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As drug discovery and development in Neuroscience push beyond symptom management to disease modification, neuroimaging becomes a key area of translational research that enables measurements of the presence of drugs and downstream physiological consequences of drug action within the living brain. As such, neuroimaging can be used to help optimize decision-making processes throughout the various phases of drug development. Positron Emission Tomography (PET) is a functional imaging technique that allows the quantification and visualization of biochemical processes, by monitoring the time dependent distribution of molecules labelled with short-lived positron-emitting isotopes. This review focuses on the application of PET to support CNS drug development, particularly in the early clinical phases, by allowing us to measure tissue exposure, target engagement, and pharmacological …