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ACS Chem Neurosci. 2018 Jun 20;9(6):1226-1229. doi: 10.1021/acschemneuro.8b00176. Epub 2018 May 15.

Classics in Neuroimaging: The Serotonergic 2A Receptor System-from Discovery to Modern Molecular Imaging.

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Neurobiology Research Unit and CIMBI , Copenhagen University Hospital , Rigshospitalet, Blegdamsvej 9 , 2100 Copenhagen , Denmark.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences , University of Copenhagen , Jagtvej 160 , 2100 Copenhagen , Denmark.
Radiation Physics, Nuclear Medicine Physics Unit , Skånes University Hospital , Barngatan 3 , Lund 222 42 , Sweden.
Department of Clinical Physiology, Nuclear Medicine and PET , University Hospital Copenhagen , Rigshospitalet Blegdamsvej 9 , 2100 Copenhagen , Denmark.


Already in 1953, Woolley and Shaw speculated that serotonin could be involved in a range of central nervous system (CNS) disorders. Lysergic acid diethylamide (LSD) displayed an important role in this respect. It was used not only to antagonize biological effects of serotonin and to study the system itself, but also to identify serotonergic subtype receptors. The 5-HT2A receptor was discovered in the 1970s and identified as the responsible receptor mediating psychedelic effects of LSD. The development of positron emission tomography (PET) allowed to study this receptor system in vivo. Parameters such as abundance of 5-HT2A neuroreceptors or receptor occupancy can be determined using PET. As such, the development of 5-HT2A receptor tracers started immediately after the introduction of PET in the mid-1970s. In this Viewpoint, we provide a historical overview from the discovery of serotonin to the identification of the 5-HT2A receptor subtype and the subsequent development of 5-HT2A receptor subtype specific PET tracers over the last four decades. We emphasize the interplay between pharmacology, medicinal chemistry, radiochemistry, and nuclear medicine that is important while developing a PET tracer. Moreover, we highlight selected examples applying 5-HT2A receptor PET tracers within neurological diseases and drug occupancy studies.


(R)-[18F]MH.MZ; 5-HT2A; PET; [11C]Cimbi-36; [11C]MDL 100907; [18F]altanserin; serotonin

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