In vivo biodistribution of a humanized anti-Lewis Y monoclonal antibody (hu3S193) in MCF-7 xenografted BALB/c nude mice.
The biodistribution characteristics of a humanized anti-Lewis(y) antibody (hu3S193) radiolabeled to three radioisotopes, 125I, 111In, and 90Y, were examined in a BALB/c nude mouse xenograft model of breast cancer. The immunoreactivity of both 125I- and 111In-bound hu3S193 exceeded 50% and was 20% for 90Y. In vivo, labeled antibody was shown by gamma camera imaging and immunohistochemical and autoradiographic techniques to localize to Lewis(y)-expressing breast xenografts with minimal normal tissue uptake. Maximal radioisotope uptake peaked at 48 h for all three isotopes; however, the percentage of injected dose/gram and tumor retention were greater for 111In- and 90Y-bound antibody than for 125I-bound antibody. Although immunoreactivity of 111In- and 125I-labeled hu3S193 in serum was stable over a 5-day period, the amount of unlabeled 111In in serum was lower than 125I, which together with higher tumor uptake indicates better retention of 111In-labeled hu3S193 and catabolites within the tumor cells. Superior tumor uptake and retention of 111In-labeled hu3S193 and similar blood clearance compared with 125I-labeled hu3S193, suggest that radiometals are the preferred radioisotope for this antibody-antigen system. Humanized 3S193 is a promising new construct for the targeting and potential therapy of Lewis(y)-expressing tumors.
Clarke
K
K
Tumour Targeting Program, Ludwig Institute for Cancer Research, Austin, Australia.
Lee
F T
FT
Brechbiel
M W
MW
Smyth
F E
FE
Old
L J
LJ
Scott
A M
AM
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D001345:Autoradiography; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D004355:Drug Stability; D005260:Female; D006207:Half-Life; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D015021:Yttrium Radioisotopes