{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:55:40Z","timestamp":1773017740366,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","award":["NRPU\u201017226"],"award-info":[{"award-number":["NRPU\u201017226"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Labelled Comp Radiopharmac"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fibroblast activation protein is highly expressed in tumor\u2010associated fibroblasts and represents a promising stromal target for cancer therapy. Actinium\u2010225 (\n                    <jats:sup>225<\/jats:sup>\n                    Ac) offers potent \u03b1\u2010emissions for targeted radiotherapy but requires exceptionally stable chelation. We report the synthesis and preclinical evaluation of the novel FAP\u2010targeted \u03b1\u2010immunoconjugate [\n                    <jats:sup>225<\/jats:sup>\n                    Ac]Ac\u2013Macropa\u2013PEG\n                    <jats:sub>4<\/jats:sub>\n                    \u2013Sibrotuzumab. Sibrotuzumab was site\u2010specifically modified with Macropa\u2013PEG\n                    <jats:sub>4<\/jats:sub>\n                    and radiolabeled with\n                    <jats:sup>225<\/jats:sup>\n                    Ac under mild conditions. Radiochemical purity, serum stability, and immunoreactivity were assessed by radio\u2010iTLC, SEC\u2013HPLC, and FAP\n                    <jats:sup>+<\/jats:sup>\n                    \/FAP\n                    <jats:sup>\u2212<\/jats:sup>\n                    cell assays. In\u00a0vivo biodistribution and therapeutic efficacy were evaluated in NIH\/3T3\u2010FAP\n                    <jats:sup>+<\/jats:sup>\n                    xenograft\u2013bearing mice. The radioconjugate was obtained in 78.5%\u2009\u00b1\u20092.2% yield with &gt;\u200998% radiochemical purity and &gt;\u200990% stability over 7\u2009days. The immunoreactive fraction was 88.7%, and the construct demonstrated strong FAP\u2010specific uptake with ~30% internalization at 24\u2009h. In\u00a0vivo, [\n                    <jats:sup>225<\/jats:sup>\n                    Ac]Ac\u2013Macropa\u2013PEG\n                    <jats:sub>4<\/jats:sub>\n                    \u2013Sibrotuzumab showed high tumor accumulation (24.1\u2009\u00b1\u20091.6 %ID\/g at 168\u2009h), rapid clearance from normal tissues, and minimal bone uptake. Treatment achieved ~62% tumor growth inhibition, prolonged survival beyond 28\u2009days, and induced partial (50%) or complete (17%) responses without systemic toxicity. These findings highlight Macropa as a robust chelation strategy and support Sibrotuzumab\u2010based \u03b1\u2010immunoconjugates for precise targeting of FAP\u2010positive desmoplastic tumors.\n                  <\/jats:p>","DOI":"10.1002\/jlcr.70020","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T23:45:09Z","timestamp":1770767109000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Evaluation of [\n                    <sup>225<\/sup>\n                    Ac]Ac\u2013Sibrotuzumab Employing a PEG\n                    <sub>4<\/sub>\n                    \u2013Macropa Site\u2010Specific Chelation Strategy for Targeted Ablation of Cancer\u2010Associated Fibroblasts in Desmoplastic Tumors"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3145-6070","authenticated-orcid":false,"given":"Syed\u00a0Qaiser","family":"Shah","sequence":"first","affiliation":[{"name":"Nuclear Medicine Research Laboratory, Institute of Chemical Sciences University of Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Santos\u2010Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Nano\u2010Radiopharmacy, Nuclear Engineering Institute Brazilian Nuclear Energy Commission  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeeha","family":"Shabnam","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Research Laboratory, Institute of Chemical Sciences University of Peshawar  Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"DeryaIlem\u2010Ozdemir","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Radiopharmacy Ege University  Bornova \u0130zmir T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0275-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.13.3.18696"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-022-05842-5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-025-07071-y"},{"key":"e_1_2_10_6_1","first-page":"1639","article-title":"A Phase I Dose\u2010Escalation Study of Sibrotuzumab in Patients With Advanced or Metastatic Fibroblast Activation Protein\u2010Positive Cancer","volume":"9","author":"Scott A. 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