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- Title
[F]-BMS-747158-02PET imaging for evaluating hepatic mitochondrial complex 1dysfunction in a mouse model of non-alcoholic fatty liver disease.
- Authors
Rokugawa, Takemi; Momosaki, Sotaro; Ito, Miwa; Iimori, Hitoshi; Kato, Yuki; Abe, Kohji
- Abstract
Background: Mitochondrial dysfunction is one of the main causes of non-alcohol fatty liver disease (NAFLD). [F]-BMS-747158-02 (F-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 F-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 F-BMS were performed after 1 and 2 weeks of the MCD diet. F-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 F-BMS uptake was significantly inhibited by the pre-injection of rotenone. The uptake of F-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 F-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.
- Subjects
FATTY liver; MYOCARDIAL perfusion imaging; MITOCHONDRIAL pathology; POSITRON emission tomography; ROTENONE
- Publication
EJNMMI Research, 2017, Vol 7, Issue 1, p1
- ISSN
2191-219X
- Publication type
Article
- DOI
10.1186/s13550-017-0345-5