Abstract:

To synthesize ［¹⁸F］Florbetapir, ¹⁸F-SPy5, ¹⁸F-SPm2 and ¹⁸F-SPm5,  ¹⁸F was labeled by nucleophilic substitution taking p-tosyloxy (OTs) as a leaving group to radiosynthesis  ［¹⁸F］Florbetapir for represent. The influences of precursor concentration, temperature and time on labeling reaction were investigated. The optimum conditions were established and taken as the labeling conditions for other ¹⁸F-labelled styryl nitrogenous heterocycles. Then, ［¹⁸F］Florbetapir,¹⁸F-SPy5, ¹⁸F-SPm2, and ¹⁸F-SPm5 were synthesized by de-protecting t-Butyloxycarboryl (Boc). The products were all separated by C18 cartridge and purified by semipreparative HPLC. Furthermore, some necessary quality inspections were conducted on the pharmaceuticals so as to investigate the parameters, such as basic physical and chemical characters, radiochemical, chemical purities and specific activity. The results showed that the optimum conditions for ¹⁸F-labeling were as follows: precursor concentration 1 g/L, temperature 120 ℃ and time 10 minutes. The injections of ［¹⁸F］Florbetapir, ¹⁸F-SPy5, ¹⁸F-SPm2 and ¹⁸F-SPm5 were obtained, which were all colorless and clear. For the injections, the pH values were all 7-8, the radiochemical purities were all greater than 99%, the chemical purities were all higher than 98%, and the specific activities were 1.09×10⁷-5.11×10⁷ MBq/g. It showed that nucleophilic substitution was an effective method for ¹⁸F-labeling. Under the selected conditions, the radiosynthesis progresses were stable and reliable, and injections of ［¹⁸F］Florbetapir, ¹⁸F-SPy5, ¹⁸F-SPm2 and ¹⁸F-SPm5 were obtained. The quality of the injections could satisfy experiment requirements.

Key words: Alzheimer’s disease (AD), positron emission tomography (PET), β-Amyloid (Aβ), ¹⁸F, styryl nitrogenous heterocycles

摘要：

为制备［¹⁸F］Florbetapir、¹⁸F-SPy5、¹⁸F-SPm2和¹⁸F-SPm5，以［¹⁸F］Florbetapir放化合成过程为代表，对甲苯磺酰氧基（OTs）为离去基团，通过亲和取代反应进行¹⁸F标记，考察前体化合物溶液的浓度、反应时间、反应温度对标记率的影响，确定优化条件，在此条件下对其他苯乙烯基氮杂环化合物进行¹⁸F标记，脱除叔丁氧羰基（Boc）保护，放化合成［¹⁸F］Florbetapir、¹⁸F-SPy5、¹⁸F-SPm2和¹⁸F-SPm5，产物均经C18柱分离和半制备HPLC纯化，并进行质量检验，考察基本理化性质、放化纯度、化学纯度和比活度。结果表明，¹⁸F标记优化条件为前体溶液浓度1 g/L，反应温度120 ℃，反应时间10 min，该条件下制备得到［¹⁸F］Florbetapir、¹⁸F-SPy5、¹⁸F-SPm2和¹⁸F-SPm5制剂溶液，均无色澄清透明，pH为7~8，放化纯度均>99%，化学纯度均>98%，比活度均为1.09×10⁷~5.11×10⁷ MBq/g。表明亲和取代反应是¹⁸F标记的有效方法，在选择的条件下能够制备［¹⁸F］Florbetapir、¹⁸F-SPy5、¹⁸F-SPm2和¹⁸F-SPm5，产物的各项质量指标满足实验研究需要，相关放化合成工艺稳定可靠。

关键词: 阿尔兹海默病（AD）, 正电子发射断层显像（PET）, &beta, 淀粉样蛋白（A&beta, ）, ¹⁸F, 苯乙烯基氮杂环化合物