Head-to-head comparison of [18F]FAPI and [18F]FDG PET/CT in the clinical value of hepatocellular carcinoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: To investigate the clinical utility of fluorine-18-labeled fibroblast activation protein (FAP) inhibitor ([ 18 F]FAPI) positron emission tomography/computed tomography (PET/CT) relative to [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) PET/CT for tumor detection and staging in hepatocellular carcinoma (HCC) patients. A cohort of 38 individuals (median age, 61 years; interquartile range, 56–68 years), all with pathologically confirmed primary or recurrent HCC, were enrolled. All participants underwent both [ 18 F]FDG and [ 18 F]FAPI PET/CT. Maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), FAP expression tumor volume (FTV), total lesion glycolysis (TLG), total lesion FAP expression (TLF), and clinical staging were compared. Each patient had at least one intrahepatic lesion confirmed by surgical resection or percutaneous biopsy. Histopathologic confirmation was available for 46/66 intrahepatic lesions, 3/56 lymph-node (LN) metastases, and 4/33 distant metastases; the remaining lesions were adjudicated using a composite reference standard based on multimodal imaging follow-up and treatment response. Additionally, correlations between PET imaging findings and serum biomarkers, comprising alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II), were analyzed. The cohort included 32 primary and 6 recurrent HCC cases. [ 18 F]FAPI PET/CT showed higher lesion detection rates than [ 18 F]FDG PET/CT for primary intrahepatic lesions (96.7% vs. 60.0%; p < 0.001), LN metastases (94.6% vs. 80.4%; p = 0.021), and distant metastases (78.8% vs. 48.5%; p = 0.002). For primary intrahepatic lesions, [ 18 F]FAPI PET/CT showed higher SUVmax (7.90 vs. 4.80, p < 0.001) and TBR (5.45 vs. 2.60, p < 0.001) than [ 18 F]FDG PET/CT. In the patient-level volumetric analysis of the 32 initial-staging patients, FTV was 21.04 vs. MTV 13.75 ( p < 0.001), and TLF was 135.36 vs. TLG 51.44 ( p < 0.001). For LN metastases, [ 18 F]FAPI PET/CT showed higher SUVmax (7.98 vs. 6.63, p = 0.048) and TBR (7.85 vs. 4.95, p < 0.001), as well as higher FTV than MTV (6.55 vs. 4.55, p < 0.001) and TLF than TLG (67.65 vs. 52.75, p < 0.001). Positive correlations were observed between [ 18 F]FAPI PET/CT tumor uptake parameters and AFP and PIVKA-II levels (nominal p < 0.05). Relative to [ 18 F]FDG, [ 18 F]FAPI PET/CT produced staging changes in 19/32 patients undergoing initial staging, including 6 true upstagings, and identified 3 additional local recurrences; a FAPI-informed management change was implemented in 57.9% (22/38) of patients. Exploratory receiver operating characteristic (ROC) analyses yielded areas under the curve (AUCs) of 0.947, 0.921, 0.895, and 0.864 for SUVmax, TBR, FTV, and TLF, respectively. [ 18 F]FAPI PET/CT showed higher lesion detection in selected HCC settings than [ 18 F]FDG PET/CT for primary intrahepatic, lymph-node, and distant metastatic lesions and may provide complementary information for staging and treatment planning in this preliminary single-center cohort. Trial registration ClinicalTrials.gov, NCT05810324; registered on 30 March 2023.
Source: Scientific Reports
Institution: Jilin University
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7223066564