切换至 "中华医学电子期刊资源库"

中华脑血管病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (05) : 287 -292. doi: 10.11817/j.issn.1673-9248.2021.05.003

专家论坛

对流增强给药治疗胶质母细胞瘤的研究进展
叶飞龙1, 杨冠英1,(), 王伟1   
  1. 1. 528000 广东佛山,佛山市第一人民医院影像科
  • 收稿日期:2021-04-28 出版日期:2021-10-09
  • 通信作者: 杨冠英
  • 基金资助:
    国家自然科学基金(12071075); 广东省医学科研基金(A2020278); 佛山市登峰计划(2019C016)

A systematic review on convection-enhancement delivery for glioblastoma treatment

Feilong Ye1, Guanying Yang1(), Wei Wang1   

  1. 1. Department of Radiology, the First People's Hospital of Foshan, Foshan 528000, China
  • Received:2021-04-28 Published:2021-10-09
  • Corresponding author: Guanying Yang
引用本文:

叶飞龙, 杨冠英, 王伟. 对流增强给药治疗胶质母细胞瘤的研究进展[J/OL]. 中华脑血管病杂志(电子版), 2021, 15(05): 287-292.

Feilong Ye, Guanying Yang, Wei Wang. A systematic review on convection-enhancement delivery for glioblastoma treatment[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2021, 15(05): 287-292.

胶质母细胞瘤是中枢神经系统最具侵袭性和最常见的恶性肿瘤,临床常选择手术切除后辅以放化疗进行治疗,但疗效不尽如人意,主要原因包括肿瘤难以完全切除、血脑屏障对药物的限制以及肿瘤细胞产生耐药性。对流增强给药(CED)是一种有望改善胶质母细胞瘤化疗效果的技术手段。本文通过查阅2000年至2020年间CED治疗胶质母细胞瘤的相关文献,从CED技术基础、动物模型、化疗药物、药物示踪、临床研究等方面进行综述。结果显示CED技术具有克服血脑屏障、诱导肿瘤内免疫反应、降低系统性毒性等优势,在胶质母细胞瘤的化疗中潜力极大。阐释药物在细胞间隙内的转运和代谢规律、研发高效的化疗-示踪多模态纳米药物是CED技术未来的发展方向。

Glioblastoma (GBM) is the most aggressive and common malignant tumor in the central nervous system. Current therapeutic regimens, including surgical resection combined with external radiation and chemotherapy, are insufficient to treat GBM. Three important factors account for the lack of efficacy. GBM can infiltrate into surrounding tissues and makes complete resection impossible. Besides, the blood-brain barrier usually prevents therapeutic agents and limits the chemotherapy efficacy. In addition, tumor cells can develop resistance to therapeutic agents. Convection-enhancement delivery (CED) is the technique that is expected to improve the efficacy of chemotherapy in GBM. The systematic overview of CED in the treatment of GBM is based on the researches from 2000 to 2020, involving in the technical basis of CED, animal models, chemotherapeutic agents, tracing, and clinical research. The results show that CED technology has advantages including overcoming the blood-brain barrier, inducing the immune reaction in the tumor, and reducing systemic toxicity. In the future, the mechanism on transportation and metabolism of drugs in the extracellular space and the development of chemotherapy-tracing multimodal nano-agents should be warranted.

