ID 113045
著者
Jin, Kideok Johns Hopkins University
Song, Hong Johns Hopkins University
Park, Sunju Johns Hopkins University
Huso, David L. Johns Hopkins University
Zhang, Zhe Johns Hopkins University
Liangfeng, Han Johns Hopkins University
Zhu, Charles Rutgers University
Bruchertseifer, Frank Institute for Transuranium Elements
Morgenstern, Alfred Institute for Transuranium Elements
Sgouros, George Johns Hopkins University
Sukumar, Saraswati Johns Hopkins University
キーワード
intraductal
radioimmunotherapy
trastuzumab
ductal carcinoma in situ
breast cancer
資料タイプ
学術雑誌論文
抄録
The standard treatment for ductal carcinoma in situ (DCIS) of the breast is surgical resection, followed by radiation. Here, we tested localized therapy of DCIS in mice using the immunoconjugate 225Ac linked-trastuzumab delivered through the intraductal (i.duc) route. Trastuzumab targets HER-2/neu, while the alpha-emitter 225Ac (half-life, 10 days) delivers highly cytotoxic, focused doses of radiation to tumors. Systemic 225Ac, however, elicits hematologic toxicity and at high doses free 213Bi, generated by its decay, causes renal toxicity. I.duc delivery of the radioimmunoconjugate could bypass its systemic toxicity. Bioluminescent imaging showed that the therapeutic efficacy of intraductal 225Ac-trastuzumab (10-40 nCi per mammary gland; 30-120 nCi per mouse) in a DCIS model of human SUM225 cancer cells in NSG mice was significantly higher (p<0.0003) than intravenous (120 nCi per mouse) administration, with no kidney toxicity or loss of body weight. Our findings suggest that i.duc radioimmunotherapy using 225Ac-trastuzumab deserves greater attention for future clinical development as a treatment modality for early breast cancer.
掲載誌名
Oncotarget
ISSN
19492553
出版者
Impact Journals, LLC
7
22
開始ページ
33306
終了ページ
33315
発行日
2016-04-23
備考
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)(https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
病院