99Tcm N核类心肌灌注显像剂的研究进展

放射性核素MPI是无创性诊断冠心病的重要手段.目前临床使用的201 Tl、99 Tcm标记的心肌灌注显像剂均存在一定的局限性.99TcmN核化学稳定性较高,使用已知配体与99TcmN核结合已成为制备新型心肌灌注显像剂的一条重要途径.笔者对以99TcmN核类新型心肌灌注显像剂的结构、生物学分布特性及显像特点进行总结,并介绍几种应用前景比较好的99TcmN核类心肌灌注显像剂.     

心肌细胞葡萄糖转运蛋白4的转运调控及与心肌活力关系的研究进展

葡萄糖是心肌能量代谢的主要底物之一,在心肌缺血时是心肌的主要能量来源。葡萄糖通过细胞膜进入细胞内是心肌细胞葡萄糖代谢的第一步,也是心肌细胞利用葡萄糖的主要限速步骤。葡萄糖是依靠细胞膜上的葡萄糖转运蛋白（GLUTs）而进入细胞内的,GLUT4是心肌细胞主要的葡萄糖转运载体。GLUT4的质和量对心肌葡萄糖的跨膜转运起着决定性作用。因此,明确心肌葡萄糖转运及心肌细胞GLUT4的基因表达调控机制、转位调控机制、内在活性调控机制,对临床诊断心肌能量代谢性疾病具有重要意义。该文对近年来有关心肌葡萄糖转运及GLUT4调控方面的研究进行综述。     

心肌代谢显像的进展及其临床应用

过去的十年,心肌代谢显像出现了飞速的发展,心肌的脂肪酸显像及201Tl的临床应用、γ照相机及SPECT的日益普及,推动了这一发展的进程;99mTc标记心肌显像剂的探索,PECT的改进及正电子核素发生器的研制,使具有良好的理化性质和生物学特性的心肌代谢显像剂出现及定量研究心肌代谢、血流及功能有了可能;而磁共振成像(MRI)的试用,从细胞分子水平上,揭示了心肌代谢的生理生化机制,将心肌代谢研究提高到新的水平。     

心脏显像剂的现状及进展

对心脏显像剂在心血池显像,心肌灌注显像、心肌代谢显像中的应用现状和进展作了综述,并介绍了分子核心脏病学显像中的展望。认为深入开展心脏显像剂的开发和利用对核心脏病学的研究具有重要意义。     

吸入液氧对高原人体力竭运动后心肌酶活性的影响

心肌细胞含有多种酶类,参与许多重要的生理及代谢过程,心血管系统是高原低氧环境下受影响较大的系统之一。心肌酶活性水平的变化,可反映低氧对心肌酶代谢的影响,同时也反映心肌细胞破坏或细胞膜通透性改变。本文采用递增负荷运动方法,观察吸人液态氧对海拔3700m高原健康青年力竭运动心肌酶活性的影响。     

SPECT扫描显像剂注射方法改进

SPECT(singie photon emission computed tmmgraphy)即单光子发射型计算机断层扫描，其显像原理是被放射性核素标记的药物(即显像剂)引入体内后，药物据其代谢和生物学特征特异地分布于体内的特定器官和病变组织，放射性核素衰变放出的射线在体外被探测处理而成像。此显像反映的是放射性药物在体内的分布。因此放射性药物(即显像剂)的质量控制对图像质量影响较大，     

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。     

胶质瘤显像剂的研究与应用进展

核医学显像在胶质瘤的诊断、分级及预后等方面有重要的临床价值,随着核医学的发展,用于胶质瘤的显像剂也越来越多样化,目前研究应用较多的SPECT显像剂有201Tl、99Tcm-MIBI、123I-碘代甲基酪氨酸以及新型受体类显像剂131I-蝎氯毒素等,PET显像剂主要有葡萄糖代谢显像剂、氨基酸代谢显像剂、胆碱代谢显像剂、核...     

