250/183 IN THE MUSCULOSKELETAL SYSTEM: DO THEY ALL REQUIRE SURGICAL INTERVENTION? Promising results in the detection of a variety of infectious complications with the Tc-99m-labelled monoclonal anti-granulocytes antibody 8W 250/183 have been reported. In the Trauma Center, Univ. of T~bingen, FRG, this method is applied since 8/88 in order to evaluate its clinical value in patients with a suspicion of bacterial infection after orthopedic surgery . The general experience, based on 80 MAb-scans, so far, was, that a pathologic uptake in the area of concern indicates an active infection which necessitates an immediate surgical re-intervention in order to avoid a chronioal infectious status. Up to now (3/89) we observed 9 out of the 80 patients with a clinically unambiguous infection and a pathologic MAb-scan, who, however, did not need undergo surgery because of spontaneous recovery in the following days; this subgroup whose scans could be considered as true positive regarding the unambiguous infection, but as false positive regarding the therapeutic consequences, was termed IYON (infection: yes; o_peration:~o)-group. In conclusion, pathologic MAD BE 250/185 scans in the museuloskeletal system after orthopedic surgery indicate active infection which, in general, necessitates surgical reintervention. A small subgroup (IYON) of patients with a pathologic scan but without any therapeutic need could be identified. The clinician should be aware of these patients in the oroeess of his therapeutic decisions.
622 I__t. B r a n d h o r s t * , G. H ~ r * *
S.
Staczewski+,
A.
Ganser+,
*Institute for Diagnostic Imaging, Frankfurt; +Ambulance for Infectious Diseases, University Hospital Frankfurt;*giv. of General Nuclear Medicine, University Hospital Frankfurt; F.R.G. THE STATIC LIVER (L), S P L E E N (S) A N D BONE MARROW (BM) SCANNING IN H I V P O S I T I V E PATIENTS USING A ONE-STEP METHOD: FIRST RESULTS. T h e L, S a n d B M s c i n t i g r a p h y is w e l l k n o w n as a good, noninvasive, one-step tool to evaluate the BM status and the rethiculoendothelial portion of BM, L and S as w e l l as t h e s i z e a n d location o f L a n d S. F u r t h e r m o r e it is a s i m p l e procedure to f i n d out focal lesions d u e to opportunistic t u m o r s a n d / or i n f e c t i o n s in a l l these organs. 762 regional scans were performed i n 46 p t s . (43 m a l e , 3 female, m.a. 36 yrs.) w i t h v a r i o u s stages of the disease. 23/46 pts. were suffering from Kaposi sarcoma (KS) a n d / o r Pneumocystis carinii Pneumonia (PEP). T c - 9 9 m labeled nanocoll~id (5.55 M B q / k g b o d y w e i g h t ) s e r v e d as radiotracer f o r t h e scans. In 2 1 / 4 6 p t s . B M , L a n d S s c a n s w e r e a b n o r m a l . 9 pts. with L A S as w e l l as 3 p t s . w i t h full AIDS had a normal BM, L and S scan. 12 pts. showed a BM extension u p to t h e k n e e s and an abnormal liver scintigraphy but normal spleen scan. I female pt. w i t h K S s h o w e d B M e x t e n s i o n u p to t h e a n k l e s with a normal liver b u t an abnormal s p l e e n image. F o c a l d e f e c t s w e r e s h o w n ! o n l y in the b o n e m a r r o w s c a n s ( 7 7 / 4 6 pts.), In our opinion BM, L and S scans demonstrate a clear involvement in H I V i n f e c t i o n ; obviously Ithe r o l e of the m a c r o p h a g e functional d e f e c t is still the most interesting p o i n t today.
624 Ruth Hardoff,Nechama Uri, Sara Gips, Avi h~a1-t~e r ~leyer.
Front,
Departments of Nuclear ~{edicine and of Otolaryngology, Lady Davis Carmel llospital, Haifa, Israel. QUANTITATIVE BONE AND Ga-67 SCINTIGRAPHY IN THE DIFFERENTIATION OF NECROTIZING EXTERNAL OTITIS FROM SEVERE EXTERNAL OTITIS. The diagnosis of necrotizing external otitis (NEd) lacks objective criteria and is often made on clinical impression only. Qualitative Tc-99m bone scintigraphy using phosphate compounds, as well as Ga-67 scintigraphy were described to be helpful in making the diagnosis, however, claimed to be non specific. In order to improve their contribution to the diagnosis of NEd, quantitative Te-99m ~DP bone and Ga-67 scintigraphy were performed in 8 patients with NEd and in 20 patients with severe external otitis (SEO). Lesion to non-lesion ratios for bone seintigraphy were 1.67~0.16 in patients with NEd and 1.08~0.09 Jn patients with SEO (~<0.001). Lesion to nonlesion ratios for Ga-67 were 1.3S-0.24 in NEd patients and 1.05~0.03 in SEO patients (p
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625
J. U. M. C A L E G A R O
E. F. GOMES,
CARVALHO,
SALINAS,
M.
L.
F. G.
E.
A.C. M a c e d o R.
COSTA,
de
BRAGA,FJHN; Rivitti,MCM; Abreu, SM; Belda Jr,W; Cuce,LC. Centre of Nuclear Medicine and Dermatology Service, Hospital das Cl{nicas, University of Sao Paulo School of Medicine. Sao Paulo, SP, Brazil.
D. M.
PEREIRA.
Hospital sil.
de Base - F.H.D.F.
67 GA IN BIASTOMYOgSIS:
Bras~lia,
DF - Bra-
OUR ~ W C E
67 Ga imaging was performed in 8 treated and 6 untreated patients with doctnnented South American Blastomycosis (Paracoceidioidomycosis) confirmed by histology. All patients were male, aged 20-68 years with evolution of the disease from 2 months to 18 years. Serologic tests were performed in 12 patients. 67 Ga images was correlated with X-ray in all patients. The images with 67 Ga showed svidency of le~ions ~nsuspacted by" clinical examination and missed by X-ray in 9 patients: parotid gland in 4 patients; testis in 2 patients; tone in 1 patient; mediastinal lymphnode involvment in one; cervical lymphnode involvment (deep cervical lymphnode causing obstruction of thoracic duct) in one patient. On the other hand, two cases with clinically diagnosed tegtm~ntar lesions particulary of the oro-nasal region were mot demonstrated on 67 Ga images. Follow-up studies after specific therapy in four patients demonstrated concordance between X-ray and 67 Ga in 2 patients with pulmonary involvment; in the others two with lymphatic involvment, showed normalization in 67 Ga images with persistence in serologic studies. This initial evaluation demonstrated that 67 Ga imaging is a useful tool for detection of suspected and, more importantly, unsuspected lesions of paracoccidioidomycosis and to evaluate the response of the disease to specific therapy.
DOUBLE SCINTIGRAI~IC EVAI/JATION WITH GALLIUM-67 (Ga-67) AND BONE STUDY (BS) IN MYCETOMAS: A POSSIBILITY OF THERAPY CHECKING. The purpose of the study was to evaluate the behaviour of Ga-67 and BS in this mycosis and determine their roles in the disease. Four patients (pts) with biopsy proved zygomycosis were studied with Ga-67 whole-body scintigraphy (seint.) performed 24 and 48 hr after the IV injection of iii MBq of Ga-67 citrate and S-phase BS with 99mTe-MDP according to the literature routine. Three of them had active disease and one was at the end of efficient treatment. The 3 with active disease hadboth studies abnormal: Ga-67 showed importsnt focal uptake in the affected areas (feet); the blood flow and the equillibrit~n phases of BS showed importantly increased blood flow for the feet and the late immages had important and focal uptake of 99mTo-MDP in the same areas, both in bone and soft tissues. The observed pattern of Ga-67 and BS was the same as noted for aeeute osteomyelitis associated to eellulitis. The 4th pt was at the end of efficient therapy and showed only small clinical findings. In this ease, Ga-67 showed just a faint focal uptake in the lesion and BS was almost normal: the blood flow and the equillibriun phases were normal and the late inmages presented only with a very faint uptake of the radiophsrmaeeutieal. It is possible that a double study with Ga-67 and S-phase bone .seintigraphy be a good way to evaluate the disease extent and the therapy efficacy in this rare mycosis.
627 J. DELFORGE, K. NAKAJIMA, J.M. VALLOIS*, C. CROUZEL, C. LOC'H, J. CAYLA, J.P. LAN~ON, B. MAZIERE, D. FOURNIER, M. CROUZEL, B.M. MAZOYER, A. SYROTA.
Service Hospitalier Fr6d~ric Joliet, CEA, 91~06 Orsay, France. * Inserm []18, H~pital Claude Bernard, 75108 Paris, France
628 Wolfgang E s c h n e r and Heribert Lulg Abteilung Nuklearmedizin Zentrum Radiologie der Universit~tt GSttingen D-3400 GSttingen, FRG ITERATIVE 3-DIMENSIONAL SPECT RECONSTRUCTION
A Q U A N T I T A T I V E M O D E L F O R P E T S T U D Y OF T H E I N T E R A C T I O N S B E T W E E N C G P 12177 A N D /%ADRENERGIC RECEPTORS . We have investigated the possibility of modelling the interactions of the C-11 labelled CGP with heart fl-adrenergic receptors from Positron Emission Tomography data obtained with a single injection in a dog. Using the plasma concentration measured by arterial samples as input function, we have tested M1 the classical models having less than 5 parameters. However, with the linear models the fits are never satisfying: these simple models cannot explain why the PET concentration is consl~ant or very hLde decreasing during the period L7min-60min] wherea~ the input function is divided by three. The only good fit was obtained with a non-linear model in which the receptor density was such that all receptors would be occupied 7 minutes after the initial tracer injection. This explanation seeming unacceptable, we concluded that we were using a wrong input function. Over-pressure-thin-layer-chromatography showed that the labelled CGP metabolites appear very quickly, the fraction of unmetabolized CGP being ranged from 10% to 15% at 5 min and less than 5% at 20 min. Using the metabolite corrected input function denoted by ](t), we obtain a satisfying fit with the threeparameter model: free ligand arrives from the capillary lumen with a flux klf(t), this free ligand can either bind directly to a free receptor site (parameter k~) or escape with the rate constant k2. The identified values are: k1=0.26 min -1, k2=0.11 min -z and k3=0.25 min -1. This modelization assumes that the metabolized CGP does not enter in the heart tissue. In the rat experiment, a metabolite analysis gave results in agreement with this hypothesis.
Our m u l t i p l i c a t i v e i t e r a t i v e SPECT r e c o n s t r u c t i o n scheme / 1 / aims at s i m u l a t i n g t h e s c i n t i g r a p h i c imaging p r o c e s s m a t h e m a t i c a l l y in order to determine t h e s o u r c e d i s t r i b u t i o n which f i t s t h e m e a s u r e d d a t a b e s t . It was s h o w n t h a t s p a t i a l r e s o l u t i o n can be i n c r e a s e d w i t h in single, i n d e p e n d e n t l y r e c o n s t r u c t e d t r a n s v e r s a l s l i c e s / 1 / . However, due to the i s o t r o p y of gamma e m i s s s i o n and limited r e s o l u t i o n of t h e imaging device t h e r e are i n t e r r e l a t i o n s h i p s b e t w e e n d a t a in n e i g h b o u r i n g rows of t h e s c i n t i g r a p h i c m a t r i c e s which call for a t r u e 3-D r e c o n s t r u c t i o n . We h a v e t h e r e f o r e e x t e n d e d our concept of r e s o l u t i o n e n h a n c e m e n t to t h e t h i r d s p a t i a l direction (i.e. t h e direction of t h e gamma camera axis of r o t a t i o n ) . Additionally, t h e d i s t a n c e d e p e n d a n c y of d e t e c t o r r e s o l u t i o n is now accounted for. This d e v e l o p m e n t r e s u l t s in a d i s t i n c t i n c r e a s e in image q u a l i t y . As t h e algorithm no longer computes i n d e p e n d e n t slices b u t r a t h e r a 3-D object volume, p l a n e s of a n y o r i e n t a t i o n (coronal, s a g i t t a l , and oblique) are of high r e s o lution. Dramatic i m p r o v e m e n t s h a v e been e n c o u n t e r e d in 99mTc-MIBI myocardial p e r f u s i o n imaging where long and s h o r t axis c u t s d i s p l a y an image q u a l i t y u n s e e n before. The diagnostic b e n e f i t of t h e new t e c h n i q u e will be d e m o n s t r a t e d . Luig H, E s c h n e r W, Biihre M, Voth E, Nolte G : Eine i t e r a t i v e Strategie zur Bestimmung der Q u e l l v e r t e i lung bei der E i n z e l p h o t o n e n - T o m o g r a p h i e mit einer r e t i e t e n d o n Gammakamera (SPECT). Nucl.-Med. 27 (1988), 140
556
629 N. TZOURIO, M. JOLIOT, B.M. MAZOYER, C. RAYNAUD. J.P. LORRE, A. SYROTA.
630 M. B~hre, P. Vieregge*, W. Eschner**, H. Luig** I n s t i t u t e of Nuclear Medicine, Clinic of Neurology (*),
Service Hospitalier Frederic Joliot, CEA, Orsay,
POSITIONING OF CORTICAL ROI'S ON S P E C T IMAGES: A CRITICAL STUDY OF THE ISOCONTOUR METHOD. The placement of cortical regions of interest (ROI) on regiona cerebral blood flow (rCBF) S P E C T images is a critical step in data analysis, often performed using isocontour as the external edge ot the cortex. We have investigated the relationship between anteroposterior diameter (APD) obtained with the isocontour method and a true anatomical measurement provided by teleradiography.i 14 normal subjehts (mean age: 20.7 yrs) had 3 rCBF examina-i tion by S P E C T and lS3Xe (TOMOMATIC 564). They were positionned using the orbito-meatal line as reference. For each study, i we computed on each of 4 CBF images, the antero-posterior CBF profile, the slice mean CBF value (mCBF) arid rCBF in 3cm 2 area ROI's located medially on the anterior and posterior cortex. APD was measured for each slice on the teleradiography. An isocontouz value was then computed by adjusting this APD to the corresponding rCBF profile. The isocontour mean value was found to be 28.1 4- 3.4 m l / 1 0 0 g / m i n (mean/=sd) and 52 4- 9 % of the slice mCBF. Using analysis of variance, the isocontour value was found to be independent of the slice level and did not show significant i changes from one study to another. It was neither correlated to the slice m C B F nor to the brain size. It was also found independent of b o t h cortical rCBF values. However, the large between subjects variability of APD isocontour values makes it improper as a reference for cortical ROI positioning, rendering necessary the superposition of S P E C T rCBF images with MRI or CT data.
631
J.L. Lear. M.M. Manco-Johnson, A. J. Feyerabend, G. Anderson, D. Robinson. Division of Nuclear Medicine (A034), University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262 USA
Medical University of Lfibeck, D-2400 Ldbeck and Division of Nuclear Medicine, University of GSttingen (**), D-3400 G6ttingen, F R G HIGH R E S O L U T I O N ggMTC-HMPAO BRAIN T O M O G R A P H Y USING MULTIPLICATIVE ITERATIVE SPECT R E C O N S T R U C T I O N (MISR) This study reports first clinical results of highresolution brain SPECT tomograms obtained by the iterative reconstruction strategy which was presented earlier by our group. In addition, the findings represent a first approach to the clinical relevance of this technique in cases with cerebrovascular disease. Five in-patients out of a larger series of neurologically ill patients investigated with 99mTc-HMPAO brain SPECT were selected. In four cases with defined brain leslons and in one with Binswanger's disease as an example for a more diffuse pattern of brain hypoperfusion, scintigrams of 128 x 128 matrices were acquired at 60 angles in a 360 degrees rotation with a preset time of 30 seconds each. Brain tomograms reconstructed iteratively in 128 x 128 matrices were compared with those of filtered backprojection. Data obtained demonstrate superior definition and resolution of brain and skull outline as well as of defined lesions in the iterative]y reconstructed tomograms. In concordance, in the case with non-circumscribed hypoperfusion the MISR-tomograms showed a more homogeneous pattern of tracer distribution while filtered backprojection images displayed an irregular pattern which 'could falsely suggest multi-infarct dementia. Conclusion: The results indicate a distinct increase in clinical information of brain tomograms reconstructed with the MISR-teehnique.
632 L. Mortelmans, J. M. De RoD
Nuyts,
P. Suetens, A. Oosterlinck,
U.Z. Gasthuisberg, Leuven, Belgium
INTEGRATED SERVICES DIGITAL NETWORK (ISDN): A P P L I C A T I O N IN N U C L E A R M E D I C I N E I M A G E TELECOMMUNICATION Remote image transmission and interpretation has been limited by slow transmission rates of telephone-based systems and by very high costs of alternative systems. A nuclear medicine image file contams approximately 1 to 5 million bits of information. The fastest personal computer modems available for use on normal phone lines can achieve data transmission rates of approximately 10,000 bits per second (baud), so transmission times per image range from 2 to 10 minutes. While tolerable, these times are impractical for routine use in situations requiring the rapid transmission of more than a few images. Systems which use earth orbiting satellites and ground receiving stations as communication ports operate at 400,000 baud but are very expensive. Clearly, a technology which could substantially increase transmission rates above those of present modems while maintaining the low cost and easy access of normal phone lines would be of enormous benefit. We developed a personal computer-based, image digitization and transmission system using a solid state CCD scanner and integrated services digital network (ISDN), a technology under development for ultra-high speed data transmission over normal phone lines. Using the system, we digitized 8 x 10 inch nuclear medicine films into 1024 x 1024 pixel images with 256 gray levels and transmitted them from our hospital to a remote review site over 15 miles away. Data rates exceeding 56,000 baud were achieved with nearly perfect accuracy. Present modification of the system hardware and software should increase the data rate to 128,000 baud, a factor of 10 greater than the fastest modems and over 30% the speed of satellite-based systems.
A NEW QUANTITATIVE METHODFOR ANALYSISOF CARDIAC PERFUSION TOMOGRAPHY. A new delineation algorithm for cardiac SPECT images is proposed for the evaluation of infarct size in patients treated with thrombolytic therapy. The tomographic data are reorganized in slices through the long axis of the heart. So, slice selection becomes user independent and three dimensional gradient information is preserved. The endo- and epicardial boundaries are delineated by a minimum cost algorithm, which uses gradient information and a model of l e f t ventricular shape. The valve plane is determined by an i t e r a t i v e least square method. Further data reduction is performed by constructing two polar maps ("Bullseyes") containing the mean countrates o f the l e f t v e n t r i c u l a r wail and the myocardial volume corresponding to each p i x e l . To detect ischaemic and infarcted regions, the actual polar map is compared to a reference image. The program is evaluated with a r t i f i c i a l images and SPECT phantom measurements. The delineation of t h e l e f t v e n t r i c l e is very reproducible and rather noise independent even in infarcted zones. Volume estimation errors for the t o t a l l e f t v e n t r i c l e vary systematically with the point spread function. Without correction, errors of lO to 30% are found. The new method improves conventional approaches by i t s volume information and by i t s delineation method which is user-independent and more accurate e s p e c i a l l y near the apex and the valve plane and in ischaemic or i n f a r c ted zones.
557
634
633 S.F.Dewhurst,S.J.Riggs,AJ.Green,R.HJ.Begent & K.D.Bagshawe
Cancer Research Campaign Laboratories, Depart ment of Medical Oncology, Charing Cross & Westminster Medical School. London W6 8RF. England. ACCURATE QUANTITATION OF latI DISTRIBUTION BY GAMMA CAMERA IMAGING An accurate estimate of the distribution of therapeutic agent is required for the development of targeted therapy of c a n c e r When the agent is radio-labelled (eg with lalt) this distribution can be estimated using a gamma camera. The data has to be acquired by SPET (Single Photon Emission Tomography) rather than planar scanning if it is to be of quantitative value due to the inaccuracies incurred by summing the activity from overlying and underlying tissues into the region of interest. This data is then corrected for Compton scatter by u=ing the du~rl energy windo,^, acquisition technique. Tb, s was verified using an IGE Gemini gamma camera with 400 keV collimator to acquire a set of data from a phantom containing sources with levels of activity similar to those found in human tumours in a background activity which was varied from 0 to 1.2gCi/ml in increments of 0.2. Scatter corrected reconstructions gave accurate estimates of the activity in the sources independant of background activity, whereas both planar scanning and SPET without scatter correction gave overestimates of 290% and 40% respectively. This accuracy of SPET with scatter correction was extended to patient data by comparing the estimated activity with that obtained from a simultaneous blood sample. A coefficient of correlation of 0.955 was ] acheived with 25 data points. A series of time points is required for I cumulative activity measurements and accurate positioning of t h e patient is essential in order that regions of interest (ROI)may be super-I imposed on successive images.There is a problem if the site of int-I erest moves within the patient itself due to normal physiological I processes (e.g. a tumour site located near the stomach or bladder). This can be reduced by careful manipulation of R(DI at each time point. SPET with scatter correction is neccessary to quantify the effici-l ency of targeted therapy. This is being applied in our studies of radioirnmunotherapy to define the radiation dose to normal tissues and to show differences in antibody uptake in tumours between individual and to compare different antibodies.
REFINING FADS CRITERIA OF LEFT VENTRICULAR WALL MOTION ABNORMALITIES.
Factor Analysis of Dynamic Structures (FADS) in equilibrium gated radionuclide ventriculography (RNV) has been presented in 1984 for the diagnosis of wall motion abnormalities (WMA). Some new criteria, based on 5 years experience in 2 institutions, can be proposed to improve the diagnostic efficiency of the method. 53 patients (27 from U o f I, 26 from Beaujon) underwent RNV (LAO VIEW) and biplane eor~trasl venticulogrgphy (CV). 8 were normal and 45 had a coronary artery disease. FADS analysis has been performed according to different modalities. The best results' were obtained by masking the extra ventricular activity and by evaluating the 3 factors display. FADS results were interpreted by taking into account the shape of the factors, their sectorial contribution, the associated factor images, global and regional left ventricular (LV) ejection fraction. An index of agreement between FADS results, Phase Analysis (PA) and CV was computed on a 8 sector basis. We conclude that while FADS is superior for detecting the main pathology (especially hypokinesia) it is markedly superior for detecting extent and location of abnormality, as demonstrated by sectorial agreement index. In general FADS is more sensitive and has a small number of false (+) wtfile PA has a significant number of false (-). Consequently the 2 methods can be considered complementary.
636
635 A. Bockisch, St. Schmidt, P. 0ehr, R. Knopp, H.-J. Biersack. Dept. Nucl. Med., Univ. Bonn, W. Germany
S~TION
F.CAVAILLOLES*, J.P. B A Z I N * * , D. P A V E L * * * , E. O L E A * * * , M. F A R A G G I * * * * , F. F R O U I N * * , R. D I P A O L A * * . * H 6 p . A n t o i n e B ~ c l ~ r e , F. - 9 2 1 4 0 C L A M A R T ; ** INSERM U 6 6 I G R , F. - 9 4 8 0 5 V I L L E J U I F ; *** U n i v e r s i t y of Illinois, C H I C A G O , IL 6 0 6 1 2 U S A ; **** H6p. B e a u j o n , F - 9 2 1 1 0 C L I C I I Y .
OF I M M U N O S C I N T I G ~ B Y
A. Hotze,
COMPUTER CALCULATION.
T h e aim of our computer simulation was to optimize the conditions for immunoscintigrams depending on the individual investigation. The parameters are: radionuclide; kinetics of the radiopharmaeeutical (antibody), localization of the suspected lesion, time of scan, accumulated counts. We therefore measured for a point source located in a water scatter phantom the transmission function for our gamma-camera operated with all available collimators. Homogeneous seintigrams were obtained for various count rates between 50 kcts and 10 Mcts per image, tcm thick sections of all relevant abdominal organs were created and stored in 128x128 pixel matrices. The simulation was calculated as follows: I.) Addition of all organ sections in a plane of given distance to the collimator. The relative organ contributions were obtained from the animal model. A spheric tumor may replace the organ contribution at any place. 2.) Calc. of the contribution of this plane to the scint, by using the measured transmission function, which is interpolated by a cubic spline function. 3.) Summing over all the planes (20 planes for a normal individual). 4.) Cale. of the statistical variance using measured statistical scatter from the homogeneous scintigram. By simulation, we may decide whether a lesion may be visualized in the anterior or the posterior projection best and which is the minimum count rate needed to detect the tumor in a given localization and activity concentration. In addition, the optimal labelling isotope can be selected by simulation calculus. Finally, the simulation can be extended to any scint, technique, for which the relative organ activities are known.
R:....~.~N~kg, G. Bittner, F.D. Maul, O..HSr
Division of Nuclear Medicine, J.W. GoetheUniversity Frankfurt, FRG
A NEW APPROACH TO THE QUANTITATION OF REGIONAL REST FUNCTION DERIVED FROM-GATED MYOCARDIAL EXERCISE PERFUSION (MIBI) IMAGES Tc-99m 2-methoxy i s o b u t y l i s o n i t r i l e (MIBI) as a myocard i a l imaging agent allows ECG gating for wall motion assessment and simultaneous perfusion imaging. DefectsI in exercise myocardial perfusion images stand for stress-induced myocardial ischemia or scars. Gated myocardial scintigraphy represents left ventricular (LV) function at rest. The mismatch between perfusion and function is a measure for exercise-induced ischemia. LV function is assessed by regional systolic wall thickening which is quantitated by the parameter of contraction fraction (CF) as the countrate difference between end systole (ES) and end diastole (ED), normalized to ED counts. We have developed a fully automated computerprogram for wall motion assessment which includes: i) selection of the ED and ES frame; 2) interpolative background subtraction; 3) radial search for the maximal myocardial uptake along each radius and generation of ED- and ES-circumferential profiles; 4) calculation of the CF-profiles. This approacb was tested in i0 patients with myocardial infarction Who also had regional LV ejection fraction by standard analysis of gated-bloodpool images (GBP-EF). The overall correlation between regional GBP-EF and CF was 0.83. Our preliminary results indicate that this method provides a new approach to the quantitation of ventricular function yielding results that correlate well with other methods, which is the basis for combined perfusion-function imaging.
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638
637 A.Z. MIDDELHEIM ANTWERP and St PETERS HOSPITAL BRUSSELS BELGIUM.
COLLIMATOR FOR SPECT : HIGH RESOLUTION (HR) OR ALL PURPOSE (AP) ? The choice of collimator for SPECT studies is an important issue, Indeed, increased measurement accuracy due to improved resolution is always accompanied by a loss of precision due to decreased sensitivity. In order to evaluate the optimal collimator, we compared commercially available AP and HR in combination with smooth and sharp reconstruction filters. Using line phantoms, the HR provided a 20 % improvement in tomografic resolution using a sharp reconstruction filter and 15 % using a smooth filter. Noise measurements were pedor~,,d with a water4illed 15¢n~ diameter, ! 20cm height cylindrical phantom. 64 projections in a 64-64 matrix were acquired and attenuation correction applied. Noise was measured in images reconstructed with a ramp, cosine, Shepp-Logan-Hanning and Parzen filter for activities varying from 30 to 800 Kc/slice. Taking into account the loss of I sensitivity of 40 % for HR, the S/N ratio is advantageous for AP. The combined effect of resolution and noise was studied using a Jaszczak phantom. 16 acquisitions were performed with AP and HR at radii of rotations of 13 and 22 cm, and slice activities varying from 80 to 3200 Kc. Reconstruction was performed with the 4 filters and interpreted by 3 observers. At low activities the results were obviously better with the AP. In brain studies (HMPAO 15 mCi) slices contain approximately 140 Kc with AP and 80 Kc with HR. Data described above indicate 38% noise for the sharpest and 1 ! % for the smoothest tilter with HR, respectively 28 % and 8 % with AP. The Jaszczak acquisitions showed for HR the best detectibility for Parzen.(21 ram) and cosine or SLH (1.8 ram) for AP. Similarly for heart studies (MIB130 mCi) the noise was 21% to 6% for HR and 15% to 6°/, for AP and the resolution was 2 mm better for HR than AP. Observer interpretation of patient studies confirmed our choice of the AP for the brain and HR for the heart. From the phantom data the choice of collimator and reconstruction tilter can be derived for other clinical studies.
