Recent Advances in Pretargeted Imaging of Tumors in Vivo

Abstract Over the past decades, the pretargeted strategy has emerged as a promising approach to improve delivery of nucleotides into tumor tissues for nuclear imaging and/or therapy. Unlike conventional nuclear imaging and therapy, in which a radiolabeled tumor targeting vector (e. g., antibody) is directly administered and allowed to circulate and accumulate in the tumor tissues, the pretargeted strategy decouples the radiolabeled reporters with the targeting vectors; these two components could specifically couple through either covalent or noncovalent interactions in vivo. Such a two‐step pretargeted approach holds a flexibility to optimize the pharmacokinetics of targeting vectors and radioactive reporters independently, facilitating to improved imaging contrast. Moreover, the short‐lived radioisotopes (e. g., 18 F, 68 Ga) can be used with an antibody of a nanoparticle that generally holds a long blood circulation time, which could be helpful to reduce the radiation burden for patients. In this Review, we summarize the recent advances in pretargeted strategies for tumor imaging, with a focus on the discussion of engineering different targeting vectors for tumor pretargeting. Different in vivo coupling approaches for pretargeted imaging of tumors are also discussed. Finally, we discuss the outlook for the potential clinical translation and the current challenges in the pretargeted imaging approach.