Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET Imaging

Abstract Traditional imaging modalities used to monitor the diameter of aortic aneurysms (AAs) often fail to follow pathological progression. Fibroblast activation protein (FAP), a key regulator of extracellular matrix (ECM) remodeling, plays a pivotal role in aortic disease. However, its expression...

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Main Authors: Chengkai Hu, Hui Tan, Yuchong Zhang, Genmao Cao, Chenye Wu, Peng Lin, Shouji Qiu, Fandi Mo, Enci Wang, Shiyi Li, Tong Yuan, Zheyun Li, Weiguo Fu, Dengfeng Cheng, Hao Lai, Xiaoyuan Chen, Lixin Wang
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202411152
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author Chengkai Hu
Hui Tan
Yuchong Zhang
Genmao Cao
Chenye Wu
Peng Lin
Shouji Qiu
Fandi Mo
Enci Wang
Shiyi Li
Tong Yuan
Zheyun Li
Weiguo Fu
Dengfeng Cheng
Hao Lai
Xiaoyuan Chen
Lixin Wang
author_facet Chengkai Hu
Hui Tan
Yuchong Zhang
Genmao Cao
Chenye Wu
Peng Lin
Shouji Qiu
Fandi Mo
Enci Wang
Shiyi Li
Tong Yuan
Zheyun Li
Weiguo Fu
Dengfeng Cheng
Hao Lai
Xiaoyuan Chen
Lixin Wang
author_sort Chengkai Hu
collection DOAJ
description Abstract Traditional imaging modalities used to monitor the diameter of aortic aneurysms (AAs) often fail to follow pathological progression. Fibroblast activation protein (FAP), a key regulator of extracellular matrix (ECM) remodeling, plays a pivotal role in aortic disease. However, its expression in the aortic wall during aneurysm progression and its potential correlation with disease severity remains unexplored. Here, utilizing histology the levels of FAP are higher in the aortic wall of patients with AA compared to healthy controls. In three distinct animal models of AA, a progressive increase in FAP expression, coincides with the advancement of ECM remodeling. Notably, the levels of 68Ga‐FAPI‐04 uptake in a rabbit model of abdominal AA (AAA) is positively correlated with aortic dilation (r = 0.84, p < 0.01), and the histological examination further confirmed that regions of high 68Ga‐FAPI‐04 uptake exhibited both increased FAP expression and more severe pathological changes. The 68Ga‐FAPI‐04 imaging in AA patients showed that the radiotracer specifically accumulated in the aortic walls of persistently dilated AA. These findings suggest that 68Ga‐FAPI‐04 positron emission tomographic (PET) imaging, by visualizing FAP localization, allows for a non‐invasive approach to potentially monitor ECM remodeling during the AA progression.
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spelling doaj-art-1fcfa895d50f4c4e9d9f0426b8965e8d2025-08-20T02:16:22ZengWileyAdvanced Science2198-38442025-04-011214n/an/a10.1002/advs.202411152Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET ImagingChengkai Hu0Hui Tan1Yuchong Zhang2Genmao Cao3Chenye Wu4Peng Lin5Shouji Qiu6Fandi Mo7Enci Wang8Shiyi Li9Tong Yuan10Zheyun Li11Weiguo Fu12Dengfeng Cheng13Hao Lai14Xiaoyuan Chen15Lixin Wang16Department of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Nuclear Medicine Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Cardiac Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Nuclear Medicine Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartment of Cardiac Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaDepartments of Diagnostic Radiology Chemical and Biomolecular Engineering, Biomedical Engineering, Pharmacy and Pharmaceutical Sciences Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore Singapore 119074 SingaporeDepartment of Vascular Surgery Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 ChinaAbstract Traditional imaging modalities used to monitor the diameter of aortic aneurysms (AAs) often fail to follow pathological progression. Fibroblast activation protein (FAP), a key regulator of extracellular matrix (ECM) remodeling, plays a pivotal role in aortic disease. However, its expression in the aortic wall during aneurysm progression and its potential correlation with disease severity remains unexplored. Here, utilizing histology the levels of FAP are higher in the aortic wall of patients with AA compared to healthy controls. In three distinct animal models of AA, a progressive increase in FAP expression, coincides with the advancement of ECM remodeling. Notably, the levels of 68Ga‐FAPI‐04 uptake in a rabbit model of abdominal AA (AAA) is positively correlated with aortic dilation (r = 0.84, p < 0.01), and the histological examination further confirmed that regions of high 68Ga‐FAPI‐04 uptake exhibited both increased FAP expression and more severe pathological changes. The 68Ga‐FAPI‐04 imaging in AA patients showed that the radiotracer specifically accumulated in the aortic walls of persistently dilated AA. These findings suggest that 68Ga‐FAPI‐04 positron emission tomographic (PET) imaging, by visualizing FAP localization, allows for a non‐invasive approach to potentially monitor ECM remodeling during the AA progression.https://doi.org/10.1002/advs.202411152aortic aneurysmextracellular matrixfibroblast activation proteinpositron emission tomography imaging
spellingShingle Chengkai Hu
Hui Tan
Yuchong Zhang
Genmao Cao
Chenye Wu
Peng Lin
Shouji Qiu
Fandi Mo
Enci Wang
Shiyi Li
Tong Yuan
Zheyun Li
Weiguo Fu
Dengfeng Cheng
Hao Lai
Xiaoyuan Chen
Lixin Wang
Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET Imaging
Advanced Science
aortic aneurysm
extracellular matrix
fibroblast activation protein
positron emission tomography imaging
title Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET Imaging
title_full Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET Imaging
title_fullStr Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET Imaging
title_full_unstemmed Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET Imaging
title_short Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga‐FAPI‐04 PET Imaging
title_sort fibroblast activation protein acts as a biomarker for monitoring ecm remodeling during aortic aneurysm via 68ga fapi 04 pet imaging
topic aortic aneurysm
extracellular matrix
fibroblast activation protein
positron emission tomography imaging
url https://doi.org/10.1002/advs.202411152
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