Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Circ Cardiovasc Imaging. 2011 Nov;4(6):729-37. doi: 10.1161/CIRCIMAGING.111.966374. Epub 2011 Aug 11.
Current techniques to image cell death in the myocardium are largely nonspecific. 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 after 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 to 18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R(1)) 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 after MI (R(1)=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.
目前用于检测心肌细胞死亡的技术在很大程度上是非特异性的。我们报告了一种新型 DNA 结合钆螯合物（Gd-TO）的应用，该螯合物可特异性检测体内急性坏死（破裂）细胞中暴露的 DNA。
20 只心肌梗死（MI）小鼠进行了体内 MRI 检查。MI 后不同时间点给小鼠注射 Gd-TO 或 Gd-DTPA。在探针注射后 2 小时进行 MRI，以避免晚期钆增强效应引起的非特异性信号。MI 后 2 小时内即可出现细胞破裂（Gd-TO 摄取），但在损伤后 9 至 18 小时达到高峰。在 MI 后 48 小时内注射 Gd-TO 的小鼠的梗死区纵向弛豫率（R（1））显著增加，但在 MI 后 72 小时以上注射的小鼠中则没有（R（1）分别为 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 小时内完全从急性梗死中冲洗出来（P<0.001）。荧光显微镜证实 Gd-TO 与急性梗死中暴露的 DNA 特异性结合。
Gd-TO 特异性结合急性坏死细胞，可用于成像损伤心肌中细胞死亡的机制和慢性。急性 MI 中的细胞破裂很早就开始，但在损伤后数小时达到高峰。破裂的细胞被免疫系统有效清除，在损伤后 72 小时内不再存在于心肌中。
