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对人体进行断层成像 辐射。我们系开发的两台核磁共振成像仪，利用 氢核的磁性行为，并描绘了它们的分布和 身体组织内的磁弛豫特性。这样做的目的是 项目是通过动物实验更好地定义诊断 无氮氧自由基的益处、毒性和药理作用 体内用作核磁共振造影剂的自由基(NSFR)。建议数 研究需要诊断成像的综合学科， 合成化学、物理学和药理学。中国的初步研究 动物表明，NSFR是一组有机顺磁化合物，用作 造影剂可增强尿液核磁共振对比度差异 肾脏的结构和周围组织，并允许评估 功能。被测试的NSFR通过肾小球滤过和 出现在尿路结构中，导致核磁共振显著增加 强度信号。像许多放射造影剂一样，NSFR在很大程度上 被正常功能排除在中枢神经系统之外 血脑屏障。据推测，这些造影剂将 在病理条件下渗透到大脑，从而帮助 神经疾病的核磁共振鉴定。实现其他器官特定的 靶向，NSFR可以共价连接到生物分子上，包括 蛋白质和脂类。NSFR-蛋白质和/或聚集颗粒 NSFR-脂质体可用于肝脏和肝脏的核磁共振成像的诊断 通过描绘脾功能的网状内皮系统。这些 NSFR的对比度增强应用将大大增加 核磁共振成像的诊断应用。初步毒性研究表明 NSFR的安全性。毒性剂量远远超过对比剂所需的剂量 增强功能。长期目标是开发临床上有用的核磁共振 用于诊断人类疾病的造影剂。

Nuclear magnetic resonance (NMR) imaging is an emerging diagnostic tool capable of tomographic imaging of humans without the use of ionizing radiation. Two NMR imagers, developed in our department, utilize the magnetic behavior of hydrogen nuclei and depict their distribution and magnetic relaxation characteristic within bodily tissues. The aims of this project are to better define by animal experimentation the diagnostic benefits, the toxicity, and the pharamacology of nitroxide stable free radicals (NSFR) used in vivo as NMR contrast agents. The proposed investigations require the combined disciplines of diagnostic imaging, synthetic chemistry, physics and pharmacology. Preliminary studies in animals show that NSFR, a group of organic paramagnetic compounds used as contrast media can enhance the NMR contrast differences between urinary structures and surrounding tissues and permit evaluation of renal function. Tested NSFR are rapidly excreted by glomerular filtration and appear within urinary structures to produce a dramatic increase in the NMR intensity signal. NSFR, like many radiographic contrast media, are largely excluded from the central nervous system by the normally functioning blood-brain barrier. It is postulated that these contrast media will penetrate into the brain in pathologic conditions and thereby aid in the NMR identification of neurologic diseases. To achieve other organ-specific targetting, NSFR may be covalently conjugated to biomolecules including proteins and lipids. Aggregated particles of NSFR-protein and/or NSFR-liposomes may be diagnostically useful in NMR imaging of the liver and spleen by depicting the functional reticulo- endothelial system. These contrast-enhancing applications of NSFR would substantially add to the diagnostic utility of NMR imaging. Preliminary toxicity studies indicate safety of NSFR. Toxic doses far exceed those necessary for contrast enhancement. The long-term goal is to develop clinically useful NMR contrast agents for use in the diagnosis of human diseases.