Structure-Activity Relationships and in Vivo Evaluation of Quinoxaline Derivatives for PET Imaging of β-Amyloid Plaques.

This letter describes the synthesis, structure-activity relationships, and in vivo evaluation of a new series of 2-phenylquinoxaline (PQ) derivatives for imaging β-amyloid (Aβ) plaques in Alzheimer's disease (AD). In experiments in vitro, the affinity of the derivatives for Aβ aggregates varied, with K i values of 0.895 to 1180 nM. In brain sections from AD patients, derivatives with a K i of less than 111 nM intensely labeled Aβ plaques, while those with values over 242 nM showed no marked labeling. In biodistribution experiments using normal mice, the derivatives showed good uptake into (4.69-7.59 %ID/g at 2 or 10 min postinjection) and subsequent washout from (1.48-3.08 %ID/g at 60 min postinjection) the brain. In addition, [(18)F]PQ-6 labeled Aβ plaques in vivo in APP transgenic mice, while it showed nonspecific binding in the white matter. Further structural optimization based on [(18)F]PQ-6 may lead to more useful PET probes for imaging Aβ plaques.