A Numerical Evaluation of the Cell Kill Distributions due to Thermal Damage in Electrochemotherapy

Electrochemotherapy(ECT) is a powerful biotechnological tool for enhancing the delivery of chemotherapeutic agents to cancer cells with the use of brief but intense pulsed electric fields (PEFs). In ECT therapies the goal is to introduce chemotherapeutics into cells in a reversible manner that will allow high cell viability to be maintained. However, application of the PEFs to the cells without the drugs can also result in cell kill due to irreversible electroporation. Additionally, if the pulse repetition frequencyis very high there is a chance of inducing cell death via thermal damage. Therefore, the main objective of this study is to evaluate the thermal effects in an ECT procedure in which we simulated the delivery of eight 100-μs pulses at a pulse repetition frequencyof 1, 10, 100, and 1000 Hz. This was performed in order to assess if the pulses induce undesired thermal damage due to excessive Joule heatingthat could compromise the viability of the tissue post- electroporationat pulse repetition frequenciesbeing evaluated in several clinical studies worldwide.