PMMCashman, P Broadhurst, A Lahiri, JCW Crawley, J Caunt, EB Raftery
Cardiology Department, Northwick Park Hospital, Watford Road, Harrow, HA1 3UJ, UK NEW PORTABLE BEDSIDE SYSTEM FOR CONTINUOUS MONITORING OF LEFT VENTRICULAR FUNCTION AND ST-SEGMENT LEVEL. A new system (OsD) has been developed for continuous on-line radionuclide monitoring of left ventricular (LV) function over long periods, using 99m-Te blood pool labelling. The system is based on a personal computer and a miniature Csl/photodiode scintillation detector (45 mm dia ; 140 g) attached to the chest by an elastic strap. The computer is an IBM-compatible Olivetti M240, fitted with special-purpose modules for detector and ECG signal processing. ECG-gated time-activity curves can be continuously displayed, with an averaged ECG for ST-segment measurement. 'Acquisition times are selectable from i0-i00 see; at the end of each period the ejection fraction (LVEF), relative volumes, diastolic filling ~arameters ~nd ST-segment level are displayed and also stored on disk for later review. A beat-to-beat LV timeactivity curve can be displayed for monitoring and to assist in detector placement and background estimation. Initial validation was performed in 15 patients undergoing radionuclide ventriculography (RNV) at two stages (30 min and 4-6 hr) of isotope decay. Over a range of 20-78% in LVEF, the mean (SD) difference between CsD and RNV Was 5.6 (7.9)% at 30 min and 4.5 (7.3)% at 4-6 hr. The small size and low cost of the system render it suitable for use in coronary care and intensive care monitoring. The rapid response time allows accurate assessment following acute interventions.
640
639 B.M.W, Tsui, J.L. Hendricks, J.R. Perry, V.L. Interrante, H. Fuchs, S.M. Pizer, and W.H. McCartney.
G.Graf *~, M.Clausen, E.Henze, F.Bitter, W.E.Adam, P.Heidenreich "~
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. University Ulm, Department of Nuclear Medicine Central hospital Augsburg, Institute of Nuclear Medicine"~ THREE-DIMENSIONAL DISPLAY METHODS FOR I~AGE DATA OBTAINED WITH SPECT We investigated various three-dimensional (3D) displa} methods for image data obtained with SPECT. The methods included cine display of reproJection images, 3D display of surface structures of the emission information, and simultaneous 3D display of emission and transmission information obtained with a SPECT system. Reprojection images are less noisy than the acquired projection data and can be obtained at any viewing angle. A 3D surface display of emission data is incapable of depicting deepseated defects. The simultaneous display method is unique in providing simultaneous presentation of anatomical and functional information from the same patient without misregistration problems. Radioactivity distributions were obtained using standard SPECT imaging techniques (lung perfusion and TI-201 SPECT studies). Data for generating 3D anatomical surfaces were acquired using a transmission CT method on a SPECT system. The transmission study provides anatomical information not contained in the emission data. An emission image slice is superimposed on the corresponding transaxial cut-plane through the 3D anatomical surfaces. The resulting 3D model is displayed on a special graphics engine, which allowed interactive selection of the cut-plane and viewing angle. Choice of surface colors, transparency of skin surface, and shadowing is also possible. The simultaneous 3D display technique may be preferrable for SPECT data because it better reveals the relationship of functional defects and anatomical landmarks.
PARAMETRIC GATED SPECT OF THE HEART (PASPECT) A direct way to regional amplitude and phase slices is presented by Fourier transforming gated image sequences of each projection angle (PASPECT). This procedure results in shortening the acquisition time (~20 minutes) and reconstruction process. Statistical significant better slice images come up with the count summing effect of the Fourier algorithm over the RR-intervall of the projection data before reconstruction. These attributes make this procedure applicable in clinical routine. The parametric oblique sine and cosine short axis slices of the left ventricle are the base for further processes to abtain I. backgroundfree functional bull's-eye displays or hemispheares of the amplitudes and phases of the threedimensional extent of the left ventricle and 2. absolute functional values like enddiastolic-endsystolic volumes, stroke volume and ejection fraction of left ventricle The bull's-eye presentation of the heart mobility especially involves good comparison to heart perfusiun studies with 2°ITI-ECT. Areas of myocardial infarction or dyscinetJc motion are precisely localised. Clinical studies are presented.
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641
;42 R.J. PIROTTE, M.J. CARROLL, J.R. THORNBACK
Christ[aan WJ Schiepers, Kal H Lee and Michael E Siegel U n i v e r s i t y of Southern C a l i f o r n i a School of Medicine Los Angeles, C a l i f o r n i a ,
USA MEDGENIX S.A., B-6220 Fleurus, Belgium
THE EFFECTS OF ANGIULARSAMPLINGFREGLIENCY IN SPECTON IMAGE QUALITY: PHANTC/ffANDCLINICAL STUDIES
A SIMPLE MATHEMATICAL MODEL FOR RECEPTOR BASED RADIOPHARMACEUTICALS.
In SPECT Poissen noise and angular sampling frequency a f f e c t contrast and resolution, and therefore the smal}est lesion detectable. We investigated image q u a l i t y as a function ef angular sampling frequency, while maintaining same total counts to simulate c l i n i c a l s e t t i n g s . Data were acquired in a 64x64 matrix with 30 , ~ and 120 sampling for 25 minutes in. a c i r c u l a r o r b i t (1800 for heart studies, otherwise 3600). Images were reconstructed using a Ramp f i l t e r modified with a Butterwerth window and i n t e r s l i c e averaging. We studied 3 radionuctldes: ~c-SSm, Ga-S7 and TI-201. Anatomical phantom studies were done with cold lesions of 2.5 and 1.8 cm in the l i v e r and 2xl cm in the heart. 22 patients were evaluated with Liver-Spleen, Bone, Gallium and Myocardial imaging using the same protocol. Phantom lesions could be resolved for a l l angular samplings. Dfsturbing streak a r t i f a c t s were present with 12° sampling. Reconstruction a r t i f a c t s due to noise were seen in low count studies with ~ sampling, and mimicked hot and cold lesions. 30 and 60 sampling yielded comparable image q u a l i t y for high count studies. Lesion contrast measured by p r o f i l e analysis was independent of sampling frequency. Conclusions: Optimum angular sampling varies with count statistics. Fer a typical half hour acquisition, sampling is preferred for high count studies such as l i v e r spleen because of fewer reconstruction a r t f f a c t s . For bone, gallium, and heart SPECT, S0 angular sampling appears the best compromise between a c q u i s i t i o n time, resolution, contrast, noise and computer storage.
unlike conlmonly used radiopharmaceuticals for hepatic imaging Tc-99m labelled ~-galactosylated albumin GALACTOSCINT ) binds specifically to hepatic binding )rotein. Thus, if a suitable mathematical model can be developed to simulate the uptake of the molecule by the liver, direct information could be obtained on the HBP concentration and thus the viability of the liver.
This model treats the liver not as a static compartment 'but as a chromatographic column with an extraction efficiency (EF) dependent upon the amount of available receptors (R). For a given R value, EF is a constant factor that account for the affinity and in vivo accessibility of the receptors. R varies with saturation (which tends to decrease it) and recycling (which tends to increase it to its i~itial value : R0). Experimental data can be predicted from curves generated by this model. (1) STOCKERT R.J. 1983, 3 : 750-757. Hepatology.
644
643 G=T. Gullberg, C. Tung, B.M.W. Tsui, J.R. Perry.
University of Utah, Salt Lake City, UT and University of North Carolina, Chapel Hill, NC.
CORRECTION FOR TRUNCATED FAN BEAM PROJECTIONS SPECT IMAGING.
In this work, We report the devel0pment of a simple dynamic model based cn a loading dose study in rabbits. In this study we did not observe a saturating dose effect of the molecule in the liver but did observe a saturationl of the rate of uptake. We consider this to be due to the recycling of the surface receptors (1).
IN CARDIAC
SPECT imaging of the heart with fan beam collimators can significantly increase the detection efficiency over that of parallel hole collimators with the same resolution. However, the magnification of the image places the radiopharmaceutical distribution in some parts of the body outside of the field of view. This ~ives projections that are truncated and the reconstruction of these projections results in severe ring artifacts. A technique, which first extrapolates the truncated projections to approximate the completed projection profile before applying a standard filtered backprojection or iterative reconstruction algorithm, works well to give accurate reconstructions without any ring artifacts, The extrapolation is accomplished by least squares fitting a second order polynomial to a few p o i n t s n e a r the truncation edge of the measured data to obtain a smooth continuation of the truncated projection profile. The technique has been verified with computer simulations and phantom studies. Also, the method has been applied to data obtained from cardiac studies using 99mTc-SnRBC and 201TI for imaging cardiac blood pool and myocardial tissue, respectively. We have found that the technique works well in these applications primarily because the background distribution is significantly lower than the organ of interest.
E . GRENILLET, A. CHANPAZLLER
Nuclear Imaging Center, P o l y c l i n i q u e de Beaulleu, 42200 5 a i n t - E t i e n n e , France. AXONOMETRY : A NEW APPROACH IN 5PECT Of 5PLAY D i s p l a y i n g tomographlc data i n a simple and comprehensive way has received various answers, e.g. : 30 shaded surfaces, b u l l ' s eye. We propose a new approach based on the axenometry concept and e s p e c i a l l y developed f o r myoc a r d i a l imaglng. Input data are 64 contiguous 64x64 s l i c e s , preprocessod with 3D-zoom, oblique r e e r i e n t a t i o n and i t e r a t i v e background s u b s t r a c t i o n u n t l l a l l the voxels outside myoc a r d i a l wail are set to zero. Four contiguous t h i c k sho~t axis s l i c e s (SA) are displayed along the main diagonal o f the c o l o r screen, from base ( u p p e r - r i g h t ) to apex ( l o w e r l e f t ) . Each 5A s l i c e ( o f thickness n p i x e l s ) i s displayed as n successive superimpositions from back to f r o n t , with one p i x e l downleft s h i f t f o r each superimposition. In other words, each s l i c e i s displayed according t o the axonometry method. The two remaining corners o f the screen are used to d i s p l a y one t h i c k v e r t i c a l iong axis (VLA) s l i c e and one t h i c k h o r i z o n t a l long axis (HLA), according to the same p a r a l i e l p r o j e c t i o n r u l e . The 70 e f fect i s enhanced by the i n c l u s i o n o f each of the g s l i c e s i n a s p e c i f i c c o l o r '~ox" with f u l l c o l o r c r o s s - r e f e r e n cing o£ the other s l i c e s . U s e r - s e l e c t i o n o f p o s i t i o n s and thicknesses l s i n t e r a c t i v e and:independent f o r 5A, VLA and HLA s l i c e s . We conclude that t h i s comprehensive s i n g l e display o f myocardial tomograms f a c i l i t a t e s the assessment o f l o c a t i o n and extent o f l e s i o n s , and provldes a dramatic c o l o r r e s u l t e a s i l y understood by r e f e r r i n g c l i n i c i a n s .
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646
P. FAUROUS, H. COLLET , J.C. ARTUS Service de M~decine Nucl~aire, Centre Anticanc@reux de VAL D'AURELLE MONTPELLIER FRANCE
AIDE A L'ANALYSE DES IMMUNOSCINTIGRAPHIES : APPLICATION D'UNE TECHNIQUE DE SEGMENTATION DE L'IMAGE.
Les diffieult~s qui peuvent ~tre reneontr~es dans l'analyse des images immunoseintiEraphiques peuvent ~tre dues au manque de contrasts des zones patholo~iques : nous proposons une technique de segmentation de l'imaEe destin~e ~ individualiser elairement des zones d'aetivit~s voisines. La m@thode utilis~e effectue automatiquement une s@paration bimodale de l'histogramme r~gional des activit~s et d~eide pour chaque point de l'ima~e s'il appartient la classe "inf@rieu~e" ou "sup~rieuFe" ; la classe "sup~rieure" peut ~ son tour subir le m~me proeessus jusqu'~ l'obtention d'histo~rammes unimodaux. L'applieation ~ 14 patients justiciables d'une immunoseinti~raphie, en correlation ayes les donn~es scanno~raphiques, ehirur~ieales et cliniques ~volutives, semble faeiliter le diagnostic et montrer une augmentation siEnifieative du nombre des l~sions d~tect~es. Des @tudes ult~rieures devraient confirmer l'int@r~t de ee type de m~thodes dans l'aide ~ l'analyse des immunoscinti~raphies.
Jacques LEVY-VEHEL, Jean-Marie ROCCHISANI, Nicholas AYACHE
AUTOMATIC CLASSIFICATION OF LUNG DISEASES USING FRACTAL CRITERIA
Fractal geometry deals with the analysis of complex irregular shapes which cannot well be described by the classical euclidean geometry. Such shapes are obtained in Nuclear Medecine with the spatial distribution of activity (H.H. Barret JNM 28:4 p 753 - 1987). We have computed two fractal parameters on three kinds of Lung's SPECT images : normal, pulmonary embolism (CPE) and chronic desease (CD). The commonly used fractal dimension (FD) gives a measurement of the irregularity of the shape. The generalized lacunarity dimension (GLD) defined as the variance of the ratio of the local activity by the mean activity is only sensitive to the distribution and the size of gaps in the surface. The results show that each slice is a fractal surface, that the FD is the sarrie for each slice and for the three kind of lungs (2.37), and that the GLD is different for normals (114 + 1), PE (62 + 0.5) and CD (56 _+ 0.5). These results indicate that automatic classification of Lung's SPECT can be achieved, and that a quantitative measurement of the evolution of the desease could be made.
647
J. FONROGET, J.B GUILHEM, V. MOULLART. Laboratoire de Physique M~dicale - Facult~ de M6decine 12 rue Frederic Petit 80000 Amiens
648
M.~dmal, H.Sdrovd~ M.K~rn~ x, K.Bakos, P . D v o ~ k , O.B~lohl~vek, Z.Dienstbier Institute of Biophysics and Nuclear Medicine, Faculty of Medicine, Charles University and /x/ Institute of Information Theory and Automation, Czechoslovak Academy of Sciences, Prague, Czechoslovakia
Emission tomographg v i t h a static detector : Poss~ilitg of regularizing the inverse problem bg using morphological data obtained bg NHR imaging.
DETECTION OF LOW-CONTRAST DIFFERENCES IN SCINTIGPAPHIC IMAGES: FACTOR ANALYSIS VERSUS PROBABILITY MAPPING
The SPECT classical technics, ~'nplg to record a great number of projections, usually by a rotating gamma camera, and therefore are not suited to dynamical studies. Th~ aim of ~is studg k to demonstrate that the 3D image of an organ can be calculated from only a small number of projections Onin~num 2), obtained simultaneousl9 with a detection modular system (for example a camera with t~,o heads each of them being equipped with either a parallel collimator or a ~ding mask), on the condition of introducing into'~the reconstruction algorithm a lot of morphological tnformation~ obtained bg ultrasound imag~ or NMR imaging. An experimental stud9 has been realized using a chest phantom, inside which the plastic hollo~, mgccard is filled With a 201 Thall!um ohlorure solution or a 99m To perteohnetate sulution. As we could expect, the inverse problem has been shown to be more especially instable as the number of projections is low. This ~'~tabflit W resulL~ in an amplification of the data noise, inf]ueno~)g the quality of the images of the reconstructed sl~.es. However, tt~ problem is shown to be well regularized bg introducing the information about the size , the shape and the ]o~alisation of the mtjocard (inside the chest). From ~e mathematical paint of view, this consists in lccking for a sulut~n (3D image) of the inverse problem among the class of the functions the domain of which coincides with the space portion occupied b%l the myocard. The results obtained prove that this r e g u ~ i n 9 techn~ permits to reconstruct from only two parpendicular projections a nNccardial transversal slice-image, the qualitg of which appears to be equivalent to that given by classical SPECT. This leads us to think that a new type of emission tomographg sgstem, suited to quantitative and dynamical cardiac studies could be envisaged,
In positive tumour imaging, the problems of contrast enhancementj background subtraction, etc., are continuously attempted. Authors suggest to detect low-contrast differences in a series of scintigraphic images using factor analysis /FA/. Efficiency of the method was examined analysing simulated image pairs containing both noisy ~adiation and 61cod backgrotmd and the structures with different degree of contrast increment. Results were compared with those of image subtraction /IS/ and probability mapping /PM/, a method suggested for the same purpose earlier by others. Both FA and PM were found to be clearly superior to IS. PM was verified to be a powerful and specific method for the detection of small increments of contrast in tissues with low initial activity, not superimposed by other structures. Under these conditions, PM was superior to FA. On the other hand, if the initial activity in accumulating regions was higher because of overlap with other tissues, PM failed to detect even high increments of contrast while results of FA were correct. It is concluded that FA and PM are not competitive but complementary methods supplying mutually each other s lack. Illustrative clinical examples confirm experimental conclusions.
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649 O. PASCAL, L. ANDRE, N. BOURGUIGNON, B. VALETTE, M.C. GREGOIRE, C. BERT, A. SYROTA.
Service Bospitalier
RESTORATION STUDIES.
IN
Frederic Joliot,
CEA, Orsay, F r a n c e .
: MYOCARDIAL PBANTOMS
TOMOSCINTIGRAFHY
iD-deconvolution was performed to measure wall thickness in 3 phantoms filled with 99mTc. Acquisitions (64x64) were performed with a gamma camera (GE-HRLE) at standard statistical level with various energy windows (EW), angular steps (AS) and total angles of revolution (AR). After standard reconstruction 7 radial profiles were selected on short axis slices in TV memory (plxel=l.53 mm). On each profile : S was the count rate integral between the maximal points o[ its second derivative and x the distance between the zero values of this derivative. Each profile was deconvoluted by a Gaussian function ! (fitting the line spread function) yielding a gate function of surface S and thickness x dee. Mean results:
thickness EW
AS
7.2
mm AR
x
9.7
x dec
x
x dee
16.1 x
x dec
9.7
:17.7 ii.0
16.8 11.7
5.6 °
360 ° 17.3 1 3600 16.0
8.9
16.2 10.7
20.4 13.0
5.6 ~
180 ° 14.6
6.9
15.8 11.5
18.2 13.5
5 Z
5.6 °
±iO Z ±I0 X
3600 116.8 7,6 117.1 I0.I 19.9 13.8 I I Myocardial thickness can be obtained by ID-deconvolution from acquisitions over 180 o . ±I0 Z
2.8 °
651 LF V~rheij, JAK Blokland, EKJ Pauwels, OLM Bijvoet, SE Papapoulos. Department of Diagnostic Radiology, division of Nuclear Medicine and Clinical Investigation Unit, department of Endocrinology, University Hospital, Leiden, The Netherlands. AUTOMATIC ROI DETERMINATION IN DUAL PHOTON ABSORPTIOMETRY IMAGES OF THE SPINE. Assessment of changes in Bone Mineral Content (BMC) of the lumbar spine of individual patients is often hampered by an inaccurate (manual or semi-automatic) selection of the ROI (L2-L4). To avoid loss of accuracy and reproducibility caused by the inter- and intra-observer variability, an algorithm is proposed that determines the ROI fully automatic. To separate soft tissue and spine, more or les~, vertical edges in the image have to be found. The intervertebral discs can be located through analysing the BMC along lines perpendicular to the spine. The in general noisy images obtained by a Novo BMC-LAB 22a densitometer are small, therefore small operators are required to process the images. To remove extreme noise without affecting the edges, the image is preprocessed by an lx5 median filter. Also, as opposed to square median filters, corners of objects are preserved by this non-linear operator. A 3x3 Gaussian filter is used to smooth the stripy result. Vertical edge enhancement is performed through a 3x3 Sobel operator in x-direction. This yields a positive peak on the transition of soft tissue to bone and a negative peak on the reverse transition. With a dynamic programming technique a contour is found that connects the pixels with the largest positive gradients on one side of the spine and similarly the largest negative gradients on the other side. The grey values between both the contours are summed along lines orthogonal to the direction of the spine, which is not necessarily straight or vertical in the image. Minima in the summation, indicating the intervertebral discs, and anatomical features present in the image are used to select the desired vertebrae. Joining the selected lines and the computed contours completes the ROI determination. The algorithm has shown to perform very well even on spines with an extreme low BMC and in images that have a poor signal to noise ratio.
~.Oriuchi, Y.Sasaki, M.Tateno, M.Inoue. K.Tomiyoshi, T.lizuka, T.Suzuki, M.Horino*, M.Hosoba* and H.Wani * Gunma University School of Medicine, Maebashi, Gunma~ Japan and *Medical Technology Research Laboratory, Shimazu Corporation, Kyoto, Japan.
A SYSTEM DEVELOPMENT A~ND CLINICAL TRIAL FOR COMPUTER AIDED DIAGNOSIS OF TL-201 ~ O C A R D I A L SPECT In order to support image interpretation and reporting a computer aided reporting system with artificial intelligence function was developed. The system was used for the evaluation of Bull's eye display of stress TI myocardial SPECT. The system consists of pts information management(PM) and consultation expert(CE) systems. The former is connected to image processors coupled with scintic~meras~ The Bull's eye dyspl~y of SPECT is transfered to the data ha~e ~f PM. When inference request is made~ the feature extraction program_ extracts information on extent severity and localization of decreased countrates comparing the data pixel by pixel with reference obtained from 7 normal controls, The inference engine is activated to determine presence of focal defects utilizing diagnostic rules in the knowledge base. The results are sent hack to PM and reported with the probability of assurance. Fifty eight pts with old myocardial infarction(0MI). angina pectoris(A1~) and other diseases were included in the study. The decision for presence of focal defects by AI agreed with that by nuclear physicians(NP) in 50 cases among 58(86%) in stress images. The presence of redistribution in delayed images agreed in 16 pts among 20(64%). Image interpretation agreed well between AI and NP in pts with 0~fI(20/21) and AP(9/II). Seven were interpreted as normal by both NP and AI. This system should prove useful in the interpretation and reporting of nuclear medicine images providing nuclear physicians with complementary and supportive information applicable to physician's decision making.
652
J.:.,C.:......L.I.E.HN, COMBE,
P. H A N N E Q U I N , C. F. B A T T E U X , J. V A L E Y R E .
Institut
THE AND
Jean
Godinot
Reims
DANGLEHANT,
O.
France
S U P E R I M P O S I T O N OF S P E C T I M M U N O S C I N T I G R A P H Y CT I M A G E S : A S I M P L E S O L U T I O N .
The simultaneous interpretation of images obtained using different modalities is a common problem in m o d e r n medicine. This is p a r t i c u l a r y t r u e for S P E C T i m m u n o s c i n t i g r a p h i c images which are o f t e n p e r f o r m e d in o r d e r to a s s e s s the m a l i g n a n t n a t u r e of a b n o r m a l p e l v i c CT images. We d e v e l o p a simple system which m a k e s it p o s s i b l e to put any X-ray document into a nuclear medicine system and performs the geometric registration and display of SPECT immunoscintigraphic and CT images. The system uses a CCD video camera connected via a PC to a SUN based Nuclear Medicine system. Translation and magnification in the 3 d i r e c t i o n s as w e l l as r o t a t i o n are m o d e l l e d by the s o f t w a r e . The p a r a m e t e r s of the g e o m e t r i c transformation are e s t i m a t e d by minimizing a distance between the c o o r d i n a t e s of l a n d m a r k s c h o s e n by the o p e r a t o r . :The m e t h o d c a n he u s e d for a n a t o m i c a l l a n d m a r k s (e.g. pelvic bones and k i d n e y s ) or s k i n m a r k e r s . A p p l i c a t i o n s to iii In a n t i - C E A and O C - 1 2 5 i m m u n o s c i n t i g r a p h y s e e m to indicate that this device is u s e f u l for image i n t e r p r e t a t i o n . The a d v a n t a g e s are i) No P A C S n e e d e d , 2) L o w cost, 3) A p p l i c a b l e to some other planar or tomographic images (e.~. b o n e scan).
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653 A. RICHEL, G. DEMONCEAU, C. BRIHAYE, F. TONDEUR, J.C. DEPRESSEUX.
654
J. L. Lear, D. Roberts, J. Pratt. Division of Nuclear Medicine (A034), University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262 USA
Cyclotron (Liege) and I n s t i t u t of Engineering (Bruxelles) ]~n!gium. AUTO?~TIC CREATION OF REGION OF INTEREST IN STATIC I}blGING The isolevel method has the disadvantage to be influenced by the variation of the background as well as by the maximum pixel count (MF~). A program was thus written, that defines a ROI by detectlng the activity variations : £be first derivative of the image is caleuled and the first significant peak is detected on each radius traged between the borderline of a large, predefin~d area of search and its center; the coordinates of this point are kept in memory only if the value of the peak is above a predefined level. Finally, an interpolation is made between the validated coordinates. The reproductibility of this method as well as of the isolevel's was estimated in planar view sj using varying signal on noise ratio (S/N). The accuracy was estimated by SPECT on various organ phantoms, the trus volume being directly measured on the phantom. For S/N in the range 160 till 1.30, variation coefficients were respectively : 1.07% with the automatic method; 6.26% with the 20% isolevel; 7.41% with the 30% isolevel; 8 . 3 8 % with the 40% isolevel; 8.25% with the 50% isolevel; 10.89% with the 60% isolevel. The accuracy of the propose d method is ranging between 102 and 108.9%,.depending on the area on v61ume ratio of the phantom used. In conclusion, this automatic creation of ROI is more accurate and more reproductible than the isolevel method. Moreover, its field of use is wider : it permits the determination of the activity of an organ when its mean pixel count is not near the }WC or in case of significant variation of the background (overlapping, for exemple).
655 Hall M.L~ Cullum I.D, Ell P.J. University College and Middlesex School (,f Medicine London, England.
HOW TO IMPROVE REPRODUCIBILITY IN HIP DENSITOMETRY SCANS. Patients were positioned with 20 degrees of internal rotation and a fixed, extended knee; all were scanned with a new dual energy X-ray densitometer. A protoc(,l tbr analysing hip scans was decided, based on ti~e m a n u f a c t u r e r s handbook and clinical experience. A hip scan sh~,ws live regions of interest and each region ba.~ ene er nmre boundaries. The impertance of each boundary was d e t e r m i , , ' d by reanalvsing one scan many times. Each analysis changed unly one boundary and t h a t was anlv changed by one pixeI (approximately lmm). It was fimnd tb.~t ~hexe_ was a greaLer variation than expected even with s,nall changes and a limit of clinically acceptable error was therefbre introduced. A t h r t h e r 9 scans were subject to multiple reanalyses within the limits of clinical error. Again a wide range of results was fbund, one example being t h a t changing a boundary by plus or minus two pixels altered the boJle density of m]e region by 0 to 2.3% in different people. There was no p a t t e r n with age, sex nr total bone mineral content t h a t explained or could predict this a m o u n t ~,f' variation. On a routine hip scan, the coefficient of variation is of the order of 3% but it is uncertain what proportion of this is accounted tbr by analysis variation. The above findings suggest t h a t tbr any one centre using a similar machine, exact positioning ~,f boundaries is essential and the range of acceptable variation of these sh(mld be stated. In this way, analysis error is reduced and the Cnefficient of Variation may also be reduced thereby improving reproducibility within and between centres.
MACINTOSH II-BASED NUCLEAR MEDICINE IMAGE AQUISITION AND PROCESSING SYSTEM We developed a Nuclear Medicine image aquisition and processing system based on the Macintosh II personal computer. Dual 100,000 samples per second analog to digital converters are interfaced to the Nu-Bus of the Macintosh II. Data from the converters is directly streamed to memory and pixel mapped to the video screen using assembly language programming for optimal speed. First pass data can also be written to the hard disk using a direct memory access controller. This configuration allows images to be generated and displayed on the Macintosh lI by direct digitization of the outputs from gamma cameras, without the need for an intermediate mini-computer. The images can then be~viewedthrough multiple windows on a 1024 x 780 display screen in gray scale or psendocolor. Image processing is performed using interactive software written in Lightspeed C. An Ethernet interface is used to send images rapidly to other computers (MicroVax II, Picker PCS 512) within the division and hospital. Also, a high speed (12,000 baud) telephone communication system is used to send nuclear medicine scans to attending physicians for home review after hours. The use of the Macintosh II personal computer as the platform for Nuclear Medicine data aquisition and processing offers distinct advantages over previous systems. Performance is equal to or better than most available dedicated systems, while the standard user and hard*are interfaces support the integration of word and image processing, mass data storage, and slide making capabilities from a wide range of manufacturers.
