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

Jochen Bauer; Heiner N. Raum; Harald Kugel; Michael Müther; Manoj Mannil; Walter Heindel

doi:10.1055/a-2285-4923

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, Inhaltsverzeichnis

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

Review

2-Hydroxyglutarat als MR-spektroskopisch erfassbarer Prädiktor einer IDH-Mutation bei Gliomen

Artikel in mehreren Sprachen: English | deutsch

Jochen Bauer

¹Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

,

Heiner N. Raum

¹Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

,

Harald Kugel

¹Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

,

Michael Müther

²Department of Neurosurgery, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

,

Manoj Mannil

¹Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

³Institute for Diagnostic and Interventional Radiology, Caritas Hospital Bad Mergentheim, Bad Mergentheim, Germany (Ringgold ID: RIN39646)

,

Walter Heindel

¹Clinic for Radiology, University of Münster and University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

› Institutsangaben

Abstract

Zusammenfassung

Hintergrund

Das mutierte Enzym Isocitrat-Dehydrogenase (IDH) 1 und 2 wurde in verschiedenen Tumorentitäten wie z.B. Gliomen nachgewiesen und kann α-Ketoglurat in den Onkometaboliten 2-Hydroxyglutarat (2-HG) konvertieren. Dieses neuroonkologisch bedeutsame Stoffwechselprodukt ist MR-spektroskopisch nachweisbar und eignet sich deshalb zur nichtinvasiven Gliomklassifizierung und Therapieüberwachung.

Methode

Die vorliegende Arbeit gibt einen aktuellen Überblick über die Methodik und Relevanz der ¹H-MR-Spektroskopie (MRS) in der onkologischen Primär- und Verlaufsdiagnostik von Gliomen. Anhand der verfügbaren Literatur werden die Möglichkeiten und Grenzen dieser MR-spektroskopischen Untersuchung beleuchtet.

Ergebnisse und Schlussfolgerung

Die MRS kann durch den Nachweis von 2-HG prinzipiell eine nicht-invasive Alternative zur immunhistologischen Analyse bieten und so in einigen Fällen einen operativen Eingriff vermeiden. Neben einem angepassten und optimierten Untersuchungsprotokoll sind aber die individuellen in der Untersuchungsregion vorliegenden Messbedingungen von entscheidender Bedeutung. Aufgrund des inhärent kleinen Signals von 2-HG können ungünstige Messbedingungen die Nachweissicherheit beeinflussen.

Kernaussagen

MR-Spektroskopie ermöglicht die nicht-invasive Detektion von 2-Hydroxyglutarat.
Hiermit ist der Nachweis einer IDH-Mutation in Gliomen möglich.
Besondere Bedeutung kommt der Wahl der MRS-Untersuchungsmethodik zu.
Die Detektionssicherheit wird beeinflusst von Gliomgröße, nekrotischem Gewebe und den vorliegenden Messbedingungen.

Zitierweise

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

Schlüsselwörter

brain - MR-spectroscopy - technical aspects - tissue characterization - glioma - metabolism

Volltext

Referenzen

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