[18F]FPyKYNE, a fluoropyridine-based alkyne reagent designed for the fluorine-18 labelling of macromolecules using click chemistry

Article abstract of DOI:10.1002/jlcr.1533

FPyKYNE (2-fluoro-3-pent-4-yn-1-yloxypyridine) is a novel fluoropyridine-based structure, designed for the fluorine-18 labelling of macromolecules using copper-catalysed Huisgen 1,3-dipolar cycloaddition (click chemistry). FPyKYNE (non-labelled as reference), as well as the 2-bromo, 2-nitro and 2-trimethylammonium analogues (as precursors for labelling with fluorine-18), was synthesized in 44, 95, 60 and 41%, respectively, from commercially available 5-chloropent-1-yne and the appropriate 2-substituted-3-hydroxypyridines. [¹⁸F]FPyKYNE was synthesized in one single radiochemical step by reaction of no-carrier-added K[ ¹⁸F]F-Kryptofix 222 (DMSO, 165°C, 3-5 min) followed by C-18 SepPak cartridge pre-purification and finally semi-preparative HPLC purification on a Hewlett Packard SiO₂ Zorbax Rx-SIL. Using the 2-nitropyridine or the pyridin-2-yltrimethylammonium trifluoromethanesulphonate precursor for labelling (30 and 10 μmol, respectively), incorporation yields up to 90% were observed and 7.0-8.9 GBq (190-240 mCi) of [¹⁸F]FPyKYNE ([¹⁸F]-1) could be isolated within 60-70 min (HPLC purification included), starting from a 37.0 GBq (1.0 Ci) [¹⁸F]fluoride batch (overall decay-corrected and isolated yields: 30-35%). Copyright