Assessment of noninvasive quantification of [

purposeThe suitability of the white matter centrum semiovale (CS) as a pseudo-reference region for simplified reference tissue model 2 (SRTM2) with [¹⁸F]SynVesT-1 PET has not been evaluated in youth cohorts. We aimed to assess noninvasive quantification methods and determine the minimum scan time needed in a sample of youth with mental health challenges.

methodsThirty-five youth participants (16–25 years old) from the Toronto Adolescent & Youth cohort underwent 120-minute scans with arterial sampling. Binding potential (BPND) was estimated using one-tissue compartment model (1TCM) as a reference method. The SRTM2 was then applied, with k2′ parameter either set to population average (k2 from 1TCM) or estimated individually by initial coupled fitting in a two-step procedure. Standardized uptake value ratio − 1 (SUVR − 1, 60–90 min) was compared with 1TCM-derived BPND. Linear regression and percent bias analyses were performed. Time stability was assessed using several truncated scans (40–100 min).

resultsCS volume (1.7 ± 0.2 mL), VT (4.0 ± 0.6 mL/cm3) and k2 (0.031 ± 0.004 min− 1) were consistent with previously reported values. The population-based k2′ (0.031) and SUVR − 1 closely matched 1TCM results (R2 > 0.9, < 5% mean bias). The coupled-k2′ approach underestimated several regions (R2 > 0.9, > 10% bias in some regions). Minimum scan durations were 60 min for 1TCM, 90 min for fixed-k2′, and ≥ 100 min for coupled-k2′.

conclusionThe population-based k2′ and semiquantitative SUVR–1 provide accurate [¹⁸F]SynVesT-1 quantification in youth with diverse clinical symptoms, supporting their use as noninvasive methods, and allowing scan time reduction to 90 minutes. This will facilitate its clinical use and wider applicability.