Continuous infusion chemotherapy as a radiation-enhancing agent for yttrium-90-radiolabeled monoclonal antibody therapy of a human tumor xenograft

Steven W. Remmenga, David Colcher, Otto Gansow, C. Greg Pippen, Andrew Raubitschek

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 adenocarcinoma 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 90 Y-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 μCi 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.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalGynecologic Oncology
Volume55
Issue number1
DOIs
StatePublished - Oct 1994
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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