99mTc-TBI、CPI及MIBI的实验及临床研究进展

心肌灌注显像剂的研制对核心脏病学的发展具有重要作用。本文介绍了三种异腈类显像剂的实验及临床研究进展,三者结构的不同决定了其生物学特性的差异。在培养心肌细胞、整体动物及人体的研究表明,TBI肺浓聚早且量多,心肌浓聚少,不适合临床应用CPI心肌浓聚较多,但肺浓聚仍高,且不能制成稳定药盒,也不适合临床应用MIBI具有较多的心肌浓聚且肺浓聚少清除快,其理化及生物学特性优良,有较大的临床应用价值。     

正电子放射性显像剂代谢及其研究方法进展

正电子放射性显像剂主要用于PET的研究,能在分子水平上反映细胞代谢、细胞受体活性、细胞核内的核酸合成以及细胞基因的改变,在临床疾病诊断和治疗中有重要的地位和作用.PET显像剂进入生物体内后会发生代谢转化,了解PET显像剂的代谢途径和转化过程,对于准确分析和解释显像结果及设计开发新型PET显像剂非常重要.该文总结了目前PET显像剂代谢研究的现状,并对PET显像剂代谢研究方法以及分析技术等进行了综述.     

Cardiac fatty acid metabolism and ischemic memory imaging with nuclear medicine techniques

There has been a dramatic improvement in the clinical management of myocardial diseases with the advent of cardiac metabolic and molecular imaging. Although both myocardial perfusion and metabolic imaging provide insight of myocardium at risk for infarction or ischemia, it is known that metabolic derangements precede perfusion abnormalities, especially after reperfusion therapy. Deranged myocyte loses its flexibility of choosing the right substrate for energy production and it switches its substrate, especially between fatty acid (FA) and glucose depending on disease condition; for example, predominance of FA metabolism is noted in diabetic heart disease, whereas glucose metabolism is enhanced in pressure overload conditions such as left ventricular hypertrophy. We thus hypothesize that with better technological advancements and different substrates, the metabolic footprint of various heart diseases can be charted out in future to help in the optimization of patient management. This review attempts to discuss the importance of radionuclide-labeled FAs in cardiac metabolic and ischemic memory imaging.     

Assessment of cardiac function and myocardial metabolism by nuclear medicine]

Simultaneous assessment of myocardial perfusion and cardiac function came to be possible by 99mTc myocardial perfusion agents. We can use ECG-gated SPECT and first pass radionuclide angiocardiography for it. ECG-gated SPECT made it possible to assess wall motion using wall thickening and QGS (quantitative gated SPECT) analysis, which are useful in various clinical situations. First pass radionuclide angiocardiography gives good assessment of cardiac function during stress, and supports the diagnosis of myocardial ischemia. On the other hand, the assessment of myocardial metabolism is another specific feature of nuclear cardiology. 123I-BMIPP SPECT is applicable to various cardiac diseases such as ischemic heart disease, and 18F-FDG PET has been considered as the gold standard of myocardial viability. Recently, gamma camera for 18F-FDG imaging has been developed, which may make FDG imaging more popular.     

Myocardial imaging with radiolabeled free fatty acids: Applications and limitations

The assessment of myocardial fatty acid metabolism using radiolabeled substrates has recently become a new diagnostic modality in noninvasive cardiology. The development of metabolic tracers has been made possible largely due to a combined increase in the understanding of myocardial biochemistry and in nuclear-medicine technology. Initially, imaging and the exploration of myocardial metabolism appeared to be the exclusive domain of positron-emission tomography. However, investigators have been successful in applying radioiodine-labeled fatty acids that can be monitored using conventional gamma cameras. These metabolic substrates can be used not only for imaging purposes, but also for the evaluation of regional metabolic clearance rates, which may serve as a parameter for myocardial fatty acid metabolism. Although the initial results have been promising, the analysis and interpretation of clearance curves appears to be rather complicated and may produce a lot of unanswered questions. A great deal remains to be done due to the complex biological behavior of the tracers employed and the difficulties encountered in quantitatively delineating the distribution of radioactivity in the beating heart in vivo. Therefore, closer integration of myocardial biochemistry and the metabolic imaging technique seems to be necessary for enhancing our knowledge of myocardial fatty acid metabolism and to make metabolic imaging clinically useful.

     

An evaluation of myocardial fatty acid and glucose uptake using PET with [18F]fluoro-6-thia-heptadecanoic acid and [18F]FDG in Patients with Congestive Heart Failure.

