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Purpose <p>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. <sup>68</sup>Ga-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 <sup>68</sup>Ga-FAPI-46 PET/CT imaging in fibroinflammatory disorders remain undefined. This exploratory study investigated early versus late <sup>68</sup>Ga-FAPI-46 PET parameters in evaluating SSc-ILD.</p> Methods <p>Early (10&#xa0;min) and late (60&#xa0;min) <sup>68</sup>Ga-FAPI-46 PET parameters were compared between progressive (<i>n</i> = 8) and non-progressive SSc-ILD (<i>n</i> = 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.</p> Results <p>Early total lesion FAPI uptake (median TL-FAPI<sub>10min</sub> 1245 vs. 714, <i>p</i> = 0.020) and affected lung volume (median AV<sub>10min</sub> 514&#xa0;ml vs. 368&#xa0;ml, <i>p</i> = 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<sub>10min</sub> threshold of 928 had the best diagnostic performance (AUC 0.80).</p> Conclusion <p>This exploratory study showed that <sup>68</sup>Ga-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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月2日

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  • Sarah Beishan Tai,
  • Wei Ming Chua,
  • Cherie Wei Qi Ng,
  • Maria Noviani,
  • Wei Ping Tham,
  • Seyed Ehsan Saffari,
  • Winnie Wing Chuen Lam,
  • David Chee Eng Ng,
  • Adrian Shoen Choon Seng Low,
  • Wanying Xie,
  • Andrea Hsiu Ling Low

摘要

Purpose

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.

Methods

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.

Results

Early total lesion FAPI uptake (median TL-FAPI10min 1245 vs. 714, p = 0.020) and affected lung volume (median AV10min 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-FAPI10min threshold of 928 had the best diagnostic performance (AUC 0.80).

Conclusion

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.