FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study

Background Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using Ga-68-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT). Methods In this prospective observational pilot study, consecutive patients with IIM and participants without rheumatic conditions or ILD serving as a control group were recruited at the Medical University of Vienna, Austria, and underwent FAPi PET/CT imaging. Standard-of-care procedures including clinical examination, assessment of severity of dyspnoea, high-resolution computed tomography (HR-CT), and pulmonary function testing (PFT) were performed on all patients with IIM at baseline and for patients with IIM-ILD at follow-up of 12 months. Baseline pulmonary FAPi-uptake was assessed by the maximum (SUVmax) and mean (SUVmean) standardized uptake values (SUV) over the whole lung (wl). SUV was corrected for blood pool background activity and target-to-background ratios (TBR) were calculated. We compared pulmonary FAPi-uptake between patients with IIM-ILD and those without ILD, as well as controls, and correlated baseline FAP-uptake with standard diagnostic tools such as HR-CT and PFT. For predictive implications, we investigated whether patients with IIM and progressive ILD exhibited higher baseline FAPi-uptake compared to those with stable ILD. Metrics are reported as mean with standard deviation (+/- SD). Findings Between November 16, 2021 and October 10, 2022, a total of 32 patients were enrolled in the study. Three participants from the control group were excluded due to cardiopulmonary disease. In individuals with IIM-ILD (n = 14), wlTBR(max) and wlTBR(mean) were significantly increased as compared with both non-ILD-IIM patients (n = 5) and the control group (n = 16): wlTBR(max): 2.06 +/- 1.04 vs. 1.04 +/- 0.22 (p = 0.019) and 1.08 +/- 0.19 (p = 0.0012) and wlTBR(mean): 0.45 +/- 0.19 vs. 0.26 +/- 0.06 (p = 0.025) and 0.27 +/- 0.07 (p = 0.0024). Similar values were observed in wlTBR(max) or wlTBR(mean) between non-ILD IIM patients and the control group. Patients with progressive ILD displayed significantly enhanced wlTBR(max) and wlTBR(mean) values at baseline compared to patients with stable ILD: wlTBR(max): 1.30 +/- 0.31 vs. 2.63 +/- 1.04 (p = 0.0084) and wlTBR(mean): 0.32 +/- 0.08 vs. 0.55 +/- 0.19 (p = 0.021). Strong correlations were found between FAPi-uptake and disease extent on HR-CT (wlTBRmax: R = 0.42, p = 0.07; wlTBRmean: R = 0.56, p = 0.013) and severity of respiratory symptoms determined by the New York Heart Association (NYHA) classification tool (wlTBRmax: R = 0.52, p = 0.022; wlTBRmean: R = 0.59, p = 0.0073). Further, pulmonary FAPi-uptake showed inverse correlation with forced vital capacity (FVC) (wlTBRmax: R = -0.56, p = 0.012; wlTBRmean: R = -0.64, p = 0.0033) and diffusing capacity of the lungs for carbon monoxide (DLCO) (wlTBRmax: R = -0.52, p = 0.028; wlTBRmean: R = -0.68, p = 0.0017). Interpretation Our study demonstrates higher fibroblast activation in patients with IIM-ILD compared to non-ILD patients and controls. Intensity of pulmonary FAPi accumulation was associated with progression of ILD. Considering that this study was carried out on a small population, FAPi PET/CT may serve as a useful non-invasive tool for risk stratification of lung disease in IIM. Copyright (c) 2024 The Authors. Published by Elsevier Ltd.