abnormalities, or both, may be considered candidates for either fantile spasms. I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol 1990;27:406—413. hemispherectomy or callosotomy. Both interventions have 6. Harvey AS, Bowe JM, Hopkins IJ, Shield LK, Cook DJ, Berkovic SF. Ictal proved to be successful strategies (21). Ictal rCBF SPECT, in @“Tc-HMPAOsingle-photon emission computed tomography in children with tem particular, showed focal to lobal hyperperfusion in all our poral lobe epilepsy. Epilepsia 1993;34:869—877. 7. Adams C, Hwang PA, Gilday DL, et al. Comparison of SPECT, EEG, CT, MRI and patients. On the basis of the small number of patients, this pathology in partial epilepsy. Pediatr Neurol 1992;8:97—I03. finding cannot be considered a recommendation for lobectomy 8. KuhI DE, Engel J, Phelps ME, 5dm C. Epileptic patterns oflocal cerebral metabolism as an alternative approach; however, larger study populations and perfusion in humans determined with emission computed tomography of ‘‘FDG and ‘3NH3.Ann Neurol I980;8:348—360. might show the ability of ictal SPECT to identify some patients 9. Gloor P. Contributions of electroencephalography and electrocorticography in the who might also benefit from more restrictive surgery. neurosurgical treatment ofepilepsies. New York: Raven Press; 1987:553—571. 10. GrOnwald F, Menzel C, Pavics L, et al. Ictal and intenctal brain SPECT imaging in epilepsy using technetium-99m-ECD. J Nuci Med I994;35: 1896—1901. CONCLUSION I 1. Menzel C, GrOnwald F, Pavics L, et al. Brain single-photon emission tomography Technetium-99m-ECD is a valuable tool for the investigation using technetium-99m-bicisate (ECD) in a case ofcomplex partial seizure. EurJNucl of childhood epilepsy, and application of the tracer appears to Med 1994;21:1243—l246. 12. GrOnwaldF, Durwen HF, Bockisch A, et al. Iechnetium-99m-HMPAO brain SPECT be safe. Generally, both interictal and ictal rCBF SPECT should in medically intractable temporal lobe epilepsy: a postoperative evaluation. JNucl Med be performed whenever possible. In childhood epilepsy, there I991;32:388—394. are two major indications for the application of rCBF SPECT if 13. Newton MR. Austin MC, Chan G, McKay Wi, Rowe CC, Bercovic SF. Ictal SPECT using technetium-99m-HMPAO: methods for rapid preparation and optimal deploy the intent is to identify only the epileptogenic area: (a) the ment of tracer during spontaneous seizures. J Nuci Med 1993;34:666—670. acceleration of ECoG application in patients with normal MRI 14. Weisner PS, Bower GR, Dollimore LA, Forster AM, Higley B, Storey AE. A method for stabilizing technetium-99m-exametazime prepared from a commercial kit. Eur scan results or low seizure frequency, or both, to shorten the J Nuci Med 1993;20:661—666. hospital period of the child; and (b) to avoid ECoG in patients 15. Radtke RA, Hanson MW, Hoffman JM, et aI. Temporal lobe hypometabolism on PET: with focal MRI abnormalities that match ictal hyperperfusion predictor ofseizure control after temporal lobectomy. Neurology I993;43:1088—1092. 16. Kuikka iT, Mervaala E, v@inen E, KilviãinenR. Does technetium-99m-bicisate seen on rCBF SPECT. Furthermore, interictal 99mTc..ECD image local brain metabolism in late ictal temporal lobe epilepsy. Eur J Nuci Med SPECT might prove helpful in estimating postsurgical clinical 1994;21:1247—1251. outcome (e.g., seizure frequency or memory impairment) (12). 17. Feistel H, SchülerP. Neubauer U, Stefan H, Wolf F. Frontal lobe seizures—focus localization with ictal @“Tc-HMPAOSPECT [Abstract]. J Nuci Med I993;34 (suppl):207P. REFERENCES 18. Alksne JF, Tecoma E, Iragui-Madoz v, et al. Development of a device to facilitate 1. O'Donohue NV. Epilepsies ofchildhood. London: Butterworths; 1981. routine ictal SPECT studies. Epilepsia 1993;34 (suppl 6):I39. 