Bioorthogonal coupling reactions are a powerful tool to create protein conjugates within living systems without interfering with the native biochemical environment. This reaction class has been increasingly utilized over the past few years in the development of new radiopharmaceuticals for medical imaging and radiotherapy. Pretargeting strategies have particularly benefited, where tissue-specific antibodies are first allowed to localize to their target site before a radiolabeled molecule is administered that can covalently bond with the antibody. These radionuclide delivery systems can enhance therapeutic efficacy, reducing radiation exposure and increasing image quality. Current applications of bioorthogonal coupling reactions in pretargeted molecular imaging and radioimmunotherapy will be reviewed.
Keywords: Antibody labeling, Bioorthogonal coupling, Click chemistry, Inverse electron demand Diels-Alder, PET imaging, Pretargeting, Radiotherapy, Radiotracer, Staudinger ligation, Strain-promoted cycloaddition.