Calculation of the electrical parameters in electrochemotherapy of solid tumours in mice.

Electrochemotherapy is a novel approach in chemotherapeutic drug delivery into tumours. Short intense direct current electric pulses are applied to tumour tissue causing electropermeabilisation thus enabling entrance of chemotherapeutic drugs into cells which otherwise do not easily penetrate. A three dimensional anatomically based finite element model of the mouse with injected subcutaneous solid tumour was built. The main goal of the study was to evaluate the influence of the electrode orientation on the distribution of electric field in the tumour and surrounding tissue during electrochemotherapy. Two electrode configurations, previously examined in experimental study, were modelled. Electric field distributions were calculated for each configuration. The main conclusion of our study is that changing electrode orientation strongly influences the distribution of the electric field inside the tumour in the electrochemotherapy of solid tumours in mice, which is in good agreement with the results of the experimental study. The efficacy of the electrochemotherapy depends on the magnitude of the electric field intensity inside tumour tissue.

The importance of electric field distribution for effective in vivo electroporation of tissues.

Cells exposed to short and intense electric pulses become permeable to a number of various ionic molecules. This phenomenon was termed electroporation or electropermeabilization and is widely used for in vitro drug delivery into the cells and gene transfection. Tissues can also be permeabilized. These new approaches based on electroporation are used for cancer treatment, i.e., electrochemotherapy, and in vivo gene transfection. In vivo electroporation is thus gaining even wider interest. However, electrode geometry and distribution were not yet adequately addressed. Most of the electrodes used so far were determined empirically. In our study we 1) designed two electrode sets that produce notably different distribution of electric field in tumor, 2) qualitatively evaluated current density distribution for both electrode sets by means of magnetic resonance current density imaging, 3) used three-dimensional finite element model to calculate values of electric field for both electrode sets, and 4) demonstrated the difference in electrochemotherapy effectiveness in mouse tumor model between the two electrode sets. The results of our study clearly demonstrate that numerical model is reliable and can be very useful in the additional search for electrodes that would make electrochemotherapy and in vivo electroporation in general more efficient. Our study also shows that better coverage of tumors with sufficiently high electric field is necessary for improved effectiveness of electrochemotherapy.