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PET Imaging of the Human Nicotinic Cholinergic Pathway in Atherosclerosis.

Bauwens M, Mottaghy FM, Bucerius J - Curr Cardiol Rep (2015)

Bottom Line: During the past years, non-neuronal vascular nicotinic acetylcholine receptors (nAChRs) increasingly have gained interest in cardiovascular research, as they are known to mediate the deleterious effects of nicotine and nitrosamines, components of tobacco smoke, on the vasculature.Accordingly, we briefly summarize the pathophysiologic role of vascular nAChRs in the atherosclerotic disease process.We also provide an overview of currently available nAChR positron emission tomography (PET) tracers and their performance in the noninvasive imaging of vascular nAChRs, as well as potential nAChR PET tracers that might be an option for vascular nAChR PET imaging in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.

ABSTRACT
During the past years, non-neuronal vascular nicotinic acetylcholine receptors (nAChRs) increasingly have gained interest in cardiovascular research, as they are known to mediate the deleterious effects of nicotine and nitrosamines, components of tobacco smoke, on the vasculature. Because smoking is a major risk factor for the development of atherosclerosis, it is obvious that understanding the pathophysiologic role of nAChRs in the atherosclerotic disease process, as well as in the development of new diagnostic and therapeutic nAChR-related options, has become more important. Accordingly, we briefly summarize the pathophysiologic role of vascular nAChRs in the atherosclerotic disease process. We also provide an overview of currently available nAChR positron emission tomography (PET) tracers and their performance in the noninvasive imaging of vascular nAChRs, as well as potential nAChR PET tracers that might be an option for vascular nAChR PET imaging in the future.

No MeSH data available.


Related in: MedlinePlus

α4β2-nAChR PET/CT scan showing [18F]-2-fluoro-A85380 uptake in the right and left common carotid arteries (upper ROIs green) and in the right and left jugular veins (lower ROIs). On a visual basis, the fused PET/CT image shows higher uptake of the tracer in the two common carotids compared with the two veins, indicating a specific tracer uptake in the arteries. Furthermore, the right common carotid artery shows a higher uptake (SUVmax 1.7 vs. SUVmax 1.2 in the left common carotid artery) compared with the left common carotid artery, whereas the uptake in the two jugular veins is almost identical (right SUVmean 1.0 vs. left SUVmean 1.1), further indicating a specific arterial uptake of the PET tracer as well as a higher density of the α4β2-nAChRs in the right than in the left common carotid artery
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Fig1: α4β2-nAChR PET/CT scan showing [18F]-2-fluoro-A85380 uptake in the right and left common carotid arteries (upper ROIs green) and in the right and left jugular veins (lower ROIs). On a visual basis, the fused PET/CT image shows higher uptake of the tracer in the two common carotids compared with the two veins, indicating a specific tracer uptake in the arteries. Furthermore, the right common carotid artery shows a higher uptake (SUVmax 1.7 vs. SUVmax 1.2 in the left common carotid artery) compared with the left common carotid artery, whereas the uptake in the two jugular veins is almost identical (right SUVmean 1.0 vs. left SUVmean 1.1), further indicating a specific arterial uptake of the PET tracer as well as a higher density of the α4β2-nAChRs in the right than in the left common carotid artery

Mentions: In a second step, we evaluated the feasibility of the [18F]-2-fluoro-A85380 PET tracer for imaging non-neuronal vascular α4β2-nAChRs in the same study population of five healthy controls and six patients with Parkinson’s disease or MSA [57••]. Again, the aim was to determine whether this tracer could noninvasively image vascular α4β2-nAChRs in vivo in humans via PET and to investigate whether neurodegenerative disorders such as Parkinson’s disease and MSA might have an impact on the vascular distribution of these nAChRs. Because of the pathophysiologic importance of nAChRs in atherosclerosis, which was mentioned earlier, proving the ability to noninvasively detect nAChRs in humans is of crucial relevance for the diagnostic and subsequent therapeutic approach in patients with atherosclerosis. We therefore quantified [18F]-2-fluoro-A85380 uptake in the ascending and descending aorta, the aortic arch, and the carotids in our aforementioned study population as the maximum target-to-background ratio (Fig. 1). The maximal standardized uptake value (SUV), single hottest segment, and percentage of active segments of [18F]-2-fluoro-A85380 uptake in the arteries also were assessed. We could clearly visualize the [18F]-2-fluoro-A85380 uptake, and the maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly greater uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [18F]-2-fluoro-A85380 uptake in the patient group when single arterial territories were compared but not when all arterial territories were pooled together [57••]. Our results clearly suggest that [18F]-2-fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Furthermore, the vascular nAChR density appears lower in patients with Parkinson’s disease or MSA, indicating an impact of both neurodegenerative disorders on human arteries [57]. Currently, our group is carrying out studies in larger populations as well as in the experimental setting to further validate the approach of noninvasive in vivo imaging of vascular nAChRs, which will provide more detailed insights into the pathogenic role of nAChRs in the human vasculature [58].Fig. 1


PET Imaging of the Human Nicotinic Cholinergic Pathway in Atherosclerosis.

