Cardiac magnetic resonance of targeted annexin-iron oxide labeling detects cardiac cell death in vivo after doxorubicin and myocardial infarction
Journal of Cardiovascular Magnetic Resonance volume 11, Article number: O8 (2009)
Heart failure from myocardial infarction (MI) or doxorubicin (DOX), used in cancer therapy, is preceded by significant cell apoptosis. Real-time, non-invasive detection of early cardiac apoptosis might impact patient treatment and outcomes. Early apoptosis is detected by Annexin V protein (ANX) binding to externalized membrane phosphatidylserine. To this end, we previously conjugated ANX to superparamagnetic iron oxide (ANX-SPIO). This conjugate specifically binds to early apoptotic cardiac cells in culture and is detectable by in vitro magnetic resonance imaging (MRI).
We tested whether ANX-SPIO could detect cardiac apoptosis, in vivo, via MRI (3 Tesla, GE Excite, WI) after ischemic or oxidative injury.
Mice underwent LAD ligation or intraperitoneal, cardiotoxic DOX (25 mg/kg) injection. After 24–48 hours, ANX-SPIO was given by tail vein, and mice were imaged by T2-weighted cardiac MRI (3 Tesla, GE Excite).
After MI and DOX, myocardial T2 MRI signal was detectable within 30 minutes of ANX-SPIO delivery, exhibiting either a focal (MI) or diffuse (DOX) signal distribution (see Figure 1). Peak signal was evident 24 hours after ANX-SPIO delivery, and decreased over the next 2 weeks.
Cardiac MRI using ANX-SPIO can accurately detect myocardial apoptosis in vivo. Distinct MRI signal distributions were noted following ischemic (MI) versus oxidative (DOX) injury. This molecular imaging strategy may help identify 'at risk' cardiac cell populations.
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Dash, R., Chan, T., Yamada, M. et al. Cardiac magnetic resonance of targeted annexin-iron oxide labeling detects cardiac cell death in vivo after doxorubicin and myocardial infarction. J Cardiovasc Magn Reson 11 (Suppl 1), O8 (2009). https://doi.org/10.1186/1532-429X-11-S1-O8