Cytotoxicity of PAI2, C595 and Herceptin vectors labeled with the alpha-emitting radioisotope Bismuth-213 for ovarian cancer cell monolayers and clusters
Received 16 December 2004; received in revised form 12 March 2005; accepted 22 March 2005.
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 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.
aCentre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, Kogarah, 2217 NSW, Australia
bUniversity of New South Wales, NSW 2052, Australia
cDepartment of Genecology, St George Hospital, NSW Australia
dEuropean Commission, Joint Research Centre, Institute for Transuranium Elements, 76125 Karlsruhe, Germany
eDepartment of Medical Physics, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK
Corresponding author. Address: Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, Kogarah, 2217 NSW, Australia. Tel.: +61 2 9350 3855; fax: +61 2 9350 2316.
ABSTRACT