Abstract
BACKGROUND: (18)F-FAPI-RGD PET/CT is a dual-target tracer imaging technique that holds promise for identifying pulmonary lesions in connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. Currently, clinical studies investigating (18)F-FAPI-RGD PET/CT for CTD-ILD diagnosis are lacking. METHODS: In this prospective study, CTD-ILD patients from the multidisciplinary clinic of Sichuan Provincial People’s Hospital were enrolled. General clinical data and laboratory parameters were collected. All participants underwent multidisciplinary ILD diagnostic evaluation and completed (18)F-FAPI-RGD PET/CT examinations to assess its clinical value in CTD-ILD diagnosis. RESULTS: The study ultimately included 52 patients (35 CTD-ILD, 17 CTD). CTD-ILD patients showed significantly elevated serum IL-6 and KL-6 levels compared to CTD patients (P < 0.05). (18)F-FAPI-RGD PET/CT imaging revealed significantly higher bilateral lung SUVmax (P < 0.001) and lower spleen SUVmax (P < 0.05) in CTD-ILD patients. Correlation analysis demonstrated significant positive association between bilateral lung SUVmax and CTD-ILD (r = 0.62, P < 0.001). Multivariate logistic regression adjusted for age, KL-6, and DLCO% identified bilateral lung SUVmax (per 10-unit increase) as an independent predictor of CTD-ILD (OR = 1.459, 95% CI= [1.031–2.065], P = 0.033). Bilateral lung SUVmax exhibited excellent predictive value for ILD (AUC = 0.94, 95% CI= [0.88-1.00], P < 0.001). Multiple linear regression showed KL-6 (β = 0.001, 95%CI [< 0.001, 0.002], P < 0.001) significantly positively influenced bilateral lung SUVmax, while DLCO% (β=-0.031 95%CI [-0.043, -0.020], P < 0.001) exerted significant negative effects. CONCLUSIONS: Our findings demonstrate that (18)F-FAPI-RGD PET/CT imaging is clinically applicable for CTD-ILD diagnosis. Future studies should explore its value in monitoring disease progression, treatment response assessment, and prognostic evaluation in CTD-ILD patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-025-03367-7.