Fang Wei, Wang Feng, Ji Shundong, Zhu Xiaoguang, Meier Heidi T, Hellman Robert S, Brindle Kevin M, Davletov Bazbek, Zhao Ming
Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.
Nucl Med Biol. 2007 Nov;34(8):917-23. doi: 10.1016/j.nucmedbio.2007.06.014. Epub 2007 Sep 4.
The C2A domain of synaptotagmin I recognizes necrotic and apoptotic cells by binding to exposed anionic phospholipids. The goal is to explore the potential imaging utility of 99mTc-labeled C2A in the detection of acute cardiac cell death in a porcine model that resembles human cardiovascular physiology.
Ischemia (20-25 min) was induced in pigs (M/F, 20-25 kg) using balloon angioplasty. 99mTc-C2A-GST (n=7) or 99mTc-BSA (n=2) was injected intravenously 1-2 h after reperfusion. Noninfarct animals were injected with 99mTc-C2A-GST (n=4). SPECT images were acquired at 3 and 6 h postinjection. Cardiac tissues were analyzed to confirm the presence of cell death.
Focal uptake was detected in five out of seven subjects at 3 h and in all infarct subjects at 6 h postinjection but not in infarct animals injected with 99mTc-BSA or in noninfarct animals with 99mTc-C2A-GST. Gamma counting of infarct versus normal myocardium yielded a 10.2+/-5.7-fold elevation in absolute radioactivity, with histologically confirmed infarction.
We present data on imaging myocardial cell death in the acute phase of infarction in pigs. C2A holds promise and warrants further development as an infarct-avid molecular probe.
突触结合蛋白I的C2A结构域通过与暴露的阴离子磷脂结合来识别坏死和凋亡细胞。目的是在类似于人类心血管生理学的猪模型中探索99mTc标记的C2A在检测急性心脏细胞死亡方面的潜在成像效用。
使用球囊血管成形术在猪（雌雄不限，体重20 - 25千克）中诱导缺血（20 - 25分钟）。再灌注后1 - 2小时静脉注射99mTc - C2A - GST（n = 7）或99mTc - BSA（n = 2）。未梗死动物注射99mTc - C2A - GST（n = 4）。在注射后3小时和6小时采集单光子发射计算机断层扫描（SPECT）图像。对心脏组织进行分析以确认细胞死亡的存在。
注射后3小时，7只受试动物中有5只检测到局灶性摄取，6小时时所有梗死受试动物均检测到局灶性摄取，但注射99mTc - BSA的梗死动物或注射99mTc - C2A - GST的未梗死动物中未检测到。梗死心肌与正常心肌的γ计数显示绝对放射性升高了10.2±5.7倍，经组织学证实为梗死。
我们展示了在猪梗死急性期成像心肌细胞死亡的数据。C2A有望成为一种梗死亲和性分子探针，值得进一步开发。
