# US 11,298,431 B2 · Method for labeling radioisotope radiolabeling compound and kit comprising the same for labeling radioisotope

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- Number: US 11,298,431 B2
- Document ID: US11298431B2
- Status: Granted
- Kind: B2
- Application number: 16/512,517
- Filed: 2019-07-16
- Published: 2020-01-23
- Granted: 2022-04-12
- Earliest claimed: 2018-07-17
- Assignees: Korea Atomic Energy Research Institute
- Applicants: Korea Atomic Energy Research Institute
- Inventors: Sang Hyun Park; Sajid Mushtaq; Dae Seong Choi; Beom Su Jang; Eui-Baek Byun; Jongho Jeon; Dong-Eun Lee
- Web page: https://patentgrep.com/patent/US11298431B2

## CPC

- A61K 51/0453: {having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole}
- A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)}
- A61K 51/025: {inorganic Tc complexes or compounds}
- A61K 51/0446: {having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil}
- A61K 51/0482: {chelates from cyclic ligands, e.g. DOTA}
- A61K 51/081: {the protein being an albumin, e.g. human serum albumin [HSA], bovine serum albumin [BSA], ovalbumin}
- A61K 51/082: {the peptide being a RGD-containing peptide}
- A61K 51/10: Antibodies or immunoglobulins; Fragments thereof {, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody}
- A61K 51/1244: {microparticles or nanoparticles, e.g. polymeric nanoparticles}
- C07B 59/008: {Peptides; Proteins}
- G01N 33/533: with fluorescent label
- G01N 33/534: with radioactive label
- 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)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure relates to a method for labeling a radioisotope, a radiolabeling compound, a kit including the same, and a method for labeling a radioisotope, including: providing a diaminophenyl compound represented by Chemical Formula I below and including a biomolecule, a fluorescent dye or a nanoparticle compound bound thereto; and reacting the diaminophenyl compound and a radioisotope-labeled aldehyde compound represented by Chemical Formula II below at room temperature; and a related technology: in Chemical Formula I, A is CH2 or O; a is 0 or an integer of 1 to 10; X is CH2 or —CONH—; Y is CH2 or and Z is the biomolecule, the fluorescent dye or the nanoparticle compound, in Chemical Formula II, b is 0 or an integer of 1 to 10; and L is CH2 or —CONH—; and Q is M, M′ and M″ in Q are radioisotopes.

## Claims

### Claim 1

A method for labeling a radioisotope, comprising:
providing a diaminophenyl compound represented by Chemical Formula I below and including a biomolecule, a fluorescent dye or a nanoparticle bound thereto; and
reacting the diaminophenyl compound and an aldehyde compound that is labeled with a radioisotope and represented by Chemical Formula II below at room temperature,
in Chemical Formula I,
A is CH2 or O; a is 0 or an integer of 1 to 10; X is CH2 or —CONH—; Y is CH2 or
and Z is the biomolecule, the fluorescent dye or the nanoparticle,
in Chemical Formula II, b is 0 or an integer of 1 to 10; and L is CH2 or —CONH—; and
Q is
each of M, M′ and M″ in Q is a radioisotope.

### Claim 2 (depends on 1)

The method of claim 1, wherein the providing of a diaminophenyl compound includes:
providing a compound represented by Chemical Formula Ia below and including a thiol moiety; and
reacting the compound represented by Chemical Formula Ia below and a compound represented by Chemical Formula Ib below to obtain the compound represented by Chemical Formula I,
Z′—SH Chemical Formula Ia
in Chemical Formula Ia, Z′ is the same as a structure except for a —SH moiety in Z when the biomolecule, fluorescent dye, or nanoparticle represented by Z in Chemical Formula I includes the thiol moiety; and Z′ is the same as Z when the biomolecule, fluorescent dye or nanoparticle represented by Z does not include a thiol moiety,
in Chemical Formula Ib, A, a and X are the same as defined in Chemical Formula I.

### Claim 3 (depends on 2)

The method of claim 2, wherein the reacting of the compound represented by Chemical Formula Ia and the compound represented by Chemical Formula Ib is performed under a Cu+2-based catalyst at room temperature and atmospheric pressure.

### Claim 4 (depends on 2)

The method of claim 2, wherein the providing of a compound represented by Chemical Formula Ia and including a thiol moiety comprises providing a compound represented by Chemical Formula Ia by further substituting the thiol moiety into the biomolecule, the fluorescent dye or the nanoparticle Z′ that does not include a thiol moiety.

### Claim 5 (depends on 1)

The method of claim 1, wherein Z is the biomolecule and is at least one selected from the group consisting of a peptide, an antibody, and an oligonucleotide.

