Claims
- 1. A library of MRI contrast agents each comprising:
a) a chelate; b) a paramagnetic metal ion; and c) a different candidate agent covalently attached to said chelate.
- 2. A library according to claim 1 wherein said MRI contrast agents each comprise:
a) said paramagnetic metal ion capable of binding n coordination atoms, wherein said metal ion is bound to said chelator such that said metal ion has coordination atoms at (n−1) or (n−2) coordination sites of said metal ion; and b) a blocking moiety covalently attached to said chelator which hinders the rapid exchange of water in the remaining coordination site or sites; wherein said blocking moiety is capable of interacting with a target substance such that the exchange of water in said remaining coordination sites is increased.
- 3. A library according to claim 1 wherein said candidate agents are peptides.
- 4. A library according to claim 2 wherein said peptides comprise fully random peptides.
- 5. A library according to claim 2 wherein said peptides comprise partially random peptides.
- 6. A library according to claim 1 wherein said candidate agents are carbohydrates.
- 7. A library according to claim 1 wherein said candidate agents are nucleic acids.
- 8. A library according to claim 1 wherein said candidate agents are lipids.
- 9. A library according to claim 1 wherein said candidate agents are attached to said chelates using a linker.
- 10. A library according to claim 5 wherein said linker is photocleavable.
- 11. A library according to claim 1 wherein each contrast agent further comprises a targeting moiety.
- 12. A library according to claim 1 wherein said library comprises at least 103 different members.
- 13. A method of screening for binding interactions comprising:
a) providing a substrate with an immobilized target analyte; b) contacting said substrate with a library of agents each comprising:
i) a chelate; ii) a metal ion; and iii) a different peptide covalently attached to said chelate; wherein said contacting is done under conditions that allow at least one of said agents to bind to said target analyte; c) rinsing said substrate to remove unbound agents; and d) detecting the presence of binding of of at least one of said agents to said target analyte.
- 14. A method according to claim 13 wherein said metal ion is a paramagnetic metal ion, said agent is an MRI contrast agent and said detecting is done by taking a magnetic resonance image of said substrate.
- 15. A method according to claim 13 wherein said metal ion confers fluorescence to said agent and said detecting is done by detecting fluorescence on said substrate.
- 16. A method according to claim 14 or 15 wherein said substrate comprises a plurality of different target analytes.
- 17. A method according to claim 14 or 15 wherein said method utilizes a robotic system.
- 18. A method of screening for protease-activated MRI contrast agents comprising:
a) providing a substrate with a plurality of test sites, each test site comprising at least one MRI contrast agent comprising a paramagnetic metal ion bound to a complex, said complex comprising:
i) a chelator; and ii) a peptide blocking moiety covalently attached to said chelator which binds in at least a first coordination site of said metal ion such that the exchange of water in said first coordination site is hindered; wherein at least two of said test sites comprising a different peptide blocking moiety; b) adding a first protease to each of said test sites; c) taking a Magnetic Resonance Image of said substrate, wherein if an increase in image intensity is observed, said test site comprises a protease-activated MRI contrast agent.
- 19. A method according to claim 18 wherein each of said test sites comprises a single MRI contrast agent.
- 20. A method according to claim 18 wherein each of said test sites comprises a plurality of MRI contrast agents.
- 21. A method according to claim 18 further comprising identifying the activated MRI contrast agent.
- 22. A method according to claim 18 wherein said method utilizes a robotic system.
- 23. A method of making a library of MRI contrast agents comprising:
a) providing a chelate with a first functional group; b) providing a library of candidate agents each with a second functional group; c) covalently attaching said first and second functional groups.
- 24. A method according to claim 23 wherein said candidate agents are peptides.
- 25. A method according to claim 23 wherein said method utilizes a robotic system.
- 26. A method of imaging an animal comprising:
a) injecting said animal with a first MRI contrast agent comprising a paramagnetic metal ion bound to a complex, said complex comprising:
i) a chelator; and ii) a first blocking moiety covalently attached to said chelator which binds in at least a first coordination site of said metal ion and which interacts with a first target substance such that the exchange of water in at least said first coordination site is increased; b) taking a first Magnetic Resonance Image; c) injecting said animal with a second MRI contrast agent comprising a paramagnetic metal ion bound to a complex, said complex comprising:
i) a chelator; and ii) a second blocking moiety covalently attached to said chelator which binds in at least a first coordination site of said metal ion and which interacts with a second target substance such that the exchange of water in at least said first coordination site is increased; and d) taking a second Magnetic Resonance Image.
- 27. A method according to claim 26 wherein said animal has been pretreated with a drug candidate before imaging.
- 28. A method according to claim 26 wherein said animal is a transgenic animal.
- 29. A method of imaging gene expression of a target gene in an animal comprising:
a) at a first time point, injecting said animal with a MRI contrast agent comprising:
i) a chelate; li) a paramagnetic metal ion; and iii) a moiety comprising a binding partner of the target protein of said target gene, wherein said moiety is covalently attached to said chelate; b) taking a first magnetic resonance image of said animal; c) at a second time point, injecting said animal with said MRI contrast agent; and d) taking a second magnetic resonance image of said animal; and e) comparing said first and second images to determine the course of gene expression.
- 30. A method of imaging disease progression in an animal comprising:
a) at a first time point, injecting said animal with a MRI contrast agent comprising:
i) a chelate; li) a paramagnetic metal ion; and iii) a moiety comprising a binding partner of a target protein correlated to said disease, wherein said moiety is covalently attached to said chelate; b) taking a first magnetic resonance image of said animal; c) at a second time point, injecting said animal with said MRI contrast agent; and d) taking a second magnetic resonance image of said animal; and e) comparing said first and second images to determine the course of said disease.
- 31. A method according to claim 29 or 30 wherein prior to said second time point, said animal is treated with a drug.
- 32. A method according to claim 29 or 30 comprising taking repeated images over time.
- 33. A method according to claim 26, 29 or 30 further comprising sacrificing said animal and performing histological or pathological analyses.
- 34. A method according to claim 29 or 30 wherein said animal is a transgenic animal.
Parent Case Info
[0001] This application claims the benefit under 35 U.S.C. §§119/120 of provisional application Ser. No. 60/288,963, filed May 2, 2001 and U.S. Ser. No. 10/139,145, filed May 2, 2002, both of which are incorporated herein in their entirety by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60288963 |
May 2001 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
10139145 |
May 2002 |
US |
Child |
10291807 |
Nov 2002 |
US |