656 A. MAGRINI *, G. IZZO *, A. FAVELLA #, M. BANCI #, F. FRINGUELLI #, M. RIZZUTI #, L. AGATENSI +, and F. FRANCHI + * Sezione di Fisica Medica, Dipartimento di Medicina Interna, Universit~ Tot Vergata; # Reparto di Medicina Nucleate, Clinica Ars M e d i c a ; + Ospedale S. Andrea, USL RMI2, Rome, Italy METHOD FOR THE MEASUREMENT OF GLOMERULAR FILTRATION RATE OF EACH KIDNEY WITHOUT BACKGROUND ROI SELECTION Reproducibility in the measurement of kidney glomerular filtration rate (GFR) with p r o p o s e d methods, using gamma-camera and no blood samples, is markedly affected by selection of extrarenal background ROIs. Purpose of this study was to develop a method of analysis of the renogram which does not require selection of background ROIs. Model analysis of the early part (3 min) of the renogram was performed using a large-field computerized ganffaa-camera (90 x 1 s + 15 x 6 s images) and 99mTc-DTPA as a tracer. The time-activity curve calculated over the left v e n t r i c l e was used as an input function to a compartmental kidney and extrarenal tissue model. Three homogeneous vascular compartments in series plus one uptake compartment were used to model each kidney. Extra-renal background in each kidney ROI was taken into account by a single homogeneous non-extractive compartment. 32 patients undergoing routine DTPA test were studied w i t h the p r e s e n t method and Gates method, using c r e a t i n i n e clearance as reference. The c o r r e l a t i o n coefficient was significa£ively greater with the p r o p o s e d m e t h o d (r=0.85) than with the Gates m e t h o d (r=0.78). Reproducibility of GFR values in independent elaborations of the same study by different operators was w i t h i n 5% with the p r e s e n t method. Moreover, extraction efficiency, vascular mean transit time and a parameter related to blood flow are estimated for each kidney with the present method.
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BEUSCART R, ROUSSEL P, DUBOIS P., DUHAMEL A.,' DEWAELE F. and G. COMYN
A. Marcu, J.H. Prince and D.A. Wilson University of Oklahoma Health Sciences Center and Oklahoma Medical Center 940 NE 13th Street Oklahoma City, Oklahoma 73126 U.S.A.
$CMN H 6 p i t a l B LILLE FRANCE CERIM F a c u l t ~ de M G d e c i n e LILLE FRANCE LIFL - CNRS BA 3 6 9 - VILLENEBVE D'ASCQ - FRANCE -
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COMPUTER-AIDED SCINTIGRAPHY
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INTERPRETATION
OF
BONE
1) PBRIN~E OF THE 5TI/DY : we define a methodology for the automatic analysis and a computer-aided interpretation of total body Bone scans. We report here the different steps of the work and our first results. 21 IMAGE ANALYSIS : the images are scintigrams obtained by means of a total Body scan (Scani-Cnmera CGR), which is not computerized. The images are digitalized using a PULNIX-Camera and the matrix is stored on a micro-computer. Currently, only the rachis is studied. Image analysis is realized using the VISILOG'SOFTWARE : specific macros, named "scenario", were written to filter and segment the images and to define the principal parameters of the hyperfixation zones : coordinates, intensity, compactness, area, . 31 IMAGE IMTE2PlCETATIOM : we used an first-order expert system to represent two types of knowledge iLL : technical knowledge, to interpret the results of the Visilog procedures, to separate bone hyperfixations from renal or vesical areas, to diagnose "significant" or "not significant" areas. W e are able to simulate the behaviors of experts using different interpretation strategies; : Medical knowledge, to propose a medical interpretation of the images. 4) F i r s t r e s u l t s : 21 total body scans were interpreted by the system in this first step of development.20/21 diagnosis were exact. So, we think that this study is a first step towards a computer-aided diagnosis of total body scan.
659 R. Lietzenmayer, E. Henze, M. Clausen, G. Schnur, R. Knorpp, C. Schwamborn, W.E. Adam
Divisions of Nuclear Medicine and Nuclear Resonance Spectroscopy, University of Ulm, West Germany A NEW EXPERIMENTAL MODEL FOR KIDNEY RESEARCH USING PHOSPHORUS-31 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY AND CADAVERIC KIDNEYS FROM SLAUGHTER HOUSE. The aim of this study was to apply a 4.7 Tesla/40 cm diameter nuclear magnetic resonance spectroscopy (MRS) system for developing a new and simple experimental model for kidney research using organs harvested from swine at the slaughterhouse. 27 pig kidneys obtained 1015 minutes post mortem were studied with the following different perfusion protocols to evaluate and to define conditions for optimum metabolic preservation: 1. Immediate plegia with cold Collins solution, 1 h cold storage, P-31-MRS. 2. Immediate plegia, cold storage 3 h, blood reperfusion in the magnet, P-31-MRS. 3. Immediate blood reperfusion, plegia, 1-4 h cold storage, blood reperfusion in the magnet, P-31-MRS. 4. Immediate blood reperfusion, plegia, 24 h cold storage, blood reperfusion in the magnet, P-31-MRS. All P-31 spectra were obtained at 81 MHz pulse frequency using a standard surface coil. The following results were obtained: perfusion protocol 1 2 3 4 ~-ATP/Pi ratio zero zero 0.13_+0.1 0.20 + 0.11 number of kidneys 8 4 9 6 In conclusion, an easy, non-expensive in vitro kidney perfusion model of swine kidneys from slaughter house together with P-31 MRS is feasible provided instant blood reperfusion is performed, which seems to revitalize the organs satisfactorily. The proposed perfusion model lends itself to a large variety of experimental protocols such as studies of new preservation solutions, effects of new kidney pharmaceuticals and radiopharmaceuticals on kidney energy metabolism and will thus decrease substantially the need for animal sacrifice in kidney research.
TEMPORAL AND SPATIAL CHARACTERISTICS OF A GLOBAL INDEX OF IMAGE UNIFORMITY IN A 1.5 TESLA MAGNETIC RESONANCE IMAGER No systematic study of operational factors which affect image uniformity in MR imagers has appeared in the literature. We have characterized the temporal and spatial features of image uniformity in a head coil to provide a baseline for future QA studies and to aid in the development of correction schemes for quantitative analysis. Cylindrical phantoms were filled with a CuSO 4 solution end imaged in a Philips Gyroscan S15 imager. Standard spin echo pulse sequences were employed which cover the range of parameters used in our clinical setting. The following parameters were studied: . short-term and long-term tempora fluctuations (STTF and LTTF), resolution matrix (RM), field of view (FOV), slice orientation (go), and slice position ($9). The uniformity index (UI) studied is the percentage of pixels ranging from C-I0% to C+I0%, where C is the average signal intensity in the central 400 pixels of an image. Data presented in a series of tables and graphs demonstrate that the following variations in the UI occur: STTF (within one day) ranges from a 2-10% (CV) over a 10-week period; LTTF (over a 10-week period), 68.5 ± 4.4%; RM, < 20% mean value from 64x64 to 256x256; FOV, 27% from 20-30 cm; SO and SP, < 30%. This study points to the need for multiple uniformity corrections for quantitative analysis. Improved system stability is also needed. Temporal fluctuations of ± 10% (CV) appear to be the limiting factor in our system for devising quantitative schemes.
660 C. R A Y N A U D , G. SALAMON, C. RUMEAU, J. REGIS, C. CHIRON, S. TRAN-DINH, C.A. CUENOD, L. DELANOY, N. TZOURIO, M. ZILBOVICIUS, O. DULAC, A. LEROY-WILLIG, M. BOURGUIGNON, A. SYROTA.
Service Hospitalier Fr6d6ric Joliet ORSAY -FranceNearo-diagnostic dept. Hopital "La Timone" MARSEILLE -FrMRI STUDY OF BRAIN ANATOMY IN CHILDREN Computed tomography (CT), positron emission tomography (PET) and single photon emission tomography (SPECT) provide images of the brain slice by slice in the three dimensions. Interpretation of results obtained with these three techniques requires a knowledge of the brain anatomy. For adults several atlases describe brain morphology. For children, cadaver studies of normal brain are exceptional and this explains the absence of anatomical atlases. If MRI is not available, adult atlases must be used assuming that a child's brain is a small adult brain. If this assumption is probably true for children over than 5 or 6 years, it cannot be taken for granted in infants during the first months of life. MRI of 17 children of various ages were selected from a large number of MRI studies made for children with neurological problems. These 17 patients were a posterieri considered free from structural abnormalities at the time of the study. Their ages varied from birth to 15 years, and the same protocol was used in all cases - T1 weighted-sequences; 5 mm-thick transversal slices every 10 ram, parallel to the orbitomeatal line; sagittal slices and in some cases frontal slices. To cover the main periods of cerebral maturation, MRI were multiplied in the first six months and then increasingly spaced after two years. Such MRI documents are essential in localizing functional areas on CT, PET and SPECT images at every age of childhood and especially in infants. Comparison of MRI images at different ages provides also data on developmental changes of the brain in children.
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661 D, PQULIOUEN. R. PERDRISOT, A. ERMIAS, S. AKOKA *, P. JALLET, J.J LE JEUNE Laboratoire de Biophysique, facult6 de Ma:lecine, 1 rue haute de Recul6e, 49100 ANGERS - FRANCE
EMTF~__~M.,HEINTZ,P. ,HUNDESHAGEN,H., ALEXANDER,K. Medizinische Hochschule Hannover, W e s t : G e r m a n y Abt. Angiologie, Abt. Nuklearmedizin und spezielle Biophysik
* Service d'/RM, Hfpital Nord, NANTES
IMPROVEMENT IN MR IMAGING OF LIVER DISEASE USING
CLINICAL VALUE OF MR - ANGIOGRAPHY FOR IMAGING OF STENOSIS IN CAROTID ARTERIES
MAGNETITE DEXTRAN NANOPARTICLES
We have developed a new superparamagnetic MRI contrast agent, Magnetite (Fe304) Dextran (MD) nanoparticles (total mean size 45 rim) which are partially sequestered by the reticulo endothelial system (RES) after I.V injection. The product has very high relaxivity and a considerable safety margins and can therefore be used at very low doses (0,5 mg/Kg iron). MD nanopardcles are also biodegradable : the -iron oxide core is metabolized and the iron salts progressively incorporated into erythrocyte hemoglobin within a few weeks. Nanoparticle uptake is modified in liver disease, this contrast agent is therefore of particular interest for the early detection of small hepatocarcinoma nodules (mean diameter : few millimeters). Further clinical investigations are necessary to evaluate MD nanoparticles as a contrast agent to differenciate normal and diseased liver tissue and to asses liver function.
664
663 J. M. Escany4, E. Drelon, B. Robin-Lherbier, J.Y. Jouzeau, P. M. Walker, P. Netter, A. Gaucher and J. Robert Laboratoire de Biophysique et URA CNRS 1288 , Facultes de Medecine, Universite de Nancy I, 18 rue Lionnois, 54000 NANCY, FRANCE COLLAGEN INDUCED ARTHRITIS RESOLUTION MRI FINDINGS
With MR - angiography it has become p o s s i b l e to v i s u a l i z e n o n - invasively and in a short time stenosis in carotid arteries. Rephasing and dephasing 3-D = sequences were used for the angiographies. With these data an evaluation of the optimal view out of the three - dimensional data was reached. Additionally spin echo - images ol the brain were done by MR. In a s t u d y 35 patients Were i n v e s t i g a t e d . All of them had have a ultrasound- Doppler- sonography and a conventional angiography, which showed stenosis. Pathological flow could be seen in every case. Localising stenosis was not possible in most of the cases in contrast to conventional angiography. Quantification of disturbances of flow in carotid arteries showed not so often place of s t e n o s i s than the visual MR - angiography. The incidence of cerebral lesions correlated with the damage of the carotid arteries.
IN
RATS
:
HIGH
Collagen induced arthritis (CIA) in rats is an experimental model characterized by peripheral synovitis, periostitis, axial and peripheral ossifying enthesopathy. We have performed high resolution proton magnetic resonance imaging of the rat tail and hind paw, to assess the articular features during MDP-CIA. A specific high quality factor resonator, of length 4 cm and diameter 2.5 cm, has been developed. The spin-echo images were acquired in a single acquisition, in an elsewhere unmodified Bruker Biospec BNT i00 spectrometer. The preliminary results indicate that, on arthritic hind paws, soft tissue oedema and periarticular inflamation are detected after day 20. After day 35, with the aid of T2weighted sequences, an increased signal is sometimes present around the discovertebral endplate, suggesting aseptic spondylodiscitis. Cicatricial ossifying enthesopathy appears as bony bridging with low signal around residual intervertebral discs.
P. M. Walker, J. M. Lherbier and J. Robert
Escanye,
B.
Robin-
Faculty-B of Medicine, University of Nancy-l, 18 rue Lionnois, F-54000 NANCY, FRANCE
OPTIMIZATION OF M.R.I. COILS WITH HATCHING BY INDUCTIVE COUPLING - A HANDtS ON APPROACH In order to obtain high signal to noise ratio, especially at low field strengths, it is often necessary to develop surface coils or volume coils with high filling factors. While such optimized coils give, in most cases, better results than the standard coils, few attempts have been made to develop practical rules for their design. We present here the results of a systematic study of receiver coils matched by inductive coupling, which in our view, is a more efficient method for low and medium field imagers than the capacitive coupling approach. The coils employed in this practical assessment utilise the self inductance-external capacitor combination for the tuned circuit, and ground rules for optimal design are suggested through a consideration of coil length and turn-spacing amongst other criteria. We derive optimum parameters for the primary coil, the secondary coil (eg. in saddle coil, Helmholtz coil and surface coil forms) and the characteristics of the inductive coupling between them: the optimization being judged on criteria such as Q-factor (loaded/unloaded) and B1 field homogeneity.
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D. POULIOUEN, R. PERDRISOT, A. ERMIAS, S. AKOKA *, P. JALLET, J. J LE JEUNE Laboratoire de Biophysique, Facult6 de Medecine, 1 me haute de Recul~e, 49100 ANGERS
bESIGNAND PERFORMANCEOF ASPECT,A SINGLE-CRYSTAL ANNULAR CAMERA FOR 3-D BRAIN IMAGING, 5, Genna and A P Smith. Digital Sclntlgraphlcs, Inc., Cambridge, hA.
* Service d'IRM, I-I6pital Nord, NANTES
COMPARISON
OF
59 Fe LABELED
SUPERPARAMAGNETIC
NANOPARTICLE AND MICROCAPSULE KINETICS IN MR LIVER IMAGING
We analysed the biodistribution and kinetics data of two formulations of 59 Fe labeled MRI contrastagent to define their use for the diagnosis of liver disease. 59 Fe labeled Magnetim Dextran (M.D) nanoparticles (total mean size 45 nm) were obtained by a modification of the Molday procedure. 59 Fe (MD) containing polyisobutylcyanoacrylatemicrocapsules (total mean size 2000 nm) were prepared with a water - in - oil emulsion technique. Both formulations were injected intravenously into normal mille Wistar rats and rodents with diethylnitrosoamine (DENA) induced hepatocarcinoma or CC14 induced cirrhosis.
ASPECT Is a unique camera designed for high performance 3-d brain imaging, comprising a stationary annular single-crystal NaI(TI) scintillator and a concentric lightweight rotaUng colUmator. Sixty-three ,5 cm. photomultipllers (PMs)are coupled to the 0.8 cm. thick crystal through a glass light pipe in a 21 by 3 array. The camera Is totally digital: all PMs are separately digitized, and scintillation position determination is performed by a high-speed digital processor. The camera has alO cm. axial by 22 cm. transaxial field of view with average Tc-99m energy and spatial resolution of 10% and 3 ram. FW~I, respectively, and an average spatial nonlinearity of 0.3 mm. Reconstructedresolutions using a high resolution collimator are 5.5 ram. at the edge, and 7 ram. at the center of the transaxiat field of view. These resolutions are futher demonstratedby phantom images and with enhancemeatof detail in braln images. It is also shown, both experimentally and by simulation studies, that the annular stationary detection geometry reduces artifacts arising from crystal nonuniformltles by a factor of up to 15 relative to a standard rotating camera.
Early differences appeared in nanoparticle and microcapsule 59 Fc biodisu:ibufion in normal rats. 59 Fe kinetic parameters and/or relaxation times (T1 and T2) were modified as a result of liver disease. This study has allowed us to define criteria which must be taken into account to improve MRI diagnosis of liver disease.
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I Loutfi, Md Myers ~.J, GILLEN, A.T. ELLIOTT, T.E. HILDITCH
Royal PostgraduateMedical School-Hammersmith Hospital Du Cane Road, London W 12 OHS U.K.
DOSIMET!qY OF AN INDIUM-I 11 ANTI-T LYMPHOCYTE MONOCLONAL ANTIBODY IN A RAT MODELAND ITS IMPLICATIONSIN MAN Due to their radiosensitive nature, lymphocytes have been difficult to label with conventional cell radiolabelling techniques ( I n - I 1 1 oxineltropolone) ,for in viva studies, l-his radiation effect is due to Iocalisotlon of the radionuclide in the nucleus and the cytoplasm, and to the radioactivity used for labelling ( I n - 1 11 maximum 0.2 pOilcell,7.4 milllBqlcell), W e have reported previously (Loutfi et el. 1988) the use of an In- 111 labelled antI-T cell monoclonal antibody (McAb) in the rat which enabled us to image lymlohoid tissue. W e have also discussed the implications of in vitro tests using In- 11 I labelled anti-lymphocyte McAbs with lymphoid cell lines end whole blood for in viva application and we calculated cellular dosimetry involved, fn this report in vitro tests are corroborated by findings in viva in the rat model. Radiation doses to individual ceils in blood and thoracic duct lymph, and in lymphoid tissues have been calculated by e microdosimetric approach. Whole body and non target tissue doses have been calculated using conventional dosimetry considering the distribution of the labelled antibody (IgG) in the extracellular fluid. The results show that In- I 1 I anti-T lymphocyte McAb results in a reduced radiation dose to the cells as compared to In- 111 oxine labelling, and there has been no evidence for cellular damage using the technique, lhe values of absorbed dose and the predicted doses in man using an equivalent preparation of In- I 11 anti-T cell McAb are discussed in detail. ( I ) Loutfi I, Batchelor dR, Chisholm PM, Epenetos AA, Lavender dP, Targeting of lymphocytes with In- I I I labelled monocional antibodies. Nucl Had Carom 9: 787-796, 1988.
West of Scotland Health Boards' Department of Clinical Physics, Glasgow, Scotland
QUALITY CONTROL OF ANALOGUE TO DIGITAL CONVERTERS FOR ARTEFACT FREE SPECT IMAGING.
(ADCS)
Accurate conversion of the analogue position signals from detected photons into digital form is of particular: importance for SPECT imaging. A differential nonlinearity which produces a nonIuniformity in the projection data of 0.5% can produce ring distortions of 5% in the reconstructed images, Thus a simple method of assessing the performance of the ADCs used by the imaging sytem has been developed. This is achieved by performing a quantitative analysis of the d a t a obtained when the camera is irradiated by a uniform photon flux. The degree of integral non-linearlty can he determined by applying a linear regression to a profile taken through the image matrix. A deviation in the gradient of the profile from unity will give a measure of the magnitude of the integral non-linearity. The level of differential nonlinearity can be determined by taking the modulus of the Fourier Transform (MTF) of the profile. The banding effect produced by differential non-llnearity is observed as a non-zero MTF value at a spatial frequency determined by the bit in the ADC which is non-llnear, ADC errors which are difficult to detect from a visual inspection of the projection data are readily demonstrated by the frequency space analysis, An assessment of a system with highly linear ADCs suggests that MTF values higher than 0.003 are significantly different from the mean (p(0,05). This is much lower than the suggested action threshold of 0.05 allowing faults to be detected before a significant deterioration in system performance occurs,
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E.Rota Kops, N.Nerzog, L.E.Feinendegen
ROUSSEAU J., LECOUFFE P,, MARCHANDISE X. Laboratoire de Biophysique, Facult4 de M4decine
Institute of Medicine, Nuclear Research Center Jfilich, FR@
CHRU de Lille, FRANCE RECOVERY COEFFICIENT, LINEARITY, AND SIGNAL-TO-NOISE RATIO OF THE PET SCANNER PC4096-15WB Falues of three performance parameters for whole body PE~ scanner PC4096-15WB: recovery coefficient (RC), linearity, and signal-to-noise ratio (S/N), are reported in this paper. For RC a cylindrical phantom (¢ 20cm), filled with 18F labelled water, contained an empty cylindrical insert (~ 15cm) in an eccentric position. RC as the ratio of measured apparent tD true isotope concentration was plotted as a function of the gap between the two cylinders. The tests were done with and without wobble motion. For linearitF and S/N a cylindrical phantom (4 20cm) was filled with 18F labelled water and the decaying activity was dynamically scanned starting at 1.55 aci/cc. The concentration as de~ termined from reconstructed images was plotted against the actual concentration. Further, the fourier transform was applied to this image series for the calculation of the power spectrum, from which S/N was calculated. As expected, without wobble motion RC reached a plateau at a gap of about 13mm, while with wobble motion a platea~ was reached at lOmm. The linearity of the system showed errors within the range of statistical accuracy for concentrations from 0.i to 1.55~Ci/cc. The S/N as a function of the cutoff frequency (CF) used for reconstruction filter increased from i0 to 30%, when CF decreased from 0.32 to 0.25mm -I. By further decreasing CF to 0.2mm-~ th~ ratio increased by only an additional 4 to I0%.
A
FLEXIBLE AUTO TUNED SURFACE COIL FOR MRI
To enable surface coils to be adapted to a wide variety of examinations and anatomical particularities, the authors present a flexible detector coupled with an auto tuning device. The conductive loop, which is a plastic mercury filled tube, can be used to obtain various shapes, such as a single flat 22 cm diameter coil or an 11 cm diameter two-turn coil. Tuning is carried out at 21 MHz (0.5 T) by a microprocessor controlled varactor. Studies conducted on a phantom are used to evaluate the signal/noise ratio and the spatial sensitivity of
the
coil
according
to
different
geometrical arrangements (saddle-shaped and two-turn). The results
are
compared
with
those
obtained
with
a
conventional spine coil. The studies of patients described show good image resolution, even in the case of short sequences with thin slices and restricted fields of view. The results obtained on the phantom and for patients, possible improvements and the prospects and potential applications of the device are discussed.
672
671 $P Mi.iller, MF Kljewski , ,SOMcore
, BL Holman , Chr Reiners
B.R. Morgan I, T.V. Sanchez I, R.H. Nord I, 2
and G. Hoorneman
Dept. Nuclear Medicine, University Essen, FRO, Harvard Medical 5oheol , Boston, MA, Worcester Polytechnic Institute
, Worce-
ster, MA, USA A IIODEL FOR THE INVESTIBATION OF HIOHER ORDER IrqABIN6 I^$KS.
]'he common models employed in the investigation of imaging systems consider the simple task of detecting a feature of known size and shape on a known background. In a Monte Carlo simulation study we investigated a realistic higher order imaging task of estimating activity, size, and position of a disk-shaped object on a circular uniform backgroundof unknown activity. We generated images, convolved them with a 6oussian point spread function describing the collimator response, addednoise, and estimated the five paremeters of interest by nonlinear fitting using the maximum-likelihcod oritrium.
For a given object configuration the standerd error of the estimates is proportional to the square root of the total image counts. The parameter estimates are unbiased. There ls a strong negative correlation between the estimates of object activityandsize, theeaestimatas also dependon the background area. The object size, actvity and backgroundestimates, however, de notcorrelate with the position estimates, a-priori knowledgeof the position does not improve their precision. Optim tzlng a col limator for this task yields an optimal resolution which is better thsn that found for simple detection; furthermore, optimum resolution improves with decreasing backgroundsize. At lower spatial frequencies the spectra of object, background, and noise overlap, causing correlations between the parameter estimates for multi parameter estimation tasks. Therefore, high spatial frequency information is required since only here the object componentsare separated from the background. Estimation and detection are mathematically related, therefore our considerations also hold for more realistic higher order detection tasks. The minimal model of higher order Imaging tasks should account for activity and size estimation and an unknown background.Position estimation must only be considered when tt is of specific interest.
I Norlsnd Corporation 2 Ft. Atkinson, Wisconsin, USA Norland Scientific Instruments, B.V. Weesp, The Netherlands PERFORMANCE CHARACTERIZATION OF THE NORLAND XR-26 X-RAY BONE DENSITOMETER A new bone densltometer developed by Norland Corporation utilizing Dual Energy X-ray Absorptiometry has been tested to determine performance characteristics critical to clinical applications. Precision expressed as the coefficient of variation of BMD was: 0.37% on the Hologic anthropomorphic spine phantom (n=15); 0.7% on in-vitro human spine (n=9); 0.5% on in-vitro human femur neck (n=9); 0.6% on in-vitro kidney stone (n=9). Accuracy compared to the known values for the Hologic spine phantom waswithin$ 0.3% BMC (g. hydroxyapatite); ~.13% Area (cm'); 0.13% BMD (g. hydroxyapatite/cm ). Linearity of response for BMC and BMD measured over eight known calcium salt concentrations yielded regressions of y=O.1300 + 0.0715 x (r=0.9999), and y=0.0169 + 0.0043 x (r=0.9999), respectively. B~D of the salt solutions ranged from 0.2 g/cm to 1.7 g/cm . A study comparing results of measurement with constant soft tissue cover and irregular soft tissue cover showed no significant difference by t-test of means for either bone mineral content or bone mineral density (BMC t=1.9344, BMD t=-I.0255, n=16). Similarly the influence of fat (paraffin), distributed uniformly, demonstrated no significant effect on BMD (t=1.2783, n=lO).
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673 R. P. DeVito and 3. 3. Hamill
M. Y.
Ide, J. H o s o k a w a , K. O o s h i m a , S u z u k i a n d Y. G o t o
Y.
Fusegawa,
Siemens Gammasonics, Inc. Des Plaines, I l l i n o i s , USA Tokai University, School Isehara-City, Japan
DETERMINATION OF WEIGHTING FUNCTIONS FOR ENERGY V(EIGHTED ACQUISITION Energy weighted acquisition (EWA) u t i l i z e s an energy dependent spatial f i l t e r of short range for image building. This weighting function embodies a probabilistic interpretation of event data that allows non-photopeak events to contribute information to the image. The imaging characteristics of EWA are governed by the weighting functions used during the acquisition of the image. The determination of appropriate weighting functions is complicated by the large increase in degrees of freedom available as compared to conventional window imaging. Developing proper functions is essential to the performanoe of EWA f o r c l i n i c a l imaging. We have investigated parameterization methods to reduce the number of degrees of freedom while maintaining f l e x i b i l i t y of imaging goals. The weighting function is determined by minimizing a generalized Chi squared parameter with variable contributions from coefficients quantifying key image characteristics, e.g. signal-to-nolse r a t i o , spatial resolution and scatter fraction. Varying the importance of these characteristics gives us a workable function generation tool, able to address a variety of c l i n i c a l needs. The resulting weighting functions exhibit good scatter reduction properties at various scatter depths, as demonstrated by measurements of line source response functions in a scattering medium at depths from 0 to I# cm. Weighting functions are investigated using planar and SPECT phantoms and by c l i n i c a l experience.
of Medicine,
Bohsedai,
Wireless telemetric monitoring of left ventricular f u n c t i o n u s i n g d u a l C a d m i u m T e l l u r i d e (CdTe) detectors We had developed a wireless telemonitoring s y s t e m u s i n g d u a l C d T e d e t e c t o r s . T h e p u r p o s e of t h i s s t u d y are d e s c r i b e s p e c i f i c a t i o n o f the s y s t e m a n d r e s u l t s of s o m e c l i n i c a l a p p l i c a t i o n s . T h e s i z e o f C d T e d e t e c t o r is 16 m m in d i a m e t e r a n d 2 m m in t h i c k n e s s , a n d the s i z e o f c o l l i m e tor is 16 m m in h e i g h t a n d 16 m m in d i a m e t e r . T h e w e i g h t o f the m o d u l e is a b o u t 250 g . O u r s y s t e m h a s two d e t e c t o r s , o n e for l e f t v e n t r i c u far c o u n t s a n d a n o t h e r one o v e r r i g h t l u n g f i e l d for b a c k g r o u n d c o u n t s . T h e d a t a c a n t r a n s m i t a b o u t 100 m in a s t r a i g h t d i r e c t i o n . T h e d a t a f r o m t h e d e t e c t o r s a r e d i s p l a y e d o n t h e C R T on real time fashon, therefore we can detect malpos i o n o f the d e t e c t o r s e a s i l y . W i t h t h i s s y s t e m , w e c a n e v a l u a t e the c h a n g e o f l e f t v e n t r i c u l a r functions and pulmonary blood volume during v a r i o u s s t i m u l a t i o n s s u c h as e r g o m e t e r e x e r c i s e , cold pressor test, smoking, drug administration. C o n c l u s i o n : W i r e l e s s t e l e m o n i t o r i n g o f the left ventricular pump functions and pulmonary blood volume with radio nuclide had been attaine d b y o u r n e w s y s t e m , w i t h t h i s s t s t e m , the r a p i d r e s p o n s e s of the l e f t v e n t r i c l e to the various interventions can be monitored continuously. Therefore, capability of this system may o p e n a n e w f i e l d in n u c l e a r c a r d i o l o g y .
