Antigenic expression of human metastatic prostate cancer cell lines for in vitro multiple-targeted α-therapy with 213Bi-conjugates

Abstract

Purpose Control of metastatic prostate cancer (CaP) is an elusive objective. Some 30% of patients with clinically localized CaP will develop micrometastatic disease. Defining the expression of tumor-associated antigens on CaP will enable appropriate selection of therapeutic targets. Methods and materials The expression of tumor-associated antigens on CaP cell lines (PC-3, DU 145, and LNCaP-LN3) was detected by immunohistochemistry and flow cytometry. Test and control α-conjugates were prepared using monoclonal antibodies, an inhibitor, plasminogen activator inhibitor type 2, that binds to the cell-membrane-bound protease, urokinase plasminogen activator, and a control protein labeled with 213Bi using standard methods. These were used singly or together against three different CaP cell lines in vitro. The cytotoxicity of the α-conjugates was assessed using the [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] (MTS) assay. Results The PC-3 and DU 145 cancer cell lines expressed antigens that bind monoclonal antibodies BLCA-38 and #394 (mouse anti-human urokinase plasminogen activator B-chain) but not J591. The LNCaP-LN3 cells bound J591 but not #394 or BLCA-38. For the PC-3, DU 145, and LNCaP-LN3 cell lines, multiple-targeted α-therapy combining four α-conjugates (one-quarter doses of each) gave D 0 (37% cell survival) values of 15, 17, and 27 μCi/mL compared with those of the controls of 272, 289, and 281 μCi/mL, respectively. Conclusion Metastatic prostate cancer-associated antigens recognized by multiple monoclonal antibodies are potential targets for α-therapy. Multiple-targeted α-therapy produced cytotoxicity specific to three CaP cell lines and may form the basis of treatment for micrometastatic CaP, overcoming the heterogeneity of expression of the targeted antigens.