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Background <p>Myocardial fibrosis is a major driver of heart failure progression, yet noninvasive tools to track its activity are limited. We evaluated fibroblast activation protein (FAP)-targeted [<sup>68</sup>Ga]Ga-FAPI-04 (FAPI = FAP inhibitor) positron emission tomography/computed tomography (PET/CT) in C57BL/6J mice subjected to transverse aortic constriction (TAC).</p> Results <p>PET/CT and echocardiography were performed at 2, 4, and 8 weeks post-surgery. Compared to the sham group, TAC mice exhibited significantly elevated myocardial [<sup>68</sup>Ga]Ga-FAPI-04 uptake at week 2, with progressive intensification at weeks 4 and 8. Although cardiac function remained preserved at week 2, pronounced systolic and diastolic dysfunction (decreased left ventricular ejection fraction [LVEF] and elevated E/A ratio) developed by week 4, deteriorating further by week 8. Correspondingly, histological (wheat germ agglutinin [WGA], Sirius Red, Masson’s) and autoradiographic analyses revealed progressive cardiomyocyte hypertrophy, accompanied by time-dependent increases in collagen deposition and FAP-specific signals. Importantly, a blocking experiment significantly suppressed myocardial uptake, confirming targeting specificity.</p> Conclusions <p>[<sup>68</sup>Ga]Ga-FAPI-04 PET/CT provides a specific, noninvasive method to track the progression of myocardial fibrosis. Crucially, increased FAPI uptake precedes the manifestation of cardiac dysfunction, highlighting its significant potential as a promising imaging tool for the early detection and longitudinal monitoring of heart failure.</p>

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Noninvasive tracking of myocardial fibrosis in pressure-overload heart failure with [68Ga]Ga-FAPI-04 PET/CT

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月27日

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  • Shanshan Liu,
  • Hui Wen,
  • Bingqing Han,
  • Fei Wang,
  • Xiangyang Gao,
  • Yi Luo,
  • Hao Zhang,
  • Xiaoyan Hao,
  • Chao Fu,
  • Zhaohui Xie,
  • Xiaojun Zhang,
  • Qiang Zeng

摘要

Background

Myocardial fibrosis is a major driver of heart failure progression, yet noninvasive tools to track its activity are limited. We evaluated fibroblast activation protein (FAP)-targeted [68Ga]Ga-FAPI-04 (FAPI = FAP inhibitor) positron emission tomography/computed tomography (PET/CT) in C57BL/6J mice subjected to transverse aortic constriction (TAC).

Results

PET/CT and echocardiography were performed at 2, 4, and 8 weeks post-surgery. Compared to the sham group, TAC mice exhibited significantly elevated myocardial [68Ga]Ga-FAPI-04 uptake at week 2, with progressive intensification at weeks 4 and 8. Although cardiac function remained preserved at week 2, pronounced systolic and diastolic dysfunction (decreased left ventricular ejection fraction [LVEF] and elevated E/A ratio) developed by week 4, deteriorating further by week 8. Correspondingly, histological (wheat germ agglutinin [WGA], Sirius Red, Masson’s) and autoradiographic analyses revealed progressive cardiomyocyte hypertrophy, accompanied by time-dependent increases in collagen deposition and FAP-specific signals. Importantly, a blocking experiment significantly suppressed myocardial uptake, confirming targeting specificity.

Conclusions

[68Ga]Ga-FAPI-04 PET/CT provides a specific, noninvasive method to track the progression of myocardial fibrosis. Crucially, increased FAPI uptake precedes the manifestation of cardiac dysfunction, highlighting its significant potential as a promising imaging tool for the early detection and longitudinal monitoring of heart failure.