Tanaka Toshihiro, Nishiofuku Hideyuki, Hukuoka Yasushi, Sato Takeshi, Masada Tetsuya, Takano Masato, Gilbert Carl W, Obayashi Chiho, Kichikawa Kimihiko
Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
J Vasc Interv Radiol. 2014 Jul;25(7):1037-1044.e2. doi: 10.1016/j.jvir.2014.04.005. Epub 2014 May 24.
To evaluate the pharmacokinetics and antitumor efficacy of 40 μm irinotecan-loaded drug-eluting microspheres (Embozene TANDEM Microspheres; CeloNova BioSciences, Inc, San Antonio, Texas) (TANDEM-IRI).
The following three groups included eight VX2 rabbits each: group 1, full-loaded (50 mg irinotecan/1 mL TANDEM)/high-dose injection (1 mg irinotecan/kg); group 2, full-loaded (50 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg); and group 3, half-loaded (25 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg). Irinotecan and SN-38 in the plasma and tumors were measured within 72 hours. Histologic examinations were conducted on days 1, 3, and 7.
Serum irinotecan levels remained near the maximum concentration for 180 minutes after transarterial chemoembolization; in group 1, levels were 351.4 ng/mL at 30 minutes, 329.0 ng/mL at 60 minutes, and 333.5 ng/mL at 180 minutes. The area under the curve for 0-24 hours of irinotecan in group 1 was approximately two times higher than the same value in groups 2 and 3. High irinotecan and SN-38 concentrations in the tumors were measured at 24 hours and 72 hours. After transarterial chemoembolization, levels of liver enzymes aspartate aminotransferase and alkaline phosphatase were significantly higher in group 1 compared with groups 2 and 3. Histologic findings showed microspheres had deeply penetrated into tumors. Significantly higher tumor necrosis ratios were observed in groups 1 (86.6%-90.0%) and 3 (90.0%-100%) compared with group 2 (63.3%-70%) (P = .031 and P = .016).
Slow drug release with high drug concentration in tumors can be provided with 40 μm TANDEM-IRI. When complete arterial embolization is performed, the dose of irinotecan loaded on 40 μm TANDEM microspheres can be reduced while maintaining efficacy.
评估载有40μm伊立替康的药物洗脱微球（Embozene TANDEM微球；CeloNova生物科学公司，得克萨斯州圣安东尼奥）（TANDEM - IRI）的药代动力学和抗肿瘤疗效。
以下三组每组包括8只VX2兔：第1组，满载（50mg伊立替康/1mL TANDEM）/高剂量注射（1mg伊立替康/kg）；第2组，满载（50mg伊立替康/1mL TANDEM）/低剂量注射（0.5mg伊立替康/kg）；第3组，半载（25mg伊立替康/1mL TANDEM）/低剂量注射（0.5mg伊立替康/kg）。在72小时内测定血浆和肿瘤中的伊立替康和SN - 38。在第1、3和7天进行组织学检查。
经动脉化疗栓塞后180分钟内，血清伊立替康水平保持在接近最大浓度；在第1组中，30分钟时水平为351.4ng/mL，60分钟时为329.0ng/mL，180分钟时为333.5ng/mL。第1组中伊立替康0 - 24小时的曲线下面积约为第2组和第3组相同值的两倍。在24小时和72小时时测量到肿瘤中伊立替康和SN - 38浓度较高。经动脉化疗栓塞后，第1组中肝酶天冬氨酸转氨酶和碱性磷酸酶水平显著高于第2组和第3组。组织学结果显示微球已深入渗透到肿瘤中。与第2组（63.3% - 70%）相比，第1组（86.6% - 90.0%）和第3组（90.0% - 100%）观察到显著更高的肿瘤坏死率（P = 0.031和P = 0.016）。
40μm TANDEM - IRI可在肿瘤中提供高药物浓度的缓慢药物释放。当进行完全动脉栓塞时，在保持疗效的同时，可降低加载在40μm TANDEM微球上的伊立替康剂量。
