Putaminal serotonergic innervation

Objective: To explore serotonergic innervation in the basal ganglia in relation to levodopa-induced dyskinesia in patients with Parkinson disease (PD).

Methods: A total of 30 patients with PD without dementia or depression were divided into 3 matched groups (dyskinetic, nondyskinetic, and drug-naive) for this study. We acquired 2 PET scans and 3T MRI for each patient using [¹¹C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (¹¹C-DASB) and N-(3-[¹⁸F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (¹⁸F-FP-CIT). Then we analyzed binding potentials of the 2 radiotracers at basal ganglia structures and correlations with clinical variables.

Results: We observed no difference in ¹⁸F-FP-CIT binding between dyskinetic and nondyskinetic patients, whereas there were differences in ¹¹C-DASB binding for the caudate and putamen. Binding potential ratios (¹¹C-DASB/¹⁸F-FP-CIT) at the putamen, which indicate serotoninergic fiber innervation relative to dopaminergic fiber availability, were highest in the dyskinetic group, followed by the nondyskinetic and drug-naive PD groups. ¹¹C-DASB/¹⁸F-FP-CIT ratios at the putamen and pallidum correlated positively with Unified Parkinson's Disease Rating Scale (UPDRS) total scores and duration of PD, and pallidal binding ratio also correlated with the UPDRS motor scores. Ratios were not dependent on dopaminergic medication dosages for any of the regions studied.

Conclusions: Relative serotonergic innervation of the putamen and pallidum increased with clinical PD progression and was highest in patients with established dyskinesia. The serotonin/dopamine transporter ratio might be a potential marker of disease progression and an indicator of risk for levodopa-induced dyskinesia in PD. A prospective evaluation is warranted in the future.