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- W3200722178 abstract "1480 Objectives: Ascorbic acid is a potent, biological antioxidant. It scavenges most reactive oxygen species (ROS) that could otherwise damage nucleic acids and promote carcinogenesis. Its potential anti-tumor effects are being studied, with many reporting the slowing of tumor growth at pharmacologic doses.At the same time, lower doses of ascorbate can be used to image/track ROS. However, the complete in vivo molecular ROS mechanisms of ascorbate in cancer largely remain unknown. PET imaging with a new generation of ascorbate-based radioligand can present an opportunity for in vivo assessment of ROS in cancer. Our laboratory reported the initial PET imaging properties of a novel ascorbate derivative, [18F]KS1, to track ROS in tumor-bearing mice (EJNMMI 2019, 9(1):43). We demonstrated high ROS binding affinity in head and neck and prostate cancer cells through cell uptake assays, microPET imaging, and biodistribution studies. Rhesus monkeys exposed to radiation experience increased target tissue ROS and persistent systemic inflammation for years after exposure. Therefore, forms an ideal animal model to validate our PET radioligand strategy to image ROS in vivo. Herein, we report the preliminary PET imaging evaluations of [18F]KS1 in normal/non-irradiated rhesus monkeys and established NHP tumor model of radiation exposure. Methods: All the NHPs were placed in the scanner and a catheter was inserted into an external vein for tracer injection. Body temperature was maintained at 40 °C with a warm air circulating blanket and vital signs including heart rate, blood pressure, respiration rate, and temperature were monitored throughout the scanning procedure. PET/CT images were acquired in both normal (n=2, 8-9 y, 8.8-9 kg) and radiated (~8 Gy radiation) renal and hepatic tumor-bearing (n=2, 9-10 y, 10-12 kg) rhesus macaques with a dose of [18F]KS1 (8 ± 1 mCi). Whole-body scanning was performed at multiple time points in the non-irradiated monkeys i.e., every 30 min post-radiotracer injection until 3.0 h, and one-time point for the tumor-bearing monkeys i.e., 90 min post-radiotracer injection. ROIs were drawn manually on the fused PET/CT images across the kidneys, liver, lungs, brain, heart, tumor, and muscle using the PMOD software analyses, and SUVavg were calculated. Additionally, ex vivo ROS was determined in the tumor and muscle tissues (collected by biopsy) from the tumor-bearing monkey using an OxylHC histopathology detection kit. Results: Whole-body PET imaging biodistribution profile based on SUVavg values in normal rhesus monkeys demonstrated excellent washout kinetics from all critical organs from 30 min to 180 min post-injection including kidneys (84.3 to 5.60 KBq/cc), liver (37.7 to 9.1 KBq/cc), heart (11.3 to 1.34 KBq/cc), lungs (16.86 to 2.53 KBq/cc), and brain (2.11 to 0.31 KBq/cc). More importantly, both the tumor-bearing monkeys demonstrated ~8-fold higher tumor to muscle ratio (72.23 Vs. 9.21 KBq/cc), and the radioactivity profile in the rest of the other organs was similar to the distribution kinetics in normal monkeys at 90 min time-point. No significant bone uptake was observed, demonstrating no defluorination of the radiotracer. Vital signs remained stable throughout the scanning procedure indicating the safety profile of [18F]KS1 in NHPs. OxylHC histopathology assay results demonstrated ~6.5-fold high ROS ex vivo in tumor (target) tissue compared to the muscle (non-target). Conclusions: Initial PET imaging evaluations of [18F]KS1 in NHP tumor model of radiation exposure exhibited (a) favorable pharmacokinetic properties, (b) high tumor uptake in vivo, (c) superior ROS in vivo selectivity (well-corroborated with the ex vivo measurements). These strong preliminary data support the high translational utility of [18F]KS1 to track ROS in vivo. Blood metabolite studies, dosimetry studies are being investigated in our lab to evaluate the comprehensive PET imaging properties of [18F]KS1." @default.
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- W3200722178 date "2021-05-01" @default.
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- W3200722178 title "Initial biological evaluations of [18F]KS1, ascorbate-based ROS imaging ligand in tumor models of non-human primates." @default.
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