IMAGING METHODS AND COMPOSITIONS COMPRISING FLUORESCENT DYES ASSOCIATED WITH VIRAL COMPONENTS FOR NERVE IMAGING
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.
1 .- 11 . (canceled)
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 herpesvirus.
19 . The method of claim 18 , wherein the herpesvirus is HSV-2.
20 . The method of claim 18 , wherein the replication-defective virus comprises HSV-2 ICP10ΔRR.
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.