Cryptate mediated nucleophilic 18F-fluorination without azeotropic drying

The radiosynthesis of the vast majority of F-18-labeled tracers rely on azeotropic drying of [F-18]fluoride and subsequent cryptate mediated introduction of [F-18]fluoride by nucleophilic substitution. The aim of this study was to develop a method for simplification of this process, based on preparation of reactive [K+subset of 2.2.2]F-18(-) by solvent drying of [F-18]fluoride adsorbed onto an anion exchange resin. Methods: Aqueous [F-18]fluoride (0.5-1 ml) obtained from the O-18(p,n)F-18 nuclear reaction was trapped on a strong anion-exchange (SAX) cartridge. After washing the cartridge with dry CH3CN, [F-18]fluoride was eluted with an anhydrous solution of [K+subset of 2.2.2]OH- in CH3CN and directly used for nucleophilic fluorination reactions. Results: [F-18]Fluoride from target water was quantitatively retained by the SAX cartridge, and water-free [F-18]fluoride recovered in an overall yield of 92 +/- 5% (n = 10). [F-18]Fluoride obtained by this procedure led to radiochemical yields of 70-90% for [F-18]FDG, [F-18]FET, [F-18]FLT, [F-18]FAZA and [F-18]Fallypride. Conclusion: SAX-resin adsorbed [F-18]fluoride can be dried with non-aqueous solvents and eluted with [K+subset of 2.2.2]OH- in (CHCN)-C-3. The reactivity of [K+subset of 2.2.2]F- generated by the new method is comparable to that of [F-18]fluoride obtained by azeotropic drying. The described procedure facilitates the automated production of F-18-radiopharmaceuticals in general, and may also simplify the use of microfluidic devices for F-18-radiotracer production.