Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1

Abstract Pulmonary fibrosis (PF) is an interstitial chronic lung disease characterized by interstitial inflammation and extracellular matrix deposition, resulting in progressive lung dysfunction and ultimate respiratory failure. However, lacking of precise and noninvasive tracers for fibrotic lesion...

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Main Authors: Jing Li, Rui Shu, Tian Peng, Zifeng Yang, Mingzi Yang, Fengjiao Hu, Zhangqian Tao, Ying Hong, Zhiwei Cai, Jing Jia, Lu Wan, Song Tian, Zhi-Gang She, Hongliang Li, Xiao-Jing Zhang, Ejuan Zhang
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Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-78068-0
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author Jing Li
Rui Shu
Tian Peng
Zifeng Yang
Mingzi Yang
Fengjiao Hu
Zhangqian Tao
Ying Hong
Zhiwei Cai
Jing Jia
Lu Wan
Song Tian
Zhi-Gang She
Hongliang Li
Xiao-Jing Zhang
Ejuan Zhang
author_facet Jing Li
Rui Shu
Tian Peng
Zifeng Yang
Mingzi Yang
Fengjiao Hu
Zhangqian Tao
Ying Hong
Zhiwei Cai
Jing Jia
Lu Wan
Song Tian
Zhi-Gang She
Hongliang Li
Xiao-Jing Zhang
Ejuan Zhang
author_sort Jing Li
collection DOAJ
description Abstract Pulmonary fibrosis (PF) is an interstitial chronic lung disease characterized by interstitial inflammation and extracellular matrix deposition, resulting in progressive lung dysfunction and ultimate respiratory failure. However, lacking of precise and noninvasive tracers for fibrotic lesions limits timely diagnosis and treatment. Here, we identified LyP-1, a cyclic peptide, as a specific and sensitive tracer for PF detection using PET/CT imaging. FITC-LyP-1 selectively recognized fibrotic regions in bleomycin-induced PF mice, indicating its targeting capability. The colocalization of FITC-LyP-1 with extracellular collagen I within the fibrotic lesions validated its specificity, and further analysis revealed several potential target molecules. In the in vivo application studies, radiolabeled [68Ga]Ga-LyP-1 showed significantly increased lung uptake in PF mice, specifically enriching fibrotic regions on PET/CT imaging. Notably, compared to CT imaging that showed increased mean lung density throughout the phases after bleomycin-administration, lung uptake of [68Ga]Ga-LyP-1 was only increased in the later phase, indicating that LyP-1 recognizes the fibrous changes rather than the inflammatory cells in vivo. These results suggest that the new radiotracer [68Ga]Ga-LyP-1 specifically detects the extracellular matrix in fibrotic lungs. LyP-1 shows promise as a noninvasive tracer for assessing human pulmonary fibrosis, offering potential for improved diagnostic accuracy and timely intervention.
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spelling doaj-art-d346dbd651944b37b8e5252cd5ac488c2025-08-20T01:57:51ZengNature PortfolioScientific Reports2045-23222025-03-0115111710.1038/s41598-024-78068-0Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1Jing Li0Rui Shu1Tian Peng2Zifeng Yang3Mingzi Yang4Fengjiao Hu5Zhangqian Tao6Ying Hong7Zhiwei Cai8Jing Jia9Lu Wan10Song Tian11Zhi-Gang She12Hongliang Li13Xiao-Jing Zhang14Ejuan Zhang15School of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Huanggang Central HospitalSchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversitySchool of Basic Medical Science, Medical Science Research Center, Zhongnan Hospital, Wuhan UniversityAbstract Pulmonary fibrosis (PF) is an interstitial chronic lung disease characterized by interstitial inflammation and extracellular matrix deposition, resulting in progressive lung dysfunction and ultimate respiratory failure. However, lacking of precise and noninvasive tracers for fibrotic lesions limits timely diagnosis and treatment. Here, we identified LyP-1, a cyclic peptide, as a specific and sensitive tracer for PF detection using PET/CT imaging. FITC-LyP-1 selectively recognized fibrotic regions in bleomycin-induced PF mice, indicating its targeting capability. The colocalization of FITC-LyP-1 with extracellular collagen I within the fibrotic lesions validated its specificity, and further analysis revealed several potential target molecules. In the in vivo application studies, radiolabeled [68Ga]Ga-LyP-1 showed significantly increased lung uptake in PF mice, specifically enriching fibrotic regions on PET/CT imaging. Notably, compared to CT imaging that showed increased mean lung density throughout the phases after bleomycin-administration, lung uptake of [68Ga]Ga-LyP-1 was only increased in the later phase, indicating that LyP-1 recognizes the fibrous changes rather than the inflammatory cells in vivo. These results suggest that the new radiotracer [68Ga]Ga-LyP-1 specifically detects the extracellular matrix in fibrotic lungs. LyP-1 shows promise as a noninvasive tracer for assessing human pulmonary fibrosis, offering potential for improved diagnostic accuracy and timely intervention.https://doi.org/10.1038/s41598-024-78068-0Pulmonary fibrosisLyP-1Positron emission tomographyTracerPeptideNon-invasive imaging
spellingShingle Jing Li
Rui Shu
Tian Peng
Zifeng Yang
Mingzi Yang
Fengjiao Hu
Zhangqian Tao
Ying Hong
Zhiwei Cai
Jing Jia
Lu Wan
Song Tian
Zhi-Gang She
Hongliang Li
Xiao-Jing Zhang
Ejuan Zhang
Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1
Scientific Reports
Pulmonary fibrosis
LyP-1
Positron emission tomography
Tracer
Peptide
Non-invasive imaging
title Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1
title_full Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1
title_fullStr Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1
title_full_unstemmed Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1
title_short Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1
title_sort targeted imaging of pulmonary fibrosis by a cyclic peptide lyp 1
topic Pulmonary fibrosis
LyP-1
Positron emission tomography
Tracer
Peptide
Non-invasive imaging
url https://doi.org/10.1038/s41598-024-78068-0
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