Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors

Cancer Res. 2013 Jul 15;73(14):4190-5. doi: 10.1158/0008-5472.CAN-13-0465. Epub 2013 May 30.

Abstract

Hyperpolarized (13)C magnetic resonance spectroscopy provides a unique opportunity to detect real-time metabolic fluxes as a means to measure metabolic treatment responses in vivo. Here, we show that pharmacologic inhibition of lactate dehydrogenase-A suppressed the conversion of hyperpolarized (13)C-pyruvate to lactate in murine xenografts of P493 human lymphoma. In contrast, a glutaminase inhibitor reduced conversion of (13)C-pyruvate to alanine without affecting conversion of pyruvate to lactate. These results illustrate the ability to monitor biomarkers for responses to antimetabolic therapy in real-time, paving the way for clinical development of imaging biomarkers to monitor metabolic pharmacodynamics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Carbon Isotopes / metabolism*
  • Cell Line, Tumor
  • Glutaminase / antagonists & inhibitors*
  • Glutaminase / metabolism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / antagonists & inhibitors*
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • Lactic Acid / metabolism
  • Lymphoma / drug therapy*
  • Lymphoma / metabolism*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Mice
  • Pyruvic Acid / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • Carbon Isotopes
  • Isoenzymes
  • Lactic Acid
  • Pyruvic Acid
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • Glutaminase