Advances in PET Imaging of α7 Nicotinic Receptors: From Radioligand Development to CNS Applications

Positron emission tomography (PET) has significantly advanced our understanding of the brain by enabling non-invasive imaging and quantification of molecular processes, including receptor binding. In this review, we explore the development and application of PET radioligands targeting the α7 nicotinic acetylcholine receptor (α7 nAChR), a receptor implicated in various central nervous system (CNS) diseases, such as Alzheimer's disease, schizophrenia and cognitive disorders. Despite challenges associated with the low density of α7 nAChRs and difficulties in achieving adequate brain penetration, several promising radioligands have been developed, including ¹¹C-(R)-MeQAA, ¹¹C-NS14492 and ¹⁸F-ASEM. These radioligands facilitate the evaluation of the ‘three pillars of survival’ in drug development: tissue accessibility, target engagement and downstream pharmacology. PET imaging offers critical insights into drug distribution across the blood–brain barrier, receptor occupancy and the pharmacodynamic effects of α7 nAChR–targeted therapies. By reviewing current radioligands and their applications, we highlight the potential of PET imaging to deepen our understanding of α7 nAChR–mediated signalling pathways and its implications for CNS drug discovery. Future innovations in radioligand development, including more selective and brain-penetrant compounds, will be key to fully realizing the potential of PET imaging in α7 nAChR–targeted research and treatment.