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Purpose <p>This prospective study aimed to compare the prognostic value of [<sup>18</sup>F]FAPI-42 (fibroblast activation protein inhibitor) and [<sup>18</sup>F]FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF).</p> Methods <p>Fifty-two patients with IPF underwent dual-tracer PET/CT. Whole-lung total uptake (wlTU) was quantified for [<sup>18</sup>F]FAPI-42 and [<sup>18</sup>F]FDG. PET parameters were correlated with percent predicted forced vital capacity (FVC% pred), percent predicted diffusing capacity for carbon monoxide (DL<sub>CO</sub>% pred), and the Gender-Age-Physiology (GAP) stage. Immunohistochemical staining (IHC) for FAP and glucose transporter 1 (GLUT-1) was performed (<i>n</i> = 4). The primary endpoint was a composite of all-cause death or lung transplantation (LuTx), analyzed using Kaplan-Meier and Cox proportional hazards models.</p> Results <p>In patients with IPF, the median wlTU-FAPI was higher in GAP stage II and III than in GAP stage I (3733 vs. 2985, <i>P</i> = 0.039), whereas wlTU-FDG was not (2247 vs. 2176, <i>P</i> = 0.911). Furthermore, wlTU-FAPI and wlTU-FDG were negatively correlated with DL<sub>CO</sub>% pred (<i>r</i><sub><i>s</i></sub> = -0.65, <i>P</i> &lt; 0.001; <i>r</i><sub><i>s</i></sub> = -0.54, <i>P</i> &lt; 0.001). Notably, wlTU-FAPI was also correlated with FVC% pred (<i>r</i><sub><i>s</i></sub> = -0.44, <i>P</i> = 0.002), whereas wlTU-FDG did not (<i>P</i> = 0.291). IHC confirmed high FAP and low GLUT-1 expression in fibroblast foci (<i>n</i> = 4). During a median follow-up of 19 (17.0–20.0) months (<i>n</i> = 48), the 13 patients reached the composite endpoint exhibited higher median wlTU-FAPI (3728 vs. 2888, <i>P</i> = 0.028). Conversely, no significant difference was observed for wlTU-FDG (2261 vs. 2139, <i>P</i> = 0.231). In multivariable Cox regression analysis, wlTU-FAPI emerged as an independent predictor of death or LuTx (hazard ratio [HR] per 1000-unit increase, 4.62; 95% CI, 1.62–13.22; <i>P</i> = 0.004), wheras wlTU-FDG did not (<i>P</i> = 0.782). Kaplan-Meier also demonstrated the prognostic value of wlTU-FAPI (cutoff = 2865, <i>P</i> = 0.018), whereas wlTU-FDG was not significant (cutoff = 2036, <i>P</i> = 0.660).</p> Conclusion <p>[<sup>18</sup>F]FAPI-42 PET/CT is a promising noninvasive imaging biomarker for predicting clinical outcomes in IPF. Compared with [<sup>18</sup>F]FDG PET/CT, [<sup>18</sup>F]FAPI-42 demonstrated stronger associations with disease severity and adverse clinical outcomes in this prospective cohort. These findings warrant further validation in larger and more diverse IPF populations.</p> Graphical abstract <p></p>

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[18F]FAPI-42 PET/CT for prognostic assessment in idiopathic pulmonary fibrosis: a prospective head-to-head comparison with [18F]FDG PET/CT

  • 期刊论文

  • 发表日期：

    2026年7月30日

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  • Qi Fang,
  • Peng Hou,
  • Shu Xia,
  • Shaonan Zhong,
  • Ruiyue Zhao,
  • Wanmei Liang,
  • Jiangyu Cui,
  • Yvlu He,
  • Xuejing Bai,
  • Youcai Li,
  • Ziyi Zhang,
  • Zhenli Fu,
  • Shaoyu Liu,
  • Jie Lv,
  • Bingpeng Guo,
  • Yimin Fu,
  • Huizhen Zhong,
  • Nanshan Zhong,
  • Qian Han,
  • Qun Luo,
  • XinLu Wang

摘要

Purpose

This prospective study aimed to compare the prognostic value of [18F]FAPI-42 (fibroblast activation protein inhibitor) and [18F]FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF).

Methods

Fifty-two patients with IPF underwent dual-tracer PET/CT. Whole-lung total uptake (wlTU) was quantified for [18F]FAPI-42 and [18F]FDG. PET parameters were correlated with percent predicted forced vital capacity (FVC% pred), percent predicted diffusing capacity for carbon monoxide (DLCO% pred), and the Gender-Age-Physiology (GAP) stage. Immunohistochemical staining (IHC) for FAP and glucose transporter 1 (GLUT-1) was performed (n = 4). The primary endpoint was a composite of all-cause death or lung transplantation (LuTx), analyzed using Kaplan-Meier and Cox proportional hazards models.

Results

In patients with IPF, the median wlTU-FAPI was higher in GAP stage II and III than in GAP stage I (3733 vs. 2985, P = 0.039), whereas wlTU-FDG was not (2247 vs. 2176, P = 0.911). Furthermore, wlTU-FAPI and wlTU-FDG were negatively correlated with DLCO% pred (rs = -0.65, P < 0.001; rs = -0.54, P < 0.001). Notably, wlTU-FAPI was also correlated with FVC% pred (rs = -0.44, P = 0.002), whereas wlTU-FDG did not (P = 0.291). IHC confirmed high FAP and low GLUT-1 expression in fibroblast foci (n = 4). During a median follow-up of 19 (17.0–20.0) months (n = 48), the 13 patients reached the composite endpoint exhibited higher median wlTU-FAPI (3728 vs. 2888, P = 0.028). Conversely, no significant difference was observed for wlTU-FDG (2261 vs. 2139, P = 0.231). In multivariable Cox regression analysis, wlTU-FAPI emerged as an independent predictor of death or LuTx (hazard ratio [HR] per 1000-unit increase, 4.62; 95% CI, 1.62–13.22; P = 0.004), wheras wlTU-FDG did not (P = 0.782). Kaplan-Meier also demonstrated the prognostic value of wlTU-FAPI (cutoff = 2865, P = 0.018), whereas wlTU-FDG was not significant (cutoff = 2036, P = 0.660).

Conclusion

[18F]FAPI-42 PET/CT is a promising noninvasive imaging biomarker for predicting clinical outcomes in IPF. Compared with [18F]FDG PET/CT, [18F]FAPI-42 demonstrated stronger associations with disease severity and adverse clinical outcomes in this prospective cohort. These findings warrant further validation in larger and more diverse IPF populations.

Graphical abstract