Molecular phenotyping with <sup>18</sup>F-FDG and <sup>18</sup>F-FAPI PET/CT: advancing risk stratification in in-stent restenosis.
prospective_cohort · Level II
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- Also identified by DOI 10.1007/s00259-026-08036-5.
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Abstract
To investigate the potential of <sup>18</sup>F-FDG and <sup>18</sup>F-FAPI PET/CT for characterizing the pathophysiological heterogeneity of in-stent stenosis (ISR) and to assess their ability to differentiate between its clinically subtypes. This prospective study enrolled participants with ISR selected from a cohort registry between December 2024 to August 2025, which was categorized into rapid recurrent ISR (R-ISR) and ordinary ISR (O-ISR) based on recurrence time interval. For vessel-level analysis, coronary arteries without intervention served as control. All participants underwent both <sup>18</sup>F-FDG and <sup>18</sup>F-FAPI PET/CT to assess coronary uptake and evaluated the performance of maximum standardized uptake value (SUV<sub>max</sub>) and maximum target-to-background ratio (TBR<sub>max</sub>) in differentiating ISR from control vessels, as well as R-ISR from O-ISR. All patients were followed-up. The primary endpoint was a composite of cardiovascular death, target-vessel-related myocardial infarction, or target-vessel-related revascularization. Differences in the diagnostic performance of PET parameters and associations with outcomes were assessed. Thirty-one participants and 84 vessels were included. ISR vessels (n = 39) demonstrated higher uptake in <sup>18</sup>F-FDG and <sup>18</sup>F-FAPI than control (n = 45). R-ISR exhibited higher uptake compared to O-ISR on both patient-level (TBR<sub>max</sub>: <sup>18</sup>F-FAPI, 4.10 ± 1.41 vs. 1.75 ± 0.50; <sup>18</sup>F-FDG, 1.18 ± 0.32 vs. 0.86 ± 0.19) and vessel-level (TBR<sub>max</sub>: <sup>18</sup>F-FAPI, 4.07 ± 1.29 vs. 1.65 ± 0.50; <sup>18</sup>F-FDG, 1.16 ± 0.31 vs. 0.90 ± 0.28) (all P ≤ 0.01). <sup>18</sup>F-FAPI showed better diagnostic efficacy compared to <sup>18</sup>F-FDG (AUC of TBR<sub>max</sub>: 0.97 [0.92-1.00] vs. 0.75 [0.58-0.91], P = 0.01]. Six of 31 participants within R-ISR group reached the endpoint. Baseline PET uptake was associated with subsequent outcome (<sup>18</sup>F-FAPI SUV<sub>max</sub>, HR, 2.28 [95%CI: 1.25-5.09], P = 0.02; <sup>18</sup>F-FDG SUV<sub>max</sub>, HR, 33.2 [95%CI: 4.93-509], P = 0.002). <sup>18</sup>F-FAPI and <sup>18</sup>F-FDG PET/CT reveals the molecular heterogeneity of ISR, with <sup>18</sup>F-FAPI better identifying the rapid-recurrence subtype for advancing risk stratification. NCT05437965. Registered 24 June 2022.