Imaging of human glioma cells by means of a Syndecan-4 directed DOTA-conjugate.
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.
Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, 72076, Tübingen, Germany. alexsturzu@yahoo.de
Alexander
A
Sturzu
Hubert
H
Kalbacher
Hartmut
H
Echner
Uwe
U
Klose
Alireza
A
Gharabaghi
Stefan
S
Heckl
D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006571:Heterocyclic Compounds / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D009942:Organometallic Compounds / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D053671:Syndecan-4 / Q000378:metabolism*
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C508304:SDC4 protein, human; D053671:Syndecan-4; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate