18F-FAPI PET/CT Reveals Intrapatient Biological Heterogeneity in FDG-Negative Hepatocellular Carcinoma: A Case Report

Abstract Background Hepatocellular carcinoma (HCC) is characterized by substantial biological heterogeneity, which may occur between different tumor nodules within the same patient. 18 F-FAPI PET/CT has demonstrated potential advantages over 18 F-FDG PET/CT in the detection of HCC, the biological determinants responsible for heterogeneous FAPI uptake remain incompletely understood. We report a rare case of FDG-negative HCC showing discordant FAPI accumulation between two lesions within the same patient. Case presentation A 53-year-old man with chronic hepatitis B-related cirrhosis underwent surveillance imaging for mildly elevated serum alpha-fetoprotein (18.70 ng/mL). MRI revealed two suspicious hepatic nodules in segments VIII and VI. Both lesions were negative on 18 F-FDG PET/CT; however, subsequent 18 F-FAPI PET/CT demonstrated markedly heterogeneous uptake, with mild accumulation in the segment VIII lesion (SUVmax 4.1 vs. liver SUVmax 3.5) and intense uptake in the segment VI lesion (SUVmax 12.3). Surgical resection confirmed two HCC lesions with distinct histopathological features and Ki-67 indices (20% and 60%, respectively). Both lesions showed hepatocellular differentiation and microvascular invasion. As FAP immunohistochemistry was unavailable, the mechanism underlying the discordant FAPI uptake remains unclear. Conclusion This case demonstrates substantial interlesional heterogeneity of 18 F-FAPI uptake among multifocal FDG-negative HCCs. The discordant tracer distribution within the same patient suggests that FAPI PET/CT may provide complementary information regarding tumor biological characteristics and microenvironmental differences beyond conventional metabolic imaging.