In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-C-13]glutamine

C. Cabella, Magnus Karlsson, C. Canape, G. Catanzaro, S. Colombo Serra, L. Miragoli, L. Poggi, F. Uggeri, L. Venturi, Pernille Rose Jensen, Mathilde Hauge Lerche, F. Tedoldi

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Glutamine metabolism is, with its many links to oncogene expression, considered a crucial step in cancer metabolism and it is thereby a key target for alteration in cancer development. In particular, strong correlations have been reported between oncogene expression and expression and activity of the enzyme glutaminase. This mitochondrial enzyme, which is responsible for the deamidation of glutamine to form glutamate, is overexpressed in many tumour tissues. In animal models, glutaminase expression is correlated with tumour growth rate and it is readily possible to limit tumour growth by suppression of glutaminase activity. In principle, hyperpolarized C-13 MR spectroscopy can provide insight to glutamine metabolism and should hence be a valuable tool to study changes in glutaminase activity as tumours progress. However, no such successful in vivo studies have been reported, even though several good biological models have been tested. This may, at least partly, be due to problems in preparing glutamine for hyperpolarization. This paper reports a new and improved preparation of hyperpolarized [5-C-13]glutamine, which provides a highly sensitive C-13 MR marker. With this preparation of hyperpolarized [5-C-13]glutamine, glutaminase activity in vivo in a rat liver tumour was investigated. Moreover, this marker was also used to measure response to drug treatment in vitro in cancer cells. These examples of [5-C-13]glutamine used in tumour models warrant the new preparation to allow metabolic studies with this conditionally essential amino acid. (C) 2013 Elsevier Inc. All rights reserved.
Original languageEnglish
JournalJournal of Magnetic Resonance
Volume232
Pages (from-to)45-52
ISSN1090-7807
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Nuclear and High Energy Physics
  • Biochemistry
  • Biophysics
  • Condensed Matter Physics
  • Dynamic nuclear polarization
  • Glutamine
  • Liver cancer
  • Biological models
  • Cancer development
  • Essential amino acids
  • Liver cancers
  • Mitochondrial enzymes
  • Strong correlation
  • C (programming language)
  • Diseases
  • Drug therapy
  • Enzyme activity
  • Magnetic resonance spectroscopy
  • Metabolism
  • Physiology
  • Tumors
  • Amino acids
  • antineoplastic agent
  • carbon
  • deoxycytidine
  • drug derivative
  • gemcitabine
  • glutaminase
  • glutamine
  • tumor marker
  • animal
  • article
  • experimental liver neoplasm
  • metabolism
  • methodology
  • nuclear magnetic resonance spectroscopy
  • rat
  • tumor cell line
  • Animals
  • Antineoplastic Agents
  • Carbon Isotopes
  • Cell Line, Tumor
  • Deoxycytidine
  • Glutaminase
  • Liver Neoplasms, Experimental
  • Magnetic Resonance Spectroscopy
  • Rats
  • Tumor Markers, Biological
  • Biomarkers, Tumor
  • BIOCHEMICAL
  • PHYSICS,
  • SPECTROSCOPY
  • C-13 MAGNETIC-RESONANCE
  • GLUTAMINE-METABOLISM
  • HEPATOCELLULAR-CARCINOMA
  • HEPATOMA-CELLS
  • TRANSPORT
  • GROWTH

Cite this

Cabella, C., Karlsson, M., Canape, C., Catanzaro, G., Serra, S. C., Miragoli, L., Poggi, L., Uggeri, F., Venturi, L., Jensen, P. R., Lerche, M. H., & Tedoldi, F. (2013). In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-C-13]glutamine. Journal of Magnetic Resonance, 232, 45-52. https://doi.org/10.1016/j.jmr.2013.04.010