Gd(Ⅲ)-DOTA类磁共振成像造影剂的合成策略与进展

近年来,基于钆(Ⅲ)的磁共振成像造影剂(GBCAs)受到了前所未有的挑战,迫切需要开发更安全、更惰性、靶向性、生化响应性钆(Ⅲ)基造影剂。由于环状多胺多羧类配体(如DOTA)更易于被功能性基团修饰,且其钆(Ⅲ)配合物比线性多胺多羧类钆(Ⅲ)配合物(如Gd-DTPA)具有更高的热力学稳定性和动力学惰性,因此在研发新型钆(Ⅲ)基造影剂领域备受青睐。以典型的DOTA类双功能造影剂配体(BFCAs)的设计、合成及应用为主线,重点介绍Gd-DOTA类造影剂的合成策略与进展。     

碘基CT造影剂的研究进展

作为一种成熟的组织成像手段, CT被广泛应用于各种科学研究和临床检测。碘作为一种经典的X-ray衰减原子,将其引入而得到的CT造影剂已被广泛应用于临床。含碘CT造影剂在增加水溶性、降低渗透压和粘度、赋予靶向功能等多方面的研究也受到广泛的关注。近年来含碘造影剂在低生物毒性和组织特异性等方面的研究成果不断被报道。本文就近年来含碘造影剂的发展及研究现状进行了综述。     

生物高分子磁性微球的制备及靶向给药应用

生物高分子磁性微球因具有磁效应、生物相容性和多种反应活性功能基团等特性,使其能广泛应用于生物医学、细胞学和生物工程等领域。综述了近年来生物高分子磁性微球的制备方法以及作为靶向给药载体的应用。     

靶向载药PLA复合微泡超声造影剂的制备

目的制备一种基于生物材料氧化石墨烯(GO)靶向性和载药性的聚乳酸(PLA)复合微泡超声造影剂,并对其理化特性和体外超声显影效果进行研究。方法采用复乳化-溶剂挥发法制备靶向载阿霉素PLA复合微泡超声造影剂(FA-DOX/GO-DOX/PLA)。对复合微泡外观形态、粒径、电位和复合微泡中DOX和GO的负载率进行表征。使用多普勒彩色超声仪观察复合微泡的超声显影效果。结果所制备靶向载药PLA复合微泡呈规则圆整的球形,粒径分布集中,平均粒度为600 nm左右,Zeta电位为(-37.5±10.0)m V,复合微泡中DOX负载率为7.42%、GO负载率为19.56%,复合微泡超声造影功能显著。结论制备的靶向载药PLA复合微泡粒径均匀、载药率较高、稳定性较好,超声显影效果理想。     

含吗啉基团三唑类化合物的合成

近些年来,随着恶性肿瘤发病率的升高,使恶性肿瘤成为了威胁人类生命的最主要疾病,这就使得对于抗肿瘤药物的研制成为了一个非常重要的热门。在研制当中,人们发现关于溶酶体的靶向定位功能对肿瘤的治疗有着关键的作用。我们通过点击反应在微波的条件下生成含吗啉基团的三唑化合物,而这种化合物与溶酶体可以进行靶向定位作用,最后通过IR、1H NMR、13C NMR、HRMS检测手段来测试其合成产物的细胞活性。     

携抗纳米超声造影剂对动脉粥样硬化的诊断研究

目的:评价靶向于易损的血管斑块的纳米级磷脂超声造影剂在诊断动脉粥样硬化中的可行性。方法:应用生物素亲和素法和乳化溶剂挥发法制备载VEGFR-2靶向抗体纳米微泡。结果:靶向纳米微泡具有可控的纳米尺度的粒径,靶向抗体特异性的绑定在纳米微泡上,具有高抗体结合率。结论:靶向纳米微泡能够用于超声对比成像,并有识别动脉粥样硬化斑块的能力。     

体内评价携抗ICAM-1聚合物微泡作为靶向超声造影剂

目的:讨论携抗ICAM-1的靶向超声造影剂在诊断动脉粥样硬化中的可行性。方法使用碳二亚胺法,在聚合物微泡表面修饰携抗ICAM-1,使这种微泡能够靶向定位于动脉粥样硬化斑块。结果:光学显微镜和扫描电镜结果指出微泡具有可控的微米级的粒径,荧光显微镜和流式细胞仪显示了靶向配体和微泡之间较高的结合率,体内超声成像实验证实了微泡在靶向超声成像的利用性。结论:制备的微泡具有大小均匀,粒径分布窄和抗体携带率高等特点,使其能够在体内识别动脉粥样硬化斑块而应用于靶向超声对比成像     

