Initial investigation of glucose metabolism in mouse brain using enriched ¹⁷ O-glucose and dynamic ¹⁷ O-MRS

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-CH₂ 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 H₂¹⁷ 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-CH₂ OH group is transformed only glycolytically by the enzyme enolase into the metabolic end-product H₂¹⁷ 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.