Site specific binding system, imaging compositions and methods

• US 6,821,506 B2
• Filed: 12/28/2001
• Issued: 11/23/2004
• Est. Priority Date: 06/08/1995
• Status: Expired due to Fees

• Current Assignee: Barnes-Jewish Hospital (BJC Health System)
• Original Assignee: Barnes-Jewish Hospital (BJC Health System)
• Inventors: Lanza, Gregory M., Wickline, Samuel A.
• Primary Examiner(s): Hartley, Michael G.
• Application Number:
  US10/036,317
• Publication Number:
  US 20020168320A1
• Time in Patent Office: 1,061 Days
• Field of Search: 424/9.3, 424/9.32, 424/9.321, 424/9.37, 424/9.34, 600/410, 600/420
• US Class Current: 424/9.3
• CPC Class Codes: A61K 49/18 characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
• CPC Class Codes: A61K 49/1812 liposomes, polymersomes, e.g. immunoliposomes
• CPC Class Codes: A61K 51/1217 Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols
• CPC Class Codes: G01N 33/586 Liposomes, microcapsules or cells

Abstract

A method for ligand-based binding of lipid encapsulated particles to molecular epitopes on a surface in vivo or in vitro comprises sequentially administering (a) a site specific ligand activated with a biotin activating agent; (b) an avidin activating agent; and (c) lipid encapsulated particles activated with a biotin activating agent, whereby the ligand is conjugated to the particles through an avidin-biotin interaction and the resulting conjugate is bound to the molecular epitopes on such surface. The conjugate is effective for imaging by x-ray, ultrasound, magnetic resonance or positron emission tomography. Compositions for use in ultrasonic imaging of natural or synthetic surfaces and for enhancing the acoustic reflectivity thereof are also disclosed.

Claims

1. A method for enhanced magnetic resonance imaging of a target tissue in a subject in vivo which method comprises

detecting a magnetic resonance image of said target tissue wherein said target tissue is bound to a ligand specific for said target tissue and wherein said ligand is directly coupled to lipid-coated particles consisting of liquid perfluorocarbon, said coated particles contained in an emulsion,

which method further comprises, prior to said detecting, administering said emulsion to said subject.

2. The method of claim 1, wherein said lipid-coated particles further comprise at least one chemotherapeutic agent or gene therapy delivery system.

3. The method claim 1, wherein said ligand comprises an antibody or fragment thereof, a virus, a receptor agonist or antagonist, a hormone, or a nucleic acid.

4. The method of claim 3, wherein the ligand is an antibody or fragment thereof.

5. A method for enhanced magnetic resonance imaging of a target tissue in a subject in vivo which method comprises administering to said subject an emulsion comprising a ligand specific for said target tissue, said ligand directly coupled to lipid-coated particles consisting of liquid perfluorocarbon, and

detecting a magnetic resonance image of said target tissue wherein said target tissue is bound to said ligand and wherein said ligand is directly coupled to lipid-coated particles contained in said emulsion.

6. The method of claim 5, wherein said lipid-coated particles further comprise at least one chemotherapeutic agent or gene therapy delivery system.

7. The method of claim 5, wherein said ligand comprises an antibody or fragment thereof, a virus, a receptor agonist or antagonist, a hormone, or a nucleic acid.

8. The method of claim 7, wherein the ligand is an antibody or fragment thereof.

9. A method for magnetic resonance imaging of a target tissue in a subject in vivo which method comprises

detecting a magnetic resonance image of said target tissue wherein said target tissue is bound to a ligand specific for said target tissue and wherein said ligand is directly coupled to lipid-coated particles consisting of liquid perfluorocarbon, said coated particles contained in an emulsion,

wherein said subject has been administered said emulsion prior to said detecting.

10. The method of claim 9, wherein said lipid-coated particles further comprise at least one chemotherapeutic agent or gene therapy delivery system.

11. The method of claim 9, wherein said ligand comprises an antibody or fragment thereof, a virus, a receptor agonist or antagonist, a hormone, or a nucleic acid.

12. The method of claim 11, wherein the ligand is an antibody or fragment thereof.