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

Nabil E Boutagy; Jing Wu; Zhengxi Cai; Wenjie Zhang; Carmen J Booth; Tassos C Kyriakides; Daniel Pfau; Tim Mulnix; Zhao Liu; Edward J Miller; Lawrence H Young; Richard E Carson; Yiyun Huang; Chi Liu; Albert J Sinusas

doi:10.1016/j.jacbts.2018.02.003

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

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

Authors

Nabil E Boutagy¹, Jing Wu², Zhengxi Cai², Wenjie Zhang^{2

3}, Carmen J Booth⁴, Tassos C Kyriakides⁵, Daniel Pfau¹, Tim Mulnix², Zhao Liu¹, Edward J Miller¹, Lawrence H Young¹, Richard E Carson², Yiyun Huang², Chi Liu², Albert J Sinusas^{1

2}

Affiliations

¹ Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut.
² Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.
³ Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China.
⁴ Section of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut.
⁵ Yale School of Public Health (Biostatistics), Yale School of Medicine, New Haven, Connecticut.

Abstract

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.

Keywords: 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.

Abstract

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