RADIOIMMUNOTHERAPY AND FRACTIONATED RADIOTHERAPY OF HUMAN COLON-CANCER LIVER METASTASES IN NUDE-MICE

Radioimmunotherapy (RIT) and radiotherapy (RT) were evaluated in nude mice developing liver metastases of human colon cancer, Without treatm ent, 90% of preconditioned nude mice, injected with LS174T cells intra splenically and splenectomized, died between 26 and 93 days after graf ting with few to several hundred liver metastases. RIT with 500 mu Ci of I-131-labeled anti-carcinoembryonic antigen monoclonal antibodies, injected i.v. in 3 weekly fractions, was initiated 1 to 3 weeks after grafting, Mean survival increase was 43 days for mice treated at 2 wee ks, From 13 mice treated at 1 week, 8 mice showed long-term survival, a significantly better cure rate compared to RIT at 2 weeks, Mice unde rgoing RIT at 3 weeks showed similar survival as untreated controls, M ice injected with I-131-labeled irrelevant IgG1 or unlabeled antibody showed no significant survival increase. Conventional fractionated ext ernal beam RT of the liver showed that 40-50 Gy treatment initiated 1 week after grafting gave long-term survival in 7 of 13 mice, significa ntly better compared to RT at 2 weeks, With combined RIT + RT initiate d 2 weeks after grafting, 5 of 11 mice had long-term survival in the a bsence of major toxicities, Thus, early RIT and RT were more efficient than later treatments, and combination therapy might give further imp rovement.