Assessment of vascular remodeling under antiangiogenic therapy using DCE‐MRI and vessel size imaging |
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| Authors: | Stefan Zwick MS Ralph Strecker PhD Valerji Kiselev PhD Peter Gall MS Jochen Huppert PhD Moritz Palmowski MD Wiltrud Lederle PhD Eva C Woenne MS Arne Hengerer PhD Matthias Taupitz PhD Wolfhard Semmler MD PhD Fabian Kiessling MD |
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| Institution: | 1. Siemens AG, Healthcare Sector, Erlangen, Germany;2. Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany;3. Department of Diagnostic Radiology, University Hospital Freiburg, Freiburg, Germany;4. Department of Experimental Molecular Imaging, RWTH‐Aachen University, Aachen, Germany;5. Department of Radiology, Charité, Berlin, Germany |
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| Abstract: | Purpose To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic contrast‐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 imaging. DCE‐MRI data were analyzed applying a two‐compartment model (Brix), calculating the parameters Amplitude and kep. Results For both experiments Amplitude decreased significantly in treated tumors while kep did not change significantly. VSI showed controversial results. VSI was significantly 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 reliable and supplementing biomarkers of antiangiogenic therapy response. The results of both methods are in excellent 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. J. Magn. Reson. Imaging 2009;29:1125–1133. © 2009 Wiley‐Liss, Inc. |
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| Keywords: | magnetic resonance imaging vessel size imaging DCE‐MRI antiangiogenic therapy therapy monitoring tumor |
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