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.
Written by:
Tan Z, Chen P, Schneider N, Glover S, Cui L, Torgue J, Rixe O, Spitz HB, Dong Z Are you the author?
Division of Hematology-Oncology, University of Cincinnati Cancer Institute, Cincinnati, OH 45267, USA.
Reference: Int J Oncol. 2012 Jun;40(6):1881-8.
doi: 10.3892/ijo.2012.1357
PubMed Abstract
PMID: 22322558