Varenika Vanja, Dickinson Peter, Bringas John, LeCouteur Richard, Higgins Robert, Park John, Fiandaca Massimo, Berger Mitchel, Sampson John, Bankiewicz Krystof
Department of Neurological Surgery, University of California, San Francisco, CA, USA.
J Neurosurg. 2008 Nov;109(5):874-80. doi: 10.3171/JNS/2008/109/11/0874.
The authors have shown that convection-enhanced delivery (CED) of gadoteridol-loaded liposomes (GDLs) into different regions of normal monkey brain results in predictable, widespread distribution of this tracking agent as detected by real-time MR imaging. They also have found that this tracking technique allows monitoring of the distribution of similar nanosized agents such as therapeutic liposomes and viral vectors. A limitation of this procedure is the unexpected leakage of liposomes out of targeted parenchyma or malignancies into sulci and ventricles. The aim of the present study was to evaluate the efficacy of CED after the onset of these types of leakage.
The authors documented this phenomenon in a study of 5 nonhuman primates and 7 canines, comprising 54 CED infusion sessions. Approximately 20% of these infusions resulted in leakage into cerebral ventricles or sulci. All of the infusions and leakage events were monitored with real-time MR imaging. The authors created volume-distributed versus volume-infused graphs for each infusion session. These graphs revealed the rate of distribution of GDL over the course of each infusion and allowed the authors to evaluate the progress of CED before and after leakage.
The distribution of therapeutics within the target structure ceased to increase or resulted in significant attenuation after the onset of leakage.
An analysis of the cases in this study revealed that leakage undermines the efficacy of CED. These findings reiterate the importance of real-time MR imaging visualization during CED to ensure an accurate, robust distribution of therapeutic agents.
作者已表明，将载有钆特醇的脂质体（GDLs）通过对流增强递送（CED）注入正常猴脑的不同区域，实时磁共振成像检测到这种示踪剂可实现可预测的广泛分布。他们还发现，这种追踪技术可用于监测类似纳米尺寸制剂（如治疗性脂质体和病毒载体）的分布。该操作的一个局限性是脂质体意外地从靶向实质或恶性肿瘤中漏出到脑沟和脑室中。本研究的目的是评估这类漏出发生后CED的效果。
作者在一项对5只非人灵长类动物和7只犬的研究中记录了这一现象，该研究包括54次CED输注过程。其中约20%的输注导致漏入脑室或脑沟。所有输注和漏出事件均通过实时磁共振成像进行监测。作者为每个输注过程绘制了体积分布与注入体积的图表。这些图表揭示了每次输注过程中GDL的分布速率，并使作者能够评估漏出前后CED的进展情况。
漏出发生后，治疗剂在靶结构内的分布停止增加或显著衰减。
对本研究中的病例分析表明，漏出会削弱CED的效果。这些发现重申了在CED过程中进行实时磁共振成像可视化以确保治疗剂准确、可靠分布的重要性。
