纳米抗体用于分子影像的研究进展

纳米抗体作为一种新型抗体片段,保留了完整的抗原结合部位,具有相对分子质量小、特异性高、亲和力强等特性,非常适于构建分子探针用于分子影像。体外实验显示,以纳米抗体为基础的分子影像探针与抗原的亲和力可达到nmol水平。在肿瘤、动脉粥样硬化、神经系统疾病等的动物模型中,纳米抗体分子探针可高特异性地结合到靶器官,未结合的部分由肾脏迅速排泄,具有较高的靶／血液（T／B）比值,可清晰显示病变组织。经结构改造或化学修饰后,纳米抗体与靶器官的亲和力和滞留量进一步提高,更有利于其在分子影像中的应用。随着相关研究的不断深入,以纳米抗体为基础的分子影像在疾病早期诊断及疗效评估中的良好应用前景日渐突显。     

纳米抗体分子影像探针的研究进展

纳米抗体凭借其优越的靶向性、稳定性、溶解度及组织穿透能力，已成为分子影像领域中的热门靶向分子。多种基于纳米抗体的分子影像探针在临床前研究和临床试验中均已展现出良好的诊断效能。笔者主要介绍纳米抗体分子影像探针在肿瘤中的最新研究进展，并进一步讨论其临床转化面临的挑战和应对策略。     

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。     

PET分子影像探针纳米颗粒的研发与应用现状

分子影像是应用影像学的方法对活体状态下的生物过程进行细胞和分子水平的定性和定量研究。其有利于疾病的早期诊断,确定疾病分期,提供病理过程基本机制以及疗效的随访。分子影像的发展有赖于细胞水平和分子水平精密影像探针的研发。纳米颗粒作为一种新兴的分子影像探针,能够提供更有效的图像对比,可在目标位置靶向聚集,同时其具有长效循环半衰期以及较高的荷载能力”[1]。     

分子影像在胶质瘤中的应用

胶质瘤是最常见的颅内肿瘤且恶性程度和致死率均较高。传统的影像技术对胶质瘤的诊断优势有限,很难提供胶质瘤分子水平的生物特性信息。分子影像学应用能与分子靶点特异性结合的探针,借助影像技术,可在体、无创、重复、实时地在细胞和分子水平上定性和定量地研究胶质瘤发生发展过程,为提高对胶质瘤生物行为、诊断及治疗方面的认识具有重要意义。目前正电子发射计算机断层显像（PET）是分子影像领域中领先的成像技术,同时也是分子影像的代表,并且随着高特异性分子成像探针的开发,将会使分子影像学在胶质瘤的诊断中彰显无尽的魅力。本文将对分子影像学在胶质瘤中的应用和研究进展进行综述。     

ICG纳米探针在早期结肠癌诊断中的应用及其价值

 

目的 评估ICG纳米探针在结肠癌荧光分子成像中的靶向性、荧光效应及其早期诊断价值。方法 建立裸鼠结肠癌皮下移植瘤模型,应用人血清白蛋白(HSA)包裹的ICG纳米探针,并以Folate RsenseTM680、吲哚菁绿作为对照组,经裸鼠结肠癌皮下移植瘤模型尾静脉注射探针后,进行活体荧光分子成像,观察HAS-ICG纳米探针的成像效果,量化分析肿瘤部位的荧光信号强度。结果 活体荧光分子成像结果显示:探针HAS-ICG、Folate RsenseTM680均在实验瘤鼠皮下肿瘤部位出现浓聚,浓聚高峰分别在注射后1 h、24 h。与对照组相比,HAS-ICG纳米探针比商业探针有较好的靶向标记性和信噪比。结论 HSA-ICG纳米探针具有很好的标记HCT116结肠肿瘤细胞的能力,可通过荧光分子成像技术诊断早期裸鼠结肠癌变。

     

放射性核素标记HER2亲和体分子探针精准诊疗的研究进展

人表皮生长因子受体2(HER2)亲和体分子因具有对靶组织亲和力高、特异性强、分子量小、制备简单、生物动力学特征良好等特点, 近年来在肿瘤分子影像方面的研究中显示出了较好的临床应用前景。放射性核素标记HER2亲和体分子探针不仅可以进行肿瘤受体显像及疗效评价, 还可以用于靶向治疗。笔者就目前放射性核素标记HER2亲和体分子探针精准诊疗的研究进展作简要综述。     

