{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:03:16Z","timestamp":1785301396665,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Fibroblast activation protein (FAP)-targeted radiopharmaceuticals have been widely applied in oncologic imaging and therapy, while their application in pulmonary fibrosis remains underexplored. This study investigated the biodistribution and therapeutic potential of [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-labeled FAP inhibitor (FAPI) in pulmonary fibrosis using two administered activity regimens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The therapeutic potential of an albumin-binder-conjugated FAPI radiopharmaceutical, [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-TEFAPI-06 was evaluated in a murine model of bleomycin-induced pulmonary fibrosis. Targeting efficiency and pharmacokinetics were evaluated by small-animal PET\/CT, SPECT\/CT, and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      biodistribution analyses. Therapeutic efficacy and tissue responses were then compared between two administered activity regimens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-TEFAPI-06 preferentially accumulated and was retained in fibrotic lungs with high uptake in FAP-positive lesions. The 11.1 MBq regimen significantly attenuated pulmonary fibrosis, reducing collagen deposition by approximately 50%, whereas the 18.5 MBq regimen failed to improve fibrosis and was accompanied by increased pulmonary macrophage infiltration and enrichment of Arg1-positive macrophages. Both regimens were well tolerated, with no detectable short-term toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study provides proof-of-concept for FAP-targeted radionuclide therapy in experimental pulmonary fibrosis. Our findings suggest that distinct therapeutic outcomes are accompanied by different local tissue responses following treatment and support further evaluation of stromal-targeted radionuclide therapy for pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1884620","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:43:12Z","timestamp":1785300192000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted depletion of activated fibroblasts via [177Lu]Lu-FAPI radionuclide therapy ameliorates bleomycin-induced lung fibrosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Lin","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Center for Rare Disease, Peking University Third Hospital","place":["Beijing, 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