(Invited) Fluorination and No-Carrier-Added Radio-Fluorination of Organic Molecules Using Cation Pool Technique

Positron emission tomography (PET) is a molecular imaging method is being employed in preclinical and clinical studies such as oncology or diagnosis of certain diffuse brain diseases. The growth of PET as a powerful method in biomedical research, needs development of more efficient methods for developing the positron-emitting radiotracers. The fluorine radioactive isotope (18F) has a short half-life of 110 min, making it as an ideal PET radiotracer. 18F labeling of electron rich moieties such as aromatic molecules is highly desirable due to their high biostability. In 1990 Yoshida and co-workers developed the cation pool method which stabilized carbamate cationic intermediates generated during a two electron oxidation followed by deprotonation that takes place in the anodic compartment of a two compartment cell under low temperatures.1 The method allows for rapid reactions with nucleophiles that may be unstable during electrolysis and can be added to the reaction mixture at the end of electrolysis to form the final product. Here, we report on the extension of the cation pool method for the application of electrochemical fluorination and radio-fluorination of methyl (phenylthio)acetate. Electrochemical fluorination and no-carrier-added radio-fluorination were successfully achieved using the cation pool method. The cation pool method has tremendous potential for radiofluorination experiments. The excess concentration of cations may provide an efficient reaction mechanism for late-stage fluorination under low fluoride concentrations encountered in radiochemistry. Furthermore, radiochemical yield, which is reduced by decay of the radioisotope, can benefit from a rapid late-stage fluorination reaction. The cation pool can be prepared prior to cyclotron production of 18F isotope, thereby, providing a rapid late-stage fluorination reaction, maximizing radiochemical yield by minimizing decay through a rapid reaction of the previously prepared cations with 18F-fluoride. Synthesis parameters such as temperature, supporting electrolyte concentration and type, and precursor concentration were studied and optimized. Optimum reaction yield was obtained at -20 °C. The products were characterized using gas chromatography–mass spectrometry (GC-MS), nuclear magnetic resonance (NMR), radio-thin-layer chromatography (radio-TLC) and high-performance liquid chromatography (HPLC). References Yoshida, J. et al. Direct Oxidative Carbon−Carbon Bond Formation Using the “Cation Pool” Method. 1. Generation of Iminium Cation Pools and Their Reaction with Carbon Nucleophiles. J. Am. Chem. Soc. 121, 9546–9549 (1999). Yoshida, J. et al. Direct Oxidative Carbon−Carbon Bond Formation Using the “Cation Pool” Method. 1. Generation of Iminium Cation Pools and Their Reaction with Carbon Nucleophiles. J. Am. Chem. Soc. 121, 9546–9549 (1999).