Systems and methods for photodynamic therapy

• US 20030167033A1
• Filed: 01/23/2003
• Published: 09/04/2003
• Est. Priority Date: 01/23/2002
• Status: Abandoned Application

• Current Assignee: Light Sciences Corporation
• Original Assignee: Light Sciences Corporation
• Inventors: Heacock, Greg, Christophersen, Julene, Chen, James, Yeo, Nick
• Application Number:
  US10/351,730
• Publication Number:
  US 20030167033A1
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61F 2009/00863 Retina
• CPC Class Codes: A61F 9/0079 using non-laser electromagnetic radiation, e.g. non-coherent light or microwaves
• CPC Class Codes: A61F 9/008 using laser
• CPC Class Codes: A61F 9/009 Auxiliary devices making contact with the eyeball and coupling in laser light, e.g. goniolenses apparatus for eye examination A61B3/0008
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 41/0061 5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: A61N 2005/0651 Diodes
• CPC Class Codes: A61N 2005/0652 Arrays of diodes
• CPC Class Codes: A61N 5/0601 Apparatus for use inside the body
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Systems and methods for performing photodynamic therapy wherein a photoreactive agent is delivered locally and activated with an external non-invasive energy source are provided. In one embodiment, a low energy light source is used to initiate fluorescence in target tissue containing photoreactive agent. The characteristic fluorescence of the abnormal target tissue is used to generate a map that is then used to direct targeted activation energy to the target tissue without collateral damage to healthy tissue.

Claims

1. A method of performing photodynamic therapy on a patient comprising:

a) locally delivering a photoreactive agent having an activation wavelength range to target tissue of a patient; and

b) photoactivating the photoreactive agent of the target tissue with electromagnetic radiation having a wavelength within the activation wavelength range that travels from outside the patient'"'"'s body to the target tissue within the patient'"'"'s body.

2. The method of claim 1, further comprising allowing the target tissue to absorb a clinically beneficial amount of the photoreactive agent prior to step b) and after step a).

3. The method of claim 1, wherein the photoreactive agent is locally delivered to the target tissue by injection with a hypodermic needle and further comprising advancing the hypodermic needle through the patient'"'"'s body to the target tissue within the patient'"'"'s body and dispensing the photoreactive agent from the tip of the hypodermic needle into the target tissue.

4. The method of claim 1, wherein the photoreactive agent is locally delivered to the target tissue by disposing a photoreactive agent depot adjacent or within target tissue with emission of the photoreactive agent from the photoreactive agent depot into the target tissue.

5. The method of claim 4, wherein the photoreactive agent depot is comprised of a polymer impregnated with the photoreactive agent.

6. The method of claim 4, wherein the target tissue comprises an intracorporeal tumor and the photoreactive agent depot is disposed within the tumor.

7. The method of claim 1, wherein the photoreactive agent is locally delivered to the target tissue by a coronary delivery catheter and further comprising:

advancing a coronary catheter having an injection lumen and outlet ports into the patient'"'"'s vasculature until the outlet ports are disposed adjacent the target tissue; and

injecting the photoreactive agent through the injection lumen and out of the outlet ports to the target tissue or tissue adjacent the target tissue.

8. The method of claim 7, wherein the coronary delivery catheter further comprises an expandable balloon on a distal end of the coronary delivery catheter with the outlet ports disposed on the expandable balloon and further comprising injecting the photoreactive agent through the injection lumen into the expandable balloon so as to expand the expandable balloon against the target tissue or tissue adjacent the target tissue and expel the photoreactive agent out of the outlet ports and into contact with the target tissue or tissue adjacent the target tissue.

9. The method of claim 1, wherein the photoreactive agent is locally delivered to the target tissue by a urinary delivery catheter and further comprising:

advancing the urinary delivery catheter having an injection lumen and outlet ports into the patient'"'"'s urethra until the delivery ports are disposed adjacent the target tissue; and

injecting the photoreactive agent through the injection lumen and out of the outlet ports to the target tissue or tissue adjacent the target tissue.

10. The method of claim 9, wherein the urinary delivery catheter further comprises an expandable balloon on a distal end of the urinary delivery catheter and further comprising advancing the distal end of the urinary delivery catheter into the patient'"'"'s bladder and expanding the expandable balloon in the patient'"'"'s bladder prior to injecting the photoreactive agent through the injection lumen and out of the outlet ports and into contact with the target tissue or tissue adjacent the target tissue.

11. The method of claim 9, wherein the target tissue comprises the patient'"'"'s prostate tissue and further comprising advancing the urinary delivery catheter into the patient'"'"'s urethra until the outlet ports are adjacent the patient'"'"'s prostate tissue prior to injecting the photoreactive agent into the injection lumen and out of the outlet ports.

12. The method of claim 1, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina.

13. The method of claim 4, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by injection into the vitreous by a thin hypodermic needle.