1
Nam L, Coll C, Erthal LCS, et al. Drug delivery nanosystems for the localized treatment of glioblastoma multiforme [J]. Materials (Basel), 2018, 11(5): 779.
2
Goodenberger ML, Jenkins RB. Genetics of adult glioma [J]. Cancer Genet, 2012, 205(12): 613-621.
3
Halle B, Mongelard K, Poulsen FR. Convection-enhanced drug delivery for glioblastoma: a systematic review focused on methodological differences in the use of the convection-enhanced delivery method [J]. Asian J Neurosurg, 2019, 14(1): 5-14.
4
付睿, 王莉莉, 杨启舟. 肿瘤相关脑梗死发病机制的研究进展 [J]. 中国卒中杂志, 2021, 16(2): 124-129.
5
付睿. 肿瘤合并缺血性卒中的研究现状及展望 [J]. 中国卒中杂志, 2021, 16(2): 119-122.
6
Dong X. Current strategies for brain drug delivery [J]. Theranostics, 2018, 8(6): 1481-1493.
7
Bobo RH, Laske DW, Akbasak A, et al. Convection-enhanced delivery of macromolecules in the brain [J]. Proc Natl Acad Sci U S A, 1994, 91(6): 2076-2080.
8
Jahangiri A, Chin AT, Flanigan PM, et al. Convection-enhanced delivery in glioblastoma: a review of preclinical and clinical studies [J]. J Neurosurg, 2017, 126(1): 191-200.
9
王艾博, 田灿, 李媛媛, 等. 经脑细胞外间隙途径对流增强给药在中枢神经系统疾病治疗中研究进展 [J]. 生物医学工程与临床, 2019, 23(4): 481-486.
10
梅国顺, 杜建新. 脑胶质瘤治疗的新途径——增强对流输送 [J]. 中华神经外科杂志, 2008, 24(4): 314-316.
11
Lonser RR, Walbridge S, Garmestani K, et al. Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion [J]. J Neurosurg, 2002, 97(4): 905-913.
12
Vogelbaum MA. Convection enhanced delivery for the treatment of malignant gliomas: symposium review [J]. J Neurooncol, 2005, 73(1): 57-69.
13
宋宇, 韩鸿宾, 杨军, 等. 脑对流增强给药对老年大鼠脑细胞外间隙微观结构的影响 [J]. 北京大学学报(医学版), 2020, 52(2): 362-367.
14
Freeman AC, Platt SR, Holmes S, et al. Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for treatment of spontaneous canine intracranial gliomas [J]. J Neurooncol, 2018, 137(3): 653-663.
15
White E, Bienemann A, Pugh J, et al. An evaluation of the safety and feasibility of convection-enhanced delivery of carboplatin into the white matter as a potential treatment for high-grade glioma [J]. J Neurooncol, 2012, 108(1): 77-88.
16
Barth RF, Kaur B. Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas [J]. J Neurooncol, 2009, 94(3): 299-312.
17
Doblas S, He T, Saunders D, et al. Glioma morphology and tumor-induced vascular alterations revealed in seven rodent glioma models by in vivo magnetic resonance imaging and angiography [J]. J Magn Reson Imaging, 2010, 32(2): 267-275.
18
Doblas S, He T, Saunders D, et al. In vivo characterization of several rodent glioma models by 1H MRS [J]. NMR Biomed, 2012, 25(4): 685-694.
19
Kondo A, Goldman S, Lulla RR, et al. Longitudinal assessment of regional directed delivery in a rodent malignant glioma model [J]. J Neurosurg Pediatr, 2009, 4(6): 592-598.
20
Jallo GI, Volkov A, Wong C, et al. A novel brainstem tumor model: functional and histopathological characterization [J]. Childs Nerv Syst, 2006, 22(12): 1519-1525.
21
Saucier-Sawyer JK, Seo YE, Gaudin A, et al. Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors [J]. J Control Release, 2016, 232: 103-112.
22
Thisgaard H, Halle B, Aaberg-Jessen C, et al. Highly effective auger-electron therapy in an orthotopic glioblastoma xenograft model using convection-enhanced delivery [J]. Theranostics, 2016, 6(12): 2278-2291.
