Ligands for imaging cardiac innervation

• US 10,010,631 B2
• Filed: 06/12/2013
• Issued: 07/03/2018
• Est. Priority Date: 12/26/2006
• Status: Active Grant

• Current Assignee: Lantheus Medical Imaging, Inc. (Lantheus Holdings, Inc.)
• Original Assignee: Lantheus Medical Imaging, Inc. (Lantheus Holdings, Inc.)
• Inventors: Purohit, Ajay, Harris, Thomas D., Radeke, Heike S., Robinson, Simon P., Yu, Ming, Casebier, David S., Azure, Michael T.
• Primary Examiner(s): Katakam, Sudhakar
• Assistant Examiner(s): Muresan, Ana Z
• Application Number:
  US13/916,205
• Publication Number:
  US 20140030189A1
• Time in Patent Office: 1,847 Days
• Field of Search: 5483315, 544392, 544394
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: A61K 51/0453 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 51/0459 having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/001 Acyclic or carbocyclic compounds
• CPC Class Codes: C07C 215/60 the chain having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/70 linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 279/06 being further substituted by halogen atoms, or by nitro or nitroso groups
• CPC Class Codes: C07C 279/08 being further substituted by singly-bound oxygen atoms

Abstract

Novel compounds that find use as imaging agents within nuclear medicine applications (PET imaging) for imaging of cardiac innervation are disclosed. These PET based radiotracers may exhibit increased stability, decreased NE release (thereby reducing side effects), improved quantitative data, and/or high affinity for VMAT over prior radiotracers. Methods of using the compounds to image cardiac innervation are also provided. In some instances the compounds are developed by derivatizing certain compounds with 18F in a variety of positions: aryl, alkyl, a keto, benzylic, beta-alkylethers, gamma-propylalkylethers and beta-proplylalkylethers. Alternatively or additionally, a methyl group a is added to the amine, and/or the catechol functionality is either eliminated or masked as a way of making these compounds more stable.

Claims

1. A compound of the structure:

2. A method of imaging cardiac innervation comprising the steps of:

administering an effective amount of the compound of claim 1 or a salt thereof to a patient;

detecting radiation emitted by said compound; and

forming an image therefrom.

3. The compound of claim 1, wherein the compound is a salt.

4. The compound of claim 1, wherein the compound is a salt of a compound selected from the group consisting of:

5. A composition for imaging cardiac innervation comprising the compound of claim 4, and optionally one or more excipients.

6. A method of imaging cardiac innervation comprising the steps of:

administering an effective amount of the compound of claim 4 to a patient;

detecting radiation emitted by said compound; and

forming an image therefrom.

7. The compound of claim 1, wherein the compound is a salt of the compound:

8. The compound of claim 7, wherein the salt has the structure N-[3-bromo-4(3-[18F]fluoropropoxy)-benzyl]-guanidine hydrochloride.

9. A composition for imaging cardiac innervation comprising the compound of claim 7, and optionally one or more excipients.

10. A method of imaging cardiac innervation comprising the steps of:

administering an effective amount of the compound of claim 7 to a patient;

detecting radiation emitted by said compound; and

forming an image therefrom.

11. A composition for imaging cardiac innervation comprising the compound of claim 1, and optionally one or more excipients.

12. A compound of the structure:

16. A method of imaging cardiac innervation comprising the steps of:

administering an effective amount of the compound of claim 12 or a salt thereof to a patient;

detecting radiation emitted by said compound; and

forming an image therefrom.

13. A compound of the structure:

17. A method of imaging cardiac innervation comprising the steps of:

administering an effective amount of the compound of claim 13 or a salt thereof to a patient;

detecting radiation emitted by said compound; and

forming an image therefrom.

20. The compound of claim 13, wherein n is 0.

22. The compound of claim 13, wherein n is 1.

14. A compound of the structure:

15. The compound of claim 14, wherein the compound has the structure:

18. A method of imaging cardiac innervation comprising the steps of:

administering an effective amount of the compound of claim 15 or a salt thereof to a patient;

detecting radiation emitted by said compound; and

forming an image therefrom.

19. A method of imaging cardiac innervation comprising the steps of:

administering an effective amount of the compound of claim 14 or a salt thereof to a patient;

detecting radiation emitted by said compound; and

forming an image therefrom.

21. The compound of claim 14, wherein n is 0.

23. The compound of claim 14, wherein n is 1.