title: 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.
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.
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158-2512, USA.
authors: Simon
authors: S
authors: Hu
authors: Hikari A I
authors: HA
authors: Yoshihara
authors: Robert
authors: R
authors: Bok
authors: Jenny
authors: J
authors: Zhou
authors: Minhua
authors: M
authors: Zhu
authors: John
authors: J
authors: Kurhanewicz
authors: Daniel B
authors: DB
authors: Vigneron
mesh_terms: D000090:Acetoacetates / Q000737:chemistry; D000108:Acetylcarnitine / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002247:Carbon Isotopes / Q000378:metabolism*; D002384:Catalysis; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D018698:Glutamic Acid / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000090:Acetoacetates; D000970:Antineoplastic Agents; D002247:Carbon Isotopes; D011768:Pyruvate Dehydrogenase Complex; D018698:Glutamic Acid; C016635:acetoacetic acid; D000108:Acetylcarnitine; D019289:Pyruvic Acid; D003999:Dichloroacetic Acid