14. The method of claim 13, wherein the needle has a diameter gauge of about 29 to about 31.

15. The method of claim 4, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by positioning of a photoreactive agent depot adjacent the sclera of the patient'"'"'s eye.

16. The method of claim 15, wherein the photoreactive agent depot is comprised of a polymer impregnated with the photoreactive agent.

17. The method of claim 12, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by gas jet injection adjacent the sclera of the patient'"'"'s eye.

18. The method of claim 12, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by an application of a contact disk disposed on the cornea of the patient'"'"'s eye.

19. The method of claim 18, wherein the contact disk comprises a polymer impregnated with the photoreactive agent.

20. The method of claim 19, wherein the contact disk further comprises a first electrical lead extending from the contact disk to a voltage source which is in electrical communication with the patient'"'"'s eye and transfer of the photoreactive agent from the contact disk to the patient'"'"'s retina is facilitated by the application of a voltage between the contact disk and the patient'"'"'s eye by the voltage source.

21. The method of claim 12, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by the application of the photoreactive agent to the patient'"'"'s eye in conjunction with ultrasonic energy being delivered to the patient'"'"'s eye adjacent the photoreactive agent.

22. The method of claim 1, wherein the photoreactive agent is selected from indocyanine green, toluidine blue, aminolevulinic acid, texaphyrins, benzoporphyrins, phenothiazines, phthalocyanines, porphyrins, chlorins, purpurins, purpurinimides, bacteriochlorins, pheophorbides, pyropheophorbides and cationic dyes.

23. The method of claim 1, wherein the photoreactive agent is mono-L-aspartyl chlorin e6.

24. The method of claim 1, wherein photoactivating the photoreactive agent of the target tissue with electromagnetic radiation comprises activating at least one light source.

25. The method of claim 24, wherein the at least one light source comprises one of a light-emitting diode, laser diode, incandescent light bulb, gas discharge device, polymeric electroluminescent device, halogen bulb, chemical luminescence, vacuum fluorescence, radio frequency excited gas, microwave excited gas, and cold cathode fluorescent tube.

50. The method of claim 1, wherein the target tissue is or results from restenosis, atheroma, benign prostatic hypertropy, age-related macular degeneration, diabetic retinopathy or a tumor.

26. A method of performing photodynamic therapy on an eye of a patient comprising:

a) administering a photoreactive agent to the patient'"'"'s body;

b) allowing the photoreactive agent to absorb into at least a portion of the patient'"'"'s retina;

c) illuminating the retina of the patient with a fluorescence generating light so that the photoreactive agent in the patient'"'"'s retina fluoresces and emits fluorescent light;

d) detecting the fluorescent light emitted from the patient'"'"'s retina with a fluorescence detector capable of spatially segregating the location of a point source of fluorescent light from different points in the patient'"'"'s retina and storage of fluorescent response data from various points of the patient'"'"'s retina;

e) processing the fluorescence response date and generating a map of at least a portion of the patient'"'"'s retina so as to create a map of the fluorescence response of the patient'"'"'s retina indicating at least one location of abnormality on the patient'"'"'s retina; and

f) delivery of photoreactive light targeted to the at least one location of abnormality on the patient'"'"'s retina.

27. The method of claim 26, wherein the at least one location of abnormality on the patient'"'"'s retina is indicated by the detection of supra-threshold photoreactive agent concentrations in the tissue at the location of abnormality.

28. The method of claim 26, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina.

29. The method of claim 28, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by injection into the vitreous by a thin hypodermic needle.

30. The method of claim 29, wherein the needle has a diameter gauge of about 29 to about 31.

31. The method of claim 28, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by positioning of a photoreactive agent depot adjacent the sclera of the patient'"'"'s eye.

32. The method of claim 31, wherein the photoreactive agent depot is comprised of a polymer impregnated with the photoreactive agent.

33. The method of claim 28, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by gas jet injection adjacent the sclera of the patient'"'"'s eye.

34. The method of claim 28, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by an application of a contact disk disposed on the cornea of the patient'"'"'s eye.

35. The method of claim 34, wherein the contact disk comprises a polymer impregnated with the photoreactive agent.

36. The method of claim 35, wherein the contact disk further comprises a first electrical lead extending from the contact disk to a voltage source which is in electrical communication with the patient'"'"'s eye and transfer of the photoreactive agent from the contact disk to the patient'"'"'s retina is facilitated by the application of a voltage between the contact disk and the patient'"'"'s eye by the voltage source.

37. The method of claim 28, wherein the photoreactive agent is locally delivered to the patient'"'"'s retina by the application of the photoreactive agent to the patient'"'"'s eye in conjunction with ultrasonic energy being delivered to the patient'"'"'s eye adjacent the photoreactive agent.

