title: (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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dzien
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.forename: Irene
authors.initials: I
authors.lastname: Marco-Rius
authors.forename: Eva M
authors.initials: EM
authors.lastname: Serrao
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Rodrigues
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Larkin
authors.forename: Kerstin N
authors.initials: KN
authors.lastname: Timm
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D000067401:Blood Alcohol Content; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D004221:Disulfiram / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D011237:Predictive Value of Tests
chemical_list: D000067401:Blood Alcohol Content; D000431:Ethanol; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; D004221:Disulfiram
keywords: acetaldehyde; acetate; alcohol dehydrogenase; aldehyde dehydrogenase; ethanol; hyperpolarized 13C