Treatment of Liver Tumors in Rabbit

Electrochemotherapy has been proven to be efficient for the treatment of subcutaneous tumors of different histological types in mice, rats and cats (1-3). Electrochemotherapy is essentially a local treatment. Indeed, it is based on the potentiation of the cytotoxicity of a low-permeant drug, typically bleomycin, by tumor cell permeabilization using brief and intense electric pulses. In the tissues exposed to such electric pulses, the so-called cell electropermeabilization is obtained only in the volume crossed by an electric field of intensity higher than a threshold value (4). The existence of this threshold for tissue permeabilization implies that the potentiation of the cytotoxic drug by the applied electric pulses is limited to the space roughly comprised between the electrodes. In the case of rather small and prominent cutaneous or subcutaneous tumors, it is easy to place two external electrodes on each side of the tumor nodule to be treated and to transcutaneously deliver the permeabilizing electric pulses. For thick and for deep subcutaneous tumors as well as for tumors located in internal organs, this electrode configuration is not appropriate because the electric pulses have to be delivered directly to the tumor tissues. Externally placed electrodes simply do not supply electric fields that extend deep enough for these situations. Intratumoral electric pulse delivery can, however, be achieved using needle-electrodes that are inserted into the tumor volume. We have designed an applicator constituted by multiple parallel and equidistant needles in order to avoid the delivery of very high-voltage electric pulses. A specifically manufactured generator ensures the multiplexed supplying of the electric current to each pair of closest needle electrodes. Thus, the entire tumor volume is divided in small units which are separately permeabilized by the different pairs of closest electrodes.