Application of hyperpolarized [1-13C]lactate for the in vivo investigation of cardiac metabolism

Dirk Mayer, Yi Fen Yen, Sonal Josan, Jae Mo Park, Adolf Pfefferbaum, Ralph E. Hurd, Daniel M. Spielman

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

In addition to cancer imaging, 13C-MRS of hyperpolarized pyruvate has also demonstrated utility for the investigation of cardiac metabolism and ischemic heart disease. Although no adverse effects have yet been reported for doses commonly used in vivo, high substrate concentrations have lead to supraphysiological pyruvate levels that can affect the underlying metabolism and should be considered when interpreting results. With lactate serving as an important energy source for the heart and physiological lactate levels one to two orders of magnitude higher than for pyruvate, hyperpolarized lactate could potentially be used as an alternative to pyruvate for probing cardiac metabolism. In this study, hyperpolarized [1-13C]lactate was used to acquire time-resolved spectra from the healthy rat heart in vivo and to measure dichloroacetate (DCA)-modulated changes in flux through pyruvate dehydrogenase (PDH). Both primary oxidation of lactate to pyruvate and subsequent conversion of pyruvate to alanine and bicarbonate could reliably be detected. Since DCA stimulates the activity of PDH through inhibition of PDH kinase, a more than 2.5-fold increase in bicarbonate-to-substrate ratio was found after administration of DCA, similar to the effect when using [1-13C]pyruvate as the substrate.

Original languageEnglish (US)
Pages (from-to)1119-1124
Number of pages6
JournalNMR in biomedicine
Volume25
Issue number10
DOIs
StatePublished - Oct 1 2012

Keywords

  • Dynamic nuclear polarization
  • Hyperpolarized C
  • Lactate
  • Rat heart, dichloroacetate

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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    Mayer, D., Yen, Y. F., Josan, S., Park, J. M., Pfefferbaum, A., Hurd, R. E., & Spielman, D. M. (2012). Application of hyperpolarized [1-13C]lactate for the in vivo investigation of cardiac metabolism. NMR in biomedicine, 25(10), 1119-1124. https://doi.org/10.1002/nbm.2778