分子成像技术的研究进展

分子成像是新时代的医学成像,它可以无创性监测活体内的细胞和分子水平的生物学过程,其中包括核医学分子显像、磁共振分子成像、超声分子成像、光学分子成像和X射线分子成像等.目前,由于多学科融合的发展,多模式融合成像技术已成功用于临床,如PET-CT和PET-MRI.随着分子探针的发展和多模式融合成像技术的成熟,越来越多的分子...     

Molecular body imaging: MR imaging, CT, and US. part I. principles

Molecular imaging, generally defined as noninvasive imaging of cellular and subcellular events, has gained tremendous depth and breadth as a research and clinical discipline in recent years. The coalescence of major advances in engineering, molecular biology, chemistry, immunology, and genetics has fueled multi- and interdisciplinary innovations with the goal of driving clinical noninvasive imaging strategies that will ultimately allow disease identification, risk stratification, and monitoring of therapy effects with unparalleled sensitivity and specificity. Techniques that allow imaging of molecular and cellular events facilitate and go hand in hand with the development of molecular therapies, offering promise for successfully combining imaging with therapy. While traditionally nuclear medicine imaging techniques, in particular positron emission tomography (PET), PET combined with computed tomography (CT), and single photon emission computed tomography, have been the molecular imaging methods most familiar to clinicians, great advances have recently been made in developing imaging techniques that utilize magnetic resonance (MR), optical, CT, and ultrasonographic (US) imaging. In the first part of this review series, we present an overview of the principles of MR imaging-, CT-, and US-based molecular imaging strategies.     

Small-animal preclinical nuclear medicine instrumentation and methodology

Molecular medicine enhances the clinician's ability to accurately diagnose and treat disease, and many technological advances in diverse fields have made the translation of molecular medicine to the clinic possible. Nuclear medicine encompasses 2 technologies--single-photon emission computed tomography (SPECT) and positron emission tomography (PET)--that have driven the field of molecular medicine forward. SPECT and PET, inherently molecular imaging techniques, have been at the forefront of molecular medicine for several decades. These modalities exploit the radioactive decay of nuclides with specific decay properties that make them useful for in vivo imaging. As recently as the mid-1990s, SPECT and PET were mostly restricted to use in the clinical setting because their relatively coarse spatial resolution limited their usefulness in studying animal (especially rodent) models of human disease. About a decade ago, several groups began making significant strides in improving resolution to the point that small-animal SPECT and PET as a molecular imaging technique was useful in the study of rodent disease models. The advances in these 2 techniques progressed as the result of improvements in instrumentation and data reconstruction software. Here, we review the impact of small-animal imaging and, specifically, nuclear medicine imaging techniques on the understanding of the biological basis of disease and the expectation that these advances will be translated to clinical medicine.     

Genomics, proteomics, MEMS and SAIF: which role for diagnostic imaging?

In these three words--genomics, proteomics and nanotechnologies--is the future of medicine of the third millennium, which will be characterised by more careful attention to disease prevention, diagnosis and treatment. Molecular imaging appears to satisfy this requirement. It is emerging as a new science that brings together molecular biology and in vivo imaging and represents the key for the application of personalized medicine. Micro-PET (positron emission tomography), micro-SPECT (single photon emission computed tomography), micro-CT (computed tomography), micro-MR (magnetic resonance), micro-US (ultrasound) and optical imaging are all molecular imaging techniques, several of which are applied only in preclinical settings on animal models. Others, however, are applied routinely in both clinical and preclinical setting. Research on small animals allows investigation of the genesis and development of diseases, as well as drug efficacy and the development of personalized therapies, through the study of biological processes that precede the expression of common symptoms of a pathology. Advances in molecular imaging were made possible only by collaboration among scientists in the fields of radiology, chemistry, molecular and cell biology, physics, mathematics, pharmacology, gene therapy and oncology. Although until now researchers have traditionally limited their interactions, it is only by increasing these connections that the current gaps in terminology, methods and approaches that inhibit scientific progress can be eliminated.     

Current research in nuclear medicine and molecular imaging: highlights of the 23rd Annual EANM Congress

The most recent research developments in nuclear medicine and molecular imaging were presented at the 2010 Annual Congress of the EANM. This review summarizes some of the most relevant contributions made in the fields of oncology, cardiovascular science, neurology and psychiatry, technological innovation and novel tracers. Presentations covered basic and clinical research in nuclear medicine and molecular imaging, and diagnostic and therapeutic applications of radioisotopes and radiopharmaceuticals on a global scale. The results reported demonstrate that investigative strategies using nuclear medicine techniques facilitate effective diagnosis and management of patients with most prevalent disease states. At the same time novel tracers and technologies are being explored, which hold promise for future new applications of nuclear medicine and molecular imaging in research and clinical practice.     

