Hyperpolarized 89Y complexes as potential in vivo imaging agents

超极化 89Y 复合物作为潜在的体内成像剂

• 批准号: 7573139
• 负责人: Zoltan Kovacs
• 金额: $ 19.63万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7573139
• 关键词: Biochemical Process; Biodistribution; Cell Nucleus; Chemicals; Clinical; Complex; Contrast Media; Data; Dependence; Electron Transport Complex III; Environment; Free Radicals; Functional Imaging; Glucose; Goals; Image; Ligands; Magnetic Resonance Imaging; Maps; Measures; Metabolic; Metabolism; Molecular; Nuclear; Nuclear Magnetic Resonance; Oxidation-Reduction; Pentetic Acid; Phase; Physiological; Preparation; Protocols documentation; Rattus; Relaxation; Resolution; Sampling; Signal Transduction; Small Animal Imaging Systems; Solutions; Spectrum Analysis; Technology; Temperature; Testing; Time; Tissues; Yttrium; base; design; imaging modality; in vivo; indexing; molecular imaging; nitroxyl; oxidation; public health relevance; quantum; research study; soft tissue; triethylenetetraminehexaacetic acid

DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) has become arguably the most important clinical imaging modality but it is less well suited for molecular and metabolic imaging because of its inherently low sensitivity. Solution phase nuclear dynamic polarization (DNP) technology can increase the sensitivity of standard NMR experiments by factors of 5000 to 25000. Such increases in sensitivity make it possible to perform molecular/functional imaging of other nuclei than 1H. The signal coming from any hyperpolarized nucleus will decay according to the spin-lattice relaxation time (T1) and one can anticipate having a detectable NMR signal for ~5T1. This poses a limitation on the biochemical processes that could be imaged and motivates the search for long T1 agents. Among the common spin 1/2 NMR active nuclei 89Y(III) has the longest T1 relaxation time (up to 600 seconds) rendering hyperpolarized yttrium-89 attractive as a potential in vivo imaging and spectroscopy probe. Our preliminary data indicated that Y(III)-complexes can be hyperpolarized with currently available commercial hardware. The goal of this project is to demonstrate that imaging of hyperpolarized Y- complexes is possible in vivo. We will first establish the optimal conditions for the DNP hyperpolarization of 89Y (Specific Aim 1). Y(III) complexes of two open chain (DTPA, TTHA) and four macrocyclic ligands, [DOTA, PCTA, DOTP, DOTA(AmP)4] will be prepared and hyperpolarized. Polarization enhancements and T1's of the complexes will be determined (Specific Aim 2). We will build a dual-tuned 89Y/1H coil for rats and develop a protocol to image the biodistribution of hyperpolarized Y(III) chelates. The samples will be hyperpolarized in the Hypersense " DNP polarizer and the in vivo imaging experiments will be performed at 4.7T (Specific Aim 3). The extreme sensitivity of 89Y(III) to its chemical environment could be exploited in the design of sensitive probes to image and map physiological parameters such as pH, temperature, and other indices of metabolism in vivo. PUBLIC HEALTH RELEVANCE Solution phase nuclear dynamic polarization (DNP) nuclear magnetic resonance (NMR) technology increases the sensitivity of standard NMR experiments by factors of 5000 to 25000 making MRI imaging of nuclei other than 1H feasible. The goal of this proposal is to demonstrate that imaging hyperpolarized yttrium-89-complexes is possible in vivo. Potential applications include the design and synthesis of sensitive probes to image and map physiological parameters such as pH, temperature, redox state and glucose levels in vivo.

描述（由申请人提供）：磁共振成像（MRI）可以说已成为最重要的临床成像方式，但由于其固有的低灵敏度，不太适合分子和代谢成像。溶液相核动态极化 (DNP) 技术可将标准 NMR 实验的灵敏度提高 5000 至 25000 倍。灵敏度的提高使得对 1H 以外的其他核进行分子/功能成像成为可能。来自任何超极化核的信号都会根据自旋晶格弛豫时间 (T1) 衰减，并且可以预期可检测到约 5T1 的 NMR 信号。这对可成像的生化过程造成了限制，并激发了对长 T1 试剂的研究。在常见的自旋 1/2 NMR 活性核中，89Y(III) 具有最长的 T1 弛豫时间（长达 600 秒），使得超极化钇 89 作为潜在的体内成像和光谱探针具有吸引力。我们的初步数据表明，Y(III)-复合物可以通过当前可用的商业硬件进行超极化。该项目的目标是证明超极化 Y 复合物在体内成像是可能的。我们将首先建立 89Y 的 DNP 超极化的最佳条件（具体目标 1）。将制备两个开链（DTPA、TTHA）和四个大环配体 [DOTA、PCTA、DOTP、DOTA(AmP)4] 的 Y(III) 配合物并进行超极化。将确定复合物的偏振增强和 T1（具体目标 2）。我们将为大鼠构建双调谐 89Y/1H 线圈，并开发一种协议来对超极化 Y(III) 螯合物的生物分布进行成像。样品将在 Hypersense“DNP 偏振器中超极化，体内成像实验将在 4.7T 下进行（具体目标 3）。89Y(III)对其化学环境的极端敏感性可用于设计敏感探针对 pH、温度和其他体内代谢指标等生理参数进行成像和绘图 溶液相核动态极化 (DNP) 核磁共振 (NMR) 技术提高了灵敏度。 5000 至 25000 倍的标准 NMR 实验使得除 1H 以外的核的 MRI 成像变得可行。该提案的目标是证明超极化钇 89 复合物在体内成像是可能的，潜在的应用包括敏感探针的设计和合成。对体内 pH、温度、氧化还原状态和葡萄糖水平等生理参数进行成像和绘制。