FAPI PET/CT for tracking disease trajectory in myositis-related interstitial lung disease

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Interstitial lung disease (ILD) is associated with morbidity and mortality in idiopathic inflammatory myopathies (IIM). Predicting ILD progression remains a significant challenge, as conventional diagnostic tools such as pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) have limited prognostic accuracy. This study evaluated whether 68 Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPI) based PET/CT at baseline predicts ILD evolution over two years. In this prospective observational study, n = 19 individuals with IIM (n = 14 with ILD) underwent [ 68 Ga] Ga-FAPI PET/CT at baseline. ILD progression was defined by three criteria: (1) FVC decline ≥10 % or FVC 5–9 % plus DLCO decline ≥15 %, (2) INBUILD criteria, and (3) a composite endpoint including INBUILD plus therapy escalation, hospitalization, or mortality. Pulmonary tracer uptake was quantified by calculating the maximum and mean target-to-background ratios across the whole lung (wlTBR max and wlTBR mean , respectively), derived from standardized uptake values corrected for blood pool activity, and their predictive value was analysed. Over two years, n = 4 (28.6 %) patients met PFT-based progression criteria, while n = 6 (42.9 %) fulfilled INBUILD criteria, and n = 8 (57.1 %) reached the composite endpoint. Baseline wlTBR max was significantly higher in INBUILD progressors compared to non-progressors (2.68 ± 1.06 vs. 1.59 ± 0.80, p = 0.04), as was wlTBR mean (0.58 ± 0.22 vs. 0.34 ± 0.10, p = 0.04). Similarly, patients meeting the composite endpoint had higher wlTBR max (2.63 ± 1.04 vs. 1.30 ± 0.31; p < 0.01) and wlTBR mean (0.55 ± 0.20 vs. 0.31 ± 0.09; p = 0.01). Logistic regression analysis showed that incorporating pulmonary wlTBR max and wlTBR mean enhanced the predictive accuracy over PFT and HRCT alone. FAPI PET/CT may serve as a non-invasive biomarker for early prediction of ILD progression in IIM, supporting personalized disease management. However, given the small, single-centre cohort, these findings should be considered as preliminary and require validation in larger, multi-centre studies. • FAPI PET/CT uptake predicts ILD progression over a two-year period in IIM. • Elevated pulmonary FAPI-uptake is associated with INBUILD and composite progression criteria. • FAPI PET/CT refines ILD risk stratification beyond pulmonary function tests and HRCT. • Findings support FAPI PET/CT as a novel non-invasive biomarker for early ILD prediction.

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