HIGH-FREQUENCY ELECTROPORATION FOR CANCER THERAPY

• US 20120109122A1
• Filed: 12/20/2011
• Published: 05/03/2012
• Est. Priority Date: 04/09/2009
• Status: Active Grant

• Current Assignee: Virginia Tech Intellectual Properties, Inc.
• Original Assignee: Virginia Tech Intellectual Properties, Inc.
• Inventors: Davalos, Rafael V., Sano, Michael B., ARENA, Christopher B.
• Granted Patent: US 10,448,989 B2
• Time in Patent Office: Days
• US Class Current: 606/41
• CPC Class Codes: A61B 18/14 Probes or electrodes therefor
• CPC Class Codes: A61B 2017/00159 Pulse shapes
• CPC Class Codes: A61B 2017/00172 Pulse trains, bursts, intermittent continuous operation
• CPC Class Codes: A61B 2018/0016 Energy applicators arranged in a two- or three dimensional array
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• CPC Class Codes: A61B 2018/00732 Frequency
• CPC Class Codes: A61B 2018/00761 Duration
• CPC Class Codes: A61B 2018/00767 Voltage
• CPC Class Codes: A61B 2018/126 bipolar
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.

Claims

1. A method of treating a subject suffering from a neoplasia comprising:

implanting at least one device for emitting electric pulses into or adjacent a neoplastic site within the body of a subject; and

delivering one or more electric pulse to the neoplastic site, such that amplitude and duration of the pulse are in the range of about 1500 V/cm to 2500 V/cm for 10 μ

s or less which is capable of inducing irreversible electroporation.

3. The method of claim 1, wherein multiple pulses are administered in a pulse burst having a duration of less than 10 ms.

5. The method of claim 1, wherein the amplitude of the pulse is in the range of about 500 V/cm to 1500 V/cm.

7. The method of claim 1, wherein the pulse duration is in the range of about 2 MHz (250 ns) to about 500 kHz (1 μ

s).

8. The method of claim 1, wherein the pulse duration is in the range of about 1 MHz (500 ns).

11. The method of claim 1, wherein two or more electrically conductive regions are used within a single device for emitting the electrical pulses.

13. The method of claim 1, wherein two or more devices are used.

15. The method of claim 1, wherein custom treatment area shapes are created through varying electrode activation patterns.

17. The method of claim 1, wherein a bipolar burst of pulses is delivered.

19. The method of claim 17, wherein a bipolar burst of pulses is delivered with multiple pulses in a single phase before a polarity switch.

21. The method of claim 1, wherein total burst width is between 1 μ

μ

s and 10,000 μ

s.

23. The method of claim 1, wherein the duration of single polarity within a bipolar burst is between 100 ns and 100,000 ns.

25. The method of claim 1, wherein the electric pulses are square, ramp, sinusoidal, exponential, or trapezoidal and are delivered with a delay between pulses on the order of microseconds.

27. The method of claim 1 comprising administering two or more electric pulse bursts with a delay between bursts on the order of seconds.

39. The method of claim 1, wherein the pulses are delivered on a short enough timescale to flow through epithelial cells but are long enough to induce electroporation in underlying cells.

40. The method of claim 39, wherein the underlying cells are cells in a layer of fat and a frequency of 500 kHz or 1 MHz or 250 kHz is used to treat the underlying fat cells in the fat layer.

41. The method of claim 1 for administering non-thermal IRE.

43. The method of claim 1 resulting in more predictable outcomes in homogeneous and heterogeneous tissues than compared with lower frequency pulsing protocols.

2. A method of treating a subject suffering from a neoplasia comprising:

non-invasively placing at least one device for emitting electric pulses around a region of the body containing a neoplastic site within; and

delivering one or more electric pulse, such that amplitude and duration of the pulse are in the range of about 1500 V/cm to 2500 V/cm for 10 μ

s or less which is capable of inducing irreversible electroporation.

4. The method of claim 2, wherein multiple pulses are administered in a pulse burst having a duration of less than 10 ms.

6. The method of claim 2, wherein the amplitude of the pulse is in the range of about 500 V/cm to 1500 V/cm.

9. The method of claim 2, wherein the pulse duration is in the range of about 2 MHz (250 ns) to about 500 kHz (1 μ

s).

10. The method of claim 2, wherein the pulse duration is in the range of about 1 MHz (500 ns).

12. The method of claim 2, wherein two or more electrically conductive regions are used within a single device for emitting the electrical pulses.

14. The method of claim 2, wherein two or more devices are used.

16. The method of claim 2, wherein custom treatment area shapes are created through varying electrode activation patterns.

18. The method of claim 2, wherein a bipolar burst of pulses is delivered.

20. The method of claim 18, wherein a bipolar burst of pulses is delivered with multiple pulses in a single phase before a polarity switch.

22. The method of claim 2, wherein total burst width is between 1 μ

s and 10,000 μ

s.

24. The method of claim 2, wherein the duration of single polarity within a bipolar burst is between 100 ns and 100,000 ns.

26. The method of claim 2, wherein the electric pulses are square, ramp, sinusoidal, exponential, or trapezoidal and are delivered with a delay between pulses on the order of microseconds.

28. The method of claim 2 comprising administering two or more electric pulse bursts with a delay between bursts on the order of seconds.

29. A method of delivering electric pulses such that amplitude and duration of single polarity are selected to be capable of administering electroporation to electrically excitable tissue without stimulation of the tissue.

31. The method of claim 29, wherein the tissue stimulation is a muscle contraction.

32. The method of claim 29, wherein the neoplastic site, region of the body, or electrically excitable tissue is nerve.

33. The method of claim 29, wherein the neoplastic site, region of the body, or electrically excitable tissue is muscle.

34. The method of claim 29, wherein the electrically excitable tissue, neoplastic site, or region of the body is an organ containing nerves and/or muscle tissue.

35. The method of claim 29, wherein the amplitude and duration of the pulse(s) are in the range of about 1500 V/cm to 2500 V/cm for 10 μ

s or less which is capable of inducing irreversible electroporation.

36. The method of claim 29, wherein general anesthesia is administered for treatment of tissues with electroporation based therapies.

37. The method of claim 29, wherein local anesthesia is administered for treatment of tissues with electroporation based therapies.

38. The method of claim 29, wherein no neural blockade is administered for treatment of tissues with electroporation based therapies.

42. The method of claim 29, wherein reversible electroporation is administered.

30. A method of delivering electric pulses such that amplitude and duration of single polarity are selected to be capable of administering electroporation to electrically excitable tissue with reduced stimulation of the tissue as compared with higher amplitude and longer duration pulse protocols.