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Imaging of human glioma cells by means of a Syndecan-4 directed DOTA-conjugate

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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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Acknowledgments

This study is supported by the Interdisciplinary Center for Clinical Research, University of Tübingen and the Hertie Foundation for Brain Research.

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Authors and Affiliations

  1. Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, 72076, Tübingen, Germany

    Alexander Sturzu, Hubert Kalbacher & Hartmut Echner

  2. Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    Alexander Sturzu, Uwe Klose & Stefan Heckl

  3. Department of Neurosurgery, University of Tübingen, Tübingen, Germany

    Alireza Gharabaghi

Authors
  1. Alexander Sturzu
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  2. Hubert Kalbacher
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  3. Hartmut Echner
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  4. Uwe Klose
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  5. Alireza Gharabaghi
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  6. Stefan Heckl
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Correspondence to Alexander Sturzu or Stefan Heckl.

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Sturzu, A., Kalbacher, H., Echner, H. et al. Imaging of human glioma cells by means of a Syndecan-4 directed DOTA-conjugate. Amino Acids 38, 1415–1421 (2010). https://doi.org/10.1007/s00726-009-0345-5

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  • DOI: https://doi.org/10.1007/s00726-009-0345-5

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