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


Authors: de la Fuente, M. I.; Young, R. J.; Rubel, J.; Rosenblum, M.; Tisnado, J.; Briggs, S.; Arevalo-Perez, J.; Cross, J. R.; Campos, C.; Straley, K.; Zhu, D.; Dong, C.; Thomas, A.; Omuro, A. A.; Nolan, C. P.; Pentsova, E.; Kaley, T. J.; Oh, J. H.; Noeske, R.; Maher, E.; Choi, C.; Gutin, P. H.; Holodny, A. I.; Yen, K.; DeAngelis, L. M.; Mellinghoff, I. K.; Thakur, S. B.
Article Title: Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma
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. © 2015 The Author(s).
Keywords: glioma; magnetic resonance spectroscopy; idh; imaging biomarker; cancer metabolism; r-2-hydroxyglutarate
Journal Title: Neuro-Oncology
Volume: 18
Issue: 2
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2016-02-01
Start Page: 283
End Page: 290
Language: English
DOI: 10.1093/neuonc/nov307
PROVIDER: scopus
PMCID: PMC4724186
PUBMED: 26691210
DOI/URL:
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
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MSK Authors
  1. Robert J Young
    114 Young
  2. Philip H Gutin
    153 Gutin
  3. Marc Rosenblum
    257 Rosenblum
  4. Antonio Marcilio Padula Omuro
    179 Omuro
  5. Thomas Kaley
    92 Kaley
  6. Sunitha Bai Thakur
    43 Thakur
  7. Jung Hun Oh
    114 Oh
  8. Craig Nolan
    45 Nolan
  9. Andrei Holodny
    136 Holodny
  10. Justin Robert Cross
    49 Cross
  11. Carl Campos
    22 Campos
  12. Samuel Royden Briggs
    16 Briggs
  13. Alissa A Thomas
    15 Thomas
  14. Jennifer Brooke Rubel
    5 Rubel