Radiopaque drug-eluting beads for transcatheter embolotherapy: experimental study of drug penetration and coverage in swine.

Radiopaque drug-eluting beads for transcatheter embolotherapy: experimental study of drug penetration and coverage in swine.
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DOI:
10.1016/j.jvir.2011.10.019
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发表时间:
2012-02
影响因子:
2.9
通讯作者:
Wood, Bradford J.
Wood, Bradford J.
中科院分区:
医学3区
文献类型:
--
作者:
Dreher, Matthew R.;Sharma, Karun V.;Woods, David L.;Reddy, Goutham;Tang, Yiqing;Pritchard, William F.;Chiesa, Oscar A.;Karanian, John W.;Esparza, Juan A.;Donahue, Danielle;Levy, Elliot B.;Willis, Sean L.;Lewis, Andrew L.;Wood, Bradford J.

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本研究的目的是确定经导管动脉化疗栓塞(TACE)后正常猪肝脏和肾脏中不透射线药物洗脱珠(DEB)周围的局部阿霉素水平。比较了珠粒尺寸(70-150µm或100-300µm)对组织渗透和珠粒空间分布以及最终药物覆盖率(即,暴露于药物的组织量)。不透射线的DEBs合成悬浮聚合,然后掺入碘化油和阿霉素。在荧光镜引导下对猪肝脏和肾脏进行化学栓塞。用microCT离体研究可成像DEB的三维组织穿透。从珠表面的药物渗透和药物覆盖率用落射荧光显微镜评价,而多柔比星的细胞定位用共聚焦显微镜评价。用H&E评价坏死。MicroCT显示70-150µm DEB存在于更远端的动脉中,并且位于更频繁和均匀的空间分布中。对于两种DEB,阿霉素从珠粒的组织渗透似乎相似(约300µm),在1小时时的最大组织药物浓度与阿霉素的核定位一致。70-150µm DEB的更大空间频率导致肾脏中药物覆盖率提高约2倍。细胞死亡主要在DEB周围观察到,从8小时开始,但在24和168小时增加。较小的DEB以更高的空间密度进一步渗透到靶组织中(宏观),导致猪体内药物覆盖范围更大且更均匀(微观)。
The objective of this study was to determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEB) in normal swine liver and kidney following transcatheter arterial chemoembolization (TACE). The influence of bead size (70–150µm or 100–300µm) was compared with regard to tissue penetration and spatial distribution of the bead as well as eventual drug coverage (i.e., amount of tissue exposed to drug). Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three dimensional tissue penetration of image-able DEB was investigated ex vivo with microCT. Drug penetration from the bead surface and drug coverage was evaluated with epi-fluorescence microscopy while cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with H&E. MicroCT demonstrated that 70–150µm DEB were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (~300µm) for both DEBs with a maximum tissue drug concentration at 1hr coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70–150µm DEBs resulted in ~2-fold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hr but increased at 24 and 168 hrs. Smaller DEBs penetrated further into targeted tissue (macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (microscopic) in swine.
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