FAPI PET/CT in post-PCI coronary disease: in-stent restenosis characterization, MACE association, and limited...

Fibroblast activation plays a key role in plaque instability and coronary artery disease (CAD) progression. In-stent restenosis (ISR) remains a major complication after percutaneous coronary intervention (PCI), increasing the risk of major adverse cardiovascular events (MACEs). This study primarily aimed to investigate whether coronary [¹⁸F]AlF-NOTA-FAPI-04 uptake is associated with major adverse cardiovascular events (MACEs) in symptomatic post-PCI patients, and secondarily to explore its ability to differentiate ISR from in-stent non-restenosis (ISnR) and to evaluate longitudinal changes under lipid-lowering therapy.

In this prospective single-centre observational cohort study, we enrolled symptomatic CAD patients with a history of PCI A total of 76 symptomatic CAD patients (30 with acute coronary syndrome [ACS] and 46 with stable coronary syndrome [SCS]) underwent FAPI PET/CT imaging. Twenty-two non-CVD individuals served as controls. Coronary SUV_max and TBR were measured. The primary endpoint was the occurrence of MACEs, while the secondary endpoint was changes in FAPI uptake on follow-up PET/CT. The effects of Lipid-lowering therapy(LLT) on coronary FAPI uptake were also evaluated.

FAPI uptake was significantly higher in ACS (SUV_max: 4.06 ± 1.81, TBR: 4.51 ± 2.20) than in SCS (SUV_max: 2.47 ± 1.82, TBR: 2.89 ± 2.23, P < 0.05). ISR plaques exhibited markedly elevated FAPI uptake (SUV_max: 4.06 ± 1.91, TBR: 4.69 ± 2.25) compared to ISnR plaques (SUV_max: 1.69 ± 0.72, TBR: 1.88 ± 0.91, P < 0.0001). Exploratory analyses suggested a trend toward higher MACE risk with elevated uptake, but survival differences were not significant.

FAPI PET/CT enables non-invasive assessment of fibroblast-driven plaque activity, particularly in ISR, and identifies high-risk coronary plaques linked to MACEs. While LLT did not significantly modify fibroblast activity in the short term, further studies are needed to explore its long-term effects on plaque stability. (FAPI-PLAQUE Study, NCT06280287).