CA2562625A1 - Enhanced systems and methods for rf-induced hyperthermia - Google Patents

Enhanced systems and methods for rf-induced hyperthermia Download PDF

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Publication number
CA2562625A1
CA2562625A1 CA002562625A CA2562625A CA2562625A1 CA 2562625 A1 CA2562625 A1 CA 2562625A1 CA 002562625 A CA002562625 A CA 002562625A CA 2562625 A CA2562625 A CA 2562625A CA 2562625 A1 CA2562625 A1 CA 2562625A1
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Prior art keywords
absorbing
absorption enhancer
signal
particle
absorption
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CA002562625A
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French (fr)
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CA2562625C (en
Inventor
John Kanzius
Michael J. Keating
Robert J. Mcdonald
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THERMMED LLC
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Thermmed Llc
John Kanzius
Michael J. Keating
Robert J. Mcdonald
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Priority claimed from US10/969,477 external-priority patent/US20050251233A1/en
Priority claimed from US11/050,422 external-priority patent/US7510555B2/en
Application filed by Thermmed Llc, John Kanzius, Michael J. Keating, Robert J. Mcdonald filed Critical Thermmed Llc
Publication of CA2562625A1 publication Critical patent/CA2562625A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
    • A61N1/403—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
    • A61N1/403—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia
    • A61N1/406—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia using implantable thermoseeds or injected particles for localized hyperthermia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Published without an Abstract

Claims (150)

1. Use of a radiofrequency (RF) signal for the activation of a targeted RF
absorption enhancer comprising a targeting moiety coupled to at least one RF absorbing particle, wherein the RF absorption enhancer is adapted to be located in the vicinity of a cancer cell.
2. Use of an RF signal for impeding the growth of a cancer cell, wherein the RF signal is adapted for the activation of a targeted RF absorption enhancer comprising a targeting moiety coupled at least one RF absorbing particle.
3. Use of an RF signal for killing a cancer cell, wherein the RF signal is adapted for the activation of a targeted RF absorption enhancer comprising a targeting moiety coupled at least one RF absorbing particle.
4. Use of an RF signal for damaging a cancer cell, wherein the RF signal is adapted for the activation of a targeted RF absorption enhancer comprising a targeting moiety coupled to at least one RF absorbing particle.
5. Use of an RF signal for damaging the membrane of a cancer cell, wherein said RF
signal is adapted for the activation of a targeted RF absorption enhancer comprising a targeting moiety coupled to at least one RF absorbing particle.
6. Use of an RF signal for the activation of a targeted RF absorption enhancer comprising a targeting moiety coupled to one or more RF absorbing particles, wherein the targeting moiety is adapted to be bound to a cancer cell.
7. The use of an RF signal according to any one of claims 1 to6, wherein said at least one RF absorbing particle is at least one RF absorbing nanoparticle.
8. The use of an RF signal according to any one of claims 1 to 6, wherein said at least one RF absorbing particle is at least one RF absorbing microparticle.
9. The use of an RF signal according to any one of claims 1 to 6, wherein said at least one RF absorbing particle is at least one RF absorbing radionuclide.
10. The use of an RF signal according to any one of claims 1 to 6, wherein said at least one RF absorbing particle is at least one RF absorbing particle of a radionuclide.
11. The use of an RF signal according to any one of claims 1 to 6, wherein said at least one RF absorbing particle is at least one RF absorbing nanoparticle of a radionuclide.
12. The use of an RF signal according to any one of claims 1 to 6, wherein said at least one RF absorbing particle is at least one RF microparticle of a radionuclide.
13. The use of an RF signal according to any of claims 1 to 12, wherein said at least one RF absorbing particle is at least one RF absorbing gold.
14. The use of an RF signal according to any of claims 1 to 13, wherein said at least one RF particle comprises an RF absorbing gold.
15. The use of an RF signal according to claim 13 or 14, wherein said RF
absorbing gold is an RF absorbing radionuclide of gold.
16. The use of an RF signal according to any one of claims 1 to 2, wherein said at least one RF absorbing particle is at least one RF absorbing copper.