Bauwens M, Mottaghy FM, Bucerius J - Curr Cardiol Rep (2015)

α4β2-nAChR PET/CT scan showing [18F]-2-fluoro-A85380 uptake in the right and left common carotid arteries (upper ROIs green) and in the right and left jugular veins (lower ROIs). On a visual basis, the fused PET/CT image shows higher uptake of the tracer in the two common carotids compared with the two veins, indicating a specific tracer uptake in the arteries. Furthermore, the right common carotid artery shows a higher uptake (SUVmax 1.7 vs. SUVmax 1.2 in the left common carotid artery) compared with the left common carotid artery, whereas the uptake in the two jugular veins is almost identical (right SUVmean 1.0 vs. left SUVmean 1.1), further indicating a specific arterial uptake of the PET tracer as well as a higher density of the α4β2-nAChRs in the right than in the left common carotid artery
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4504985&req=5

Fig1: α4β2-nAChR PET/CT scan showing [18F]-2-fluoro-A85380 uptake in the right and left common carotid arteries (upper ROIs green) and in the right and left jugular veins (lower ROIs). On a visual basis, the fused PET/CT image shows higher uptake of the tracer in the two common carotids compared with the two veins, indicating a specific tracer uptake in the arteries. Furthermore, the right common carotid artery shows a higher uptake (SUVmax 1.7 vs. SUVmax 1.2 in the left common carotid artery) compared with the left common carotid artery, whereas the uptake in the two jugular veins is almost identical (right SUVmean 1.0 vs. left SUVmean 1.1), further indicating a specific arterial uptake of the PET tracer as well as a higher density of the α4β2-nAChRs in the right than in the left common carotid artery
Mentions: In a second step, we evaluated the feasibility of the [18F]-2-fluoro-A85380 PET tracer for imaging non-neuronal vascular α4β2-nAChRs in the same study population of five healthy controls and six patients with Parkinson’s disease or MSA [57••]. Again, the aim was to determine whether this tracer could noninvasively image vascular α4β2-nAChRs in vivo in humans via PET and to investigate whether neurodegenerative disorders such as Parkinson’s disease and MSA might have an impact on the vascular distribution of these nAChRs. Because of the pathophysiologic importance of nAChRs in atherosclerosis, which was mentioned earlier, proving the ability to noninvasively detect nAChRs in humans is of crucial relevance for the diagnostic and subsequent therapeutic approach in patients with atherosclerosis. We therefore quantified [18F]-2-fluoro-A85380 uptake in the ascending and descending aorta, the aortic arch, and the carotids in our aforementioned study population as the maximum target-to-background ratio (Fig. 1). The maximal standardized uptake value (SUV), single hottest segment, and percentage of active segments of [18F]-2-fluoro-A85380 uptake in the arteries also were assessed. We could clearly visualize the [18F]-2-fluoro-A85380 uptake, and the maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly greater uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [18F]-2-fluoro-A85380 uptake in the patient group when single arterial territories were compared but not when all arterial territories were pooled together [57••]. Our results clearly suggest that [18F]-2-fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Furthermore, the vascular nAChR density appears lower in patients with Parkinson’s disease or MSA, indicating an impact of both neurodegenerative disorders on human arteries [57]. Currently, our group is carrying out studies in larger populations as well as in the experimental setting to further validate the approach of noninvasive in vivo imaging of vascular nAChRs, which will provide more detailed insights into the pathogenic role of nAChRs in the human vasculature [58].Fig. 1

Bottom Line: During the past years, non-neuronal vascular nicotinic acetylcholine receptors (nAChRs) increasingly have gained interest in cardiovascular research, as they are known to mediate the deleterious effects of nicotine and nitrosamines, components of tobacco smoke, on the vasculature.Accordingly, we briefly summarize the pathophysiologic role of vascular nAChRs in the atherosclerotic disease process.We also provide an overview of currently available nAChR positron emission tomography (PET) tracers and their performance in the noninvasive imaging of vascular nAChRs, as well as potential nAChR PET tracers that might be an option for vascular nAChR PET imaging in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.

ABSTRACT
During the past years, non-neuronal vascular nicotinic acetylcholine receptors (nAChRs) increasingly have gained interest in cardiovascular research, as they are known to mediate the deleterious effects of nicotine and nitrosamines, components of tobacco smoke, on the vasculature. Because smoking is a major risk factor for the development of atherosclerosis, it is obvious that understanding the pathophysiologic role of nAChRs in the atherosclerotic disease process, as well as in the development of new diagnostic and therapeutic nAChR-related options, has become more important. Accordingly, we briefly summarize the pathophysiologic role of vascular nAChRs in the atherosclerotic disease process. We also provide an overview of currently available nAChR positron emission tomography (PET) tracers and their performance in the noninvasive imaging of vascular nAChRs, as well as potential nAChR PET tracers that might be an option for vascular nAChR PET imaging in the future.

No MeSH data available.


Related in: MedlinePlus