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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:p>\n                    Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3 (DLL3) on their cell surface. Taking advantage of DLL3 overexpression, we developed and evaluated lutetium-177 (\n                    <jats:sup>177<\/jats:sup>\n                    Lu)\u2013labeled DLL3-targeting antibody SC16 (\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16) as a treatment for NEPC. SC16 was functionalized with DTPA-CHX-A\" chelator and radiolabeled with\n                    <jats:sup>177<\/jats:sup>\n                    Lu to produce\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16. Specificity and selectivity of\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16 were evaluated in\u00a0vitro and in\u00a0vivo using NCI-H660 (NEPC, DLL3-positive) and DU145 (adenocarcinoma, DLL3-negative) cells and xenografts. Dose-dependent treatment efficacy and specificity of\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16 radionuclide therapy were evaluated in H660 and DU145 xenograft\u2013bearing mice. Safety of the agent was assessed by monitoring hematologic parameters.\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16 showed high tumor uptake and specificity in H660 xenografts, with minimal uptake in DU145 xenografts. At all three tested doses of\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16 (4.63, 9.25, and 27.75 MBq\/mouse), complete responses were observed in H660-bearing mice; 9.25 and 27.75 MBq\/mouse doses were curative. Even the lowest tested dose proved curative in five (63%) of eight mice, and recurring tumors could be successfully re-treated at the same dose to achieve complete responses. In DU145 xenografts,\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16 therapy did not inhibit tumor growth. Platelets and hematocrit transiently dropped, reaching nadir at 2 to 3 wk. This was out of range only in the highest-dose cohort and quickly recovered to normal range by week 4. Weight loss was observed only in the highest-dose cohort. Therefore, our data demonstrate that\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DTPA-SC16 is a potent and safe radioimmunotherapeutic agent for testing in humans with NEPC.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2203820119","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T15:09:27Z","timestamp":1656342567000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["Delta-like ligand 3\u2013targeted radioimmunotherapy for neuroendocrine prostate cancer"],"prefix":"10.1073","volume":"119","author":[{"given":"Joshua A.","family":"Korsen","sequence":"first","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9024-7482","authenticated-orcid":false,"given":"Julia A.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Tully","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4848-4190","authenticated-orcid":false,"given":"Lukas M.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6639-5402","authenticated-orcid":false,"given":"Zachary V.","family":"Samuels","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-0282","authenticated-orcid":false,"given":"Samantha","family":"Khitrov","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Poirier","sequence":"additional","affiliation":[{"name":"Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5204-3465","authenticated-orcid":false,"given":"Charles M.","family":"Rudin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10021"},{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9454-0096","authenticated-orcid":false,"given":"Michael J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Department of 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