# US 12,178,886 B2 · Imaging and treatment of pathophysiologic conditions by Cerenkov radiation

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- Number: US 12,178,886 B2
- Document ID: US12178886B2
- Status: Granted
- Kind: B2
- Application number: 17/449,766
- Filed: 2021-10-01
- Published: 2022-06-30
- Granted: 2024-12-31
- Earliest claimed: 2014-01-31
- Assignees: Washington University
- Applicants: Washington University
- Inventors: Samuel Achilefu; Nalinikanth Kotagiri
- Web page: https://patentgrep.com/patent/US12178886B2

## CPC

- A61K 49/0056: {Peptides, proteins, polyamino acids}
- A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)}
- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61K 49/0013: {Luminescence}
- A61K 49/0021: {the fluorescent group being a small organic molecule}
- A61K 51/0474: {complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group}
- A61K 51/0482: {chelates from cyclic ligands, e.g. DOTA}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present disclosure discloses methods and compositions for administering Cerenkov radiation-induced therapy (CRIT).

## Claims

### Claim 1

A composition, comprising a photoinitiator, one or more photosensitizers and a targeting agent, wherein the photoinitiator is titanocene or titanocene dichloride and the targeting agent is albumin.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the composition further comprises at least one radionuclide.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the radionuclide is selected from the group consisting of 18F, 18F-FDG, 64Cu, 90Y, 124I, and 89Zr.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the radionuclide is 18F-FDG.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the one or more photosensitizers is selected from a pyrrole derived macrocyclic compound, porphyrins, chlorins, bacteriochlorins, isobacteriochlorins, phthalocyanines, naphthalocyanines, porphycenes, porphycyanines, pentaphyrins, sapphyrins, benzochlorins, chlorophylls, azaporphyrins, 5-amino levulinic acid, diporphyrin, dichlorin, phenyl-substituted tetraphenyl porphyrin, indium chloride methyl pyropheophorbide, 3,1-meso tetrakis (o-propionamido phenyl) porphyrin, verdin, purpurin, and etiopurpurin (ET2)), zinc naphthalocyanines, anthracenediones, anthrapyrazoles, aminoanthraquinone, phenoxazine dye, benzoporphyrin derivative, sulfonated aluminum phthalocyanine (Pc), sulfonated aluminum naphthalocyanine, chloroaluminum sulfonated phthalocyanine (CASP)), phenothiazine derivative, pheophorbide alpha, hydroporphyrins, phthalocyanines, hematoporphyrin (HP), protoporphyrin, uroporphyrin III, coproporphyrin III, protoporphyrin IX, 5-amino levulinic acid, pyrromethane boron difluoride, indocyanine green, zinc phthalocyanine, dihematoporphyrin, benzoporphyrin derivatives, carotenoporphyrins, hematoporphyrin and porphyrin derivatives, rose bengal, bacteriochlorin A, epigallocatechin, epicatechin derivatives, hypocrellin B, urocanic acid, indoleacrylic acid, rhodium complexes, etiobenzochlorins, octaethylbenzochlorins, sulfonated Pc-naphthalocyanine, silicon naphthalocyanines, chloroaluminum sulfonated phthalocyanine, phthalocyanine derivatives, iminium salt benzochlorins, Merocyanin 540, Hoechst 33258, psoralens, acridine compounds, suprofen, tiaprofenic acid, methylpheophorbide-a-(hexyl-ether), furocoumarin hydroperoxides, Victoria blue BO, methylene blue, and toluidine blue.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the photosensitizer is an inorganic nanoparticle selected from the group consisting of ZnO nanoparticles, Si nanoparticles, TiO2 nanoparticles, CdSe nanoparticles, CdS nanoparticles, InP nanoparticles, PbS nanoparticles, PbSe nanoparticles, and combinations thereof.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the inorganic nanoparticle is TiO2 nanoparticles.

