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 and Albert J. Sinusas
Animals were treated with either doxorubicin HCl (DOX) (15 mg/kg total, n = 10) or saline (control [CTL], n = 10) every 3 days (2.15 mg/kg/dose) for 21 days. Left ventricular function was assessed in all animals with echocardiography (echo) at baseline and 4 weeks after the initiation of DOX (n = 20). At this time, a subgroup of animals (CTL, n = 5; DOX, n = 5) were imaged with 18F-DHMT positron emission tomography (PET)/computed tomography (CT). Myocardial MMP activity (99mTc-RP805), cellular cardiotoxicity and apoptosis were also assessed in these animals following euthanasia. In the remaining rats, echo (CTL, n = 5; DOX, n = 5) and 18F-DHMT PET/CT (CTL, n = 4; DOX, n = 4) imaging were repeated at 6 weeks. At 8 weeks, the remaining animals (CTL, n = 5; DOX, n = 4) underwent echo imaging and evaluation of myocardial 99mTc-RP805, and histological assessment of cardiotoxicity and apoptosis following euthanasia. μPET = micro-positron emission tomography.