Association of Atherosclerosis [68Ga]Ga-FAPI-04 Uptake with Calcified Plaque Burden and Cardiovascular Risk Factors: Comparison with [18F]FDG PET/CT.

PURPOSE: This study aimed to evaluate the association of atherosclerosis [68Ga]Ga-FAPI-04 uptake with calcified plaque burden, cardiovascular risk factors (CVRFs), and to compare these findings with [18F]FDG PET/CT. METHODS: A retrospective analysis was performed on 69 patients (referred for non-cardiovascular indications) who underwent both [68Ga]Ga-FAPI-04 and [18F]FDG PET/CT between August 2020 and November 2023. Tracer uptake was quantified using target-to-background ratio (TBR). The wilcoxon signed-rank test was used to compare two tracers' uptake, while partial correlation and generalized linear model adjusted for age and sex were applied to assess associations with calcified plaque (CP) and CVRFs. RESULTS: FAPI-TBR was significantly higher than that of [18F]FDG in patient-based analyses, in PET-positive arterial wall regions on both modalities, and in the subgroup with concomitant calcification (all P < 0.001). The number of FAPI-positive lesions exhibited significant positive correlations with CP burden and the number of CVRFs; mean TBR‑FAPI was also positively associated with CVRF count (r = 0.250 ~ 0.257, all P < 0.05). Subgroup analyses revealed that high-risk patients (CVRFs ≥ 4) had significantly higher TBR-FAPI than low-risk patients [median (IQR): 1.77 (0.32) vs. 1.54 (0.31); P = 0.047], whereas no such difference was observed for [18F]FDG uptake. Furthermore, TBR-FAPI was significantly elevated in overweight patients compared to normal-weight patients (P < 0.001). CONCLUSION: [⁶⁸Ga]Ga-FAPI-04 PET provides complementary information to [1⁸F]FDG by reflecting fibrotic remodeling, and may aid in refining cardiovascular risk stratification; however, prospective studies are warranted to establish its clinical utility.