New method for the chelation of indium-111 to monoclonal antibodies: biodistribution and imaging of athymic mice bearing human colon carcinoma xenografts.
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-isothiocyanatobenzyl)-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 (approximately 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.
D000818:Animals; D000911:Antibodies, Monoclonal; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D004492:Edetic Acid; D006801:Humans; D007204:Indium; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D004369:Pentetic Acid; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007204:Indium; D004369:Pentetic Acid; D004492:Edetic Acid