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Control of prostate cancer spheroid growth using 213 Bi‐labeled multiple targeted α radioimmunoconjugates
Author(s) -
Wang Jian,
Abbas Rizvi Syed M.,
Madigan Michele C.,
Cozzi Paul J.,
Power Carl A.,
Qu Chang F.,
Morgenstern Alfred,
Apostolidis Christos,
Russell Pamela J.,
Allen Barry J.,
Li Yong
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20502
Subject(s) - spheroid , lncap , cancer research , growth inhibition , prostate cancer , monoclonal antibody , flow cytometry , plasminogen activator , microbiology and biotechnology , pathology , cell culture , cell growth , chemistry , cancer , medicine , biology , immunology , antibody , biochemistry , genetics
BACKGROUND Micrometastasis is a major problem for prostate cancer (CaP) patients. Our study investigated the therapeutic potential of multiple targeted α‐therapy (MTAT) in the treatment of CaP micrometastases (spheroids) using 213 Bi‐labeled multiple targeted α‐radioimmunoconjugates. METHODS The expression of multiple tumor‐associated antigens (TAAs) on frozen sections of human fresh CaP tissues and spheroids cultured from DU 145 and LNCaP‐LN3 CaP cell lines was detected by immunohistochemistry and flow cytometry. Targeting vectors were two monoclonal antibodies (MAbs), and plasminogen activator inhibitor type 2 (PAI2) that binds to cell surface urokinase plasminogen activator (uPA). These vectors were labeled with 213 Bi using standard methodology. DU 145 and LNCaP‐LN3 spheroids were incubated with different activities of test and control α‐conjugates (ACs), and spheroid growth was measured for volume change and growth delay over a 50‐day period using light microscopy. RESULTS TAAs were expressed heterogeneously on frozen sections from human CaP tissues and CaP spheroids. MTAT combining three ACs (one‐third dose of each) with an activity of 6.4 MBq/ml completely targeted small DU 145 and LNCaP‐LN3 spheroids (diameter <100 µm) and slightly regressed the growth of medium spheroids (180–200 µm); MTAT with 2.2 or 4.8 MBq/ml activities delayed the growth of tumor spheroids. CONCLUSIONS Our results suggest that the cytotoxicity of MTAT to CaP spheroids is highly dependent on antigenic expression, concentration of radioactivity and spheroid size. MTAT may be a potent therapeutic agent for micrometastases, effectively targeting small CaP cell clusters, and overcoming the heterogeneous expression of targeted antigens. Prostate © 2006 Wiley‐Liss, Inc.