title: Use of 3-[(18)F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides.
abstract: 3-[(18)F]Fluoropropanesulfonyl chloride, a recently proposed prosthetic agent for fluorine-18 labelling, was prepared in a two-step radiosynthesis via 3-[(18)F]fluoropropyl thiocyanate as an intermediate. Two benzenesulfonate-based radiolabelling precursors were prepared by various routes. Comparing the reactivities of 3-thiocyanatopropyl nosylate and the corresponding tosylate towards [(18)F]fluoride the former proved to be superior accounting for labelling yields of up to 85%. Conditions for a reliable transformation of 3-[(18)F]fluoropropyl thiocyanate to the corresponding sulfonyl chloride with the potential for automation have been identified. The reaction of 3-[(18)F]fluoropropanesulfonyl chloride with eight different aliphatic and aromatic amines was investigated and the identity of the resulting (18)F-labelled sulfonamides was confirmed chromatographically by comparison with their nonradioactive counterparts. Even for weakly nucleophilic amines such as 4-nitroaniline the desired radiolabelled sulfonamides were accessible in satisfactory yields owing to systematic variation of the reaction conditions. With respect to the application of the (18)F-fluoropropansulfonyl group to the labelling of compounds relevant as imaging agents for positron emission tomography (PET), the stability of N-(4-fluorophenyl)-3-fluoropropanesulfonamide against degradation catalysed by carboxylesterase was investigated and compared to that of the analogous fluoroacetamide.
authors.affiliation: Institute of Radiopharmaceutical Cancer Research (formerly Institute of Radiopharmacy), Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Bautzner Landstraße 400, 01328 Dresden, Germany ; Department of Chemistry and Food Chemistry, Technical University of Dresden, Bergstraße 66c, 01062 Dresden, Germany.
authors.forename: Reik
authors.initials: R
authors.lastname: Löser
authors.forename: Steffen
authors.initials: S
authors.lastname: Fischer
authors.forename: Achim
authors.initials: A
authors.lastname: Hiller
authors.forename: Martin
authors.initials: M
authors.lastname: Köckerling
authors.forename: Uta
authors.initials: U
authors.lastname: Funke
authors.forename: Aurélie
authors.initials: A
authors.lastname: Maisonial
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
keywords: fluorine-18; hydrolytic metabolism; prosthetic groups; radiochemistry; sulfonamides