Detecting Validated Intracellular ROS Generation with 18 F-dihydroethidine-Based PET

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