全自动合成3-^18F-2-羟基丙烷-2-硝基咪唑及临床前研究

Fully Automated Synthesis of [^(18)F]Fluoromisonidazole and Preclinical Study

目的研究一种全自动合成肿瘤乏氧显像剂3-18F-2-羟基丙烷-2-硝基咪唑(18F-FMISO)的方法。方法采用改良的FDG(氟代脱氧葡萄糖)模块,在密闭体系下4～6mg前体与F-18离子在110℃反应300s,1mol/LHCl120℃下水解180s,经柱色层纯化得18F-FMISO。检测正常小鼠、荷瘤鼠的生物学分布及PET显像。结果采用FDG模块自动化合成18F-FMISO,合成效率为67%,时间为25min,放化纯度>99%,体外稳定性良好。生物学分布及PET显像表明,肿瘤明显摄取18F-FMISO,120min时瘤/肌比为2.99,但肝、肾、肠的放射性较高。结论改良的FDG模块可高效、快速合成18F-FMISO,其产品质量符合临床要求。18F-FMISO适于胸、颈部肿瘤的乏氧评价。

Objective To study a new fully automated method for the synthesis of [ ^18F ] fluoromisonidazole （^18F-FMISO） by a home made FDG synthesizer. Methods The optimal labeling conditions for the automated synthesis of ^18F-FMISO was 4 ～ 6 mg precursor in 1 mL acetonitrile heated at 110℃for 300 s at pressurized vessel, and hydrolyzed with 1 mol/L HCl at 120 ℃ for 180 s with modified FDG synthesizer. The biodistribution and PET scan were performed in normal and lung tumor bearing mice. Results The yield of ^18F- FMISO was 67% with modified FDG module. It took 25 min. The radiochemical purity was over 99%. The stabilization of ^18F-FMISO was good in vitro. The PET scan showed that the tumor took up ^18F-FMISO. The ratio of tumor to muscle was 2.99 at 120 min. The liver, kidney and intestines took up ^18F-MISO abundantly. Conclusion The modified FDG module can be used for synthesis of high yield ^18F-FMISO. It could be used in clinical practice as a potential radiopharmaceutical for the non - invasive detection of hypoxia in thorax and neck tumors.