Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma

Fuente, Macarena I. de la; Young, Robert J.; Rubel, Jennifer; Rosenblum, Marc K.; Tisnado, Jamie; Briggs, Samuel; Arévalo-Pérez, Julio; Cross, Justin R.; Campos, Carl; Straley, Kimberly; Zhu, Dongwei; Dong, Chuanhui; Thomas, Alissa A.; Omuro, Antonio A.; Nolan, Craig; Pentsova, Elena; Kaley, Thomas; Oh, Jung Hun; Noeske, Ralph; Maher, Elizabeth A.; Choi, Changho; Gutin, Philip H.; Holodny, Andrei I.; Yen, Katharine; DeAngelis, Lisa M.; Mellinghoff, Ingo K.; Thakur, Sunitha B.

doi:10.1093/neuonc/nov307

Cited by 173 publications

(146 citation statements)

References 30 publications

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“…Mutations in IDH lead to elevated levels of 2-hydroxyglutarate within tumors, which can be identified by MR spectroscopy. 20,21 This technique is advancing rapidly and is now in clinical use at some centers. 22 Alternatively, methods such as MR perfusion and diffusion tensor imaging have been shown to correlate with IDH-mutation status.…”

Section: Discussionmentioning

confidence: 99%

Genetically Defined Oligodendroglioma Is Characterized by Indistinct Tumor Borders at MRI

Johnson

Diehn

Giannini³

et al. 2017

AJNR Am J Neuroradiol

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Section: Discussionmentioning

confidence: 99%

Genetically Defined Oligodendroglioma Is Characterized by Indistinct Tumor Borders at MRI

Johnson

Diehn

Giannini³

et al. 2017

AJNR Am J Neuroradiol

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“…80 Other groups have linked 2-HGMRS quantitative measurements to the amount of metabolically active cells in gliomas. 81 It remains to be determined whether monitoring 2-HGlevels with MRS can provide a more sensitive or specific or an earlier marker of treatment response.…”

Section: Clinical Applications Of Advanced Mrimentioning

confidence: 99%

Conventional and advanced magnetic resonance imaging in patients with high-grade glioma

Pope¹,

Brandal²

2018

Q J Nucl Med Mol Imaging

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Magnetic resonance imaging is integral to the care of patients with high-grade gliomas. Anatomic detail can be acquired with conventional structural imaging, but newer approaches also add capabilities to interrogate image-derived physiologic and molecular characteristics of central nervous system neoplasms. These advanced imaging techniques are increasingly employed to generate biomarkers that better reflect tumor burden and therapy response. The following is an overview of current strategies based on advanced magnetic resonance imaging that are used in the assessment of high-grade glioma patients with an emphasis on how novel imaging biomarkers can potentially advance patient care.

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“…The ability to monitor the activity of the mutant IDH enzyme through quantification of 2-HG levels in blood (69) or Magnetic Resonance Spectroscopy in tumors (70–72) will be instrumental to develop such strategies.…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer

Clark

Yen

Mellinghoff

2016

Clinical Cancer Research

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IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced nicotinamide adenine dinucleotide phosphate (NADPH) from NADP+. Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the ‘oncometabolite’ R(−)-2-hydroxyglutarate (2HG). 2-HG competitively inhibits α-KG-dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials and have shown encouraging results in patients with IDH2 mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.

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Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma

Abstract: Our study demonstrates that 2HG-MRS can be linked with routine MR imaging to provide quantitative measurements of 2HG in glioma and may be useful as an imaging biomarker to monitor the abundance of IDH-mutant tumor cells noninvasively during glioma therapy and disease monitoring.

Cited by 173 publications

References 30 publications

Genetically Defined Oligodendroglioma Is Characterized by Indistinct Tumor Borders at MRI

Genetically Defined Oligodendroglioma Is Characterized by Indistinct Tumor Borders at MRI

Conventional and advanced magnetic resonance imaging in patients with high-grade glioma

Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer

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