Spirocyclic Iodonium Ylides for Fluorine-18 Radiolabeling of Non-Activated Arenes: From Concept to Clinical Research

Positron emission tomography (PET) is a powerful imaging tool for drug discovery, clinical diagnosis, and monitoring of disease progression. Fluorine-18 is the most common radionuclide used for PET, but advances in radiotracer development have been limited by the historical lack of methodologies and precursors amenable to radiolabeling with fluorine-18. Radiolabeling of electron-rich (hetero)aromatic rings remains a long-standing challenge in the production of PET radiopharmaceuticals. In this personal account, we discuss the history of spirocyclic iodonium ylide precursors, from inception to applications in clinical research, for the incorporation of fluorine-18 into complex non-activated (hetero)aromatic rings.

Automated summary

Positron emission tomography (PET) is a powerful imaging tool used for drug discovery, clinical diagnosis, and disease monitoring. However, the lack of compatible methods and precursors for radiolabeling with fluorine-18 has limited the development of radiotracers. The radiolabeling of electron-rich (hetero)aromatic rings has been a long-standing challenge in producing PET radiopharmaceuticals. In this personal account, the history and applications of spirocyclic iodonium ylide precursors are discussed for the incorporation of fluorine-18 into complex non-activated (hetero)aromatic rings.