BMS-747158-02: A novel PET myocardial perfusion imagingagent
BMS-747158-02: A novel PET myocardial perfusion imagingagent
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DOI：
10.1016/j.nuclcard.2007.07.008
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发表时间：
2007-11-01
影响因子：
2.4
通讯作者：
Robinson, Simon P.
中科院分区：
文献类型：
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作者：
Yu, Ming;Guaraldi, Mary T.;Robinson, Simon P.
背景。 BMS-747158-02 是一种氟 18 标记的哒苯衍生物，设计作为一种新型心肌灌注显像剂，用于正电子发射断层扫描 (PET)。本研究评估了 BMS-747158-02。在心脏灌注的动物模型中，并将其与已建立的单光子发射计算机断层扫描剂进行比较。方法和结果。在一项大鼠生物分布研究中，BMS-747158-02 (15 mu Ci) 在 15 分钟（3.5% +/- 0.3% %ID/g vs 1.9% +/- 0.1% %ID/g）和 120 分钟（每次注射剂量的 3.2 % +/- 0.4%）时的心肌摄取量显着高于锝 99m sestamibi（100 mu Ci）。克与 静脉内给药后，每克注射剂量的 1.8% +/- 0.0%。 60 分钟时，BMS-747158-02 的心肺和肝脏摄取比（分别为 12.7 +/- 1.4 和 3.7 +/- 0.2）也高于 Tc-99m sestamilhi（分别为 5.9 +/- 0.5 和 2.4 +/- 0.4）。在离体兔心脏模型中，流速为 1.66 至 5.06 mL center dot min(-1)center dot g(-1) 湿左心室重量时，净 BMS-747158-02 心脏摄取量按比例增加（0.93 +/- 0.15 至 2.44 +/- 0.40 mL center dot min(-1)center dot g(-1)），且程度高于铊201 （0.76 +/- 0.02 至 1.11 0.02 mL 中心点 min(-1) 中心点 g(-1)）或 Tc-99m sestamilhi（0.49 +/- 0.03 至 0.77 +/- 0.08 mL 中心点 min(-1) 中心点 g (-1)）。 BMS-747158-112 的 PET 成像显示大鼠、兔子和非人灵长类动物具有清晰且持续的心脏摄取，肺部干扰最小，肝脏清除速度快。 BMS-747158-02的PET心脏图像上可以清楚地识别大鼠永久左冠状动脉结扎或结扎后再灌注产生的心肌灌注缺损区，并且与体外组织学具有良好的一致性。结论。 BMS-747158-02 表现出与血流量成正比的高且持续的心脏摄取，它代表了一类新型 PET 心肌灌注显像剂。 (J Nucl Cardiol 2007；14:189-98)。
Background. BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02. in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents.Methods and Results. In a rat biodistribution study, BMS-747158-02 (15 mu Ci) had substantially higher myocardial uptake than technetium 99m sestamibi (100 mu Ci) at 15 minutes (3.5% +/- 0.3% %ID/g vs 1.9% +/- 0.1% %ID/g) and 120 minutes (3.2 % +/- 0.4% of injected dose per gram vs 1.8% +/- 0.0% of injected dose per gram) after intravenous administration. Uptake ratios of heart to lung and liver at 60 minutes were also higher for BMS-747158-02 (12.7 +/- 1.4 and 3.7 +/- 0.2, respectively) than Tc-99m sestamilhi (5.9 +/- 0.5 and 2.4 +/- 0.4, respectively). In an isolated rabbit heart model at flow rates of 1.66 to 5.06 mL center dot min(-1)center dot g(-1) wet left ventricular weight, the net BMS-747158-02 heart uptake increased proportionally (0.93 +/- 0.15 to 2.44 +/- 0.40 mL center dot min(-1)center dot g(-1)) and to a greater extent than that of thallium 201 (0.76 +/- 0.02 to 1.11 0.02 mL center dot min(-1)center dot g(-1)) or Tc-99m sestamilhi (0.49 +/- 0.03 to 0.77 +/- 0.08 mL center dot min(-1)center dot g (-1)). PET imaging with BMS-747158-112 showed a clear and sustained cardiac uptake in rats, rabbits, and nonhuman primates with minimal lung interference and rapid liver clearance. Myocardial perfusion deficit zones created by either permanent left coronary ligation or reperfusion after ligation in rats were both clearly identified on PET cardiac images of BMS-747158-02 and had good agreement with in vitro histology.Conclusions. BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent. (J Nucl Cardiol 2007;14:189-98).