Unité MéDIAN, MEDyC, CNRS UMR 6237, Université de Reims Champagne Ardennes, Reims, France.
J Vasc Interv Radiol. 2010 Feb;21(2):259-67. doi: 10.1016/j.jvir.2009.10.026.
To evaluate the local tissue concentrations of the antineoplastic agent doxorubicin and the amount of drug still present inside drug delivery embolization beads at different time points after embolization and to compare doxorubicin levels with histologic modifications around the beads in a pig liver model. It was hypothesized that doxorubicin-eluting beads maintain cytotoxic concentrations of drug locally over a period of several weeks, as suggested by in vitro elution tests.
Left lobe hepatic artery embolization was performed in 10 pigs with 100-300-microm or 700-900-microm beads loaded with 37.5 mg doxorubicin/mL. Control unloaded 100-300-microm beads were injected in five pigs. Livers were sampled 28 days or 90 days after embolization. The amount of drug retained inside the beads was assessed with infrared microspectroscopy. Doxorubicin concentration and distribution in the tissue around the beads were determined with microspectrofluorimetry and compared with tissue modifications on hematein eosin saffron-stained sections.
Doxorubicin-eluting beads eluted 43% of their initial drug load after 28 days and 89% after 90 days. Doxorubicin was present in tissues around the beads at both time points, with a significant decrease over time (P = .0004). The drug was detected at distances as far as 600 microm from the bead edge. Doxorubicin tissue concentrations ranged from 0.55 microM to 6.80 microM, [corrected] which are cytotoxic levels in hepatocyte cell cultures. High concentrations of drug were associated with coagulative necrosis of liver parenchyma. Doxorubicin-eluting beads 100-300 microm in size induced more necrosis than 700-900-microm beads (P = .0036).
Doxorubicin-eluting beads deliver high concentrations of the drug over a period of at least 3 months at several hundred micrometers from the bead, leading to significant cytotoxic effects.
评估抗肿瘤药物阿霉素在栓塞后不同时间点的局部组织浓度和药物输送栓塞珠内残留的药物量，并在猪肝模型中比较珠周围组织的阿霉素水平与组织学改变。假设阿霉素洗脱珠在数周内保持局部细胞毒性药物浓度，正如体外洗脱试验所表明的那样。
对 10 头猪的左叶肝动脉进行栓塞，使用 37.5 mg 阿霉素/mL 负载的 100-300 微米或 700-900 微米珠。5 头猪注射未负载的 100-300 微米珠作为对照。栓塞后 28 天或 90 天，采集肝脏样本。用红外显微镜评估珠内残留的药物量。用微荧光光谱法测定珠周围组织中阿霉素的浓度和分布，并与苏木精-伊红-藏红花染色切片上的组织改变进行比较。
阿霉素洗脱珠在 28 天后洗脱其初始药物负荷的 43%，90 天后洗脱 89%。在两个时间点，阿霉素都存在于珠周围的组织中，随着时间的推移，其浓度显著下降（P =.0004）。药物在距离珠边缘最远达 600 微米的地方被检测到。阿霉素组织浓度范围为 0.55 至 6.80 微摩尔，这是在肝细胞培养物中具有细胞毒性的水平。高浓度的药物与肝实质的凝固性坏死有关。100-300 微米大小的阿霉素洗脱珠比 700-900 微米大小的珠引起更多的坏死（P =.0036）。
阿霉素洗脱珠在几百微米范围内的药物浓度至少在 3 个月内保持高浓度，导致显著的细胞毒性作用。
