Journal Article Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis

Hatori, Akiko  ,  Yui, Joji  ,  Xie, Lin  ,  Kumata, Katsushi  ,  Yamasaki, Tomoteru  ,  Fujinaga, Masayuki  ,  Wakizaka, Hidekatsu  ,  Ogawa, Masanao  ,  Nengaki, Nobuki  ,  Kawamura, Kazunori  ,  Wang, Feng  ,  Ming-Rong, Zhang

Hepatic fibrosis is the wound healing response to chronic hepatic injury caused by various factors.In this study, we aimed to evaluate the utility of translocator protein (18 kDa) (TSPO) as a molecularimaging biomarker for monitoring the progression of hepatic fibrosis to cirrhosis. Model rats wereinduced by carbon tetrachloride (CCl4), and liver fibrosis was assessed. Positron emission tomography(PET) with N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[18F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]-acetamide ([18F]FEDAC), a radioprobe specific for TSPO, was used for noninvasive visualisationin vivo. PET scanning, immunohistochemical staining, ex vivo autoradiography, and quantitativereverse-transcription polymerase chain reaction were performed to elucidate the relationshipsamong radioactivity uptake, TSPO levels, and cellular sources enriching TSPO expression in damagedlivers. PET showed that uptake of radioactivity in livers increased significantly after 2, 4, 6, and 8weeks of CCl4 treatment. Immunohistochemistry demonstrated that TSPO was mainly expressed inmacrophages and hepatic stellate cells (HSCs). TSPO-expressing macrophages and HSCs increasedwith the progression of liver fibrosis. Interestingly, the distribution of radioactivity from [18F]FEDACwas well correlated with TSPO expression, and TSPO mRNA levels increased with the severity of liverdamage. TSPO was a useful molecular imaging biomarker and could be used to track the progressionof hepatic fibrosis to cirrhosis with PET.

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