PET imaging of cardiomyocyte apoptosis in a rat myocardial infarction model

AbstractCardiomyocyte apoptosis has been observed in several cardiovascular diseases and contributes to the subsequent cardiac remodeling processes and progression to heart failure. Consequently, apoptosis imaging is helpful for noninvasively detecting the disease progression and providing treatment guidance. Here, we tested18F-labeled 2-(5-fluoropentyl)-2-methyl-malonic acid (18F-ML-10) and18F-labeled 2-(3-fluoropropyl)-2-methyl-malonic acid (18F-ML-8) for apoptosis imaging in rat models of myocardial infarction (MI) and compared them with18F-fluorodeoxyglucose (18F-FDG). MI was induced in Sprague-Dawley rats by permanent left coronary artery ligation. Procedural success was confirmed by echocardiography and positron emission tomography (PET) imaging with18F-FDG. In vivo PET imaging with18F-ML-10 and18F-ML-8 was performed in the MI models at different time points after operation. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and immunohistochemical analyses were used to evaluate myocardial apoptosis. In vitro cell binding assays were performed to validate18F-ML-8 binding to apoptotic cardiomyocytes. PET imaging demonstrated high18F-ML-10 and18F-ML-8 uptake where18F-FDG uptake was absent. The focal accumulation of the two tracers was high on days 1 and 3 but was not notable on days 5 and 7 after surgery. The infarct-to-lung uptake ratio was 4.29  ± 0.30 for18F-ML-10 and 3.51  ± 0.18 for18F-ML-8 (n  = 6, analyzed by averaging the upt...
Source: Apoptosis - Category: Molecular Biology Source Type: research