Oncotarget

Research Papers: Pathology:

Positron emission tomography imaging of cardiomyocyte apoptosis with a novel molecule probe [18F]FP-DPAZn2

Ting Sun _, Ganghua Tang, Hua Tian, Kongzhen Hu, Shaobo Yao, Yifan Su and Changqian Wang

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Oncotarget. 2015; 6:30579-30591. https://doi.org/10.18632/oncotarget.5769

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Abstract

Ting Sun1, Ganghua Tang2, Hua Tian3, Kongzhen Hu2, Shaobo Yao2, Yifan Su1 and Changqian Wang1

1 Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China

2 Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China

3 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute and Cancer Institute of Shanghai Jiao Tong University, Shanghai, P.R. China

Correspondence to:

Ting Sun, email:

Changqian Wang, email:

Ganghua Tang, email:

Keywords: radiosynthesis, Zinc(II)-dipicolylamine, apoptosis, cardiomyocyte, positron emission tomography imaging, Pathology Section

Received: August 08, 2015 Accepted: September 12, 2015 Published: September 21, 2015

Abstract

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.


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