Use of Dichloroacetate to Aid the Investigation of Krebs Cycle Metabolism in vivo in Normal Rat with Hyperpolarized [1-13C]Pyruvate and [2-13C]Pyruvate

Simon Hu¹, Hikari Yoshihara¹, Robert A. Bok¹, John Kurhanewicz¹, Daniel B. Vigneron¹

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of ¹³C metabolism in vivo at very high 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 if 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 (PDK). In this work, hyperpolarized [1-¹³C]pyruvate and [2-¹³C]pyruvate were used to probe mitochondrial metabolism in normal rats. In the case of [1-¹³C]pyruvate, increased bicarbonate was observed after DCA was given. In the case of [2-¹³C]pyruvate, increased acetoacetate and acetylcarnitine were detected.