17. The use of an RF signal according to any one of claims 1 to 112 and 16, wherein said at least RF absorbing particle comprises an RF absorbing copper.
18. The use of an RF signal according to claim 16 or 17, wherein said RF
absorbing copper is an RF absorbing radionuclide of copper.
19. The use of an RF signal according to any one of claims 1 to 112, wherein said at least one RF absorbing particle is at least one RF absorbing metal.
20. The use of an RF signal according to any one of claims 1 to 112 and 19, wherein said at least RF absorbing particle comprises an RF absorbing metal.
21. The use of an RF signal according to any one of claims 1 to 20, wherein said at least one RF absorbing particle is a single RF absorbing particle.
22. The use of an RF signal according to any one of claims 1 to 21, wherein the cancer cell is at least one of an ovarian cancer cell, a lung cancer cell, a small cell lung cancer cell, a breast cancer cell, a colon-rectal cancer cell, a blood cancer cell, a lymphoma cell, a leukemia cell and a multiple myeloma cell.
23. The use of an RF signal according to any one of claims 1 to 22, wherein the RF signal is coupled to the RF absorption enhancer via an RF generator having a high-Q
circuit.
24. The use of an RF signal according to any of one of claims 1 to 23, wherein the RF
signal is coupled to the RF absorption enhancer via a high-Q resonant circuit.
25. The use of an RF signal according to any one of claims 1 to 24, wherein the targeting moiety is an antibody.
26. The use of an RF signal according to any one of claim 1 to 25, wherein the cancer cell has been previously weakened by a procedure.
27. The use of an RF signal according to claim 26, wherein said procedure comprises chemotherapy.
28. The use of an RF signal according to claim 26 or 27, wherein said procedure comprises radiotherapy.
29. The use of an RF signal according to any one of claims 26 to 28, wherein said procedure comprises radioimmunotherapy.
30. The use of an RF signal according to claim 28 or 29, wherein said at least one RF
absorbing particle comprise a radioactive material for the radiotherapy.
31. The use of an RF signal according to any one of claims 1 to 30, wherein said at least one RF absorbing particle comprises at least one of an RF absorbing 2FDG, an RF absorbing copper-67 and an RF absorbing copper-64.
32. The use of an RF signal according to any one of claims 1 to 31, wherein the RF
absorption enhancer comprise a partially depleted radioactive material.
33. Use of an RF absorption enhancer comprising a targeting moiety coupled to at least one RF absorbing particle and an RF signal for the treatment of cancer in a subject, wherein the RF absorption enhancer is adapted to be activated by exposure to the RF
signal.
34. Use of an RF absorption enhancer comprising a targeting moiety coupled to an RF
absorbing particle in the manufacture of a medicament for the treatment of cancer in a subject, wherein the RF absorption enhancer is adapted to be activated by exposure to an RF
signal transmitted by an RF transmitter.
35. The use of an RF absorption enhancer according to claim 33 or 34, wherein said least one RF absorbing particle is at least one RF absorbing nanoparticle.
36. The use of an RF absorption enhancer according to claim 33 or 34, wherein said least one RF absorbing particle is at least one RF absorbing microparticle.
37. The use of an RF absorption enhancer according to claim 33 or 34, wherein said at least one RF absorbing particle is at least one RF absorbing radionuclide.
38. The use of an RF absorption enhancer according to claim 33 or 34, wherein said at least one RF absorbing particle is at least one RF absorbing particle of a radionuclide.
39. The use of an RF absorption enhancer according to claim 33 or 34, wherein said at least one RF absorbing particle is at least one RF absorbing nanoparticle of a radionuclide.
40. The use of an RF absorption enhancer according to claim 33 or 34, wherein said at least one RF absorbing particle is at least one RF absorbing microparticle of a radionuclide.
41. The use of an RF absorption enhancer according to any one of claims 33 to 40, wherein said at least one RF absorbing particle is at least one RF absorbing gold.
42. The use of an RF absorption enhancer according to any one of claims 33 to 41, wherein said at least one RF absorbing particle comprises an RF absorbing gold.
