Abstract No. 469 Improved intra-arterial tumor targeting using an omniphobic oil in a pig model

Abstract

Intra-arterial lipiodol is specifically retained in HCC and other tumors, due to leaky tumor vasculature, and poor clearance from the tumor. Suboptimal lipiodol retention and early lipiodol washout after chemoembolization are associated with residual or recurrent tumor. We hypothesize that tumor targeting could be improved using a low viscosity omniphobic oil. The low viscosity could improve tumor uptake via leaky tumor vasculature. The omniphobic oil interacts poorly with both water and hydrocarbon oils, and should thus be difficult for the body to remove from the tumor. Liver tumors (n=3) were induced in an Oncopig (a transgenic pig with Cre-inducible p53 and Kras mutations) using an adenoviral vector carrying the Cre recombinase gene. We injected lipiodol versus FC-70 (a radiopaque omniphobic fluorocarbon oil) selectively into hepatic artery branches supplying tumor. 3 days after injection, we quantified oil retention in the tumors or background liver (v/v%), by measuring the Hounsfield units on non-contrast CT, compared to the Hounsfield units of pure oil. Lipiodol was retained in tumor at a concentration of 1.9%, and in background liver at a concentration of 0.6% (3.5x specificity for tumor). FC-70 was retained in tumor at a concentration of 6.8%, and in background liver at a concentration of 1.4% (4.9x specificity for tumor). Intra-arterial FC-70 is an alternative to lipiodol, which can result in improved tumor uptake and specificity. FC-70 is a fluorocarbon oil that has no functional groups in common with lipiodol, indicating a non-specific tumor-targeting mechanism, and suggesting that tumor targeting can be modulated by changing the physical properties of the oil.