Novel 18F-Labeled Benzoxazole Derivatives as Potential Positron Emission Tomography Probes for Imaging of Cerebral 尾-Amyloid Plaques in Alzheimer鈥檚 Disease

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• 作者：Mengchao Cui ; Masahiro Ono ; Hiroyuki Kimura ; Masashi Ueda ; Yuji Nakamoto ; Kaori Togashi ; Yoko Okamoto ; Masafumi Ihara ; Ryosuke Takahashi ; Boli Liu ; Hideo Saji
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：November 8, 2012
• 年：2012
• 卷：55
• 期：21
• 页码：9136-9145
• 全文大小：488K
• 年卷期：v.55,no.21(November 8, 2012)
• ISSN：1520-4804

文摘

Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[¹⁸F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N-methylaniline ([¹⁸F]24) and 4-(5-(2-(2-(2-[¹⁸F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([¹⁸F]32), were synthesized and evaluated as probes for imaging cerebral 尾-amyloid (A尾) plaques in living brain tissue by PET. [¹⁸F]24 and [¹⁸F]32 displayed high affinity for A尾_1鈥?2 aggregates (K_i = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [¹⁸F]24 also displayed excellent binding to A尾 plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [¹⁸F]24 between Tg2576 and wild-type mice. The results suggest [¹⁸F]24 to be a useful PET agent for detecting A尾 plaques in the living human brain.