title: 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas.
abstract: 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.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA. changho.choi@utsouthwestern.edu
authors.forename: Changho
authors.initials: C
authors.lastname: Choi
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Ganji
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.forename: Kimmo J
authors.initials: KJ
authors.lastname: Hatanpaa
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Yang
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mashimo
authors.forename: Jack M
authors.initials: JM
authors.lastname: Raisanen
authors.forename: Isaac
authors.initials: I
authors.lastname: Marin-Valencia
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pascual
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Madden
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Mickey
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bachoo
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Maher
mesh_terms: D000465:Algorithms; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D001931:Brain Mapping; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D005977:Glutarates; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009154:Mutation / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D001224:Aspartic Acid; C000179:N-acetylaspartate; D007521:Isocitrate Dehydrogenase; D003401:Creatine; D002794:Choline