反应型阻燃聚氨酯研究进展

综述了具有含磷基团、含氮基团、含磷-氮基团以及含磷-卤基团等功能基团的聚氨酯用反应型阻燃剂的研究现状,以及不同反应型阻燃剂对聚氨酯的阻燃机理,并展望了反应型阻燃聚氨酯的发展趋势。     

杜仲胶/聚丙烯酸甲酯合金的制备与性能

制备了丙烯酸甲酯类杜仲胶合金,采用核磁共振波谱仪以及红外光谱仪确定了丙烯酸甲酯类功能基团的改性,研究了丙烯酸甲酯类功能基团的引入对合金材料结晶性能、极性以及相对分子质量的影响。结果表明,功能基团可成功引入到杜仲胶体系中,聚丙烯酸甲酯/杜仲胶合金仍然具有较高的相对分子质量;在杜仲胶用量固定的情况下,随着丙烯酸甲酯类功能基团的引入,合金的结晶度不断降低直到基本消失,熔点也呈降低趋势。     

轮状病毒结构蛋白自组装修饰金纳米粒子

通过轮状病毒结构蛋白VP6自组装的方式对金纳米粒子进行了修饰,获得了VP6包覆的金纳米复合材料,改善了金纳米粒子的生物相容性,使其表面带有丰富的化学基团,更易在靶向药物输运、热疗及造影等方面获得新应用。     

PARACEST agents: modulating MRI contrast via water proton exchange

Scientific interest in optimizing the properties of gadolinium (III) complexes as MRI contrast agents has led to many new insights into lanthanide ion coordination chemistry in the last two decades. Among these was the surprising observation that water exchange in lanthanide (III) derivatives of DOTA can be modulated dramatically by judicious choice of ligand side chain and Ln(3+) ionic radii. This resulted in the discovery of paramagnetic CEST agents for altering MRI image contrast based upon the chemical exchange saturation transfer mechanism. The goal of this article is to review the factors that govern water molecule and water proton exchange in these complexes and to compare the potential sensitivity of PARACEST agents versus Gd(3+)-based T(1) relaxation agents for altering tissue contrast.     

Synthesis and evaluation of paramagnetic particulates as contrast agents for magnetic resonance imaging (MRI)

Formulations based on novel particulate ion-exchange resins, containing a wide range of paramagnetic transition and rare-earth metals bound to their surfaces, have been synthesised as potential contrast agents for the magnetic resonance imaging (MRI) of the gastro-intestinal (GI) tract of man. They have been evaluated in terms of their effects upon the spin-lattice (R₁) and spin-spin (R₂) relaxation rates of the protons of water. Careful selection of the polymer, spacer-arm, ligand and paramagnetic ion provides a means for subtle molecular tailoring. Further potential applications have been highlighted based on the observed properties of such formulations.     

Nanoparticle-Based Systems for T1-Weighted Magnetic Resonance Imaging Contrast Agents

Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T₁-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T₁-weighted MRI/computed X-ray tomography (CT) and T₁-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality.     

Water-dispersible multiwalled carbon nanotube/iron oxide hybrids as contrast agents for cellular magnetic resonance imaging

Novel magnetic resonance imaging (MRI) contrast agents composed of multiwalled carbon nanotubes decorated with magnetic iron oxide nanoparticles were explored. They were functionalized with multilayer polyelectrolytes through layer-by-layer assembling and were shown to be hydrophilic, biocompatible, and have a high MRI contrast. A targeted ligand folic acid was chemically bonded to the functionalized nanotubes for specific targeting and imaging of cancer cells in MRI. The results demonstrate that the material can be used as ideal targeted imaging agents and is sufficient to obtain strong MRI contrast.     