43. The use of an RF absorption enhancer according to claim 41 or 42, wherein said RF
absorbing gold is an RF absorbing radionuclide of gold.
44. The use of an RF absorption enhancer according to any one of claims 33 to 40, wherein at least one RF absorbing particle is at least one RF absorbing copper.
45. The use of an RF absorption enhancer according to any one of claims 33 to 40 and 44, wherein said at least one RF absorbing particle comprises an RF absorbing copper.
46. The use of an RF absorption enhancer according to claim 44 or 45, wherein said RF
absorbing copper is an RF absorbing radionuclide of copper.
47. The use of an RF absorption enhancer according to any one of claims 33 to 40, wherein said at least one RF absorbing particle is at least one RF absorbing metal.
48. The use of an RF absorption enhancer according to any one of claims 33 to 40 and 47, wherein said at least one RF absorbing particle is at least one RF absorbing metal.
49. The use of an RF absorption enhancer according to any one of claims 33 to 40, wherein said at least one RF absorbing particle is a single RF absorbing particle.
50. The use of an RF absorption enhancer according to any one of claims 33 to 49, wherein the cancer is at least one of ovarian cancer, lung cancer, small cell lung cancer, breast cancer, colon-rectal cancer, blood cancer, lymphoma, leukemia and multiple myeloma.
51. The use of an RF absorption enhancer according to any one of claims 33 to 50, wherein the RF signal is coupled to the RF absorption enhancer via an RF
generator having a high-Q circuit.
52. The use of an RF absorption enhancer according to any one of claims 33 to 51, wherein the RF signal is coupled to the RF absorption enhancer via a high-Q
resonant circuit.
53. The use of an RF absorption enhancer according to any one of claims 33 to 52, wherein the targeting moiety is an antibody.
54. The use of an RF absorption enhancer according to any one of claim 33 to 53, wherein the cancer has been previously weakened by a procedure.
55. The use of an RF absorption enhancer according to claim 54, wherein said procedure comprises chemotherapy.
56. The use of an RF absorption enhancer according to claim 54 or 55, wherein said procedure comprises radiotherapy.
57. The use of an RF absorption enhancer to any one of claims 54 to 56, wherein said procedure comprises radioimmunotherapy.
58. The use of an RF absorption enhancer according to claim 56 or 57, wherein said at least one RF absorbing particle comprise a radioactive material for the radiotherapy.
59. The use of an RF absorption enhancer according to any one of claims 33 to 58, wherein said at least one RF absorbing particle comprises at least one of an RF absorbing 2FDG, an RF absorbing copper-67 and an RF absorbing copper-64.
60. The use of an RF absorption enhancer according to of any one of claims 33 to 59, wherein the RF absorption enhancer comprise a partially depleted radioactive material.
61. Use of an RF absorption enhancer comprising a metal sulfate for the treatment of cancer, wherein the RF absorption enhancer is adapted to be activated by exposure to an RF
signal.
62. Use of an RF absorption enhancer comprising a metal sulfate for the manufacture of a medicament for the treatment of cancer, wherein the RF absorption enhancer is adapted to be activated by exposure to an RF signal.
63. The use of an RF absorption enhancer according to claim 61 or 62, wherein the metal sulfate of the RF absorption enhancer comprises at least one of copper sulfate, iron sulfate and magnesium sulfate.
64. Use of an RF absorption enhancer comprising an injectable metal salt for the treatment of cancer, wherein the RF absorption enhancer is adapted to be activated by exposure to an RF signal.
65. Use of an RF absorption enhancer comprising an injectable metal salt for the manufacture of a medicament for the treatment of cancer, wherein the RF
absorption enhancer is adapted to be activated by exposure to an RF signal.
66. The use of an RF absorption enhancer according to claim 64 or 65, wherein the injectable metal salt of the RF absorption enhancer comprises a gold salt.
