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. TCMC-Trastuzumab was radiolabeled with 212Pb. The 
212Pb-trastuzumab generated from the procedure was intact and had high binding 
affinity with a dissociation constant (of 3.9±0.99 nM. PC-3MM2 cells, which 
expressed a lower level of HER2 both in culture and in tumors, were used in 
therapy studies. A single intravenous 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 glutamic pyruvic transaminase (SGPT), 
blood urea nitrogen (BUN), hematological profiles, and histological morphology 
of several major organs of tumor-bearing mice. These findings suggest that a 
systemic delivery of 212Pb-trastuzumab could be an effective modality for 
management of advanced human prostate cancer.