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Early in vivo assessment of angiostatic therapy efficacy by molecular MRI

Willem J. M. Mulder^*,1, Daisy W. J. van der Schaft, Petra A. I. Hautvast, Gustav J. Strijkers^*, Gerben A. Koning, Gert Storm, Kevin H. Mayo^||, Arjan W. Griffioen and Klaas Nicolay^*

^* Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands;

Angiogenesis Laboratory, Research Institute for Growth and Development, Department of Pathology/Internal Medicine, Maastricht University and University Hospital, Maastricht, The Netherlands;

Department of Radiation, Radioisotopes, and Reactors, Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands;

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands; and

^|| Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA

¹Correspondence: Biomedical NMR, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. E-mail: w.j.m.mulder{at}tue.nl

Noninvasive diagnostic imaging methods to establish the efficacy of angiostatic therapies are becoming increasingly important with the first Food and Drug Administration approvals of such agents. Magnetic resonance molecular imaging is an imaging technique that allows the visualization of pathological processes in vivo with a better spatial resolution as compared with nuclear methods, such as photon emission tomography and single photon emission computed tomography. In this study, we used vß3 targeted bimodal liposomes to quantitate angiogenesis in a tumor mouse model with magnetic resonance imaging (MRI) and to evaluate the therapeutic efficacy of the angiogenesis inhibitors anginex and endostatin. The MRI findings were validated with fluorescence microscopy and showed a very good correlation with the microvessel density. In conclusion, this study provides evidence that molecular MRI can be used to noninvasively measure the efficacy of angiogenesis inhibitors during the course of therapy.—Mulder, W. J. M., van der Schaft, D. W. J., Hautvast, P. A. I., Strijkers, G. J., Storm, G., Mayo, K. H., Griffioen, A. W., Nicolay, K. Early in vivo assessment of angiostatic therapy efficacy by molecular MRI.

Key Words: molecular imaging • tumor angiogenesis • vß3-integrin