Strained Ammonium Precursors for Radiofluorinations

The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile techniques to introduce fluorine-18 especially for the radiolabelling of biologically or pharmacology active molecules. Taking into consideration that the introduction of fluorine-18 (t_1/2 = 109.8 min) mostly proceeds under harsh conditions, radiolabelling of such molecules represents a challenge and is of enormous interest. Ideally, it should proceed in a regioselective manner under mild physiological conditions, in an acceptable time span, with high yields and high specific activities. Special attention has been drawn to 2-fluoroethyl and 3-fluoropropyl groups, respectively, which are often the active site of radiofluorinated compounds. Precursors containing an ammonium leaving group which consists of a strained azetidinium or aziridinium moiety can help to overcome these obstacles leading to a mild introduction of [¹⁸F]fluoride with high radiochemical yields.