6-[¹⁸F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors

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• 作者：Horti ; Andrew G. ; Chefer ; Svetlana I. ; Mukhin ; Alexey G. ; Koren ; Andrei O. ; Gü ; ndisch ; Daniela ; et. al.
• 关键词：Nicotinic acetylcholine receptor ; Positron emission tomography (nAChRs) ; 6-[¹⁸F]fluoro-3-(2(S)-azetidinyl-methoxy)pyridine (6-[¹⁸F]fluoro-A-85380 ; 6-[¹⁸F]FA)
• 刊名：Life Sciences
• 出版年：2000
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：June 16, 2000
• 卷：67
• 期：4
• 页码：463-469
• 文件大小：617 K

摘要

A novel positron emission tomography (PET) radiotracer, 6-[¹⁸F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[¹⁸F]fluoro-A-85380, 6-[¹⁸F]FA) was synthesized by a no-carrier-added fluorination. In vitro 6-[¹⁸F]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (K_d 28 pM). In PET studies, 6-[¹⁸F]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the α₄β₂ subtype of nAChR. 6-[¹⁸F]FA exhibited a target-to-non-target ratio (estimated as radioactivity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [¹⁸F]FPH. In contrast to [¹⁸F]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[¹⁸F]FA, appears to be a suitable candidate for imaging nAChRs in human brain. Published by Elsevier Science Inc.