19F‐MRI: From Molecular Design to In Vivo Applications

Bioimaging is an essential tool for investigating biological processes and detecting disease biomarkers improving both diagnosis and therapy monitoring. 19F-Magnetic resonance imaging (19F-MRI) has recently emerged as a powerful imaging technique with high translational potential to clinic enabling direct in vivo quantification without use of ionizing radiations. In fact, the lack of organic fluorine in living systems allows unambiguous quantitative detection of exogenous fluorinated probes as colored “hot spots” on the anatomical images obtained by conventional 1H-MRI protocols. If anatomical resolution is a strength, low sensitivity is a drawback of 19F-MRI, which requires the use of highly fluorinated contrast agents (CAs). Fluorinated CAs are twofold biorthogonal due to their innate chemical and biological inertness, linked to strong CF bonds, and to the total absence of endogenous organic fluorine. In this chapter, the main classes of 19F-MRI CAs, which are highly fluorinated molecules formulated with biocompatible emulsifiers, partially fluorinated amphiphilic polymers, and fluorinated inorganic nanoparticles, will be described highlighting how their chemical design is critical to achieve an effective 19F-MRI response. Moreover, for each class of compounds representative examples of the most important biomedical applications will be illustrated addressing the main challenges for their translation to clinic and possible future perspectives in different still unexplored fields.