Translational Research & Development Project 3

The primary goal of TR&D 3 is to develop imaging probes to image interplay between inflammation and oxidative.  Oxidative stress represents an imbalance between production of reactive oxygen species (ROS) and their elimination or mitigation by antioxidants.  Excess ROS is involved in the pathogenesis of a wide range of diseases.  Importantly, a key mediator of oxidative stress is nitric oxide (NO) which is generated by the nitric oxide synthase (NOS) family of enzymes.  The inducible form of NO has been implicated in a variety of diseases where either acute or chronic inflammation is central to disease pathogenesis.  Moreover, excess NO can react with free radicals to generate reactive nitrogen species (RNS) such as peroxynitirites, which are destructive to cell function.  Finally, ROS and RNS can arise from the influx of pro-inflammatory cells and monocytes/macrophages through the activity of myeloperoxidase (MPO).  Increased MPO activity has been implicated in multiple diseases including and presents a potential prognostic indicator. 

In light of the significance of abovementioned targets in the pathogenesis of disease, the specific aims of TR&D 3 are to design, synthesize and validate 1) radiotracers targeting inducible nitric oxide synthase (iNOS); and 2) gallium-68 incorporated PET tracers for imaging ROS/RNS-mediated oxidative stress and MPO-driven activity.  Radiotracers developed in TR&D 3 will be initially validated in animal models which expand the dynamic range target expression/load.  In addition, TR&D 3 will collaborate with CPs to further optimize the technology for applications in prostate cancer, cardiac dysfunction, Parkinson’s disease, and pulmonary diseases.  The availability of novel translational techniques will represent a paradigm shift in how we study inflammation/oxidative stress.