Evaluation of the anti-tumoral effect of 70-150μm sunitinib eluting beads in VX2 carrying rabbits

Purpose To evaluate the antitumoral effect of smaller size (70-150 μm) sunitinib eluting beads (DC-SU). Materials and Methods VX2 tumors were implanted in the left liver lobe of New-Zealand white rabbits. 70-150μm DC Bead® (Biocompatibles UK, Ltd) were loaded with sunitinib at a concentration of 30mg/ml, before transcatheter injection in the left hepatic artery. Animals were separated in 4 groups. DC-SU (n=9) received 0.05ml DC-SU, SU (n=7) received oral sunitinib at 6mg/day, DC (n=9) received 0.05cc 70-150μm bland DC Bead® and control group (n=3). One animal in each group was sacrificed at 24h and the others were followed-up for survival until day 15. Tumor growth was monitored by ultrasound imaging (US). At day 15 all living animals were sacrificed and the livers were harvested. Sunitinib concentration in the tumor and untreated liver were measured by LC MS/MS tandem mass spectroscopy. Determination of the VEGF receptor tyrosine kinase (RTK) activity was determined by western blot. Thourough histopathological examination was performed. Results During follow-up, 2 animals died in the DC-SU group and control group respectively. No animal died in the other groups. At day 0, the mean tumor volume measured by US was 0.89 +/- 0.7cc. At day 15 the mean tumor size measured on pathology specimen was 1.15 +7- 0.75 cc in the DC-SU group and 12.4 +/- 13cc, 11.1 +/- 20 cc, and 14cc in the SU, DC and control groups respectively. On histology specimens, DC-SU were associated with extensive tumor necrosis, involving the liver surrounding the tumor in 5 out of 6 animals. There was a similar concentration of sunitinib in the tumor at day 15 in the DC-SU and SU groups (16’600ng/ml and 21’300ng/ml) while the concentration of sunitinib in the normal liver was much lower in the DC-SU group compared to the SU group (192ng/ml and 32’300ng/ml). Inhibition of the phosphorylation of the RTK could be confirmed up to day 15 by western blots in the DC-SU group. Conclusion Administration of 70-150μm DC-SU seems to be effective in inhibiting tumor growth. It might cause more damage to the surrounding liver parenchyma than bland DC Bead® of the same size. Inhibition of the RTK can be observed until day 15 after a single administration.