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J.R. Prince, A. Kouvelis and J.C. Leonard K. J o r d a n , U. G e t t n e r , H. H a g e m a n n , R. W e i s e
L. G e w o r s k i ,
B. K n o o p ,
A b t e i l u n g fur N u k l e a r m e s s t e c h n i k und Strahlenschutz, Medizinische Hochschule Hannover, Konstanty-Gutschow-Str. 8, D - 3 0 0 0 H a n n o v e r , F R G A HARDWARE BASED SIMULATOR FOR A POSITRON EMISSION TOMOGRAPH. REQUIREMENTS AND REALIZATION The p e r f o r m a n c e of m o d e r n P E T s c a n n e r s is h i g h l y d e p e n d e n t on a l a r g e n u m b e r of s p e c i a l d e s i g n p a r a m e t e r s , m a t e r i a l , size, a n d s h a p e of c r y s t a l s , w a y of m o u n t i n g the c r y s t a l s , size a n d s h a p e of s e p t a a n d s i d e s h i e l d s , d i a m e t e r of the d e t e c t o r ring, k i n d of w o b b l e m o t i o n , w a y of d a t a p r o c e s s i n g , a n d so on. T h e v a r i a t i o n of one p a r a m e t e r u s u a l l y h a s i n f l u e n c e on some o t h e r p a r a m e t e r s , a n d an i s o l a t e d o p t i m i z a t i o n of o n e p a r a m e t e r o f t e n is h a r d to a s s e s s . The c o m p u t e r s i m u l a t i o n of the t o t a l p e r f o r m a n c e is s u c c e s s f u l o n l y to a c e r t a i n d e g r e e of p r e c i sion. T h a t ' s w h y w e s t a r t e d to b u i l d u p a m e c h a n i c a l s i m u l a t o r w h i c h is a b l e to s i m u l a t e the p e r f o r m a n c e of a c o m p l e t e P E T s c a n n e r b y u s i n g o n l y t w o s m a l l r i n g s e g m e n t s o u t of a P E T ring. T h e s e s m a l l s e g m e n t s c o n s i s t of s i d e s h i e l d s , septa, a n d c r y s t a l s a n d are a r r a n g e d on the s i m u l a t o r in o p p o s i t e p o s i t i o n . One of t h e s e s e g m e n t s is fixed, the o t h e r o n e is m o v e d on a c i r c l e to s i m u l a t e a p r o j e c t i o n fan. The o b j e c t , h e r e a p h a n t o m , is m o v e d by l i n e a r a n d r o t a r y m o t i o n in s u c h a way, t h a t a c o m p l e t e r i n g t y p e P E T s c a n n e r c a n be s i m u l a t e d s t e p b y step. The v a r i a t i o n of one or m o r e d e s i g n p a r a m e t e r s is e a s y a n d r e l a t i v e l y i n e x p e n s i v e and the i n f l u e n c e on the o v e r a l l p e r f o r m a n c e c a n be studied.
University of Oklahoma Health Sciences Center and Oklahoma Medical Center 940 NE 13th Street Oklahoma City, Oklahoma 73126 U.S.A.
PSYCHOPHYSICAL EVALUATION OF SELECTED FILMS USED IN NUCLEAR MEDICINE There are no published reports of the psychophysical performance of films used in radioscintigraphy. We present the first studies of 5 films evaluated by lesion detectability curves (LDC) using a standard Rollo phantom. Films evaluated were: DuPont MRF31, DuPont MRF32, DuPont 6+, Fuji MI-MC and Kodak NMP. Films were processed using standard methods providing a range of contrasts from 1.3 to 2.2 optical density units/log (cts/cm2). The results of this investigation, presented in a series of tables and graphs, demonstrate the effect of film selection on LDC's. A rank order correlation between area-under-the-LDC's and average film contrast yielded an r = 0.71. The low r value may indicate that factors other than contrast are pertinent to LDC's. However, a higher r value would be expected with a larger range of contrasts available for evaluation. Any factor which affects lesion detection is assumed to affect the diagnostic process. Thus, these results suggest that film selection may impact diagnostic performance more than has been previously appreciated and that care is needed when visual comparisons require the use of differing films and/or processing conditions, a practice common to certain quality assurance survey programs.
568
678
677 M.Clausen, E.Henze, W.Kfistermeier E.Weller, J.Langhans, A . S c h m i d t , W . E . A d a m
(i),
i
i
i
K.W. Lau~erbach , V~ Beaker , W. §chaden , S. Kara- I katsanis-, L. Lampe-, W. Hollmann~, L.E. Feinendegen !
Departments of Nuclear Cardiology, U n i v e r s i t y of Ulm, Ulm, W e s t - G e r m a n y
Medicine and (1) Siemens AG,
INTEGRATED SPECT ARTEFACTS.
FOR MYOCARDIAL AVOID MOVEMENT
A
HEAD-ARM-SUPPORT TECHNIQUE TO
For myocardial SPECT stable p a t i e n t positioning is of paramount importance. The purpose of this study is to engineer a gamma-ray transparent device, that will facilitate comfortable positioning for the patient and t~ereby b~l~ to avoid u~wanted m o v e m e n t s d~ { h ~ %horax. A rectangular block with a m o u l d i n g for the head is the center piece and helps to avoids flat p o s i t i o n i n g , w h i c h our older patients can not comply with. A flat e x t e n s i o n b e l o w the p a t i e n t s c h e s t helps to stabilize the block by the p a t i e n t s own weight. On the opposite side a thick extension gives support to the left forearm at a level just above and a n t e r i o r l y to the face. This c o m p a r a t i v e l y high positioning puts less stress to the left shoulder joint. A slight slant of the f o r e a r m support tends to hold the arm in this p o s i t i o n by its o w n weight, which is further a s s i s t e d by a sling, w h i c h may be held by the patient. In conclusion, this integrated head-armsupport is well a c c e p t e d by both the patients and the techniCians, is b e l i e v e d to be an important mean for q u a l i t y control in SPECT, and should be i m p l e m e t e d before s o p h i s t i c a t e d m o v e m e n t c o r r e c t i o n a l g o r i t h m s are applied.
Institute of Medicine, Nuclear Research Center 2 J~llch, FRG Institute for Cardiology and Sports Medicine, German Uni. of Sports Sciences, Cologne, FRG ASSESSMENT OF LEFT VENTRICULAR FUNCTION, GLOBAL HEART FUNCTION, CENTRAL CIRCULATION AND PERFUSION OF LUNGS, LIVER AND KIDNEYS WITH A NEW MULTI-PROBE MULTI-PURPOSE DEVICE UNDER AIR AND OXYGEN VENTILATION. A new multl-probe multl-purpose device offers a mean to measure function of heart, central circulation and organ perfusion after a single injection of 20 mCi Tc-99m labelled erythroeytes. We used this device for the functional analysis of the left ventricle, total heart and central circulation at rest and after exercise (EE) comparing room-air (Ai) and Oxygen (Ox) ventilation in 20 male and 8 female volunteers. During Ex we measured relative perfusion of lungs, liver and kidneys with probes directly attached to the body. Our results show no increase of left ventrieular performance under Ox but a relative decrease of hepatic and renal perfusion. At rest central circulatory Blood flow is reduced under Ox. No differences between male and female were found. This new non-lmaging device allows rapid functional measurements of clinically important hemodynamic parameters in terms of ejection-fractions, blood-flow-times and relative organ perfusions, Showing excellent correlations with standard methods (gamma camera and angiography). It is inexpenslve and can be easily adapted to various clinical problems.
680
679 ES Bue and MW L i n d e g a a r d ; Department o f N u c l e a r M e d i c i n e , l h e N o r w e g i a n Radium H o s p i t a l ,
M . l . O s h t r a k h and V.A.Semionkin* Division of Applied Biophysics and Oslo, Norway
*Faculty of ExperimentalPhysics, Ural Polytechnical Institute, Sverdlovsk,
SIANDARDIZAIION AND QUALIIY CONIROL IN PRODUCING ARCHIVAL SCINIIGRAM HARD COPIES ON SHEE[ FILM
Digital graphic
processing permits manipulating i m a g e s . H o w e v e r , when t h e s c a n s
described
scialiare
from and stored as sheet film hard
copies, important diagnostic information may be l o s t due t o f a u l t y F i l m e x p o s u r e and d e v e l o p meot. [o permit comparing serial scintigrams, consistent procedures are essential. Ihis technical note presents our standardization and quality eonlrol routines. F o r each scan c a t e g o r y (bone, liver, etc.), a selected scintigram is h a r d c o p i e d on s h e e t f i l m u s i n g d i f f e r e n t gammacamera and image p r o c e s s i n g u n i t s e t t i n g s , lhe combination yielding t h e b e s t image r e s o l u l i o n and c o n t r a s t i s c h o s e n as l ~ e s t a n d a r d f o r L h i s category. Exposure tests using a standard grey s c a l e and d e n s i t o m e t e r analysis of the developed film are performed daily. The d e n s i L y o f t h e f i l m bas e and o f two s e l e c t e d p o i n t s on t h e g r e y scale are plotled against reference values. lhese objective criteria permit a slrJcl quality control and s i m p l i f i e s maintaining a consisLent image q u a l i t y . A Jaw d e n s i I y i n t h e e x p o s e d
areas signals JnsuffJeJenl developer replenishment. D e v e l o p e r c o n t a m i n a t i o n c a u s e s i n c r e a s e d base f o g , and t h e d e n s i t y s c a l e becomes distorted. If the final rinse is insufficient, and h y p o s a l t s remain in the film emulsion, image degradation will result with time.
620002, USSR
M 6 S S B A U E R S F E C T R O S C O P Y OF HUMAN BLOOD DURING ERYTHREMIA We examined the red blood cells from five patients with erythremia in the course of the M6ssbauer study of the Fe(ll) electronic structure in h e m o g l o b i n from patients with malignanf blood system diseases. MSssbauer spectra of r e d blood cells containing oxyhemoglobin(Hb02) and hemolysates with deoxyhemoglobin(Hb) were measured at 87 K. M~ssbauer parameters(quadrupole splitting and isomer shift) were evaluated and compared with those of Hb02 and Hb from normal adults and leukaemic patients. It was found that values of quadrupole splitting of Hb02 samples from p a t i e n t s with erythremia were slightly higher than that of normal adult Hb02 and were in agreement with differences of leukaemic Hb02 MSssbauer parameters previously observed. M6ssbmuer parameters of Hb from patient with erythremia were the same as those of normal ones. It was interesting to observe an additional component in M6ssbauer spectra of red blood cells and hemolysates in two cases of erythremia which have not been detected in normal and leukaemic samples. We supposed that this component was r e l a t e d with ferritin-like iron content of which was evaluated to be from 5 to 15%. It is possible modifications in the distal hsme region and changes of the hemoglobin biosynthesis during erythremia occur.
569
682
681 M.l.Oshtrakh Division *Faculty
W H Thomson, A Mills, G Palethorpe*, L K Harding
and V . A . S e m i o n k i n *
of A p p l i e d
Biophysics
of E x p e r i m e n t a l
Ural Polytechnical Sverdlovsk,
and
Physics,
Institute,
620002,
Department of Physics & Nuclear Medicine, Dudley Road Hospital, and Regional Radiation Physics and Protection Service*, Birmingham, UK
USSR
A P P L I C A T I O N S OF THE M O S S B A U E R E F F E C T IN MEDICAId-BIOLOGICAL R E S E A R C H R e s ul ts of the a p p l i c a t i o n s of the M ~ s s b a u e r e f f e c t ( n u c l e a r g a m m a - r e s o n a n c e ) in a n u m b er of medlcal-biological i n v e s t i g a t i o n s are reviewed. Data o b t a i n e d d u r i n g studies of different path o l o g i c a l states of the body by M 6 s s b a u e r spect r o sc op y u s i n g Fe-57, Co-57, Sn-119, Sm-153, and Tb-161 n u c l e i are discussed. The m a i n directions in %~ese r e s e a r c h e s are: I) e v a l u a t i o n of the q u a n t i t a t i v e changes of b i o m o l e c u l e s and other compounds c o n t a i n i n g M 6 s s b a u e r n u c l e i in blood and tissues of p a t i e n t s with h e m o g l o b i n o pathies, erythremla, hemosiderosis, diseases of lung, in e r y t h r o l e u k a e m i a cells, during m e tabolic processes; 2) studies of the F e ( I I ) electronic structure in h e m o g l o b i n from p a t i e n t s with hemoglobinopathies and m a l i g n a n t blood system diseases; 3) studies of the e n v i r o n m e n tal factors ac ti o n on the body(X-ray, gamma and e x t r e m e l y h i g h f r e q u e n c y radiation, hydrazine derivatives, and m a l a r i a l p a r a s i t e s influence on hemoglobin; dust influence on lungs of i n d u strial workers); 4) i n v e s t i g a t i o n s of dynamic p r o p e r t i e s of b i o s y s t e m s ( c e l l membrane, basilar m e m b r a n e and eye surface); 5) study of p h armac o l o g i c a l l y important compounds c o n t a i n i n g Fe57 and Au -1 97 nuclei. It is shown that M ~ s s b a u er s p e c t r o s c o p y is a u s e f u l technique in several fields of m e d i c a l - b l o l o g i c a l research.
683
THE EFFICACYOF S~ANDARDTC99MSYRINGE SHIELDS FOR HIGH ENERGYB EMITTERS The surface dose rate of syringes c~ntaining radiopharmaceuticals can be high, of the order of 8mSv.min- . Within the UK recent Guidance Notes have stated that syringes used for handling Tc99m or high energy beta emitters should be shielded. We have developed a syringe shield of a simpler design, constructed from a bismuth alloy. This shleId offers essentially the same dose reduction for Tc99m as tungsten shields yet it is half their weight and cost. However, low atomic number materials are usual]y recommended to shield B- emitters due to the reduced levels of bremsstrahlung radiation. P32 and Ygo are two commonly used radionuclides with maximum B energies of 1.71 MeV and 2.27 MeV respectively. However the path length of a 2.27 MeV B- is'11mm in a low atomic number substance such as perspex, making a plastic syringe shield impracticably thick. Also, the efficiency of bremsstrablung production is only 4% for high atomic number" tungsten (Z=74) or bismuth (Z=83). We have measured with TLD dosemeters the surface dose reduction of syringes containing Y90 and P32 using our bismuth alloy shields. A plastic shield of similar wall thickness (3mm) was also used for comparison. The results in Table I show that the surface dose is reduced by a factor of >2000 using a standard syringe shield. The plastic shield only reduced the surface dose by 15 for Y90 and by 140 for P32. Table q P52
Y90
Surface doses for 185MBq in 5ml syringe (mSv/h) Syringe o n l y BismuthShield Plastlc Shleld 490 0.2 5.4
2190
0.8
150
Standard syringe shields provide effective surface dose reduction for high energy B emitters.
684
I Loutfl,MJ Myers
G Valle*, J Ghiron, L Stringham, W A Volkert, R A Holmes
Royal Postgraduate Medical School-Hammersmith Hospital Du Cane Road, London W 12 OHS U.K.
Nuclear Medicine Department, University of Missouri and HS Truman VA Hospital, Columbia, MO, USA, and *Servizio Radioterapia e Medicina Nucleare, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo , Foggia, Italy
DOSIMETRY OF AN INDIUM-I i I AHTI-T LYMPHOCYTE MONOCLONAL
ANTIBOD'~ IN A RAT MODEL AND ITS IMPLICATIONS IN MAN Due to their radlosensIUve nature, lymphocytes have been difficult to labelwlth conventlonal cell radiolabelllngtechniques ( In- 111 oxlneltropolone),for In vlvo studies.Thls radiationeffect Is due to IocalIsatlonof the radlonUclIde In the nucleus and the cytoplasm, and to the radloactlvityused for labelling(In- I i I maximum 0.2 pCilcell,7.4 millIBqlceII).We have reported previously (Loutfl et el.1988) the use of an In- I I I labelledantI-T cell monoclonel antibody (McAb) In the rat which enabled us to image lymphoid tissue.We have also discussed the implicationsof in vitro testsusihg In- i I i labelledentl-lymphocyte McAbs with lymphoid cell linesend whole bloodfor in viva applicationand we calculated cellulardoslmetry Involved. In thls report In vitro t~t~ are corroborated by flndlngs in viva In the rat model. Radiation dose~ to Indlvldualcells In blood and thoracicduct lymph, end in lymphoid tissues have been calculatedby e microdosimetric approach. Whole body,and non targettissuedoses have been calculatedusing conventional doslmetry considering the distributionof the labell~ antibody (IgO) In the extracellularfluid.The results show that In- i 11 anti-T lymphocyte McAb results in a reduced redietion dose to the ceilsas compared to In- 111 oxine labelling,and there has been no evidence for cellulardamage using the technique.The values of absorbed dose and l.hepredicteddoses in man using an equivaleot preparation of In- i I i antI-T cellMcAb are discussed In detail. ( I ) Loutfi I, Batchelor JR, Chisholm PM, Epenetos AA, Lavender dP Targetlng of lymphocytes with In- I i i labelledmoneclonal antibodies.Nucl Med Carom 9: 787-796, 1988.
VERTEBRAL UPTAKE OF 153Sm-EDTMP. -A'B~ECINNIN@INTHE ASSESSMENT OF THE SPINAL CORD DOSIMETRIC BURDEN Samarium-153-EDTMP, a promising new agent for metabolic radiotherapy of primary and secondary skeletal tumors, localizes in high concentration in bone. As high doses are needed to treat patients, the dosimetric burden to the cord becomes a potential problem. We addressed this by determining both the uptake and the spatial distribution of the tracer in the vertebrae. A group of 3 New Zealand whit~ rabbits (2.3 - 2.9 kg) were given 1.0 mCi intravenously of Sm-153-EDTMP. Three hours post injection the animals were sacrificed and dissected. Five vertebrae (C4, C7, T4, T7, and LI) and the right femur were weighed and their total radioactivity counted. The uptake, expressed as percentage of the dose per gram of tissue, was similar (m = 0.31; sd = 0.041; cv = 13%) in all 15 vertebrae and was close to the general bone uptake as expressed by femoral determinations (m = 0.27; range 0.24-0.36). Autoradiographic studies demonstrated almost homogeneous distribution of the tracer inside the vertebrae and a lower uptake in the cortical compact bone. The lower cortical bone uptake (m ~ 0.16; range 0.15-0.17) was confirmed on samples from femoral shafts. These preliminary data suggest that spinal cord irradiation would not be a major problem in patients' treatment,
570
685
686 P.J. MOUNTFORD AND A.J. COAKLEY
A. Bockisch, k. Hotze, M. Niemeyer, F. GrUnwald, J. Ruhlmann, H.-J. Biersack. Dept. Nucl. Med., Univ. Bonn, W. Germany
Department of Nuclear Medicine, Kent Hospital, Canterbury, Kent CTI 3NG, U.K.
OPTINIZATION OF DOSE DETERNINATION FOR 1-13| 3'HK.APy. Both during test (7 NBq) and therapy (150-1400 MBq), the kinetics of 1-131 were measured in 54 patients who underwent radioiodine thyroid therapy. From these kinetic data the radition dose of the thyr. achieved per MBq was then calculated. In each case the thyr. uptake was measured 9 times over a 5-day period, and the test pretended therapy. 28 of the patients suffered from toxic adenoma, 13 from Plummer's disease, 5 from Grave's disease ~nd 8 from euthyroid goiter. Results: In all groups the maximal mean uptake (% of-.activityT was decreased under therapeutic conditions, a n d the binl. half-life (days) was decreased. These effects are most likely results from irradiation of the thyr. by the accumulated 1-131. The actual therapeutic dose is .thus considerably lower than expected from the kinetic studies with the test activity 1-131. IMBq uptake/% half live/d II-131-activity test therapy test therapy I test therapy all 45±2 40!2 15.9±.3 5.2±.5 1459±56 685±50 Plummer's d. 41±4 44±5 15.9±.7 5.1!.7 1666i160 866±140 Grave's d. 65±8 61i9 7 i.2 4 ±.2 377±78 755±67 toxi~ ad. 41±2 33±2 5.4±.4 5.1±.4 370±52 548±52 euth. g. 50±4 42i6 7.0±.6 6.3±.6 481±159 736±170 Comclusiom The calculated radioactivity for absorbed organ dose is thus clearly underestimated when derived from the kinetics of a tracer activity, and depends upon the therapeutic activity required and the disease which should be treated. The administered therpeutic activity, therefore, has to be increased by approx. 10% to 1OO% more than the calculated activity in order to achieve the desired absorbed energy dose.
687
&
Canterbury
SECRETION OF RADIOACTIVITY IN HUMAN BREAST MILK AND A COMPREHENSIVE SET OF RADIATION PROTECTION RECOMMENDATIONS The concentration of radioactivity secreted in breast milk has been measured in 16 breast-feeding mothers administered Tc-99m pertechnetate, Tc-99m MAA + Tc-99m DTPA (aerosol), Tc-99m glucoheptonate, Tc-99m DTPA, 1-123 OIH, In-Ill leucocytes, and sodium P-32 phosphate. Of the Tc-99m compounds, although the effective half lives were all around 4hr, the concentrations following administration of pertechnetate and MAA were two orders of magnitude greater than for glucoheptonate and DTPA. To identify the potential hazard to an infant, a method has been developed to quantify the dose to an infant based on these measurements of concentration, and it has been appl~ed to this data$ to all other published data, and data received following an appeal by the British Nuclear Medicine Society. The appropriate recommendation to interrupt feeding for each radiopharmaceutical was drawn from one of the following: (I) not essential, (II) for a fixed period of time, (III) for a period given by direct measurements, (IV) cease breast feeding. It was concluded that only Tc-99m MAA had sufficient secretion data to fall into category II, quality control, measurements of the injected compound must be made before categories I and II could be issued, and if the mother was producing colostrum, then only category III could be issued for all radiopharmaceuticals unless it otherwise fell into category IV.
688 W H Thomson, N J Harding, A Mills, H Warren L K Harding
Department of Physics & Nuclear Medicine, Dudley Road Hospital Birmingham, UK
TWO WAITING ROOMSOR ONE? There has been much dispute as to whether nuclear medicine patients after injection with radiophermeceuticals should stay in separate waiting rooms from non-injected patients, relatives, and other hospital staff, e.g. accompanylng nurses. We have been unable to find any radiation dose measurements to help resolve this questlon. Over a period of 8 working days we observedthe poaltlon of everyone in the waiting room of cur nuclear medicine department at intervals of 5 minutes. A computer program was written to calculate the radiation dose to each person in the room from injected patients, taking into account the attenuation of intervening persons where appropriate. In addition e comparison between the resuIts for 5 and 15 minute observations was made.
Results for patients were expressedas e percentage of the effective dose equivalent appropriate for their test. In the case of relatlvas or hospital staff the relevant annual dose figure was used. 100% 5 min observatlons (mSv) median max Patients (67) Visitors (27) Hospital staff (17)
ede 5 15
<0.03% <0.5% <0.05% <0.?% <0.02% <0.2%
q5 min observations median max <0.03% <0.05% <0.02%
<0.3% <0.?% <0.2%
No patient received an additional dose >0.3% of their study ede, and no visitor or nurse >%0% of their dose limit. Our conclusions are firstly that two waiting rooms are not required. Secondly 15 min observations are satisfactory for anyone who wishes to calculate radiation doses in their own waiting room.
B. GOLD; D. BRIKNER; Y. LEICHTER
SOROKA MEDICAL CENTER BEER-SHEVA BEN GURION UNIVERSITY NUCLEAR RESEARCHCENTER, NEGEV . (NRCN) THE MEDICAL CONSEQUENCESOF THE CHERNOBYLACCIDENT TO THE POPULATION OF ISRAEL The nuc]ear accident in Chernobyl, USSR, resulted in the release of s i g n i f i c a n t amounts of r a d i o a c t i v e isotopes and an ±crease in the environmental r a d i o a c t i v i t y in many countries. A continious sampling of the f a l l o u t and measuring network was performed i n - t h e southern areas o f Israel during the days f o l l o w i n g the Chernobyl event. Ganlma-s~ectrometric me~surement~ w~re p~rformedwfth Ge(L~) mnd Nal detectors on a i r samples, vegetation, milk and water. Additional assessments were carried out with f a l l o u t trays with thermoluminescent dosimetry, and on human beeings with whole body counting and d i r e c t I 131 counting o f the t h y r o i d gland. The estimated equiValent e f f e c t i v e dose f o r adults was about 35 uSv (3.5 mRem) and 520 uSv to the t h y r o i d gland. This level is f a r below the doses o f 200 - 800 mRem to the Thyroid recorded in the European countries I t a l y , Sweden, United Kingdom, Poland, Hungary and USSR. These values are much lower than the estimated annual equivalent e f f e c t i v e dose due to background r a d i a t i o n to the population o f Israel - about 2000 uSv (200 mRem). Estimation o f a d d i t i o n a l cancer cases due to Chernobyl r a d i o a c t i v e f a l l o u t in Israel i s , t h e r e f o r e , s t a t i s t i c a l l y impractical.
571
689
690 A. Brocchi, M.S.Tommasi,
B. Orsini*, C. Surrenti*,
A. Calabr~*, U. Meldolesi.
Dept. of Clin. Pathophysiology, Nucl. M e d i c i n e Unit, * Gastroenterology Unit, U n i v e r s i t y of Florence, viale G.B. Morgagni 85, 50134 Florence, Italy EGF
RIA
IN HUMAN
GASTRIC
JUICE
AND
SALIVA
To e v a l u a t e the role of E p i d e r m a l G r o w t h Factor (EGF) in the control of g a s t r o i n t e s t i n a l cell proliferation, a RIA was d e v e l o p e d (modifying the m e t h o d o r i g i n a l l y p r o p o s e d by A m e r s h a m kit) and EGF levels were d e t e r m i n e d in saliva and gastric j u i c e of h e a l t h y volunteers. After c e n t r i f u g a t i o n (2,500 g, 4 °C, 30 min), 1 ml of each sample was l y o p h i l i s e d and r e c o n s t i t u t e d with PBS. 0.2 ml of a n t i s e r u m (1:40,000), 0.1 ml of standard "EGF or sample were p r e i n c u b a t e d for 24 h at 4 °C. 0.i ml 1-125 EGF (4 nCi/tube) was then added and the incubation continued for further 24 h at 4 °C. 0.5 ml of A m e r l e x - M was used for the separation of f r e e a n d b o u n d fractions. S e n s i t i v i t y (1.d.l.) was 3 pg/tube. The i m p r e c i s i o n p r o f i l e of EGF s t a n d a r d curve was less than 10% in the range of 0.1-3,0 ng/ml. W i t h i n assay C.V. was 14.8% at 163.3 pg/ml, 6.7% at 915.6 pg/ml and 8.5% at 4037.2 pg/ml, for gastric j u i c e a n d 4 . 1 % at 1 0 5 4 . 1 p g / m l for saliva. Between-assay C.V. w a s 1 7 . 5 % at 143 pg/ml, 15.2% at 846 pg/ml and 11.9% at 4167.7 pg/ml, for g a s t r i c juice and 11.3% at 1048.8 pg/ml for saliva. The a c c u r a c y (evaluated by r e c o v e r y test) was 9 3 . 7 ± 1 1 . 3 % for g a s t r i c juice and 93.9 + 8.7% for saliva (M ! SD). EGF i m m u n o r e a c t i v i t y in saliva and g a s t r i c juice coelutes w i t h pure EGF on S e p h a d e x G-50 fine. EGF c o n c e n t r a t i o n (R±SD) was 1498.7±630.4 pg/ml in saliva and 4 3 5 . 7 ± 1 3 2 . 7 pg/ml in g a s t r i c juice.
