分子探针助于解决心血管显像尚未满足的临床需求(第1部分)：技术要点、心肌灌注和心脏神经显像

新型PET和SPECT显像剂的研发主要针对于未能满足的临床诊断需求, 这一需求体现了心血管医学中与分子表征和个性化治疗相关的全系统趋势。该文将分2部分讨论一些新型的放射性显像剂, 其可能有助于解决心血管医学核心领域中尚未解决的诊断方面的需求, 如心力衰竭、心律失常、瓣膜病、动脉粥样硬化和血栓。该文第1部分回顾了与心血管放射性显像剂研发相关的关键技术要点, 并综述了用于心肌灌注显像和心脏神经显像的新型放射性显像剂, 重点讨论了包括新型PET心肌灌注显像剂2-叔丁基-4-氯-5-[4-(2-氟-18F-乙氧基甲基)苯基甲氧基]-3(2H)-哒嗪酮(18F-flurpiridaz)、18F标记心脏神经显像剂(如18F-氟溴苯胍)等的研发;第2部分主要讨论了包括用于炎性反应、纤维化、血栓形成、钙化和心脏淀粉样变显像等的新型放射性显像剂。     

血池显像剂的标记方法及其比较

近十年来,心血管核医学迅速发展,新的血池显像剂不断出现,由过去的131I-标记人血清白蛋白(HSA)发展到99mTc标记红细胞(99mTc-RBC)。     

正电子核素心肌代谢显像剂的研究进展

心肌细胞利用葡萄糖、脂肪酸、乳酸及酮体等多种底物产生能量,以维持自身的正常舒缩功能。心肌细胞能量代谢的异常改变与多种心脏疾病相关,如心肌缺血和心力衰竭等。放射性核素显像作为一种无创性功能检查方法,能够用于心肌细胞代谢状况的评价。放射性核素心肌代谢显像剂是由放射性核素标记的心肌代谢底物及其类似物,在临床上分为氧代谢显像剂...     

用于心肌显像的放射性碘标记示踪剂

~(123)I标记的苯基脂肪酸、间碘苄胍在心肌显像中发挥了重要作用,前者可以作为局部心肌缺血定位和心肌代谢的探针,后者能用作肾上腺素能障碍和心脏功能的指示剂.本文介绍了这些药物的标记方法及其在心肌显像中的价值,并简要叙述了心肌内β-肾上腺素能受体显像剂心得静的应用前景.     

多肽的放射性标记

目前,放射性核素标记的多肽作为一类新型显像剂已越来越多应用于肿瘤、感染、血栓等的诊断和治疗。在该类显像剂的研制过程中,多肽的选择、修饰是基础,而放射标记技术则是关键。本从标记方法、双功能螯合剂和放射性核素3个方面进行阐述。     

心脏神经显像

正常心血管功能有赖于其完整的神经支配。心脏对机体在生理及病理状态下血流动力学需求的适应性，特别是心脏的节律、传导和收缩力等，多受心脏自主神经系统（ANS）调节。许多疾病时，心脏ANS改变可能发生于心脏出现明显结构和功能异常前，但以往对心脏ANS的在体评价主要局限于一些有创的检查方法。随着放射性示踪技术的发展，用SPECT或PET无创性评价心脏ANS功能、获取疾病状态下心脏ANS的病理生理信息已成为可能。心脏神经显像是通过SPECT或PET显像研究心脏ANS神经末梢、     

医用回旋加速器及正电子核素生产

PET(正电子发射体层)显像是利用解剖形态方式对体内各种生物化学过程如代谢和受体功能改变等进行评价和定量观测的核医学技术,PET的发展在一定程度上取决于正电子显像剂的研制与应用。PET所采用的正电子显像剂主要是用由回旋加速器生产的正电子核素-11C、13N、15I、18F等标记。因此,了解并掌握医用回旋加速器的基本组成和工作原理,选择适当的正电子核素及其标记前体,对正电子显像剂的常规生产和研究开发有重要的指导意义。主要介绍了回旋加速器的操作原理、医用回旋加速器的类型和正电子核素及其标记前体的生产。     

