Biodistribution of monoclonal IgG1, F(ab')2, and Fab' in mice after intravenous injection. Comparison between anti-B cell (anti-Lyb8.2) and irrelevant (MOPC-21) antibodies.
Quantitative pharmacokinetic measurements of uptake and metabolism for two murine immunoglobulin G1 (IgG1) monoclonal antibodies (anti-Lyb8.2, MOPC-21) and their F(ab')2 and Fab' fragments were obtained following i.v. administration into C57BL/6 mice. Anti-Lyb8.2 antibody, reactive with the allelic Lyb8.2 murine B cell antigen, was labeled with 125I, and MOPC-21, an antibody with no known target antigen, was labeled with 131I. The two IgG or their fragments were co-injected, and all major organs were analyzed. Specific uptake of anti-Lyb8.2 IgG, F(ab')2, and Fab' was observed in the spleen with maximum peak values occurring at 1 to 2 hr. For MOPC-21, blood and organ kinetics was indicative of a nontargeted IgG molecule. The kidneys showed significant and rapid uptake of anti-Lyb8.2 and MOPC-21 Fab' fragments. This uptake by kidneys attenuated the maximum peak values of anti-Lyb8.2 Fab' in spleen. Multiexponential data fitting provided mean residence times (MRT) for each organ. The MRT for anti-Lyb8.2 in all organs were greater than those for its F(ab')2 and Fab' fragments. Only the kidneys showed greater MRT for Fab' than for F(ab')2. Blood, spleen, kidneys, and carcass exhibited substantial differences across fragments. When total body MRT for each fragment was compared with that of the respective parent IgG molecule, a progressive decline was observed. For MOPC-21, the decrease in total body MRT for F(ab')2 demonstrates the influence of the Fc portion of the molecule on IgG1 metabolism. This organ-by-organ data set may be pertinent to other monoclonal antibodies and their fragments and should help in optimizing delivery of these molecules to specific sites in vivo for immunologic and clinical purposes.
D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007518:Isoantibodies / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007518:Isoantibodies