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

• Main Authors: Andronesi, Ovidiu C. (Author), Kim, Grace S. (Author), Gerstner, Elizabeth R. (Author), Batchelor, Tracy T. (Author), Tzika, Aria A. (Author), Fantin, Valeria R. (Author), Vander Heiden, Matthew G. (Contributor), Sorensen, A. Gregory (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: American Association for the Advancement of Science, 2014-03-07T16:46:26Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (NIH R01 1200-206456)
National Institutes of Health (U.S.) (NIH S10RR013026)
National Institutes of Health (U.S.) (NIH S10RR021110)
National Institutes of Health (U.S.) (NIH S10RR023401)
Harvard Catalyst. Harvard Clinical and Translational Science Center (NIH Award #KL2 RR 025757)