ml9b00456_si_001.pdf (971.65 kB)
Structure–Activity Relationships of Radioiodinated 6,5,6-Tricyclic Compounds for the Development of Tau Imaging Probes
journal contribution
posted on 2020-01-09, 17:46 authored by Hiroyuki Watanabe, Haruka Tatsumi, Sho Kaide, Yoichi Shimizu, Shimpei Iikuni, Masahiro OnoTau aggregate, which is the main
component of the neurofibrillary
tangle, is an attractive imaging target for diagnosing and monitoring
the progression of Alzheimer’s disease (AD). In this study,
we designed and synthesized six radioiodinated 6,5,6-tricyclic compounds
to explore novel scaffolds for tau imaging probes. On in vitro autoradiography of AD brain sections, pyridoimidazopyridine and
benzimidazopyrimidine derivatives ([125I]21 and [125I]22, respectively) showed selective
binding affinity for tau aggregates, whereas carbazole, pyrrolodipyridine,
and pyridoimidazopyrimidine derivatives ([125I]10, [125I]12, and [125I]23, respectively) bound β-amyloid aggregates. In a biodistribution
study using normal mice, [125I]21 and [125I]22 showed high initial uptakes (5.73 and
5.66% ID/g, respectively, at 2 min postinjection) into and rapid washout
(0.14 and 0.10% ID/g, respectively, at 60 min postinjection) from
the brain. Taken together, two novel scaffolds including pyridoimidazopyridine
and benzimidazopyrimidine may be applied to develop useful tau imaging
probes.