Organic anion transporting peptide-based cancer imaging and therapy

• US 10,307,489 B2
• Filed: 12/22/2015
• Issued: 06/04/2019
• Est. Priority Date: 12/22/2014
• Status: Active Grant

• Current Assignee: Da Zen Theranostics, Inc.
• Original Assignee: Da Zen Theranostics, Inc.
• Inventors: Chung, Leland W. K.
• Primary Examiner(s): Hartley, Michael G.
• Assistant Examiner(s): Perreira, Melissa J
• Application Number:
  US15/538,359
• Publication Number:
  US 20170360945A1
• Time in Patent Office: 1,260 Days
• Field of Search: None
• CPC Class Codes: A61K 47/558 the modifying agent being a chemiluminescent acceptor
• CPC Class Codes: A61K 49/0017 Fluorescence in vivo
• CPC Class Codes: A61K 51/0446 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C09B 23/0066 the polymethine chain being part of a carbocyclic ring,(e.g. benzene, naphtalene, cyclohexene, cyclobutenene-quadratic acid)
• CPC Class Codes: G01N 33/57407 Specifically defined cancers

Abstract

A dye-drug conjugate for preventing, treating, or imaging cancer having the following structure:

wherein R₁ and R₂ are independently selected from the group consisting of —H, alkyl, alkyl-sulphonate, alkylcarboxylic, alkylamino, aryl, —SO₃H, —PO₃H, —OH, —NH₂, and -halogen; wherein Y₁ and Y₂ is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylsulphonate, alkylcarboxylic, alkylamino, ω-alkylaminium, ω-alkynyl, PEGyl, PEGylcarboxylate, ω-PEGylaminium, ω-acyl-NH, ω-acyl-lysinyl-, ω-acyl-triazole, ω-PEGylcarboxyl-NH—, ω-PEGylcarboxyl-lysinyl, and ω-PEGylcarboxyl-triazole; wherein X is selected from the group consisting of a hydrogen, halogen, CN, Me, NH₂, SH and OH; and R₃ and R₄ are independently a hydrogen, a therapeutic agent, or an imaging moiety, wherein the therapeutic agent is selected from the group consisting of a platinum-based therapeutic agent, a small molecule therapeutic agent, a peptide, a protein, a polymer, an siRNA, a microRNA, and a nanoparticle, wherein the imaging is a radio-isotope selected from the group consisting of F18, I-125, I-124 I-123, I-131, and small molecule labeled with any of these isotopes, or wherein the imaging moiety is a chelator-complexed radioactive isotope, wherein the radioactive isotope is selected from the group consisting of Cu-64, In-111, Tc-99m, Ga-68, Lu-177, Zo-89, Th-227 and Gd-157.

Claims

1. A method for diagnosing, detecting or treating a brain tumor, or a brain metastase of a cancer, comprising the step of administering to a subject suffering or suspected to suffer from a brain tumor or brain metastase, an effective amount of a dye-drug conjugate, and optionally imaging the subject or a sample of the subject, wherein the dye-drug conjugate comprises the following structure:

2. The method according to claim 1, wherein the cancer is one selected from the group consisting of prostate cancer, breast cancer, renal cancer, pancreatic cancer, lung cancer, and hepatic cancer.

3. The method according to claim 1, wherein one of R₃ and R₄ is hydrogen and the other one of R₃ and R₄ is gemcitabine conjugated to one of Y₁ and Y₂.

4. The method according to claim 1, wherein one of R₃ and R₄ is hydrogen and the other one of R₃ and R₄ is gemcitabine connected to an alkylcarboxylic Y₁ or Y₂ moiety.

5. The method according to claim 1, wherein one of R₃ and R₄ is hydrogen and the other one of R₃ and R₄ is gemcitabine connected to an alkylamino Y₁ or Y₂ moiety.

6. The method according to claim 1, wherein one of R₃ and R₄ is hydrogen and the other one of R₃ and R₄ is a platin-based therapeutic agent conjugated to Y₁ and Y₂.

7. The method according to claim 1, wherein one of R₃ and R₄ is hydrogen and the other one of R₃ and R₄ is a platin-based therapeutic agent connected to an alkylcarboxylic Y₁ or Y₂ moiety.

8. The method according to claim 1, wherein one of R₃ and R₄ is hydrogen and the other one of R₃ and R₄ is a platin-based therapeutic agent connected to an alkylamino Y₁ or Y₂ moiety.

9. The method according to claim 6, wherein the platin-based therapeutic agent is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin and one or more derivative thereof.

10. The method according to claim 7, wherein the platin-based therapeutic agent is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin and one or more derivative thereof.

11. The method according to claim 8, wherein the platin-based therapeutic agent is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin and one or more derivative thereof.

12. The method according to claim 1, wherein the dye-drug conjugate is selected from one or more of the compounds designated DZ-2, DZ-3, DZ-6, DZ-7, as depicted in the formulae below:

13. The method according to claim 1, wherein the dye-drug conjugate is DZ-2.

14. The method according to claim 1, wherein the dye-drug conjugate is DZ-3.

15. The method according to claim 1;

wherein the dye-drug conjugate is DZ-6.

16. The method according to claim 1, wherein the dye-drug conjugate is DZ-7.

17. A method for diagnosing, detecting or treating a brain tumor, or a brain metastase of a cancer, comprising the step of administering to a subject suffering or suspected to suffer from a brain tumor or brain metastase, or to a sample of the subject, an effective amount of a dye-drug conjugate, and optionally imaging the subject or sample of the subject, wherein the dye-drug conjugate comprises the following structure:

18. The method according to claim 17, wherein the cancer is one selected from the group consisting of prostate cancer, breast cancer, renal cancer, pancreatic cancer, lung cancer, and hepatic cancer.