DEVELOPMENT OF TC-99M MYOCARDIAL IMAGING AGENTS

这项研究的主要目标是开发新的， 有效的、基于化学和药物的心肌灌注显像剂 ~(99m)Tc的核性质这将通过合并 无机化学的技术、设备和专业知识 核医学。重点将放在(1)无机物的阐明上 利用相对稳定的同位素~(99)T和~(99)T的氚的化学 单晶x射线衍射和薄层等物理技术 光谱电化学法只需要极少量的样品， (2)99m-Tc放射性药物合成路线的开发 不涉及锡(II)还原；(3)~(99m)Tc心肌显影 基于明确定义的单阳离子氚的灌注显像剂 络合物，(4)化学和作用机理的阐明 单阳离子99m-Tc心肌灌注显像剂的研究进展 在该项目内开发的，例如(99m-Tc(Dmpe)2Cl2)和 (99m-Tc(Dmpe)3)式中dmpe=1，2-二(二甲基膦)乙烷，(5) 体外筛选程序的发展以帮助选择 单阳离子99m-Tc络合物需要广泛的体内评价，以及(6) 新型氚放射性药物的设计与合成 它的分子和化学性质可以微妙和系统地 为了增加对心肌的特异性而进行修改。动物 测试，包括犬诱发急性心肌梗死的成像 脑梗塞，将被用来评估新的疗效 放射性药物，从而描绘出这些分子和化学物质 这些特性比增强心肌摄取更重要。最有希望的心肌 灌注显像剂将在人体内进行评估。

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.