*2.3. [11C]Erlotinib PET*

To confirm the lack of an effect of the decreased abundance of ABCG2 on the brain distribution of [11C]tariquidar, we performed PET scans with a second ABCB1/ABCG2 substrate radiotracer ([11C]erlotinib) [35]. In contrast to [11C]tariquidar, PET scans were only performed under conditions of full ABCB1/ABCG2 activity, i.e., no ABCB1 or ABCG2 inhibitors were administered. To mimic the therapeutic usage of erlotinib, we co-injected [11C]erlotinib with a pharmacological dose of unlabeled erlotinib (2 mg/kg) [36]. Whole brain TACs of [11C]erlotinib were very similar in the two mouse strains (Figure 6a). Moreover, *K*p,brain values were not significantly different between APP/PS1-21 and wild-type mice in the three examined brain regions (hippocampus, cortex and cerebellum) (Figure 6b–d).

**Figure 6.** Time-activity curves (mean <sup>±</sup> SD) of [11C]erlotinib in whole brains of 6-months-old APP/PS1-21 mice (closed circles, *n* = 4) and age-matched wild-type mice (open circles, *n* = 4) (**a**). Regional brain-to-plasma radioactivity concentration ratios (*K***p,brain**) in (**b**) hippocampus, (**c**) cortex and (**d**) cerebellum at the end of the [11C]erlotinib PET scan in APP/PS1-21 mice and wild-type mice (ns, not significant; 2-sided *t*-test).
