Purpose: Compare deposition of doxorubicin in the periphery of thermal lesions in swine liver using free doxorubicin or a heat-sensitive liposomal vector containing doxorubicin as an adjuvant therapy to radiofrequency ablation (FRA).
Materials and Methods: Three pigs underwent RFA of the liver during intravenous administration of a low-temperature sensitive formulation of liposomal doxorubicin that deploys its contents at predominantly 39 to 42C. Two pigs were treated with identical RFA with intravenous free doxorubicin without liposome. Doxorubucin dosing was 0.7mg/kg body weight. Two pigs underwent ablation without drug, serving as controls. Liver tissue specimens collected at regular intervals from the thermal ablation center were analyzed for doxorubicin and its metabolites (aglycone and doxorubicinol)). Thermal maps and corresponding drug levels were analyzed and the area under the time temperature curve for specific distances was correlated.
Results: Between 2 to 4 times as much doxorubicin was deposited in and around the thermal lesions with the low temperature sensitive formulation of liposomal doxorubicin compared with free doxorubicin.
Conclusion: Liposome-encapsulated doxorubicin (with special low temperature deployment chemistry) may be deposited at the periphery of thermal lesions in the swine model. This combination treatment may prove more effective as a therapy for focal liver tumor than either treatment alone.(M.A. is a paid consultant for Celsion, Inc; Celsion Inc. provided the liposomal carrier.)