Electroporation-Mediated Transcatheter Arterial Chemoembolization in the Rabbit VX2 Liver Tumor Model

Rationale and Objectives: Electropermeabilization involves the application of electrical pulses to increase cell membrane permeability. The purpose of our study was to demonstrate the potential to use electroporation-mediated transcatheter arterial chemoembolization (E-TACE) approaches to increase liver tumor drug uptake while using magnetic resonance imaging (MRI) for intraprocedural optimization of these procedures. Methods: Fourteen VX2 tumors were grown in the left hepatic lobes of 8 rabbits. Two tumors were grown in each of 6 rabbits (1 tumor serving as E-TACE-treated tumor and the other as nonelectroporated control), and solitary larger tumors were grown in 2 rabbits (half of the tumor treated with E-TACE, remaining half serving as control). Each rabbit was selectively catheterized under digital subtraction angiography guidance. Baseline MRI was performed to generate tumor contrast enhancement curves following catheter-directed infusion of gadopentetate dimeglumine to estimate the proper time delay between subsequent bolus infusion of cisplatin and application of electrical pulses (electrodes were used to deliver 8, 100-mu s, 1300-V pulses at the selected delay interval postinfusion). Three hours after E-TACE, rabbits were euthanized, and tumors were sectioned for inductively coupled plasma mass spectroscopy measurements of platinum concentration (serving as reference standard of cisplatin uptake levels). Results: Inductively coupled plasma mass spectroscopy results demonstrated significantly increased cisplatin uptake in E-TACE-treated tumor tissues, increases of 6.0 +/- 3.3-fold compared with transcatheter infusion alone (P = 0.017). Conclusions: Our findings suggest that our E-TACE approach may significantly increase liver tumor drug uptake after targeted transcatheter infusion. MRI measurements permitted intraprocedural guidance during these catheter-directed E-TACE procedures.