Synthesis and Evaluation
of Novel <sup>18</sup>F Labeled
2‑Pyridinylbenzoxazole and 2‑Pyridinylbenzothiazole
Derivatives as Ligands for Positron Emission Tomography (PET) Imaging
of β‑Amyloid Plaques
Mengchao Cui
Xuedan Wang
Pingrong Yu
Jinming Zhang
Zijing Li
Xiaojun Zhang
Yanping Yang
Masahiro Ono
Hongmei Jia
Hideo Saji
Boli Liu
10.1021/jm300973k.s001
https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Evaluation_of_Novel_sup_18_sup_F_Labeled_2_Pyridinylbenzoxazole_and_2_Pyridinylbenzothiazole_Derivatives_as_Ligands_for_Positron_Emission_Tomography_PET_Imaging_of_Amyloid_Plaques/2470579
A 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 Aβ<sub>1–42</sub> aggregates that
varied from 2.7 to 101.6 nM. Seven ligands with high affinity were
selected for <sup>18</sup>F 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 (<i>n</i> = 1) displayed high initial uptake
into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole
derivatives, [<sup>18</sup>F]-5-(5-(2-fluoroethoxy)benzo[<i>d</i>]oxazol-2-yl)-<i>N</i>-methylpyridin-2-amine ([<sup>18</sup>F]<b>32</b>) (<i>K</i><sub>i</sub> = 8.0 ± 3.2
nM) displayed a brain<sub>2min</sub>/brain<sub>60min</sub> ratio of
4.66, which is highly desirable for Aβ imaging agents. Target
specific binding of [<sup>18</sup>F]<b>32</b> to Aβ plaques
was validated by ex vivo autoradiographic experiment with transgenic
model mouse. Overall, [<sup>18</sup>F]<b>32</b> is a promising
Aβ imaging agent for PET and merits further evaluation in human
subjects.
2012-11-08 00:00:00
binding affinities
radiotracer
autoradiography results
affinity
derivative
vivo biodistribution experiments
Positron Emission Tomography
pyridinylbenzoxazole
β imaging agents
brain 2min ratio
101.6 nM
FPEG chain
vivo autoradiographic experiment
β plaques
model mouse
18 F
β imaging agent