Towards selective CNS PET Imaging of the 5-HT7 Receptor System: Past, Present and Future

Since its discovery in 1993, the serotonin receptor subtype 7 (5-HT7) has attracted significant attention as a potential drug target; due to its elucidated roles in conditions such as insomnia, schizophrenia, and more. Therefore, it is unsurprising that there has been relatively early efforts undertaken to develop a positron emission tomography (PET) imaging agent for said receptor system. PET can be clinically used to probe receptor systems in vivo, permitting information such as a drug's occupancy against this system to be investigated. This review focuses on the efforts towards the development of a 5-HT7R selective PET CNS tracer over the last 20 years, critically reflecting on applied strategies and commonly employed chemical frameworks and suggests future considerations that are needed to successfully develop a PET tracer for this clinically relevant target.