67. A system for inducing hyperthermia in at least target cells of a patient, comprising:

(a) a Radio Frequency (RF) transmitter having an RF generator in circuit communication with a transmission head, the RF generator capable of generating a hyperthermia-inducing RF signal having at least one frequency for transmission via the transmission head;

(b) targeted RF absorption enhancers adapted for binding to the target cells to thereby increase heating of the target cells responsive to the RF signal by interaction between the RF signal and the targeted RF absorption enhancers;

(c) a means for introducing the targeted RF absorption enhancers into the patient;
(d) a means for arranging the transmission head proximate to at least one body part of the patient containing the target cells in such a manner that the RF
signal transmitted via the transmission head passes through and warms at least the targeted RF absorption enhancers bound to the target cells;

(e) a means for transmitting the RF signal via the transmission head, thereby warming the targeted RF absorption enhancers bound to the target cells; and (f) a means for receiving at least a portion of the RF signal that passes through the patient.
68. The system according to claim 67, wherein some of the targeted RF
absorption enhancers are adapted to bind to one of a cell membrane of the target cells and a molecular structure within the target cells.
69. The system according to claim 67, wherein some of the targeted RF
absorption enhancers are adapted to be ingested by the target cells.
70. The system according to claim 67, wherein the means for receiving at least a portion of the RF signal that passes through the patient comprises an RF receiver having a resonant circuit in circuit communication with a reception head.
71. The system according to claim 67, further comprising a means for selecting the targeted RF absorption enhancers from a plurality of different types of targeted RF absorption enhancers based on at least one characteristic of the target cells in which hyperthermia can be induced.
72. The system according to claim 67, wherein a plurality of the targeted RF
absorption enhancers each comprise at least one biomolecule bound to at least one RF
absorbing particle, the biomolecule characterized by targeting a target biomolecule of at least one of the target cells.
73. The system according to claim 72, wherein the at least one biomolecule comprises at least one antibody, antibody fragment and targeting moiety and further wherein a plurality of the targeted RF absorption enhancers each comprise at least one antibody, antibody fragment and targeting moiety bound to at least one RF absorbing particle, the at least one antibody, antibody fragment and targeting moiety being characterized by targeting a target biomolecule of at least one of the target cells.
74. The system according to claim 72, wherein the at least one RF absorbing particle comprises at least one piezoelectric crystal having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one biomolecule bound to said at least one piezoelectric crystal and small enough to be bound to and carried with the at least one biomolecule to a target cell via a vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF
transmitter has at least one frequency corresponding to the at least one particle frequency.
75. The system according to claim 74, wherein the at least one particle frequency comprises a resonant frequency of the at least one RF absorbing particle.
76. The system according to claim 72, wherein the at least one RF absorbing particle comprises at least one tuned electronic circuit having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one biomolecule bound to the at least one tuned electronic circuit and small enough to be bound to and carried with the at least one biomolecule to a target cell via a vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF transmitter has at least one frequency corresponding to the at least one particle frequency.
77. The system according to claim 76, wherein the at least one tuned electronic circuit comprises at least one tuned RF (TRF) circuit having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one biomolecule bound to the at least one TRF circuit and small enough to be bound to and carried with the at least one biomolecule to a target cell via the patient's vascular system, and further wherein the hyperthermia-inducing RF signal transmitted by the RF transmitter has at least one frequency corresponding to the at least one particle frequency.
78. The system according to claim 77, wherein the at least one TRF circuit comprises at least one rectifier for rectification of a received RF signal.
79. The system according to claim 77, wherein the at least one tuned electronic circuit comprises at least one LC tank circuit having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one biomolecule bound to the at least one LC tank circuit and small enough to be bound to and carried with the at least one biomolecule to a target cell via a vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF
transmitter has at least one frequency corresponding to the at least one particle frequency.
80. The system according to claim 77, wherein the at least one tuned electronic circuit comprises at least one LC tank circuit in circuit communication with at least one rectifier for rectification of a received RF signal and having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one biomolecule bound to the at least one LC tank circuit in circuit communication with the at least one rectifier and small enough to be bound to and carried with the at least one biomolecule to a target cell via a vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF transmitter has at least one frequency corresponding to the at least one particle frequency.
