IMAGING METHODS AND COMPOSITIONS COMPRISING FLUORESCENT DYES ASSOCIATED WITH VIRAL COMPONENTS FOR NERVE IMAGING

• US 20090285762A1
• Filed: 05/14/2009
• Published: 11/19/2009
• Est. Priority Date: 05/14/2008
• Status: Active Grant

• Current Assignee: Stryker Corporation
• Original Assignee: Novadaq Technologies, Inc. (Stryker Corporation)
• Inventors: Flower, Robert W.
• Granted Patent: US 8,361,775 B2
• Time in Patent Office: Days
• US Class Current: 424/9.600
• CPC Class Codes: A61K 35/76 Viruses; Subviral particles; Bacteriophages
• CPC Class Codes: A61K 35/763 Herpes virus
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0034 Indocyanine green, i.e. ICG, cardiogreen
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0043 Fluorescein, used in vivo
• CPC Class Codes: A61K 49/0045 the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: A61K 49/0097 Cells, viruses, ghosts, red blood cells, viral vectors, used for imaging or diagnosis in vivo

Abstract

Disclosed herein are compositions and methods for imaging nerve cells. The composition comprises a fluorescent dye; and a viral component selected from a neurotropic, replication-defective virus, a viral protein of a neurotropic virus, and a capsid of a neurotropic virus. Although the fluorescent dye in itself cannot penetrate nerve cells, the fluorescent dye is bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.

Claims

1. A composition comprising:

a fluorescent dye; and

a viral component selected from a neurotropic, replication-defective virus, a viral protein of a neurotropic virus, and a capsid of a neurotropic virus,

wherein the fluorescent dye is bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.

2. The composition of claim 1, wherein the dye is selected from indocyanine green, infracyanine green, green fluorescent dye, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, fluorescamine, Rose Bengal, trypan blue, fluoro-gold, 3-indocyanine-green-acyl-1,3-thiazolidine-thione, green fluorescent protein, red fluorescent protein, yellow fluorescent protein, blue fluorescent protein and other fluorescent proteins.

3. The composition of claim 2, wherein the dye is indocyanine green.

4. The composition of claim 1, wherein the viral component is a neurotropic, replication-defective virus.

5. The composition of claim 4, wherein the virus is herpes virus or a mutant or variant thereof.

6. The composition of claim 5, wherein the herpes virus is HSV-2.

7. The composition of claim 4, wherein the virus is herpes varicellae.

8. The composition of claim 4, wherein the virus comprises HSV-2 ICP10Δ

RR.

9. The composition of claim 4, wherein the virus is rendered replication-defective by UV-inactivation, mutation, chemical treatment, or heat treatment.

10. The composition of claim 4, wherein the replication-defective virus is selected from an attenuated virus, a mutated virus, and a vaccine.

11. A vaccine, comprising:

a fluorescent dye; and

a viral component selected from a neurotropic virus, a viral protein of a neurotropic virus, and a capsid of a neurotropic virus,

wherein the fluorescent dye is bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.

12. A method of making a composition, comprising:

combining a fluorescent dye with a viral component selected from a neurotropic, replication-defective virus, a viral protein of a neurotropic virus, and a capsid of a neurotropic virus,

allowing the fluorescent dye to be bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.

13. The method of claim 12, wherein the viral component is a neurotropic, replication-defective virus.

14. The method of claim 13, wherein the virus is rendered replication-defective by mutation, UV radiation, chemical treatment, or heat treatment.

15. A method for reducing the risk of iatrogenic injury to a subject during a surgical procedure, comprising:

(a) administering a composition to the subject, the composition comprising;

a fluorescent dye; and

a viral component selected from a neurotropic, replication-defective virus, a viral protein of a neurotropic virus, and a capsid of a neurotropic virus,

wherein the fluorescent dye is bound to the viral component to form a dye/viral component complex;

(b) allowing the dye/viral component complex to penetrate nerve cells;

(c) applying a sufficient amount of radiant energy to the subject such that the dye fluoresces;

(d) intraoperatively obtaining a fluorescence image of the subject; and

(e) observing the fluorescence image to view one or more nerves in the subject.

16. The method of claim 15, wherein the fluorescent dye is selected from indocyanine green, infracyanine green, green fluorescent dye, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, fluorescamine, Rose Bengal, trypan blue, fluoro-gold, 3-indocyanine-green-acyl-1,3-thiazolidine-thione, green fluorescent protein, red fluorescent protein, yellow fluorescent protein, blue fluorescent protein and other fluorescent proteins.

17. The method of claim 16, wherein the fluorescent dye is indocyanine green.

18. The method of claim 15, wherein the composition comprises replication-defective herpes virus.

19. The method of claim 18, wherein the herpes virus is HSV-2.

20. The method of claim 18, wherein the replication-defective virus comprises HSV-2 ICP10Δ

RR.

21. A method for diagnosing a nerve condition, comprising:

(a) administering a composition to the subject, the composition comprising;

a fluorescent dye; and

a viral component selected from a neurotropic, replication-defective virus, a viral protein of a neurotropic virus, and a capsid of a neurotropic virus,

wherein the fluorescent dye is bound to the viral component to form a dye/viral component complex;

(b) allowing the dye/viral component complex to penetrate nerve cells;

(c) applying a sufficient amount of radiant energy to the subject such that the dye fluoresces;

(d) intraoperatively obtaining a fluorescence image of the subject; and

(e) observing the fluorescence image to determine whether the nerve is transected.