Preservation of ligand functionality by click chemistry

Click chemistry reactions have had a considerable impact in the effort to develop efficient synthetic strategies towards new radiopharmaceutical agents. This is largely due to the ability of these reactions to proceed rapidly under ambient conditions, resulting in an easily isolated product. These reaction properties are particularly desirable in the synthesis of positron emission tomography (PET) imaging agents containing short-lived radioisotopes, such as carbon-11 and fluorine-18. Striving to further improve on the suitability of these reactions, chemists have succeeded in developing new, streamlined click chemistry reactions with additional advantages. These versatile reactions have now been used extensively in the preparation of radiolabeled small molecules, peptides, proteins, and nanomaterials for nuclear imaging applications. A small number of these click chemistry reactions are also bioorthogonal as they have the ability to proceed efficiently and selectively within the complex biological medley of a living system. This rare and valuable attribute has led to their utilisation in pretargeted imaging strategies which have the potential to provide superior image quality and reduced radiation burden compared with conventional imaging approaches. In this chapter, we aim to introduce the click chemistry reactions which have had the greatest impact in the preparation of radiolabeled ligands for nuclear imaging applications, with special focus on the application of nanoparticles. In addition, we also describe the use of these reactions in combination with nanoparticle vectors to facilitate a pretargeted imaging strategy