691 M. Tommasi, ° A. Brocchi, ° V. Chiarugi. °° °Nuclear Medicine Unit, Department of C l i n i c a l Pathophysiology; °°Laboratory of Molecular Biology I n s t i t u t e of General Pathology. U n i v e r s i t y of Florence, I t a l y . DEVELOPMENT OF A RADIOIMMUNOASSAYFOR HUMAN PLATELET DERIVED GROWTHFACTOR. Together with Insulin and EGF, P l a t e l e t derived Growth Factor is one of the most relevant and powerful mitogen. Therefore we attempted to develop a radioimmunoassay f o r PDGF in b i o l o g i c a l f l u i d s . The incubation volume contained 100 ul of incubation buffer (pH 7.4) with standard PDGF c-sis (from 1000102~o 78.1 p g / m l ) o r 100 ul of unknown sample, 100 ul of Il a b e l l e d PDGF c - s i s (3 nCi/tube) and 100 ul of goat a n t i human PDGF immune serum d i l u t e d to 1/50000 in incubation buffer. The mixtures were incubated at 4°C f o r 24 hrs, a f t e r which bound and free labels were separated by the a d d i t i o n of 1000 ul of a solution of anti-gamma-globulin immunoadsorbant d i l u t e d to 1/200 in incubation buffer containing PEG 6000 (8%). S e n s i t i v i t y was- 80 pg/ml and the c o e f f i c i e n t of v a r i a t i o n was < 10% in the dose range from 250 to 3000 pg/ml, as indicated by the precision p r o f i l e . The percent recovery of standard PDGF from tissue c u l t u r e medium (DEM), f o l l o w i n g the e x t r a c t i o n by I M CH_COOH ( I / 5 , v o l / v o l ) , was 94.7 ~ 14.8 (mean value - SD~ in the dose range from 600 to 5000 pg/ml. This study may also be considered as a preliminary one to the measurement of PDGF in human plasma.
D. H e r n a l s t e e n , 3. D e w e l d e , J . P L e o n a r d . Centre de M~decine B r u s s e l s , Belgium.
Nucl~aire,
Clinique
du
Parc
L~opold,
E V A L U A T I O N O F T H E T U M O R M A R K E R C A 509 IN THE F O L L O W U P O F P A T I E N T S WITH A D V A N C E D S T A G E BREAST CANCER.
In a retrospective longitudinal study, performed using a minimum of 3 serial samples over a 1 - 2 years period, we examined the clinical relevance of CA 549 (Tandem IRMA HYBRITECH), a recently described breast tumor associated antigen, in the evaluation of the course of the malignity. We compared the results with CEA and with CA 15-3. 124 patients were tested: 17 heathly normal female subjects, 7g patients with breast cancer : 15 stage ], I7 stage II, i7 stage Ill, 29 stage ]V ; and 29 patients, with other malignancies. The relative sensitivity in advanced stages is as follows: n_ C E A (+) C A 15-3 (+) C A 549 (+) S t a g e llI S t a g e IV
17 29
lg % ~45 %
47 % 62 %
ttl % 59 %
In s t a g e s Ill a n d IV, t h e c h a n g e s of t h e t w o m a r k e r s , C A 5t~9 a n d C A 15 - 3, w e r e v e r y c l o s e l y c o r r e l a t e d a n d w e r e a s s o c i a t e d w i t h t h e c l i n i c a l c o u r s e of t h e d i s e a s e : 6 c a s e s of b r e a s t cancer regressive after therapy ; 9 cases with recurrence ; 5 cases with established advanced cancer. CEA provided a d d i t i o n a l i n f o r m a t i o n , s i n c e it w a s t h e only m a r k e r e l e v a t e d in 3 p a t i e n t s . In s t a g e s I a n d II, t h e l o n g i t u d i n a l s t u d y c o n f i r med. 3 p a t i e n t s w e r e f a l s e - p o s i t i v e f o r C A 15-3 a n d C A 5~49. 3 r e c u r r e n c e s w e r e e q u a l l y d e m o n s t r a t e d by b o t h m a r k e r s . In o t h e r c a n c e r s , 77 % of t h e c a s e s p o s i t i v e f o r C A 15-3 w e r e p o s i t i v e f o r C A 5/49. C A 5t~9 a n d C A 15-3 a r e p r o b a b l y r e l a t e d to e p i t o p e s p r e s e n t on a s a m e m a c r o m o l e c u l e . C A 549 a p p e a r s as a u s e f u l a n d ' s e n s i t i v e tool f o r m o n i t o r i n g b r e a s t c a n c e r .
692 M.H. SCHLAGE~ER1, M.E. TOUB~BT1, B. J.M. DECAZESL and Y. NAJEAN-
CABTIER-D'OIRON 2,
1 Service de M@decine Nucl@aire (Professeur NAJEAN) 2 Service des Maladies I n f e c t i e u s e s (Professeur MODAl) H 6 p i t a l S a i n t - L o u i s , ~, avenue Claude V e l l e f a u x , 75010 PARIS. PHARMACOKINETIC STUDY RADIO-IMMUNOASSAY
OF
ZIDOVUDINE
(AZT) BY
Z i d o v u d i n e (AZT or ZDV) i s a c t u a l l y the only clinically a c t i v e drug in the t r e a t m e n t of acquired immunedeficiency syndrome (AIDS) and related diseases. We have undertaken clinical pharmaco-kinetic studies in patients in order to better define doses, to precise eventual drug interactions and to demonstrate kinetic abnormalities in relation to disease complications. Quantitative determination of zidovudine serum levels is carried out by a radio-immunoassay commercialized by Baxter. The method is based on the competition between AZT and 125I-labelled AZT for a rabbit polyclonal antibody. Sensitivity of the dosage is 0.27 ug/1. Reproducibility (within - and between assays variations) is satisfactory. Cross-reactivity with the major metabolite of zidovudine (G-AZT) is low (1~). However this could potentially limit the interpretation of results in case of severe renal insufficiency where G-AZT blood accumulation is markedly increased. A minimum of B veinous blood samples are collected until 4 to 6 hrs after oral administration of zidovudine, allowing quantitation of the drug in serum, and calculation of pharmecokinetic data according to a biexponential curve. The results in various clinical conditions will be presented, with the resulting modifications of drug schedule, way of administration and posology.
572
693
694
SO Karam~zrak~
C Yaman,
xx
H D e r i n xx x Ege University Medical Dept. Izmir Turkey. xx E g e U n i v e r s i t y Medical Dept. I z m i r T u r k e y .
H Ozk~llq,
xx
.. x N Akgun,
~,_~t~, P,lbuelli,~.Fraschini, Faculty
Sports
Faculty
Nuclear
Medicine ~dicina Nucleate0spedale"Maggiore"U.S.],. 4 Parma Med. C/05-3SE~IIMLEVELIN )~ffORI~GOFBREASTCANC~ PATII~TS
THE EFFECTS OF THE USE OF A RELAXATION TECHNIQUE PROGRAMME ON T H E R E S T Z N G A N D P O S T - E X E R C ~ S E SERUM CORT~SOL L E V E L S IN T R A C K A N D F ~ E L D A T H L E T E S T h e e f f e c t s of a r e l a x a t i o n technique programm e on r e s t i n g a n d p o s t - e x e r c i s e s e r u m l e v e l s of the s t r e s s h o r m o n e c o r t i s o l h a s b e e n i n v e s t i g a ted in t r a c k a n d f i e l d a t h l e t e s . Athletes(n:15) have performed a maximal bicycle ergometer test at t h e s t a r t a n d the e n d of w h i c h v e n o u s b l o o d samples have been drawn. The procedure was repeated after following the relaxation programme of 9-15 w e e k s . T h e e r g o m e h e r test consisted of three uninterrupted p h a s e s of 2 m i n u t e s each, at 80, 90 a n d l O 0 r p m a g a i n s t r e s i s t a n c e s of 35, 42 a n d 5 0 g / k g b o d y w e i g h t r e s p e c t i v e l y . Thechang e s in t h e h e a r t r a t e a n d b l o o d p r e s s u r e s were indicative of a m a x i m a l exercise (p(0.0001).The determination of s ~ r u m c o r t i s o l levels has been done by RIA technique. The increases in s e r u m cortisol levels following the t e s t s w e r e n o t significant, b u t the r e s t i n g s e r u m c o r t i s o l levels have dropped significantly (p(0.01). The athletes had also the subjective f e e l i n g of b e ing'less emotional and more confident at m e e t ings. T h e s e f i n d i n g s a r e i n d i c a t i v e that such a relaxation technique m a y r e d u c e the s e r u m l e v e l of t h e s t r e s s h o r m o n e c o r t i s o l a n d t h a t t h e r e s p o n s e s of e p i n e p h r i n e and norepinephrine to such a technique m a y be i n v e s t i g a t e d too.
We have examined98 p~tientswho alreadyuadersentsurgicaloperationfor breastcancer to check up the possibilitythatC~15-3serumlevelallowsa earlydiagnosisof recurrences of the diseaseand a monitoringof the therapy, and 49 aBoegthesehad so boseor parenchiel Retastasesat the momentof the assay. CA15-2leveles higherthan400/mlis B of these 49 Mtiests, uhereasis 7 il es includedbetween30 and 40U/st, All patientssith C115-3higherthan40U/el,2 withlevelincludedbetuees30 and @U/ml, and
3 with level loverthan the cut-oil (30U/)I}developedrecurrencesis the followingm0nths Of 49 patientswithdiftoseddiseaseat the momentof the first~rker'sassay, 30 (61t)had CI15-3 securelevelhigherthan40U/el, 5 (10t)had CA15-3seem levelbetween30 asd 40Wml asd 14 (29t)had Ck15-3securelevelloverthanthe cut-oil, and the relationshipbetneesthe siteof the mtastasesa,d CI15-3ser~nlevelyes as follos: ptz >40 30>-,-(40 430 e, a. s. soft tissue l0 2 1 7 bone 21 14 3 4 vis~er~ 18 14, 1 3 hit peticutswithboseor pareechJmlmetastasesand 3 ant of 7 with local recurrence,with the CRtS-3level lowerthan 30U/it weresubmittedto an antiblastic therapyat the )encutel the assay, We )olIoved with accuracythe changesof marker'slevelssad the clinic bohaviosr of 32 patients for abosta year, ~ong these12 sereapparentlysithout diseaseat the ~o~est uI the fi~t mrker's assayand8 of these12 serethe patientssith C115-3serst level higher thap 40U/elthat developedrecurrencesin the following~onthe, while 18 patientsoat of 20 withrecurrenceof diseasehad ~r~er's levelhigherthanthe cut-off,
ls all these c~sesthe increaseof Ch15-3 level sas associated with the recurresce or aggravatips o! the disease, shereasthe decreaseel the marker'slevel is all cases has associatedwith the effectivesess0t the therapy.
696
695
Dumas A, Kostak~ p, Salem N, Giavroglou I~ Raptou E, Frangou V , Lo Prestt D, Apostolldes P.
G y . A . 3 d n o k i , L . K O r ~ s i , E . f a l ~ and J . L d n g ~ "F3C N a t l . R e s . I n s t . f o r Radiobiology and Radiohygiene, P.O.Bo× i01 H-1775 Budapest, Hungary • I n s t i t u t e o f L i f e Sciences 3erusalem, I s r a e l • ~A. Szent-GyOrgyi Medical Univ., P.O.Box 469 H-6720 Szeged, Hungary
"rheagenion" Anticancer Institute. Thessaloniki, Greece
RELATIONSHIP BETVEEN L I V E R S C A N AND AMINOTERMINAL PROPEPTIDE OF TYPE III COLLAGEN (PIIINP) IN METASTATIC LIYER DISEASE ThE
RADIOIMMUNOASSAY DEVELOPMENT FOR THYROTROPIN RELEASING HORMONE DETERMINATION T h y r o t r o p i n r e l e a s i n g hormone
amide was t h e f i r s t
(TRH) p y r o g l u t a m y l - b i s t y d i l
hypothalamic
releasing
f a c t o r t o be
p u r i f i e d and i d e n t i f i e d , by Burgus e t a l . , ( 1 9 7 0 ) . We s e t o u t t o d e v e l o p a RIA system f o r the measurement o f IRH d u r i n g drug t r e a t m e n t and i n b i o l o g i c a l samples. To r a i s e a n t i b o d y , TRH was coupled tO BSA a t d i f f e r e n t molar r a t i o s (1:10, 1:5, h 4 ) using d i a z o t i z e d b e n z i d i n e . For c o u p l i n g e f f i c i e n c y d e t e r m i n a t i o n a t r a c e r amount o f 1 2 5 - I - I R H was used. T h e r e a f t e r , the crude c o n j u g a t e was purified on a Sephadex-G-lO0 column and b y d i a l y s i s . The final purification o f the c o n j u g a t e was done by HPLC. Chroma¢ographic s e p a r a t i o n was p e r f o r m e d u s i n g the BIORAD HPLC system. ( B i o - S i l ISK-250 a n a l . columo,TSK b u f f e r o f pH 6 . 8 , f l o w r a t e 1 m l / m i n . ) A f t e r r e p u r i f l c a t i o n , t h e TRHBDB-BSA c o n j u g a t e was d i l u t e d w i t h 0.15 M NaG1 so t h a t t h e TRH c o n c e n t r a t i o n was 2 0 0 / u l / m ] . One ml o f d i l u t e d TRHBDB-BSA and c o m p l e t t e F r e b n d ' s a d j u v a n t w e r e h e m o g e n i z e d , and 2 ml o f t h i s m i x t u r e was i n j e c t e d i n t r a c u t a d e o u s l y i n t o 15 r a b b i t s . A n t i b o d y t o TRH was d e t e c t e d by methods o f Quchterlony and radioimmonoassay after the 4th immunization. We measured 20-25 % t o t a l b i n d i n g with our antibody. Tracer was p r e p a r e d by a m o d i f i e d Greenwood-Hunter procedure and w i t h the a n t i s e r a o b t a i n e d from t h e Weitzean
Institute
of
Science,
Israel,
and
produced
in
our
l a b o r a t o r y , we measured immonoreactive TRH i n the drug and i n r a t hypothalamus and a d r e n a l homogenates.
The Type III collagen is a major constituent of most dense and loose connective tissues in the body. It is synthetized as a procollagen with propeptide extensions at both ends at the molecule. Some of this aminoterminal propeptidss (PIIINP) during the proccess of the collagen formation are set free and consequently they can be found in serum, by RIA methods, in the cases where accumulation and/or degradation of connective tissue takes plase (liver fibrosis, hepatitis, mali_mnantdiseases).
~/e tried to find out if there is a f'eJationshlp between liver scan and the titer of the above substance, in 20 patients vlth positive liver scan due to metastatic disease (14 breast cancers, 5 cancer of colon, I mallgnant melanoma) ,GROUP I, in 20 cancer patients without liver involvement (GROUP If) and in 20 healthy volunteers (GROUP lID. The tlters of PIIINP were 15.5±8.5 in the patients of GROUP I, 6.1=+13 in GROUP Ill and 2.9=+0.8 in the h e a l t h y volunteers. Statistically significant differences were seen between all the three groups. Ve conclude that PIIINP is a useful1 marker in detecting the liver involvement in cancer patients. We are already investigating if the above substance could be used as a prognostic market" for the f u t u r e appearance of metastases in equivocal liverScans.
573
698
697
A. R.Novakovi6,
Lj.Gli~i6, B.Bani6evi6,
M.RaU<0vi6,
Lj.Petr0nijevii,
thiversity Clinical Center of Bel~9~ade Yugoslavia Institute of ~hclear Medicine Institute of Castroeateroloi~j and Hepatolo~f Institute of Hematology I}E VALUEOF lIE u s " t ~ T I ~ OF II~ I ~ OF C ~ { , PIll, B12 ~ IN I ~ S ~ OFII~ P A T I ~ ~91~ ( I ~ C A T ~ C C@kb-am-I].5, P~CKOgSANAI~ AND C ~ C ( ~ 1he I1WIxx~e: of the study: I t is known that is for pathological lesion of the ftmdus is important the determination of Pepsincgea I and B12 but for antrt~n of the stomaeh the level of serum Castrin. ~ authors wanted to point out one or two parameters ~ c t e r i s t i c for each of these diseases. MM~hods: In 420 .patients i t ~ s examined simulataneously (ETA) the level of ser~n GasLrin (CZ3), ?ep~ir~o~ l ~ d .312 (3ur'ir~-Bio,~dica).
.~m~m,y of the results: the mean values ( ~ ) of Gastrin, Pepsinogen I, and B12 in control ~F~up were: 80 pg/ml, 120 r~g/ml and 260 ~g/ml. No. Osstrin PeDsincgan I B12 01~,ic a t e . B~strltt~ 160 210+12 " ~6~5~ 205~15 Gastric a t * ~ (Pe~n.~.) a)P.A, with int.r.m.taplazia 5 1480~85 40+12 16~3 and pseudopylorie metapl. b)P.A.with phyloric metapl. 9 360+24 45~9 2L~5 c)P.A.~dth intest.metapl. 12 740+62 ~q~6 21bi d)P.A. (early phase) 20 220+16 56~I 3 48~9 e)P.A. - Cgstritis AB 24 150+I2 52+I8 ~I 2 Gastrlc nmdal cmnclm0ma 190 160~4 35~6 210-26 Conclusion: Pepsinogen I is especialiy decreased in ~stric carcinoma. 1]~e level of B12 vitamin is of ,great value for pernicious anaemia (very Ic~ level). ~he level of serum gastrin is different in these five ~bgxxlps of P.A. 3he change of Gastrin depends from the localization, intensity and stage of histopathlcgical lesions of parietal, chief, and G cells, the presence of G-cells in the focus of pseudopy!oric, pyloric and intestinal metaplesia in atrofic fUndus mucosa, r.e~ite diferent high levels of serum gastrin.
699 C. JUBAULT*, P. OIOT*, D. NOLIBE**, N. VERNEUIL*, G- NORMIER***, H. BINZ***, A.M. PINEL***, L. DUSSOURD D'HINTERLAND*** and A. LE PAPE*. * Laboratoire de Biophysique Cellulaire - Universit~ de TOURS, France. ** I.N.S.T.N. - C.E.A., 5ACLAY, France. *** Centre Immunologie et Biologie Pierre Fsbre, CASTRES, France.
USE OF D25, A GLYCOPEPTIDIC IMMUNOMODULATOR ISOLATEDFROMKLEBSIELLAFOR THE SCINTIGRAPHIC IMAGINGOF LUNGTUMDURSAND GRANULOMATOSI5 DISORDERS : RESULTS IN EXPERIMENTAL MODELSIN BABOONS. Maerophsges, mainly in their activated state, have been found to bind eleetively bacterial immunomodulators such as NSPD ( Noeardia Soluble Peptidoglycan berivate) or D25, a fully characterized molecule, isolated from s non pathogenic strain of K1ebsiella pneumonim.'The potential use
of the targeting of macrophages with such ligands for the early scintigraphic imaging of inflammatory lymph nodes, and granulomas and carcinomas in lungs, was assessed using experlmentally induced berylliosis and radio-induced carcinogenesis in baboons. Lung Berylliosis is a granulomatosis whose immunologic and clinical characteristics are very similar to those of sarcoidosis. 6 baboons were contaminated by depositing into the lower lobe of their right lung beryl~ lium metal doses ranging from 10 to 50 mg. Animals were explored monthly for 1.5 year by radiologic and scintigraphic techniques including 67 Gallium scintigraphy as a reference test. Radio-induced carcinogenesis was obtained in 2 baboons by depositing in the right lower lobe i14.7 KBq of an ~ emitter in suspension in saline. Radiologic and scintigraphic explorations were performed i year after the contamination. The scintigraphy of macrophsges was performed 2 hours after inhalation of 1 mg D25 labelled with 370 MBq 99m Technetium in the presence of stannous chloride. 3 months after beryllium administration, the beryllic alveolitis Was highly fixing. From 3 to 15 months later, paratrscheal inflammatory lymph nodes were detected near the carena. At the time of the autopsy, their sizes were usually less than 6 m m. 2 fixations in parenchymal 6~ e granulomas were also observed. All these lesions were not evidenced by In baboons Contaminated by an ~ emitter, a significant fixation of D25 was observed in lymph nodes hlstologically characterized by a macrophage infiltration, a lymphoid depletion and an evoluttve fibrosis that were associated to the csrcinogenetie process.
CO~UEREL,
G.
OZENNE
and
C.
DUMONT
Laboratoire de Radioanalyse Th~rapeutique. Centre Hespitalier de Rouen. 76031 ROUEN Cedex, Laboratoires Mallinckrodt-France, EVRY Cedex, FRANCE.
(*).
et Clinique Universitaire FRANCE. (*) BP 50, 91002
AN U L T R A S E N S I T I V E M E T H O D FOR DETFA~MINATION OF ADRENOCORTICOTROPIC HORMONE (ACTH) IN HUMAN P L A S M A S BY AN I M M U N O - R A D I O M E T R I C ASSAY. ACTH measurement is helpful in the assessment of the hypothalamo-hypophyso-adrenal axis diseases. Until now the ACTH determination in h u m a n plasma was done with classical RadioImmune Assays (RIA). These last months an Immuno-RadioMetric Assay (IRMA) has been available from Nichols Institute (California, USA). We tested this kit with human samples obtained from healthy controls and during various adreno-corticotropic dysfunctions. While the RIAs (International-CIS, France; INCSTAR, USA) measured levels f r o m 15 t o 5 0 0 pg/ml w e c a n directly quantify levels from 1.5 to 1500 pg/ml with the IRMA procedure. Intra and inter assay c o e f f i c i e n t s of v a r i a t i o n ( C V % ) w e r e 3-3.5 and 4.5-7.5 for 20 to 700 pg/ml respectively. CV% of dilution and recovery tests are g 5.5% ; correlation coefficients with RIA were r ~ 0.99. On the c o n t r a r y to RIAs which cross-react to 100 % with 1-24 ACTH (Synacthene) the I R M A d o e s not cross-reacts with 1-24 ACTH and related peptides. During the s y n a t h e n e tests 1-39 ACTH levels decrease with closed correlation to synacthene and certisol level increases. We conclude this IRMA method for ACT}{ is a real advance in easiness of task, sensitivity and precision for the human plasma ACTH measurment.
700 K. S c h o m ~ c k e r I , R. M U n z e I S h u k l a 2, W , G . F r a n k e S
D.
Mocker I
S.K.
I Central Institute for Nuclear Research doff, G.D.R., 2Institute for Isotopes, Rome, Italy, 3Medical Academy Dresden,
THE TREATMENT OF S O F T AFFINE 90y-PREPARATIONS
TISSUE
TUMOURS
RossenC.N.R., G.D.R.
WITH
TUMOUR
0 . 3 7 M B q of a t u m o u r - a f f i n e 90y-preparation (containing an o p t i m i z e d mixture of c a r r i e r - f r e e 90y and organic ligands) were injected into mice bearing mamma adenocarcinoma, melanoma or s o l i d EHRLICH-tumour in t h e h i n d u p p e r l i m b . We o b s e r ved both the tumour growth and the median surviv a l t i m e of t h e a n i m a l s . In a d d i t i o n we r e g i s t e red the leucocyte number a f t e r i.p. i n j e c t i o n of different 90y-radioactivities into normal mice. The 90y-treatment resulted in a d r a s t i c decrease of t h e t u m o u r growth a n d an i n c r e a s e of t h e s u r v i v a l t i m e by t h e f a c t o r 5 - 10 in a l l c a s e s . The mamma adenoearcinoma c o u l d be c u r e d c o m p l e t e l y by m e a n s of o u r 9 0 y - p r e p a r a t i o n without any influence on t h e s u r v i v a l t i m e of t h e c o r r e s p o n ding tumour hosts compared with normal controls. We o b s e r v e d a distinct decrease of t h e l e u c o c y t e number after the application of 0 . 3 7 M B q 9 0 y and a normalization a f t e r a b o u t 15 d a y s p . i . T h e decrease of t h e l e u c o c y t e number h a d no c o n s e quence for the survival t i m e of t h e a n i m a l s investigated.
574
701
702 -
w
O. STULZAFT, C. LOC'H, B. MAZIERE, A. STROTA.
Service B o s p l t a l l e r Frederic J o l l o t ,
T. Forster,
Gy.
Sdskuthy,
t. Bursics
CEA, Orsay, France.
Institute Sciences, INVESTIGATION OF THE BINDING PARAMETERS 76Br-BROMOLISURIDE, A NEW LIGAND USED FOR VISUALIZATION OF BRAIN DOPAMINED2 RECEPTORS.
OF PET
Bromollsuride (BLIS),an ergolene derivative, has high affinity and selectivity for dopamlne D2 receptors. BLIS labelled wlth the positron emitter Bromlne-76 can be used for, in-vlvo, PET visualization of brain D2 receptors. In this work, we compare the values of In-vitro and In-vivo binding parameters of 76Br-BLIS on central animal'or human D2 receptors. In-vltro, studies have been performed on strlatal membrane homogenates by using increasing masses of high specific radioactivity radioligand. Non linear fitting of experimental results allow us to calculate the afflnity of the radioligand and the density of striatal D2 receptors (Kd = 0.2 nH, Bmax : 34 pmole/g). In-vlvo, the specific binding of 76Br-BLIS has been studied by PET in primates, In equilibrium conditions, by using a saturation model. The correlation found between these in-vitro and In-vlvo results, prove that equilibrium model can be used, in clinical situation, for the quantltation of D2 receptors in neurologic or/and mental diseases.
703
of I s o t o p e s o f the Hungarian Academy Budapest P.O.Box 77, H-1525 Hungary
of
Tc-99m-CHELATING BIOTIN-DERIVAIIVES FOR IMMUNOSCIHTIGRAPHIC APPLICATIONS The use of the biotin-avidin system in immunoscintigraphy is a promising method. Our aim was to synthesize Tc-99m-chelating biotin-derivatives with which the lull potentials of the biotin-avidin system could be exploited in clinical use. We syntesized a number of compounds with different function-groups and tested these for labeling efficiency (by PC and TLC), blood-clearance (in rats) and for affinity to avidin. Some of the compounds was tested for imaging applicability in model-experiments: we injected immobilized avidin into rats intramuscularly followed by an iv injection of Ic-99m labeled biotin-derivative. We have fwund a few compounds (for example biotinil-hydrazino-diacetic acid ) that complied with our requirements: at least 95% labeling efficiency, retained affinity to avidin and fast b l o o d - c l e a r a n c e via the kidneys (70-80% of the non-bound labeled biotin-derivative cleared from the blood in 2 hours). In the model-experiments the label was localised at the site of the avidin.injection in 2 hours with no significant accumulation in other organs (except, of course the kidneys and the bladder). Conclusion: these biotin-derivatives can possibly be used for two-step immunoscintigraphic examinations.
704 B.Zmbova, M.Jovanovid, S.Vladimirov* and D.~ivanov-Stakid~
A. Bockisch, S. Ai-Hasani*, H. v.d.Ven*, K. Diedrich*, Ch. Posch, A. Hotze, J. Ruhlmann, D. Krebs*, H.-J. Biersack. Dept. Nucl. Med., Dept. Oynecol. (*), Univ. Bonn, W. Germany
Tc-99m-HMPAO ~ STABLE LABELLING A G ~ T FOR S P ~ T O Z O A AND IN-VIVO VISUALIZATION OF SPERM MICRATION BY SCINTIGRAPHIC TECHNIQUES. There are no procedures described for radiolabelling of spermatozoa (SP) for in-rive scintigraphy. In addition there are no reports about using human SP or Tc-99m as labelling nuclide. We optimized the labelling conditions for SP using Tc-99m-HMPAO. Our method involves incubation of the SP, obtained by "swim up" technique, in isotonic saline solution at r o o m temperature followed by washing the storage in Ham's (F-IO) medium. For optimizing the labelling yield we varied the activity (30 - 700 MBq), t h e volume of incubation solution (.4 - 2.5mi), duration of incubation (5 - 30 min), and the number of SP (10 100 mill.). The results demonstrated the best labelling yield at lowest volume (.4ml), and an incubation time of app. 20 min. The labelling yield increased in a non linear way with the number of SP up to > 60% for 100 million SP. The 24h stability of the labelled SP was found to be > 93%. The viability and motiltity did not appear to be influenced noticeably by the procedure. Conclusion: Rsdiolebelling SP with Tc-99m-HMPAO is easy to perform and effective. Our technique combines the excellent radiation characteristics of Tc-99m, the ready availability of this nuclide, and a high labelling yield and stability. In preliminary studies in female rabbits we could clearly demonstrate the in rive migration of labelled sperms by gamma camera imaging. Kinetic studies were performed employing dynamic scintigraphy.
