Increasing the Utility of Contrast Agents for MRI

提高 MRI 造影剂的实用性

• 批准号: 7753605
• 负责人: MATTHEW J ALLEN
• 金额: $ 24.75万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7753605
• 关键词: Address; Air; Area; Biological Monitoring; Biology; Chelating Agents; Chemistry; Clinical; Collaborations; Complex; Contrast Media; Dendrimers; Development; Diagnostic; Electronics; Enhancers; Future; Generations; Goals; Image; Ions; Knowledge; Lanthanoid Series Elements; Lead; Ligands; Magnetic Resonance Imaging; Mentors; Mentorship; Metals; Methods; New Agents; Oxygen; Phase; Polymers; Postdoctoral Fellow; Property; Protein Biochemistry; Proteins; Public Health; Research; Scientist; Staging; Technology; Testing; Time; Training; Universities; Water; Work; base; career; design; disease diagnosis; experience; improved; in vivo; macromolecule; novel; oxidation; polymerization; professor; research study; skills; stability testing

The long-term goals of this proposal are to address critical barriers to progress in the field of contrast agent-enhanced magnetic resonance imaging (MRI). My plan to overcome these barriers is to increase the utility of lanthanide-based contrast agents. Efforts will be focused on the development of contrast agents for high field MRI and activatable agents that are physiologically viable. Mentored K99 Phase: The postdoctoral phase (aim 1) of the proposal will be carried out under the mentorship of Professors L. L. Kiessling and R. T. Raines at the University of Wisconsin¿Madison. The K99 phase goal is to develop exquisitely sensitive MRI agents using polymeric hydroxypyridonate (HOPO)-based chelates. This training at the interface of chemistry and biology will provide expertise in conjugation chemistries, manipulation and characterization of macromolecules, and the synthesis of novel lanthanide chelators. The acquired knowledge will prove invaluable for completion of aims 2-4 and transition into a successful career as an independent scientist. Independent ROO Phase: In the independent phase (aims 2-4), aims 2 and 3 focus on the development of biologically responsive contrast agents for MRI. Aim 2 involves the development of a novel class of activatable agents using dendrimer chemistry that have a true zero-background state. Zero background enhancement would enable concentration-independent imaging, overcoming a major barrier to the clinical use of activatable agents for diagnostic purposes. The experiments described in aim 3 focus on modulation of the innersphere water coordination number of HOPO-based agents. The new agents will have advantages over similar poly(aminocarboxylate)-based agents due to differences in water exchange rate and number of innersphere water molecules. In aim 4, methods to stabilize Eu(ll) complexes from oxidation are proposed. Stable Eu(ll) complexes will enhance contrast at high field strengths filling the void where Gd(lll) complexes cease to be viable contrast agents because of long electronic correlation times. Relevance: This proposal has the potential to greatly improve public health through advancement of the diagnostic capabilities of MRI by overcoming current technological limitations. The proposed research may lead to the ability to diagnose diseases at the earliest stages where treatments are often more effective.

这项建议的长期目标是解决在对比领域取得进展的关键障碍

项目成果

Multilanthanide Systems for Medical Imaging Applications.

• DOI: 10.2174/1877912311101020088
• 发表时间: 2011-12-01
• 期刊: Recent patents on nanomedicine
• 作者: Moore JD;Allen MJ
• 通讯作者: Allen MJ

Strategies for optimizing water-exchange rates of lanthanide-based contrast agents for magnetic resonance imaging.

• DOI: 10.3390/molecules18089352
• 发表时间: 2013-08-05
• 期刊: Molecules (Basel, Switzerland)
• 作者: Siriwardena-Mahanama BN;Allen MJ
• 通讯作者: Allen MJ

Eu(II)-containing cryptates as contrast agents for ultra-high field strength magnetic resonance imaging.

• DOI: 10.1039/c1cc15219j
• 发表时间: 2011-12-28
• 期刊: Chemical communications (Cambridge, England)
• 作者: Garcia J;Neelavalli J;Haacke EM;Allen MJ
• 通讯作者: Allen MJ

Dynamic measurements of aqueous lanthanide triflate-catalyzed reactions using luminescence decay.

• DOI: 10.1021/ja900630d
• 发表时间: 2009-05-13
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Dissanayake P;Allen MJ
• 通讯作者: Allen MJ

Physical Properties of Eu(2+)-Containing Cryptates as Contrast Agents for Ultra-High Field Magnetic Resonance Imaging.

• DOI: 10.1002/ejic.201101166
• 发表时间: 2012-04-01
• 期刊: EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
• 影响因子: 2.3
• 作者: Garcia, Joel;Kuda-Wedagedara, Akhila N. W.;Allen, Matthew J.
• 通讯作者: Allen, Matthew J.