Comparison of lesion detection rates between FAPI PET/CT and 18F-FDG PET/CT in hepatocellular carcinoma: a systematic review and meta-analysis of head-to-head studies.

OBJECTIVES: To compare the lesion detection rates of fibroblast activation protein inhibitor (FAPI) PET/CT and 18F-FDG PET/CT in hepatocellular carcinoma (HCC) using currently available head-to-head evidence. METHODS: Databases including PubMed, Embase, Cochrane Library, Scopus, and Web of Science were searched for head-to-head studies comparing FAPI and FDG for HCC lesion detection up to March 2026. Two researchers independently performed literature screening and data extraction, and assessed the risk of bias using the QUADAS-2 tool. Meta-analysis was conducted using R 4.5.3 software. The primary outcome was lesion detection-rate difference, expressed as risk difference (RD) with 95% confidence intervals (CIs). Random-effects models were used for pooled analyses. Subgroup analyses were performed according to lesion size and treatment status when data were available. Anatomical-site findings were summarized descriptively because pooled analysis was not considered appropriate. RESULTS: Eight reports were included in the qualitative synthesis, and 5 studies/outcomes providing HCC-specific paired comparative data were included in the main quantitative synthesis. Overall, FAPI PET/CT showed a significantly higher lesion detection rate than 18F-FDG PET/CT, with a pooled RD of 0.41 (95% CI 0.28-0.53; I2 = 75.5%). In subgroup analyses, the pooled RD was 0.57 (95% CI 0.47-0.67; I2 = 18.7%) for lesions ≤ 2 cm and 0.26 (95% CI 0.08-0.44; I2 = 87.6%) for lesions > 2 cm. According to treatment status, the pooled RD was 0.32 (95% CI 0.15-0.50; I2 = 60.3%) in the pretreatment subgroup and 0.46 (95% CI 0.28-0.64; I2 = 57.4%) in the post-treatment/restaging subgroup. Site-specific findings descriptively suggested a more consistent detection advantage of FAPI PET/CT for intrahepatic lesions than for some extrahepatic metastatic sites. CONCLUSION: In the available HCC-specific head-to-head studies, FAPI PET/CT was associated with a higher lesion detection rate than 18F-FDG PET/CT, particularly for small lesions and in both pretreatment and post-treatment/restaging settings. However, the current evidence remains limited by the small number of studies, methodological heterogeneity, lesion-level analysis constraints, and insufficient specificity-related data. Larger prospective comparative studies are needed to better define the clinical role of FAPI PET/CT in HCC.