{"doi":"10.1073/pnas.2203820119","title":"Delta-like ligand 3–targeted radioimmunotherapy for neuroendocrine prostate cancer","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)–labeled 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 vitro and in vivo 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–bearing 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>","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":649196,"datarank":0.6166310796259968,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":0.0,"self_endowment_contribution":0.6166310796259968,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1019749,"name":"Julia Gutierrez","orcid":"0000-0002-9024-7482","position":1,"is_corresponding":false},{"id":828494,"name":"Kathryn M. Tully","orcid":"0000-0003-4933-7651","position":2,"is_corresponding":false},{"id":268011,"name":"Lukas M. Carter","orcid":"0000-0003-4848-4190","position":3,"is_corresponding":false},{"id":751471,"name":"Zachary V. Samuels","orcid":"0000-0001-6639-5402","position":4,"is_corresponding":false},{"id":870778,"name":"Samantha Khitrov","orcid":"0000-0002-3275-0282","position":5,"is_corresponding":false},{"id":65360,"name":"John T. Poirier","orcid":"0000-0001-9795-5644","position":6,"is_corresponding":false},{"id":1555,"name":"Charles M. Rudin","orcid":"0000-0001-5204-3465","position":7,"is_corresponding":false},{"id":905059,"name":"Yu Chen","orcid":"0000-0002-2266-994X","position":8,"is_corresponding":false},{"id":311748,"name":"Michael J. Morris","orcid":"0000-0002-9454-0096","position":9,"is_corresponding":false},{"id":107710,"name":"Lisa Bodei","orcid":"0000-0001-6930-7383","position":10,"is_corresponding":false},{"id":291557,"name":"Nagavarakishore Pillarsetty","orcid":"0000-0002-1750-7436","position":11,"is_corresponding":false},{"id":235762,"name":"Jason S. Lewis","orcid":"0000-0001-7065-4534","position":12,"is_corresponding":false},{"id":751884,"name":"Joshua A. Korsen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Delta-like ligand 3–targeted radioimmunotherapy for neuroendocrine prostate cancer","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)–labeled 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 vitro and in vivo 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–bearing 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>","is_dataset_classified":null,"base_score":4.110873864173311,"endowment":4.110873864173311,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35759660","pmcid":"PMC9271187","openalex_id":"https://openalex.org/W4283577156","authors":[],"funders":[{"funder_name":"HHS | NIH | National Cancer Institute","grant_id":"NIH R35 CA232130","title":null},{"funder_name":"HHS | NIH | National Cancer Institute","grant_id":"NIH R35 CA263816","title":null},{"funder_name":"HHS | NIH | National Cancer Institute","grant_id":"NIH U0I-CA213359","title":null},{"funder_name":"Geoffrey Beene Cancer Research Center","grant_id":"Not applicable","title":null},{"funder_name":"DOD | US Army | MEDCOM | CDMRP | DOD Prostate Cancer Research Program","grant_id":"W81XWH-19-1-0536","title":null},{"funder_name":"HHS | NIH | National Institute of General Medical Sciences","grant_id":"NIH T32 GM073546","title":null},{"funder_name":"HHS | NIH | National Cancer Institute","grant_id":"P50CA092629","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R35 CA263816","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA008748","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R35 CA232130","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U01 CA213359","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM073546","title":null},{"funder_name":"National Institutes of Health","grant_id":"2P30CA008748-43","title":"MOUSE GENETICS"},{"funder_name":"National Institutes of Health","grant_id":"5U01CA213359-02","title":"Preclinical development of a DLL3-targeted theranostic for small cell lung cancer"},{"funder_name":"National Institutes of Health","grant_id":"1T32GM073546-01A1","title":"Predoctoral Training in Pharmacological Sciences"},{"funder_name":"National Institutes of Health","grant_id":"5R35CA263816-02","title":"Novel therapeutic development for small cell lung cancer"},{"funder_name":"National Institutes of Health","grant_id":"5P50CA092629-10","title":"RATIONAL DESIGN OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN DNA VACCINES"},{"funder_name":"National Institutes of Health","grant_id":"3R35CA232130-03S1","title":"Annotating Cancer Biology through Non-Invasive Molecular Imaging"}],"total_grants":18,"fwci":6.3818,"citation_percentile":0.97623305,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":16},{"year":2024,"count":13},{"year":2025,"count":19},{"year":2026,"count":11}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9271187","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9271187","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2203820119","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.2203820119","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35759660","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9271187","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9271187?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1073/pnas.2203820119","host_type":""}],"fields_of_study":["Radiopharmaceutical Chemistry and Applications","Prostate Cancer Treatment and Research","Neuroendocrine Tumor Research Advances","03 medical and health sciences","0302 clinical medicine","Animals","Antibodies, Monoclonal, Humanized","Carcinoma, Neuroendocrine","Chelating Agents","Humans","Intracellular Signaling Peptides and Proteins","Ligands","Lutetium","Male","Membrane Proteins","Mice","Pentetic Acid","Prostatic Neoplasms","Radioimmunotherapy","Radioisotopes","Xenograft Model Antitumor Assays"],"mesh_terms":["Animals","Chelating Agents","Pentetic Acid","Humans","Ligands","Lutetium","Male","Membrane Proteins","Prostatic Neoplasms","Radioisotopes","Radioimmunotherapy","Carcinoma, Neuroendocrine","Xenograft Model Antitumor Assays","Intracellular Signaling Peptides and Proteins","Mice","Antibodies, Monoclonal, Humanized"],"keywords":["DU145","Radioimmunotherapy","Prostate cancer","Medicine","In vivo","Cancer research","Adenocarcinoma","Nuclear medicine","DOTA","Cancer","Internal medicine","Antibody","Immunology","LNCaP","Biology","Monoclonal antibody","Neuroendocrine Prostate Cancer","Lutetium-177","Dll3","Male","Radioisotopes","Intracellular Signaling Peptides and Proteins","Membrane Proteins","Prostatic Neoplasms","Biological Sciences","Lutetium","Pentetic Acid","Antibodies, Monoclonal, Humanized","Ligands","Xenograft Model Antitumor Assays","Carcinoma, Neuroendocrine","Mice","Animals","Humans","Chelating Agents"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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