Hydroxypyridonate Gd Complexes: MRI Agents

羟基吡啶酮酸钆复合物:MRI 试剂

基本信息

  • 批准号:
    7189046
  • 负责人:
  • 金额:
    $ 23.21万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-04-01 至 2010-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) has provided dramatic new capabilities for diagnostic medicine. MRI enables the acquisition of high resolution, three-dimensional images in the detection of a wide variety of physical abnormalities, and recent advances in dynamic MRI are providing real-time imaging. Over 30% of MRI scans are now acquired using a paramagnetic contrast agent, which enhances the proton relaxation and hence image quality. Gadolinium complexes are most widely used, and these complexes currently are all based on a poly(amino-carboxylate) ligand scaffold . While effective, the relaxivity values (3 - 5mM-1s-1) of these agents are only a few percent of that theoretically possible, requiring gram amounts of Gd per administration. Attachment of the agent to macromolecules increases the relaxivity by lowering the rotational correlation time, but the rate of water exchange from the gadolinium center then becomes the limiting factor. This project has developed gadolinium complexes (based on a hexadentate hydroxypyridonate ligand scaffold) that are stable and have substantially higher relaxivity due to a water exchange rate at least two orders of magnitude higher than commercial agents. Having developed the agents and demonstrated their stability and fast rates of water exchange, it is now proposed to continue their development for enabling new kinds of imaging. Relaxivities of more than 100mM-1s-1 are the target. This would require much less Gd for images and, more significantly, enable new types of imaging with MRI. Aims include the development of stable agents with 3 (as opposed to the current 1) coordinated water molecules, thus tripling the relaxivity; novel designs of supramolecular Gd clusters; agents that dock to specific targeted biomolecules; and full characterization of those thermodynamic and kinetic properties of these complexes in aqueous solution that are related to their MRI enhancement. The goal is a second generation of MRI agents that utilize relaxivities of up to two orders of magnitude greater than the clinical agents in use today.
描述(由申请人提供):磁共振成像(MRI)为诊断医学提供了引人注目的新功能。MRI使得能够在检测各种各样的身体异常中获取高分辨率的三维图像,并且动态MRI的最新进展提供了实时成像。现在超过30%的MRI扫描是使用顺磁造影剂获得的,这增强了质子弛豫,从而提高了图像质量。钆配合物是最广泛使用的,并且这些配合物目前都是基于聚(氨基-羧酸酯)配体支架。虽然有效,但这些药物的弛豫率值(3 - 5 mM-1 s-1)仅为理论上可能的百分之几,每次给药需要克量的Gd。附着剂的大分子通过降低旋转相关时间增加弛豫率,但从钆中心的水交换率则成为限制因素。该项目已经开发了钆络合物(基于六齿羟基吡啶酮配体支架),其是稳定的并且由于水交换速率比商业试剂高至少两个数量级而具有显著更高的弛豫率。在开发了这些试剂并证明了它们的稳定性和快速的水交换率之后,现在建议继续开发它们以实现新的成像类型。弛豫率大于100 mM-1 s-1是目标。这将需要更少的Gd用于图像,更重要的是,能够使用MRI进行新类型的成像。目标包括开发具有3个(与当前的1个相反)配位水分子的稳定剂,从而使弛豫率增加两倍;超分子Gd簇的新设计;与特定靶向生物分子对接的试剂;以及这些络合物在水溶液中与其MRI增强相关的热力学和动力学性质的充分表征。目标是第二代MRI试剂,其利用的弛豫率比目前使用的临床试剂高两个数量级。

项目成果

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KENNETH N RAYMOND其他文献

KENNETH N RAYMOND的其他文献

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{{ truncateString('KENNETH N RAYMOND', 18)}}的其他基金

A proposal for the purchase of a new Cu anode Microsource X-ray Diffractometer wi
关于购买新型铜阳极微源X射线衍射仪的提案
  • 批准号:
    7794643
  • 财政年份:
    2010
  • 资助金额:
    $ 23.21万
  • 项目类别:
Biomimetic Lanthanide & Actinide Decorporation Agents: Preclinical Development
仿生镧系元素
  • 批准号:
    7585996
  • 财政年份:
    2006
  • 资助金额:
    $ 23.21万
  • 项目类别:
Biomimetic Lanthanide & Actinide Decorporation Agents: Preclinical Development
仿生镧系元素
  • 批准号:
    7267890
  • 财政年份:
    2006
  • 资助金额:
    $ 23.21万
  • 项目类别:
Hydroxypyridonate Gd Complexes:MRI Agents
羟基吡啶酮酸钆复合物:MRI 试剂
  • 批准号:
    6865433
  • 财政年份:
    2002
  • 资助金额:
    $ 23.21万
  • 项目类别:
Hydroxypyridonate Gd Complexes: MRI Agents
羟基吡啶酮酸钆复合物:MRI 试剂
  • 批准号:
    7885681
  • 财政年份:
    2002
  • 资助金额:
    $ 23.21万
  • 项目类别:
Hydroxypyridonate Gd Complexes: MRI Agents
羟基吡啶酮酸钆复合物:MRI 试剂
  • 批准号:
    7588891
  • 财政年份:
    2002
  • 资助金额:
    $ 23.21万
  • 项目类别:
Hydroxypyridonate Gd Complexes:MRI Agents
羟基吡啶酮酸钆复合物:MRI 试剂
  • 批准号:
    6456410
  • 财政年份:
    2002
  • 资助金额:
    $ 23.21万
  • 项目类别:
Hydroxypyridonate Gd Complexes: MRI Agents
羟基吡啶酮酸钆复合物:MRI 试剂
  • 批准号:
    7021488
  • 财政年份:
    2002
  • 资助金额:
    $ 23.21万
  • 项目类别:
Hydroxypyridonate Gd Complexes:MRI Agents
羟基吡啶酮酸钆复合物:MRI 试剂
  • 批准号:
    6622801
  • 财政年份:
    2002
  • 资助金额:
    $ 23.21万
  • 项目类别:
Hydroxypyridonate Gd Complexes: MRI Agents
羟基吡啶酮酸钆复合物:MRI 试剂
  • 批准号:
    8239545
  • 财政年份:
    2002
  • 资助金额:
    $ 23.21万
  • 项目类别:

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