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Magnetic Resonance Imaging of Human Glioma Cells by means of an Interleukin‐6 Receptor‐Targeted Contrast Agent
Author(s) -
Sturzu Alexander,
Heckl Stefan
Publication year - 2010
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00936.x
Subject(s) - conjugate , cancer research , receptor , chemistry , fluorescence lifetime imaging microscopy , vascular endothelial growth factor , biophysics , angiogenesis , autocrine signalling , magnetic resonance imaging , cytoplasm , microbiology and biotechnology , biology , medicine , biochemistry , fluorescence , vegf receptors , mathematical analysis , physics , mathematics , quantum mechanics , radiology
The interleukin 6 receptor (IL‐6R) and its ligand interleukin 6 (IL‐6) play a crucial role in glioma growth and development accomplished by autocrine growth promotion and induction of angiogenesis via activation of vascular epithelial growth factor A (VEGF‐A). Therefore, IL‐6R represents a target for both therapy (preventing VEGF‐A activation by blocking the receptor) and imaging (higher receptor density on tumor cells). A short heptapeptide that selectively binds to IL‐6R and which inhibits the effect of IL‐6 was coupled to the magnetic resonance imaging (MRI) contrast agent gadolinium (Gd)‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) and the fluorescent dye rhodamine. MRI, confocal laser scanning microscopy, and flow cytometry showed that our IL‐6‐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. The cytoplasm specificity of the conjugate also makes it a potential building block for the design of future cytoplasm‐directed imaging and therapeutic conjugates.