Abstract |
These studies demonstrate the feasibility of targeted therapy for the treatment of disseminated peritoneal disease using (212)Pb-labeled Herceptin as an in vivo generator of (212)Bi. In vitro studies compare the potential of the bismuth radioisotopes, (213)Bi and (212)Bi, to that of (212)Pb. Overall, (212)Pb results in a higher therapeutic index than either bismuth radioisotope, requiring lower radioactivity (microCi) for effective cytotoxic response. A pilot radioimmunotherapy (RIT) experiment treating mice bearing 5 d LS-174T intraperitoneally (i.p.) xenografts determined a maximum tolerated dose (MTD) of 20-40 microCi with i.p. administration. A specific dose response was observed and 10 microCi was selected as the effective operating dose for future experiments. Median survival of tumor-bearing mice receiving 10 microCi increased from 19 to 56 days (p = 0.008). The efficacy of (212)Pb-Herceptin was also assessed in a human pancreatic carcinoma xenograft (Shaw; i.p.) animal model previously reported as unresponsive to 213Bi-Herceptin (p = 0.002). Multiple dosing of (212)Pb-Herceptin was evaluated in both animal models. The median survival of mice bearing 3 d LS-174T i.p. xenografts increased to 110 days, with up to 3 doses of (212)Pb-Herceptin given at approximately monthly intervals; however, there was no evidence of a correlation with the second and third doses (p = 0.98). No improvement in median survival was noted with a similar regimen in the Shaw xenograft model.
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Authors | Diane E Milenic, Kayhan Garmestani, Erik D Brady, Paul S Albert, Dangshe Ma, Alia Abdulla, Martin W Brechbiel |
Journal | Cancer biotherapy & radiopharmaceuticals
(Cancer Biother Radiopharm)
Vol. 20
Issue 5
Pg. 557-68
(Oct 2005)
ISSN: 1084-9785 [Print] United States |
PMID | 16248771
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Immunoconjugates
- Lead Radioisotopes
- Receptor, ErbB-2
- Trastuzumab
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Topics |
- Alpha Particles
- Animals
- Antibodies, Monoclonal
(chemistry)
- Antibodies, Monoclonal, Humanized
- Cell Line, Tumor
- Flow Cytometry
- Genes, erbB-2
- Humans
- Immunoconjugates
(chemistry)
- Lead Radioisotopes
- Maximum Tolerated Dose
- Mice
- Neoplasm Transplantation
- Peritoneal Diseases
(therapy)
- Radioimmunoassay
- Radioimmunotherapy
(methods)
- Receptor, ErbB-2
(immunology, metabolism)
- Time Factors
- Trastuzumab
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