From protein–protein interaction to therapy response: Molecular imaging of heat shock proteins

HSP70 promoter-driven gene therapy and inhibition of HSP90 activity with small molecule inhibitors are two shining points in a newly developed cohort of cancer treatment. For HSP70 promoters, high efficiency and heat inducibility within a localized region make it very attractive to clinical translation. The HSP90 inhibitors exhibit a broad spectrum of anticancer activities due to the downstream effects of HSP90 inhibition, which interfere with a wide range of signaling processes that are crucial for the malignant properties of cancer cells. In this review article, we summarize exciting applications of newly emerged molecular imaging techniques as they relate to HSP, including protein–protein interactions of HSP90 complexes, therapeutic response of tumors to HSP90 inhibitors, and HSP70 promoters-controlled gene therapy. In the HSPs context, molecular imaging is expected to play a vital role in promoting drug development and advancing individualized medicine.     

Molecular imaging of musculoskeletal diseases

Chronic musculoskeletal diseases such as arthritis, malignancy, chronic injury/ inflammation, and chronic musculoskeletal pain often pose challenges for current clinical imaging modalities. There is hope that a growing field, referred to as "molecular imaging," will shed new light on these chronic phenomenon as it aims to noninvasively detect special molecular and physiologic effects such as metabolism rate, specific proteins, cell death, and particular gene-related events. Molecular imaging represents recent advances in imaging technology, engineering, chemistry, molecular biology, and genetics that have coalesced into a multidisciplinary and multimodality effort. Molecular probes are currently being developed not only in radionuclide-based techniques but also in magnetic resonance imaging, magnetic resonance spectroscopy, ultrasound, and the emerging field of optical imaging. Furthermore, molecular imagers are fueling the development of novel molecular therapies and gene therapy, as tracking these efforts in living subjects is now possible with molecular imaging protocols.     

Nuclear medicine at a crossroads

The growth of molecular imaging heightens the promise of clinical nuclear medicine as a tool for individualization of patient care and for improvement of health-care outcomes. Together with greater use of integrated structure-function imaging, clinical nuclear medicine reaches beyond traditional specialty borders into diagnostic radiology and oncology. Yet, there are concerns about the future of nuclear medicine, including progressively declining reimbursement, the competitive advantages of diagnostic radiology, limited translation of research accomplishments to clinical diagnostic imaging and patient care, and an insufficient pool of incoming highly qualified nuclear medicine clinicians. Thus, nuclear medicine views itself as being at a critical crossroads. What will be important is for nuclear medicine to be positioned as the quintessential molecular imaging modality more centrally within medical imaging and for the integration of nuclear medicine with primary care specialties to be driven more by patient needs than by specialty needs. In this way, the full potential of nuclear medicine as an effective and efficient tool for improving patient outcomes can be realized.     

放射性核素标记的凋亡显像剂的研究进展

细胞凋亡存在于多种病理过程中, 包括神经系统变性疾病、缺血性损伤、自身免疫性疾病和多种肿瘤等。凋亡检测的可视化对疾病的诊断、新的治疗方法的开发与疗效评价具有重要意义。传统的凋亡检测方法包括光学显微镜观察、原位末端标记法分析、流式细胞仪检测等, 但其侵入性方式限制了之后的随访研究。而活体内凋亡显像有助于无创观察、直观了解凋亡发生的体内过程。PET与SPECT的发展, 以及新的针对靶点的放射性核素标记显像剂的合成, 使核医学进入了分子影像学的新时代。近年来, 细胞凋亡PET与SPECT显像剂的研发应用, 使活体内无创PET与SPECT检测细胞凋亡成为现实。笔者主要介绍用于在体凋亡显像的放射性标记探针及其最新研究应用进展。     

Receptors and markers: toward a science of imaging through hybridization

Genomic- and proteomic-based imaging will enable the selection of populations and individuals "at risk"of suffering a certain disease before the clinical symptoms appear, identifying the existence, location, and extension of the bases of the disease, stratifying the risk, and making it possible to carry out and control treatments designed for each patient. In order to be efficacious, these molecular imaging techniques must generate both functional and structural information. The use of imaging probes together with advanced equipment allows numerous molecular complexes and cellular structures to be seen. Molecular imaging makes it possible to acquire, whether directly or indirectly, information about the spatial and temporal distribution of molecular or cellular processes that have not only clinical (diagnostic and therapeutic) applications but also basic (biochemical and physiological) applications. In the clinical area, nuclear medicine and radiology must work together to lead the development, implementation, and technological evaluation of molecular imaging. From this perspective, molecular hybridization techniques must progress toward the coordination of efforts, in training and in application as well as in research, to enable us to develop fully as imaging professionals in the service of healthcare. Molecular imaging provides imaging physicians with the possibility to advance substantially in early diagnosis, in the stratification of risk and prognosis, as well as in treatment monitoring in numerous biological and cellular processes related to the disease.     

