Synthesis of Bio-Inorganic Tracers for Diagnostic Radiol

放射诊断用生物无机示踪剂的合成

• 批准号: 7319241
• 负责人: Terry M. Phillips
• 金额: --
• 依托单位: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7319241
• 关键词: Synthesis; Bio; Inorganic; Tracers; Diagnostic

Molecular and cellular imaging is a rapidly developing field whose results have the potential to contribute to the successes of cellular therapies. The development and testing of novel tools, reagents, and methods to image specific molecular pathways in vivo, particularly those that are key targets in disease processes may further the understanding of the pathology. The intrinsic magnetic resonance image (MRI) contrast of tissues can be augmented by the use of contrast agents (CA) in both clinical and experimental settings. CA increases the 1/T-1 and 1/T-2, often referred to as the inner and outer sphere relaxation water in the case of in vivo MRI. Inner sphere relaxation is enhanced by increasing the primary water-metal interaction, while outer sphere relaxation is enhanced by increasing the primary water-secondary water interaction. The current 1/T-1 FDA approved contrast agents are all Gadolinium (Gd) based. Their contrast enhancement in the primary cardiovascular system is merely satisfactory and severely limited by the short retention time of these compounds in the subject. Thus, the development of Gd-based 1/T-1 contrast agents, with greater contrast enhancement or increased retention times, is the basis for this research collaboration. Current research has yielded the synthesis of a novel Gd-, Calix-arene compound which can potentially interact with human serum albumin through electrostatic interactions, leading to increased retention times in the cardiovascular system for more in depth imaging by MRI. Thorough characterization of this new synthetic product, and all synthetic steps leading to it, has been accomplished. Future work includes insertion of Gd, stability testing and relaxation measurements to determine the compounds potential as an imaging agent. While progress continues on the development of the calix-arene compound and the successful insertion of gadolinium, further characterization of iron oxide T2 imaging agents, currently used in cell labeling, was completed. Superparamagnetic Iron Oxide (SPIO) nanoparticles, either modified or in combination with other macromolecules, are being used for magnetic labeling of stem cells and other cells to monitor cell trafficking by Magnetic Resonance Imaging (MRI) in experimental models. The correlation of histology to MRI depends on the ability to detect SPIO labeled cells using Prussian blue (PB) stain and fluorescent tags to cell surface markers. Exposure of PB positive sections to ultraviolet light at a wavelength of 365 nanometers commonly used in fluorescence microscopy can result in color transformation of PB positive material from blue to brown. Although this color transformation is primarily an artifact that may occur during fluorescence microscopy, when the color transformation occurs of PB weakly positive cells and when this is used in combination with image processing, the detection of low levels of iron labeled cells in tissues samples can be correlated to cellular MRI.

分子和细胞成像是一个快速发展的领域，其结果有可能有助于细胞治疗的成功。开发和测试新的工具，试剂和方法来成像体内特定的分子途径，特别是那些在疾病过程中的关键目标，可以进一步了解病理。在临床和实验环境中，可以通过使用造影剂（CA）来增强组织的固有磁共振图像（MRI）对比度。CA增加了1/T-1和1/T-2，在体内MRI的情况下通常称为内球和外球弛豫水。内球弛豫通过增加主水-金属相互作用而增强，而外球弛豫通过增加主水-次水相互作用而增强。 目前FDA批准的1/T-1造影剂均为钆（Gd）造影剂。它们在主要心血管系统中的对比度增强仅仅是令人满意的，并且受到这些化合物在受试者中的短保留时间的严重限制。因此，具有更大对比度增强或增加保留时间的Gd基1/T-1造影剂的开发是这项研究合作的基础。 目前的研究已经合成了一种新的Gd-，杯芳烃化合物，其可以通过静电相互作用与人血清白蛋白潜在地相互作用，导致在心血管系统中的保留时间增加，用于通过MRI进行更深入的成像。已经完成了对这种新合成产品及其所有合成步骤的彻底表征。未来的工作包括插入Gd，稳定性测试和弛豫测量，以确定化合物作为成像剂的潜力。 在杯芳烃化合物的开发和钆的成功插入方面继续取得进展的同时，完成了目前用于细胞标记的氧化铁T2显像剂的进一步表征。超顺磁性氧化铁（SPIO）纳米粒子，无论是修改或与其他大分子组合，正在用于干细胞和其他细胞的磁性标记，以监测细胞贩运的磁共振成像（MRI）在实验模型。组织学与MRI的相关性取决于使用普鲁士蓝（PB）染色和荧光标记检测SPIO标记的细胞表面标记物的能力。将PB阳性切片暴露于荧光显微镜中常用的波长为365 nm的紫外光下，可导致PB阳性材料从蓝色变为棕色。虽然这种颜色转换主要是在荧光显微镜检查期间可能发生的伪影，但是当PB弱阳性细胞发生颜色转换时，并且当其与图像处理结合使用时，组织样品中低水平铁标记细胞的检测可以与细胞MRI相关。