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
ductal carcinoma in situ
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.
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