In vivo biodistribution of a humanized anti-Lewis Y monoclonal antibody (hu3S193) in MCF-7 xenografted BALB/c nude mice

• Published in: Cancer research (Chicago, Ill.) Ill.), 2000-09, Vol.60 (17), p.4804-4811
• Main Authors: CLARKE, Kerrie, LEE, Fook-Thean, BRECHBIEL, Martin W, SMYTH, Fiona E, OLD, Lloyd J, SCOTT, Andrew M
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - diagnostic imaging; Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Antineoplastic agents; Autoradiography; Biological and medical sciences; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Drug Stability; Female; Half-Life; Humans; Immunohistochemistry; Indium Radioisotopes - pharmacokinetics; Iodine Radioisotopes - pharmacokinetics; Isotope Labeling; Lewis Blood-Group System - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Pharmacology. Drug treatments; Radionuclide Imaging; Tissue Distribution; Transplantation, Heterologous; Tumor Cells, Cultured; Yttrium Radioisotopes - pharmacokinetics
• ISSN: 0008-5472; 1538-7445

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.