Robinson P J, Rapoport S I
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
J Cereb Blood Flow Metab. 1990 Mar;10(2):153-61. doi: 10.1038/jcbfm.1990.30.
A mathematical model describing drug uptake into brain tumors, directly from blood and indirectly from neighboring tissue, is presented. The model quantitatively describes uptake into tumor, brain surrounding tumor (BST), and normal brain and uptake following reversible osmotic blood-brain barrier (BBB) and blood-tumor barrier disruption. It employs published data on the time course for reclosure of the BBB following osmotic treatment and on the brain and tumor uptake of [14C]alpha-aminoisobutyric acid by Walker 256 carcinomas and C6 gliomas implanted into the rat brain. Constant infusion and bolus injection infusion schedules are considered. In untreated brain, the BST acts as a sink, reducing the integrated exposure of the adjacent tumor to the drug, whereas following osmotic treatment, tumor exposure to drug is enhanced, not only by increased delivery from blood but also by diffusion (and bulk flow) from neighboring brain. The model provides a quantitative framework for examining the efficacy of osmotic treatment to enhance chemotherapy of brain tumors.
本文提出了一个数学模型，该模型描述了药物直接从血液以及间接从邻近组织进入脑肿瘤的过程。该模型定量描述了药物在肿瘤、肿瘤周围脑组织（BST）、正常脑组织中的摄取情况，以及在可逆性渗透性血脑屏障（BBB）和血肿瘤屏障破坏后的摄取情况。它采用了已发表的关于渗透性治疗后血脑屏障重新闭合的时间进程数据，以及植入大鼠脑内的Walker 256癌和C6胶质瘤对[14C]α-氨基异丁酸的脑摄取和肿瘤摄取数据。考虑了持续输注和推注注射的给药方案。在未经治疗的脑中，BST起到一个汇的作用，减少了相邻肿瘤对药物的综合暴露，而在渗透性治疗后，肿瘤对药物的暴露增加，这不仅是因为从血液中输送的药物增加，还因为来自邻近脑组织的扩散（和大量流动）。该模型为研究渗透性治疗增强脑肿瘤化疗疗效提供了一个定量框架。
