Targeting peptides and methods of use

Patent metadata

Field	Value
Publication number	US-10124073-B2
Application number	US-201515502160-A
Country	US
Kind code	B2
Filing date	Aug 4, 2015
Priority date	Aug 4, 2014
Publication date	Nov 13, 2018
Grant date	Nov 13, 2018

Abstract

A compound includes at least one targeting peptide coupled to a detectable moiety. The targeting peptide binds to EDB-FN or EDA-FN and includes at least one of amino acid sequence selected from the group consisting of SEQ ID NOs: 1-30.

First claim

Having described the invention, the following is claimed:

1. A molecular probe for use in detecting, monitoring, and/or imaging cancer cells and/or cancer cell aggressiveness, the molecular probe comprising:
at least one targeting peptide coupled to a detectable moiety, the targeting peptide binding to EDB-FN or EDA-FN and comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30.

2. The probe of claim 1 , the detectable moiety comprising an imaging agent and the probe being detectable upon administration to a subject by at least one of gamma imaging, positron emission tomography (PET) imaging, computer tomography (CT) imaging, magnetic resonance imaging, near infrared imaging, or fluorescent imaging.

3. The probe of claim 1 , the detectable moiety including at least one of an optical dye, MRI contrast agent, a PET agent, a SPECT agent, a CT contrast agent, radiolabel, or an ultrasound contrast agent.

4. The probe of claim 1 , the at least one targeting peptide being covalently linked to the detectable moiety.

5. The probe of claim 1 , further comprising a linker that couples the targeting peptide to the detectable moiety.

6. The probe of claim 5 , wherein the linker is a peptide linker or polymer linker.

7. A method comprising:
contacting a tissue of a subject with a molecular probe comprising at least one targeting peptide coupled to a detectable moiety, the targeting peptide binding to EDB-FN or EDA-FN and comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30; and
detecting the molecular probes in the tissue of the subject.

8. The method of claim 7 , determining the location and/or distribution of cancer cells in the tissue by detecting the molecular probes.

9. The method of claim 7 , wherein the contacting step is in vivo, ex vivo, or in vitro.

10. The method of claim 7 , the detectable moiety comprising an imaging agent and the probe being detectable upon administration to the subject by at least one of gamma imaging, positron emission tomography (PET) imaging, computer tomography (CT) imaging, magnetic resonance imaging, near infrared imaging, or fluorescent imaging.

11. The method of claim 7 , the detectable moiety including at least one of an optical dye, MRI contrast agent, a PET agent, a SPECT agent, a CT contrast agent, radiolabel, or an ultrasound contrast agent.

12. The method of claim 7 , the at least one targeting peptide being covalently linked to the detectable moiety.

13. The method of claim 7 , further comprising a linker that couples the targeting peptide to the detectable moiety.

14. The method of claim 13 , wherein the linker is a peptide linker or polymer linker.

15. The method of claim 7 , the probe being systemically administered to a subject having or suspected of having cancer.

16. The method of claim 15 , the cancer comprising at least one of breast cancer, liver cancer, stomach cancer, colon cancer, pancreatic cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, testicular cancer, glioblastoma, sarcoma, bone cancer, brain cancer, head and neck cancers, or skin cancer.

17. The method of claim 7 , the subject having cancer and the probe being administered to the tissue of the subject to determine cancer aggressiveness.

18. A method of detecting cancer cells in a subject having or suspected of having cancer, the method comprising:
administering to the subject a molecular probe comprising at least one targeting peptide coupled to a detectable moiety, the targeting peptide binding to EDB-FN or EDA-FN and comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30; and
detecting the molecular probes in the subject to determine the location and/or distribution of the cancer cells in the subject.

19. The method of claim 18 , the detectable moiety comprising an imaging agent and the probe being detectable upon administration to the subject by at least one of gamma imaging, positron emission tomography (PET) imaging, computer tomography (CT) imaging, magnetic resonance imaging, near infrared imaging, or fluorescent imaging.

20. The method of claim 18 , the detectable moiety including at least one of an optical dye, MRI contrast agent, a PET agent, a SPECT agent, a CT contrast agent, radiolabel, or an ultrasound contrast agent.

21. The method of claim 18 , the probe being systemically administered to a subject having or suspected of having cancer.

22. The method of claim 18 , the cancer comprising at least one of breast cancer, liver cancer, stomach cancer, colon cancer, pancreatic cancer, ovarian cancer, lung cancer, kidney cancer, prostate cancer, testicular cancer, glioblastoma, sarcoma, bone cancer, brain cancer, head and neck cancers, or skin cancer.

Assignees

• Univ Case Western Reserve

Inventors

• Lu Zheng-Rong
• Han Zheng
• Zhu Hui

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• A61K51/082

  the peptide being a RGD-containing peptide · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• A61K49/0032

  Methine dyes, e.g. cyanine dyes · CPC title

• A61K49/0056 Primary

  Peptides, proteins, polyamino acids · CPC title