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Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

机译:中枢神经系统肿瘤的局部靶向治疗的分子影像学进展

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摘要

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.
机译:由于化学疗法发展的最新进展,许多癌症的发病率和死亡率已大大降低。但是,与一般的肿瘤学相比,神经肿瘤学领域落后了。尽管出现了新的分子靶向化学治疗药物,但血脑屏障(BBB)的不渗透性使这些临床药物的全身递送效果欠佳。为了规避血脑屏障,临床上正在采用新颖的给药途径,从动脉内输注和直接输注到目标组织(对流增强输送(CED))到使用聚焦超声来暂时破坏血脑屏障。但是,当前系统依赖于“观望”方法,只有在观察到特定的临床结果时,才认为药物输送成功。这种方法的缺点很明显,因为无法观察和纠正需要立即改进的失败交付。针对这一问题,正在开发具有成像和治疗潜力的新型治疗药物,为改善和监测向中枢神经系统(CNS)恶性肿瘤的递送铺平了道路。在这篇综述中,我们关注于这些新药物的开发所带来的改进早期癌症检测,靶向治疗选择和治疗效果评估的进展和挑战。

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