Background and aims Serotonergic terminals play an important role in levodopa-induced dyskinesias (LIDs) in patients with Parkinson’s disease (PD). An increased SERT-over-DAT terminal ratio in the putamen has been proposed to be a risk factor for the appearance of LIDs. We investigated the temporal relationship between serotonergic terminal changes and dopaminergic loss in the putamen and the appearance of LIDs. Methods Twelve PD patients underwent PET with 11C-DASB and 11C-PE2I; which are specific in vivo markers of serotonin (SERT) and dopamine transporters (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, the mean 11C-PE2I BP was (1.39±0.41) reduced by 14.52% from baseline (p0.10). Percentage changes in 11C-PE2I BP at follow-up were significantly greater than percentage changes in 11C-DASB BP (p<0.05). The SERT-to-DAT ratios significantly increased by 12.76% (p<0.01) over this time. Three PD patients became dyskinetic;their SERT-to-DAT ratios were 0.978, 0.878, and 1.282. Conclusion The imbalance in the rate of SERT and DAT decline reflects the increase of the SERT–to–DAT ratio over time. Our findings suggest that there may be a threshold of SERT-over-DAT availability in the putamen, above which PD patients are likely to become dyskinetic
