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。     

小动物PET及PET-CT及其在分子影像学中的应用

阐述小动物PET及PET-CT技术特点及在分子影像学中的应用。小动物PET及PET-CT采用多项新技术,分辨率明显提高,结合小动物CT实现了图像融合。小动物PET及PET-CT实现了在活体上非侵入性分子水平显像,是研究分子影像的尖端设备。     

PET分子显像技术在药代动力学研究中的应用

药代动力学是药理学研究的重要内容之一,对于指导临床合理用药、预防药物不良反应、探究药物的作用机制和药物相互作用等具有重要意义。PET分子显像技术可以动态监测体内生理、生化等过程,可应用于血浆药代动力学、药物组织分布以及药物相互作用等研究,可缩短新药研发周期。笔者对近年来PET分子显像技术用于药代动力学的各个方面研究进行综述。     

动物PET研究进展

分子医学研究需要在活体实验动物上观察分子水平的生物学过程，因而正电子发射体层（PET）显像作为目前最成熟的分子显像方法，正被直来越多地用于动物实验。新开发的实验动物专用PET扫描仪的各项性能也逐步趋于完善。该技术将在疾病研究、新药开发、基因治疗等领域发挥重要作用。     

动物PET研究进展

分子医学研究需要在活体实验动物上观察分子水平的生物学过程,因而正电子发射体层(PET)显像作为目前最成熟的分子显像方法,正被越来越多地用于动物实验。新开发的实验动物专用PET扫描仪的各项性能也逐步趋于完善。该技术将在疾病研究、新药开发、基因治疗等领域发挥重要作用。     

微型PET及其在医药研究中的应用

由于基因表达和基因治疗方面的需要 ,使得分子显像尤为重要。PET是分子显像技术的一种 ,可用于发现、研究和早期诊断疾病 ,测定心肌活力 ,发现早期肿瘤 ,鉴别良恶性病变 ,判定肿瘤有无转移及监测疗效。而临床使用的PET系统对小动物研究分辨率不够 ,这促使人们开发了专用的微型PET。一、微型PET技术上的改进微型PET仪使用了新的技术 ,使得分辨率大大提高 ,在小鼠、大鼠、猴和人活体分子显像方面具有相似的显像能力。Chatziioannou等[1 ] 开发的微型PETⅠ应用了单个晶体光纤读出技术以及新的闪烁材料硅酸镥 (lutetiumoxyorthosili cat…     

肿瘤MR分子影像学研究进展

MR分子影像学以分子生物学为基础,借助MRI技术在活体状态下从分子、基因水平对肿瘤进行更早期、更特异性诊断与监测治疗效果。目前关于MR分子影像研究多集中于MR特异性分子探针的制备、肿瘤血管形成显像、报告基因显像、波谱显像等方面,由于MR具有精确的空间定位及功能成像等优势,因此在肿瘤分子影像研究中具有极大的发展潜力,将在21世纪肿瘤的诊断与治疗中发挥重要作用。MR分子影像学以分子生物学为基础,借助MRI技术在活体状态下从分子、基因水平对肿瘤进行更早期、更特异性诊断与监测治疗效果。目前关于MR分子影像研究多集中于MR特异性分子探针的制备、肿瘤血管形成显像、报告基因显像、波谱显像等方面,由于MR具有精确的空间定位及功能成像等优势,因此在肿瘤分子影像研究中具有极大的发展潜力,将在21世纪肿瘤的诊断与治疗中发挥重要作用。     

PET/CT正电子心肌灌注显像剂的研究进展

正电子发射型计算机体层摄影术/计算机辅助断层(positron emission computed tomography/computed tomography,PET/CT)作为一种代谢/解剖于一身的高级显像手段,可以从分子水平无创地定量显示人体内的生理、生化过程。核心脏病学已成为放射性核素显像中一门独立的医学分支学科。早在20世纪70年代,PET显像已先后用于心肌血流灌注、心肌葡萄糖代谢、脂肪酸代谢及心脏受体功能等研究[1]。在国外,     

