title: Initial investigation of glucose metabolism in mouse brain using enriched17O-glucose and dynamic17O-MRS.
abstract: In this initial work, the in vivo degradation of17O-labeled glucose was studied during cellular glycolysis. To monitor cellular glucose metabolism, direct17O-magnetic resonance spectroscopy (MRS) was used in the mouse brain at 9.4 T. Non-localized spectra were acquired with a custom-built transmit/receive (Tx/Rx) two-turn surface coil and a free induction decay (FID) sequence with a short TR of 5.4 ms. The dynamics of labeled oxygen in the anomeric 1-OH and 6-CH2OH groups was detected using a Hankel-Lanczos singular value decomposition (HLSVD) algorithm for water suppression. Time-resolved17O-MRS (temporal resolution, 42/10.5 s) was performed in 10 anesthetized (1.25% isoflurane) mice after injection of a 2.2 M solution containing 2.5 mg/g body weight of differently labeled17O-glucose dissolved in 0.9% physiological saline. From a pharmacokinetic model fit of the H217O concentration-time course, a mean apparent cerebral metabolic rate of17O-labeled glucose in mouse brain of CMRGlc= 0.07 ± 0.02 μmol/g/min was extracted, which is of the same order of magnitude as a literature value of 0.26 ± 0.06 μmol/g/min reported by18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). In addition, we studied the chemical exchange kinetics of aqueous solutions of17O-labeled glucose at the C1 and C6 positions with dynamic17O-MRS. In conclusion, the results of the exchange and in vivo experiments demonstrate that the C6-17OH label in the 6-CH2OH group is transformed only glycolytically by the enzyme enolase into the metabolic end-product H217O, whereas C1-17OH ends up in water via direct hydrolysis as well as glycolysis. Therefore, dynamic17O-MRS of highly labeled17O-glucose could provide a valuable non-radioactive alternative to FDG PET in order to investigate glucose metabolism.
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0002-6513-5526
authors.initials: R
authors.lastname: Borowiak
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Reichardt
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kurzhunov
authors.affiliation: NUKEM Isotopes Imaging GmbH, Alzenau, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schuch
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Leupold
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Axel Joachim
authors.initials: AJ
authors.lastname: Krafft
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Reisert
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lange
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Fischer
authors.affiliation: Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bock
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016001:Confidence Intervals; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008810:Mice, Inbred C57BL; D010103:Oxygen Isotopes / Q000378:metabolism*; D012996:Solutions; D013997:Time Factors; D014867:Water
chemical_list: D001786:Blood Glucose; D010103:Oxygen Isotopes; D012996:Solutions; D014867:Water; D005947:Glucose
keywords: 17O-MRS; cerebral rate of glucose consumption (CMRGlc); chemical exchange kinetics; glucose metabolism; glycolysis; non-proton MRS