Comparative biodistribution and radioimmunotherapy of monoclonal antibody rs7 and its f(ab′) 2 in nude mice bearing human tumor xenografts

Background . RS7 is a murine monoclonal antibody immunoglobulin G 1 with pancarcinoma reactivity, which was raised against human squamous cell carcinoma of the lung. To optimize the use of monoclonal antibody RS7 as a carrier of radionuclides for tumor targeting and therapeutic applications, whole RS7 immunoglobulin G and its F(ab′) 2 fragment were radiolabeled, and their biodistribution and effectiveness as radioimmunotherapeutic agents in nude mice bearing established human tumor xenografts were evaluated. The contributions of the tumor model, monoclonal antibody form (fragment vs. intact), radioisotope ( 131 I, 111 In, 90 Y, and 188 Re), and antigen target were evaluated. Methods . Cumulative absorbed radiation doses were calculated from biodistribution data, and doses were normalized to blood to estimate expected relative toxicities. Two tumor models expressing different levels of RS7‐antigen were studied: ME180, a cervical carcinoma cell line, and Calu‐3, an adenocarcinoma of the lung cell line. In addition, the therapeutic effectiveness of 131 I‐RS7‐F(ab′) 2 was compared to that of 131 I‐RS7‐IgG. Results and Conclusions . Doses delivered to tumor (normalized to blood) calculated for 131 I‐RS7‐F(ab′) 2 and 90 Y‐RS7‐IgG were 4.7 times and 1.8 times greater, respectively, than 13 I‐RS7‐IgG, and therefore would be expected to yield greater therapeutic efficacy when equitoxic doses are administered. This expectation was confirmed in the radioimmunotherapy study with 131 I‐RS7‐F(ab′) 2 . At equivalent absorbed dose to tumor, 131 I‐RS7‐F(ab′) 2 was found to effect a slightly longer suppression of tumor growth than the intact 131 I‐RS7 IgG, and a 50% dose escalation yielded tumor regression for a prolonged period with the fragment, whereas a similar 50% dose escalation with 131 I‐RS7‐IgG could not be tolerated. Cancer 1994; 73:816–23.