Radiolabeled monoclonal antibody B72.3 localization in metastatic lesions of colorectal cancer patients

Abstract

We have previously demonstrated a high degree of selective binding of monoclonal antibody (MAb) B72.3 to carcinomas of the colon, ovary, and breast in contrast to normal adult tissues using in vitro assays. In this report we demonstrate selective tumor localization in colorectal cancer patients after intravenously administering 131I-labeled MAb B72.3 IgG. Radiolocalization Indices (RI) (i.e. cpm 131I-labeled MAb per gram of tumor vs cpm per gram of normal tissues), were obtained by direct analyses of biopsy materials. Using an RI of ≥3 as a positive localization, tumor lesions in various sites from 17 20 patients scored positive. In eight of these patients, all tumor lesions demonstrated RIs of >3, while in five patients RIs of some lesions were > 10 and as high as 30–46. Seventy percent ( 99 142 ) of the tumor lesions showed RIs of > 3, while only 12 of 210 histologically confirmed normal tissues examined showed RIs of > 3. These tissues were either adjacent to the tumor or the draining tumor masses or, as in the case of two patients, was caused by high levels of circulating immune complexes that deposited in the spleen. Positive scintigraphic images (confirmed at surgery) were observed in 14 27 patients. No toxicity or adverse reactions were observed with either MAb. These studies provide absolute quantitative analyses of the actual delivery of radiolabeled MAb to carcinoma lesions vs a wide range of adjacent and distal normal tissues and establishes the means for other diagnostic and potential therapeutic applications of this antibody alone, or in combinations with other monoclonal antibodies.