Fibroblast activation protein（FAP），a serine protease highly upregulated in activated fib roblasts but minimally expressed in healthy tissues，represents an ideal target for molecular imaging of fibrosis. This prospective cohort study evaluated the utility of 18F AIF 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 AIF 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，including modufied Rodnan Skin Score（mRSS），pulmonary fuction test （FVC%，FEV1%，DLCO），HRCT，echocardiography，and electrocardiography. Selective supplementary tests included cardiac speckle tracking imaging，cardiac MRI，muscle MRI，electromyography，and muscke biopsies. Quantitative uptake paramenters were independently measured in the lung，heart，kidneys，skeletal muscles，esoohagus，and skin by two blinded nuclear medicine physicians. Inter-organ metabolic correlations were analyzed.

Abnormally elevated FAPI uptake was prevalent in the lungs （96.8%，30/31），heart（35.5%，11/31），kidneys，and skeletal muscles（12.9%，4/31）.Compared with the non-SSc cohort，patients with SSc exhibited significantly elevated whole lung SUV_mean（wlSUV_mean：overall adjusted P-value <0.001）and cardiac SUV_max （cSUV_max：median 1.37，IQR 1.17-1.87，P<0.001）. Reduced pulmonary function showed significant negative correlations with wlSUV_mean（P<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- value <0.001），suggesting potential value of FAPI PET/CT as an early predictor of renal injury. Muscular uptake aligned with elevated creatine kunase and biopsy-proven myopathy，which showed severe fiber atrophy with CD4+ T cell/macrophage infiltration. No significant tracer accumulation was observed in the esophagus or skin. Inter-organ correlation analysis  revealed metabolic coupling across pulmonary，cardiac，and renal system（wlSUV_mean vs. rSUV_max：r=0.722；cSUV_mean vs. rSUV_mean：r=0.632）.

18F AIF 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.