Effects of Adenosine and a Selective A2A Adenosine Receptor Agonist on Hemodynamic and Thallium-201 and Technetium-99m–SestaMIBI Biodistribution and Kinetics

Abstract

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. 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. 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. 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. 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.