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Updated: Aug 14, 2026

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy
David M Goldenberg1, Robert M Sharkey, Giovanni Paganelli
1Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA. dmg.gscancer@att.net
Abstract:
This article reviews the methods of pretargeting, which involve separating the targeting antibody from the subsequent delivery of an imaging or therapeutic agent that binds to the tumor-localized antibody. This provides enhanced tumor:background ratios and the delivery of a higher therapeutic dose than when antibodies are directly conjugated with radionuclides, as currently practiced in cancer radioimmunotherapy. We describe initial promising clinical results using streptavidin-antibody constructs with biotin-radionuclide conjugates in the treatment of patients with malignant gliomas, and of bispecific antibodies with hapten-radionuclides in the therapy of tumors expressing carcinoembryonic antigen, such as medullary thyroid and small-cell lung cancers.
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