心脏肾上腺素能神经的PET应用

心脏肾上腺素能PET对于鉴别原发性和继发性心脏神经病,以及心肌病治疗效果评价均具有重要价值。主要介绍心脏肾上腺素能神经PET成像原理、所使用正电子显像剂、PET成像方法和临床应用,尤其对心脏。肾上腺素能神经正电子显像剂进展进行重点介绍。     

^18F-FLT PET显像原理及肿瘤显像研究进展

^18F-脱氧葡萄糖（FDG）PET显像被广泛应用于肿瘤的诊断与分期,但这种显像技术仍有不足之处,其诊断肿瘤的灵敏度高,特异性低,常受到生理性摄取、炎性反应、结节病等良性疾病的干扰,易出现假阳性,因此临床亟需一种肿瘤特异性更好的显像剂。无限制增殖是肿瘤细胞的特性,因而用正电子核素标记的核苷及其类似物成为一种极具潜力的肿瘤显像剂。     

心脏神经受体显像的实验及临床研究进展

论述了心脏神经受体显像的原理,实验研究及临床应用。在体外实验中,神经显像剂123I-MIBG可明显浓聚于正常心肌组织,心肌梗塞、心衰及心肌肥厚时其浓聚明显降低,且显示的缺损区大于201Tl心肌显像所显示的缺损区。受体显像剂131I-PIN亦可明显浓聚于正常心肌组织,并清晰显示心梗的范围。临床研究表明,123I-MIBG在正常心肌中浓聚均匀,心肌梗塞等去神经元的疾病时,病变区浓聚显著降低,受体显像相应区也呈缺损。心脑神经受体显像为引起心脏神经受体结构和功能改变的疾病诊断,提供了很有价值的信息。     

Cardiac autonomic innervation

The autonomic nervous system plays a key role in regulating changes in the cardiovascular system and its adaptation to various human body functions. The sympathetic arm of the autonomic nervous system is associated with the fight and flight response, while the parasympathetic division is responsible for the restorative effects on heart rate, blood pressure, and contractility. Disorders involving these two divisions can lead to, and are seen as, a manifestation of most common cardiovascular disorders. Over the last few decades, extensive research has been performed establishing imaging techniques to quantify the autonomic dysfunction associated with various cardiovascular disorders. Additionally, several techniques have been tested with variable success in modulating the cardiac autonomic nervous system as treatment for these disorders. In this review, we summarize basic anatomy, physiology, and pathophysiology of the cardiac autonomic nervous system including adrenergic receptors. We have also discussed several imaging modalities available to aid in diagnosis of cardiac autonomic dysfunction and autonomic modulation techniques, including pharmacologic and device-based therapies, that have been or are being tested currently.     

Assessment of cardiac sympathetic nerve integrity with positron emission tomography

The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation.     

123Ⅰ-间碘苄胍心脏神经显像的临床应用进展

心脏神经分布在心脏的功能中起决定性作用,很多心脏疾患常常会引起心脏自主神经功能的损害.123Ⅰ-间碘苄胍心脏神经显像是评定心脏自主神经功能的一种方法,它不仅可以评价各种心脏疾病状态下交感神经的损伤程度,决定是否植入机械装置、进行心脏移植或指导药物治疗等,而且可以在分子水平可视化及定量分析心肌的基本病变.     

Assessment of cardiac sympathetic neuronal function using PET imaging

The autonomic nervous system plays a key role for regulation of cardiac performance, and the importance of alterations of innervation in the pathophysiology of various heart diseases has been increasingly emphasized. Nuclear imaging techniques have been established that allow for global and regional investigation of the myocardial nervous system. The guanethidine analog iodine 123 metaiodobenzylguanidine (MIBG) has been introduced for scintigraphic mapping of presynaptic sympathetic innervation and is available today for imaging on a broad clinical basis. Not much later than MIBG, positron emission tomography (PET) has also been established for characterizing the cardiac autonomic nervous system. Although PET is methodologically demanding and less widely available, it provides substantial advantages. High spatial and temporal resolution along with routinely available attenuation correction allows for detailed definition of tracer kinetics and makes noninvasive absolute quantification a reality. Furthermore, a series of different radiolabeled catecholamines, catecholamine analogs, and receptor ligands are available. Those are often more physiologic than MIBG and well understood with regard to their tracer physiologic properties. PET imaging of sympathetic neuronal function has been successfully applied to gain mechanistic insights into myocardial biology and pathology. Available tracers allow dissection of processes of presynaptic and postsynaptic innervation contributing to cardiovascular disease. This review summarizes characteristics of currently available PET tracers for cardiac neuroimaging along with the major findings derived from their application in health and disease.     

