Antitumoral Effect of Sunitinib-eluting Beads in the Rabbit VX2 Tumor Model

Abstract

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 (Comité d'Ethique en Expérimentation 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-μm 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-μm SEBs (1.5 mg of sunitinib), seven received 0.05 mL of 70-150-μm 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-μm SEBs was 0.002 μg/mL on day 1. ITSC was 17.8 μg/g on day 1 and 0.16 μg/g on day 14. After TACE with 70-150-μm SEBs, ITSC was 40.4 μg/g on day 1 and 27.4 μg/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-μm SEB TACE increased less (-2%) 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. (©) RSNA, 2016.

Vandetanib-eluting Radiopaque Beads: In vivo Pharmacokinetics, Safety and Toxicity Evaluation following Swine Liver Embolization

“…There is in general however, a significant issue of adverse side effects related to the systemic exposure of these types of agents 21-23 and therefore intra-arterial delivery from a DEB could be a feasible approach. Sunitinib has been successfully loaded into DC Bead™ 24, 25 and although significant antitumoral efficacy of the Sunitinib-eluting Beads was observed in the VX2 rabbit tumor model 26, serious issues concerning systemic toxicity of sunitinib (18.5% death due to drug toxicity) 27 has led to exploring alternative candidates.…”

Advances in transarterial therapies for hepatocellular carcinoma: is novel technology leading to better outcomes?

“…TACE with sunitinib-loaded beads resulted in high intratumoral sunitinib concentration in a rabbit VX2 model (17.8-40.4 µg/g at day 1 and 27.4 µg/g at day 14) with minimal plasmatic concentration (0.002 µg/ml at day 1) and achieved significantly better tumor control compared with bland embolization and oral sunitinib', probably through sustained inhibition of VEGFR2 phosphorylation that was demonstrated until day 14 [71].…”

The Mechanism of Computed Tomography-Guided 125I Particle in Treating Lung Cancer

“…Nevertheless, the mechanism of CT-guided 125 I particles in the treatment of lung cancer has not yet been fully elucidated. In this article, we retrospectively observed CT-guided 125 I particles in the medical treatment of advanced lung cancer in patients, and established a rabbit VX2 tumor model to analyze its specific mechanism [17]. …”