title: Radiosynthesis of racemic and enantiomerically pure (-)-[18F]flubatine--a promising PET radiotracer for neuroimaging of α4β2 nicotinic acetylcholine receptors.
abstract: (-)-[(18)F]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 (-)-[(18)F]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 >350GBq/μmol. The radiosynthesis is easily transferable to an automated synthesis module.
authors: Department of Neuroradiopharmaceuticals, Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, Permoserstrasse 15, Leipzig, Germany.
authors: Steffen
authors: S
authors: Fischer
authors: Achim
authors: A
authors: Hiller
authors: René
authors: R
authors: Smits
authors: Alexander
authors: A
authors: Hoepping
authors: Uta
authors: U
authors: Funke
authors: Barbara
authors: B
authors: Wenzel
authors: Paul
authors: P
authors: Cumming
authors: Osama
authors: O
authors: Sabri
authors: Jörg
authors: J
authors: Steinbach
authors: Peter
authors: P
authors: Brust
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C115362:fluoronorchloroepibatidine; C403531:nicotinic receptor alpha4beta2