Radiolocalization of xenografted human lung cancer with monoclonal antibody 8 in nude mice

A monoclonal antibody (MAb) 8 [immunoglobulin G3 (IgG3)], directed against a Mr 48,000 human lung cancer-associated antigen, was radiolabeled with either 125I or 131I, and its biodistribution was studied in nude mice bearing human lung cancer (TKB-2) over a 7-day period. 125I-labeled MAb 8 increased its binding to the tumor during the period, while the binding of 125I-labeled control IgG3 declined after initial uptake. At Day 7, percentages of injected dose of 125I-labeled MAb 8 bound to the tumor rose to 7.4%, which was a 4.4-fold increase from Day 1 and 16-fold binding of 125I-labeled control IgG3 at the same day. Tumor:blood ratios became 2.7:1 at Day 7, and tumor:liver, tumor:spleen, and tumor:kidney ratios were more than 9:1. Normal organs showed no significant uptake of 125I-labeled MAb 8, compared with those of 125I-labeled control IgG3. A clear image of the xenografted tumor was obtained at Day 5, and it further improved at Day 7, when 60% of whole body radioactivity was localized to the tumor. Autoradiography of the mouse with tumor confirmed the excellent localization of 125I-labeled MAb 8 to the tumor, although the radioactivity of the tumor was not uniformly distributed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that most of the radioactivity was present at the tumor in the form of degraded immunoglobulin. MAb 8 has a potential usefulness in the diagnosis and treatment of lung cancer.