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

被引:122
作者
Gallagher, Ferdia A. [1 ,2 ,3 ]
Kettunen, Mikko I. [1 ,2 ]
Day, Sam E. [1 ,2 ]
Lerche, Mathilde [4 ]
Brindle, Kevin M. [1 ,2 ]
机构
[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
[2] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England
[3] Univ Cambridge, Addenbrookes Hosp, Hosp NHS Fdn Trust, Dept Radiol, Cambridge CB2 2QQ, England
[4] Imagnia AB, Malmo, Sweden
关键词
hyperpolarized C-13; dynamic nuclear polarization; glutamine metabolism; hepatocellular carcinoma;
D O I
10.1002/mrm.21650
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Dynamic nuclear polarization (DNP) is an emerging technique for increasing the sensitivity of C-13 MR spectroscopy (MRS). [5-C-13(1)]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 C-13-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.
引用
收藏
页码:253 / 257
页数:5
相关论文
共 19 条
[1]   Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR [J].
Ardenkjaer-Larsen, JH ;
Fridlund, B ;
Gram, A ;
Hansson, G ;
Hansson, L ;
Lerche, MH ;
Servin, R ;
Thaning, M ;
Golman, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (18) :10158-10163
[2]   MODULATION OF CELLULAR PROLIFERATION ALTERS GLUTAMINE TRANSPORT AND METABOLISM IN HUMAN HEPATOMA-CELLS [J].
BODE, BP ;
SOUBA, WW .
ANNALS OF SURGERY, 1994, 220 (04) :411-424
[3]   Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells [J].
Bode, BP ;
Fuchs, BC ;
Hurley, BP ;
Conroy, JL ;
Suetterlin, JE ;
Tanabe, KK ;
Rhoads, DB ;
Abcouwer, SF ;
Souba, WW .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2002, 283 (05) :G1062-G1073
[4]   Recent molecular advances in mammalian glutamine transport [J].
Bode, BP .
JOURNAL OF NUTRITION, 2001, 131 (09) :2475S-2485S
[5]   Glutamine availability up-regulates expression of the amino acid transporter protein ASCT2 in HepG2 cells and stimulates the ASCT2 promoter [J].
Bungard, CI ;
McGivan, JD .
BIOCHEMICAL JOURNAL, 2004, 382 :27-32
[6]  
Collins CL, 1998, J CELL PHYSIOL, V176, P166, DOI 10.1002/(SICI)1097-4652(199807)176:1<166::AID-JCP18>3.0.CO
[7]  
2-5
[8]   Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy [J].
Day, Sam E. ;
Kettunen, Mikko I. ;
Gallagher, Ferdia A. ;
Hu, De-En ;
Lerche, Mathilde ;
Wolber, Jan ;
Golman, Klaes ;
Ardenkjaer-Larsen, Jan Henrik ;
Brindle, Kevin M. .
NATURE MEDICINE, 2007, 13 (11) :1382-1387
[9]   Molecular imaging with endogenous substances [J].
Golman, K ;
Ardenær-Larsen, JH ;
Petersson, JS ;
Månsson, S ;
Leunbach, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (18) :10435-10439
[10]   Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis [J].
Golman, Klaes ;
in't Zandt, Rene ;
Lerche, Mathilde ;
Pehrson, Rikard ;
Ardenkjaer-Larsen, Jan Henrik .
CANCER RESEARCH, 2006, 66 (22) :10855-10860