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Journal of Biomedical Optics

In vivo optical imaging of CD13/APN-expression in tumor xenografts
Author(s): Angelika von Wallbrunn; Jens Waldeck; Carsten Hoeltke; Michael Zühlsdorf; Rolf Mesters; Walter L. Heindel; Michael Schäfers; Christoph Bremer
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Paper Abstract

The metalloexopeptidase CD13/aminopeptidase N (APN) has been shown to be involved in cancer angiogenesis, invasion, and metastasis. Therefore, a CD13/APN–targeted <b<NGR</b<-peptide was labeled with the cyanine dye Cy 5.5 and applied to image tumor xenografts with different APN-expression levels using both planar and tomographic optical imaging methods. In vitro, the peptide-dye conjugate showed a clear binding affinity to APN-positive HT-1080 cells, while negative MCF-7 cells and predosing with the free <b<NGR</b<-peptide revealed little to no fluorescence. In vivo, tumor xenografts (n≥5) were clearly visualized by two-dimensional (2-D) planar fluorescence reflectance imaging (FRI) and three-dimensional (3-D) fluorescence mediated tomography (FMT) up to 24 h after injection. FMT also allowed us to quantify fluorochrome distribution in deeper tissue sections, showing an average fluorochrome concentration of 306.7±54.3 nM Cy 5.5 (HT-1080) and 116.0±18.3 nM Cy 5.5 (MCF-7) in the target tissue after 5 h. Competition with the free <b<NGR</b<-peptide resulted in a reduction of fluorochrome concentration in HT-1080 tumor tissue (195.3±21.9 nM; 5 h). We thus conclude that <b<NGR</b<-Cy 5.5 combined with novel tomographic optical imaging methods allows us to image and quantify tumor-associated CD13/APN expression noninvasively. This may be a promising strategy for a sensitive evaluation of tumor angiogenesis in vivo.

Paper Details

Date Published: 1 January 2008
PDF: 9 pages
J. Biomed. Opt. 13(1) 011007 doi: 10.1117/1.2839046
Published in: Journal of Biomedical Optics Volume 13, Issue 1
Show Author Affiliations
Angelika von Wallbrunn, Univ. Münster (Germany)
Jens Waldeck, Univ. Münster (Germany)
Carsten Hoeltke, Univ. Münster (Germany)
Michael Zühlsdorf, Univ. Münster (Germany)
Rolf Mesters, Univ. Münster (Germany)
Walter L. Heindel, Westfälische Wilhelms-Univ. Münster (Germany)
Michael Schäfers, Univ. Münster (Germany)
Christoph Bremer, Univ. Münster (Germany)


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