Microdistribution of specific rat monoclonal antibodies to mouse tissues and human tumor xenografts.

摘要: Detailed evaluations of the microdistribution 125I-labeled monoclonal antibodies (MoAbs) to normal tissue antigens were conducted in BALB/c mice. MoAb 273-34A, which binds a target molecule on lumenal surface lung endothelial cells, localizes quickly and efficiently throughout vasculature. 133-13A, an antigen macrophage-like cells expressed nearly equal amounts lung, liver, spleen, most spleen less well liver lung. The 133-13A is consistent with distribution these organs, but more diffuse observed, indicating poor access antigen-positive alveolar macrophages. These findings are hypothesis that tight endothelium (lung) represents significant barrier extravasation into while fenestrated (spleen) sinusoidal (liver) easily penetrated. In human tumor bearing nu/nu mice, beta 4 alpha 6 subunits integrin was studied. MoAbs do not cross-react murine integrins thus tumor-specific mouse model. Localization 450-11A, reacts intercellular domain integrin, very weak diffuse. All extracellular domains (mouse 450-9D, 450-30A1, rat 439-9B) localize tumor. Microdistribution 3 different tumors nonuniform heavy near blood vessels, whereas as determined by immunoperoxidase shows much uniform pattern tumors. experiments 439-9B F(ab')2, changed. Gross doses percent injected dose per g at 48 h did vary significantly (P greater than 0.1) up 500 micrograms/mouse, active recovered comparable serum from animals all doses. contrast, high low At 100 perivascular obtained, micrograms/mouse distributed evenly data indicate penetrate deeply portions distant vessels.(ABSTRACT TRUNCATED AT 400 WORDS)