Granted Patent
B2
US 12,257,327 · App. 17/319,780 · Granted Mar 25, 2025
Compositions and methods for treatment and imaging using nanoparticles
Assignee:
Washington University
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Abstract
The present invention encompasses compositions comprising two spectrally distinct radionuclides separated by a site susceptible to cleavage. Compositions of the invention may be used to detect enzyme activity and/or image diseases associated with said enzyme activity.
Claims (27)
1. A composition comprising:
(a) a peptide comprising a Tyr residue, a Cys residue, and a Matrix metallopeptidase 9 (MMP9)-sensitive site, wherein the peptide comprises the amino acid sequence set forth in SEQ ID NO: 1;
(b) a chelator coupled to the peptide; and
(c) a first radionuclide and a second radionuclide, wherein the first radionuclide is 125 I and second radionuclide is one of 111 In and 64 Cu, wherein the radionuclides are attached or coupled at positions on the peptide separated by the MMP9-sensitive site.
2. The composition of claim 1 , wherein one of the radionuclides is conjugated to the Tyr residue.
3. The composition of claim 2 , wherein the radionuclide is 125 I.
4. The composition of claim 1 , wherein one of the radionuclides is conjugated to the chelator.
5. The composition of claim 4 , wherein the radionuclide is one of 111 In and 64 Cu.
6. The composition of claim 1 , wherein the chelator is coupled to an amino acid residue at an N terminus of the peptide.
7. The composition of claim 6 , wherein the chelator is a diethylenetriaminepentaacetic acid (DTPA).
8. The composition of claim 1 , wherein the chelator is a DTPA and is conjugated to the N-terminal Gly residue of SEQ ID NO: 1.
9. The composition of claim 1 , further comprising a nanoparticle conjugated to the Cys residue of SEQ ID NO: 1.
10. The composition of claim 1 , wherein the peptide further comprises a polyethylene glycol (PEG).
11. The composition of claim 10 , wherein the PEG is conjugated to the Cys residue directly or indirectly through a linker.
12. The composition of claim 11 , wherein the PEG is further conjugated to a nanoparticle.
13. The composition of claim 1 , wherein the peptide further comprises a terminal-NH 2 acylation.
14. A method of detecting an enzyme activity in a subject, the method comprising:
(a) administering to the subject an effective amount of a composition of claim 9 ;
b) imaging the subject for a signal corresponding to the 125 I and one of 111 In and 64 Cu to determine the biodistribution for the 125 I and one of 111 In and 64 Cu; and
c) comparing the biodistribution of the 125 I to the biodistribution of one of 111 In and 64 Cu,
wherein when the biodistribution for 125 I differs from the biodistribution for one of 111 In and 64 Cu, an enzyme activity is detected.
15. The method of claim 14 , wherein the subject is imaged about 4 to about 48 hours after administration.
16. The method of claim 14 , wherein the subject is imaged using single photon emission computed tomography (SPECT).
17. A composition comprising:
a peptide comprising the sequence set forth in SEQ ID NO: 1 comprising an N-terminal Gly residue, a Tyr residue, a Cys residue and an Ahx residue; wherein a DTPA is conjugated at the Gly residue, a radionuclide 125 I is attached to the Tyr residue, one of a radionuclide 111 In and 64 Cu is coupled to the DTPA, a nanoparticle is conjugated to the Cys residue, and Ahx is a 6-aminocaproic acid.
18. A composition comprising:
a peptide comprising the sequence set forth in SEQ ID NO: 1 comprising an N-terminal Gly residue, a Tyr residue, a Cys residue and an Ahx residue; wherein a DTPA is conjugated at the Gly residue, a PEG is conjugated at the Cys residue through a DBCO-malemide linker, one of a radionuclide 111 In and 64 Cu is coupled to the DTPA, a nanoparticle is conjugated to the PEG through a thiol, and Ahx is a 6-aminocaproic acid.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 18, 2025
From: BLACK, KVAR; ACHILEFU, SAMUEL
To: WASHINGTON UNIVERSITY
Reel/Frame 070242/0219 →
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 065775/0115 →
Continuity (5)
Provisional Application
62137628
· Mar 24, 2015
Provisional Application
62009481
· Jun 9, 2014
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