2. Gomez MR. Klass DW. Epilepsies of infancy and childhood. Ann Neurol 1983;I3: 19. Leveille J, Demonceau 0, Walovitch RC. Intrasubject comparison between techne I13—127. tium-99m-ECD and technetium-99m-HMPAO in healthy human subjects. JNucI Med 3. Niedermeyer E. The Lennox-Gastaut syndrome and its frontiers. Clin Electroencepha I992;33:480—484. Iogr1986;I7:117—126. 20. Moretti JL, Defer G, Cinotti L, Cesaro P, ving@on N, Pethe C. Comparative 4. Grattan-SmithJD, HarveyAs, DesmondPM, Chow CW. Hippocampalsclerosisin tomoscintigraphic study of strokes using @“Tc-ECD,@“Tc-HMPAOand ‘231-IMP children with intractable temporal lobe epilepsy: detection with MR imaging. AJR Am [Abstract]. EurJNuclMed l988;l2:311. JRoentgenol 1993;161:I045—1048. 21. vigevano F, Bertini E, Boldrini R, et al. Hemimegalencephaly and intractable 5. Chugani HI, Shields WD, 5hewmon DA, Olson DM, Phelps ME, Pearson Wi. In epilepsy: benefits of hemispherectomy. Epilepsia l989;30:833—843.

Iodine- 123-Iodobenzamide Binding in Parkinsonism: Reduction by Agonists but Not L-Dopa

Johannes Schwarz, Wolfgang H. Oertel and Klaus Tatsch Departments ofNeurology and Nuclear Medicine, Klinikum Grosshadern, Ludwig Maximilians University and German Ministry for Research and Technology Research Program Munich “Parkinson‘sDisease and Other Basal Ganglia Disorders, “Munich, Germany

unchanged in 10 patients treated with L-Dopa alone. However, after The aim of the present study was to investigatethe effect of treatment with a dopamine agonist there was a significant decline in treatment with L-Dopa or a dopamine agonist, or both, on specific specffic r@[email protected] (p < 0.05). After treatment with a corn striatal 1@I-iodobenzamide (IBZM)binding using an intraindividual bination of L-Dopa and a dopamine agonist, specific r23wBzM longitudinaldesign. Method: We prospectivelystudied the effectof binding was reduced without reaching a level of significance (p = dopaminomimetic treatment on specific r23wBzM binding mea 0.08).Conclusion: Short-term treatment with a dopamine agonist sured by SPECT in 29 patients with a clinical diagnosis of Parkin but not with L-Dopa reduces specific r23I]IBzM binding. Therefore, son's disease, none of whom had previousiy received dopaminomi before performing an r23olBzM SPECT scan in patients previously metic drugs. The patients had been Selected on the basis of normal treated with dopaminomimetic drugs, dopamine agonists should be subsequent specific r23wBzM binding, semiquantitatively calcu discontinued. lated as the basal ganglia/frontal cortex ratio, and a positive re Key Words Parkinson's disease; diagnosis; iodine-123-iodobenz sponse to the dopamine agonist before initiation of amide; SPECT; L-Dopa; dopamine agonist dopaminomimetic therapy. A second 1@I-IBZMSPECT invest@a tion was performed after 3-6 mo of treatment with L-Dopa or a J Nuci Med 1996;37:1112-1115 dopamine agonist, or both. Results: Specific r23olBzM bindingwas Iodine-123-iodobenzamine (IBZM) SPECT is a predictor of Received May 18, 1995; revision accepted Aug. 18, 1995. For correspondenceer reprintscontact Johannes Schwarz, MD,Departhientof dopaminergic responsiveness in previously untreated patients Neurology, University of Ulm, RKU, Oborer Eselsberg 65, 84081 UIm, Germany. with parkinsonism (1 ). This capacity may also help to differ

