Tumor oxygenation and acidification are increased in melanoma xenografts after exposure to hyperglycemia and meta-iodo-benzylguanidine

Randy Burd, Stephanie N. Lavorgna, Constantine Daskalakis, Phyllis R. Wachsberger, Miriam L. Wahl, John E. Biaglow, Craig W. Stevens, Dennis B. Leeper

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Tumor oxygen tension and extracellular pH (pHe) are physiological parameters that can be manipulated to improve current cancer therapies. Many human tumors consist of cells that are chronically exposed to low pHe. Exposure of tumor cells in culture to glucose decreases oxygen consumption (oxygen sparing or Crabtree effect), and while this effect is absent in low pH-adapted tumor cells, it can be restored by combining the respiratory inhibitor meta-iodo-benzylguanidine (MIBG) with glucose (Burd et aL, Cancer Res. 61, 5630-5635, 2001). The effects of hyperglycemia and MIBG on tumor oxygen tension and on pHe were investigated in human melanoma xenografts in SCID mice. An oral gavage of 1 M glucose (2 g/kg) increased the average blood glucose concentration from <140 mg/dl to ∼400 mg/dl. Although tumor pHe decreased from pH 6.7 to pH 6.5 (P < 0.01) after about 60 min, no change in tumor oxygen tension was observed. However, when oral glucose and MIBG (15 mg/kg) were administered together, oxygen tension increased from 2.8 mmHg to ∼17 mmHg, and tumor pHe decreased from pH 6.7 to pH 6.3 (P < 0.01) after about 115 min. In conclusion, administration of glucose together with MIBG increases tumor oxygen tension and also increases the magnitude and duration of acidification. Hyperglycemia plus MIBG has the potential to improve response to radiation therapy as well as to hyperthermia and some chemotherapies.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalRadiation Research
Volume159
Issue number3
DOIs
StatePublished - Mar 1 2003

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Tumor oxygenation and acidification are increased in melanoma xenografts after exposure to hyperglycemia and meta-iodo-benzylguanidine'. Together they form a unique fingerprint.

  • Cite this