Delivery of proteins to CNS as seen and measured by positron emission tomography.
Delivery of proteins to CNS as seen and measured by positron emission tomography.
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DOI：
10.1007/s13346-012-0073-3
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发表时间：
2012-06
影响因子：
5.4
通讯作者：
Gillooly, C.
中科院分区：
文献类型：
--
作者：
Papisov, Mikhail I.;Belov, V.;Fischman, A. J.;Belova, E.;Titus, J.;Gagne, M.;Gillooly, C.
关键词：
目前，多种涉及中枢神经系统（CNS）的疾病还没有有效的治疗方法。虽然正在开发几种新颖的分子方法，但其中许多方法需要将大分子或超分子药物输送到受血脑和血蛛网膜屏障保护的中枢神经系统组织。正在开发的各种用于克服或绕过障碍的方法都是基于复杂的转移过程。生物药品和其他大分子和颗粒向中枢神经系统的输送，特别是通过软脑膜（鞘内）途径，包括多个阶段，例如软脑膜传播、引流到体循环以及渗透到中枢神经系统。复杂的药代动力学研究，包括对流、扩散和主动转移过程，极大地受益于药物转运的实时无创体内监测。药理学正电子发射断层扫描（PET）成像可以实现这种监测，在药物输送和生物药理学中发挥着越来越重要的作用。 PET 是一种强大的工具，用于定量体内跟踪正电子发射放射性核素标记的分子。数据的高灵敏度、格式和准确性（类似于传统组织采样生物分布研究）使 PET 成为一种易于采用的药理学技术。与传统研究相比，PET 还允许进行纵向非末端同动物研究。后者不仅可以改善数据统计，而且还可以实现传统方法下不可行的临床前研究（特别是在大型和/或稀有动物中）。本文旨在展示 PET 获得的数据的特征，并展示如何使用该方法研究软脑膜途径药代动力学的主要模式。数据处理的例子取自我们最近对大鼠和非人类灵长类动物的五种模型蛋白的研究。
Presently, there are no effective treatments for several diseases involving the central nervous system (CNS). While several novel molecular approaches are being developed, many of them require delivery of macromolecular or supramolecular agents to the CNS tissues protected by the blood–brain and blood–arachnoid barriers. A variety of approaches that are being developed for overcoming or bypassing the barriers are based on complex transfer processes. The delivery of biopharmaceuticals and other macromolecules and particulates to the CNS, especially through the leptomeningeal (intrathecal) route, includes a variety of stages, such as leptomeningeal propagation, drainage to the systemic circulation, and penetration into the CNS. The investigation of complex pharmacokinetics that includes convective, as well as diffusional and active transfer processes, greatly benefit from real-time non-invasive in vivo monitoring of the drug transport. Pharmacological positron emission tomography (PET) imaging, which enables such monitoring, plays an increasingly significant role in drug delivery and biopharmacology. PET is a powerful tool for quantitative in vivo tracking of molecules labeled with positron-emitting radionuclides. The high sensitivity, format, and accuracy of the data (similar to those of conventional tissue sampling biodistribution studies) make PET a readily adoptable pharmacological technique. In contrast to the conventional studies, PET also allows for longitudinal nonterminal same-animal studies. The latter may not only improve the data statistics, but also enable preclinical studies (especially in large and/or rare animals) not feasible under the conventional approach. This paper is intended to demonstrate the character of data that can be obtained by PET and to demonstrate how the main patterns of the leptomeningeal route pharmacokinetics can be investigated using this method. Examples of data processing are taken from our recent studies of five model proteins in rats and nonhuman primates.
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影响因子：
3.7
作者：
Calias, Pericles;Papisov, Mikhail;Heartlein, Michael W.
通讯作者：
Heartlein, Michael W.
影响因子：
2.9
作者：
RENNELS, ML;GREGORY, TF;GRADY, PA
通讯作者：
GRADY, PA
影响因子：
158.5
作者：
RIESELBACH, RE;DICHIRO, G;FREIREICH, EJ
通讯作者：
FREIREICH, EJ
影响因子：
4.9
作者：
Belov, Vasily V.;Bonab, Ali A.;Papisov, Mikhail I.
通讯作者：
Papisov, Mikhail I.
DOI：
10.1201/9781420023404.sec2
发表时间：
2005-01-01
期刊：
BLOOD-CEREBROSPINAL FLUID BARRIER
影响因子：
--
作者：
Segal, MB
通讯作者：
Segal, MB