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New Method for the Chelation of Indium-111 to Monoclonal Antibodies: Biodistribution and Imaging of Athymic Mice Bearing Human Colon Carcinoma Xenografts

Laboratory of Tumor Immunology and Biology and Inorganic and Radioimmunochemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Correspondence: For reprints contact: David Colcher, PhD, Building 10, Room 8B13, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892.

ABSTRACT

B72.3, a murine monoclonal antibody (MAb) that reacts with 85% of human colon carcinomas as well as other epithelial neoplasias, was labeled with ¹¹¹In using four chelating agents: 1-(p-isothtocyanatobenzyl)-DTPA (SCN-Bz-DTPA), isobutylcarboxycarbonic anhydride (MA-DTPA), cyclic anhydride (CA-DTPA), and 1-(p-isothiocyanatobenzyl)-ethylenediaminetetraacetic acid (SCN-Bz-EDTA). Comparative biodistribution and imaging studies were performed in athymic mice bearing human colon carcinoma xenografts (LS-174T). Tumor uptake of radiolabel was very similar between the chelates (30% ID/g) and tumors were identified in scintigraphic images with all the chelate-antibody complexes. The uptake by normal organs, especially the liver, was greater for MA-DTPA, CA-DTPA, and SCN-Bz-EDTA chelate-B72.3 IgG (1.3:1 to 2.5:1) in comparison to that found with the B72.3-SCN-Bz-DTPA (5:1) and abdominal organ, and uptake was very prominent on imaging with these chelate-MAb complexes but was virtually absent in the mice injected with B72.3-SCN-Bz-DTPA. Purification of the MAb-chelate complex by Sephadex G-50 chromatography followed by HPLC using a TSK-3000 column provided better subsequent biodistribution and also resulted in clearer images as compared to MAb chelate complexes purified by less rigorous purification protocols. We conclude that the ¹¹¹In-SCN-Bz-DTPA complex is superior, at least when bound to MAb B72.3, to other chelate-complexes currently in use.

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