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Imaging metabotropic glutamate receptor system: Application of positron emission tomography technology in drug development

The diversity seen in the mode of pharmacology and the numerous glutamate receptor subtypes have previously complicated drug development efforts. Nonetheless, recent clinical trials of drug candidates that accommodate the glutamatergic intricate pharmacology have yielded encouraging results. Target engagement is an important requirement for the advancement of central nervous system drug candidates into clinical trial. Positron emission tomography (PET) tracer technology has the unique ability to give the direct insight into the relationship between the level of receptor occupancy and the administered dose, thus establishing a direct link between the level of target exposure and the drug efficacy in human. This review is focused on the advancement of mGlu5, mGlu 1, and mGlu 2 receptor‐related PET tracer technology: PET tracer development strategies, PET tracer selection in receptor occupancy studies, the scopes and limitations to use PET to measure receptor occupancy for the drug candidates with different pharmacology, and how to use the measurements of receptor occupancy as a translational biomarker for decision‐making in an innovative drug development program.