Title: Inhibition ofMicrometastatic Prostate Cancer Cell Spread in Animal Models By 213BilabeledMultipleTargeted Alpha-Radioimmunoconjugates
Authors: LI Y.SONG E.ABBAS RIZVI S. M.POWER C. A.BERETOV J.RAJA C.COZZI P. J.MORGENSTERN AlfredAPOSTOLIDIS ChristosALLEN B. J.RUSSELL P. J.
Citation: CLINICAL CANCER RESEARCH vol. 15 no. 3 p. 865-875
Publisher: AMER ASSOC CANCER RESEARCH
Publication Year: 2009
JRC Publication N°: JRC50507
ISSN: 1078-0432
URI: http://www.aacrjournals.org
http://publications.jrc.ec.europa.eu/repository/handle/JRC50507
DOI: 10.1158/1078-0432.CCR-08-1203
Type: Articles in Journals
Abstract: Purpose: To investigate the therapeutic potential of 213Bilabeled multiple targeted a-radioimmunoconjugates for treatingprostate cancer (CaP)micrometastases inmousemodels. Experimental Design: PC-3 CaP cells were implanted s.c., in the prostate, and intratibially in NODSCID mice. The expression of multiple tumor ^ associated antigens on tumor xenografts andmicrometastaseswas detected by immunohistochemistry.Targeting vectorswere twomonoclonal antibodies, and a plasminogen activator inhibitor type 2 that binds to cell surface urokinase plasminogen activator, labeledwith 213Bi using standardmethodology. In vivo efficacy ofmultiple a conjugates (MTAT) at different activities was evaluated in these mouse models.Tumor growth was monitored during observations and local regional lymph node metastases were assessed at the end of experiments. Results:The take rate of PC-3 cells was100% for each route of injection.The tumor-associated antigens (MUC1, urokinase plasminogen activator, and BLCA-38) were heterogeneously expressed on primary tumors and metastatic cancer clusters at transit. A single i.p. injection of MTAT (test) at high and low doses caused regression of the growth of primary tumors and prevented local lymph nodemetastases in a concentration-dependent fashion; it also caused cancer cells to undergo necrosis and apoptosis. Conclusions: Our results suggest thatMTATcan impede primary PC-3 CaP growth at three different sites in vivo through induction of apoptosis, and can prevent the spread of cancer cells and target lymph node micrometastases in a concentration-dependent manner. MTAT, by targeting multiple antigens, can overcome heterogeneous antigen expression to kill small CaP cell clusters, thus providing a potent therapy for micrometastases.
JRC Institute:Institute for Transuranium Elements

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