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

Author:
Sturzu, Alexander, Kalbacher, Hubert, Echner, Hartmut, Klose, Uwe, Gharabaghi, Alireza, Heckl, Stefan
Source:
Amino acids 2010 v.38 no.5 pp. 1415-1421
ISSN:
0939-4451
Subject:
amino acids, antibodies, brain, confocal laser scanning microscopy, cytoplasm, cytotoxicity, flow cytometry, fluorescent dyes, gadolinium, glycoproteins, humans, image analysis, magnetic resonance imaging, neoplasms, radiolabeling
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.
Agid:
2262054