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|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 Alfred; APOSTOLIDIS Christos; ALLEN B. J.; RUSSELL P. J.|
|Citation:||CLINICAL CANCER RESEARCH vol. 15 no. 3 p. 865-875|
|Publisher:||AMER ASSOC CANCER RESEARCH|
|JRC Publication N°:||JRC50507|
|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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