1112 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 7 •July 1996 entiate patients with Parkinson's disease (PD) from those with before treatment: 40 ±12; during treatment 38 ±11 [mean ± related basal ganglia disorders, such as multiple-system atrophy s.d.]; p = ns. by Wicoxon Signed Rank). A computer program for (MSA) with predominant parkinsonism (MSA of the striatoni superimposing MM and SPECT images was not available; such a gral type) (2,3) or progressive supranuclear palsy (PSP) (4). In program would have enabled more accurate determination of the the latter patients, in contrast to those with PD, the striatum is ROIs. We did not observe any adverse reactions to intravenous affected, and response to dopaminomimetic drugs is usually injections of [‘23I]IBZM. poor (5). Normal specific [‘231]IBZMbinding was assessed in 14 control There are conflicting reports concerning the effect of dopami subjects and measured as 1.54 ±0.05. nomimetic drugs on dopamine-D2 receptor binding in vivo as The diagnosis of PD is supported by a clear improvement in measured by PET or SPECT (6—9). clinical signs under dopaminomimetic therapy. The response to Therefore, we prospectively investigated the effect of L apomorphine, a potent dopamine agonist, predicts this benefit from Dopa or a dopamine agonist, or both, on specific [123I}IBZM oral dopaminomimetic therapy (12,13). binding after 3—6mo of treatment in previously untreated Testing with the dopamine agonist apomorphine was performed patients with clinically diagnosed PD. after [‘231]IBZMSPECT, as previously described (12—14).Patients were rated clinically using part III of the Unified Parkinson's MATERIALS AND METhODS Disease Rating Scale (UPDRS) before and 30 mm after subcuta neous injection of 2—5mg apomorphine. Apomorphine test results Patients were considered positive in the case of a reduction in UPDRS Twenty-nine previously untreated patients (Hoehn and Yahr stages I to III) were investigated. All patients presented with scores by at least 20% and negative for a reduction of less than clinical signs compatible with Parkinson's disease according to the 10%. If the reduction in UPDRS scores was between 10% and 20%, or if sideeffectsprecludedanadequaterating,thetestresults United Kingdom (Parkinson's Disease Society) brain bank criteria (10). These patients had normal [‘23I]IBZMbinding and a positive were considered equivocal. Testing with apomorphine was gener response to apomorphine before the initiation of oral therapy with ally well tolerated. The investigator (JS) performing the apomor L-Dopa, , or . Lisuride, bro phine test had no knowledge of the [‘231]IBZMSPECT results. Likewise, the investigator (KT) calculating the basal ganglia/ mocnptine and pramipexole are all dopamine agomsts that act mainly by stimulation of the dopamine-D2 receptor. Ten patients frontal cortex (BG/FC) ratios had no knowledge ofthe clinical data and the results ofthe apomorphine test. The Wilcoxon Signed Rank (mean age 64.2 yr, range 40—75yr) received L-Dopa (300—600mg daily, plus PDI) alone; 11 patients (mean age 56.7 yr. range 44—73 test was used for statistical analysis. yr) received lisuride (0.8—1.6 mg daily, 10 patients) or pramipexole RESULTS alone (1 mg daily, 1 patient); and 8 patients (mean age 55.8 yr, Twenty-nine patients (mean age 59. 1 yr, range 40—75yr) range 42—70yr) received a combination of L-Dopa (200—450mg previously untreated with dopaminomimetic drugs were inves daily) and a dopamine agonist (lisuride, 0.6—1.2mg daily, 6 tigated before and after therapy with L-Dopa or a dopamine patients, or bromocnptine, 7.5 mg daily, 2 patients). There was no agonist, or both. Clinical rating performed after a mean fol significant difference in age between the three patient groups low-up period of 6 mo revealed a mean reduction in UPDRS (analysis of variance, p = ns). All patients improved clinically scores by 20% in patients treated with