[18F]SynVesT-1 PET tracer in Parkinson’s disease: A preliminary assessment of SUVR and BPnd

Introduction: Synaptic density has emerged as a promising diagnostic biomarker for Parkinsonian disorders. The target of new PET radiotracers for quantifying synaptic density is the ubiquitously expressed synaptic vesicle protein SV2A. Here we present a preliminary assessessment of standardized uptake value ratio (SUVR) and non-displaceable binding potential (BPnd) using [18F]-SynVesT-1 in individuals with Parkinson’s and healthy controls.

Methods: Six individuals diagnosed with Parkinson's disease (3 males and 1 female) and three healthy controls (2 males and 1 female), participated in a 90-minute [18F]-SynVesT-1 PET scan conducted on a GE Discovery MI PET-CT system. PET scans underwent attenuation correction using a CT scan and were aligned with the T1-weighted MRI of each participant. The SUVR and BPnd was calculated using Pmod (v4.203). SUVR was calculated for the 60–90-minute time window (as recommended by <w:sdt docpart="D0A0A479A02046D083C0208A4BB9E1B9" id="-1644417003" 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et al., 2021)</w:sdt>. The BPnd was calculated using a simplified reference tissue model (SRTM2) for the 0-90-minute time window. The centrum semiovale (CS) was used as the reference region for both methods due to its very low specific binding of SV2A (Smart et al., 2023). Volumes of interest (VOIs) were generated using the Hammers AAL atlas. Group differences in overall and VOIs SUVR and BPnd were investigated via ANOVA.

Results: SUVR and BPnd showed comparable results. Overall SUVR and BPnd was lower in the PD cohort, however, this difference disappeared when age was included as a covariate. VOI analysis (controlled for age) highlighted reductions of SUVR and BPnd in the substantia nigra (SN) and thalamus within the PD cohort (Figure 1).

Conclusions: The reduction in overall pre-synaptic density, as well as within the SN and thalamus, is consistent with previous preclinical and clinical studies quantifying SV2A density <w:sdt docpart="8A29661761C7407987143A9667123DF8" id="-2018069596" 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">(Binda et al., 2023; Martin et al., 2023; Wilson et al., 2020)</w:sdt>. SV2A can be quantified without blood sampling, with SUVR and BPnd showing comparable differences. Validation of these findings is required in a larger sample. Subsequent studies will investigate the relationship between SV2A density and various clinical metrics of the disease.

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