NITROXIDE FREE RADICAL CONTRAST MEDIA FOR NMR IMAGING

用于 NMR 成像的氮氧自由基对比介质

• 批准号: 3230431
• 负责人: Robert Charles Brasch
• 金额: $ 21.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-02-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230431
• 关键词: contrast media; disease /disorder model; ionizing radiation; nitrous oxide; radiodiagnosis; toxicology

Nuclear magnetic resonance (NMR) imaging is an emerging diagnostic tool capable of providing clinically-useful images without the use of ionizing radiation. Contrast enhancing drugs, used in conjunction with NMR imaging, have been shown to supplement the information yield from images by better localizing and characterizing normal and diseased tissues. The development of NMR contrast agents is in an early stage; NMR contrast agents have been shown to be effective and useful in experimental studies, but no agent has yet met criteria of safety and efficacy for clinical use in humans. The principle aim of this continuing research program is to further test the safety, diagnostic benefits, and pharmacology of nitroxide spin labels (NSL), a group of synthetic, paramagnetic, organic molecules, applies as in vivo contrast agents for NMR imaging. Specific aims include 1) to select and synthesize candidate nonionic and polyradical NSL pharmaceuticals with superior properties of tolerance, relaxivity, and inertness, 2) to conduct extensive toxicological evaluatios of super-selected NSL's in preparation for clinical trails, 3) to continue NSL metabolic studies, including the definition of cellular and extracellular bioreduction pathways, to better apply NSL as extracellular space contrast enhancers and to identify candidate NSL's to be tested as redox-sensitive, metabolic contrast agents, 4) to synthesize and test potentially function-specific NSL contrast agents and 5) to assess the diagnostic efficacy of using NSL for image contrast enhancement in normal and diseased (tumor, inflammatory, ischemic) experimental animals. The proposed investigations require a combination of disciplines including diagnostic imaging, synthetic and analytical chemistry, NMR physics, and pharmacology. Specific techniques to be emphasized will be pulsed nuclear magnetic resonance (NMR), electron paramagnetic resonane (EPR), NMR imaging, and radiotracer detection. Experimental models of neoplastic, inflammatory, and vascular disases and obstructive uropathy will be studied by NMR before and after NSL administration to assess the diagnostic utility of contrast enhancement. The long-term goal is to develop clinically useful NMR contrast agents for use in the diagnosis of human disease.

核磁共振成像是一种新兴的诊断工具 能够提供临床上有用的图像而不使用电离 辐射 与核磁共振成像结合使用的对比增强药物， 已被证明可以通过更好地补充来自图像的信息产量， 定位和表征正常和患病组织。 发展 核磁共振造影剂的研究还处于早期阶段;核磁共振造影剂已经 在实验研究中显示出有效和有用，但没有试剂 但仍符合临床应用于人体的安全性和有效性标准。 这项持续研究计划的主要目的是进一步测试 氮氧自旋标记物的安全性、诊断益处和药理学 (NSL)，一组合成的顺磁性有机分子，适用于 用于NMR成像的体内造影剂。 具体目标包括：（1）选择 并合成候选的非离子和多自由基NSL药物， 上级特性的耐受性，弛豫性，和惰性，2）进行 超选择NSL制剂的广泛毒理学评价 对于临床试验，3）继续NSL代谢研究，包括 细胞和细胞外生物还原途径的定义，以更好地 应用NSL作为细胞外间隙对比度增强剂， 作为氧化还原敏感的代谢造影剂测试的候选NSL， 4)合成和测试潜在的功能特异性NSL造影剂 5）评价NSL用于图像对比的诊断效果 正常和病变（肿瘤、炎性、缺血性）增强 实验动物 拟议的调查需要结合各种学科，包括 诊断成像，合成和分析化学，核磁共振物理，和 药理学 具体技术将强调脉冲核 核磁共振（NMR），电子顺磁共振（EPR）， 成像和放射性示踪剂检测。 肿瘤的实验模型， 炎症，血管疾病和阻塞性尿路病将进行研究 在NSL给药前后通过NMR评估诊断效用 对比度增强。 长期目标是开发临床上有用的核磁共振造影剂， 用于人类疾病的诊断。