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