Targeting of an anti-CR3 (CD11b/CD18) monoclonal antibody to spleen but not brain, in vivo in mice.
Monoclonal antibodies against the complement receptor CR3 (CD11b/CD18) interfere with leukocyte recruitment and have potential as immunotherapeutics. However, the pharmacokinetic behavior as well as the tissue uptake and organ distribution of antibodies against CR3 are largely unknown. The present study examined the organ uptake (brain, heart, lung, liver, kidney, and spleen) and the pharmacokinetics of the anti-CR3 antibody, 5C6, and its isotype control, rat IgG2b, in mice. The clearance of 5C6 was biexponential with half-times of 6.4 +/- 2.4 min and 2.9 +/- 0.9 hours. The clearance of the IgG2b was also biexponential with half-times of 27.0 +/- 12.8 minutes and 36.1 +/- 1.2 hours. The uptake of 5C6 by the brain was negligible even 24 hours after injection, and there was only a minor uptake by heart and kidney. The uptake of 5C6 by spleen at 2 hours after injection was 44.7 +/- 26.6% of injected dose per gram tissue, and this value was 60-fold greater than the uptake by liver at 2 hours. The early and selective uptake by spleen indicates that 5C6 may be utilized for delivery of therapeutics to this organ.
Skarlatos
S
S
Department of Medicine, UCLA School of Medicine 90024, USA.
Pardridge
W M
WM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems; D006207:Half-Life; D007074:Immunoglobulin G / Q000276:immunology; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000187:drug effects*; D013154:Spleen / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011951:Receptors, Complement