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

Autor: Waters ECT; Division of Imaging Sciences and Biomedical Engineering, Kings College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH, UK., Baark F; Division of Imaging Sciences and Biomedical Engineering, Kings College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH, UK., Yu Z; Division of Imaging Sciences and Biomedical Engineering, Kings College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH, UK., Mota F; 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., Eykyn TR; Division of Imaging Sciences and Biomedical Engineering, Kings College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH, UK., Yan R; Division of Imaging Sciences and Biomedical Engineering, Kings College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH, UK., Southworth R; Division of Imaging Sciences and Biomedical Engineering, Kings College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH, UK. richard.southworth@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Molecular imaging and biology [Mol Imaging Biol] 2022 Jun; Vol. 24 (3), pp. 377-383. Date of Electronic Publication: 2021 Nov 24.
DOI: 10.1007/s11307-021-01683-0
Abstrakt: Purpose: To determine the sensitivity of the 18 F-radiolabelled dihydroethidine analogue ([ 18 F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.
Procedures: The sensitivity of [ 18 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 [ 18 F]DHE (50-150 kBq.min -1 ) 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.
Results: [ 18 F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [ 18 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.
Conclusion: [ 18 F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.
(© 2021. Crown.)
Databáze: MEDLINE
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