摘要
1-H-1-(3-[18F]氟-2-羟基丙基)-2-硝基咪唑(18F-FMISO)是特异性肿瘤乏氧分子影像探针,其PET/CT显像指导肿瘤放疗靶区的勾画具有重要的临床应用价值。本文旨在建立18F-FMISO的改进的自动化合成方法,开展其肿瘤乏氧Micro-PET/CT显像研究。基于标记前体NITTP和简便的"一锅法",利用升级、改进的Explora GN模块,依次完成放射氟化反应(NITTP(10 mg),MeCN(1.0 mL),120 oC,5.0 min)、水解反应(HCl(1.0 mol/L,1.0 mL),130 oC,8.0 min)和HPLC分离纯化,自动化合成18F-FMISO。同时,采取分析型Radio-HPLC和Radio-TLC等方法检测各项质量控制指标,利用Micro-PET/CT进行荷SW1990胰腺肿瘤乏氧显像实验。结果表明,18F-FMISO的自动化生产时间约为65 min,放射化学产率为(30 5.0)%(未衰变校正,n=20),放射化学纯度大于99%,比活度为(2.04 0.17)×1011Bq·mol–1,化学纯度得到改善。Micro-PET/CT显像表明,18F-FMISO在荷SW1990瘤鼠体内均呈全身分布,最佳的肿瘤乏氧显像时间为注射后3.0 h,肿瘤/肌肉吸收比为3.00 0.08。本研究建立了基于HPLC分离纯化而改进的18F-FMISO的自动化合成方法,而且其Micro-PET/CT肿瘤乏氧显像对比度高,为乏氧显像研究提供了可靠的制备方法和基本的实验参考依据。
Background： 1-H-l-（3-[18F]fluoro-2-hydroxypropyl）-2-nitroimidazole（18F-FMISO） is a specific molecular imaging probe for tumor hypoxia imaging, and its PET/CT imaging has an important clinical value for planning cancer radiotherapy target volume. Purpose： This study aimed to develop an improved, automated production of 18F-FMISO and to perform Micro-PET/CT imaging of tumor hypoxia. Methods： Based on the labeling precursor NITTP and a simple ＂one-pot＂ method, an upgraded Explora GN module together with Explora LC was adopted to run radiofluorination （NITTP （10 mg）, MeCN （1.0 mL）, 120 ℃, 5.0 min）, hydrolysis （HC1 （1.0 tool/L, 1.0 mL）, 130 ℃, 8.0 min） and high performance liquid chromatography（HPLC） purification to produce 18F-FMISO automatically. Moreover, Radio-HPLC and Radio-TLC were applied for the quality control, and Micro-PET/CT scanner for hypoxia imaging of SW1990 pancreatic tumor-bearing mice. Results： As results, 18F-FMISO was obtained with the synthesis time for about 65 rain, the radiochemical yield of （30＋5.0）% （no decay corrected, n=20）, the radiochemical purity of above 99%, the specific activity of （2.04＋0.17）×1011 Bq.iamol 1, plus with the enhanced chemical purity. Moreover, MicroPET/CT imaging showed that 18F-FMISO presented whole-body distribution in SW1990 tumor-bearing mice, and the optimized time point for tumor hypoxia imaging was 3 h post injection with the uptake ratios of tumor-to-muscle of 3.00＋0.08. Conclusion： In sum, we developed an improved, automated production of 18F-FMISO with high performance liquid chromatography purification, high radiochemical yield, high specific activity and high reliability, and also verified its MicroPET/CT imaging of tumor hypoxia for providing experimental reference data.
出处
《核技术》
CAS
CSCD
北大核心
2013年第10期38-43,共6页
Nuclear Techniques
基金
国家自然科学基金(11275050
30700188)
教育部留学回国人员科研启动基金资助
