TARGETED METAL CHELATORS FOR DIAGNOSTIC IMAGING

用于诊断成像的靶向金属螯合剂

• 批准号: 2007586
• 负责人: MICHAEL J. WELCH
• 金额: $ 29.78万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2007586
• 关键词: autoradiography; baboons; chelating agents; chemical association; chemical binding; chemical conjugate; chemical kinetics; contrast media; copper; drug design /synthesis /production; drug screening /evaluation; gadolinium; gallium; hamsters; indium; laboratory rat; ligands; magnetic resonance imaging; metal complex; outcomes research; positron emission tomography; radionuclide imaging /scanning; radiopharmacology; stereochemistry; thermostability

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.

金属放射性核素广泛用于诊断成像。 放射性同位素 镓、铟、锝和铜的元素被用于核医学 研究，而钆螯合物作为顺磁性造影剂， 与核磁共振成像（MRI）结合使用。 新的改进 已经设计了用于这些金属离子的螯合剂。 性能 这些新的螯合剂将预测利用分子 机械计算，将合成配体， 用物理化学方法研究金属配合物的特性 以及体内和体外生物学评价。 螯合物已经 通过使用具有供体的配体， 对特定金属具有高度选择性的基团。 充 螯合物的亲脂性将通过改变供体基团而改变 以及加入烷基和其它取代基。 金属 螯合物将用几种类型的键官能化 与蛋白质和肽共价连接。 特别强调， 给出了金属铟和铜的新配体。 稳定性 新配体的常数将被确定和金属的动力学 测量解离。 两种配体和 将测定连接到蛋白质和肽的双功能螯合物 在体外和动物模型中。 本论文将进行合成、表征和理化性质的研究 在得克萨斯A&M大学， 药物准备工作将在华盛顿进行 大学