Systems and methods for combined RF-induced hyperthermia and radioimmunotherapy

• US 20050273143A1
• Filed: 02/03/2005
• Published: 12/08/2005
• Est. Priority Date: 05/07/2004
• Status: Active Grant

• Current Assignee: NeoTherma Oncology, Inc.
• Original Assignee: Therm Med, LLC
• Inventors: Keating, Michael J., Steinbrink, William Harry, Kanzius, John, McDonald, Robert J.
• Granted Patent: US 7,627,381 B2
• Time in Patent Office: Days
• US Class Current: 607/101
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61N 1/403 for thermotherapy, e.g. hyperthermia
• CPC Class Codes: A61N 1/406 using implantable thermoseeds or injected particles for localized hyperthermia preparations of seeds and particles A61K41/0052
• CPC Class Codes: A61N 5/1001 using radiation sources introduced into or applied onto the body; brachytherapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

A combined radiotherapy and hyperthermia therapy is provided, including inducing hyperthermia in at least a portion of a target area—e.g., a tumor or a portion of a tumor or targeted cancerous cells—is provided. Biomolecules labeled with at least one radionuclide suitable for radiotherapy are provided and introduced into a patient; targeted RF absorption enhancers are provided and introduced into a patient; and a hyperthermia generating RF signal is directed via toward the target cells, thereby warming the radionuclide-labeled biomolecules and targeted RF absorption enhancers bound to target cells. The targeted RF absorption enhancers may, in a manner of speaking, add one or more RF absorption frequencies to cells in the target area, which will permit a hyperthermia generating RF signal at that frequency or frequencies to heat the targeted cells. Biomolecules labeled with at least one radionuclide suitable for radiotherapy may be used for both radiotherapy and as RF absorption enhancers for the hyperthermia generating RF signal.

Claims

1. A method of inducing hyperthermia in at least target cells of a patient, comprising the steps of:

(a) providing 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 the one frequency for transmission via the transmission head;

(b) providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radiotherapy and characterized by targeting a target biomolecule of at least one of the target cells;

(c) introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient;

(d) waiting for at least some of the radiometal-labeled antibodies or antibody fragments or other targeting moieties to bind to some of the target cells;

(e) 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 radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells;

(f) transmitting the RF signal via the transmission head, thereby warming the radiometal-labeled monoclonal antibodies bound to target cells; and

(g) receiving at least a portion of the RF signal that passed through the patient.

2. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient via an intravenous (IV) system.

3. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing monoclonal antibodies labeled with at least one β

-emitting lanthanide and wherein the step of introducing the radiometal-labeled monoclonal antibodies into the patient comprises the step of introducing the monoclonal antibodies labeled with at least one emitting lanthanide into the patient.

4. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radionuclide of copper and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least one radionuclide of copper into the patient.

5. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radionuclide of gold and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least one radionuclide of gold into the patient.

6. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Copper-67 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Copper-67 into the patient.

7. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Copper-64 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Copper-64 into the patient.

8. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Lutetium-177 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Lutetium-177 into the patient.

9. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Yttrium-90 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Yttrium-90 into the patient.

10. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Bismuth-213 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Bismuth-213 into the patient.

11. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Rhenium-186 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Rhenium-186 into the patient.

12. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Rhenium-188 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Rhenium-188 into the patient.

13. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Actinium-225 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Actinium-225 into the patient.

14. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least Gold-127 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least Gold-127 into the patient.

15. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 further comprising the steps of (i) providing targeted RF absorption enhancers characterized by binding to the target cells to thereby increase heating of target cells responsive to the RF signal by interaction between the RF signal and the targeted RF absorption enhancer and (ii) introducing the targeted RF absorption enhancers into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the targeted RF absorption enhancers bound to target cells.

16. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 further comprising the steps of (i) providing a plurality of the same monoclonal antibody or antibody fragment or other targeting moiety labeled with at least one other RF absorbing particle and (ii) introducing the plurality of other RF absorbing particle-labeled monoclonal antibody or antibody fragment or other targeting moiety into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the other RF absorbing particle-labeled monoclonal antibody bound to target cells.

