Method for producing radiolabeled aryl compound by electrolytic oxidation reaction

Patent metadata

Field	Value
Publication number	US-2025188625-A1
Application number	US-202318844320-A
Country	US
Kind code	A1
Filing date	Mar 6, 2023
Priority date	Mar 8, 2022
Publication date	Jun 12, 2025
Grant date	—

Abstract

Provided is a novel method for labeling a radionuclide such as 211At with a high radiochemical yield under more convenient and stable conditions.A production method of an aryl compound labeled with a radionuclide includes a step of applying a voltage to a solution A containing a radionuclide and electrolytically oxidizing the radionuclide; and a step of mixing the solution A and a solution B containing a compound S having a halogenated aryl group to substitute a halogen atom on the aryl group of the compound S with the radionuclide.

First claim

1 . A production method of an aryl compound labeled with a radionuclide, the method comprising:
a step of applying a voltage to a solution A containing a radionuclide and electrolytically oxidizing the radionuclide; and a step of mixing the solution A and a solution B containing a compound S having a halogenated aryl group to substitute a halogen atom on the aryl group of the compound S with the radionuclide.

2 . The production method according to claim 1 , wherein each of the steps is performed while allowing the solution A and/or the solution B to flow in a flow path at an arbitrary flow rate.

3 . The production method according to claim 1 , wherein each of the steps is performed without allowing the solution A and/or the solution B to flow.

4 . The production method according to claim 2 or 3 , wherein the application of the voltage is performed in an electrolytic bath installed in a flow path.

5 . The production method according to any one of claims 1 to 4 , wherein a radiochemical purity of the aryl compound labeled with the radionuclide is 80.9% or more.

6 . The production method according to any one of claims 1 to 4 , wherein a radiochemical yield of the aryl compound labeled with the radionuclide is 56.3% or more.

7 . The production method according to any one of claims 1 to 4 , wherein a radiochemical purity and a radiochemical yield of the aryl compound labeled with the radionuclide are 71.5% or more and 55.9% or more, respectively.

8 . The production method according to any one of claims 1 to 7 , wherein the voltage is 800 mV or more (vs Ag/AgCl).

9 . The production method according to any one of claims 1 to 7 , wherein the voltage is 800 to 1,200 mV (vs Ag/AgCl).

10 . The production method according to any one of claims 1 to 7 , wherein the voltage is 800 to 1,000 mV (vs Ag/AgCl).

11 . The production method according to any one of claims 1 to 10 , wherein the solution A contains at least one anion selected from the group consisting of an iodide ion, a bromide ion, a chloride ion, and a fluoride ion.

12 . The production method according to claim 11 , wherein a concentration of the anion is in a range of 0.01 M to 0.3 M.

13 . The production method according to any one of claims 1 to 12 , wherein the radionuclide is selected from the group consisting of 211 At, 210 At, 123 I, 124 I, 125 I, 131 I, 76 Br, and 18 F.

14 . The production method according to any one of claims 1 to 13 , wherein the radionuclide is 211 At, and the halogen is an iodine atom.

15 . The production method according to any one of claims 1 to 14 , wherein the aryl group in the compound S is a C 6-14 aryl group optionally having a substituent.

16 . The production method according to any one of claims 1 to 15 , wherein the compound S is an amino acid derivative, a peptide, or a protein.

17 . The production method according to any one of claims 1 to 16 , wherein the compound S is a compound represented by the following Formula (I) or a salt thereof:

(wherein, X is a halogen atom; Y is a hydrogen atom or 1 to 4 arbitrary substituents; L is a direct bond or an optionally substituted C 1 -C 5 alkylene group; R 1 is a hydrogen atom or an optionally substituted C 1 -C 5 alkyl group; R 2 is a hydrogen atom, a C 1 -C 5 alkyl group, a C 6 -C 14 aryl group, or a C 7 -C 16 arylalkyl group; and R 3 is a hydrogen atom, a C 1 -C 3 alkyl group, or an acyl group).

18 . The production method according to claim 17 , wherein at least one Y is a hydroxyl group and R 3 is an acyl group.

19 . The production method according to claim 18 , wherein the protein is an antibody or an antibody fragment.

20 . A flow electrolysis apparatus for use in the production method according to any one of claims 1 to 19 , the flow electrolysis apparatus comprising:
a plurality of inlets for injecting a solution; a plurality of flow paths through which the solution flows, the plurality of flow paths extending from the inlets; a mixing point at which the plurality of flow paths merge; a discharge flow path extending downstream from the mixing point; an outlet connected to the discharge flow path; an electrolytic bath provided between any one inlet of the plurality of inlets and the mixing point; a voltage application device connected to the electrolytic bath; and a liquid feeding pump for feeding the solution at a desired flow rate.

21 . The flow electrolysis apparatus according to claim 20 , further comprising a sample injection portion for adding a solution containing a radionuclide between the inlet and the electrolytic bath.

22 . A stopped-flow type electrolysis apparatus for use in the production method according to any one of claims 1 to 19 .

23 . The stopped-flow type electrolysis apparatus according to claim 22 , further comprising a sample injection portion for adding a solution containing a radionuclide.

Assignees

• Univ Osaka

Inventors

• Fukase Koichi
• Toyoshima Atsushi
• Shinohara Atsushi
• Shirakami Yoshifumi
• Kaneda Kazuko
• Shimoyama Atsushi
• KADONAGA Yuichiro

Classifications

• C25B1/24

  Halogens or compounds thereof · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C25B9/15

  Flow-through cells · CPC title

• C25B3/11

  Halogen containing compounds · CPC title

• C25B3/13

  Organo-metallic compounds · CPC title