Fluorescent probe for imaging lymph nodes

Patent metadata

Field	Value
Publication number	US-9957392-B2
Application number	US-201615010612-A
Country	US
Kind code	B2
Filing date	Jan 29, 2016
Priority date	May 31, 2010
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

Disclosed is a near-infrared fluorescent imaging agent comprising an indocyanine-based fluorescent dye and a liposome. The near-infrared fluorescent imaging agent of the present invention demonstrates high fluorescence intensity and a long anchoring time in sentinel lymph nodes, thereby making it useful for detecting sentinel lymph nodes in sentinel lymph node navigation surgery. Also disclosed is an indocyanine green derivative that is particularly suitable for use in the near-infrared fluorescent imaging agent of the present invention.

First claim

The invention claimed is:

1. A fluorescent probe for near-infrared fluorescent imaging in sentinel lymphadenography comprising a liposome containing a fluorescent dye having a hexatriene skeletal structure, wherein the fluorescent dye having a hexatriene skeletal structure is a compound represented by chemical formula (V):

wherein, n represents an integer of 4 to 18.

2. The fluorescent probe for near-infrared fluorescent imaging in sentinel lymphadenography according to claim 1 , wherein the particle diameter of the liposome is 100 nm to 300 nm.

3. The fluorescent probe for near-infrared fluorescent imaging in sentinel lymphadenography according to claim 1 , wherein the particle diameter of the liposome is 150 nm to 250 nm.

4. A near-infrared fluorescent imaging agent comprising a compound represented by chemical formula (V):

wherein, n represents an integer of 4 to 18.

5. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the fluorescent probe according to claim 1 and detecting fluorescence generated from the fluorescent probe.

6. A compound represented by chemical formula (V):

wherein, n represents an integer of 4 to 18.

7. A liposome comprising the compound according to claim 6 .

8. The compound according to claim 6 , wherein n is 4.

9. The compound according to claim 6 , wherein n is 6.

10. The compound according to claim 6 , wherein n is 8.

11. The compound according to claim 6 , wherein n is 10.

12. The compound according to claim 6 , wherein n is 18.

13. A liposome comprising the compound according to claim 8 .

14. A liposome comprising the compound according to claim 9 .

15. A liposome comprising the compound according to claim 10 .

16. A liposome comprising the compound according to claim 11 .

17. A liposome comprising the compound according to claim 12 .

18. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the compound according to claim 8 and detecting fluorescence generated from the compound.

19. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the compound according to claim 9 and detecting fluorescence generated from the compound.

20. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the compound according to claim 10 and detecting fluorescence generated from the compound.

21. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the compound according to claim 11 and detecting fluorescence generated from the compound.

22. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the compound according to claim 12 and detecting fluorescence generated from the compound.

23. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the liposome according to claim 13 and detecting fluorescence generated from the liposome.

24. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the liposome according to claim 14 and detecting fluorescence generated from the liposome.

25. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the liposome according to claim 15 and detecting fluorescence generated from the liposome.

26. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the liposome according to claim 16 and detecting fluorescence generated from the liposome.

27. A method for identifying a sentinel lymph node in a subject, comprising administering to the subject the liposome according to claim 17 and detecting fluorescence generated from the liposome.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Hayashi Hideki
• Fujinami Masanori
• Toyota Taro
• Tamura Yutaka
• Aoki Akira
• Muraki Yutaka
• Onoue Kazuki

Classifications

• C09B23/086

  more than five >CH- groups · CPC title

• A61K49/0084

  liposome, i.e. bilayered vesicular structure · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• C07D209/60

  Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles · CPC title

• C09B23/083 Primary

  five >CH- groups · CPC title