Bioluminescent endoscopy methods and compounds

• US 8,431,698 B2
• Filed: 08/29/2008
• Issued: 04/30/2013
• Est. Priority Date: 08/29/2007
• Status: Active Grant

• Current Assignee: Biolume, Inc.
• Original Assignee: Biolume, Inc.
• Inventors: Neff, Philip T., Murphy, Randall B., Bryan, Bruce
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): Donohue, Sean R
• Application Number:
  US12/201,680
• Publication Number:
  US 20090081129A1
• Time in Patent Office: 1,705 Days
• Field of Search: None
• US Class Current: 544/350
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/763 Bioluminescence

Abstract

Bioluminescent endoscopy methods and compounds, wherein an anatomical object is examined by means of filling, perfusing, intubating, injecting, or otherwise administering a solution containing a bioluminescent substance or a mixture of luciferin and luciferase which produces bioluminescence, wherein a color or monochrome image of the object is constituted using the images and information based on bioluminescent emitted by the bioluminescent substance. Procedures are demonstrated which allow bioluminescent solutions to be perfused into certain tissue regions, such as but not limited to the common biliary duct, genitourinary tract, gastro-intestinal tract, cardiovascular system and lymphatic system wherein said structures may be conveniently visualized during surgery to avoid damage to these structures. Such images may also be combined with visual light images. Methods of detection of cancer cells using bioluminescence are provided. Preferred embodiments disclosed include membrane permeant coelenterazine analogs.

Claims

1. A method of using a bioluminescence system to illuminate internal body structures of a subject comprising:

administering to the subject or one or more portions thereof at least one coelenterazine analog selected from the group consisting of Structure II,

Structure II

2. The method of claim 1 wherein said method is used for illumination of one or more components of a circulatory system, nervous system, body organ, or lymphatic system of the subject.

3. The method of claim 2 wherein said one or more components is a hollow viscous.

4. The method of claim 1 wherein the bioluminescence system is used post-operatively to inspect the body structures.

5. The method of claim 1, wherein the step of administering comprises

perfusing, administering, injecting, superfusing, infiltrating, or otherwise applying the at least one coelenterazine analog selected from the group consisting of Structure II,

Structure II

6. The method of claim 5, wherein said one or more images are obtained in dim visible light conditions.

7. The method of claim 5, wherein said one or more images are color or monochrome images.

8. The method of claim 5, wherein the step of visualizing and/or imaging further comprises obtaining one or more images of said object with visible light illumination, said visible light comprising visible light in a wavelength range which does not include light in a wavelength range of light emitted by the bioluminescence system.

9. The method of claim 8, wherein said images are obtained with a camera system sensitive to the wavelength of emission of the visible light illumination.

10. The method of claim 9, wherein the visible light illumination is a red light illumination.

11. The method of claim 9, further comprising:

comparing said image with bioluminescent illumination with said image with visible light illumination.

12. The method of claim 11 further comprising a step of switching between said image with bioluminescent illumination with said image with visible light illumination.

13. The method of claim 5, wherein the object comprises a component of a animal, avian or human circulatory system, nervous system, body organ, or lymphatic system.

14. The method of claim 13, wherein the object comprises gallbladder, ureter, lung, heart, or intestine.

15. The method of claim 5, wherein said images are obtained by an endoscopic examination of the object.

16. The method of claim 9, wherein said images are obtained by an endoscopic examination of the object.

17. A method of using a bioluminescence system post-operatively to illuminate a surgical tissue in order to inspect the surgical tissue comprising:

administering to the subject or one or more portions thereof a coelenterazine analog selected from the group consisting of Structure II,

Structure II

18. A method of examining an animal, avian or human object, comprising the steps of:

perfusing, administering, injecting, superfusing, infiltrating, or otherwise applying a bioluminescent generating system comprising a coelenterazine analog selected from the group consisting of Structure II,

Structure II

19. The method of claim 18, wherein said one or more images are obtained in dim visible light conditions.

20. The method of claim 18, wherein said one or more images are color or monochrome images.

21. The method of claim 18, further comprising obtaining one or more images of said object with visible light illumination, said visible light comprising visible light in a wavelength range which does not include light in a wavelength range of light emitted by the bioluminescent generating system.

22. The method of claim 21, wherein said images are obtained with a camera system sensitive to the wavelength of emission of the visible light illumination.