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The anti-histamine-succinyl-glycine (HSG) arm of the TF2 bispecific antibody serves as a synthetic docking receptor in a multi-step pre-targeted radioimmunotherapy (PRIT) strategy [PMID: 18381681]. TF2 is a trivalent molecule constructed using Dock-and-Lock (DNL) technology, featuring two binding sites for carcinoembryonic antigen (CEA) and one binding site for the HSG hapten [PMID: 21903775]. In clinical applications, TF2 is administered first to saturate CEA-expressing tumor cells, such as those found in colorectal or medullary thyroid cancers. Once the unbound antibody has cleared from the circulation, a small, radiolabeled HSG-containing peptide (e.g., IMP288) is administered, which rapidly binds to the anti-HSG arm of the localized TF2 [PMID: 23447444]. This approach decouples the slow-clearing antibody from the fast-clearing radionuclide, significantly improving the tumor-to-background ratio and reducing systemic radiation exposure [PMID: 25139059]. The anti-HSG arm essentially acts as a high-affinity artificial receptor, enabling the delivery of various diagnostic or therapeutic isotopes to the tumor microenvironment.
Pre-targeted radioimmunotherapy (PRIT) and immuno-PET imaging
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