Myocardial perfusion imaging methods and compositions
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.