Project Summary Sigma 1 receptor (σ1R) has been implicated in multiple functions and associated with various human diseases, including brain diseases/disorders. σ1R has been reported to interact with numerous neurotransmitter receptors and ion channels, and involved in diverse basic biochemical processes and pathological conditions related to neurodegeneration, pain sensitization, psychiatric disorders, and drug addiction. Therefore, it is important to have a tool for non-invasive measurement of σ1R expression and function in vivo, and PET imaging would be an ideal tool. Unfortunately, to date, there are no suitable non-invasive neuroimaging tools for investigating these processes in animals or in man. The development of techniques for visualizing σ1R in vivo represents a key step in understanding both the normal function and pathophysiology of σ1R in brain. Moreover, these techniques will accelerate the discovery of small molecule therapeutics that selectively interacts with σ1R. The project is designed to validate a novel PET imaging probe, [18F]CNY-05, for σ1R imaging in rodents and non-human primates.