PET imaging of in vivo caspase-3/7 activity following myocardial ischemia-reperfusion injury with the radiolabeled isatin sulfonamide analogue [(18)F]WC-4-116.
PET imaging of in vivo caspase-3/7 activity following myocardial ischemia-reperfusion injury with the radiolabeled isatin sulfonamide analogue [(18)F]WC-4-116.
复制标题
DOI：
--
复制
发表时间：
2016-04
影响因子：
2.5
通讯作者：
Arun K. Thukkani;K. Shoghi;Dong Zhou;Jinbin Xu;W. Chu;E. Novak;Delphine L. Chen;R. Gropler;R. Mach
中科院分区：
文献类型：
--
作者：
Arun K. Thukkani;K. Shoghi;Dong Zhou;Jinbin Xu;W. Chu;E. Novak;Delphine L. Chen;R. Gropler;R. Mach
[(18)F]WC-4-116（一种用于成像 caspase-3 激活的 PET 示踪剂）的效用在心肌细胞凋亡的动物模型中进行了评估。在Sprague-Dawley大鼠中暂时闭塞左冠状动脉前降支引起的缺血30分钟后3小时，将[(18)F]WC-4-116注射到大鼠中。 [(18)F]WC-4-116 摄取通过 1) 放射自显影术、2) microPET 成像研究和 3) PET 后生物分布研究进行量化。 MicroPET 成像还评估了缺血后 3 小时非 caspase-3 靶向示踪剂 [(18)F]ICMT-18 的摄取。酶测定和蛋白质印迹评估了有风险和无风险区域的 caspase-3 激活。 Caspase-3 酶活性在有风险的心肌中增加，但在无风险的心肌中没有增加。 [(18)F]WC-4-116 的定量放射自显影分析表明，与假手术动物相比，缺血再灌注 (IR) 动物的摄取量高出近 2 倍。 [(18)F]WC-4-116 microPET 成像研究表明，IR 动物与假手术动物相比也同样升高。尽管有 caspase-3 激活的证据，但危险心肌中的 [(18)F]ICMT-18 摄取并未增加。 [(18)F]WC-4-116 的生物分布研究证实了 microPET 的发现。这些数据表明 caspase-3-PET 示踪剂 [(18)F]WC-4-116 可以对心肌细胞凋亡期间的体内 caspase 活性进行无创成像，并且可能对人类临床成像有用。
The utility of [(18)F]WC-4-116, a PET tracer for imaging caspase-3 activation, was evaluated in an animal model of myocardial apoptosis. [(18)F]WC-4-116 was injected into rats at 3 hours after a 30 min period of ischemia induced by temporary occlusion of the left anterior descending coronary artery in Sprague-Dawley rats. [(18)F]WC-4-116 uptake was quantified by 1) autoradiography, 2) microPET imaging studies, and 3) post-PET biodistribution studies. MicroPET imaging also assessed uptake of the non-caspase-3-targeted tracer [(18)F]ICMT-18 at 3 hours postischemia. Enzyme assays and Western blotting assessed caspase-3 activation in both at-risk and not-at-risk regions. Caspase-3 enzyme activity increased in the at-risk but not in the not-at-risk myocardium. Quantitative autoradiographic analysis of [(18)F]WC-4-116 demonstrated nearly 2-fold higher uptake in the ischemia-reperfusion (IR) versus sham animals. [(18)F]WC-4-116 microPET imaging studies demonstrated that the IR animals was similarly elevated in relation to sham. [(18)F]ICMT-18 uptake did not increase in at-risk myocardium despite evidence of caspase-3 activation. Biodistribution studies with [(18)F]WC-4-116 confirmed the microPET findings. These data indicate that the caspase-3-PET tracer [(18)F]WC-4-116 can noninvasively image in vivo caspase activity during myocardial apoptosis and may be useful for clinical imaging in humans.