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The iodine-131-labeled control single-domain antibody (specifically [131I]SGMIB-R3B23) is a non-targeting radiopharmaceutical used as a negative control in the development of HER2-targeted theranostics. It consists of a camelid-derived single-domain antibody (sdAb or nanobody), R3B23, which was specifically selected for its lack of affinity for human epidermal growth factor receptor 2 (HER2) or other known human antigens. The antibody is radiolabeled with iodine-131 using the residualizing prosthetic group N-succinimidyl 4-guanidinomethyl-3-iodobenzoate (SGMIB). This prosthetic group is designed to reduce kidney retention of radioactivity and trap the radioisotope within cells upon internalization, although internalization is minimal for this non-targeting control. It serves as a critical benchmark in preclinical and clinical studies to differentiate between specific tumor targeting and non-specific accumulation or clearance, supporting the development of targeted agents like [131I]SGMIB-2Rs15d for HER2-overexpressing cancers.
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