METABOLIC IMAGING AGENTS

代谢显像剂

• 批准号: 8171634
• 负责人: Dean Sherry
• 金额: $ 15.69万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171634
• 关键词: Characteristics; Complex; Computer Retrieval of Information on Scientific Projects Database; Diffusion; Drug or chemical Tissue Distribution; Extracellular Space; Frequencies; Funding; Glucose; Grant; Heart Neoplasms; Image; Injection of therapeutic agent; Institution; Kidney; Lanthanoid Series Elements; Lipid Bilayers; Liposomes; Liver; Magnetic Resonance Imaging; Maps; Metabolic; Methods; Monitor; Mus; Protocols documentation; Reagent; Research; Research Personnel; Resources; Source; Surface; Testing; Tissues; United States National Institutes of Health; Water; extracellular; in vivo; particle; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims are to: 1) Optimize our existing glucose-responsive PARACEST agent for mapping the tissue distribution of glucose in vivo. We have demonstrated that changes in extracellular glucose concentration can be mapped by MRI in isolated mouse liver by CEST imaging using a glucose-responsive PARACEST agent. This assumes that the boronate agent is equally distributed throughout all extracellular space of liver. Further experiments are envisioned to test this hypothesis. 2) Develop a single injection method for mapping tissue pH by MRI. We were first to demonstrate that tissue pH can be mapped by MRI in kidney, heart & tumors in vivo by monitoring dynamic contrast enhancement (DCE) after injection of two agents, a pH insensitive agent (GdDOTp5-) and a pH sensitive agent (GdDOTA-4Amp5-). In an effort to make pH imaging of tissue more feasible clinically, we propose to develop a single injection protocol using a mixture T1 and T2 agents. 3) Develop high sensitivity LlPOCEST particles for imaging low pH regions of tissues. It has been demonstrated that the sensitivity of CEST can be magnified many fold by using liposomes containing high concentrations of lanthanide shift reagent trapped in the inner core. All water trapped in the inner core along with a complex is shifted to a different frequency than extra-liposomal water and this new resonance can be used as an antenna to initiate CEST. Since exchange of water in this case is determined by the diffusion characteristics of the lipid bilayer, one should be able to prepare liposomes with surface functionalities that respond to changes in extraliposomal pH.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 具体目标是：1）优化我们现有的葡萄糖响应性 PARACEST 试剂，以绘制体内葡萄糖的组织分布图。我们已经证明，细胞外葡萄糖浓度的变化可以通过 MRI 在离体小鼠肝脏中通过使用葡萄糖反应性 PARACEST 剂的 CEST 成像来绘制。这假设硼酸盐试剂均匀地分布在肝脏的所有细胞外空间中。预计将进行进一步的实验来检验这一假设。 2) 开发一种通过 MRI 绘制组织 pH 值的单次注射方法。我们首次证明，通过注射 pH 不敏感剂 (GdDOTp5-) 和 pH 敏感剂 (GdDOTA) 两种药剂后监测动态对比增强 (DCE)，可以通过 MRI 来绘制肾脏、心脏和肿瘤体内的组织 pH 值-4Amp5-)。为了使组织 pH 成像在临床上更加可行，我们建议使用 T1 和 T2 制剂的混合物开发单次注射方案。 3) 开发高灵敏度 LlPOCEST 颗粒，用于组织低 pH 区域成像。已经证明，通过使用含有高浓度镧系元素位移试剂的脂质体，CEST的灵敏度可以放大许多倍。所有被困在内核中的水以及复合物都会转移到与脂质体外水不同的频率，这种新的共振可以用作启动 CEST 的天线。由于在这种情况下水的交换是由脂质双层的扩散特性决定的，因此应该能够制备具有响应脂质体外pH变化的表面功能的脂质体。