Autoradiographic Evaluation of [18F]FECUMI-101, a High Affinity 5-HT1AR Ligand in Human Brain

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• 作者：J. S. Dileep Kumar ; Mark D. Underwood ; Norman R. Simpson ; Suham A. Kassir ; Jaya Prabhakaran ; Vattoly J. Majo ; Mihran J. Bakalian ; Ramin V. Parsey ; J. John Mann ; Victoria Arango
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：May 12, 2016
• 年：2016
• 卷：7
• 期：5
• 页码：482-486
• 全文大小：277K
• 年卷期：0
• ISSN：1948-5875

文摘

[¹⁸F]FECUMI-101 ([¹⁸F]1) is a 5HT_1AR ligand demonstrating specific binding in brain regions corresponding to the distribution of 5-HT_1AR in baboons. However, we detected moderate uptake of [¹⁸F]1 in baboon thalamus, a brain region lacking 5-HT_1AR. We sought to investigate the relative binding of [¹⁸F]1 to 5-HT_1AR, α₁R, and 5-HT₇R in vitro. Using autoradiography in human brain sections, specific binding of [¹⁸F]1 to 5-HT_1AR was confirmed. However, [¹⁸F]1 also showed 26% binding to α₁R in PFC. The hippocampal formation exhibited 51% and 92% binding of [¹⁸F]1 to α₁R and 5-HT_1AR, respectively. Thalamus and cerebellum showed very little binding. There is no measurable specific binding of [¹⁸F]1 to 5-HT₇R and no effect of temperature on [¹⁸F]1 specific binding to 5-HT_1AR or α₁R. These results indicate that, while [¹⁸F]FECUMI-101 is not a completely selective 5-HT_1AR ligand for receptor quantification, it may be useful for occupancy measurements of drugs acting at 5-HT_1AR in vivo.