The Radiopharmaceutical Chemistry of Fluorine-18: Nucleophilic Fluorinations

The positron-emitting radionuclide fluorine-18 plays a prominent role in radiopharmaceuticals for positron emission tomography (PET) due to its favourable nuclear decay properties. Depending on the production method, 18F can be obtained in two different chemical forms: electrophilic [18F]fluorine gas and nucleophilic [18F]fluoride. Nucleophilic [18F]fluoride exhibits several advantages with respect to accessibility and chemical handling. Therefore, nucleophilic 18F-substitution reactions are of pivotal importance for the production of PET radiotracers. This chapter is devoted to this class of reactions, and in the following pages, we seek to provide a general overview of 18F itself as well as insights into nucleophilic 18F-substitution reactions. More specifically, the prerequisites for this reaction with regard to solvent, leaving groups, reactants, etc. are examined. Furthermore, several examples are discussed which demonstrate the potential of this reaction to create highly clinical relevant PET tracers. Finally, this chapter also provides practical tips and tricks for those performing this reaction in the laboratory

18F-labelling innovations and their potential for clinical application

An impressive variety of new methodologies for the preparation of 18F-labelled tracers and ligands has appeared over the last decade. Most strategies of the newly developed radiofluorination methods predominantly aim at products of high molar activity by ‘late-stage’ labelling of small (hetero)aromatic molecules and the use of transition metals. This is accompanied by the improvement of technical procedures, like preparation of reactive [18F]fluoride and automated syntheses. The newly introduced procedures reflect a high innovative level and creativity in radio(pharmaceutical) chemistry at present, which are based on modern chemical methods and deep mechanistic insights. Taking also automation and quality control into consideration, major recently developed radiofluorination methods, most of those still under development, are compiled here in view of their potential for clinical PET imaging and thus the ability to advance molecular imaging