Comparison of Al18F-NOTA-FAPI-74 and 18F-FDG PET/CT in the Evaluation and Staging of Hepatobiliary Malignancies

BACKGROUND: Accurate diagnosis and staging are crucial for the management of patients with hepatobiliary malignancies. Here, we investigated the efficacy of Al 18 F-NOTA-FAPI-74 PET/CT in detecting hepatobiliary malignancies and compared the results with 18 F-FDG PET/CT. PATIENTS AND METHODS: Participants with hepatobiliary malignancies were prospectively enrolled and underwent paired Al 18 F-NOTA-FAPI-74 and 18 F-FDG PET/CT from April 2023 to March 2024. Histopathology and/or follow-up imaging served as the reference standard. The SUVmax of the primary and metastatic lesions between Al 18 F-NOTA-FAPI-74 and 18 F-FDG PET/CT were compared using the Wilcoxon signed-rank test. The association between Al 18 F-NOTA-FAPI-74 uptake intensity and immunohistochemical FAP expression was analyzed with Spearman r correlation. RESULTS: Our cohort comprised of 28 patients with hepatobiliary malignancies, including 12 with hepatocellular carcinoma, 13 with intrahepatic cholangiocarcinoma (ICC), 2 with perihilar cholangiocarcinoma, and 1 with gallbladder carcinoma. Of these 28 patients, 13 underwent PET/CT for initial staging and 15 for restaging. Al 18 F-NOTA-FAPI-74 PET/CT showed higher sensitivity than 18 F-FDG PET/CT for detecting primary tumors [100% (13/13) vs 92.3% (12/13)], lymph node metastases [79.2% (42/53) vs 54.7% (29/53)], and bone and visceral metastases [97.6% (164/168) vs 69.0% (116/168)]. Al 18 F-NOTA-FAPI-74 PET/CT findings led to upstaging or restaging in 6 of 28 patients compared with the 18 F-FDG PET/CT-based stage. In addition, Al 18 F-NOTA-FAPI-74 PET/CT detected tumor-related obstructive inflammation in 7 patients, while 18 F-FDG PET/CT detected it in only 1 patient (25% vs 3.6%). All these 7 patients suffered from cholangiocarcinomas, including 5 with ICC and 2 with perihilar cholangiocarcinomas. The SUVmax of obstructive inflammation on Al 18 F-NOTA-FAPI-74 PET/CT was significantly lower than that of tumor (median SUVmax, 4.0 vs 8.8; P = 0.008). A positive correlation was found between FAPI uptake and FAP expression ( r = 0.730, P = 0.04). CONCLUSIONS: In patients with hepatobiliary malignancies, Al 18 F-NOTA-FAPI-74 PET/CT outperformed 18 F-FDG PET/CT in detecting primary tumors and metastatic lesions, resulting in more accurate staging or restaging. In addition, Al 18 F-NOTA-FAPI-74 PET/CT showed good detection efficacy for tumor-related obstructive inflammation, which was only found in cholangiocarcinoma, thus rendering Al 18 F-NOTA-FAPI-74 the potential to differentiate ICC from hepatocellular carcinoma.