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

Prasanta Dutta, Anne Le, David L. Vander Jagt, Takashi Tsukamoto, Gary V. Martinez, Chi V. Dang, Robert J. Gillies

Research output: Contribution to journalArticlepeer-review

Abstract

Hyperpolarized 13C 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 13C-pyruvate to lactate in murine xenografts of P493 human lymphoma. In contrast, a glutaminase inhibitor reduced conversion of 13C-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.

Original languageEnglish (US)
Pages (from-to)4190-4195
Number of pages6
JournalCancer Research
Volume73
Issue number14
DOIs
StatePublished - Jul 15 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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