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

动脉内一过性破坏血脑屏障 甘露醇等高渗剂的给药已用于 人类患有脑瘤，试图增加局部递送 化疗药物。对这种方法的分析一直受到以下因素的阻碍 难以量化输送到脑组织的溶质。 使用正电子发射断层扫描(PET)的技术现在可用于 研究其潜在的生理机制。具体地说， 跨组织毛细血管的单向转移速率常数(KI)可以 使用RB-82静脉注射测定，同时局部血流和血液 体积可以用其他发射正电子的示踪剂测量。短小的 这些放射性示踪剂的半衰期允许顺序研究来表征 屏障修饰的生理学和时程 瞬变性质，大约30分钟。 该协议有两个主要目标。第一个是发展和 实施特定的PET方法以执行所需的 测量。我们计划实施局部大脑的测量 血容量和放出正电子的一氧化碳。此外，我们计划 开发和实施一种快速重复测量的方法 局部脑血流，每隔一段时间用正电子发射计算机断层扫描和推注0-15水。 比现在用于顺序流动的12分钟周期更快 确定，即重复测量将在 之前测量的放射性本底已经衰变。这个 该协议的第二个目标是将这些方法与使用 第三种放射性示踪剂RB-82用于研究瞬变的生理学 动脉内给药对血脑屏障的破坏作用 高渗剂，甘露醇。这些研究将在 麻醉的狒狒。

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.