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Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent
[Image: see text] Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen asso...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nanjing University and American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302889/ https://www.ncbi.nlm.nih.gov/pubmed/37388961 http://dx.doi.org/10.1021/cbmi.3c00023 |
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author | Ibhagui, Oluwatosin Y. Li, Dongjun Han, Hongwei Peng, Guangda Meister, Maureen L. Gui, Zongxiang Qiao, Jingjuan Salarian, Mani Dong, Bin Yuan, Yi Xu, Yiting Yang, Hua Tan, Shanshan Satyanarayana, Ganesh Xue, Shenghui Turaga, Ravi Chakra Sharma, Malvika Hai, Yan Meng, Yuguang Hekmatyar, Khan Sun, Phillip Sica, Gabriel Ji, Xiangming Liu, Zhi-ren Yang, Jenny J. |
author_facet | Ibhagui, Oluwatosin Y. Li, Dongjun Han, Hongwei Peng, Guangda Meister, Maureen L. Gui, Zongxiang Qiao, Jingjuan Salarian, Mani Dong, Bin Yuan, Yi Xu, Yiting Yang, Hua Tan, Shanshan Satyanarayana, Ganesh Xue, Shenghui Turaga, Ravi Chakra Sharma, Malvika Hai, Yan Meng, Yuguang Hekmatyar, Khan Sun, Phillip Sica, Gabriel Ji, Xiangming Liu, Zhi-ren Yang, Jenny J. |
author_sort | Ibhagui, Oluwatosin Y. |
collection | PubMed |
description | [Image: see text] Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.collagen) to specifically bind to collagen I overexpressed in multiple lung diseases. When compared to clinically approved Gd(3+) contrast agents, hProCA32.collagen exhibits significantly better r(1) and r(2) relaxivity values, strong metal binding affinity and selectivity, and transmetalation resistance. Here, we report the robust detection of early and late-stage lung fibrosis with stage-dependent MRI signal-to-noise ratio (SNR) increase, with good sensitivity and specificity, using a progressive bleomycin-induced IPF mouse model. Spatial heterogeneous mapping of usual interstitial pneumonia (UIP) patterns with key features closely mimicking human IPF, including cystic clustering, honeycombing, and traction bronchiectasis, were noninvasively detected by multiple MR imaging techniques and verified by histological correlation. We further report the detection of fibrosis in the lung airway of an electronic cigarette-induced COPD mouse model, using hProCA32.collagen-enabled precision MRI (pMRI), and validated by histological analysis. The developed hProCA32.collagen is expected to have strong translational potential for the noninvasive detection and staging of lung diseases, and facilitating effective treatment to halt further chronic lung disease progression. |
format | Online Article Text |
id | pubmed-10302889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nanjing University and American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-103028892023-06-29 Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent Ibhagui, Oluwatosin Y. Li, Dongjun Han, Hongwei Peng, Guangda Meister, Maureen L. Gui, Zongxiang Qiao, Jingjuan Salarian, Mani Dong, Bin Yuan, Yi Xu, Yiting Yang, Hua Tan, Shanshan Satyanarayana, Ganesh Xue, Shenghui Turaga, Ravi Chakra Sharma, Malvika Hai, Yan Meng, Yuguang Hekmatyar, Khan Sun, Phillip Sica, Gabriel Ji, Xiangming Liu, Zhi-ren Yang, Jenny J. Chem Biomed Imaging [Image: see text] Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.collagen) to specifically bind to collagen I overexpressed in multiple lung diseases. When compared to clinically approved Gd(3+) contrast agents, hProCA32.collagen exhibits significantly better r(1) and r(2) relaxivity values, strong metal binding affinity and selectivity, and transmetalation resistance. Here, we report the robust detection of early and late-stage lung fibrosis with stage-dependent MRI signal-to-noise ratio (SNR) increase, with good sensitivity and specificity, using a progressive bleomycin-induced IPF mouse model. Spatial heterogeneous mapping of usual interstitial pneumonia (UIP) patterns with key features closely mimicking human IPF, including cystic clustering, honeycombing, and traction bronchiectasis, were noninvasively detected by multiple MR imaging techniques and verified by histological correlation. We further report the detection of fibrosis in the lung airway of an electronic cigarette-induced COPD mouse model, using hProCA32.collagen-enabled precision MRI (pMRI), and validated by histological analysis. The developed hProCA32.collagen is expected to have strong translational potential for the noninvasive detection and staging of lung diseases, and facilitating effective treatment to halt further chronic lung disease progression. Nanjing University and American Chemical Society 2023-05-22 /pmc/articles/PMC10302889/ /pubmed/37388961 http://dx.doi.org/10.1021/cbmi.3c00023 Text en © 2023 The Authors. Co-published by Nanjing University and American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Ibhagui, Oluwatosin Y. Li, Dongjun Han, Hongwei Peng, Guangda Meister, Maureen L. Gui, Zongxiang Qiao, Jingjuan Salarian, Mani Dong, Bin Yuan, Yi Xu, Yiting Yang, Hua Tan, Shanshan Satyanarayana, Ganesh Xue, Shenghui Turaga, Ravi Chakra Sharma, Malvika Hai, Yan Meng, Yuguang Hekmatyar, Khan Sun, Phillip Sica, Gabriel Ji, Xiangming Liu, Zhi-ren Yang, Jenny J. Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent |
title | Early Detection and
Staging of Lung Fibrosis Enabled
by Collagen-Targeted MRI Protein Contrast Agent |
title_full | Early Detection and
Staging of Lung Fibrosis Enabled
by Collagen-Targeted MRI Protein Contrast Agent |
title_fullStr | Early Detection and
Staging of Lung Fibrosis Enabled
by Collagen-Targeted MRI Protein Contrast Agent |
title_full_unstemmed | Early Detection and
Staging of Lung Fibrosis Enabled
by Collagen-Targeted MRI Protein Contrast Agent |
title_short | Early Detection and
Staging of Lung Fibrosis Enabled
by Collagen-Targeted MRI Protein Contrast Agent |
title_sort | early detection and
staging of lung fibrosis enabled
by collagen-targeted mri protein contrast agent |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302889/ https://www.ncbi.nlm.nih.gov/pubmed/37388961 http://dx.doi.org/10.1021/cbmi.3c00023 |
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