[18F]FEDAC translocator protein positron emission tomography–computed tomography for early detection of mitochondrial dysfunction secondary to myocardial ischemia

• Published in: Annals of nuclear medicine 2021-08, Vol.35 (8), p.927-936
• Main Authors: Luo, Rui, Wang, Lei, Ye, Fei, Wang, Yan-Rong, Fang, Wei, Zhang, Ming-Rong, Wang, Feng
• Format: Article
• Language: English
• Subjects: Animals; Biodistribution; Computed tomography; Early Diagnosis; Electron microscopy; Emission analysis; Fluorine isotopes; High performance liquid chromatography; Imaging; Immunohistochemistry; Injury prevention; Ischemia; Kinetics; Male; Medicine; Medicine & Public Health; Mice; Mitochondria; Mitochondria - metabolism; Myocardial ischemia; Myocardial Ischemia - diagnostic imaging; Myocardial Ischemia - metabolism; Myocardium; Nuclear Medicine; Original; Original Article; Permeability; Positron emission; Positron emission tomography; Positron Emission Tomography Computed Tomography; Proteins; Pyrazoles; Radioactivity; Radiochemical analysis; Radiology; Rats; Rats, Sprague-Dawley; Receptors, GABA - metabolism; Stability analysis; Tissue Distribution; Tomography; Ultrastructure
• ISSN: 0914-7187; 1864-6433
• DOI: 10.1007/s12149-021-01630-7

Background This study aimed to evaluate the biodistribution and kinetics of [ 18 F]FEDAC targeting the translocator protein TSPO in the myocardium, and to explore its use for the identification of mitochondrial dysfunction. We also assessed the feasibility of [18F]FEDAC for the early detection of mitochondrial dysfunction associated with myocardial ischemia (MI). Methods The radiochemical purity and stability of [ 18 F]FEDAC were analyzed by radio-high-performance liquid chromatography (radio-HPLC). Its biodistribution and kinetics were evaluated by dissection and dynamic imaging using micro-positron emission tomography–computed tomography (micro-PET–CT) in healthy mice. [ 18 F]FEDAC was also applied in an MI rat model and in sham-operated controls. Mitochondrial changes were observed by immunohistochemical staining and electron microscopy. Results Radioactivity levels (%ID/g) in the myocardium in normal mice, determined by [ 18 F]FEDAC, were 8.32 ± 0.80 at 5 min and 2.40 ± 0.10 at 60 min. PET showed significantly decreased uptake by injured cardiac tissue in MI rats, with maximal normal-to-ischemic uptake ratios of 10.47 ± 3.03 (1.5 min) and 3.92 ± 1.12 (27.5 min) ( P  = 0.025). Immunohistochemistry confirmed that TSPO expression was decreased in MI rats. Mitochondrial ultrastructure demonstrated significant swelling and permeability. Conclusion [ 18 F]FEDAC uptake is reduced in the injured myocardium, consistent with mitochondrial dysfunction. These results may provide new evidence to aid the early detection of mitochondrial dysfunction associated with myocardial ischemic injury.