Method for labeling radioisotope radiolabeling compound and kit comprising the same for labeling radioisotope

Patent metadata

Field	Value
Publication number	US-2020023085-A1
Application number	US-201916512517-A
Country	US
Kind code	A1
Filing date	Jul 16, 2019
Priority date	Jul 17, 2018
Publication date	Jan 23, 2020
Grant date	—

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 CH 2 or O; a is 0 or an integer of 1 to 10; X is CH 2 or —CONH—; Y is CH 2 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 CH 2 or —CONH—; and
Q is or

M, M′ and M″ in Q are radioisotopes.

First claim

What is claimed is:

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 compound bound thereto; and reacting the diaminophenyl compound and a radioisotope-labeled aldehyde compound represented by Chemical Formula II below at room temperature,

in Chemical Formula I,
A is CH 2 or O; a is 0 or an integer of 1 to 10; X is CH 2 or —CONH—; Y is CH 2 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 CH 2 or —CONH—; and
Q is

M, M′ and M″ in Q are radioisotopes.

2 . 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 compound 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 compound 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.

3 . 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 conditions.

4 . 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 compound Z′ that does not include a thiol moiety.

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

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

7 . The method of claim 1 , wherein the metal nanoparticle 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).

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

9 . 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.

10 . 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.

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 CH 2 or O; a is 0 or an integer of 1 to 10; X is CH 2 or —CONH—; Y is CH 2 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 CH 2 or —CONH—; and
Q is or

M, M′ and M″ in Q are radioisotopes.

12 . The kit of claim 11 , wherein the biomolecule is at least one selected from the group consisting of a peptide, an affibody, an antibody, and an oligonucleotide; the nanoparticle is at least one selected from the group consisting of a metal nanoparticle, a synthetic polymer nanoparticle, and a biopolymer nanoparticle; the metal nanoparticle 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-based dye, a fluorescein-based dye, and a rhodamine-based dye.

13 . 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.

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 CH 2 or O; a is 0 or an integer of 1 to 10; X is CH 2 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 CH 2 or —CONH—; and
Q is

M, M′ and M″ in Q are radioisotopes.

15 . A composition for medical diagnosis comprising:
the radioisotope-labeled biomolecule, the radioisotope-labeled fluorescent dye or the radioisotope-labeled nanoparticle compound represented by Chemical Formula IV of claim 14 , as an active ingredient.

16 . 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.

Assignees

• Korea Atomic Energy Res

Inventors

• Park Sang Hyun
• Mushtaq Sajid
• Choi Dae Seong
• Jang Beom Su
• Byun Eui-Baek
• Jeon Jongho
• Lee Dong-Eun

Classifications

• G01N33/533

  with fluorescent label · CPC title

• A61K51/082

  the peptide being a RGD-containing peptide · CPC title

• C07B59/008

  Peptides; Proteins · CPC title

• G01N33/534

  with radioactive label · CPC title

• A61K51/081

  the protein being an albumin, e.g. human serum albumin [HSA], bovine serum albumin [BSA], ovalbumin · CPC title