Hyperpolarized amino acids

Patent metadata

Field	Value
Publication number	US-9925280-B2
Application number	US-201314389404-A
Country	US
Kind code	B2
Filing date	Mar 28, 2013
Priority date	Apr 2, 2012
Publication date	Mar 27, 2018
Grant date	Mar 27, 2018

Abstract

Method for manufacturing a hyperpolarized amino acid, in particular glutamine, which substantially limits the formation of by-products, with respect to conventional aqueous preparations of sodium hydroxide with amino acids. The amino acid is in particular admixed with the hydroxide in the substantial absence of water and the dry mixture is dissolved in an anhydrous solvent in the presence of a polarizing agent. The obtained mixture is then subjected to a DNP process and can be used in metabolic MR imaging.

First claim

The invention claimed is:

1. A method for manufacturing hyperpolarized glutamine, which comprises the steps of:
(a) admixing (i) glutamine and (ii) Rb + or Cs + hydroxide as dry powders to prepare a powder mixture;
(b) preparing an initial mixture by admixing the powder mixture of step (a) with (iii) a polarizing agent and (iv) an anhydrous solvent, wherein essentially no water in free form is added to the initial mixture; and
(c) subjecting the initial mixture to a dynamic nuclear polarization (DNP) process to obtain a hyperpolarized mixture comprising said glutamine in hyperpolarized form.

2. The method according to claim 1 wherein said anhydrous solvent is a glass forming agent.

3. The method according to claim 2 wherein the initial mixture consists essentially of glutamine, Rb + or Cs + hydroxide, a polarizing agent and an anhydrous solvent.

4. The method according to claim 2 wherein the initial mixture subjected to the DNP process of step (c) comprises less than 10% (w/w) of water.

5. The method according to claim 4 wherein said amount of water is less than 8%.

6. The method according to claim 4 wherein said amount of water is less than 5%.

7. The method according to claim 1 wherein the initial mixture subjected to the DNP process of step (c) comprises less than 10% (w/w) of water.

8. The method according to claim 7 wherein said amount of water is less than 8%.

9. The method according to claim 7 wherein said amount of water is less than 5%.

10. The method according to claim 7 wherein the anhydrous solvent contains less than 1% w/w of water.

11. The method according to claim 10 wherein the anhydrous solvent contains less than 0.5% w/w of water.

12. The method according to claim 10 wherein the anhydrous solvent contains less than 0.1% w/w of water.

13. The method according to claim 10 wherein the anhydrous solvent contains a maximum amount of 0.005% w/w water.

14. The method according to claim 1 wherein the anhydrous solvent is dimethylsulfoxide (DMSO).

15. The method according to claim 14 wherein the hydroxide is Cs + hydroxide.

16. The method according to claim 1 wherein the hydroxide is Cs + hydroxide.

17. The method according to claim 1 wherein the initial mixture of step (b) is frozen, at a temperature lower than 4° K, before the DNP process.

18. The method according to claim 17 wherein the hyperpolarized mixture of step (b) is in frozen form.

19. The method according to claim 18 which further comprises the step of dissolving the frozen hyperpolarized mixture of step (c) in an aqueous solvent.

20. The method according to claim 19 wherein the polarizing agent is completely or partially separated from the dissolved hyperpolarized mixture.

21. The method according to claim 1 , wherein the polarizing agent is a trityl radical.

22. A method for MRI imaging comprising the steps of:
(a) admixing (i) glutamine and (ii) Rb + or Cs + hydroxide as dry powders to prepare a powder mixture;
(b) preparing an initial mixture by admixing the powder mixture of step (a) with (iii) a polarizing agent and (iv) an anhydrous solvent, wherein essentially no water in free form is added to the initial mixture;
(c) subjecting the initial mixture to a dynamic nuclear polarization (DNP) process to obtain a hyperpolarized mixture comprising said glutamine in hyperpolarized form;
(d) administering said hyperpolarized mixture to a subject;
(e) positioning the subject in a MRI system;
(f) submitting the subject to a radiation frequency selected to excite nuclear spin transitions in a non-zero nuclear spin nuclei of said glutamine; and
(g) recording a MR signal from said excited nuclei.

23. The method according to claim 22 wherein the anhydrous solvent is dimethylsulfoxide (DMSO) and the hydroxide is Cs + hydroxide.

Assignees

• Bracco Imaging Spa

Inventors

• Jensen Pernille Rose
• Karlsson Magnus
• Lerche Mathilde H

Classifications

• A61K49/10 Primary

  Organic compounds · CPC title

• C07C231/12

  by reactions not involving the formation of carboxamide groups · CPC title