COMPLEMENTARY POSITRON EMISSION TOMOGRAPHIC STUDIES OF THE STRIATAL DOPAMINERGIC SYSTEM IN PARKINSONS-DISEASE

Objective: To assess the relationship between striatal dopa decarboxyl ase capacity, D-2 dopamine receptor binding, and energy metabolism in Parkinson's disease (PD). Design: Positron emission tomographic (PET) studies of glucose and dopa metabolism and D-2 dopamine receptor bindi ng the caudate nucleus and putamen of patients with PD at different Ho ehn and Yahr (HY) stages using PET and the tracers (18)-F-fluorodeoxyg lucose (FDG), 6-F-18-fluoro-L-dopa (FDOPA), and C-11-raclopride (RACLO ). Setting: Positron emission tomography research program at the Paul Scherrer Institute. Subjects: Twenty patients with PD at different sta ges of the disease (HY stages I through IV; five patients for each sta ge) compared with separate groups of age-matched healthy subjects. Mai n Outcome Measures: Influx constant (K-i) for specific FDOPA uptake; u ptake index ratio for RACLO binding to D-2 dopamine receptors; normali zed to global FDG metabolic rate for glucose consumption; and semiquan titative score for assessment of tremor, rigidity, and bradykinesia in PD. Results: Patients with PD at HY stage I to II (hereafter HY-I-II PD) revealed reduced FDOPA metabolism, particularly in the putamen. Th e FDOPA uptake in the putamen and caudate nucleus declined with increa sing HY staging and scoring for bradykinesia and rigidity. Putamen RAC LO binding to D-2 dopamine receptors was up-regulated in patients with HY-I-II PD but declined toward control values, with increasing diseas e severity. Putamen side-to-side asymmetries of FDOPA metabolism and R ACLO binding revealed a significant correlation. Putamen FDG metabolis m showed a relative increase in all patients with PD. Conclusions: Our results show that FDOPA, RACLO, and FDG PET measurements provide comp lementary information to characterize metabolic and receptor changes i n the striatum of PD with different degrees of motor disability. The F DOPA uptake reflects the best motor-related pathologic features, as in dicated by the significant correlation between K-i values and clinical scores. The significant association between RACLO and FDOPA in the pu tamen suggests that D-2 dopamine receptor changes are related to the r eduction of presynaptic dopaminergic nerve terminals. Putamen FDG incr ease is probably the result of more complex feedback mechanisms that a re primarily induced by striatal dopamine deficiency.