||18F-FEDAC Translocator Protein PET/CT for the early detection of mitochondria dysfunction secondary to myocardial ischemia
Luo, Rui ,
WANG, FengMing-Rong, Zhang
Objectives: ranslocator Protein (TSPO) of the mitochondrial membrane has been recognized as a potential therapeutic target for mitigation of myocardial ischemia-reperfusion injury. [18F]FEDAC was synthesized automatically, the aim of this study is to evaluate it’s biodistribution and kinetics and further address the feasibility for the early detection of myocardial ischemia. Methods: [18F]FEDAC was synthesized with automated module, radiochemical purity and stability was performed by HPLC assay. The biodistribution and kinetics were evaluated by the dissection method and dynamic imaging with micro PET/CT in normal mice. ROI was drawn to access TAC (time-activity curve) in main organs. Myocardial ischemia-reperfusion injury rats were induced by the surgery of ligation of anterior descending coronary artery in rat model. [18F]FEDAC PET/CT was performed in 5 myocardial ischemia-reperfusion rat models(n=5) and 3 sham-operated animals. Immunohistochemistry staining were performed to clarify the relationships between radioactivity and TSPO levels in damaged myocardium, electron microscope was used to observe the mitochondria untrastructure. Results: [18F]FEDAC predominantly cleared from kidneys, myocardium showed stable radiouptake, the SUVmax was 8.41±0.02, adrenal glands showed significant uptake, SUVmax was 16.08±0.04. PET showed that uptake of ischemia myocardium decreased significantly at 24h post-surgery, SUVmax was 2.48±0.12. Immunohistochemistry showed TSPO expression was decreased in ischemic myocardium. Interestingly, the defects of 18F-FEDAC were well consistent with TSPO expression. Mitochondria ultrastructure presented with significant swelling and permeability. Conclusion: [18F]FEDAC showed favorable biodistribution profiles, which may serve as new PET tracer for the early detection of myocardial reperfusion injury and shed light on mitochondria dysfunction .
SNMMI 2018 Annual Meeting