Studies on the uptake mechanisms of 99mTc-labeled antibodies by liver tissue.
In this study, the roles of various protein alterations on the uptake of 99mTc labeled antibodies by isolated hepatocytes and by selected tissues in vivo were explored. In vitro binding studies of radiolabeled antibodies with hepatocytes demonstrated that the uptake of the radiolabel was a function of incubation duration and dose dependent. The uptake of 99mTc-antibodies could be inhibited by excess unlabeled F(ab')2 and Fc fragments as well as intact antibody. Liver uptake could not be reduced by a large insert pretreatment dose of unlabeled or aggregated antibody. These observations indicated that both Fab and Fc portions on the antibody molecule as well as the intact antibody may play important roles in the uptake of the radiolabel by liver tissue.
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Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Noujaim
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Sykes
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Peng
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D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007136:Immunoglobulins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013667:Technetium / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors
D000906:Antibodies; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007136:Immunoglobulins; D013667:Technetium