38. The method of claim 26, wherein the at least one location of abnormality comprises age-related macular degeneration.

39. The method of claim 26, wherein the at least one location of abnormality comprises diabetic retinopathy.

40. The method of claim 26, further comprising evaluation of a treatment response of the patient'"'"'s retina using real-time monitoring of fluorescence signal intensity as an indicator of vascular leakage.

41. The method of claim 26, wherein the photoreactive agent is selected from indocyanine green, toluidine blue, aminolevulinic acid, texaphyrins, benzoporphyrins, phenothiazines, phthalocyanines, porphyrins, chlorins, purpurins, purpurinimides, bacteriochlorins, pheophorbides, pyropheophorbides and cationic dyes.

42. The method of claim 26, wherein the photoreactive agent is mono-L-aspartyl chlorin e6.

43. The method of claim 26, wherein delivery of photoreactive light is accomplished by activating at least one light source comprised of one of a light-emitting diode, laser diode, incandescent light bulb, gas discharge device, polymeric electroluminescent device, halogen bulb, chemical luminescence, vacuum fluorescence, radio frequency excited gas, microwave excited gas, and cold cathode fluorescent tube.

44. A system for performing photodynamic therapy on a patient'"'"'s retina comprising:

a) a source of fluorescence generating light configured to illuminate the retina of the patient;

b) a fluorescence detector configured to detect fluorescent light emanating from the retina of the patient;

c) a source of photoactivating light configured to deliver photoactivating light to the patient'"'"'s retina; and

d) a processor programmed to accumulate, store and analyze fluorescence response data from the fluorescence detector in response to fluorescent light from the patient'"'"'s retina and generate a map of the patient'"'"'s retina based on the fluorescence data indicating locations of tissue abnormality and thereafter direct light from the source of photoactivating light which is targeted to the locations of tissue abnormality in the patient'"'"'s retina.

45. The system of claim 44, wherein the source of fluorescence generating light comprises a laser having a characteristic wavelength of about 600 to about 700 nanometers.

46. The system of claim 44, wherein the source of fluorescence generating light comprises a laser having a characteristic wavelength of about 660 to about 670 nanometers.

47. The system of claim 44, wherein the source of photoactivating light comprises a laser having a characteristic wavelength of about 500 to about 800 nanometers.

48. The system of claim 47, wherein the source of photoactivating light comprises a laser having a characteristic wavelength of about 600 to about 700 nanometers.

49. The system of claim 47, wherein the source of photoactivating light comprises one of a light-emitting diode, laser diode, incandescent light bulb, gas discharge device, polymeric electroluminescent device, halogen bulb, chemical luminescence, vacuum fluorescence, radio frequency excited gas, microwave excited gas, and cold cathode fluorescent tube.

51. A device for performing photodynamic therapy on the eye of a patient, comprising:

an elongate arm, wherein at least a portion of the arm follows a curvature that substantially conforms to the curvature of the eye;

a photoactivating light source that emits light along a light path, the light source positioned at a distal end of the elongate arm, wherein the elongate arm is sized to be positioned adjacent an outer surface of the eye such that a target portion of the eye is positioned in the light path.

52. A device as defined in claim 51, wherein the light source is one of a light-emitting diode, laser diode, incandescent light bulb, gas discharge device, polymeric electroluminescent device, halogen bulb, chemical luminescence, vacuum fluorescence, radio frequency excited gas, microwave excited gas, and cold cathode fluorescent tube.

53. A device as defined in claim 51, additionally comprising a lens positioned in the light path, wherein the lens focuses light from the light source.

54. A device as defined in claim 51, wherein the arm follows a curvature defined by a radius, and wherein the radius is approximately 12 mm.

55. A device as defined in claim 51, wherein the light source emits light having a characteristic wavelength of about 500 to about 800 nanometers.

56. A device for delivering a photoreactive agent to the eye of a patient, comprising:

a hypodermic needle, wherein at least a portion of the needle follows a curvature that substantially conforms to the curvature of the eye, wherein the photoreactive agent can be dispensed from a distal end of the needle;

a sheath that at least partially surrounds the needle, wherein the sheath follows a curvature that substantially conforms to the curvature of the eye.

57. A device as defined in claim 56, wherein the needle can be retracted such that the distal end of the needle is contained within the sheath, and wherein the needle can be advanced so that the distal end of the needle protrudes outwardly from the sheath.

58. A device as defined in claim 57, wherein the distal end of the needle can only be advanced outwardly a fixed distance from a distal edge of the sheath.

59. A device as defined in claim 56, additionally comprising a syringe attached to the needle, wherein the syringe can be actuated to dispense the photoreactive agent through the distal end of the needle.

60. A device as defined in claim 56, wherein a flexible coupling attaches the needle to the syringe so that the needle can be moved to various orientations relative to the syringe.

61. A device as defined in claim 56, wherein the needle follows a curvature defined by a radius, and wherein the radius is approximately 12 mm.