A non-anhydrous, minimally basic protocol for the simplification of nucleophilic ¹⁸F-fluorination chemistry

Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [¹⁸F]fluoride from an anion exchange cartridge with a basic solution of K₂CO₃ or KHCO₃ and Kryptofix 2.2.2. in mixture of acetonitrile and water followed by rigorous azeotropic drying to remove the water. In this work we describe an alternative "non-anhydrous, minimally basic" ("NAMB") technique that simplifies the process and avoids the basic conditions that can sometimes limit the scope and efficiency of [¹⁸F]fluoride incorporation chemistry. In this approach, [¹⁸F]F^- is eluted from small (10-12 mg) anion-exchange cartridges with solutions of tetraethylammonium bicarbonate, perchlorate or tosylate in polar aprotic solvents containing 10-50% water. After dilution with additional aprotic solvent, these solutions are used directly in nucleophilic aromatic and aliphatic ¹⁸F-fluorination reactions, obviating the need for azeotropic drying. Perchlorate and tosylate are minimally basic anions that are nevertheless suitable for removal of [¹⁸F]F^- from the anion-exchange cartridge. As proof-of-principle, "NAMB" chemistry was utilized for the synthesis of the dopamine D₂/D₃ antagonist [¹⁸F]fallypride.