{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T02:47:49Z","timestamp":1782096469346,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01CA112503"],"award-info":[{"award-number":["R01CA112503"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:p>\n                    Lutetium\u2010177 is a \u03b2\u2010particle\u2010emitting radionuclide widely used in targeted radionuclide therapy (TRT). The recent FDA approvals of\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010based radiopharmaceuticals including Lutathera and Pluvicto have accelerated research efforts to develop more effective TRT agents. A critical component for the generation of effective\n                    <jats:sup>177<\/jats:sup>\n                    Lu radiopharmaceuticals is a bifunctional chelator that can rapidly and stably sequester\n                    <jats:sup>177<\/jats:sup>\n                    Lu under mild labeling conditions. Herein, we introduce a novel bifunctional chelator (2E\u2010\n                    <jats:italic>C<\/jats:italic>\n                    \u2010NETA) for applications in\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010based TRT. The chelator 2E\u2010\n                    <jats:italic>C<\/jats:italic>\n                    \u2010NETA was synthesized and evaluated for radiolabeling efficiency with\n                    <jats:sup>177<\/jats:sup>\n                    Lu. 2E\u2010\n                    <jats:italic>C<\/jats:italic>\n                    \u2010NETA rapidly bound\n                    <jats:sup>177<\/jats:sup>\n                    Lu at room temperature, and the resulting complex exhibited excellent serum stability for over 2 weeks. To demonstrate its utility in antibody\u2010targeted radionuclide therapy, the chelator was further structurally modified for conjugation to Herceptin, an FDA\u2010approved monoclonal antibody for metastatic breast cancer. The 2E\u2010\n                    <jats:italic>C<\/jats:italic>\n                    \u2010NETA\u2010Herceptin conjugate was also rapidly labeled with\n                    <jats:sup>177<\/jats:sup>\n                    Lu at room temperature. The\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010labeled 2E\u2010\n                    <jats:italic>C<\/jats:italic>\n                    \u2010NETA\u2010Herceptin conjugate displayed high stability in human serum for 2 weeks. In mice bearing human colorectal carcinoma (LS\u2010174T) tumors,\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u20102E\u2010\n                    <jats:italic>C<\/jats:italic>\n                    \u2010NETA\u2010Herceptin demonstrated favorable biodistribution, showing fast blood clearance, minimal uptake in normal tissues, and significant and prolonged tumor accumulation. In summary, these results support 2E\u2010C\u2010NETA as a promising bifunctional chelator for the development of\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010based radiopharmaceuticals.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70325","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:20:56Z","timestamp":1781666456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Highly Effective Bifunctional Ligand 2E\u2010\n                    <i>C<\/i>\n                    \u2010NETA for Targeted Lu\u2010177 Therapy: Synthesis, Radiolabeling, In Vitro Stability, and In Vivo Biodistribution"],"prefix":"10.1002","volume":"21","author":[{"given":"Yenwei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Chemistry Illinois Institute of Technology  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeseul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry Illinois Institute of Technology  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Soo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Illinois Institute of Technology  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Chemistry Illinois Institute of Technology  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Illinois Institute of Technology  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Illinois Institute of Technology  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilantha","family":"Bandara","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Washington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buck E.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Washington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-7601","authenticated-orcid":false,"given":"Hyun\u2010Soon","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Chemistry Illinois Institute of Technology  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1413"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0073-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500171e"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00294"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.8b00341"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607427"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107322"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc950097s"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(03)00033-7"},{"key":"e_1_2_9_11_1","first-page":"1384","article-title":"Prevention of Radiolysis of Monoclonal Antibody during Labeling","volume":"37","author":"Chakrabarti M. 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