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 Bachoo; Elizabeth A Maher

doi:10.1038/nm.2682

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 Bachoo, Elizabeth A Maher

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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.

Original language	English (US)
Pages (from-to)	624-629
Number of pages	6
Journal	Nature medicine
Volume	18
Issue number	4
DOIs	https://doi.org/10.1038/nm.2682
State	Published - Apr 2012

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Choi, C., Ganji, S. K., DeBerardinis, R. J., Hatanpaa, K. J., Rakheja, D., Kovacs, Z., Yang, X. L., Mashimo, T., Raisanen, J. M., Marin-Valencia, I., Pascual, J. M., Madden, C. J., Mickey, B. E., Malloy, C. R., Bachoo, R., & Maher, E. A. (2012). 2-Hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nature medicine, 18(4), 624-629. https://doi.org/10.1038/nm.2682

Choi, C, Ganji, SK, DeBerardinis, RJ , Hatanpaa, KJ , Rakheja, D , Kovacs, Z, Yang, XL, Mashimo, T, Raisanen, JM, Marin-Valencia, I, Pascual, JM , Madden, CJ , Mickey, BE , Malloy, CR , Bachoo, R & Maher, EA 2012, '2-Hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas', Nature medicine, vol. 18, no. 4, pp. 624-629. https://doi.org/10.1038/nm.2682

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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.",

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

note = "Funding Information: This work was supported by US National Institutes of Health grants RC1NS0760675, R21CA159128, and RR02584 and by the Cancer Prevention Research Institute of Texas grant RP101243-P04. We thank C. Sheppard for expert management of the patient database and for coordinating research scans and tissue samples; S. McNeil for expert human subject care during scanning; C. Foong for expert assistance with pathological analysis of tumor; and R.L. Boriack for expert assistance with 2HG measurements by mass spectrometry.",

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doi = "10.1038/nm.2682",

language = "English (US)",

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AU - DeBerardinis, Ralph J

AU - Hatanpaa, Kimmo J

AU - Rakheja, Dinesh

AU - Kovacs, Zoltan

AU - Yang, Xiao Li

AU - Mashimo, Tomoyuki

AU - Raisanen, Jack M

AU - Marin-Valencia, Isaac

AU - Pascual, Juan M

AU - Madden, Christopher J

AU - Mickey, Bruce E

AU - Malloy, Craig R

AU - Bachoo, Robert

AU - Maher, Elizabeth A

N1 - Funding Information: This work was supported by US National Institutes of Health grants RC1NS0760675, R21CA159128, and RR02584 and by the Cancer Prevention Research Institute of Texas grant RP101243-P04. We thank C. Sheppard for expert management of the patient database and for coordinating research scans and tissue samples; S. McNeil for expert human subject care during scanning; C. Foong for expert assistance with pathological analysis of tumor; and R.L. Boriack for expert assistance with 2HG measurements by mass spectrometry.

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AB - 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.

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

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