Head-to-head comparison of (18)F-FAPI and (18)F-FDG PET/CT in staging and therapeutic management of hepatocellular carcinoma

BACKGROUND: Fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has limitations in staging hepatocellular carcinoma (HCC). The recently introduced (18)F-labeled fibroblast-activation protein inhibitor (FAPI) has shown promising prospects in detection of HCC lesions. This study aimed to investigate the initial staging and restaging performance of (18)F-FAPI PET/CT compared to (18)F-FDG PET/CT in HCC. METHODS: This prospective study enrolled histologically confirmed HCC patients from March 2021 to September 2022. All patients were examined with (18)F-FDG PET/CT and (18)F-FAPI PET/CT within 1 week. The maximum standard uptake value (SUV(max)), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. RESULTS: A total of 67 patients (57 men; median age, 57 [range, 32–83] years old) were included. (18)F-FAPI PET showed higher SUV(max) and TBR values than (18)F-FDG PET in the intrahepatic lesions (SUV(max): 6.7 vs. 4.3, P < 0.0001; TBR: 3.9 vs. 1.7, P < 0.0001). In diagnostic performance, (18)F-FAPI PET/CT had higher detection rate than (18)F-FDG PET/CT in intrahepatic lesions [92.2% (238/258) vs 41.1% (106/258), P < 0.0001] and lymph node metastases [97.9% (126/129) vs 89.1% (115/129), P = 0.01], comparable in distant metastases [63.6% (42/66) vs 69.7% (46/66), P > 0.05]. (18)F-FAPI PET/CT detected primary tumors in 16 patients with negative (18)F-FDG, upgraded T-stages in 12 patients and identified 4 true positive findings for local recurrence than (18)F-FDG PET, leading to planning therapy changes in 47.8% (32/67) of patients. CONCLUSIONS: (18)F-FAPI PET/CT identified more primary lesions, lymph node metastases than (18)F-FDG PET/CT in HCC, which is helpful to improve the clinical management of HCC patients. TRIAL REGISTRATION: Clinical Trials, NCT05485792. Registered 1 August 2022, Retrospectively registered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40644-023-00626-y.