Sun Ting, Tang Ganghua, Tian Hua, Hu Kongzhen, Yao Shaobo, Su Yifan, Wang Changqian
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China.
Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
Oncotarget. 2015 Oct 13;6(31):30579-91. doi: 10.18632/oncotarget.5769.
Cardiomyocyte apoptosis plays a causal role in the development and progression of heart failure. Currently, there is no effective imaging agent that can be used to detect cardiomyocyte apoptosis in vivo. To target phosphatidylserine (PS) on the surface of the dying cell, we synthesized a novel 18F-labeled Zn2+-dipicolylamine (DPA) analog, [18F]FP-DPAZn2, and evaluated it for noninvasive imaging of cardiomyocyte apoptosis. In vitro, the fluorescence imaging of dansyl-DPAZn2 was suitable for detecting cardiomyocyte apoptosis, which was confirmed by confocal immunofluorescence imaging, terminal dUTP nick-end labeling (TUNEL) assay, and western blot assay. The in vivo biodistribution showed that the uptake ratios of [18F]FP-DPAZn2 in the heart were 4.41±0.29% ID/g at 5 min, 2.40 ± 0.43% ID/g at 30 min, 1.63 ± 0.26% ID/g at 60 min, and 1.43% ± 0.07 ID/g at 120 min post-injection. In vivo, the [18F]FP-DPAZn2 PET images showed more cardiac accumulation of radioactivity 60 min post-injection in acute myocardial infarction (AMI) rats than in normal rats, which was consistent with the findings of a histological analysis of the rat cardiac tissues in vitro. [18F]FP-DPAZn2 PET imaging has the capability for myocardial apoptosis detection, but the method will require improved myocardial uptake for the noninvasive evaluation of cardiomyocyte apoptosis in clinical settings.
心肌细胞凋亡在心力衰竭的发生和发展中起因果作用。目前，尚无有效的成像剂可用于在体内检测心肌细胞凋亡。为了靶向死亡细胞表面的磷脂酰丝氨酸（PS），我们合成了一种新型的18F标记的Zn2 + -二吡啶甲胺（DPA）类似物[18F] FP-DPAZn2，并对其进行心肌细胞凋亡的无创成像评估。在体外，丹磺酰-DPAZn2的荧光成像适用于检测心肌细胞凋亡，这通过共聚焦免疫荧光成像、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）测定和蛋白质印迹测定得到证实。体内生物分布显示，注射后5分钟时[18F] FP-DPAZn2在心脏中的摄取率为4.41±0.29％ID/g，30分钟时为2.40±0.43％ID/g，60分钟时为1.63±0.26％ID/g，120分钟时为1.43％±0.07 ID/g。在体内，[18F] FP-DPAZn2 PET图像显示，急性心肌梗死（AMI）大鼠注射后60分钟时心脏放射性积聚比正常大鼠更多，这与体外大鼠心脏组织的组织学分析结果一致。[18F] FP-DPAZn2 PET成像具有检测心肌细胞凋亡的能力，但该方法需要提高心肌摄取率，以便在临床环境中对心肌细胞凋亡进行无创评估。
