Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth

Michael B. Sano, Christopher B. Arena, Katelyn R. Bittleman, Matthew R. Dewitt, Hyung J. Cho, Christopher S. Szot, Dieter Saur, James M. Cissell, John Robertson, Yong W. Lee, Rafael V. Davalos

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 ìs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models.

Original languageEnglish
Article number14999
JournalScientific Reports
Volume5
DOIs
StatePublished - 13 Oct 2015

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