表皮生长因子受体-酪氨酸激酶肿瘤分子显像剂的研究进展

目前治疗肿瘤最重要的分子靶向药物是以表皮生长因子受体（EGFR）为靶点的一类化合物,为了更好地实现靶向治疗效果,需要借助分子显像技术实现快速、定量地检测体内EGFR的分布及突变等情况。利用不同核素标记的分子探针实施PET或SPECT显像能够实现快速、无创地对患者进行遴选、疗效评价和监测EGFR靶向治疗,从而提高肿瘤治疗效果。该文介绍了EGFR-酪氨酸激酶小分子显像剂及其最新的研究进展。     

除FDG以外的用于肿瘤PET显像的18F标记物

综述了除FDG以外的用于肿瘤PET显像的18F标记物的研究和应用.这些18F标记物主要包括与相应受体结合的18F标记的蛋白质和多肽,18F标记的乏氧显像剂,用于评价基因治疗的18F标记物等.此外,还介绍了用于诊断不同恶性肿瘤的18F标记的组织特异性PET显像剂.     

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.     

碳-11乙酸盐正电子断层显像临床应用

正电子断层显像（positron emission tomography,PET）作为一种影像检查方法其临床应用价值已经得到广泛的认可,PET显像过程中必须使用的正电子显像剂有很多种,目前全世界范围内临床常规应用的正电子显像剂是氟-18标记的脱氧葡萄糖（18↑F-FDG）,与18↑F-FDG同期进入美国药典的正电子显像剂还有碳-11乙酸盐（11↑C-Acetate,以下简称11↑C-AC）.20世纪80年代初英国皇家医学研究生院Allan教授等发现11↑C-AC PET显像（简称AC-PET）可以用于心脏疾病诊断和疗效观察,早期其应用范围主要集中在心脏方面,1995年美国密西根大学安娜堡分校的Shreve等发现肾透明细胞病灶在AC-PET上显示为＂热灶＂,因此认为其有可能用于肿瘤显像.虽然作为一种短半衰期（20min）的显像剂,11↑C-AC临床应用受到很大限制,但因其在肿瘤中的应用价值独特,目前世界上越来越多的有加速器的PET中心开始常规使用该显像剂,     

除FDG以外的用于肿瘤PET显像的^18F标记物

综述了除FDG以外的用于肿瘤PET显像的^18F标记物的研究和应用。这些^18F标记物主要包括：与相应受体结合的^18F标记的蛋白质和多肽，^18F标记的乏氧显像剂，用于评价基因治疗的^18F标记物等。此外，还介绍了用于诊断不同恶性肿瘤的^18F标记的组织特异性PET显像剂。     

放射性核素显像探针在细胞凋亡中的研究进展

目前细胞凋亡的体外检测方法很多，但这些检测方法在取材、组织活检时具有创伤性，大多需要处死动物，且只能离体研究，限制了其在临床中的应用与转化。体内检测方法因可在活体内无创、实时监测凋亡，成为目前研究的热点。放射性核素凋亡细胞显像技术因具备无创、早期、动态、灵敏、定量、可在活体内检测等优势，具有良好的研究前景，是目前研究最为广泛、技术最为成熟的体内细胞凋亡检测技术。核素凋亡显像已广泛应用于心血管疾病、中枢神经系统疾病、器官移植排斥反应中的细胞凋亡检测，以及恶性肿瘤放化疗的疗效评价和预后判断等方面。笔者主要通过对放射性核素显像探针在细胞凋亡中的研究进展作一综述。     

68Ga标记的SSR靶向多肽PET/CT显像的研究进展及其在神经内分泌肿瘤中的初步应用

近年来,68Ga标记的多肽PET/CT显像为神经内分泌肿瘤（NET）的诊断提供了新的方法和视角。68Ge/68Ga发生器已经商业化,容易获得,并且68Ga标记过程简单方便,显像剂稳定性好。在此基础上,越来越多的研究比较了68Ga标记的多肽PET/CT与传统的形态学显像方法（CT、MRI）及生长抑素受体扫描对NET病灶的诊断效能,发现68Ga标记的多肽PET/CT远远优于后者。此外,68Ga标记的多肽PET/CT显像还能为患者治疗方案的选择、辐射剂量的调整甚至预后效果的评估提供多种重要信息,其有望成为NET患者肿瘤显像的临床首选。笔者就近年来68Ga标记的多肽PET/CT显像在临床上的初步应用研究作一综述。     

靶向表皮生长因子受体小分子类PET显像剂研究进展

表皮生长因子受体（EGFR）在多种癌症的发生发展中起着重要作用,目前已有多种EGFR靶向药物被美国食品与药品管理局批准用于临床,但因个体敏感程度不同,总体疗效偏低。研究表明EGFR高表达或突变患者对靶向药物敏感,因此明确EGFR表达水平和突变状态对临床用药有重要指导意义。PET成像技术能实现分子水平无创显像,并能通过SUV进行半定量研究,使得在体内无创明确EGFR表达、突变情况,指导靶向药物的精准治疗成为可能。笔者综述了靶向EGFR的小分子类PET显像剂,以期为新的探针研发及其临床应用提供一定帮助。     

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...     

