Oxidative stress, defined as the excessive production of reactive oxygen species (ROS), is a crucial factor in the pathogenesis of various neurodegenerative diseases, including the 4-repeat (4R) tauopathies. Collectively, the 4R tauopathies are characterized by the progressive aggregation of tau protein isoforms with four microtubule-binding domains in and around brain cells. The cyclical relationship between oxidative stress and 4R tau aggregation suggests that a means of imaging ROS noninvasively could be a valuable tool for the study and treatment of 4R tauopathy in both humans and animal models. To demonstrate the potential of the ROS-sensitive positron emission tomography (PET) radiotracer [