[ super(11)C]UCB-A, a novel PET tracer for synaptic vesicle protein 2 A

Introduction: Development of a selective and specific high affinity PET tracer, [ super(11)C]UCB-A, for the in vivo study of SV2A expression in humans. Radiochemistry and preclinical studies in rats and pigs including development of a tracer kinetic model to determine V sub(T). A method for the measurement of percent intact tracer in plasma was developed and the radiation dosimetry was determined in rats. Results: 3-5 GBq of [ super(11)C]UCB-A could be produced with radiochemical purity exceeding 98% with a specific radioactivity of around 65 GBq/ mu mol. In vitro binding showed high selective binding towards SV2A. [ super(11)C]UCB-A displayed a dose-dependent and reversible binding to SV2A as measured with PET in rats and pigs and the V sub(T) could be determined by Logan analysis. The dosimetry was favorable and low enough to allow multiple administrations of [ super(11)C]UCB-A to healthy volunteers, and the metabolite analysis showed no sign of labeled metabolites in brain. Conclusions: We have developed the novel PET tracer, [ super(11)C]UCB-A, that can be used to measure SV2A expression in vivo. The dosimetry allows up to 5 administrations of 400 MBq of [ super(11)C]UCB-A in humans. Apart from measuring drug occupancy, as we have shown, the tracer can potentially be used to compare SV2A expression between individuals because of the rather narrow range of baseline V sub(T) values. This will have to be further validated in human studies.