This Article Full Text Full Text (PDF) All Versions of this Article: 0008-5472.CAN-09-1828v1 69/23/8941    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Song, H. Articles by Sgouros, G. PubMed PubMed Citation Articles by Song, H. Articles by Sgouros, G.

Radioimmunotherapy of Breast Cancer Metastases with -Particle Emitter ²²⁵Ac: Comparing Efficacy with ²¹³Bi and ⁹⁰Y

¹ Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, and ² Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland and ³ Institute for Transuranium Elements, Karlsruhe, Germany

Requests for reprints: George Sgouros, Johns Hopkins University School of Medicine, Cancer Research Building II, Room 4M.61, 1550 Orleans Street, Baltimore, MD 21231. Phone: 410-614-0116; Fax: 413-487-3753; E-mail: gsgouros{at}jhmi.edu.

-Particles are suitable to treat cancer micrometastases because of their short range and very high linear energy transfer. -Particle emitter ²¹³Bi-based radioimmunotherapy has shown efficacy in a variety of metastatic animal cancer models, such as breast, ovarian, and prostate cancers. Its clinical implementation, however, is challenging due to the limited supply of ²²⁵Ac, high technical requirement to prepare radioimmunoconjugate with very short half-life (T_1/2 = 45.6 min) on site, and prohibitive cost. In this study, we investigated the efficacy of the -particle emitter ²²⁵Ac, parent of ²¹³Bi, in a mouse model of breast cancer metastases. A single administration of ²²⁵Ac (400 nCi)–labeled anti-rat HER-2/neu monoclonal antibody (7.16.4) completely eradicated breast cancer lung micrometastases in 67% of HER-2/neu transgenic mice and led to long-term survival of these mice for up to 1 year. Treatment with ²²⁵Ac-7.16.4 is significantly more effective than ²¹³Bi-7.16.4 (120 µCi; median survival, 61 days; P = 0.001) and ⁹⁰Y-7.16.4 (120 µCi; median survival, 50 days; P < 0.001) as well as untreated control (median survival, 41 days; P < 0.0001). Dosimetric analysis showed that ²²⁵Ac-treated metastases received a total dose of 9.6 Gy, significantly higher than 2.0 Gy from ²¹³Bi and 2.4 Gy from ⁹⁰Y. Biodistribution studies revealed that ²²⁵Ac daughters, ²²¹Fr and ²¹³Bi, accumulated in kidneys and probably contributed to the long-term renal toxicity observed in surviving mice. These data suggest ²²⁵Ac-labeled anti–HER-2/neu monoclonal antibody could significantly prolong survival in HER-2/neu–positive metastatic breast cancer patients. [Cancer Res 2009;69(23):8941–8]

Key Words: -particle • ²²⁵Ac • ²¹³Bi • radioimmunotherapy • metastasis • rat HER-2/neu