posted on 2021-07-20, 19:08authored byAshley
C. Knight, Cassis Varlow, Junchao Tong, Neil Vasdev
Glycogen
synthase kinase-3 (GSK-3) is a positron emission tomography
(PET) imaging target with implications in the pathogenesis of Alzheimer’s
disease (AD). This preliminary study evaluates human AD and transgenic
P301L mouse brain tissues using the GSK-3-targeting radiotracers [3H]PF-367 and [3H]OCM-44 in radioligand binding
assays. A saturation analysis showed decreased GSK-3 density in female
human AD compared to a normal healthy brain. Equivalence in density
(Bmax), affinity (Kd), and apparent affinity (Ki)
of both radiotracers was demonstrated to enable their interchangeability
for in vitro evaluations of GSK-3 expression. An evaluation of P301L
mouse brain by [3H]/[11C]OCM-44 delineated differences
in the Bmax of GSK-3 between the control
and transgenic mice within male subjects. PET imaging showed similar
trends to those observed in vitro. Sex differences are revealed as
a potential parameter to consider in the development of GSK-3-targeted
diagnostics and therapeutics and could guide recruitment for clinical
studies.