Hypoxic cell cytotoxin tirapazamine induces acute changes in tumor energy metabolism and pH: A 31P magnetic resonance spectroscopy study

Eric O. Aboagye, Larry E. Dillehay, Zaver M. Bhujwalla, Ding Jen Lee

Research output: Contribution to journalArticle

Abstract

Tirapazamine is a hypoxic cell cytotoxin in phase II/III trials. To further understand its mechanism of action in vivo, we examined the effect of tirapazamine on tumor energy metabolism and pH. RIF-1 and SCCVII tumors were grown subcutaneously in the flanks of C3H mice. Tumor energy metabolism, expressed as the ratio of inorganic phosphate to nucleotide triphosphate (Pi/NTP), and intracellular pH (pHi), were measured by 31P magnetic resonance spectroscopy (MRS). In RIF-1 and SCCVII tumors, tirapazamine increased the Pi/NTP ratio by 2.6-fold and 3-fold, respectively, within the first hour after an intraperitoneal dose of 0.3 mmol/kg. A corresponding decrease in pHi from 7.05 ± 0.07 to 6.48 ± 0.06, and 7.21 ± 0.09 to 6.45 ± 0.02 in RIF-1 and SCCVII tumors, respectively, was observed. The decrease in tumor 31P bioenergetics and pH was reversible, as exemplified by RIF-1 tumors, which showed a further increase in Pi/NTP ratio of 3.5-fold by 5-8 hr, returning to normal range at 24 hr. Corresponding pHi of RIF-1 tumors was 6.88 ± 0.05 at 5-8 hr and 7.16 ± 0.05 at 24 hr. We concluded that tirapazamine induces acute changes in tumor energy metabolism and pHi. These findings are relevant to the rational selection and optimal timing of coadministered therapy.

Original languageEnglish (US)
Pages (from-to)249-254
Number of pages6
JournalRadiation Oncology Investigations
Volume6
Issue number6
DOIs
StatePublished - Dec 1 1998

Keywords

  • Magnetic resonance spectroscopy
  • Tirapazamine
  • Tumor energy metabolism
  • pH

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Hypoxic cell cytotoxin tirapazamine induces acute changes in tumor energy metabolism and pH: A <sup>31</sup>P magnetic resonance spectroscopy study'. Together they form a unique fingerprint.

  • Cite this