23
Shi M, Fortin D, Sanche L, et al. Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model [J]. Invest New Drugs, 2015, 33(3): 555-563.
24
王林, 李新平. 铂类药物的毒性作用与预防措施 [J]. 医药导报, 2005, 24(3): 254-256.
25
宇文利霞, 孔应利, 时绘绘. 铂类抗癌药毒性及其与药物化学结构的关系 [J]. 临床合理用药, 2017, 10(2C): 107-108.
26
Shi M, Fortin D, Paquette B, et al. Convection-enhancement delivery of liposomal formulation of oxaliplatin shows less toxicity than oxaliplatin yet maintains a similar median survival time in F98 glioma-bearing rat model [J]. Invest New Drugs, 2016, 34(3): 269-276.
27
Arshad A, Yang B, Bienemann AS, et al. Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma [J]. PLoS One, 2015, 10(7): e0132266.
28
任林强, 蒋正方. 脑胶质瘤的化疗现状及进展 [J]. 川北医学院学报, 2011, 26(1): 87-91.
29
Brem S, Tyler B, Li K, et al. Local delivery of temozolomide by biodegradable polymers is superior to oral administration in a rodent glioma model [J]. Cancer Chemother Pharmacol, 2007, 60(5): 643-650.
30
Fritzell S, Sanden E, Eberstal S, et al. Intratumoral temozolomide synergizes with immunotherapy in a T cell-dependent fashion [J]. Cancer Immunol Immunother, 2013, 62(9): 1463-1474.
31
Mathios D, Kim JE, Mangraviti A, et al. Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM [J]. Sci Transl Med, 2016, 8(370): 370ra180.
32
Bernal GM, LaRiviere MJ, Mansour N, et al. Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma [J]. Nanomedicine, 2014, 10(1): 149-157.
33
Enriquez Perez J, Kopecky J, Visse E, et al. Convection-enhanced delivery of temozolomide and whole cell tumor immunizations in GL261 and KR158 experimental mouse gliomas [J]. BMC Cancer, 2020, 20(1): 7.
34
Grahn AY, Bankiewicz KS, Dugich-Djordjevic M, et al. Non-PEGylated liposomes for convection-enhanced delivery of topotecan and gadodiamide in malignant glioma: initial experience [J]. J Neurooncol, 2009, 95(2): 185-197.
35
Cirpanli Y, Allard E, Passirani C, et al. Antitumoral activity of camptothecin-loaded nanoparticles in 9L rat glioma model [J]. Int J Pharm, 2011, 403(1-2): 201-206.
36
Noble CO, Krauze MT, Drummond DC, et al. Novel nanoliposomal CPT-11 infused by convection-enhanced delivery in intracranial tumors: pharmacology and efficacy [J]. Cancer Res, 2006, 66(5): 2801-2806.
37
Han H, Li K, Yan J, et al. An in vivo study with an MRI tracer method reveals the biophysical properties of interstitial fluid in the rat brain [J]. Sci China Life Sci, 2012, 55(9): 782-787.
38
Han H, Shi C, Fu Y, et al. A novel MRI tracer-based method for measuring water diffusion in the extracellular space of the rat brain [J]. IEEE J Biomed Health Inform, 2014, 18(3): 978-983.
39
Xu F, Han H, Zhang H, et al. Quantification of Gd-DTPA concentration in neuroimaging using T(1)3D MP-RAGE sequence at 3.0 T [J]. Magn Reson Imaging, 2011, 29(6): 827-834.
40
Ding D, Kanaly CW, Cummings TJ, et al. Long-term safety of combined intracerebral delivery of free gadolinium and targeted chemotherapeutic agent PRX321 [J]. Neurol Res, 2010, 32(8): 810-815.
41
Sampson JH, Brady M, Raghavan R, et al. Colocalization of gadolinium-diethylene triamine pentaacetic acid with high-molecular-weight molecules after intracerebral convection-enhanced delivery in humans [J]. Neurosurgery, 2011, 69(3): 668-676.
