Solvent exchange radiofluorination: High yield production of fluorine-18 compounds without water evaporation

Objectives The goal of this study was to evaluate a new method for the rapid introduction of fluorine-18 into useful intermediates by eliminating the resolubilization step. Resolubilization is the process whereby water is azeotropically removed from aqueous [¹⁸F]fluoride ion (¹⁸F^-) in the presence of a phase transfer catalyst and the residue is dissolved in a polar aprotic solvent suitable for subsequent nucleophilic radiofluorination reactions. Elimination of this step would lead to more efficient radiofluorination reactions.

Methods A device was built for the concentration of aqueous ¹⁸F^- using a small anion exchange cartridge. The trapped ¹⁸F^- was rinsed with DMSO. The ¹⁸F^- was eluted from the cartridge with a DMSO/ water (20-25 μL ) solution of potassium carbonate and kryptofix into the reaction vial containing the desired precursor. The reaction mixture was heated to 150°C for 15 minutes. The products were analyzed by radioTLC and radioHPLC.

Results The ¹⁸F^- ion was quantitatively trapped and released from the anion exchange cartridge. The radiochemical yields for the initial reactions with aryl precursors using this system are shown in Table 1. The aryl [¹⁸F]fluoride yields in Table 1 are comparable to those achieved for conventional radiofluorination conditions where the water is azeotropically dried. Initial results with alkyl tosylates did not produce the desired corresponding [¹⁸F]fluoroalkanes.

Conclusions This new automated method is suitable for the efficient preparation of aryl [¹⁸F]fluoride intermediates and may be applicable to a broader spectrum of intermediates and tracers.

Research Support This research was supported in part by the Office of Biological and Environmental Research, US DOE under grant no DE-FG02-08ER64699

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Table 1: Radiofluorination reactions