Spin resonance heating and/or imaging in medical applications

• US 20050118102A1
• Filed: 04/28/2004
• Published: 06/02/2005
• Est. Priority Date: 04/28/2003
• Status: Abandoned Application

• Current Assignee: Intematix Corporation
• Original Assignee: Intematix Corporation
• Inventors: Sun, Ted, Wang, Gang, Yang, Haitao, Xiang, Xiao Dong, Dionne, Gerald
• Application Number:
  US10/835,247
• Publication Number:
  US 20050118102A1
• Time in Patent Office: Days
• US Class Current: 424/9.340
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

This invention pertains to the use of spin resonance absorption heating as a therapeutic treatment method. It was a surprising discovery that electron spin resonance absorption of superparamagnetic (SPM) nanoparticles can be used as a heating method, more preferably as an in vivo heating method that can be utilized in a variety of therapeutic contexts.

Claims

1. A composition for selectively heating and/or imaging a cell, or tissue, said composition comprising:

a superparamagnetic nanoparticle attached to a targeting moiety that specifically binds to a biological target comprising said cell or tissue.

2. The composition of claim 1, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q greater than than 10.

3. The composition of claim 1, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q ranging from about 100 to about 1000.

4. The composition of claim 1, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel.

5. The composition of claim 4, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel selected from Table 2.

6. The composition of claim 1, wherein said superparamagnetic nanoparticle comprises yttrium ion garnet (YIG).

7. The composition of claim 6, wherein said yttrium ion garnet is substituted with a material selected from the group consisting of aluminum, gallium, indium, and a ferrite.

8. The composition of claim 1, wherein said superparamagnetic nanoparticle comprises gamma-Fe2O3.

9. The composition of claim 6, wherein said yttrium ion garnet is substituted with lithium ferrite.

10. The composition of claim 1, wherein said targeting moiety is directly attached to said superparamagnetic nanoparticle.

11. The composition of claim 1, wherein said targeting moiety is attached to said sperparamagnetic nanoparticle through a linker.

12. The composition of claim 1, wherein said superparamagnetic nanoparticle is attached to a single targeting moiety.

13. The composition of claim 1, wherein said superparamagnetic nanoparticle is attached to a plurality of targeting moieties.

14. The composition of claim 1, wherein a plurality of superparamagnetic nanoparticles are attached to a single targeting moiety.

15. The composition of claim 1, wherein said targeting moiety is selected from the group consisting of a protein, an antibody, a lectin, a saccharide, a vitamin, a steroid, a steroid analogue, a hormone, and a nucleic acid.

16. The composition of claim 1, wherein said cell or tissue is a cancer cell.

17. The composition of claim 16, wherein said targeting moiety is a protein.

18. The composition of claim 16, wherein said targeting moiety is an antibody.

19. The composition of claim 1, wherein said biological target is a cancer marker.

20. The composition of claim 19, wherein said biological target is a cancer marker selected from the group consisting of Caf-1, C-myc, p53, Ki67, Her2, Her4, BRCA1, BRCA2, Lewis Y (Le^Y), CA 15-3, G250, HLA-DR cell surface antigen, CEA, CD20, CD22, integrin, cea, 16, EGFr, AR, PSA, and other growth factor receptors.

21. The composition of claim 6, wherein said superparamagnetic nanoparticle has at least one dimension less than about 500 nm.

22. The composition of claim 6, wherein said superparamagnetic nanoparticle has no dimension greater than about 500 nm.

23. The composition of claim 6, wherein said superparamagnetic nanoparticle has at least one dimension less than about 100 nm.

24. A composition for selectively heating or imaging a cell, tissue, or organ, said composition comprising superparamagnetic nanoparticles in a pharmacologically acceptable excipient.

25. The composition of claim 24, wherein said superparamagnetic nanoparticles comprise a material that has electron spin resonance (ESR) Q greater than 10.

26. The composition of claim 24, wherein said superparamagnetic nanoparticles comprise a material that has an electron spin resonance (ESR) Q ranging from about 100 to about 1000.

27. The composition of claim 24, wherein said superparamagnetic nanoparticles comprises a garnet or a spinel.

28. The composition of claim 24, wherein said superparamagnetic nanoparticles comprises a garnet or a spinel selected from Table 2.

29. A method of selectively heating a cell, tissue, or molecule, said method comprising:

contacting said cell, tissue, or molecule with a composition comprising a superparamagnetic nanoparticle attached to a targeting moiety that specifically binds to a biological target comprising said cell, tissue, or molecule; and

heating said superparamagnetic nanoparticle using electron spin resonance.

30. The method of claim 29, wherein said electron spin resonance is at an RF ranging from about RF frequency ranging from 200 to 2,000 MHz MHz.

