Assessment of Vascular Remodeling Under Antiangiogenic Therapy Using DCE-MRI and Vessel Size Imaging

Abstract

Purpose: To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic con- trast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index (VSI) as a novel biomarker of therapy response. Materials and Methods: In two independent experiments, nude mice bearing human skin squamous cell carcinoma xenografts were treated with a vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or a multitargeted tyrosine kinase inhibitor (SU11248). Changes in tumor vascularity were assessed by DCE-MRI and vessel size im- aging. DCE-MRI data were analyzed applying a two-com- partment model (Brix), calculating the parameters Ampli- tude and kep. Results: For both experiments Amplitude decreased signif- icantly in treated tumors while k ep did not change signifi- cantly. VSI showed controversial results. VSI was signifi- cantly increased in SU11248-treated A431 tumors, whereas no changes were found in bevacizumab-treated HaCaT-ras-A-5RT3 tumors. Immunohistology confirmed these results and suggest differences in the maturation of tumor vascularization as a possible explanation. Conclusion: DCE-MRI and vessel size imaging provide re- liable and supplementing biomarkers of antiangiogenic therapy response. The results of both methods are in ex- cellent agreement with histology. Nevertheless, our results also indicate that vascular remodeling is complex and that a uniform response cannot be expected for different tumors and therapies.