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In vivo characterization of brain metabolism by 1 H MRS, 13 C MRS and 18 FDG PET reveals significant glucose oxidation of invasively growing glioma cells
Author(s) -
Lai Marta,
Vassallo Irene,
Lanz Bernard,
PoitryYamate Carole,
Hamou MarieFrance,
Cudalbu Cristina,
Gruetter Rolf,
Hegi Monika E.
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31299
Subject(s) - in vivo , glioma , glucose uptake , positron emission tomography , anaerobic glycolysis , metabolism , carbohydrate metabolism , glycolysis , biology , cancer research , chemistry , endocrinology , neuroscience , insulin , microbiology and biotechnology
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 1 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 13 C MRS with infusion of [1,6‐ 13 C]glucose and 18 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.