Fiandaca Massimo S, Forsayeth John R, Dickinson Peter J, Bankiewicz Krystof S
Department of Neurological Surgery, University of California San Francisco, San Francisco, California 94103, USA.
Neurotherapeutics. 2008 Jan;5(1):123-7. doi: 10.1016/j.nurt.2007.10.064.
Convection-enhanced delivery (CED) of substances within the human brain is becoming a more frequent experimental treatment option in the management of brain tumors, and more recently in phase 1 trials for gene therapy in Parkinson's disease (PD). Benefits of this intracranial drug-transfer technology include a more efficient delivery of large volumes of therapeutic agent to the target region when compared with more standard delivery approaches (i.e., biopolymers, local infusion). In this article, we describe specific technical modifications we have made to the CED process to make it more effective. For example, we developed a reflux-resistant infusion cannula that allows increased infusion rates to be used. We also describe our efforts to visualize the CED process in vivo, using liposomal nanotechnology and real-time intraoperative MRI. In addition to carrying the MRI contrast agent, nanoliposomes also provide a standardized delivery vehicle for the convection of drugs to a specific brain-tissue volume. This technology provides an added level of assurance via visual confirmation of CED, allowing intraoperative alterations to the infusion if there is reflux or aberrant delivery. We propose that these specific modifications to the CED technology will improve efficacy by documenting and standardizing the treatment-volume delivery. Furthermore, we believe that this image-guided CED platform can be used in other translational neuroscience efforts, with eventual clinical application beyond neuro-oncology and PD.
对流增强递送（CED）技术在人脑中输送物质，正日益成为脑肿瘤治疗中一种更为常用的实验性治疗选择，最近在帕金森病（PD）基因治疗的1期试验中也有应用。与更标准的递送方法（如生物聚合物、局部输注）相比，这种颅内药物输送技术的优势在于能够更有效地将大量治疗剂输送至靶区域。在本文中，我们描述了为使CED过程更有效而对其进行的特定技术改进。例如，我们开发了一种抗反流输注套管，可提高输注速率。我们还介绍了我们利用脂质体纳米技术和实时术中磁共振成像（MRI）在体内可视化CED过程的工作。除了携带MRI造影剂外，纳米脂质体还为将药物对流至特定脑组织结构提供了标准化的递送载体。这项技术通过对CED进行视觉确认，提供了更高的保障水平，若出现反流或异常递送情况，可在术中对输注进行调整。我们认为，对CED技术的这些特定改进将通过记录和标准化治疗体积递送提高疗效。此外，我们相信这个图像引导的CED平台可用于其他转化神经科学研究，最终临床应用范围将超越神经肿瘤学和帕金森病。
