Abstract
BackgroundDuring anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction. The objective of the present study was to compare [18F]FDG and [123I]MIBG (metaiodobenzylguanidine) in a longitudinal study in a doxorubicin-induced cardiotoxicity rat model.MethodsMale Wistar Han rats were intravenously administered 3 times at 10 days’ interval with saline or doxorubicin (5 mg/kg). [123I]MIBG SPECT/CT (single photon emission computed tomography-computed tomography) and simultaneous [18F]FDG PET (positron emission tomography)/7 Tesla cardiac MR (magnetic resonance) imaging acquisitions were performed at 24 h interval before first doxorubicin / saline injection and every 2 weeks during 6 weeks. At 6 weeks, the heart tissue was collected for histomorphometry measurements.ResultsAt week 4, left ventricle (LV) end-diastolic volume was significantly reduced in the doxorubicin group. At week 6, the decreased LV end-diastolic volume was maintained, and LV end-systolic volume was increased resulting in a significant reduction of LV ejection fraction (47 ± 6% vs. 70 ± 3%). At weeks 4 and 6, but not at week 2, myocardial [18F]FDG uptake was decreased compared with the control group (respectively, 4.2 ± 0.5%ID/g and 9.2 ± 0.8%ID/g at week 6). Moreover, [18F]FDG cardiac uptake correlated with cardiac function impairment. In contrast, from week 2, a significant decrease of myocardial [123I]MIBG heart to mediastinum ratio was detected in the doxorubicin group and was maintained at weeks 4 and 6 with a 45.6% decrease at week 6.ConclusionThis longitudinal study precises that after doxorubicin treatment, cardiac [123I]MIBG uptake is significantly reduced as early as 2 weeks followed by the decrease of the LV end-diastolic volume and [18F]FDG uptake at 4 weeks and finally by the increase of LV end-systolic volume and decrease of LV ejection fraction at 6 weeks. Cardiac innervation imaging should thus be considered as an early key feature of anthracycline cardiac toxicity.
Highlights
During anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction
While body weight regularly increased in the control group, it remained at about the same level in doxorubicin-treated rats
The [123I]MIBG H to M ratio did not correlate with ejection fraction as shown on Fig. 6b (p > 0.05). We showed that both glucose metabolism evaluated by [18F]Fluorodeoxy‐ glucose (FDG)/positron emission tomography (PET) and cardiac innervation evaluated by [123I]MIBG / Single photon emission computed tomography (SPECT) were impacted by a doxorubicin repeated administration in rats
Summary
During anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction. Anthracyclines remain important drugs often mandatory in the treatment of many cancers despite their known cardiotoxicity. Anthracyclines mechanisms of action are multiple and still need to be better understood. They include DNA damage, apoptosis, inflammation, calcium dysregulation and reactive oxygen species production [4]. The recent European guidelines [5] recommend both baseline assessment and close monitoring of cardiac function to better prevent cardiotoxicity. Cardiotoxicity induced by anticancer treatment is today defined as any reduction of ejection fraction to below 50% or a > 10% reduction from baseline falling below the lower limit of normal [5]. There is no validated tool to detect cardiotoxicity before any change of cardiac function in clinical routine and that could be of interest in investigating cardioprotective strategies
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