L-Dopa, by 15% in under these treatments. A second [‘231]IBZMSPECT investigation patients treated with a dopamine agonist alone and by 40% in was performed after 3—6mo of treatment. Patients continued patients who received a combination of L-Dopa and a dopamine taking their daily dose even on the day of the second study. All agonist. patients have been followed up for at least 2 yr. Treatment with L-Dopa alone did not reduce specific All patients underwent MM scanning, which did not show any [‘23I]IBZMbinding (pretreatment BGIFC ratio: 1.50 ±0.06 frontal atrophy or marked vascular lesions. A few white matter [mean ±s.d.]; post-treatment BG/FC ratio: 1.49 ±0.07; n — lesions were present in 17 patients. 10; p = ns (Fig. 1). Treatment with a dopamine agonist alone SPECT Imaging All patients gave informed consent before the [‘23I]IBZM 1,8 SPECT study. Iodine-l23-IBZM binding was assessed by 2 hr after intravenous n= 10 injection of 185 MBq [‘23I]IBZM(3-iodo-6-methoxybenzamide). The specific activity of [‘231}IBZMwas 195—222TBq/mmole. A rotating dual-head gamma camera with a high-resolution collima 0 1,6 .@ tor and a commercially available computer system were used for acquisition and data processing. The head was positioned in a U LA@ 1.50±0.06 —@— 1.49±0.07 special headholder and fixed with strips. Data were collected for 60 projections (360°rotation) in a 64 X 64 matrix. The acquisition 1,4 time was 50 sec per projection. Image reconstruction was per formed by filtered backprojection (Butterworth filter). Selected transverse slices (slice thickness 6.0 mm) were corrected for n.s. attenuation as described elsewhere (11 ). For semiquantitative evaluation of specific traceruptake, regions of interest (ROIs) were 1,2 I placed over the basal ganglia (isocontour ROIs with a threshold of 80% of the striatal maximum) and the frontal cortex (irregular de novo under treatment ROIs). A basal ganglia-to-frontal cortex activity ratio was calcu with L-DOPA lated. The size of all ROIs was at least twice full width at half FiGURE1.lodine-123-IBZMSPECTresultsinpreviouslyuntreatedpatients maximum (14 mm). There was no significant change in ROI size withPD(de novo)beforeQeft)and after(right)treatment withL-Dopafor3-6 between the scans before and during treatment (number of pixels mo. BG/FC= basal ganglia-to-frontalcortex ratio.

IoDi@E-123-IBZM SPECT ANDTHERAPYINPA@xNsoNIsM•Schwarz et al. 1113 resulted in a significant reduction of specific [123I]IBZM binding (pretreatment BGIFC ratio: 1.51 ±0.03; post-treatment BG/FC ratio: 1.43 ± 0.08; n = 11; p < 0.05) (Fig. 2). @ Treatment with a combination of L-Dopa and a dopamine :: n=8 agonist led to reduction of specific [‘231]IBZMbinding, which, however, failed to reach statistical significance (pretreatment @ BG/FC: 1.57 ±0.09; post-treatment BG/FC: 1.51 ±0.08; n = 1.57± 8; p = 0.08 [ns]) (Fig. 3). When all patients treated with a @ 1.51±0.08 dopamine agonist (alone or in combination with L-Dopa) were considered, a highly significant reduction of specific [‘23I]IBZMbinding was detected (pretreatment BG/FC: 1.53 ± 1,4 0.07; post-treatment BG/FC: 1.47 ±0.09; n = 19; p < 0.01). In contrast, there was no significant reduction of specific [‘23IJIBZMbinding when those patients treated with L-Dopa n.s. (p = 0.08) alone were combined with those patients who received L-Dopa and a dopamine agonist (pretreatment BG/FC: 1.53 ±0.08; 1,2 , post-treatment BG/FC: 1.50 ±0.07; n = 18; p = 0.07 [ns}). de novo under treatment with a When all 29 patients were considered, we observed a significant dopamine agonist and L-DOPA decrease in specific [1231]IBZM binding (pretreatment BGIFC: 1.52 ±0.07; post-treatment BGIFC: 1.47 ±0.08; p < 0.05). FIGUREa lodine-123-IBZMSPECTresultsinpreviouelyuntreated patients @ PD (de novo) before (left)and after (nght)treatment with L-Dopa and a We did not observe a correlation of the daily dose of the dopamineagonistfor3-6 mo. BG/FC= basal ganglia-to-frontalcortexratio. dopamine agonist with the reduction of specific dopamine-D2 receptor binding, which may be explained by the relatively to conclude only that treatment with L-Dopa for this period of small number of patients. time does not change [1231]IBZM binding. Long-term follow-up Of all 29 previously untreated patients, none has developed ofthese patients is needed to investigate whether treatment with clinical signs suggesting a disorder other than Parkinson's L-Dopa for several years may reduce [123I}IBZMbinding. Two disease. After a mean clinical follow-up period of 3 yr (range likely explanations for the reduction of [1231]IBZM binding 2—4yr) since the beginning ofdopaminomimetic therapy, all 29 after treatment with dopamine agonists are: (a) displacement of patients still respond well to this treatment; however, 12 of the tracer from the receptor by competition or (b) downregula these patients have since developed mild motor fluctuations. tion of the receptor density. A similar study in previously untreated patients with Parkinson's disease using PET and the DISCUSSION ligand 11C- showed that the reduction of specific The present report proposes that treatment for 3—6mo with 11C-raclopride binding after treatment with lisuride is reversed dopamine agonists but not with L-Dopa reduces specific after 3 days of drug holiday (9). Thus, it is very likely that [‘23I]IBZMbinding. Our results are in agreement with previous treatment with dopamine agonists, at least for 3—6mo, causes studies in patients with the clinical diagnosis of Parkinson's displacement of the ligand from the receptor rather than disease that reported a reduction of specific dopamine-D2 receptor downregulation. To further investigate this question it receptor binding under therapy compared with previously may be necessary to perform Scatchard binding curves by untreated patients (6,8). However, none of these previous measuring [1231]IBZMbinding at different doses of agonist. In studies tried to prospectively evaluate the effect of L-Dopa and the aforementioned PET study, the effect of oral treatment with dopamine agonists separately. The reduction of specific a dopamine agonist did not lead to a reduction of specific [123IJIBZMbinding is obviously due to treatment with dopa dopamine-D2 receptor binding below normal levels (9). In our mine agonists. The relatively short follow-up period allows us study, 6 of 11 patients showed a reduction of specific [1231]IBZMbinding below normal levels. This difference may be explained by the different binding capacities of the two 1,8 tracers, inducing more pronounced displacement by dopamine agonists of [123I]IBZM than 1‘C-raclopride,and by the disad vantages of SPECT in terms of correcting for scatter and n= 11 attenuation that lead to a less accurate quantification of receptor 1,6 densities and a greater variability of intraindividual scans. 0 In all three treatment groups there were two patients who

.@ 1.51 ±0.03 showed an increase in specific [123I]IBZM binding after treat ment. This increase may also point to the variability of @ 1.43±0.08 intraindividual SPECT studies. An alternative explanation @ 1,4 could be a further loss of dopaminergic drive, which may lead to less competition ofendogenous dopamine with [1231]IBZMat the receptor site in these patients. However, we were not able to p < 0.05 find a correlation of clinical deterioration with this increased

