Imaging of human glioma cells by means of a Syndecan-4 directed DOTA-conjugate |
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Authors: | Alexander Sturzu Hubert Kalbacher Hartmut Echner Uwe Klose Alireza Gharabaghi Stefan Heckl |
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Institution: | 1. Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, 72076, Tübingen, Germany 2. Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany 3. Department of Neurosurgery, University of Tübingen, Tübingen, Germany
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Abstract: | The extracellular glycoprotein Tenascin-C (TN-C) is highly upregulated in gliomas. Therefore, many chemotherapies with radiolabeled
antibodies against TN-C have been performed. However, TN-Cs binding partner Syndecan-4 did not play any role as a therapeutic
or imaging target in gliomas. We constructed an imaging compound containing the magnetic resonance imaging (MRI) contrast
agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the fluorescence dye sulforhodamine
and a synthetic Syndecan-4-specific 21 amino acid peptide derived from TN-C. Magnetic resonance relaxometry, confocal laser
scanning microscopy, and flow cytometry showed that the Syndecan-4-DOTA-Rhodamine conjugate was taken up into the cytoplasm
of human U373 glioma cells without any cytotoxic effects. Competition experiments indicate that this uptake was receptor-mediated.
This conjugate might be used for future MRI studies of brain tumors after systemic or intraoperative local application. |
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