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.