期刊
NEURO-ONCOLOGY
卷 18, 期 2, 页码 283-290出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/nov307
关键词
cancer metabolism; glioma; IDH; imaging biomarker; magnetic resonance spectroscopy; R-2-hydroxyglutarate
资金
- National Institutes of Health [1R01NS080944-01, P30-CA008748]
- Memorial Sloan Kettering Brain Tumor Center
- Society of Memorial Sloan Kettering Cancer Center
- Dana Foundation
- Memorial Sloan Kettering Translational and Integrative Medicine Research Fund
- B*CURED
- Ben and Catherine Ivy Foundation
- Woman's Cancer Association of University of Miami
- Sylvester Comprehensive Cancer Center
- Defeat GBM Initiative of the National Brain Tumor Society
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. We developed an MR imaging protocol to integrate 2HG-MRS into routine clinical glioma imaging and examined its performance in 89 consecutive glioma patients. 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. 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.
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