*4.6. PET Data Analysis*

The dynamic PET data were binned into 23 frames, which increased incrementally in time length. PET images were reconstructed using Fourier re-binning of the 3-dimensional sinograms followed by a

2-dimensional filtered back-projection with a ramp filter giving a voxel size of (0.4 <sup>×</sup> 0.4 <sup>×</sup> 0.796) mm<sup>3</sup> . Using Amide (version 1.0.4.) [53] or PMOD software (version 3.6, PMOD Technologies Ltd., Zurich, Switzerland) volumes of interest (VOI) covering the whole brain as well as the cortex, hippocampus and cerebellum region were outlined on the PET images with the aid of the Mirrione Mouse Atlas and guided by representative magnetic resonance (MR) images obtained in comparable animals on a 1 Tesla benchtop MR scanner (ICON, Bruker BioSpin GmbH, Ettlingen, Germany). From the VOIs, time-activity curves (TACs) were derived and expressed in SUV units. Whole brain and regional brain uptake was expressed as the brain-to-plasma radioactivity concentration ratio in the last PET frame (*K*p,brain) [28]. For calculation of *K*p,brain, the radioactivity concentration derived from the last PET time frame (from 50–60 min after injection) was divided by the radioactivity concentration measured with the gamma-counter in the plasma sample obtained after the PET scan.
