Use of aniline in the radiostabilization of oxime ligation

Patent metadata

Field	Value
Publication number	US-9567372-B2
Application number	US-201113996020-A
Country	US
Kind code	B2
Filing date	Dec 15, 2011
Priority date	Dec 21, 2010
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

A method of radiostabilizing an oxime ligation or imine formation reaction using aniline is described.

First claim

What is claimed is:

1. A radiostabilizing method for preparing a radioimaging agent comprising the step of reacting a radiolabeled aldehyde (I) with an aminooxy (II) in the presence of aniline (III) at pH 2.8-3.5 to form imine-oxy (IV):

wherein aniline is present in an amount that provides a catalytic effect and a radiostabilizing effect, wherein the amount of aniline includes a radiostabilizing amount of aniline that is additive to the amount of aniline that provides the catalytic effect, and wherein the radiochemical yield % of imine-oxy (IV) is increased above the yield % of said method without said radiostabilizing amount of aniline.

2. The radiostabilizing method of claim 1 , wherein said radiolabeled aldehyde (I) is a compound of formula (VIII):

wherein R 1 * is a radiolabeled organic or biological moiety.

3. The radiostabilizing method of claim 2 , wherein said radiolabeled organic moiety is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, or cycloalkyl and wherein said radiolabeled biological moiety is an amino acid, peptide, or vector.

4. The radiostabilizing method of claim 1 , wherein the radiolabel of R 1 * is a radioisotope suitable for PET or SPECT imaging.

5. The radiostabilizing method of claim 1 , wherein said radiolabeled aldehyde is [18F]parabenzaldehyde.

6. The radiostabilizing method of claim 1 wherein said aminooxy (II) is a compound of formula (IX):
R 2 —O—NH 2   (IX)

wherein R2 can be any organic or biological moiety.

7. The radiostabilizing method of claim 6 , wherein said aminooxy (II) is

8. The radiostabilizing method of claim 6 , wherein said radiolabeled imine-oxy is a compound of formula (X):

9. A radiostabilizing method comprising the step of reacting a radiolabeled aldehyde (VIII) with an aminooxy (IX) in the presence of aniline (III) at pH 2.8-3.5 to form imine-oxy (X):

wherein:
R 1 * is organic or biological moiety labeled with at least one radioisotope or radionuclide;
R 2 is an organic or biological moiety; and
aniline is present in an amount that provides a catalyzing effect and a radiostabilizing effect, wherein the amount of aniline includes a radiostabilizing amount of aniline that is additive to the amount of aniline that provides the catalytic effect, and wherein the radiochemical yield % of imine-oxy (X) is increased above the yield % of said method without said radiostabilizing amount of aniline.

10. The radiostabilizing method of claim 1 , wherein said aniline is of the following formula:

a salt or derivative thereof or a mixture thereof.

11. The radiostabilizing method of claim 10 , wherein said aniline is:

12. The radiostabilizing method of claim 10 , wherein said aniline is used in combination with para-amino benzoic acid or with a radiostabilizer.

Assignees

• Engell Torgrim
• Osborn Nigel
• Ge Healthcare Ltd

Inventors

• Engell Torgrim
• Osborn Nigel

Classifications

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• A61K51/0497 Primary

  conjugates with a carrier being an organic compounds · CPC title

• A61K47/50

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title

• A61K51/04 Primary

  Organic compounds · CPC title

• A61K51/08

  Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins} · CPC title