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.
Remmenga
S W
SW
Department of Obstetrics and Gynecology, Naval Medical Center, Portsmouth, Virginia 23708-5000.
Colcher
D
D
Gansow
O
O
Pippen
C G
CG
Raubitschek
A
A
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