Imaging reactive oxygen species (ROS) in nonhuman primate brain with [18F]ROStrace

195 Objectives: High levels of reactive oxygen species (ROS) can lead to oxidative stress, which has been implicated in cancer, cardiovascular, and neurodegenerative diseases. Recently, Hou et al. developed the Positron Emission Tomography (PET) radiotracer [18F]ROStrace, which is oxidized by superoxide [1] and demonstrated increased uptake and trapping in a preclinical mouse model with lipopolysaccharide (LPS) induced inflammation. The aim of this study was to evaluate further the imaging properties of [18F]ROStrace in nonhuman primate brain. Methods: [18F]ROStrace was synthesized as previously described [1] and adapted to the GE Tracerlab FXFN module. Tosyl precursor was radiolabeled with nucleophilic [18F] fluoride followed by deprotection in HCl. Product was purified by semipreparative HPLC and formulated for dose. PET scans in rhesus monkey with [18F]ROStrace were acquired for 240 min, one on a FOCUS 220 and the second on a Siemens Biograph mCT PET/CT. Arterial blood samples were drawn for metabolite analysis and construction of the input function. Regions of interest were defined with the INIA atlas [2] and individual subjects’ MR image to generate time-activity curves (TACs). Results: [18F]ROStrace was synthesized in high molar activity (16.58 mCi/nmol). Injected activity of [18F]ROStrace was 4.59 +/- 0.31 mCi ( 0.13 +/- 0.02 µg injected mass, n=2). [18F]ROStrace metabolized fairly quickly with 28 +/- 6.4% of parent fraction at 30 minutes after injection (n=2). Plasma free fraction (fp) was low, 3.5% +/- 0.5% (n=2). [18F]ROStrace exhibited homogenous regional brain uptake that peaked at SUV values of 1.4 at 5 min post injection, followed by rapid washout to SUV values ranging from 0.15-0.3 within 1 hour of injection (see Figure 1). Conclusions: We report the successful radiochemical synthesis of [18F]ROStrace and its imaging evaluation in nonhuman primate. Low brain uptake was observed, which may result from low levels of superoxide in the baseline state. Future work will include PET imaging after LPS stimulation to evaluate the sensitivity of [18F]ROStrace to elevated levels of oxidative species, and full kinetic modeling to determine suitable quantification approaches. Funding Support: P30 (P30DA046345)