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