Significant systemic therapeutic effects of high-LET immunoradiation             by 212Pb-trastuzumab against prostatic tumors of androgen-independent human prostate             cancer in mice.
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.
Division of Hematology-Oncology, University of Cincinnati Cancer                     Institute, Cincinnati, OH 45267, USA.
Zongqing
Z
Tan
Pingping
P
Chen
Nathan
N
Schneider
Samuel
S
Glover
Lingling
L
Cui
Julien
J
Torgue
Olivier
O
Rixe
Henry B
HB
Spitz
Zhongyun
Z
Dong
D000728:Androgens / Q000502:physiology*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007856:Lead Radioisotopes / Q000627:therapeutic use*; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab; D047368:Tumor Burden / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D007856:Lead Radioisotopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human