Objective: This study was designed to detect whether in Parkinson’s disease (PD) the putaminal serotonin–over–dopamine transporter ratio has a threshold that is critical for the development of levodopa–induced–dyskinesias (LIDs).

Background: Serotonergic terminals play an important role in LIDs. Both an increased SERT–over–DAT terminal ratio in the putamen and longer disease duration have been proposed to be risk factors for the appearance of dyskinesias in PD patients treated with levodopa. Nonetheless, it remains unclear whether there is a critical threshold in the terminal ratio for the appearance of dyskinesias.

Methods: PET imaging with 5[11C]-3-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)-benzonitrile (11C–DASB), and [11C]N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl)nortropane (11C–PE2I), which are specific in vivo markers of the serotonin (SERT) and dopamine transporter (DAT), were used to assess the SERT–to–DAT terminal ratio. We studied 17 PD patients with stable response to levodopa and 7 PD patients with LIDs.  Of the 17 stable patients, 12 were followed up clinically and had repeated 11C–DASB and 11C–PE2I PET imaging after 17 months. We analysed PET data using the simplified reference tissue model and cerebellum as the reference region. 11C–DASB–to–11C–PE2I binding ratios were calculated for the putamen.

Results: At baseline, and in line with previous studies, the PD patients with LIDs (N=7) had higher SERT–to–DAT ratios (mean=0.99±0.02) as compared to the non–dyskinetic patients (N=17) (0.74±0.01; p<0.001).  At follow–up, 3 of the 12 stable patients had developed LIDs. Each of these 3 patients had a putaminal SERT–to–DAT ratio that was within the range of the group of patients who were dyskinetic (N=7) at baseline (range: 0.85-1.25).

Conclusions: Our findings suggest that the SERT–over–DAT putaminal ratio may have a threshold value of 0,85, above which PD patients treated with levodopa are likely to be dyskinetic.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/serotonin-to-dopamine-transporter-ratios-in-parkinsons-dyskinesias-the-longitudinal-study/