81. The system according to claim 72, wherein the at least one RF absorbing particle comprises at least one metallic particle and further wherein a plurality of the targeted RF
absorption enhancers each comprise at least one biomolecule bound to the at least one metallic particle and small enough to be bound to and carried with the at least one biomolecule to the target cells via a vascular system of the patient.
82. The system according to claim 72, wherein the at least one RF absorbing particle comprises at least one gold particle and further wherein a plurality of the targeted RF
absorption enhancers each comprise at least one biomolecule bound to the at least one gold particle and small enough to be bound to and carried with the at least one biomolecule to the target cells via a vascular system of the patient.
83. The system according to claim 72, wherein the at least one RF absorbing particle comprises at least one metallic nanoparticle and further wherein a plurality of the targeted RF

absorption enhancers each comprise at least one biomolecule bound to the at least one nanoparticle.
84. The system according to claim 72, wherein the at least one RF absorbing particle comprises at least one gold nanoparticle and further wherein a plurality of the targeted RF
absorption enhancers each comprise at least one biomolecule bound to the at least one gold nanoparticle.
85. 85. The system according to claim 72, wherein the at least one biomolecule comprises at least one antibody, antibody fragment and targeting moiety, wherein the at least one RF absorbing particle comprises at least one piezoelectric crystal having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one of an antibody, antibody fragment, and other targeting moiety bound to the at least one piezoelectric crystal and small enough to be bound to and carried with the at least one of an antibody, antibody fragment, and other targeting moiety to the target cells via a vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF transmitter has at least one frequency corresponding to the at least one particle frequency.
86. 86. The system according to claim 72, wherein the at least one biomolecule comprises at least one antibody, antibody fragment and targeting moiety, wherein the at least one RF absorbing particle comprises at least one tuned electronic circuit having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one antibody, antibody fragment and targeting moiety bound to the at least one tuned electronic circuit and small enough to be bound to and carried with the at least one of an antibody, antibody fragment, and targeting moiety to the target cells via a vascular system of the patient, and further wherein the hyperthermia-inducing RF
signal transmitted by the RF transmitter has at least one frequency corresponding to the at least one particle frequency.
87. 87. The system according to claim 86, wherein the at least one tuned electronic circuit comprises at least one tuned RF (TRF) circuit having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one antibody, antibody fragment and targeting moiety bound to the at least one TRF circuit and small enough to be bound to and carried with the at least one antibody, antibody fragment and targeting moiety to the target cells via the the vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF
transmitter has at least one frequency corresponding to the at least one particle frequency.
88. The system according to claim 87, wherein the at least one TRF circuit comprises at least one rectifier for rectification of a received RF signal.
89. The system according to claim 86, wherein the at least one tuned electronic circuit comprises at least one LC tank circuit having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one of an antibody, antibody fragment, and other targeting moiety bound to the at least one LC tank circuit and small enough to be bound to and carried with the at least one antibody, antibody fragment, and other targeting moiety to the target cells via the vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF
transmitter has at least one frequency corresponding to the at least one particle frequency.
90. The system according to claim 86, wherein the at least one tuned electronic circuit comprises at least one LC tank circuit in circuit communication with at least one rectifier for rectification of a received RF signal and having at least one particle frequency associated therewith, wherein a plurality of the targeted RF absorption enhancers each comprise at least one of an antibody, antibody fragment, and other targeting moiety bound to the at least one LC tank circuit in circuit communication with the at least one rectifier and small enough to be bound to and carried with the at least one of an antibody, antibody fragment, and other targeting moiety to the target cells via the vascular system of the patient, and further wherein the hyperthermia-inducing RF signal transmitted by the RF transmitter has at least one frequency corresponding to the at least one particle frequency.
91. The system according to claim 72, wherein the at least one biomolecule comprises at least one antibody, antibody fragment and targeting moiety, wherein the at least one RF
absorbing particle comprises at least one metallic particle and further wherein a plurality of the targeted RF absorption enhancers each comprise at least one antibody, antibody fragment and targeting moiety bound to the at least one metallic particle and small enough to be bound to and carried with the at least one antibody, antibody fragment, and targeting moiety to the target cells via a vascular system of the patient.
