Our group has pioneered the development of PET radiotracers for imaging oxidative stress in tissue.  The lead compound for radiotracer development for this project was dihydroethidine (DHE), which is oxidized by superoxide to ethidium and trapped in tissues.  The most promising radiotracer based on this lead compound is [<sup>18</sup>F]ROStrace, which is also oxidized by superoxide to form a charged species that is trapped in tissues with high levels of ROS.  Since this compound readily crosses the BBB it can measure the proinflammatory form of neuroinflammation, and [<sup>18</sup>F]ROStrace was validated using a murine model of  lipopolysaccharide (LPS)-induced neuroinflammation (ACS Chem Neurosci 2018; 9: 578).  Ex vivo staining studies in tissue revealed this radiotracer is localized in activated microglia (Iba-1) and neurons but not astrocytes (BBRC 2019; 516: 397).  This presentation will focus on the use of the radiotracer in murine models of Alzheimer’s disease (AD), and will present evidence that female mice are more prone to oxidative stress than male mice, and may explain the clinical observations that AD has a more severe phenotype in female versus male subjects.

Imaging reactive oxygen species in vivo with PET

ACS Spring 2022

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