In vivo PET imaging of beta-amyloid deposition in mouse models of Alzheimer's disease with a high specific activity PET imaging agent [(18)F]flutemetamol

BACKGROUND: The purpose of the study was to evaluate the applicability of (18)F-labelled amyloid imaging positron emission tomography (PET) agent [(18)F]flutemetamol to detect changes in brain beta-amyloid (Aβ) deposition in vivo in APP23, Tg2576 and APPswe-PS1dE9 mouse models of Alzheimer's disease. We expected that the high specific activity of [(18)F]flutemetamol would make it an attractive small animal Aβ imaging agent. METHODS: [(18)F]flutemetamol uptake in the mouse brain was evaluated in vivo at 9 to 22 months of age with an Inveon Multimodality PET/CT camera (Siemens Medical Solutions USA, Knoxville, TN, USA). Retention in the frontal cortex (FC) was evaluated by Logan distribution volume ratios (DVR) and FC/cerebellum (CB) ratios during the late washout phase (50 to 60 min). [(18)F]flutemetamol binding to Aβ was also evaluated in brain slices by in vitro and ex vivo autoradiography. The amount of Aβ in the brain slices was determined with Thioflavin S and anti-Aβ(1−40) immunohistochemistry. RESULTS: In APP23 mice, [(18)F]flutemetamol retention in the FC increased from 9 to 18 months. In younger mice, DVR and FC/CB(50-60) were 0.88 (0.81) and 0.88 (0.89) at 9 months (N = 2), and 0.98 (0.93) at 12 months (N = 1), respectively. In older mice, DVR and FC/CB(50-60) were 1.16 (1.15) at 15 months (N = 1), 1.13 (1.16) and 1.35 (1.35) at 18 months (N = 2), and 1.05 (1.31) at 21 months (N = 1). In Tg2576 mice, DVR and FC/CB(50-60) showed modest increasing trends but also high variability. In APPswe-PS1dE9 mice, DVR and FC/CB(50-60) did not increase with age. Thioflavin S and anti-Aβ(1−40) positive Aβ deposits were present in all transgenic mice at 19 to 22 months, and they co-localized with [(18)F]flutemetamol binding in the brain slices examined with in vitro and ex vivo autoradiography. CONCLUSIONS: Increased [(18)F]flutemetamol retention in the brain was detected in old APP23 mice in vivo. However, the high specific activity of [(18)F]flutemetamol did not provide a notable advantage in Tg2576 and APPswe-PS1dE9 mice compared to the previously evaluated structural analogue [(11)C]PIB. For its practical benefits, [(18)F]flutemetamol imaging with a suitable mouse model like APP23 is an attractive alternative.