Imaging of metabolism and autonomic innervation of the heart by positron emission tomography.

Positron emission tomography (PET) allows, in combination with multiple radiopharmaceuticals, unique physiological and biochemical tissue characterization. Tracers of blood flow, metabolism and neuronal function have been employed with this technique for research application. More recently, PET has emerged in cardiology as a useful tool for the detection of coronary artery disease and the evaluation of tissue viability. Metabolic tracers such as fluorine-18 deoxyglucose (FDG) permit the specific delineation of ischaemically compromised myocardium. Clinical studies have indicated that the metabolic imaging is helpful in selecting patients for coronary artery bypass surgery or coronary angioplasty. More recent research work has concentrated on the use of carbon-11 acetate as a marker of myocardial oxygen consumption. Together with measurements of left ventricular performance, estimates of cardiac efficiency can be derived from dynamic 11C-acetate studies. The non-invasive evaluation of the autonomic nervous system of the heart was limited in the past. With the introduction of radiopharmaceuticals which specifically bind to neuronal structures, the regional integrity of the autonomic nervous system of the heart can be evaluated with PET. Numerous tracers for pre- and postsynaptic binding sites have been synthesized. 11C-hydroxyephedrine represents a new catecholamine analogue which is stored in cardiac presynaptic sympathetic nerve terminals. Initial clinical studies with it suggest a promising role for PET in the study of the sympathetic nervous system in various cardiac diseases such as cardiomyopathy, ischaemic heart disease and diabetes mellitus. The specificity of the radio-pharmaceuticals and the quantitative measurements of tissue tracer distribution provided by PET make this technology a very attractive research tool in the cardiovascular sciences with great promise in the area of cardiac metabolism and neurocardiology.     

Cardiac neurotransmission spect imaging

The sympathetic nervous system has great influence on cardiovascular physiology. Cardiac neurotransmission single photon emission computed tomography (SPECT) imaging allows in vivo noninvasive assessment of presynaptic reuptake and storage of neurotransmitters, which offers characterization of the cardiac neuronal function in different diseases of the heart and other altered metabolic or functional conditions. Therefore assessment of the integrity of cardiac sympathetic innervation may help in the diagnosis of these disorders, as well as in prognostication, and will result in better therapy and outcome. At present, the most widely available SPECT tracer by which to assess cardiac neurotransmission is metaiodobenzylguanidine labeled with iodine 123. This article focuses on reviewing the characteristics of cardiac SPECT imaging with I-123 metaiodobenzylguanidine and its role in the assessment of pathophysiologic changes during relevant clinical conditions.     

Cardiac neuronal imaging: Application in the evaluation of cardiac disease

Conclusion  The sympathetic nervous system plays an important role in cardiovascular physiology. Both SPECT with MIBG and PET can be used to visualize the sympathetic innervation of the heart and the abnormalities in innervation caused by, for example, ischemia, heart failure, and arrhythmogenic disorders. Furthermore, cardiac neuronal imaging allows early detection of autonomic neuropathy in diabetes mellitus. Although SPECT imaging is widely available and technically less demanding than PET, the latter has important advantages. PET can be used to achieve high spatial and temporal resolution, as well as absolute quantification, in a noninvasive manner. It also can provide a wide range of different radiolabeled catecholamines, catecholamine analogs, and receptor ligands. It should be noted, however, that most experience has been obtained with SPECT and MIBG. Assessment of sympathetic nerve activity in patients with heart failure has been shown to provide important prognostic information, and cardiac neuronal imaging can potentially identify patients who are at increased risk of sudden death. Moreover, therapeutic effects of different treatment strategies can be evaluated by MIBG SPECT as well as by PET imaging. To establish the clinical utility of cardiac neuronal imaging, it will be necessary to determine the incremental value of innervation imaging to triage heart failure patients to medical therapy, CRT (with or without ICD), or heart transplantation.     

