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JACC Basic Transl Sci. 2018 May 30;3(3):378-390. doi: 10.1016/j.jacbts.2018.02.003. eCollection 2018 Jun.

In Vivo Reactive Oxygen Species Detection With a Novel Positron Emission Tomography Tracer, 18F-DHMT, Allows for Early Detection of Anthracycline-Induced Cardiotoxicity in Rodents.

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Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut.
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.
Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China.
Section of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut.
Yale School of Public Health (Biostatistics), Yale School of Medicine, New Haven, Connecticut.


Reactive oxygen species (ROS) are involved in doxorubicin-induced cardiotoxicity. The authors investigated the efficacy of 18F-DHMT, a marker of ROS, for early detection of doxorubicin-induced cardiotoxicity in rats. Echocardiography was performed at baseline and 4, 6, and 8 weeks post-doxorubicin initiation, whereas in vivo superoxide production was measured at 4 and 6 weeks with 18F-DHMT positron emission tomography. Left ventricular ejection fraction (LVEF) was not significantly decreased until 6 weeks post-doxorubicin treatment, whereas myocardial superoxide production was significantly elevated at 4 weeks. 18F-DHMT imaging detected an elevation in cardiac superoxide production before a fall in LVEF in rodents and may allow for early cardiotoxicity detection in cancer patients.


2D, 2-dimensional; CT, computed tomography; DOX, doxorubicin HCl; H&E, hematoxylin and eosin; LV, left ventricle/ventricular; LVEF, left ventricular ejection fraction; MMP, matrix metalloproteinase; MT, Masson’s trichrome; PET, positron emission tomography; ROS, reactive oxygen species; SUV, standardized uptake value; TUNEL, terminal deoxynucleotidyl transferase-mediated nick-end labeling; VOI, volume of interest; cardiotoxicity; doxorubicin; positron emission tomography; reactive oxygen species

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