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Bevacizumab enhances efficiency of radiotherapy in a lung adenocarcinoma rodent model: Role of αvβ3 imaging in determining optimal window.

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.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Becker S,Bohn P,Bouyeure-Petit AC,Modzelewski R,Gensanne D,Picquenot JM,Dubray B,Vera P

doi

10.1016/j.nucmedbio.2015.08.002

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

923-30

issue

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(15)00144-4

journal_volume

pub_type

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Bevacizumab enhances efficiency of radiotherapy in a lung adenocarcinoma rodent model: Role of αvβ3 imaging in determining optimal window.