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Review
. 2013 Sep;123(9):3659-63.
doi: 10.1172/JCI67229. Epub 2013 Sep 3.

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

Ovidiu C Andronesi  1 , Otto Rapalino, Elizabeth Gerstner, Andrew Chi, Tracy T Batchelor, Dan P Cahill, A Gregory Sorensen, Bruce R Rosen
Affiliations
Review

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

Ovidiu C Andronesi et al. J Clin Invest. 2013 Sep.

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.

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Figures

Figure 1
Figure 1. In vivo D-2HG measurements: (A) J-difference spectroscopy with MEGA-LASER sequence in a patient with GBM with mutant IDH1.
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.
See this image and copyright information in PMC

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