Work

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

Year: 2026

Type: article

Abstract: 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 [ 68 Ga]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 [ 68 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. [ 68 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.

Source: EJNMMI Research

DOI: 10.1186/s13550-026-01461-5