NEW PET RADIOTRACERS--MONOAMINE TRANSPORTERS

描述：许多重要的神经系统、心理健康和药物滥用 这些问题涉及单胺能系统的功能障碍或丧失， 人类大脑，特别是多巴胺能神经元。 体内 使用放射性药物和正电子发射对这些系统进行成像 断层扫描（PET）提供了一种独特而有价值的方法来研究 这些疾病在活着的人脑中。 选择合适的 放射性示踪剂，单独和组合，将是至关重要的成功， 例如体内成像。 本项目将研究动物模型， 疾病，使用双重体内放射性示踪剂研究的新方法， 囊泡单胺转运体（VMAT 2）和多巴胺神经元膜 转运蛋白（DAT）。 这些结合位点的潜在体内调节 疾病过程和慢性药物治疗将进行评估。 的 这种转运蛋白B激酶介导磷酸化的短期调节 将对反应进行研究。 两个传送者之间的关系， 本文提出作为神经末端完整性（VMAT 2）和神经传导的标志物。 终末功能（DAT）将在变性模型中随时间进行检查 帕金森病和药物滥用的动物模型的恢复。 随后将进行研究，以确定是否测量的人数， 终端（VMAT 2）、功能状态（DAT）或每个终端上的功能 基础（DAT/VMAT '2）提供了最佳的灵敏度，用于测量体内 目前和新的治疗方法对改变病程的影响 这些疾病。 该项目将提供有关适当的关键信息 单胺能放射性核素在体断层显像方法 终末相关疾病的发生、进展或治疗， 患者人群。 最后，合成放射化学的努力将是 承诺将这种方法扩展到测量VMAT 2以外的 多巴胺能神经支配的纹状体，开辟了新的途径， 研究单胺能（特别是多巴胺能和 肾上腺素能）终端在更广泛的各种神经，心理健康和 药物滥用疾病。

DESCRIPTION: A number of important neurologic, mental health and drug abuse problems involve dysfunctioning or losses of the monoarninergic systems of the human brain, and in particular the dopaminergic neurons. In vivo imaging of these systems using radiopharmaceuticals and Positron Emission Tomography (PET provides a unique and valuable approach to the study of these diseases in the living human brain. Choices of appropriate radiotracers, alone and in combinations, will be crucial for the success of such in vivo imaging. This Project will examine animal models of such diseases, using a novel approach of dual in vivo radiotracer studies of the vesicular monoamine transporter (VMAT2 and the dopamine neuronal membrane transporter (DAT). The potential in vivo regulation of these binding sites by disease processes and chronic drug treatments will be evaluated. The short term regulation of such transporters b kinase-mediated phosphorylation reactions will be studied. The relationship between the two transporters, proposed here as markers of nerve terminal integrity (VMAT2) and nerve terminal function (DAT), will be examined over tim in models of degeneration and recovery in animal models of Parkinson's disease and drug abuse. Studies will subsequently be done to determine whether measure of numbers of terminals (VMAT2), functional status (DAT), or function on a per terminal basis (DAT/VMAT'2) provides the best sensitivity for measuring in viv the effects of current and new therapeutic approaches to changing the course o these diseases. This Project will provide crucial information on the proper approach to be taken for in vivo tomographic radionuclide of monoaminergic terminal-related disease inception, progression or treatment in a general patient population. Finally, synthetic radiochemistry efforts will be undertaken to extend this approach to measuring the VMAT2 outside the heavily-dopaminergic innervated striaturn, opening up new avenues of research into the role of monoaminergic (particularly, serotonergic and adrenergic) terminals in a wider variety of neurologic, mental health and drug abuse diseases.