RADIOPHARMACEUTICALS LABELED WITH METAL RADIONUCLIDES

该项目的目标是开发新的和改进的 放射性药物设计，使核医学利用 一些金属放射性核素的吸引人的核特性。 的 该项目的主要重点将是血流示踪剂的发展 用发生器产生的正电子发射核素（铜-62和 镓-68）。 这种示踪剂可能有助于更广泛地使用正电子 发射断层扫描（PET）在临床诊断中通过减少依赖 PET的核心是需要内部回旋加速器生产的核素。 一些研究在锝化学也提出，再次强调 这些化合物作为灌注示踪剂的潜在作用。 底层 这些努力是为了阐明无机化学原理 和药物设计，可能会在研究中找到广泛的普遍应用， 提供新的金属标记的放射性药物。 金属络合物，具有被认为是重要的性能， 实现与局部血流速率成比例的组织摄取， 在宏观（10-3 × 10- 1 M）和示踪剂下制备和表征 浓度的 将筛选这些放射性标记的金属络合物， 通过测定它们的放射性，评价它们作为放射性药物的潜力。 静脉注射后在大鼠中的生物分布。 这些研究将 用于识别最佳示踪剂以供进一步评估。 此外，本发明还提供了一种方法， 生物分布研究将提供数据， 构效关系描述了分子特征至关重要， 在感兴趣的组织（脑，心脏， 肾和肿瘤）。 研究中发现的最有前途的示踪剂 将在动物模型中通过比较它们的 使用标准参考示踪剂测量的具有血流的组织摄取 （标记的微球和碘安替比林）。 PET成像实验， 已经开发的铜-62示踪剂将与 教授Steven R。Bergmann和Marcus E.莱克尔在华盛顿 大学，允许这些化合物的性能进行评估 相对于动物模型中标准回旋加速器产生的PET示踪剂 系统. 铜（II）双（缩氨基硫脲）的合成工作 已经开发的复合体也将继续，以完善其 制备成方便可靠的试剂盒制剂， 铜-62发生器的洗脱液。

The goal of this project is the development of new and improved radiopharmaceuticals designed to allow nuclear medicine to exploit the attractive nuclear properties of a number of metallic radionuclides. The main focus of the project will be the development of blood flow tracers labeled with generator-produced positron-emitting nuclides (copper-62 and gallium-68). Such tracers might facilitate more widespread use of positron emission tomography (PET) in clinical diagnosis by reducing the dependence of PET centers on nuclides that require in-house cyclotron production. Some studies in technetium chemistry are also proposed, again emphasizing the potential role of these compounds as perfusion tracers. Underlying these efforts is a desire to elucidate principles of inorganic chemistry and drug design that might find broad general application in research to deliver new metal-labeled radiopharmaceuticals. Metal complexes, possessing properties believed to be important for achieving tissue uptake in proportion to regional rates of blood flow, will be prepared and characterized at both macroscopic (10-3 10-1M) and tracer concentrations. These radiolabeled metal complexes will be screened to evaluate their potential as radiopharmaceuticals by determination of their biodistribution in rats following intravenous injection. Such studies will serve to identify the best tracers for further evaluation. In addition, the biodistribution studies will provide data for the definition of structure-activity relationships describing the molecular features vital to tracer uptake and tracer retention in tissues of interest (brain, heart, kidney, and tumor). The most promising tracers identified in the studies with rats will be further assessed in animal models by comparison of their tissue uptake with blood flow measured using standard reference tracers (labeled microspheres and iodoantipyrine). PET imaging experiments with the copper-62 tracers already developed will be conducted in collaboration with Professors Steven R. Bergmann and Marcus E. Raichle at Washington University, allowing the performance of these compounds to be evaluated relative to standard cyclotron-produced PET tracers in animal model systems. Synthetic work with the copper (II) bis(thiosemicarbazone) complexes already developed will also continue, in order to refine their preparation into a convenient and reliable kit formulation for use with the eluent of a copper-62 generator.