Cryptate mediated nucleophilic ¹⁸F-fluorination without azeotropic drying

The radiosynthesis of the vast majority of ¹⁸F-labeled tracers rely on azeotropic drying of [ ¹⁸F]fluoride and subsequent cryptate mediated introduction of [ ¹⁸F]fluoride by nucleo-philic substitution. The aim of this study was to develop a method for simplification of this process, based on preparation of reactive [K ⁺⊂2.2.2] ¹⁸F- by solvent drying of [ ¹⁸F]fluor-ide adsorbed onto an anion exchange resin. Methods: Aqueous [ ¹⁸F]fluoride (0.5-1 ml) obtained from the ¹⁸O(p,n) ¹⁸F nuclear reaction was trapped on a strong anion-exchange (SAX) cartridge. After washing the cartridge with dry CH ₃CN, [ ¹⁸F]fluoride was eluted with an anhydrous solution of [K ⁺⊂2.2.2]OH- in CH ₃CN and directly used for nucleophilic fluorination reactions. Results: [ ¹⁸F]Fluoride from target water was quantitatively retained by the SAX cartridge, and water-free [ ¹⁸F]-fluoride recovered in an overall yield of 92 ± 5% (n = 10). [ ¹⁸F]Fluoride obtained by this procedure led to radiochemical yields of 70-90% for [ ¹⁸F]FDG, [ ¹⁸F]FET, [ ¹⁸F]FLT, [ ¹⁸F]FAZA and [ ¹⁸F]Fallypride. Conclusion: SAX-resin adsorbed [ ¹⁸F]fluoride can be dried with non-aqueous solvents and eluted with [K ⁺⊂2.2.2]OH ^- in CH ₃CN. The reactivity of [K ⁺⊂2.2.2]F ^- generated by the new method is comparable to that of [ ¹⁸F]fluoride obtained by azeotropic drying. The described procedure facilitates the automated production of ¹⁸F-radiopharmaceuticals in general, and may also simplify the use of microfluidic devices for ¹⁸F-radiotracer production. ^© Schattauer 2012.