42
Li K, Han H, Zhu K, et al. Real-time magnetic resonance imaging visualization and quantitative assessment of diffusion in the cerebral extracellular space of C6 glioma-bearing rats [J]. Neurosci Lett, 2013, 543: 84-89.
43
Guan X, Wang W, Wang A, et al. Brain interstitial fluid drainage alterations in glioma-bearing rats [J]. Aging Dis, 2018, 9(2): 228.
44
Perlstein B, Ram Z, Daniels D, et al. Convection-enhanced delivery of maghemite nanoparticles: Increased efficacy and MRI monitoring [J]. Neuro Oncol, 2008, 10(2): 153-161.
45
Young JS, Bernal G, Polster SP, et al. Convection-enhanced delivery of polymeric nanoparticles encapsulating chemotherapy in canines with spontaneous supratentorial tumors [J]. World Neurosurg, 2018, 117: e698-e704.
46
Croteau D, Walbridge S, Morrison PF, et al. Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer [J]. J Neurosurg, 2005, 102(1): 90-97.
47
Miyata S, Kawabata S, Hiramatsu R, et al. Computed tomography imaging of transferrin targeting liposomes encapsulating both boron and iodine contrast agents by convection-enhanced delivery to F98 rat glioma for boron neutron capture therapy [J]. Neurosurgery, 2011, 68(5): 1380-1387; discussion 1387.
48
Laske DW, Youle RJ, Oldfield EH. Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors [J]. Nat Med, 1997, 3(12): 1362-1368.
49
Bruce JN, Fine RL, Canoll P, et al. Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan [J]. Neurosurgery, 2011, 69(6): 1272-1279; discussion 1279-1280.
[1] 洪玮, 叶细容, 刘枝红, 杨银凤, 吕志红. 超声影像组学联合临床病理特征预测乳腺癌新辅助化疗完全病理缓解的价值[J/OL]. 中华医学超声杂志(电子版), 2024, 21(06): 571-579.
[2] 刘晨鹭, 刘洁, 张帆, 严彩英, 陈倩, 陈双庆. 增强MRI 影像组学特征生境分析在预测乳腺癌HER-2 表达状态中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 339-345.
[3] 常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[4] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[5] 许杰, 李亚俊, 冯义文. SOX新辅助化疗后腹腔镜胃癌D2根治术与常规根治术治疗进展期胃癌的近期随访比较[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 647-650.
[6] 薛庆, 施赛叶, 徐雅文, 盛夏, 张芹芹. 追踪方法学联合失效模式与效应分析在膀胱灌注化疗患者中的应用[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 553-559.
[7] 宋小飞, 巫嘉文, 孙阳. 输尿管开口周围膀胱黏膜预离断联合早期膀胱灌注化疗在上尿路尿路上皮癌根治术中的应用[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 479-484.
[8] 李佳伟, 庞建智, 闫鹏宇, 卫阳兵, 杨晓峰. 术中输尿管识别技术研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 520-524.
[9] 赵磊, 刘文志, 林峰, 于剑, 孙铭骏, 崔佑刚, 张旭, 衣宇鹏, 于宝胜, 冯宁. 深部热疗在改善结直肠癌术后辅助化疗副反应及生活质量中的作用研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 488-493.
[10] 韩加刚, 王振军. 梗阻性左半结肠癌的治疗策略[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 450-458.
[11] 石阳, 于剑锋, 曹可, 翟志伟, 叶春祥, 王振军, 韩加刚. 可扩张金属支架置入联合新辅助化疗治疗完全梗阻性左半结肠癌围手术期并发症分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 464-471.
[12] 梁轩豪, 李小荣, 李亮, 林昌伟. 肠梗阻支架置入术联合新辅助化疗治疗结直肠癌急性肠梗阻的疗效及其预后的Meta 分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 472-482.
[13] 张立俊, 孙存杰, 胡春峰, 孟冲, 张辉. MSCT、DCE-MRI 评估术前胃癌TNM 分期的准确性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 519-523.
[14] 张颖, 赵鑫, 陈佳梅, 李雁. 术前化疗对CRS+HIPEC 治疗腹膜假黏液瘤预后影响的meta 分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 826-835.
[15] 蔡晓雯, 李慧景, 丘婕, 杨翼帆, 吴素贤, 林玉彤, 何秋娜. 肝癌患者肝动脉化疗栓塞术后疼痛风险预测模型的构建及验证[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 722-728.
阅读次数
全文


摘要