### Claim 8

A method for treating a cancer or tumor in a subject in need thereof, the method comprising:
a) administering to the subject a composition comprising a photoinitiator and a targeting agent, wherein the photoinitiator is titanocene or titanocene dichloride and the targeting agent is albumin; and
b) administering concurrently or subsequently to the subject a composition comprising an amount of a radionuclide effective to activate the composition in step a), thereby treating the cancer or tumor.

### Claim 9 (depends on 8)

The method of claim 8, wherein the radionuclide is 18F-FDG.

### Claim 10 (depends on 8)

The method of claim 8, wherein the method further comprises administering to the subject one or more therapeutic agent for the cancer.

### Claim 11 (depends on 10)

The method of claim 10, wherein the one or more therapeutic agent is an immune-checkpoint blockade therapeutic.

### Claim 12 (depends on 11)

The method of claim 11, wherein the immune-checkpoint blockade therapeutic is anti-PD-1 and anti-CTLA4.

### Claim 13

A composition, comprising a photoinitiator, at least one radionuclide and a targeting agent, wherein the photoinitiator is titanocene or titanocene dichloride and the targeting agent is albumin.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the radionuclide is selected from the group consisting of 18F, 18F-FDG, 64Cu, 90Y, 124I, and 89Zr.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the radionuclide is 18F-FDG.

### Claim 16 (depends on 13)

The composition of claim 13, wherein the composition further comprises one or more photosensitizers.

### Claim 17 (depends on 16)

The composition of claim 16, wherein the one or more photosensitizers is selected from a pyrrole derived macrocyclic compound, porphyrins, chlorins, bacteriochlorins, isobacteriochlorins, phthalocyanines, naphthalocyanines, porphycenes, porphycyanines, pentaphyrins, sapphyrins, benzochlorins, chlorophylls, azaporphyrins, 5-amino levulinic acid, diporphyrin, dichlorin, phenyl-substituted tetraphenyl porphyrin, indium chloride methyl pyropheophorbide, 3,1-meso tetrakis (o-propionamido phenyl) porphyrin, verdin, purpurin, and etiopurpurin (ET2)), zinc naphthalocyanines, anthracenediones, anthrapyrazoles, aminoanthraquinone, phenoxazine dye, benzoporphyrin derivative, sulfonated aluminum phthalocyanine (Pc), sulfonated aluminum naphthalocyanine, chloroaluminum sulfonated phthalocyanine (CASP)), phenothiazine derivative, pheophorbide alpha, hydroporphyrins, phthalocyanines, hematoporphyrin (HP), protoporphyrin, uroporphyrin III, coproporphyrin III, protoporphyrin IX, 5-amino levulinic acid, pyrromethane boron difluoride, indocyanine green, zinc phthalocyanine, dihematoporphyrin, benzoporphyrin derivatives, carotenoporphyrins, hematoporphyrin and porphyrin derivatives, rose bengal, bacteriochlorin A, epigallocatechin, epicatechin derivatives, hypocrellin B, urocanic acid, indoleacrylic acid, rhodium complexes, etiobenzochlorins, octaethylbenzochlorins, sulfonated Pc-naphthalocyanine, silicon naphthalocyanines, chloroaluminum sulfonated phthalocyanine, phthalocyanine derivatives, iminium salt benzochlorins, Merocyanin 540, Hoechst 33258, psoralens, acridine compounds, suprofen, tiaprofenic acid, methylpheophorbide-a-(hexyl-ether), furocoumarin hydroperoxides, Victoria blue BO, methylene blue, and toluidine blue.

### Claim 18 (depends on 16)

The composition of claim 16, wherein the photosensitizer is an inorganic nanoparticle selected from the group consisting of ZnO nanoparticles, Si nanoparticles, TiO2 nanoparticles, CdSe nanoparticles, CdS nanoparticles, InP nanoparticles, PbS nanoparticles, PbSe nanoparticles, and combinations thereof.

### Claim 19 (depends on 18)

The composition of claim 18, wherein the inorganic nanoparticle is TiO2 nanoparticles.