Synthetic methodologies and PET imaging applications of fluorine-18 radiotracers: a patent review

Fluorine-18 is a promising radionuclide for developing novel PET radiotracers due to its characteristic features such as convenient half-life, metabolic stability, good imaging properties, and easy access to various clinical PET centers. Currently, many ¹⁸F-radiotracers are available to study disease status in the fields of oncology, cardiology, and neurology.

In this review, the authors have covered patents and research papers of ¹⁸F-radiotracers with clinical applications in various diseases using PET modality since 2015 until the present through SciFinder database.

Despite other PET radionuclides ¹¹C, ¹³N, and ¹⁵O, the ¹⁸F is widely used for radiotracer development because of maximum half-life of 109.8 min. The major limitations of PET radiotracer development include low radiochemical yields and less regioselectivity of the radiofluorination reactions. Therefore, various synthetic methodologies were developed for radiofluorination via nucleophilic, electrophilic with specific precursors, transition metal mediated, and prosthetic groups mediated radiofluorination. Automated radiosynthesis methods have been adapted for easy and convenient synthesis of various ¹⁸F-radiotracers, whereas the PET provides functional information about a disease condition through its pharmacology and physiological processes in vivo, and it is also an essential tool in drug discovery to study therapeutic drug development, and pharmacokinetic profiles.