RADIOTRACER RANDD IN NUCLEAR MEDICINE AND NEUROSCIENCES

50多年来，示踪技术的应用增强了我们的 了解生物化学和生理过程。 PET是一种独特的 跟踪方法中的工具，因为它能够跟踪分布 标记化合物在完整的活的人和动物中的动力学 身体 PET的这些特殊特性可以被 应用于生物学和医学的问题是紧密耦合到 生物选择性和敏感的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发”计划 放射性示踪剂化学的最终目标是推进和 促进在神经科学、临床实践和 药物研究和开发。 这种方法是多方面的， 协同作用，包括三个主要领域的研究：回旋加速器靶向技术; 合成方法学;放射性示踪剂生物学和机制。 过去 7年的奖励期内，我们取得了重大进展，包括第一次 无载体添加（NCA）F-18标记的儿茶酚胺的合成和 使用亲核芳族化合物的新应用的氟代多巴 在富电子芳环上的取代反应;首次使用 动力学同位素效应与PET表征的分子机制 单胺氧化酶B（MAO B）示踪剂[11 C] L-丙炔苯丙胺在 脑; PET在药物研究和开发中的应用， 新的中枢神经系统药物; 2-脱氧-2- [18F]氟-D-葡萄糖（FDG）引入高灵敏度分析 方法;优化生产碘-123和碘- 124从一个中等能量回旋加速器和;机器人技术的应用， 定量PET研究。 这次更新的主要科学推动力 应用程序将建立在这些进步的基础上，并进行新的研究 包括：（1）回旋加速器靶技术，包括低温 针对当前短缺的氟-18生产的C18 O2目标 富O-18水的生产和碘-124生产的优化， （2）合成化学（C-11、F-18和1-124） 包括NCA F-18全氯酰氟（[18F] ClO 3）的合成， 亲电异构化;新的C-1烷基化方法; 用于提高体内放射性碘稳定性的二苯碘鎓缀合物 超临界流体色谱作为一种新的色谱技术， 放射性示踪剂的纯化方法（3）放射性示踪剂的生物学和机理 包括NCA F-18标记的儿茶酚胺的研究， 它们在神经心脏病学中的应用以及[11 C]RO 19 6327（一种新的可逆MAO B） 抑制剂药物是潜在的第二代单胺氧化酶B示踪剂。 本研究 建立在布鲁克海文集团的优势和多样性及其 在PET领域的主要贡献的历史。 的成就 过去的资助期表明，这种多方面的方法 生产力和协同支持的假设，一个坚实的基础 在放射性示踪剂化学和生物学方面的进展可以导致PET的重要进展 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.