In vivo assessment of intracellular redox state in rat liver using hyperpolarized [1‐ 13 C]Alanine

Purpose The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD + ]. In this study, we assessed the use of hyperpolarized [1‐ 13 C]alanine and the subsequent detection of the intracellular products of [1‐ 13 C]pyruvate and [1‐ 13 C]lactate as a useful substrate for assessing redox levels in the liver in vivo. Methods Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion. A solution of 80‐mM hyperpolarized [1‐ 13 C]alanine was injected intravenously at baseline (n = 8) and 45 min after ethanol infusion (n = 4), immediately followed by the dynamic acquisition of 13 C MRS spectra. Results In vivo rat liver spectra showed peaks from [1‐ 13 C] alanine and the products of [1‐ 13 C]lactate, [1‐ 13 C]pyruvate, and 13 C‐bicarbonate. A significantly increased 13 C‐lactate/ 13 C‐pyruvate ratio was observed after ethanol infusion (8.46 ± 0.58 at baseline versus 13.58 ± 0.69 after ethanol infusion; P  < 0.001) consistent with the increased NADH produced by liver metabolism of ethanol to acetaldehyde and then acetate. A decrease in 13 C‐bicarbonate production was also noted, potentially reflecting ethanol‐induced mitochondrial redox changes. Conclusion A method to measure in vivo tissue redox using hyperpolarized [1‐ 13 C]alanine is presented, with the validity of the proposed 13 C‐pyruvate/ 13 C‐lactate metric tested using an ethanol challenge to alter liver redox state. Magn Reson Med 77:1741–1748, 2017. © 2017 International Society for Magnetic Resonance in Medicine.