Image-guided therapy of myocardial disease: composition, manufacturing and applications

• US 8,440,168 B2
• Filed: 12/19/2008
• Issued: 05/14/2013
• Est. Priority Date: 03/24/2008
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Yang, David J., Oh, Chang-Sok, Kohanim, Saady, Yu, Dong-Fang, Mendez, Richard, Kim, E. Edmund
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US12/340,338
• Publication Number:
  US 20090238756A1
• Time in Patent Office: 1,607 Days
• Field of Search: 424/9.2, 424/94.6, 424/489, 424/490, 424/494, 424/1.65, 424/9.36, 424/9.42, 424/9.5, 514/46, 514/171, 514/188, 514/186, 514/184, 514/352
• US Class Current: 424/1.65
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07C 235/34 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07F 13/00 Compounds containing elements of Groups 7 or 17 of the Periodic Table
• CPC Class Codes: C07F 13/005 Compounds without a metal-carbon linkage

Abstract

Compositions and methods for imaging and for chemotherapy and radiotherapy are disclosed. More particularly, the invention concerns agents comprising a targeting moeity comprising a beta-adrenergic receptor targeting compound conjugated or embedded with ethylenediamine. The present invention also concerns methods of application of such agents for imaging and treatment of cardiovascular diseases, and kits for preparing a radiolabeled therapeutic or diagnostic agent.

Claims

1. An imaging agent comprising a beta-adrenergic receptor ligand conjugated to a terminal nitrogen of a polyethylene amine derived chelator.

2. The agent of claim 1, wherein the beta-adrenergic receptor ligand is selected from the group consisting of AC 623, acebutolol, alprenolol, amosulalol, arotinolol, atenolol, befunolol, betaxolol, bevantolol, bisoprolol, bopindolol, bucindolol, bucumolol, bufetolol, bufuralol, bunitrolol, bupranolol, butidrine hydrocholoride, butofilolol, carazolol, carteolol, carvedilol, celiprolol, cetamolol, cloranolol, dilevalol, esmolol, indenolol, labetalol, landiolol, levobunolol, mepindolol, metipranolol, metoprolol, moprolol, nadolol, nadoxolol, nebivolol, nifenalol, nipradilol, oxprenolol, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, sulfinalol, talinolol, tertatolol, tilisolol, timolol, toliprolol, xibenolol and combinations thereof.

3. The agent of claim 2, wherein the beta-adrenergic receptor ligand is esmolol.

4. The agent of claim 1, further comprising a valent metal ion chelated to the polyethylene amine derived chelator.

5. The agent of claim 4, wherein the valent metal ion is selected from the group consisting of Gd, Fe, Tc-99m, Cu-60, Cu-61, Cu-62, Cu-64, Cu-67, In-111, Tl-201, Ga-67, Ga-68, As-72, Re-186, Re-188, Ho-166, Y-90, Sm-153, Sr-89, Bi-212, and Bi-213.

6. The agent of claim 4, wherein the valent metal ion is selected from the group consisting of a therapeutic metal selected from the group consisting of arsenic, cobolt, copper, selenium, thallium, and platinum.

7. The agent of claim 1, further comprising an imaging moiety.

8. The agent of claim 7, wherein the imaging moiety is a contrast media.

9. The agent of claim 8, wherein the contrast media is selected from the group consisting of a CT contrast media, an MRI contrast media, and optical contrast media, and an ultrasound contrast media.

10. A method of imaging a subject having a cardiovascular disease, comprising:

a) administering to the subject a composition comprising an effective amount of an agent in accordance with claim 1; and

b) performing imaging using a first imaging modality by detecting a first signal from said agent; and

c) performing imaging using a second imaging modality by detecting a second signal from said agent,

wherein the first imaging modality and the second imaging modality are performed either concurrently or consecutively.

11. The method of claim 10, wherein the first imaging modality and the second imaging modality are each selected from the group consisting of PET, CT, SPECT, MRI, optical imaging, and ultrasound.

12. The method of claim 10, wherein the first imaging modality and the second imaging modality are identical.

13. A kit for preparing a diagnostic or therapeutic composition comprising a sealed container including a predetermined quantity of an agent in accordance with claim 1.

14. The kit of claim 13, further comprising a radionuclide selected from the group consisting of Tc-99m, Cu-60, Cu-61, Cu-62, Cu-67, In-111, Tl-201, Ga-67, Ga-68, As-72, Re-188, Ho-166, Y-90, Sm-153, Sr-89, Gd-157, Bi-212, and Bi-213.

15. The agent of claim 1, wherein the polyethylene amine derived chelator is a diethylenetriamine, triethylenetetramine, tetraethylenepentamine, pentaethylenehexamine or ethylenediamine chelator.

16. The method of claim 15, wherein the polyethylene amine derived chelator is a ethylenediamine chelator.

17. The agent of claim 16, wherein the beta-adrenergic receptor ligand is esmolol.