Cell-based therapies and imaging in cardiology

Cell therapy for cardiac repair has emerged as one of the most exciting and promising developments in cardiovascular medicine. Evidence from experimental and clinical studies is increasing that this innovative treatment will influence clinical practice in the future. But open questions and controversies with regard to the basic mechanisms of this therapy continue to exist and emphasise the need for specific techniques to visualise the mechanisms and success of therapy in vivo. Several non-invasive imaging approaches which aim at tracking of transplanted cells in the heart have been introduced. Among these are direct labelling of cells with radionuclides or paramagnetic agents, and the use of reporter genes for imaging of cell transplantation and differentiation. Initial studies have suggested that these molecular imaging techniques have great potential. Integration of cell imaging into studies of cardiac cell therapy holds promise to facilitate further growth of the field towards a broadly clinically useful application.     

Current Status of Optical Imaging for Evaluating Lymph Nodes and Lymphatic System

Optical imaging techniques use visual and near infrared rays. Despite their considerably poor penetration depth, they are widely used due to their safe and intuitive properties and potential for intraoperative usage. Optical imaging techniques have been actively investigated for clinical imaging of lymph nodes and lymphatic system. This article summarizes a variety of optical tracers and techniques used for lymph node and lymphatic imaging, and reviews their clinical applications. Emerging new optical imaging techniques and their potential are also described.     

分子核医学的发展和应用前景

分子核医学是分子影像学的重要组成部分,主要包括PET和SPECT技术。目前,CT、MRI、超声、光学成像等影像技术与分子核医学影像技术的融合,以及多模式放射性药物探针的研究及应用成为核医学的主要发展方向。分子核医学在疾病的生物治疗疗效评估研究,基因治疗及其监测,干细胞生长、繁殖、迁移监测,以及新药的开发和筛选等生命科学研究方面将有越来越广泛的应用。     

分子核医学的发展和应用前景

分子核医学是分子影像学的重要组成部分,主要包括PET和SPECT技术.目前,CT、MRI、超声、光学成像等影像技术与分子核医学影像技术的融合,以及多模式放射性药物探针的研究及应用成为核医学的主要发展方向.分子核医学在疾病的生物治疗疗效评估研究,基因治疗及其监测,干细胞生长、繁殖、迁移监测,以及新药的开发和筛选等生命科学研究方面将有越来越广泛的应用.     

The molecular imaging approach to image infections and inflammation by nuclear medicine techniques

Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine techniques, by contrast, allow the in vivo detection in humans of different physiologic and pathologic phenomena and offer noninvasive tools to detect early pathophysiological changes before anatomical changes occur. In this review, we highlight the role of nuclear medicine in inflammation/infection with emphasis on molecular imaging for in vivo histological characterization of affected tissues for diagnostic purposes and follow-up of therapies. We also describe the clinical indications of all available radiopharmaceuticals in the light of the newly available guidelines.     

Regulatory and reimbursement challenges for molecular imaging

Molecular imaging is being hailed as the next great advance for imaging. Since molecular imaging typically involves the use of specific imaging probes that are treated like drugs, they will require regulatory approval. As with any drug, molecular imaging probes and techniques will also require thorough assessment in clinical trials to show safety and efficacy. The timeline for the regulatory approval will be long and potentially problematic because of the mounting costs of obtaining final regulatory approval. The current article is a detailed review of the regulatory and reimbursement process that will be required for molecular imaging probes and techniques to become a widespread clinical reality. The role of molecular imaging in the therapeutic drug discovery process will also be reviewed, as this is where these exciting new techniques have the potential to revolutionize the drug discovery and development process and, it is hoped, make it less costly. [(18)F]fluoro-2-deoxy-2-D-glucose positron emission tomography, one of the first molecular imaging techniques to be widely used, will be used as an example to illustrate the process of obtaining eventual reimbursement for widespread clinical use.     

Alternative breast-imaging approaches

Although conventional breast-imaging techniques routinely include mammography and ultrasound, growing interest in other approaches, perhaps most notably MR imaging, has drawn increasing attention to exploiting the anatomic and physiologic basis for understanding breast cancer. Nuclear medicine techniques have been applied in several circumstances with the intent of approaching or defining a role for molecular imaging, exemplified by the use of F-18 fluorodeoxyglucose and positron emission tomography. Other techniques, including exploitation of additional components of the electromagnetic spectrum, have provided novel concepts that may ripen into clinical use.     

Gene expression and gene therapy imaging

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters.     

放射性核素标记的成纤维细胞活化蛋白抑制剂在肿瘤诊疗一体化中的研究进展

癌相关成纤维细胞（CAFs）是实体瘤肿瘤微环境中的重要成分之一。成纤维细胞活化蛋白（FAP）特异性高表达于CAFs,在大多数正常组织中不表达或低表达,是一种很有前景的肿瘤诊断与治疗靶点。近年来,放射性核素标记靶向FAP的分子探针在肿瘤的诊断和治疗中已取得一系列研究进展。笔者对FAP抑制剂（FAPI）新型分子影像探针在肿瘤诊断、辅助临床治疗决策优化及核素靶向治疗等方面进行综述,以期更深入地了解FAPI探针在核医学肿瘤诊疗中的临床应用价值。