NEW PET RADIOTRACERS--MONOAMINE TRANSPORTERS

描述：一些重要的神经学、心理健康和药物滥用 问题涉及单胺能系统的功能障碍或丧失。 人类的大脑，特别是多巴胺能神经元。活体内 使用放射性药物和正电子发射对这些系统进行成像 体层摄影术(PET)提供了一种独特而有价值的研究方法 这些疾病存在于活着的人脑中。选择合适的 放射性示踪剂，无论是单独的还是组合的，都将是取得成功的关键。 这样的活体成像。本项目将研究这样的动物模型 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(VMAT2)与多巴胺神经元膜 传输器(DAT)。这些结合位点在体内的潜在调节 将根据疾病进程和慢性药物治疗进行评估。这个 这类转运体的短期调节--b激酶介导的磷酸化 我们将对反应进行研究。这两个运输商之间的关系， 建议作为神经末梢完整性(VMAT2)和神经的标志物 终端功能(DAT)将在退行性变模型中随时间进行检查 帕金森氏病和药物滥用的动物模型的康复。 随后将进行研究，以确定衡量 端子(VMAT2)、功能状态(DAT)或每个端子上的功能 Basis(DAT/VMAT‘2)为VIV测量提供了最佳的灵敏度 当前和新的治疗方法对改变病程的影响 这些疾病。该项目将提供适当的关键信息 单胺类核素活体断层显像应采取的方法 终末期相关疾病的开始、进展或治疗 病人群体。最后，合成放射化学的努力将是 承诺将此方法扩展到在外部测量VMAT2 大量多巴胺能神经支配的纹状体，开辟了 单胺能(特别是5-羟色胺能和 肾上腺素能)终末在更广泛的神经学、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.