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


ABSTRACT:

Purpose

To determine the sensitivity of the 18F-radiolabelled dihydroethidine analogue ([18F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.

Procedures

The sensitivity of [18F]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 [18F]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

[18F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [18F]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

[18F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.

SUBMITTER: Waters ECT 

PROVIDER: S-EPMC9085669 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Detecting Validated Intracellular ROS Generation with <sup>18</sup>F-dihydroethidine-Based PET.

Waters Edward C T ECT   Baark Friedrich F   Yu Zilin Z   Mota Filipa F   Eykyn Thomas R TR   Yan Ran R   Southworth Richard R  

Molecular imaging and biology 20211124 3


<h4>Purpose</h4>To determine the sensitivity of the <sup>18</sup>F-radiolabelled dihydroethidine analogue ([<sup>18</sup>F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress.<h4>Procedures</h4>The sensitivity of [<sup>18</sup>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 [<sup>18</sup>F]DHE (50-150 kBq.m  ...[more]

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