THE CHEMISTRY OF TECHNETIUM RELATED TO NUCLEAR MEDICINE

本研究的目的是进一步研究 含取代异腈配体的锝配合物 常规临床核医学。 目标是利用 这些实验室最初开发的技术， 导致了新的心肌灌注的临床试验 代理（99 mTc-MIBI）目前正在美国和欧洲的医疗 中心. 异腈类化合物原则上构成了一个非常重要的 大量不同的化学物质， 生物分布特性。 这可能是因为 配体（CN-R）与中心金属原子碳键合，因此 允许内部协调领域的性质， 通过改变取代基R基团来修饰络合物。 到 要想充分挖掘这门课的潜力， 化学、生物化学和生物学研究的 宏观和示踪剂浓度使用长寿命 放射性核素Tc-99和短寿命伽马发射体Tc-99 m。 因此，本提案描述了一个综合和 表征含有多种的锝络合物， 取代的异腈配体，并评估它们作为 新的放射性药物 这些程序将包括完整的 载体添加水平下化合物的化学鉴别 并将化学物质转移到不添加载体的浓度 进行生物学评估。 这部分研究将涉及 开发新的合成和分析方法， 结构-活性关系可以通过体内和体内 使用明确定义的化学物质进行体外研究。 的 类的那些成员的行动机制， 已经被证明对人体心脏成像有效 将被审查。 此外，这种多功能的其他应用 将研究一系列复合物，例如，心脏 反映除简单灌注以外的过程的试剂， 用于研究肺、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.