Abstract 1317: inovivo: a dedicated system for delivery of therapeutic level Tumor Treating Fields (TTFields) to mice
Authors: Davidi Shiri , Blatt Roni , Munster Mijal , Shteingauz Anna , Porat Yaara , Zeidan Adel , Marciano Tal , Bomzon Zeev , Giladi Moshe , Weinberg Uri , Palti Yoram 
Published: July 2021

Abstract
Purpose/objective: Tumor Treating Fields (TTFields) therapy is a noninvasive antineoplastic treatment modality that is FDA approved for treatment of glioblastoma and malignant pleural mesothelioma. TTFields are delivered to the patient continuously by 2 pairs of transducer arrays attached to the skin. In vivo TTFields experiments were so far limited due to the lack of a dedicated animal delivery system. Two main challenges are associated with TTFields application to the animal: 1) there is an absolute requirement for adequate and continuous contact between the electrodes and the animal skin throughout treatment; and 2) the wires connected to the electrodes require individual housing and limit animal movement, thus imposing stress. This work aimed to develop an in vivo system for continuous TTFields delivery to mice bearing cancer tumors in the torso or flank while addressing these challenges. Materials/Methods: To tackle the challenges and develop a viable in vivo system, several solutions were tested: 1) various electrode layouts; 2) a variety of adhesive materials; and 3) devices for preventing wire entanglement. Results: The final design of the transducer array electrodes included 2 adhesive layers, an inner layer for improved adherence, and an outer layer for securing the electrodes to the skin. Conductors were compacted into a single printed circuit cable connected to a novel electric swivel machine, that prevented cable coiling by sensing and rotating according to animal movement. These improvements resulted in fewer electrode entanglements and replacements, and thus in higher compliance (continuity) and less need for animal handling. To further reduce the impact of stress factors on the mice, a new cage was developed, that allows for 2 mice to be housed separately while still maintaining an interaction with one another. Indeed, animals treated with the inovivo system for 1-week displayed lower weight loss than animals treated with the previous non-dedicated system, indicative of reduced stress. Simulation were performed to ensure electric fields were indeed generated at the desired locations, showing above threshold TTFields intensities around the tumor for the flank subcutaneous model. For the torso orthotopic model, TTFields were shown to generate effective electric fields in the lung, liver, and pancreas, suggesting tumors in these organs may be treated effectively using the inovivo system. Conclusion: The new inovivo system provides means for continuous, 2 directions TTFields delivery to tumors in the torso or flank while minimizing stress on the mice. The inovivo system thus provides a tool for conducting TTFields experiments in mice, facilitating further in vivo studies for gaining additional mechanistical insight. The development of mouse head arrays to allow further research of the effect TTFields on glioblastoma, an application of widespread interest, is currently underway.
Citation Format: Shiri Davidi, Roni Blatt, Mijal Munster, Anna Shteingauz, Yaara Porat, Adel Zeidan, Tal Marciano, Zeev Bomzon, Moshe Giladi, Uri Weinberg, Yoram Palti. inovivo: a dedicated system for delivery of therapeutic level Tumor Treating Fields (TTFields) to mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1317.