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Verapamil Does Not Inhibit ^99mTcN-NOET Uptake In Situ in Normal or Ischemic Canine Myocardium

¹ Laboratoire d’Etude de Radiopharmaceutiques, University Hospital of Grenoble, Grenoble, France
² Cis Bio International, Gif-sur-Yvette, France

Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) (^99mTc) (^99mTcN-NOET) is a new myocardial perfusion imaging agent currently undergoing phase III clinical trials in the United States and in Europe. ^99mTcN-NOET cellular uptake has been shown to be inhibited by the calcium channel inhibitor verapamil in cultured newborn rat cardiomyocytes. However, the effect of verapamil on in situ ^99mTcN-NOET myocardial uptake remains unknown. Therefore, the aim of this study was to evaluate whether the inhibitory effect of verapamil on the cellular uptake of ^99mTcN-NOET shown in vitro could be reproduced in situ in a canine model of normal and ischemic myocardium. Methods: ^99mTcN-NOET uptake in normal and ischemic myocardium (70% flow reduction in the left anterior descending coronary artery) was measured in the absence or presence of verapamil (0.015 mg/kg/min x 10 min) in anesthetized, open-chest dogs (n = 17). Control animals were infused with adenosine (0.2 mg/kg/min) to match the verapamil-induced increase in flow. Results: By verapamil treatment, a clinically relevant plasma concentration of the calcium channel inhibitor was attained (mean ± SEM, 290 ± 152 ng/mL). In normal myocardium (n = 8), regional blood flow at the time of ^99mTcN-NOET injection was not statistically different in verapamil- and adenosine-treated dogs (1.69 ± 0.03 vs. 1.61 ± 0.04 mL/min/g, respectively). ^99mTcN-NOET uptake was slightly higher in the presence of verapamil (0.39 ± 0.01 vs. 0.38 ± 0.01 counts per minute [cpm]/[Bq/kg]/g for adenosine; P = 0.04). However, no significant difference in ^99mTcN-NOET myocardial uptake was observed after normalization of the tracer uptake to regional myocardial blood flow. In ischemic myocardium (n = 9), regional blood flow was lower in verapamil-treated than in adenosine-treated animals (0.22 ± 0.02 vs. 0.29 ± 0.03 mL/min/g; P < 0.05). ^99mTcN-NOET uptake in the ischemic area was not inhibited by verapamil (0.09 ± 0.01 vs. 0.10 ± 0.01 cpm/[Bq/kg]/g; P = not significant). Conclusion: Verapamil does not inhibit ^99mTcN-NOET uptake in situ in normal and ischemic canine myocardium. These results suggest that verapamil should not affect ^99mTcN-NOET myocardial uptake in patients referred for myocardial perfusion imaging.

Key Words: bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) • verapamil • myocardial perfusion imaging