PET NEURONAL TRACES KINETICS IN ISOLATED DISEASED HEARTS

PET 神经元追踪离体患病心脏的动力学

• 批准号: 6330143
• 负责人: DAVID M RAFFEL
• 金额: $ 9.92万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-17 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6330143
• 关键词: amines; bioimaging /biomedical imaging; blood chemistry; carbon; catecholamines; diabetic neuropathy; disease /disorder model; doxorubicin; drug metabolism; heart disorder diagnosis; heart failure; heart innervation; laboratory rat; mechanical pressure; membrane transport proteins; nervous system disorder diagnosis; neurons; noninvasive diagnosis; norepinephrine; pharmacokinetics; positron emission tomography; radiotracer; streptozotocin; sympathetic nervous system; tissue /cell culture

DESCRIPTION: (Adapted from the applicant's abstract) The structurally related norepinephrine analogues [C-11]meta-hydroxyephedrine, [C-11]phenylephrine, and [C-11]epinephrine have been developed as radiotracers for non-invasive imaging studies of cardiac sympathetic innervation using positron emission tomography (PET). Striking alterations in the kinetic behavior of these neuronal tracers have been seen in PET studies of patients with diabetic autonomic neuropathy and heart failure. Associating the altered tracer kinetics with specific neuronal abnormalities has been difficult, as several hypothetical changes in neuronal function could cause such alterations. The major goal of the proposed studies is to correlate changes in the kinetics of these radiotracers to specific neuronal changes in cardiac sympathetic neurons using rat models of diabetic autonomic neuropathy and heart failure. The proposed studies will build on an existing foundation of kinetic studies performed in the isolated working rat heart. Kinetic studies in hearts isolated from rat models of diabetes and heart failure will be used to assess the sensitivity of the tracer kinetics to pathology-induced changes in cardiac sympathetic nerve populations. Following the tracer kinetic studies, direct in vitro measurements of several key components of cardiac sympathetic neurons will be performed in the same hearts to characterize the extent and severity of the pathology-induced neuronal changes. The in vitro studies will include determinations of the densities of neuronal norepinephrine transporters (NET) and vesicular monoamine transporters (VMAT), as well as tissue catecholamine levels. By identifying correlations between the kinetic data and the in vitro findings, insight into the specific underlying causes of perturbations in the tracer kinetics may be gained. This information should assist clinicians, who are studying cardiac sympathetic neurons with these agents, to interpret their clinical findings. In addition, these studies will provide new information concerning the affects of these diseases upon cardiac sympathetic nerve populations.

描述：（从申请人的摘要中进行了改编） 相关的去甲肾上腺素类似物[C-11] meta-羟基麻黄碱， [C-11]苯肾上腺素和[C-11]肾上腺素已开发为 用于心脏交感的非侵入性成像研究的放射性示例 使用正电子发射断层扫描（PET）神经化。 引人注目的改变 在这些神经元示踪剂的动力学行为中 糖尿病自主神经病和心力衰竭患者的研究。 将改变的示踪剂动力学与特定的神经元异常相关联 很难，因为神经元功能的几种假设变化 可能会引起这种改变。 拟议研究的主要目标是 这些放射性示例的动力学的变化与特定的神经元的变化 使用糖尿病大鼠模型的心脏交感神经元的变化 自主神经病和心力衰竭。 拟议的研究将基于 在孤立的工作中进行的现有动力学研究基础 老鼠心。 从糖尿病大鼠模型中分离出的心脏的动力学研究 心力衰竭将用于评估示踪剂的灵敏度 病理学引起的心脏交感神经变化的动力学 人群。 遵循示踪动力学研究，直接在体外直接 心脏交感神经元的几个关键组成部分的测量将 在同一心中进行表征 病理引起的神经元变化。 体外研究将包括 确定神经元去甲肾上腺素转运蛋白的密度 （NET）和囊泡单胺转运蛋白（VMAT）以及组织 儿茶酚胺水平。 通过识别动力学数据之间的相关性 以及体外发现，深入了解 可以获得示踪剂动力学中的扰动。 这些信息应该 协助临床医生，他们正在研究心脏交感神经元 代理商，解释他们的临床发现。 另外，这些研究 将提供有关这些疾病影响的新信息 心脏交感神经种群。