Abstract 5713: Significant systemic therapeutic effects of high-LET immunoradiation by 212Pb-Trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice

Abstract

Abstract Purpose The purpose of this study was to determine therapeutic effects and systemic toxicity of 212Pb-Trastuzumab in an orthotopic model of human prostate cancer cells in nude mice. Experimental Design TCMC-Trastuzumab was radiolabeled with 212Pb. The activity and integrity of 212Pb-Trastuzumab was confirmed by a competitive binding assay and SDS-PAGE analysis. Therapeutic effects were determined in an orthotopic model of human prostate cancer in nude mice. Body weight, blood cell counts, serum alanine transaminase (ALT), blood urea nitrogen (BUN), and tissue histology were examined to evaluate systemic toxicity of 212Pb-Trastuzumab therapy. Results The 212Pb-Trastuzumab generated from the procedure was intact and had high binding affinity with a dissociation constant (Kd) of 3.9 ± 0.99 nM. PC-3MM2 cells, which expressed relatively a lower level of Her2 both in culture and in tumors, were used in the study. A single injection of 212Pb-Trastuzumab reduced tumor growth by 60-80%, reduced aortic lymph node metastasis, and prolonged the survival of tumor-bearing mice. Treatment with 212Pb-Trastuzumab did not cause significant changes in body weight, serum SGPT and BUN, hematological profiles, and histological morphology of several major organs of tumor-bearing mice. Conclusion The data presented in this report demonstrated that the 212Pb-Trastuzumab therapy did not cause significant systemic toxicity and was very effective in retarding tumor growth and prolonging survival of mice bearing tumors that express very low levels of Her2. These findings suggest that 212Pb-Trastuzumab, used alone or in combination with other means, could be an effective modality for management of advanced human prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5713. doi:1538-7445.AM2012-5713