Temperature Dependence of High Frequency Irreversible Electroporation Evaluated in a 3D Tumor Model

Electroporation is a bioelectric phenomenon used to deliver target molecules into cells in vitro and irreversible electroporation (IRE) is an emerging cancer therapy used to treat inoperable tumors in situ . These phenomena are generally considered to be non-thermal in nature. In this study, a 3D tumor model was used to investigate the correlation between temperature and the effectiveness of standard clinical IRE and high frequency (H-FIRE) protocols. It was found for human glioblastoma cells that in the range of 2 to 37 °C the H-FIRE lethal electric field threshold value, which describes the minimum electric field to cause cell death, is highly dependent on temperature. Increasing the initial temperature from 2 to 37 °C resulted in a significant decrease in lethal electric field threshold from 1168 to 507 V/cm and a 139% increase in ablation size for H-FIRE burst treatments. Standard clinical protocol IRE treatments resulted in a decrease in lethal threshold from 485 to 453 V/cm and a 7% increase in ablation size over the same temperature range. Similar results were found for pancreatic cancer cells which indicate that tissue temperature may be a significant factor affecting H-FIRE ablation size and treatment planning in vivo while lower temperatures may be useful in maintaining cell viability for transfection applications.