31. The method of claim 29, wherein said electron spin resonance is at an RF ranging from about 500 to about 1,000 MHz.

32. The method of claim 29, wherein said electron spin resonance is spatially localized by a magnetic field gradient over a region smaller than the region over which the superparamagnetic nanoparticles are distributed.

33. The method of claim 29, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q greater than 10.

34. The method of claim 29, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q ranging from about 100 to about 1000.

35. The method of claim 29, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel.

36. The method of claim 35, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel selected from Table 2.

37. The method of claim 29, wherein said superparamagnetic nanoparticle comprises yttrium ion garnet (YIG).

38. The method of claim 37, wherein said yttrium ion garnet is substituted with a material selected from the group consisting of aluminum, gallium, indium, and a ferrite.

39. The method of claim 29, wherein said superparamagnetic nanoparticle comprises gamma-Fe2O3.

40. The method of claim 37, wherein said yttrium ion garnet is substituted with lithium ferrite.

41. The method of claim 29, further comprising imaging said cell, tissue, or molecule using a method selected from the group consisting of thermography, MRI, ESR, and x-ray.

42. The method of claim 29, wherein said targeting moiety is directly attached to said superparamagnetic nanoparticle.

43. The method of claim 29, wherein said targeting moiety is attached to said superparamagnetic nanoparticle through a linker.

44. The method of claim 29, wherein said superparamagnetic nanoparticle is attached to a single targeting moiety.

45. The method of claim 29, wherein said superparamagnetic nanoparticle is attached to a plurality of targeting moieties.

46. The method of claim 29, wherein a plurality of superparamagnetic nanoparticles are attached to a single targeting moiety.

47. The method of claim 29, wherein said targeting moiety is selected from the group consisting of a protein, an antibody, a lectin, a saccharide, a vitamin, a steroid, a steroid analogue, a hormone, and a nucleic acid.

48. The method of claim 29, wherein said cell or tissue is a cancer cell.

49. The method of claim 48, wherein said targeting moiety is a protein.

50. The method of claim 48, wherein said targeting moiety is an antibody.

51. The method of claim 29, wherein said biological target is a cancer marker.

52. The method of claim 51, wherein said biological target is a cancer marker selected from the group consisting of Caf-1, C-myc, p53, Ki67, Her2, Her4, BRCA1, BRCA2, Lewis Y (Le^Y), CA 15-3, G250, HLA-DR cell surface antigen, CEA, CD20, CD22, integrin, cea, 16, EGFr, AR, PSA, and other growth factor receptors.

53. The method of claim 29, wherein said superparamagnetic nanoparticle has at least one dimension less than about 500 nm.

54. The method of claim 29, wherein said superparamagnetic nanoparticle has no dimension greater than about 500 nm.

55. The method of claim 29, wherein said superparamagnetic nanoparticle has at least one dimension less than about 100 nm.

56. A method of selectively heating a cell, tissue, or organ, said method comprising:

delivering a plurality of superparamagnetic nanoparticles to a location adjacent to or contacting said cell, tissue, or organ; and

heating said superparamagnetic nanoparticles using electron spin resonance.

57. The method of claim 56, wherein said superparamagnetic nanoparticles are delivered directly into said cell, tissue, or organ.

58. The method of claim 57, wherein said superparamagnetic nanoparticles are delivered directly into said cell, tissue, or organ by injection or via a catheter.

59. The method of claim 57, wherein said superparamagnetic nanoparticles are delivered directly into said cell, tissue, or organ during a surgical procedure.

60. The method of claim 56, wherein said superparamagnetic nanoparticles systemically administered to an organism.

61. The method of claim 56, wherein said electron spin resonance is at an RF ranging from about 200 to about 2,000 MHz.

62. The method of claim 56, wherein said electron spin resonance is at an RF ranging from about 500 to about 1,000 MHz.

63. The method of claim 56, wherein said electron spin resonance is spatially localized by a magnetic field gradient over a region smaller than the region over which the superparamagnetic nanoparticles are distributed.

64. The method of claim 56, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q greater than 10.

65. The method of claim 56, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q ranging from about 100 to about 1000.

66. The method of claim 56, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel.

67. The method of claim 66, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel selected from Table 2.

68. The method of claim 66, wherein said superparamagnetic nanoparticle comprises yttrium ion garnet (YIG).

69. The method of claim 68, wherein said yttrium ion garnet is substituted with a material selected from the group consisting of aluminum, gallium, indium, and a ferrite.

70. The method of claim 66, wherein said superparamagnetic nanoparticle comprises gamma-Fe2O3.

71. The method of claim 68, wherein said yttrium ion garnet is substituted with lithium ferrite.

72. The method of claim 56, further comprising imaging said cell, tissue, or molecule using a method selected from the group consisting of thermography, MRI, ESR, and x-ray.

