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

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.

[1]  Kent Harris,et al.  Clinical experience with 13C MRS in vivo , 2003, NMR in biomedicine.

[2]  Jan Henrik Ardenkjaer-Larsen,et al.  Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. , 2006, Cancer research.

[3]  A. Dennison,et al.  Prognostic molecular markers in hepatocellular carcinoma: a systematic review. , 2007, European journal of cancer.

[4]  Peter Magnusson,et al.  13C imaging—a new diagnostic platform , 2005, European Radiology.

[5]  W. Souba,et al.  Determinants of glutamine dependence and utilization by normal and tumor‐derived breast cell lines , 1998, Journal of cellular physiology.

[6]  J Stefan Petersson,et al.  Metabolic imaging and other applications of hyperpolarized 13C1. , 2006, Academic radiology.

[7]  Jan H. Ardenkjær-Larsen,et al.  Molecular imaging with endogenous substances , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[8]  L. Reitzer,et al.  Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. , 1979, The Journal of biological chemistry.

[9]  W. Souba,et al.  Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[10]  Otto Muzik,et al.  Imaging proliferation in vivo with [F-18]FLT and positron emission tomography , 1998, Nature Medicine.

[11]  J. Mcgivan,et al.  Glutamine availability up-regulates expression of the amino acid transporter protein ASCT2 in HepG2 cells and stimulates the ASCT2 promoter. , 2004, The Biochemical journal.

[12]  B. Bode Recent molecular advances in mammalian glutamine transport. , 2001, The Journal of nutrition.

[13]  G. Dodd,et al.  Malignancies in patients with cirrhosis: CT sensitivity and specificity in 200 consecutive transplant patients. , 1994, Radiology.

[14]  W. Souba,et al.  Modulation of Cellular Proliferation Alters Glutamine Transport and Metabolism in Human Hepatoma Cells , 1994, Annals of surgery.

[15]  Jan Wolber,et al.  Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy , 2007, Nature Medicine.

[16]  T R Brown,et al.  Cellular applications of 31P and 13C nuclear magnetic resonance. , 1979, Science.

[17]  J. Ardenkjær-Larsen,et al.  Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Miguel Angel Medina,et al.  Relevance of glutamine metabolism to tumor cell growth , 1992, Molecular and Cellular Biochemistry.