两种交换柱分离~(18)F阴离子的效果比较

目前,以^18F-FDG为代表的正电子类放射性药物被广泛应用于PET／CT的检查中。医用回旋加速器生产的常用正电子类放射性核素^18F在临床应用具有最佳性能价格比,特别是因一次合成可以多次使用并且能够为周围PET／CT提供正电子类放射性药物等优点而受到广泛关注。提高正电子类放射性药物的放化产率已经成为全球正电子类放射性药物研究的热点和方向。     

^18F标记肿瘤显像剂的研究进展

为提高正电子发射断层影像术的临床诊断价值,近10余年来作为肿瘤显像剂的18F标记的各类放射性药物发展很快,本文对其研究现状进行小结,重点介绍应用潜力大的高选择性放射性药物.     

参加IAEA关于正电子放射性药品会议后的思考

目的为加强我国正电子放射性药品的监督管理提供参考。方法简要介绍了国际原子能机构于2008年3月在泰国曼谷举行的＂建立回旋加速器放射性药物生产设施和实施GMP的主题会议＂有关情况。结果与结论通过参加这次国际会议,认识到我国医疗机构制备正电子放射性药品管理上的不足,并提出了相关建议以加强正电子放射性药品的管理。     

探讨氟[(18)~F]脱氧葡糖注射液的稳定性

氟[18F]脱氧葡糖注射液是通过利用放射性核素标记的葡萄糖类似物,是正电子类放射性药物的代表,是目前临床最常用的糖代谢显像剂,在肿瘤分期,寻找肿瘤原发灶和疗效观察方面发挥着重要作用。氟[18F]脱氧葡糖注射液其物理半衰期比较短,因此一般于临用前由医疗机构自行制备和合成。由于正电子类放射性药物的特殊性,临床使用前不可能     

如何保证正电子类放射性药品的质量

正电子类放射性药品系指含有发射正电子的放射性核素的药品.鉴于18F的半衰期稍长,目前广泛用于临床的为含18F的放射性药品,且18F-FDG应用最为广泛.由于正电子类放射性药品的特点,临床使用前不可能对每批正电子类放射性药品进行全项检验,所以必须在生产过程中保证正电子类放射性药品的质量,确保用药安全有效.     

正电子类放射性药品质量控制指导原则

正电子类放射性药品系指含有发射正电子的放射性核素的药品。它一般由医疗机构或者正电子类放射性药品生产企业于临床使用前制备。发射正电子的放射性核素主要有两种来源：通过回旋加速器制备和发生器制备。本指导原则仅适用于回旋加速器制备的正电子类放射性药品的质量控制。发生器制备的正电子类放射性药品，参照《锝[^99mTc]放射性药品质量控制指导原则》进行质量控制。     

关于我国正电子放射性药品新药注册管理的建议

目前国际上已经有数十种正电子显像剂,而只有一种氟标记的正电子放射性药品氟脱氧葡萄糖F18(18F-FDG)已经获得国家注册批准,这大大的限制了正电子放射性药品在中国的发展。本文针对我国正电子放射性药品的注册管理现状,尝试提出科学、合理、规范的正电子放射性药品注册管理的法规建议。     

减少分装正电子药物过程中的辐射危害简易的分装装置

随着全国范围内PET或PET-CT中心逐年递增,越来越多的PET-CT中心（PET中心）配备了医用回旋加速器以及一种或者多种正电子药物自动合成模块,有的中心负责自身和周边医院正电子药物的供应,分装正电子药物成为这些配有医用回旋加速器每日必须的工作内容,本文主要介绍一种简单的分装正电子药物的一种装置,目的用来尽可能的减少操作者在分装过程中放射性辐射带来的伤害。     

正电子药物生产及使用中的辐射防护

PET是正电子发射断层显像，主要是利用放射性示踪剂原理显示活体生物活动的医学影像技术，可探测机体的代谢情况。PET／CT是在PET和CT基础上发展起来的当今世界上最先进的医疗影像设备，具有PET的定性功能，同时又有CT的定位功能。随着近几年国内PET、PET／CT的应用越来越多，正电子放射性药物也备受关注，特别是其生产和使用过程中的辐射问题。     

国家食品药品监督管理局关于《医疗机构制备正电子类放射性药品管理规定》

<正> 根据《中华人民共和国药品管理法》、《大型医疗设备配置与使用管理办法》、《放射性药品管理办法》的有关规定,为规范医疗机构正电子类放射性药品的制备和使用,2006年1月5日,国家食品药品监督管理局印发了《医疗机构制备正电子类放射性药品管理规定》,同时要求各医疗机构应严格执行《医疗机构制备正电子类放射性药品管理规定》,自2006年3月1日起,医疗机构凡未按该规定向所在地省、自治区、直辖市药品监督管理部门备案的,不得制备正电子类放射性药品。《规定》中明确规定,医疗机构配置 PET-CT 或 PET 设备,应当持有卫生行政主管部门的配置与使用许可证明文件;医疗机构使用正电子类放射性药品应当持有第Ⅱ类以上(含第Ⅱ类)《放射性药品使用许可证》,医疗机构制备正电子类放射性药品应当持有第Ⅲ类以上(含第Ⅲ     

