Detection of 2-Hydroxyglutarate in IDH-Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy

被引：317

作者：

Andronesi, Ovidiu C. ^{[1
]}

Kim, Grace S. ^{[1
]}

Gerstner, Elizabeth ^{[2
]}

Batchelor, Tracy ^{[2
]}

Tzika, Aria A. ^{[1
,3
,7
]}

Fantin, Valeria R. ^{[4
]}

Vander Heiden, Matthew G. ^{[5
,6
]}

Sorensen, A. Gregory ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, Boston, MA 02114 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pappas Ctr Neurooncol, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA

[4] Agios Pharmaceut, Cambridge, MA 02139 USA

[5] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[6] Dana Farber Canc Inst, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2012年 / 4卷 / 116期

关键词：

H-1-NMR SPECTROSCOPY; WATER-SUPPRESSION; GENOMIC ANALYSIS; HR-MAS; MUTATIONS; H-1; GLIOBLASTOMA; ASTROCYTOMAS; METABOLITES; ACIDURIA;

D O I：

10.1126/scitranslmed.3002693

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mutations in the gene isocitrate dehydrogenase 1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized in vivo spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG noninvasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG was also detected using 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting mutated IDH1.

引用

页数：11

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