小动物PET及其在生物医学研究中的应用

通过对正电子核素标记的示踪分子参与活体的生理生化过程进行PET，能够从分子水平反映活体的生理生化变化。PET作为目前核医学诊断和研究最先进的分子显像方法，已从临床应用推广到了小动物科学实验。近几年来，随着新的探测技术的不断涌现，专门用于小动物显像的PFT扫描仪的各项性能日臻完善，它正逐渐成为现代生物医学研究的一项重要工具。小动物PET将在药物寻找和开发、疾病研究、基因显像等领域发挥重要作用。     

分子核医学浅议

概述了Ｗａｇｎｅｒ关于分子核医学概念的要点，对Ｗａｇｎｅｒ关于“通过化学型将表型与基因型联系起来”的观点进行了浅议，并结合我国具体情况提出了值得特别关注的几个研究领域，即受体显像、标记反义探针基因显像、重组单抗片段、肽类放射性药物等。提出：分子识别是分子核医学的重要理论基础之一，应将分子生物学技术引入核医学中来     

小动物PET及其在生物医学研究中的应用

通过对正电子核素标记的示踪分子参与活体的生理生化过程进行PET,能够从分子水平反映活体的生理生化变化。PET作为目前核医学诊断和研究最先进的分子显像方法,已从临床应用推广到了小动物科学实验。近几年来,随着新的探测技术的不断涌现,专门用于小动物显像的PET扫描仪的各项性能日臻完善,它正逐渐成为现代生物医学研究的一项重要工具。小动物PET将在药物寻找和开发、疾病研究、基因显像等领域发挥重要作用。     

生长抑素受体显像剂99Tcm-奥曲肽的SPECT研究

核医学SPECT在20世纪已进入分子显像时代,受体显像尤其是生长抑素受体显像更是目前核医学显像研究的热点.利用111In、123I、99Tcm、90Y等放射性核素标记生长抑素类似物奥曲肽进行生长抑素受体显像的方法,已经比较成熟,且部分已用于临床显像.该文对99Tcm标记奥曲肽的方法(直接法、间接法)、99Tcm-奥曲肽SPECT显像方法及其临床应用等作简要概述.     

基因表达正电子发射断层显像

分子生物学与核医学的结合形成了分子核医学，基因表达正电子发射断层（PET）显像是当今分子核医学研究的热点和前沿领域之一。基因表达PET显像包括反义PET显像和报告基因PET显像，反义PET显像由于技术上的问题，远不如报告基因PET显像那样发展迅速，报告基因PET显像已广泛用于动物实验研究，可望不久的将来会用于临床研究。     

视网膜神经受体及其分子显像研究进展

视网膜的合成、代谢等各项生理功能主要是由视网膜内的神经递质（谷氨酸、γ-氨基丁酸、多巴胺、5-羟色胺、σ受体等）协同作用完成。近年来核医学显像仪器及显像剂的蓬勃发展促进了全身各器官系统功能的分子水平研究,视网膜受体分子显像是将核医学、眼科学、分子生物学相结合的新医学技术,是当前核医学研究领域的一个开拓性的新进展。笔者将从视网膜内的各种神经递质的生理病理变化及其在核医学分子显像领域的研究进行综述。     

微米级超顺磁性氧化铁颗粒在细胞影像学上的应用

细胞影像学是指借助影像学方法在活体内无创可重复性地显示靶细胞生物学行为,并对其进行定量和定性研究的科学[1],是影像学从大体形态显像走向细胞分子显像的重大突破.目前,细胞影像技术主要包括核医学成像、MRI及光学成像等[1].     

放射性核素治疗的发展与思考

放射性核素内照射治疗是近年来发展较快的领域之一，也是核医学主要的组成部分之一。学科之间的交叉融合和各种技术的综合应用是核素治疗的主要发展趋势。分子生物学的发展促进了分子核医学的发展，放射免疫显像、受体显像、反义显像和报告基因表达显像促使放射免疫治疗、受体介导放射性核素靶向治疗、     

以氯离子通道蝎毒素为靶分子的分子影像研究进展

分子影像学是利用影像学手段研究在体条件下细胞内的正常或病理状态分子过程,在分子或细胞水平反映生物体生理、病理变化,为疾病过程在体监测、基因治疗在体示踪、药物在体疗效评测和功能分子在体活动规律研究提供新的技术,具有无创、实时、在体、特异、精细显像等优点[1]。主要     

放射性核素标记Anx Ⅴ细胞凋亡分子成像在肿瘤化疗疗效评估中的价值

细胞凋亡是评价肿瘤化疗疗效的一个重要方面,在靶向凋亡的分子成像技术中,核素显像技术是目前最敏感的技术,以放射性核素标记Anx Ⅴ的凋亡显像技术应用较为广泛.就放射性核素标记AnxV凋亡成像的原理、示踪剂种类、标记法和生物分布特征、体内外研究及临床研究结果进行综述.     

