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Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1‐ 13 C]‐ l ‐lactate
Author(s) -
Chen Jun,
Hackett Edward P.,
Kovacs Zoltan,
Malloy Craig R.,
Park Jae Mo
Publication year - 2021
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.28489
Subject(s) - pyruvate carboxylase , in vivo , chemistry , sodium pyruvate , alanine , sodium lactate , bicarbonate , endocrinology , medicine , sodium , biochemistry , biology , amino acid , enzyme , microbiology and biotechnology , organic chemistry
Purpose To evaluate the utility of hyperpolarized [1‐ 13 C]‐ l ‐lactate to detect hepatic pyruvate carboxylase activity in vivo under fed and fasted conditions. Methods [1‐ 13 C]‐labeled sodium L‐lactate was polarized using a dynamic nuclear polarizer. Polarization level and the T 1 were measured in vitro in a 3 Telsa 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‐ 13 C]‐ l ‐lactate, immediately followed by dynamic acquisition of 13 C (carbon‐13) MR spectra from the liver at 3 Tesla. The dosage‐dependence of the 13 C‐products was also investigated by performing another injection of an equal volume of 30‐mM hyperpolarized [1‐ 13 C]‐ l ‐lactate. Results T 1 and liquid polarization level of [1‐ 13 C]‐ l ‐lactate were estimated as 67.8 s and 40.0%, respectively. [1‐ 13 C]pyruvate and [1‐ 13 C]alanine, [ 13 C]bicarbonate ( HCO 3 ‐ ) and [1‐ 13 C]aspartate were produced from hyperpolarized [1‐ 13 C]‐ l ‐lactate in rat liver. Smaller HCO 3 ‐ 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 HCO 3 ‐ and aspartate production was consistent between 30‐mM and 60‐mM lactate injections. Conclusion This study demonstrates that a unique biomarker of pyruvate carboxylase flux, the appearance of [1‐ 13 C]aspartate from [1‐ 13 C]‐ l ‐lactate, is sensitive to nutritional state and may be monitored in vivo at 3 Tesla. Because [ 13 C] HCO 3 ‐ is largely produced by pyruvate dehydrogenase flux, these results suggest that the ratio of [1‐ 13 C]aspartate and [ 13 C] HCO 3 ‐ (aspartate/ HCO 3 ‐ ) reflects the saturable pyruvate carboxylase/pyruvate dehydrogenase enzyme activities.