Abstract
Macrophages are activated during the early phase of paracetamol-induced liver injury (PLI). [18F]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. [18F]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. [18F]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 [18F]GE180 hepatic uptake in both groups (SUVmax p = 0.019; SUVav p = 0.007). [18F]GE180 hepatic uptake in the PLI group showed a significant positive correlation with ALT24 and ALT48 (ALT24 p = 0.016; ALT48 p = 0.002). [18F]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.
Highlights
Drug-induced liver injury (DLI) is a common adverse event encountered in clinical practice
After the induction of paracetamol-induced liver injury (PLI), a significant increase in the in vivo [18F]GE180 hepatic uptake corresponded to ex vivo translocator protein (TSPO) expression
The increase in the in vivo [18F]GE180 hepatic uptake correlated significantly with an increase in liver enzymes, which is the current standard of monitoring liver injury
Summary
Drug-induced liver injury (DLI) is a common adverse event encountered in clinical practice. A sterile inflammatory response is known to be the main mechanism of paracetamol-induced liver injury (PLI). Targeting and visualization of macrophages in patients with paracetamol-overdosing may enable early detection of liver injury, as well as prediction of liver failure. The translocator protein (TSPO), an 18 kDa protein with five transmembrane domains primarily localized in the outer membrane of mitochondria, is overexpressed in activated macrophages and can serve as an attractive surrogate marker for Alzheimer’s disease, multiple sclerosis, Huntington’s disease, various cancers, ischemic brain injury, myocarditis, DLI and rheumatoid arthritis [7,8,9,10,11,12,13,14,15,16]. The aim of this study, was to investigate the feasibility of the TSPO-specific radiotracer [18F]GE180 to visualize PLI using positron emission tomography (PET) by targeting activated macrophages. The relationships between [18F]GE180 hepatic uptake by PET imaging and ex vivo TSPO expression and serum markers of liver injury were analyzed
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