BRAIN EXTRACTION AND BLOOD FLOW WITH THE 123-I AMINES

使用 123-I 胺进行脑提取和血流

• 批准号: 3401162
• 负责人: JOEL H GREENBERG
• 金额: $ 13.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3401162
• 关键词: acid base balance; amines; autoradiography; blood brain barrier; brain metabolism; cerebrovascular disorder diagnosis; disease /disorder model; epilepsy; radiotracer; single photon emission computed tomography; stroke

Recently, the 123I-amines, N-isopropyl-P-123 I-iodoamphetamine (123I-IMP) and N,N,N'-Trimethyl-N'-(2-hydroxy-3-methyl-5-123I-iodobenzyl)-1,3-prpanediamine (123I-HIPDM) have been proposed as agents for the measurement of cerebral blood flow in pathology. In this proposal we wish to study the relationship between the distribution of these 123I-amines in various conditions to ascertain whether they can be used as quantitative indicators of cerebral blood flow and to study the mechanism of brain uptake and retention. These new agents have potential use both in the study of many pathological conditions, both in animal models using autoradiography and in humans using single photon emission tomography (SPECT). To use these indicators with autoradiography in animals and with SPECT in humans, we propose to extend the measurement interval from 30 sec or 5 min. We also propose to compare these two 123I-amines in pathological conditions to evaluate their usefulness as CBF agents in human pathology. The brain extraction and blood flow will be determined under conditions of varying arterial pH and amine specific activity to evaluate the mechanism of bran uptake and retention. The techniques needed for this study have been developed in this laboratory and involve the use of 123I and 14C labeled tracers using quantitative double radionuclide autoradiography. The direct evaluation of the 123I-amines distribution will be compared to CB1, as measured with the established CBF tracer, 14C-iodoantipyrine on a highly regional basis. The mechanism of 123I-amines brain uptake and retention is not known exactly, but has been proposed to be due to either their high lipid solubility, their interaction with nonspecific amine binding situes, or some influence exerted by the pH gradient across the brain blood barrier. The study of the behavior of these 123I-amines during stroke, epilepsy, in the ibotenic acid lesion model, and as a function of pH and amine specific activity will define the brain uptake mechanism and usefulness of the I-123 amines as CBF tracers.

最近，123I-胺，N-异丙基-P-123I-碘苯丙胺（123I-IMP） 和 N,N,N'-三甲基-N'-(2-羟基-3-甲基-5-123I-碘苄基)-1,3-丙二胺 (123I-HIPDM) 已被提议作为测量脑功能的试剂。 病理学中的血流。 在本提案中，我们希望研究 这些 123I-胺在各种物质中的分布之间的关系 确定是否可以作为定量指标的条件 脑血流量并研究脑摄取和机制 保留。 这些新药物在许多研究中都有潜在用途 病理条件，无论是在使用放射自显影的动物模型中还是在 人类使用单光子发射断层扫描（SPECT）。 要使用这些 通过动物放射自显影和人类 SPECT 的指标，我们 建议将测量间隔从 30 秒或 5 分钟延长。 我们也 建议在病理条件下比较这两种 123I-胺 评估它们作为 CBF 制剂在人类病理学中的有用性。 大脑 提取和血流量将在不同的条件下确定 动脉pH值和胺比活性评价麸皮作用机制 吸收和保留。 本研究所需的技术已在本实验室开发 并涉及使用 123I 和 14C 标记的示踪剂进行定量 双放射性核素放射自显影。 直接评价 123I-胺分布将与 CB1 进行比较，用 在高度区域性的基础上建立了 CBF 示踪剂 14C-碘安替比林。 这 123I-胺脑摄取和保留的机制尚不清楚， 但有人提出是由于它们的高脂溶性， 它们与非特异性胺结合位点的相互作用，或一些影响 由跨脑血屏障的 pH 梯度产生。 对这些 123I-胺在中风、癫痫期间的行为的研究 鹅膏菌酸损伤模型，以及 pH 值和胺特异性的函数 活动将决定 I-123 的大脑摄取机制和用途 胺作为 CBF 示踪剂。