Closing the gap between 19F and 18F chemistry
Javier Ajenjo, Gianluca Destro, Bart Cornelissen, Véronique Gouverneur
Abstract
Abstract Positron emission tomography (PET) has become an invaluable tool for drug discovery and diagnosis. The positron-emitting radionuclide fluorine-18 is frequently used in PET radiopharmaceuticals due to its advantageous characteristics; hence, methods streamlining access to 18 F-labelled radiotracers can make a direct impact in medicine. For many years, access to 18 F-labelled radiotracers was limited by the paucity of methodologies available, and the poor diversity of precursors amenable to 18 F-incorporation. During the last two decades, 18 F-radiochemistry has progressed at a fast pace with the appearance of numerous methodologies for late-stage 18 F-incorporation onto complex molecules from a range of readily available precursors including those that do not require pre-functionalisation. Key to these advances is the inclusion of new activation modes to facilitate 18 F-incorporation. Specifically, new advances in late-stage 19 F-fluorination under transition metal catalysis, photoredox catalysis, and organocatalysis combined with the availability of novel 18 F-labelled fluorination reagents have enabled the invention of novel processes for 18 F-incorporation onto complex (bio)molecules. This review describes these major breakthroughs with a focus on methodologies for C– 18 F bond formation. This reinvigorated interest in 18 F-radiochemistry that we have witnessed in recent years has made a direct impact on 19 F-chemistry with many laboratories refocusing their efforts on the development of methods using nucleophilic fluoride instead of fluorination reagents derived from molecular fluorine gas.