[18F]Fluoromethyl triflate, a novel and reactive [18F]fluoromethylating agent:: preparation and application to the on-column preparation of [18F]fluorocholine

The production and use of [F-18]fluoromethyl triflate ([F-18]CH2FOTf), a more reactive [F-18]fluoromethylating agent than [F-18]fluoromethyl bromide ([F-18]CH2BrF), is described. [F-18]CH2FOTf was prepared from [F-18]CH2BrF. The latter was synthesized by nucleophilic substitution of CH2Br2 with no-carrier-added [F-18]fluoride and purified by four Sep-Pak Plus silica cartridges connected in series. It was then quantitatively converted on-line to [F-18]CH2FOTf by passing through a heated AgOTf column. Decay-corrected radiochemical yields of [F-18]CH2FOTf based on [F-18]fluoride were 47 +/- 8% (n=20). Both [F-18]CH2BrF and [F-18]CH2FOTf were applied to solid-supported [F-18]fluoromethylation of N,N-dimethylaminoethanol on a Sep-Pak Plus C18 cartridge to produce the F-18-labeled choline analogue, (beta-hydroxyethyl)dimethyl-[F-18]fluoromethylammonium ([F-18]fluorocholine). Depending on flow rate and amount of precursor used, decay corrected radiochemical yields of [F-18]fluorocholine from [F-18]CH2BrF ranged from 6% to 63%, while [F-18]CH2FOTf afforded yields of more than 80%. Thus, by using the latter reagent and a subsequent purification on a Sep-Pak Accell CM cartridge, [F-18]fluorocholine was produced from [F-18]fluoride in overall radiochemical yields of 40% (decay corrected) in less than 30 min. (C) 2002 Elsevier Science Ltd. All rights reserved.