磁性纳米氧化铁粒子在肿瘤影像及治疗中的应用及进展

磁性纳米氧化铁粒子是指直径在纳米范围的氧化铁粒子,具有化学性质稳定、血液滞留时间长、低毒性、顺磁性、生物可降解性等特点,可通过静电作用或化学作用耦联多肽、单克隆抗体、化疗药物、基因片段等靶肿瘤功能分子,因而在肿瘤影像、治疗、研究中有着广泛的应用.该文对近年来磁性纳米氧化铁粒子在肿瘤影像及治疗中的应用及进展进行了评述.     

19F-MRI纳米探针设计及其肿瘤诊疗应用

【摘要】磁共振成像在肿瘤诊疗中扮演着重要角色,其中氢质子（1H）是MRI时最常用的原子核,但存在对比度不足、敏感度较低等问题,而利用19F原子核进行成像具有无内源性背景干扰的独特优势和能选择性成像的巨大潜力。近年来,纳米技术与分子影像技术充分融合使得基于19F的MRI纳米探针在癌症精准诊疗中凸显成效。本文概述了19F纳米探针的多功能制备策略,归纳其作为理想纳米诊疗探针应具备的材料性能,重点阐述其介导癌症诊疗的最新研究进展,并分析了该领域中存在的一些挑战和前景展望,旨在加深对19F MRI纳米诊疗探针研究现状的认识,推动探针分子设计和功能修饰进一步优化,使其早日实现临床转化。     

阿尔茨海默病分子影像探针的研究进展

阿尔茨海默病（AD）是一种进行性神经退行性疾病。β淀粉样蛋白（Aβ）沉积和过度磷酸化的Tau蛋白形成的神经原纤维缠结（NFT）是该病的病理学特征。在过去的20年中，分子影像探针在AD的诊疗中取得了很大进展，其作用已经超越了传统的脑灌注和葡萄糖代谢显像。与Aβ或NFT特异性结合的分子影像探针可成为准确和早期诊断AD的有价值工具，且其已被提出作为最近修订的临床诊断标准中的生物标志物。笔者主要对Aβ和NFT分子影像探针的研究进展进行综述。     

乳腺癌核素靶向诊疗一体化的研究进展

近年来,核医学仪器设备的发展以及新型特异性显像剂的出现和深入研究使乳腺癌特异性分子显像技术得以快速发展,这有利于乳腺癌的特异性诊断。同时,利用特定靶点进行的放射性核素靶向治疗还能逐步推进乳腺癌个体化治疗的发展。随着靶向分子探针的不断出现和分子靶向技术的不断完善,乳腺癌核素特异性显像和放射性核素靶向治疗将成为乳腺癌个体化诊疗的重要手段。笔者对受体、抗体和基因介导的乳腺癌核素靶向诊疗的研究进展进行综述,并介绍其诊疗一体化的改进策略和发展前景。     

Molecular imaging of reporter gene expression in prostate cancer: an overview

Prostate cancer remains an important and growing health problem. Advances in imaging of prostate cancer may help to achieve earlier and more accurate diagnosis and treatment. We review the various strategies using reporter genes for molecular imaging of prostate cancer. These approaches are emerging as valuable tools for monitoring gene expression in laboratory animals and humans. Further development of more sensitive and selective reporters, combined with improvements in detection technology, will consolidate the position of reporter gene imaging as a versatile method for understanding of intracellular biological processes and the underlying molecular basis of prostate cancer, as well as potentially establishing a future role in the clinical management of patients afflicted with this disease.     

Accelerating the development of novel molecular imaging probes: a role for high-throughput screening

Molecular imaging is a rapidly emerging research tool and clinical discipline aimed at noninvasive, quantitative visualization of in vivo molecular processes occurring at cellular and subcellular levels. At present, advancement of the molecular imaging field is driven by the development of improved imaging hardware for use in preclinical and clinical settings, the identification and validation of new, biologically relevant imaging targets, and the development of improved imaging probes derived from novel chemistries. Of these 3 essential facets, which comprise a majority of current molecular imaging research, hardware development and novel target discovery significantly outpace the development and clinical advancement of new molecular imaging probes, particularly with respect to cancer imaging.     

