2-hydroxyglutarate detection by magnetic resonance spectroscopy in subjects with IDH-mutated gliomas

被引：614

作者：

Choi, Changho ^{[1
,2
]}

Ganji, Sandeep K. ^{[1
,2
]}

DeBerardinis, Ralph J. ^{[3
,4
,5
]}

Hatanpaa, Kimmo J. ^{[5
,6
,7
]}

Rakheja, Dinesh ^{[6
,8
]}

Kovacs, Zoltan ^{[1
]}

Yang, Xiao-Li ^{[5
,7
,9
]}

Mashimo, Tomoyuki ^{[5
,7
,9
]}

Raisanen, Jack M. ^{[5
,6
,7
]}

Marin-Valencia, Isaac ^{[3
]}

Pascual, Juan M. ^{[3
,10
,11
]}

Madden, Christopher J. ^{[5
,7
,12
]}

Mickey, Bruce E. ^{[5
,7
,12
]}

Malloy, Craig R. ^{[1
,2
,9
,13
]}

Bachoo, Robert M. ^{[5
,7
,9
,10
]}

Maher, Elizabeth A. ^{[5
,7
,9
,10
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA

[5] Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Dallas, TX 75390 USA

[6] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[7] Univ Texas SW Med Ctr Dallas, Annette Strauss Ctr Neurooncol, Dallas, TX 75390 USA

[8] Childrens Med Ctr, Dallas, TX 75235 USA

[9] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

[10] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA

[11] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA

[12] Univ Texas SW Med Ctr Dallas, Dept Neurol Surg, Dallas, TX 75390 USA

[13] Vet Affairs N Texas Hlth Care Syst, Dallas, TX USA

来源：

NATURE MEDICINE | 2012年 / 18卷 / 04期

基金：

美国国家卫生研究院;

关键词：

METABOLITE QUANTIFICATION; BRAIN-METABOLITES; RELAXATION-TIMES; NMR-SPECTRA; PROTON; H-1; MUTATIONS; ACIDURIA; TUMORS; WATER;

D O I：

10.1038/nm.2682

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D-2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker.

引用

页码：624 / 629

页数：6

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