Radioiodinated 9-fluorenone derivatives for imaging α7-nicotinic acetylcholine receptors.,RSC Medicinal Chemistry

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Radioiodinated 9-fluorenone derivatives for imaging α7-nicotinic acetylcholine receptors.
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2019-11-19 , DOI: 10.1039/c9md00415g
Hang Gao ₁ , Shuxia Wang ₁ , Bingchao Qiang ₁ , Sixuan Wang ₁ , Huabei Zhang ₁

Affiliation

A series of 9H-fluoren-9-one substituents were synthesized and evaluated for imaging cerebral α7-nAChRs. Meta-iodine substituted 9-fluorenone 5 with high binding affinity (K_i = 9.3 nM) and selectivity was radiolabeled with ¹²⁵I. Fully in vitro and in vivo studies of [¹²⁵I]5 have been performed. [¹²⁵I]5 exhibited well brain uptake with a peak concentration of 7.5 ± 0.9% ID/g in mice brains. Moreover, ex vivo autoradiography studies and micro single-photon emission computed tomography (micro-SPECT/CT) dynamic imaging in mice confirmed its in vivo imaging properties. Besides, molecular docking and MD studies were also performed to interpret the binding mechanisms of the two series of ligands towards α7-nAChRs. To conclude, the meta-iodine substituted 9-fluorenone [¹²⁵I]5 could be a promising tracer for imaging α7-nAChRs.

中文翻译：

放射碘化的9-芴酮衍生物，用于成像α7-烟碱乙酰胆碱受体。

合成了一系列9个H-氟-9-取代基，并对脑α7-nAChRs成像进行了评估。元-碘取代的9-芴酮5具有高的结合亲和力（ķ_我= 9.3纳米）和选择性用放射性标记的¹²⁵ I.完全在体外和体内[研究¹²⁵ I] 5已经执行。[ ¹²⁵ I] 5表现出良好的脑摄取，小鼠脑中的峰值浓度为7.5±0.9％ID / g。而且，离体放射自显影研究和小鼠微单光子发射计算机断层扫描（micro-SPECT / CT）动态成像证实了其体内成像特性。此外，还进行了分子对接和MD研究，以解释两个系列的配体对α7-nAChRs的结合机理。总而言之，间碘取代的9-芴酮[ ¹²⁵ I] 5可能是用于成像α7-nAChRs的有前途的示踪剂。

更新日期：2019-11-19

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