Young Jacob S, Bernal Giovanna, Polster Sean P, Nunez Luis, Larsen Gustavo F, Mansour Nassir, Podell Michael, Yamini Bakhtiar
Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
Section of Neurosurgery, Department of Surgery, The University of Chicago, Chicago, Illinois, USA.
World Neurosurg. 2018 Sep;117:e698-e704. doi: 10.1016/j.wneu.2018.06.114. Epub 2018 Jun 27.
Despite aggressive multimodal treatment, survival for patients with glioblastoma remains dismal. One obstacle to improving patient outcomes is the difficulty in delivering adequate therapeutic to the central nervous system due to the presence of the blood-brain barrier. Although direct drug infusion by convection-enhanced delivery (CED) can bypass the blood-brain barrier and facilitate delivery to intracranial tumors, determining the distribution of delivered therapeutic remains problematic. Image guidance is a strategy that can optimize the accuracy of therapeutic delivery.
Here we performed an open-label clinical trial in 10 pet dogs with spontaneous intracranial tumors to examine the target coverage accuracy of delivering polymeric magnetite nanoparticles (PMNPs) encapsulating temozolomide (TMZ). A modified small animal frame was applied to the head of each subject, and PMNPs were delivered stereotactically to the center of the tumor. Magnetic resonance imaging (MRI) was performed immediately postoperatively to examine PMNP distribution, and the animals were followed until death.
Nine of the 10 dogs underwent PMNP infusion without complications. No infusate backflow was observed during any procedure. In 70% of the cases, the infusion accurately targeted the tumor mass, as determined by the presence of PMNP signal in the tumor on immediate postoperative MRI.
These data suggest that CED of PMNPs carrying TMZ is safe in dogs with intracranial tumors and can lead to nanoparticle distribution in the region of the target. Image guidance is an important adjunct to CED, because distribution is unpredictable, with the potential for missed target delivery.
尽管采用了积极的多模式治疗，但胶质母细胞瘤患者的生存率仍然很低。改善患者预后的一个障碍是由于血脑屏障的存在，难以向中枢神经系统提供足够的治疗药物。虽然通过对流增强递送（CED）进行直接药物输注可以绕过血脑屏障并促进向颅内肿瘤的递送，但确定所递送治疗药物的分布仍然存在问题。图像引导是一种可以优化治疗递送准确性的策略。
在此，我们对10只患有自发性颅内肿瘤的宠物狗进行了一项开放标签临床试验，以检查递送包裹替莫唑胺（TMZ）的聚合磁铁矿纳米颗粒（PMNPs）的靶区覆盖准确性。将改良的小动物框架应用于每个受试者的头部，并通过立体定向将PMNPs递送至肿瘤中心。术后立即进行磁共振成像（MRI）以检查PMNP分布，并对动物进行随访直至死亡。
10只狗中有9只接受了PMNP输注，无并发症发生。在任何操作过程中均未观察到注入液回流。根据术后立即进行的MRI上肿瘤中PMNP信号的存在情况确定，在70%的病例中，输注准确地靶向了肿瘤块。
这些数据表明，携带TMZ的PMNPs的CED在患有颅内肿瘤的狗中是安全的，并且可以导致纳米颗粒在靶区分布。图像引导是CED的重要辅助手段，因为分布是不可预测的，存在错过靶区递送的可能性。
