Use of hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate to probe the effects of the anticancer agent dichloroacetate on mitochondrial metabolism in vivo in the normal rat.

Simon Hu, Hikari A I Yoshihara, Robert Bok, Jenny Zhou, Minhua Zhu, John Kurhanewicz, Daniel B Vigneron

Index: Magn. Reson. Imaging 30(10) , 1367-72, (2012)

Full Text: HTML

Abstract

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of (13)C metabolism in vivo at very high signal-to-noise ratio (SNR). In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine whether the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase. In this work, hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate were used to probe mitochondrial metabolism in normal rats. Increased conversion to bicarbonate (+181±69%, P=.025) was measured when [1-(13)C]pyruvate was injected after DCA administration, and increased glutamate (+74±23%, P=.004), acetoacetate (+504±281%, P=.009) and acetylcarnitine (+377±157%, P=.003) were detected when [2-(13)C]pyruvate was used.Copyright © 2012 Elsevier Inc. All rights reserved.