分子成像技术在监测RNA干扰治疗中的研究进展

RNA干扰（RNAi）技术因其高效、特异性强等特点被广泛应用于肿瘤、病毒感染性及代谢性疾病的临床治疗。无创示踪RNAi相关分子在体内的递送过程及监测RNAi的疗效对提高RNAi的效率、促进该技术在临床中的应用具有重要意义。分子成像技术能够使活体内细胞和分子水平的生物学过程可视化,具有无创、动态、实时、定量、高特异性、高灵敏度等优点,在监测RNAi相关分子在体内的生物学过程、评估RNAi的治疗效果、加快RNAi技术的临床转化等方面有着广阔的应用前景。笔者就分子成像技术监测RNAi递送过程和评估RNAi治疗效果的研究进展进行综述。     

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.

     

Molecular imaging of small animals with fluorescent proteins: from projection to multimodality

Fluorescent proteins (FPs) have been widely adopted in cell research for protein trafficking and reporter gene expression studies, as well as to study other biological processes. However, biological tissue has high light scattering and high absorption coefficients of visible light; hence, using FPs in small animal imaging remains a challenge, especially when the FPs are located deep in the tissue. In small animals, fluorescence molecular imaging could potentially address this difficulty. We constructed fluorescence molecular imaging systems that have two modes: a planner mode (projection imaging) and a multimodality mode (fluorescence molecular tomography and micro-CT). The planner mode can provide projection images of a fluorophore in the whole body of a small animal, whereas three-dimensional information can be offered by multimodality mode. The planner imaging system works in the reflection mode and is designed to provide fast imaging. The multimodality imaging system is designed to allow quantification and three-dimensional localization of fluorophores. A nude mouse with a tumour targeted with a far-red FP, which is appropriate for in vivo imaging, was adopted to validate the two systems. The results indicate that the planner imaging system is probably suitable for high throughput molecular imaging, whereas the multimodality imaging system is fit for quantitative research.     

间充质干细胞外泌体治疗脊髓损伤作用机制的研究进展

脊髓损伤后继发性损伤及胶质瘢痕,使神经细胞在微环境中出现再生障碍,导致治疗困难.间充质干细胞(MSCs)具有多向分化、自我更新能力、参与免疫调节等功能,可用于治疗脊髓损伤,但存在不易通过血脊屏障、高致瘤性等缺点.MSCs外泌体是由MSCs分泌的纳米级外囊泡,包裹多种活性物质,在脊髓损伤研究中具有极强的神经修复作用,且具...     

多模态纳米分子探针在动物模型易损斑块中靶向分子成像的研究进展

易损斑块的破裂常常导致急性冠状动脉综合征,造成严重的心血管事件。早期监测易损斑块对于预防急性冠状动脉综合征具有重要意义。目前,分子影像技术能在细胞和分子水平对疾病进行早期检测,其中,用于监测易损斑块的分子影像技术有核医学分子显像、超声分子成像、MRI和光学成像等。近年来,多模态分子影像技术由于结合了多种分子影像技术的优势,能够提供更多解剖与生物代谢信息,因此在监测易损斑块中具有更高的价值。多模态分子探针的制备与构建对疾病的分子影像诊断至关重要,寻找合适的靶点、增强分子探针的靶向性有利于提高疾病的检出率,为更敏感地检出早期易损斑块提供可能。纳米颗粒因其特殊的性能与优点已被广泛应用于多模态分子探针的研究中,然而,此类探针尚处于临床前研究阶段,主要应用于动物模型中。笔者针对易损斑块在组织学以及细胞与分子生物学变化中出现的各种生物标志物,综述多模态纳米分子探针在动物模型易损斑块中靶向分子成像的研究进展。     

乏氧微环境下外泌体对肿瘤进展及辐射抵抗的影响

肿瘤的发生发展是一个复杂的生物学过程,涉及诸多的因素。乏氧是实体肿瘤微环境的显著特征之一,乏氧微环境可导致肿瘤的适应性更强、恶性程度更高并产生耐药性。研究发现,外泌体是介导肿瘤生物学过程的重要因子,而乏氧环境下产生的外泌体在某些生物学过程中的作用更为显著。因而,研究乏氧环境下外泌体对了解肿瘤的发展进程,控制肿瘤的生长具有重要意义。笔者简单概述了外泌体在肿瘤乏氧微环境中的作用,以期为肿瘤生物学的研究提供一定的理论基础。     

