TARGETED METAL CHELATORS FOR DIAGNOSTIC IMAGING

金属放射性核素广泛应用于诊断成像。放射性同位素 镓、铟、氚和铜被用于核医学 在磁共振成像中，使用Gd络合物作为顺磁性造影剂的研究 结合核磁共振成像(MRI)。新的改进 设计了针对这些金属离子的络合剂。这些属性 这些新的螯合剂将利用分子预测 力学计算，配体将被合成，并且 用物理化学方法研究金属络合物的性质 以及体内和体外生物学评价。络合物一直是 通过使用带有给体的配体来实现最大的热动力学稳定性 对特定金属具有高度选择性的基团。指控和 通过改变供体基团来改变络合物的亲脂性 以及烷基和其他取代基的添加。这块金属 螯合物将通过几种类型的连接进行功能化，以允许 蛋白质和多肽的共价结合。特别强调的是 给出了金属铟和铜的新配体。稳定性 新配体的常数将被测定，金属的动力学 测量到离解。配体和配体的生物学行为 蛋白质和多肽上的双功能螯合物将被确定 在体外和动物模型中。 将进行合成、表征和物理化学研究。 在德克萨斯A&M大学进行了体外和体内评价 药物准备工作将在华盛顿进行 大学。

Metal radionuclides are widely used in diagnostic imaging. Radioisotopes of gallium, indium, technetium and copper are used in nuclear medicine studies while gadolinium chelates act as paramagnetic contrast agents in conjunction with nuclear magnetic resonance imaging (MRI). New improved chelating agents for these metal ions have been designed. The properties of these new chelating agents will be predicted utilizing molecular mechanic calculations, the ligands will be synthesized and the characteristics of the metal complexes studied by physicochemical methods as well as in vivo and in vitro biological evaluation. Chelates have been designed for maximum thermadynamic stability by using ligands with donor groups highly selective for the particular metals. The charge and lipophilicity of the chelates will be altered by changing the donor groups as well as the addition of alkyl groups and other substituents. The metal chelates will be functionalized with several types of linkages to allow covalent attachment to proteins and peptides. Particular emphasis is being given to new ligands for the metal indium and copper. The stability constants of the new ligands will be determined and the kinetics of metal dissociation measured. The biological behavior of both the ligands and bifunctional chelates attached to proteins and peptides will be determined in vitro and in animal models. The synthesis characterization and physicochemical studies will be carried out at Texas A&M University while the in vitro and in vivo evaluation of the pharmaceutical preparations will be undertaken at Washington University.