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|Title:||213Bi-radioimmunotherapy Defeats Early-stage Disseminated Gastric Cancer in Nude Mice|
|Authors:||BECK R.; SEIDL C.; PFOST B.; MORGENSTERN ALFRED; BRUCHERTSEIFER FRANK; BAUM M.; SCHWAIGER M.; SENEKOWITSCH-SCHMIDTKE R.|
|Citation:||CANCER SCIENCE vol. 98 no. 8 p. 1215-1222|
|Type:||Articles in periodicals and books|
|Abstract:||The a-emitter 213Bi is characterized by a high relative biological effectiveness. 213Bi-immunoconjugates targeting tumor-specific d9-E-cadherin have been proven to effectively kill tumor cells in a murine peritoneal carcinomatosis model. The aim of the present study was to optimize the efficacy of 213Bi-radioimmunotherapy for disseminated gastric cancer in a mouse model of early- and advanced-stage disease and to evaluate the long-term toxicity of 213Bi-immunoconjugates. For that purpose, nude mice were treated with different activities of 213Bi-d9 monoclonal antibody (MAb) targeting d9-E-cadherin or unspecific 213Bi-d8MAb at days 1 or 8 after inoculation of HSC45-M2 gastric cancer cells expressing mutant d9-E-cadherin. Therapeutic efficacy was evaluated by monitoring survival for up to 300 days. Long-term toxicity was evaluated by the survival of tumor-free mice injected with 213Bi-immunoconjugates, kidney function parameters and histopathological examination of kidneys. We showed that survival was significantly prolonged following treatment of mice with 213Bi-immunoconjugates (0.37¿22.2 MBq) at day 1 after tumor cell inoculation (P < 0.002). Therapy with 1.85 MBq of 213Bi-d9MAb was most successful, defeating early-stage disease in 87% of all cases. Treatment at day 8 after tumor cell inoculation was less efficient. Long-term nephrotoxicity could only be observed following application of 22.2 MBq of 213Bi-d9MAb, the highest activity applied in the therapy trials. As treatment with 1.85 MBq 213Bi-d9MAb showed excellent therapeutic efficacy without any signs of acute or chronic toxicity, radioimmunotherapy with the a-emitter 213Bi is a promising concept for treatment of early peritoneal carcinomatosis. (Cancer Sci 2007; 98: 1215¿1222)|
|JRC Institute:||Nuclear Safety and Security|
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