{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:38:49Z","timestamp":1787060329502,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2024YFC2419400"],"award-info":[{"award-number":["2024YFC2419400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFA1206100"],"award-info":[{"award-number":["2022YFA1206100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U24A20758"],"award-info":[{"award-number":["U24A20758"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["92159201"],"award-info":[{"award-number":["92159201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82472023"],"award-info":[{"award-number":["82472023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L242062"],"award-info":[{"award-number":["L242062"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-D-001"],"award-info":[{"award-number":["2022-PUMCH-D-001"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-D-002"],"award-info":[{"award-number":["2022-PUMCH-D-002"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-C-020"],"award-info":[{"award-number":["2022-PUMCH-C-020"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-A-107"],"award-info":[{"award-number":["2022-PUMCH-A-107"]}]},{"name":"Nuclear Energy R&D project","award":["HNKF202223(36)"],"award-info":[{"award-number":["HNKF202223(36)"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2023-I2M-2-005"],"award-info":[{"award-number":["2023-I2M-2-005"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-005"],"award-info":[{"award-number":["2021-I2M-1-005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objectives: Early and noninvasive detection of fibrotic interstitial lung disease (fILD) is a critical but unmet clinical necessity. This study aimed to evaluate the feasibility of using 99mTc-HYNIC-Glu(PEG4-oncoFAPi)2 (denoted as 99mTc-H-PoFP2), a novel 99mTc-labeled radiopharmaceutical that targets fibroblast activation protein (FAP), for single-photon emission computed tomography (SPECT) imaging of pulmonary fibrosis in a mouse model and preliminary clinical studies. Methods:\u00a099mTc-H-PoFP2 could be conveniently afforded using a kit formula with high radiochemical purity and stability. The binding specificity and affinity of 99mTc-H-PoFP2 for FAP were validated by an in vitro binding assay. The in vivo characteristics of 99mTc-H-PoFP2 were also determined. Results:\u00a099mTc-H-PoFP2 was eliminated quickly via the urinary system, leading to low normal tissue uptake and a high target\/background ratio. SPECT imaging demonstrated significantly enhanced uptake of the 99mTc-H-PoFP2 in bleomycin-induced fibrotic lung tissues, with visual effects superior to those of normal mice. Thus, a pilot clinical study of 99mTc-H-PoFP2 SPECT\/CT imaging was conducted in 12 patients diagnosed with fILD. The physiological biodistribution of 99mTc-H-PoFP2 in patients was predominantly observed in the kidneys, bladder, liver, and pancreas, with relatively minor accumulation in the thyroid, salivary glands, and spleen. fILD patients exhibited elevated pulmonary 99mTc-H-PoFP2 uptake in the affected lung regions. Furthermore, the uptake of 99mTc-HPoFP2 demonstrated moderate correlations with the results of pulmonary function tests (PFTs). A higher gender\u2013age\u2013physiology (GAP) index was associated with elevated standardized uptake value maximum (SUVmax) and target-to-background ratio (TBR) values. Conclusions: Collectively, this study demonstrates the potential of 99mTc-HPoFP2 for SPECT imaging and assessing fILD by targeting FAP overexpressed in fibrotic lung tissues. This strategy offers new possibilities for noninvasive and precise assessment of pulmonary fibrosis.<\/jats:p>","DOI":"10.3390\/ph18121779","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:24:17Z","timestamp":1763979857000},"page":"1779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel FAPI-Based Radiopharmaceutical for SPECT Imaging of Fibrotic Interstitial Lung Disease"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9071-5664","authenticated-orcid":false,"given":"Guangjie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4929-1923","authenticated-orcid":false,"given":"Jingnan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7220-9637","authenticated-orcid":false,"given":"Jiyun","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangzhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4166-5776","authenticated-orcid":false,"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1001\/jama.2024.3669","article-title":"Interstitial Lung Disease: A Review","volume":"331","author":"Maher","year":"2024","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1056\/NEJMra2005230","article-title":"Spectrum of Fibrotic Lung Diseases","volume":"383","author":"Wijsenbeek","year":"2020","journal-title":"N. 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