The Boris Kidri~ I n s t i t u t e of Nuclear Sciences Vin~a, Beograd, Yugoslavia *Faculty of Pharmacy, University of Beograd, Yugoslavia
INFLUENCE OF BILIRUBIN ON THE BIODISTRIBUTION OF 99mTcHIDA AND 99mTc-IODIDA IN RATS AND THEIR INTERACTION WITH HSA The mechanism of i n t e r a c t i o n of b i l i r u b i n with 99mTcHIDA and 99mTc-IODIDA was investigated on Wistar rats. The i n t e r a c t i o n of those complexes with proteins was also studied in v i t r o . A group of animals was at f i r s t injected i . v . with bil i r u b i n and then a f t e r 1 min with 99mTc-HIDA, while the second group was injected in the sameway with 99mTc-IODIDA A control groups of animals were investigated at the same time i n t e r v a l s without b i l i r u b i n . The animals were s a c r i ficed and the d i s t r i b u t i o n of a c t i v i t y at d i f f e r e n organs was measured at various time i n t e r v a l s a f t e r i n j e c t i o n . At animals treated with b i l i r u b i n and 99mTc-HIDA an e f f e c t of b i o d i s t r i b u t i o n was observed in decreased accumulation in l i v e r (ca 30%) and in slowed excretion through the i n t e s t i n a l t a c t (ca 30-40%) of the injected dose. No such e f f e c t was found with 99mTc-lODIDA-bilirubin. The protein binding for HSA-99mTc-IODIDA with and without b i l i r u b i n was determined by the p r e c i p i t a t i o n method with t r i c h l o r o a c e t i c acid. I t was found that protein binding with b i l i r u b i n is s I i g h t l y higher. The measured protein binding was u~ed to calculate the a f f i n i t y constant, e.g. 1.3xlO4(mol.dm-3) - I for system 99mTc-IODIDA-HSA and 4.0xlO3(mol.dm-3)-I with b i l i r u b i n . The results on p r o t e i n binding and a f f i n i t y constants indicate a p o s s i b i l i t y that b i l i r u b i n binds to the same protein receptors in serum as the radiopharmaceuticals.
575
705
706 F. Scopinaro, M. Liberatore, C. Manni, G. Ruggiero, Di Loreto, A. Centi Colella
M.
M.Moragas, C.Piera, A.Pavia, M.Minoves R.Fern~,ndez, A.Nuxi and J.Setoain
Dpt. Medicina Sperimentale, Nucleare, University "La Sapienza", Roma
Nuclear Medu:xne Set'vice, Clinic Nosp~tal. Barcelona, Spain.
Eigthy leukocyte ]abel!ing with 99mTc-HHPA0 have been made to improve the techn,que.The leukocyte pellet was obtained from 30 ml of HES sedimented blood and centrifugated at 250 g f o r 5 mln. The ,nfluence o f Rad:ochemicat purely (RP) o f 99mTc-NMPA0 at different time--_., PLgsm3 c o n c e n t r a t i o n in label![rig media, Leukocyte concentration, Temperature and Time o f incubation, Cell associated a c t i w t y (separation w~th Perooll-saline), In vitro viabihty (VV) (T.?ypan-Blue t e s t ) and In' vlvo evaluation imaging in 45 patients" on the labelblg was studied. At 10 mm about 90z o f the a c t i w t y was in tile lipophlllc form o¢ 99mTc-HMPAO. A decr.ease w~th time in RP wttich Ilmitated radiopharmaceut,cal use was observed. The labelling e f f i c i e n c y (LE) was significantly higher (p<.0! and p<.O01) with OX plasma (70.7 t 14.2Z) than with 25Z (50.7tla.5Z) and 507 (49.5t12.1Z), respectively. NO signify'cant d~fference ;n tile LE was found w,th 85Z and 50Z pbsma.There was an rncrease ,n LE as the number of leukocytes increased. The LE was significantly h~gher w~th a leukocyte concentration o f >13000 x 109/] plasma than with a concentration o f <7000 x 109/1 plasma (p<.O5).No s~gnlf~cant d i f f e r e n c e m the LE was found at RTa- and 37-oc and from 20 m,n o f incubation. The cell bound a c t w , t y was: granulocytes (51Z), mononuclear leukocytes and p!atelets (46z) and red blood celb(£,9X). The VV was about 90Z at OZ, 25Z and 50z o f plasma. In vivo distr,but~on was ¢~siolog~cal and very stmilar t o t h a t seen w~tl~ l!lh~-Merc-!eukocytes. In addition activity was seen always ~n bladder and occas~onally =n kidney and renal pelvls; in large vessels lh and 4hi and in colon at 24 h. The activity in bone marrow was remarkably higher than with 1111n-lterc leukocytes.
707
Medicina
708
R v s e r , B M i a z z a 1, J - P P a c c a u d 2 a n d
Div. de
M~decine
Nucl~aire,
et C l i n . M ~ d i c a l e 2 , 1211
di
ENCEPHALIC UPTAKE OF 201TI-DIETHYLDITHIOCARBAMATE(DDC) Aim of this work is to evaluate the oerebral uptake of the lipophilic complex 201-TI DDC and its intracerebral distribution in animals and the clinical usefulness of the 201-TI DDC SPECT in ht~nans. DDC was labeled as reported by Vyth and o311 (I). The product was then filtered by a sterile anionic and cationic exchange resin that holds 23% of the activity. A carrier free and 100% labeled 201-TI DDC complex was obtained. 5 Wistar rats and 5 sheeps were injected i.v. with 201-TI DDC and sacrificed 20 min p.i. The cerebral uptake was 3% in rats and 2,8% in sheeps. Samples (50 mg) of brain cortex (B.C.), brain stems IB.S.) and cerebellar cortex (C.C.) were drawn from the sheep. The residual encephalon was cut in slices 0.5 cm tick and scintigraphic images (sc.im.) were registered. Values obtained from cerebral samples (B.C. = 100%) were: 95% B.S.; 52% + 9 C.C. Values obtained from sc. im. (cp/pixel) were: 106 + 30 B.C.; 103 + 26 B.S.; 51 + 13 C.C. Ht~nan study: planar scintigraphy and SPECT were performed in 2 normal volunteers, 2 patients with Parkinson's disease (P.D.), 2 patients with multiple sclerosis (M.S.), 2 patients with cerebrovascular disease (C.D.), previously studied using 99m-Tc ~4PAO. Cerebellar uptake was higher in the 99m-Tc HMPAO than in the 201-TI DDC SPECT. In patients with P.D. and M.S. 201-TI DDC SPHCT showed wider lesions than 99m-Tc HP~AO. Conclusions: the collected data suggest that the 201-TI DDC is a useful scintigraphic agent for the evaluation of the tissue damage in the brain diseases. (1)Vyth A et al., PharmWeekbl Sci Ed 1983; 5 : 2 1 3 - 6
99mTc-HHPAO-LEuKocyTE$: EVALUATIONOF THE LABELLINGTECHNIQUE
J-E
Sezione
- Geneva
,
div. de
Geneva
A
Donath
Gastroent~rologie
University
1
Hospital
Switzerland.
S. GORE, D. BILLINGTON, A.I. MORRIS, I.T. GILMORE, E. JOIRIS. Natural Sciences, LIVERPOLL POLYTECHNIC, Byrom Street, LIVERPOOL L3 3AF
L . . . . . . . . . . .
INDIUM-111 OXINE METHOD GRANULOCYTES PREFERENTIALLY.
THE
LABELS
"ACTIVATED"
The measurement of the fecal excretion of I n - I l l - l a b e l e d leucocytes has been shown to be a sensitive index of the activity of the inflammatory bowel diseases. We found > 35 % ID in the feces (24h) in 10 from a series of 49 patients with colitis and a positive imaging. The patient granulocytes were purified on a Percoll gradient and labeled (200-300 ~Ci In-111) in the absence of serum.
Two hypothesis could account for this high excretion rate : the exsudation of a very high fraction of the total circulating blood granulocytes, or the selectivity of the labeling (or purification) method for a subset of "activated" cells, which would localize preferentially in the inflammatory lesions. The second hypothesis is supported by the following results : - the autoradiography of smears of I n - I l l - l a b e l e d granulocytes shows an heterogeneous labeling (heavily and lightly labeled cells). - when the granulocytes are separated by adherence in vitro into 2 fractions, the specific radioactivity of the adherent cells is 1.8 to 7.5 times higher than that of the non-adherent cells ( mean of 3 . 2 , 5 experiments ). The seleciivity of the In-111 oxine labeling method for "activated" granulocytes could be related to the membrane modification of the activated cells, and could explain the long transit time of the labeled granulocyles in the lungs.
HEPATIC UPTAKE AND BILIARY EXCRETION OF RADIOIODINATED GALACTOSYL NEO GLYCO ALBUMIN. Galactosyl Neo Glyco Albumin (NGA) is a synthetic ligand to hepatic binding protein, a hepatocyte specific membrane receptor (i). It has been proposed as a useful agent for assessing hepatocyte function (2). The hepatic uptake and biliary excretion of radio-iodinated NGA (28-32 galactose residues per albumin) were investigated using an isolated perfused rat liver system. A single pass method was employed, and perfusate Collected via the thoracic inferior cava for 60 minutes, and bile via the cannulated bile duct. Both perfusate and bile were assessed for radioactivity before and after the addition of 15 % trichloracetic acid. Acid soluble material (small molecular weight metabolites of NGA) appeared in the perfusate after i0 - 13 minutes, which is probably an indication of receptor recycling time. Although biliary output was small, less than 2 % of infused dose, that which was excreted in bile became increasingly acid precipitable. This probably indicates the misdirection of vesicles direct to the bile canaliculus, bypassing the pathway to lysosomes which has become saturated. (I) STOCKERT R.J. et al 1983, 3 : 750-757, Hepatology. (2) VERA D.R. et al 1985, 26 : 1157-117, J. Nucl. Med.
576
709
710 J.Weininger, D.Rintlsr, J.Shalev, N.Kanion, D.Zemach and D.Issachar
Nikula, T., Hiltunen, ]. and Johnsson R SOREQ - NRC 70600 YAVNE, ISRAEL
Technical Research Centre of Finland, Reactor Laboratory SF-02150 Espoo, Laakso Hospital, City of Helsinki, Finland
INFLUENCE OF 19lOs - 191mIr GENERATOR AGE AND BUFFER
THE STRUCTURE STUDIES OF LOW pH 1111n-BLMC C0MPLEX
SYSTEMS ON THE BIOLOGICAL BEHAVIOR OF 191Os
The low pH 111In-Bleomycin (111In-BLMC) complex has been suggested to be a tumor seeking radiopharmaceutical with better properties than 57Co-Bleomycin (57Co-BLM); the considerably shorter half-life, faster kinetics and higher tumor to background ratio (Hou et al, 1985). We used it to four patients with poor results. which a r e summarized as follows: * 1111n-BLMC is in vivo stable * itis slower kinetically than 57Co-BLM * itshows almost no tumor uptake into lung tumors. On the other hand the quite good resultsusing the same compound for mazillofacial tumors (Matejka et al 1987) combined with our results lead'usto study the differences in the structure. We separated the Bleomycin using Sephadex C cation exchanger and labeled each separated B L M subgroup with lllln at low pH to find out if formation of the complex is associated to any subgroup. We eluted the normal IIIIn-BLMC through the same column and also we performed the Sephadex G gel chromatography for the normal IIIIn-BLMC preparation to reveal the ionic nature and size of the complex
One of the main advantages of 191mlr for cardiac studies is the very low radiation dose to the patient. Due to its 5 sec. half-life contribution
very low. The radiation doses are mainly due to the breakthrough of its 16 days half-life parent, 191Os. The 191mIr activity necessary for imaging is generally accompanied by a few micrecuries of 19los. The influence on the biological
behavior of generator age and of
different buffer systems used for the pH adjustment of the eluants was studied in mice. Extende~ to.xicity, body clearance and biodistribution studies were performed for several generator batches. The solution to be injected was obtained by eluting generators 5 to 49 days old with a 0.9% NaCI solution at pH 1. The pH of these solutions was adjusted to 5-9 with phosphate, succinate or lysine buffer or NaOH. Our studies showed that both factors do influence
biological behavior of 19lOs in
mice. The body clearance, mainly urinary clearance, is much quicker upto 3 weeks after generator preparation than thereafter with each one of the pH adjustments.
The results are summarized as follows: * formation of 111In-BLMC seems to be connected to a2 subgroup * the complex is anionic at pH 6 * 1111n-BLMC is not a minority fraction of normal BLM * it is not a combination of BLM molecules with 111 In * it seem to have slightly smaller molecular size than In-BLM.
the
of 191mIr to the radiation absorbed by the patient is
The buffering with |ysine seems to be the most
suitable: the mice show no reaction after the injection of more than 100 human doses and it results in the quickest body clearance. This rapid urinary clearance reduces by a factor of 2-3 the radiation dose to the liver, the organ with the highest 19los uptake.
712
711 *
**
***
E. Wittendorp-Rechenmann , C. Demangeat M. Finck and S. L~vy**** ' * Laboratolre de Biophysique des Rayonnements et de M~thodologie - I.N.S.E.R.M.U. 220 ** Institut ~e Physique Biologlque *** Centre Paul Strauss **** Ins tltut d 'H~ma tologie
I.Nakatsuka, H.Saji*, K. Shiba, A Yoshitake, Y.Iida*, Y.Magata*, Y.Yonekura*, J.Konishi*, and A.Yokoyama*. Toxicology and Biochemistry Laboratory, Sumitomo Chemical Co. Ltd., Osaka, *Faculty of Pharmaceutical Sciences and School of Medicine, Kyoto University, Kyoto, Japan.
Universlt~ Louis Pasteur - 67085 STRASBOURG CEDEX - FRANCE
FA~, HIGH EFFICIENCY MICROAUTORADIOGRAPHIC PROCEDURE FOR THE LOCALIZATION OF T-DECAYING RADIONUCLIDES CASE OF I N D I O N - I I I Autoradiography with isotopes emitting internal conversion- and Auger electrons showed to be an interesting method for the microscopic evaluation of tracer distribution patterns as well as a basis to calculate absorbed dose distributions. The present paper proposes a microautor~dlographic approach to the simultaneous localization of both the low energy electrons~ known to be very effective in damaging radiosensitive targets, and the relatlvely far reaching high energy electrons. On the basis notably of a judicious adaptation of the photographic imaging parameters to the characteristics of the radiations emitted by a given radionuclide, a fast, efficient autoradiographic procedure has been developed and applied to the specific case of Indium-ill. For this purpose, labeled, isolated lymphocytes have been used as a source-model to test the autoradlographic method. Different amounts of Indium-ill oxine (30 ~ C i / l ~ - down to 3 ~Ci[lO6 lymphocytes) have been employed in combination with two types of nuclear emulsions (Kodak NTB2, llford K5) at various thicknesses (5 pm up to 30 ~m) and short exposure times (24 to 48 hours). The preparations have been submitted to specific photographic signal enhancement treatments which lead to a considerable increase of the information stored within the autoradiographic preparations. The preliminary results obtained will be discussed, notably in terms of detection efficiency and resolution and illustrated by numerous microphotographs of Indlum-ill labeled lymphocytes.
2'-IODODIAZEPAM : A NEW RADIOPHARMACEUTICAL FOR SPECT STUDIES OF BENZODIAZEPINE RECEPTOR. The studies on benzodiazepine (BZ) receptor function by SPECT calls for the development of radioiodinated compounds with high affinity for BZ receptors. A review on the extensiye structure-activity relationship studies of the series of 1,4-benzodiazepine derivatives, offered us the basis for the selection of the 2' position of 5phenyl ring of diazepam (DZ) as the best exploitable site for the introduction of iodine. Since iodination at 2' position by accesible methodology was difficult, a synthetic methodology through the O-iodobenzyl chloride reaction with N-(4-chlorophenyl)-4-methylethylenediamine w a s estimated: after cyclization and oxidation, the 2'-iododiazepam (2'-IDZ) was obtained. The radiolabeling of 2'-IDZ with high specific activity easily caused by bromine-iodine exchange reaction of 2'brominated DZ with sodium radioiodine. In the in vitro binding assay, the new 2'-IDZ showed high affinity for BZ receptor in the cortex of rat, reaching several times higher than the corresponding parent compound, DZ. In rive mice biodistribution study with 1-125-2'-IDZ (>200 Ci/mmol) demonstrated high accumulation in the cortex, which was displaced by t h e a d m i n i s t r a t i o n of pharmacologically active benzodiazepines. These results was also assessed by SPECT imaging studies of dog brain after the administration of 1-123-2'-IDZ. Gathered data indicate that 2'-IDZ constitutes a very promissing caditate for the SPECT studies of BZ receptor.
577
713
714
O-d. Meyer, F. Orth, P. Oialow, H. Hundeshagen
T.R. DeGredo, H.H. Coenen, G. StOcklin
Ableilung Nuklearmedizin und spezielle Biopbysik der Medizinisehen Hachschule Hannover, D- 3000 Hannaver 61 Institut f~r Chemle 1 (Nuklearchemle), Kernforschungsanlage JUlich GmbH, D-5170 J~lich, FRG COMPARISON OF BRAIN UPTAKE AND PROTEIN INCORPORATION PHENYLALANINE AND p-IODO-PHENYLALANINE IN RAT&
OF
Amino acid uptake and metabolism in brain tissue is of interest becauseof its diagnostic potential for grading of brain tumors. In order to transfer same of the potentiel, identified by PET users, to conventional nuclear medicine, we have analysed the biokinetics of labeled p-lodo-phenylolanine in rot brain and compared them with the natural amino acid phenylMonine. p_ 1ZSiodo_phenylManine w~ prepared by exchange labelling. [ 1'tC] _ penylalanine w~ obtained from Amersham. Rats were injected 0.9 mBq of either, compound intravenously and sacrificed at tifhe in(enrolls ranging from 5 to 120 rain. Brains were removed, dissected and homo~nized. Protein bounO activity was precipitated by trlchloro acatlc acid The nonbound fraction was separated from the protein fraction by cantr ifugation. In plasma phenylalanine is clearedrapidly likemany other amino acids. Metobolit~ appear in plasma after I0 rain.p-l-phenyl- alanineremains at a constant levelafteritsdistributionfor at least 120 rain,indicatingthat it is not metabolized. The uptake of phenylalonine in brain tissue is fastand completed in a short time for as for other amino acids.The uptake of p-Iphenylalanine ischaracterizedby s fastinitialriseto nserly the same level as for phenylslanine,followedby a further but slower uptake phase which continues for 60 minutes. The protein incorporation of phenylalanine reaches 90 % of the uptakeat 120 rain.In contrastp-l-phenylalanineis not incorporated intoproteinsat all.The coIIuaruptake consistsat all timesof fr~ p-l-phenylalanine. The uptake of both amino acids can be bl~k.ed efficientlyby saturationof the carMerenzyme in the BBB by methionine. In conclusionwe have found thatp-l-phenylalanineis carriedacross the blood brain barrier by the same carrier as phenylalsnine,despite a total lack of further"metabolism In brain tissue.
715 H.Herzo~*, L.V.Hankes*, E.H.Coenen=, E.Rota*, E.-J.Lang enl, W.Wutz 2, G.St6cklin 2, and L.E.Feinendegen I. i) Institute of Medicine and 2) Institute of Chemistry, Nuclear Research Center JQlich, D-5170 J~lich, FEG.
INCORPORATION OF L-2[18F]FLUORTYROSINE INTO MYOCARDIAL PROTEINI NORMAL VALUES IN MICE AND EFFECTS OF ANOXIA IN ISOLATED RAT HEARTS Previous work in this laboratory has shown L-2[18F]fluorotyrosine (2FTyr) to be accepted for protein synthesis in brain. Uptake of 2FTyr in hearts of mice given bolus injections was 4.3~0.4 Zdose/g at 5 min p.l. and declined slowly to 2.0±0.8 Zdose/g at 2 hr p.i. Heart-tobl.ood ratios ~ange~ from ! n-~.a t~rnu~bou~ ~ 9 ~r period. TCA precipitation of heart homogenates showed a 75I incorporation of 18F into heart protein within the first 40 min, correlaglng with earlier results in the brain. In parallel expeKiments, the effects of anoxia on protein incorporation and myocardial kinetics of 2FTyr were investigated in Langendorff perfused, isolated rat hearts. Nofmoxlc or anoxic condltions were maintained throughout each study and 2FTyr was administered to the hearts within the perfusion medium (0.2-1.0 ~Ci/ml) for a period of 20 mln, followed by a 40 mln washout period. Analysis of heart homogenates indicated a 58~17I reduction of protein synthesis rate by anoxia, a result which compares well to literature data with 14C-phenylalanlne (Jefferson et el. 1971). Time-courses of 18F radioactivity within hearts measured by q,7-coincldence cou~tlng of the whole heart also showed significant changes with anoxia due to increased washout of unincorporated 2FTyr from tissue. Jefferson LS, Wolpert EB, Giger KE, Morgan HE. Regulation of protein synthesis in heart muscle, J Biol Chem 246. 2171-2178 (1971)
716 S OSMAN and H J DANPURE MRC Cyclotron Unit, Hammersmith Hospital Ducane Road, London W I 2 0 H S ,
CEREBRAL UPTAKE OF NICOTINIC ACID AND NICOTINAMIDE IN THE HUMAN BRAIN MEASURED BY PET IN VIVO Although deficiencies of nicotinic acid and nicotinamide can cause disturbances of the central nervous system, the cerebral uptake of these vitamins has not ~et been studied in man in vivo. This pilot study was done to quantify the cerebral uptake of these vitamins using PET. tiC-nicotinic acid (NAC) was produced by carboxylation of 3-bi-pyridine with i'CO= and **C-nicotinamcide (NAH) by amidation of NAC. One normal control (NC) and one patient with Huntington's disease (HD) were studied with NAC, and two NC and one HD with NAY. After injection of 70-400 MBq of the tracer dynamic PET scans of the brain were made with a tomograph PC4096-15WB up to 50 min. Plasma activity was obtained from arterialized venous blood. Data were analyzed by Patlak plots and compartmental models. PET images showed very low cerebral uptake of NAC compared to the vascular tracer, whereas NAN was clearly visualized in cortical areas. The uptake in the whole brain was (0.56% of injected NAC and 2.6% of injected NAM (p<0.001). Patlak plots revealed a third compartment for NAC and NAM with similar values for ks of about 0.024 min-*. Subsequent fits with a 3-compartment model gave acceptable results only for NAM, because NAC data had too much noise. The mean rate constants were: K,=0.19 ml/g/min, ks= 0.08min -I, ks= 0.06min-t and kd= 0,02mln -t. All results were similar for NC and HD. The first in vivo data of cerebral uptake of NAC and NAM in man show significant differences for the two vitamins. With its higher uptake, labelled NAM may he useful in the study of nervous disorders caused by vitamin deficiences.
England
FLUORINE-18-2-FLUORODE~XY-D-GLUCOSE (18-FDG) LABELLING OF HUMAN GRANULOCYTES TO STUDY INFLAMMATION BY POSITRON-EMISSION TOMOGRAPHY ( PET ) The aim of this study was to evaluate 18-FDG, produced from no-carrier added 18-fluoride as a potential agent for radiolabelling granulocytes to investigate inf]ammatory processess by PET. The e f f e c t of g l u c o s e , c e l l c o n c e n t r a t i o n and a c t i v a t i n g a g e n t s on t h e u p t a k e o f 18-FDG by g r a n u l o c y t e s i n v i t r o was m e a s u r e d . The p e r c e n t a g e . t , t a k ~ of 18-FDG b5 l x l 0 V / m l g r a n u l o c y t e s i n a medium c o n t a i n i n g 0 . 0 1 5 , 0.1 and 1 mg/ml of glucose was 80%, 40% and 2% respectively after 30 min at 37oc. When the granulocyte concentration was raised to IxlOS/ml, the uptake of ]8-FDG containing 15 pg/ml was increased to 97%. The viability of tile cells measured by trypan blue exclusion ~as 97%, Activating the granulocytes with FMLP and PAF also increased the uptake of 18FDG. ~\Ithough 18-FDG was i~hosphorylated to 18FD{J-phosphate within the cell, 18F was released fr,~m the labelled ce] Ls in proportion to the amount of exogenous glucose. We therefore conclude thai t b~ uptake of 18-FDG by granulocytes may be usefu] in studying inflammation by PET as recently demonstrated l)5' Clark e t a l (1989) [ C l i n S~i 76 (Sup!,l 90) 33P].
578
717
718
F. Szelecs6nyi, Z. Kov~cs, B. Spett +, F. T6rk6nyi Institute of'Nuclear Research of the Hungarian Academy of Sciences, Debrecen, Hungary
D.R. Vera K.A. Krohn, R.C. Stadalnik: Departments of Radiology, University of California, Davis; Sacramento, California, USA; and University of Washington, Seattle, Washington, USA.
F.J.C. Natl. Research Inst. Radiobiol. and Radiohygiene Budapest, Hungary PRODUCTION OF 66GA BY COHPACT CYCLOTRON FOR PET STUDIES For studying some slow dynamic processes such as lymphatic transport, by positron camera the 66 Ga, (T~=9,4 h, 8 =56,5%) seems to be potencially useful label for serum albumin colloids. Present work deals with the production and preparation of high-purity carrier free 66Ga using a small compact cyclotron. The production ~s performed via the 66Zn(p,~)56Ga reaction on enriched 6 Zn(99%) target. The yield, as a function of incident energy, was studied in the range from 6 to 18 MeV. The ±arget was prepared by electrodeposition on Ni plated Cu backing in a tickness of 500p m. After irradialion it was dissolved from the backing in cc. HCL. The separation of radiogallidm from In matrix and traces of Cu, Ni and Fe was carried out on DOWEX 50 WX2 ca%ion exchanger resin. The 66GaC13 intermedier in physiological saline solution is suitable for labelling of co~lercially available albumin colloid kit. At 15 HeV energy the produciion yield was II mCi/pAh which is about ten times higher than it was obtained in reaction 63Cu(~He,n) 6~a used by Goethals P.at a1.(1987). The chemical procedures took place 2 h and the overall yieldwas 90%. Dynamic processes in rats and rabbits has been studied. For the hospitals having Small cyclotrons %he mentioned rear%ion is convenient to produce great amount of 6 % a allowing the investigation of longer dynamic processes. Goethals P, Coene H, Slegers 6, Agon P, Deman J, Schelctra. ere K. Cyclotron production of 6~ Ga to labe 1 serum album~n colloids for imaging by PET. Nucl.- Hed. 26, 171 (1987)
719
[6SGa]DEFEROXAMINE-GALACTOSYL-NEOGLYCOALBUMIN: A POSITRON AGENT FOR REGIONAL MEASUREMENT OF HEPATIC PLASMA FLOW AND RECEPTOR BIOCHEMISTRY. We have characterized a new radlopharmaeeutlcal for the regional evaluation of hepatic receptor biochemistry: [eSGa]deferoxamine-galactosyl-neoglycoalbumln ([Ga]DfNGA). To achieve coupling to NGA, we elected to use the two-step glutaraldehyde method, followed by diafiltratlon against l0 exchange volumes of normal saline. Our Initial concern with this method was the formation of albumin polymers which did not occur for products with less than 5 Df per NGA. In addition, the Df-coupllng was stable during storage. Labeling was complete within 10mln at DfNGA concentration as low. as 0.05mg/cc. HPLC absorhance and activity profiles of [e7Ga]Df-NGA (I.i Df/NGA) revealed two significant features: 1) extremely low amount of polymeric Df-NGA, and 2) the absence of free [eYGa]Df. Scatchard assay of [SYGa]Df-NGA revealed binding affinities equal to [12SI]NGA of similar carbohydrate density. Biodlstributlon in rabbits and liver timeactivity data of TONGA and [SYGa]Df-NGA of similar galactose density and molar dose were equivalent. Based on preliminary PET studies in dogs, we developed a kinetic model for regional measurement of receptor biochemistry. Using local identifiability analysis, we concluded that adequate precision for receptor concentration and affinity (CVs < 10%) could be achieved if: i) high receptor occupancy is achieved, 2) a [eaGa]Df- NGA of high receptor affinity is used, 3) an independent measurement of plasma volume is obtained, and 4) the entire liver is observed.
720
K. Wakita,
Y. Imahori,
M. Yamashita,
H. Horii , R. F u j i i , T. Yagyu,
Y.KUNIYASU, S.HIGASHI, Y.NIIO, S.OKADA*, M.OHTO*, K.IMAZEKI** and N.ARIMIZU**
T . Inaba, Y. Oda, H. Nakahashi. Nishijin Hospital , Kyoto Prefectural University of Medicine (Neurnsurgery, Radiology )
MEASUREMENT OF THE IN VITRO STUDIES.
