Method for producing 18F-labeled compound and high molecular compound to be used in the method

Patent metadata

Field	Value
Publication number	US-9073802-B2
Application number	US-201113578569-A
Country	US
Kind code	B2
Filing date	Feb 8, 2011
Priority date	Feb 12, 2010
Publication date	Jul 7, 2015
Grant date	Jul 7, 2015

Abstract

The present invention aims at solving the problems of conventional methods for producing an 18 F-labeled compound, that is, the problem of purification of a compound in a liquid phase synthesis method and the problem of an insufficient yield due to the reduction of reactivity in a solid phase synthesis method. There is provided a method for producing an 18 F-labeled compound including: allowing a high molecular compound containing a residue of a precursor compound to be labeled and a residue of a phase transfer catalyst in the molecule thereof to react with 18 F − ; and removing the 18 F-labeled compound from the high molecular compound.

First claim

The invention claimed is:

1. A method for producing an 18 F-labeled compound, comprising:
contacting a high molecular compound with 18 F − , wherein covalently attached to the high molecular compound are both a precursor compound to be labeled and a phase transfer catalyst, thereby labeling the precursor compund with 18 F; and
separating the 18 F labeled compound from the high molecular compound.

2. The method for producing an 18 F-labeled compound according to claim 1 , wherein the high molecular compound is a high molecular compound obtained by copolymerization of a monomer comprising a residue of a precursor compound to be labeled and a monomer comprising a residue of a phase transfer catalyst.

3. The method for producing an 18 F-labeled compound according to claim 2 , wherein the monomer comprising the residue of the precursor compound to be labeled is represented by the following formula (I):
CH 2 ═C═CH-L 1 -SO 2 —X  (I)

wherein L 1 represents a linker, and X represents the residue of the precursor compound to be labeled; and the monomer comprising the residue of the phase transfer catalyst is represented by the following formula (II):
CH 2 ═C═CH-L 2 -Y  (II)

wherein L 2 represents a linker, and Y represents the residue of the phase transfer catalyst.

4. The method for producing an 18 F-labeled compound according to any one of claims 1 to 3 , wherein the high molecular compound comprises structural units represented by formulas (Ia), (Ib), (IIa), and (IIb):

wherein L 1 and L 2 each represents a linker; X represents the residue of the precursor compound to be labeled; and Y represents the residue of the phase transfer catalyst.

5. The method for producing an 18 F-labeled compound according to claim 1 , wherein the phase transfer catalyst is 1,10-diaza-4,7,13,16,21,24-hexaoxabicyclo[8.8.8]hexacosane, 12-crown-4, 15-crown-5, 18-crown-6, benzo-12-crown-4,benzo-15-crown-5, or benzo-18-crown-6.

6. The method for producing an 18 F-labeled compound according to claim 1 , wherein the precursor compound to be labeled is represented by formula (A) or (B):

wherein R 1 , R 2 , and R 3 each represents any group.

7. The method for producing an 18 F-labeled compound according to claim 1 , wherein the 18 F-labeled compound is 2- 18 F-fluoro-2-deoxy-D-glucose, 2- 18 F-fluoro-2-deoxy-D-mannose, 3- 18 F-fluoro-3-deoxy-D-glucose, O-(2-[ 18 F]fluoroethyl)-L-tyrosine, 3′-[ 18 F]-fluoro-3′-deoxythymidine, 16α-[ 18 F]-fluoro-17β-estradiol, or [ 18 F]-fluoromisonidazole.

8. A high molecular compound comprising structural units represented by the following formulas (Ia), (Ib), (IIa), and (IIb):

wherein L 1 and L 2 each represents a linker; X represents a residue of a precursor compound to be labeled with 18 F; and Y represents a residue of a phase transfer catalyst.

9. The high molecular compound according to claim 8 , wherein the phase transfer catalyst is 1,10-diaza-4,7,13,16,21,24-hexaoxabicyclo[8.8.8]hexacosane, 12-crown-4, 15-crown-5, 18-crown-6, benzo-12-crown-4,benzo-15-crown-5, or benzo-18-crown-6.

10. The high molecular compound according to claim 8 or 9 , wherein the precursor compound to be labeled is represented by formula (A) or (B):

wherein R 1 , R 2 , and R 3 each represents any group.

Assignees

• Takahashi Takashi
• Tanaka Hiroshi
• Nakada Tsutomu
• Tokyo Inst Tech
• Univ Niigata

Inventors

• Takahashi Takashi
• Tanaka Hiroshi
• Nakada Tsutomu

Classifications

• C07B59/00 Primary

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title

• C07H15/26 Primary

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• C08F236/20

  unconjugated · CPC title

• A61K51/0491

  Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers · CPC title