Author + information
- Received September 2, 2008
- Revision received June 4, 2009
- Accepted June 10, 2009
- Published online October 1, 2009.
- Choukri Mekkaoui, PhD⁎,
- Farid Jadbabaie, MD⁎,
- Donald P. Dione, BS⁎,
- David F. Meoli, MD, PhD⁎,
- Kailasnath Purushothaman, PhD†,
- Luiz Belardinelli, MD‡ and
- Albert J. Sinusas, MD⁎,†,⁎ ()
Reprint requests and correspondence:
Dr. Albert J. Sinusas, Yale University School of Medicine, Nuclear Cardiology, 3FMP, P.O. Box 208017, New Haven, Connecticut 06520-8017
Objectives The purpose of this study was to compare a selective A2A adenosine receptor agonist (regadenoson) with adenosine in clinically relevant canine models with regard to effects on hemodynamics and thallium-201 (201Tl) and technetium-99m (99mTc)-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 μg/kg) or 4.5-min infusion of adenosine (280 μg/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 201Tl and 99mTc-sestaMIBI biodistribution and kinetics. The arterial blood clearance half-time was significantly faster for 99mTc-sestaMIBI (regadenoson: 1.4 ± 0.03 min; adenosine: 1.5 ± 0.08 min) than for 201Tl (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 99mTc-sestaMIBI (0.69 ± 0.03%, p < 0.001) or 201Tl (0.53 ± 0.02%, p < 0.001), although 201Tl tracked the flow deficit within the ischemic region better than 99mTc-sestaMIBI. The perfusion defect score was larger with 201Tl (22 ± 2.8% left ventricular) than with 99mTc-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 201Tl and 99mTc-sestaMIBI during regadenoson were similar to adenosine vasodilation. Ex vivo perfusion images under the most ideal conditions permitted detection of a critical stenosis, although 201Tl offered significant advantages over 99mTc-sestaMIBI for perfusion imaging during regadenoson vasodilator stress.
This research was supported in part by a grant-in-aid from the Heritage Affiliate of American Heart Association (to Dr. Purushothaman), Robbinsville, New Jersey, and a grant from CV Therapeutics, Inc. (to Dr. Sinusas).
- Received September 2, 2008.
- Revision received June 4, 2009.
- Accepted June 10, 2009.
- American College of Cardiology Foundation