Potential of α7 nicotinic acetylcholine receptor PET imaging in atherosclerosis.

Atherosclerotic events are usually acute and often strike otherwise asymptomatic patients. Although multiple clinical risk factors have been associated with atherosclerosis, as of yet no further individual prediction can be made as to who will suffer from its consequences based on biomarker analysis or traditional imaging methods like CT, MRI or angiography. Previously, non-invasive imaging with 18 F-fluorodeoxyglucose (18 F-FDG) PET was shown to potentially fill this niche as it offers high sensitive detection of metabolic processes associated with inflammatory changes in atherosclerotic plaques. However, 18 F-FDG PET imaging of arterial vessels suffers from non-specificity and has still to be proven to reliably identify vulnerable plaques, carrying a high risk of rupture. Therefore, it may be regarded only as a secondary marker for monitoring treatment effects and it does not offer alternative treatment options or direct insight in treatment mechanisms. In this review, an overview is given of the current status and the potential of PET imaging of inflammation and angiogenesis in atherosclerosis in general and special emphasis is given to imaging of α7 nicotinic acetylcholine receptors (α7 nAChRs). Due to the gaps that still exist in our understanding of atherogenesis and the limitations of the available PET tracers, the search continues for a more specific radioligand, able to differentiate between stable atherosclerosis and plaques prone to rupture. The potential role of the α7 nAChR as imaging marker for plaque vulnerability is explored. Today, strong evidence exists that nAChRs are involved in the atherosclerotic disease process. They are suggested to mediate the deleterious effects of the major tobacco component, nicotine, a nAChR agonist. Mainly based on in vitro data, α7 nAChR stimulation might increase plaque burden via increased neovascularization. However, in animal studies, α7 nAChR manipulation appears to reduce plaque size due to its inhibitory effects on inflammatory cells. Thus, reliable identification of α7 nAChRs by in vivo imaging is crucial to investigate the exact role of α7 nAChR in atherosclerosis before any therapeutic approach in the human setting can be justified. In this review, we discuss the first experience with α7 nAChR PET tracers and developmental considerations regarding the "optimal" PET tracer to image vascular nAChRs.