Systems and methods for RF-induced hyperthermia using biological cells and nanoparticles as RF enhancer carriers

• US 20050251234A1
• Filed: 02/03/2005
• Published: 11/10/2005
• Est. Priority Date: 05/07/2004
• Status: Abandoned Application

• Current Assignee: Akesogenx Corp.
• Original Assignee: Akesogenx Corp.
• Inventors: Keating, Michael J., Steinbrink, William Harry, Kanzius, John, McDonald, Robert J.
• Application Number:
  US11/050,481
• Publication Number:
  US 20050251234A1
• 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 method of 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. Targeted RF absorption enhancers, e.g., tumor infiltrating lymphocytes (TILs) containing RF absorbing particles, are introduced into a patient. These targeted RF absorption enhancers will target certain cells in the target areas and enhance the effect of a hyperthermia generating RF signal directed toward the target area. 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.

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 means for targeted RF absorption enhancement 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 means for targeted RF absorption enhancement;

(c) introducing the means for targeted RF absorption enhancement into the patient;

(d) waiting for at least some of the means for targeted RF absorption enhancement 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 means for targeted RF absorption enhancement bound to target cells; and

(f) transmitting the RF signal via the transmission head, thereby warming the means for targeted RF absorption enhancement bound to target cells.

2. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 wherein the means for targeted RF absorption enhancement comprises targeted RF absorption enhancers.

3. The method of inducing hyperthermia in at least target cells of a patient according to claim 1 further comprising the step of 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 is induced.

4. The method of inducing hyperthermia in at least target cells of a patient according to claim 2 wherein a substantial number of the targeted RF absorption enhancers each comprise an organometallic molecule.

5. The method of inducing hyperthermia in at least target cells of a patient according to claim 2 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.

6. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 wherein the 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.

7. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 wherein the at least one biomolecule comprises at least one protein and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one protein bound to at least one RF absorbing particle, the protein characterized by targeting a target biomolecule of at least one of the target cells.

8. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 wherein the at least one biomolecule comprises at least one virus and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one virus bound to at least one RF absorbing particle, the virus characterized by targeting a target biomolecule of at least one of the target cells.

9. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 wherein the at least one biomolecule comprises RNA and further wherein a substantial number of the targeted RF absorption enhancers each comprise RNA bound to at least one RF absorbing particle, the RNA characterized by targeting a target biomolecule of at least one of the target cells.

10. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 wherein the at least one biomolecule comprises DNA and further wherein a substantial number of the targeted RF absorption enhancers each comprise DNA bound to at least one RF absorbing particle, the DNA characterized by targeting a target biomolecule of at least one of the target cells.

11. The method of inducing hyperthermia in at least target cells of a patient according to claim 5 wherein the at least one RF absorbing particle comprises at least one particle containing an RF absorbing substance and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one biomolecule bound to at least one particle containing an RF absorbing substance 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.

12. The method of inducing hyperthermia in at least target cells of a patient according to claim 2 wherein a substantial number of the targeted RF absorption enhancers each comprise at least one biological cell bound to at least one RF absorbing particle, the at least one targeting cell characterized by targeting one of the target cells.

13. The method of inducing hyperthermia in at least target cells of a patient according to claim 12 wherein the at least one biological cell comprises at least one white blood cell and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one white blood cell bound to at least one RF absorbing particle, the at least one white blood cell characterized by targeting one of the target cells.

14. The method of inducing hyperthermia in at least target cells of a patient according to claim 12 wherein the at least one biological cell comprises at least one T-cell and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one T-cell bound to at least one RF absorbing particle, the at least one T-cell characterized by targeting one of the target cells.

15. The method of inducing hyperthermia in at least target cells of a patient according to claim 12 wherein the at least one biological cell comprises at least one tumor infiltrating lymphocyte (TIL) and further wherein a substantial number of the targeted RF absorption enhancers each comprise at least one TIL bound to at least one RF absorbing particle, the at least one TIL characterized by targeting one of the target cells.

16. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1 or 4-15 wherein the RF signal is a frequency modulated (FM) hyperthermia-inducing RF signal having parameters selected to correspond to the specific RF absorbing particles being used in the targeted RF absorption enhancers.

17. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1 or 4-15 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 the modulation of the FM hyperthermia generating signal corresponds to a size tolerance of the RF absorbing particles being used in the targeted RF absorption enhancers.

18. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1 or 4-15 wherein the RF absorbing particles of the substantial number 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 the range of resonant frequencies associated with the manufacturing tolerance of the RF absorbing particles of the substantial number of the targeted RF absorption enhancers.

19. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of modifying at least some of the target cells with a virus that causes target cells to produce a biomolecule that is targeted by targeted RF absorption enhancers.

20. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing quantum dots into the patient for imaging associated with inducing hyperthermia.

21. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing one radioisotope into the patient for imaging associated with inducing hyperthermia.

22. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing nanoparticles into the patient for imaging associated with inducing hyperthermia.

23. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing 2FDG into the patient for imaging associated with inducing hyperthermia.

24. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing at least one radioisotope into the patient for radioimmunotherapy.

25. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing at least one radioisotope into the patient for radiotherapy.

26. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing radiogallium into the patient for imaging associated with inducing hyperthermia.

27. The method of inducing hyperthermia in at least target cells of a patient according to claim 2 wherein a substantial number of the targeted RF absorption enhancers each comprise organometallic technetium, the organometallic technetium characterized by targeting a target biomolecule of at least one of the target cells.

28. The method of inducing hyperthermia in at least target cells of a patient according to claim 2 wherein a substantial number of the targeted RF absorption enhancers each comprise organometallic radiogallium, the organometallic radiogallium characterized by targeting a target biomolecule of at least one of the target cells.

29. The method of inducing hyperthermia in at least target cells of a patient according to claim 2 wherein a substantial number of the targeted RF absorption enhancers each comprise organometallic technetium bound to at least one RF absorbing particle, the organometallic technetium 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 2 wherein a substantial number of the targeted RF absorption enhancers each comprise organometallic radiogallium bound to at least one RF absorbing particle, the organometallic radiogallium characterized by targeting a target biomolecule of at least one of the target cells.

31. The method of inducing hyperthermia in at least target cells of a patient according to any of claims 1, 4, 5, or 12 further comprising the step of introducing a radioisotope into the patient for PET imaging associated with inducing hyperthermia.

32. The method of inducing hyperthermia in at least target cells of a patient according to claim 2 wherein a substantial number of the targeted RF absorption enhancers each comprise at least one antibody or antibody fragment or other targeting moiety bound to at least one PET radioisotope and at least one RF absorbing particle, the antibody or antibody fragment or other targeting moiety characterized by targeting a target biomolecule of at least one of the target cells.