title: Optical molecular imaging of lymph nodes using a targeted vascular contrast agent.
abstract: We develop a highly specific antibody-dye conjugate for optical imaging of peripheral lymph nodes. The contrast agent consists of the monoclonal antibody recognizing endothelial ligands for the lymphocyte homing receptor L-selectin, MECA-79, and a near-infrared (near-IR) fluorescent indotricarbocyanine dye. The targeting and biodistribution behavior of MECA-79 is studied after radio-iodination and intravenous injection into mice demonstrating specific uptake in lymph nodes and accumulation in high endothelial venules (HEV). After conjugation of MECA-79 with indotricarbocyanine dye, the fluorescence imaging properties of the MECA-79 dye conjugate are examined by intravenous injection in nude mice and laser-induced fluorescence whole-body imaging in vivo. The MECA-79 antibody-dye conjugate accumulates in peripheral lymph nodes, whereas an isotype antibody-dye conjugate does not. Specific lymph node near-IR fluorescent signals become detectable within minutes after injection, and stable imaging persists for more than 24 h. The results demonstrate that vascular targeting of endothelial expression of glyocproteins is feasible to visualize the accumulation of near-IR fluorescent MECA-79 in lymph nodes, making this technology potentially useful to characterize processes of inflammation.
authors.affiliation: Schering AG, Research Laboratories, D-13342 Berlin, Germany. kai.licha@schering.de
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.forename: Niels
authors.initials: N
authors.lastname: Debus
authors.forename: Sonja
authors.initials: S
authors.lastname: Emig-Vollmer
authors.forename: Birte
authors.initials: B
authors.lastname: Hofmann
authors.forename: Michael
authors.initials: M
authors.lastname: Hasbach
authors.forename: Dietger
authors.initials: D
authors.lastname: Stibenz
authors.forename: Sabine
authors.initials: S
authors.lastname: Sydow
authors.forename: Michael
authors.initials: M
authors.lastname: Schirner
authors.forename: Bernd
authors.initials: B
authors.lastname: Ebert
authors.forename: Diethard
authors.initials: D
authors.lastname: Petzelt
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
authors.forename: Wolfhard
authors.initials: W
authors.lastname: Semmler
authors.forename: Rudolf
authors.initials: R
authors.lastname: Tauber
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000187:drug effects / Q000493:pharmacokinetics; D000954:Antigens, Surface / Q000378:metabolism*; D003287:Contrast Media; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes; D008198:Lymph Nodes / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D013055:Spectrophotometry, Infrared / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003287:Contrast Media; D005456:Fluorescent Dyes; C069886:L-selectin counter-receptors; D008565:Membrane Proteins