摘要/Abstract

氟18是用于临床和临床前研究的正电子发射计算机断层扫描(PET)放射性药物中最常用的放射性同位素, 至今已发现发展出多种标记方法. 亲核性¹⁸F氟源由于易于操作且具有高放射性比活度, 在氟标记反应中得到广泛应用. 同时, 引入氟原子可调节药物分子的空间构象和电性, 也能影响其极性、亲脂性和解离常数等药物代谢动力学参数. 芳香环本身代谢稳定性好, 是理想的氟标记载体. 亲核型氟源参与的芳香环氟-18标记反应为放射性药物的标记, 具有高效、操作简便、反应条件温和及原子经济性等优点, 为氟-18标记提供了一条新途径. 根据标记前体结构的不同, 综述了近年来亲核型氟源参与的芳香环氟-18标记方法领域研究进展, 同时探讨了部分反应的机理, 并对本领域未来发展进行了展望.
关键词: 氟-18, 亲核取代反应, 标记反应, 放射性药物, 正电子发射计算机断层扫描
Fluorine-18 is the most frequently used radioisotope in positron emission tomography radiopharmaceuticals for both clinical and preclinical researches. A variety of labeling methodologies have also been developed in recent years. For most purposes, nucleophilic ¹⁸F-fluoride is preferentially used for ¹⁸F-labeling because this reagent is easy to handle and made available with high specific activity. Meanwhile, fluorine substitution has also served the purpose of modulating conformational and stereoelectronic properties, and favorably influences pharmacokinetic parameters such as polarity, lipophilicity and pK_a values. Arenes and heteroarenes are privileged candidates for ¹⁸F-incorporation as they are metabolically robust and therefore widely used for ¹⁸F-labeling. Nucleophilic fluoride mediated fluorine-18 labeling reaction has emerged as a promising green and efficient synthetic tool and provides a novel approach for ¹⁸F-labeling. The recent developments in nucleophilic fluoride mediated fluorine-18 labeling of arenes and heteroarenes are summarized on the basis of different labeling precursor, including phenols, aryl iodoniums, aryl sulfoniums, aromatic metallic compounds and C(sp²)—H bond. The scope of labeling substrate, some application for radiopharmaceuticals and mechanism of several reactions are also discussed.
Key words: fluorine-18, nucleophilic substitution reaction, labeling reaction, radiopharmaceuticals, positron emission tomography


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