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

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 18; no. 2; pp. 283 - 290
• Main Authors: de la Fuente, Macarena I, Young, Robert J, Rubel, Jennifer, Rosenblum, Marc, Tisnado, Jamie, Briggs, Samuel, Arevalo-Perez, Julio, Cross, Justin R, Campos, Carl, Straley, Kimberly, Zhu, Dongwei, Dong, Chuanhui, Thomas, Alissa, Omuro, Antonio A, Nolan, Craig P, Pentsova, Elena, Kaley, Thomas J, Oh, Jung H, Noeske, Ralph, Maher, Elizabeth, Choi, Changho, Gutin, Philip H, Holodny, Andrei I, Yen, Katharine, DeAngelis, Lisa M, Mellinghoff, Ingo K, Thakur, Sunitha B
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2016
• Series: Editor's choice
• Subjects: Adult; Aged; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Female; Follow-Up Studies; Glioma - metabolism; Glioma - pathology; Glioma - therapy; Glutarates - metabolism; Humans; Isocitrate Dehydrogenase - metabolism; Male; Middle Aged; Neoplasm Grading; Neuroimaging; Practice Guidelines as Topic; Prognosis; Proton Magnetic Resonance Spectroscopy - methods; Young Adult; cancer metabolism; glioma; magnetic resonance spectroscopy; imaging biomarker; IDH; R-2-hydroxyglutarate
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nov307

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.