Practical microscale one-pot radiosynthesis of ¹⁸ F-labeled probes

High specific activity is often a significant requirement for radiopharmaceuticals. To achieve that with fluorine-18 (¹⁸ F)-labeled probes, it is mandatory to start from no-carrier-added fluoride and to reduce to a minimum the amount of precursor in order to decrease the presence of any pseudocarrier. In the present study, a feasible and efficient method for microscale one-pot radiosynthesis of ¹⁸ F-labeled probes is described. It allows a substantial reduction in precursor, solvent, and reagents, thus reducing also possible side reaction in the case of base-sensitive precursors. The method is based on the use of a small amount of Kryptofix 2.2.2/potassium [¹⁸ F]fluoride in MeOH (K.222/K[¹⁸ F]F-MeOH) obtained using Oasis MAX and MCX cartridges. Five methods, differing in terms of MeOH evaporation and precursor addition, for the radiosynthesis of [¹⁸ F]fallypride and [¹⁸ F]FET in ≤50-μL scale, were examined and evaluated. The method using the addition of DMSO to the K.222/K[¹⁸ F]F-MeOH solution prior to MeOH evaporation is proposed as a versatile procedure for feasible one-pot 10- to 20-μL scale radiosyntheses. This method was successfully applied also to the radiosynthesis of [¹⁸ F]FES, [¹⁸ F]FLT, and [¹⁸ F]FMISO, with radiochemical yields comparable with those reported in the literature. Purification of a crude product by an analytical HPLC column was also demonstrated.