RADIOTRACER RANDD IN NUCLEAR MEDICINE AND NEUROSCIENCES

五十多年来，示踪技术的应用加强了我们的 了解生化和生理过程。宠物是独一无二的 示踪剂方法中的工具，因为它能够跟踪分布 标记化合物在完整活人和动物体内的动力学 尸体。PET的这些特殊特性可以达到的速度 应用于生物和医学问题是紧密结合在一起的 生物选择性和敏感性放射性示踪剂的可用性。这 《核医学和神经科学中的放射性示踪剂研究与开发》提案 关于放射性示踪剂化学的终极目标是推进和 促进神经科学、临床实践和 药物研发。这种方法是多方面的，而且 协同作用，涵盖三个主要领域的研究：回旋加速器靶标； 综合方法论；放射性示踪剂生物学和机理。在过去的时间里 7年的获奖期，我们取得了重大进展，包括第一 无载体(NCA)F-18标记儿茶酚胺及其衍生物的合成 利用亲核芳香族化合物的新应用的氟多巴 富含电子的芳环上的取代反应；a的第一次使用 用动力学同位素效应的正电子发射体素表征分子机制 单胺氧化酶B(MAO B)示踪剂[11C]L-苯丙烯基的结合 PET在药物研发和应用中的应用 新的中枢神经系统药物；2-脱氧-2-脱氧-2-酮化学纯度的批判性研究 [18F]氟-D-葡萄糖(FDG)引入高灵敏分析 方法：优化~(123)I和~(123)I的生产目标。 124来自中能回旋加速器；机器人技术在 定量正电子发射计算机断层扫描研究。这次更新中的主要科学推动力 应用程序将在这些进展的基础上进行新的研究 包括：(1)回旋加速器靶标，包括低温加速器的研制 应对当前短缺的C18O2氟-18生产目标 O-18富集水和碘-124生产工艺的优化 计划放射治疗；(2)合成化学(用于C-11、F-18和1-124) 包括NCA F-18高氯化氟([18F]ClO_3)的合成 亲电氟化；新的C-1烷基化方法；a 二苯碘结合物提高体内放射性碘稳定性的研究 超临界流体色谱作为一种新的研究方向 放射性示踪剂提纯方法的探讨(3)放射性示踪剂生物学及其作用机制 包括对NCA F-18标记的儿茶酚胺的研究，以期 它们在神经心脏病学中的应用和[11C]RO 19 6327一种新的可逆MAO B 一种潜在的第二代MAO B示踪剂。这项研究 建立在Brookaven集团及其 在聚酯领域的主要贡献的历史。在中国取得的成就 过去的资助期表明，这种多方面的方法既是 生产性和协同性支持这样一种假设，即坚实的基础 在放射性示踪剂化学和生物学方面可以导致PET的重要进展 和核医学。

For over fifty years, the application of tracer techniques has enhanced our understanding of biochemical and physiological processes. PET is a unique tool in tracer methodology because of its ability to track the distribution and kinetics of labeled compounds in the intact living human and animal body. The rate at which these special characteristics of PET can be applied to problems in biology and medicine is tightly coupled to the availability of biologically selective and sensitive radiotracers. This proposal, "Radiotracer R & D in Nuclear Medicine and Neuroscience" focusses on radiotracer chemistry with the ultimate goal of advancing and facilitating applications in the neurosciences, in clinical practice and in drug research and development. This approach is multifaceted and synergistic, covering research in three major areas: cyclotron targetry; synthetic methodology; radiotracer biology and mechanisms. Over the past 7 year award period, we have made major advances including the first synthesis of no-carrier-added (NCA)F-18 labeled catecholamines and fluoroDOPA using a novel application of the nucleophilic aromatic substitution reaction on electron-rich aromatic rings; the first use of a kinetic isotope effect with PET to characterize the molecular mechanism for the binding of the monoamine oxidase B (MAO B) tracer, [11C]L-deprenyl in brain; the use of PET in drug research and development and application to new CNS drugs; a critical study of the chemical purity of 2-deoxy-2- [18F]fluoro-D-glucose (FDG) introducing highly sensitive analytical methods; the optimization of targetry for producing iodine-123 and iodine- 124 from a medium energy cyclotron and; the application of robotics in quantitative PET studies. Major scientific thrusts in this renewal application will build on these advances and undertake new research including: (1) cyclotron targetry including the development of a cryogenic C18O2 target for fluorine-18 production in response to the current shortage of O-18 enriched water and the optimization of iodine-124 production for planning radiotherapy; (2) synthetic chemistry (for C-11, F-18 and 1-124) including the synthesis of NCA F-18 perchloryl fluoride ([18F]CIO3) for electrophilic fluorination; new C-1 alkylation methods; a diphenyleneiodonium conjugate for increased radioiodine stability in vivo and; the investigation of supercritical fluid chromatography as a new approach to radiotracer purification (3) radiotracer biology and mechanisms including a study of the NCA F-18 labeled catecholamines with a view to their use in neurocardiology and of [11C]RO 19 6327 a new reversible MAO B inhibitor drug an potential second generation MAO B tracer. This research builds on the strengths and diversity of the Brookhaven group and its history of major contributions in the PET field. Accomplishments in the past funding period have demonstrated this multifaceted approach to be both productive and synergistic supporting the hypothesis that a firm foundation in radiotracer chemistry and biology can lead to important advances in PET and nuclear medicine.