转铁蛋白导向脂质体核磁造影剂纳米粒子(TfNTR-LipNBD-Magnevist)——一种肿瘤靶向磁共振造影剂

造影剂辅助的核磁共振成像是目前肿瘤诊断的最好方法之一.但是由于核磁共振成像内在的低灵敏性以及造影剂的非特异性,导致肿瘤早期诊断较为困难.文章将一种新的肿瘤靶向核磁造影剂纳米粒子应用于早期肿瘤的影像诊断.这种新的肿瘤靶向核磁造影剂纳米粒子由配体转铁蛋白(Tf)、纳米水平的正电脂质体(Lip)载体和临床常用的造影剂Magnevist(TfNIR-LipNBD-Magnevist)三部分构成.另外转铁蛋白和脂质体粒子上,亦标记了荧光物质用于确定转铁蛋白-脂质体-造影剂纳米粒子的靶向性,以及肿瘤的光学影像诊断.在体外实验中,利用激光共聚焦显微镜和光学影像证明了靶向纳米粒子介导的细胞内吞和特异性结合.在裸鼠肿瘤模型中,造影剂纳米粒子TfNIR-LipNBD-Magnevist经尾静脉注入后,显著增强了肿瘤内信号与周围组织的对比度.由造影剂纳米粒子介导的肿瘤内信号显著强于单独Magnevist辅助的肿瘤内信号.同时,利用光学影像方法,在肿瘤内检测到特异的荧光信号.其结果进一步支持了转铁蛋白-脂质体-造影剂(TfNIR-LipNBD-Magnevist)纳米粒子的靶向性和肿瘤影像诊断的有效性.     

纳米粒子在肝癌靶向治疗中的应用研究进展

增强抗癌药物对癌细胞的选择性、降低其毒副作用及提高疗效一直是肝癌治疗领域一项重要的研究课题,纳米药物载体的研究有望解决这些问题。目前纳米粒子在肝癌靶向治疗中的应用研究集中于被动靶向治疗、主动靶向治疗、基因治疗、栓塞化疗及纳米粒子的直接治疗作用等方面。     

纳米递送系统线粒体靶向策略在肿瘤诊疗中的应用

肿瘤是危害人类健康的重大疾病之一。目前用于肿瘤治疗的方法有手术治疗、化学药物治疗、放射治疗等。然而,传统的治疗方法存在治疗效果不佳、易引发多药耐药、毒副作用大等缺点,仍需进一步探索新的肿瘤治疗靶点和策略。线粒体作为细胞的能量转换器,被认为是肿瘤、心血管和神经性疾病新药设计的最重要靶点之一。纳米药物递送载体具有易被主动靶向基团修饰的特点,可实现细胞乃至细胞器的精准靶向给药。本文从抑制肿瘤细胞增殖、促进肿瘤细胞凋亡、抑制肿瘤复发与转移、诱导细胞自噬等方面综述了线粒体靶向纳米载体在肿瘤诊疗中的应用。     

多功能磁共振造影剂研究进展

磁共振成像技术因对人体无创、任意方向断层扫描三维图像且分辨率较高、提供形态与功能两方面诊断评价等突出优点,成为了临床上用于疾病诊断的重要手段之一。临床上使用磁共振造影剂可以提高成像的分辨率和灵敏度,提高图像质量,增强对比度和可读性。但是,各种成像技术由于实现原理不同,具有各自的优势和缺陷,靠传统单一的诊断模式无法提供疾病的全面信息,因而在对各种复杂疾病进行诊断时会受到一定的限制。因此,将磁共振成像与其他成像技术如CT成像、超声成像等联合起来使用,则可以达到优势互补的效果,能为疾病的临床诊断提供更快捷精确的信息,同时可将磁共振成像与各种治疗方式结合在一起,即开发基于磁共振成像的诊断治疗一体化试剂,以实现对疾病的即时治疗和实时监控。本文主要介绍了磁共振成像造影剂的原理和种类,并且综述了目前国内外在基于磁共振成像的多功能造影剂/诊疗制剂这一领域的研究进展,最后就未来可能的研究方向进行了展望。     

肿瘤靶向纳米载药系统的设计与构建

近年来将纳米载药系统应用于肿瘤靶向递药的研究层出不穷。与正常组织相比,肿瘤组织具有较低的pH环境、大量新生血管生成、 不规则的血流灌注、局部缺氧等特异性的微环境,利用这些特点进行合理的纳米载药系统设计能够实现肿瘤部位的高效递药及深层穿透, 显著提高肿瘤治疗效果。针对现有的肿瘤靶向纳米载药系统的构建与设计方法进行综述,以阐述纳米载药系统在肿瘤靶向传递中的研究进展     