Molecular imaging of small animals with dedicated PET tomographs

Biological discovery has moved at an accelerated pace in recent years, with a considerable focus on the transition from in vitro to in vivo models. As a result, there has been a significant increase in the need to adapt clinical imaging methods, as well as for novel imaging technologies for biological research. Positron emission tomography (PET) is a clinical imaging modality that permits the use of positron-labeled molecular imaging probes for non-invasive assays of biochemical processes. The imaging procedure can be repeatedly performed before and after interventions, thereby allowing each animal to be used as its own control. Positron-labeled compounds that target a range of molecular targets have been and continue to be synthesized, with examples of biological processes ranging from receptors and synthesis of transmitters in cell communication, to metabolic processes and gene expression. In animal research, PET has been used extensively in the past for studies of non-human primates and other larger animals. New detector technology has improved spatial resolution, and has made possible PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents the challenges facing PET technology as applied to small animal imaging, provides a historical overview of the development of small animal PET systems, and discusses the current state of the art in small animal PET technology.     

Maligne Tumoren des Pharynx

BACKGROUND: Malignant tumors of the head and neck region are amongst the six most often occurring tumors of the body. They can be associated with the different anatomical compartments as well as different histologic types. The way of tumor spread of these malignancies depends on their histologic type and on the region. These compartments can be separated into the nasopharynx, the oropharynx, and the hypopharynx. Most of the malignant tumors belong to the squamous cell carcinomas, other histologic types are depicted less frequently. The histologic types of the other groups which are seen more often comprise of lymphomas and adenoid cystic carcinomas. The undifferentiated carcinoma of the nasopharynx is supposed to be a special type of tumor. The malignant tumors of the pharynx can also involve all three compartments. Beside these tumors, malignancies of mesenchymal origin can also be delineated. IMAGING MODALITIES: The imaging modalities most frequently used to detect these tumors and to clarify their extension are contrast enhanced computed tomography, magnetic resonance imaging, nuclear-medicine imaging modalities such as positron emission tomography. Other scintigraphic imaging methods play a less important role. CONCLUSION: The different imaging modalities of malignant pharyngeal tumors and of potentially infiltrated lymph nodes with the weightness on computed tomography and magnetic resonance imaging and their appearance in these imaging techniques shall be enhanced in this paper.     

Advances in radionuclide molecular imaging in myocardial biology

Molecular imaging is a new and evolving field that employs a targeted approach to noninvasively assess biologic processes in vivo. By assessing key elements in specific cellular processes prior to irreversible end-organ damage, molecular tools will allow for earlier detection and intervention, improving management and outcomes associated with cardiovascular diseases. The goal of those working to expand this field is not just to provide diagnostic and prognostic information, but rather to guide an individual’s pharmacological, cell-based, or genetic therapeutic regimen. This article will review molecular imaging tools in the context of our current understanding of biological processes of the myocardium, including angiogenesis, ventricular remodeling, inflammation, and apoptosis. The focus will be on radiotracer-based molecular imaging modalities with an emphasis on clinical application. Though this field is still in its infancy and may not be fully ready for widespread use, molecular imaging of myocardial biology has begun to show promise of clinical utility in acute and chronic ischemia, acute myocardial infarction, congestive heart failure, as well as in more global inflammatory and immune-mediated responses in the heart-like myocarditis and allogeneic cardiac transplant rejection. With continued research and development, molecular imaging promises to be an important tool for the optimization of cardiovascular care.     

It's not just about anatomy: in vivo bioluminescence imaging as an eyepiece into biology

Among the newly described tools that enable analyses of cellular and molecular events in living animals, in vivo bioluminescence imaging (BLI) offers important opportunities for investigating a wide variety of disease processes. BLI utilizes luciferase as an internal biological light source that can be genetically programmed to noninvasively "report" the presence or activation of specific biological events. Applications of BLI have included the use of luciferase to demonstrate expression of cell- and tissue-specific promoters, label cell populations, guide detection by other imaging modalities, and detect protein-protein interaction. These applications of BLI technology have allowed quantitative measurements of tumor burden and treatment response, immune cell trafficking, and detection of gene transfer. Spatiotemporal information can be rapidly obtained in the context of whole biological systems in vivo, which can accelerate the development of experimental therapeutic strategies. This paper provides a review of the biological applications in which in vivo BLI has been utilized to nondestructively monitor biological processes in intact small animal models, and highlights some of the advancements that will increase the versatility of BLI as a molecular imaging tool.