Kim Minhyung, Barone Tara A, Fedtsova Natalia, Gleiberman Anatoli, Wilfong Chandler D, Alosi Julie A, Plunkett Robert J, Gudkov Andrei, Skitzki Joseph J
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.
Department of Neuro Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
J Neurooncol. 2016 Jan;126(1):37-45. doi: 10.1007/s11060-015-1942-7. Epub 2015 Sep 16.
Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.
从历史上看,对包括多形性胶质母细胞瘤(GBM)在内的恶性脑肿瘤进行动脉内(IA)给药是为了改善药物递送。随着经皮神经血管技术和现代微导管的出现,颅内药物递送已切实可行;然而,与静脉内(IV)或口服给药等其他递送方式相比,IA给药是否安全且更有效仍是个问题。临床前大型动物模型可用于比较不同治疗途径并测试新型药物,但成本高昂,且难以大量快速产出结果。因此,我们开发了一种用于GBM的IA药物递送小鼠模型,该模型可重复,能清晰显示肿瘤反应和神经毒性。在此,我们描述了一种通过进入颈内动脉来治疗同侧植入GBM肿瘤的新型IA药物递送小鼠模型,该模型操作简便,结果一致且可重复。建立这个独特平台的目的是高效研究可能利用针对脑肿瘤的定向区域治疗方法设计的靶向抗肿瘤药物。