Radiolabeled nanobodies for tumor targeting: From bioengineering to imaging and therapy

So far, numerous molecules and biomolecules have been evaluated for tumor targeting purposes for radionuclide-based imaging and therapy modalities. Due to the high affinity and specificity against tumor antigens, monoclonal antibodies are appropriate candidates for tumor targeting. However, their large size prevents their comprehensive application in radionuclide-based tumor imaging or therapy, since it leads to their low tumor penetration, low blood clearance, and thus inappropriate tumor-to-background ratio. Nowadays, the variable domain of heavy-chain antibodies from the Camelidae family, known as nanobodies (Nbs), turn into exciting candidates for medical research. Considering several innate advantages of these new tumor-targeting agents, including excellent affinity and specificity toward antigen, high solubility, high stability, fast washout from blood, convenient production, ease of selection, and low immunogenicity, it assumes that they may overcome generic problems of monoclonal antibodies, their fragments, and other vectors used for tumor imaging/therapy. After three decades of Nbs discovery, the increasing number of their preclinical and clinical investigations, which have led to outstanding results, confirm their application for tumor targeting purposes. This review describes Nbs characteristics, the diagnostic and therapeutic application of their radioconjugates, and their recent advances.