IP Library Granted Patent US 12,569,576
Granted Patent B2
US 12,569,576 · App. 17/344,739 · Granted Mar 10, 2026

Compositions and methods for measuring oxidative stress

Inventor: Vijay Sharma (St. Louis, MO)
Assignee: Washington University
A61K51/0459A61K51/0482
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Quick Facts
Patent No.
US 12,569,576
App. No.
17/344,739
Granted
Mar 10, 2026
Kind
B2
Abstract

The present disclosure provides for imaging agents and methods of making and using the same. The imaging agent comprises a luminol component comprising a luminol moiety or functional analogue thereof; a chelator; a linker group bonding or complexing the luminol component to the chelator; and a radiolabel component bound to the chelator. The imaging agent described herein is capable of monitoring, targeting, or imaging oxidative stress, reactive oxygen species (ROS), superoxide generation, or hydrogen peroxide generation, mediating pathophysiology of different disease states.

Claims (30)

1 . An imaging agent, wherein the imaging agent is a compound of formula (IIa) or (IIb):

where R is a radiometal; and Y is O or S; or

a compound of formula (IIIa) or (IIIb):

where M-X is the radiolabeled component with M is a metal and X is a halogen radioisotope, and Y is O or S.

2 . The imaging agent of claim 1 , wherein the imaging agent is:

wherein Ga in the formula is 68 Ga or 67 Ga.

3 . The imaging agent of claim 1 , wherein the imaging agent is:

wherein Y is O or S.

4 . The imaging agent of claim 1 , wherein the imaging agent is a magnetic resonance imaging (MRI) contrast agent, a positron emission tomography (PET) imaging agent, a single-photon emission computerized tomography (SPECT) imaging agent, or a PET-MRI imaging agent.

5 . The imaging agent of claim 1 , wherein the imaging agent is capable of targeting or imaging oxidative stress, reactive oxygen species (ROS), superoxide generation, or hydrogen peroxide generation.

6 . A pharmaceutical composition comprising the imaging agent of claim 1 and one or more pharmaceutically acceptable carriers and/or excipients.

7 . A method of detecting reactive oxygen species (ROS) or imaging reactive oxygen species (ROS) mediated pathophysiology in a subject comprising:

administering a detectable amount of an imaging agent according to claim 1 ; and

detecting the imaging agent or radiation thereof to identify and/or quantify the ROS.

8 . A method of imaging reactive oxygen species (ROS) in a subject or region of a subject comprising:

administering the imaging agent, according to claim 1 ; and

detecting the imaging agent or radiation thereof to identify and/or quantify the ROS, wherein the method of imaging is PET, PET-MRI, MRI, or single-photon emission computed tomography (SPECT).

9 . The method of claim 8 , wherein the region of the subject is an organ or organ system.

10 . The method of claim 9 , wherein the organ comprises a lung.

11 . The method of claim 8 , wherein the subject is being treated for, has, or is suspected of having inflammation, ischemia, tissue injury, acute lung injury, chronic lung allograft dysfunction, oxidative stress-induced inflammation within lungs, and/or oxidative stress in other diseases selected from the group consisting of tissue inflammation, cardiovascular disease, diabetes, atherosclerosis, asthma, Alzheimer's disease, psoriasis, rheumatoid arthritis, aging, acute lung injury (ALI), cancer, and breast cancer.

12 . The imaging agent of claim 1 , wherein the imaging agent is:

wherein Gd in the formula is 153 Gd.

13 . The imaging agent of claim 1 , wherein R or M is selected from the group consisting of 22 Na, 26 Al, 38 K, 40 K, 52 Fe, 55 Co, 62 Zn, 63 Zn, 63 Zn, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 82 Rb, 89 Zr, 89 Sr, 86 Y, 90 Y, 94 Tc, 99 Tc, 110 In, 111 In, 153 Gd, 155 Tb, 177 Lu, 186 Re, 188 Re, and 201 Tl.

14 . The imaging agent of claim 1 , wherein R or M is selected from the group consisting of 22 Na, 26 Al, 82 Rb, 38 K, 62 Cu, 63 Zn, 68 Ga, 61 Cu, 52 Fe, 62 Zn, 64 Cu, 86 Y, 55 Co, 68 Ge, 40 K, 110 In, 94 Tc, and 89 Zr.

15 . The imaging agent of claim 1 , wherein R or M is selected from the group consisting of 68 Ga, 67 Ga, 99m Tc, and 111 In.

16 . The imaging agent of claim 1 , wherein X is selected from the group consisting of 18 F, 36 Cl, 75 Br, 76 Br, 77 Br, 82 Br, 122 Xe, 120 I, 121 I, 123 I, 124 I, 125 I, and 131 I.

17 . The imaging agent of claim 1 , wherein X is selected from the group consisting of 18 F, 76 Br, 121 I, 120 I, and 124 I.

18 . The imaging agent of claim 1 , X is selected from the group consisting of 18 F, 123 I, and 131 I.

19 . The imaging agent of claim 1 , wherein R is 68 Ga or M-X is Al 18 F.

20 . The imaging agent of claim 1 , where M is a transition metal ion or a metal ion of groups 8-13.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 5, 2023
From: WASHINGTON UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065776/0879 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 24, 2021
From: SHARMA, VIJAY
To: WASHINGTON UNIVERSITY
Reel/Frame 056646/0169 →
Continuity (2)
Provisional Application 63037219 · Jun 10, 2020
Related Publication 20210386874A1 · Dec 16, 2021
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