13C MR spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine

Authors

  • Ferdia A. Gallagher,

    1. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, and Department of Biochemistry, University of Cambridge, Cambridge, UK
    2. Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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  • Mikko I. Kettunen,

    1. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, and Department of Biochemistry, University of Cambridge, Cambridge, UK
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  • Sam E. Day,

    1. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, and Department of Biochemistry, University of Cambridge, Cambridge, UK
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  • Mathilde Lerche,

    1. Imagnia AB, Malmö, Sweden
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  • Kevin M. Brindle

    Corresponding author
    1. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, and Department of Biochemistry, University of Cambridge, Cambridge, UK
    • Department of Biochemistry, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
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  • Conflicts of interest: The hyperpolarizer is on loan from GE Healthcare and is the subject of a research agreement between the University of Cambridge and GE Healthcare. GE supplied the trityl radical used in the hyperpolarization and Imaginia provided the glutamine formulation. The polarizer and related materials were provided by GE-Healthcare

Abstract

Dynamic nuclear polarization (DNP) is an emerging technique for increasing the sensitivity of 13C MR spectroscopy (MRS). [5-13C1]Glutamine was hyperpolarized using this technique by up to 5%, representing a 6000-fold increase in sensitivity. The conversion of hyperpolarized glutamine to glutamate by mitochondrial glutaminase was demonstrated using 13C-MRS measurements in cultured human hepatoma cells (HepG2). These results represent the first step in developing an imaging technique for detecting glutamine metabolism in vivo. Furthermore, since glutamine utilization has been correlated with cell proliferation, the study suggests a new technique for detecting changes in tumor cell proliferation. Magn Reson Med 60:253–257, 2008. © 2008 Wiley-Liss, Inc.

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