title: Multimodality Imaging Identifies Distinct Metabolic Profiles In Vitro and In Vivo.
abstract: The study of alterations of tumor metabolism should allow the identification of new targets for innovative anticancer strategies. Metabolic alterations are generally established in vitro, and conclusions are often extrapolated to the in vivo situation without further tumor metabolic phenotyping. To highlight the key role of microenvironment on tumor metabolism, we studied the response of glycolytic and oxidative tumor models to metabolic modulations in vitro and in vivo. MDA-MB-231 and SiHa tumor models, characterized in vitro as glycolytic and oxidative, respectively, were studied. Theoretically, when passing from a hypoxic state to an oxygenated state, a Warburg phenotype should conserve a glycolytic metabolism, whereas an oxidative phenotype should switch from glycolytic to oxidative metabolism (Pasteur effect). This challenge was applied in vitro and in vivo to evaluate the impact of different oxic conditions on glucose metabolism.18F-fluorodeoxyglucose uptake, lactate production, tumor oxygenation, and metabolic fluxes were monitored in vivo using positron emission tomography, microdialysis, electron paramagnetic resonance imaging, and13C-hyperpolarizated magnetic resonance spectroscopy, respectively. In vitro, MDA-MB-231 cells were glycolytic under both hypoxic and oxygenated conditions, whereas SiHa cells underwent a metabolic shift after reoxygenation. On the contrary, in vivo, the increase in tumor oxygenation (induced by carbogen challenge) led to a similar metabolic shift in glucose metabolism in both tumor models. The major discordance in metabolic patterns observed in vitro and in vivo highlights that any extrapolation of in vitro metabolic profiling to the in vivo situation should be taken cautiously and that metabolic phenotyping using molecular imaging is mandatory in vivo.
authors.affiliation: Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Marie-Aline
authors.initials: MA
authors.lastname: Neveu
authors.affiliation: Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Géraldine
authors.initials: G
authors.lastname: De Preter
authors.affiliation: Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Valérie
authors.initials: V
authors.lastname: Marchand
authors.affiliation: Radiation Oncology Department & Center for Molecular Imaging, Radiotherapy & Oncology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.affiliation: Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, USA.
authors.forename: Jeffery R
authors.initials: JR
authors.lastname: Brender
authors.affiliation: Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, USA.
authors.forename: Keita
authors.initials: K
authors.lastname: Saito
authors.affiliation: Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, USA.
authors.forename: Shun
authors.initials: S
authors.lastname: Kishimoto
authors.affiliation: Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Paolo E
authors.initials: PE
authors.lastname: Porporato
authors.affiliation: Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.affiliation: Radiation Oncology Department & Center for Molecular Imaging, Radiotherapy & Oncology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.affiliation: Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.affiliation: Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
authors.affiliation: Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, USA.
authors.forename: Murali C
authors.initials: MC
authors.lastname: Krishna
authors.affiliation: Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Brussels, Belgium. Electronic address: bernard.gallez@uclouvain.be.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D064593:Heterografts; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D064847:Multimodal Imaging; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D000072078:Positron Emission Tomography Computed Tomography
chemical_list: D005947:Glucose; D010100:Oxygen