Namur Julien, Pascale Florentina, Maeda Noboru, Sterba Manon, Ghegediban Saida Homayra, Verret Valentin, Paci Angelo, Seck Atmane, Osuga Keigo, Wassef Michel, Reb Philippe, Laurent Alexandre
Archimmed, 12 rue Charles de Gaulle, 78350 Jouy-en-Josas, France..
Archimmed, 12 rue Charles de Gaulle, 78350 Jouy-en-Josas, France.
J Vasc Interv Radiol. 2015 Jul;26(7):1067-1075.e3. doi: 10.1016/j.jvir.2015.03.014. Epub 2015 May 4.
To compare irinotecan-eluting HepaSphere (BioSphere Medical, Roissy-en-France, France) and DC Bead (Biocompatibles UK Ltd, London, United Kingdom) embolization microspheres for distribution in tumors, release properties, tolerance, and antitumor effects in a model of liver metastases in the rabbit.
Multiple liver tumors were created by injection of a VX2 cell suspension in the portal vein of rabbits. After 2 weeks, embolization of the proper hepatic artery was performed with a fixed volume of bland HepaSphere (n = 5), irinotecan-loaded HepaSphere (n = 6), or irinotecan-loaded DC Bead (n = 5) microspheres. Untreated animals injected with VX2 cells served as control animals (n = 5). Plasma pharmacokinetics of irinotecan and its metabolite SN38 were assessed. Histopathology and gene expression analysis were performed 3 days after treatment.
Among all treated groups, there was no significant difference in liver enzymes or liver damage on histology. Irinotecan-loaded HepaSphere microspheres showed a faster release of drug than DC Bead microspheres leading to a twofold higher concentration of drug in plasma for HepaSphere microspheres. HepaSphere microspheres were less frequently found inside tumor nodules on histology than DC Bead microspheres (11% vs 48%, P < .001) because of their larger size. Tumor necrosis was significantly greater for rabbits given irinotecan-loaded HepaSphere microspheres (69% of total tumor surface) and rabbits given DC Bead microspheres (50% of total tumor surface) compared with control animals (24% of total tumor surface, P = .006 and P = .047).
HepaSphere and DC Bead microspheres loaded with irinotecan caused significant necrosis of tumor nodules in a model of VX2 liver metastases. This outcome was mostly due to irinotecan delivery rather than vascular occlusion by the microspheres and was greater for HepaSphere microspheres compared with DC Bead microspheres.
比较伊立替康洗脱型HepaSphere微球（法国罗西耶的BioSphere Medical公司）和DC Bead微球（英国伦敦的Biocompatibles UK Ltd公司）在兔肝转移模型中在肿瘤内的分布、释放特性、耐受性及抗肿瘤效果。
通过向兔门静脉注射VX2细胞悬液制造多个肝肿瘤。2周后，用固定体积的空白HepaSphere微球（n = 5）、载伊立替康的HepaSphere微球（n = 6）或载伊立替康的DC Bead微球（n = 5）栓塞肝固有动脉。注射VX2细胞但未接受治疗的动物作为对照动物（n = 5）。评估伊立替康及其代谢产物SN38的血浆药代动力学。治疗3天后进行组织病理学和基因表达分析。
在所有治疗组中，肝酶或组织学上的肝损伤无显著差异。载伊立替康的HepaSphere微球比DC Bead微球显示出更快的药物释放，导致HepaSphere微球血浆中药物浓度高出两倍。由于HepaSphere微球尺寸较大，组织学上在肿瘤结节内发现HepaSphere微球的频率低于DC Bead微球（11%对48%，P <.001）。与对照动物（肿瘤总表面积的24%，P =.006和P =.047）相比，给予载伊立替康的HepaSphere微球的兔（肿瘤总表面积的69%）和给予DC Bead微球的兔（肿瘤总表面积的50%）的肿瘤坏死明显更严重。
在VX2肝转移模型中，载伊立替康的HepaSphere微球和DC Bead微球导致肿瘤结节显著坏死。这一结果主要归因于伊立替康的递送而非微球的血管闭塞，且HepaSphere微球比DC Bead微球的效果更显著。
