Dihydroethidine analogues and uses thereof

• US 9,035,057 B2
• Filed: 12/16/2010
• Issued: 05/19/2015
• Est. Priority Date: 12/16/2009
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Mach, Robert H., Chu, Wenhua, Dugan, Laura, Mintun, Mark
• Primary Examiner(s): DESAI, RITA J
• Application Number:
  US13/516,783
• Publication Number:
  US 20130079522A1
• Time in Patent Office: 1,615 Days
• Field of Search: 546/109
• US Class Current: 546/109
• CPC Class Codes: C07D 221/12 Phenanthridines
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

Tracers for imaging distribution of reactive oxygen species (ROS) are disclosed. The tracers include radiolabeled dihydroethidine (DHE) analogues. Further disclosed are uses of the compounds, including methods of imaging tissue distribution of ROS in vivo by positron emission tomography (PET). Methods of synthesizing the compounds are also disclosed.

Claims

1. A radiolabeled compound or salt thereof of structure

2. A radiolabeled compound or salt thereof in accordance with claim 1, wherein the radioisotope is a positron-emitting radioisotope.

3. A radiolabeled compound or salt thereof in accordance with claim 1 wherein R₁ is H.

4. A radiolabeled compound or salt thereof in accordance with claim 1, wherein the compound or salt thereof comprises an ¹¹CH₃.

5. A radiolabeled compound or salt thereof in accordance with claim 1, wherein R₃ is (CH₂)_q—

CH₃ and q is 0.

6. A radiolabeled compound or salt thereof in accordance with claim 5, wherein R₃ is ¹¹CH₃.

7. A radiolabeled compound or salt thereof in accordance with claim 1, wherein R₃ is

8. A radiolabeled compound or salt thereof in accordance with claim 1, wherein R₁ is O—

R₃, R₃ is CH₃.

9. A radiolabeled compound or salt thereof in accordance with claim 8, wherein R₁ is O—

R₃, wherein R₃ is ¹¹CH₃.

10. A radiolabeled compound or salt thereof in accordance with claim 1, wherein R₁ is O—

R₃, R₃ is

11. A radiolabeled compound or salt thereof in accordance with claim 10, wherein n is 1.

12. A radiolabeled compound or salt thereof in accordance with claim 10, wherein m is 2.

13. A radiolabeled compound or salt thereof in accordance with claim 10, wherein n is 1 and m is 2.

14. A radiolabeled compound or salt thereof in accordance with claim 1, wherein R₃ is,

15. A radiolabeled compound or salt thereof in accordance with claim 13, wherein p is 2.

16. A radiolabeled compound or salt thereof in accordance with claim 1, wherein the compound is selected from the group consisting of