Cardiac sympathetic neuronal imaging using PET

INTRODUCTION: Balance of the autonomic nervous system is essential for adequate cardiac performance, and alterations seem to play a key role in the development and progression of various cardiac diseases. PET AS AN IMAGING TOOL: PET imaging of the cardiac autonomic nervous system has advanced extensively in recent years, and multiple pre- and postsynaptic tracers have been introduced. The high spatial and temporal resolution of PET enables noninvasive quantification of neurophysiologic processes at the tissue level. Ligands for catecholamine receptors, along with radiolabeled catecholamines and catecholamine analogs, have been applied to determine involvement of sympathetic dysinnervation at different stages of heart diseases such as ischemia, heart failure, and arrhythmia. REVIEW: This review summarizes the recent findings in neurocardiological PET imaging. Experimental studies with several radioligands and clinical findings in cardiac dysautonomias are discussed.     

Cardiac autonomic neuropathy in the diabetic patient: does 123I-MIBG imaging have a role to play in early diagnosis?

OBJECTIVES: In diabetes, extended adrenergic receptor stimulation with hyperglycemia and insulin deficiency is associated with cardiac autonomic dysfunction. Clinically evident diabetic cardiac autonomic neuropathy (CAN) is associated with a poor prognosis. Research studies indicate that autonomic function tests, which are traditionally used to diagnose diabetic CAN, are less sensitive than (123)I-metaiodobenzylguanidine (MIBG) imaging, particularly in the early stages of the disease. This established imaging technique makes use of the noradrenaline analog MIBG, which is radiolabeled with (123)I to assess the noradrenaline uptake-1 mechanism of the sympathetic nervous system. Although scintigraphic studies indicate that long-standing cardiac autonomic dysfunction is permanent, some authors have shown partial reversibility with early metabolic intervention. (123)I-MIBG imaging could therefore have an important clinical role to play in the early diagnosis and treatment monitoring of diabetic CAN. METHODS: A PubMed/MEDLINE Internet search was performed using MIBG, diabetes, and cardiac autonomic neuropathy as key words. CONCLUSION: The general expense of (123)I-MIBG imaging, together with the lack of commercial availability of this radiopharmaceutical in the United States, has limited the clinical use of this technique. As such, the clinical role of (123)I-MIBG imaging in the early diagnosis of diabetic CAN has yet to be validated and defined in most regions of the world, and further study is required.     

Tissue-specific MR contrast agents

The purpose of this review is to outline recent trends in contrast agent development for magnetic resonance imaging. Up to now, small molecular weight gadolinium chelates are the workhorse in contrast enhanced MRI. These first generation MR contrast agents distribute into the intravascular and interstitial space, thus allowing the evaluation of physiological parameters, such as the status or existence of the blood-brain-barrier or the renal function. Shortly after the first clinical use of paramagnetic metallochelates in 1983, compounds were suggested for liver imaging and enhancing a cardiac infarct. Meanwhile, liver specific contrast agents based on gadolinium, manganese or iron become reality. Dedicated blood pool agents will be available within the next years. These gadolinium or iron agents will be beneficial for longer lasting MRA procedures, such as cardiac imaging. Contrast enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Metastatic involvement will be seen either after the injection of ultrasmall superparamagnetic iron oxides or dedicated gadolinium chelates. The accumulation of both compound classes is triggered by an uptake into macrophages. It is likely that similar agents will augment MRI of atheriosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on small gadolinium labeled peptides are on the horizon. It is very obvious that the future of cardiovascular MRI will benefit from the development of new paramagnetic and superparamagnetic substances. The expectations for new tumor-, pathology- or receptor-specific agents are high. However, is not likely that such a compound will be available for daily routine MRI within the next decade.