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Effects of Adenosine and a Selective A_2A Adenosine Receptor Agonist on Hemodynamic and Thallium-201 and Technetium-99m–SestaMIBI Biodistribution and Kinetics

Choukri Mekkaoui, PhD^_*, Farid Jadbabaie, MD^_*, Donald P. Dione, BS^_*, David F. Meoli, MD, PhD^_*, Kailasnath Purushothaman, PhD, Luiz Belardinelli, MD, Albert J. Sinusas, MD^_*,,_*

^_* Division of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
CV Therapeutics, Inc., Palo Alto, California

^_* 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 (Email: albert.sinusas{at}yale.edu).

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 (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.

Key Words: regadenoson • myocardial perfusion imaging • adenosine • biodistribution • tracer kinetics

Abbreviations and Acronyms   AoP = aortic pressure   DPI = dynamic planar Imaging   HR = heart rate   IS = ischemic   LAD = left anterior descending artery   LCX = left circumflex artery   LV = left ventricular   MBF = myocardial blood flow   MPI = myocardial perfusion imaging   NI = nonischemic   %ID = percent injected dose   SPECT = single-photon emission computed tomography   99mTc = technetium-99m   201Tl = thallium-201

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