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

Abstract

AbstractFPyKYNE (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 © 2008 John Wiley & Sons, Ltd.