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

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-min ¹⁸F-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 (R² ⩾ 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 ¹⁸F-SynVesT-1 DVR_CSO (~2%/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 V_T (-7% ± 9%) but higher DVR_CSO (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).