Tumor imaging with x-rays and other high energy sources using as contrast agents photon-emitting phosphors having therapeutic properties

Patent metadata

Field	Value
Publication number	US-11865359-B2
Application number	US-201916728803-A
Country	US
Kind code	B2
Filing date	Dec 27, 2019
Priority date	Apr 22, 2014
Publication date	Jan 9, 2024
Grant date	Jan 9, 2024

Abstract

A system and method for imaging or treating a disease in a human or animal body. The system provides to the human or animal body a pharmaceutical carrier including one or more phosphors which are capable of emitting ultraviolet or visible light into the body and which provide x-ray contrast. The system includes one or more devices which infuse a diseased site with a photoactivatable drug and the pharmaceutical carrier, an initiation energy source comprising an x-ray or high energy source which irradiates the diseased site with at least one of x-rays, gamma rays, or electrons to thereby initiate emission of said ultraviolet or visible light into the body, and a processor programmed to at least one of 1) produce images of the diseased site or 2) control a dose of said x-rays, gamma rays, or electrons to the diseased site for production of said ultraviolet or visible light at the diseased site to activate the photoactivatable drug.

First claim

The invention claimed is:

1. A system for imaging and treating a disease in a human or animal body, comprising:
a pharmaceutical carrier including one or more phosphors which are capable of emitting ultraviolet or visible light into the body and which provide x-ray contrast;
one or more devices which infuse a diseased site with a photoactivatable drug and the pharmaceutical carrier;
an initiation energy source comprising an x-ray or high energy source which irradiates the diseased site with at least one of x-rays, gamma rays, or electrons to thereby initiate emission of said ultraviolet or visible light into the body; and
a processor programmed to 1) produce images of the diseased site and 2) control a dose of said x-rays, gamma rays, or electrons to the diseased site for production of said ultraviolet or visible light at the diseased site to activate the photoactivatable drug,
wherein the processor further controls the x-ray, gamma rays, or electrons during a booster treatment repeated on a periodic basis after an initial treatment of the diseased site, wherein, in the booster treatment, at least one of phosphor concentration, photoactivatable drug concentration, and the dose of x-rays, gamma rays, or electrons is increased by a factor of at least two times, five times, or ten times respective initial values, wherein the booster treatment comprises one of (i) an additional administration of the photoactivatable drug to the diseased site followed by radiating the diseased site with the x-rays, gamma rays, or electrons; (ii) an additional administration of the photoactivatable drug and the pharmaceutical carrier including the one or more phosphors to the diseased site followed by radiating the diseased site with the x-rays, gamma rays, or electrons; or (iii) irradiating the diseased site with x-rays, gamma rays, or electrons at a palliative or therapeutic level; wherein the booster treatment activates an immune response that was initially or originally generated within the human or animal body prior to the booster treatment during initial treatments.

2. The system of claim 1 , wherein the initiation energy source comprises an x-ray source configured to generate x-rays from a peak applied cathode voltage at or below 300 kVp, at or below 200 kVp, at or below 120 kVp, at or below 105 kVp, at or below 80 kVp, at or below 70 kVp, at or below 60 kVp, at or below 50 kVp, at or below 40 kVp, at or below 30 kVp, at or below 20 kVp, at or below 10 kVp, or at or below 5 kVp.

3. The system of claim 1 , wherein the phosphors comprise:
a first plurality of energy-converting particles in the medium which, upon radiation from the x-ray source, radiate at a first energy lower than the x-ray source; and
a second plurality of energy-converting particles which, upon radiation from the x-ray source, radiate at a second energy lower than the x-ray source.

4. The system of claim 3 , wherein
a combination of the first and second plurality of energy-converting particles comprises a weighted composition, and
emission from the weighted composition activates the photoactivatable drug.

5. The system of claim 4 , wherein emission overlaps an absorption spectrum of the photoactivatable drug.

6. The system of claim 1 , wherein the phosphors are injected nearby the diseased site for illumination of the photoactivatable drug to treat the diseased site.

7. The system of claim 6 , wherein the phosphors injected nearby the diseased site comprise a mixture of micron-size and nanometer-size particles.

8. The system of claim 1 , further comprising:
a source for an externally applied electric field or a magnetic field distribution which concentrates the phosphors at the diseased site.

9. The system of claim 1 , wherein the initiation energy source comprise an x-ray or high energy electron source utilizing carbon nanotubes as a source of electrons.

10. The system of claim 1 , wherein the processor assembles said images of the diseased site into tomographic views of the diseased site.

