Meixin Zhao, Hui Wei, Meng Wang, Zeyang Wang, Xinwei Li, Hui Li, Annan Zhang, Song Xue, Marcus Hacker, Weifang Zhang, Rong Mu, Xiangyang Li
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 SUVmean(wlSUVmean:overall adjusted P-value(padj) < 0.001) and cardiac SUVmax (cSUVmax: median1.37, IQR 1.17–1.87 vs.1.01 ± 0.15, padj <0.001). Reduced pulmonary function showed significant negative correlations with wlSUVmean (padj <0.01). SSc patients with renal impairment demonstrated markedly higher renal SUVmax(rSUVmax)and renal SUVmean (rSUVmean) compared to both SSc patients with preserved renal function and the non-SSc cohort(both overall padj < 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 (wlSUVmean vs. rSUVmean: r = 0.722; cSUVmean vs. rSUVmean: 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.