Therapeutic target metabolism observed using hyperpolarized 15N choline

被引:100
作者
Gabellieri, Cristina [1 ]
Reynolds, Steven [2 ]
Lavie, Amon [3 ]
Payne, Geoffrey S. [1 ]
Leach, Martin O. [1 ]
Eykyn, Thomas R. [1 ]
机构
[1] Royal Marsden NHS Fdn Trust, Inst Canc Res, Canc Res UK Clin Magnet Resonance Res Grp, Sutton SM2 5PT, Surrey, England
[2] Oxford Instruments Mol Biotools, Abingdon OX13 5QX, Oxon, England
[3] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA
基金
英国工程与自然科学研究理事会;
关键词
D O I
10.1021/ja8001293
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Choline is a precursor of cellular phospholipid metabolism that provides Magnetic Resonance (MR) and Positron Emission Tomography (PET) biomarkers for cancer detection and response assessment. Employing Dynamic Nuclear Polarization we show that the MR signal of N-15 in choline can be enhanced by at least 4 orders of magnitude with a relaxation time of ca. 4 min, providing a method to observe the action of choline kinase, an important target for novel cancer therapeutics.
引用
收藏
页码:4598 / +
页数:3
相关论文
共 14 条
[1]   Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of the choline kinase inhibitor MN58b in human carcinoma models [J].
Al-Saffar, NMS ;
Troy, H ;
Ramírez de Molina, A ;
Jackson, LE ;
Madhu, B ;
Griffiths, JR ;
Leach, MO ;
Workman, P ;
Lacal, JC ;
Judson, IR ;
Chung, YL .
CANCER RESEARCH, 2006, 66 (01) :427-434
[2]   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
[3]   Identification of magnetic resonance detectable metabolic changes associated with inhibition of phosphoinositide 3-kinase signaling in human breast cancer cells [J].
Beloueche-Babari, M ;
Jackson, LE ;
Al-Saffar, NMS ;
Eccles, SA ;
Raynaud, FI ;
Workman, P ;
Leach, MO ;
Ronen, SM .
MOLECULAR CANCER THERAPEUTICS, 2006, 5 (01) :187-196
[4]   Hyperpolarized c-13 spectroscopic imaging of the TRAMP mouse at 3T - Initial experience [J].
Chen, Albert P. ;
Albers, Mark J. ;
Cunningham, Charles H. ;
Kohler, Susan J. ;
Yen, Yi-Fen ;
Hurd, Ralph E. ;
Tropp, James ;
Bok, Robert ;
Pauly, John M. ;
Nelson, Sarah J. ;
Kurhanewicz, John ;
Vigneron, Daniel B. .
MAGNETIC RESONANCE IN MEDICINE, 2007, 58 (06) :1099-1106
[5]   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
[6]   Phosphocholine as a biomarker of breast cancer: Molecular and biochemical studies [J].
Eliyahu, Galit ;
Kreizman, Tamar ;
Degani, Hadassa .
INTERNATIONAL JOURNAL OF CANCER, 2007, 120 (08) :1721-1730
[7]   Choline metabolism in cancer: implications for diagnosis and therapy [J].
Glunde, Kristine ;
Jacobs, Michael A. ;
Bhujwalla, Zaver M. .
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 2006, 6 (06) :821-829
[8]   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
[9]   Real-time metabolic imaging [J].
Golman, Klaes ;
in't Zandt, Rene ;
Thaning, Mikkel .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (30) :11270-11275
[10]  
Hernández-Alcoceba R, 1999, CANCER RES, V59, P3112