Development of a Three-Dimensional Multi-Modal Perfusion-Thermal Electrode System for Complete Tumor Eradication

Simple Summary Image-guided thermal-ablation techniques, such as radiofrequency ablation (RFA), have become the principal tools for treatment of unresectable primary and secondary tumors. However, tumor recurrences post-thermal ablation of medium to large-sized tumors frequently occur due to incomplete ablation of tumor margins. In the present study, we aim to specifically conquer this clinical problem through revolutionizing current thermal ablation technology by development of an innovative three-dimensional, multi-modal, perfusion-thermal electrode system, with the evidence of potential to simultaneously deliver therapeutics and RFA-medicated peritumoral hyperthermia into the difficult-to-treat tumor margins, to further eradicate the residual tumor cells during the thermal ablation. Background: Residual viable tumor cells after ablation at the tumor periphery serve as the source for tumor recurrence, leading to treatment failure. Purpose: To develop a novel three-dimensional (3D) multi-modal perfusion-thermal electrode system completely eradicating medium-to-large malignancies. Materials and Methods: This study included five steps: (i) design of the new system; (ii) production of the new system; (iii) ex vivo evaluation of its perfusion-thermal functions; (iv) mathematic modeling and computer simulation to confirm the optimal temperature profiles during the thermal ablation process, and; (v) in vivo technical validation using five living rabbits with orthotopic liver tumors. Results: In ex vivo experiments, gross pathology and optical imaging demonstrated the successful spherical distribution/deposition of motexafin gadolinium administered through the new electrode, with a temperature gradient from the electrode core at 80 degrees C to its periphery at 42 degrees C. An excellent repeatable correlation of temperature profiles at varying spots, from the center to periphery of the liver tumor, was found between the mathematic simulation and actual animal tumor models (Pearson coefficient >= 0.977). For in vivo validation, indocyanine green (ICG) was directly delivered into the peritumoral zones during simultaneous generation of central tumoral lethal radiofrequency (RF) heat (>60 degrees C) and peritumoral sublethal RF hyperthermia (<60 degrees C). Both optical imaging and fluorescent microscopy confirmed successful peritumoral ICG distribution/deposition with increased heat shock protein 70 expression. Conclusion: This new 3D, perfusion-thermal electrode system provided the evidence on the potential to enable simultaneous delivery of therapeutic agents and RF hyperthermia into the difficult-to-treat peritumoral zones, creating a new strategy to address the critical limitation, i.e., the high incidence of residual and recurrent tumor following thermal ablation of unresectable medium-to-large and irregular tumors.