Complementary positron emission tomographic studies of the striatal dopaminergic system in Parkinson's disease

Abstract

Objective: To assess the relationship between striatal dopa decarboxylase capacity, D2 dopamine receptor binding, and energy metabolism in Parkinson's disease (PD).

Design: Positron emission tomographic (PET) studies of glucose and dopa metabolism and D2 dopamine receptor binding in the caudate nucleus and putamen of patients with PD at different Hoehn and Yahr (HY) stages using PET and the tracers 18F-fluorodeoxyglucose (FDG), 6-18F-fluoro-L-dopa (FDOPA), and 11C-raclopride (RACLO).

Setting: Positron emission tomography research program at the Paul Scherrer Institute.

Subjects: Twenty patients with PD at different stages of the disease (HY stages I through IV; five patients for each stage) compared with separate groups of age-matched healthy subjects.

Main outcome measures: Influx constant (Ki) for specific FDOPA uptake; uptake index ratio for RACLO binding to D2 dopamine receptors; normalized to global FDG metabolic rate for glucose consumption; and semiquantitative score for assessment of tremor, rigidity, and bradykinesia in PD.

Results: Patients with PD at HY stages I to II (hereafter HY-I-II PD) revealed reduced FDOPA metabolism, particularly in the putamen. The FDOPA uptake in the putamen and caudate nucleus declined with increasing HY staging and scoring for bradykinesia and rigidity. Putamen RACLO binding to D2 dopamine receptors was up-regulated in patients with HY-I-II PD but declined toward control values, with increasing disease severity. Putamen side-to-side asymmetries of FDOPA metabolism and RACLO binding revealed a significant correlation. Putamen FDG metabolism showed a relative increase in all patients with PD.

Conclusions: Our results show that FDOPA, RACLO, and FDG PET measurements provide complementary information to characterize metabolic and receptor changes in the striatum of PD with different degrees of motor disability. The FDOPA uptake reflects the best motor-related pathologic features, as indicated by the significant correlation between Ki values and clinical scores. The significant association between RACLO and FDOPA in the putamen suggests that D2 dopamine receptor changes are related to the reduction of presynaptic dopaminergic nerve terminals. Putamen FDG increase is probably the result of more complex feedback mechanisms that are primarily induced by striatal dopamine deficiency.