Stéphanie Becker1, Pierre Bohn2, Anne-Charlotte Bouyeure-Petit2, Romain Modzelewski2, David Gensanne3, Jean-Michel Picquenot4, Bernard Dubray3, Pierre Vera2. 1. Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF LITIS (Equipe d'Accueil (EA) 4108-Federation Recherche (FR) National Center for Scientific Research (CNRS) 3638), Faculty of Medicine, University of Rouen, Rouen, 76821, France. Electronic address: stephanie.becker@chb.unicancer.fr. 2. Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF LITIS (Equipe d'Accueil (EA) 4108-Federation Recherche (FR) National Center for Scientific Research (CNRS) 3638), Faculty of Medicine, University of Rouen, Rouen, 76821, France. 3. Department of Radiation Oncology, Henri Becquerel Cancer Center, Rouen, 76821, France. 4. Pathology Department, Henri Becquerel Cancer Center, Rouen, 76821, France.
Abstract
INTRODUCTION: Earlier studies indicated that bevacizumab could favorably be combined with radiation. However excessive damage to tumor vasculature can result in radioresistance and clinical data suggest that treatment sequencing may be important when combining bevacizumab with radiation. The aim of this study was to evaluate whether αvβ3 scintigraphic imaging could provide information to determine the optimal combination schedule of bevacizumab and radiotherapy on a lung adenocarcinoma model in mice. METHODS: The tumor volume and angiogenesis changes induced after bevacizumab and radiation treatment were evaluated using (99m)Tc-RGD on a microSPECT/CT. First, we determined the optimal dose regimen for bevacizumab and radiotherapy alone. Second, the combined effects of bevacizumab and radiation were evaluated according to the combination timing (radiation 2, 24, 48 hours after bevacizumab and 48 hours before bevacizumab). RESULTS: The optimal dose regimen is 20mg/kg for bevacizumab and 12.5 Gy for radiotherapy with a significant decrease of tumoral uptake and volume at day 9 compared to the controls (+8.8%, +7.7%, and +44% volume, respectively, and +9.8%, +3.8%, and +207% uptake, respectively). Scintigraphic imaging showed a significant increased RGD tumor uptake two hours after bevacizumab treatment compared to 24 hours and controls (p=0.02). When bevacizumab treatment was combined with radiation, the best combination appears to be the administration of bevacizumab two hours prior to radiation with better results than single treatments (p < 0.05). On the contrary, bevacizumab given 24 hours prior to radiation led to less tumor growth delay compared to a single agent, without significant difference compared to the controls. Histological results confirmed these data with an increased percentage of necrosis (p=0.04) and a decrease of angiogenesis (p=0.04) in the optimal combination group. CONCLUSIONS: The RGD tracer helps us identify the vascular normalization window and it shows a supra-additive effect of bevacizumab when administered two hours before radiotherapy.
INTRODUCTION: Earlier studies indicated that bevacizumab could favorably be combined with radiation. However excessive damage to tumor vasculature can result in radioresistance and clinical data suggest that treatment sequencing may be important when combining bevacizumab with radiation. The aim of this study was to evaluate whether αvβ3 scintigraphic imaging could provide information to determine the optimal combination schedule of bevacizumab and radiotherapy on a lung adenocarcinoma model in mice. METHODS: The tumor volume and angiogenesis changes induced after bevacizumab and radiation treatment were evaluated using (99m)Tc-RGD on a microSPECT/CT. First, we determined the optimal dose regimen for bevacizumab and radiotherapy alone. Second, the combined effects of bevacizumab and radiation were evaluated according to the combination timing (radiation 2, 24, 48 hours after bevacizumab and 48 hours before bevacizumab). RESULTS: The optimal dose regimen is 20mg/kg for bevacizumab and 12.5 Gy for radiotherapy with a significant decrease of tumoral uptake and volume at day 9 compared to the controls (+8.8%, +7.7%, and +44% volume, respectively, and +9.8%, +3.8%, and +207% uptake, respectively). Scintigraphic imaging showed a significant increased RGD tumor uptake two hours after bevacizumab treatment compared to 24 hours and controls (p=0.02). When bevacizumab treatment was combined with radiation, the best combination appears to be the administration of bevacizumab two hours prior to radiation with better results than single treatments (p < 0.05). On the contrary, bevacizumab given 24 hours prior to radiation led to less tumor growth delay compared to a single agent, without significant difference compared to the controls. Histological results confirmed these data with an increased percentage of necrosis (p=0.04) and a decrease of angiogenesis (p=0.04) in the optimal combination group. CONCLUSIONS: The RGD tracer helps us identify the vascular normalization window and it shows a supra-additive effect of bevacizumab when administered two hours before radiotherapy.
Authors: Ana P S Silva; Priscila V Coelho; Maristella Anazetti; Patricia U Simioni Journal: Hum Vaccin Immunother Date: 2016-11-10 Impact factor: 3.452
Authors: Florian Guisier; Pierre Bohn; Maxime Patout; Nicolas Piton; Insaf Farah; Pierre Vera; Luc Thiberville; Mathieu Salaün Journal: PLoS One Date: 2017-07-03 Impact factor: 3.240