11. The system of claim 10 , wherein the processor assembles images of a tumor or a malignancy.

12. The system of claim 1 , wherein the phosphors comprise at least one of:
phosphor particles;
ionic doped phosphor particles;
single crystal or poly-crystalline powders;
single crystal or poly-crystalline monoliths;
scintillator particles;
a metallic shell encapsulating at least a fraction of a surface of the phosphors;
a semiconductor shell encapsulating at least a fraction of a surface of the phosphors; and
an insulator shell encapsulating at least a fraction of a surface of the phosphors; and
phosphors of a distributed particle size.

13. The system of claim 12 , wherein the metallic shell comprises a plasmonic shell configured to enhance at least one of said absorption or said emission.

14. The system of claim 1 , wherein the phosphors comprise particles having a dielectric core.

15. The system of claim 14 , wherein the phosphors comprise a metallic shell at least partially covering said dielectric core and comprises at least one of Au, Ag, Cu, Ni, Pt, Pd, Co, Ru, Rh, or a combination thereof.

16. The system of claim 1 , wherein the phosphors comprise at least one of Y 2 O 3 ; ZnS; ZnSe; MgS; CaS; Mn, Er ZnSe; Mn, Er MgS; Mn, Er CaS; Mn, Er ZnS; Mn,Yb ZnSe; Mn,Yb MgS; Mn, Yb CaS; Mn,Yb ZnS:Tb 3+ , Er 3+ ; ZnS:Tb 3+ ; Y 2 O 3 :Tb 3+ ; Y 2 O 3 :Tb 3+ , Er 3+ ; ZnS:Mn 2+ ; ZnS:Mn,Er 3+ ; CaWO 4 , YaTO 4 , YaTO 4 :Nb, BaSO 4 :Eu, La 2 O 2 S:Tb, BaSi 2 O 5 :Pb, NaI(TI), CsI(TI), CsI(Na), CsI(pure), CsF, KI(TI), Lil(Eu), BaF 2 , CaF, CaF 2 (Eu), ZnS(Ag), CaWO 4 , CdWO 4 , YAG(Ce) (Y 3 Al 5 O 12 (Ce)), BGO bismuth germanate, GSO gadolinium oxyorthosilicate, LSO lutetium oxyorthosilicate, LaCl 3 (Ce), LaBr 3 (Ce), LaPO 4 ; Ce, Tb (doped), and Zn 2 SiO 4 :Mn with Mn doped between 0.05-10%.

17. The system of claim 1 , wherein the phosphors comprise at least one of down conversion or up conversion media, and combinations and agglomerations thereof with or without plasmonic agents.

18. The system of claim 1 , wherein the one or more devices administer the photoactivatable drug in accordance with a volume of the diseased site.

19. The system of claim 18 , wherein
an amount of the phosphors in the pharmaceutical carrier ranges from 0.1 to 0.66 milligrams of phosphor per cm 3 of the volume of the diseased site, and
a concentration of the photoactivatable drug in the pharmaceutical carrier ranges from 10 μg/mL to 50 μg/mL.

20. The system of claim 1 , wherein the photoactivatable drug comprises a psoralen compound mixed with the phosphors.

21. The system of claim 1 , wherein the photoactivatable drug is selected from psoralens, pyrene cholesteryloleate, acridine, porphyrin, fluorescein, rhodamine, 16-diazorcortisone, ethidium, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin organoplatinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and derivatives thereof having planar molecular conformations, porphorinporphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones, and anthroquinones.

22. The system of claim 1 , wherein the photoactivatable drug comprises a psoralen, a coumarin, a porphyrin or a derivative thereof.

23. The system of claim 1 , wherein the photoactivatable drug comprises 8-MOP, TMP, or AMT.

24. The system of claim 1 , wherein the photoacti

Assignees

• Immunolight Llc
• Univ Duke

Inventors

• Walder Harold
• Bourke Jr Frederic A
• Fathi Zakaryae
• Beyer Jr Wayne F
• Dewhirst Mark
• Oldham Mark
• Adamson Justus
• Nolan Michael

Classifications

• A61K39/0011

  Cancer antigens · CPC title

• A61N5/062 Primary

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

• A61K41/0066

  Psoralene-activated UV-A photochemotherapy (PUVA-therapy), e.g. for treatment of psoriasis or eczema, extracorporeal photopheresis with psoralens or fucocoumarins · CPC title

• A61K41/17

  by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays · CPC title

• A61K49/0423

  Nanoparticles, nanobeads, nanospheres, nanocapsules, i.e. having a size or diameter smaller than 1 micrometer · CPC title