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., 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.

Cathepsin B-Activated PET Tracer for In Vivo Tumor Imaging

“…Consequently, it was demonstrated that [ 68 Ga]­NOTA-SF-CV could be served as a feasible small-molecule PET tracer for sensitively and specifically monitoring cathepsin B activity in vivo . By combining the advantages of small-molecule probes and nanoprobes, − the successful application of the tracer [ 68 Ga]­NOTA-SF-CV also demonstrated the applicability and universality of the SF scaffold designed by our group.…”

Recent Advances in Activatable Probes for Molecular Imaging by Stimuli‐Controlled Disassembly

“…Previous results have shown that stimuli‐triggered in situ self‐assembly is capable of prolonging the retention of small‐ molecule radionuclides in the tumor tissues, producing enhanced PET signals. [ 86–92 ] It is envisioned that stimuli‐controlled cascade in‐situ assembly and disassembly process may be adopted to design PET or SPECT imaging probes for sensitive imaging of multiple molecular targets or processes in vivo , benefiting to improve diagnosis of diseases. However, how to choose stimuli to sequentially control these complicated processes in vivo should be carefully considered.…”

The Inverse Electron Demand Diels‐Alder Reaction Between Tetrazine and Trans‐Cyclooctene for Pretargeted Bioimaging Applications

“…In the first step, Tz/TCO moiety accumulates at TOI through noncovalent high‐affinity interactions (e. g., antibody/peptide‐antigen recognition, streptavidin−biotin interaction, complementary oligonucleotide hybridization, etc. ), enhanced permeability and retention (EPR) effect, in situ self‐assembly, or covalent reactions [10,28] . In the second step, the signal agent is attached to the TOI via the Tz−TCO click reaction, or the signal agent is generated or released at TOI by the Tz−TCO click reaction, thus enabling the acquisition of the imaging signal at TOI.…”

“…Bioorthogonal reactions, which can occur in living organisms without interfering with any biochemical processes or negatively affecting native biological activities, have evolved as highly useful tools for constructing imaging probes with high selectivity and high imaging contrast [9] . The combined use of pretargeted imaging and bioorthogonal reactions has proven highly efficacious in comprehending and manipulating biological processes [10] …”