Compounds for targeting and imaging infection and inflammation

• US 6,491,893 B1
• Filed: 04/20/2000
• Issued: 12/10/2002
• Est. Priority Date: 01/19/1999
• Status: Expired due to Fees

• Current Assignee: Molecular Insight Pharmaceuticals Incorporated (Lantheus Holdings, Inc.)
• Original Assignee: Biostream, Inc.
• Inventors: Babich, John W.
• Primary Examiner(s): Hartley, Michael G.
• Application Number:
  US09/553,006
• Time in Patent Office: 964 Days
• Field of Search: 424/1.69, 424/1.41, 424/1.85, 424/1.89, 424/9.3, 424/9.34, 424/9.36, 424/9.4, 424/9.5, 424/9.6, 424/9.1, 534/10, 534/14
• US Class Current: 424/1.41
• CPC Class Codes: A61K 47/642 the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
• CPC Class Codes: A61K 51/08 Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals

Abstract

The present invention provides novel agents for specifically targeting and detecting or treating focal sites of infection or inflammation in a subject.

Claims

1. A method of detecting a site of infection or inflammation in a subject comprising the steps of:

a) administering to the subject a diagnostically effective amount of an imaging agent comprising a colony stimulating actor (CSF) and a label, and

b) detecting a sufficient amount of the label as an indication of a site of infection or inflammation.

2. The method of claim 1, wherein the imaging agent is administered intaveneously, subcutaneously, parenterally, intraperitoneally, or intrathecally.

3. The method of claim 1, wherein the CSF is selected from the group consisting of:

granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte colony stimulating factor (M-CSF or CSF-1) and binding fragments thereof.

4. The method of claim 1, wherein the CSF is recombinant.

5. The method of claim 1, wherein the CSF is wildtype.

6. The method of claim 1, wherein the CSF is fully glycosylated.

7. The method of claim 1, wherein the CSF is a full-length protein.

8. The method of claim 1, wherein the CSF is a polypeptide.

9. The method of claim 1, wherein the CSF is a peptide.

10. The method of claim 1, wherein the CSF is human.

11. The method of claim 1, wherein the agent exhibits a target to non-target ratio of at least about 5:

1.

12. The method of claim 1, wherein the agent is stable in vivo.

13. The method of claim 1, wherein the agent substantially localizes to a site of infection or inflammation, whereby a lesion can be delineated, within about 18 hours after administration.

14. The method of claim 1, wherein the agent substantially localizes to a site of infection or inflammation within about 8 hours after administration.

15. The method of claim 1, wherein the label is a radionuclide.

16. The method of claim 1, wherein the radionuclide is selected from the group consisting of ¹²³I, ^99mTc, ¹⁸F, ⁶⁸Ga, ⁶⁴Cu, ⁶²Cu, ⁵⁵Co and ¹¹¹In.

17. The method of claim 16, wherein the radionuclide is ^99mTc.

18. The method of claim 16, wherein the radionuclide is ¹¹¹In.

19. The method of claim 1, wherein the CSF is a component of a fusion protein.

20. The method of claim 1, wherein the infection is caused by a microorganism.

21. The method of claim 20, wherein the microorganism is a bacteria, virus, fungi, or protozoa.

22. The method of claim 21, wherein the microorganism is selected from the group consisting of Escherichia Coli, Enterobacteriaceae sp., Enterococcus sp., Haemophilus influenza, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Plasmodium falciparum, Pseudomonas aeruginosa, Shigella dysenteriae, Staphylococcus aureus, Streptococcus pneumonia, HIV, herpes, hepatitis, and Candida sp.

23. The method of claim 1, wherein the site of inflarmmation is caused by a microbial invasion, autoimnune process, tissue or organ allograft rejection, neoplasia, idiopathic disease, or mechanical trauma.

24. The method of claim 1, wherein the label is detected by a gamma camera. positron emission tomography (PET), single photon emission tomography (SPECT), or magnetic resonance imaging (MRI).

25. The method of claim 1, wherein the subject is a human, rat, mouse, cat, dog, horse, sheep, cow, monkey, avian, or amphibian.

26. The method of claim 1, wherein the label is conjugated to CSF via a chelating agent.

27. The method of claim 26, wherein the chelating agent is selected from the group consisting of diethylene trianine pentaacetic acid (DTPA), ethylene diarine tetraacetic acid (EDTA), dioxirne ligand, functionalized cyclam, N₂S₂ ligand, N₃S ligand, isonitrile, hydrazine, HYNIC (hydrazinonicotinic acid), 2-methylithiolnicotinic acid, and a carboxylate.