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PMID: 22238332 Published · ppublish English Journal Article

Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy.

Science translational medicine ·Vol. 4 ·No. 116 ·2012-01-11 ·Pages 116ra4

Andronesi OC, Kim GS, Gerstner E, Batchelor T, Tzika AA, Fantin VR, Vander Heiden MG, Sorensen AG

Abstract

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.

MeSH Terms
Adult Aged Biopsy Brain Neoplasms/enzymology,genetics,metabolism,pathology Epilepsy/pathology Female Glioma/enzymology,genetics,metabolism,pathology Glutarates/metabolism Humans Isocitrate Dehydrogenase/genetics Magnetic Resonance Spectroscopy/methods Male Middle Aged Mutation/genetics Phantoms, Imaging Young Adult
Chemicals
Glutarates alpha-hydroxyglutarate Isocitrate Dehydrogenase IDH1 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Andronesi Ovidiu C
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ovidiu@nmr.mgh.harvard.edu
Kim Grace S
Gerstner Elizabeth
Batchelor Tracy
Tzika Aria A
Fantin Valeria R
Vander Heiden Matthew G
Sorensen A Gregory
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Article Info
Journal
Science translational medicine
Abbr.
Sci Transl Med
ISSN
1946-6242
DOI
10.1126/scitranslmed.3002693
Email
ovidiu@nmr.mgh.harvard.edu
Published
2012-01-11
Pages
116ra4
Language
English
Region
United States
NLM ID
101505086
PMCID
PMC3720836
Subset
IM
Grants
NCI NIH HHS · P30 CA014051 · United States
NCRR NIH HHS · S10 RR021110 · United States
NCRR NIH HHS · S10 RR023401 · United States
External Links
PubMed source DOI: 10.1126/scitranslmed.3002693 PMC Full Text View journal details
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