BRAIN EXTRACTION AND BLOOD FLOW WITH THE 123-I AMINES

最近合成的123I-胺，N-异丙基-P-123I-碘苯丙胺(123I-IMP) 和 N、N、N‘-Trimethyl-N’-(2-hydroxy-3-methyl-5-123I-iodobenzyl)-1，3-prpanediamine (123I-HIPDM)已被提出作为脑部测量的试剂 病理学中的血液流动。在这项建议中，我们希望研究 ~(123)I-胺在不同组织中的分布关系 确定它们是否可用作数量指标的条件 脑血流量的变化，并研究脑摄取的机制和 留存。这些新试剂在许多研究中都有潜在的用途 在动物模型中使用放射自显影和在 人类使用单光子发射断层扫描(SPECT)。要使用这些工具 动物放射自显影和人类SPECT的指示物，我们 建议将测量间隔从30秒或5分钟延长。我们也 建议将这两种123I-胺在病理条件下与 评估它们作为CBF制剂在人类病理学中的有效性。大脑 提取和血流量将在不同的条件下测定 动脉pH和胺比活度评价麸皮作用机制的研究 摄取和保留。 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 双重放射性核素放射自显影。对学生的直接评价 123I-胺的分布将与CB1进行比较，如用 在高度区域性的基础上建立了CBF示踪剂14C-安替比林。这个 ~(123)I-胺脑摄取和滞留的机制尚不清楚。 但已被认为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某些影响 由穿过脑血屏障的pH梯度施加的。 ~(123)I-胺在中风、癫痫等疾病中的行为研究 鹅膏糖酸损伤模型，以及作为pH和胺特异性的函数 活性将定义大脑摄取I-123的机制和有用性 作为CBF示踪剂的胺。

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.