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

PURPOSE: The aim of this study was to compare [(11)C]Pittsburgh compound B ([(11)C]PiB) and [(18)F]florbetaben ([(18)F]FBB) for preclinical investigations of amyloid-β pathology.

PROCEDURES: We investigated two aged animal models of cerebral amyloidosis with contrasting levels of amyloid-β relating to "high" (APPPS1-21 n = 6, wild type (WT) n = 7) and "low" (BRI1-42 n = 6, WT n = 6) target states, respectively.

RESULTS: APPPS1-21 mice (high target state) demonstrated extensive fibrillar amyloid-β deposition that translated to significantly increased retention of [(11)C]PiB and [(18)F]FBB in comparison to their wild type. The retention pattern of [(11)C]PiB and [(18)F]FBB in this cohort displayed a significant correlation. However, the relative difference in tracer uptake between diseased and healthy mice was substantially higher for [(11)C]PiB than for [(18)F]FBB. Although immunohistochemistry confirmed the high plaque load in APPPS1-21 mice, correlation between tracer uptake and ex vivo quantification of amyloid-β was poor for both tracers. BRI1-42 mice (low target state) did not demonstrate increased tracer uptake.

CONCLUSIONS: In cases of high fibrillar amyloid-β burden, both tracers detected significant differences between diseased and healthy mice, with [(11)C]PiB showing a larger dynamic range.