Sarah Beishan Tai, Wei Ming Chua, Cherie Wei Qi Ng, Maria Noviani, Wei Ping Tham, Seyed Ehsan Saffari, Winnie Wing Chuen Lam, David Chee Eng Ng, Adrian Shoen Choon Seng Low, Adrian Shoen Choon Seng Low, Wanying Xie, Andrea Hsiu Ling Low, Andrea Hsiu Ling Low
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a severe complication of SSc, characterised by progressive fibrosis and inflammation. Current diagnostic tools do not accurately differentiate progressors from non-progressors, limiting timely intervention. 68 Ga-FAPI-46 is a positron emission tomography (PET) tracer targeting fibroblast activation protein alpha (FAP), a marker of activated fibroblasts, with high affinity and retention. Optimal imaging timepoints and PET parameters for 68 Ga-FAPI-46 PET/CT imaging in fibroinflammatory disorders remain undefined. This exploratory study investigated early versus late 68 Ga-FAPI-46 PET parameters in evaluating SSc-ILD. Early (10 min) and late (60 min) 68 Ga-FAPI-46 PET parameters were compared between progressive ( n = 8) and non-progressive SSc-ILD ( n = 14), defined by INBUILD trial criteria. PET parameters were correlated with pulmonary function test (PFT) and HRCT parameters. Optimal thresholds for identified PET parameters were determined by closest-to-(0,1) criterion. Early total lesion FAPI uptake (median TL-FAPI 10min 1245 vs. 714, p = 0.020) and affected lung volume (median AV 10min 514 ml vs. 368 ml, p = 0.042) were significantly higher in progressors than non-progressors. Early PET parameters showed stronger, more consistent correlations with PFT and quantitative HRCT parameters than late PET parameters. Volume-based compared to intensity-based PET parameters more consistently correlated with PFT and quantitative HRCT parameters. TL-FAPI 10min threshold of 928 had the best diagnostic performance (AUC 0.80). This exploratory study showed that 68 Ga-FAPI-46 PET/CT imaging, specifically early volume-based PET parameters, was associated with patients with recent disease progression of SSc-ILD. Prospective validation in treatment-response studies is needed to confirm the clinical utility of these PET parameters and their identified preliminary thresholds.