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

MacArena I. De La Fuente, Robert J. Young, Jennifer Rubel, Marc Rosenblum, Jamie Tisnado, Samuel Briggs, Julio Arevalo-Perez, Justin R. Cross, Carl Campos, Kimberly Straley, Dongwei Zhu, Chuanhui Dong, Alissa Thomas, Antonio A. Omuro, Craig P. Nolan, Elena Pentsova, Thomas J. Kaley, Jung H. Oh, Ralph Noeske, Elizabeth MaherChangho Choi, Philip H. Gutin, Andrei I. Holodny, Katharine Yen, Lisa M. Deangelis, Ingo K. Mellinghoff, Sunitha B. Thakur

Research output: Contribution to journalArticle

97 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalNeuro-oncology
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2016

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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  • Cite this

    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., ... Thakur, S. B. (2016). Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma. Neuro-oncology, 18(2), 283-290. https://doi.org/10.1093/neuonc/nov307