18F-FAPI-74 Positron Emission Tomography/Computed Tomography Noninvasively Monitoring the Fibrosis of Cardiac Allograft Vasculopathy.

IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Journal of the American Heart Association Pub Date : 2025-10-07 Epub Date: 2025-09-30 DOI:10.1161/JAHA.125.041169
Huiling Li, Yufei Wei, Zhuoqi Qin, Qiyao Cheng, Yu Hong, Huibin Ru, Tingrui Song, Li Li, Xinzhong Hao, Jianhua Jin, Yan Cheng, Zhifang Wu, Sijin Li
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引用次数: 0

Abstract

Background: Cardiac allograft vasculopathy (CAV) is the primary cause of limited long-term survival among heart transplant recipients. This study aimed to evaluate the feasibility of 18F-FAPI-74 positron emission tomography/computed tomography (PET/CT) imaging for monitoring the fibrosis of CAV.

Methods: Rat models of CAV were established and 1 hour dynamic PET/CT imaging was performed in the 15th week postoperation. Serial static 18F-FAPI-74 PET/CT imaging in the allograft and isograft groups were performed from week 3 to 17. Blocking experiments were performed on allograft rats to confirm the tracer's targeting specificity. In vivo PET/CT imaging findings were further corroborated by ex vivo PET/CT imaging and biodistribution studies. Histological examination was conducted to validate the model's effectiveness, and the correlation between FAP expression levels and imaging results was ascertained.

Results: Dynamic PET/CT imaging revealed peak graft heart (Ht) uptake in the allograft group at 60 minutes post 18F-FAPI-74 injection. PET/CT imaging and biodistribution studies at all time points confirmed significantly higher radioactivity uptake in Ht of the allograft group, as compared with both their native hearts and Ht of the isograft group, and peaking at week 15. There was almost no radioactive accumulation of Ht in the allograft rats blocked by FAPI. Histological analysis confirmed significantly elevated FAP expression in Ht of the allograft group compared with the isograft group, consistent with the severity of CAV.

Conclusions: We successfully achieved molecular imaging of activated fibroblasts in CAV rat models, indicating that 18F-FAPI-74 PET/CT may be a valuable means of evaluating fibrosis progression of CAV.

18F-FAPI-74正电子发射断层扫描/计算机断层扫描无创监测同种异体心脏移植血管病变纤维化。
背景:同种异体心脏移植血管病变(CAV)是心脏移植受者长期生存受限的主要原因。本研究旨在评价18F-FAPI-74正电子发射断层扫描/计算机断层扫描(PET/CT)成像监测CAV纤维化的可行性。方法:建立大鼠CAV模型,术后第15周进行1小时动态PET/CT成像。同种异体移植组和同种异体移植组于第3 ~ 17周进行连续静态18F-FAPI-74 PET/CT成像。对同种异体移植大鼠进行阻断实验,证实示踪剂的靶向特异性。体内PET/CT成像结果进一步证实了离体PET/CT成像和生物分布研究。通过组织学检查验证模型的有效性,并确定FAP表达水平与影像学结果的相关性。结果:动态PET/CT成像显示同种异体移植组在注射18F-FAPI-74后60分钟移植物心脏(Ht)摄取达到峰值。所有时间点的PET/CT成像和生物分布研究证实,与原生心脏和同种移植组相比,同种异体移植组的Ht放射性摄取明显更高,并在第15周达到峰值。FAPI阻断的同种异体移植大鼠体内几乎没有放射性的Ht积累。组织学分析证实,与同种异体移植组相比,同种异体移植组的FAP在Ht中的表达明显升高,与CAV的严重程度一致。结论:我们成功地在CAV大鼠模型中实现了活化成纤维细胞的分子成像,表明18F-FAPI-74 PET/CT可能是评估CAV纤维化进展的一种有价值的手段。
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来源期刊
Journal of the American Heart Association
Journal of the American Heart Association CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
9.40
自引率
1.90%
发文量
1749
审稿时长
12 weeks
期刊介绍: As an Open Access journal, JAHA - Journal of the American Heart Association is rapidly and freely available, accelerating the translation of strong science into effective practice. JAHA is an authoritative, peer-reviewed Open Access journal focusing on cardiovascular and cerebrovascular disease. JAHA provides a global forum for basic and clinical research and timely reviews on cardiovascular disease and stroke. As an Open Access journal, its content is free on publication to read, download, and share, accelerating the translation of strong science into effective practice.
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