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Noninvasive Visualization of the Activated alphavbeta3 Integrin in Cancer Patients by Positron Emission Tomography and [18F]Galacto-RGD

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Author(s): Haubner Roland | Weber Wolfgang A | Beer Ambros J | Vabuliene Eugenija | Reim Daniel | Sarbia Mario | Becker Karl-Friedrich | Goebel Michael | Hein Rüdiger | Wester Hans-Jürgen | Kessler Horst | Schwaiger Markus

Journal: PLoS Medicine
ISSN 1549-1277

Volume: 2;
Issue: 3;
Date: 2005;
Original page

Keywords: Oncology

ABSTRACT
Background The integrin alphavbeta3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of alphavbeta3 expression. We developed [18F]Galacto-RGD, a 18F-labeled glycosylated alphavbeta3 antagonist, allowing monitoring of alphavbeta3 expression with positron emission tomography (PET). Methods and Findings Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of [18F]Galacto-RGD in the tumor correlates with alphavbeta3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize alphavbeta3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that [18F]Galacto-RGD with PET enables noninvasive quantitative assessment of the alphavbeta3 expression pattern on tumor and endothelial cells in patients with malignant tumors. Conclusions Molecular imaging with [18F]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the alphavbeta3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases.
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