Figure 1: Schematic of Experimental Design

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.