DEVELOPMENT OF TC-99M MYOCARDIAL IMAGING AGENTS

本研究的主要目标是开发新的， 有效的心肌灌注显像剂， 99 m-Tc的核特性 这将通过合并 无机化学的技术、设备和专业知识与 核医学 重点将放在（1）无机物的阐明 锝化学，利用相对稳定的同位素99-Tc， 物理技术如单晶X射线衍射和薄层 光谱电化学仅需要非常少量样品， (2)开发99 m-Tc放射性药物的合成路线， 不涉及Sn（II）还原，（3）99 m-Tc心肌的发展 基于定义明确的单阳离子锝的灌注显像剂 配合物，（4）阐明的化学和作用机制， 近年来，单阳离子99 m-Tc心肌灌注显像剂 在本项目中开发的，例如（99 m-Tc（dmpe）2Cl 2）+和 （99 m-Tc（dmpe）3）+，其中dmpe = 1，2-双（二甲基膦）乙烷，（5） 开发体外筛选程序，以帮助选择 单阳离子99 m-Tc配合物保证了广泛的体内评价，和（6） 新型锝放射性药物的设计与合成 其分子和化学性质可以被巧妙而系统地 为了增加对心肌的特异性而修改。 动物 试验，包括对诱发急性心肌梗死的犬进行成像 梗死，将用于评估新药物的疗效 放射性药物，从而描述这些分子和化学物质 比增强心肌摄取的性质。 最有前途的心肌 将在人类受试者中评价灌注成像剂。

The primary objective of this research is the development of new, efficacious, myocardial perfusion imaging agents based on the chemistry and nuclear properties of 99m-Tc. This will be accomplished by merging the techniques, equipment and expertise of inorganic chemistry with those of nuclear medicine. Emphasis will be on (1) elucidation of the inorganic chemistry of technetium, utilizing the relatively stable isotope 99-Tc and physical techniques such as single crystal x-ray diffraction and thin-layer spectroelectrochemistry which require only very small quantities of sample, (2) development of synthetic routes to 99m-Tc radiopharmaceuticals that do not involve Sn(II) reduction, (3) development of 99m-Tc myocardial perfusion imaging agents based on well defined, monocationic technetium complexes, (4) elucidation of the chemistry and mechanism of action of those monocationic 99m-Tc myocardial perfusion imaging agents recently developed within this project, e.g. (99m-Tc(dmpe)2Cl2)+ and (99m-Tc(dmpe)3)+ where dmpe = 1,2-bis(dimethylphosphine)ethane, (5) development of in vitro screening procedures to aid in selecting which monocationic 99m-Tc complexes warrant extensive in vivo evaluation, and (6) design and synthesis of new classes of technetium radiopharmaceuticals, the molecular and chemical properties of which can be subtly and systematically modified in order to increase specificity for the myocardium. Animal testing, including the imaging of dogs with induced acute myocardial infarction, will be used to evaluate the efficacy of new radiopharmaceuticals and thereby delineate those molecular and chemical properties than enhance myocardial uptake. The most promising myocardial perfusion imaging agents will be evaluated in human subjects.