The feasibility of imaging myocardial ischemic/reperfusion injury using (99m)Tc-labeled duramycin in a porcine model.
The feasibility of imaging myocardial ischemic/reperfusion injury using (99m)Tc-labeled duramycin in a porcine model.
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DOI：
10.1016/j.nucmedbio.2014.09.002
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发表时间：
2015-02
影响因子：
3.1
通讯作者：
Zhao M
中科院分区：
文献类型：
--
作者：
Wang L;Wang F;Fang W;Johnson SE;Audi S;Zimmer M;Holly TA;Lee DC;Zhu B;Zhu H;Zhao M
当病理外化时，磷脂酰乙醇胺(PE)是检测组织损伤的潜在替代标记物。99mTc标记的硬霉素是一种多肽类显像剂，与PE结合具有很高的亲和力和特异性。本研究的目的是在一个大型动物模型(正常猪)中研究99mTc标记的硬霉素的清除动力学，并利用猪的心肌缺血-再灌注损伤模型来评估其在心脏中的摄取。以假手术动物(n=5)为模型，研究了静脉注射~(99m)Tc-硬霉素的清除和分布特征。在闭胸心肌缺血模型上，用球囊成形术建立冠状动脉闭塞模型(n=9)。再灌注后1h静脉注射99mTc-硬霉素(10~15mCI)。分别于注射后1h和3h行SPECT/CT扫描。分析心脏组织与急性细胞损伤相关的变化。放射自显影和伽马计数用于确定放射性摄取。其余动物于第二天行99mTC-四磷胺扫描以确定梗死灶。静脉注射99mTc-杜拉霉素后，主要通过肾/尿路清除循环，α时相半衰期为3.6min±0.3min，β时相半衰期为179.9±64.7min。对照组动物注射后0.5、1、2、3h心肺比值分别为1.76±0.21、1.66±0.22、1.50±0.20和1.75±0.31。正常心脏和肝脏的比值分别为0.88±0.13、0.80±0.13、0.82±0.19和0.88±0.14。缺血心脏局部放射性摄取的活体可视化最早可在注射后30分钟实现。注射后1h和3h，缺血/正常摄取比分别为3.57±0.74和3.69±0.91。缺血/肺比值分别为4.89±0.85和4.93±0.57，缺血/肝脏比值分别为2.05±0.30和3.23±0.78。~(99m)Tc-TRAF摄取显示阳性心肌的大小定性大于灌注缺陷所示的心肌梗死范围。这与组织分析和放射自显影的发现是一致的。在一个大的动物模型中，99mTC-杜拉霉素被证明具有适合于成像的清除度和生物分布曲线。该试剂具有强烈的靶向摄取和快速的背景清除。该方法适用于缺血/再灌注性心肌损伤的成像。
When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. 99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of 99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia-reperfusion injury. The clearance and distribution of intravenously injected 99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). 99mTc-duramycin (10-15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting was used to determine radioactivity uptake. For the remaining animals, 99mTc-tetrafosamin scan was performed on the second day to identify the infarct site. Intravenously injected 99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3.23 ± 0.78. The size of 99mTc-duramycin positive myocardium was qualitatively larger than the infarct size delineated by the perfusion defect in 99mTc-tetrafosmin uptake. This was consistent with findings from tissue analysis and autoradiography. 99mTc-duramycin was demonstrated, in a large animal model, to have suitable clearance and biodistribution profiles for imaging. The agent has an avid target uptake and a fast background clearance. It is appropriate for imaging myocardial injury induced by ischemia/reperfusion.