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Purpose <p>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.</p> Methods <p>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.</p> Results <p>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<sub>mean</sub>(wlSUV<sub>mean</sub>:overall adjusted P-value(<i>p</i><sub><i>adj</i></sub>) &lt; 0.001) and cardiac SUVmax (cSUV<sub>max</sub>: median1.37, IQR 1.17–1.87 vs.1.01 ± 0.15, <i>p</i><sub><i>adj</i></sub> &lt;0.001). Reduced pulmonary function showed significant negative correlations with wlSUV<sub>mean</sub> (<i>p</i><sub><i>adj</i></sub> <i>&lt;</i>0.01). SSc patients with renal impairment demonstrated markedly higher renal SUV<sub>max</sub>(rSUV<sub>max</sub>)and renal SUV<sub>mean</sub> (rSUV<sub>mean</sub>) compared to both SSc patients with preserved renal function and the non-SSc cohort(both overall <i>p</i><sub><i>adj</i></sub> &lt; 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<sub>mean</sub> vs. rSUV<sub>mean</sub>: <i>r</i> = 0.722; cSUV<sub>mean</sub> vs. rSUV<sub>mean</sub>: <i>r</i> = 0.632).</p> Conclusion <p>[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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月6日

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  • Meixin Zhao,
  • Hui Wei,
  • Meng Wang,
  • Zeyang Wang,
  • Xinwei Li,
  • Hui Li,
  • Annan Zhang,
  • Song Xue,
  • Marcus Hacker,
  • Weifang Zhang,
  • Rong Mu,
  • Xiang Li

摘要

Purpose

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.

Methods

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.

Results

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).

Conclusion

[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.

Graphical Abstract