Magnetic resonance imaging of human glioma cells by means of an interleukin-6 receptor-targeted contrast agent.
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.
Sturzu
Alexander
A
Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany. alexsturzu@yahoo.de
Heckl
Stefan
S
D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D005910:Glioma / Q000737:chemistry* / Q000188:drug therapy; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008279:Magnetic Resonance Imaging; D019947:Receptors, Interleukin-6 / Q000032:analysis* / Q000037:antagonists & inhibitors; D012235:Rhodamines / Q000737:chemistry
D003287:Contrast Media; D056831:Coordination Complexes; D005456:Fluorescent Dyes; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D019947:Receptors, Interleukin-6; D012235:Rhodamines; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium