Myocardial perfusion imaging during coronary vasodilation with selective adenosine A.sub.2 receptor agonists

• US 6,026,317 A
• Filed: 02/06/1998
• Issued: 02/15/2000
• Est. Priority Date: 02/06/1998
• Status: Expired due to Fees

• Current Assignee: Baylor College of Medicine (Baylor College)
• Original Assignee: Baylor College of Medicine (Baylor College)
• Inventors: Verani, Mario S.
• Primary Examiner(s): Kamm, William E.
• Assistant Examiner(s): Imam, Ali M.
• Application Number:
  US09/020,121
• Time in Patent Office: 739 Days
• Field of Search: 600/431, 600/436, 600/437, 600/420, 600/425, 600/407, 424/9.1-9.8, 250/363.02, 514/45, 514/46
• US Class Current: 600/420
• CPC Class Codes: A61B 6/4258 for detecting non x-ray radiation, e.g. gamma radiation A61B6/037 takes precedence
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: A61K 49/222 characterised by a special physical form, e.g. emulsions, liposomes
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3

Abstract

Potent pharmacological coronary vasodilators, of the family of compounds represented by the known compound CGS-21680, as an adjunct in the detection of coronary artery disease form the basis of this application.

Claims

1. A method for determining myocardial perfusion and dysfunction comprising administering to a patient suspected of having coronary artery disease, the compound CGS-21680, in an amount appropriate to achieve near maximum coronary vasodilation.

2. The method of claim 1 comprising the additional step of identifying the presence of coronary disease by perfusion scintigraphy or contrast echocardiography (or other imaging modalities).

3. The method of claim 2 wherein said scintigraphy is performed using single-photon tracers selected from the group consisting of thallium-201, ^99m Tc sestamibi, ^99m Tc teboroxime, and ^99m Tc tetrofosmin.

4. The method of claim 2 wherein said scintigraphy is performed using positron emitters selected from the group consisting of oxygen-15 water, nitrogen-13 ammonia, or rubidium-82.

5. A method for assessing myocardial function (cardiac contraction or wall motion) in a mammal comprising:

administering to said mammal a compound, or a salt thereof, having the formula

wherein R'"'"' represents hydrogen or C₁ -C₄ -alkyl;

R₁ '"'"' represents (C₅ - or C6)-cycloalkyl-C₁ -C₄ -alkyl, or R₁ '"'"' represents aryl-C₁ -C₄ alkyl in which aryl represents 2- or 3-thienyl, 2-, 3- or 4-pyridyl, phenyl, or phenyl monosubstituted by halogen, trifluoromethyl, lower alkoxy, lower alkyl or by a substitutent--W-Z in which W represents a direct bond, C₁ -C₄ -alkylene, thio-C₁ -C₃ -alkylene or oxy-C₁ -C₃ -alkylene and Z represents cyano, carboxy, lower alkoxycarbonyl, carbamoyl, N-mono- or N,N-di-lower alkylcarbamoyl;

or R₁ '"'"' represents aryl-hydroxy-C₁ -C₄ -alkyl in which aryl has meaning as defined above;

R₄ '"'"' represents C₁ -C₄ -alkyl, cyclopropyl or hydroxy-C₂ -C₄ -alkyl;

R₅ and R₆ represent hydrogen, lower alkanoyl, lower alkoxy-lower alkanoyl, aroyl, carbamoyl, or mono- or di-lower alkylcarbamoyl;

or a pharmaceutically acceptable salt thereof,

measuring myocardial function in said mammal.

6. The method of claim 5 wherein said compound is 2-p-(2-Carboxymethyl)phenethylamino-5'"'"'-N-ethylcarboxamidoadenosine hydrochloride.

7. The method of claim 5 wherein said measuring step is myocardial scintigraphy.

8. The method of claim 5 comprising the additional step of injecting said mammal with a myocardial perfusion imaging agent.

9. The method of claim 8 wherein said myocardial perfusion imaging agent is selected from the group consisting of thallium-201, ^99m Tc sestamibi, ^99m Tc teboroxime, and ^99m Tc tetrofosmin.

10. The method of claim 8 wherein said agent is administered by injection between about 1 and 15 minutes after the maximum concentration, in the case of continuous infusion.

11. The method of claim 8 wherein said agent is administered by injection between about 1 to 15 minutes after the administration of the compound, in the case of bolus injection.

12. The method of claim 8 wherein said compound is administered for between about 1 and 4 minutes after administration of the agent.

13. The method of claim 5 wherein said measuring step comprises assessing myocardial blood flow by determining the ratio of the left anterior descending artery flow over the circumflex artery flow.

14. The method of claim 5 wherein said measuring step is myocardial perfusion imaging.

15. The method of claim 12 wherein said myocardial imaging is a technique selected from the group consisting of planar scintigraphy, single photon emission computed tomography, positron emission tomography, nuclear magnetic resonance imaging, myocardial contrast echocardiography, digital subtraction angiography, and ultrafast (electron-beam) x-ray computed tomography.

16. The method of claim 13 wherein said myocardial perfusion imaging is performed immediately after administration of said compound.

17. The method of claim 14 comprising the additional step of obtaining a second imaging wherein said imaging is performed between about 1 and about 6 hours after administration of said compound.

18. The method of claim 5 wherein said myocardial function is measured during substantially maximum coronary vasodilation.

19. The method of claim 5 wherein said mammal is administered said compound by continuous infusion over a period of between about 2 and 10 minutes.

20. The method of claim 10 wherein said compound is administered at a rate of between about 25 and 150 μ

g/kg/min.

21. The method of claim 5 wherein said mammal is administered said compound by bolus injection.

22. The method of claim 19 wherein said compound is administered between about 100 and 500 μ

g.

23. A method for assessing myocardial function in a mammal comprising:

administering to said mammal the compound 2-p-(2-carboxymethyl)phenethylamino-5'"'"'-N-ethylcarboxamidoadenosine hydrochloride in sufficient quantity to produce vasodilation;

thereafter

measuring myocardial function in said mammal.