Imaging of CNS systems: Importance for drug development

Despite major scientific and technological advances in drug discovery over the past 10-15 years, the success rate of compounds in clinical development has shown a continued decline. This trend is particularly pronounced for diseases of the central nervous system, including neurologic conditions such as Alzheimer's disease and stroke, and psychiatric disorders such as schizophrenia and major depression. The discipline of Translational Medicine aims to impact on this process by identifying novel biomarkers to help validate and understand disease models and pathophysiology, drug targets, and the action of investigational compounds in vivo. In this regard, imaging technologies are particularly useful for biomarker development, because of the relative inaccessibility of the central nervous system to direct sampling and examination of cells or tissues. In the present chapter, we illustrate examples of how neuroimaging can provide information about aspects of drug discovery such as target engagement or disease pathophysiology and of how it can ultimately be used to drive improved decision making in early clinical development.