Molecular imaging of cancer cells in vivo

Patent metadata

Field	Value
Publication number	US-10406248-B2
Application number	US-201214240305-A
Country	US
Kind code	B2
Filing date	Sep 5, 2012
Priority date	Sep 10, 2011
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

Cellular targets on cancer cells have been identified that can be used with targeted molecular imaging to detect the cancer cells in vivo. Non-invasive methods for detecting cancer cells, such as metastasized cancer cells, are therefore provided. Also provided are compositions and kits for use in the disclosed methods.

First claim

We claim:

1. A composition comprising a targeting imaging probe that has the structure

wherein R 1 is —CO—R 6 , wherein R 6 is C 12 to C 18 alkyl;
wherein R 2 is —CH 2 —O—CO—R 7 , wherein R 7 is C 12 to C 18 alkyl;
wherein R 3 is R 8 -detectable label, wherein R 8 is acetyl-PEGO- (Ac-PEGO), palmitoyl-, acetyl-6-aminohexanoyl- (Ac-Aha), adapalenoyl-, acetyl-11-aminoundecanoyl- (Ac-Aun), or tretinoyl-;
wherein R 4 is -Gly- D Ser-PEGO-NH 2 , -Gly- D Ser-NH 2 , -Ser-(Lys) 4 -NH 2 , -Gly-Asn-Asn-Asp-Glu-Ser-Asn-Ile-Ser-Phe-Lys-Glu-Lys-NH 2 , -Ser-Arg-Phe-Asp-Glu-Asp-Asp-Leu-Glu-NH 2 , -Gly-Ser-Gln-Asn-Leu-Ala-Ser-Leu-Glu-Glu-NH 2 , or -serine methyl ester; and
wherein R 5 is —S—.

2. The composition of claim 1 , wherein the targeted imaging probe comprises dipalmitoyl-S-glyceryl-L-Cys-Ser-(Lys) 4 (Pam 2 CSK 4 ).

3. The composition of claim 1 , wherein the targeted imaging probe comprises tripalmitoyl-S-glyceryl-L-Cys-Ser-Lys-Lys-Lys-Lys (Pam 3 CSK 4 ).

4. The composition of claim 1 , wherein the targeted imaging probe comprises Ac-PEGO-Dhc(Pam) 2 -Gly-Ser-PEGO-NH 2 (T-02).

5. The composition of claim 1 , wherein the targeted imaging probe comprises Ac-PEGO-Dhc(Pam) 2 -Ser-Arg-Phe-Asp-Glu-Asp-Asp-Leu-Glu-NH 2 (T-03; SEQ ID NO:5).

6. The composition of claim 1 , wherein the targeted imaging probe comprises Ac-PEGO-Dhc(Pam) 2 -Gly-Ser-Gln-Asn-Leu-Ala-Ser-Leu-Glu-Glu-NH 2 (T-05; SEQ ID NO:6).

7. The composition of claim 1 , wherein the detectable label is a near-infrared fluorophore.

8. The composition of claim 7 , wherein the near-infrared fluorophore is IRDye800CW or Europium diethylenetriaminepentaacetic acid (Eu-DTPA).

9. The composition of claim 1 , wherein R 4 is -Gly-Asn-Asn-Asp-Glu-Ser-Asn-Ile-Ser-Phe-Lys-Glu-Lys-NH 2 .

10. A kit comprising two or more targeted imaging probes in two or more containers, wherein at least one of the two or more targeted imaging probes comprises the composition according claim 1 , wherein the detectable label is a near-infrared (NIR) fluorophore.

11. A non-invasive method for in vivo detection of cancer cells in a subject, the method comprising: administering to the subject a targeted imaging probe of claim 1 ; and
imaging the subject with a molecular imaging device to detect the targeted imaging probe in the subject,
wherein detection of the targeted imaging probe in an organ of a subject is an indication of cancer cells in the organ.

12. The method of claim 11 , wherein the molecular imaging device comprises a gamma radiation detector.

13. The method of claim 11 , wherein the targeted imaging probe comprises Ac-PEGO-Dhc(Pam) 2 -Gly-Ser-Gln-Asn-Leu-Ala-Ser-Leu-Glu-Glu-NH 2 (T-05; SEQ ID NO:6).

14. The method of claim 11 , wherein the targeted imaging probe comprises dipalmitoyl-S-glyceryl-L-Cys-Ser-(Lys) 4 (Pam 2 CSK 4 ).

15. The method of claim 11 , wherein the targeted imaging probe comprises tripalmitoyl-S-glyceryl-L-Cys-Ser-Lys-Lys-Lys-Lys (Pam 3 CSK 4 ).

16. The method of claim 11 , wherein the targeted imaging probe comprises Ac-PEGO-Dhc(Pam) 2 -Gly-Ser-PEGO-NH 2 (T-02).

17. The method of claim 11 , wherein the targeted imaging probe comprises Ac-PEGO-Dhc(Pam) 2 -Ser-Arg-Phe-Asp-Glu-Asp-Asp-Leu-Glu-NH 2 (T-03; SEQ ID NO:5).

18. The method of claim 11 , wherein the detectable label is a near-infrared (NIR) fluorophore.

19. The method of claim 11 , wherein the cancer cells are metastasized cancer cells.

20. The method of claim 11 , wherein the cancer cells are pancreatic cancer cells.

21. The method of claim 18 , wherein the near-infrared fluorophore is IRDye800CW or Europium diethylenetriaminepentaacetic acid (Eu-DTPA).

22. The method of claim 11 , wherein R 4 is -Gly-Asn-Asn-Asp-Glu-Ser-Asn-Ile-Ser-Phe-Lys-Glu-Lys-NH 2 .

Assignees

• Morse David L
• Gillies Robert J
• Huynh Amanda
• Vagner Josef
• H Lee Moffitt Cancer Ct & Res
• Univ Arizona

Inventors

• Morse David L
• Gillies Robert J
• Huynh Amanda
• Vagner Josef

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/0021

  the fluorescent group being a small organic molecule · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K49/0056 Primary

  Peptides, proteins, polyamino acids · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title