title: γ-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph Nodes, Binds to the Mannose Receptor (CD206).
abstract: γ-Tilmanocept ((99m)Tc-labeled-tilmanocept or [(99m)Tc]-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 γ-tilmanocept. Identification of CD206 as the γ-tilmanocept-binding receptor enables opportunities for designing receptor-targeted advanced imaging agents and therapeutics for cancer and other diseases.
authors.affiliation: Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210;
authors.forename: Abul K
authors.initials: AK
authors.lastname: Azad
authors.affiliation: Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210;
authors.forename: Murugesan V S
authors.initials: MV
authors.lastname: Rajaram
authors.affiliation: Clinical and Medical Groups, Navidea Biopharmaceuticals, Inc., Dublin, OH 43017; and.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Metz
authors.affiliation: Clinical and Medical Groups, Navidea Biopharmaceuticals, Inc., Dublin, OH 43017; and.
authors.forename: Frederick O
authors.initials: FO
authors.lastname: Cope
authors.affiliation: Clinical and Medical Groups, Navidea Biopharmaceuticals, Inc., Dublin, OH 43017; and.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Blue
authors.affiliation: Department of Radiology, UC San Diego Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: David R
authors.initials: DR
authors.lastname: Vera
authors.affiliation: Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210; larry.schlesinger@osumc.edu.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
mesh_terms: D002232:Carbocyanines / Q000737:chemistry; D002478:Cells, Cultured; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008351:Mannans / Q000737:chemistry / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D019275:Radiopharmaceuticals / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D016284:Technetium Tc 99m Pentetate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D002232:Carbocyanines; D003911:Dextrans; D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface; C089187:cyanine dye 3; C431884:technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran; D016284:Technetium Tc 99m Pentetate