Cytotoxicity of PAI2, C595 and Herceptin vectors labeled with the alpha-emitting radioisotope Bismuth-213 for ovarian cancer cell monolayers and clusters

The vectors PAI2, C595 and Herceptin target the membrane-bound uPA, MUC1 and HER2 antigens expressed by cancer cells, respectively. The expression of these receptors was tested in the ovarian cancer cell line OVCAR-3; MUC-1 was strongly expressed (3+), uPA moderately expressed (2+), but HER2 was neg...

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Bibliographic Details
Published in:Cancer letters 2006-03, Vol.234 (2), p.176-183
Main Authors: Song, Yan J., Qu, Chang F., Rizvi, Syed M.A., Li, Yong, Robertson, G., Raja, Chand, Morgenstern, Alfred, Apostolidis, Christos, Perkins, Alan C., Allen, Barry J.
Format: Article
Language:English
Subjects:
Alpha Particles - therapeutic use
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal, Humanized
Apoptosis
Bismuth - administration & dosage
Bismuth-213
Breast cancer
Cancer therapies
Cytotoxicity
Drug Delivery Systems - methods
Female
Flow cytometry
HER2
Humans
Immunohistochemistry
Medical prognosis
MUC1
Mucin-1 - metabolism
Ovarian cancer
Ovarian cancer cell line
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
Plasminogen Activator Inhibitor 2 - administration & dosage
Proteins
Radioimmunotherapy
Radioisotopes - administration & dosage
Radioisotopes - metabolism
Receptor, ErbB-2
Spheroids, Cellular - drug effects
Trastuzumab
Tumor Cells, Cultured
uPA
Urokinase-Type Plasminogen Activator - metabolism
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Summary:The vectors PAI2, C595 and Herceptin target the membrane-bound uPA, MUC1 and HER2 antigens expressed by cancer cells, respectively. The expression of these receptors was tested in the ovarian cancer cell line OVCAR-3; MUC-1 was strongly expressed (3+), uPA moderately expressed (2+), but HER2 was negative (−). The α-emitting radionuclide Bismuth-213 was chelated with these targeting vectors to form alpha conjugates (ACs), the cytotoxicity of which were tested with OVCAR-3 cells. The PAI2 and C595 ACs are highly cytotoxic to the ovarian monolayer cancer cells and cell clusters in a concentration-dependent fashion and cause morphological changes of treated cancer cells, inducing apoptosis. These ACs are potential candidates for the control of ovarian cancer at the minimum residual disease (MRD) stage.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2005.03.060