Tumor Reoxygenation Following Administration of the EGFR Inhibitor, Gefitinib, in Experimental Tumors
It is well recognized that tumor hypoxia is a critical determinant for response to therapy. The effect of an EGFR inhibitor/gefitinib (Iressa®) on tumor oxygenation was monitored daily using in vivo EPR (electron paramagnetic resonance) oximetry on TLT and FSaII tumor models. An increase in pO2 was shown at a dose of 45 mg/kg i.p. (n = 4/group/tumor model). This allowed the identification of a window of reoxygenation in both tumor models (with a maximum between 15 and 20 mmHg after 2 days of treatment). The increase in tumor oxygenation was shown to be the result of a decrease in oxygen consumption. This is the first report on the effect of gefitinib on oxygen consumption by tumor cells and subsequent increase in tumor oxygenation in vivo.
KeywordsElectron Paramagnetic Resonance Oxygen Consumption Oxygen Consumption Rate Tumor Oxygenation Small Animal Positron Emission Tomography
This study was supported by grants from the Belgian National Fund for Scientific Research (FNRS), the Fonds Joseph Maisin, the Saint-Luc Foundation, the “Actions de Recherches Concertées-Communauté Française de Belgique-ARC 09/14-020,” and the “ Pôle d’Attraction Interuniversitaire PAI VI (P6/38).” OK is “Televie” researcher, and BFJ is Research Associate of the Belgian National Fund for Scientific Research (FNRS).