title: Conditions for (13)C NMR detection of 2-hydroxyglutarate in tissue extracts from isocitrate dehydrogenase-mutated gliomas.
abstract: (13)C NMR (nuclear magnetic resonance) spectroscopy of extracts from patient tumor samples provides rich information about metabolism. However, in isocitrate dehydrogenase (IDH)-mutant gliomas, (13)C labeling is obscured in oncometabolite 2-hydroxyglutaric acid (2 HG) by glutamate and glutamine, prompting development of a simple method to resolve the metabolites. J-coupled multiplets in 2 HG were similar to glutamate and glutamine and could be clearly resolved at pH 6. A cryogenically cooled (13)C probe, but not J-resolved heteronuclear single quantum coherence spectroscopy, significantly improved detection of 2 HG. These methods enable the monitoring of (13)C-(13)C spin-spin couplings in 2 HG expressing IDH-mutant gliomas.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: kumar.pichumani@utsouthwestern.edu.
authors.forename: Kumar
authors.initials: K
authors.lastname: Pichumani
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mashimo
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Magnetic Resonance Research, Korea Basic Science Institute, Chungbuk 363-883, Republic of Korea.
authors.forename: Hyeon-Man
authors.initials: HM
authors.lastname: Baek
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: James
authors.initials: J
authors.lastname: Ratnakar
authors.affiliation: Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Mickey
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Maher
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bachoo
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Veterans Affairs North Texas HealthCare System, Lancaster, TX 75216, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
mesh_terms: D002247:Carbon Isotopes / Q000032:analysis; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D018698:Glutamic Acid / Q000032:analysis; D005973:Glutamine / Q000032:analysis; D005977:Glutarates / Q000032:analysis*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009154:Mutation
chemical_list: D002247:Carbon Isotopes; D005977:Glutarates; D005973:Glutamine; C019417:alpha-hydroxyglutarate; D018698:Glutamic Acid; D007521:Isocitrate Dehydrogenase
keywords: (13)C NMR; 2-Hydroxyglutarate; Cryoprobe; IDH-mutant gliomas