BOUND/FREE
RATIOS
OF 6 8 G a - E D T A
68Ga EDTA ( G a ) may be used as a macromolecular tracer for estimation of the vascular permeability and vessel pore size. However, the existence of the a l b u m i n - Ga bound type in human blood is unclear which is a significant problem when quantitative compartment analyses are performed. This study was designed to investigate the percentage of the fraction of the a l b u m i n - G a bound type and calculate the binding constant between albumin and Ga in in vitro studies, We employed agarose gel (Blue Sepharose),which has a specific affinity to human albumin in a buffer solution, to measure the bound and free ( B / F ) ratios of G a . The plasma samples from the human subjects were incubated in the buffer solution (tris buffer, pH 7 . 0 ) containing Ga for 60 minutes. Several time sequence plasma samples were separated using an agaroee gel column. The B / F rratios reached an equilibrium at 10-15 minutes and demonstrated various percentages. The binding constant (K 1 / K 2 ) between albumin and Ga was represented by the follwing equation, g (t) = Kl*exp
( - K 2 t ) J" f ( t ) * exp ( K 2 t ) d t ,
where f ( t ) is constant when t is infinite. The mean binding constant value obtained from normal human subjects ( n = 4 ) was 0 . 0 8 ~ 0 . 0 1 which was almost constant in spite of the differing albumin content in the blood. This data suggests that it is necessary to correct for the a l b u m i n - Ga bound fraction in the quantitative compartment analyses in dynamic P E T studies.
The Dept. of Radiology, Teikyo University Hospital, Tokyo, Japan. and Dept. of Ist Internal Medicine* and Radiology**, Chiba University Hospital, Chiba, Japan. CLINICAL APPLICATION UF A NEW EIVER SUANNING A~ENT LABELED WITH GENERATOR-PRODUCED POSITRON EMITTERS. We have developed a new liver scanning agent in convenient kit type for use of positron emission CT (PET). The labeling procedure for Ga-68 HSA microspheres can be completed in I0 to 15 min using NEN generator coupled with an acetate buffer system. For the clinical application of this scanning agent, we have got approval by the ethical committee of Chiba University. In this study, this agent was evaluated for clinical usefulness in detection of SOLs of the liver on routine examination and usefulness as a function test for the reticuloendotherial cells. Forty six patients(5 normal, II with chronic hepatitis, 12 with liver cirrhosis and 18 with liver cirrhosis and hepatocellular carcinoma) were studied for PET imaging of the liver using HEADTOME-III(SHIMADZU whole body PET scanner). The sizes of hepatoma ranged from 1.2cm to 6cm in diameter, and all tumors more than 2cm were detected. The volumes of the liver and spleen were calculated as an index of reticuloendotherial cell function using the method of summation of the liver and spleen in each slice, and with differential absorption ratio. Liver uptake of radioactivity decreased with progression of chronic liver injury. Patients with liver cirrhosis showed significantly lower uptake of radioactivity compared with normal volunteers. It was concluded that Ga-68 microspheres is clinically promising agent for liver scanning.
579
722
721
K. OZKER, t . URGANC]O~LU, i .
USLU, E. VARDAREL|, A. ~OTUK
and A. SUNGUR, A. ERGUN, N. ARDAGIL, N. HO~KAN
G. Kliv~nyi, S. Matzku, and J. Schuhmacher. Institut f~r R a d i o l o g i e und P a t h o p h y s i o l o g i e , Deutsches Krebsforschungszentrum, Heidelberg, FRG
NUCLEAR MEDICINE DEPARTMENT, CERRAHPA~AMEDICAL FACULTY, FACULTY of SCIENCE, tSTANBUL UNIVERSITY and ~EKMECENUCLEARRESEARCHCENTER, ISTANBUL, TURKEY 99mTc-CYSTEINEAS A MARKERFORIN VIVOTISSUEMETABOLISMBYSPECT Amino acid transport and protein synthesis of normal and pathologic tissue have been studied using 11C labelled amino acids and PET. In order to deveIope an agent for studying the tissue metabolism by SPECT, 99mTc-cysteine has been synthesized by an e l e c t r o l y t i c procedure using t i n electrodes and an e l e c t r i c a l charge of 0.12 coulombs. A labelling y i e l d of 98.9 ~1.9 % was reached. Transplantab]e Ehrlich solid tumour and spontaneous carcinoma of dermal appendices of-.mice were selected as an in vivo model tissues to study.~he f u n c t i o n a l i t y of this agent. Biological d i s t r i b u t i o n of vvmTc-cysteine in normal mice at various time intervals was also studied. 99mTc-cysteine showed a rapid and high tumour accumulation. The highest concentration of the injected dosewas found in the kidneys indicating the renal clearanceof the aminoacid. A markeduptakewas shownin the pancreas. k~ole--body ~cintigraphyof tt~ur bearingmicewas acquired at various time intervals for 3 hours using a gatm~camerainterfaced to a ccmputer. Time-activity curves weregeneratedusing the ROIsover the ttmour and the bodybackground.EhrHch solid tumur curve reachedto a maxim~ at 30 rain and there was a flattening of the curve revealing a tissue retention of the tracer whereasthe total bodycurve showeda continuous' clearancepattern, allowing increasedtmDur to backgrotmdratios in the late images. In tunour tissue, the averageuptakewas 3 and 4.5 times of the normaltissue values at I0 and 180 min post injection respectively. Spontaneouscarcincmaof dental appendiceswas easily detectableat 5 rain reachingto a maximuntLmourto normal tissue ratio of 3.5 at 90 min post injection. The significant uptake in these ~ r s , selected as medeItissues for enhancedprotein synthesis, supports the hypothesis that 99mTc-cysteinehas a potential for the funotional diagnosis of tissue metaboI i sm.
723
R. Berberich I, A. Steinstr~er 2, S. Zabori 1 L. Kuhlmann ~ iAbteiiung f0r Nuklearmedizin der Radiologischen 2Universit~tsklinik, D 6650 Homburg /Saar Hoechst AG, Radiochemisches Labor D 6230 Frankfur£ / Main 80
IIIIN IN THE MOUSE LIVER AFTER APPLICATION OF I I I I N - D T P A L A B E L E D M O N O C L O N A L A N T I B O D I E S (MABS). Increased liver uptake after clinical a p p l i c a t i o n of I I I I n - D T P A labeled MAbs severely limits immunoscintigraphy in the abdominal region. This has been t e n t a t i v e l y e x p l a i n e d by several hypotheses, eg. Fc r e c e p t o r interaction, trans-chelation, scavenging o~damaged MAbs. Furthermore, h e p a t i c u p t a k e of xX±In in mice and m a n was found to d e c r e a s e w i t h i n c r e a s i n g dose of i n j e c t e d MAb. We sought to discriminate e f f e c t s r e l a t e d to the radiopharmaceutical from those r e l a t e d to ~the host s y s t e m by t e s t i n g 3 MAbs in 3 d i f f e r e n t mice strains. Liver uptake of lllIn was i n d e p e n d e n t from dose o v e r a range of 0.i-i0 ~g/mouse, i.e. 8-9% and 6.5% iD/organ w e r e a c c u m u l a t e d after lh ' and 48h, respectively. With 131I-labeled MAbs, no d i f f e r e n c e in the early distribution was found. However, dosedependent accumulation in the liver was noted with b a t c h e s p r e p a r e d under less than optimal l a b e l i n g conditions, i.e. 25% and 8.5% iD/organ with 0.2~g and 8~g, respectively. Re-injection of b l o o d from h i g h l y a c c u m u l a t i n g animals into n e w m i c e failed to p r o d u c e the effect. Thus, elevated liver u p t a k e in mice is an a r t e f a c t r a t h e r than a p h y s i o l o g i c a l phenomenon. In patients, dose d e p e n d e n t liver u p t a k e m a y r e s u l t from partial t r a p p i n g of x e n o g e n e i c IgG a n d / o r cross-expression of the t a r g e t antigen on liver cells.
724
A. Steinstr~Ser,
L. Kuhlmann, K. Bosslet, A. Sch~arz
Hoechst Aktiengeseilschaft, Frankfurt / Main, FRG Behringmmrke Aktienqesellschaft, Marburg / Lahm, FRG
INFLUENCE OP AMOUNTOF ANTIBODYON THE RESULT OF INNUNOSCINTIGRAPHY
KINETICS OF THE ACTIVITY OF GRANULOCYTES FOLLOWING IN VIVO AND VITRO LABELLING WITH A TC-99M OR IN-Ill LABELLED MONOCLONAL ANTIBODY BW 250/183 In the clinical trial of the monoclonal antibody we have used the Tc-99m labelled IgG 250/183 in 14 cases. The amount of protein applied to the patients lied in the range of 200-100 pg. The cell bound activity (total cell bound activity in the whole blood) raised from 17,6 ± 9% to 23,4 ± 9% after 4 hours and 24,~ ± 9% after 24 hours. On the assumption that an antibody with a higher spezific activity would result in higher cell binding rate, we applied in 3 patients 20 Pg of In-lll labelled IgG 250/183 with an activity of 74 MBq. The bell bound activity from 24 to 26% with aut any change in a time period of 26 hours. In 5 normal subjects we have performed an in vitro labelling of leucocytes with I0 Hg Tc-99m labelled IgG 250/183. The labelling efficiency was 39 ± 13% after 1 hour incubationtime and 45 ± 13% after 2 hours. The cells have been isolated in the same way as for labelling with In-lll-oxine. In 7 normal subjects, which were informed and had given their consent, we applied leucocytes, labelled in vitro with 20 Dg IgG 250/183. The mean labelling efficiency was 9,6 ± 4,8. The cell bound activity varied 30 to 26% after 24 hours with only small variations. It seems that independent of the labelling method, in vitro or in vivo, and indipendent of the amount of protein appplied, ass equilibrium between cell bound and plasma activity is reached after 20 hours.
The aim of these experiments was to determine the " i d e a l " antibody f o r an immunoscintigraph[c study.
amount of
In l i t m r a t u r e contradictive results have been discussed concerning the influence of high amount of antibody on unspecific uptake by organs o£ the RES. We showed in animal experiments that there is no influence of F -receptors on the degree of l i v e r uptake. A high protein dose c (140 mg: converted to human s i t u a t i o n ) bad no influence on uptake of the antibody t i n t o the l i v e r ( r a t s ; MAb: BW431/25 Tc-ggm; proteindose 40 ng up to 408 #g). So that there is no r a t i o n a l need to increase the protein mass in case of p u r i f i e d antibody-preparatlons. In case of the tumor, one can estimate the amount of antibody belm~ able to be f i x e d to c e l l s Assuming an average epitopedensity of I0 6 - i0 per c e i l , about i #g ( - !0 #g) can be bound by i g of tumortlssue. The present c l i n i c a l data assure, that this order of magnitude is v a l i d f o r most of the presently used antibodies. Animal experiments on nude mice xenografted with an antigen positive tumor confirmed this l i m i t a t i o n . Variation of antibody dose from 10 ng up to 10 mg per animal showed a decreased s p e c i f i c uptake when increasing the proteinmass over i0 #g. But i n i t l a l i s a t l o n of antibodies into the cells is a p o s s i b i l i t y to increase the specific uptake in some cases. These data sho~, that in case of immunoscintigraphy (but at least in ease of radioimmunotherapy) not increasing the proteindose is of importance but in contrary the reduction of dose. A l i m i t a t i o n would be given only by the achievable specific during the l a b e l l i n g process.
activity
580
725
726
G_y_.A.3dnoki, L.K6rSsi, B.Spett, M.FOzy ,3.Holland,3.L@ng "FJC" Natl.Res.Inst.for Radiobiology and Radiohygiene, Budapest, P.O.Box i01 H-1775 Hungary Natl.Inst.of Oncology, Budapest, R~th Gy~rgy 7. H-I122 Hungary ~ A.Szent-Gy5rgyi Medical Univ., Szeged, P.O.Box 469, H-6720 Hungary EFFECT OF RADIgLADELLING MEIHOI] ON BIODISTRIBUTION OF ANTI-MELANOMA NONOCLONALNo F ( a b ' ) 2 FRAGRENT During,clinical use of the 9~Tc and l i t - I n l a b e l l e d a n t i melanoma Ab (clone 225.285) F ( a b ' ) ~ fragment, a high background a c t i v i t y was observed in tNO abdominal and u r i nary t r a c t . T o understand the reasu~behied t h i s phenomenon~ radiochemical analysis using h i g h - r e s o l u t i o n c a p a c i t y methods, ng. SlYS-PAGE, radio-HPLC and electroimmunoassay, mere used. D u r i n g patient application (Natl. Inst. Pharm. t i c e n c e No: ~}68/77/86 and 24)1/77/88), several blood and urine samples were c o l l e c t e d f o r analysis of phaz'macok i n e t i c s , r a t e and route of excretion. Data were compared: with in v i t r o a n a l y t i c a l r e s u l t s on r a d i o l a h e l l e d antibody fragments.
Co~.
Blood i n I.D. % 30'
60'
Urine 60'
Trans- Dissoformat, c l o t . to Fob' % %
Labe11. yield
(~r~tarsd6ti~Ir jl), Forssell Aronsson E I), Jacobsson Hafstelnsd6ttlr 6 I}, Holmberg SB 2), Hafstr6m
LIndegren S 3), Karlsson B 3) Department of i) Radiation Physics and 2) Surgery, University of G6teborg, 3) Pharmacla CanAg, G6teborg, ._.S_~e_den. . . . . KINETICS FOR THE MONOKLONAL ANTIBODY C215
LABELLED WITH 75Se OR
%
50.6+10.9
16-20
15-60
5-15
90-96
In
80.5± 5.9
2.~-3.6
i-5
1-5
91-97
?2.9± 4.3
..........................................................
Dimer t o monomer t r a n s f o m a t i o n was observed f o l l o w i n g T~ l a b e l l i n g and l a b e l dissoeiaticm from the No after i . v . in3ectien. We presome t h a t the difference in d i s t r i b u t i o t t and excretion ste~s fro~ the techni~Je and chemistry involved in the l a b e l l i n g of anti-melanoma menoclonal antibody F ( a b ' ) ~ fragment o r i g i n a t i n g from the same Batch.
1d
M. EBER* , M. FREUND ° , R. MILLON-COLLARD* , C. LALLOT* , O. FELLER° , J.P. CAZENAVE° and G. METHLIN "~" Explorations par les Centre Paul S t r a u s s o INSERM U 511 et Transfusion Sanguine -
1311-C215 Rig (SEM) 3d 6d 9d
1d
755e-C215 ~/g (SEM) 3d 6d 10d
Blood 9.5(.7) 5.2(.4)2.1(A).68(.32) 16(1) 12(1) 5.4(.5) 2.9(,5) Turnout 5.6(,4) 3.1(.2)1,8(.1).77(.09) 7.8(.9) 13(1) 9.8(~5) 6.6(,5} T/B .61(.06).62(.05)1.1(,1) 3,9(1.1) ,52(.06) 1.2(,1) 1.9(.2) 2.5(,2) ~PLC showedthat 13tl and 7sSe in blood were mainly bound to Ig9 sized molecules. Conclusion. The observedHAb kinetic dependson the redtonuclldeusedfor labelling the monoclona] antibody. Labelling with 7s~e may show more accurateMAb klnetic.
728
727
*
1511
Intraductlon. ]'he moderate tumourlblood ratios (T/B) ashteved wlth ledlne labelled monoclonalantibodies(MAb) might be due to breakageof the bound betweenthe radlonucllde and HAb, ]'he HAb, C215 was Internally labelled and Its ktnettc was comparedwith that of ledlnatedC215. Material and melheds. 0215 reacts with a carcinomaassociatedantigen on colo-205 cells. C215 was 1311labelledaccordingto the ledogen® method or Internally labelled with 7SSe-methlonlne.Nudemice, bearing human cole-205 turnouts, were i.v.Injectedwith either 7s~-0215 or 13=1-C215. I The mice were killed 1. 3, 6, 9 or 10 days later, and the activity concentrationwas determinedas per cant of Injectedactivity per gram. for organsand tumours(~/g). HPLCwas usedfor saparatlonof plasmasamples. Results. The redlonucllde content for the measured tlsauas varies dependingon the redtonucllde usedfor labelling C215. The 13q-centaur ts ]ower for ell measuredorgansduring the experiment.
..........................................................
To" 60.8+12.7
L I), L 2},
moyens physiques et Laboratoire des radioisotopes STRA5BOURG Unitd de fractionnement - Centre Rdgiona] de 5TRASBOURG
111-INDIUM LABELLING OF HUMAN FIBRINOGEN The availability of human F[brinogen (Fg), ready to use for labelling with 111-Indium chloride would overcome the major disadvantages of the Iodine labelled proteins (low energy and tissue absorption of the gamma r a y of 125-I ; short half-life of 123-I which implies extemporaneous iodination ; 151-1 which has an energy not adapted to the gamma camera). Human Fg~ vffo inactivated (Centre Rdgional de Transfusion Sanguine, Strasbourg), was coupled with DTPA dianhydride at different starting molar ratios. After extensive dialysis, both biochemical and functional characteristics of the Fg-DTPA, were studied, and optimal coupling conditions were determined. After labelling with 111-InC]3 (CIS International, France) the in vitro stability of the label was studied. The in vivo biodistribution of the Fg-DTPA was studied in rats (normals and animals with vena cava thrombosis) by scintigraphy and organs and thrombus counting after autopsy. The results obtained showed that : 1) E311gomers of Fg are generated, in proportion with the DTPA-Fg molar ratio. 2) The three subunits of the Fg are labelled. 5) "[he clottabi]ity of the labelled Fg is 957~ that of the uncoupled Fg, measured either by protein concentration or by 111-1n radioactivity. 4) The biodistribution in rats with experimental thrombosis shows a significant uptake 24 hours after injection, by the thrombus ( about 10 times the blood activity ) and a good visualisation by qamma camera scint igr aphy.
S.N.Reske/ U.Bnell Dept. Nucl. Ned., RWTB Aachen, FRG
REDUCED Tc-99m-ANTIBODY LIVER UPTAK~DUETO GENTLEAI~IBODY RECONSTITI]TIOB Tc-99m labelled monoclonal antibodies (TcNCAA), directed against noR-specific cross reacting antigen and CEA, have been successfully used for in rive labelling of ~anulocytes and bone marrow scintiqraphy. Clinical and ani=al experimental studies indicated a significant antibody uptake in the liver. Occasional observations showed a narkedly increased antibody liver uptake when harsh recon~titutian conditions of the lyopbilized kit during Tc-99= labelling were applied. We thus compared systenatically antibody soft tissue uptake in dependence on reconstitufion conditions. ~rtibody uptake in the liver, spleen, bone =arrow and a precordial backqroand regiun was detsrmined in a consecutive series of 25 patients, investigated by hearts of an antibody preparation, reconstituted routinely according to the =aunfecturers recommendations and in 14 patients, where the antibody kit was reconstituted with special care, avoiding bubble formation and dropping of buffer or Tc-99= generator eluate into the antibody containing vial. Patientswere exaeined 3 hrs after i.v. injectionof 300 f 10 ]eq TcNC// by aeons of a LFOVgammacamera equipped with a LF/P collimtor. Spot views of the axial and proxinat appendicular skeleton were recorded and stored in a =inico~putsr.Area normalized count rates were obtained frou anterior views over a liver, spleen, sternu= and left ventricularbockqround region by a standard ~I technique. Gentle compared to routine antibody preparation caused a significant reductionof ~I-liver count rates (!7.5 ± 3.7 vs 32.1 f $.5; p
581
729
730 E. Lavie 1. I. Hellstrom2, L. Brodzinsky2 and K.E. Hellstrom2
1) Soreq N.R.C., Yavne, Israel 2) Oncogen, Seattle WA, U.S.A
P.K0m~rek ~, R.Poledne, M.Konopkov~ ~Postgraduate Medical and Pharmaceutical Institute; I n s t i t u t e f o r C l i n i c a l and Experimental Medicine, Prague, Czechoslovakia
PHARMACOKINETICS AND TUMOR-UPTAKE OF LABELED L6, WHOLE MONOCLONAL ANTIBODY AND ITS FRAGMENTS.
PREPARATION OF 99mTc-LIPOPROTEINS
L6 is a murine monoclonal IgG2a antibody (MAb), which recognizes a carbohydrate antigen expressed at the surface of many human carcinomas. Antibodies such as L6, may serve for delivering various anti-tumor agents including radioisotopes, chemotherapeutic drugs and toxins. The purpose of this study was to evaluate the in-vivo ldnetics and the tumor localization of Fab and F(ab')2 fragments of L6, as well ~{S intact antibody in nude mice xenograftod with human lung carcinoma. The antibody preparations were labeled with 1-125 or 1-131. Fab. was also labeled with Ga-67 via a desferrioxamine bridge. The plasma half-life of the whole iodinated MAb was 19h, 6h for F(ab')2 and 2h for Fab. The half-life of Ga-67 labeled Fab was 4.5h. Uptake of L 6 in tumor was 18% I.DJg at 2 days as compared with 4% I.D./g uptake of P 1.17, a non-specific MAb. 1-125 F(ab')2 also gaveimrnunospecific tumor-uptake with a maximum of 6% I.D/g at 24}1 post - injection. After 16h the localization index of iodine and gallium labeled Fab were about 2.2. The kidney uptake of the iodinated Fab was significantly greater (90-10% I.D/g) than that of the Ga-67 labeled fragment (30-45% I.D/g). The data obtained using the Ga-67 chelation approach suggest that this complex is mere stable in vivo than the iodine - labeled preparation. It is concluded that MAb L6, as well as F(ab')2 and Fab fragments have favorable characteristics with respect to localization in tumor and may be considered as potential immunodiagnostic reagent in man.
The metabolism of very low d e n s i t y l i p o p r o t e i n s (VLDL) plays an imp o r t a n t r o l e in i n creased risk of atherosclerosis. For experimental and clinical metabolic studies, iodinated LDL are usually used. The aim of our study was to explore the possibility of lipoprotein labelling with technetium (99mTc). Lipoproteins were separated using standard ultracentrifugation at 100,000 G for 22 hours. Separated lipoproteins were labelled with sodium pertechnetat~ (99mTc) using sodium dithionite as a reductant. Reaction conditions and labelling efficiency.of 99mTc-VLDL were evaluated by means of paper and thin-layer chromatography using various solvents and by column Sephadex 62"5 chromatography. The highest labelling efficiency was 95%. 99mTc-VLDL were used for studies of specific receptors in the liver of hereditary hypercholesterolemic rats and New Zealand rabbits with dietary induced experimental atherosclerosis. The decrease in these specific receptors determined with 99mTc co~relates with cholesterol concentration in hepatocytes.
732
731
~o. n iCnool,o mZ.b o , J i aF.n g , L uK.n g l i ]L,i b s~o.n , DJe.l ~ iBdeel,l e tM.i r e , MF.a ~ a rFraezsieo,
A.A. Noujaim*
~. and
~. D e u t s c h . * Biomira Inc,, Edmonfon, Alberta, C~nada * * Cross Cancer I n s t i t u t e , Edmonton, Alberta, Canada I~IUNORADIObIETRIC ASSAY FOR l~IE DETECTIONOF CIRCULATINGANTIBODIESTO MURINE MONOCL~HALANTIBODIES IN HUMANS (HAMA) The i n t e r e s t i n human anti-mouse a n t i b o d i e s (HAMA) has e s c a l a t e d in the past few years w i t h the i n c r e a s i n g c l i n i c a l use o f murine r a d i o l a b e l e d a n t i b o d i e s (F~Ab) f o r the d i a g n o s i s and t h e r a p y of cancer. E l i c i t i n g an immune response not o n l y poses a t h r e a t to the p a t i e n t ' s h e a l t h but has a l s o been associated w i t h reduced image q u a l i t y , a c c e l e r a t e d I~Ab clearance r a t e s , h i g h l i v e r and spleen uptake of ~ A b , J tumour escape from t h e r a p y and i n t e r f e r e n c e i n i n v i t r o assays f o r c i r c u l a t i n g tumour markers. We are now r e p o r t i n g the development of a two step immunoradiom e t r i c assay (IF~IA) f o r d e t e c t i n g c i r c u l a t i n g HAHA. P r e l i m i n a r y r e s u l t s have been generated u s i n g s p e c i f i c The a p p r o p r i a t e l y d i l u t e d serum sample i s coated beads, f o l l o w e d by a wash s t e p end 1-125 l a b e l e d goat anti-human IgG. A f t e r assayed for 1-125 i n a s c i n t i l l a t i o n as percent of the i n p u t bound.
MAb coated p o l y s t y r e n e beads. f i r s t incubated w i t h the MAb a second i n c u b a t i o n w i t h a f i n a l wash, the beads are
c o u n t e r end r e s u l t s are expressed
We have compared this prototype assay with on existing commercially aveilabie ELISA kit using patient sere obtained at various time periods up to 3 months after IV MAb injection for radioimmunoscintigraphy, Both assays detected the presence of MAb specific HAMA in the majority of sere drawn at least 2 weeks post-injection. The results indicate that the magnitude of the response was more readily apparent with the IF~A format and in addition, this assay was generally more consistent than the ELISA. Therefore, the development of this assay should enable more reliable and more quantitative assessment of the HANA response,
T.B.A.-C.N.R., University of M i l a n o , Istituto S. affaele, Milano, Sorin Biomedica S.p.A., Saluggia, aly, and Biomedical Chemistry Research Center, n i v e r s i t y of C i n c i n n a t i , C i n c i n n a t i , O h i o .
I
~ ' ' T c d,I-CB-PAO: A NEW CEREBRAL PERFUSION AGENT WITH IN VITRO STABILITY. " ' " T c d , ] - H M - P A O , h a s p r o v e n to b e a n e f f i c a c i o u s eerebr~al perfusion imaging agent, but it is inherently Wmstable. This instability limits its clinical utility, but is l s o b e l i e v e d to u n d e r l i e t h e i n v i v o m e c h a n i s m b y w h i c h is trapped in the brain. In order to eliminate the in i n s t a b i l i t y of ° ' ~ " T c d , I - H M - P A O , while retaining ~he .in v i v o i n s t a b i l i t y n e c e s s a r y f o r b r a i n r e t e n t i o n , w e h a v e ~ t o d i f i e d t h e s t r u c t u r e of t h e p a r e n t a l PAO l i g a n d to eStriet its flexibility. This has been accomplished by c o r p o r a t i n g a c y c l o b u t a n e r i n g i n t o t h e PAO m o i e t y t o enerate the ligand d,1 CB-PAO [d,l-4,8-diaza-3,9imethyl-6,6- (trymethylene) undecane -2,10-dione bis (oxime)]. The ""~Tc d,I-CB-PAO agent is generated in >95% r a d i o c h e m i c a l purity via a simple "instant kit" preparation wherein stannous ion reduces 99mpertechnetate in the presence of d , I - C B - P A O . HPLC ~nalysis shows that in vitro the new "'mTc d,I-HM-PAO agent is significantly more stable than is "gmTc d,I-HMPAO. " " ' " T c d , I - C B - P A O f o r m u l a t i o n s u n d e r g o l e s s t h a n 5% i n v i t r o d e c o m p o s i t i o n i n 6 h o u r s . D e s p i t e t h e m a r k e d d i f f e r e n c e i n t h e i n v i t r o s t a b i l i t i e s of t h e t w o a g e n t s , both "'mTc d,I-CB-PAO and "'mTc d,I-HM-PAO have similar biodistributions in rats. Thus, the significantly n h a n c e d i n v i t r o s t a b i l i t y of " ' ' T c d,I-CB-PAO obviates h e m a j o r l i m i t a t i o n of S g m T c d , I - H M - P A O a n d s h o u l d ~ n h a n c e t h e c l i n i c a l p o t e n t i a l of t h e g e n e r a l c l a s s o n " ' T c PAO c e r e b r a l p e r f u s i o n a g e n t s .
~
E
582
733 E. Barloarics,
734 Gy.A. J~noki
=G. Bormans, M. Hoogmartens, B. IM. De Roe and A. Verbruggen
"FJC" Natl.Res.lnst.for Radiobiology and Radiohyglene, P.O.Box 101 H-1775Budapest, Hungary
Cleynhens, D.
