Mass transfer of electrolytic species during electric field-based tumor treatments

Abstract

To attain a reliable outcome in electric field-based tumor treatments, dose planning is a must, and dose planning, in turn, requires establishing the dose-response relationship. But finding reliable dose and response parameters implies analyzing the electric field-tissue interaction, in particular, the inevitable appearance of complex electrolytic mass transfer processes and the inherent tissue damage. This review of electric field-based tumor treatments highlights the fundamental role played by the mass transfer of electrolytic species in the dose-response relationship. During the electrolysis process in electric field-based tumor treatments, electrochemical reactions take place at the electrodes, producing at the anode oxygen, chlorine, and protons as the main by-products, while hydrogen and hydroxide ions are released at the cathode. Proton and hydroxyls generation yields strong pH fronts. Since these fronts are the main product of electrolytic reactions, it is reasonable to assume that they are the main cause of tissue damage. The amount of electrolytic products emerging from chemical reactions is proportional to the amount of electric charges or Coulomb dose passing through the tissue; thus, Coulomb dose is proportional to tissue damage. Theory shows that in a constant electric field such as in electrolytic ablation, an optimal dose-response relationship is the minimum Coulomb dose necessary to achieve total tumor destruction while minimizing healthy tissue damage. In a pulsed electric field such as in gene electrotransfer, unwanted damage due to electrolysis is non-negligible; here, an optimal gene electrotransfer treatment is predicted as the critical Coulomb dose yielding maximum electroporated area with minimum damage. Theory shows that when tissue natural buffer is taken into account, damage is attenuated (though still remaining non-negligible), and the critical Coulomb dose for optimal gene electrotransfer increases.