Radioactive material for inhibiting cancer and preparation method thereof

• US 20090324496A1
• Filed: 06/27/2008
• Published: 12/31/2009
• Est. Priority Date: 06/27/2008
• Status: Abandoned Application

• Current Assignee: ATOMIC ENERGY COUNCIL-INSTITUTE OF NUCLEAR ENERGY RESEARCH
• Original Assignee: ATOMIC ENERGY COUNCIL-INSTITUTE OF NUCLEAR ENERGY RESEARCH
• Inventors: Yeh, Yuen-Han, Sheng, Chang-Mau, Wu, Yu-Lung, Liu, Hsiu-Wen, Luo, Tasi-Yueh, Cheng, Shan-Yun, TANG, I-Chung, Lin, Wuu-Jyh
• Application Number:
  US12/147,733
• Publication Number:
  US 20090324496A1
• Time in Patent Office: Days
• US Class Current: 424/1.69
• CPC Class Codes: A61K 51/1051 the tumor cell being from breast, e.g. the antibody being herceptin
• CPC Class Codes: A61K 51/1093 conjugates with carriers being antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A radioactive material for inhibiting cancer and a preparation method thereof are disclosed. The radioactive material for inhibiting cancer is M-SOCTA-Z and M is a radioactive nuclide such as ¹⁸⁸Re or ^99mT while Z is protein or peptides having amino acid with NH or NH2 group. The preparation method of the radioactive material for inhibiting cancer includes steps of: reacting SOCTA with protein or peptide. Ester (—COOR) in SOCTA reacts with amines (—NH, —NH2) in protein or peptide to form peptide bond. Thus SOCTA-protein or SOCTA-peptide complex is produced. Then these SOCTA-protein complex reacts with radioactive nuclide M so as to generate M-SOCTA-protein or M-SOCTA-peptide. In an embodiment of the present invention, monoclonal antibody Herceptin is applied to bind with SOCTA and in combination with radiation-based therapy, effects of cancer treatment (such as breast cancer) are enhanced.

Claims

1. A radioactive material for inhibiting cancer comprising:

wherein M is selected from a group of ¹⁸⁸Re and ^99mTc while Z is selected from a group consisting of protein having amino acid with amino group and peptide having amino acid with amino group.

2. The radioactive material for inhibiting cancer as claimed in claim 1, wherein the amino group is selected from a group of —

NH and —

NH₂.

3. The radioactive material for inhibiting cancer as claimed in claim 1, wherein the amino acid with amino group is selected from a group consisting of Lysine, Arginine, Glutamine, and Asparagine.

4. The radioactive material for inhibiting cancer as claimed in claim 1, wherein the protein having amino acid with amino group is a monoclonal antibody.

5. The radioactive material for inhibiting cancer as claimed in claim 4, wherein the monoclonal antibody is Herceptin.

6. A preparation method of the radioactive material for inhibiting cancer comprising the steps of:

reacting SOCTA with protein or peptide to form SOCTA complex while the SOCTA complex is SOCTA-protein complex or SOCTA-peptide complex; and

reacting the SOCTA complex with material M to form M-SOCTA complex while M is selected from a group of ¹⁸⁸Re and ^99mTc, and the M-SOCTA complex is selected from a group consisting of ¹⁸⁸Re-SOCTA-protein complex, ¹⁸⁸Re-SOCTA-peptide complex, ^99mTc-SOCTA-protein complex, and ^99mTc-SOCTA-peptide complex;

wherein the M-SOCTA complex is a radioactive material for inhibiting cancer.

7. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 6, wherein the protein is a monoclonal antibody Herceptin, the SOCTA-protein complex is SOCTA-Herceptine complex and the M-SOCTA-protein complex is ¹⁸⁸Re-SOCTA-Herceptine complex.

8. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein in the step of reacting the SOCTA with the monoclonal antibody Herceptin to form SOCTA-Herceptin complex, a coupling reaction occurs between the SOCTA and the Herceptin.

9. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein in the step of reacting the SOCTA with the monoclonal antibody Herceptin to form SOCTA-Herceptin complex, the method further comprising a step of dissolving SOCTA in dimethylformamide (DMF) solution as well as dissolving the Herceptin in HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer.

10. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein in the step of reacting the SOCTA with the monoclonal antibody Herceptin to form SOCTA-Herceptin complex, the molecular ratio of SOCTA to Herceptin is 1:

1.

11. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein the step of reacting the SOCTA with the monoclonal antibody Herceptin to form SOCTA-Herceptin complex is carried out at room temperature.

12. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein the step of reacting the SOCTA with the monoclonal antibody Herceptin to form SOCTA-Herceptin complex further comprising a step of dialysis.

13. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein in the step of reacting the SOCTA-Herceptin complex with the ¹⁸⁸Re to form the ¹⁸⁸Re-SOCTA-Herceptin, the ¹⁸⁸Re is provided by ¹⁸⁸Re perrhenate solution.

14. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein the step of reacting the SOCTA-Herceptin complex with the ¹⁸⁸Re to form the ¹⁸⁸Re-SOCTA-Herceptin further comprising two-stage steps of:

reacting the ¹⁸⁸Re, glucoheptonate and stannous chloride (SnCl₂) with one another to produce ¹⁸⁸Re-Glucoheptonate; and

reacting the ¹⁸⁸Re-Glucoheptonate with SOCTA-Herceptin to get the ¹⁸⁸Re-SOCTA-Herceptin.

15. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 14, wherein in the step of reacting the ¹⁸⁸Re, glucoheptonate and stannous chloride (SnCl₂) with one another to produce ¹⁸⁸Re-Glucoheptonate, weight ratio of the glucoheptonate to the stannous chloride ranges from 1.5:

1 to 5.4;

1

16. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 15, wherein in the step of reacting the ¹⁸⁸Re, glucoheptonate and stannous chloride (SnCl₂) with one another to produce ¹⁸⁸Re-Glucoheptonate, weight ratio of the glucoheptonate to the stannous chloride is 1.6:

1.

17. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 14, wherein in the step of reacting the ¹⁸⁸Re, glucoheptonate and stannous chloride (SnCl₂) with one another to produce ¹⁸⁸Re-Glucoheptonate, the glucoheptonate is a chelating agent.

18. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 14, wherein the step of reacting the ¹⁸⁸Re-Glucoheptonate with SOCTA-Herceptin to get the ¹⁸⁸Re-SOCTA-Herceptin is taken place at room temperature or 37 degrees Celsius.

19. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 7, wherein the step of reacting the SOCTA-Herceptin complex with the ¹⁸⁸Re to form the ¹⁸⁸Re-SOCTA-Herceptin comprising a one-stage step of:

reacting ¹⁸⁸Re, glucoheptonate, stannous chloride (SnCl₂), and SOCTA-Herceptin with one another to produce ¹⁸⁸Re-SOCTA-Herceptin.

20. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 19, wherein in the one-stage step of reacting ¹⁸⁸Re, glucoheptonate, stannous chloride (SnCl₂), and SOCTA-Herceptin with one another to produce ¹⁸⁸Re-SOCTA-Herceptin, weight ratio of the glucoheptonate to the stannous chloride is from 1.5:

1 to 5.4;

1

21. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 20, wherein in the one-stage step of reacting ¹⁸⁸Re, glucoheptonate, stannous chloride (SnCl₂), and SOCTA-Herceptin with one another to produce ¹⁸⁸Re-SOCTA-Herceptin, weight ratio of the glucoheptonate to the stannous chloride is 1.6:

1.

22. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 19, wherein the one-stage step of reacting ¹⁸⁸Re, glucoheptonate, stannous chloride (SnCl₂), and SOCTA-Herceptin with one another to produce ¹⁸⁸Re-SOCTA-Herceptin is carried out at room temperature or 37°

C.

23. The preparation method of the radioactive material for inhibiting cancer as claimed in claim 6, wherein in the step of reacting SOCTA with protein or peptide to form SOCTA complex, ester (—

COOR) in the SOCTA reacts with amines (—

NH, —

NH2) in the protein or peptide to form peptide bond so as to produce the SOCTA complex.