Carbon-11 patents (2012-2022): synthetic methodologies and novel radiotracers for PET imaging.

INTRODUCTION: Carbon-11 is a short-lived radionuclide with versatile applications in synthetic methodologies to develop a variety of novel PET radiotracers. Different primary and secondary carbon-11 precursors are generated from cyclotron produced [11C]CO2 and used to insert carbon-11 radionuclide into the target-specific bioactive molecules. AREAS COVERED: In this review, the patents as well as specific research articles on carbon-11 radiotracer synthesis and PET imaging applications in various diseases are mentioned since 2012 to 2022 through SciFinder database. EXPERT OPINION: Carbon-11 is generally easier to insert into more organic scaffolds as a greater variety of functional groups. Despite the short half-life of carbon-11 radionuclide (t1/2 = 20.4 min), it is widely used in PET radiotracer development due to its direct insertion into bioactive compounds and less isotopic dilution unlike other positron emitters like fluorine-18. Various synthons can be easily generated using the primary and secondary carbon-11 precursors . The carbon-11 radiotracers provide target-oriented information associated with the pharmacology, and physiological conditions of the disease status. Various protocols and automated methods were adapted for easy and convenient synthesis of carbon-11 radiotracers. The PET advances drug development and clinical trials by revealing biological target engagement, proof of mechanism, pharmacokinetic, and pharmacodynamic profiles of new drug candidates using selective radiotracers.

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

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.