Radioligands for the study of the 5-HT transporter in vivo

Loss of 5-HT transporter (SERT) sites has been implicated in various neurodegenerative diseases and users of some amphetamine derivatives such as MDMA. Therefore, the development of suitable radioligands for neuroimaging of the SERT in the human brain is important. A large number of drugs have been labeled with ¹¹C, ¹⁸F or ¹²³I over the last ten years in order to achieve such radioligands. Despite these attempts most of the compounds were found unsuitable because of low target-to-nontarget ratios. Some cocaine- derived radioligands allow SERT imaging of the human brain using positron emission tomography (PET) although they have a limited selectivity. Among the various specific 5-HT uptake inhibitors only [¹²³I]iodonitroquipazine for single photon emission computed tomography (SPECT) and [¹¹C](+)McN5652 for PET appear to meet the criteria of a useful radioligand. There is still a need for the development of new radioligands for SERT imaging. Advances in tracer synthetic methodologies may bring further progress in this field.