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Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate
Ovidiu C. Andronesi, … , A. Gregory Sorensen, Bruce R. Rosen
Ovidiu C. Andronesi, … , A. Gregory Sorensen, Bruce R. Rosen
Published September 3, 2013
Citation Information: J Clin Invest. 2013;123(9):3659-3663. https://doi.org/10.1172/JCI67229.
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Review Series

Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate

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Abstract

The investigation of metabolic pathways disturbed in isocitrate dehydrogenase (IDH) mutant tumors revealed that the hallmark metabolic alteration is the production of D-2-hydroxyglutarate (D-2HG). The biological impact of D-2HG strongly suggests that high levels of this metabolite may play a central role in propagating downstream the effects of mutant IDH, leading to malignant transformation of cells. Hence, D-2HG may be an ideal biomarker for both diagnosing and monitoring treatment response targeting IDH mutations. Magnetic resonance spectroscopy (MRS) is well suited to the task of noninvasive D-2HG detection, and there has been much interest in developing such methods. Here, we review recent efforts to translate methodology using MRS to reliably measure in vivo D-2HG into clinical research.

Authors

Ovidiu C. Andronesi, Otto Rapalino, Elizabeth Gerstner, Andrew Chi, Tracy T. Batchelor, Dan P. Cahill, A. Gregory Sorensen, Bruce R. Rosen

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Figure 1

In vivo D-2HG measurements: (A) J-difference spectroscopy with MEGA-LASER sequence in a patient with GBM with mutant IDH1.

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In vivo D-2HG measurements: (A) J-difference spectroscopy with MEGA-LASE...
Adapted with permission from Science Translational Medicine (29). (B) Spectral editing with PRESS sequence of TE 97 ms (TE1: 32 ms, TE2: 65 ms) in a patient with mutant IDH1 oligodendroglioma. Adapted with permission from Nature Medicine (30). (C) Spectra acquired with PRESS sequence of TE 30 ms in a patient with mutant IDH1 anaplastic astrocytoma. Adapted with permission from Journal of Neuro-Oncology (24). Cho, choline; Cre, creatine; Gln, glutamine; Glu, glutamate; Lac, lactate; MM, macromolecules; NAA, N-acetyl-aspartate.

Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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