Assessment of liver fibrosis and tumor burden in hepatocellular carcinoma using [18F]AlF-NOTA-FAPI-04 PET/CT: a prospective study.

PURPOSE: Hepatocellular carcinoma (HCC) commonly develops in the setting of cirrhosis, highlighting the need for reliable noninvasive biomarkers to assess both tumor burden and hepatic function. Conventional [18F]FDG PET/CT has limited sensitivity for HCC. In contrast, FAPI PET/CT targets fibroblast activation protein (FAP), enabling visualization of cancer-associated fibroblasts (CAFs) and stromal fibrosis, and offering a novel imaging strategy for HCC.

METHODS

In this prospective single-center study, 57 HCC patients underwent [18F]AlF-NOTA-FAPI-04 PET/CT. Quantitative tumor variables included SUVmax, SUVmean, metabolic tumor volume, and total lesion FAP expression (TLF). Total liver segmentation yielded the Total liver SUVmean (TSUVmean) and Total liver FAP expression (TTLF); Boolean operations were used to derive background metrics (BSUVmean, BTLF). Associations with Child–Pugh score, FIB-4 fibrosis index, alpha-fetoprotein (AFP), tumor size, portal vein tumor thrombosis (PVTT), and CAF immunohistochemical markers were analyzed. Prognostic value of imaging and clinical variables was assessed by Kaplan–Meier analysis, Cox regression, and a nomogram.

RESULTS

SUVmean and TTLF were associated with Child–Pugh score, tumor burden, and liver dysfunction. Patients with higher SUVmean (≥ 6.32) or TTLF (≥ 3226.31) had shorter progression-free and overall survival, and TTLF remained an independent predictor (P = 0.02). Our nomogram integrating imaging and clinical variables showed good discrimination (AUC = 0.875, 95% CI 0.733–1.000). Background uptake reflected fibrosis severity, as patients with FIB-4 grade ≥ 3.25 had higher TTLF and BTLF. FAPI uptake correlated with FAP immunohistochemical staining and intratumoral fibrosis, suggesting that it may serve as a noninvasive surrogate of tumor stromal activity.

CONCLUSION

[18F]AlF-NOTA-FAPI-04 PET/CT provides an integrated assessment of tumor activity, CAF activation, and hepatic fibrosis in HCC. SUVmean and TTLF are robust prognostic biomarkers and background uptake captures fibrosis severity, supporting its role as a noninvasive tool for risk stratification and personalized management.