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

(-)-[F-18]flubatine is a promising agent for visualization by PET of cerebral alpha(4)beta(2) nicotinic acetylcholine receptors (nAChRs), which are implicated in psychiatric and neurodegenerative disorders. Here, we describe a substantially improved two-step radiosynthesis strategy for (-)-[F-18]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/mu mol. The radiosynthesis is easily transferable to an automated synthesis module. (C) 2013 Elsevier Ltd. All rights reserved.