17. The method of inducing hyperthermia in at least target cells of a patient according to claim 3 further comprising the steps of (i) providing targeted RF absorption enhancers characterized by binding to the target cells to thereby increase heating of target cells responsive to the RF signal by interaction between the RF signal and the targeted RF absorption enhancer and (ii) introducing the targeted RF absorption enhancers into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the targeted RF absorption enhancers bound to target cells.

18. The method of inducing hyperthermia in at least target cells of a patient according to claim 3 further comprising the steps of (i) providing a plurality of the same monoclonal antibody or antibody fragment or other targeting moiety labeled with at least one other RF absorbing particle and (ii) introducing the plurality of other RF absorbing particle-labeled monoclonal antibody or antibody fragment or other targeting moiety into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the other RF absorbing particle-labeled monoclonal antibody bound to target cells.

19. The method of inducing hyperthermia in at least target cells of a patient according to claim 4 further comprising the steps of (i) providing targeted RF absorption enhancers characterized by binding to the target cells to thereby increase heating of target cells responsive to the RF signal by interaction between the RF signal and the targeted RF absorption enhancer and (ii) introducing the targeted RF absorption enhancers into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the targeted RF absorption enhancers bound to target cells.

20. The method of inducing hyperthermia in at least target cells of a patient according to claim 4 further comprising the steps of (i) providing a plurality of the same monoclonal antibody or antibody fragment or other targeting moiety labeled with at least one other RF absorbing particle and (ii) introducing the plurality of other RF absorbing particle-labeled monoclonal antibody or antibody fragment or other targeting moiety into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the other RF absorbing particle-labeled monoclonal antibody bound to target cells.

21. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 further comprising the steps of (i) providing targeted RF absorption enhancers characterized by binding to the target cells to thereby increase heating of target cells responsive to the RF signal by interaction between the RF signal and the targeted RF absorption enhancer and (ii) introducing the targeted RF absorption enhancers into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the targeted RF absorption enhancers bound to target cells.

22. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 further comprising the steps of (i) providing a plurality of the same monoclonal antibody or antibody fragment or other targeting moiety labeled with at least one other RF absorbing particle and (ii) introducing the plurality of other RF absorbing particle-labeled monoclonal antibody or antibody fragment or other targeting moiety into the patient, and wherein the step of transmitting the RF signal via the transmission head results in the warming of the radiometal-labeled antibodies or antibody fragments or other targeting moieties bound to target cells and the warming of the other RF absorbing particle-labeled monoclonal antibody bound to target cells.

39. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal comprises the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one alpha emitting Bi-213 and wherein the step of introducing the radiometal-labeled antibodies or antibody fragments or other targeting moieties into the patient comprises the step of introducing the antibodies or antibody fragments or other targeting moieties labeled with at least one emitting lanthanide into the patient.

40. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the antibodies are monoclonal antibodies.

41. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing monoclonal antibodies labeled with at least one α

-emitting lanthanide and wherein the step of introducing the radiometal-labeled monoclonal antibodies into the patient comprises the step of introducing the monoclonal antibodies labeled with at least one α

-emitting lanthanide into the patient.

42. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the step of providing antibodies or antibody fragments or other targeting moieties labeled with at least one radiometal suitable for radioimmunotherapy comprises the step of providing monoclonal antibodies labeled with at least one Auger-emitting lanthanide and wherein the step of introducing the radiometal-labeled monoclonal antibodies into the patient comprises the step of introducing the monoclonal antibodies labeled with at least one Auger-emitting lanthanide into the patient.

