Paramagnetic polymerized protein microspheres and methods of preparation thereof

• US 6,797,257 B2
• Filed: 10/12/2001
• Issued: 09/28/2004
• Est. Priority Date: 06/26/2001
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Watkin, Kenneth L., McDonald, Michael A.
• Primary Examiner(s): Hartley, Michael G.
• Application Number:
  US09/976,746
• Publication Number:
  US 20030003054A1
• Time in Patent Office: 1,082 Days
• Field of Search: 424/9.3, 424/9.32, 424/9.31, 424/9.322, 424/9.323, 424/9.4, 424/9.42, 424/9.5, 424/9.51, 424/9.52, 424/489
• US Class Current: 424/9.32
• CPC Class Codes: A61K 41/009 Neutron capture therapy, e.g. using uranium or non-boron material
• CPC Class Codes: A61K 49/1821 coated or functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 49/225 Microparticles, microcapsules gas-filled to be classified in A61K49/223
• CPC Class Codes: A61K 9/5052 Proteins, e.g. albumin
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention relates to a composition that includes gadolinium particles encapsulated in microsphere shells. The composition is suitable for use as a contrast agent with a plurality of imaging modalities, including, for example, ultrasound, magnetic resonance imaging, and computed temography. The compositions also are useful for therapeutic applications, including neutron capture therapy.

Claims

1. An imaging composition for obtaining images by medical diagnostic imaging procedures comprising in combination:

one or more particles comprising gadolinium oxide; and

one or more microsphere shells including a protein comprising albumin each shell having an inner wall and an outer wall and encapsulating the one or more particles between the inner and outer walls, one or more said microsphere shells having an average diameter of no more than about 70,000 Å

,

the composition effective in a single dose without administration of additional doses of an imaging composition in an in vivo administration for obtaining images using more than one imaging modality.

2. A composition in accordance with claim 1, wherein said particles are spherical.

3. A composition in accordance with claim 2, wherein said particles have diameters of no more than about 450 angstroms.

5. A composition in accordance with claim 1, wherein said particles have diameters of between about 50 Å

and about 20.000 Å

.

6. A composition in accordance with claim 5, wherein said particles have diameters of between about 50 Å

and about 750 Å

.

7. A composition in accordance with claim 6, wherein said particles have diameters of between about 200 Å

and about 400 Å

.

8. A composition in accordance with claim 1, wherein said microsphere shells have an average diameter between about 5,000 Å

and about 40,000 Å

.

9. A composition in accordance with claim 1, wherein one or more particles are pegylated.

10. A composition in accordance with claim 9, wherein said particles have diameters of between about 200 Å

and about 400 Å

.

11. A composition in accordance with claim 1, wherein the albumin is selected from the group consisting of bovine serum albumin, human serum albumin and combinations thereof.

4. A method of obtaining images using medical diagnostic imaging modalities comprising:

administering in vivo an imaging composition comprising a suspension of microsphere shells including a protein comprising albumin and having inner and outer walls encapsulating between the inner and outer walls one or more particles comprising gadolinium oxide, the imaging composition administered in an amount effective for obtaining images using two or more imaging modalities;

obtaining a first image using a first imaging modality selected from the group consisting of ultrasound, magnetic resonance and computed tomography; and

obtaining a second image using a second imaging modality different from the first imaging modality without administration of an additional amount of the imaging composition or an amount of another imaging composition to obtain the second image.

12. The method in accordance with claim 4, wherein said particles have diameters of between about 50 Å

and about 20,000 Å

.

13. The method in accordance with claim 12, wherein said particles have diameters of between about 50 Å

and about 750 Å

.

14. The method in accordance with claim 13, wherein said particles have diameters of between about 200 Å

and about 400 Å

.

15. The method in accordance with claim 14, wherein said microsphere shells have an average diameter between about 5,000 Å

and about 40,000 Å

.

16. The method in accordance with claim 4, wherein one or more particles are pegylated.

17. The method in accordance with claim 16, wherein said particles have diameters of between about 200 Å

and about 400 Å

.

18. The method in accordance with claim 14, wherein the albumin is selected from the group consisting of bovine serum albumin, human serum albumin and combinations thereof.