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, MUCl 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.