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。     

肿瘤MR分子影像学研究进展

MR分子影像学以分子生物学为基础，借助MRI技术在活体状态下从分子、基因水平对肿瘤进行更早期、更特异性诊断与监测治疗效果。目前关于MR分子影像研究多集中于MR特异性分子探针的制备、肿瘤血管形成显像、报告基因显像、波谱显像等方面，由于MR具有精确的空间定位及功能成像等优势，因此在肿瘤分子影像研究中具有极大的发展潜力，将在21世纪肿瘤的诊断与治疗中发挥重要作用。     

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.     

Ultra-high-resolution imaging of small animals: Implications for preclinical and research studies

Recent developments in the use of pinhole SPECT and dedicated PET for UHR small animal imaging have identified the technology that can be used to provide images with spatial resolution of the order of 1 to 3 mm. In SPECT imaging, rotating camera pinhole SPECT has provided the means to use existing equipment to achieve UHR images. It has the disadvantages of low sensitivity and requires special image software to reconstruct tomographic slices. However, with minimal additional cost to an imaging laboratory, pinhole SPECT can provide a quantitatively accurate imaging technique for small-animal studies. New detector technology offers considerable promise; however, more studies are required before any one system can be singled out as offering major advantages over the pinhole SPECT method for general purpose small-animal SPECT imaging. The search for the means to achieve better sensitivity with UHR continues. In PET imaging, with few exceptions, the general trend has been to design systems dedicated to small-animal imaging to achieve UHR images with satisfactory sensitivity for quantitative UHR imaging. Several of the ring configuration, small-animal PET imaging systems provide good sensitivity and high spatial resolution. The cost of many of these systems, however, is relatively high, and investigators continue to explore different detector materials and imaging geometries to develop an instrument with acceptable levels of sensitivity with UHR imaging capability. We believe that both small-animal SPECT and PET imaging techniques now offer practical UHR imaging methods for quantitative small-animal imaging. As these tools are implemented in the investigation of new radiopharmaceuticals, we expect the utility of in vivo small animal assays will support further research in optimizing this technology.     

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。     

PET/MRI hybrid imaging: devices and initial results

The combination of functional and morphological imaging technologies such as positron emission tomography (PET) and X-ray computed tomography (CT) has shown its value in the clinical and preclinical field. However, CT provides only very limited soft-tissue contrast and exposes the examined patient or laboratory animal to a high X-ray radiation dose. In comparison to CT, magnetic resonance tomography (MRI) provides excellent soft-tissue contrast and allows for nuclear magnetic resonance spectroscopy (NMRS) or functional MRI (fMRI). Thus, the combination of PET and MRI has been pursued for several years. First approaches have succeeded using conventional photo multiplier tube (PMT) technology together with light fibers to transfer scintillation light away from the high magnetic field. Latest PET/MRI developments use solid-state light detectors that can be operated even at high magnetic fields. Initial pilot studies with prototype animal PET/MRI systems have shown promising results by combining high resolution morphology with multifunctional information isochronously.     

Myocardial viability assessment using nuclear imaging

Myocardial assessment continues to be an issue in patients with coronary artery disease and left ventricular dysfunction. Nuclear imaging has long played an important role in this field. In particular, PET imaging using 18F-fluorodeoxyglucose is regarded as the metabolic gold standard of tissue viability, which has been supported by a wide clinical experience. Viability assessment using SPECT techniques has gained more wide-spread clinical acceptance than PET, because it is more widely available at lower cost. Moreover, technical advances in SPECT technology such as gated-SPECT further improve the diagnostic accuracy of the test. However, other imaging techniques such as dobutamine echocardiography have recently emerged as competitors to nuclear imaging. It is also important to note that they sometimes may work in a complementary fashion to nuclear imaging, indicating that an appropriate use of these techniques may significantly improve their overall accuracy. In keeping these circumstances in mind, further efforts are necessary to further improve the diagnostic performance of nuclear imaging as a reliable viability test.     

