In vivo characterization of brain metabolism by <sup>1</sup> H MRS, <sup>13</sup> C MRS and <sup>18</sup> FDG PET reveals significant glucose oxidation of invasively growing glioma cells.

Détails

ID Serval
serval:BIB_2B0968766E68
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
In vivo characterization of brain metabolism by <sup>1</sup> H MRS, <sup>13</sup> C MRS and <sup>18</sup> FDG PET reveals significant glucose oxidation of invasively growing glioma cells.
Périodique
International journal of cancer
Auteur(s)
Lai M., Vassallo I., Lanz B., Poitry-Yamate C., Hamou M.F., Cudalbu C., Gruetter R., Hegi M.E.
ISSN
1097-0215 (Electronic)
ISSN-L
0020-7136
Statut éditorial
Publié
Date de publication
01/07/2018
Peer-reviewed
Oui
Volume
143
Numéro
1
Pages
127-138
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Glioblastoma are notorious for their highly invasive growth, diffusely infiltrating adjacent brain structures that precludes complete resection, and is a major obstacle for cure. To characterize this "invisible" tumor part, we designed a high resolution multimodal imaging approach assessing in vivo the metabolism of invasively growing glioma xenografts in the mouse brain. Animals were subjected longitudinally to magnetic resonance imaging (MRI) and <sup>1</sup> H spectroscopy (MRS) at ultra high field (14.1 Tesla) that allowed the measurement of 16 metabolic biomarkers to characterize the metabolic profiles. As expected, the neuronal functionality was progressively compromised as indicated by decreasing N-acetyl aspartate, glutamate and gamma-aminobutyric acid and reduced neuronal TCA cycle (-58%) and neurotransmission (-50%). The dynamic metabolic changes observed, captured differences in invasive growth that was modulated by re-expression of the tumor suppressor gene WNT inhibitory factor 1 (WIF1) in the orthotopic xenografts that attenuates invasion. At late stage mice were subjected to <sup>13</sup> C MRS with infusion of [1,6- <sup>13</sup> C]glucose and <sup>18</sup> FDG positron emission tomography (PET) to quantify cell-specific metabolic fluxes involved in glucose metabolism. Most interestingly, this provided the first in vivo evidence for significant glucose oxidation in glioma cells. This suggests that the infiltrative front of glioma does not undergo the glycolytic switch per se, but that environmental triggers may induce metabolic reprograming of tumor cells.
Mots-clé
Adaptor Proteins, Signal Transducing/genetics, Adaptor Proteins, Signal Transducing/metabolism, Animals, Aspartic Acid/analogs & derivatives, Aspartic Acid/metabolism, Brain/diagnostic imaging, Brain/metabolism, Brain Neoplasms/diagnostic imaging, Brain Neoplasms/genetics, Brain Neoplasms/metabolism, Cell Line, Tumor, Fluorodeoxyglucose F18/metabolism, Glioma/diagnostic imaging, Glioma/genetics, Glioma/metabolism, Glucose/metabolism, Glutamic Acid/metabolism, Humans, Male, Mice, Neoplasm Transplantation, Oxidation-Reduction, Positron-Emission Tomography/methods, Proton Magnetic Resonance Spectroscopy/methods, Repressor Proteins/genetics, Repressor Proteins/metabolism, gamma-Aminobutyric Acid/metabolism, glioblastoma, glioma invasion, glucose oxidation, in vivo magnetic resonance spectroscopy, metabolism
Pubmed
Web of science
Création de la notice
20/02/2018 11:43
Dernière modification de la notice
20/08/2019 14:10
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