1,2 , I [‘23I]IBZMbinding. These limitations and the relatively small number of patients may also have precluded a dose-dependent de novo under treatment with a effect of dopamine agonists on the reduction of specific dopamine agonist [‘23I]IBZMbinding. FIGURE2@lodine-123-IBZMSPECTresuttsinpreviouslyuntreatedpatients Previous SPECT studies in patients with L-Dopa or apomor with PD (de novo) before Qeft)and after (right)treatment with a dopamine phine-responsive parkinsonism have found normal as well as agonistfor3-6 mo. BG/FC= basal ganglia-to-frontalcortex ratio. decreased specific [‘231]IBZMbinding (6,8) and reported a

1114 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 7 ‘July 1996 marked overlap of binding results in untreated and treated 2. Quinn N. Multiple system atrophy: the nature of the beast. J Neurol Neurosurg Psychiatry I989;52(suppl):78 —89. patients with the clinical diagnosis of PD, MSA or PSP. 3. Schulz JB, Klockgether I, Petersen D, Ctal. Multiple system atrophy: natural history, However, in those studies the investigators did not distinguish MRI morphology and dopamine receptor imaging with [‘23I]IBZM5PECT. J Neurol untreated from treated patients with parkinsonism. On the basis NeurosurgPsychiatryl994;57:I047—1056. ofour data, we propose that therapy with dopamine agonists, by 4. van Royen E, vethocif NF, Speelman JD, Wolters EC, Kuiper MA, Janssen AG. Multiple system atrophy and progressive supranuclear palsy: diminished striatal reducing [123IJIBZM binding, may in part account for the dopamine-D2 receptor activity demonstrated by [‘23I]IBZMsingle-photon emission reported overlap (8). In agreement with this hypothesis, a recent computed tomography. Arch Neurol I993;50:5 I3—516. study that compared patients with the clinical diagnosis of 5. Wenning GK, Ben Shlomo Y, Magalhaes M, Daniel 5E, Quinn NP. Clinical features and natural history of multiple system atrophy: an analysis of 100 cases. Brain probable MSA or PSP with normal age-matched volunteers 1994;l 17:835—845. showed little or no overlap of specific [ 31]IBZM binding (4). 6. BrOcke I, Podreka I, Angelberger P. et al. Imaging of dopamine D2 receptors with 5PECT: studies in patients with extrapyramidal disorders and under neuroleptic treatment. J Cereb Blood Flow Metab 1991 ;l 1:220—228. CONCLUSION 7. Brooks DJ, Ibanez V. Sawle GV, et al. Striatal D2 receptor status in patients with Treatment with L-Dopa does not influence [‘231]IBZMbind Parkinson's disease, striatonigral degeneration and progressive supranuclear palsy, ing, at least after a ?eriod of 3—6mo, whereas dopamine measured with ‘‘C-racloprideand positron emission tomography. Ann Neurol 1992; agonists can reduce [I 31]IBZM binding. Because the reduction 31: 184—192. 8. Schelosky L, Hierholzer J, Wissel J, Cordes M, Poewe W. Correlation of clinical in specific I‘C-raclopride under treatment with a dopamine response in apomorphine test with D2 receptor status as demonstrated by [‘231]IBZM agonist reversed after a drug holiday of 3 days (9), we propose SPEd. Mov Disord 1993;8:453—458. that these drugs be stopped about 7 days before an [1231]IBZM 9. Antonini A, Schwarz J, Oertel WH, Beer HF, Madeja UD, Leenders KL. Carbon-l I- raclopride positron emission tomography in previously untreated patients with Parkin SPECT investigation. Under this condition, [‘231]IBZMSPECT son's disease: influence of L-Dopa and lisuride therapy on striatal dopamine D2 should equally predict dopaminergic responsiveness in patients receptors. Neurology 1994;44:1325—l329. previously treated with dopamimetic drugs compared with 10. Gibb WRG, Lees AJ. The relevance ofthe Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 1988;51 :745—52. previously untreated patients. Reduction of specific [‘231}IBZM I I. Tatsch K, Schwarz J, Oertel WH, Kirsch CM. SPECT imaging of dopamine D2 binding during treatment with a dopamine agonist most likely receptors with [‘23I]IBzM:initial experiences in controls and patients with Parkinson does not correlate with a functional striatal defect; rather, it syndromes and Wilson's disease. Nucl Med Commun 1991;I2:699—70l. reflects a pharmacological effect. 