Quantification of 18 F-SynVesT-1 binding in healthy aging and head-to-head comparison with 11 C-UCB-J

Synaptic vesicle glycoprotein 2A (SV2A) PET imaging enables the estimation of synaptic density in the brain. The most widely used SV2A tracer, 11 C-UCB-J, shows age-related effects in healthy volunteers (HV) and its short radioactive half-life limits clinical applicability. 18 F-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-min 18 F-SynVesT-1 PET–MR with arterial sampling. Distribution volumes ( V T ) and distribution volume ratios (DVR) were estimated using one-tissue (1TC) and two-tissue (2TC) compartment models, and Logan graphical analysis (LGA). 1TC and LGA showed strong agreement with 2TC V T ( R 2 ⩾ 0.97). Standardised uptake value ratios (SUVR) were evaluated across different time windows, using the centrum semiovale (CSO) and cerebellar (pseudo-)reference regions. SUVR CSO 60–90 min correlated best with DVR CSO . The thalamus and cingulate cortex showed age-related decreases in 18 F-SynVesT-1 DVR CSO (~2%/decade). Ten subjects (52 ± 21 years; 5F/5M) also underwent 11 C-UCB-J PET for a head-to-head comparison. 18 F-SynVesT-1 showed lower cortical V T (−7% ± 9%) but higher DVR CSO (37% ± 4%). This study shows that 18 F-SynVesT-1 can be reliably quantified by SUVR in healthy volunteers, and correlates well with 11 C-UCB-J. These findings support the broader application of 18 F-SynVesT-1. This study was registered on clinicaltrial.gov (NCT05384353).