Summary Spheroids of a small-cell lung cancer (SCLC) cell line POC were used to evaluate the uptake and penetration of two antibodies recognising different SCLC antigens. Spheroids approximately 300-400 gm in diameter were incubated with 1 jig ml-"25I-labelled NY.3DI 1, an antibody which reacts with the cluster I group antigen (neural cell adhesion molecule; NCAM) and ['25I]SWAI 1, which binds to the cluster w4 antigen. The rate of uptake of both antibodies was similar; an initially rapid phase was seen during the first 8 h and maximum uptake occurred by 24 h. This increased to about 100 txm after 4 h incubation with I or 100 fig ml-' SWAI 1. The results with I lg mlh' NY.3D1 were similar, but in the presence of 100 jg ml-' NY.3DI I penetration into the spheroid was deep and diffuse. These results demonstrate a major concentration-dependent difference in the uptake and penetration of cluster I and cluster w4 antibodies in this spheroid model and they have implications for the selection of antibodies for targeted therapy of SCLC.
Summary The biodistribution of radiolabelled SWAl 1, a mouse monoclonal antibody recognising the cluster w4 group antigen associated with small cell lung cancer (SCLC) was studied in patients with SCLC. Five patients were injected intravenously with approximately 5 mCi of '31I conjugated to I mg of SWA II. The half-life of the radiolabel in blood was short but there was a prolonged second phase of clearance with a half-life of about 40 h. Tumour was detected by gamma camera imaging two patients. However, most of the whole body radioactivity was located in the bone marrow. At least 35% of the radioactivity in blood 18 h after injection was bound to circulating granulocytes and this probably accounted for the unusual biodistribution of the radiolabel in man. This study shows that the biodistribution of radiolabelled SWA 11 in man differs from human tumour xenograft models and that the antibody in unsuitable for targeting therapy to SCLC in man.
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