INTRODUCTION Intra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated IA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of IA therapy for the treatment of brain tumors and refinement of its potential applications are necessary. METHODS We have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSIACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of IA therapy for the treatment of brain tumors. RESULTS Trends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the IA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy. CONCLUSION IA drug delivery may significantly affect the way treatments are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of IA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, IA therapy may offer significant benefits for the treatment of brain tumors.

中文翻译：

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血脑屏障破坏后的现代化学疗法的超选择性动脉内脑灌注：我们现在在哪里，我们要去哪里。

引言治疗剂跨血脑屏障（BBB）的动脉内（IA）输送是一种不断发展的策略，它可以使高浓度治疗剂通过目标血管区域分布，同时有可能限制全身毒性。研究表明，IA方法对于多种治疗方法都是安全有效的。但是，有必要进一步表征IA治疗脑肿瘤的临床疗效并完善其潜在应用。方法我们回顾了支持BBB破坏的超选择性动脉内脑输注（SSIACI）用于治疗脑肿瘤的临床前和临床证据。此外，我们回顾了正在进行的临床试验，这些试验扩大了IA治疗脑肿瘤的适用性并研究了其疗效。结果最近的研究趋势包括使用SSIACI和较少的神经毒性化学疗法。大多数试验继续使用甘露醇作为高渗性BBB破坏的首选方法。近期对贝伐单抗IA递送的临床前和人类初步研究表明，它单独或与化学疗法联合用作抗肿瘤药的安全性和有效性。结论IA药物输送可能会显着影响脑肿瘤患者尤其是GBM患者的治疗方式。随着IA药物递送技术的完善和标准化，药物选择和制剂的改进，