Josan, S., Xu, T., Yen, Y. F., Hurd, R., Ferreira, J., Chen, C. H., . . . Spielman, D. (2013). In vivo measurement of aldehyde dehydrogenase-2 activity in rat liver ethanol model using dynamic MRSI of hyperpolarized [1-(13) C]pyruvate. NMR in Biomedicine, 26(6), 607-612. doi: 10.1002/nbm.2897
Abstract
To date, measurements of the activity of aldehyde dehydrogenase-2 (ALDH2), a critical mitochondrial enzyme for the elimination of certain cytotoxic aldehydes in the body and a promising target for drug development, have been largely limited to in vitro methods. Recent advancements in MRS of hyperpolarized 13C-labeled substrates have provided a method to detect and image in vivo metabolic pathways with signal-to-noise ratio gains greater than 10 000-fold over conventional MRS techniques. However aldehydes, because of their toxicity and short T1 relaxation times, are generally poor targets for such 13C-labeled studies. In this work, we show that dynamic MRSI of hyperpolarized [1-13C]pyruvate and its conversion to [1-13C]lactate can provide an indirect in vivo measurement of ALDH2 activity via the concentration of NADH (nicotinamide adenine dinucleotide, reduced form), a co-factor common to both the reduction of pyruvate to lactate and the oxidation of acetaldehyde to acetate. Results from a rat liver ethanol model (n = 9) show that changes in 13C-lactate labeling following the bolus injection of hyperpolarized pyruvate are highly correlated with changes in ALDH2 activity (R2 = 0.76). Copyright © 2012 John Wiley & Sons, Ltd.