Effect of interstitial and/or systemic delivery of tirapazamine on the radiosensitivity of human glioblastoma multiforme in nude mice

Robert M. Cardinale, Larry E. Dillehay, Jeffery A. Williams, Kevin Tabassi, Henry Brem, Ding Jen Lee

Research output: Contribution to journalArticlepeer-review

Abstract

The purpose of this study was to investigate the feasibility and the efficacy of administering tirapazamine by a slow-releasing polymer disc that was implanted interstitially into a U251 (human glioblastoma multiforme) tumor grown in nude mice. Tumorbearing animals, with a tumor nodule 0.8 cm3 in size, were distributed to groups receiving combinations of empty or drug-containing polymer implants in the tumor or contralateral leg, intraperitoneal (i.p.) drug, and/or irradiation. The drug (i.p.) alone (14 mg/kg ×6) or in combination with tumor drug implant (2 mg) did not significantly increase the tumor volume doubling time compared to that of control animals. Given with 12 Gy of irradiation in twice a day 2-Gy fractions, combined i.p. drug and tumor drug implant significantly delayed tumor growth compared to irradiation alone, which was not achieved with either drug treatment alone added to irradiation. Toxicity, as manifested by transient weight loss, was primarily seen in animals receiving radiation and i.p. tirapazamine. These results indicated that a slow-releasing tirapazamine disc can be produced and the addition of an interstitially implanted tirapazamine disc further increased the effectiveness of i.p. tirapazamine.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalRadiation Oncology Investigations
Volume6
Issue number2
DOIs
StatePublished - Jan 1 1998

Keywords

  • Glioblastoma multiforme
  • Hypoxic cell cytotoxin
  • Implantable polymer disc
  • Tirapazamine (SR 4233)

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging

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