Detection of vulnerable atherosclerosis plaques in a mice model by ¹⁸F-ML-10 PET/CT imaging targeting apoptotic macrophages

Objectives: Apoptosis is a key factor in vulnerable plaques. [18F]ML-10 (2-(5-fluoro-pentyl)-2-methylmalonic acid) is a positron emission tomography (PET) radiotracer that accumulates in cells presenting apoptosis-specific membrane alterations. The aim of this study is to evaluate the utility of visualizing atherosclerotic plaques with 18F-ML-10.

Methods: ApoE−/− mice were fed with a high-fat diet to develop atherosclerosis at 20 weeks and 32 weeks, C57 mice as a control. 18F-ML-10 was obtained using a routine conjugation protocol, which were applied for in vivo imaging of atherosclerotic plaques in the animal model in vitro imaging of aorta by PET/CT. Oil Red O staining, TUNEL and hematoxylin-eosin (HE) were used to evaluate the deposition of lipids and presence of apoptotic macrophages in the lesions where focal intensity positively correlated with the uptake of 18F-ML-10.

Results: 18F-ML-10 with a high radiochemical purity (100%) and a well stability at room temperature was used. The plaque-to-background ratio (P/B) at 32 weeks ApoE−/− mice was significant higher than that at 20 weeks ApoE−/− mice, with the value of P/B was 2.96 ± 0.93 and 1.93 ± 0.38, respectively (P=0.002). No plaques were found in C57 control mice. Furthermore, Oil Red O staining showed lipid deposition areas were significantly increased in ApoE−/− mice at 20 and 32 weeks, and TUNEL staining confirmed that the focal uptake of 18F-ML-10 contained abundant apoptotic macrophages. Conclusions: The 18F-ML-10 can be useful for the quantification of vulnerable atherosclerotic plaques riching in apoptotic cells. Key Words: Atherosclerosis, Plaque vulnerability, 18F-ML-10, Micro-PET/CT