DRUG TRANSPORT IN BRAIN

大流量输沙的理论模型和实验模型 脑组织内的微量输注表明了 以灰色或白色在厘米距离上传送大分子 物质。要解决输液控制的剩余问题和 在监测中，一项在猴子身上进行的研究 111-in-DTPA-转铁蛋白测定：(A)穿透距离和 使用长期脑白质输注可达到的体积 植入式可编程泵；(B)可植入泵的长期净空率 来自输注区的蛋白质；(C)影响的程度 微量灌注对脑血流灌注率的影响；以及(D)SPECT是否 可用于在治疗过程中无创地评估这些因素 输液。输注药物的平均流速为 1.9microl/min，87小时，平面和SPECT图像 获得输注蛋白和区域灌注标志物HMPAO 开始输液后第1、3、4、8和11天；放射自显影 取自另一只输液后9小时处死的猴子。一个 将39%的强度阈值应用于D-V SPECT图像 产生了与测量的D-V白质扩散相匹配的宽度 直接放在放射自显影上。A-P、M-L和D-V期末价差 输液量分别为2.7 cm、2.2 cm和2.9 cm。输液 3只猴子输液后输液量从4.9毫升到6.7毫升不等。 从经吸收校正的平面图像确定组织间隙 是0.118加-0.033微升/分钟/毫升，提示 脉管外液体的产生和流动。局部灌注量减少 规模较小(约为3.4%)。

Theoretical and experimental transport models of high-flow microinfusion into brain tissue have indicated the feasibility of delivering macromolecules over cm distances in either grey or white matter. To address remaining issues of infusion control and monitoring, a study was undertaken in monkeys with 111-In-DTPA-transferrin to determine: (a) penetration distances and volumes achievable with long-term white matter infusions using implantable programmable pumps; (b) long-term clearance rates of the protein from the infused region; (c) the magnitude of the effect of microinfusion on blood perfusion rates to brain; and (d) whether SPECT could be used to assess these factors noninvasively during the course of infusion. Drug was infused at an average flow rate of 1.9microl/min for 87 hrs, and planar and SPECT images of both the infused protein and regional perfusion marker HMPAO were obtained on days 1,3,4,8, and 11 following beginning of infusion; autoradiography was obtained from another monkey sacrificed 9 hrs post-infusion. An intensity threshold of 39% that was applied to the D-V SPECT image yielded a width matched to the D-V white matter spread measured directly on autoradiograms. A-P, M-L, and D-V spreads at end of infusion were 2.7 cm, 2.2 cm, and 2.9 cm, respectively. Infusion volumes over 3 monkeys ranged from 4.9 ml to 6.7 ml. Post-infusion tissue clearance determined from absorption-corrected planar images was 0.118 plus minus 0.033 microl/min/ml, suggestive of clearance by extrachoroidal fluid production and flow. Local perfusion reduction was small (on the order of 3.4%).