Rofo 2024; 196(12): 1228-1235
DOI: 10.1055/a-2285-4923
Review

2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas

Artikel in mehreren Sprachen: English | deutsch
1   Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)
,
1   Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)
,
1   Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)
,
Michael Müther
2   Department of Neurosurgery, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)
,
Manoj Mannil
1   Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)
3   Institute for Diagnostic and Interventional Radiology, Caritas Hospital Bad Mergentheim, Bad Mergentheim, Germany (Ringgold ID: RIN39646)
,
1   Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)
› Institutsangaben

Abstract

Background

The mutated enzyme isocitrate dehydrogenase (IDH) 1 and 2 has been detected in various tumor entities such as gliomas and can convert α-ketoglutarate into the oncometabolite 2-hydroxyglutarate (2-HG). This neuro-oncologically significant metabolic product can be detected by MR spectroscopy and is therefore suitable for noninvasive glioma classification and therapy monitoring.

Method

This paper provides an up-to-date overview of the methodology and relevance of 1H-MR spectroscopy (MRS) in the oncological primary and follow-up diagnosis of gliomas. The possibilities and limitations of this MR spectroscopic examination are evaluated on the basis of the available literature.

Results and Conclusion

By detecting 2-HG, MRS can in principle offer a noninvasive alternative to immunohistological analysis thus avoiding surgical intervention in some cases. However, in addition to an adapted and optimized examination protocol, the individual measurement conditions in the examination region are of decisive importance. Due to the inherently small signal of 2-HG, unfavorable measurement conditions can influence the reliability of detection.

Key Points

  • MR spectroscopy enables the non-invasive detection of 2-hydroxyglutarate.

  • The measurement of this metabolite allows the detection of an IDH mutation in gliomas.

  • The choice of MR examination method is particularly important.

  • Detection reliability is influenced by glioma size, necrotic tissue and the existing measurement conditions.

Citation Format

  • Bauer J, Raum HN, Kugel H et al. 2-Hydroxyglutarate as an MR spectroscopic predictor of an IDH mutation in gliomas. Fortschr Röntgenstr 2024; DOI 10.1055/a-2285-4923



