Angelika von Wallbrunn1,2, Carsten Höltke1,3, Michael Zühlsdorf4, Walter Heindel1, Michael Schäfers2,5,6, Christoph Bremer7,8. 1. Department of Clinical Radiology, University of Münster, Albert-Schweitzer-Strasse 33, 48129, Münster, Germany. 2. Interdisciplinary Center for Clinical Research (IZKF Muenster, FG3), University of Münster, Münster, Germany. 3. Departments of Nuclear Medicine and Clinical Radiology, University of Münster, Münster, Germany. 4. Department of Hematology and Oncology, University of Münster, Münster, Germany. 5. Department of Nuclear Medicine, University of Münster, Münster, Germany. 6. Interdisciplinary Center for Clinical Research (IZKF Muenster, ZPG 4b), University of Münster, Münster, Germany. 7. Department of Clinical Radiology, University of Münster, Albert-Schweitzer-Strasse 33, 48129, Münster, Germany. bremerc@uni-muenster.de. 8. Interdisciplinary Center for Clinical Research (IZKF Muenster, FG3), University of Münster, Münster, Germany. bremerc@uni-muenster.de.
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 alpha v beta(3) targeted fluorochrome and imaged tumour xenografts with different alpha v beta(3) expression levels using both planar and tomographic optical imaging methods. METHODS: An alpha v beta(3)-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 alpha v beta(3)-positive M21 and HT-1080 cells while alpha v beta(3)-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 417.61 +/- 105.82 nM Cy 5.5 (M21), 353.68 +/- 54.02 nM Cy 5.5 (HT-1080) and 262.83 +/- 155.36 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 (294.35 +/- 84.27 nM). CONCLUSION: RGD-Cy 5.5 combined with novel tomographic optical imaging methods allows non-invasive imaging of tumour-associated alpha v beta(3) expression and may thus be a promising strategy for sensitive evaluation of tumour target expression.
PURPOSE: Optical imaging would be desirable for cancer diagnostics since it can potentially resolve relevant oncological target structures in vivo. We therefore synthesised an alpha v beta(3) targeted fluorochrome and imaged tumour xenografts with different alpha v beta(3) expression levels using both planar and tomographic optical imaging methods. METHODS: An alpha v beta(3)-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 alpha v beta(3)-positive M21 and HT-1080 cells while alpha v beta(3)-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 417.61 +/- 105.82 nM Cy 5.5 (M21), 353.68 +/- 54.02 nM Cy 5.5 (HT-1080) and 262.83 +/- 155.36 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 (294.35 +/- 84.27 nM). CONCLUSION: RGD-Cy 5.5 combined with novel tomographic optical imaging methods allows non-invasive imaging of tumour-associated alpha v beta(3) expression and may thus be a promising strategy for sensitive evaluation of tumour target expression.
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