title: Positron emission tomography imaging of cardiomyocyte apoptosis with a novel molecule probe [18F]FP-DPAZn2.
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.
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Ganghua
authors.initials: G
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute and Cancer Institute of Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Kongzhen
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China.
authors.forename: Changqian
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis*; D002460:Cell Line; D004195:Disease Models, Animal; D004452:Echocardiography; D005462:Fluorine Radioisotopes; D006333:Heart Failure / Q000473:pathology; D006334:Heart Function Tests; D020287:In Situ Nick-End Labeling; D008297:Male; D015335:Molecular Probes; D032383:Myocytes, Cardiac / Q000502:physiology*; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D010847:Picolines / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005462:Fluorine Radioisotopes; D015335:Molecular Probes; D009942:Organometallic Compounds; D010847:Picolines; C509592:zinc(II) dipicolylamine
keywords: Pathology Section; Zinc(II)-dipicolylamine; apoptosis; cardiomyocyte; positron emission tomography imaging; radiosynthesis