{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:24:59Z","timestamp":1791181499668,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,10,21]],"date-time":"2008-10-21T00:00:00Z","timestamp":1224547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>This study investigated the biodistribution and therapeutic efficacy of Lutetium\u2010177 (<jats:sup>177<\/jats:sup>Lu) radiolabeled anti\u2010Lewis Y monoclonal antibody hu3S193 radioimmunotherapy (RIT) in mice bearing prostate cancer xenografts. The ability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 and docetaxel chemotherapy to enhance the efficacy of RIT was also assessed in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The in vitro cytotoxicity of <jats:sup>177<\/jats:sup>Lu labeled hu3S193 on Le<jats:sup>y<\/jats:sup> positive DU145 prostate cancer cells was assessed using proliferation assays, with induction of apoptosis measured by ELISA. The in vivo biodistribution and tumor localization of <jats:sup>177<\/jats:sup>Lu\u2010hu3S193 was assessed in mice bearing established DU145 tumor xenografts. The efficacy and maximum tolerated dose of <jats:sup>177<\/jats:sup>Lu\u2010hu3S193 RIT in vivo was determined by a dose escalation study. EGFR inhibitor AG1478 or docetaxel chemotherapy was administered at sub\u2010therapeutic doses in conjunction with RIT in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p><jats:sup>177<\/jats:sup>Lu\u2010hu3S193 mediated significant induction of cytotoxicity and apoptosis in vitro. In vivo analysis of <jats:sup>177<\/jats:sup>Lu\u2010hu3S193 biodistribution demonstrated specific targeting of DU145 prostate cancer xenografts, with maximal tumor uptake of 33.2\u2009\u00b1\u20093.9%ID\/g observed at 120 hr post\u2010injection. In RIT studies, <jats:sup>177<\/jats:sup>Lu\u2010hu3S193 caused specific and dose\u2010dependent inhibition of prostate cancer tumor growth. A maximum tolerated dose of 350 \u00b5Ci was determined for <jats:sup>177<\/jats:sup>Lu\u2010hu3S193. Combination of <jats:sup>177<\/jats:sup>Lu\u2010hu3S193 RIT with EGFR inhibitor AG1478 or docetaxel chemotherapy both significantly improved efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p><jats:sup>177<\/jats:sup>Lu\u2010hu3S193 RIT is effective as a single agent in the treatment of Le<jats:sup>y<\/jats:sup> positive prostate cancer models. The enhancement of RIT by AG1478 or docetaxel indicates the promise of combined modality strategies. Prostate 69: 92\u2013104, 2009. \u00a9 2008 Wiley\u2013Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.20856","type":"journal-article","created":{"date-parts":[[2008,10,21]],"date-time":"2008-10-21T19:37:14Z","timestamp":1224617834000},"page":"92-104","source":"Crossref","is-referenced-by-count":48,"title":["Therapeutic efficacy of <sup>177<\/sup>Lu\u2010CHX\u2010A\u2033\u2010DTPA\u2010hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy"],"prefix":"10.1002","volume":"69","author":[{"given":"Marcus P.","family":"Kelly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sze Ting","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.\u2010T.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona E.","family":"Smyth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin W.","family":"Brechbiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,21]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80054-4"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2330"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2003.11.004"},{"issue":"4","key":"e_1_2_1_5_2","first-page":"297","article-title":"Radioimmunotherapy of prostate cancer","volume":"48","author":"Smith\u2010Jones PM","year":"2004","journal-title":"Q J Nucl Med Mol Imaging"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.903"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.09.154"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.160"},{"issue":"1","key":"e_1_2_1_9_2","first-page":"141S","article-title":"Current status of therapy of solid tumors","volume":"46","author":"Jhanwar YS","year":"2005","journal-title":"J Nucl Med"},{"issue":"6","key":"e_1_2_1_10_2","first-page":"967","article-title":"Radioimmunotherapy of a human lung cancer xenograft with monoclonal antibody RS7: Evaluation of (177)Lu and comparison of its efficacy with that of (90)Y and residualizing (131)I","volume":"42","author":"Stein R","year":"2001","journal-title":"J Nucl Med"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2006.21.81"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1141"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2005.08.008"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.10.044"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1667\/0033-7587(2003)159[0439:EGFAIR]2.0.CO;2"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0420"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611693104"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2006.04.003"},{"key":"e_1_2_1_19_2","doi-asserted-by":"crossref","unstructured":"BaselgaJ ArribasJ.Treating cancer's kinase \u2018addiction\u2019.2004;10(8):786\u2013787.","DOI":"10.1038\/nm0804-786"},{"issue":"10","key":"e_1_2_1_20_2","first-page":"3773","article-title":"The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 selectively potentiates radiation response of human tumors in nude mice, with a marked improvement in therapeutic index","volume":"9","author":"She Y","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20000620)90:3<113::AID-IJC1>3.0.CO;2-C"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10303"},{"issue":"3","key":"e_1_2_1_23_2","first-page":"S71","article-title":"A new paradigm for the treatment of high\u2010risk prostate cancer: Radiosensitization with docetaxel","volume":"5","author":"Kumar P","year":"2003","journal-title":"Rev Urol"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.10029"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20638"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0037"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)67464-0"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(95)90220-1"},{"issue":"4","key":"e_1_2_1_29_2","first-page":"716","article-title":"Enhanced efficacy of 90Y\u2010radiolabeled anti\u2010Lewis Y humanized monoclonal antibody hu3S193 and paclitaxel combined\u2010modality radioimmunotherapy in a breast cancer model","volume":"47","author":"Kelly MP","year":"2006","journal-title":"J Nucl Med"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-1004-0019"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2005.05.029"},{"issue":"12","key":"e_1_2_1_32_2","first-page":"3254","article-title":"Construction, production, and characterization of humanized anti\u2010Lewis Y monoclonal antibody 3S193 for targeted immunotherapy of solid tumors","volume":"60","author":"Scott AM","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2329"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(97)00130-2"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0969-8051(94)00126-5"},{"issue":"17","key":"e_1_2_1_36_2","first-page":"4804","article-title":"In vivo biodistribution of a humanized anti\u2010Lewis Y monoclonal antibody (hu3S193) in MCF\u20107 xenografted BALB\/c nude mice","volume":"60","author":"Clarke K","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2036503100"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2653"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10308"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19940201)73:3 <993::AID-CNCR2820731337>3.0.CO;2-7"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-003-1216-z"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181560dcc"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0284"},{"issue":"11","key":"e_1_2_1_44_2","first-page":"2889","article-title":"Monoclonal antibody\u2010based therapy of a human tumor xenograft with a 177Lu\u2010labeled immunoconjugate","volume":"51","author":"Schlom J","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980703)77:1<13::AID-IJC3>3.0.CO;2-2"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.9-suppl_2-3"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19950501)75:9<2262::AID-CNCR2820750912>3.0.CO;2-5"},{"issue":"9","key":"e_1_2_1_48_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3727\/0965040041791455","article-title":"Radiosensitization of colon cancer cell lines by docetaxel: Mechanisms of action","volume":"14","author":"Dunne AL","year":"2004","journal-title":"Oncol Res"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568011033482422"},{"key":"e_1_2_1_50_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0211"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1089\/108497801753131381"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.20856","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.20856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T18:21:49Z","timestamp":1699899709000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.20856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,21]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,1]]}},"alternative-id":["10.1002\/pros.20856"],"URL":"https:\/\/doi.org\/10.1002\/pros.20856","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,21]]}}}