73. The method of claim 56, wherein said cell or tissue is a cancer cell.

74. The method of claim 56, wherein said superparamagnetic nanoparticle has at least one dimension less than about 500 nm.

75. The method of claim 56, wherein said superparamagnetic nanoparticle has no dimension greater than about 500 nm.

76. The method of claim 56, wherein said superparamagnetic nanoparticle has at least one dimension less than about 100 nm.

77. A method of selectively heating or visualizing a cancer cell, said method comprising:

contacting a cancer cell with a chimeric molecule comprising a targeting moiety attached to an epitope tag, wherein said targeting moiety specifically binds to a cancer cell;

contacting said chimeric molecule with a superparamagnetic nanoparticle attached to a binding moiety that specifically binds to said epitope tag thereby associating said superparamagnetic nanoparticle with said cancer cell; and

performing electron spin resonance to heat said superparamagnetic nanoparticle.

78. The method of claim 77, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q greater than 10.

79. The method of claim 77, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q ranging from about 100 to about 1000.

80. The method of claim 77, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel.

81. The method of claim 80, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel selected from Table 2.

82. The method of claim 77, wherein said superparamagnetic nanoparticle comprises yttrium ion garnet (YIG).

83. The method of claim 82, wherein said yttrium ion garnet is substituted with a material selected from the group consisting of aluminum, gallium, indium, and a ferrite.

84. The method of claim 77, wherein said superparamagnetic nanoparticle comprises gamma-Fe2O3.

85. The method of claim 82, wherein said yttrium ion garnet is substituted with lithium ferrite.

86. The method of claim 77, further comprising imaging said cell, tissue, or molecule using a method selected from the group consisting of thermography, MRI, ESR, and x-ray.

87. The method of claim 77, wherein said superparamagnetic nanoparticle attached to binding moiety comprises a chelate binding said superparamagnetic nanoparticle attached to said binding moiety.

88. The method of claim 87, wherein said chelate comprises DOTA.

89. The method of claim 77, wherein said epitope tag is an avidin or a biotin.

90. The method of claim 77, wherein said binding moiety is selected from the group consisting of an avidin, a biotin, and an antibody.

91. The method of claim 77, wherein said targeting moiety is directly attached to said epitope tag.

92. The method of claim 77, wherein said targeting moiety is attached to said epitope tag through a linker.

93. The method of claim 77, wherein said targeting moiety is selected from the group consisting of a protein, an antibody, a lectin, a saccharide, a vitamin, a steroid, a steroid analogue, a hormone, a nucleic acid, and an antibody.

94. The method of claim 93, wherein said targeting moiety is a protein.

95. The method of claim 93, wherein said targeting moiety is an antibody.

96. The method of claim 77, wherein said targeting moiety specifically or preferentially binds a cancer marker selected from the group consisting of Caf-1, C-myc, p53, Ki67, Her2, Her4, BRCA1, BRCA2, Lewis Y (Le^Y), CA 15-3, G250, HLA-DR cell surface antigen, CEA, CD20, CD22, integrin, cea, 16, EGFr, AR, PSA, and other growth factor receptors.

97. The method of claim 77, wherein said superparamagnetic nanoparticle has at least one dimension less than about 500 nm.

98. The method of claim 77, wherein said superparamagnetic nanoparticle has no dimension greater than about 500 nm.

99. The method of claim 77, wherein said superparamagnetic nanoparticle has at least one dimension less than about 100 nm.

100. A kit for selectively heating or imaging a cell or tissue, said kit comprising:

a container containing a superparamagnetic nanoparticle attached to a targeting moiety that specifically binds to a biological target comprising said cell or tissue.

101. The kit of claim 100, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q greater than 10.

102. The kit of claim 100, wherein said superparamagnetic nanoparticle comprises a material that has an electron spin resonance (ESR) Q ranging from about 100 to about 1000.

103. The kit of claim 100, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel.

104. The composition of claim 100, wherein said superparamagnetic nanoparticle comprises a garnet or a spinel selected from Table 2.

105. The kit of claim 100, wherein said a superparamagnetic nanoparticle attached to a targeting moiety is in a pharmaceutically acceptable excipient.

106. The kit of claim 100, wherein said kit further comprises instructional materials teaching the use of said superparamagnetic nanoparticles to selectively heat or image a cell or tissue.

107. A kit for selectively heating or imaging a cell or tissue, said kit comprising:

a container containing a superparamagnetic nanoparticle wherein said nanoparticle is derivatized for coupling to a targeting moiety.

108. The kit of claim 107, further comprising a targeting moiety for attaching to said superparamagnetic nanoparticle.

109. The kit of claim 107, wherein said kit further comprises instructional materials teaching the use of said superparamagnetic nanoparticle to selectively heat or image a cell or tissue.

110. The kit of claim 107, wherein said targeting moiety is a moiety that specifically binds to a cancer cell.