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用于图像引导化疗栓塞的可成像聚乙烯醇微球的合成与表征

Synthesis and characterization of image-able polyvinyl alcohol microspheres for image-guided chemoembolization.

作者信息

Negussie Ayele H, Dreher Matthew R, Johnson Carmen Gacchina, Tang Yiqing, Lewis Andrew L, Storm Gert, Sharma Karun V, Wood Bradford J

机构信息

Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814, USA,

出版信息

J Mater Sci Mater Med. 2015 Jun;26(6):198. doi: 10.1007/s10856-015-5530-3. Epub 2015 Jun 24.

Abstract

Therapeutic embolization of blood vessels is a minimally invasive, catheter-based procedure performed with solid or liquid emboli to treat bleeding, vascular malformations, and vascular tumors. Hepatocellular carcinoma (HCC) affects about half a million people per year. When unresectable, HCC is treated with embolization and local drug therapy by transarterial chemoembolization (TACE). For TACE, drug eluting beads (DC Bead(®)) may be used to occlude or reduce arterial blood supply and deliver chemotherapeutics locally to the tumor. Although this treatment has been shown to be safe and to improve patient survival, the procedure lacks imaging feedback regarding the location of embolic agent and drug coverage. To address this shortcoming, herein we report the synthesis and characterization of image-able drug eluting beads (iBeads) from the commercial DC Bead(®) product. Two different radiopaque beads were synthesized. In one approach, embolic beads were conjugated with 2,3,5-triiodobenzyl alcohol in the presence of 1,1'-carbonyldiimidazol to give iBead I. iBead II was synthesized with a similar approach but instead using a trimethylenediamine spacer and 2,3,5-triiodobenzoic acid. Doxorubicin was loaded into the iBeads II using a previously reported method. Size and shape of iBeads were evaluated using an upright microscope and their conspicuity assessed using a clinical CT and micro-CT. Bland and Dox-loaded iBeads II visualized with both clinical CT and microCT. Under microCT, individual bland and Dox loaded beads had a mean attenuation of 7904 ± 804 and 11,873.96 ± 706.12 HU, respectively. These iBeads have the potential to enhance image-guided TACE procedures by providing localization of embolic-particle and drug.

摘要

血管治疗性栓塞是一种微创的、基于导管的操作,使用固体或液体栓塞剂来治疗出血、血管畸形和血管肿瘤。肝细胞癌(HCC)每年影响约50万人。当无法切除时,HCC通过经动脉化疗栓塞术(TACE)进行栓塞和局部药物治疗。对于TACE,药物洗脱微球(DC Bead®)可用于闭塞或减少动脉血供,并将化疗药物局部递送至肿瘤。尽管这种治疗已被证明是安全的,并能提高患者生存率,但该操作缺乏关于栓塞剂位置和药物覆盖范围的成像反馈。为了解决这一缺点,我们在此报告了从商业DC Bead®产品合成和表征可成像药物洗脱微球(iBeads)的过程。合成了两种不同的不透射线微球。一种方法是,在1,1'-羰基二咪唑存在下,将栓塞微球与2,3,5-三碘苄醇共轭,得到iBead I。iBead II采用类似方法合成,但使用三亚甲基二胺间隔基和2,3,5-三碘苯甲酸。使用先前报道的方法将阿霉素加载到iBeads II中。使用直立显微镜评估iBeads的大小和形状,并使用临床CT和微型CT评估其显影性。空白和载有阿霉素的iBeads II在临床CT和微型CT上均可见。在微型CT下,单个空白和载有阿霉素的微球的平均衰减分别为7904±804和11873.96±70

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