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Purpose <p>Fibroblast activation protein (FAP) may contribute to radiotherapy resistance. This study aimed to compare baseline <sup>18</sup>F-labeled fibroblast activation protein inhibitor (<sup>18</sup>F-FAPI) PET/CT and <sup>18</sup>F-FDG PET/CT in short-term target lesion response (TLR) and clinical outcome prediction in unresectable hepatocellular carcinoma (uHCC) patients treated with Yttrium-90(<sup>90</sup>Y) resin microsphere selective internal radiation therapy (SIRT).</p> Methods <p>Patients with uHCC undergoing pre-SIRT <sup>18</sup>F-FDG and <sup>18</sup>F-FAPI PET/CT were prospectively recruited. Semiquantitative parameters, including target/whole-body metabolic tumor volume (MTV-target/MTV-WB) and total lesion glycolysis (TLG-target/TLG-WB), were obtained from <sup>18</sup>F-FDG PET/CT, while target/whole-body FAPI-avid tumor volume (FTV-target/FTV-WB) and total lesion FAP expression (TLF-target/TLF-WB) were derived from <sup>18</sup>F-FAPI PET/CT. Voxel-based tumor absorbed dose(TAD) parameters for target lesions were calculated from post-SIRT PET/CT, including the mean TAD (Dmean) and TAD to 50%, 75%, and 90% of the tumor volume (D50, D75, D90). Short-term (3-month) target lesion response was assessed by mRECIST 1.1 criteria. Primary endpoints were short-term TLR and progression-free survival (PFS). The secondary endpoint was overall survival (OS).</p> Results <p>Forty-three uHCC patients (mean age 51.0 ± 10.2 years, 88.4% male) were included. The short-term TLR rate was 60.5% (26/43), with a control rate of 88.4%. The TLR group showed significantly lower MTV-target, TLG-target, FTV-target, and TLF-target than the non-target lesion response group (NTLR), with similar trends for Dmean/D50/D75. Higher pre-SIRT FTV-target (&gt; 303.5&#xa0;cm³) and TLF-target (&gt; 1129.1) were independent predictors of short-term response [odds ratio = 6.33, 95% confidence interval (CI): 1.43–28.00, <i>P</i> = 0.015]. Median PFS was 6.6(95%CI:4.4–10.5) months, and median OS was 13.1(95%CI:10.5-not reached) months. Higher FTV-WB(&gt; 333.9cm<sup>3</sup>)/TLF-WB (&gt; 1256.1) predicted worse PFS, though not independently. Post-SIRT monotherapy [hazard ratio (HR) = 3.27, 95%CI:1.18–9.06, <i>P</i> = 0.023), higher alpha-fetoprotein (&gt; 343.1ng/mL) (HR = 3.25, 95%CI:1.84–8.90, <i>P</i> = 0.022), and lower Dmean (≤ 151&#xa0;Gy)/D50(≤ 142&#xa0;Gy) (HR = 2.64, 95%CI:1.07–6.55, <i>P</i> = 0.036) were independent prognostic factors for PFS.</p> Conclusion <p>Pre-SIRT FAPI-avid volumetric parameters demonstrated potential value for predicting short-term TLR in uHCC patients receiving SIRT, in addition to TAD. <sup>18</sup>F-FAPI PET/CT may facilitate uHCC patient selection before SIRT.</p> Trial registration <p>Chinese Clinical Trial Registry (ChiCTR2500107817), registered on 19 August 2025, retrospectively registered.</p>

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The predictive value of 18F-FAPI PET/CT and voxel-based tumor absorbed dose for the response and clinical outcome of unresectable hepatocellular carcinoma patients treated with Yttrium-90 resin microsphere selective internal radiation therapy

  • 期刊论文

  • 发表日期：

    2026年1月10日

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  • Huanyu Gong,
  • Yong Cheng,
  • Qiang Li,
  • Yulong Liu,
  • Jingjie Shang,
  • Yingxin Li,
  • Lu Kuang,
  • Xueying Ling,
  • Changjing Zuo,
  • Lu Wang,
  • Jian Gong,
  • Hao Xu

摘要

Purpose

Fibroblast activation protein (FAP) may contribute to radiotherapy resistance. This study aimed to compare baseline 18F-labeled fibroblast activation protein inhibitor (18F-FAPI) PET/CT and 18F-FDG PET/CT in short-term target lesion response (TLR) and clinical outcome prediction in unresectable hepatocellular carcinoma (uHCC) patients treated with Yttrium-90(90Y) resin microsphere selective internal radiation therapy (SIRT).

Methods

Patients with uHCC undergoing pre-SIRT 18F-FDG and 18F-FAPI PET/CT were prospectively recruited. Semiquantitative parameters, including target/whole-body metabolic tumor volume (MTV-target/MTV-WB) and total lesion glycolysis (TLG-target/TLG-WB), were obtained from 18F-FDG PET/CT, while target/whole-body FAPI-avid tumor volume (FTV-target/FTV-WB) and total lesion FAP expression (TLF-target/TLF-WB) were derived from 18F-FAPI PET/CT. Voxel-based tumor absorbed dose(TAD) parameters for target lesions were calculated from post-SIRT PET/CT, including the mean TAD (Dmean) and TAD to 50%, 75%, and 90% of the tumor volume (D50, D75, D90). Short-term (3-month) target lesion response was assessed by mRECIST 1.1 criteria. Primary endpoints were short-term TLR and progression-free survival (PFS). The secondary endpoint was overall survival (OS).

Results

Forty-three uHCC patients (mean age 51.0 ± 10.2 years, 88.4% male) were included. The short-term TLR rate was 60.5% (26/43), with a control rate of 88.4%. The TLR group showed significantly lower MTV-target, TLG-target, FTV-target, and TLF-target than the non-target lesion response group (NTLR), with similar trends for Dmean/D50/D75. Higher pre-SIRT FTV-target (> 303.5 cm³) and TLF-target (> 1129.1) were independent predictors of short-term response [odds ratio = 6.33, 95% confidence interval (CI): 1.43–28.00, P = 0.015]. Median PFS was 6.6(95%CI:4.4–10.5) months, and median OS was 13.1(95%CI:10.5-not reached) months. Higher FTV-WB(> 333.9cm3)/TLF-WB (> 1256.1) predicted worse PFS, though not independently. Post-SIRT monotherapy [hazard ratio (HR) = 3.27, 95%CI:1.18–9.06, P = 0.023), higher alpha-fetoprotein (> 343.1ng/mL) (HR = 3.25, 95%CI:1.84–8.90, P = 0.022), and lower Dmean (≤ 151 Gy)/D50(≤ 142 Gy) (HR = 2.64, 95%CI:1.07–6.55, P = 0.036) were independent prognostic factors for PFS.

Conclusion

Pre-SIRT FAPI-avid volumetric parameters demonstrated potential value for predicting short-term TLR in uHCC patients receiving SIRT, in addition to TAD. 18F-FAPI PET/CT may facilitate uHCC patient selection before SIRT.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2500107817), registered on 19 August 2025, retrospectively registered.