{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:02:28Z","timestamp":1785250948438,"version":"3.55.0"},"reference-count":23,"publisher":"American Chemical Society (ACS)","issue":"29","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02395"],"award-info":[{"award-number":["24K02395"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K02537"],"award-info":[{"award-number":["25K02537"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22H02928"],"award-info":[{"award-number":["JP22H02928"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epithelial cell adhesion molecule (EpCAM) is overexpressed in various epithelial malignancies and represents an attractive target for molecular imaging and radionuclide therapy. This study aimed to develop and evaluate a novel EpCAM-targeted monoclonal antibody for single-photon emission computed tomography (SPECT) imaging. To this end, Ep4-1, a high-affinity anti-EpCAM monoclonal antibody, was conjugated to the bifunctional chelator p-SCN-Bn-diethylenetriaminepentaacetic acid (DTPA) and radiolabeled with indium-111 (111In). In vitro EpCAM-binding affinity, plasma stability, and cellular internalization were examined using high-EpCAM-expressing DLD-1 cells. In vivo biodistribution, blocking studies, and SPECT\/computed tomography (CT) imaging were performed in DLD-1 tumor-bearing mice. Results showed that [111In]In-DTPA-Ep4-1 retained high, EpCAM-specific binding after chelator conjugation and showed excellent plasma stability. The radiolabeled antibody exhibited pronounced cellular internalization; approximately 93% of cell-associated radioactivity was internalized in DLD-1 cells at 6 h, exceeding the reported internalization efficiency of previously described EpCAM-targeted antibodies. In vivo biodistribution indicated progressive and selective tumor uptake, reaching 15.1 \u00b1 1.3% ID\/g at 72 h after injection. Co-injection of excess unlabeled Ep4-1 reduced tumor accumulation, consistent with EpCAM-specific targeting. Uptake in the liver and spleen was consistent with the expected pharmacokinetics of intact IgG antibodies. SPECT\/CT imaging enabled clear visualization of EpCAM-expressing tumors at 72 h after injection. In conclusion, Ep4-1 is a highly specific and strongly internalizing EpCAM-targeted monoclonal antibody that enables robust SPECT imaging of EpCAM-positive tumors. Given the favorable internalization properties of Ep4-1, it may serve as a promising imaging platform and a potential candidate for future EpCAM-directed radiotheranostics applications, including \u03b1-particle-based radionuclide therapy.<\/jats:p>","DOI":"10.1021\/acsomega.6c04410","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T19:04:44Z","timestamp":1784315084000},"page":"44225-44233","source":"Crossref","is-referenced-by-count":0,"title":["Development and\nPreclinical Evaluation of a Novel\nEpCAM-Targeted 111In-Labeled Antibody for SPECT Imaging"],"prefix":"10.1021","volume":"11","author":[{"given":"Sato","family":"Oshige","sequence":"first","affiliation":[{"name":"Kanazawa University , , ,","place":["Ishikawa, Japan, 920-8640"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Iwasawa","sequence":"additional","affiliation":[{"name":"Toyo University , , ,","place":["Tokyo, Japan, 115-8650"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Naito","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University , , ,","place":["Kyoto, Japan, 607-8414"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University , , ,","place":["Kyoto, Japan, 607-8412"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kozaka","sequence":"additional","affiliation":[{"name":"Kanazawa University , , ,","place":["Ishikawa, Japan, 920-8640"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Omokawa","sequence":"additional","affiliation":[{"name":"Okayama University , , ,","place":["Okayama, Japan, 700-8558"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Kyoto University , , ,","place":["Kyoto, Japan, 606-8501"]},{"name":"Kyoto University , , ,","place":["Kyoto, Japan, 606-8501"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takiko","family":"Daikoku","sequence":"additional","affiliation":[{"name":"Kanazawa University , , ,","place":["Ishikawa, Japan, 920-8640"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0937-3746","authenticated-orcid":true,"given":"Yusuke","family":"Yagi","sequence":"additional","affiliation":[{"name":"Kyoto University of Medical Science , , ,","place":["Kyoto, Japan, 622-0022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yasui","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University , , ,","place":["Kyoto, Japan, 607-8414"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Kato","sequence":"additional","affiliation":[{"name":"Toyo University , , ,","place":["Tokyo, Japan, 115-8650"]},{"name":"Toyo University , , ,","place":["Tokyo, Japan, 115-8650"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4291-3524","authenticated-orcid":true,"given":"Hiroyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Kyoto University , , ,","place":["Kyoto, Japan, 606-8501"]},{"name":"Kyoto University , , ,","place":["Kyoto, Japan, 606-8501"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"2026072810115180900_cit1","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1007\/s10555-020-09898-3","article-title":"Expression and function\nof epithelial cell adhesion molecule EpCAM: where are we after 40\nyears?","volume":"39","author":"Gires","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"2026072810115180900_cit2","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1056\/NEJMoa040766","article-title":"Circulating tumor cells, disease\nprogression, and survival in metastatic breast cancer","volume":"351","author":"Cristofanilli","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"2026072810115180900_cit3","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1200\/JCO.2007.15.8923","article-title":"Relationship of circulating tumor cells to tumor response,\nprogression-free survival, and overall survival in patients with metastatic\ncolorectal cancer","volume":"26","author":"Cohen","year":"2008","journal-title":"J. Clin. Oncol."