92. The system according to claim 72, wherein the at least one biomolecule comprises at least one antibody, antibody fragment and targeting moiety, wherein the at least one RF
absorbing particle comprises at least one gold particle and further wherein a plurality of the targeted RF absorption enhancers each comprise at least one of an antibody, antibody fragment, and other targeting moiety bound to the at least one gold particle and small enough to be bound to and carried with the at least one antibody or antibody fragment or other targeting moiety to the target cells via a vascular system of the patient.
93. The system according to claim 72, wherein the at least one biomolecule comprises at least one antibody, antibody fragment and targeting moiety, wherein the at least one RF
absorbing particle comprises at least one metallic nanoparticle and further wherein a plurality of the targeted RF absorption enhancers each comprise at least one of an antibody, antibody fragment, and other targeting moiety bound to the at least one metallic nanoparticle.
94. The system according to claim 72, wherein the at least one biomolecule comprises at least one antibody, antibody fragment and targeting moiety, wherein the at least one RF
absorbing particle comprises at least one gold nanoparticle and further wherein a plurality of the targeted RF absorption enhancers each comprise at least one antibody, antibody fragment and targeting moiety bound to the at least one gold nanoparticle.
95. The system according to any one of claims 67, 71, 72, 73, 75, 80, 82, 84, 85, 90 and 92 wherein the RF signal is a frequency modulated (FM) hyperthermia-inducing RF signal having parameters selected to correspond to specific RF absorbing particles being used in the targeted RF absorption enhancers.
96. The system according to any one of claims 67, 71, 72, 73, 75, 80, 82, 84, 85, 90, and 92, wherein the RF signal is a frequency modulated (FM) hyperthermia-inducing RF signal having a center frequency corresponding to a resonant frequency of a nominal RF absorbing particle being used in the targeted RF absorption enhancers and a modulation of an FM
hyperthermia generating signal corresponds to a range of a parameter of the RF
absorbing particles being used in the targeted RF absorption enhancers.
97. The system according to any one of claims 80 to 83 and claims 90 to 93 wherein the RF signal is a frequency modulated (FM) hyperthermia-inducing RF signal having a center frequency corresponding to a resonant frequency of nominally sized RF
absorbing particles being used in the targeted RF absorption enhancers and a modulation of an FM
hyperthermia generating signal corresponds to a size tolerance of the RF absorbing particles being used in the targeted RF absorption enhancers.
98. The system according to any one of claims 67, 71, 72, 73, 75, 80, 82, 84, 85, 90, and 92, wherein the RF absorbing particles of the plurality of the targeted RF
absorption enhancers have an associated manufacturing tolerance resulting in an associated range of resonant frequencies and further wherein the RF signal comprises a plurality of frequencies corresponding to a range of resonant frequencies associated with a manufacturing tolerance of the RF absorbing particles of the plurality of the targeted RF absorption enhancers.
99. The system according to any one of claims 67 to 98, wherein the RF signal is coupled to the RF absorption enhancer via a high-Q circuit.
100. The system according to any one of claims 67 to 98, wherein the RF signal is coupled to the RF absorption enhancer via a high-Q resonant circuit.
101. The system according to any one of claims 81, 91 and 97, wherein the RF
absorption enhancer comprises a targeting moiety coupled to a least one RF absorbing microparticle.
102. The system according to any one of claims 81, 91 and 97, wherein the RF
absorption enhancer comprises a targeting moiety coupled to at least one RF absorbing particle of a radionuclide.
103. The system according to any one of claims 81, 91 and 97, wherein the RF
absorption enhancer comprises a targeting moiety coupled to at least one RF absorbing microparticle of a radionuclide.
104. The system according to any one of claims 81, 91 and 97, wherein the RF
absorption enhancer comprises a targeting moiety coupled to at least one RF absorbing nanoparticle of a radionuclide.
105. The system according to any one of claims 67, 95, 96 and 98 wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to RF absorbing gold.
106. The system according to any one of claims 67, 95, 96 and 98, wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to RF absorbing copper.
