Molecular imaging of fibroblast activation in systemic sclerosis using [¹⁸F]AlF-NOTA-FAPI-04 PET/CT: a prospective cohort study.

Abstract

This prospective cohort study evaluated the utility of [¹⁸F]AlF-NOTA-FAPI-04 PET/CT for whole-body assessment of fibroblast activation in systemic sclerosis (SSc), correlating organ-specific uptake with clinical indicators of severity and multi-organ dysfunction. 31 patients with SSc and 21 patients from a non-SSc cohort underwent total-body [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging. Quantitative uptake parameters were measured in lungs, heart, kidneys, skeletal muscles, esophagus, and skin. Clinical assessments were completed within ± 14 days. Inter-organ metabolic correlations were analyzed. Abnormally elevated FAPI uptake was prevalent in the lungs (96.8%), heart (35.5%), kidneys, and skeletal muscles (12.9%). Compared with the non-SSc cohort, patients with SSc exhibited significantly elevated whole lung SUV_mean(wlSUV_mean:overall adjusted P-value(p_adj) < 0.001) and cardiac SUVmax (cSUV_max: median1.37, IQR 1.17-1.87 vs.1.01 ± 0.15, p_adj <0.001). Reduced pulmonary function showed significant negative correlations with wlSUV_mean (p_adj <0.01). SSc patients with renal impairment demonstrated markedly higher renal SUV_max(rSUV_max)and renal SUV_mean (rSUV_mean) compared to both SSc patients with preserved renal function and the non-SSc cohort(both overall p_adj < 0.001). Muscular uptake aligned with elevated creatine kinase and biopsy-proven myopathy. No significant tracer accumulation was observed in the esophagus or skin. Inter-organ correlation analysis revealed metabolic coupling across pulmonary, cardiac, and renal systems (wlSUV_mean vs. rSUV_mean: r = 0.722; cSUV_mean vs. rSUV_mean: r = 0.632). [¹⁸F]AlF-NOTA-FAPI-04 PET/CT provides a noninvasive, integrative imaging platform for mapping fibroblast activation across multiple organs in SSc. It demonstrated potential for detection of fibrotic burden and inter-organ metabolic profiling. Its sensitivity in gastrointestinal and cutaneous involvement remains limited, warranting further optimization.