Recent PET radioligands with optimal brain kinetics for imaging nicotinic acetylcholine receptors

Cerebral neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in various neurophysiological processes and in the pathophysiology and/or treatment strategies of various disorders. Positron emission tomography (PET) imaging of nAChR and, especially, the most prominent cerebral subtype α4β2-nAChR is important in smoking, epilepsy, attention deficit hyperactivity disorder, depression, schizophrenia, cognition, behavior, memory, and in research involving aging, cognitive impairments, and dementia. Most human α4β2-nAChR PET imaging has been performed with 2-[¹⁸F]FA, but slow brain kinetics is the substantial drawback of 2-[¹⁸F]FA that precludes widespread PET imaging research of nAChR in humans. Development of a better PET radioligand for α4β2-nAChR was a focus of substantial investigation that has been thoroughly reviewed (up to 2009) previously. This article attempts to summarize the peer-reviewed publications of the most recent development and preclinical studies of novel α4β2-nAChR PET radioligands with improved brain kinetics and first human studies with one of these radioligands ([¹⁸F]AZAN).