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Initial investigation of glucose metabolism in mouse brain using enriched 17 O‐glucose and dynamic 17 O‐MRS
Author(s) -
Borowiak Robert,
Reichardt Wilfried,
Kurzhunov Dmitry,
Schuch Christian,
Leupold Jochen,
Krafft Axel Joachim,
Reisert Marco,
Lange Thomas,
Fischer Elmar,
Bock Michael
Publication year - 2017
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.3724
Subject(s) - chemistry , in vivo , carbohydrate metabolism , nuclear magnetic resonance spectroscopy , metabolism , radiochemistry , nuclear magnetic resonance , positron emission tomography , kinetics , metabolite , analytical chemistry (journal) , nuclear medicine , biochemistry , chromatography , stereochemistry , medicine , physics , microbiology and biotechnology , quantum mechanics , biology
In this initial work, the in vivo degradation of 17 O‐labeled glucose was studied during cellular glycolysis. To monitor cellular glucose metabolism, direct 17 O‐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‐CH 2 OH groups was detected using a Hankel–Lanczos singular value decomposition (HLSVD) algorithm for water suppression. Time‐resolved 17 O‐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 labeled 17 O‐glucose dissolved in 0.9% physiological saline. From a pharmacokinetic model fit of the H 2 17 O concentration–time course, a mean apparent cerebral metabolic rate of 17 O‐labeled glucose in mouse brain of CMR Glc = 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 by 18 F‐fluorodeoxyglucose ( 18 F‐FDG) positron emission tomography (PET). In addition, we studied the chemical exchange kinetics of aqueous solutions of 17 O‐labeled glucose at the C1 and C6 positions with dynamic 17 O‐MRS. In conclusion, the results of the exchange and in vivo experiments demonstrate that the C6‐ 17 OH label in the 6‐CH 2 OH group is transformed only glycolytically by the enzyme enolase into the metabolic end‐product H 2 17 O, whereas C1‐ 17 OH ends up in water via direct hydrolysis as well as glycolysis. Therefore, dynamic 17 O‐MRS of highly labeled 17 O‐glucose could provide a valuable non‐radioactive alternative to FDG PET in order to investigate glucose metabolism.