目的 开发一种高效合成氟标记放射性药物的方法。方法 使用4-硝基苯硼酸频哪醇酯为反应底物，探索化合物氟标记的有效方法。考察反应配体、反应溶剂、反应温度和反应时间对4-氟硝基苯收率的影响，并通过¹H-NMR、¹³C-NMR、¹⁹F-NMR方法对目标产物的结构进行表征，采用HPLC法对反应条件进行定量评价。结果 确定了芳基硼酸频哪醇酯类化合物的氟-19标记的最佳反应条件：以3-溴咪唑并[1，2-b]哒嗪为最优配体，在100 ℃反应10 min即可得到目标化合物。在自动合成仪上重现了最优条件，并用此方法成功合成了11β-羟化酶显像剂美托咪酯。结论 本方法为氟-18标记芳基硼酸频哪醇酯类放射性药物前体提供重要合成依据。

Objective To develop an efficient method for synthesis of fluorine-labeled radiopharmaceuticals. Methods 4- Nitrophenylboronic acid pinacol ester was employed as the substrates to develop a convenient and efficient method for the synthesis of 4-fluoronitrobenzene. The effects of reaction ligands, solvents, temperature, and time on the yield of the product were systematically investigated. The structures of all compounds were confirmed by ¹H-NMR, ¹³C-NMR, and ¹⁹F-NMR methods, and the yield of 4-fluoronitrobenzene was obtained by HPLC method. Results The optimum conditions for fluorine-19 labeling were determined. The target compound was obtained by reaction at 100 ℃ for 10 min with 3-bromine [1,2-b]pyridazine as the optimal ligand. Meanwhile, the method was reproduced on an automatic synthesizer, and the 11β-hydroxylase imaging agent medetomide was successfully labeled with this method. Conclusion This method provided an important guidance for further fluorine-18 label aryl boronic acid pinacol ester radiopharmaceutical precursors.

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天津市科技计划项目（18ZXXYSY00110）；天津市自然科学基金资助项目（18JCQNJC09500）；北京协和医学院中央高校基本科研业务费资助（3332020057）