Using 18F-ML-10 PET/CT imaging to detect atherosclerosis lesions and apoptotic processes in mice
Year: 2025
Type: article
Abstract: Background: Apoptosis plays a critical role in the development and progression of atherosclerotic plaques. [18F] fluoride 2-(5-fluoro-pentyl)-2-methylmalonic acid (18F-ML-10), a positron emission tomography (PET) radiotracer, selectively targets cells undergoing apoptosis by binding to apoptosis-associated membrane alterations. This study evaluated the efficacy of 18F-ML-10 PET/computed tomography (CT) in visualizing apoptotic activity in atherosclerotic plaques. Methods: Apolipoprotein E knockout (ApoE−/−) mice were fed a high-fat diet to induce atherosclerosis, and imaged at 20 and 32 weeks, with C57BL/6J (C57) mice serving as controls. 18F-ML-10 was synthesized using a standard conjugation protocol and subsequently used for the in-vivo PET/CT imaging of the atherosclerotic plaques in this animal model. Oil-red-O staining, hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL), and caspase-3 staining were performed to evaluate the deposition of lipids and amount of apoptosis in the lesions where focal intensity was positively correlated with the uptake of 18F-ML-10. Results: 18F-ML-10 was synthesized with a high radiochemical purity (>99%), a quick clearance rate, and a favorable biodistribution. In the 18F-ML-10 PET/CT imaging, the plaque-to-background (P/B) ratio of the ApoE−/− mice at 32 weeks was significantly higher than that of the ApoE−/− mice at 20 weeks. Specifically, the P/B ratio values of the ApoE−/− mice were 2.28±0.20 at 32 weeks, and 1.69±0.22 at 20 weeks (P=0.002, n=5). No plaque was found in the PET images of the control mice. Further, oil-red-O staining revealed a significant increase in lipid deposition in the ApoE−/− mice from 20 to 32 weeks, which was consistent with the 18F-ML-10 PET/CT findings. Immunohistochemically, the apoptosis index (AI) on TUNEL (r=0.950, P<0.001) and the integrated optic density (IOD)/area on caspase-3 staining (r=0.955, P<0.001) were significantly correlated with the P/B ratio of the lesions on 18F-ML-10 PET/CT in the corresponding area. Conclusions: The 18F-ML-10 PET/CT imaging technique enables the visualization of atherosclerotic plaques that are rich in apoptotic cells.
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4414483707
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