Functional imaging in drug discovery and development. 30 September-1 October 1999, Paris, France

Functional diagnostic imaging techniques, including planar radioscintography, single photon emission tomography, positron emission tomography and computed magnetic resonance imaging, are universally-accepted procedures in medical diagnosis. This symposium focused on the evolving role of these techniques in the discovery and development of new drugs for human use. The relationships between academic/clinical imaging units and the pharmaceutical industry, were examined and assessed in terms of current drug development collaborations. The status of imaging data in new drug submission files and clinical trial files was used as a basis to develop paradigms to facilitate broad-based acceptance of imaging data by the industry and regulatory agencies.     

基于突触囊泡蛋白2A成像的正电子发射断层显像剂的合成及临床研究进展

神经突触异常与多种神经精神疾病有关，包括癫痫、阿尔茨海默病和精神分裂症等。神经突触囊泡蛋白2A（synaptic vesicle protein 2A，SV2A）在中枢神经系统的神经元中广泛表达，由于靶向SV2A的药物在神经退行性疾病和精神疾病中的潜在价值，研究人员对使用靶向SV2A的正电子发射断层扫描显像剂表现出越来越多的关注。在过去的十年中，已经开发了几种SV2A的正电子发射断层显像剂，以实现体内突触的可视化和定量。研究人员使用C-11或F-18对药物进行放射性标记，然后注入啮齿动物和非人类灵长类动物体内进行临床前研究，应用不同的动力学建模方法对药物进入体内效果进行定量分析。本文综述了这些正电子发射断层扫描显像剂的放射合成方法，并通过聚焦其放射化学特性介绍它们的前景和局限性，以及临床前概念验证和目前进行的主要临床研究。     

Radionuclide imaging technologies and their use in evaluating asthma drug deposition in the lungs

Whole lung and regional lung deposition of inhaled asthma drugs in the lungs can be quantified using either two-dimensional or three-dimensional radionuclide imaging methods. The two-dimensional method of gamma scintigraphy has been the most widely used, and is currently considered the industry standard, but the three-dimensional methods (SPECT, single photon emission computed tomography; and PET, positron emission tomography) give superior regional lung deposition data and will undoubtedly be used more frequently in future. Recent developments in radionuclide imaging are described, including an improved algorithm for assessing regional lung deposition in gamma scintigraphy, and a patent-protected radiolabelling method (TechneCoat), applicable to both gamma scintigraphy and SPECT. Radionuclide imaging data on new inhaled asthma products provide a milestone assessment, and the data form a bridge between in vitro testing and a full clinical trials program, allowing the latter to be entered with increased confidence.     

PET imaging in clinical drug abuse research

Over the last two decades, SPECT (single photon emission computed tomography) and especially PET (positron emission tomography) have proven increasingly effective imaging modalities in the study of human psychopharmacology. Abusing populations can be studied at multiple times after abstinence begins, to give information about neurochemical and physiological adaptations of the brain during recovery from addiction. Individual human subjects can be studied using multiple positron labeled radiotracers, so as to probe more than one facet of brain function. PET and SPECT have been used to help our understanding of many aspects of the pharmacokinetics and pharmacodynamics of abused drugs, and have made valuable contributions in terms of drug mechanisms, drug interactions (e.g. cocaine and alcohol) and drug toxicities. They have also been employed to study the acute effects of drugs on populations of active drug abusers and of normal controls, and to evaluate the neurochemical consequences of candidate therapies for drug abuse. A particularly productive strategy has been the use of PET in conjunction with neuropsychological testing of subjects, to allow correlation of imaging data with uniquely human aspects of the effects of drugs, such as euphoria and craving.     

Functional neuroimaging in schizophrenia: diagnosis and drug discovery

Functional neuroimaging provides a direct way of investigating the pathophysiology of schizophrenia in vivo. The function of neurotransmitters implicated in schizophrenia, such as dopamine and glutamate, can be assessed using molecular imaging techniques such as positron emission tomography (PET), single-photon emission tomography (SPET) and magnetic resonance spectroscopy (MRS). Regional brain activity, particularly that associated with the cognitive processes and symptoms associated with the disorder, can be studied using functional magnetic resonance imaging (fMRI). Here, we focus on the potential for the use of these techniques in the diagnosis of schizophrenia and in the development of new drugs for its treatment.     

Current radiosynthesis strategies for 5‐HT2A receptor PET tracers

Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been made to develop a suitable 5‐HT_2AR positron emission tomography‐tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5‐HT_2AR radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning outcomes that can be made from these tracer development processes.     

