NITROXIDE FREE RADICAL CONTRAST MEDIA FOR NMR IMAGING

核磁共振成像是一种新兴的诊断工具 能够在不使用电离的情况下提供临床有用的图像 辐射。对比度增强药物，与核磁共振成像结合使用， 已经被证明可以更好地补充图像产生的信息 对正常组织和病变组织进行定位和表征。最新进展 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 在实验研究中被证明是有效和有用的，但没有一种药剂 但仍符合临床使用的安全性和有效性标准。 这一持续研究计划的主要目的是进一步测试 氮氧化物自旋标记物的安全性、诊断益处和药理学 (NSL)是一组合成的、顺磁性的有机分子，在 用于核磁共振成像的体内造影剂。具体目标包括：1)选择 和合成候选的非离子和多自由基NSL药物 容忍性、松弛性和惰性的优越特性，2)指挥 超选NSL制剂的广泛毒理学评价 对于临床试验，3)继续进行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 候选的NSL将作为氧化还原敏感的代谢造影剂进行测试， 4)合成和测试潜在的功能特异性NSL造影剂 5)评价NSL图像对比度的诊断效果 正常和病变(肿瘤、炎症、缺血)的增强 实验动物。 拟议的调查需要一系列学科的结合，包括 诊断成像、合成和分析化学、核磁共振物理学和 药理学。要强调的具体技术将是脉冲核技术 核磁共振、电子顺磁共振、核磁共振 成像和放射性示踪剂检测。肿瘤的实验模型， 将研究炎性疾病、血管疾病和梗阻性尿路疾病 在服用NSL前后进行核磁共振检查，以评估其诊断价值 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。

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 trials, 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.