CONTINUOUS-INFUSION CHEMOTHERAPY AS A RADIATION-ENHANCING AGENT FOR YTTRIUM-90-RADIOLABELED MONOCLONAL-ANTIBODY THERAPY OF A HUMAN TUMOR XENOGRAFT

Radioimmunotherapy using monoclonal antibodies is a promising investig ational treatment modality for solid tumors. Use of radiation-enhancin g agents could significantly impact on the therapeutic response of thi s treatment. We evaluated the potential interaction of a known radiati on-enhancing agent, 5-fluorouracil (5-FU), with the radioimmunotherape utic effect of a yttrium-90 (Y-90)-labeled monoclonal antibody in a hu man adenocarcinoma xenograft. Athymic mice were inoculated subcutaneou sly with the human colon carcinoma cell line LS-174T. All mice had int raperitoneal 3-day osmotic infusion pumps placed by laparotomy. Half o f the pumps were filled with 0.9% saline solution and half were filled with a solution containing 5-FU. Three activity levels of Y-90-radiol abeled CC49 antibody were injected into tail veins of the mice. Each a ctivity level was injected into a group of animals with saline-filled pumps and a group with 5-FU-filled pumps. A significant interaction be tween treatment group and time was found suggesting that the rate of t umor growth for the group of animals receiving Y-90 at 100 muCi plus 5 -FU compared to the group of animals receiving Y-90 alone was signific antly delayed (P = 0.0055), showing a radiation enhancing effect by 5- FU. These results suggest that the addition of the radiation-enhancing agent 5-FU to radiolabeled antibody may increase the ability to treat solid tumors. Further investigations with other antibodies, radionucl ides, and tumor models are indicated. (C) 1994 Academic Press, Inc.