Evaluation of 18F-UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain

Synaptic vesicle protein 2 isoforms are critical for proper nervous system function and are involved in vesicle trafficking. The synaptic vesicle protein 2A (SV2A) isoform has been identified as the binding site of the antiepileptic levetiracetam (LEV), making it an interesting therapeutic target for epilepsy. (18)F-UCB-H is a novel PET imaging agent with a nanomolar affinity for human SV2A.

Preclinical PET studies were performed with isoflurane-anesthetized rats. The arterial input function was measured with an arteriovenous shunt and a β-microprobe system. (18)F-UCB-H was injected intravenously (bolus of 140 ± 20 MBq).

Brain uptake of (18)F-UCB-H was high, matching the expected homogeneous distribution of SV2A. The distribution volume (Vt) for (18)F-UCB-H was calculated with Logan graphic analysis, and the effect of LEV pretreatment on Vt was measured. In control animals the whole-brain Vt was 9.76 ± 0.52 mL/cm(3) (mean ± SD; n = 4; test-retest), and the reproducibility in test-retest studies was 10.4% ± 6.5% (mean ± SD). The uptake of (18)F-UCB-H was dose dependently blocked by pretreatment with LEV (0.1-100 mg/kg intravenously).

Our results indicated that (18)F-UCB-H is a suitable radiotracer for the imaging of SV2A in vivo. To our knowledge, this is the first PET tracer for the in vivo quantification of SV2A. The necessary steps for the implementation of (18)F-UCB-H production under good manufacturing practice conditions and the first human studies are being planned.