Myocardial perfusion imaging methods and compositions

Abstract

A myocardial imaging method that is accomplished by administering one or more adenosine A 2A adenosine receptor agonist to a human undergoing myocardial imaging as well as pharmaceutical compositions comprising at least one A 2a receptor agonist, at least one liquid carrier, and at least one co-solvent.

1 . A pharmaceutical composition comprising at least one A 2a  receptor agonist, at least one liquid carrier, and at least one co-solvent.  
     
     
         2 . The pharmaceutical composition of  claim 1  wherein the A 2a  receptor agonist is selected from the group consisting of CVT-3033, CVT-3146, and combinations thereof.  
     
     
         3 . The pharmaceutical composition of  claim 1  wherein the liquid carrier comprises water, distilled water, de-ionized water, saline, a buffer, or combinations thereof.  
     
     
         4 . The pharmaceutical composition of  claim 1  wherein the co-solvent comprises methylboronic acid, borate buffer, propylene glycol, or polyethylene glycol.  
     
     
         5 . The pharmaceutical composition of  claim 4  wherein the co-solvent is methylboronic acid.  
     
     
         6 . The pharmaceutical composition of  claim 5  wherein the A 2a  receptor agonist is CVT-3146.  
     
     
         7 . The pharmaceutical composition of  claim 6  wherein the CVT-3146 is present in an amount ranging from about 50 micrograms/ml to about 250 micrograms/ml and the methylboronic acid is present in an amount from about 0.4% to about 0.6% (w:v).  
     
     
         8 . The pharmaceutical composition of  claim 7  wherein the liquid carrier is at least one buffer.  
     
     
         9 . The pharmaceutical composition of  claim 8  wherein the pH of the said composition is from about 8.5 to about 10.  
     
     
         10 . The pharmaceutical composition of  claim 9  wherein the pH is from about 9.1 to about 9.4.  
     
     
         11 . The pharmaceutical composition of  claim 3  wherein the co-solvent is a borate buffer.  
     
     
         12 . The pharmaceutical composition of  claim 6  wherein the co-solvent is about 0.5% (w:v) methylboronic acid.  
     
     
         13 . The pharmaceutical composition of  claim 12  wherein said composition also comprises a buffer to bring the pH of the composition to about 9.3.  
     
     
         14 . The pharmaceutical composition of  claim 13  wherein the CVT-3146 in said composition is present in an amount from about 50 to about 150 micrograms/ml.  
     
     
         15 . The pharmaceutical composition of  claim 14  wherein the said composition also comprises about 0.55% (w:v) sodium chloride and about 50 mM sodium bicarbonate.  
     
     
         16 . The pharmaceutical composition of  claim 4  wherein the co-solvent is propylene glycol and the propylene glycol is present in an amount from about 5% to about 25% (w:v).  
     
     
         17 . The pharmaceutical composition of  claim 16  wherein the propylene glycol is present in an amount from about 8% to about 20% (w:v).  
     
     
         18 . The pharmaceutical composition of  claim 17  wherein the liquid carrier includes a buffer to bring said composition to a pH of from about 6 to about 8.  
     
     
         19 . The pharmaceutical composition of  claim 18  wherein the said composition further comprises EDTA.  
     
     
         20 . The pharmaceutical composition of  claim 16  wherein the A 2a  receptor agonist is CVT-3146 and said CVT-3146 is present in an amount from about 50 to about 150 micrograms.  
     
     
         21 . A method of producing coronary vasodilation without peripheral vasodilation comprising administering to a human the pharmaceutical composition of claims  1  or  5  or  16  wherein said composition contains about 10 to about 600 micrograms of at least one A 2a  receptor agonist.  
     
     
         22 . The method of  claim 21  wherein the A 2a  receptor agonist is CVT-3146.  
     
     
         23 . The method of  claim 22  wherein said pharmaceutical composition is administered by iv bolus.  
     
     
         24 . The method of  claim 23  wherein said pharmaceutical composition is administered in about 10 to about 20 seconds.  
     
     
         25 . A method of myocardial perfusion imaging of a human comprising administering a radionuclide and the composition of claims  1  or  5  or  16  either simultaneously or sequentially to a human wherein the myocardium is examined for areas of insufficient blood flow following administration of the radionuclide and the composition.  
     
     
         26 . The method of  claim 25  wherein the myocardium examination begins within about 1 minute after the radionuclide and the composition are administered.  
     
     
         27 . The method of  claim 26  wherein the A 2a  receptor agonist in said composition causes at least a 2.5 fold increase in coronary blood flow, such increase in blood flow being achieved for less than about 5 minutes.  
     
     
         28 . The method of  claim 25  wherein the A 2a  receptor agonist in said composition is CVT-3146, which CVT-3146 is administered in an amount of from about 10 to about 600 micrograms in a single iv bolus.  
     
     
         29 . The method of  claim 28  wherein the CVT-3146 amount is from about 100 to about 500 micrograms.  
     
     
         30 . The method of  claim 28  wherein the CVT-3146 amount is about 400 micrograms.  
     
     
         31 . The method of  claim 28  wherein said composition is administered in about 10 to about 30 seconds or less.  
     
     
         32 . A method of producing coronary vasodilation without peripheral vasodilation comprising administering at least 10 μg of at least one A 2A  receptor agonist to a human.  
     
     
         33 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount that does not exceed about 1000 μg.  
     
     
         34 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount ranging from about 10 to about 600 μg.  
     
     
         35 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in a single dose.  
     
     
         36 . The method of  claim 32  wherein the A 2A  receptor agonist is administered by iv bolus.  
     
     
         37 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount ranging from about 0.05 to about 60 μg/kg and wherein the A 2A  receptor agonist is administered by iv bolus.  
     
     
         38 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount ranging from about 0.1 to about 30 μg/kg wherein the A 2A  receptor agonist is administered by iv bolus.  
     
     
         39 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount no greater than about 20 μg/kg to a supine patient and wherein the A 2A  receptor agonist is administered by iv bolus.  
     
     
         40 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount no greater than about 10 μg/kg to a standing patient wherein the A 2A  receptor agonist is administered by iv bolus.  
     
     
         41 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount ranging from about 10 to about 600 μg wherein the wherein the A 2A  receptor agonist is administered in about 20 seconds.  
     
     
         42 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount ranging from about 10 to about 600 μg wherein the A 2A  receptor agonist is administered in less than about 10 seconds.  
     
     
         43 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount greater than about 100 μg.  
     
     
         44 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount no greater than 600μ.  
     
     
         45 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount no greater than 500 μg.  
     
     
         46 . The method of  claim 32  wherein the A 2A  receptor agonist is administered in an amount ranging from about 100 μg to about 500 μg.  
     
     
         47 . The method of  claim 32  wherein the A 2A  receptor agonist is selected from the group consisting of CVT-3033, CVT-3146 and combinations thereof.  
     
     
         48 . A method of myocardial perfusion imaging of a human, comprising administering a radionuclide and a A 2A  receptor agonist to the human wherein the myocardium is examined for areas of insufficient blood flow following administration of the radionuclide and the A 2A  receptor agonist.  
     
     
         49 . The method of  claim 48  wherein the myocardium examination begins within about 1 minute from the time the A 2A  receptor agonist is administered.  
     
     
         50 . The method of  claim 48  wherein the administration of the A 2A  receptor agonist causes at least a 2.5 fold increase in coronary blood flow.  
     
     
         51 . The method of  claim 48  wherein the administration of the A 2A  receptor agonist causes at least a 2.5 fold increase in coronary blood flow that is achieved within about 1 minute from the administration of the A 2A  receptor agonist.  
     
     
         52 . The method of  claim 48  wherein the radionuclide and the A 2A  receptor agonist are administered separately.  
     
     
         53 . The method of  claim 48  wherein the radionuclide and the A 2A  receptor agonist are administered simultaneously.  
     
     
         54 . The method of  claim 48  wherein the administration of the A 2A  receptor agonist causes at least a 2.5 fold increase in coronary blood flow for less than about 5 minutes.  
     
     
         55 . The method of  claim 48  wherein the administration of the A 2A  receptor agonist causes at least a 2.5 fold increase in coronary blood flow for less than about 3 minutes.  
     
     
         56 . The method of  claim 48  wherein the A 2A  receptor agonist is CVT-3146 which is administered in an amount ranging from about 10 to about 600 μg in a single iv bolus.  
     
     
         57 . The method of  claim 56  wherein CVT-3146 is administered in an amount ranging from about 100 to about 500 μg in a single iv bolus.  
     
     
         58 . The method of  claim 48  wherein the a A 2A  receptor agonist is CVT-3146 which is administered in a single dose in an amount ranging from 10 to about 600 μg that is independent of the weight of the human being dosed.  
     
     
         59 . The method of  claim 48  wherein the dose is administered in about 30 seconds or less.  
     
     
         60 . The method of  claim 48  wherein the dose is administered in about 20 seconds or less.  
     
     
         61 . The method of  claim 48  wherein the A 2A  receptor agonist is administered in a single dose.