Polydisulfide Based Biodegradable Macromolecular Magnetic Resonance Imaging Contrast Agents

Macromolecular Gd(III) complexes are advantageous over small molecular Gd(III) complexes in contrast enhanced magnetic resonance imaging (MRI) because of their prolonged blood circulation and preferential tumor accumulation. However, macromolecular contrast agents have not been approved for clinical applications because of the safety concerns related to their slow body excretion. Polydisulfide Gd(III) complexes have been designed and developed as biodegradable macromolecular MRI contrast agents to alleviate the concerns by facilitating the clearance of Gd(III) complexes from the body. These agents initially behave as macromolecular agents and result in superior contrast enhancement in the vasculature and tumor tissues. They can then be readily degraded in vivo into small molecular chelates that can rapidly excrete from the body via renal filtration after the MRI examinations. Various polydisulfide Gd(III) complexes have been prepared as biodegradable macromolecular MRI contrast agents. These agents have resulted in strong contrast enhancement in the vasculature and tumor tissue in animal models with minimal long-term tissue accumulation comparable to small molecular contrast agents. Polydisulfide Gd(III) complexes are promising for further clinical development as safe and effective biodegradable macromolecular MRI contrast agents for cardiovascular and cancer imaging. The review summarizes the chemistry and properties of polydisulfide Gd(III) complexes.     

Migration of divalent ions in nylon 6 films

The migration of ions through a nylon-6 film is studied by MRI. For this study the paramagnetic ions Mn²⁺ and Cu²⁺ are used as they act as a contrast agent and are detectable by MRI.     

Recent Advances in Bifunctional Paramagnetic Chelates for MRI

Magnetic resonance imaging (MRI) is a non-invasive diagnostic modality routinely employed in modern clinical medicine to collect images of the internal organs of the human body. Contrast agents (CA) are usually administered to patients to improve the sensitivity of this technique and nowadays these agents are gadolinium complexes. Bifunctional chelating agents (BFCAs) are dual molecules containing a multidentate ligand, able to strongly coordinate a metal ion, and a reactive moiety for conjugation purposes. With BFCAs an easy labelling of biomolecules or vectors with paramagnetic ions is possible, allowing the in vivo MRI visualization of diseases at cellular or molecular level.     

Synthesis and Characterization of Amphiphilic Gd(III) Complexes: Gd‐DTPA‐BA

Magnetic resonance imaging (MRI) is widely used to identify different diseases. MRI contrast agents, used to enhance the MRI signal, have been studied extensively for precise diagnosis. Based on the advantages of macromolecular MRI contrast agents of higher contrast imaging ability and a longer cycle time, this article modified the most common micromolecular contrast agent (Gd‐diethylene triamine pentaacetic acid [DTPA]). 2 long saturated aliphatic chains were attached to both sides of DTPA. DTPA derivatives with 12, 14, and 16 carbon lengths were synthesized and chelated to Gd³⁺. 3 amphiphilic MRI contrast agents were obtained and their structures were characterized using mass spectrometry, ¹H NMR, and Fourier transform infrared. Furthermore, the surface tension of the compounds was measured, and liposomes were prepared by mixing the synthesized amphiphilic molecules with egg lecithin and cholesterol. The assembly behavior of the liposomes was studied using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurements. TEM showed that the liposomes possessed bilayer vesicle structures. The liposome size distribution determined by DLS was from 10 to 1000 nm, and as the aliphatic chain length increased, the polydispersity index (PDI) and zeta potential increased. No obvious changes in the PDI and zeta potential of the liposomes were observed after 5 days at room temperature, suggesting that they possess good stability.     

The challenge of T1 contrast agents for high-magnetic field MRI

Magnetic resonance imaging (MRI) is one of the most powerful diagnostic techniques used in clinics. The need for higher spatial resolution and better sensitivity led to the development of imagers working at high magnetic fields. The routine clinical use of 3 T MR systems raised the demand for MRI contrast agents working at this field or above. In the following we summarize the research in our research group on such high-field contrast agents.     

The Design of Abnormal Microenvironment Responsive MRI Nanoprobe and Its Application

Magnetic resonance imaging (MRI) is often used to diagnose diseases due to its high spatial, temporal and soft tissue resolution. Frequently, probes or contrast agents are used to enhance the contrast in MRI to improve diagnostic accuracy. With the development of molecular imaging techniques, molecular MRI can be used to obtain 3D anatomical structure, physiology, pathology, and other relevant information regarding the lesion, which can provide an important reference for the accurate diagnosis and treatment of the disease in the early stages. Among existing contrast agents, smart or activatable nanoprobes can respond to selective stimuli, such as proving the presence of acidic pH, active enzymes, or reducing environments. The recently developed environment-responsive or smart MRI nanoprobes can specifically target cells based on differences in the cellular environment and improve the contrast between diseased tissues and normal tissues. Here, we review the design and application of these environment-responsive MRI nanoprobes.