Research Papers:

Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models

Marie-Aline Neveu _, Géraldine De Preter, Nicolas Joudiou, Anne Bol, Jeffery R. Brender, Keita Saito, Shun Kishimoto, Vincent Grégoire, Bénédicte F. Jordan, Murali C. Krishna, Olivier Feron and Bernard Gallez

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:81741-81749. https://doi.org/10.18632/oncotarget.13176

Metrics: PDF 1669 views  |   HTML 2166 views  |   ?  


Marie-Aline Neveu1, Géraldine De Preter1, Nicolas Joudiou1, Anne Bol2, Jeffery R. Brender3, Keita Saito3, Shun Kishimoto3, Vincent Grégoire2, Bénédicte F. Jordan1, Murali C. Krishna3, Olivier Feron4, Bernard Gallez1

1Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium

2Radiation Oncology Department & Center for Molecular Imaging, Radiotherapy & Oncology, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium

3Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, USA

4Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium

Correspondence to:

Bernard Gallez, email: [email protected]

Keywords: tumor metabolism, DCA, 17O MRS, hyperpolarized 13C-MRI, 18F-FDG PET

Received: September 08, 2016     Accepted: October 19, 2016     Published: November 07, 2016


Reverting glycolytic metabolism is an attractive strategy for cancer therapy as upregulated glycolysis is a hallmark in various cancers. Dichloroacetate (DCA), long used to treat lactic acidosis in various pathologies, has emerged as a promising anti-cancer drug. By inhibiting the pyruvate dehydrogenase kinase, DCA reactivates the mitochondrial function and decreases the glycolytic flux in tumor cells resulting in cell cycle arrest and apoptosis. We recently documented that DCA was able to induce a metabolic switch preferentially in glycolytic cancer cells, leading to a more oxidative phenotype and decreasing proliferation, while oxidative cells remained less sensitive to DCA treatment. To evaluate the relevance of this observation in vivo, the aim of the present study was to characterize the effect of DCA in glycolytic MDA-MB-231 tumors and in oxidative SiHa tumors using advanced pharmacodynamic metabolic biomarkers. Oxygen consumption, studied by 17O magnetic resonance spectroscopy, glucose uptake, evaluated by 18F-FDG PET and pyruvate transformation into lactate, measured using hyperpolarized 13C-magnetic resonance spectroscopy, were monitored before and 24 hours after DCA treatment in tumor bearing mice. In both tumor models, no clear metabolic shift was observed. Surprisingly, all these imaging parameters concur to the conclusion that both glycolytic tumors and oxidative tumors presented a similar response to DCA. These results highlight a major discordance in metabolic cancer cell bioenergetics between in vitro and in vivo setups, indicating critical role of the local microenvironment in tumor metabolic behaviors.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 13176