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Small amounts of monoclonal antibodies bind to tumors, and monoclonal antibodies bound to cytotoxic agents continue to circulate in the bloodstream and normal tissues. Biotin can be conjugated to monoclonal antibodies, enhancing the binding site and delivering monoclonal antibodies. Designing a pre-targeting strategy needs to take into account the following factors: tumor imaging contrast and tumor therapeutic index (TI), antibody immunogenicity and specificity, applicability of radionuclides, and ease of use in the clinic. Pretargeting strategies can be widely applied to different tumor targets, tumor types or radionuclides. The multifunctionality of pre-targeting provides great application potential for the diagnosis and treatment of tumors, but its development still faces great challenges. Cancer diagnosis and experimental therapy have been performed using radiolabeled monoclonal antibodies with encouraging results.
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A disadvantage of pretargeting techniques is repeated injections at defined time intervals. The immunogenicity of avidin is another disadvantage of pretargeting techniques using these proteins. Internalization of the antigen-antibody complex renders the radiolabel inaccessible to the target molecule for antibody delivery.
Pretargeting strategies can play an important role in addressing the high toxicity of RIT. Key to pretargeting is the concept of decoupling the targeting vector from the cytotoxic agent and administering it separately. Tumor targeting with slow pharmacokinetic drugs is a major challenge in nuclear imaging and targeted radionuclide therapy because they often result in low imaging contrast and high radiation dose to healthy tissue.
Biotinylated antibodies or streptavidin-conjugated antibodies were used as antibody conjugates. Streptavidin or biotin is labeled as a carrier for the radionuclide. Current pretargeting protocols involving the avidin-biotin system are as follows:
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