A non-anhydrous, minimally basic protocol for the simplification of nucleophilic 18F-fluorination chemistry
James A. H. Inkster, Vamsidhar Akurathi, Anna W. Sromek, Yen‐Ju Chen, John L. Neumeyer, Alan B. Packard
Abstract
Abstract Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [ 18 F]fluoride from an anion exchange cartridge with a basic solution of K 2 CO 3 or KHCO 3 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 [ 18 F]fluoride incorporation chemistry. In this approach, [ 18 F]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 18 F-fluorination reactions, obviating the need for azeotropic drying. Perchlorate and tosylate are minimally basic anions that are nevertheless suitable for removal of [ 18 F]F - from the anion-exchange cartridge. As proof-of-principle, “NAMB” chemistry was utilized for the synthesis of the dopamine D 2 /D 3 antagonist [ 18 F]fallypride.