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Updated: Oct 3, 2026
Refined CLARITY-Based Tissue Clearing for Three-Dimensional Fibroblast Organization in Healthy and Injured Mouse Hearts
Published on: May 16, 2021
Fibroblast activation protein inhibitor positron emission tomography reveals active fibroblast-driven remodeling
Mohammad Reza Pourbehi1, Malik E Juweid2, Esmail Jafari3
1Bushehr Medical Heart Center, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
Background:
Post-myocardial infarction (MI) remodeling is driven by dynamic interactions between inflammatory and fibrotic processes. Conventional imaging techniques primarily detect established scar but fail to capture active fibroblast-mediated remodeling.
Objectives:
The aim of the present study was to determine whether [68Ga]Ga-FAPI-46 PET/CT (gallium-68 fibroblast activation protein inhibitor-46 positron emission tomography/computed tomography) can identify biologically active myocardial remodeling beyond established infarct scar using a multi-radiotracer molecular imaging approach in patients with early post-MI (≤1 month after MI) and late post-MI (greater than 1 month after MI).
Methods:
In this prospective study, 31 patients with early post-MI (≤1 month after MI) (N = 10) or late post-MI (greater than 1 month after MI) (N = 21) and 10 control subjects underwent [68Ga]Ga-FAPI-46 PET/CT, 18F-fluorodeoxyglucose ([18F]FDG PET/CT), and myocardial perfusion imaging (MPI) using [99mTc]Tc-MIBI SPECT [technetium-99m methoxyisobutylisonitrile single-photon emission computed tomography combined with computed tomography]. FAPI uptake was quantified using maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), fibroblast activation volume (FAV), and total lesion FAPI (TLF). FAPI uptake patterns were characterized, according to their spatial relationship with FDG metabolism, distinguishing infarct-associated and mixed phenotypes.
Results:
Myocardial FAPI uptake was observed in 87% of patients with MI and was significantly higher than in controls (SUVmax: 4.21 vs 2.64, P = 0.01; SUVmean: 2.46 vs 1.35, P = 0.001). In our cohort, 2 patient-level phenotypes were observed: A reparative pattern restricted to metabolically inactive infarct regions (48%) and a mixed pattern showing FAPI uptake in both infarct regions and FDG-preserved myocardium (52%). No patient exhibited a purely FDG-preserved FAPI-positive pattern. No significant differences in quantitative FAPI parameters were observed between early- and late post-MI. Notably, in a subset of patients, myocardial FAPI uptake extended beyond metabolically inactive infarct regions into adjacent FDG-preserved myocardium, suggesting spatially heterogeneous fibroblast-associated remodeling. Stratification based on median TLF demonstrated that higher FAPI burden was more frequently associated with mixed fibrosis patterns. Multi-radiotracer imaging enabled identification of hibernating myocardium in a subset of patients.
Conclusions:
[68Ga]Ga-FAPI-46 PET/CT enables noninvasive visualization of active fibroblast-associated myocardial remodeling following MI. Integrated assessment with [18F]FDG PET demonstrated spatially heterogeneous FAPI uptake involving metabolically inactive infarct regions and, in a subset of patients, adjacent FDG-preserved myocardium. The complementary information provided by these radiotracers may improve biological characterization of post-infarction myocardial remodeling, although the significance of FAPI uptake within FDG-preserved myocardium requires further investigation.
