Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans

Synaptic vesicle glycoprotein 2A (SV2A) is ubiquitously present in presynaptic terminals. Here we report kinetic modeling and test-retest reproducibility assessment of the SV2A positron emission tomography (PET) radioligand [C-11]UCB-J in humans. Five volunteers were examined twice on the HRRT after bolus injection of [C-11]UCB-J. Arterial blood samples were collected for measurements of radiometabolites and free fraction. Regional time-activity curves were analyzed with 1-tissue (1T) and 2-tissue (2T) compartment models to estimate volumes of distribution (V-T). Parametric maps were generated using the 1T model. [C-11]UCB-J metabolized fairly quickly, with parent fraction of 36 +/- 13% at 15 min after injection. Plasma free fraction was 32 +/- 1%. Regional time-activity curves displayed rapid kinetics and were well described by the 1T model, except for the cerebellum and hippocampus. V-T values estimated with the 2T model were similar to 1T values. Parametric maps were of high quality and V-T values correlated well with time activity curve (TAC)-based estimates. Shortening of acquisition time from 120 min to 60 min had a negligible effect on V-T values. The mean absolute test-retest reproducibility for V-T was 3-9% across regions. In conclusion, [C-11]UCB-J exhibited excellent PET tracer characteristics and has potential as a general purpose tool for measuring synaptic density in neurodegenerative disorders.