Simple SummaryAround 248,530 newly diagnosed in 2021, prostate cancer has been the most frequently diagnosed cancer in the USA. Rapid decellularization preserving acellular tissues is essential for accurate treatment and regeneration in affected areas. Our study aimed to assess the safety and efficacy of high-frequency pulsed electric field (HF-PEF) in a beagle model for the treatment of prostate cancer. We confirmed that HF-PEF of 1800 V/cm, 100 μs width, 2 ms interval successfully decellularized the prostate tissue after 4 hours, and the tissues were almost regenerated in 28 days. IRE with HF-PEF has therapeutic potential to treat prostate cancer while minimizing damage to the surrounding tissues.Conventional irreversible electroporation (IRE) with low-frequency pulsed electric field (LF-PEF) is used to induce cell death; however, it has several disadvantages including a long procedure time and severe muscle contraction due to high-voltage electric field. This study investigates a novel IRE protocol with high-frequency pulsed electric field (HF-PEF) of 500 Hz repetition to ablate the prostate tissue in beagles for treatment of prostate cancer. A finite element analysis was performed to validate optimal electrical field strength for the procedure. In total, 12 beagles received HF-PEF of 500 Hz and were sacrificed at 4 h, 4 days, and 28 days (3 each). The remaining three beagles underwent sham procedure. The outcomes of HF-PEF were assessed by histological responses. HF-PEF successfully decellularized the prostate tissues 4 h after the treatment. The prostate glands, duct, and urethra were well preserved after IRE with HF-PEF. The ablated prostatic tissues were gradually regenerated and appeared similar to the original tissues 28 d after IRE with HF-PEF. Moreover, electrocardiography and hematology demonstrated that IRE with HF-PEF did not seriously affect the cardiac tissue. HF-PEF was effective and safe in the beagle prostate and effectively induced the ablation and gradually recovered with cellular regeneration.
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