Feasibility of TSPO-Specific Positron Emission Tomography Radiotracer for Evaluating Paracetamol-Induced Liver Injury

Abstract

Macrophages are activated during the early phase of paracetamol-induced liver injury (PLI). [F-18]GE180 is a radiolabeled ligand that recognizes the macrophage translocator protein (TSPO). In this study, we evaluated the feasibility of a TSPO-specific radiotracer in a rat model of PLI. A rat model of liver injury was induced by intraperitoneal administration of paracetamol. [F-18]GE180 positron emission tomography (PET) images were obtained after 24 h. The maximal and mean standardized uptake values (SUVmax and SUVav) of the liver and serum biomarker levels were examined. The TSPO expression level was examined using real-time polymerase chain reaction and Western blot analysis. [F-18]GE180 hepatic uptake in the PLI group was significantly higher than that in the control group (SUVmax p = 0.001; SUVav p = 0.005). Both mRNA and protein TSPO expression levels were higher in the PLI group. The mRNA expression level of TSPO was significantly correlated with [F-18]GE180 hepatic uptake in both groups (SUVmax p = 0.019; SUVav p = 0.007). [F-18]GE180 hepatic uptake in the PLI group showed a significant positive correlation with ALT(24) and ALT(48) (ALT(24) p = 0.016; ALT(48) p = 0.002). [F-18]GE180 enabled visualization of PLI through TSPO overexpression. Our results support the potential utility of hepatic uptake by TSPO-PET as a non-invasive imaging biomarker for the early phase of PLI.