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Quantitative Molecular Magnetic Resonance Imaging of Tumor Angiogenesis Using cNGR-Labeled Paramagnetic Quantum Dots

¹ Department of Radiology, Maastricht University Hospital, ² Cardiovascular Research Institute Maastricht (CARIM), Departments of ³ Biomedical Engineering, ⁴ Biochemistry, and ⁵ Physiology, and ⁶ Research Institute GROW, Maastricht University, Maastricht, the Netherlands; and ⁷ Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands

Requests for reprints: Walter H. Backes, Maastricht University Hospital, Department of Radiology, P.Debyelaan 25, 6229 HX, Maastricht, the Netherlands. Phone: 0031-43-3876948; Fax: 0031-43-3876909; E-mail: wbac{at}rdia.azm.nl.

Key Words: molecular magnetic resonance imaging • tumor angiogenesis • quantum dots • cNGR • two-photon laser scanning microscopy

The objective of this study was to develop and apply cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (cNGR-pQDs) for the noninvasive assessment of tumor angiogenic activity using quantitative in vivo molecular magnetic resonance imaging (MRI). cNGR was previously shown to colocalize with CD13, an aminopeptidase that is highly overexpressed on angiogenic tumor endothelium. Because angiogenesis is important for tumor growth and metastatization, its in vivo detection and quantification may allow objective diagnosis of tumor status and evaluation of treatment response. I.v. injection of cNGR-pQDs in tumor-bearing mice resulted in increased quantitative contrast, comprising increased longitudinal relaxation rate and decreased proton visibility, in the tumor rim but not in tumor core or muscle tissue. This showed that cNGR-pQDs allow in vivo quantification and accurate localization of angiogenic activity. MRI results were validated using ex vivo two-photon laser scanning microscopy (TPLSM), which showed that cNGR-pQDs were primarily located on the surface of tumor endothelial cells and to a lesser extent in the vessel lumen. In contrast, unlabeled pQDs were not or only sparsely detected with both MRI and TPLSM, supporting a high specificity of cNGR-pQDs for angiogenic tumor vasculature. [Cancer Res 2008;68(18):7676–83]

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