Energy metabolism, pH changes, and lactate production in RIF-1 tumors following intratumoral injection of glucose

Zaver M. Bhujwalla, Ioannis Constantinidis, John C. Chatham, Janna P. Wehrle, Jerry D. Glickson

Research output: Contribution to journalArticlepeer-review

Abstract

The metabolic consequences of increased glucose availability were examined in subcutaneous RIF-1 tumors in vivo, using 13C and 31P NMR spectroscopy. Significant increases in the levels of nucleotide triphosphates and phosphocreatine relative to low energy phosphates and in tumor pH were observed within 30 min following injection of 1 g/kg of glucose directly into the tumor. These changes did not occur following an equivalent intratumoral dose of the non-metabolizable sugar alcohol, mannitol. When [1-13C]-glucose was administered, [3-13C-lactate and [3-13C]-alanine were the only labeled metabolites detected in the in vivo 13C NMR spectra during the period of bioenergetic improvement. Biochemical analysis revealed a substantial increase in tumor and plasma glucose concentration, but no increase in either tumor or plasma lactate, consistent with the absence of acidosis. Evaluation of the distribution of glucose in the tumor by quantitative autoradiography of [1-14C]-2-deoxyglucose administered with the glucose indicated that, on average, 7 mM of the added glucose distributed over the entire tumor within 10 min. The significant improvement in overall metabolic status of the tumors following glucose administration is attributed to the existence of substrate limited regions within the tumor.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalInternational journal of radiation oncology, biology, physics
Volume22
Issue number1
DOIs
StatePublished - 1992

Keywords

  • C and P NMR in vivo
  • C-deoxyglucose autoradiography
  • Glucose
  • Lactate
  • Phosphate metabolites
  • RIF-1 tumors
  • pH

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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