Abstract：
BACKGROUND: 2-[18F]Fluoroethyltosylate ([18F]FEtOTs) is a well-known 18F-fluoroalkylating agent widely used to synthesize radiotracers for positron emission tomography. The widespread use of [18F]FEtOTs is due in part to its low volatility when compared to other halide and sulfonate building blocks. In this work, the radioactive volatile side-products formed during the synthesis of [18F]FEtOTs were identified and characterized for the first time, and an optimization of the reaction conditions to minimize their formation was proposed.
RESULTS: In order to characterize the volatiles produced during [18F]FEtOTs synthesis, the reaction mixtures of both cold FEtOTs and [18F]FEtOTs were co-injected onto the HPLC system. The radioactive peaks corresponding to the volatile compounds were collected, analyzed through headspace gas chromatography mass spectrometry sampler (HS-GC-MS) and identified as vinyl fluoride ([19F]VF) and 2-fluoroethanol ([19F]FEOH). By using a rotatable central composite design with a two-level full factorial core of two factors (22), it was determined that temperature and time are independent variables which affect the generation of [18F]VF and [18F]FEOH during the radiosynthesis of [18F]FEtOTs. In addition, in order to reduce the formation of the volatiles ([18F]VF and [18F]FEOH) and increase the yield of [18F]FEtOTs, it was demonstrated that the molar ratio of base to precursor must also be considered.
CONCLUSIONS: [18F]VF and [18F]FEOH are volatile side-products formed during the radiosynthesis of [18F]FEtOTs, whose yields depend on the reaction time, temperature, and the molar ratio of base to precursor. Therefore, special care should be taken during the radiosynthesis and subsequent reactions using [18F]FEOTs in order to avoid environmental contamination and to improve the yield of the desired products.
RESULTS: In order to characterize the volatiles produced during [18F]FEtOTs synthesis, the reaction mixtures of both cold FEtOTs and [18F]FEtOTs were co-injected onto the HPLC system. The radioactive peaks corresponding to the volatile compounds were collected, analyzed through headspace gas chromatography mass spectrometry sampler (HS-GC-MS) and identified as vinyl fluoride ([19F]VF) and 2-fluoroethanol ([19F]FEOH). By using a rotatable central composite design with a two-level full factorial core of two factors (22), it was determined that temperature and time are independent variables which affect the generation of [18F]VF and [18F]FEOH during the radiosynthesis of [18F]FEtOTs. In addition, in order to reduce the formation of the volatiles ([18F]VF and [18F]FEOH) and increase the yield of [18F]FEtOTs, it was demonstrated that the molar ratio of base to precursor must also be considered.
CONCLUSIONS: [18F]VF and [18F]FEOH are volatile side-products formed during the radiosynthesis of [18F]FEtOTs, whose yields depend on the reaction time, temperature, and the molar ratio of base to precursor. Therefore, special care should be taken during the radiosynthesis and subsequent reactions using [18F]FEOTs in order to avoid environmental contamination and to improve the yield of the desired products.
摘要：
背景:2-[18F]氟乙基甲苯磺酸酯([18F]FEtOTs)是众所周知的18F-氟烷基化剂,其广泛用于合成用于正电子发射断层扫描的放射性示踪剂。[18F]FEtOTs的广泛使用部分是由于其与其他卤化物和磺酸盐结构单元相比的低挥发性。在这项工作中,首次对[18F]FEtOTs合成过程中形成的放射性挥发性副产物进行了鉴定和表征，并提出了优化反应条件以最大程度地减少其形成的方法。
结果：为了表征[18F]FEtOTs合成过程中产生的挥发物，将冷FEtOTs和[18F]FEtOTs的反应混合物共同注射到HPLC系统上。收集对应于挥发性化合物的放射性峰，通过顶空气相色谱-质谱采样器（HS-GC-MS）进行分析，并鉴定为氟乙烯（[19F]VF）和2-氟乙醇（[19F]FEOH）。通过使用具有两个因素的两级全阶乘核心的可旋转中心复合设计（22），确定温度和时间是在[18F]FEtOTs的放射合成期间影响[18F]VF和[18F]FEOH的产生的独立变量。此外,为了减少挥发物（[18F]VF和[18F]FEOH）的形成并增加[18F]FEtOTs的产量，已经证明,还必须考虑碱与前体的摩尔比。
结论：[18F]VF和[18F]FEOH是[18F]FEtOTs放射合成过程中形成的挥发性副产物，其收率取决于反应时间，温度,和碱与前体的摩尔比。因此,在使用[18F]FEOTs的放射合成和随后的反应期间应特别小心,以避免环境污染并提高所需产物的产率。
结果：为了表征[18F]FEtOTs合成过程中产生的挥发物，将冷FEtOTs和[18F]FEtOTs的反应混合物共同注射到HPLC系统上。收集对应于挥发性化合物的放射性峰，通过顶空气相色谱-质谱采样器（HS-GC-MS）进行分析，并鉴定为氟乙烯（[19F]VF）和2-氟乙醇（[19F]FEOH）。通过使用具有两个因素的两级全阶乘核心的可旋转中心复合设计（22），确定温度和时间是在[18F]FEtOTs的放射合成期间影响[18F]VF和[18F]FEOH的产生的独立变量。此外,为了减少挥发物（[18F]VF和[18F]FEOH）的形成并增加[18F]FEtOTs的产量，已经证明,还必须考虑碱与前体的摩尔比。
结论：[18F]VF和[18F]FEOH是[18F]FEtOTs放射合成过程中形成的挥发性副产物，其收率取决于反应时间，温度,和碱与前体的摩尔比。因此,在使用[18F]FEOTs的放射合成和随后的反应期间应特别小心,以避免环境污染并提高所需产物的产率。
