Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-13C]-L-lactate

Details

• Alternative Title:
  Magn Reson Med
• Personal Author:
  Chen, Jun ; Hackett, Edward P. ; Kovacs, Zoltan ; Malloy, Craig R. ; Park, Jae Mo
• Description:
  Purpose:
  
  To evaluate the utility of hyperpolarized [1-13C]-L-lactate to detect hepatic pyruvate carboxylase (PC) activity in vivo under fed and fasted conditions.
  
  Methods:
  
  [1-13C]-labeled sodium L-lactate was polarized using a SPINlab polarizer. Polarization level and the T1 were measured in vitro in a 3T MR scanner. Two groups of healthy rats (fasted vs. fed) were prepared for in vivo studies. Each rat was anesthetized and intravenously injected with 60-mM hyperpolarized [1-13C]-L-lactate, immediately followed by dynamic acquisition of 13C MR spectra from the liver at 3T. The dosage-dependence of the 13C-products was also investigated by performing another injection of an equal volume of 30-mM hyperpolarized [1-13C]-L-lactate.
  
  Results:
  
  T1 and liquid polarization level of [1-13C]-L-lactate were estimated as 67.8 sec and 40.0%, respectively. Besides [1-13C]pyruvate and [1-13C]alanine, [13C]HCO3– and [1-13C]aspartate were produced from hyperpolarized [1-13C]-L-lactate in rat liver. Smaller HCO3– and larger aspartate were measured in the fed group compared to the fasted group. Pyruvate and alanine production were increased in proportion to the lactate concentration, whereas the amount of HCO3– and aspartate production was consistent between 30-mM and 60-mM lactate injections.
  
  Conclusion:
  
  This study demonstrates that a unique biomarker of PC flux, the appearance of [1-13C]aspartate from [1-13C]-L-lactate, is sensitive to nutritional state and may be monitored in vivo at 3T. Since [13C]HCO3– is largely produced by PDH flux, these results suggest that the ratio of [1-13C]aspartate and [13C]HCO3– (aspartate/HCO3–) reflects the saturable PC/PDH enzyme activities.
  
  
• Subjects:
  Article Aspartate Bicarbonate Hyperpolarized 13C Lactate Liver Pyruvate Carboxylase Pyruvate Dehydrogenase
• Source:
  Magn Reson Med. 85(3):1175-1182
• Pubmed ID:
  32936474
• Pubmed Central ID:
  PMC7718288
• Document Type:
  Journal Article
• Funding:
  I-2009-20190330/Welch Foundation/ ; UTD 1907789/UT Dallas Collaborative Biomedical Research Award/ ; The Mobility Foundation/ ; Texas Institute for Brain Injury and Repair, University of Texas Southwestern Medical Center/ ; S10 OD018468/CD/ODCDC CDC HHS/United States ; P41 EB015908/EB/NIBIB NIH HHS/United States ; S10 RR029119/RR/NCRR NIH HHS/United States ; S10 OD018468/CD/ODCDC CDC HHS/United States ; P41 EB015908/EB/NIBIB NIH HHS/United States ; S10 RR029119/RR/NCRR NIH HHS/United States
• Volume:
  85
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5fa585cb4f54860412405bedf77a69510c1861cb602427989bb71a8ff552c0e3
• Download URL:
  https://stacks.cdc.gov/view/cdc/98095/cdc_98095_DS1.pdf
• File Type:
  [PDF - 1.15 MB ]