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Feasibility of using 18F-ML-10 to monitor cardiotoxicity induced by doxorubicin |
HUANG Shiming1, CHEN Wei1, ZHANG Jinming2, MA Yongqiang3, YUE Jianlan1, LI Yanfeng1, and LIN Zhichun1 |
1.Department of Nuclear Medicine, Affiliated Hospital of Logistics University of Chinese People’s Armed Police Force, Tianjin 300162, China; 2. Department of Nuclear Medicine, the PLA General Hospital, Beijing 100853, China; 3. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury Institute of Cardiovascular Disease and Heart Center, Tianjin 300162,China |
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Abstract Objective To investigate the feasibility of noninvasive monitoring of doxorubicin-induced cardiotoxicity by radionuclide apoptosis imaging agent 18F-ML-10.Methods Thirty-six KM mice were randomly and equally divided into control group, low dose (15 mg / kg) model group and high dose (20 mg/kg) model group. The mice in control group were injected with normal saline. Doxorubicin was injected into model group at some dose. After 48 hours, mice were subjected to cardiac ultrasonography and the biodistribution of 18F-FDG and 18F-ML-10 was determined with gamma counting. The mice were sacrificed to remove the heart for caspase 3 immunohistochemical detection of myocardial cell apoptosis.Results The left ventricular ejection fraction was significantly lower in low dose group (LVEF=59.49±5.32%) and high dose group (LVEF=52.41±6.47%) than that in control group (LVEF=70.58±5.06%), but the uptake of 18F-FDG in low dose group (%ID/g=0.50±0.11) and high dose group (%ID/g=15.58±1.92) was significantly lower than that in control group (%ID/g=36.18±3.65).The uptake of apoptotic imaging agent 18F-ML-10 in low dose group (%ID/g=0.50±0.11) and high dose group(%ID/g=1.10±0.55)was significantly higher than that in control group (%ID/g=0.02±0.02) (P<0.05). Caspase 3 immunohistochemistry showed obvious apoptosis of myocardial cells in model group, which was consistent with the uptake of 18F-ML-10 in the heart.Conclusions Apoptosis is an important pathway for doxorubicin-induced cardiotoxicity. 18F-ML-10 may contribute to the detection of doxorubicin-induced myocardial apoptosis.
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Received: 11 August 2016
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