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., 18F, 68Ga) 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.
Comprehensive SummaryStimuli‐controlled disassembly process has shown promise to direct delivery of probes and/or spatial‐temporally control imaging signals for molecular imaging in vivo. Via the disassembly process, well defined nanoprobes with a stimulus‐responsive moiety can be controllably converted into small‐molecular imaging agents in response to a stimulus, leading to a switch in imaging signals. Moreover, the on‐site released small‐molecule probes could enhance penetration into the deep tissue for improved imaging of deep‐seated molecular targets. Therefore, such a stimuli‐controllable disassembly approach has been widely utilized to build activatable molecular imaging probes for the noninvasive detection of various molecular targets in living subjects. In this review article, we first briefly introduce the general principle of stimuli‐controlled disassembly. We then summarize the activatable probes based on different internal or external stimulus that has been utilized to control disassembly process. Activatable probes by using multiple stimuli to control cascaded in situ self‐assembly and disassembly processes are also discussed. Finally, we close with a conclusion of current challenges and perspective in this field. We wish this review paper will give readers useful information on molecular imaging via the intelligent stimuli‐controlled disassembly process.
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