Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model.
Contrast Media Mol Imaging
; 9(3): 237-45, 2014.
Article
de En
| MEDLINE
| ID: mdl-24700751
ABSTRACT
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 (18) F-Fluoromisonidazole (FMISO) and (18) F-Fluorodeoxyglucose (FDG) positron emission tomography or magnetic resonance imaging before and 2, 6 and 10 days after the start of treatment. Tumors were harvested after imaging to determine hypoxia and vascular density immunohistochemically. The T2 * 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 T2 * 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Radiosensibilisants
/
Tumeurs colorectales
/
Inhibiteurs de l'angiogenèse
/
Anticorps monoclonaux humanisés
/
Hypoxie
/
Néovascularisation pathologique
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Contrast Media Mol Imaging
Sujet du journal:
DIAGNOSTICO POR IMAGEM
Année:
2014
Type de document:
Article
Pays d'affiliation:
Pays-Bas