Pretargeted

Pretargeted refers to strategies that separate the targeting step from the delivery of the therapeutic or diagnostic payload. In medicine, pretargeting is used to improve the localization of radiolabeled, fluorescent, or cytotoxic agents to tumors while reducing exposure to normal tissues. The typical scheme involves first administering a targeting agent that binds a tumor-associated antigen and presents a docking handle. After the targeting agent has localized and cleared from the bloodstream, a second, smaller effector molecule carrying the radioactive label, drug, or imaging probe is given. The effector binds to the docking handle with high affinity, generating selective accumulation at the tumor site.

Common platforms include bispecific antibodies that recognize both the tumor antigen and a small molecule hapten or tag, and non-antibody docking strategies such as streptavidin-biotin systems or bioorthogonal click chemistry. Pretargeted radioimmunotherapy (PRIT) and pretargeted imaging for PET or SPECT are prominent applications, aiming to enhance tumor-to-background ratios and reduce radiation dose to normal tissues.

Benefits of pretargeting include improved contrast for imaging and potentially lower systemic toxicity in therapy, due to the rapid clearance of unbound effector molecules and better temporal separation of targeting and payload delivery. Limitations involve manufacturing complexity, potential immunogenicity of bridging components, the need for precise timing and dosing, and variability in antigen expression or tumor perfusion. As a result, pretargeting approaches remain an area of active research, with multiple multipart strategies under evaluation in clinical trials and ongoing development in theranostic cancer care.