Synthesis and in vivo evaluation of [F-18]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)

摘要

PurposeSynaptic abnormalities have been implicated in a variety of neuropsychiatric disorders, including epilepsy, Alzheimer's disease, and schizophrenia. Hence, PET imaging of the synaptic vesicle glycoprotein 2A (SV2A) may be a valuable in vivo biomarker for neurologic and psychiatric diseases. We previously developed [C-11]UCB-J, a PET radiotracer with high affinity and selectivity toward SV2A; however, the short radioactive half-life (20min for C-11) places some limitations on its broader application. Herein, we report the first synthesis of the longer-lived F-18-labeled counterpart (half-life: 110min), [F-18]UCB-J, and its evaluation in nonhuman primates.Methods[F-18]UCB-J was synthesized from the iodonium precursors. PET imaging experiments with [F-18]UCB-J were conducted in rhesus monkeys to assess the pharmacokinetic and in vivo binding properties. Arterial samples were taken for analysis of radioactive metabolites and generation of input functions. Regional time-activity curves were analyzed using the one-tissue compartment model to derive regional distribution volumes and binding potentials for comparison with [C-11]UCB-J.Results[F-18]UCB-J was prepared in high radiochemical and enantiomeric purity, but low radiochemical yield. Evaluation in nonhuman primates indicated that the radiotracer displayed pharmacokinetic and imaging characteristics similar to those of [C-11]UCB-J, with moderate metabolism rate, high brain uptake, fast and reversible binding kinetics, and high specific binding signals.ConclusionWe have accomplished the first synthesis of the novel SV2A radiotracer [F-18]UCB-J. [F-18]UCB-J is demonstrated to be an excellent imaging agent and may prove to be useful for imaging and quantification of SV2A expression, and synaptic density, in humans.