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Imaging methods and compositions comprising fluorescent dyes associated with viral components for nerve imaging

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Title: Imaging methods and compositions comprising fluorescent dyes associated with viral components for nerve imaging.
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. ...


USPTO Applicaton #: #20120078093 - Class: 600431 (USPTO) - 03/29/12 - Class 600 
Surgery > Diagnostic Testing >Detecting Nuclear, Electromagnetic, Or Ultrasonic Radiation >Detectable Material Placed In Body

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The Patent Description & Claims data below is from USPTO Patent Application 20120078093, Imaging methods and compositions comprising fluorescent dyes associated with viral components for nerve imaging.

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RELATED APPLICATION

This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Prov. App. No. 61/127,659, filed May 14, 2008, and U.S. Prov. App. No. 61/082,981, filed Jul. 23, 2008, the disclosures of which are incorporated herein by reference.

FIELD OF THE INVENTION

Disclosed herein are compositions and methods relating to the field of medical imaging.

BACKGROUND OF THE INVENTION

Iatrogenic nerve injury can result in debilitating loss of function in humans. Common causes of iatrogenic nerve injury include surgical failure, traction or pressure lesions, hematoma, or inadequate positioning of the patient (Fercan Komurcu, MD et al., 2005, Annals of Plastic Surgery, 54(2):135-139).

For example, nerves are often imaged during prostatectomy procedures. By way of background, prostate cancer is the most common type of cancer in American men. One common treatment option is removal of cancerous prostate tissue (i.e., prostatectomy) before the cancer spreads locally and before metastasis. Radical prostatectomy complications include incontinence and impotence. A significant percentage of men undergoing radical prostatectomy procedures become impotent due to injury to the cavernous nerves during the surgery.

The risk of iatrogenic nerve injury may be reduced by avoiding injury to the bundles of nerves that run along the surface of the prostate gland and are needed for an erection. Successful nerve sparing surgery, however, is often difficult to achieve because of the difficulty in distinguishing between the prostate tissue and the innervating nerve tissue.

There exists a need for improved imaging methods and compositions for nerve imaging.

SUMMARY

OF THE INVENTION

Disclosed herein are compositions and methods for imaging nerves. The nerves can be located in different areas of a subject.

Also disclosed herein is the discovery that binding a fluorescent dye to a viral component (e.g., virus, viral proteins, capsids) capable of penetrating nerve axons can form a dye/viral component complex that can penetrate nerve axons, thus allowing improved nerve cell imaging. One embodiment provides 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.

In this and other embodiments disclosed herein, neurotropic, replication-defective viruses can be, for example, attenuated or inactivated viral components that are capable of penetrating nerve cells. In another embodiment, the composition can be a vaccine comprising the 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. Accordingly, another embodiment provides 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.

Another embodiment provides 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.

Another embodiment provides methods for imaging nerves and/or diagnosing nerve abnormalities and/or conditions. The methods include the steps of (a) administering a composition, as disclosed herein, to the subject, (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) intra-operatively obtaining a fluorescence image of the subject. The method can include the step of observing the fluorescence image to view one or more nerves in the subject, or observing the fluorescence image to determine whether one or more nerves is transected.

Accordingly, another embodiment provides 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.

Another embodiment provides 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.

Other embodiments provide a kit containing the compositions disclosed herein along with instructions to use the composition according to one or more of the methods described herein. In other embodiments, the kit includes one or more ingredients, reagents, dyes, viruses, precursors, or other tools that can be used to make the compositions disclosed herein, along with instructions to use the composition according to one or more of the methods described herein.



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stats Patent Info
Application #
US 20120078093 A1
Publish Date
03/29/2012
Document #
13314418
File Date
12/08/2011
USPTO Class
600431
Other USPTO Classes
4352351
International Class
/
Drawings
12


Capsid
Fluorescent Dyes


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