Abstract | PURPOSE: EXPERIMENTAL DESIGN: Immunodeficient nude mice bearing established HER2/neu-positive MDA-MB-361/DYT2 tumors treated with N-succinimidyl N-(4-[(211)At]astatophenethyl)succinamate ((211)At-SAPS)-C6.5 diabody. Additional cohorts of mice were treated with (211)At-SAPS T84.66 diabody targeting the carcinoembryonic antigen or (211)At-SAPS on a diabody specific for the Müllerian inhibiting substance type II receptor, which is minimally expressed on this tumor cell line. RESULTS: A single i.v. injection of (211)At-SAPS C6.5 diabody led to a 30-day delay in tumor growth when a 20 muCi dose was administered and a 57-day delay in tumor growth (60% tumor-free after 1 year) when a 45 muCi dose was used. Treatment of mice bearing the same tumors with (211)At-SAPS T84.66 diabody at the same doses led to a delay in tumor growth, but no complete responses, likely due to substantially lower expression of this antigen on the MDA-MB-361/DYT2 tumors. In contrast, a dose of 20 muCi of (211)At-SAPS on the anti-Müllerian-inhibiting substance type II receptor diabody did not affect tumor growth rate, demonstrating specificity of the therapeutic effect. CONCLUSIONS:
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Authors | Matthew K Robinson, Calvin Shaller, Kayhan Garmestani, Paul S Plascjak, Kathryn M Hodge, Qing-An Yuan, James D Marks, Thomas A Waldmann, Martin W Brechbiel, Gregory P Adams |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 14
Issue 3
Pg. 875-82
(Feb 01 2008)
ISSN: 1078-0432 [Print] United States |
PMID | 18245551
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Peptide Fragments
- Erbb2 protein, mouse
- Receptor, ErbB-2
- Astatine
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Topics |
- Animals
- Astatine
(therapeutic use)
- Breast Neoplasms
(radiotherapy)
- Female
- Humans
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred ICR
- Mice, Nude
- Mice, SCID
- Peptide Fragments
- Radioimmunotherapy
- Receptor, ErbB-2
(immunology)
- Tissue Distribution
- Transplantation, Heterologous
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