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(13) C magnetic resonance spectroscopic imaging of hyperpolarized [1-(13) C, U-(2) H5 ] ethanol oxidation can be used to assess aldehyde dehydrogenase activity in vivo.
- Source :
-
Magnetic resonance in medicine [Magn Reson Med] 2015 May; Vol. 73 (5), pp. 1733-40. Date of Electronic Publication: 2014 May 06. - Publication Year :
- 2015
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (© 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.)
- Subjects :
- Animals
Blood Alcohol Content
Disulfiram pharmacology
Dose-Response Relationship, Drug
Female
Liver drug effects
Liver enzymology
Mice
Oxidation-Reduction drug effects
Predictive Value of Tests
Alcohol Dehydrogenase metabolism
Carbon-13 Magnetic Resonance Spectroscopy methods
Ethanol metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-2594
- Volume :
- 73
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Magnetic resonance in medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24800934
- Full Text :
- https://doi.org/10.1002/mrm.25286