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伊立替康肝动脉灌注和 EmboCept S 导致结直肠癌肝转移大鼠模型中肿瘤 SN-38 浓度高。

Hepatic arterial infusion of irinotecan and EmboCept S results in high tumor concentration of SN-38 in a rat model of colorectal liver metastases.

机构信息

Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch Str. 40, 37099, Göttingen, Germany.

Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.

出版信息

Clin Exp Metastasis. 2019 Feb;36(1):57-66. doi: 10.1007/s10585-019-09954-5. Epub 2019 Jan 24.

DOI:10.1007/s10585-019-09954-5
PMID:30680598
Abstract

Intraarterial chemotherapy for colorectal liver metastases (CRLM) can be applied alone or together with embolization particles. It remains unclear whether different types of embolization particles lead to higher intratumoral drug concentration. Herein, we quantified the concentrations of CPT-11 and its active metabolite SN-38 in plasma, liver and tumor tissue after hepatic arterial infusion (HAI) of irinotecan, with or without further application of embolization particles, in a rat model of CRLM. Animals underwent either systemic application of irinotecan, or HAI with or without the embolization particles Embocept S and Tandem™. Four hours after treatment concentrations of CPT-11 and SN-38 were analyzed in plasma, tumor and liver samples by high-performance liquid chromatography. Additionally, DNA-damage and apoptosis were analyzed immunohistochemically. Tumor tissue concentrations of SN-38 were significantly increased after HAI with irinotecan and EmboCept S compared to the other groups. The number of apoptotic cells was significantly higher after both HAI with irinotecan and EmboCept S or Tandem™ loaded with irinotecan compared to the control group. HAI with irinotecan and EmboCept S resulted in an increased SN-38 tumor concentration. Both HAI with irinotecan and EmboCept S or Tandem™ loaded with irinotecan were highly effective with regard to apoptosis.

摘要

经肝动脉化疗栓塞（TACE）治疗结直肠癌肝转移（CRLM）时，可单独应用或联合应用栓塞微球。目前尚不清楚不同类型的栓塞微球是否会导致肿瘤内药物浓度更高。本研究通过建立大鼠 CRLM 模型，定量分析了伊立替康肝动脉灌注（HAI）联合或不联合栓塞微球 Embocept S 和 TandemTM 后，伊立替康在血浆、肝脏和肿瘤组织中的浓度，及其活性代谢产物 SN-38。动物模型接受全身应用伊立替康、HAI 联合或不联合栓塞微球治疗。治疗 4 小时后，采用高效液相色谱法分析血浆、肿瘤和肝脏样本中 CPT-11 和 SN-38 的浓度。同时，采用免疫组化法分析 DNA 损伤和细胞凋亡。与其他组相比，伊立替康联合 EmboCept S 行 HAI 治疗后，肿瘤组织中 SN-38 的浓度显著增加。与对照组相比，伊立替康联合 EmboCept S 或 TandemTM 行 HAI 治疗后，细胞凋亡数量明显增加。伊立替康联合 EmboCept S 行 HAI 治疗可增加 SN-38 肿瘤浓度。伊立替康联合 HAI 治疗与 EmboCept S 或 TandemTM 加载伊立替康均可显著诱导细胞凋亡。

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Critical considerations for targeting colorectal liver metastases with nanotechnology.用纳米技术靶向结直肠癌肝转移的关键考虑因素。
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