基于国产氟多功能合成模块的18F-FMISO自动合成工艺验证

摘要

为验证特异性肿瘤PET乏氧显像剂1-H-1-(3-18F-2-羟基丙基)-2-硝基咪唑(18F-FMISO)注射液的临床前即时标记工艺的可行性、可靠性和稳定性,采用国产氟多功能自动化合成装置,以1-(2'-硝基-1'-咪唑基)-2-O-四氢吡喃基-3-O-甲苯磺酰基丙二醇(NITTP)为前体,经氟化、水解反应制备18F-FMISO注射液,按照优化的制备工艺进行18F-FMISO三批连续生产,并对其关键工艺参数和产品质量标准进行验证.结果表明:总合成时间小于40 min,产品放化产率大于45％(未衰减校正,n=5),比活度大于3.7×1010 Bq/mmol,放置3个半衰期后放化纯度仍大于95％,体外稳定性良好.该自动合成工艺稳定可行,三批产品各项指标均符合质量标准规定,满足临床PET显像要求.%1-H-1-(3-[18 F] fluoro-2-hydroxypropyl)-2-nitroimidazole (18 F-FMISO) is a special tumor hypoxia imaging agent for PET.Its PET/CT imaging has an important guiding significance on planning cancer radiotherapy target volume.18F-FMISO was synthesized on domestic fluorine multifunctional automated synthesis apparatus.By using 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulphonyl-propanediol as the precursor,18F-FMISO was obtained via two-step reactions,including the nucleophilic fluoration of the precursor and the acidic hydrolysis of the intermediate.To verify the feasibility,reliability and stability of the automated synthesis process,three continuous batches of 18F-FMISO were produced with optimized preparation process.The key parameters in the pilot production and the quality standard of the product were verified.The procedure could be completed within 40 minutes.The radiochemical yield and specific activity were higher than 45％ (no decay corrected,n-=5) and 3.7 × 1010 Bq/mmol.The radiochemical purity was more than 95％ after three half-life,indicating its good stability.The automated synthesis process of 18F-FMISO is feasible.All the indicators for each batch of 18F-FMISO meet the quality standard and the requirements of clinical PET imaging.