Sosnovik David E, Schellenberger Eyk A, Nahrendorf Matthias, Novikov Mikhail S, Matsui Takashi, Dai George, Reynolds Fred, Grazette Luanda, Rosenzweig Anthony, Weissleder Ralph, Josephson Lee
Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Magn Reson Med. 2005 Sep;54(3):718-24. doi: 10.1002/mrm.20617.
The ability to image cardiomyocyte apoptosis in vivo with high-resolution MRI could facilitate the development of novel cardioprotective therapies. The sensitivity of the novel nanoparticle AnxCLIO-Cy5.5 for cardiomyocyte apoptosis was thus compared in vitro to that of annexin V-FITC and showed a high degree of colocalization. MRI was then performed, following transient coronary artery (LAD) occlusion, in five mice given AnxCLIO-Cy5.5 and in four mice given an identical dose (2 mg Fe/kg) of CLIO-Cy5.5. MR signal intensity and myocardial T2* were evaluated, in vivo, in hypokinetic regions of myocardium in the LAD distribution. Ex vivo fluorescence imaging was performed to confirm the in vivo findings. Myocardial T2* was significantly lower in the mice given AnxCLIO-Cy5.5 (8.1 versus 13.2 ms, P<0.01), and fluorescence target to background ratio was significantly higher (2.1 versus 1.1, P<0.01). This study thus demonstrates the feasibility of obtaining high-resolution MR images of cardiomyocyte apoptosis in vivo with the novel nanoparticle, AnxCLIO-Cy5.5.
利用高分辨率磁共振成像（MRI）对体内心肌细胞凋亡进行成像的能力，可能会促进新型心脏保护疗法的开发。因此，在体外将新型纳米颗粒AnxCLIO-Cy5.5对心肌细胞凋亡的敏感性与膜联蛋白V-异硫氰酸荧光素（annexin V-FITC）的敏感性进行了比较，结果显示二者高度共定位。然后，在5只给予AnxCLIO-Cy5.5的小鼠和4只给予相同剂量（2 mg铁/千克）CLIO-Cy5.5的小鼠中，在冠状动脉（左前降支）短暂闭塞后进行MRI检查。在体内评估左前降支分布区域中心肌运动减弱区域的磁共振信号强度和心肌T2*。进行离体荧光成像以确认体内研究结果。给予AnxCLIO-Cy5.5的小鼠心肌T2*显著更低（8.1对13.2毫秒，P<0.01），荧光靶本比显著更高（2.1对1.1，P<0.01）。因此，本研究证明了使用新型纳米颗粒AnxCLIO-Cy5.5在体内获得心肌细胞凋亡高分辨率磁共振图像的可行性。
