Contrast agents

• US 8,337,813 B2
• Filed: 09/15/2008
• Issued: 12/25/2012
• Est. Priority Date: 09/14/2007
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Schultz Sikma, Elise A., Dravid, Vinayak P., Meade, Thomas J., Ulrich, Bradley D., Aslam, Mohammad
• Primary Examiner(s): Jones, D L
• Application Number:
  US12/210,829
• Publication Number:
  US 20090269284A1
• Time in Patent Office: 1,562 Days
• Field of Search: 424/1.11, 424/1.65, 424/9.1, 424/9.3, 424/9.32, 424/9.321, 424/9.322, 424/9.323, 424/9.33, 424/9.34, 424/9.341, 424/9.35, 424/9.351, 424/9.36, 424/9.361, 424/9.362, 424/9.363, 424/9.364, 424/9.365, 424/9.7, 424/1.69
• US Class Current: 424/9.34
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/416 the spleen
• CPC Class Codes: A61K 49/085 conjugated systems
• CPC Class Codes: A61K 49/14 Peptides, e.g. proteins
• CPC Class Codes: A61K 49/1824 coated or functionalised nanoparticles liposomes A61K49/1812; nanoemulsions A61K49/1806; micelles A61K49/1809
• CPC Class Codes: A61K 49/183 having a (super)(para)magnetic core coated or functionalised with an inorganic material or being composed of an inorganic material entrapping the MRI-active nucleus, e.g. silica core doped with a MRI-active nucleus
• CPC Class Codes: A61K 49/186 the organic macromolecular compound being polyethyleneglycol [PEG]
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/811 Of specified metal oxide composition, e.g. conducting or semiconducting compositions such as ITO, ZnOx
• CPC Class Codes: Y10S 977/838 Magnetic property of nanomaterial
• CPC Class Codes: Y10S 977/93 MRI contrast agent

Abstract

The present invention relates generally to multimodal magnetic resonance imaging (MRI) contrast agents. In particular, the present invention provides a MRI contrast agent configured to manipulate both the longitudinal (T₁) and transverse (T₂) relaxation times of surrounding water proton spins.

Claims

1. A magnetic resonance contrast agent composition comprising one or more T₁ contrast agent portions, and one or more T₂ contrast agent portions, wherein said one or more T₁ contrast agent portions comprise a paramagnetic metal ion chelate, and wherein said one or more T₂ contrast agent portions comprise a cobalt ferrite nanoparticle coated with a SiO₂ shell.

2. The magnetic resonance contrast agent composition of claim 1, further comprising one or more linker regions.

3. The magnetic resonance contrast agent composition of claim 1, wherein said paramagnetic metal ion is Gd(III).

4. The magnetic resonance contrast agent composition of claim 2, wherein said linker region is a cleavable linker region.

5. The magnetic resonance contrast agent composition of claim 4, wherein said cleavable linker region comprises a peptide linker portion.

6. The magnetic resonance contrast agent composition of claim 5, wherein said peptide linker portion comprises a MMP-7 peptide linker.

7. The magnetic resonance contrast agent composition of claim 2, wherein said linker region connects one said T₁ contrast agent portion to one said T₂ contrast agent.

8. The magnetic resonance contrast agent composition of claim 2, wherein a T₂ contrast agent portion is connected to more than one T₁-relaxation contrast agent portions by multiple linkers.

9. The magnetic resonance contrast agent composition of claim 1, wherein more than one T₂ contrast agent portions are connected to more than one T₁ contrast agent portions by multiple linkers.

10. The magnetic resonance contrast agent composition of claim 1, further comprising an imaging tag.

11. The magnetic resonance contrast agent composition of claim 10, wherein said imaging tag is and optical imaging tag.

12. The magnetic resonance contrast agent composition of claim 1, further comprising a targeting moiety.

13. A pharmaceutical formulation comprising a contrast agent of claim 1 and a pharmaceutically acceptable carrier, wherein the formulation is suitable for administration as an imaging enhancing agent and the contrast agent is present in an amount sufficient to enhance a magnetic resonance image.

14. A method of generating an image of at least a part of a subject comprising administering the composition of claim 1 to a subject, and generating an image of at least a part of said subject to which said composition has distributed.