Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
JACC Cardiovasc Imaging. 2012 May;5(5):528-36. doi: 10.1016/j.jcmg.2011.11.024.
The aim of this feasibility study was to evaluate [(18)F]-2-Fluoro-A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs) in humans. Furthermore, potentially different vascular uptake patterns of this new tracer were evaluated in healthy volunteers and in patients with neurodegenerative disorders.
[(18)F]-2-Fluoro-A85380 was developed for in vivo positron emission tomography (PET) imaging of nAChR subunits in the human brain. These nAChRs are also found in arteries and seem to mediate the deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It has been previously shown that uptake patterns of the radiotracer in the brain differs in patients with neurodegenerative disorders compared with healthy controls.
[(18)F]-2-Fluoro-A85380 uptake was quantified in the ascending and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers and in 6 patients with either Parkinson's disease or multiple system atrophy, respectively, as the maximum target-to-background ratio. The maximal standardized uptake value values, the single hottest segment, and the percent active segments of the [(18)F]-2-Fluoro-A85380 uptake in the arteries were also assessed.
[(18)F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly higher uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [(18)F]-2-Fluoro-A85380 uptake in the patient group when comparing single arterial territories but not when all arterial territories were pooled together.
[(18)F]-2-Fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Vascular nAChR density seems to be lower in patients with Parkinson's disease or multiple system atrophy. Once confirmed in larger study populations and in the experimental setting, this approach might provide insights into the pathogenic role of nAChRs in the human vasculature.
本可行性研究旨在评估 [(18)F]-2-氟-A85380 在人体动脉烟碱型乙酰胆碱受体 (nAChR) 体内成像中的应用。此外，还评估了这种新型示踪剂在健康志愿者和神经退行性疾病患者中的潜在不同血管摄取模式。
[(18)F]-2-氟-A85380 是为了在人体大脑中的 nAChR 亚单位的体内正电子发射断层扫描 (PET) 成像而开发的。这些 nAChR 也存在于动脉中，并且似乎介导了尼古丁作为烟草烟雾的一部分在血管中的有害作用。先前已经表明，与健康对照相比，患有神经退行性疾病的患者的放射性示踪剂摄取模式存在差异。
在 5 名健康志愿者和 6 名帕金森病或多系统萎缩患者中，分别对升主动脉、降主动脉、主动脉弓和颈动脉中的 [(18)F]-2-氟-A85380 摄取进行了定量，取最大目标与背景的比值。还评估了动脉中 [(18)F]-2-氟-A85380 摄取的最大标准化摄取值、单个最热段和活跃段的百分比。
[(18)F]-2-氟-A85380 的摄取清晰可见，并且对示踪剂背景活性进行校正后的最大目标与背景的比值摄取值显示出动脉壁中存在特定的示踪剂摄取。降主动脉中的摄取值明显更高。志愿者和患者之间的比较显示出显著差异，与健康志愿者相比，患者组的 [(18)F]-2-氟-A85380 摄取较低，但当将所有动脉区域合并在一起时，差异并不显著。
[(18)F]-2-氟-A85380 可以提供有关人类动脉中 nAChR 分布的特定信息。在帕金森病或多系统萎缩患者中，血管 nAChR 密度似乎较低。一旦在更大的研究人群和实验环境中得到证实，这种方法可能会深入了解 nAChR 在人类血管中的致病作用。
