Open AccessSignificant systemic therapeutic effects of high-LET immunoradiation by 212Pb-trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice
Author(s) -
Zhongyun Dong
Publication year - 2012
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2012.1357
Subject(s) - trastuzumab , prostate cancer , medicine , prostate , cancer , cancer research , lymph node , oncogene , metastasis , oncology , pathology , cell cycle , breast cancer
The purpose of this study was to determine therapeutic effects and systemictoxicity of 212Pb-trastuzumab in an orthotopic model of human prostate cancercells in nude mice. TCMC-Trastuzumab was radiolabeled with 212Pb. The 212Pb-trastuzumabgenerated from the procedure was intact and had high binding affinity with a dissociationconstant (of 3.9±0.99 nM. PC-3MM2 cells, which expressed a lower level of HER2both in culture and in tumors, were used in therapy studies. A single intravenousinjection of 212Pb-trastuzumab reduced tumor growth by 60-80%, reduced aorticlymph node metastasis, and prolonged the survival of tumor-bearing mice. Treatmentwith 212Pb-trastuzumab did not cause significant changes in body weight, serumglutamic pyruvic transaminase (SGPT), blood urea nitrogen (BUN), hematologicalprofiles, and histological morphology of several major organs of tumor-bearingmice. These findings suggest that a systemic delivery of 212Pb-trastuzumab couldbe an effective modality for management of advanced human prostate cancer.