Radiofluorination of diaryliodonium tosylates under aqueous–organic and cryptand-free conditions

Abstract

Positron emission tomography (PET) has growing importance as a molecular imaging technique in clinical research and drug development. Methods for producing PET radiotracers utilizing cyclotron-produced [(18)F]fluoride ion (t1/2 = 109.7 min) without the need for complete removal of irradiated target [(18)O]water and addition of cryptand are keenly sought for practical convenience and efficiency. Several structurally diverse diaryliodonium tosylates, XArI(+)Ar'Y TsO(-) (X = H or p-MeO), were investigated in a microfluidic apparatus for their reactivity towards radiofluorination with high specific activity (no-carrier-added) [(18)F]fluoride ion in mixtures of DMF and irradiated target [(18)O]water in the absence of cryptand. Salts bearing a para or ortho electron-withdrawing group Y (e.g., Y = p-CN) reacted rapidly (∼3 min) to give the expected major [(18)F]fluoroarene product, [(18)F]FArY, in useful moderate radiochemical yields even when the solvent had an [(18)O]water content up to 28%. Salts bearing electron-withdrawing groups in meta position (e.g., Y = m-NO2), or an electron-donating substituent (Y = p-OMe), gave low radiochemical yields under the same conditions.