Fe3O4磁性纳米粒子在生物医学领域的应用

Fe_3O_4磁性纳米粒子由于其良好的磁学性能,被广泛应用到了化学、生物、物理、环境保护等各个领域。尤其是在生物医学领域中的应用越来越受到研究者的关注。由于其所具有的优秀的超顺磁性性质,Fe_3O_4磁性纳米粒子可以作为造影剂,增强核磁共振成像的对比度和成像效果;也可以结合到纳米载药系统内用于药物的靶向输送;也可以包埋到蛋白内部用于蛋白的磁性分离;也可以用于基因治疗,提高靶细胞的转染效率;由于其在近红外光的作用下具有很好的光热转换效果,使温度升高,展现出的良好热疗效果,Fe_3O_4磁性纳米粒子又可以用于癌细胞的热疗。本文针对其在该领域中作为药物的靶向传递,蛋白的磁分离,核磁共振成像,热疗,以及基因治疗的载体等方面的研究应用进行了系统性的总结,阐述了Fe_3O_4磁性纳米粒子在生物医学领域中各种应用进展和优势。     

纳米粒子在肿瘤干细胞治疗方面的研究进展

癌症是严重威胁人类生命健康的常见疾病之一。肿瘤细胞中存在一小部分细胞,它们具有自我更新能力,增殖分化潜能,还具有很强的成瘤能力和耐受化疗、放疗的特性,它们被称之为肿瘤干细胞。肿瘤干细胞被认为是肿瘤发生、耐药性和术后复发的根源。因此消灭肿瘤干细胞是治愈肿瘤的关键。针对肿瘤干细胞治疗的纳米药物逐渐引起人们的重视,它们具有可控缓释、靶向、生物相容性高等优点,特别是在纳米药物载体和纳米基因载体方面已经取得了显著的研究成果。然而,这些纳米药物在体内的靶向效率、稳定性、代谢途径和毒性等还需要系统的考察和检验,为其在临床上的应用打下良好的基础。本文主要综述了纳米粒子在肿瘤干细胞治疗方面的应用研究,并对纳米粒子在肿瘤干细胞治疗中存在的问题和未来的研究方向进行了展望。     

碳包铁纳米粒子作为磁性靶向药物载体的物理性能研究

一种全新的磁靶向纳米药物载体——用直流碳弧法制备的碳包铁纳米粒子,它具有独特的纳米结构,在石墨碳层中完全包裹进铁纳米颗粒,实现在纳米碳包围中的纳米磁性粒子分散状态,其中的纳米碳具有大的比表面积和较高的化疗药物吸附量,达到每毫克吸附160μg的表阿霉素。铁纳米粒子磁场强,靶向效果好,有较佳的磁靶向发热效应,在动物病灶局部放置0.1g碳包铁纳米粒子将能使发热温度平均升到52℃;而将碳包铁纳米粒子均匀与猪肝混合也有明显的产热效果:含量0.4%碳包铁纳米粒子的一组猪肝能将温度升到42℃,而含量0.6%碳包铁纳米粒子的一组猪肝能将温度升到48℃。X射线衍射表明借助于碳的包裹,碳包铁纳米粒子有好的抗氧化性和稳定性。碳包铁纳米粒子有可能作为一种全新的磁性靶向药物载体用于癌症治疗。     

硫化铜纳米粒子应用于肿瘤诊断和治疗的研究进展

癌症是当今威胁人类健康的主要疾病之一。近年来提出的近红外光介导的光热治疗,能够对肿瘤组织进行定点清除并且对正常组织具有较低的毒副作用,为肿瘤的治疗提供了新的方法。开发具有良好生物相容性的高效光热偶联剂是发展光热治疗的首要条件。随着纳米技术的飞速发展,一些金属纳米结构由于具有独特的光学特性作为光热偶联剂被广泛应用到肿瘤的光热治疗中。然而,成本高昂、制备过程繁琐以及光热稳定性较差等不足,限制了这些纳米材料的进一步应用。最新报道的新型光热偶联剂半导体硫化铜纳米粒子(copper sulfide nanoparticles,CuS NPs),由于其具有制备工艺简单、成本低廉、突出的光热稳定性和良好的生物相容性等优势,成为了当今纳米医学领域研究的热点。本文主要综述了CuS纳米粒子在肿瘤光热治疗和影像诊断方面的应用研究,并对CuS纳米粒子在生物医学领域应用中存在的问题和未来的研究方向进行了展望。     

