Preparation of ¹⁸F-Labeled Styryl Nitrogenous Heterocycles

To synthesize ¹⁸FFlorbetapir, ¹⁸F-SPy5, ¹⁸F-SPm2 and ¹⁸F-SPm5, ¹⁸F was labeled by nucleophilic substitution taking p-tosyloxy (OTs) as a leaving group to radiosynthesis ¹⁸FFlorbetapir 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, ¹⁸FFlorbetapir,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 ¹⁸FFlorbetapir, 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 ¹⁸FFlorbetapir, ¹⁸F-SPy5, ¹⁸F-SPm2 and ¹⁸F-SPm5 were obtained. The quality of the injections could satisfy experiment requirements.