[18F]-BMS-747158-02PET imaging for evaluating hepatic mitochondrial complex 1dysfunction in a mouse model of non-alcoholic fatty liver disease

Takemi Rokugawa, Sotaro Momosaki, Miwa Ito, Hitoshi Iimori, Yuki Kato, Kohji Abe

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Mitochondrial dysfunction is one of the main causes of non-alcohol fatty liver disease (NAFLD). [18F]-BMS-747158-02 (18F-BMS) which was originally developed as a myocardial perfusion imaging agent was reported to bind mitochondrial complex-1 (MC-1). The aim of this study was to investigate the potential use of 18F-BMS for evaluating hepatic MC-1 activity in mice fed a methionine- and choline-deficient (MCD) diet. Male C57BL/6J mice were fed a MCD diet for up to 2 weeks. PET scans with 18F-BMS were performed after 1 and 2 weeks of the MCD diet. 18F-BMS was intravenously injected into mice, and the uptake (standardized uptake value (SUV)) in the liver was determined. The binding specificity for MC-1 was assessed by pre-administration of rotenone, a specific MC-1 inhibitor. Hepatic MC-1 activity was measured using liver homogenates generated after each positron emission tomography (PET) scan. Blood biochemistry and histopathology were also assessed. Results: In control mice, hepatic 18F-BMS uptake was significantly inhibited by the pre-injection of rotenone. The uptake of 18F-BMS was significantly decreased after 2 weeks of the MCD diet. The SUV at 30–60 min was well correlated with hepatic MC-1 activity (r = 0.73, p < 0.05). Increases in plasma ALT and AST levels were also noted at 1 and 2 weeks. Mild hepatic steatosis with or without minimal inflammation was histopathologically observed at 1 and 2 weeks in mice liver on the MCD diet. However, inflammation was observed only at 2 weeks in mice on the MCD diet. Conclusions: The present study demonstrated that 18F-BMS is a potential PET probe for quantitative imaging of hepatic MC-1 activity and its mitochondrial dysfunction induced by steatosis and inflammation, such as in NAFLD.

Original languageEnglish
Article number96
JournalEJNMMI Research
Volume7
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Methionine- and choline-deficient diet
  • Mitochondrial complex-1
  • Non-alcoholic fatty liver disease
  • Non-alcoholic steatohepatitis
  • Positron emission tomography
  • [F]-BMS747158-02

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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