Neuroimaging in Psychiatric Drug Development and Radioligand Development for New Targets

Abstract

Positron emission tomography (PET) is an imaging modality used to measure physiological and biochemical markers in brain. Neuroreceptors, transporters, or enzymes are visualized and quantified with appropriate PET radioligands. In the development of drugs for treatment of psychiatric disorders, there are three major applications of PET. First, PET microdosing is used for pharmacokinetic evaluation. By injection of minute amount of radiolabeld drug, information about brain exposure can be obtained already at the early phase of drug development. Another application is receptor occupancy studies. Here, the competition between a drug and a PET radioligand binding is examined at the target sites. The competitive effect is useful to have when selecting the doses tested in further clinical trials. The third application is to use imaging biomarkers for diagnosis or efficacy. To widen the use of PET, the development of the PET radioligands for new targets is vital. Several criteria and characteristics such as binding affinity, selectivity and lipophilicity are important when selecting new PET radioligand candidates for targets in brain.