Department of Nuclear Medicine/Radiology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Department of Nuclear Medicine/Radiology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands; School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
Methods. 2017 Nov 1;130:90-104. doi: 10.1016/j.ymeth.2017.06.008. Epub 2017 Jun 8.
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 F-fluorodeoxyglucose (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, 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.
动脉粥样硬化事件通常是急性的，经常袭击无症状的患者。尽管已经有多种临床危险因素与动脉粥样硬化相关，但迄今为止，基于生物标志物分析或 CT、MRI 或血管造影等传统成像方法，还不能进一步预测谁将遭受其后果。以前，使用 F-氟脱氧葡萄糖（F-FDG）PET 的非侵入性成像被证明有可能填补这一空白，因为它能够高度敏感地检测与动脉粥样硬化斑块炎症变化相关的代谢过程。然而，动脉血管的 F-FDG PET 成像存在非特异性，仍需证明能够可靠地识别易破裂的斑块，这些斑块破裂的风险很高。因此，它可能只能被视为监测治疗效果的次要标志物，并且不能提供替代的治疗选择或直接了解治疗机制。在这篇综述中，概述了炎症和血管生成在动脉粥样硬化中的 PET 成像的现状和潜力，特别强调了α7 烟碱型乙酰胆碱受体（α7 nAChR）的成像。由于我们对动脉粥样硬化形成的理解仍然存在差距，以及可用的 PET 示踪剂的局限性，因此仍在寻找更具特异性的放射性配体，能够区分稳定的动脉粥样硬化和易破裂的斑块。探索了α7 nAChR 作为斑块易损性成像标志物的潜在作用。今天，有强有力的证据表明 nAChRs 参与了动脉粥样硬化疾病过程。它们被认为介导了主要烟草成分尼古丁的有害作用，尼古丁是一种 nAChR 激动剂。主要基于体外数据，α7 nAChR 刺激可能通过增加新生血管化来增加斑块负担。然而，在动物研究中，α7 nAChR 处理似乎由于其对炎症细胞的抑制作用而减少斑块大小。因此，通过体内成像可靠地识别α7 nAChR 对于在人类环境中进行任何治疗方法之前，研究α7 nAChR 在动脉粥样硬化中的确切作用至关重要。在这篇综述中，我们讨论了使用α7 nAChR PET 示踪剂的初步经验，并讨论了关于成像血管 nAChR 的“最佳”PET 示踪剂的发展考虑因素。
