Molecular MRI of acute necrosis with a novel DNA-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium.
Molecular MRI of acute necrosis with a novel DNA-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium.
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DOI：
10.1161/circimaging.111.966374
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Sosnovik DE
中科院分区：
文献类型：
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作者：
Huang S;Chen HH;Yuan H;Dai G;Schuhle DT;Mekkaoui C;Ngoy S;Liao R;Caravan P;Josephson L;Sosnovik DE
目前的心肌细胞死亡成像技术在很大程度上是非特异性的。在这里，我们报告了使用一种新型的DNA结合格拉络合物(Gd-TO)来特异性地检测体内急性坏死性(破裂)细胞中暴露的DNA。对20只心肌梗塞(MI)小鼠进行了活体MRI检查。分别于心肌梗死后不同时间点注射Gd-TO或Gd-DTPA。在注射探头后2小时行MRI检查，以避免晚期Gd增强效应带来的非特异性信号。细胞破裂(Gd-TO摄取)在梗死后2小时内出现，但在损伤开始后9-18小时达到高峰。心肌梗死后48h内注射Gd-TO的小鼠，心肌梗死后48h内注射Gd-TO后，梗死灶的纵向松弛速率(R1)显著增加，而超过72h后注射Gd-TO的小鼠则无明显变化(r1=1.24±0.08和0.92±0.03 S−1，p<；0.001)。与Gd-TO不同，Gd-DTPA在注射后2小时内完全清除急性脑梗塞(p<；0.001)。荧光显微镜观察证实Gd-TO与急性脑梗塞裸露DNA的结合。Gd-TO与急性坏死细胞特异性结合，可用于显示受损心肌细胞死亡的机制和慢性化。急性心肌梗死的细胞破裂开始较早，但在损伤开始后数小时达到高峰。破裂的细胞被免疫系统有效地清除，并在受伤72小时后不再存在于心肌中。
Current techniques to image cell death in the myocardium are largely non-specific. Here we report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo. In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points post-MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction, but peaked 9–18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R1) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours post MI (R1 = 1.24 ± 0.08 and 0.92 ± 0.03 s−1, respectively, p < 0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection (p < 0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy. Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury.