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<p>Hepatic fibrosis, a precursor to cirrhosis and hepatocellular carcinoma, affects millions worldwide but lacks effective therapies and depends on invasive liver biopsies for diagnosis, which hinder early intervention and monitoring. Non-invasive imaging with [<sup>68</sup>Ga]Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) targets fibroblast activation protein (FAP) in fibrotic tissues, enabling assessment of disease progression without biopsy risks. This preclinical study evaluated pharmacological TGF-β inhibition using A83-01 and assessed [<sup>68</sup>Ga]Ga-FAPI-46 PET as a quantitative imaging biomarker. Hepatic fibrosis was induced in rats by thioacetamide (TAA) and evaluated at 4, 6, and 8&#xa0;weeks. TAA administration caused progressive liver injury, increased collagen deposition, and elevated fibrotic marker expression. Although A83-01 effectively suppressed serum TGF-β1 levels and markedly reduced SMAD2/3 phosphorylation, fibrosis progression was not attenuated. Instead, α-SMA and FAP expression remained elevated, with higher levels observed at 8&#xa0;weeks in the TAA + A83-01 group, indicating persistent fibroblast activation despite canonical pathway inhibition. Importantly, [<sup>68</sup>Ga]Ga-FAPI-46 PET demonstrated a time-dependent increase in hepatic tracer uptake and provided clear differentiation between control and fibrotic livers, closely reflecting histological and molecular findings. These results support [<sup>68</sup>Ga]Ga-FAPI-46 PET as a sensitive non-invasive tool for fibrosis staging and longitudinal monitoring during therapeutic intervention.</p>

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[68Ga]Ga-FAPI-46 PET enables non-invasive monitoring of hepatic fibrosis progression during TGF-β inhibition

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Yeeun Kim,
  • Myeongguk Jeong,
  • Go-Eun Choi,
  • Hyeokjin Kwon,
  • Hyun Jin Yoon,
  • Young-Jin Jeong,
  • Ji Yong Park,
  • Do-Young Kang,
  • Sungmin Jun

摘要

Hepatic fibrosis, a precursor to cirrhosis and hepatocellular carcinoma, affects millions worldwide but lacks effective therapies and depends on invasive liver biopsies for diagnosis, which hinder early intervention and monitoring. Non-invasive imaging with [68Ga]Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) targets fibroblast activation protein (FAP) in fibrotic tissues, enabling assessment of disease progression without biopsy risks. This preclinical study evaluated pharmacological TGF-β inhibition using A83-01 and assessed [68Ga]Ga-FAPI-46 PET as a quantitative imaging biomarker. Hepatic fibrosis was induced in rats by thioacetamide (TAA) and evaluated at 4, 6, and 8 weeks. TAA administration caused progressive liver injury, increased collagen deposition, and elevated fibrotic marker expression. Although A83-01 effectively suppressed serum TGF-β1 levels and markedly reduced SMAD2/3 phosphorylation, fibrosis progression was not attenuated. Instead, α-SMA and FAP expression remained elevated, with higher levels observed at 8 weeks in the TAA + A83-01 group, indicating persistent fibroblast activation despite canonical pathway inhibition. Importantly, [68Ga]Ga-FAPI-46 PET demonstrated a time-dependent increase in hepatic tracer uptake and provided clear differentiation between control and fibrotic livers, closely reflecting histological and molecular findings. These results support [68Ga]Ga-FAPI-46 PET as a sensitive non-invasive tool for fibrosis staging and longitudinal monitoring during therapeutic intervention.