Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model

作者：Heijmen L^*; ter Voert E G W; Punt C J A; Heerschap A; Oyen W J G; Bussink J; Sweep C G J; Laverman P; Span P N; de Geus Oei L F; Boerman O C; van Laarhoven H W M

来源：Contrast Media and Molecular Imaging, 2014, 9(3): 237-245.

DOI：10.1002/cmmi.1564

• bevacizumab
• colorectal cancer
• hypoxia
• mechanism of resistance
• tumor vasculature and microenvironment

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.

• 出版日期2014-5