PET and SPET molecular imaging: focus on serotonin system

Emission tomography techniques and, in particular, positron emission tomography (PET) enable the in vivo study of several physiological and neurochemical variables in human subjects using methods originally developed for quantitative autoradiography. In particular, PET allows one to evaluate in human subjects: (a) the effect of specific neurochemical challenges on regional brain function at rest or under activation; (b) the activity of neurotransmitters and the regional expression of specific molecular targets during pathology including their modulation by drug treatment; (c) the kinetics of drug disposition and activity directly in the target organ. This is of primary interest in the field of biological psychiatry and in psychoactive drugs development, where it is particularly difficult to reproduce human diseases using animal models in view of the peculiarity of this field and the large heterogeneity of each psychiatric illness also inside the same clinical definition. The aim of this paper is to review the principal strategies and the main results of the use of PET or single photon emission tomography (SPET) molecular imaging for the in vivo study of serotonin receptors and the main results obtained from their application in the study of major depression.     

Microdialysis: current applications in clinical pharmacokinetic studies and its potential role in the future

Microdialysis is a probe-based sampling method, which, if linked to analytical devices, allows for the measurement of drug concentration profiles in selected tissues. During the last two decades, microdialysis has become increasingly popular for preclinical and clinical pharmacokinetic studies. The advantage of in vivo microdialysis over traditional methods relates to its ability to continuously sample the unbound drug fraction in the interstitial space fluid (ISF). This is of particular importance because the ISF may be regarded as the actual target compartment for many drugs, e.g. antimicrobial agents or other drugs mediating their action through surface receptors. In contrast, plasma concentrations are increasingly recognised as inadequately predicting tissue drug concentrations and therapeutic success in many patient populations. Thus, the minimally invasive microdialysis technique has evolved into an important tool for the direct assessment of drug concentrations at the site of drug delivery in virtually all tissues. In particular, concentrations of transdermally applied drugs, neurotransmitters, antibacterials, cytotoxic agents, hormones, large molecules such as cytokines and proteins, and many other compounds were described by means of microdialysis. The combined use of microdialysis with non-invasive imaging methods such as positron emission tomography and single photon emission tomography opened the window to exactly explore and describe the fate and pharmacokinetics of a drug in the body. Linking pharmacokinetic data from the ISF to pharmacodynamic information appears to be a straightforward approach to predicting drug action and therapeutic success, and may be used for decision making for adequate drug administration and dosing regimens. Hence, microdialysis is nowadays used in clinical studies to test new drug candidates that are in the pharmaceutical industry drug development pipeline.     

Measuring receptor occupancy with PET

Many physiological and biochemical measurements can be performed noninvasively in humans with modern imaging techniques like magnetic resonance imaging (MRI), positron emission tomography (PET) or single-photon emission computed tomography (SPECT). This review focuses on the monitoring of drug-receptor interactions in patients and healthy volunteers with PET. Such studies depend on the availability of a suitable radioligand; they are already possible for classical and atypical neuroleptics, anxiolytics, antidepressants, anticholinergics, antihistamines, antiepileptics, beta-blockers and hypnotic drugs. In Phase I-II human studies, measurements of plasma pharmacokinetics can be combined with images of receptor occupancy and be quantitatively related to pharmacologic effects which are induced in the same subjects. Optimal dosing schedules can be defined and valuable information for the design of Phase III studies can be acquired. Moreover, the effect of interventions (e.g. change of dose, additional medication) can be predicted. Medical imaging techniques will play an increasing role in clinical pharmacology and allow well-informed go/no-go decisions in future drug development.     

Meta-analysis: the detection of pancreatic malignancy with positron emission tomography

BACKGROUND: Several factors contribute to the high mortality of pancreatic cancer, including limitations of diagnostic imaging. AIM: To perform a meta-analysis to assess the diagnostic accuracy of Fluro-deoxy-glucose positron emission tomography with computed tomography compared with computed tomography alone. METHODS: Articles were identified through a MEDLINE search and bibliography review. Summary estimates and receiver operating curves were calculated using Meta-Test 0.6. Publication bias and heterogeneity were assessed with a funnel plot and chi-squared test. RESULTS: The summary estimate and 95% confidence interval for sensitivity and specificity were as follows: computed tomography 81% (72-88%) and 66% (53-77%), PET after a positive computed tomography 92% (87-95%) and 68% (51-81%), PET after a negative computed tomography 73% (50-88%) and 86% (75-93%) and PET after an indeterminate computed tomography 100 and 68%. The area under the summary receiver operating curve was 0.82 for computed tomography and 0.94 for PET. There was no heterogeneity or publication bias. CONCLUSIONS: Our results suggest that although adding Fluro-deoxy-glucose positron emission tomography to the diagnostic work-up may enhance the diagnosis of pancreatic malignancy, its usefulness will vary depending upon the pretest probability of the patient, the results of computed tomography and the provider's testing thresholds. Further evaluation using a well-designed prospective study with a cost-effectiveness analysis is needed to clarify the appropriate role of Fluro-deoxy-glucose positron emission tomography.