体内凋亡细胞显像的研究进展

目前,疾病的诊断及治疗已进入分子水平阶段,细胞凋亡的检测技术也不断更新和发展。活体内细胞凋亡显像符合生理代谢的特点,能够对疾病实行早期、活体、无创及定量检查。其主要显像方法有:磁共振成像、光学成像、超声检查及放射性核素显像等。其中,以放射性核素凋亡显像的研究应用尤为突出,已应用于心血管疾病、中枢神经系统疾病、移植排斥反应以及肿瘤诊治等方面。     

Myocardial perfusion imaging agents: SPECT and PET

The advent of myocardial perfusion imaging 30 years ago was a major landmark, which heralded the emergence of the field of nuclear cardiology into clinical practice. Over the years, the different tracers cited in this review have been used with SPECT or PET imaging technologies for the noninvasive evaluation of regional myocardial blood flow, which has enhanced our ability to diagnose CAD, assess prognosis, detect viable myocardium, and evaluate the efficacy of therapies aimed at improving myocardial blood flow. In the future, new SPECT perfusion agents should be developed and validated in the experimental laboratory for feasibility in the clinical setting. Hopefully, such new radiolabeled perfusion agents will have a high first-pass extraction, will be more linear with flow increases in the hyperemic range, and will be labeled with Tc-99m. The clearance rates from the myocardium after initial uptake should be slow enough, as with Tl-201, to acquire high-quality poststress gated SPECT images. Ideally, such perfusion agents should also be extracted intracellularly with quantitative uptake reflecting the degree of viability (eg, as with Tl-201). Absolute quantitation of myocardial blood flow in milliliters per minute per gram by use of SPECT technology would be highly desirable, particularly to increase the detection rate of multivessel disease in which flow reserve is uniformly diminished. This is often categorized as balanced ischemia. Absolute quantitation is a major strength of PET perfusion tracers, as is the ability to accurately correct for attenuation, thereby providing high sensitivity and specificity for CAD detection. The roll-off or plateau in myocardial uptake with hyperemia is also seen with the PET perfusion tracers such as N-13 ammonia and Rb-82. Despite the advent of molecular imaging and the introduction of new imaging agents by which to noninvasively evaluate biologic processes such as apoptosis and angiogenesis in vivo, myocardial perfusion imaging will remain the mainstay of nuclear cardiology in the near future. Continued research and development for this imaging technique are warranted for the reasons cited in this review.     

Advances in PET myocardial perfusion imaging: F-18 labeled tracers

Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI.     

How many PET tracers do we need?

The recognized need for new PET tracers is associated with increases in available PET instrumentation and with unmet clinical challenges in the early diagnosis and staging of diseases. The clinical success of (18)F-FDG PET has resulted in the acceptance of biologic signals as part of disease management. The advantages of PET technology over SPECT will lead to the introduction of new PET tracers for established nuclear medicine imaging indications. Disease-specific markers such as amyloid ligands will lead to new applications of PET to neurodegenerative diseases that are prevalent in aging societies. The translation of molecular imaging to clinical applications will require combining specific tracer approaches with targeted therapy for the realization of personalized medicine. An important aspect of the introduction of new PET tracers will be the emergence of a specialized radiopharmaceutical industry and professional distribution networks. The number of available PET tracers not only will follow rules of demand and supply but also will be dependent on the regulatory environment of individual health care systems.     

Multimodality molecular imaging of apoptosis in oncology

OBJECTIVE: The purposes of this review are to describe the signaling pathways of and the cellular changes that occur with apoptosis and other forms of cell death, summarize tracers and modalities used for imaging of apoptosis, delineate the relation between apoptosis and inhibition of protein translation, and describe spectroscopic technologies that entail high-frequency ultrasound and infrared and midinfrared light in characterizing the intracellular events of apoptosis. CONCLUSION: Apoptosis is a highly orchestrated set of biochemical and morphologic cellular events. These events present many potential targets for the imaging of apoptosis in vivo. Imaging of apoptosis can facilitate early assessment of anticancer treatment before tumor shrinkage, which may increase the effectiveness of delivery of chemotherapy and radiation therapy and speed drug development.     

Cardiac neurotransmission imaging.

