Hyperpolarized [5-13C,4,4-2H2,5-15N]-L-glutamine provides a means of annotating in vivo metabolic utilization of glutamine

Roozbeh Eskandari, Nathaniel Kim, Arsen Mamakhanyan, Michelle Saoi, Guannan Zhang, Marjan Berishaj, Kristin L. Granlund, Alex J. Poot, Justin Cross, Craig B. Thompson, Kayvan R. Keshari

Research output: Contribution to journalArticlepeer-review

Abstract

Glutamine is consumed by rapidly proliferating cells and can provide the carbon and nitrogen required for growth through various metabolic pathways. However, delineating the metabolic fate of glutamine is challenging to interrogate in vivo. Hyperpolarized magnetic resonance, by providing high transient nuclear magnetic resonance signals, provides an approach to measure fast biochemical processes in vivo. Aminohydrolysis of glutamine at carbon-5 plays an important role in providing nitrogen and carbon for multiple pathways. Here, we provide a synthetic strategy for isotope-enriched forms of glutamine that prolongs glutamine-C5 relaxation times and thereby reveals in vivo reactions involving carbon-5. We investigate multiple enrichment states, finding [5-13C,4,4-2H2,5-15N]-L-glutamine to be optimal for hyperpolarized measurement of glutamine conversion to glutamate in vivo. Leveraging this compound, we explore pancreatic cancer glutamine metabolism in vivo. Taken together, this work provides a means for studying glutamine metabolic flux in vivo and demonstrates on-target effects of metabolic enzyme inhibitors.

Original languageEnglish (US)
Article numbere2120595119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number19
DOIs
StatePublished - May 10 2022
Externally publishedYes

Keywords

  • cancer metabolism
  • magnetic resonance imaging
  • pancreatic cancer

ASJC Scopus subject areas

  • General

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