Chapter 3. Recent Developments in PET and SPECT Radioligands for CNS Imaging

Abstract

The human brain is an extraordinarily complex organ with elaborate mechanisms to isolate it from xenobiotic processes, limiting our understanding of brain pathology throughout the history of medicine to what can be derived from post-mortem examination or analysis of circulating or excreted metabolites. The development of three-dimensional nuclear imaging techniques (single photon emission computed tomography and positron emission tomography) has opened the way to the noninvasive real-time and quantifiable in vivo observation of brain functions in pathological and normal states, allowing a better understanding of the etiology of psychiatric and neurological disorders. Coupled with the power of the physical instruments for imaging, the development of specific target-binding radiotracers allows measurement of biochemical processes in normal and disease states and in response to pharmacological challenges. The past ten years have seen tomographic imaging techniques involved more and more closely in CNS drug discovery by providing access to brain pharmacokinetic parameters of new drugs, as well as allowing a precise measure of the effectiveness of new therapy in clinical trials of therapeutic drugs. In this chapter, we summarize recent developments in imaging agents for selected brain targets (amyloid, mGluR1, mGluR5, DAT, SERT, NET, VMAT2, D3, 5-HT4, 5-HT6, PBR, PDE4, PDE10, A1, A2A, CB1, CB2) that are of clinical relevance in modern psychiatry and neurology and of pharmacological interest in the area of drug discovery and drug development.