Cardiac neurotransmission imaging with SPECT and PET allows in vivo assessment of presynaptic reuptake and neurotransmitter storage as well as of regional distribution and activity of postsynaptic receptors. In this way, the biochemical processes that occur during neurotransmission can be investigated in vivo at a micromolar level using radiolabeled neurotransmitters and receptor ligands. SPECT and PET of cardiac neurotransmission characterize myocardial neuronal function in primary cardioneuropathies, in which the heart has no significant structural abnormality, and in secondary cardioneuropathies caused by the metabolic and functional changes that take place in different diseases of the heart. In patients with heart failure, the assessment of sympathetic activity has important prognostic implications and will result in better therapy and outcome. In diabetic patients, scintigraphic techniques allow the detection of autonomic neuropathy in early stages of the disease. In conditions with a risk of sudden death, such as idiopathic ventricular tachycardia and arrhythmogenic right ventricular cardiomyopathy, PET and SPECT reveal altered neuronal function when no other structural abnormality is seen. In patients with ischemic heart disease, heart transplantation, drug-induced cardiotoxicity, and dysautonomias, assessment of neuronal function can help characterize the disease and improve prognostic stratification. Future directions include the development of tracers for new types of receptors, the targeting of second messenger molecules, and the early assessment of cardiac neurotransmission in genetically predisposed subjects for prevention and early treatment of heart failure.     

Properties of an ideal PET perfusion tracer: New PET tracer cases and data

An ideal positron emission tomography (PET) tracer should be highly extractable by the myocardium and able to provide high-resolution images, should enable quantification of absolute myocardial blood flow (MBF), should be compatible with both pharmacologically induced and exercise-induced stress imaging, and should not require an on-site cyclotron. The PET radionuclides nitrogen-13 ammonia and oxygen-15 water require an on-site cyclotron. Rubidium-82 may be available locally due to the generator source, but greater utilization is limited because of its relatively low myocardial extraction fraction, long positron range, and generator cost. Flurpiridaz F 18, a novel PET tracer in development, has a high-extraction fraction, short positron range, and relatively long half-life (as compared to currently available tracers), and may be produced at regional cyclotrons. Results of early clinical trials suggest that both pharmacologically and exercise-induced stress PET imaging protocols can be completed more rapidly and with lower patient radiation exposure than with single-photon emission computerized tomography (SPECT) tracers. As compared to SPECT images in the same patients, flurpiridaz F 18 PET images showed better defect contrast. Flurpiridaz F 18 is a potentially promising tracer for assessment of myocardial perfusion, measurement of absolute MBF, calculation of coronary flow reserves, and assessment of cardiac function at the peak of the stress response.     

Molecular imaging of hypoxia with radiolabelled agents

Tissue hypoxia results from an inadequate supply of oxygen (O₂) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant progression. This has led to the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments. A variety of invasive and non-invasive approaches have been developed to measure tumour oxygenation including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), autoradiography and immunohistochemistry. This review aims to give a detailed overview of non-invasive molecular imaging modalities with radiolabelled PET and SPECT tracers that are available to measure tumour hypoxia.     

German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.     

Current status and prospects of new radionuclides and radiopharmaceuticals for cardiovascular nuclear medicine

The rapid emergence of new imaging modalities like positron emission tomography (PET) and single photon emission computerized tomography (SPECT) and their advance into the clinical arena offered new opportunities for, but also stimulated research and development of new radiopharmaceuticals suitable for cardiac imaging. While tracers of myocardial blood flow remained in the center of interest, other trends heralded possibilities of studying more comprehensively cardiac physiology and pathophysiology as, for example, metabolism, the severity of tissue injury, neural activity and membrane function. N-13 ammonia and rubidium-82 became the primary tracers for evaluating and possibly quantifying regional myocardial blood flow with PET, while cationic Tc-99m isonitrile complexes have now reached a stage where high contrast images of the human heart are obtained on planar scintigraphy and SPECT. These radiopharmaceuticals hold considerable promise for routine clinical use. Tracers of metabolism, especially those labeled with positron emitting isotopes as for example, C-11 palmitate, F-18 2-deoxyglucose, are approaching the phase of clinical use and provide information on regional myocardial substrate metabolism and oxidative processes. Less successful and more limited were developments of single photon emitting tracers of metabolism which remained largely confined to radioiodinated fatty acid analogs. Exploration and characterization of the metabolic fate of the radiolabel in tissue and its relation to the externally observed signal have been truly impressive. Tested in humans primarily in western European countries, these tracers promise to yield metabolic information on a more limited scope. Most widely applied are iodohepta- and hexadecanoic acid and, more recently, the aromatic fatty acid analog, paraiodophenylpentadecanoic acid. Labeled monoclonal antibodies rapidly advanced to the point of clinical use. Accurate identification and sizing of acute myocardial infarction is now possible with Tc-99m or indium-111 labeled specific antimyosin antibody fragments. This success stimulated new research activities for use of labeled antibody techniques in other areas as for example, scintigraphic evaluation of formation and presence of vascular thrombi. While promising, these efforts have however remained in an early stage of development. The same holds true for single photon and positron emitting tracers that are suitable for assessing sympathetic neuron densities in myocardium as well as imaging of both cholinergic and adrenergic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry

OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. CONCLUSION: Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.