title: Cytotoxicity of PAI2, C595 and Herceptin vectors labeled with the alpha-emitting radioisotope Bismuth-213 for ovarian cancer cell monolayers and clusters.
abstract: 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 alpha-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.
authors.affiliation: Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, Kogarah, 2217 NSW, Australia.
authors.forename: Yan J
authors.initials: YJ
authors.lastname: Song
authors.forename: Chang F
authors.initials: CF
authors.lastname: Qu
authors.forename: Syed M A
authors.initials: SM
authors.lastname: Rizvi
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Robertson
authors.forename: Chand
authors.initials: C
authors.lastname: Raja
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.forename: Christos
authors.initials: C
authors.lastname: Apostolidis
authors.forename: Alan C
authors.initials: AC
authors.lastname: Perkins
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Allen
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001729:Bismuth / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018396:Mucin-1 / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000008:administration & dosage*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D018874:Spheroids, Cellular / Q000187:drug effects; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001729:Bismuth; D018396:Mucin-1; D017396:Plasminogen Activator Inhibitor 2; D011868:Radioisotopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014568:Urokinase-Type Plasminogen Activator