In vivo measurement of nicotinic acetylcholine receptors with [18F]norchloro-fluoro-homoepibatidine
In vivo measurement of nicotinic acetylcholine receptors with [18F]norchloro-fluoro-homoepibatidine
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DOI：
10.1002/syn.20480
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发表时间：
2008-03-01
期刊：
影响因子：
2.3
通讯作者：
Sabri, Osama
中科院分区：
文献类型：
--
作者：
Brust, Peter;Patt, Joerg Thomas;Sabri, Osama
烟碱乙酰胆碱受体（nAChR）的功能改变在年龄相关性神经元变性中是重要的。最近的研究证实了nAChR配体2-[F-18]F-A-85380在痴呆患者神经影像学中的适用性。然而，其结合动力学需要7小时的采集时间，限制了其在临床PET研究中的实用性。因此，作者开发了用于nAChR成像的[F-18]去氯-氟异戊代丁（[F-18]NCFHEB）。将[18F]NCFHEB的两种对映体与2-[F-18]F-A85380在猪脑中的动力学进行比较，以评价它们在人类神经成像方面的潜力。采用[18F]NCFHEB对24头幼年母猪进行PET研究。9只动物在给予放射性示踪剂前静脉注射nAChR激动剂A81418 (1mg /kg)，随后静脉注射（2mg /kg/7h）。应用数个室模型进行量化。（-）-和(+)-[F-18]NCFHEB的脑吸收量比2-[F-18]F-A-85380高两到三倍。所有三种放射性示踪剂在高、中等或低特异性结合区域显示出空间异质性结合动力学。（-）-[18F]NCFHEB比(+)-[F-18]NCFHEB和2-[F-18]F-A85380更早达到特异性结合平衡。持续给药nAChR激动剂A81418抑制(-)-和(+)-[F-18]NCFHEB特异性结合，但对2[18 F]F- a85380无抑制作用。（+）-[F-18]NCFHEB的外周代谢比其他放射性示踪剂稍慢。[F-18]NCFHEB的两种对映体都是猪nAChR神经成像的合适放射性示踪剂。它们在体内的结合谱似乎比2-[F-18]F-A85380更具选择性。（-）-[F-18]NCFHEB比2-[18F]F-A85380具有更快的特异性结合平衡。
Functional changes of nicotinic acetylcholine receptors (nAChR) are important during age-related neuronal degeneration. Recent studies demonstrate the applicability of the nAChR ligand 2-[F-18]F-A-85380 for neuroimaging of patients with dementias. However, its binding kinetics demands a 7-h acquisition time limiting its practicality for clinical PET studies. Thus, the authors developed [F-18]norchloro-fluorohomoepibatidine ([F-18]NCFHEB) for nAChR imaging. The kinetics of the two enantiomers of [18F]NCFHEB were compared with 2-[F-18]F-A85380 in porcine brain to evaluate their potential for human neuroimaging. Twenty-four juvenile female pigs were studied with PET using [18F]NCFHEB. Nine animals received an additional i.v. injection (1 mg/kg) of the nAChR agonist A81418 before radiotracer administration followed by infusion (2 mg/kg/7h) thereafter. Several compartment models were applied for quantification. (-)- and (+)-[F-18]NCFHEB showed a twofold to threefold higher brain uptake than 2-[F-18]F-A-85380. All three radiotracers displayed spatially hetereogenous binding kinetics in regions with high, moderate, or low specific binding. The equilibrium of specific binding of (-)-[18F]NCFHEB was reached earlier than that of (+)-[F-18]NCFHEB or 2-[F-18]F-A85380. Continuous administration of the nAChR agonist A81418 inhibited the specific binding of (-)- and (+)-[F-18]NCFHEB but not of 2[18 F]F-A85380. The peripheral metabolism of (+)-[F-18]NCFHEB proceeded somewhat slower than that of the other radiotracers. Both enantiomers of [F-18]NCFHEB are appropriate radiotracers for neuroimaging of nAChR in pigs. Their binding profile in vivo appears to be more selective than that of 2-[F-18]F-A85380. (-)-[F-18]NCFHEB offers a faster equilibrium of specific binding than 2-[18F]F-A85380.