Tumor localization of CEA-containing human tumors in nude mice by means of monoclonal anti-CEA antibodies

Abstract

Three different monoclonal antibodies (mabs) directed against conformation-dependent protein determinants in carcinoembryonic antigen (CEA) were evaluated for tumorimmunolocalization of CEA-containing human tumors grown in nude mice. The antibodies were of high affinity and of the IgG₁ subclass. They did not react with non-specific cross-reacting antigen (NCA), biliary glyco-protein 1 (BGP 1) or orosomucoid. 10–20 μCi(1–2 μg) of ¹³¹I-labelled mab was injected intraperitoneally into mice bearing heterografts of the CEA-containing human tumor cell lines LS 174T, Detroit 562 or HT-29 or into mice bearing grafts of the non-CEA-containing human tumor cell line RD. The concentration of radiolabelled mab in the tumor compared with the mean concentration in the mouse increased up to day 4 after injection. In contrast, the concentration ratios of radioactivity in the other tissues decreased with time. Excellent tumor localization was obtained with mab 38SI in mice bearing LS 174T tumors. The concentration of radioactivity (cpm/g) tissue wet weight) was 24–390 times higher in the tumor than in the muscle. The difference between tumor and liver and between tumor and blood was 4–89 times and 2–25 times, respectively. A mean value of 40% of the total radioactivity in the mouse at day 4 was localized to the tumor. Mab 38SI also showed positive tumor localization in mice carrying Detroit and HT-29 tumors. Means of 22% and 18% of the total radioactivity in the mouse at day 4 were found in these tumors, respectively. Mab 38SI was, however, not enriched in the tumor of mice bearing the non-CEA-containing sarcoma RD. Furthermore, when LS 174T tumor-bearing mice were injected with normal mouse IgG, no enrichment of radioactivity in the tumor was seen. Positive tumor localization with mab 48 was obtained while mab 9 was not enriched in the tumor. Scanning pictures of LS 174T-grafted mice on day 4 after injection of ¹³¹I-mab 38SI showed a definite radioactive spot corresponding to the tumor and in addition a spot corresponding to the liver or the heart.