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- Title:
213Bi-radioimmunotherapy defeats early-stage disseminated gastric cancer in nude mice.
- Document type:
- Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
- Author(s):
- Beck, R; Seidl, C; Pfost, B; Morgenstern, A; Bruchertseifer, F; Baum, H; Schwaiger, M; Senekowitsch-Schmidtke, R
- Abstract:
- The alpha-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 alpha-emitter 213Bi is a promising concept for treatment of early peritoneal carcinomatosis.
- Journal title abbreviation:
- Cancer Sci
- Year:
- 2007
- Journal volume:
- 98
- Journal issue:
- 8
- Pages contribution:
- 1215-22
- Language:
- eng
- Fulltext / DOI:
- doi:10.1111/j.1349-7006.2007.00525.x
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/17561973
- Print-ISSN:
- 1347-9032
- TUM Institution:
- Institut für Klinische Chemie und Pathobiochemie; Klinik und Poliklinik für Nuklearmedizin
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