TY - JOUR T1 - Increased superoxide levels in a transgenic mouse model of Parkinson’s disease measured with the PET probe [<sup>18</sup>F]ROStrace. JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 186 LP - 186 VL - 60 IS - supplement 1 AU - Catherine Hou AU - Chia-Ju Hsieh AU - Chi-Chang Weng AU - Kuiying Xu AU - Shihong Li AU - Robert Mach Y1 - 2019/05/01 UR - http://jnm.snmjournals.org/content/60/supplement_1/186.abstract N2 - 186Objectives: Previous studies from our group have shown that the PET radiotracer, [18F]ROStrace, is capable of imaging elevated superoxide levels which occur in the proinflammatory form of neuroinflammation.[1] The goal of the current study was to determine if [18F]ROStrace is capable of imaging elevated superoxide levels associated with neuroinflammation in a transgenic mouse model of Parkinson’s disease (PD). Methods: Mice overexpressing the A53T mutation of human alpha synuclein (i.e., A53T mice) were chosen since this transgenic mouse model has been shown to mimic the pathology found in PD.[2] [18F]ROStrace was synthesized according to the published method.[1] A series of PET imaging studies was conducted in both A53T and non-transgenic (non-tg) control animals at 4 different ages, 6, 7, 8 and 12 months. A second series of studies was conducted in A53T and control mice that received a dose of LPS (5 mg/kg, i.p.) and PET imaging studies were conducted at 24 hrs and 1- and 5-months post-LPS treatment. PET imaging data were collected at 40 - 60 min post-injection of the radiotracer (plateau region of tracer accumulation) and data were represented as %ID/cc tissue. Results: The results of the baseline studies indicate that there is an age-related increase in the uptake of [18F]ROStrace in the A53T mice versus a slight decrease in tracer uptake in the control group. The increase in [18F]ROStrace uptake parallels the rate of formation of Asyn pathology in these animals. Furthermore, treatment of the A53T mice with LPS resulted in a higher uptake of [18F]ROStrace relative to that observed in the non-tg controls. The increase in [18F]ROStrace was not persistent and returned to the level observed in the non-tg controls at 1- and 5-months post-LPS treatment. Conclusions: These data indicate that there is an increase in neuroinflammation-associated superoxide levels in PD mice relative to their non-tg controls. There is also an enhanced neuroinflammatory response in the mice overexpressing aggregated Asyn relative to the control group. These data support the use of [18F]ROStrace to study the role of increased levels of superoxide that occurs in the proinflammatory form of neuroinflammation in patients with PD. References: [1] Hou C, Hsieh C-J, Li S, et al. ACS Chem Neurosci 2018; 9: 578-586. [2] Lim Y, Kehm V, Lee E, et al. J Neurosci 2011; 31: 10076-10087. ER -