Abstract
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Objectives: ackgrounds: Apoptosis of cardiocytes occurs in most cardic disease and contributes to the subsequent heart failure. Imaging apoptosis is helpful to noninvasively detect the progression of disease and the effect of preventing heart failure. Here, we tested 18F-labeled-2-(5-fluoropentyl)-2-methyl-malonic acid (18F-ML-10) and 18F-labeled-2-(3-fluoropropyl)-2-methyl-malonic acid (18F-ML-8) to image apoptosis in a rat model of myocardial infarction (MI) and compared with 18F-fluorodeoxyglucose (18F-FDG).
Methods: MI was induced by permanent left coronary artery ligation in Sprague-Dawley rats and was confirmed by echocardiography. Serial Positron Emission Tomography (PET)/Computed Tomography (CT) images with 18F-ML-10 and 18F-ML-8 were performed in MI models, and compared with 18F-FDG image. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and immunohistochemical analysis were used to evaluate myocardical apoptosis. Results: The infarct area absent from 18F-FDG uptake showed high uptake of 18F-ML-10 and 18F-ML-8. The infarct-to-lung ratio was 4.29 ± 0.30 for 18F-ML-10 and 3.51 ± 0.18 for 18F-ML-8 (n=6, p<0.05). Apoptosis analysis showed that 18F-ML-8 uptake was better correlated with apoptosis rate than 18F-ML-10 uptake. However, there was no correlation between 18F-FDG uptake and apoptosis index.Conclusion: Both 18F-ML-10 and 18F-ML-8 PET/CT can be used to noninvasively detect myocardial apoptosis in the early phase and 18F-ML-8 can be better than 18F-ML-10 for apoptosis imaging. We infer that 18F-ML-10 or 18F-ML-8 combined with 18F-FDG is an alternative for detect and assess MI. Keywords: Apoptosis, Myocardial infarction, PET, 18F-ML-10, 18F-ML-10 (A) The representative images of 18F-FDG PET-CT(left), 18F-ML-10 PET-CT (right), and their fusion PET-CT (middle) (B) The representative transverse section (left) and coronal section (right) PET-CT images with 18F-ML-10 for sham rats (top) and MI rats (bottom). (C) The representative transverse and coronal PET-CT images with 18F-FDG (top) and 18F-ML-8 (bottom) for MI rats (red arrows indicate negative uptake in PET/CT images; blue arrows indicate hot-uptake in PET/CT images; white arrows indicate the uptake of wound in PET/CT images). (D) the average uptake ratios of the ratios on the 1st and 3rd day after operation for the infarct-to-remote (I/N) area in acute myocardial infarct rats with injection of 18F-FDG, 18F-ML-10 or 18F-ML-8 (P<0.0001, one-way ANOVA)