Monoclonal antibody B72.3 binds to human breast and colon tumor associated antigens. IgG was purified and radiolabeled with I-125, and I-131 and In-111 without loss of immunoreactivity. The radiolabeled antibody was injected without loss of immunoreactivity. The radiolabeled antibody was injected into athymic mice bearing antigen positive human colon tumors or an antigen-negative melanoma as a negative control. With iodinated B72.3 IgG activity in the tumor rose for the first 2 days and remained constant over the 19 day period of study. Tumor-to- normal tissue ratios rose over this period of time with ratios of approximately 18:1 for liver, spleen and kidney at 7 days. At 19 days approximately 40% of the radiolabeled B72.3 IgG was found in the tumor. Various chelates (MA, CA, SCN-Bz-EDTA and SCN- Bz-DTPA) were attached to B72.3 IgG and radiolabeled with In- 111. Comparative biodistribution and imaging studies were performed using all four chelates showed that the tumor uptake of radiolabel expressed as a percentage of the injected dose per gram was very similar when three of the chelates were ligated to the B72.3 IgG (30% ID/g). The uptake by normal organs, especially the liver, was greater when MA-DTPA, CA-DTPA, and SCN-Bz-EDTA chelate-B72.3 IgG was used in comparison to that found with the B72.3-SCn-Bz-DTPA. Tumor to liver ratios rose over time with the In-111-B72.3-SCN-Bz-DTPA complex reaching approximately 5:1 by 72h. The tumor to liver ratios for the other MAb-chelate complexes, on the other hand, ranged from only 1.3:1 to 2.5:1. Tumors could easily be identified in scintigraphic images with all the chelate-antibody complexes. However, a progressive accumulation of activity in the abnormal organs, predominantly in the liver, was seen with the MA-DTPA CA- DTPA and SCN-Bz-EDTA chelate-antibody complexes. This uptake was very prominent with these chelate-MAb complexes but was virtually absent in the mice injected with B72.3-SCN-Bz- DTPA.
