Zhu Xiaoguang, Li Zhixin, Zhao Ming
Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
J Nucl Med. 2007 Jun;48(6):1031-6. doi: 10.2967/jnumed.106.037754.
The exposure of anionic phospholipids is a near-universal molecular signature for cell death. Based on our prior finding that the (99m)Tc-labeled C2A domain of synaptotagmin I accumulates intensely in the area at risk, this study quantitatively characterized the temporal and spatial distribution of the radiotracer in a rat model of myocardial ischemia and reperfusion.
Myocardial ischemia and reperfusion were induced by occlusion of the left anterior descending coronary artery in rats. The temporal uptake of the labeled fusion protein of C2A and glutathione-s-transferase (C2A-GST) in the area at risk was investigated by intravenously injecting the radiotracer at 0, 1, 3, 6, and 24 h after reperfusion, and the radioactivity uptake was quantified by gamma-counting of infarcted and ischemic noninfarcted cardiac tissues. Alternatively, the radiotracer was injected at 2 h after reperfusion, and the uptake was measured at 1, 3, 6, and 24 h after injection. In vivo planar imaging was performed on a gamma-camera using a parallel-hole collimator. The distribution of radioactivity was qualitatively examined by autoradiography. The relationship between the uptake of the radiotracer in the area at risk and the ischemic duration was examined by gamma-counting.
Temporally, the radioactivity uptake in the area at risk maximized when the radiotracer was injected before 3 h after reperfusion. Injections at 6 and 24 h after reperfusion resulted in a 30% and 50% reduction in uptake, respectively. However, when the injection was done early (2 h after reperfusion), the tracer was retained in the area at risk with little washout for at least 24 h. Spatially prominent hot-spot uptake was seen in all cases of planar imaging. In autoradiography, the distribution of radioactivity predominantly coregistered with the infarcted regions. This distribution profile was confirmed by direct gamma-counting. In addition, the absolute radiotracer uptake in the infarcted and ischemic noninfarcted tissues, in terms of percentage injected dose per gram, was independent of the ischemic duration.
(99m)Tc-C2A-GST has an uptake profile in the area at risk that is appropriate for imaging cardiac cell death in the acute phase.
阴离子磷脂的暴露是细胞死亡几乎普遍存在的分子特征。基于我们之前的发现，即（99m）Tc标记的突触结合蛋白I的C2A结构域在危险区域强烈聚集，本研究定量表征了放射性示踪剂在大鼠心肌缺血再灌注模型中的时间和空间分布。
通过结扎大鼠左冠状动脉前降支诱导心肌缺血再灌注。在再灌注后0、1、3、6和24小时静脉注射放射性示踪剂，研究标记的C2A与谷胱甘肽 - S - 转移酶融合蛋白（C2A - GST）在危险区域的时间摄取情况，并通过对梗死和缺血未梗死心脏组织进行γ计数来量化放射性摄取。或者，在再灌注后2小时注射放射性示踪剂，并在注射后1、3、6和24小时测量摄取情况。使用平行孔准直器在γ相机上进行体内平面成像。通过放射自显影定性检查放射性分布。通过γ计数检查危险区域放射性示踪剂摄取与缺血持续时间之间的关系。
在时间上，当在再灌注后3小时之前注射放射性示踪剂时，危险区域的放射性摄取达到最大值。再灌注后6小时和24小时注射分别导致摄取减少30%和50%。然而，当早期（再灌注后2小时）注射时，示踪剂在危险区域保留，至少24小时几乎没有洗脱。在所有平面成像病例中均可见空间上突出的热点摄取。在放射自显影中，放射性分布主要与梗死区域重合。这种分布情况通过直接γ计数得到证实。此外，梗死和缺血未梗死组织中放射性示踪剂的绝对摄取量，以每克注射剂量的百分比表示，与缺血持续时间无关。
（99m）Tc - C2A - GST在危险区域具有适合急性期心脏细胞死亡成像的摄取特征。