},{"issue":"20","key":"2026072810115180900_cit4","doi-asserted-by":"publisher","first-page":"6302","DOI":"10.1158\/1078-0432.CCR-08-0872","article-title":"Circulating tumor cells\npredict survival benefit from treatment in metastatic castration-resistant\nprostate cancer","volume":"14","author":"de Bono","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"2026072810115180900_cit5","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-10-44","article-title":"Side-by-side analysis of five clinically tested anti-EpCAM monoclonal\nantibodies","volume":"10","author":"Mu\u0308nz","year":"2010","journal-title":"Cancer Cell Int."},{"key":"2026072810115180900_cit6","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1517\/14712598.2010.482098","article-title":"Adecatumumab: an anti-EpCAM monoclonal antibody, from\nthe bench to the bedside","volume":"10","author":"Kurtz","year":"2010","journal-title":"Expert Opin. Biol.\nTher."},{"key":"2026072810115180900_cit7","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1111\/IGC.0b013e3181a8331f","article-title":"Overexpression of epithelial cell\nadhesion molecule in primary, metastatic, and recurrent\/chemotherapy-resistant\nepithelial ovarian cancer","volume":"19","author":"Bellone","year":"2009","journal-title":"Int. J. Gynecol.\nCancer"},{"key":"2026072810115180900_cit8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/annonc\/mdp314","article-title":"An open-label, randomized\nphase II study of adecatumumab, a fully human anti-EpCAM antibody,\nas monotherapy in patients with metastatic breast cancer","volume":"21","author":"Schmidt","year":"2010","journal-title":"Ann. Oncol."},{"key":"2026072810115180900_cit9","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1200\/JCO.1998.16.5.1788","article-title":"Monoclonal antibody therapy for resected Dukes\u2019\nC colorectal cancer: seven-year outcome of a multicenter randomized\ntrial","volume":"16","author":"Riethmu\u0308ller","year":"1998","journal-title":"J. Clin. Oncol."},{"issue":"Suppl 1","key":"2026072810115180900_cit10","first-page":"115S","article-title":"Perspectives\non cancer therapy with radiolabeled monoclonal\nantibodies","volume":"46","author":"Sharkey","year":"2005","journal-title":"J. Nucl. 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Med."},{"key":"2026072810115180900_cit15","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1111\/j.1349-7006.2011.01855.x","article-title":"Neural cell\nadhesion molecule 2 as a target molecule\nfor prostate and breast cancer gene therapy","volume":"102","author":"Takahashi","year":"2011","journal-title":"Cancer Sci."},{"key":"2026072810115180900_cit16","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation\nof the freely available easy-to-use software \u201cEZR\u201d for\nmedical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"2026072810115180900_cit17","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/sj.bjc.6602924","article-title":"Br. Frequent high-level\nexpression\nof the immunotherapeutic target EpCAM in colon, stomach, prostate\nand lung cancers","volume":"94","author":"Went","year":"2006","journal-title":"Br. J. Cancer"},{"key":"2026072810115180900_cit18","doi-asserted-by":"publisher","first-page":"5818","DOI":"10.1158\/0008-5472.CAN-04-0754","article-title":"EpCAM is\noverexpressed in breast cancer and is a potential target for breast\ncancer gene therapy","volume":"64","author":"Osta","year":"2004","journal-title":"Cancer Res."},{"key":"2026072810115180900_cit19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/ijms18010057","article-title":"Immuno-PET\nfor clinical theranostic approaches","volume":"18","author":"Bailly","year":"2017","journal-title":"Int. J.\nMol. Sci."},{"key":"2026072810115180900_cit20","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1007\/s00259-021-05670-z","article-title":"Preclinical evaluation of [99mTc]Tc-labeled\nanti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT\/CT","volume":"49","author":"Liu","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"2026072810115180900_cit21","doi-asserted-by":"publisher","first-page":"4719","DOI":"10.3390\/molecules25204719","article-title":"Radionuclide\nmolecular imaging of EpCAM expression\nin triple-negative breast cancer using the scaffold protein DARPin\nEc1","volume":"25","author":"Vorobyeva","year":"2020","journal-title":"Molecules"},{"key":"2026072810115180900_cit22","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1021\/acs.bioconjchem.1c00188","article-title":"EpCAM-targeting\naptamer radiotracer for tumor-specific PET imaging","volume":"32","author":"Li","year":"2021","journal-title":"Bioconjugate Chem."},{"key":"2026072810115180900_cit23","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S0168-3659(99)00248-5","article-title":"Tumor vascular permeability\nand the EPR effect in macromolecular therapeutics: a review","volume":"65","author":"Maeda","year":"2000","journal-title":"J. Controlled Release"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c04410","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/29\/44225\/66014467\/acsomega.6c04410.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/29\/44225\/66014467\/acsomega.6c04410.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:42:09Z","timestamp":1785249729000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/29\/44225\/5214746\/Development-and-Preclinical-Evaluation-of-a-Novel"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":23,"journal-issue":{"issue":"29","published-online":{"date-parts":[[2026,7,17]]},"published-print":{"date-parts":[[2026,7,28]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c04410","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}