title: Hyperpolarized [(13)C]ketobutyrate, a molecular analog of pyruvate with modified specificity for LDH isoforms.
abstract: OBJECTIVE
  The purpose of this study was to investigate (13) C hyperpolarization of α-ketobutyrate (αKB), an endogenous molecular analog of pyruvate, and its in vivo enzymatic conversion via lactate dehydrogenase (LDH) using localized MR spectroscopy.
  
  
  METHODS
  Hyperpolarized (HP) (13) C MR experiments were conducted using [(13) C]αKB with rats in vivo and with isolated LDH enzyme in vitro, along with comparative experiments using [(13) C]pyruvate. Based on differences in the kinetics of its reaction with individual LDH isoforms, HP [(13) C]αKB was investigated as a novel MR probe, with added specificity for activity of LDHB-expressed H ("heart"-type) subunits of LDH (e.g., constituents of LDH-1 isoform).
  
  
  RESULTS
  Comparable T1 and polarization values to pyruvate were attained (T1  = 52 s at 3 tesla [T], polarization = 10%, at C1 ). MR experiments showed rapid enzymatic conversion with substantially increased specificity. Formation of product HP [(13) C]α-hydroxybutyrate (αHB) from αKB in vivo was increased 2.7-fold in cardiac slabs relative to liver and kidney slabs. In vitro studies resulted in 5.0-fold higher product production from αKB with bovine heart LDH-1, as compared with pyruvate.
  
  
  CONCLUSIONS
  HP [(13) C]αKB may be a useful MR probe of cardiac metabolism and other applications where the role of H subunits of LDH is significant (e.g., renal cortex and brain).
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Cornelius
authors.initials: C
authors.lastname: von Morze
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bok
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ohliger
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Vigneron
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
mesh_terms: D000818:Animals; D002087:Butyrates / Q000737:chemistry*; D002247:Carbon Isotopes / Q000737:chemistry*; D002417:Cattle; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000737:chemistry*; D008099:Liver / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000737:chemistry; D019289:Pyruvic Acid / Q000737:chemistry*; D011817:Rabbits
chemical_list: D002087:Butyrates; D002247:Carbon Isotopes; D020033:Protein Isoforms; C005087:alpha-ketobutyric acid; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase
keywords: 13C; DNP; LDHA; LDHB; hydroxybutyrate; isoenzyme