Key result
[68Ga]Ga-FAPI-04 PET reveals ~96% higher myocardial uptake in mice with pressure-overload heart failure.
Why the study?
Myocardial fibrosis is a major driver of heart failure progression, but noninvasive tools to track its activity are limited.
Does [68Ga]Ga-FAPI-04 PET/CT imaging track the progression of myocardial fibrosis in a mouse model of pressure-overload heart failure?
Does [68Ga]Ga-FAPI-04 PET/CT imaging track the progression of myocardial fibrosis in a mouse model of pressure-overload heart failure?
[68Ga]Ga-FAPI-04 PET/CT provides a specific, noninvasive method to track myocardial fibrosis progression, with uptake preceding the onset of cardiac dysfunction.
May enable early fibrosis detection in experimental HF models; hypothesis-generating and requires human validation before clinical consideration.
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). 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. [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.
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Liu et al. (2026) studied Pressure-overload heart failure / Myocardial fibrosis. [68Ga]Ga-FAPI-04 vs. Sham was evaluated on Myocardial [68Ga]Ga-FAPI-04 uptake (%ID/g) at 8 weeks (p=<0.01). [68Ga]Ga-FAPI-04 PET/CT revealed progressively increased myocardial uptake in a mouse model of pressure-overload heart failure, reaching 2.14 %ID/g at 8 weeks compared to 1.09 %ID/g in shams.
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