DIAGNOSTIC RADIOLOGY-IMAGING, CHEMOTHERAPY-BRAIN TUMOR

诊断放射学-成像、化疗-脑肿瘤

• 批准号: 3174567
• 负责人: JAMES H ANDERSON
• 金额: $ 24.24万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-05-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3174567
• 关键词: brain neoplasms; carmustine; computed axial tomography; drug metabolism; edema; floxuridine; image processing; intraarterial administration; laboratory rabbit; mathematical model; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neuropharmacology; nitrosourea; nonhuman therapy evaluation; pharmacokinetics; steroids

The long term objective of our animal research is to provide important information necessary to improve the clinical application of intraarterial chemotherapy for treating brain tumors. More specifically, we will continue our current studies aimed at delineating the pharmacokinetic parameters associated with intraarterial administration of chemotherapeutic agents. Emphasis will be placed on evaluating how the intraarterial advantage (Rd) of drug delivery can be improved through (1) modifying the manner in which BCNU is dissolved for infusion; (2) using steroids and non steroid agents to reduce brain tumor edema and improve drug delivery, and; (3) using a short half-life experimental chemotherapeutic agent ideally suited for intraarterial delivery. Attention will also be given to evaluating the pharmacokinetics of IA and IV administered FUDR, which could theoretically have positive practical application as a drug to be used in combination with nitrosoureas in treating brain tumors. Experimental results will be compared to theoretical models of intraarterial drug delivery. In addition, physiological and morphologic parameters such as blood flow, brain tissue edema, and brain tumor ultrastructure will be measured and correlated with the pharmacokinetic measured parameters of drug delivery. This work is particularly important since very few quantitative studies of intraarterial chemotherapy for brain tumors have been reported. The incidence of human brain tumors is significant and the results of conventional forms of therapy are poor. Although intraarterial chemotherapy for brain tumors has provided some hope of improving patient prognosis, information regarding the basic pharmacokinetics of this approach is lacking. Such basic information is essential in order to optimize drug delivery parameters. This information is particularly important to the Interventional Radiology community which is directly involved in intraarterial chemotherapy of brain tumors.

我们动物研究的长期目标是提供 改善临床应用所需的重要信息 用于治疗脑肿瘤的动脉内化疗。更多 具体地说，我们将继续目前的研究，旨在 描述与以下各项相关的药代动力学参数 动脉内注射化疗药物。重点 将放在评估动脉内优势(RD)方面 可以通过(1)改变给药方式来提高给药效率 其中BCNU溶解输注；(2)使用类固醇和非类固醇 减少脑瘤水肿和改善药物的类固醇类药物 给药，以及；(3)使用短半衰期实验 非常适合动脉内给药的化疗药物。 还将注意评估阿司匹林的药代动力学 IA和IV注射了FUDR，理论上可能有 作为配伍用药的积极实际应用 使用亚硝脲治疗脑肿瘤。实验结果 将其与动脉内药物的理论模型进行比较 送货。此外，生理和形态参数 如血流、脑组织水肿、脑瘤等 超微结构将被测量并与 测定了药物释放的药代动力学参数。这部作品 尤其重要，因为很少有定量研究 脑肿瘤的动脉内化疗已有报道。 人类脑肿瘤的发病率是显著的，其结果是 传统的治疗方式都很差。虽然动脉内 脑瘤的化疗提供了一些改善的希望 患者预后，有关基本药代动力学的信息 这种方法是缺乏的。这些基本信息是必不可少的。 以优化给药参数。此信息 对介入放射学社区来说尤其重要 它直接参与脑部动脉内化疗 肿瘤。