Abstract 4393: MRI-guided electroporation-mediated transarterial chemoembolization (E-TACE)
Authors: Guo Yang , Lewandowski Robert J. , Zhang Yue , Jin Ning , Rachel Klein , Nicolai Jodi , Ryu Robert K. , Omary Reed , Larson Andrew 
Published: June 2012

INTRODUCTION: Electropermeabilization involves the application of electrical pulses to increase cell membrane permeability; electrochemotherapy (ECT) takes advantage of this phenomenon to increase tumor uptake of drugs. The purpose of this study was to demonstrate the potential to use MRI for intra-procedural optimization of an electroporation-mediated TACE (E-TACE) approach intended to increase liver tumor drug uptake compared to transcatheter infusion alone.

MATERIALS & METHODS: Eight New Zealand White rabbits were used for our ACUC-approved experiments. Two VX2 tumor portions were implanted in the left medial hepatic lobe of each rabbit and a total of fourteen VX2 tumors were grown in these rabbits. Two tumor were grown in 6 rabbits (one as E-TACE treated tumor and other as control) and solitary larger tumors was grown in 2 rabbits (half of tumor treated with E-TACE, remaining half as control). Each rabbit was catheterized under DSA guidance with catheter placed in the left hepatic artery. Next, Baseline transcatheter intraarterial perfusion (TRIP) MRI (1.5T, Siemens Medical) was performed to generate tumor enhancement curves with an intra-arterial (IA) injection of Gd-DTPA. These contrast enhancement curves were generated to estimate time delay between IA bolus infusion and the period of maximum tumor uptake (for planning purposes to optimize delay interval, Td, between later IA Cisplatin infusion and application of electrical pulses). For E-TACE treated tumors (one tumor in each rabbit) bi-polar electrodes (1cm spacing) were inserted straddling the targeted tumor and 8 100μs 1300V pulses applied at the selected delay interval Td after the administration of Cisplatin solution through the catheter. Next, a post TRIP-MRI scan was performed to assess tumor perfusion alterations and treatment related tumor signal intensity changes. After allowing 3 hours for Cisplatin wash out, rabbits were euthanized and each tumor sectioned for ICP-MS measurement of intra-tumoral platinum concentrations.

RESULTS: ICP-MS results demonstrated significantly increased Cisplatin uptake in E-TACE treated tumors, increases of 6.0-fold compared to transcatheter infusion alone in six of the rabbits (n=6/8, p=0.017). Follow-up T2W-TSE images showed significant intra-tumoral T2W signal decreases in five rabbits (n=5/8) whereas no such signal changes were observed in other rabbits (two of which showed negligible Cisplatin uptake increases).

CONCLUSION: Our findings suggest that E-TACE may be effective for increasing tumor uptake of chemotherapeutic agents and that intra-procedural MRI should permit immediate confirmation of targeted drug delivery based upon signal changes only present in sufficiently treated tissues. Additional longitudinal studies are required to evaluate and compare treatment response between animals treated with E-TACE and those treated with conventional TACE approaches.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4393. doi:10.1158/1538-7445.AM2011-4393