18F-labelled vesamicol derivatives: Syntheses and preliminary in vivo small animal positron emission tomography evaluation

Abstract As possible presynaptic tracers for cholinergic function in humans, three 18 F-labelled vesamicol analogs were synthesized for use in positron emission tomography (PET): cis -[ 18 F]-4-fluoromethylvesamicol (FMV), [ 18 F]- N -fluoroacetamidobenzovesamicol (FAA) and [ 18 F]- N -ethyl- N -fluoroacetamidobenzovesamicol (NEFA). Radiolabelling was accomplished using [ 18 ]fluoride and the corresponding tosylates, the syntheses of which are also described. Yields were on the order of 40–60, 5 and 40–60%, respectively. Dynamic studies of the biodistribution in rats of [ 18 F]FAA and [ 18 F]NEFA using PET were compared with those previously reported for [ 18 F]FMV. Due to probable rapid metabolism, [ 18 F]FAA was considered unsuitable as a ligand for in vivo imaging. [ 18 F]NEFA, similar to [ 18 F]FAA, displayed a more moderate cerebral uptake than that of [ 18 F]FMV (2 vs 20–30%). Pretreatment with vesamicol blocked the cerebral uptake, indicating a specific interaction with the vesamicol binding site. The biodistribution of high specific activity [ 18 F]NEFA with time could be described with a three-compartmental model. The evaluation of [ 18 F]NEFA as a tracer for cholinergic function is currently being pursued in monkeys and humans.