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.