Synthesis and evaluation of (S)-[18F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:26

Article

Pithia, Neema K.¹  Liang, Christopher¹  Pan, Xiang-Zuo¹  Pan, Min-Liang¹  Mukherjee, Jogeshwar¹ 

[1] Univ Calif Irvine, Dept Radiol Sci, Preclin Imaging, Med Sci B140, Irvine, CA 92697 USA

关键词: Fesetron;    Serotonin 5-HT3 receptors;    PET;    Autoradiography;    Palonosetron;    Zacopride;    Cancer chemotherapy;   

DOI  :  10.1016/j.bmcl.2016.03.018

来源: Elsevier

【 摘 要 】

Serotonin 5-HT3 receptors are involved in various brain functions including as an emesis target during cancer chemotherapy. We report here the development of (S)-2,3-dimethoxy-5-(3'-[F-18]fluoropropyl)-N-( 1-azabicyclo[2.2.2]oct-3-yl)benzamide ([F-18]fesetron) as a potential PET imaging agent for serotonin 5-HT3 receptors. By radiolabeling((S)-2,3-dimethoxy-5-(3'-tosyloxypropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl) benzamide) with fluorine-18, (S)-[F-18] fesetron was obtained in 5 to 10% decay-corrected yields and with specific activities >74 GBq/mu mol at the end of radiosynthesis. PET imaging in rats showed low uptake of [F-18] fesetron in the brain with retention of binding in the striatal and cerebellar regions. Using colliculi as a reference region, ratios were 3.4 for striata and 2.5 for cerebellum. Ex vivo brain PET analysis displayed binding of [F-18] fesetron in the hippocampus, striatum and cerebellar regions. Cerebellar regions corresponded to area postrema and nucleus tract solitaris known to contain 5-HT3 receptors. Dorsal hippocampus showed the highest uptake with ratio of >17 with respect to colliculi, while area postrema and striata had ratios of >10. Thus, [F-18] fesetron exhibited a unique binding profile to rat brain regions known to contain significant amounts of serotonin 5-HT3 receptors. However, the very low brain uptake limits its usefulness as a PET radiotracer in this animal model. (C) 2016 Elsevier Ltd. All rights reserved.

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