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摘要
Purpose: To measure plasmatic sunitinib concentration (PSC) and intratumoral sunitinib concentration (ITSC) after transcatheter arterial chemoembolization (TACE) with two different sizes of sunitinib-eluting beads (SEBs) in rabbits with VX2 hepatic allografts and to investigate treatment effects on vascular endothelial growth factor receptor type 2 (VEGFR2) phosphorylation, tumor volume, and histopathologic changes. Materials and Methods: The protocol was approved by the French Ethics Committee for Animal Experiments (Comite d'Ethique en Experimentation Animale du Centre INRA de Jouy-en-Josas et AgroParisTech, or COMETHEA, approval no. 11/028). Two experiments were performed. In the first, seven animals received 0.05 mL of 100-300-mu m SEBs (1.5 mg of sunitinib) in the hepatic artery, and six animals received saline injections. In the second, eight animals received 0.05 mL of 70-150-mu m SEBs (1.5 mg of sunitinib), seven received 0.05 mL of 70-150-mu m unloaded beads, and seven received oral sunitinib (6 mg every day). Tumor size was monitored with ultrasonography. PSC, ITSC, and phosphorylation of VEGFR2 were assessed on days 1 and 14. After the animals were sacrificed, histopathologic analysis was performed. The Kruskal-Wallis test, Mann-Whitney U test, and Fisher exact test were used to look for statistically significant differences between groups. Results: Maximum PSC after TACE with 100-300-mu m SEBs was 0.002 mu g/mL on day 1. ITSC was 17.8 mu g/g on day 1 and 0.16 mu g/g on day 14. After TACE with 70-150-mu m SEBs, ITSC was 40.4 mu g/g on day 1 and 27.4 mu g/g on day 14. Phosphorylation of VEGFR2 was inhibited until day 14 after TACE with both sizes of SEBs. The size of VX2 tumors treated with 70-150-mu m SEB TACE increased less (-22%) than that of tumors treated with unloaded beads (+42%) and oral sunitinib (6 mg every day; +1853%; P = .044). Conclusion: SEB TACE resulted in minimal PSC, high ITSC, and sustained VEGFR2 phosphorylation inhibition until day 14.
- 出版日期2016-8
