Riou Laurent M, Ghezzi Catherine, Vanzetto Gérald, Broisat Alexis, Mathieu Jean-Paul, Bontron René, Pasqualini Roberto, Fagret Daniel
Laboratoire d'Etude de Radiopharmaceutiques, University Hospital of Grenoble, Grenoble, France.
J Nucl Med. 2003 Jun;44(6):981-7.
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.
(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.
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).
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.
双（N - 乙氧基，N - 乙基二硫代氨基甲酰）氮（V）锝（（99m）Tc）（（99m）TcN - NOET）是一种新型心肌灌注显像剂，目前正在美国和欧洲进行III期临床试验。在培养的新生大鼠心肌细胞中，已证明钙通道抑制剂维拉帕米可抑制（99m）TcN - NOET的细胞摄取。然而，维拉帕米对原位（99m）TcN - NOET心肌摄取的影响尚不清楚。因此，本研究的目的是评估在正常和缺血心肌犬模型中，体外显示的维拉帕米对（99m）TcN - NOET细胞摄取的抑制作用是否能在原位再现。
在麻醉的开胸犬（n = 17）中，测量在不存在或存在维拉帕米（0.015 mg/kg/min×10 min）的情况下，正常和缺血心肌（左前降支冠状动脉血流减少70%）中（99m）TcN - NOET的摄取。对照动物输注腺苷（0.2 mg/kg/min）以匹配维拉帕米诱导的血流增加。
通过维拉帕米治疗，达到了临床相关的钙通道抑制剂血浆浓度（平均值±标准误，290±152 ng/mL）。在正常心肌（n = 8）中，维拉帕米治疗组和腺苷治疗组犬在注射（99m）TcN - NOET时的局部血流无统计学差异（分别为1.69±0.03 vs. 1.61±0.04 mL/min/g）。在维拉帕米存在的情况下，（99m）TcN - NOET摄取略高（腺苷组为0.38±0.01计数每分钟[cpm]/[Bq/kg]/g，维拉帕米组为0.39±0.01；P = 0.04）。然而，将示踪剂摄取归一化至局部心肌血流后，未观察到（99m）TcN - NOET心肌摄取的显著差异。在缺血心肌（n = 9）中，维拉帕米治疗组的局部血流低于腺苷治疗组（0.22±0.02 vs. 0.29±0.03 mL/min/g；P < 0.05）。维拉帕米未抑制缺血区域的（99m）TcN - NOET摄取（0.09±0.01 vs. 0.10±0.01 cpm/[Bq/kg]/g；P = 无显著性差异）。
维拉帕米不抑制正常和缺血犬心肌原位的（99m）TcN - NOET摄取。这些结果表明，维拉帕米不应影响接受心肌灌注显像患者的（99m）TcN - NOET心肌摄取。
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