靶向吲哚菁绿纳米探针介导的光声治疗

光声治疗是一种利用纳米材料的光声效应选择性破坏癌细胞的方法。本研究采用叶酸作为肿瘤靶向分子,以聚乙二醇包裹吲哚菁绿形成纳米粒子(ICG-PL-PEG-FA),利用此纳米粒子在近红外区的光吸收特性,开展光声治疗研究。实验结果表明,这种叶酸标记的纳米探针对高表达叶酸的EMT6细胞具有高靶向选择性和靶向光杀伤性。这种基于包含吲哚菁绿纳米探针的光声治疗将有潜力发展为一种安全,高效的癌症治疗技术。     

Contrast Enhanced MRI Assessment of Tumor Blood Volume After Application of Electric Pulses

The effect of application of short, intense electric pulses on tumor blood volume was investigated using albumin-(Gd-DTPA)₃₀ contrast-enhanced magnetic resonance imaging (MRI). One of paired SA-1 fibrosarcoma tumors implanted in each flank of A/J mice was treated with electric pulses. MRI was performed dynamically before and after intravenous administration of albumin-(Gd-DTPA)₃₀ (0.02 mmol Gd/kg), and fractional tumor blood volume was estimated. MRI images of tumors exposed to electric pulses showed no enhancement at 30 min after injection of albu-min-(Gd-DTPA)₃₀. However, marked enhancement was observed in paired tumors of the same mice that were not exposed to electric pulses. A significant difference in blood volume was observed between nontreated tumors and tumors treated with electric pulses. Application of electric pulses to the tumors significantly reduced blood volume in the tumors. Therefore, through a reduction in tumor blood volume, electric pulses may, besides producing electroporation of cells, exert antitumor effectiveness by entrapping drugs within the tumors.     

MRI在甲状腺肿瘤的肿块定位和良恶性判断中的应用研究

目的:总结甲状腺肿瘤的核磁共振成像(MRI)影像学表现,评价MRI在甲状腺肿瘤的肿块定位及良恶性判断中的应用价值。方法:选取我院外科收治的经MRI诊断为甲状腺癌的患者60例,总结所有患者的影像学资料,并将其与诊断金标准(病理学检查结果)相比较,分析MRI检查诊断累及组织和鉴别良恶性甲状腺肿瘤的准确率等。结果:MRI影像学结果清晰可见甲状腺肿瘤的部位、形态、密度、边界及是否有钙化等重要征象;MRI对良恶性肿瘤诊断准确性为95.0%。MRI对肿瘤累积膜外脂肪、肿瘤的淋巴结以及肿瘤的食管转移均有较高的准确性、敏感性与特异性。结论:MRI影像学检查清晰可见甲状腺肿瘤的部位、形态、密度、边界及是否有钙化等重要征象,对临床上甲状腺肿瘤的肿块定位及良恶性鉴别诊断具有重要的参考意义。     

In vivo assessment of nodularin-induced hepatotoxicity in the rat using magnetic resonance techniques (MRI, MRS and EPR oximetry)

Acute nodularin-induced hepatotoxicity was assessed in vivo, in rats using magnetic resonance (MR) techniques, including MR imaging (MRI), MR spectroscopy (MRS), and electron paramagnetic resonance (EPR) oximetry. Nodularin is a cyclic hepatotoxin isolated from the cyanobacterium Nodularia spumigena. Three hours following the intraperitoneal (i.p.) administration of nodularin (LD50), a region of 'damage', characterized by an increase in signal intensity, was observed proximal to the porta hepatis (PH) region in T2-weighted MR images of rat liver. Image analysis of these regions of apparent 'damage' indicated a statistically significant increase in signal intensity around the PH region following nodularin administration, in comparison with controls and regions peripheral to the PH region. An increase in signal intensity was also observed proximal to the PH region in water chemical shift selective images (CSSI) of nodularin-treated rat livers, indicating that the increased signal observed by MRI is an oedematous response to the toxin. Microscopic assessment (histology and electron microscopy) and serum liver enzyme function tests (aminotransferase (ALT) and aspartate ALT (AST)) confirmed the nodularin-induced tissue injury observed by MRI. In vivo and in vitro MRS was used to detect alterations in metabolites, such as lipids, Glu+Gln, and choline, during the hepatotoxic response (2-3 h post-exposure). Biochemical assessment of perchloric acid extracts of nodularin-treated rat livers were used to confirm the MRS results. In vivo EPR oximetry was used to monitor decreasing hepatic pO2 (approximately 2-fold from controls) 2-3 h following nodularin exposure. In vivo MR techniques (MRI, MRS and EPR oximetry) are able to highlight effects that may not have been evident in single end point studies, and are ideal methods to follow tissue injury progression in longitudinally, increasing the power of a study through repeated measures, and decreasing the number of animals to perform a similar study using histological or biochemical techniques.     

