PH-sensitive imaging agents
View Patent ↗Composition and method for surface-functionalized SPION-based agents. Such agents can provide highly pH-sensitive MRI contrast in tissue.
1. A magnetic resonance imaging agent comprising:
(a) a superparamagnetic core;
(b) a linker group; and
(c) a pH sensitive macromolecule comprising a monomer unit comprising a dendron and having a pKa between 6 and 10;
wherein,
the linker group is affixed to the superparamagnetic core;
the pH sensitive macromolecule is attached to the linker group;
the dendron comprises a melamine, an imidazole, a polyimidazole, a vinyl imidazole, a nitrilotriacetic acid, a polyethylene glycol (PEG), a histidine, a lysine, an amino carboxylate, a histidine-lysine, or an amino sulfonate;
the imaging agent exhibits a pH sensitive magnetic resonance response; and
the imaging agent is biocompatible.
2. The agent of claim 1 , wherein the dendron comprises a melamine dendron.
3. The agent of claim 1 , wherein the superparamagnetic core comprises one or more of iron oxide or iron platinum.
4. The agent of claim 3 , wherein the superparamagnetic core comprises iron oxide.
5. The agent of claim 4 , wherein the superparamagnetic core comprises an iron oxide nanoparticle.
6. The agent of claim 1 , wherein the linker group is a dopamine, carboxylic acid, silane, 2,3-diaminopropanoic acid, ascorbic acid, lysine methyl ester, or aminopropyltrimethoxysilane (APTMS).
7. The agent of claim 1 , wherein the imaging agent comprises a hyperpolarized agent.
8. The agent of claim 1 , wherein the pH sensitive macromolecule is a first generation dendron, a second generation dendron, or a third generation dendron.
9. The agent of claim 1 , wherein the linker group does not comprise a carboxylic acid.
10. The agent of claim 1 , wherein the pH sensitive macromolecule causes a transient or reversible pH-dependent magnetic resonance response.
11. The agent of claim 10 , wherein the transient or reversible pH-dependent magnetic resonance response occurs on a timescale of milliseconds or less.
12. The agent of claim 1 , wherein the pH sensitive macromolecule further comprises:
an imidazole, a polyimidazole, a vinyl imidazole, a nitrilotriacetic acid, a polyethylene glycol (PEG), a histidine, a lysine, an amino carboxylate, a histidine-lysine, an amino suifonate;
13. A method of imaging a biological tissue comprising:
administering the agent of claim 1 (i) in vivo to a subject comprising a biological tissue or (ii) to an ex vivo biological tissue; and
detecting
(a) contrast associated with the agent in the biological tissue; or
(b) contrast associated with pH variations in the biological tissue.
14. The method of claim 13 , wherein detecting contrast comprises magnetic resonance imaging.
15. The method of claim 13 , wherein detecting contrast comprises identifying changes in a magnetic resonance parameter.
16. The method of claim 15 , wherein the magnetic resonance parameter is T1, T2, T2*, D, perfusion, oxygenation, R 1 , R 2 , R 2 *, R 2 m , or R 2 m *.
17. The method of claim 16 , wherein the magnetic resonance parameter is a ratio of R 2 m and R 2 m *.
18. The method of claim 15 , wherein the magnetic resonance parameter is mapped onto a corresponding magnetic resonance image.
19. The method of claim 15 , wherein the magnetic resonance parameter is a map or a magnetic resonance image.
20. The method of claim 19 , wherein the magnetic resonance image is selected from the group consisting of density-weighted, T1-weighted, T2-weighted, and T2*-weighted magnetic resonance image, or a combination thereof.
21. The method of claim 20 , wherein the magnetic resonance image is T2-weighted or T2*-weighted.