Metal complexes with bisphophonate or pyrophosphate useful as imaging agents
Provided herein are magnetic resonance imaging (MRI) contrast agents comprising a compound having a structure represented by: Y—X—Z, wherein, X is: Fe(III) or Mn(II), and Y and Z are each independently selected from pyrophosphate and bisphosphonate (e.g., 1-hydroxybisphosphonate), or a pharmaceutically acceptable hydrate and/or salt thereof. Methods of use of the MRI contrast agent are also provided.
1. A composition comprising a magnetic resonance imaging (MRI) contrast agent comprising a compound having a structure represented by:
Y—X—Z
wherein,
X is Fe(III) and Y and Z are each independently selected from the group consisting of pyrophosphate and bisphosphonate;
or a pharmaceutically acceptable hydrate and/or salt thereof,
in a pharmaceutically acceptable carrier,
wherein said composition is formulated for intravenous or intraarterial administration.
2. The composition of claim 1 , wherein the contrast agent has a molecular weight of less than 2,000 daltons.
3. The composition of claim 1 , wherein the contrast agent has a molecular weight of less than 800 daltons.
4. The composition of claim 1 , wherein the compound is octahedral.
5. The composition of claim 1 , wherein the compound is a monohydrate or a dihydrate.
6. The composition of claim 1 , wherein the compound is a salt comprising from 1 to 3 cations.
7. The composition of claim 6 , wherein the cations are selected from sodium and meglumine.
8. The composition of claim 1 , wherein said MRI contrast agent comprises at least one alkaline earth metal selected from calcium and magnesium.
9. The composition of claim 6 , wherein said MRI contrast agent comprises sodium.
10. The composition of claim 1 , wherein said compound is Fe(III):(P 2 O 7 ) 2 :(H 2 O) 2 , or a pharmaceutically acceptable salt thereof.
11. The composition of claim 1 , wherein said compound is:
12. A magnetic resonance imaging (MRI) contrast agent comprising a compound having a structure represented by:
Y—X—Z
wherein,
X is Fe(III) and Y and Z are each independently selected from the group consisting of pyrophosphate and bisphosphonate;
or a pharmaceutically acceptable hydrate and/or salt thereof, wherein said compound is coupled to one or more therapeutic agents.
13. The Mill contrast agent of claim 12 , wherein said one or more therapeutic agents are covalently coupled to Y and/or Z.
14. A composition comprising the MRI contrast agent of claim 12 in a pharmaceutically acceptable carrier.
15. The composition of claim 14 , wherein said composition is formulated for intravenous or intraarterial administration.
16. The composition of claim 14 , wherein said pharmaceutically acceptable carrier is water or phosphate buffered saline.
17. The composition of claim 14 , wherein said composition has a pH of from 6.0 to 8.0.
18. The composition of claim 14 , wherein said composition has a pH of from 7.0 to 7.4.
19. A method of performing a magnetic resonance imaging (MRI) scan on a subject comprising administering the composition of claim 1 to said subject prior to and/or during said MRI scan.
20. A method of administering a therapeutic agent to a subject in need thereof, comprising administering the MRI contrast agent of claim 12 to said subject in a treatment effective amount.
21. The method of claim 20 , further comprising detecting the MRI contrast agent with MRI in said subject.
22. The composition of claim 1 , wherein said pharmaceutically acceptable carrier is water or phosphate buffered saline.
23. The MRI contrast agent of claim 12 , wherein said compound is Fe(III):(P 2 O 7 ) 2 :(H 2 O) 2 , or a pharmaceutically acceptable salt thereof.