23. A method of inducing hyperthermia in at least target cells of a patient, comprising the steps of:

(a) providing 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 the one frequency for transmission via the transmission head;

(b) providing biomolecules labeled with at least one radionuclide and characterized by targeting a target biomolecule of at least one of the target cells;

(c) introducing the radionuclide-labeled biomolecules into the patient;

(d) providing targeted RF absorption enhancers characterized by binding to the target cells to thereby increase heating of target cells responsive to the RF signal by interaction between the RF signal and the targeted RF absorption enhancer;

(e) introducing the targeted RF absorption enhancers into the patient;

(f) waiting for at least some of the radionuclide-labeled biomolecules to bind to some of the target cells;

(g) 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 radionuclide-labeled biomolecules and targeted RF absorption enhancers bound to target cells;

(h) transmitting the RF signal via the transmission head, thereby warming the radionuclide-labeled biomolecules and targeted RF absorption enhancers bound to target cells; and

(i) receiving at least a portion of the RF signal that passed through the patient.

24. The method of inducing hyperthermia in at least target cells of a patient according to claim 23 wherein the steps of introducing the plurality of targeted RF absorption enhancers into the patient and introducing the radionuclide-labeled biomolecules into the patient comprises the step of introducing the plurality of targeted RF absorption enhancers and the radionuclide-labeled biomolecules into the patient via an intravenous (IV) system.

25. The method of inducing hyperthermia in at least target cells of a patient according to claim 23 wherein the radionuclide-labeled biomolecules and targeted RF absorption enhancers are introduced into the patient at the same time.

26. The method of inducing hyperthermia in at least target cells of a patient according to claim 23 wherein the step of providing biomolecules labeled with at least one radionuclide comprises the step of providing biomolecules labeled with at least one β

-emitting lanthanide and wherein the step of introducing the radionuclide-labeled biomolecules into the patient comprises the step of introducing the biomolecules labeled with at least one β

-emitting lanthanide into the patient.

27. The method of inducing hyperthermia in at least target cells of a patient according to claim 23 wherein the step of providing biomolecules labeled with at least one radionuclide comprises the step of providing biomolecules labeled with at least one radionuclide of copper and wherein the step of introducing the radionuclide-labeled biomolecules into the patient comprises the step of introducing the biomolecules labeled with at least one radionuclide of copper into the patient.

28. The method of inducing hyperthermia in at least target cells of a patient according to claim 23 wherein the step of providing biomolecules labeled with at least one radionuclide comprises the step of providing biomolecules labeled with at least one radionuclide of gold and wherein the step of introducing the radionuclide-labeled biomolecules into the patient comprises the step of introducing the biomolecules labeled with at least one radionuclide of gold into the patient.

29. The method of inducing hyperthermia in at least target cells of a patient according to claim 23 wherein a substantial number 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.

30. The method of inducing hyperthermia in at least target cells of a patient according to claim 29 wherein the at least one RF absorbing particle comprises at least one piezoelectric crystal having at least one particle frequency associated therewith, wherein a substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one piezoelectric crystal 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.

31. The method of inducing hyperthermia in at least target cells of a patient according to claim 30 wherein the at least one particle frequency comprises a resonant frequency of the at least one RF absorbing particle.

32. The method of inducing hyperthermia in at least target cells of a patient according to claim 29 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 substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one tuned electronic circuit 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.

33. The method of inducing hyperthermia in at least target cells of a patient according to claim 32 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 substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one TRF circuit 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.

34. The method of inducing hyperthermia in at least target cells of a patient according to claim 33 wherein the at least one TRF circuit comprises at least one rectifier for rectification of a received RF signal.

35. The method of inducing hyperthermia in at least target cells of a patient according to claim 32 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 substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one LC tank circuit 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.

36. The method of inducing hyperthermia in at least target cells of a patient according to claim 32 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 substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one LC tank circuit in circuit communication with at least one rectifier 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.

37. The method of inducing hyperthermia in at least target cells of a patient according to claim 29 wherein the at least one RF absorbing particle comprises at least one metallic particle and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one metallic particle small enough to be bound to and carried with the at least one biomolecule to a target cell via the patient'"'"'s vascular system.

38. The method of inducing hyperthermia in at least target cells of a patient according to claim 29 wherein the at least one RF absorbing particle comprises at least one metallic nanoparticle and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one nanoparticle.