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Synthesis and Evaluation of Novel 18F Labeled 2‑Pyridinylbenzoxazole and 2‑Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β‑Amyloid Plaques
journal contribution
posted on 2012-11-08, 00:00 authored by Mengchao Cui, Xuedan Wang, Pingrong Yu, Jinming Zhang, Zijing Li, Xiaojun Zhang, Yanping Yang, Masahiro Ono, Hongmei Jia, Hideo Saji, Boli LiuA series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole
and
2-pyridinylbenzothiazole derivatives were synthesized and evaluated
as novel β-amyloid (Aβ) imaging probes for PET. They displayed
binding affinities for Aβ1–42 aggregates that
varied from 2.7 to 101.6 nM. Seven ligands with high affinity were
selected for 18F labeling. In vitro autoradiography results
confirmed the high affinity of these radiotracers. In vivo biodistribution
experiments in normal mice indicated that the radiotracers with a
short FPEG chain (n = 1) displayed high initial uptake
into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole
derivatives, [18F]-5-(5-(2-fluoroethoxy)benzo[d]oxazol-2-yl)-N-methylpyridin-2-amine ([18F]32) (Ki = 8.0 ± 3.2
nM) displayed a brain2min/brain60min ratio of
4.66, which is highly desirable for Aβ imaging agents. Target
specific binding of [18F]32 to Aβ plaques
was validated by ex vivo autoradiographic experiment with transgenic
model mouse. Overall, [18F]32 is a promising
Aβ imaging agent for PET and merits further evaluation in human
subjects.