### Claim 6 (depends on 1)

The method of claim 1, wherein Z is the nanoparticle and is at least one selected from the group consisting of a metal nanoparticle, a synthetic polymer nanoparticle, and a biopolymer nanoparticle.

### Claim 7 (depends on 6)

The method of claim 6, wherein Z is the metal nanoparticle and is any one metal selected from the group consisting of gold (Au), platinum (Pt), palladium (Pd), silver (Ag), and copper (Cu); or any one metal oxide nanoparticle selected from the group consisting of cobalt (Co), manganese (Mn), iron (Fe), nickel (Ni), gadolinium (Gd), molybdenum (Mo), zinc (Zn), and chromium (Cr).

### Claim 8 (depends on 1)

The method of claim 1, wherein Z is the fluorescent dye and is at least one selected from the group consisting of a cyanine dye, a fluorescein dye, and a rhodamine dye.

### Claim 9 (depends on 1)

The method of claim 1, wherein the radioisotope is selected from the group consisting of I, F, Tc, Re, Ga, In, Zr, Y, Ho, Sm, and Lu.

### Claim 10 (depends on 9)

The method of claim 9, wherein the radioisotope M is I or F, M′ is Tc or Re, and M″ is an element selected from the group consisting of Ga, In, Y and Zr.

### Claim 11

A kit for labeling a radioisotope comprising:
a diaminophenyl compound represented by Chemical Formula I and including a biomolecule, a fluorescent dye or a nanoparticle compound bound thereto; and
a radioisotope-labeled aldehyde compound represented by Chemical Formula II,
in Chemical Formula I,
A is CH2 or O; a is 0 or an integer of 1 to 10; X is CH2 or —CONH—; Y is CH2 or
and Z is the biomolecule, the fluorescent dye or the nanoparticle compound,
in Chemical Formula II, b is 0 or an integer of 1 to 10; and L is CH2 or —CONH—; and
Q is
each of M, M′ and M″ in Q is a radioisotope.

### Claim 12 (depends on 11)

The kit of claim 11, wherein the biomolecule is at least one selected from the group consisting of a peptide, an antibody, and an oligonucleotide; the nanoparticle compound is at least one selected from the group consisting of a metal nanoparticle compound, a synthetic polymer nanoparticle compound, and a biopolymer nanoparticle compound; the metal nanoparticle compound is any one metal selected from the group consisting of gold (Au), platinum (Pt), palladium (Pd), silver (Ag), and copper (Cu); or any one metal oxide selected from the group consisting of cobalt (Co), manganese (Mn), iron (Fe), nickel (Ni), gadolinium (Gd), molybdenum (Mo), zinc (Zn), and chromium (Cr); and the fluorescent dye is at least one selected from the group consisting of a cyanine dye, a fluorescein dye, and a rhodamine dye.

### Claim 13 (depends on 11)

The kit of claim 11, wherein the radioisotope is selected from the group consisting of I, F, Tc, Re, Ga, In, Zr, Y, Ho, Sm, and Lu.

### Claim 14

A radioisotope-labeled biomolecule, a radioisotope-labeled fluorescent dye or a radioisotope-labeled nanoparticle compound, represented by Chemical Formula IV below:
in Chemical Formula IV,
A is CH2 or O; a is 0 or an integer of 1 to 10; X is CH2 or —CONH—; Z′ is a structure excluding a thiol group in a biomolecule, fluorescent dye or nanoparticle compound including the thiol group or substituted with the thiol group; b is 0 or an integer of 1 to 10; and L is CH2 or —CONH—; and
Q is
each of M, M′ and M″ in Q is a radioisotope.

### Claim 15

A composition for medical diagnosis comprising:
a radioisotope-labeled biomolecule, a radioisotope-labeled fluorescent dye or a radioisotope-labeled nanoparticle compound represented by Chemical Formula IV below, as an active ingredient:
in Chemical Formula IV,
A is CH2 or O; a is 0 or an integer of 1 to 10; X is CH2 or —CONH—; Z′ is a structure excluding a thiol group in a biomolecule, fluorescent dye or nanoparticle compound including the thiol group or substituted with the thiol group; b is 0 or an integer of 1 to 10; and L is CH2 or —CONH—; and
Q is
each of M, M′ and M″ in Q is a radioisotope.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the medical diagnosis is a diagnosis by single photon emission computed tomography (SPECT), positron emission tomography (PET), micro-PET, computed tomography (CT), magnetic resonance imaging (MRI) or target imaging of radiological diagnostic equipment.