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![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)
Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
Published on: July 1, 2021
Using 18F-ML-10 PET/CT imaging to detect atherosclerosis lesions and apoptotic processes in mice
Lifang Pang1,2,3, Guobing Liu1,2,3, Yan Hu1,2,3
1Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
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.
Insights
Positron emission tomography (PET) imaging with 18F-ML-10 effectively visualizes apoptotic activity in atherosclerotic plaques. This technique shows increased plaque uptake in advanced atherosclerosis, correlating with cell death markers.
Area of Science:
- Cardiovascular Research
- Molecular Imaging
- Biomedical Engineering
Background:
- Apoptosis is a key factor in atherosclerotic plaque development and progression.
- 18F-ML-10 is a novel PET radiotracer targeting apoptotic cells via membrane alterations.
Purpose of the Study:
- To evaluate the efficacy of 18F-ML-10 PET/CT for visualizing apoptotic activity in atherosclerotic plaques.
- To correlate imaging findings with established markers of atherosclerosis and apoptosis.
Main Methods:
- Apolipoprotein E knockout (ApoE-/-) mice on a high-fat diet were imaged at 20 and 32 weeks.
- 18F-ML-10 PET/CT was performed, followed by Oil-red-O, H&E, TUNEL, and caspase-3 staining.
- Plaque-to-background (P/B) ratios were correlated with lipid deposition and apoptosis indices.
Main Results:
- 18F-ML-10 PET/CT demonstrated significantly higher P/B ratios in ApoE-/- mice at 32 weeks compared to 20 weeks (2.28 vs 1.69, P=0.002).
- Increased lipid deposition and apoptosis (TUNEL, caspase-3) were observed from 20 to 32 weeks.
- P/B ratios strongly correlated with apoptosis markers (r=0.950 for TUNEL, r=0.955 for caspase-3).
Conclusions:
- 18F-ML-10 PET/CT is a viable imaging technique for visualizing atherosclerotic plaques with high apoptotic cell content.
- The tracer shows promise for non-invasively assessing plaque activity and progression.
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