Preclinical Comparison of the Amyloid-β Radioligands [11C]Pittsburgh compound B and [18F]florbetaben in Aged APPPS1-21 and BRI1-42 Mouse Models of Cerebral Amyloidosis

The aim of this study was to compare [C-11]Pittsburgh compound B ([C-11]PiB) and [F-18]florbetaben ([F-18]FBB) for preclinical investigations of amyloid-beta pathology. We investigated two aged animal models of cerebral amyloidosis with contrasting levels of amyloid-beta relating to high (APPPS1-21 n = 6, wild type (WT) n = 7) and low (BRI1-42 n = 6, WT n = 6) target states, respectively. APPPS1-21 mice (high target state) demonstrated extensive fibrillar amyloid-beta deposition that translated to significantly increased retention of [C-11]PiB and [F-18]FBB in comparison to their wild type. The retention pattern of [C-11]PiB and [F-18]FBB in this cohort displayed a significant correlation. However, the relative difference in tracer uptake between diseased and healthy mice was substantially higher for [C-11]PiB than for [F-18]FBB. Although immunohistochemistry confirmed the high plaque load in APPPS1-21 mice, correlation between tracer uptake and ex vivo quantification of amyloid-beta was poor for both tracers. BRI1-42 mice (low target state) did not demonstrate increased tracer uptake. In cases of high fibrillar amyloid-beta burden, both tracers detected significant differences between diseased and healthy mice, with [C-11]PiB showing a larger dynamic range.