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

• Published in: Nature medicine Vol. 18; no. 4; pp. 624 - 629
• Main Authors: Choi, Changho, Ganji, Sandeep K, DeBerardinis, Ralph J, Hatanpaa, Kimmo J, Rakheja, Dinesh, Kovacs, Zoltan, Yang, Xiao-Li, Mashimo, Tomoyuki, Raisanen, Jack M, Marin-Valencia, Isaac, Pascual, Juan M, Madden, Christopher J, Mickey, Bruce E, Malloy, Craig R, Bachoo, Robert M, Maher, Elizabeth A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2012; Nature Publishing Group
• Subjects: 631/208/737; 692/699/375/1922; 692/700/1421/1628; Algorithms; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Biomedical and Life Sciences; Biomedicine; Brain - enzymology; Brain cancer; Brain Mapping; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Cancer Research; Choline - metabolism; Creatine - metabolism; Enzymes; Female; Gene expression; Glioma - genetics; Glioma - metabolism; Glutarates; Humans; Infectious Diseases; Isocitrate Dehydrogenase - genetics; Magnetic Resonance Spectroscopy; Male; Mass spectrometry; Medical imaging; Metabolic Diseases; Molecular Medicine; Mutation; Mutation - genetics; Neurosciences; Spectroscopy; Spectrum analysis; Statistics as Topic; technical-report; Tumors
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.2682

Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) in the majority of people with grade 2 and 3 gliomas is associated with elevated levels of 2-hydroxyglutarate (2HG) within the tumor. As harboring IDH1 or IDH2 mutations confers a considerable survival benefit in these individuals, there has been considerable interest in studying this metabolite as a potential biomarker. Here, Changho Choi et al . report the successful noninvasive detection of 2HG in 30 subjects with gliomas using a proton magnetic resonance spectroscopy approach. 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.