Abstract 2163: Magnetic field stimuli improve hepatic delivery of oxaliplatin ensuing survival benefit to colorectal liver metastatic tumor bearing rats

Abstract

Abstract Treatment of unresectable liver tumors with a systemic chemotherapeutic agent is severely limited by the systemic toxicities. Therefore, the aim of the current study was to site selectively release high concentration of therapeutic agents to alleviate the off target effects of the drugs. Rats orthotopically implanted colorectal liver metastases (CC-531 cells) were randomly divided into different treatment groups. The rats were treated with magnetic field sensitive and MR imageable oxaliplatin loaded liposomes or by drug alone via different routes of administration, establishing appropriate controls. Liposomes containing oxaliplatin at 6.0 mg/kg per were infused into rats via the portal vein or with free form of oxaliplatin via tail vein or with saline. Three groups were subjected to alternative magnetic fields to trigger drug release for 30 minutes. Post treatment MRI was performed to follow the tumor growth. R2* maps were constructed from the T2* MRI images acquired immediately post-infusion and one week later. ROIs were drawn within the acquired maps to measure R2* values in the tumor regions and surrounding tissues. At 8 weeks or earleir the rats were euthanized, tissues explanted and digested with nitric acid and hydrogen peroxide mix. The digestates were subjected to ICP-MS analysis of elemental platinum at the indicated time points to determine the localized delivery of Oxaliplatin. The R2* MRI maps showed changes in the tumor regions at one-week post-infusion compared to the surrounding liver parenchyma (p<.001) and to the same regions immediately after infusion (p<.001). The localized delivery of iron oxide resulted in low signal intensity immediately after infusion. Significantly higher levels of oxaliplatin was delivered to the liver tissues compared to the lungs (p<.001) and intestines (p<.001) in the animals that received site selective delivery and magnetic field triggering following liposome administration. Although, there was no significant difference between the animals treated with single or multiple cycles of magnetic field triggers, the animals tolerated 3 trigger cycles with 100% survival rates. The survival of animals treated with portal vein route delivery was significantly higher compared to tail vein delivery (p<.05). Similarly, prominent necrotic zones were observed in the primary tumors of rats which site selective delivery followed by triggering compared to those which did not get triggered and those which received systemic oxaliplatin (via tail vein). In conclusion, site selective delivery allows for high concentrations of oxaliplatin and improves survival outcomes in colorectal liver metastasis tumor bearing rats. Key words: Triggered release, Oxaliplatin, Liposomes, Colorectal liver metastasis Citation Format: Venkateswara R. Gogineni, Dilip R. Maddirela, Woo Ram Park, Dong-Hyun Kim, Amit Joshi, Sarah B. White. Magnetic field stimuli improve hepatic delivery of oxaliplatin ensuing survival benefit to colorectal liver metastatic tumor bearing rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2163.