Synthesis, Radiosynthesis, and Biological Evaluation of Fluorine-18-Labeled 2β-Carbo(fluoroalkoxy)-3β-(3′-((Z)-2-haloethenyl)phenyl)nortropanes: Candidate Radioligands for In Vi

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• 作者：Jeffrey S. Stehouwer ; Nachwa Jarkas ; Fanxing Zeng ; Ronald J. Voll ; Larry Williams ; Vernon M. Camp ; Eugene J. Malveaux ; John R. Votaw ; Leonard Howell ; Michael J. Owens ; Mark M. Goodman
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：December 25, 2008
• 年：2008
• 卷：51
• 期：24
• 页码：7788-7799
• 全文大小：354K
• 年卷期：v.51,no.24(December 25, 2008)
• ISSN：1520-4804

文摘

The meta-vinylhalide fluoroalkyl ester nortropanes 1−4 were synthesized as ligands of the serotonin transporter (SERT) for use as positron emission tomography (PET) imaging agents. In vitro competition binding assays demonstrated that 1−4 have a high affinity for the SERT (K_i values = 0.3−0.4 nM) and are selective for the SERT over the dopamine and norepinephrine transporters (DAT and NET). MicroPET imaging in anesthetized cynomolgus monkeys with [¹⁸F]1−[¹⁸F]4 demonstrated that all four tracers behave similarly with peak uptake in the SERT-rich brain regions achieved after 45−55 min, followed by a steady washout. An awake monkey study was performed with [¹⁸F]1, which demonstrated that the uptake of [¹⁸F]1 was not influenced by anesthesia. Chase studies with the SERT ligand 15 displaced [¹⁸F]1−[¹⁸F]4, but chase studies with the DAT ligand 16 did not displace [¹⁸F]1−[¹⁸F]4 thus indicating that the tracers were binding specifically to the SERT.