Identification of inflammation-dominant endotypes in refractory and recurrent in-stent restenosis by [18F]-FAPI PET/CT

Background Refractory and recurrent in-stent restenosis (RISR) remains a major clinical challenge following percutaneous coronary intervention, with an incompletely understood pathophysiology. Beyond traditional mechanical and neoatherosclerotic mechanisms, accumulating evidence suggests an immune-inflammatory etiology; however, reliable assessment of local vascular inflammatory activity is lacking. Although [18F]-FAPI PET/CT has emerged as a promising noninvasive approach for imaging fibro-inflammatory processes, its value in characterizing RISR and its association with inflammatory signatures have yet to be established. Purpose To determine whether [18F]-FAPI PET/CT can identify a distinct inflammatory endotype in patients with RISR through principal component analysis (PCA). Methods Fourteen patients with angiographically confirmed RISR (defined as ≥2 episodes at the same stented segment), in whom common ISR mechanisms were excluded by intracoronary imaging, underwent [18F]-FAPI PET/CT. A panel of inflammatory and clinical variables was integrated using principal component analysis (PCA). PCA-derived component scores were compared between FAPI-positive and FAPI-negative patients, and their discriminatory performance was assessed using receiver operating characteristic (ROC) analysis. Results Four principal components (PC1–PC4) accounted for 85% of the total variance. Only PC2 differed significantly between FAPI-positive and FAPI-negative groups (P < 0.05). PC2 was dominated by a strong positive loading of hsCRP (+0.790) and a strong negative loading of monocytes (–0.711), reflecting a CRP-associated inflammatory axis. FAPI-positive patients exhibited markedly higher PC2 scores, whereas FAPI-negative patients showed a monocyte-dominant profile. ROC analysis showed that PC2 discriminated FAPI positivity with an AUC of 0.80 (95% CI, 0.52–1.00). PC1, PC3, and PC4 showed no significant group differences or discriminatory performance. Conclusion [18F]-FAPI PET/CT identifies a biologically distinct inflammation–dominant RISR endotype, characterized by elevated hsCRP and reduced monocytes. These findings support the feasibility of integrating molecular imaging with inflammatory phenotyping to improve risk stratification and guide personalized therapeutic strategies in RISR.FAPI_PETCT_RISR_Positive_vs_NegativePC2_ROC_Curve_for_FAPI_Status