This study reported the design, synthesis and bio-evaluation of 2-phenylbenzoheterocycles with chiral dihydroxyl side chains as β-amyloid (Aβ) imaging probes. This strategy of introducing two hydroxyls offered a simplified method for effectively reducing the lipophilicity. The probes (R, S)/(S, R)-14-15 with benzothiazole scaffold displayed good binding affinities toward Aβ_1-42 aggregates with K_i values ranging from 47.63 to 56.28 nM. Further biological studies shown that (R, S)/(S, R)-[¹⁸F]14 have no obvious chirality-related discrepancy in binding ability and mice bio-distribution, while (S, R)-enantiomer exhibited slightly faster brain washout rate than (R, S)-enantiomer. Compared to the FDA approved [¹⁸F]Florbetapir and the fluoro-peglated 2-phenylbenzothiazole derivatives, (S, R)-[¹⁸F]14 displayed improved brain kinetics (6.40% ID/g at 2 min, brain_{2 min}/brain_{60 min} = 7.80) that is favorable for further application. In vitro autoradiography studies validated its high affinity and specificity to Aβ plaques. Overall, (S, R)-[¹⁸F]14 deserved further detailed study as a potential PET imaging probe for AD early diagnosis.

该研究报告的2- phenylbenzoheterocycles与手性二羟基侧链的设计，合成和生物评估β淀粉样蛋白（β）成像探针。这种引入两个羟基的策略提供了一种有效降低亲油性的简化方法。带有苯并噻唑支架的探针 ( R, S )/( S, R )- 14-15对 A β _1-42聚集体显示出良好的结合亲和力，K _i值范围为 47.63 至 56.28 nM。进一步的生物学研究表明，( R, S )/( S, R )-[ ¹⁸ F] 14在结合能力和小鼠生物分布方面没有明显的手性相关差异，而( S, R )-对映体的脑冲洗速度略快于( R, S )-对映体。与 FDA 批准的 [ ¹⁸ F] Florbetapir 和氟聚乙二醇化 2-苯基苯并噻唑衍生物相比，( S, R )-[ ¹⁸ F] 14显示出改善的脑动力学（2 分钟时 6.40% ID/g，脑_{2 分钟}/脑_{60 分钟}= 7.80），这有利于进一步应用。体外放射自显影研究证实了其对 A β斑块的高亲和力和特异性。总体而言，( S, R )-[ ¹⁸F] 14作为 AD 早期诊断的潜在 PET 成像探针，值得进一步详细研究。