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Abstract #0991

EPR Study of the Tumor Reoxygenation Following Inhibition of the MAPKinase Pathway: Underlying Mechanisms & Radiosensitizing Effects

Oussama Karroum1, Julie Kengen1, Pierre Danhier1, Julien Verrax2, Pedro Buc Calderon2, Pierre Sonveaux3, Vincent Gregoire4, Bernard Gallez1, Benedicte F. Jordan1

1Louvrain Drug Research Institute, Biomedical Magnetic Resonance Group, Universite Catholique de Louvain, Brussels, Belgium; 2Louvrain Drug Research Institute, Pharmacokinetics, Metabolism, Nutrition, & Toxicology Group, Universite Catholique de Louvain; 3IREC, Pole of Pharmacology & Therapeutics, Universite Catholique de Louvain; 4IREC, Molecular Imaging & Radiotherapy, Universite Catholique de Louvain

The effects of different MAPKinase inhibitors (Sorafenib, Gefitinib, FTS, and PD-0325901) were monitored in FSaII experimental mouse tumors. In vivo EPR oximetry (L-band) showed an increase in tumor pO2 for all MAPK inhibitors and allowed the identification of a window of reoxygenation, which was further exploited for improving radiation response. The increase in tumor oxygenation was shown to be the result of two major factors: (i) an increase in blood flow for sorafenib only and, (ii) a decrease in oxygen consumption for all MAPK inhibitors, as measured ex vivo using X-band EPR oximetry.