American Association for Cancer Research
00085472can150934-sup-147876_2_supp_3121866_ntrj8x.png (54.52 kB)

Supplementary Figure S2 from Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations

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posted on 2023-03-30, 23:25 authored by Uzay E. Emir, Sarah J. Larkin, Nick de Pennington, Natalie Voets, Puneet Plaha, Richard Stacey, Khalid Al-Qahtani, James Mccullagh, Christopher J. Schofield, Stuart Clare, Peter Jezzard, Tom Cadoux-Hudson, Olaf Ansorge

Amplitudes of 2-hydroxyglutarate (2-HG) signal for density matrix simulation of pulse acquire and semi-LASER at TE = 110 ms (TE1 =11 ms, TE2 = 65 ms and TE3 = 34 ms) acquisitions.



Mutations in the isocitrate dehydrogenase genes (IDH1/2) occur often in diffuse gliomas, where they are associated with abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Monitoring 2-HG levels could provide prognostic information in this disease, but detection strategies that are noninvasive and sufficiently quantitative have yet to be developed. In this study, we address this need by presenting a proton magnetic resonance spectroscopy (1H-MRS) acquisition scheme that uses an ultrahigh magnetic field (≥7T) capable of noninvasively detecting 2-HG with quantitative measurements sufficient to differentiate mutant cytosolic IDH1 and mitochondrial IDH2 in human brain tumors. Untargeted metabolomics analysis of in vivo 1H-MRS spectra discriminated between IDH-mutant tumors and healthy tissue, and separated IDH1 from IDH2 mutations. High-quality spectra enabled the quantification of neurochemical profiles consisting of at least eight metabolites, including 2-HG, glutamate, lactate, and glutathione in both tumor and healthy tissue voxels. Notably, IDH2 mutation produced more 2-HG than IDH1 mutation, consistent with previous findings in cell culture. By offering enhanced sensitivity and specificity, this scheme can quantitatively detect 2-HG and associated metabolites that may accumulate during tumor progression, with implications to better monitor patient responses to therapy. Cancer Res; 76(1); 43–49. ©2015 AACR.

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