Abstract 2890: Image-guided transcatheter intraarterial drug delivery of doxorubicin encapsulated iron oxide nanoparticles to liver tumors: Safety and feasibility

Abstract

Abstract Purpose To investigate the feasibility and safety of transcatheter intraarterial drug delivery of novel doxorubicin encapsulated iron oxide nanoparticles to the VX-2 rabbit liver tumor model. Materials and Methods Paramagnetic iron oxide (IO) nanoparticles (core and hydrodynamic size of 10 and 23 nm) coated with amphiphilic polymers were mixed with hydrophobic doxorubicin molecules, and their presence within the nanoparticles was confirmed by optical absorption spectrum. 16 New Zealand White rabbits with VX-2 tumors implanted in the liver were treated when a 2.0 cm lesion was visible on MRI. The rabbits were placed into 4 treatment groups, each receiving doxorubicin at a concentration of 1.0 mg/ kg. Group A received image-guided intraarterial (IA) transcatheter delivery of doxorubicin encapsulated IO nanoparticles to the hepatic artery; Group B received intravenous (IV) injection of doxorubicin encapsulated IO nanoparticles through the marginal ear vein; Group C received intraarterial injection of doxorubicin alone; Group D received intravenous injection of doxorubicin alone. Rabbits were closely monitored for toxicity or any complications for the entire study duration. Blood was collected before treatments and at 1 hour, 24 hours, and 7 days post treatment to analyze liver function and follow post treatment response by quantitative determinations of alanine aminotransferase (ALT), albumin (ALB), alkaline phosphatase (ALP), bile acids (BA), total bilirubin (TBIL), total cholesterol (CHOL), gamma glutamyl transferase (GGT), and blood urea nitrogen (BUN). Results There were no significant changes in the baseline pretreatment levels of the mammalian liver profile and biomarkers at the 1 hour, 24 hour, and 7 day time points in comparison to rabbits receiving IA doxorubicin nanoparticle or doxorubicin therapy (Groups A and C) versus IV doxorubicin nanoparticle or doxorubicin therapy (Groups B and D). Group A median pretreatment 1 hour, 24 hour, and 7 day ALP levels were as follows: 57, 51.8, 59.2, & 29 U/L; Group B was 73.5, 72.25, 54.25, & 45.5 U/L; Group C was 51, 35, 40, & 37 U/L; Group D was 48.8, 49.3, 47.2, & 47.5 U/L (p=<0.001). ALT median levels were as follows: Group A was 24.4, 25, 104, Group B was 28.8, 15.5, & 61, Group C was 21, 14, and 233, Group d was 25.5, 24, & 29.8 U/L (p=<0.001). GGT, BA, TBIL, ALB, BUN, and CHOL levels for all treatment groups were within normal reference ranges, and did not differ significantly from each other. Conclusion Novel doxorubicin encapsulated iron oxide nanoparticles can be safely delivered intraarterially to the VX-2 rabbit liver cancer model at a dose of 1.0 mg/kg of doxorubicin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2890. doi:1538-7445.AM2012-2890