PERMEABILITY AND BLOOD FLOW IN EXPERIMENTAL GLIOMAS

这些研究的目的是为了获得有关药物传递的信息 实验性脑瘤。我们之前的研究表明， 水溶性化合物在实验性脑内的血到组织转运 肿瘤。具体目的是：1)研究皮质类固醇的作用 和x射线对血液流动和血液到组织运输的影响；2)研究 可能提高血液到组织在脑中的运输速度的方法 肿瘤(高渗紊乱、高血压、高碳酸血症、高热 和二甲基亚砜)；3)建立一种体内测量方法 使用计算机断层扫描(CT)的血液到组织传输的速率； 4)测定几种常见的血液到组织的转运速率。 使用癌症化疗药物，以及；5)关联 毛细血管和组织超微结构特征下的血到组织转运 测量可供跨毛细管使用的毛细血管表面积 交换。血流量将用Kty-Schmidt方程测量。这个 血液到组织的传输速度将用以下方法测量 α-氨基异丁酸(具有单向血液到组织 交通)或使用坡度截取数据分析方法 具有双向毛细传输的化合物。组织浓度 放射性标记药物的数量将通过定量放射自显影进行测量。 在染色后将测量肿瘤毛细血管的表面积 毛细血管与因子VIII/von Willebrand抗血清和 过氧化物酶-抗过氧化物酶。因为大多数化疗药物都是水 可溶的，因为水溶性的化合物具有较低的跨毛细管速率 在脑瘤中的传输，我们希望找到药物输送的方法 可能会增加到脑瘤。为了应用这些方法 对人体来说，一种测量体内毛细血管转运速度的方法 将需要，我们计划使用CT扫描仪和 图解分析的斜截法。我们亦计划研究 脑肿瘤毛细血管传输特性的研究 化疗药物的跨毛细血管转运可以预测，基于 无论是药物的水溶性还是分子大小。如果这些 目标可以实现，它们将直接适用于 治疗人脑肿瘤患者。

These studies are designed to obtain information about drug delivery in experimental brain tumors. Our previous work has shown low rates o blood-to-tissue transport of water soluble compounds in experimental brain tumors. The specific aims are: 1) to study the effects of corticosteroids and x-irradiation on blood flow and blood-to-tissue transport; 2) to study methods that may increase the rate of blood-to-tissue transport in brain tumors (hyperosmotic disruption, hypertension, hypercapnia, hyperthermia and dimethyl sulfoxide); 3) to develop an in vivo method to measure the rate of blood-to-tissue transport using computed tomographic (CT) scanning; 4) to measure the rates of blood-to-tissue transport of several commonly used cancer chemotherapeutic drugs, and; 5) to correlate the rate of blood-to-tissue transport with ultrastructural features of capillaries and measure the surface area of capillaries available for transcapillary exchange. Blood flow will be measured with Kety-Schmidt equations. The rate of blood-to-tissue transport will be measured with alpha-aminoisobutyric acid (which has unidirectional blood-to-tissue transport) or with the slope-intercept method of data analysis for compounds with bi-directional capillary transport. Tissue concentrations of radiolabeled drugs will be measured by quantitative autoradiography. The surface area of tumor capillaries will be measured after staining the capillaries with Factor VIII/von Willebrand antiserum and peroxidase-antiperoxidase. Since most chemotherapeutic drugs are water soluble, and since water soluble compounds have low rates of transcapillary transport in brain tumors, we hope to find methods with which drug delivery can be increased to brain tumors. In order for these methods to be applied to humans, a method to measure the rate of transcapillary transport in vivo will be needed, for whic we plan to use the CT scanner and the slope-intercept methd of graphical analysis. We also plan to study the transport properties of brain tumor capillaries to see if the rate of transcapillary transport of chemotherapeutic drugs can be predicted, based on either the water solubility or molecular size of the drug. If these objectives can be accomplished, they will have direct applicability in the treatment of human brain tumor patients.