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: Abul K Azad, Murugesan V S Rajaram, Wendy L Metz, Frederick O Cope, Michael S Blue, David R Vera, Larry S Schlesinger
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 195 Issue 5 Pg. 2019-29 (Sep 01 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 26202986 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• Carbocyanines
• Dextrans
• Lectins, C-Type
• Mannans
• Mannose Receptor
• Mannose-Binding Lectins
• Radiopharmaceuticals
• Receptors, Cell Surface
• cyanine dye 3
• technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran
• Technetium Tc 99m Pentetate

Topics

• Carbocyanines (chemistry)
• Cells, Cultured
• Dextrans (chemistry, metabolism)
• Flow Cytometry
• HEK293 Cells
• Humans
• Immunohistochemistry
• Lectins, C-Type (genetics, metabolism)
• Lymph Nodes (metabolism)
• Macrophages (metabolism)
• Mannans (chemistry, metabolism)
• Mannose Receptor
• Mannose-Binding Lectins (genetics, metabolism)
• Microscopy, Confocal
• Molecular Structure
• Neoplasms (diagnosis, metabolism)
• Protein Binding
• RNA Interference
• Radiopharmaceuticals (metabolism)
• Receptors, Cell Surface (genetics, metabolism)
• Sentinel Lymph Node Biopsy (methods)
• Technetium Tc 99m Pentetate (analogs & derivatives, chemistry, metabolism)