In vitro binding profile and radiosynthesis of a novel 18F‐labeled azaspirovesamicol analog as potential ligand for imaging of the vesicular acetylcholine transporter
In vitro binding profile and radiosynthesis of a novel 18F‐labeled azaspirovesamicol analog as potential ligand for imaging of the vesicular acetylcholine transporter
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新型 18F 标记的阿扎螺维沙醇类似物作为囊泡乙酰胆碱转运蛋白成像潜在配体的体外结合谱和放射合成
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发表时间：
2011
期刊：
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通讯作者：
J. Steinbach
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作者：
B. Wenzel;A. Hiller;S. Fischer;D. Sorger;W. Deuther;M. Scheunemann;P. Brust;O. Sabri;J. Steinbach
放射性标记的维沙米醇类似物是作为囊泡乙酰胆碱转运蛋白 (VAChT) 配体的有希望的候选者，以实现大脑早期胆碱能变性的体内成像。 4-氟苯甲酰基取代的阿扎螺维沙考衍生物 FBASV 是六种新型维沙考类似物之一，并已证明最合适的体外结合数据。 18F-放射性标记是通过微波辅助相应硝基前体的亲核芳香取代来进行的，并开发了两种纯化[18F]FBASV的方法。利用方法 A，将剩余的硝基前体还原为其相应的胺，并通过半制备型 HPLC 在常规 RP 柱上进行分离。在方法B中，使用苯基柱直接分离[18F]FBASV及其硝基前体，从而改变了洗脱顺序并获得了更好的分离参数。因此，合成的[18F]FBASV的RCY为16-18%，比活性>300 GBq/μmol，放射化学纯度>99.5%，适合未来的体内研究。版权所有 © 2011 约翰·威利父子有限公司
Radiolabeled vesamicol analogs are promising candidates as ligands for the vesicular acetylcholine transporter (VAChT) to enable in vivo imaging of early cholinergic degenerations in brain. The 4-fluorobenzoyl-substituted azaspirovesamicol derivative FBASV is one out of six novel vesamicol analogs and demonstrated most appropriate in vitro binding data. 18F-radiolabeling was performed by microwave-assisted nucleophilic aromatic substitution of the corresponding nitro precursor and two methods were developed for the purification of [18F]FBASV. Utilizing method A, the remaining nitro precursor was reduced to its corresponding amine, which was separated via semi-preparative HPLC on a conventional RP column. In method B a phenyl column was used for the direct separation of [18F]FBASV and its nitro precursor, resulting in a change of the elution order and better separation parameters. Thus, [18F]FBASV was synthesized with a RCY of 16–18%, a specific activity >300 GBq/µmol, and a radiochemical purity of >99.5% suitable for future in vivo studies. Copyright © 2011 John Wiley & Sons, Ltd.