{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:13:24Z","timestamp":1775020404900,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T00:00:00Z","timestamp":1594339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21371124"],"award-info":[{"award-number":["21371124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11434001"],"award-info":[{"award-number":["11434001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11875079"],"award-info":[{"award-number":["11875079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Targeted alpha therapy (TAT) is a promising tumor therapy that can specifically transport \u03b1 particle to the vicinity of tumor cells while the normal cells are only slightly irradiated. Mesothelin is a highly promising molecular signature for many types of solid tumors including malignant mesothelioma, pancreatic cancer, ovarian cancer and lung adenocarcinoma etc., while the expression in normal human tissues are limited, thus making mesothelin a promising antigen for TAT. Previously we developed a theoretical model that could predict and optimize in vitro screening of potential TAT drugs. The aim of the study is construction and preclinical evaluation of 211At labeled anti-mesothelin antibodies as potential TAT drugs. Mesothelin expression of two tumor cell lines were confirmed by flow cytometry, and their radiosensitivities were also evaluated. We used two kinds of anti-mesothelin antibodies, ET210\u20136 and ET210\u201328, to construct TAT drugs. Then, radiochemical purity, stability in vitro, affinity of the conjugates and mesothelin expression level were assessed. The specific killing of mesothelin-positive cancer cells treated by 211At-ET210\u201328 and 211At-ET210\u20136 were studied via Cell Counting Kit-8 assay and colony formation assay. 211At-ET210\u201328 and 211At-ET210\u20136 revealed excellent affinity and stability in both phosphate buffer saline and fetal bovine serum environment. Radiolabeled antibody conjugates bound specifically to mesothelin-positive cells in vitro. Both 211At-ET210\u201328 and 211At-ET210\u20136 could specifically kill mesothelin-positive cells with negligible damages to mesothelin-negative cells. Our findings provide initial proof-of-concept for the potential use of 211At labeled ET210\u201328\/ET210\u20136 anti-mesothelin antibody in specific killings of mesothelin-positive tumor cells.<\/jats:p>","DOI":"10.1093\/jrr\/rraa049","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:11:03Z","timestamp":1592478663000},"page":"684-690","source":"Crossref","is-referenced-by-count":10,"title":["Construction and Preclinical Evaluation of 211At Labeled Anti-mesothelin Antibodies as Potential Targeted Alpha Therapy Drugs"],"prefix":"10.1093","volume":"61","author":[{"given":"Xudong","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzong","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihao","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Radiation Physics and Technology, Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Radiation Physics and Technology, Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyou","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Radiation Physics and Technology, Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yugang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Radiation Physics and Technology, Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, P. R. 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