Pharmacokinetics, biodistribution and tumor localization of two anti-human B-cell chronic lymphocytic leukemia monoclonal antibodies and their F(ab)'2 fragments in a xenograft model.
We investigated the pharmacokinetics, biodistribution and tumor localization of intravenously injected Dal B01 and Dal B02, two monoclonal antibodies (MoAbs) directed against tumor associated antigens on human chronic lymphocytic leukemia (CLL) B cells, and their F(ab)'2 fragments in nude mice bearing xenografts of the human B cell CLL line D10-1. More of the percentages of the injected dose (% ID) of these two MoAbs and their F(ab)'2 fragments specifically localized in the tumor xenografts than in normal tissues. Compared to intact MoAbs, their F(ab)'2 fragments had lower % ID in tumors and were cleared from circulation faster. Well-defined tumor images were obtained at 24 and 48 h after administration of [131I]Dal B02 F(ab)'2 fragment and at 96-192 h after administration of [131I]Dal B02. A comparison between intravenous and intraperitoneal routes of administration of [131I]Dal B02 did not reveal any difference in the localization of % ID in tumor or normal tissues.
Zhu
Z
Z
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ghose
T
T
Iles
S
S
Yang
C
C
Lee
S H
SH
Fernandez
L A
LA
Lee
C L
CL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D001345:Autoradiography; D004195:Disease Models, Animal; D005260:Female; D015902:Gamma Cameras; D006801:Humans; D007128:Immunoglobulin Fragments / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D000922:Immunotoxins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D007457:Iodine Radioisotopes