Understanding the metabolic consequences of heart failure is important in evaluating potential mechanisms for disease progression and assessing targets for therapies designed to improve myocardial metabolism in patients with heart failure. PET is uniquely suited to noninvasively evaluate myocardial metabolism. In this study, we investigated the kinetics of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) and [18F]FDG in patients with stable New York Heart Association functional class III congestive heart failure and a left ventricular ejection fraction of no more than 35%. METHODS: Twelve fasting patients underwent dynamic PET studies using [18F]FTHA and FDG. From the dynamic image data, the fractional uptake rates (Ki) were determined for [18F]FTHA and FDG. Subsequently, serum free fatty acid and glucose concentrations were used to calculate the myocardial free fatty acid and glucose uptake rates, respectively. Uptake rates were compared with reported values for [18F]FTHA and FDG in subjects with normal left ventricular function. RESULTS: The average Ki for [18F]FTHA was 19.7 +/- 9.3 mL/100 g/min (range, 7.2-36.0 ml/100 g/min). The average myocardial fatty acid use was 19.3 +/- 2.3 mmol/100 g/min. The average Ki for FDG was 1.5 +/- 0.37 mL/100 g/min (range, 0.1-3.3 mL/100 g/min), and the average myocardial glucose use was 12.3 +/- 2.3 mmol/100 g/min. CONCLUSION: Myocardial free fatty acid and glucose use in heart failure can be quantitatively assessed using PET with [18F]FTHA and FDG. Myocardial fatty acid uptake rates in heart failure are higher than expected for the normal heart, whereas myocardial glucose uptake rates are lower. This shift in myocardial substrate use may be an indication of impaired energy efficiency in the failing heart, providing a target for therapies directed at improving myocardial energy efficiency.     

Creatine depletion and altered fatty acid metabolism in diseased human hearts: clinical investigation using 1H magnetic resonance spectroscopy and 123I BMIPP myocardial scintigraphy

BACKGROUND: In the heart, the creatine kinase system plays an important role in energy reserves, and myocardial energy production essentially depends upon fatty acid metabolism. PURPOSE: To examine myocardial creatine (CR) concentration and altered cardiac fatty acid metabolism in various forms of heart disease. MATERIAL AND METHODS: Myocardial CR concentration of the septum was measured by gated 1H magnetic resonance spectroscopy (MRS), applying a point-resolved spectroscopy (PRESS) sequence in 34 patients with heart disease. Of these patients, 14 underwent 123I BMIPP (radioactive fatty acid analogue) myocardial scintigraphy to evaluate myocardial fatty acid metabolism. Cardiac 123I BMIPP uptake was calculated as the heart-to-mediastinum count ratio. RESULTS: Myocardial CR concentration correlated positively with the left ventricular ejection fraction (LVEF) by echocardiography (R = 0.61, P<0.001, n = 34), suggesting that the degree of reduced CR is related to the severity of contractile dysfunction. Cardiac 123I BMIPP uptake also correlated positively with LVEF (initial image, R = 0.60, P<0.05; delayed image, R = 0.63, P<0.05; n = 14). There was a significant correlation between myocardial CR and cardiac 123I BMIPP uptake (initial image, R = 0.77, P<0.01; delayed image, R = 0.82, P<0.001; n = 14). CONCLUSION: Our study suggests an association between CR depletion and impaired fatty acid metabolism in various forms of heart diseases.     

Radionuclide assessment of myocardial fatty acid metabolism by PET and SPECT

Although fatty acid is a major energy source in the normal myocardium, fatty acid oxidation is easily suppressed in a variety of cardiac disorders. Therefore assessment of fatty acid metabolism may hold an important role for early detection of myocardial abnormalities and provide insights into cardiac pathologic states. C-11 palmitate is a well-established PET tracer to probe myocardial fatty acid metabolism. On the other hand, a variety of iodinated fatty acid compounds have been introduced for assessment of fatty acid metabolism with conventional gamma cameras. These include straight-chain, such as iodopheyl pentadecanoic acid (IPPA), and branch-chain fatty acid compounds, such as beta-methyl iodopheyl pentadecanoic acid (BMIPP). This review article includes the characterization of these tracers and clinical experiences with these tracers for detection and characterizing patients with ischemic heart disease and cardiomyopathy.     