107. The system according to any one of claims 67, 95, 96 and 98 wherein at least one particle of the targeted RF absorption enhancer comprises RF absorbing copper.
108. The system according to any one of claims 67, 95, 96 and 98, wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to RF absorbing metal.
109. The system according to any one of claims 67, 95, 96 and 98, wherein the RF
absorption enhancer comprises a targeting moiety coupled to RF absorbing radionuclide.
110. The system according to any one of claims 67, 95, 96 and 98, wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to RF absorbing 2FDG.
111. The system according to any one of claims 67, 95, 96 and 98, wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to RF absorbing copper-67.
112. The system according to any one of claims 67, 95, 96 and 98, wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to RF absorbing copper-64.
113. The system according to any one of claims 67, 95, 96 and 98, wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to an RF absorbing radionuclide of copper.
114. The system according to any one of claims 67, 95, 96 and 98, wherein the targeted RF
absorption enhancer comprises a targeting moiety coupled to an RF absorbing radionuclide of gold.
115. The system according to any one of claims 67, 95, 96 and 98, wherein the RF
absorption enhancer comprises a partially depleted radioactive material.
116. A system for inducing hyperthermia in at least target cells of a patient, comprising :
(a) an RF transmitter having an RF generator in circuit communication with a transmission head, the RF generator capable of generating a hyperthermia-inducing RF signal having at least one frequency for transmission via the transmission head;

(b) RF absorption enhancers to thereby increase heating of the target cells responsive to the RF signal by interaction between the RF signal and the RF
absorption enhancers, wherein the RF absorption enhancers have an associated manufacturing tolerance resulting in an associated range of corresponding frequencies and further wherein the RF signal comprises a plurality of frequencies corresponding to a range of resonant frequencies associated with the manufacturing tolerance of the RF absorption enhancers;

(c) a means for introducing the RF absorption enhancers into the patient;

(d) a means for arranging the transmission head proximate to at least one body part of the patient containing the target cells in such a manner that the RF
signal transmitted via the transmission head passes through and warms at least the RF
absorption enhancers; and (e) a means for transmitting the RF signal via the transmission head, thereby warming the RF absorption enhancers.
117. The system according to claim 116, wherein the RF signal is a frequency modulated (FM) hyperthermia-inducing RF signal having parameters selected to correspond to the RF
absorption enhancers.
118. The system according to claim 116, wherein the RF signal is a frequency modulated (FM) hyperthermia-inducing RF signal having a center frequency corresponding to a resonant frequency of nominal RF absorption enhancers and a modulation of an FM
hyperthermia generating signal corresponds to a tolerance of the RF absorption enhancers.
119. The system according to claim 116, wherein the range of corresponding frequencies comprises a range of resonant frequencies.
120. An RF absorption enhancer comprising a targeting moiety coupled to an RF
absorbing particle for the treatment of cancer in a subject, wherein the RF absorption enhancer is adapted to be activated by exposure to an RF signal transmitted by an RF
transmitter.
121. The RF absorption enhancer according to claim 120, wherein said RF
absorbing particle is at least one RF absorbing nanoparticle.
122. The RF absorption enhancer according to claim 120, wherein said RF
absorbing particle is at least one RF absorbing microparticle.
123. The RF absorption enhancer according to claim 120, wherein said RF
absorbing particle is at least one RF absorbing radionuclide.
124. The RF absorption enhancer according to claim 120, wherein said RF
absorbing particle is at least one RF absorbing particle of a radionuclide.
125. The RF absorption enhancer according to claim 120, wherein said RF
absorbing particle is at least one RF absorbing nanoparticle of a radionuclide.
126. The RF absorption enhancer according to claim 120, wherein said RF
absorbing particle is at least one RF absorbing microparticle of a radionuclide.
127. The RF absorption enhancer according to any one of claims 120 to 126, wherein said RF absorbing particle is at least one RF absorbing gold.
128. The RF absorption enhancer according to any one of claims 120 to 127, wherein said RF absorbing particle comprises an RF absorbing gold.
