PET Imaging for The Early Evaluation of Ocular Inflammation in Diabetic Rats by Using [ 18 F]-DPA-714

Abstract

Abstract Ocular complications of diabetes mellitus (DM) are the key leading cause of vision loss worldwide. Ocular inflammation is estimated to occur in the early stage of DM; however, there is no effective quantitative method for evaluating the inflammatory status in eye under diabetic status. The 18 kDa translocator protein (TSPO), an evolutionary conserved cholesterol binding protein localized in the outer mitochondrial membrane, is the biomarker of activated microglia/macrophages, while its role in ocular inflammation is rarely reported. Primary microglia/macrophages (PMs) extracted from the cornea, retina, choroid and sclera of neonatal rats were treated with or without high glucose (50 mM) and used as in vitro model, and SD rats with intraperitoneal administration of streptozotocin (STZ, 60 mg kg−1 once) were used as in vivo model. Then, fluorine-18-DPA-714 ([18F]-DPA-714), as a specific TSPO tracer, was used for cell uptake and cell binding experiments as well as micro positron emission tomography (microPET) imaging. Increased cell uptake and high binding affinity of [18F]-DPA-714 were observed in primary PMs under hyperglycemia stress, which was consistent with morphological changes, cell activation and TSPO overexpression (p<0.05). Then, [18F]-DPA-714 uptake and biodistribution in eye of DM rats was found to be significantly increased at early stage (3 week and 6 week), which was consistent with microglia/macrophages activation and up-regulated TSPO in eye (p<0.05). [18F]-DPA-714 microPET imaging may be an important method for the early evaluation of ocular inflammation in DM.