Effects of adenosine and a selective A2A adenosine receptor agonist on hemodynamic and thallium-201 and technetium-99m-sestaMIBI biodistribution and kinetics.

Abstract

OBJECTIVES:

The purpose of this study was to compare a selective A(2A) adenosine receptor agonist (regadenoson) with adenosine in clinically relevant canine models with regard to effects on hemodynamics and thallium-201 ((201)Tl) and technetium-99m ((99m)Tc)-sestaMIBI biodistribution and kinetics.

BACKGROUND:

The clinical application of vasodilator stress for perfusion imaging requires consideration of the effects of these vasodilating agents on systemic hemodynamics, coronary flow, and radiotracer uptake and clearance kinetics.

METHODS:

Sequential imaging and arterial blood sampling was performed on control, anesthetized closed-chest canines (n = 7) to evaluate radiotracer biodistribution and kinetics after either a bolus administration of regadenoson (2.5 microg/kg) or 4.5-min infusion of adenosine (280 microg/kg). The effects of regadenoson on coronary flow and myocardial radiotracer uptake were then evaluated in an open-chest canine model of a critical stenosis (n = 7). Results from ex vivo single-photon emission computed tomography were compared with tissue well-counting.

RESULTS:

The use of regadenoson compared favorably with adenosine in regard to the duration and magnitude of the hemodynamic effects and the effect on (201)Tl and (99m)Tc-sestaMIBI biodistribution and kinetics. The arterial blood clearance half-time was significantly faster for (99m)Tc-sestaMIBI (regadenoson: 1.4 +/- 0.03 min; adenosine: 1.5 +/- 0.08 min) than for (201)Tl (regadenoson: 2.5 +/- 0.16 min, p < 0.01; adenosine: 2.7 +/- 0.04 min, p < 0.01) for both vasodilator stressors. The relative microsphere flow deficit (0.34 +/- 0.02%) during regadenoson stress was significantly greater than the relative perfusion defect with (99m)Tc-sestaMIBI (0.69 +/- 0.03%, p < 0.001) or (201)Tl (0.53 +/- 0.02%, p < 0.001), although (201)Tl tracked the flow deficit within the ischemic region better than (99m)Tc-sestaMIBI. The perfusion defect score was larger with (201)Tl (22 +/- 2.8% left ventricular) than with (99m)Tc-sestaMIBI (17 +/- 1.7% left ventricular, p < 0.05) on ex vivo single-photon emission computed tomography images.

CONCLUSIONS:

The bolus administration of regadenoson produced a hyperemic response comparable to a standard infusion of adenosine. The biodistribution and clearance of both (201)Tl and (99m)Tc-sestaMIBI during regadenoson were similar to adenosine vasodilation. Ex vivo perfusion images under the most ideal conditions permitted detection of a critical stenosis, although (201)Tl offered significant advantages over (99m)Tc-sestaMIBI for perfusion imaging during regadenoson vasodilator stress.

• Authors: Choukri Mekkaoui, Farid Jadbabaie, Donald P Dione, David F Meoli, Kailasnath Purushothaman, Luiz Belardinelli, Albert J Sinusas
• Journal: JACC. Cardiovascular imaging (JACC Cardiovasc Imaging) Vol. 2 Issue 10 Pg. 1198-208 (Oct 2009) ISSN: 1876-7591 [Electronic] United States
• PMID: 19833310 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A2 Receptor Agonists
• Purines
• Pyrazoles
• Radiopharmaceuticals
• Receptor, Adenosine A2A
• Thallium Radioisotopes
• Vasodilator Agents
• regadenoson
• Technetium Tc 99m Sestamibi
• Adenosine

Topics

• Acute Disease
• Adenosine (administration & dosage, pharmacology)
• Adenosine A2 Receptor Agonists
• Animals
• Blood Flow Velocity (drug effects)
• Chronic Disease
• Coronary Circulation (drug effects)
• Coronary Stenosis (diagnostic imaging, metabolism, physiopathology)
• Disease Models, Animal
• Dogs
• Hyperemia (diagnostic imaging, physiopathology)
• Infusions, Intravenous
• Injections, Intravenous
• Metabolic Clearance Rate
• Myocardial Perfusion Imaging (methods)
• Myocardium (metabolism, pathology)
• Predictive Value of Tests
• Purines (administration & dosage, pharmacology)
• Pyrazoles (administration & dosage, pharmacology)
• Radiopharmaceuticals (blood, pharmacokinetics)
• Receptor, Adenosine A2A (metabolism)
• Technetium Tc 99m Sestamibi (blood, pharmacokinetics)
• Thallium Radioisotopes (blood, pharmacokinetics)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon
• Vasodilator Agents (administration & dosage, pharmacology)