Prospective Head-to-Head Comparison of Fibroblast Imaging with [ 68 Ga]Ga-FAPI-46 PET/CT and [ 18 F]FDG PET/CT in Unclear Hepatic Lesions

This study aimed to compare the performance of ⁶⁸Ga-labeled fibroblast activation protein inhibitor 46 ([⁶⁸Ga]Ga-FAPI-46) PET/CT and [¹⁸F]FDG PET/CT in characterizing unclear hepatic lesions. Methods: 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 [⁶⁸Ga]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. Results: 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 (n = 162) and radiologic examinations (n = 129). On the basis of visual analysis, 44 patients showed elevated [⁶⁸Ga]Ga-FAPI-46 uptake (sensitivity, 100%; specificity, 94%), whereas 32 patients showed [¹⁸F]FDG–avid lesions (sensitivity, 70%; specificity, 88%). Sensitivity was significantly higher in [⁶⁸Ga]Ga-FAPI-46 PET/CT than in [¹⁸F]FDG PET/CT (P < 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 [¹⁸F]FDG uptake alone. [⁶⁸Ga]Ga-FAPI-46 PET/CT revealed 10 extrahepatic primary tumors, versus 3 in [¹⁸F]FDG PET/CT. SUV_max for PHBTs, maximum tumor-to-background ratio for PHBTs, and mean tumor-to-background ratio for PHBTs were significantly higher on [⁶⁸Ga]Ga-FAPI-46 PET/CT than on [¹⁸F]FDG PET/CT (all P < 0.05). Conclusion: [⁶⁸Ga]Ga-FAPI-46 PET/CT is superior to [¹⁸F]FDG PET/CT in characterizing unclear hepatic lesions.