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

Background Mitochondrial dysfunction is one of the main causes of non-alcohol fatty liver disease (NAFLD). [ 18 F]-BMS-747158-02 ( 18 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 18 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 18 F-BMS were performed after 1 and 2 weeks of the MCD diet. 18 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 18 F-BMS uptake was significantly inhibited by the pre-injection of rotenone. The uptake of 18 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