Nuclear medicine applications in molecular imaging

With the emergence of the new field of molecular imaging, there is an increasing demand for development of sensitive and safe novel imaging agents that can be rapidly translated from small animal models into patients. Nuclear medicine and positron emission tomography (PET) techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes, usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at doses free of pharmacologic side effects, unlike the current generation of intravenous agents required for magnetic resonance (MR) and computed tomography (CT) scanning. In this article, we will review a representative sampling of the wide array of radiopharmaceuticals developed specifically for nuclear medicine radionuclide imaging that have been approved for clinical use, and those in pre-clinical trials. We will also review the existing strategies used to select the appropriate biologic markers and targets for radionuclide labeling that have been employed in the development of novel radiotracers and the imaging of small animals with new microSPECT (single photon emission computed tomography) technologies.     

Experiment assessment of mass effects in the rat: implications for small animal PET imaging

In vivo imaging using positron emission tomography (PET) is important in the development of new radiopharmaceuticals in rodent animal models for use as biochemical probes, diagnostic agents, or in drug development. We have shown mathematically that, if small animal imaging studies in rodents are to have the same "quality" as human PET studies, the same number of coincidence events must be detected from a typical rodent imaging "voxel" as from the human imaging voxel. To achieve this using the same specific activity preparation, we show that roughly the same total amount of radiopharmaceutical must be given to a rodent as to a human subject. At high specific activities, the mass associated with human doses, when administered to a rodent, may not decrease the uptake of radioactivity at non saturable sites or sites where an enzyme has a high capacity for a substrate. However, in the case of binding sites of low density such as receptors, the increased mass injected could saturate the receptor and lead to physiologic effects and non-linear kinetics. Because of the importance of the mass injected for small animal PET imaging, we experimentally compared high and low mass preparations using ex vivo biodistribution and phosphorimaging of three compounds: 2-fluoro-2-deoxyglucose (FDG), 6-fluoro-L-metatyrosine (FMT) and one receptor-directed compound, the serotonin 5HT1A receptor ligand, trans-4-fluoro-N-[2-[4-(2-methoxylphenyl) piperazino]ethyl]-N-(2-pyridyl) cyclohexane- carboxamide (FCWAY). Changes in the mass injected per rat did not affect the distribution of FDG, FMT, and FCWAY in the range of 0.6-1.9 nmol per rat. Changes in the target to nontarget ratio were observed for injected masses of FCWAY in the range of approximately 5-50 nmol per rat. If the specific activity of such compounds and/or the sensitivity of small animal scanners are not increased relative to human studies, small animal PET imaging will not correctly portray the "true" tracer distribution. These difficulties will only be exacerbated in animals smaller than the rat, e.g., mice.     

In vivo molecular-genetic imaging: multi-modality nuclear and optical combinations

Multi-modality, noninvasive in vivo imaging is increasingly being used in molecular-genetic studies and will soon become the standard approach for reporter gene imaging studies in small animals. The coupling of nuclear and optical reporter genes, as described here, represents only the beginning of a far wider application of this technology in the future. Optical imaging and optical reporter systems are cost-effective and time-efficient; they require less resources and space than PET or MRI, and are particularly well suited for imaging small animals, such as mice. Optical reporter systems are also very useful for the quantification and selection of transduced cells using FACS, and for performing in vitro assays to validate the function and sensitivity of constitutive and specific-inducible reporter systems. However, optical imaging techniques are limited by depth of light penetration and do not yet provide optimal quantitative or tomographic information. These issues are not limiting for PET- or MRI-based reporter systems, and PET- and MRI-based animal studies are more easily generalized to human applications. Many of the shortcomings of each modality alone can be overcome by the use of dual- or triple-modality reporter constructs that incorporate the opportunity for PET, fluorescence and bioluminescence imaging.