Phase 3 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating fatty acid metabolism--a multi-center trial]

A multi-center trial of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP) was performed to assess its clinical usefulness in the evaluation of myocardial fatty acid metabolism in 587 patients with various heart diseases. 123I-BMIPP showed relatively decreased uptake compared with 201Tl in the myocardial lesions of 62% of patients with ischemic heart disease (IHD), 39% of those with cardiomyopathy and 32% of those with other heart diseases. In case of myocardial infarction, less uptake of 123I-BMIPP (Type B) than 201Tl was more frequently seen in patients with successful recanalization than in those without recanalization. The patients with matched distribution of the two tracers (Type E) increased in the direct proportion to the interval between the onset of myocardial infarction and the radionuclide studies. The uptake of 123I-BMIPP correlated well with myocardial viability evaluated by 201Tl exercise-redistribution studies. Type B was frequently seen in the areas with 201Tl redistribution, while Type E was seen in the fixed defect areas. In the other heart diseases studied, Type E was observed in approximately 60% of patients with dilated or secondary cardiomyopathies. Type B was seen in about 45% of patients with valvular heart diseases and myocarditis. Various types of mismatch between the two tracers were demonstrated in hypertrophic cardiomyopathy and hypertensive heart disease. It is concluded that 123I-BMIPP is a safe and useful agent for the diagnosis of various heart diseases, since it reflects myocardial fatty acid metabolism.     

Studies of cardiac metabolism with 123I-labelled fatty acids and 11C-methylglucose (author's transl)

To characterize externally detectable changes in the myocardial metabolism of free fatty acids (FFA) and glucose, which are associated with ischemia and cardiomyopathy, omega-123I-heptadecanoic acid (stearic acid analogue), 75Br-phenylpentadecanoic acid, and 3-0-11C-methyl-D-glucose were used as indicators. It could be demonstrated that in the metabolism of free fatty acids at least two different patho-physiological situations may exist. Disturbances in the mechanism of the accumulation of free fatty acids lead to a decrease of the amount of the free fatty acids which are available for energy production (these disturbances can be recognized as indicator accumulation defects). Disturbances associated with the mechanism of free fatty acid catabolism lead to a decrease of the ability of the myocardial cell to utilize the free fatty acids (these disturbances can be recognized as changes in indicator elimination rates). Whereas in ischaemic heart disease, the areas with altered FFA accumulation correlate with the areas of altered FFA-elimination, no correlation was found in the case of cardiomyopathy. The 11C-methylglucose seems to be an excellent indicator for the in-vivo assessment of the function of transport system in the myocardial cell membrane.     

Phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating myocardial fatty acid metabolism]

A phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), a myocardial imaging agent developed for evaluating myocardial fatty acid metabolism, was performed in 197 patients with various heart diseases. The myocardial distribution of 123I-BMIPP did not change from early to late images in 88% of 91 patients with ischemic heart disease (IHD), while washout and/or fill-in were observed in 45% of 55 patients with hypertrophic cardiomyopathy (HCM). In comparison with 201Tl in 165 patients with various heart diseases, the decrease in uptake was more profound with BMIPP in 56% and with 201Tl in only 4%. 123I-BMIPP showed more severely decreased uptake in 83% of the patients with subacute myocardial infarction (15 to 30 days after the onset) and in 73% of the patients with HCM. High-quality SPECT images were obtained with 123I-BMIPP in 93% of 194 patients analyzed. However, the image quality in cardiomyopathy was inferior to that in IHD. The optimal injection dose range and standard dose of 123I-BMIPP were considered to be 74-148 MBq and 111 MBq, respectively. These findings suggest that 123I-BMIPP myocardial imaging is safe and useful for evaluating myocardial fatty acid metabolism in various heart diseases.     

Radiopharmaceuticals for cardiac imaging

A number of new radiopharmaceuticals have been developed to increase the diagnostic utility of nuclear medicine in cardiac diseases. The radiochemistry and dosimetry of and clinical experience with these new agents are summarized, and are compared with more widely used methods for assessing myocardial perfusion (thallium-201 scintigraphy) and ventricular function (technetium-99m radioangiography). Emerging techniques for the evaluation of myocardial necrosis and metabolism are also presented, with emphasis on the use of radiolabeled antimyosin antibody and fatty acid analogue imaging in ischemic heart disease.