MAGNETIC RESONANCE IMAGING STUDIES OF HEAVY METAL DISTRIBUTION

最近已经可以获得空间分辨的“图像”， 生物和化学材料的核自旋。 磁共振 磁共振成像（MRI）正在迅速发展成为临床诊断的重要工具。 诊断各种人类病理。 临床MRI研究是 越来越多地依赖于使用补充的“造影剂”， 提高这些研究的诊断价值。 其中两类 通过改变核弛豫性质起作用的试剂， 利用：螯合顺磁性离子，已发现广泛的临床 应用和稳定的有机氮氧自由基。 使用这种 代理人提出了关于决定他们的因素的基本问题。 分布和代谢，以及短期或长期的问题， 毒性 我们以前研究过几种 这些试剂，包括裸过渡金属离子，GD-DTPA，螯合物， 目前临床使用的镧系元素化合物，和GdHAM， 带净正电荷的实验药剂。 代理人介绍 以评价该途径的潜在诊断效用 行政管理。 根据初步结果，净电荷可能 在确定这些化合物的分布中起重要作用， 一系列的研究使用裸过渡金属离子和CDTA螯合 形式进行了。 研究结果有力地支持了 电荷在确定组织分布中的重要性， 未螯合的过渡金属离子以及GdHAM的管腔壁 可能与带负电荷的 唾液酸残基存在于这些结构中。 在一系列相关的 研究中，一系列稳定的氮氧化合物被类似地施用， 脑内 这些药物使用这种途径更有效， 由于这些减少的最小速率， CSF中的化合物，这与血液中的短寿命形成鲜明对比 和细胞中。 在这些应用中， 实现，与代理人的寿命显然与他们的速度 细胞膜的运输。

It has recently become possible to obtain spatially resolved "images" of the nuclear spins of biological and chemical materials. Magnetic resonance imaging (MRI) is rapidly evolving into an important tool for the clinical diagnosis of a wide range of human pathologies. Clinical MRI studies are increasingly relying on the use of supplemental "contrast agents" to enhance the diagnostic value of these studies. Two classes of these agents, which act by altering nuclear relaxation properties, have been utilized: chelated paramagnetic ions, which have found widespread clinical applications, and stable organic nitroxide radicals. The use of such agents raises basic questions about the factors which determine their distribution and metabolism, as well as questions about short or long term toxicity. We have previously investigated the distribution of several of these agents, including bare transition metal ions, GD-DTPA, a chelated lanthanide compound which is currently in clinical use, and GdHAM, an experimental agent with a net positive charge. Agents were introduced intracerebrally to evaluate the potential diagnostic utility of this route of administration. Based on initial results suggesting that net charge may play an important role in determining the distribution of these compounds, a series of studies using both bare transition metal ions and CDTA chelated forms was carried out. The results provide strong support for the importance of charge in determining tissue distribution, with the adherence of unchelated transition metal ions as well as GdHAM to the luminal walls of the cerebral ventricles presumably related to the negatively charged sialic acid residues present in these structures. In a related series of studies, a series of stable nitroxides has been similarly administered intracerebrally. These agents are much more effective using this route of administration as a consequence of the minimal rate of reduction of these compounds in CSF, which contrasts sharply with the short lifetimes in blood and in cells. In these applications, significant contrast has been achieved, with the lifetime of the agents apparently related to their rate of transport across cell membranes.