Neuroimaging of indoleamine 2,3-dioxygenase 1 (Ido1) in Alzheimer's disease: Development of a novel 18F-labeled PET tracer
TL;DR
A novel PET tracer, [18F]XW-032, was developed via ruthenium-mediated deoxyfluorination and effectively visualized regional IDO1 heterogeneity in the AD brain, positioning it as a potent molecular tool for early AD diagnosis and for monitoring the efficacy of IDO1-targeted therapeutic interventions.
Abstract
IDO1-mediated dysregulation of the kynurenine pathway is a pivotal driver of neuroinflammation in Alzheimer's disease (AD). Despite its clinical significance, PET probes specifically targeting IDO1 in the AD brain remain scarce. In this study, we first established a strong correlation between IDO1 expression and AD progression through bioinformatic analysis. Subsequently, a novel PET tracer, [18F]XW-032, was developed via ruthenium-mediated deoxyfluorination. [18F]XW-032 demonstrated superior blood-brain barrier (BBB) permeability and a favorable metabolic profile. In vitro autoradiography and in vivo dynamic PET/CT imaging in 5XFAD mice confirmed its high binding specificity and robust imaging performance, further validated by competitive blocking studies with unlabeled IDO1 inhibitors. Notably, [18F]XW-032 effectively visualized regional IDO1 heterogeneity in the AD brain. These findings position [18F]XW-032 as a potent molecular tool for early AD diagnosis and for monitoring the efficacy of IDO1-targeted therapeutic interventions.