THE CHEMISTRY OF TECHNETIUM RELATED TO NUCLEAR MEDICINE

这项研究的目的是进一步调查 含取代异腈配体的氚络合物 常规临床核医学。这样做的目的是为了利用 基于这些实验室最初开发的技术 已经导致了一种新的心肌灌注的临床试验 目前在美国和欧洲的医疗机构正在使用99mTc-MIBI试剂 中锋。 异腈类化合物原则上构成一个非常 大量不同的化学物种，差异很大 生物分布特性。这是可能的，因为 配体(CN-R)以碳键连接到中心金属原子上，因此 允许内部协调范围的性质 通过改变取代基R基来修饰的络合物。至 研究这一类的全部潜力需要一个组合 化学、生物化学和生物学研究 使用长寿命的宏观和示踪剂浓度 放射性核素TC-99和短命伽马发射体TC-99m。 因此，这项提案描述了一项计划，以合成和 表征含有各种不同元素的氚络合物 取代异腈配体并评价其作为 新的放射性药物。这些程序将包括完成 载体添加水平上化合物的化学鉴定 以及将化学反应转移到不添加载体的浓度 用于生物学评估。这部分研究将涉及 开发新的合成和分析方法，以便 构效关系可通过体内和体内研究。 使用明确定义的化学物种的体外研究。这个 班级成员的行动机制 已经被证明对人类心脏成像有效 将会被检查。此外，此多功能的其他应用程序 将对一系列络合物进行研究，例如心脏 反映过程而不是简单灌流和 研究肺、肝胆和肾的放射性药物 功能。

The aims of this research are to investigate further the uses of technetium complexes containing substituted isonitrile ligands in routine clinical nuclear medicine. The objective is to capitalize upon technology originally developed in these laboratories that has since led to the clinical trials of a new myocardial perfusion agent (99mTc-MIBI) now underway in U.S. and European medical centers. The isonitrile class of compounds in principle constitute a very large number of different chemical species with widely differing biological distribution properties. This is possible because the ligands (CN-R) are carbon-bonded to the central metal atom, thus allowing the nature of the inner coordination sphere of the complexes to be modified by varying the substituent R group. To investigate the full potential of this class requires a combination of chemical, biochemical and biological studies at both macroscopic and tracer concentrations using the long-lived radionuclide Tc-99 and the short-lived gamma emitter Tc-99m. This proposal describes, therefore, a program to synthesize and characterize technetium complexes containing a variety of substituted isonitrile ligands and to evaluate their potential as new radiopharmaceuticals. The procedures will include complete chemical identification of the compounds at carrier added levels and transfer of the chemistry to no carrier added concentrations for biological evaluation. This portion of the research will involve developing new methods of synthesis and analysis, so that structure-activity relationships can be examined by in vivo and in vitro studies using well-defined chemical species. The mechanisms of action of those members of the class that have already been shown to be effective for imaging the human heart will be examined. In addition, other applications of this versatile series of complexes will be investigated, for example, cardiac agents that reflect processes other than simple perfusion and radiopharmaceuticals for studying lung, hepatobiliary, and renal function.