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 investigational treatment modality for solid tumors. Use of radiation-enhancing agents could significantly impact on the therapeutic response of this treatment. We evaluated the potential interaction of a known radiation-enhancing agent, 5-fluorouracil (5-FU), with the radioimmunotherapeutic effect of a yttrium-90 (90Y)-labeled monoclonal antibody in a human adeno-carcinoma xenograft. Athymic mice were inoculated subcutaneously with the human colon carcinoma cell line LS-174T. All mice had intraperitoneal 3-day osmotic infusion pumps placed by laparotomy. Half of the pumps were filled with 0.9% saline solution and half were filled with a solution containing 5-FU. Three activity levels of 90Y-radiolabeled CC49 antibody were injected into tail veins of the mice. Each activity level was injected into a group of animals with saline-filled pumps and a group with 5-FU-filled pumps. A significant interaction between treatment group and time was found suggesting that the rate of tumor growth for the group of animals receiving 90Y at 100 microCi plus 5-FU compared to the group of animals receiving 90Y alone was significantly 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, radionuclides, and tumor models are indicated.
Department of Obstetrics and Gynecology, Naval Medical Center, Portsmouth, Virginia 23708-5000.
S W
SW
Remmenga
D
D
Colcher
O
O
Gansow
C G
CG
Pippen
A
A
Raubitschek
D002288:Adenocarcinoma, Mucinous / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D016499:Radioimmunotherapy; D014183:Transplantation, Heterologous; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D011838:Radiation-Sensitizing Agents; D015021:Yttrium Radioisotopes; D005472:Fluorouracil