In Vitro and In Vivo Evaluation of GSK-3 Radioligands in Alzheimer’s Disease: Preliminary Evidence of Sex Differences

• DOI: 10.1021/acsptsci.1c00132
• Publication Date: 2021-07-20T19:30:41Z
• Authors: Ashley C. Knight; Cassis Varlow; Junchao Tong; Neil Vasdev
• Keywords: Radioligand; Binding potential; Human brain

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 GSK-3-targeting radiotracers [3H]PF-367 [3H]OCM-44 radioligand binding assays. A saturation analysis showed decreased GSK-3 density female compared to normal healthy brain. Equivalence (Bmax), affinity (Kd), apparent (Ki) both was demonstrated enable their interchangeability for vitro evaluations expression. An evaluation by [3H]/[11C]OCM-44 delineated differences Bmax between control mice within male subjects. PET similar trends those observed vitro. Sex are revealed as potential parameter consider development GSK-3-targeted diagnostics therapeutics could guide recruitment clinical studies.