Optical molecular imaging of lymph nodes using a targeted vascular contrast agent.
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.
Licha
Kai
K
Schering AG, Research Laboratories, D-13342 Berlin, Germany. kai.licha@schering.de
Debus
Niels
N
Emig-Vollmer
Sonja
S
Hofmann
Birte
B
Hasbach
Michael
M
Stibenz
Dietger
D
Sydow
Sabine
S
Schirner
Michael
M
Ebert
Bernd
B
Petzelt
Diethard
D
Bührer
Christoph
C
Semmler
Wolfhard
W
Tauber
Rudolf
R
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
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003287:Contrast Media; D005456:Fluorescent Dyes; C069886:L-selectin counter-receptors; D008565:Membrane Proteins