Publikationsverlauf

Eingereicht: 28. November 2023

Angenommen nach Revision: 04. März 2024

Artikel online veröffentlicht:
22. April 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Louis DN, Perry A, Wesseling P. et al. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro-Oncology 2021; 23: 1231-1251
  • 2 Dang L, White DW, Gross S. et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009; 462: 739-744
  • 3 Ward PS, Patel J, Wise DR. et al. The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate. Cancer Cell 2010; 17: 225-234
  • 4 Xu W, Yang H, Liu Y. et al. Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases. Cancer Cell 2011; 19: 17-30
  • 5 Brat DJ, Verhaak RG. Cancer Genome Atlas Research Network. et al. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. New England Journal of Medicine 2015; 372: 2481-2498
  • 6 Losman JA, Kaelin WG. What a difference a hydroxyl makes: mutant IDH, ( R )-2-hydroxyglutarate, and cancer. Genes & Development 2013; 27: 836-852
  • 7 Noushmehr H, Weisenberger DJ, Diefes K. et al. Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma. Cancer Cell 2010; 17: 510-522
  • 8 Turcan S, Rohle D, Goenka A. et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012; 483: 479-483
  • 9 Yen KE, Bittinger MA, Su SM. et al. Cancer-associated IDH mutations: Biomarker and therapeutic opportunities. Oncogene 2010; 29: 6409-6417
  • 10 Choi C, Ganji SK, DeBerardinis RJ. et al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nature Medicine 2012; 18: 624-629
  • 11 Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR in Biomedicine 2000; 13: 129-153
  • 12 Suh CH, Kim HS, Jung SC. et al. 2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma: A systemic review and meta-analysis using individual patient data. Neuro-Oncology 2018; 20: 1573-1583
  • 13 Berrington A, Voets NL, Larkin SJ. et al. A comparison of 2-hydroxyglutarate detection at 3 and 7 T with long-TE semi-LASER. NMR in Biomedicine 2018; 31: e3886
  • 14 Shen X, Voets N, Larkin S. et al. A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy. Metabolites 2019; 9: 35
  • 15 An Z, Tiwari V, Baxter J. et al. 3D high-resolution imaging of 2-hydroxyglutarate in glioma patients using DRAG-EPSI at 3T in vivo. Magnetic Resonance in Medicine 2019; 81: 795-802
  • 16 Bottomley P. Spatial localization in NMR spectroscopy in vivo. Ann NY Acad Sci 1987; 508: 333-348
  • 17 Ordidge R, Bendall M, Gordon R. et al. Volume selection for in vivo biological spectroscopy. In: Magnetic Resonance in Biology and Medicine. New Delhi: Tata McGraw-Hill; 1985: 387-397
  • 18 Frahm J, Merboldt KD, Hänicke W. Localized proton spectroscopy using stimulated echoes. Journal of Magnetic Resonance (1969) 1987; 72: 502-508
  • 19 Scheenen TWJ, Klomp DWJ, Wijnen JP. et al. Short echo time1H-MRSI of the human brain at 3T with minimal chemical shift displacement errors using adiabatic refocusing pulses. Magnetic Resonance in Medicine 2008; 59: 1-6
  • 20 Pope WB, Prins RM, Albert Thomas M. et al. Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. Journal of Neuro-Oncology 2012; 107: 197-205
  • 21 Natsumeda M, Motohashi K, Igarashi H. et al. Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. Neurosurgical Review 2018; 41: 641-647
  • 22 Nagashima H, Tanaka K, Sasayama T. et al. Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. Neuro-Oncology 2016; 18: now090
  • 23 Emir UE, Larkin SJ, De Pennington N. et al. Noninvasive quantification of 2-hydroxyglutarate in human gliomas with IDH1 and IDH2 mutations. Cancer Research 2016; 76: 43-49
  • 24 Branzoli F, Liserre R, Deelchand DK. et al. Neurochemical Differences between 1p/19q Codeleted and Noncodeleted IDH-mutant Gliomas by in Vivo MR Spectroscopy. Radiology 2023; 308: e223255
  • 25 Mescher M, Merkle H, Kirsch J. et al. Simultaneous in vivo spectral editing and water suppression. NMR in Biomedicine 1998; 11: 266-272
  • 26 Shams Z, van der Kemp WJM, Emir U. et al. Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T. Frontiers in Neurology 2021; 12: 1-10
  • 27 Branzoli F, Di Stefano AL, Capelle L. et al. Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy. Neuro-Oncology 2018; 20: 907-916
  • 28 Wang Y, Li SJ. Differentiation of metabolic concentrations between gray matter and white matter of human brain by in vivo 1H magnetic resonance spectroscopy. Magnetic Resonance in Medicine 1998; 39: 28-33
  • 29 Hattingen E, Raab P, Franz K. et al. Prognostic value of choline and creatine in WHO grade II gliomas. Neuroradiology 2008; 50: 759-767
  • 30 Keevil SF, Barbiroli B, Brooks JCW. et al. Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain. Magnetic Resonance Imaging 1998; 16: 1093-1106
  • 31 Gasparovic C, Song T, Devier D. et al. Use of tissue water as a concentration reference for proton spectroscopic imaging. Magnetic Resonance in Medicine 2006; 55: 1219-1226
  • 32 Ernst T, Kreis R, Ross BD. Absolute Quantitation of Water and Metabolites in the Human Brain. I. Compartments and Water. Journal of Magnetic Resonance, Series B 1993; 102: 1-8
  • 33 Mikkelsen M, Rimbault DL, Barker PB. et al. Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites. NeuroImage 2019; 191: 537-548
  • 34 Mikkelsen M, Barker PB, Bhattacharyya PK. et al. Big GABA: Edited MR spectroscopy at 24 research sites. NeuroImage 2017; 159: 32-45
  • 35 Near J, Harris AD, Juchem C. et al. Preprocessing, analysis and quantification in single-voxel magnetic resonance spectroscopy: experts’ consensus recommendations. NMR in Biomedicine 2021; 34: 1-23
  • 36 Choi C, Raisanen JM, Ganji SK. et al. Prospective longitudinal analysis of 2-hydroxyglutarate magnetic resonance spectroscopy identifies broad clinical utility for the management of patients with IDH-mutant glioma. Journal of Clinical Oncology 2016; 34: 4030-4039
  • 37 Di Stefano AL, Nichelli L, Berzero G. et al. In Vivo 2-Hydroxyglutarate Monitoring With Edited MR Spectroscopy for the Follow-up of IDH -Mutant Diffuse Gliomas. Neurology 2023; 100: e94-e106
  • 38 Zhou M, Zhou Y, Liao H. et al. Diagnostic accuracy of 2-hydroxyglutarate magnetic resonance spectroscopy in newly diagnosed brain mass and suspected recurrent gliomas. Neuro-Oncology 2018; 20: 1262-1271
  • 39 de la Fuente MI, Young RJ, Rubel J. et al. Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma. Neuro-Oncology 2016; 18: 283-290
  • 40 Suh CH, Kim HS, Paik W. et al. False-positive measurement at 2-hydroxyglutarate MR spectroscopy in isocitrate dehydrogenase wild-type glioblastoma: A multifactorial analysis. Radiology 2019; 291: 752-762
  • 41 Weller M, van den Bent M, Preusser M. et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nature Reviews Clinical Oncology 2021; 18: 170-186
  • 42 Andronesi OC, Loebel F, Bogner W. et al. Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate. Clinical Cancer Research 2016; 22: 1632-1641
  • 43 Mellinghoff IK, Lu M, Wen PY. et al. Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nature Medicine 2023; 29: 615-622
  • 44 Barth PG, Hoffmann GF, Jaeken J. et al. L-2-hydroxyglutaric acidemia: A novel inherited neurometabolic disease. Annals of Neurology 1992; 32: 66-71
  • 45 Hußmann O, Haas D, Neubauer BA. et al. L-2-hydroxy-glutarazidurie – Eine seltene Differenzialdiagnose der Makrozephalie. Klin Padiatr 2006; 218: 72-73