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Neuro Oncol. 2016 Feb;18(2):283-90. doi: 10.1093/neuonc/nov307. Epub 2015 Dec 20.

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

Author information

1
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (M.I.d., S.B., A.T., A.A.O., C.P.N., E.P., T.J.K., L.M.D., I.K.M.); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (R.J.Y., J.R., J.T., J.A.-P., A.I.H., S.B.T.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York (J.R.C.); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York (C.C., I.K.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (P.H.G.); Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (J.H.O., S.B.T.); Agios Pharmaceuticals, Cambridge, Massachusetts (K.S., D.Z., K.Y.); Department of Neurology, Evelyn F. McKnight Brain Institute, University of Miami, Miami, Florida (C.D.); Advanced Imaging Research Center, University Of Texas Southwestern Medical Center, Dallas, Texas (E.M., C.C.); GE Healthcare, Berlin, Germany (R.N.); Department of Pharmacology, Weill-Cornell Graduate School of Biomedical Sciences, New York, New York (I.K.M.).

Abstract

BACKGROUND:

The majority of WHO grades II and III gliomas harbor a missense mutation in the metabolic gene isocitrate dehydrogenase (IDH) and accumulate the metabolite R-2-hydroxyglutarate (R-2HG). Prior studies showed that this metabolite can be detected in vivo using proton magnetic-resonance spectroscopy (MRS), but the sensitivity of this methodology and its clinical implications are unknown.

METHODS:

We developed an MR imaging protocol to integrate 2HG-MRS into routine clinical glioma imaging and examined its performance in 89 consecutive glioma patients.

RESULTS:

Detection of 2-hydroxyglutarate (2HG) in IDH-mutant gliomas was closely linked to tumor volume, with sensitivity ranging from 8% for small tumors (<3.4 mL) to 91% for larger tumors (>8 mL). In patients undergoing 2HG-MRS prior to surgery, tumor levels of 2HG corresponded with tumor cellularity but not with tumor grade or mitotic index. Cytoreductive therapy resulted in a gradual decrease in 2HG levels with kinetics that closely mirrored changes in tumor volume.

CONCLUSIONS:

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.

KEYWORDS:

IDH; R-2-hydroxyglutarate; cancer metabolism; glioma; imaging biomarker; magnetic resonance spectroscopy

PMID:
26691210
PMCID:
PMC4724186
DOI:
10.1093/neuonc/nov307
[Indexed for MEDLINE]
Free PMC Article

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