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Evaluation of N-Succinimidyl S-Acetylthioacetate Ligand for Radiolabeling of Humanized Antibodies with 188 Rhenium.
Cancer Biotherapy & Radiopharmaceuticals 2018 October
Radioimmunotherapy offers an effective way to direct ionizing radiation to cancer cells through attachment of radionuclides to antibodies while limiting negative effects of off-target irradiation. This, however, requires effective facile methods for attachment of therapeutic radionuclides onto antibodies. Herein, the authors report their efforts in evaluating N-succinimidyl S-acetylthioacetate (SATA), a commercially available reagent, for use as a bifunctional chelating agent (BCA) to attach 188 Rhenium (188 Re) onto h8C3, a humanized IgG antibody that can effectively target extracellular melanin present in malignant melanoma. Micro single photon emission computer tomography/computer tomography was used to determine an effective timeline for antibody uptake in B16-F10 tumor bearing C57BL6 mice guiding the selection of 188 Re with its 16.9 h physical half-life. Radio instant thin layer chromatography coupled with radio high-performance liquid chromatography was used to assess radioisotope incorporation, as well as stability during the labeling process for SATA conjugated h8C3. It was determined that despite the relatively mild conditions used, incorporation of the SATA conjugate resulted in antibody instability during labeling requiring a different BCA to facilitate rhenium incorporation onto the antibodies.
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