9:12 AM Abstract No. 194 - Expression of angiogenic factors and tumoral response after transcatheter intraarrterial treatment of rabbit VX-2 liver tumors using a novel iron-oxide nanoparticle drug delivery system

Abstract

Purpose To investigate tissue response and expression of angiogenic factors after targeted transcatheter intraarterial (IA) treatment of the rabbit VX-2 liver tumor using iron-oxide nanoparticles (IONP) for drug delivery. Materials and Methods VX-2 tumors were implanted in the left liver lobe of 30 New Zealand White rabbits which were subsequently treated when tumor size reached 2 cm. Two groups received 1.0 mg/kg Doxorubicin (Dox) either by IA IONP delivery via the left hepatic artery (n=14) or IV IONP delivery via the marginal ear vein. Another 2 groups received free Doxorubicin either by IA (n=4) or IV (n=6) administration. Animals were sacrificed serially at 3 hours, 24 hours, and 7 days after treatment. Liver explants were collected for immunohistochemistry with hypoxia-inducible factor 1-alpha (HIF1-α), vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor alpha (PDGFR-α), and platelet-derived growth factor receptor beta (PDGFR-β) in addition to histologic scoring of necrosis and microvascular invasion in both tumoral and peritumoral areas. Results were analyzed using statistical software. Results For IA IONP delivery of Doxorubicin, tumoral PDGR-α levels decreased significantly as sacrifice times increased from 3 to 24 hrs (3 vs 2.12; p=0.0367). Additionally, tumoral HIF1-α levels increased significantly as sacrifice time increased from 3 hrs to 7 days (2 vs 3; p=0.0179). Post-treatment peritumoral levels of PDGR-α were significantly higher for the IA IONP treatment group compared to IV IONP delivery (2.428 vs 1.8333; p=0.0436). Overall, as sacrifice times increased from 3 hrs, 24 hrs, and 7 days, peritumoral levels of VEGF increased significantly (2.25 vs 2.77; p=.0294). Post-treatment levels of VEGF also increased in tumoral areas from 24 hrs to 7 days (2.5 vs 3; p=.0415). Conclusion Targeted intraarterial iron-oxide nanoparticle-mediated delivery of chemotherapy induces an exact tissue response and sustained differential expression of immunohistocemical indicators of angiogenesis and hypoxia in both tumoral and peritumoral areas for several days after treatment.