Division of Imaging Sciences and Biomedical Engineering, Kings College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH, UK.
Center for Infection and Inflammation Imaging Research, Center for Tuberculosis Research, and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Mol Imaging Biol. 2022 Jun;24(3):377-383. doi: 10.1007/s11307-021-01683-0. Epub 2021 Nov 24.
To determine the sensitivity of the F-radiolabelled dihydroethidine analogue ([F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
The sensitivity of [F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [F]DHE (50-150 kBq.min) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress.
[F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation.
[F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.
在已验证的组织氧化应激体外模型中，确定 F-放射性标记二氢乙啶类似物 ([F]DHE) 对 ROS 的灵敏度。
首先在体外确定 [F]DHE 对各种 ROS 生成系统的灵敏度。然后，离体大鼠心脏在恒流下灌注，通过心室内球囊监测收缩功能。通过 γ 检测监测输注的 [F]DHE（50-150 kBq.min）的摄取，同时通过平行测量心脏氧化应激来验证通过 menadione 输注（0、10 或 50 μm）引发的 ROS 生成。
[F]DHE 对超氧化物和羟自由基的氧化最敏感。与对照组（0.81±0.07）相比，在 menadione 处理的心脏中，归一化的 [F]DHE 摄取显著更高（1.44±0.27）（p<0.05，n=4/组），同时伴有心脏收缩功能障碍、谷胱甘肽耗竭和 PKG1α 二聚化。
[F]DHE 在已验证的氧化应激模型中报告 ROS，其中灌注（和示踪剂输送）不太可能影响其药代动力学。
