64 Cu-ATSM Positron Emission Tomography/Magnetic Resonance Imaging of Hypoxia in Human Atherosclerosis

作者：Xingyu Nie, Andrew Elvington, Richard Laforest, Jie Zheng, Thomas Voller, Mohamed A. Zayed, Dana R. Abendschein, Nilantha Bandara, Jinbin Xu, Ran Li, Gwendalyn J. Randolph, Robert J. Gropler, Suzanne E. Lapi, Pamela K. Woodard · 发表于：Circulation Cardiovascular Imaging · 年份：2020 · DOI：10.1161/circimaging.119.009791 · 被引用次数：21 · 研究领域：Cerebrovascular and Carotid Artery Diseases、Advanced MRI Techniques and Applications、MRI in cancer diagnosis

he macrophage-rich core of advanced human atheroma has been shown to be hypoxic, which may have implications for plaque stability.1 Recently, we showed that the hypoxia positron emission tomography (PET) imaging agent 64 Cu-diacetyl-bis(N4-methylthiosemicarbazone) ( 64 Cu-ATSM) could be used for visualizing hypoxic cells in atherosclerosis in animal models.2 In this study, we investigated the feasibility of 64 Cu-ATSM Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) for detecting hypoxic cells in human atherosclerotic plaque.The cellular retention mechanism of 64 Cu-ATSM is that in vitro Cu-ATSM undergoes bioreductive trapping under hypoxic conditions.Cu-ATSM Cu(II) is a lipophilic molecule, with high membrane permeability and low redox potential, and is reduced only in hypoxic cells.On intracellular reduction, Cu-ATSM becomes trapped irreversibly, and thus the radioactivity accumulates in these cells.3 This prospective human study was approved by the Institutional Review Board at Washington University, and all patients provided informed consent.The data that support the findings of this study are available from the corresponding author on reasonable request.Images of sufficient diagnostic quality for further analysis were obtained in 7 neurologically asymptomatic patients (74.3±6.2 years old) with carotid atherosclerosis and ≥50% diameter stenosis in at least one carotid artery.Dynamic PET imaging was done 0 to 60 minutes after intravenous injection of 740 t...