A review of technical aspects of T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in human brain tumors

In the last few years, several imaging methods, such as magnetic resonance imaging (MRI) and computed tomography, have been used to investigate the degree of blood–brain barrier (BBB) permeability in patients with neurological diseases including multiple sclerosis, ischemic stroke, and brain tumors. One promising MRI method for assessing the BBB permeability of patients with neurological diseases in vivo is T₁-weighted dynamic contrast-enhanced (DCE)-MRI. Here we review the technical issues involved in DCE-MRI in the study of human brain tumors. In the first part of this paper, theoretical models for the DCE-MRI analysis will be described, including the Toft–Kety models, the adiabatic approximation to the tissue homogeneity model and the two-compartment exchange model. These models can be used to estimate important kinetic parameters related to BBB permeability. In the second part of this paper, details of the data acquisition, issues related to the arterial input function, and procedures for DCE-MRI image analysis are illustrated.     

Magnetic resonance imaging and spectroscopy (MRI, MRS) of seasonal patterns of body composition: A methodological pilot study in White Storks (Ciconia ciconia)

Summary Here we present a systematic application of magnetic resonance imaging (in the following called MRI) and magnetic resonance spectroscopy (MRS) to the White Stork. The main aim was to demonstrate the annual cycle of fat deposition in the same individuals for comparison to wild conspecifics, to clarify the energy metabolism of this migratory species. To obtain sharp, high-contrast images of the interior of the body, the birds were kept still by enclosing them in simple plastic tubes with additional fixation of legs and head, avoiding the problematic sedation with drugs. Altogether 12 test birds (young storks) were monitored systematically for 15 months, to follow seasonal changes in the internal organs (mainly breast muscles) and tissues (mainly fat depots). At each examination 22 high-contrast pixel images representing serial dorsoventral sections through the body were generated with the computer program MatLab, after which the pixels per section image were converted to tissue components in cm² and the distances between consecutive sections used to calculate the tissue volumes in cm³. To measure the fat in the breast muscle spectroscopy was used to determine the fat : water ratio, from which changes in fat content could be derived. The study revealed pronounced seasonal changes in the visceral and cutaneous/subcutaneous fat depots, which precisely paralleled the annual variation in body weight of the birds (see also the preceding paper, Berthold et al. 2001). The breast muscles exhibited the prolonged growth typical of the juveniles of large species but no conspicuous change at the migration periods. In this project MRI and MRS proved to be successful methods that show great promise.

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Magnet-Resonanz-Tomographie und -Spektroskopie der jahreszeitlichen Muster der Körperzusammensetzung: Eine methodische Pilotstudie am Weißstorch (Ciconia ciconia)

Zusammenfassung In der vorliegenden Arbeit stellen wir eine systematische Anwendung der Magnet-Resonanz-Tomographie (Kernspin-Tomographie, im Folgenden MRT) und der Magnet-Resonanz-Spektroskopie (im Folgenden MRS) am Weißstorch vor. Hauptaufgabe war es, die Jahresperiodik der Fettdeposition an denselben Individuen zu ermitteln, um Aufschluss über den Energiehaushalt dieser Zugvogelart durch Vergleiche mit freilebenden Vögeln zu bekommen. Die erforderliche Ruhigstellung der Vögel zum Erreichen scharfer kontrastreicher Bilder des Körperinneren war in einfachen Plastikröhren mit zusätzlicher Fixierung von Beinen und Kopf möglich, so dass auf die problematische Sedierung mit Narkotika verzichtet werden konnte. Insgesamt 12 Versuchsvögel (Jungstörche) wurden 15 Monate lang systematisch auf jahresperiodische Veränderungen von inneren Organen (v. a. Brustmuskeln) und Geweben (v. a. Fettdepots) untersucht. Aus je 22 seriellen kontrastreichen dorsoventralen Schnittbildern durch den Vogelkörper ließen sich mit dem Computerprogramm MatLab Pixelbilder erstellen und dann die Pixel pro Schnittbild in Gewebeanteile in cm² umrechnen und anschließend aus den aufeinander folgenden Schnittbildern die Gewebevolumina in cm³ ermitteln. Für die Fettbestimmung im Brustmuskel wurde durch Spektroskopie das Verhältnis von Fett: Wasser bestimmt, aus dem Veränderungen des Fettgehalts abgeleitet wurden. Die Studie ergab ausgeprägte jahresperiodische Änderungen der viszeralen und kutanen/subkutanen Fettdepots, die genau parallel zum Jahresgang des Körpergewichts der Vögel verliefen (s. auch die vorangehende Arbeit, Berthold et al. 2001). Für die Brustmuskeln ergab sich ein für Jungvögel großer Arten typisches lang anhaltendes Wachstum, aber keine auffallende Veränderung zu den Zugperioden. MRT und MRS erwiesen sich in dieser Arbeit als erfolgreich und vielversprechend.