129. The RF absorption enhancer according to claim 127 or 128, wherein said RF
absorbing gold is an RF absorbing radionuclide of gold.
130. The RF absorption enhancer according to any one of claims 120 to 126, wherein at least one RF absorbing particle is at least one RF absorbing copper.
131. The RF absorption enhancer according to any one of claims 120 to 126 and 130, wherein said at least one RF absorbing particle comprises an RF absorbing copper.
132. The RF absorption enhancer according to claim 130 or 131, wherein said RF
absorbing copper is an RF absorbing radionuclide of copper.
133. The RF absorption enhancer according to any one of claims 120 to 126, wherein said RF absorbing particle is at least one RF absorbing metal.
134. The RF absorption enhancer according to any one of claims 120 to 126 and 133, wherein said RF absorbing particle is at least one RF absorbing metal.
135. The RF absorption enhancer according to any one of claims 120 to 126, wherein said RF absorbing particle is a single RF absorbing particle.
136. The RF absorption enhancer according to any one of claims 120 to 135, wherein the cancer is at least one of ovarian cancer, lung cancer, small cell lung cancer, breast cancer, colon-rectal cancer, blood cancer, lymphoma, leukemia and multiple myeloma.
137. The RF absorption enhancer according to any one of claims 120 to 136, wherein the RF signal is coupled to the RF absorption enhancer via an RF generator having a high-Q
circuit.
138. The RF absorption enhancer according to any one of claims 120 to 137, wherein the RF signal is coupled to the RF absorption enhancer via a high-Q resonant circuit.
139. The RF absorption enhancer according to any one of claims 120 to 138, wherein the targeting moiety is an antibody.
140. The RF absorption enhancer according to any one of claims 120 to 139, wherein the cancer has been previously weakened by a procedure.
141. The RF absorption enhancer according to claim 140, wherein said procedure comprises chemotherapy.
142. The RF absorption enhancer according to claim 140 or 141, wherein said procedure comprises radiotherapy.
143. The RF absorption enhancer to any one of claims 140 to 142, wherein said procedure comprises radioimmunotherapy.
144. The RF absorption enhancer according to claim 142 or 143, wherein said at least one RF absorbing particle comprise a radioactive material for the radiotherapy.
145. The RF absorption enhancer according to any one of claims 120 to 144, wherein said at least one RF absorbing particle comprises at least one of an RF absorbing 2FDG, an RF
absorbing copper-67 and an RF absorbing copper-64.
146. The RF absorption enhancer according to of any one of claims 120 to 145, wherein the RF absorption enhancer comprise a partially depleted radioactive material.
147. An RF absorption enhancer comprising a metal sulfate for the treatment of cancer, wherein the RF absorption enhancer is adapted to be activated by exposure to an RF signal.
148. The RF absorption enhancer according to claim 147, wherein the metal sulfate of the RF absorption enhancer comprises at least one of copper sulfate, iron sulfate and magnesium sulfate.
149. An RF absorption enhancer comprising an injectable metal salt for the treatment of cancer, wherein the RF absorption enhancer is adapted to be activated by exposure to an RF
signal.
150. The RF absorption enhancer according to claim 149, wherein the injectable metal salt of the RF absorption enhancer comprises a gold salt.
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US11/050,422 2005-02-03
US11/050,478 US7627381B2 (en) 2004-05-07 2005-02-03 Systems and methods for combined RF-induced hyperthermia and radioimmunotherapy
US11/050,478 2005-02-03
US11/050,481 2005-02-03
US11/050,422 US7510555B2 (en) 2004-05-07 2005-02-03 Enhanced systems and methods for RF-induced hyperthermia
US11/050,481 US20050251234A1 (en) 2004-05-07 2005-02-03 Systems and methods for RF-induced hyperthermia using biological cells and nanoparticles as RF enhancer carriers
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US20050273143A1 (en) 2005-12-08
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CA2562625C (en) 2010-01-19
WO2005110261A2 (en) 2005-11-24
EP1758648A1 (en) 2007-03-07
US7627381B2 (en) 2009-12-01
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WO2005120639A2 (en) 2005-12-22

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