Radiosynthesis of racemic and enantiomerically pure (−)-[18F]flubatine—A promising PET radiotracer for neuroimaging of α4β2 nicotinic acetylcholine receptors

(−)-[18F]flubatine is a promising agent for visualization by PET of cerebral α4β2 nicotinic acetylcholine receptors (nAChRs), which are implicated in psychiatric and neurodegenerative disorders. Here, we describe a substantially improved two-step radiosynthesis strategy for (−)-[18F]flubatine, based on the nucleophilic radiofluorination of an enantiomerically pure precursor followed by deprotection of the intermediate. An extensive leaving group/protecting group library of precursors was tested. Application of a trimethylammonium-iodide precursor with a Boc-protecting group provided the best results: labeling efficiencies of 80–95%, RCY of 60±5%, radiochemical purity of >98%, and a specific activity of >350 GBq/μmol. The radiosynthesis is easily transferable to an automated synthesis module.

► Two-step radiosynthesis for (−)-[18F]flubatine as α4β2 nAChR imaging agent was developed. ► Numerous leaving and protecting groups for optimal precursor design were tested. ► A NMe3-iodide/Boc-protected precursor provided the best radiochemical parameters. ► The procedure can be easily transferred to an automated synthesis module.