PERMEABILITY AND BLOOD FLOW IN EXPERIMENTAL GLIOMAS

这些研究旨在获得关于药物输送的信息， 实验性脑瘤 我们以前的工作表明， 实验性脑内水溶性化合物的血液-组织转运 肿瘤的 具体目的是：1）研究皮质类固醇的作用 和X射线照射对血流和血液到组织运输的影响; 2）研究 可能增加大脑中血液向组织转运速率的方法 肿瘤（高渗破坏、高血压、高碳酸血症、高热 和二甲亚砜）; 3）开发体内方法来测量 使用计算机断层扫描（CT）扫描的血液到组织的转运率; 4)为了测量几种常见的血液到组织的运输速率， 使用癌症化疗药物，以及; 5）将 具有毛细血管超微结构特征的血液至组织转运， 测量可用于经毛细血管的毛细血管表面积 交易所 将使用Kety-Schmidt方程测量血流量。 的 将测量血液至组织的转运速率， α-氨基异丁酸（其具有单向血液-组织 运输）或斜率截距数据分析方法， 具有双向毛细管输送的化合物。 组织浓度 将通过定量放射自显影术测量放射性标记药物的量。 肿瘤毛细血管的表面积将在染色后测量。 含有因子VIII/von Willebrand抗血清的毛细血管， 过氧化物酶-抗过氧化物酶 因为大多数化疗药物都是水 水溶性的化合物，并且由于水溶性化合物具有低的跨毛细血管速率， 我们希望找到一种方法， 会增加到脑肿瘤。 为了使这些方法得以应用 对于人类，测量体内跨毛细血管转运速率的方法 将需要，为此，我们计划使用CT扫描仪和 斜率截距图解法 我们亦计划研究 脑肿瘤毛细血管的运输特性，以观察 化疗药物的跨毛细血管转运可以根据 取决于药物的水溶性或分子大小 如果这些 目标可以实现，它们将直接适用于 治疗人类脑肿瘤患者。

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.