Johnson Carmen Gacchina, Tang Yiqing, Beck Avi, Dreher Matthew R, Woods David L, Negussie Ayele H, Donahue Danielle, Levy Elliot B, Willis Sean L, Lewis Andrew L, Wood Bradford J, Sharma Karun V
Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Biocompatibles UK Ltd, a BTG International group company, Farnham, United Kingdom.
J Vasc Interv Radiol. 2016 Jan;27(1):117-126.e3. doi: 10.1016/j.jvir.2015.09.011. Epub 2015 Nov 6.
To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo.
An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model.
Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology.
A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.
开发一种简单的方法来制备可用于当前临床经导管动脉化疗栓塞工作流程的不透射线的药物洗脱微球（药物洗脱微球[DEB]），并在体外和体内评估其性能。
在装载阿霉素之前，将碘化油（碘油；Guerbet公司，法国维勒班特）和乙醇溶液添加到冻干的100 - 300 µm微球中。对这些不透射线的药物洗脱微球（DEB；英国生物相容性有限公司，英国法纳姆）进行体外X射线衰减、成分、尺寸、药物装载和洗脱以及衰减与阿霉素浓度之间相关性的评估。在VX2肿瘤模型中评估体内显影性。
使用两个玻璃注射器和一个三通旋塞将碘油装载到冻干微球中。30分钟内实现了微球的最大衰减。不透射线微球的X射线衰减随微球量（0.4 - 12.5体积%）呈线性增加（21 - 867 HU；R² = 0.9989）。阿霉素装载效率和洗脱总量与DC Bead（英国生物相容性有限公司）相似；然而，不透射线DEB的洗脱速率较慢（P < 0.05）。阿霉素浓度与不透射线DEB的X射线衰减呈线性相关（R² = 0.99）。通过荧光透视、计算机断层扫描和微型计算机断层扫描给药后，在肿瘤供血动脉中可见不透射线的DEB，其位置经组织学证实。
开发了一种简单、快速制备不透射线DEB的方法。这些不透射线的DEB具有足够的显影性，可用X射线成像技术进行可视化。
