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PURPOSE: Aldehyde dehydrogenase (ALDH2) is an emerging drug target for the treatment of heart disease, cocaine and alcohol dependence, and conditions caused by genetic polymorphisms in ALDH2. Noninvasive measurement of ALDH2 activity in vivo could inform the development of these drugs and accelerate their translation to the clinic. METHODS: [1-(13) C, U-(2) H5 ] ethanol was hyperpolarized using dynamic nuclear polarization, injected into mice and its oxidation in the liver monitored using (13) C MR spectroscopy and spectroscopic imaging. RESULTS: Oxidation of [1-(13) C, U-(2) H5 ] ethanol to [1-(13) C] acetate was observed. Saturation of the acetaldehyde resonance, which was below the level of detection in vivo, demonstrated that acetate was produced via acetaldehyde. Irreversible inhibition of ALDH2 activity with disulfiram resulted in a proportional decrease in the amplitude of the acetate resonance. CONCLUSION: (13) C magnetic resonance spectroscopy measurements of hyperpolarized [1-(13) C, U-(2) H5 ] ethanol oxidation allow real-time assessment of ALDH2 activity in liver in vivo.

Original publication

DOI

10.1002/mrm.25286

Type

Journal article

Journal

Magn Reson Med

Publication Date

05/2015

Volume

73

Pages

1733 - 1740

Keywords

acetaldehyde, acetate, alcohol dehydrogenase, aldehyde dehydrogenase, ethanol, hyperpolarized 13C, Alcohol Dehydrogenase, Animals, Blood Alcohol Content, Carbon-13 Magnetic Resonance Spectroscopy, Disulfiram, Dose-Response Relationship, Drug, Ethanol, Female, Liver, Mice, Oxidation-Reduction, Predictive Value of Tests