Prospective Head-to-Head Comparison of Fibroblast Imaging with [Ga]Ga-FAPI-46 PET/CT and [F]FDG PET/CT in Unclear Hepatic Lesions.

This study aimed to compare the performance of Ga-labeled fibroblast activation protein inhibitor 46 ([Ga]Ga-FAPI-46) PET/CT and [F]FDG PET/CT in characterizing unclear hepatic lesions. We prospectively evaluated 59 patients with suspected intrahepatic lesions. Tumor radiologic features, pathology, or follow-up examinations were assessed as reference methods in correlation with PET scans. On [Ga]Ga-FAPI-46 PET/CT, additional abdominal dynamic imaging was performed. We measured the SUV and calculated tumor-to-liver background ratios for both scans. Fibroblast activation protein expression was assessed by immunohistochemistry in samples obtained from 16 patients with hepatocellular carcinoma/cholangiocarcinoma, intrahepatic metastases (IMs) from extrahepatic malignancies, or benign lesions. Primary hepatobiliary tumors (PHBTs), including 76 hepatocellular carcinomas in 22 patients, 24 cholangiocarcinomas in 5 patients, 136 IMs in 16 patients, and 55 benign lesions in 16 patients, were determined by histology ( = 162) and radiologic examinations ( = 129). On the basis of visual analysis, 44 patients showed elevated [Ga]Ga-FAPI-46 uptake (sensitivity, 100%; specificity, 94%), whereas 32 patients showed [F]FDG-avid lesions (sensitivity, 70%; specificity, 88%). Sensitivity was significantly higher in [Ga]Ga-FAPI-46 PET/CT than in [F]FDG PET/CT ( < 0.001). Fifty (90.9%) benign liver lesions in 14 patients (87.5%) showed negligible uptake on both PET scans, and 1 (1.8%) benign liver lesion in 1 patient showed increased [F]FDG uptake alone. [Ga]Ga-FAPI-46 PET/CT revealed 10 extrahepatic primary tumors, versus 3 in [F]FDG PET/CT. SUV for PHBTs, maximum tumor-to-background ratio for PHBTs, and mean tumor-to-background ratio for PHBTs were significantly higher on [Ga]Ga-FAPI-46 PET/CT than on [F]FDG PET/CT (all < 0.05). [Ga]Ga-FAPI-46 PET/CT is superior to [F]FDG PET/CT in characterizing unclear hepatic lesions.