12. Hughes AJ, Lees AJ, 5tern GM. Challenge test to predict the dopaminergic response. Neurology1991:41:1723—1725. 13. Gasser I, Schwarz J, Amold G, Irenkwalder C, Oertel WH. Apomorphine test for REFERENCES dopaminergic responsiveness in patients with previously untreated Parkinson syn 1. Schwarz J, Tatsch K, Amold G, et al. lodine-123-iodobenzamide-SPECT predicts drome. Arch Neurol l992;49:l 131—I134. dopaminergic responsiveness in patients with “denovo―parkinsonism. Neurology 14. Oertel @H,Gasser I, Trenkwalder C, lppisch R. Poewe W. Apomorphine test for I992;42:556—561. dopaminergic responsiveness. Lance: l989;l :1262—1263.

Determination of Regional Rate Constants from Dynamic FDG-PET Studies in Parkinson's Disease

M. Piert, R.A. Koeppe, B. Giordani, S. Minoshima and D.E. Kuhi Division ofNuclear Medicine, Department oflnternal Medicine and Neuropsychology Program, University of Michigan Medical Center, Ann Arbor, Michigan

with progression of disease and development of dementia, partic Dynamic [18F]fluorodeoxyglucose (FDG) PET was used in Parkin ularly in the parietal and occipital cortex. This suggested that the son's disease patients and normal controls to determine kinetic rate metabolic disturbance may be a global dysfunction throughout the constants for FDG. The goal was to assess whether the metabolic brain. Because altered rate constants are specificaity taken into decreases observed in Parkinson's disease are associated with account, dynamic measurements has shown to provide higher transport or phosphorylation processes or both. Methods Fluorine sensitivityfordetecting diminishedglucose utilizationin Parkinson's 18-FDGwasadministeredto 18 Parkinson'sdiseaseand 15 normal disease than static approaches. control subjects. Dynamic PET scanning was performed for 1 h and rate constants were obtained by nonlinear, least-squares analysis. Key Words: Parkinson's disease; dementia; kinetic rate constants; Regional glucose metabolic rate was calculated from the indMdually glucose metabolism fitted rate constants and by two standard static scan analyses. J NuciMed1996;37:1115-1122 Results: Global CMRgIu was decreased in Parkinson's disease (mean reduction 22%), reaching statistical significance in all regions investigated. K1was significantly reduced in parietal cortex, tempo InParkinson'sdisease,littlegrossstructuralbraindamage ral cortex and striatum while k@was significantly reduced only in accompanies a specific biochemical lesion of the substantia parietal cortex. The rate constant k@was unchanged. Conclusion: nigra and its dopaminergic projections in the striatum (1). In @ K, k@and CMRgIu all demonstrated greater deficits across the brain living parkinsonian patients, PET has provided valuable patho physiological information concerning altered pre- and postsyn aptic compartments of the striatal dopaminergic neurotransmit Received Jun. 12, 1995; revision accepted Oct. 8,1995. Forcorrespondenceor reprintscontact:RobertA.Koeppe,PhD,DMsionofNuclear ter system (2—4).In earl@'asymmetrical Parkinson's disease Med@ine,3480KresgeIll,Box0552,UnaversftyofMichigan,Mn Arbor,Ml48109. patients, [‘@O]O2and [l F]fluorodeoxyglucose (FDG) PET

FDG RATECONSTANTSINPARKINSON'SDISEASE•Piert et al. 1115