BRAIN EXTRACTION AND BLOOD FLOW WITH THE 123-I AMINES

最近，123 I-胺，N-异丙基-P-123 I-碘苯丙胺（123 I-IMP） 和 N，N，N'-三甲基-N'-（2-羟基-3-甲基-5-碘苄基）-1，3-丙二胺 （123I-HIPDM）已被提议作为用于测量脑损伤的试剂。 病理学中的血流 在本提案中，我们希望研究 这些123 I-胺在各种不同的分布之间的关系 确定它们是否可用作定量指标的条件 脑血流的变化，并研究脑摄取和 潴留 这些新药物在许多研究中具有潜在的用途， 病理条件下，无论是在动物模型中使用放射自显影， 使用单光子发射断层扫描（SPECT）对人类进行检测。 使用这些 在动物中使用放射自显影和在人类中使用SPECT， 建议将测量间隔从30秒或5分钟延长。我们还 我建议比较这两种123 I-胺在病理条件下， 评价它们作为CBF试剂在人类病理学中的有用性。 大脑 将在不同的条件下确定浸提液和血流 动脉pH和胺比活性，以评估麸皮的作用机制 吸收和保留。 这项研究所需的技术已经在这个实验室里开发出来了 并涉及使用123I和14C标记的示踪剂， 双放射性核素放射自显影术 直接评价 123 I-胺分布将与CB1进行比较，如使用 在高度区域性的基础上建立了CBF示踪剂14C-碘安替比林。 的 123I-胺脑摄取和保留的机制尚不确切， 但已经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 通过跨脑血屏障的pH梯度施加。 这些123 I-胺在脑卒中、癫痫、脑梗死和脑梗死患者中的行为研究 鹅膏蕈氨酸损伤模型，并作为pH和胺特异性的函数 活性将定义脑摄取机制和I-123的有用性 胺作为CBF示踪剂。

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.