Background/Aim Serotonergic terminals play an important role in levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD). In particular the SERT/DAT ratio changes may be critical for the appearance of LIDs. We investigated serotonergic terminal changes and dopaminergic loss in the putamen over time and their relationship to LIDs.
Methods Twelve PD patients underwent PET with 11C-DASB and 11C-PE2I; which are specific in vivo markers of SERT and DAT respectively. All patients repeated 11C-DASB and 11C-PE2I PET after 17 months (±11 weeks).
The simplified reference tissue model was employed using the cerebellum as a reference. 11C-DASB binding potential (BP), 11C-PE2I BP and 11C-DASB-to-11C-PE2I BP ratios were calculated.
Results At baseline, all PD patients were non-dyskinetic. The mean 11C-DASB BP was 1.28 (±0.14), the mean 11C-PE2I BP was 1.63 (±0.41), and the median of the SERT-to-DAT ratio was 0.779 (±0.19).
At follow-up, mean 11C-PE2I BP was reduced by 14.52% from baseline (p<0.001), while the 11C-DASB BP was only reduced by 4.32% (p>0.10).). The SERT-to-DAT ratios significantly increased by 12.76% (p<0.01) over this time. Three PD patients at follow up had developed dyskinesia.
Conclusion The imbalance in the rate of decline of SERT and DAT is reflected by the increase of the SERT–to–DAT ratio over time. There may be a threshold of SERT-over-DAT availability in the putamen, above which PD patients are likely to become dyskinetic.