     

Contrast agents for magnetic resonance angiographic applications: 1H and 17O NMR relaxometric investigations on two gadolinium(III) DTPA-like chelates endowed with high binding affinity to human serum albumin

N,N′,N″,N‴ -pentaacetic acid) bearing different substituents for binding to human serum albumin (HSA) are compared. In spite of the structural differences of the recognition synthon and of the residual electric charge, the two chelates display an analogous binding affinity for the serum protein. Upon formation of the adducts with HSA, the exchange rates of the coordinated water appear slowed down by an amount corresponding to ca. 50% of the rates found for the free complexes. The relaxivity of [Gd(BOM)₃DTPA (H₂O)]^2 − is significantly higher than that of MS-325 either in the free complex or in the macromolecular adduct. Finally, the effect of pH on the stability of the HSA adducts and on the values of their relaxivities has been investigated. Received: 11 June 1999 / Accepted: 15 September 1999     

A prospective comparative dosimetric study between diffusion weighted MRI (DWI) & T2-weighted MRI (T2W) for target delineation and planning in cervical cancer brachytherapy

AimTo evaluate the difference between GTVBT (Gross Tumor Volume at Brachytherapy) and HR CTV (High Risk Clinical Tumor Volume) delineated with DWI and T2W MRI. To evaluate doses to organs at risk and targets from plans generated using T2W and DWI.BackgroundFunctional imaging with DWI can improve cervical tumor distinction as it is more sensitive than T2W MRI even in detecting parametrial invasion. This study does a dosimetric comparison between a T2W and DWI based plan.MethodsFifty carcinoma cervix patients were subjected to MRI based brachytherapy. T2W and a diffusion weighted sequence were acquired. Target delineation and brachytherapy planning was done on both T2W and DWI. Standard DVH parameters were recorded and the treatment was given using the plan generated from T2W images.ResultsGTVBT and HRCTV contours on DWI were different when compared with T2W. Mean GTVBT volume on T2W and DWI was 5.25 and 5.23, respectively (p value 0.8). Mean HRCTV on T2W and DWI was 28.3 and 27 cc, respectively (p value 0.003). Planning on the above volumes resulted in a superior coverage in terms of HRCTV D90 and D100 for DWI based plan, HRCTV D90 — 735.1 and 741 cGy for T2W and DWI, respectively (p value 0.006), HRCTV D100 — 441.05 and 444.5 for T2W and DWI plans, respectively (p value = 0.006). Doses to the OAR were not significantly increased.ConclusionGEC ESTRO based contouring guidelines cover all the functionally abnormal areas on DWI. DWI should only be used as a supplement to T2W for contouring target volumes.     

Water uptake and oil distribution during imbibition of seeds of western white pine (<Emphasis Type="Italic">Pinus monticola</Emphasis> Dougl. ex D. Don) monitored in vivo using magnetic resonance imaging

Dry or fully imbibed seeds of western white pine (Pinus monticola Dougl. ex D. Don) were studied using high-resolution magnetic resonance imaging (MRI). Analyses of the dry seed revealed many of the gross anatomical features of seed structure. Furthermore, the non-invasive nature of MRI allowed for a study of the dynamics of water and oil distribution during in situ imbibition of a single seed with time-lapse chemical shift selective MRI. During soaking of the dry seed, water penetrated through the seed coat and megagametophyte. The cotyledons of the embryo (located in the chalazal end of the seed) were the first to show hydration followed by the hypocotyl and later the radicle. After penetrating the seed coat, water in the micropylar end of the seed likely also contributed to further hydration of the embryo; however, the micropyle itself did not appear to be a site for water entry into the seed. A model that describes the kinetics of the earlier stages of imbibition is proposed. Non-viable pine seeds captured with MRI displayed atypical imbibition kinetics and were distinguished by their rapid and uncontrolled water uptake. The potential of MR microimaging for detailed studies of water uptake and distribution during the soaking, moist chilling (stratification), and germination of conifer seeds is discussed.Electronic Supplementary Material Supplementary material is available for this article if you access the article at . A link in the frame on the left on that page takes you directly to the supplementary material.