Abstract
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Introduction: It has been shown that the non-invasive detection of amyloid-β peptide (Aβ) might be a promising method for the early diagnosis of Alzheimer's disease (AD). The present study focused to investigate the feasibility of visualizing Aβ in a mouse model of early AD using pet positron emission tomography (PET) with 18F-FINH-Me.
Methods: 18F-FINH-Me PET imaging was performed at 3, 6, 9, 13- and 22-month-old APP/PS1 mice and age-matched wild-type (WT) mice. Dynamic imaging for 60 minutes and the whole brain was outlined as the area of interest to quantify the 18F-FINH-Me uptake. The brains of these mice were used for the Aβ immunohistochemistry. The distribution of 18F-FINH-Me in the brain of 3, 6, 9, 13-and 22-month-old APP/PS1 mice and age-matched WT mice was investigated to quantify the uptake of 18F-FINH-Me in the hippocampus, cortex and cerebellum. In addition, we used brain slices from patients with AD and healthy volunteers to study the binding of 18F-FINH-Me to Aβ plaque by autoradiography.
Results: The PET images revealed a significantly higher accumulation of 18F-FINH-Me in the brain of 22-month-old AD mice, when compared to age-matched WT mice (43.92±0.60 vs. 15.56±0.49, P<0.01). Furthermore, this was also higher than that of the other age of mice in the same group. In addition, the difference in 18F-FINH-Me uptake in the different brain regions of these mice was quantified by ex vivo brain distribution study. The 22-month-old AD mice had significantly higher uptake in the hippocampus and cortex, when compared to the cerebellum (P<0.01). However, the 18F-FINH-Me uptake in the different regions of the brain of WT mice exhibited no significant differences at different ages. The PET results of AD mice were closely correlated to the immunohistochemical results (that is, compared with WT mice, the more the Aβ plaques in AD mice, the higher the uptake of 18F-FINH-Me in the brain).
Conclusions: The results show that 18F-FINH-Me has great potential as a tool for visualizing Aβ plaques in the early diagnosis and intervention of Alzheimer's disease. Acknowledge: This research was supported by the National Natural Science Foundation of China (11775143 and 51703126) and Innovative research team of high-level local universities in Shanghai, Shanghai Jiaotong University Multidisciplinary Interdisciplinary Project cultivation (Medical Engineering) Fund: no. YG2017QN63.