Assessment of test-retest reproducibility of [${}^{18}$F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A

Synaptic abnormalities are associated with many brain disorders. Recently, we developed a novel synaptic vesicle glycoprotein 2A (SV2A) radiotracer [${}^{18}$F]SynVesT-1 and demonstrated its excellent imaging and binding properties in nonhuman primates. The aim of this study was to perform dosimetry calculations in nonhuman primates and to evaluate this tracer in humans and assess its test-retest reliability in comparison with [${}^{11}$C]UCB-J. Three rhesus monkeys underwent whole body dynamic PET scanning to estimate the absorbed dose. PET scans in six healthy human subjects were acquired. Time-activity curves (TACs) were generated with defined regions of interest (ROI). Reproducibility of distribution volume (V${}_T$) values and its sensitivity to scan duration were assessed with the one-tissue compartment (1TC) model. Non-displaceable binding potential (BP${}_{ND}$) was calculated using centrum semiovale as the reference region. The dosimetry study showed high uptake in the urinary bladder and brain. In humans, [${}^{18}$F]SynVesT-1 displayed high uptake with maximum SUV of ~10 and appropriate kinetics with a quick rise in tracer uptake followed by a gradual clearance. Mean 1TC VT values (mL/cm${}^3$) ranged from 3.4 (centrum semiovale) to 19.6 (putamen) and were similar to those of [${}^{11}$C]UCB-J. Regional BP${}_{ND}$ values were 2.7–4.7 in gray matter areas, and mean BP${}_{ND}$ values across all ROIs were ~ 21% higher than those of [${}^{11}$C]UCB-J. The absolute test-retest variability of V${}_T$ and BP${}_{ND}$ was excellent (< 9%) across all brain regions. [${}^{18}$F]SynVesT-1 demonstrates outstanding characteristics in humans: fast and high brain uptake, appropriate tissue kinetics, high levels of specific binding, and excellent test-retest reproducibility of binding parameters. As such, [${}^{18}$F]SynVesT-1 is proved to be a favorable radiotracer for SV2A imaging and quantification in humans.