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

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.