Exploratory evaluation of early ⁶⁸Ga-FAPI-46 PET/CT volume-based parameters in systemic sclerosis-associated interstitial lung disease.

Abstract

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. ⁶⁸Ga-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 ⁶⁸Ga-FAPI-46 PET/CT imaging in fibroinflammatory disorders remain undefined. This exploratory study investigated early versus late ⁶⁸Ga-FAPI-46 PET parameters in evaluating SSc-ILD. Early (10 min) and late (60 min) ⁶⁸Ga-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 ⁶⁸Ga-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.