Prognostic and diagnostic value of [¹⁸F]FDG, ¹¹C-acetate, and [⁶⁸Ga]Ga-FAPI-04 PET/CT for hepatocellular carcinoma

Objectives: To assess the prognostic value of Fluorine 18-labeled fluorodeoxyglucose [¹⁸F]FDG, gallium 68-labeled fibroblast-activation protein inhibitor-04 [⁶⁸Ga]Ga-FAPI-04, ¹¹C-acetate in hepatocellular carcinoma (HCC) and evaluate the potential usefulness and advantages of different combinations for accurate diagnosis.

Materials and methods: Thirty-six patients with suspected hepatic masses were prospectively enrolled from May 2021 to September 2022 and underwent [¹⁸F]FDG, [⁶⁸Ga]Ga-FAPI-04, and ¹¹C-acetate PET/CT scans before surgery. PET/CT results and histopathologic examinations were independently interpreted by two radiologists and pathologists, respectively. Kaplan-Meier overall survival curves were calculated and the sensitivity among [¹⁸F]FDG, ¹¹C-acetate, [⁶⁸Ga]Ga-FAPI-04, and different combinations were compared.

Results: Of the 36 included patients (mean age, 59 years ± 10 (standard deviation)), 29 were diagnosed with HCC, four with non-HCC malignant tumors, and three with benign tumors. Patients with HCC lesions negative for ¹¹C-acetate or [⁶⁸Ga]Ga-FAPI-04 exhibited poorer overall survival. Out of 36 patients, 44 HCC lesions were detected. The dual-tracer [⁶⁸Ga]Ga-FAPI-04/¹¹C-acetate exhibited the highest sensitivity (39 of 44 lesions (88.6%)) among all schemes. HCC lesions with higher histological grade and microvascular invasion (MVI) showed higher maximum standardized uptake value (SUV_max) and tumor-to-background ratio (TBR) of [¹⁸F]FDG, but no evidence of significant differences was found in [⁶⁸Ga]Ga-FAPI-04 and ¹¹C-acetate PET/CT. Higher expression of fibroblast activation protein (FAP) showed higher uptake of [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG.

Conclusion: [⁶⁸Ga]Ga-FAPI-04 and ¹¹C-acetate PET/CT exhibited good predictive value for HCC patients, with their combination showing the highest sensitivity for HCC detection, suggesting potential for improved diagnostic protocols.

Key points: Question What are the prognostic and diagnostic values of PET/CT tracers, including [¹⁸F]FDG, [⁶⁸Ga]FAPI-04, and ¹¹C-acetate? Findings Hepatocellular carcinoma, with differing findings across [¹⁸F]FDG, [⁶⁸Ga]GaFAPI-04, and ¹¹C-acetate PET/CT, showed varied prognoses; [⁶⁸Ga]GaFAPI-04 and ¹¹C-acetate combined offered the highest detection sensitivity. Clinical relevance Evaluating the prognostic value and diagnostic efficacy of different tracer combinations in patients with hepatocellular carcinoma helps to guide the optimal selection of tracers in clinical practice.