乳腺癌分子成像研究进展

乳腺癌的早期诊断及个体化治疗是提高病人生存率的关键。传统影像检查(如X线钼靶摄片、超声等)在早期诊断及对微转移灶检出能力上有明显的局限性,而基于靶向分子探针的分子成像可以在肿瘤瘤体形成前和/或形成后早期检测到细胞甚至分子水平上的异常,多功能的分子探针还可以集多模态成像和治疗于一体,获得更精确的影像学信息并进行针对性治疗。就乳腺癌分子成像研究进展进行综述。     

PET imaging of cancer immunotherapy.

Immune system activation can be elicited in viral infections, active immunization, or cancer immunotherapy, leading to the final common phenotype of increased glycolytic use by immune cells and subsequent detection by 18F-FDG PET. Because 18F-FDG is also used in baseline staging PET/CT scans and in tumor response assessment, physicians are faced with a unique challenge when evaluating tumor response in patients receiving cancer immunotherapy. The burgeoning field of cancer immunotherapy and the paucity of PET probes that can reliably differentiate activated immune cells from metabolically active cancer cells underscore the pressing need to identify and develop additional molecular imaging strategies. In an effort to address this concern, investigators have taken several molecular imaging approaches for cancer immunotherapy. Direct ex vivo labeling of T lymphocytes with radioactive probes before reinfusion represents the earliest attempts but has proven to be clinically limited because of significant PET probe dilution from proliferation of activated immune cells. Another approach is the indirect in vivo labeling of immune cells via PET reporter gene expression and involves the ex vivo genetic engineering of T lymphocytes with a reporter gene, reinfusion into the host, and the subsequent use of a PET probe specific for the reporter gene. The most recent approach involves the direct in vivo labeling of immune cells by targeting endogenous immune cell biochemical pathways that are differentially expressed during activation. In conclusion, these novel PET-based imaging approaches have demonstrated promise toward the goal of in vivo, noninvasive immune monitoring strategies for evaluating cancer immunotherapy.     

Targeted Molecular Imaging

Molecular imaging aims to visualize the cellular and molecular processes occurring in living tissues, and for the imaging of specific molecules in vivo, the development of reporter probes and dedicated imaging equipment is most important. Reporter genes can be used to monitor the delivery and magnitude of therapeutic gene transfer, and the time variation involved. Imaging technologies such as micro-PET, SPECT, MRI and CT, as well as optical imaging systems, are able to non-invasively detect, measure, and report the simultaneous expression of multiple meaningful genes. It is believed that recent advances in reporter probes, imaging technologies and gene transfer strategies will enhance the effectiveness of gene therapy trials.     

Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes

The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of vulnerable plaque and may allow for monitoring the efficacy of antiatherosclerotic therapies. In this review we focus on MR imaging strategies for the detection and evaluation of atherosclerotic plaques and their composition. We highlight recent advancements in the development of MR pulse sequences, computer image analysis, and the use of commercially available MR contrast agents, such as gadopentic acid (Gd-DTPA), for plaque characterization. We also discuss molecular imaging strategies that are currently being used to design specific imaging probes targeted to biochemical and cellular markers of atherosclerotic plaque vulnerability.     

靶向Tau蛋白PET分子探针的研究进展

Tau蛋白的异常累积是阿尔茨海默病（AD）及非AD类Tau蛋白病的主要病理学特征,并且与神经变性和认知障碍密切相关。近年来,第一代特异性Tau蛋白PET分子探针已经被研发,并进行了临床试验。因第一代PET分子探针中常出现脱靶结合,促进了具有更高结合力和选择性的第二代特异性Tau蛋白PET分子探针的研发。笔者综述了Tau蛋白PET显像作为AD病理学生物标志物的潜力和Tau蛋白分子探针的最新进展。     

Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell accumulation, endothelial activation, proteolysis, neoangiogenesis, hypoxia, apoptosis, and calcification. Many preclinical and clinical studies have been conducted with various imaging probes and some of them have exhibited promising results. Despite some limitations in imaging technology, molecular imaging is expected to be used both in the research and clinical fields as imaging instruments become more advanced.