Myocardial uptake of 7'-(Z)-[(123)I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses.
Myocardial uptake of 7'-(Z)-[(123)I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses.
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DOI：
10.1161/circimaging.110.961763
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发表时间：
2011-11
期刊：
影响因子：
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通讯作者：
Glover DK
中科院分区：
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作者：
Broisat A;Ruiz M;Goodman NC;Hanrahan SM;Reutter BW;Brennan KM;Janabi M;Schaefer S;Watson DD;Beller GA;VanBrocklin HF;Glover DK
人们普遍认识到需要新一代单光子发射计算机断层扫描 (SPECT) 灌注示踪剂，以在宽流量范围内改善心肌提取。靶向线粒体电子传递链复合物 I 的放射性示踪剂已被提议作为一类新型心肌灌注显像剂。 7-(Z)-[125I]碘藤酮 (125I-ZIROT) 在大鼠和离体灌注兔心脏中表现出优异的心肌提取和保留特性。我们试图在完整的大型动物模型中全面表征 123I-ZIROT 的生物分布和心肌提取与血流关系。在 5 只患有严重左前降支 (LAD) 狭窄的麻醉犬中，在腺苷 A2A 激动剂诱导充血期间给予 123I-ZIROT。当左回旋支(LCx)流量最大时，共注射123I-ZIROT和微球，5分钟后对狗实施安乐死。通过体内平面成像在另外 2 只狗中评估了 123I-ZIROT 生物分布。注射 123I-ZIROT 时，跨壁 LAD 流量与基线相比没有变化（平均值±SEM，0.90±0.22 与 0.87±0.11 mL/[min·g]；P=0.92），而 LCx 区流量显着增加（平均值±SEM，3.25±0.51 与 1.00±0.17 mL/[min·g]；P<0.05）。心肌 123I-ZIROT 提取比先前使用类似模型的研究中的 201 铊或 99mTc-sestamibi 更好地跟踪局部心肌血流。此外，通过离体成像或孔计数得出的 123I-ZIROT LAD/LCx 活性比（平均值±SEM，分别为 0.42±0.08 和 0.45±0.1）仅略微低估了 LAD/LCx 微球流量比（0.32±0.09）。 123I-ZIROT 在大范围内更线性地跟踪血流的能力使其成为一种有前途的新型 SPECT 心肌灌注显像剂，具有改善冠状动脉疾病检测和更好地定量估计血流损伤严重程度的潜力。
There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[125I]iodorotenone (125I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of 123I-ZIROT in an intact large-animal model. The 123I-ZIROT was administered during adenosine A2A agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, 123I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. 123I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At 123I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial 123I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or 99mTc-sestamibi from previous studies using a similar model. Furthermore, the 123I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09). The ability of 123I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.