目的 開(kāi)發(fā)一種高效合成氟標(biāo)記放射性藥物的方法。方法 使用4-硝基苯硼酸頻哪醇酯為反應(yīng)底物，探索化合物氟標(biāo)記的有效方法?？疾旆磻?yīng)配體、反應(yīng)溶劑、反應(yīng)溫度和反應(yīng)時(shí)間對(duì)4-氟硝基苯收率的影響，并通過(guò)¹H-NMR、¹³C-NMR、¹⁹F-NMR方法對(duì)目標(biāo)產(chǎn)物的結(jié)構(gòu)進(jìn)行表征，采用HPLC法對(duì)反應(yīng)條件進(jìn)行定量評(píng)價(jià)。結(jié)果 確定了芳基硼酸頻哪醇酯類化合物的氟-19標(biāo)記的最佳反應(yīng)條件：以3-溴咪唑并[1，2-b]噠嗪為最優(yōu)配體，在100 ℃反應(yīng)10 min即可得到目標(biāo)化合物。在自動(dòng)合成儀上重現(xiàn)了最優(yōu)條件，并用此方法成功合成了11β-羥化酶顯像劑美托咪酯。結(jié)論 本方法為氟-18標(biāo)記芳基硼酸頻哪醇酯類放射性藥物前體提供重要合成依據(jù)。

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.

R914

天津市科技計(jì)劃項(xiàng)目（18ZXXYSY00110）；天津市自然科學(xué)基金資助項(xiàng)目（18JCQNJC09500）；北京協(xié)和醫(yī)學(xué)院中央高校基本科研業(yè)務(wù)費(fèi)資助（3332020057）