Therapy and Imaging of Pancreatic Carcinoma Xenografts with Radioiodine‐labeled Chimeric Monoclonal Antibody A10 and Its Fab Fragment

Open Access
Publisher Website
Google Scholar
Abstract
Recombinant mouse/human chimeric monoclonal antibody A10 (ch‐A10) and its Fab fragment (ch‐Fab) react with carcinoembryonic antigen on various gastrointestinal carcinomas. We performed biodistribution studies with 125I‐labeled ch‐Al0 and ch‐Fab in an antigen‐positive human pancreatic carcinoma (BxPC‐3) xenograft model. We also evaluated the anti‐tumor effect of 131I‐labeled ch‐Al0 and studied the detection of BxPC‐3 xenografts with 123I‐labeIed ch‐Fab in whole body scintigraphy. In comparative biodistribution studies, the tumor uptake of 125I‐labeled ch‐Al0 was significantly greater than that of 125I‐labeIed ch‐Fab 24 h post‐injection. However, the tumor‐to‐blood ratio was 46.8 for ch‐Fab at 24 h post‐injection, while it was only 1.4 for ch‐Al0. Microautoradiography studies showed that ch‐Fab penetrated more uniformly into the tumor nodules than did ch‐Al0. In mice given a therapeutic dose of 131I‐labeled ch‐AlO, a significant inhibition of tumor growth was seen, while control I31l‐labeled human IgG did not affect tumor growth. Leukocyte toxicity was observed within 3 weeks after injection of 131I‐labeled ch‐Al0, but leukocyte counts recovered to normal levels at 8 weeks post‐injection. In whole‐body scintigraphy, clear and rapid tumor imaging was obtained with 200 (Ci of 123I‐labeled ch‐Fab 24 h post‐injection. These results suggest that radioiodine‐labeled chimeric A10 antibodies could potentially be useful candidates for radioimmunotherapy and radio‐immunodetection of pancreatic carcinomas.