Real-time visualization and characterization of liposomal delivery into the monkey brain by magnetic resonance imaging

Michal T. Krauze , Tracy R. Mcknight , Yoji Yamashita , John Bringas , Charles O. Noble , Ryuta Saito , Karsten Geletneky , John Forsayeth , Mitchel S. Berger , Pamela Jackson , John W. Park , Krystof S. Bankiewicz
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引用次数: 97

Abstract

Liposomes loaded with Gadoteridol, in combination with convection-enhanced delivery (CED), offer an excellent option to monitor CNS delivery of therapeutic compounds with MRI. In previous studies, we investigated possible clinical applications of liposomes to the treatment of brain tumors. In this study, up to 700 μl of Gadoteridol/rhodamine-loaded liposomes were distributed in putamen, corona radiata and brainstem of non-human primates. Distribution was monitored by real-time MRI throughout infusion procedures and allowed accurate calculation of volume of distribution within anatomical structures. We found that different regions of the brain gave various volumes of distribution when infused with the same volume of liposome. Based on these findings, distinct distribution pathways within infused structures can be predicted. This work underlines the importance of monitoring drug delivery to CNS and enables accurate delivery of drug-loaded liposomes to specific brain regions with a standard MRI procedure. Findings presented in this manuscript may allow for modeling of parameters used for direct delivery of therapeutics into various regions of the brain.

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利用磁共振成像技术实时可视化和表征脂质体进入猴子大脑的过程
负载Gadoteridol的脂质体与对流增强递送(CED)相结合,为MRI监测治疗性化合物的中枢神经系统递送提供了一个极好的选择。在之前的研究中,我们研究了脂质体在脑肿瘤治疗中的可能临床应用。在本研究中,非人灵长类动物壳核、辐射冠和脑干中分布着高达700 μl的加多啶醇/罗丹明脂质体。在整个输注过程中,通过实时MRI监测分布,并精确计算解剖结构内的分布体积。我们发现,当注入相同体积的脂质体时,大脑的不同区域具有不同的分布体积。基于这些发现,可以预测注入结构内不同的分布路径。这项工作强调了监测药物递送到中枢神经系统的重要性,并使载药脂质体能够通过标准MRI程序准确递送到特定的大脑区域。在这篇手稿中提出的发现可能允许用于治疗药物直接输送到大脑的各个区域的参数建模。
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