Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain
Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain
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DOI：
10.1016/j.expneurol.2005.08.016
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Bankiewicz, KS
中科院分区：
文献类型：
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作者：
Saito, R;Krauze, MT;Bankiewicz, KS
长期以来，向脑肿瘤输送药物一直是一个重大挑战。对流增强递送（CED）已被开发为克服这一困难的药物递送策略。理想地，通过CED输注的药物的组织分布的直接可视化将确保治疗剂成功递送至脑肿瘤，同时使正常脑的暴露最小化。我们先前开发了一种基于磁共振成像（MRI）的方法，以可视化CED后脂质体药物在啮齿动物大脑中的分布。在本研究中，在非人灵长类动物脑中进一步检查脂质体的CED（n = 6）。将含有钆特醇、DiI-DS和罗丹明的脂质体注入放射冠壳核和脑干。通过组织学和MR成像分析所有递送位置的分布容积。含钆脂质体的实时MRI监测允许直接可视化稳健的分布。脂质体钆的MRI在确定组织分布方面高度准确，这一点通过与同时给予荧光脂质体的组织学结果进行比较得到证实。在所有靶向位置建立了脂质体输注量与分布量之间的线性相关性。我们的结论是，脂质体/纳米颗粒技术，CED和MRI相结合的综合策略可能为脑肿瘤的治疗提供新的机会。当使用CED管理患者时，我们直接监测和控制脂质体药物局部给药的能力很可能会导致更大的临床疗效。(c)2005年爱思唯尔公司All rights reserved.
Drug delivery to brain tumors has long posed a major challenge. Convection-enhanced delivery (CED) has been developed as a drug delivery strategy to overcome this difficulty. Ideally, direct visualization of the tissue distribution of drugs infused by CED would assure successful delivery of therapeutic agents to the brain tumor while minimizing exposure of the normal brain. We previously developed a magnetic resonance imaging (MRI)-based method to visualize the distribution of liposomal agents after CED in rodent brains. In the present study, CED of liposomes was further examined in the non-human primate brain (n = 6). Liposomes containing Gadoteridol, DiI-DS, and rhodamine were infused in corona radiata putamen nucleus, and brain stem. Volume of distribution was analyzed for all delivery locations by histology and MR imaging. Real-time MRI monitoring of liposomes containing gadolinium allowed direct visualization of a robust distribution. MRI of liposomal gadolinium was highly accurate at determining tissue distribution, as confirmed by comparison with histological results from concomitant administration of fluorescent liposomes. Linear correlation for liposomal infusions between infusion volume and distribution volume was established in all targeted locations. We conclude that an integrated strategy combining liposome/nanoparticle technology, CED, and MRI may provide new opportunities for the treatment of brain tumors. Our ability to directly monitor and to control local delivery of liposomal drugs will most likely result in greater clinical efficacy when using CED in management of patients. (c) 2005 Elsevier Inc. All rights reserved.