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Purpose <p>This study aimed to investigate in vivo fibroblast activation in hypereosinophilic syndrome (HES) with cardiac involvement, and to explore the correlation between fibroblast activation protein inhibitor (FAPI) uptake and eosinophil-related biomarker-eosinophil extracellular traps (EETs).</p> Methods <p>This study enrolled 20 patients diagnosed with HES and cardiac involvement. All patients underwent Al<sup>18</sup>F-FAPI-04 PET/CT imaging, transthoracic echocardiography, as well as measurement of absolute eosinophil count (AEC) and EETs levels.</p> Results <p>Among the 20 patients enrolled, 16 patients were diagnosed with reactive HES and 4 with idiopathic HES. Elevated FAPI uptake was observed across different stages of disease course. Myocardial Al<sup>18</sup>F-FAPI uptake was observed in all patients (20/20), with an extensive pattern in 15 and a patchy pattern in 5. Quantitative uptake was significantly higher in the extensive pattern group (maximum standardized uptake value (SUV<sub>max</sub>): 6.58 [5.01–8.62] vs. 2.44 [1.91–2.76], <i>p</i> &lt; 0.001). Segmental analysis revealed higher FAPI uptake in apical and mid-ventricular segments compared to basal segments (SUV<sub>max</sub>: apical, 4.67 [1.94–6.89] vs. middle, 4.25 [2.33–5.61] vs. basal, 3.44 [2.46–5.23], <i>p</i> = 0.022). FAPI-PET/CT identified a higher proportion of involved myocardial segments (83.2%) than echocardiographic longitudinal strain (55%). Clinically, patients with higher FAPI uptake had significantly elevated N-Terminal pro-B-type natriuretic peptide levels. Of note, higher FAPI uptake was significantly associated with elevated levels of EETs (e.g., SUV<sub>max</sub>-high vs. low: 278.4 ± 74.3 vs. 105.9 ± 13.5), but not with AEC.</p> Conclusions <p>Al<sup>18</sup>F-FAPI PET/CT demonstrated good utility and sensitivity for visualizing active myocardial fibrosis across different disease stages in HES with cardiac involvement. Fibroblast activation was detectable in early phases. FAPI uptake could be correlated with elevated EETs, suggesting their potential role in fibrosis. Al<sup>18</sup>F-FAPI PET/CT is a valuable tool for comprehensive evaluation, and EET may represent a promising therapeutic target to mitigate eosinophil-mediated cardiac damage in HES.</p>

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Al18F-FAPI PET/CT in hypereosinophilic syndrome with cardiac involvement and its potential association with eosinophil extracellular traps

  • 期刊论文

  • 发表日期：

    2026年4月22日

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  • Xiaohang Liu,
  • Yifan Liu,
  • Yu Qiu,
  • Jingdai Zhang,
  • Keting Xu,
  • Tianchen Guo,
  • Yanwei Wang,
  • Xueqian Yang,
  • Siyu Wang,
  • Yining Wang,
  • Zhenyu Liu,
  • Dachun Zhao,
  • Na Niu,
  • Li Huo,
  • Wei Chen

摘要

Purpose

This study aimed to investigate in vivo fibroblast activation in hypereosinophilic syndrome (HES) with cardiac involvement, and to explore the correlation between fibroblast activation protein inhibitor (FAPI) uptake and eosinophil-related biomarker-eosinophil extracellular traps (EETs).

Methods

This study enrolled 20 patients diagnosed with HES and cardiac involvement. All patients underwent Al18F-FAPI-04 PET/CT imaging, transthoracic echocardiography, as well as measurement of absolute eosinophil count (AEC) and EETs levels.

Results

Among the 20 patients enrolled, 16 patients were diagnosed with reactive HES and 4 with idiopathic HES. Elevated FAPI uptake was observed across different stages of disease course. Myocardial Al18F-FAPI uptake was observed in all patients (20/20), with an extensive pattern in 15 and a patchy pattern in 5. Quantitative uptake was significantly higher in the extensive pattern group (maximum standardized uptake value (SUVmax): 6.58 [5.01–8.62] vs. 2.44 [1.91–2.76], p < 0.001). Segmental analysis revealed higher FAPI uptake in apical and mid-ventricular segments compared to basal segments (SUVmax: apical, 4.67 [1.94–6.89] vs. middle, 4.25 [2.33–5.61] vs. basal, 3.44 [2.46–5.23], p = 0.022). FAPI-PET/CT identified a higher proportion of involved myocardial segments (83.2%) than echocardiographic longitudinal strain (55%). Clinically, patients with higher FAPI uptake had significantly elevated N-Terminal pro-B-type natriuretic peptide levels. Of note, higher FAPI uptake was significantly associated with elevated levels of EETs (e.g., SUVmax-high vs. low: 278.4 ± 74.3 vs. 105.9 ± 13.5), but not with AEC.

Conclusions

Al18F-FAPI PET/CT demonstrated good utility and sensitivity for visualizing active myocardial fibrosis across different disease stages in HES with cardiac involvement. Fibroblast activation was detectable in early phases. FAPI uptake could be correlated with elevated EETs, suggesting their potential role in fibrosis. Al18F-FAPI PET/CT is a valuable tool for comprehensive evaluation, and EET may represent a promising therapeutic target to mitigate eosinophil-mediated cardiac damage in HES.