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

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).

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 (DL_CO% 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.

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 DL_CO% pred (r_s = -0.65, P < 0.001; r_s = -0.54, P < 0.001). Notably, wlTU-FAPI was also correlated with FVC% pred (r_s = -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).

[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.