2-Hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas

Changho Choi, Sandeep K. Ganji, Ralph J. DeBerardinis, Kimmo J. Hatanpaa, Dinesh Rakheja, Zoltan Kovacs, Xiao Li Yang, Tomoyuki Mashimo, Jack M. Raisanen, Isaac Marin-Valencia, Juan M. Pascual, Christopher J. Madden, Bruce E. Mickey, Craig R. Malloy, Robert M. Bachoo, Elizabeth A. Maher

Research output: Contribution to journalArticlepeer-review

654 Scopus citations


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.

Original languageEnglish
Pages (from-to)624-629
Number of pages6
JournalNature Medicine
Issue number4
StatePublished - Apr 2012
Externally publishedYes


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