'Radiopharm. Chem. I.F.W. and Nuclear Medicine, Gasthuisberg, K.U. Leuven, Belgium SYNIIESIS, CHARACTERIZATION AND BIOOISTRIBUTION OFNEW TE~TIUM-9~m LABELLEDEIHER-ISONIIRILE COMPLEXES Radiolabelled isenltrlle complexes are undergoing wide-ranging evaluation f o r the develepment of an 1deal agent f o r myocardial perfusien scintig~aphy. We have synthesized three e t h e r - i s o n i t r i l e d e r i v a t i v e s : 2 - m e t h o x y - 2 - m e t h y l - p r e p y l i s o n i t r i l e (A), 2-methexy-2m e t h y l - b u t y l i s e n i t r t l e (B), and 2-methoxy-2-eth~l-butyli s e n i t r i l e (C); the l a t t e r two have not been described p r e v i o u s l y . Ihe synthesized compounds were i d e n t i f i e d by N5 and NNR spectroscopy. Compounds A,B & C mere l a b e l I e d with T c - ~ p e r t e c h n e t a t e
v i a use of t i n ( I I ) c h l o r i d e . TLC and reversed phase HPLC mere a~plied f o r analysis of the l a b e l l i n g y i e l d ahd the complex s t a b i l i t y . Both methods demonstrated complex formation of over 94 4, and an e x c e l l e n t in vitro stability for B hours (decomposition less than 2 4) f o r a l l three compounds. lhe b i o d i s t r i b u t i o n o f the three i s e n i t r i l e s was investigated i n r a t s . The heart uptake was as follows: A: 1.84 + 0 . 2 4,
B: 1.42 + 0.25 4 ,
C: 1.65 + 0.2 ~
of
I.D/organ
60 min. postin3ectien. The lung uptake Was IA: O.G + 0.05 4, B: 1.3 + 0.07 ~, C: 2.5 + 0.2 4 of ( I . D / o r g a o 60 min. p e s t i n j e c t i e n . I n a l l c a s e s we found 'minimel myocardial clearance / longer than 6 hours) and f a s t hlncd clearance. (T1"2 Our results show t h a t a l l three Tc-99m-iennitrile compounds prepared i n our l a b o r a t o r y are promising new agents f o r imaging of myncardial perfusien.
735 ~.Barbarics,
Jos6,
U.Z.
!EVALUATION OF THE FOUR ISOMERSOF 99mTc-CO2DADS IN MICE AND A BABOON. 99mTc-DL-CO.DADS, described as a mixture of two isomers, contains actually 4 isomers; D-syn, D-anti, L-syn and L-anti (resp. DA, DB, LA, LB). We have isolated these isomers by labeling optically pure D- or L-CO2DADS f o l lowed by RP-HPLC of the reaction mixtures. We evaluated biodistribution and renal excretion characteristics of the isomers in mice and baboon. In mice DA, LA, DB and 1311-OIH behave rather similarly: at 30 min p . i . urinary excretion is respectively 92, 9l, 86 and 91% of I.D., l i v e r uptake resp. 1.3, 2.9, 3.9 and 0.5% of I.D~ The LB-isomer however shows a high l i v e r uptake (25% of I.D. at 30 min) and a clearly lower urinary excretion (58% of I.D.). The baboon renograms of DA and LA are very similar, except for" the s l i g h t l y lower renal maximum (at 2.5-3 min) and higher renal retention at 30 min for LA. The time to renal maximumof DB is the same as for DA and LA, but the maximum is significant]y lower, indicating a poor renal extraction efficiency. Rena] wash-out is also slower. LB is clearly different from the other isomers as its renal a c t i v i t y builds up during 26 min to 19% of I.D. Liver uptake at 35 min p.i. is 0.89, 2.77, O.lO and 3.40% of I.D. for respectively DA, DB, LA and LB-isomer. Plasma clearance is highest for DA (45% of coinjected OIH value) versus 32% for LA, 16% for DB and 12% for LB. The results demonstrate the drastic influence of configurational changes, and the remarkable species difference with regard to renal handling of the studied substances.
736 GymA~J~noki, K.Mohari
Th. Maina, E. ChiotelIis
"FJC" Natl.Res.Inst.for Radiobiology and Radiohygiene, P.O.Box 101 H-1775 Budapest, Hungary
Nuclear Research Center of Physical Sciences "Demokritos", Athens, Greece.
RAI)IOL~LC ~[T~IB-OTNEW TEtlINETIUI~:-9%~ ETFERZISI]NITRILE COMPLEXES
COMPLEXES OF 3,6-DITHIA-1,8-BIS-(SALiCYLAMINO)-OCTANE(DDSO) WITH REDUCEDTc-99m,
We have synthesized three isonitrile analogues: 2-methexy-2-methyl-propylisonitrile ( A ) , 2-methoxy2-methyl-butyiieenitrile (B) and 2-metboxy-2-ethyl-butylisonitrile (C); the latter two have not been reported previously. The Tc-99m-isonitrile complexes w e r e fotlned via the t i n ( H ) c h l o r i d e reduction of Tc-99m-perteehnetate. HPLC was used for analysis of the radiochemical purity and decomposition kinetics in v i t r o . To determine the pussible metabolism of the con~lexes, b i l e and urine wore collected and studied by HPLC. IIPLC analysis was performed on a reversed phase BIO-RAD RP-304 column, interfaced with a flow-througll gamma-ray detector. After injection of the s a b l e (20/ul) a linear solvent gradient program (0.05 M (NH4)2SO~ + HeOH) was used at a flow r a t e of 1.0 ml/min. The radio-HPLC revealed A: 96.B + 1.3 ~; B: 97.4 + 1.2 ~ ; C:97.7 + 1.2 ~ complex formation 15 min a f t e r l a b e l l i n g . The radiochemical p u r i t y decreased by 2 ~ w i t h i n @hours. Radinchrometograme of urine and b i l e showed t h a t the r a t e of metabolism f o r A was 15 ~ during 2 hours, 8: 90~ d u r i n g 2 hours, C: 100 4 during 1 hour. lhe metabolized compounds were more hydrophilic, but no free Ic-99m-perteehnetate was detected. Our HPLC analytical reeults indicate that the labelling efficiency and stability of compounds A, B and C are sufficient for detailed biological studies.
In previous work we have reported technetium complexes of 1,8-diamine-3,6-dithiaoctane derivatives (DDO). In the pre. sent work 3,6-dithia-l,8-bis-(salicylamino)-octane (DDSO) is studied as a ligand of reduced technetium-99m.Labeling of DDSOwas performed using sodium borohydride as reducing agent. The reaction mixture was extracted in chloroform and the extracts were subjected to HPLC analysis. Four complexes were isolated, Ii20.8~, II:21.9%, III:23.8% and IV:33.4%, with retention times 2.2,4.1,4.6 and 5.2min respectively. L i p o p h i l i c i t y studies of the fractions resulted to partition coefficient values of I:0.9, II:10, I l l : , 21 and IV:35. The lipophilic complexes II-IV were biodistributed in mice at various time intervals. Selective animal data are presented in the fpllo.wing table. 99mTc-DDSO complexes In mlce (%dose/g) blood brain heart lungs Fr 2min 15min 2min 15min 2min 15min 2min 15min II 42.185 9.660 0.642 0.421 18.424 5.774 82.957 22.584 I l l 19.775 7.567 1.094 0.522 13.844 4.564 52.439 23.137 IV 9.109 3.803 2.303 2.022 8.026 6.491 73.588 61.019 The animal data demonstrate that DDSOcan form complexes with Tc-99m, which are characterized by different biodistribution patterns. Complex IV shows interestingbiological properties, such as rapid blood clearance and prolonged retention in brain tissue. A study of the chemical structure of the above complexesusing Tc-99 (carrier) is programmed.
583
738
737 _
_
T
N.Vanlid-RazumeniE and N.Vukidevid
V Ivan~evid, ~ Ku~ter, Z Ma~trovid, D lvan~evid
Radioisotope Laboratory, The Boris K i d r i a I n s t i t u t e of Nuclear Sciences, Vin~a, P.O.Box 522 11001 Belgrade, Yugoslavia
Department of nuclear medicine, University Hospital Rebro, Zagreb, Yugoslavia
CHEMICAL AND BIOLOGICAL PROPERTIES OF 99mTc-HMPAO COMPLEX FOR RCBF IMAGING HMPAO was prepared by condensation of the p u r i f i e d substances 2,3-butanedione monoxime and 2,2-dimethyl1,3-propanediamine and reduction by NaBH4 (the o v e r a l l y i e l d 49*10%), followed by repeated c r y s t a l l i z a t i o n s from ethyl acetate and a c e t o n i t r i l e , as well a~ by HPLC i s o l a t i o n of dI-HMPAO. The p u r i t y of the i s o l a t e d d l - i s omer was conf?rmed by HPLC and NMR. Conditions o f the l a b e l l i n g reaction have been radiochemically examined and found out as optimum: pH 9-9.5; molar r a t i o HMPAO:Sn/II/ in the range 40:1 to 60:1; reagent concentrations: HMPAO 400-520 ¢umol/L, while Sn/11/ 7-13~umol/L. On the basis of the determined stab i l i t y constants of Sn-HMPAO complexes by p o t e n t i o m e t r i c and spectrophotometric methods, the f o l l o w i n g procedure f o r the preparation of Sn-HMPAO solutions f o r the f r e eze-drying was u t i l i z e d : HMPAO solutions 7.3 mmol/L (pH 8.8) were a c i d i f i e d u n t i l pH 6, then SnCI 2 added in a small volume, f~llowed by b a c k - a l k a l i z a t i o n to pH 9.4-9.7, adjusting of i s o t o n i c i t y and s t a b i l i t y , and then f r e e z e - d r y i n g . The k i t s were checked by radiochromatograpbic methods (lip.complex>90%; sec. about 5%; Tc04(1%, and TcO2 3%), and by assessment of b i o d i s t r i b u t i o n in rats (brain uptake 2.1*0.3%). The f i r s t c l i n i c a l t r i a l s showed high q u a l i t y of the radiopharmaceutical.
739
RADIOCHEMICAL PURITY OF D,L-HM-PAO AND ANALYSIS OF URINE EXCRETED HM-PAO DECOMPOSITION SPECIES Some chromatographic findings differing from published data are reported. The radiochemical purity of HM-PAO was dctermined in 16 preparations using the 3-strip method. Immediately post formulation(pf) 90,3+/-4.0%(mean+/-SD) of the activity was associated with the primary lipophilic com- ! plex having an Rf of 0.45+/-0.11. The pH of the 99m-TcHM-PAO solution ranged from 6.0 to 6.5.We noticed a significantly higher pertechnetate content in 2-butanone (MEK) (21.1+/-8.5%) than in saline(5.0+/-3.7%, p<0.O01), producing a sharp peak with an Rf of 0.95+/-0.02. in an attempt to clarify this finding we ran sequential chromatograms (t=1,2,3h) and found that the primary complex had a halflife of 2.2h. There is, to our knowledge, no data concerning the chemical nature pf 99m-Tc-HM-PAO decomposition species in urine. In 11 examinees who received originally lipophilic complex through labelled leukocytes we obtained chromatograms(t=l and 3h) of urine samples. One hour after application urinary activity consisted of a hydrophilie complex (84.8+/-9.2%) and perteehnetate(15.2+/-9.2%). The values after 3h were markedly different(gl.4+/-4.8% and 8.6+/4.8%, p<0.001). Our results suggest that conversion of primary complex during chromatography in MEK takes place thus increasing 'the pertechnetate amount. Eluate composition might influence t~e Rf of the lipophilic complex and the rate of its in vitro conversion. Urinary activity mostly consists of hydrophilic complex increasing with time.
740 K. OZKER, T. CANSIZ and t. URGANCIO~LU
*J.C. Watkinson, C.R. Lazarus, S. Allen, S.E.M, Clarke. *Department of Otolaryngology & Department of Nuclear Medicine, Guy's Hospital, London. SEI 9RT.
SOME ASPECTS OF THE PHARMACOKINETICS AND BIODISTR!BUTION OF 99mTc-(V)-DMSA (PENTAVALENT DMSA) IN AN ANIMAL TUMOUR MODEL. The Furpose of this study was to establish an animal tumour model to evaluate the pharmacokineties and biodistribntion of 99mTc-(v)-DMSA, a new radiopharmaeeutical used successfully to image medullary carcinoma of the thyroid and squamous carcinoma (SCC) of the head
and neck, Sixty NZW rabbits, of which 35 had a superficial transplanted VX2 SCC, were injected with 99mTc-(v)-DMSA. Blood and urine samples were collected at timed intervals P.I. Some rabbits were dissected and radioactivity in tumours and body organs measured. Mean blood clearance was biexponential and the same for tumour (27 and 352 mins) and non-tumour (28 and 325 mins) animals. Mean cumulative urinary excretion of radioactivity was also the same for both groups (200 and 240 mins). The maximum amount of radioactivity was found in bone (32.1% of dose/g), kidney (1.6% of dose/g) at 4 hours, and 0.16% of dose/g in bladder at 2 hours. Optimal uptake of radioactivity into tumours was 0.026% of dose/g at 2 hours P.I). Tumour : blood ratio increased from 0.6:1 to 5.0:] 24 hours. A successful rabbit tumour model has been used to show no significant difference in biodlstribution and pharmacokinetics in SCC-bearing and non-tumour bearing rabbits.
NUCLEAR MEDICINE DEPARTMENT, CERRAHPASAMEDICAL FACULTY, tSTANBUL UNIVERSITY, TURKEY 99mTc-LABELLED L-LEUCINE: CHEMICAL AND BIOLOGICAL EVALUATION Amino acids labelled with ~ositron emitting radionuclides are a t t r a c t i n g great interest in the functional diagnosis of tissue metabolism by PET. Our interest has beendirected o study the synthesis and b i o l o g i c a l d i s t r i b u t i o n of of 99mTc. 9mTc-Ieucine because of the prompt avazlab111ty " ' " Labelling y i e l d of 97.6±1.3 % was achieved in 30 min by a ligand exchange reaction involving the transfer of technetium from previously prepared 99mTc-citrate at pH 7.4. LabeLling yield and optimal l a b e l l i n g parameters such as pH~ SnL + concentratlon and incubation period of leucine with 99mTc-citrate solution were determined by paper and t h i n - l a y e r chromatography. Chromatograms run upto 24 h showed no decomposition into pertechnetate (Tc04) reduced and hydrolized technetium (Tc-HR) and 99mTc-citrate. Organ d i s t r i b u t i o n in normal mice at various time intervals after i . v . injection of 99mTc-leucine showed that radioa c t i v i t y was taken up by the l i v e r and cleared in a short period. The kidneys accumulated the highest radioactivity amongthe biopsy specimensindicating the main route of clearanceof the aminoacid moleculethrough the urinary system. Therewas no in vivo breakthroguh to Tc04 and insoluble Tc-HRas demonstratedby nonlocalization of the thyroid and gastric glands and the liver respectively in the late imagesand organ SeTtles. In conclusion a highly stable chelate was formedby the substitution route using WmTc-citrate. The longer the incubation period, the greater was the yield of exchangeof 99mTc (97.2±1.6 %at 10 rain, g~.5±I.3 %at 24 h). Furthermorethe procedure can be useful for labelling such biologically active nolecules since the labelling conditions are gentle.
~
584
741
742 • ++ l.Szilv~si, J.Kbrnyei +, l.Preda , • + • .++ . + J.Marton , K.Zamolyl , Gy. Blrd
,C. VAN NEROM, G. BORMANS, D. CROMBEZ, M. DE RO0 and A. VERBRUGGEN
k.Najor,
Radiopharm. Chem. I.F.W. and Nucl. Med., U.Z. Gasthuisberg, K.U.Leuven, Belgium
Postgraduate Medical School Dept.of Radiology and C a r d i o l o g y + ; I n s t . o f Isotopes++,Budapest
SIMPLE RADIO-TLC AND RADIO-HPLC METNODSFOR THE QUALITY CONTROL OE 9gmTc-MIBI and 9gmTc-ECD. The methods for the determination of radiochemical purity (RP) proposed by the manufacturer use Whatman RP-CI8 glass~ plates/acetone-O.OSM NHaOAc pH4 (3:2 v/v) for 99mTc-ECD and Baker Flex alumiflium oxide plates/absolute 'ethanol for ggmTc-MIBI. Practically the major disadvantages a~e (a) developing time > 20 min (b) d i f f i c u l t quantitative_ determination of the RP in the case of g9mTc-ECD (glass plates!). Moreover, both systems require wetting of the origin with ethanol and no distinction can be made between colloidal ggmTc and ggmTcO 4 as impurity i f the chromatogramsare not scanned. We have developed a fast quality control method for both tracer agents based on the combination of two TLC ~systems. The stationary phase is ITLC-SG or paper, the mobile phase is acetone or NaCl- solutions and develoiping time is less than 5 min. Quantitative results for percentage of 99mTcO4, ggmTcO~and 99mTc-radiopharmaceut i c a l s are obtained by cutting the chromatograms and counting the activity On each part. A more detailed quantitation of different 99mTc-species fin these radiopharmaceuticaIs, e.g. mono-ester and dilacid in ggmTc-ECD, can be achieved by HPLC. Both preparations can be analysed on the same HPLC-system, equiped with a polystyrene-divenylbenzene column at 50 °C" as stationary phase, but eluted with different gradient mixtures of acetone and O;05M NH4OAc buffer pH4. At a flow rate of 1.5 ml/min typical retention times are 12 min for 99mTc-MIBI and 21 min for 99mTc-ECD.
RELIABILITY OF T C - 9 9 M - I S O N I T R I L E SCINTIGRAPHY IN REFLECTING NORMAL INITIAL PERFUSION IN DOGS UNDERWENT TO SUBSEQUENT MYOCARDIAL INFARCTION
743 G. DEHONCEAU, D. HEBBELINCK, P. CARLIER, M. BRASSEUR, R. LECLERCQ, P. BOURGEOIS.
l.Balogh,
Ic-99m-isonitrile scintigraphy before and afte~ reperfusion interventions has been advocated td evaluate therapeutic effect in acute myocardial, i n f a r c t i o n . W e studied reliability of Ic-99m-isoy nitrile s c i n t i g r a p h y in reflecting normal initial myocardial perfusion in dogs underwent to subsequent myocardial infarction. 37-37HBq Tc~gm--methoxy-isobutyl,-isopropyl,-t-bulyl-isonitH rile /MIBI,IPI,T@I/ were i n t r a v e n o u s l y administered to 3-3 anes~hetised dogs.After one hour chests were opened and left anterior d e s c e n d i n ~ arteries were ligated. Hearts were excised two hours l ~ t e r . P l a n a r s c i n t i g r a p h y of ex-vivo hearts and transversal slices of ventricles were performed. Homogenous d i s t r i b u t i o n of isonitriles were found on scintiphotos. Tc-99m ac, tivity ratios of infarcted to normal myocardiai tissue samples were 1 . 0 5 + o . o 8 , o.98+o.12 and i.o3+o.o7 for MIBI,IPI a~d TBI respectively. In conclusion : Initial regional d i s t r i b u t i o n of Tc-99m isonitriles /MIBI,IPI,TBI/ are not disturbed by subsequent reduction of m y o c a r d i al blood flow in dogs,thus initial Tc-99m-isonitrile s c i n t i g r a p h y seems to be a reliable base-line to evaluate reperfusion interventions in patients with acute myocardial infarction.
744 D.C. Costa, M. Hubank, A. Sinha, D. Lui, P.J. Ell.
I n s t i t u t e of Nuclear Medicine and Department of Molecular
Endocrinology, UCMSM, London, UK. Bracops Hospital, Bruxelles. FACTORS INFLUENCING THE LABELING OF PLATELETS WITH TC-HH-PAO The influence of some blood chemical and pharmacological parameters on the in vitro platelets labeling with Tc99m-HH-PAO was quantitatively and qualitatively tested. The blood values of platelets, cholesterol, triglycerid~, phospholipids, apolipoproteins and total proteins and its subfractions were measured in 68 patients who underwent platelets labeling performed by the same technician. The labeling was estimated by the efficiency as well as by the 24h liver on spleen ratio (L/S). Statistical signification was performed by multiple regression as well as, when possible, by ~NOVA. For labeling efficiency, a significant correlation was observed with cholesterol, apolipoproteins and platelets. The alpha-I fraction of the proteins is correlated with the L/S, mainly the liver activity but it is thought to be more probably an index of hepatic function than of the platelet quality. A higher amount of platelets in the circulating blood increases the labeling, as demonstrated by modifying the blood volume -and thus the platelet amount- used for labeling. The cholesterol and its subfractions influence the efficiency, not the quality of the labeling. It could be related to the fact that diet influences the amount and the composition of lipids inside the plasma membrane and thus, its lipophilicity.
INFLUENCE-OF TIME, TEMPERATURE. SODIUM-POTASSIUM PUMF INHIBITION AND GLUTATHIONE ON THE 99Tcm-HMPA0 UPTAKE BYI CULTURED ASTROCYTES. We have investigated the influence of several parameters on the
uptake of 99Tcm-HMPAO by primary astrocytic culture from rat brain (Sprague-Dawiey). Confluent^astrocytes in 90 mm petri dishes were incubated with 2MBq of v'ffcm-HMPAO (freshly prepared; >90% lipophilic complex) for 1 and 10 minutes. The petri dishes were grouped as follows: C o n t r o l - incubated at 37"C;TO - incubated at 0"C; V e r - incubated' after treatment with VerapamiI (10gM); Ou 1 incubated post-treatment with lttM of ouabain; Ou 5 - incubated after, treatment with 5raM of ouabain; Glut - simultaneous incubation with 1 mM of glutathione; GLIIT - incubated after 10 minutes treatment' with lmM of glutathione. The following table shows the statistically significant results: Control T@O Ou 5 Glut GLIYr Mean 0.05 0.04 0.02c 0.08c 0.I0c I rain ISD 0.03 0.02 0.01 0.03 0.01 n 25 9 5 4 4 Mean 0.12a 0.03b 0.14 0,09 0.I1
10 rain
ISD
0.03
0.02
0.04
0.01
n 29 7 5 4 a = p <0.001(vs. I rain); b = p <0.001 (vs.Control); ¢ = p <0.03 (vs.Control)
0.003 4
ConClusions: uptake of 99fcm-HMPAO by confluent astrocytes in cultur~e is time dependent, reduced by low temperature, delayed by high (5raM) concentrations of ouabain, and seems to be accelerated by glutathione (without changing the final retention) 99Tcm-HMPA~
uptake by primary astrocytic culture may be dependent on carrier-mediated mechanism, not only a simple passive diffusion.
585
745
746
KORNYEI, Joseph I ;MARTON ,Josep~ ; S ZILVASI, Is tv~n 2 ;
M. Subhani, C. Van Nerom, G. Bormans, M. Hoogmartens, M. De Roo and A. Verbruggen
HORV~TH,L~szl61 1. Institute of Isotopes of Hung.Acad.Sci. H-1525 Budapest, POB.77. HUNGARY 2. Postgraduate Medical University Budapest,Xlll. Szabolcs u.26. HUNGARY
CHROMATOGRAPHIC DATA AND BIODISTRIBUTION OF MAG ~ KITS WITH DIFFERENT COMPOSITION Two years ago the MAG 3 compound was introduced to the nuclear medicine as a very promising kidney agent to replace iodohippurate. Till now lots of clinical data were published and at the same time discussions arg. continu~ng, about the stability and optimal formuzlon
Ot
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KIte
this paper our results are presented of the kits rio acid, asoorbic ac~d or malic acid. TLC, HPLC data and biodistribution as well as kinetics in rabbits will also be discussed. The following molar ratios were found optimal from point of view of the high radiochemical purity and biokinetics: MA@ 3/tiff = 44, tartaric/ascorbic acid= = % ascorbic acid/tin = 50. The Tc-99m MAG 3 obtained with a kit of such composition was stable for at le~t hours after labelling and showed kinetics in rabbit like iodohippurate. This kit could be the solution for the stability problems of the labelled MAG 3,
747 G. DEMONCEA_U, P, COLSON, E. HEINEN, P. BOURGEOIS, C, BRIHAYE, J.C. DEPRE,SSEUX, M. CUILLAUME
Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U. Leuven, Belgium COMPARATIVE EVALUATIONOF THE BIODEGRADABILITYOF 99mTc'COLLOIDS 99mTc-colloids can be classified on basis of the colloid forming substance as albumin, sulphur, t i n , Ca-phytate and inorganic colloids. We have studied the biodegrad a b i l i t y of 14 such colloids, belonging to these 5 ~roups, by comparing t h e i r b i o d i s t r i b u t i o n and excretion in mice at 15 min and 24 h after injection. Collection of t o t a l urine and faeces was realised by housing the animals in metabolic cages. Preparations were analysed by TLC and gel chromatography before use. I n i t i a l uptake in l i v e r + spleen was exceptionally low (< 60%) for the 99mTc-Ca-phytates, compared to 80-94% for the other colloids. However, as already mentioned by some authors, this 'may be an indication that mice are not a good animal model for 99mTc-Ca-phytates. After 24 h the albumin-colloids and some t i n colloids showed the" lowest retention i~n l i v e r (38-43%) and highest excretion through intestines and urine (45-54%). Inorganic colloids on basis of antimony or stannous sulphide and phytate-colloids remained in the l i v e r for 50-65% whereas total excretion varied between 18% (Sn+Sc o l l o i d ) and 39% (Sb?S~-colloid). Liver retention of sulphur colloids was~ 91% after 24 h and renal or i n t e s t i n a l excretion was negligible, indicating a very long biological TI/2. The results suggest that 99mTc-albumin colloids and some 99mTc-Sn-colloids show the most favourable biological behaviour, characterized by an e f f i c i e n t uptake in l i v e r and spleen combined with a reasonably rapid eliminatibn of the colloidal particles from the body.
748 ~Melioh~r,
Z. S t o j n o v +, K.
Svoboda
v
Cyclotron, Physical Chemistry aad Human Histology Institute. University of Liege. I,OCALISATION INSIDE THE HUMAN PLATELET OF TC-99M-MN-PAO A~D IN-III-TROPOLOTIATE, A higher clution is observed as well in vitro as in vivo for platelets labeled with Tc-HM-PAO than with Iu-tropo]onate (In-TRO). This fact unables the accurate evalnatiot of the platelet survival ~ith the former tracer. We studied the localisation of both tracers inside the human platelets, to know if the different extent of elution could be due to different uptake by the p!atelet plasma meu~rane. Platelets were labeled as classically with In-TRO and as t~e previously described tzith Tc~IM-PAO, in 4 cases. Therefore, after being loaded intracellularly with glyce = rol, they were subjected to hypotonlc lysis. Hemogenebu~ me,~rane fractions, free of intracellular organellas, were isolated for both tracers after a single density step cen otrifugation. Thepurity wss controled by electronic microscopy. The different fractions were counted and expressed in % of the total activity. The amount of impurities in the platelet fractions was negligible The amount of membranes in the cytoplasmic fraction was, in the worst case, less than 10%. No significant difference in the relative plasma membrane activities was observed for the 2 tracers. In conclusion, the elution differences between TC-HM-PAO aNdIN-TRO-labeled platelets might not be due to different uptake of the tracer by the plasma membrane. A washout from the cytoplasmic fraction has to be assessed.
v
N u c l e a r R e s e a r c h I n s t i t u t e , 250 68 Rez, ~ S S R + I n s t i t u t e of N u c l e a r R e s e a r c h a n d N u c l e a r E n e r g y , 1784 Sofia. B u l g a r i a
D E T E R M I N A T I O N OF THE E L U T I Q N C U R V E A N D THE E L U T I O N E F F I C I E N C Y OF THE ~ m T c GEL G E N E R A T O R T h e h i s t o r y of the p r e p a r a t i o n c a n i n f l u e n c e the e l u t i o n e f f i c i e n c y of the Tc g e l generator (as a l r e a d y p u b l i s h e d on the N M C o n g r e s s 1987 in B u d a p e s t a n d 1988 in H i l a n o ) . The d e n s i t y of the n e u t r o n f l u x as well as the d r y i n g t e m p e r a ture of the X s r o g e l of the Z r - p o l y m o l y b d a t e m a t r i x b e l o n g to the m o s t i m p o r t a n t f a c t o r s . T h e r e f o r e , the e f f e c t of b o t h the factors on the c o u r s e of the e l u t i o n c u r v e s as w e l l as the e l u t i o n e f f i c i e n c y was tested in detail. A m a t h e m a t i c a l p r o c e d u r e - s u b s t i t u t i o n f u n c t i o n of the n o r m a l a n d l o g a r i t m i c - n o r m a l distribution as w e l l as the f u n c t i o n s of H e y w o o d a n d M a r t i n - w a s a p p l i e d to the d e s c r i p t i o n of the elution c u r v e s . A l s o the e q u a t i o n s d e r i v e d f o r the s o r p t i o n processes were u s e d for the d e s c r i p t i on. The a p p l i c a b i l i t y of t h e s e f u n c t i o n ~ f o r the d e s c r i p t i o n a n d the t e s t i n g of the ~ m T c _ g e n e r a t o r elution curves was c o n s i d e r e d a n d the s i g n i f i c a n c e of the p r e p a r a t i o n f a c t o r s f o r the q u a l i t y of the g e l g e n e r a t o r was d e t e r m i n e d . The d r y i n g t e m p e r a t u r e w i t h i n 4 0 - 100 °C, sim i l a r l y as the d e n s i t y of the n e u t r o n f l u x w i t h i n the r a n g e of 0.7 - 3 . 0 x 1017 m - 2 s -I, ~ d n o t a f f e c t d i s t i n c t l y the e f f i c i e n c y of the y>inTc e l u t i o n .
