Synaptic vesicle glycoprotein 2A (SV2A) PET imaging enables the estimation of synaptic density in the brain. The most widely used SV2A tracer, 11C-UCB-J, shows age-related effects in healthy volunteers (HV) and its short radioactive half-life limits clinical applicability. 18F-SynVesT-1 has a longer half-life, but its quantification and dependence on age/sex need further validation. In this study, 40 HV aged 24-85 (21F/19M) underwent 90-minute 18F-SynVesT-1 PET-MR with arterial sampling. Distribution volumes (VT) and distribution volume ratios (DVR) were estimated using 1-tissue (1TC) and 2-tissue (2TC) compartment models, and Logan Graphical Analysis (LGA). 1TC and LGA showed strong agreement with 2TC VT (R²≥0.97). Standardized uptake value ratios (SUVR) were evaluated across different time windows, using the centrum semiovale (CSO) and cerebellar (pseudo)reference regions. SUVRCSO 60-90 min correlated best with DVRCSO. The thalamus and cingulate cortex showed age-related decreases in 18F-SynVesT-1 DVRCSO (~2% per decade). Ten subjects (52±21 years; 5F/5M) also underwent 11C-UCB-J PET for a head-to-head comparison. 18F-SynVesT-1 showed lower cortical VT (-7±9%) but higher DVRCSO (37±4%). This study shows that 18F-SynVesT-1 can be reliably quantified by SUVR in healthy volunteers, and correlates well with 11C-UCB-J. These findings support the broader application of 18F-SynVesT-1. This study was registered on clinicaltrial.gov (NCT05384353).
Vanderlinden et al. (Mon,) studied this question.