Methods for radiotherapy to trigger light activation drugs

Patent metadata

Field	Value
Publication number	US-11135294-B2
Application number	US-201615770926-A
Country	US
Kind code	B2
Filing date	Oct 26, 2016
Priority date	Oct 26, 2015
Publication date	Oct 5, 2021
Grant date	Oct 5, 2021

Abstract

A method and system for treating a subject with a disorder which provides within the subject at least one photoactivatable drug for treatment of the subject, applies initiation energy from at least one source to generate inside the subject a preferential x-ray flux for generation of Cherenkov radiation (CR) light capable of activating at least one photoactivatable drug, and from the CR light, activating inside the subject the at least one photoactivatable drug to thereby treat the disorder.

First claim

The invention claimed is:

1. A method for treating a subject with a disorder, comprising:
providing within the subject at least one photoactivatable drug for treatment of the subject;
applying initiation energy from at least one source to generate inside the subject a preferential x-ray flux for generation of Cherenkov radiation (CR) light capable of activating the at least one photoactivatable drug, wherein the initiation energy is applied through a filter preferentially removing lower energy x-rays while transmitting higher energy x-rays; and
from said CR light, activating inside the subject the at least one photoactivatable drug to thereby treat the disorder.

2. The method of claim 1 , wherein applying comprises applying the initiation energy through a low mass filter.

3. The method of claim 2 , wherein applying the initiation energy through a low mass filter comprises applying the initiation energy through a section of carbon-containing material which is between 1 cm and 20 cm thick.

4. The method of claim 2 , wherein applying the initiation energy through a low mass filter comprises applying the initiation energy through a section of carbon-containing material which is between 5 cm and 15 cm thick.

5. The method of claim 2 , wherein applying the initiation energy through a low mass filter comprises applying the initiation energy through a section of carbon-containing material which is between 7 cm and 12 cm thick.

6. The method of claim 2 , wherein applying the initiation energy through a low mass filter comprises applying the initiation energy through a section of carbon-containing material containing at least one of H, F, Si, N, P, and B.

7. The method of claim 2 , wherein applying the initiation energy through a low mass filter comprises applying the initiation energy through a section of carbon-containing material containing in a minority amount at least one of H, F, Si, N, P, and B.

8. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises bonding the photoactivatable drug to a cellular structure.

9. The method of claim 8 , wherein the bonding comprises at least one of 1) bonding the photoactivatable drug to at least one of nuclear DNA, mRNA, rRNA, ribosome, mitochondrial DNA and 2) bonding the photoactivatable drug to lipid bilayers of a virus.

10. The method of claim 8 , wherein the bonding comprises bonding the photoactivatable drug to lipid bilayers of at least one virus selected from the group consisting of an ebola virus, an encephalitis virus, a West Nile virus, and an HIV virus.

11. The method of claim 1 , further comprising activating inside the subject the at least one photoactivatable drug comprises activating a psoralen.

12. The method of claim 1 , further comprising activating inside the subject the at least one photoactivatable drug comprises activating 8 MOP or AMT.

13. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises activating an alkylating agent.

14. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises activating 1,5-iodonophthylazide.

15. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises activating a drug for treating a cell proliferation disorder.

16. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises activating a drug for treating at least one of a virus or a bacterium.

17. The method of claim 1 , further comprising energy modulating the CR light with a fluorophore.

18. The method of claim 17 , further comprising activating a biological response inside the subject.

19. The method of claim 1 , wherein applying initiation energy comprises applying a filtered set of x-rays to the subject having an energy of at least 0.5 MeV and less than 10 MeV.

20. The method of claim 1 , wherein applying initiation energy comprises applying a filtered set of x-rays to the subject having an energy of at least 1.0 MeV and less than 10 MeV.

21. The method of claim 1 , wherein applying initiation energy comprises applying a filtered set of x-rays to the subject having an energy of at least 1.5 MeV and less than 10 MeV.

22. The method of claim 1 , wherein applying initiation energy comprises applying a filtered set of x-rays to the subject having an energy of at least 1.0 MeV and less than 10 MeV.

23. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises activating at least one of photoactivating a drug, sterilizing the target structure, photoactivating a psoralen, photoactivating iodonophthylazide, generating a reactive oxygen species or a combination thereof.

24. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises inducing an autoimmune response, exciting a DNA strand of a cancer cell, redirecting a metabolic pathway, up-regulating genes, down-regulating genes, secreting cytokines, altering cytokine receptor responses, releasing metabolites, generating a vaccine, or a combination thereof.

25. The method of claim 1 , wherein activating inside the subject the at least one photoactivatable drug comprises altering a cellular response or a metabolic rate of the target structure.

26. The method of claim 1 , further comprising administering at least one energy modulation agent which adsorbs, intensifies or modifies said CR light.

27. The method of claim 26 , wherein said energy modulation agent comprises at least one of a biocompatible fluorescing metal nanoparticle, fluorescing metal oxide nanoparticle, fluorescing metal coated metal oxide nanoparticle, fluorescing dye molecule, gold nanoparticle, silver nanoparticle, gold-coated silver nanoparticle, a water soluble quantum dot encapsulated by polyamidoamine dendrimers, a luciferase, a fluorophore, a fluorescent material, a phosphorescent material, a biocompatible phosphorescent molecule, and a lanthanide chelate.

28. The method of claim 26 , wherein said energy modulation agent comprises a down-converting agent.

29. The method of claim 28 , wherein said energy modulation agent comprises inorganic materials selected from the group consisting of: metal oxides; metal sulfides; doped metal oxides; and mixed metal chalcogenides.

30. The method of claim 28 , wherein said energy modulation agent comprises at least one of Y 2 O 3 , Y 2 O 2 S, NaYF 4 , NaYbF 4 , YAG, YAP, Nd 2 O 3 , LaF 3 , LaC 1 3 , La 2 O 3 , TiO 2 , LuPO 4 , YVO 4 , YbF 3 , YF 3 , Na-doped YbF 3 , ZnS; ZnSe; MgS; CaS, CaWO 4 , CaSiO 2 :Pb, and alkali lead silicate including compositions of SiO 2 , B 2 O 3 , Na 2 O, 1 ( 2 0 , PbO, MgO, or Ag, and combinations or alloys or layers thereof.

31. The method of claim 28 , wherein said energy modulation agent comprises at least one of ZnSeS:Cu, Ag, Ce, Tb; CaS: Ce,Sm; La 2 O 2 S:Tb; Y 2 O 2 S:Tb;
Gd 2 O 2 S:Pr, Ce, F; LaPO 4 .

32. The method of claim 28 , wherein said energy modulation agent comprises at least one of ZnS:Ag, ZnS:Cu, Pb, and alloys of the ZnSeS.

33. The method of claim 28 , wherein said energy modulation agent comprises at least one of sodium yttrium fluoride (NaYF 4 ), lanthanum fl

Assignees

• Immunolight Llc
• Univ Duke

Inventors

• Oldham Mark
• Adamson Justus
• Dewhirst Mark W
• Yoon Paul
• Walder Harold
• Bourke Jr Frederic A
• Fathi Zakaryae
• Beyer Jr Wayne F

Classifications

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K33/244

  Lanthanides; Compounds thereof (medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00) · CPC title

• A61K33/02

  Ammonia; Compounds thereof · CPC title

• A61N2005/065

  Light sources therefor · CPC title

• A61N5/062

  Photodynamic therapy, i.e. excitation of an agent · CPC title