# US 2021/0330823 A1 · Methods for Cell Labeling and Medical Imaging

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- Number: US 2021/0330823 A1
- Document ID: US20210330823A1
- Status: Published application
- Kind: A1
- Application number: 17/358,544
- Filed: 2021-06-25
- Published: 2021-10-28
- Earliest claimed: 2015-03-06
- Assignees: Mayo Foundation for Medical Education and Research
- Applicants: Mayo Foundation for Medical Education and Research
- Inventors: Aditya Bansal; Timothy R. DeGrado; Mukesh K. Pandey
- Web page: https://patentgrep.com/patent/US20210330823A1

## CPC

- A61K 51/0478: {complexes from non-cyclic ligands, e.g. EDTA, MAG3}
- A61K 49/103: {the complex-forming compound being acyclic, e.g. DTPA}
- A61K 49/106: {the complex-forming compound being cyclic, e.g. DOTA}
- A61K 49/1896: {not provided for elsewhere, e.g. cells, viruses, ghosts, red blood cells, virus capsides}
- A61K 51/1203: {in a form not provided for by groups A61K51/1206 - A61K51/1296, e.g. cells, cell fragments, viruses, virus capsides, ghosts, red blood cells, viral vectors}
- 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

Methods of ex vivo labeling of a biological material for in vivo imaging, methods of labeling a biological material in vivo, methods for preparing a labeling agent, and methods for in vivo imaging of a subject using a biological material labeled with a labeling agent are disclosed. In one non-limiting example, the biological material is selected from cells and the labeling agent is a 89Zr-Desferrioxamine-NCS labeling agent.

## Claims

### Claim 1

A method for preparing a labeling agent, the method comprising:
(a) providing a compound including a chelating moiety and a conjugation moiety; and
(b) mixing the compound with a radionuclide to create the labeling agent before reacting the compound with an additional moiety,
wherein the chelating moiety includes a hydroxamic acid group and the conjugation moiety includes an isothiocyanate group.

### Claim 2 (depends on 1)

The method of claim 1, wherein the additional moiety is a lysine residue.

### Claim 3 (depends on 1)

The method of claim 1, wherein the additional moiety is at least one of a liposome, DNA aptamer, RNA aptamer, a virus, nanoparticles, microorganisms, antibodies, proteins, peptides, scaffolds, polymers, and nucleic acids.

### Claim 4 (depends on 1)

The method of claim 1, wherein the chelating moiety is a desferrioxamine group.

### Claim 5 (depends on 1)

The method of claim 1, wherein the conjugation moiety includes a benzyl group.

### Claim 6 (depends on 1)

The method of claim 1, wherein the labeling agent is a 89Zr-isothiocyanato-benzyl-desferrioxamine.

### Claim 7 (depends on 1)

The method of claim 1, wherein the additional moiety is a cell.

### Claim 8 (depends on 1)

The method of claim 1 wherein:
the additional moiety is a cell selected from microorganisms, blood-derived cells, cancer cells, stem cells, and dendritic cells.

### Claim 9 (depends on 1)

The method of claim 1, wherein the additional moiety is a stem cell.

### Claim 10 (depends on 1)

The method of claim 1, wherein the additional moiety is a cell surface protein.

### Claim 11 (depends on 1)

The method of claim 1 wherein the additional moiety is a virus.

### Claim 12 (depends on 1)

The method of claim 1 wherein:
the radionuclide is selected from the group consisting of 11C, 13N, 15O, 18F, 34mCl, 38K, 45Ti, 51Mn, 52Mn, 52mMn, 52Fe, 55Co, 60Cu, 61Cu, 62Cu, 64Cu, 66Ga, 68Ga, 71As, 72As, 74As, 75Br, 76Br, 82Rb, 86Y, 89Zr, 90Nb, 94mTc, 99mTc, 110mIn, 111In, 118Sb, 120I, 121I, 122I, 123I and 124I.

### Claim 13 (depends on 1)

The method of claim 1 wherein:
the radionuclide is a positron emitter.

### Claim 14 (depends on 13)

The method of claim 13 wherein:
the positron emitter is 89Zr.

### Claim 15 (depends on 1)

The method of claim 1 wherein:
the additional moiety is a cell, and
the method further comprises reacting the compound with the cell to create a labeled cell that has stable retention of radioactivity for at least 1 day after reacting the compound with the cell.

### Claim 16 (depends on 15)

The method of claim 15, wherein the labeled cell has stable retention of radioactivity for at least 4 days.

### Claim 17 (depends on 15)

The method of claim 15, wherein the labeled cell has stable retention of radioactivity for at least 7 days.

### Claim 18 (depends on 1)

The method of claim 1 wherein:
the additional moiety is a cell, and
the method further comprises reacting the compound with the cell to create a labeled cell having no loss in cellular viability after 7 days of culture.

### Claim 19 (depends on 1)

The method of claim 1 wherein:
the method further comprises reacting the compound with the additional moiety at a pH range of 7.5-9.

### Claim 20 (depends on 1)

The method of claim 1 wherein:
the method further comprises reacting the compound with the additional moiety in a time period of 10-40 minutes.