{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:10Z","timestamp":1792787590405,"version":"4.5.0"},"reference-count":43,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland","award":["NIDDK Intramural Program ZIE DK 04705313"],"award-info":[{"award-number":["NIDDK Intramural Program ZIE DK 04705313"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,8]]},"abstract":"<jats:p>\n                    Integrin \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    , a transmembrane receptor involved in tumor growth and metastasis, specifically recognizes and binds proteins with the Arg-Gly-Asp (RGD) peptide sequence. Using mRNA and\/or protein expression data from 496 thyroid cancer (TC) samples in The Cancer Genome Atlas, 14 TC cell lines, and 70 TC and 10 normal thyroid tissues, we found that papillary TC exhibits the highest \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    integrin expression. We then evaluated the therapeutic efficacy of a radiolabeled RGD analog,\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-EB-cRGDfK, in TC. Genetic knockout and overexpression of \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    in TC cell lines confirmed the target specificity of\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-EB-cRGDfK. In mouse xenograft models established from human TC cell lines with high \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    expression,\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-EB-cRGDfK demonstrated superior antitumor efficacy compared with standard-of-care lenvatinib and placebo. However, no synergistic benefit was observed with combination therapy. Biodistribution studies identified the kidneys as the dose-limiting organ. RNA-seq analysis of resected tumors demonstrated that\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-EB-cRGDfK induced a type I IFN response, characterized by upregulation of\n                    <jats:italic>IFI6<\/jats:italic>\n                    ,\n                    <jats:italic>IFIT1-2<\/jats:italic>\n                    , and\n                    <jats:italic>MX1<\/jats:italic>\n                    , compared with both lenvatinib-treated tumors and placebo. These findings identify \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    integrin as a promising therapeutic target in a subset of TCs and demonstrate that\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-EB-cRGDfK exhibits superior efficacy to lenvatinib, supporting its potential clinical translation for progressive TC refractory to standard therapies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.200594","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:00:57Z","timestamp":1791396057000},"source":"Crossref","is-referenced-by-count":0,"title":["177Lu-labeled DOTA-EB-RGD as a candidate for thyroid cancer therapy"],"prefix":"10.1172","volume":"11","author":[{"given":"Sonam","family":"Kumari","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhitajit","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhantong","family":"Wang","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Thakur","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Abaandou","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney 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