期刊
JOURNAL OF IMMUNOLOGY
卷 195, 期 5, 页码 2019-2029出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1402005
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资金
- Navidea Biopharmaceuticals, Inc.
- National Institutes of Health, National Institute of Allergy and Infectious Diseases [R01 AI059639]
gamma-Tilmanocept (Tc-99m-labeled-tilmanocept or [Tc-99m]-tilmanocept) is the first mannose-containing, receptor-directed, radiolabeled tracer for the highly sensitive imaging of sentinel lymph nodes in solid tumor staging. To elucidate the mannose-binding receptor that retains tilmanocept in this microenvironment, human macrophages were used that have high expression of the C-type lectin mannose receptor (MR; CD206). Cy3-labeled tilmanocept exhibited high specificity binding to macrophages that was nearly abolished in competitive inhibition experiments. Furthermore, Cy3-tilmanocept binding was markedly reduced on macrophages deficient in the MR by small interfering RNA treatment and was increased on MR-transfected HEK 293 cells. Finally, confocal microscopy revealed colocalization of Cy3-tilmanocept with the macrophage membrane MR and binding of labeled tilmanocept to MR+ cells (macrophages and/or dendritic cells) in human sentinel lymph node tissues. Together these data provide strong evidence that CD206 is a major binding receptor for gamma-tilmanocept. Identification of CD206 as the gamma-tilmanocept-binding receptor enables opportunities for designing receptor-targeted advanced imaging agents and therapeutics for cancer and other diseases.
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