Imaging the Reactivity of Myeloperoxidase In Vivo

Abstract

This chapter describes the progress in the development of imaging methods to detect myeloperoxidase (MPO) activity in vivo. Taking advantage of its highly reactive products and the unique oxidative feature of MPO in pathologic conditions, various activatable imaging agents have been developed covering imaging modalities from fluorescence imaging to bioluminescence imaging (BLI) to MRI and to positron emission tomography (PET). In the presence of these reactive species generated by MPO, among which hypochlorous acid (HOCl) is recognized as the specific product, the imaging agents are switched from an “off” state with little to no signal to an “on” state to visualize MPO activity. Most optical imaging agents belong to this category. 5-Hydroxytryptamine (5-HT)-based imaging agents represent another category of activatable imaging agents that detect MPO activity. These agents are substrates of MPO that can be oxidized (activated) by MPO to form oligomers or bind to proteins at sites of inflammation. MPO-mediated activation of 5-HT-based agents generates higher contrast-to-noise ratio (CNR) making them highly specific and sensitive. As these imaging agents are further developed and translated, MPO imaging will provide valuable insights in the pathogenesis of various inflammatory diseases and a useful tool for diagnosis and drug development targeting MPO and inflammation.