Striatal Distribution of Dopamine Transporters and Dopamine D 2 Receptors at Different Stages of Parkinson's Disease

Abstract

We investigated the alteration of dopaminergic system in striata of Parkinson's disease (PD) at different stages using positron emission tomography (PET), [¹¹C]2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) for dopamine transporter (DAT), and [¹¹C]raclopride (RAC) for dopamine D₂ receptor (D2R). We studied eight elderly healthy volunteers (Group A), 13 drug naïve patients with PD (Group B), and seven advanced PD patients with mild dyskinesia (Group D). Six patients in Group B were re-examined after antiparkinsonian therapy (Group C). Regions of interest were drawn on the cerebellar hemisphere, head of the caudate nucleus (CN), and anterior (AP) and posterior putamen (PP) in the PET images. We calculated uptake ratio index (URI), asymmetry index (AI) and presynapse-to-postsynapse ratio (PPR) to evaluate dopaminergic function. DAT was smaller in the three PD groups than the Group A. URI of RAC in the PP was significantly larger in Group B than in Groups A and C. AI of CFT in the putamen was larger in the PD groups than in normal subjects, and AI of RAC in the PP was the largest in the Group B. PPRs in the AP and PP were smaller in the three PD groups than in Group A. DAT decreased with disease progression in patients with PD. Binding of RAC was largest in the putamen of drug-naïve PD patients, but the enhanced binding could not be detected in the therapeutic patients with PD because of weak D2R affinity of RAC.