Document Detail


Embryo-Fetal Transfer of Bevacizumab (Avastin) in the Rat Over the Course of Gestation and the Impact of Neonatal Fc Receptor (FcRn) Binding.
MedLine Citation:
PMID:  22969064     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: There is concern about embryo-fetal exposure to antibody-based biopharmaceuticals based on the increase of such therapies being prescribed to women of childbearing potential. Therefore, there is a desire to better characterize embryo-fetal exposure of these molecules. The pregnant rat is a standard model for evaluating the potential consequences of exposure but placental transfer of antibody-based biopharmaceuticals is not well understood in this model. METHODS: The relative embryo-fetal distribution of an antibody-based biopharmaceutical was evaluated in the rat. Bevacizumab (Avastin) was chosen as a tool antibody since it does not have significant target binding in the rat that might influence embryo-fetal biodistribution. Avastin was labeled with a fluorescent dye, characterized, and injected into pregnant rats at different gestation ages. Labeled Avastin in fetal tissues was visualized ex vivo using an IVIS 200 (Caliper, A PerkinElmer Company, Alameda, CA). RESULTS: Avastin localized to the fetus as early as 24-hr post intravenous injection of the dam, and was taken up by the fetus in a dose-dependent manner. Avastin was detectable in the developing embryo as early as gestation day 13 and continued to be transferred until the end of gestation. Fetal transfer of Avastins mutated in the portion of the antibody that binds the neonatal Fc receptor (FcRn) was tested in late gestation and was found to correlate with affinities of the mutant Avastin antibody to FcRn. CONCLUSIONS: The novel application of this imaging technology was used to characterize the onset and duration of Avastin maternal-fetal transfer in rats and the importance of FcRn binding.
Authors:
Mitchell Thorn; Nicole Piche-Nicholas; Donald Stedman; Scott W Davenport; Ning Zhang; Mark Collinge; Christopher J Bowman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-11
Journal Detail:
Title:  Birth defects research. Part B, Developmental and reproductive toxicology     Volume:  -     ISSN:  1542-9741     ISO Abbreviation:  Birth Defects Res. B Dev. Reprod. Toxicol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101155115     Medline TA:  Birth Defects Res B Dev Reprod Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Wiley Periodicals, Inc.
Affiliation:
Drug Safety Research & Development, Pfizer, Inc., Groton, Connecticut.
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