Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH -Mutant Glioma
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Purpose: Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods: 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. Results: Quantitative 2HG MRS was technically and biologically reproducible. 2HG concentration > 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than ± 1 mM, and it increased sharply with tumor progression. 2HG concentration was positively correlated with tumor cellularity and significantly differed between high- and lower-grade gliomas. In response to cytotoxic therapy, 2HG concentration decreased rapidly in 1p/19q codeleted oligodendrogliomas and with a slower time course in astrocytomas and mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in tumor volume did not differ between oligodendrogliomas treated with temozolomide or carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a surgical procedure. Conclusion: 2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated gliomas.
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2-HG accumulation in IDH1- and IDH2-mutant tumors is a rare example in which the metabolite directly reports the oncogenic driver and potential therapy, and proton magnetic resonance spectroscopy can noninvasively track 2-HG abundance in IDH-mutant gliomas, predicting disease progression and response to therapy through longitudinal measurements.
“First, 2-HG accumulation in IDH1- and IDH2-mutant tumors is a rare example in which the metabolite directly reports the oncogenic driver and potential therapy (Fig. 4). Proton magnetic resonance spectroscopy can noninvasively track 2-HG abundance in IDH-mutant gliomas, predicting both disease progression and response to therapy through longitudinal 2-HG measurements (120).”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [120]
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References 17 · Cited by 201
- Authors
- Choi, C., Raisanen, J. M., Ganji, S. K., Zhang, S., McNeil, S. S., An, Z., Madan, A., Hatanpaa, K. J., Vemireddy, V., Sheppard, C. A., Oliver, D., Hulsey, K. M., Tiwari, V., Mashimo, T., Battiste, J., Barnett, S., Madden, C. J., Patel, T. R., Pan, E., Malloy, C. R., Mickey, B. E., Bachoo, R. M., & Maher, E. A.
- Affiliations
- VA North Texas Health Care System (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2016-11-20
- Volume
- 34
- Issue
- 33
- Pages
- 4030-4039
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC5477829
- OpenAlex
- W2527733398
- Cited by
- 201
- References
- 17
- Citations by year
- 2026: 16 · 2025: 12 · 2024: 17 · 2023: 16 · 2022: 20 · 2021: 19 · 2020: 26 · 2019: 22 · 2018: 27 · 2017: 23 · 2016: 2 · 2015: 1
- FWCI
- 17.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Association for Cancer Research
- Cancer Prevention and Research Institute of Texas (RP130427)
- Memorial Sloan-Kettering Cancer Center
- University of Texas Southwestern Medical Center
- National Institutes of Health (RP130427, EB015908)
- National Cancer Institute (R01CA154843, R01CA184584, R21CA159128, P30CA142543)
- National Institute of Neurological Disorders and Stroke (RC1NS070675)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015908)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- 2-hydroxyglutarate, IDH-mutant glioma, 1H NMR, oncometabolites, imaging biomarkers, astrocytoma, mixed glioma, tumor progression, tumor cellularity, temozolomide, BCNU, longitudinal imaging
- MeSH terms
- Adolescent, Adult, Aged, Brain Chemistry, Brain Neoplasms, Female, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Longitudinal Studies, Male, Middle Aged, Magnetic Resonance Spectroscopy, Prospective Studies, Reproducibility of Results, Biomarkers
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