Gao Hang, Wang Shuxia, Qiang Bingchao, Wang Sixuan, Zhang Huabei
Key Laboratory of Radiopharmaceuticals of Ministry of Education , College of Chemistry , Beijing Normal University , Beijing 100875 , China . Email:
Medchemcomm. 2019 Nov 19;10(12):2102-2110. doi: 10.1039/c9md00415g. eCollection 2019 Dec 1.
A series of 9-fluoren-9-one substituents were synthesized and evaluated for imaging cerebral α7-nAChRs. -iodine substituted 9-fluorenone with high binding affinity ( = 9.3 nM) and selectivity was radiolabeled with I. Fully and studies of [I] have been performed. [I] exhibited well brain uptake with a peak concentration of 7.5 ± 0.9% ID/g in mice brains. Moreover, autoradiography studies and micro single-photon emission computed tomography (micro-SPECT/CT) dynamic imaging in mice confirmed its 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 -iodine substituted 9-fluorenone [I] could be a promising tracer for imaging α7-nAChRs.
合成了一系列9-芴酮取代基，并对其进行了脑α7-烟碱型乙酰胆碱受体成像评估。具有高结合亲和力（Kd = 9.3 nM）和选择性的碘取代9-芴酮用碘进行了放射性标记。已对[碘]进行了全面研究。[碘]在小鼠脑中表现出良好的脑摄取，峰值浓度为7.5±0.9% ID/g。此外，小鼠的放射自显影研究和微单光子发射计算机断层扫描（micro-SPECT/CT）动态成像证实了其成像特性。此外，还进行了分子对接和分子动力学研究，以解释这两类配体与α7-烟碱型乙酰胆碱受体的结合机制。总之，碘取代9-芴酮[碘]可能是一种有前景的α7-烟碱型乙酰胆碱受体成像示踪剂。
