title: Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth.
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 μs 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.
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.|Department of Radiation Oncology, Division of Radiation Physics, Stanford University, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sano
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Arena
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: Katelyn R
authors.initials: KR
authors.lastname: Bittleman
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: DeWitt
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: Hyung J
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Szot
authors.affiliation: Technische Universität München, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.affiliation: Virginia-Maryland College of Veterinary Medicine, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Cissell
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: John
authors.initials: J
authors.lastname: Robertson
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: Yong W
authors.initials: YW
authors.lastname: Lee
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, USA.
authors.forename: Rafael V
authors.initials: RV
authors.lastname: Davalos
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018274:Electroporation / Q000379:methods*; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays