PET STUDIES OF HYPEROSMOTIC OPENING OF THE BLOOD-BRAIN BARRIER IN BABOONS

狒狒血脑屏障高渗打开的 PET 研究

• 批准号: 3874320
• 负责人: P HERSCOVITCH
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874320
• 关键词: Cercopithecidae; blood brain barrier; blood flow measurement; blood osmolarity; blood volume; diagnosis design /evaluation; drug delivery systems; mannitol; physiology; positron emission tomography; radionuclide diagnosis

Transient disruption of the blood-brain barrier by intraarterial administration of hyperosmotic agents such as mannitol has been used in humans with brain tumors in an attempt to increase the local delivery of chemotherapeutic agents. Analysis of this approach has been hampered by difficulties in quantifying the delivery of solutes to brain tissue. Techniques using positron emission tomography (PET) are now available to study the underlying physiologic mechanisms. Specifically, the unidirectional transfer rate constant (KI) across tissue capillaries can be determined using Rb-82 administered IV, while local blood flow and blood volume can be measured with other positron-emitting tracers. The short half-lives of these radiotracers permit sequential studies to characterize the physiology and time course of barrier modification in spite of its transient nature, about 30 min. This protocol has two major goals. The first is the development and implementation of specific PET methods to perform the required measurements. We plan to implement the measurement of regional cerebral blood volume with positron-emitting carbon monoxide. In addition, we plan to develop and implement a method for the rapid repeat measurement of regional cerebral blood flow with PET and bolus 0-15 water, at intervals more rapid than the 12 min period now used for sequential flow determinations, i.e. repeat measurements will be made before the radioactive background from the previous measurements has decayed. The second goal of this protocol is to apply these methods along with the use of a third radiotracer, Rb-82 to study the physiology of transient disruption of the blood-brain barrier by intraarterial administration of a hyperosmotic agent, mannitol. These studies will be performed in anesthetized baboons.

动脉内注射对血脑屏障的短暂破坏 高渗剂如甘露醇的给药已经被用于 患有脑肿瘤的人，试图增加局部递送 化疗剂。对这种方法的分析受到以下因素的阻碍： 难以定量溶质向脑组织的递送。 使用正电子发射断层扫描（PET）的技术现在可用于 研究潜在的生理机制。具体而言是 通过组织毛细血管的单向转移速率常数（KI）可以 使用IV施用的Rb-82测定，而局部血流和血液 可以用其它正电子发射示踪剂测量体积。短 这些放射性示踪剂的半衰期允许连续研究来表征 屏障修饰的生理学和时间过程， 瞬变性质，约30 min。 该协议有两个主要目标。首先是发展和 实施特定的PET方法，以执行所需的 测量.我们计划实施局部脑的测量， 正电子释放一氧化碳的血容量。此外，我们计划 开发和实施快速重复测量的方法， 局部脑血流量与PET和推注0-15水，间隔 比现在用于顺序流动的12分钟周期更快 测定，即在测定前进行重复测量。 先前测量的放射性背景已经衰减。的 本协议的第二个目标是沿着使用这些方法 第三种放射性示踪剂Rb-82，用于研究短暂的 通过动脉内给药的血脑屏障的破坏 高渗剂甘露醇这些研究将在 麻醉的狒狒