Silicon-Fluoride Acceptors (SiFA) for ¹⁸F-Radiolabeling: From Bench to Bedside

Fluorine-18 (¹⁸F) is undoubtedly one of the most frequently applied radionuclides for the development of new radiotracers for positron emission tomography (PET) in the context of clinical cancer, neurological, and metabolic imaging. Until recently, the available radiochemical methodologies to introduce ¹⁸F into organic molecules ranging from small- to medium- and large-sized compounds were limited to a few applicable protocols. With the advent of late-stage fluorination of small aromatic, nonactivated compounds and various noncanonical labeling strategies geared toward the labeling of peptides and proteins, the molecular toolbox for PET radiotracer development was substantially extended. Especially, the noncanonical labeling methodologies characterized by the formation of Si-¹⁸F, B-¹⁸F, and Al-¹⁸F bonds give access to kit-like ¹⁸F-labeling of complex and side-group unprotected compounds, some of them already in clinical use. This chapter will particularly focus on silicon-fluoride acceptor (SiFA) chemistry and cover the history of its conceptual design and its translation into the clinical practice.