[18F]FAPI PET/CT in the evaluation of focal liver lesions with [18F]FDG non-avidity

Purpose: This prospective study was aimed to investigate the potential utility of [F-18]fibroblast activation protein inhibitor (FAPI) PET/CT for evaluating focal liver lesions (FLLs) with [F-18]FDG non-avidity. Methods: From January 2021 to March 2022, this prospective study included 80 FLLs that were not avid on [F-18]FDG PET/CT from 37 patients, then underwent [F-18]FAPI PET/CT. All patients with FLL(s) with biopsy-proof or follow-up confirmation were categorized into four subgroups (20 hepatocellular carcinomas [HCCs]/5 non-HCC malignancies/4 inflammatory FLLs/8 benign noninflammatory FLLs). The diagnostic value of [F-18]FAPI for detecting liver malignancy was determined by visual evaluation. Differences in the maximum standardized uptake value (SUVmax) and lesion-to-background ratio (LBR) obtained from [F-18]FAPI PET/CT among the four subgroups were analyzed by semiquantitative analysis. Results: Among the thirty-seven enrolled participants (34 males; median age 57 years, range 48-67 years), on visual evaluation, the sensitivity, specificity, and accuracy of [F-18]FAPI PET for detecting liver malignancy in the patient-based analysis were 96.0% (24/25), 58.3% (7/12), and 83.8% (31/37), respectively. On semiquantitative analysis, the SUVmax and LBR of [F-18]FAPI PET in liver malignancy (33 HCC lesions; 19 non-HCC malignant lesions) were significantly higher than those in 11 benign noninflammatory FLLs [HCC: SUVmax: 6.4 vs. 4.5, P = 0.017; LBR: 5.1 vs. 1.5, P = 0.003; non-HCC: SUVmax: 5.5 vs. 4.5, P = 0.008; LBR: 4.4 vs. 1.5, P = 0.042]. Notably, there was no significant difference in the SUVmax of [F-18]FAPI PET between 33 HCC lesions and 17 inflammatory FLLs (6.4 vs. 8.2, P = 0.37), but the LBR of [F-18]FAPI PET in HCC were significantly lower than that in inflammatory FLLs (5.1 vs. 9.1, P = 0.003). Conclusions: [F-18]FAPI PET/CT shows high sensitivity in detecting HCC and non-HCC malignancy with [F-18]FDG non-avidity. [F-18]FAPI might be a promising radiopharmaceutical for the differential diagnosis of benign noninflammatory FLLs and liver malignancy with [F-18]FDG non-avidity.