Verapamil does not inhibit 99mTcN-NOET uptake in situ in normal or ischemic canine myocardium.
Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN-NOET) is a new myocardial perfusion imaging agent currently undergoing phase III clinical trials in the United States and in Europe. (99m)TcN-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 (99m)TcN-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 (99m)TcN-NOET shown in vitro could be reproduced in situ in a canine model of normal and ischemic myocardium.


METHODS
(99m)TcN-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 (99m)TcN-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). (99m)TcN-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 (99m)TcN-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). (99m)TcN-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).


CONCLUSIONS
Verapamil does not inhibit (99m)TcN-NOET uptake in situ in normal and ischemic canine myocardium. These results suggest that verapamil should not affect (99m)TcN-NOET myocardial uptake in patients referred for myocardial perfusion imaging.
Riou
Laurent M
LM
Laboratoire d'Etude de Radiopharmaceutiques, University Hospital of Grenoble, Grenoble, France.
Ghezzi
Catherine
C
Vanzetto
Gérald
G
Broisat
Alexis
A
Mathieu
Jean-Paul
JP
Bontron
René
R
Pasqualini
Roberto
R
Fagret
Daniel
D
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011874:Radiometry / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012016:Reference Values; D013859:Thiocarbamates / Q000493:pharmacokinetics*; D014700:Verapamil / Q000494:pharmacology*
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013859:Thiocarbamates; D014700:Verapamil; D000241:Adenosine; C093922:technetium Tc 99m, bis(N-ethoxy-N-ethyldithiocarbamato)nitrido-