Journal
CONTRAST MEDIA & MOLECULAR IMAGING
Volume 9, Issue 3, Pages 237-245Publisher
WILEY-HINDAWI
DOI: 10.1002/cmmi.1564
Keywords
bevacizumab; colorectal cancer; hypoxia; mechanism of resistance; tumor vasculature and microenvironment
Funding
- Dutch Cancer Society (KWF Kankerbestrijding) [KUN 2008-4098]
Ask authors/readers for more resources
The purpose of this study was to assess the effect of bevacizumab on vasculature and hypoxia in a colorectal tumor model. Nude mice with subcutaneous LS174T tumors were treated with bevacizumab or saline. To assess tumor properties, separate groups of mice were imaged using F-18-Fluoromisonidazole (FMISO) and F-18-Fluorodeoxyglucose (FDG) positron emission tomography or magnetic resonance imaging before and 2, 6 and 10days after the start of treatment. Tumors were harvested after imaging to determine hypoxia and vascular density immunohistochemically. The T-2* time increased significantly less in the bevacizumab group. FMISO uptake increased more over time in the control group. Vessel density significantly decreased in the bevacizumab-treated group. The Carbonic anhydrase 9 (CAIX) and glucose uptake transporter 1 (GLUT1) fractions were higher in bevacizumab-treated tumors. However, the hypoxic fraction showed no significant difference. Bevacizumab led to shorter T-2* times and higher GLUT1 and CAIX expression, suggesting an increase in hypoxia and a higher glycolytic rate. This could be a mechanism of resistance to bevacizumab. The increase in hypoxia, however, could not be demonstrated by pimonidazole/FMISO, possibly because distribution of these tracers is hampered by bevacizumab-induced effects on vascular permeability and perfusion. Copyright (c) 2014 John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available