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Eur J Nucl Med Mol Imaging (2007) 34:745754 DOI 10.1007/s00259-006-0269-1
MOLECULAR IMAGING
In vivo imaging of integrin 3 expression using fluorescence-mediated tomography
Angelika von Wallbrunn & Carsten Hltke &
Michael Zhlsdorf & Walter Heindel & Michael Schfers &
Christoph Bremer
Received: 17 January 2006 / Accepted: 15 August 2006 / Published online: 28 November 2006 # Springer-Verlag 2006
Abstract Purpose Optical imaging would be desirable for cancer diagnostics since it can potentially resolve relevant oncological target structures in vivo. We therefore synthesised an v3 targeted fluorochrome and imaged tumour xenografts with different v3 expression levels using both planar and tomographic optical imaging methods.Methods An v3-targeted RGD peptide was labelled with a cyanine dye (Cy 5.5). Binding of the optical tracer was
tested on M21 melanoma (n=5), HT-1080 fibrosarcoma (n=6) and MCF-7 adenocarcinoma (n=5) cells and their tumour xenografts. All optical imaging studies were performed using two-dimensional planar fluorescence reflectance imaging (FRI) technology and three-dimensional fluorescence-mediated tomography (FMT).Results In vitro, the peptide-dye conjugate showed a clear binding affinity to v3-positive M21 and HT-1080 cells while v3-negative MCF-7 cells and pre-dosing with the free RGD peptide revealed little to no fluorescence. In vivo, tumour xenografts were clearly visualised by FRI and FMT up to 24 h post injection. FMT allowed quantification of the fluorochrome distribution in deeper tissue sections showing an average fluorochrome concentration of 417.61105.82 nM Cy 5.5 (M21), 353.6854.02 nM Cy 5.5 (HT-1080) and 262.83155.36 nM Cy 5.5 (MCF-7) in the target tissue 60 min after tracer administration. Competition with the free RGD peptide resulted in a reduction in the fluorochrome concentration in M21 tumour tissue (294.3584.27 nM).Conclusion RGD-Cy 5.5 combined with novel tomographic optical imaging methods allows non-invasive imaging of tumour-associated v3 expression and may thus be a promising strategy for sensitive evaluation of tumour target expression.
Keywords Optical imaging . Integrin v3 . RGD-Cy 5.5 .
Fluorescence-mediated tomography .Fluorescence reflectance imaging
Introduction
Emerging optical imaging techniques have recently been proven to be powerful tools for in vivo molecular imaging of specific target structures. Combining new quantitative
A. von Wallbrunn : C. Hltke : W. Heindel : C. Bremer (*) Department of Clinical Radiology, University of Mnster, Albert-Schweitzer-Strasse 33,48129 Mnster, Germanye-mail: [email protected]
A. von Wallbrunn : M. Schfers : C. Bremer Interdisciplinary Center for...