{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:25:23Z","timestamp":1793838323541,"version":"4.6.1"},"reference-count":42,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We used a pretargeting technique to treat a nonobese diabetic\/severe combined immunodeficient murine model of human adult T-cell leukemia with an anti-Tac antibody-streptavidin (HAT-SA) conjugate, which recognizes CD25, followed by bismuth 213 (213Bi)-1,4,7,10-tetraazacyclododecane-N,N\u2032,N\u2032\u2032,N\u2032\u2032\u2032-tetraacetic acid (DOTA)- biotin. In the 3-step pretargeting radioimmunotherapy protocol, HAT-SA (140 or 400 \u03bcg) was administered intravenously (i.v.) to bind to the interleukin 2 receptor \u03b1 (IL-2R\u03b1; CD25)\u2013expressing tumor cells. After 24 hours, 100 \u03bcg of a synthetic clearing agent was administered i.v. to remove unbound circulating HAT-SA conjugate from the circulation. Four hours later,213Bi\u2013DOTA-biotin was administered i.v. for therapy. Tumor growth was significantly inhibited in 3 trials by using 250 \u03bcCi (9.25 MBq) of 213Bi\u2013DOTA-biotin with a pretargeting technique as monitored by serum levels of soluble IL-2R\u03b1 and\/or human \u03b2-2-microglobulin (P\u2009&amp;lt;\u2009.05, t test) and by survival of tumor-bearing mice in the treatment groups (P\u2009&amp;lt;\u2009.02, log rank test) as compared with the control groups. No prolongation of survival was observed with a nonspecific antibody-SA conjugate or in the absence of the radionuclide. Additionally, no prolongation of survival resulted from administration of 213Bi directly linked to intact HAT. Furthermore, there was no prolongation of survival when the \u03b2-emitting radionuclide yttrium 90 instead of the \u03b1-emitting radionuclide213Bi was used. The pretargeting approach with213Bi inhibited tumor growth more effectively than did immunotherapy with unmodified HAT. The best results were obtained with combination therapy that involved 213Bi\u2013DOTA-biotin with a pretargeting technique supplemented by 4 weekly doses of HAT. The findings of this study support the use of this combination approach in a clinical trial in patients with IL-2R\u03b1\u2013expressing leukemias.<\/jats:p>","DOI":"10.1182\/blood-2002-01-0107","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T18:33:52Z","timestamp":1034361232000},"page":"208-216","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":84,"title":["Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with the \u03b1-emitting radionuclide, bismuth 213"],"prefix":"10.1182","volume":"100","author":[{"given":"Meili","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengsheng","family":"Yao","sequence":"additional","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayhan","family":"Garmestani","sequence":"additional","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald B.","family":"Axworthy","sequence":"additional","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Mallett","sequence":"additional","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis J.","family":"Theodore","sequence":"additional","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn K.","family":"Goldman","sequence":"additional","affiliation":[{"name":"From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin W.","family":"Brechbiel","sequence":"additional","affiliation":[{"name":"From the 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