Synthesis, Fluorine-18 Radiolabeling, and Biological Evaluation of N-((E)-4-Fluorobut-2-en-1-yl)-2β-carbomethoxy-3β-(4′-halophenyl)nortropanes: Candidate Radioligands for

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• 作者：Jeffrey S. Stehouwer ; Lauryn M. Daniel ; Ping Chen ; Ronald J. Voll ; Larry Williams ; Susan J. Plott ; John R. Votaw ; Michael J. Owens ; Leonard Howell ; Mark M. Goodman
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：August 12, 2010
• 年：2010
• 卷：53
• 期：15
• 页码：5549-5557
• 全文大小：955K
• 年卷期：v.53,no.15(August 12, 2010)
• ISSN：1520-4804

文摘

The N-(E)-fluorobutenyl-3β-(para-halo-phenyl)nortropanes 9−12 were synthesized as ligands of the dopamine transporter (DAT) for use as ¹⁸F-labeled positron emission tomography (PET) imaging agents. In vitro competition binding assays demonstrated that compounds 9−12 have a high affinity for the DAT and are selective for the DAT compared to the serotonin and norepinephrine transporters. MicroPET imaging with [¹⁸F]9−[¹⁸F]11 in anesthetized cynomolgus monkeys showed high uptake in the putamen with lesser uptake in the caudate, but significant washout of the radiotracer was only observed for [¹⁸F]9. PET imaging with [¹⁸F]9 in an awake rhesus monkey showed high and nearly equal uptake in both the putamen and caudate with peak uptake achieved after 20 min followed by a leveling-off for about 10 min and then a steady washout and attainment of a quasi-equilibrium. During the time period 40−80 min postinjection of [¹⁸F]9, the ratio of uptake in the putamen and caudate vs cerebellum uptake was ≥4.