Abstract: Two styryl pyrimidine derivatives substituted by p-tosyloxymethyl, Boc-SPm2-OTs and Boc-SPm5-OTs, were designed and successful synthesized, which were labeled by ¹⁸F to prepared ¹⁸F-SPm2 and ¹⁸F-SPm5 by nucleophilic substitution. The radiochemical purities of both ¹⁸F-SPm2 and ¹⁸F-SPm5 were more than 99%. Both ¹⁸F-SPm2 and ¹⁸F-SPm5 had ideal lipophilicity (LogP=1-2.5) and can maintaining stability in normal saline for over 3 h and can bind to Aβ selectively, but both ¹⁸F-SPm2 and ¹⁸F-SPm5 displayed less binding affinity (the K_i values were 246.6 nmol/L and 318.2 nmol/L, respectively). The results of biodistribution in mice demonstrated that both ¹⁸F-SPm2 and ¹⁸F-SPm5 showed relatively high initial brain uptake, with slow washout from normal brain and obvious defluorination in vivo. In conclusion, both ¹⁸F-SPm2 and ¹⁸F-SPm5 might not be ideal Aβ imaging agents, and further modifications were needed to improve the disadvantages.

Key words: alzheimer’s disease (AD), positron emission tomography (PET), β-Amyloid (Aβ), styryl pyrimidine derivatives

摘要： 为研发新型Aβ正电子显像剂，设计合成对甲苯磺酰氧基取代的苯乙烯基嘧啶化合物Boc-SPm2-OTs和Boc-SPm5-OTs，并通过亲核取代反应进行¹⁸F标记，得到¹⁸F-SPm2和¹⁸F-SPm5，放化纯度均大于99%。¹⁸F-SPm2和¹⁸F-SPm5均具有适宜的亲脂性（LogP=1~2.5），在生理盐水中可稳定存在3 h以上，能选择性结合Aβ，但其亲和性较弱（K_i分别为246.6 nmol/L和318.2 nmol/L），体内生物分布实验表明，两者初始脑放射性摄取均相对较高，但正常脑组织清除较慢，而且存在明显脱氟现象。初步的研究结果表明，¹⁸F-SPm2和¹⁸F-SPm5不是理想的Aβ显像剂，需要进行进一步的结构修饰以克服其缺点。

关键词: 阿兹海默病（AD）, 正电子发射断层显像（PET）, β淀粉样蛋白（Aβ）, 苯乙烯基嘧啶化合物