The goal of this project is utilize a novel radiotracer developed in our group for imaging oxidative stress in patients at risk for developing Alzheimer's disease (AD) with the imaging method Positron Emission Tomography (PET). Oxidative stress caused by the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) from activated glial cells is thought to play a key role in the ?toxic? form of neuroinflammation in AD. The identification of PET probes that can image this process will be important for monitoring disease progression and disease-modifying therapeutics aimed at delaying the progression of PD. In the proposed study we will evaluate a PET probe, [18F]ROStrace, that reacts with superoxide and is trapped in tissue. The radiotracer will be evaluated in a transgenic model of AD in order to assess their ability to measure ?neurotoxic?, M1-polarized neuroinflammation in AD patients. This study will complement research being conducted in our lab evaluating this probe in a transgenic model of Parkinson's disease, a study which is currently funded by the Michael J. Fox Foundation.
The goal of the research described in this grant proposal is to conduct in vivo studies to validate the ability of a novel radiotracer developed in our lab for imaging oxidative stress. The availability of an ROS-based radiotracer which can be used in PET imaging studies can provide a direct assessment of the potential role of chronic, persistent neuroinflammation on the clinical progression of AD. This radiotracer may serve as a novel method for following disease progression in patients at risk for AD, as well as for measuring the efficacy of disease-modifying therapeutics aimed at slowing disease progression by blocking neuroinflammation.
