Original Research

Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging†

  1. Stefan Zwick MS1,2,*,
  2. Ralph Strecker PhD1,
  3. Valerji Kiselev PhD3,
  4. Peter Gall MS3,
  5. Jochen Huppert PhD1,
  6. Moritz Palmowski MD4,
  7. Wiltrud Lederle PhD4,
  8. Eva C. Woenne MS2,
  9. Arne Hengerer PhD1,
  10. Matthias Taupitz PhD5,
  11. Wolfhard Semmler MD, PhD2,
  12. Fabian Kiessling MD4

Article first published online: 22 APR 2009

DOI: 10.1002/jmri.21710

Issue

Journal of Magnetic Resonance Imaging

Journal of Magnetic Resonance Imaging

Volume 29, Issue 5, pages 1125–1133, May 2009

Additional Information

How to Cite

Zwick, S., Strecker, R., Kiselev, V., Gall, P., Huppert, J., Palmowski, M., Lederle, W., Woenne, E. C., Hengerer, A., Taupitz, M., Semmler, W. and Kiessling, F. (2009), Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging. J. Magn. Reson. Imaging, 29: 1125–1133. doi: 10.1002/jmri.21710

Author Information

  1. 1

    Siemens AG, Healthcare Sector, Erlangen, Germany

  2. 2

    Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

  3. 3

    Department of Diagnostic Radiology, University Hospital Freiburg, Freiburg, Germany

  4. 4

    Department of Experimental Molecular Imaging, RWTH-Aachen University, Aachen, Germany

  5. 5

    Department of Radiology, Charité, Berlin, Germany

*Dept. of Medical Physics in Radiology E020, German Cancer Research Center (DKFZ), INF 280, D-69120 Heidelberg, Germany

  1. †

    Part of this work was presented at the 16th Annual Meeting of ISMRM, 2008.

Publication History

  1. Issue published online: 22 APR 2009
  2. Article first published online: 22 APR 2009
  3. Manuscript Accepted: 5 DEC 2008
  4. Manuscript Received: 4 SEP 2008

Funded by

  • Bundesministerium für Bildung und Forschung (BMBF)
  • NanoAG. Grant Number: 13N8873
  • European Commission
  • CANCERDEGRADOME. Grant Number: LSHC-CT-2003-503297

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Keywords:

  • magnetic resonance imaging;
  • vessel size imaging;
  • DCE-MRI;
  • antiangiogenic therapy;
  • therapy monitoring;
  • tumor

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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