Electrochemical Radiofluorination of Small Molecules: New Advances

The development of new ¹⁸ F-based radiopharmaceuticals constantly demands innovations in the search for new radiofluorination methods. [¹⁸ F]fluoride is the simplest and most convenient chemical form of the isotope for the synthesis of ¹⁸ F-based radiopharmaceuticals. The ease of production and handling, as well as the possibility of obtaining high molar activities, makes it the preferred choice for radiofluorination. However, the use of [¹⁸ F]fluoride in late-stage radiofluorination comes with challenges, especially for the radiolabeling of electron-rich molecules where S_N 2 and S_N Ar reactions are not suitable. New developments in fluorination chemistry have been extensively studied to overcome these difficulties. Selective electrochemical oxidation of precursors, using a controlled potential, is one method to create reactive intermediates and overcome the activation energy required for nucleophilic fluorination of electron-rich moieties. This method has been used for years in cold fluorination of organic molecules and more recently has been adapted as an alternative to traditional radiofluorination methods. Although relatively young, this field stands out as a promising route for the synthesis of new PET probes as well as fluorinated pharmaceuticals. This review focuses on recent advances in electrochemical radiofluorination as an alternative for the late-stage radiolabeling of organic molecules.