In vitro binding profile and radiosynthesis of a novel 18F‐labeled azaspirovesamicol analog as potential ligand for imaging of the vesicular acetylcholine transporter

Radiolabeled vesamicol analogs are promising candidates as ligands for the vesicular acetylcholine transporter (VAChT) to enable in vivo imaging of early cholinergic degenerations in brain. The 4‐fluorobenzoyl‐substituted azaspirovesamicol derivative FBASV is one out of six novel vesamicol analogs and demonstrated most appropriate in vitro binding data. ¹⁸F‐radiolabeling was performed by microwave‐assisted nucleophilic aromatic substitution of the corresponding nitro precursor and two methods were developed for the purification of [¹⁸F]FBASV. Utilizing method A, the remaining nitro precursor was reduced to its corresponding amine, which was separated via semi‐preparative HPLC on a conventional RP column. In method B a phenyl column was used for the direct separation of [¹⁸F]FBASV and its nitro precursor, resulting in a change of the elution order and better separation parameters. Thus, [¹⁸F]FBASV was synthesized with a RCY of 16–18%, a specific activity >300 GBq/ µ mol, and a radiochemical purity of >99.5% suitable for future in vivo studies. Copyright © 2011 John Wiley & Sons, Ltd.