Detection of 2-Hydroxyglutarate in IDH -Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy
Year: 2012
Type: article
Abstract: Mutations in the gene isocitrate dehydrogenase 1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized in vivo spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG noninvasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG was also detected using 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting mutated IDH1.
Source: Science Translational Medicine
Institutions: Harvard University, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Center for Neuro-Oncology, Agios Pharmaceuticals (United States), Dana-Farber Cancer Institute, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2011526905