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Automated Radiosynthesis and Bio-distribution of [18F]Fluoromethyl Choline

LI Yan-peng;WEN Xin;CHENG Bin;XIE Xin-li;DU Xiao-guang;HAN Xing-min   

  1. Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • Online:2017-02-20 Published:2017-03-06

(N-[18F]氟甲基)-胆碱的自动化合成及其生物分布研究

李彦鹏;温馨;程兵;谢新立;杜晓光;韩星敏   

  1. 郑州大学第一附属医院 核医学科,河南 郑州450052

Abstract:

To develop a rapid and automated synthetic method for making [18F]Fluoromethyl choline (18F-FCH), the automatic synthesis module from Sumitomo corporation was used to synthesize 18F-FCH, the bio-distribution in normal mice and the PET/CT imaging on pancreatic tumor xenograft murine models were also evaluated. CH2Br2 was used as precursor, intermediate product of 18FCH2Br was produced by the gaseous reaction with 18F-. Then, the 18FCH2OTf, more reactive 18F fluotomethylating agent than the 18FCH2Br, was converted on-line by passing 18FCH2Br through a heated Ag-Triflate column. 18FC2H4SO3CF3 reacted with N, N-dimethylaminoethanol (DMAE) on SEP-PAK C-18 cartridge, followed by purification on SEP-PAK Accell CM cartridge. The 18F-FCH was intravenously injected into mice, the mice were sacrificed at 5,  10, 30, 60, 90, 120 minutes post injection respectively. The major organs were removed and weighed before radioactive γ-counting. PET/CT imaging was carried out at 10 minutes after injection of  18F-FCH in nude mice xenografted with pancreatic cancer. The results showed that [18F]fluorocholine was produced from [18F]fluoride in overall radiochemical yields of (25±5)% (uncorrected, n=23) in 32 minutes, radiochemical purity was higher than 97%. The biodistribution datas showed high uptake in liver, kidney, low uptake in brain, lung, muscle and rapid clearance in blood. Most organs reached its radioactive peak within 5 minutes and then decreasing or in a relatively stable state. The bio-distribution of 18F-FCH was similar with the reported data of 11C-choline. PET/CT imaging showed high accumulation in the kidney, liver and spleen, however, the uptake of 18F-FCH in the pancreatic cancer was very low. It has very low potential as a positive pancreatic cancer imaging agent. This new automated synthesis technique provides high and reproducible yields that could be dedicated for routine use.

Key words: 18F-FCH, automated radiosynthesis, Ag-Triflate, bio-distribution

摘要:

采用住友CFN-multi-P100多功能模块快速、自动化合成(N-[18F]氟甲基)胆碱(18F-FCH),并评价其在正常小鼠体内生物分布,以及胰腺癌裸鼠模型的PET/CT显像情况。前体CH2Br218F-气相反应生成18FCH2Br,18FCH  2Br经4个Si柱纯化后与三氟甲基磺酰银(Ag-Triflate)反应生成活性更高的氟代三氟甲基磺酰基甲烷(18FCH2OTf),新中间体与预先加在C-18柱子上的N,N-二甲基乙醇胺(DMAE)反应再经SEP-PAK CM柱纯化得到18F-FCH。将18F-FCH静脉给予正常小鼠,分别在给药后5、10、30、60、90、120 min处死,测定主要脏器的质量及放射性计数。将18F-FCH静脉给予胰腺癌裸鼠,注射10 min后观察荷瘤裸鼠的PET/CT显像情况。结果显示,18F-FCH合成时间32 min,未校正的合成效率为(25±5)%(n=23),放化纯度大于97%。小鼠体内生物分布实验显示,18F-FCH在血液中清除快,绝大多数脏器在5 min时放射性分布达最高值,后逐渐降低或处于相对稳定状态。放射性主要分布在肾脏、肝脏,而脑、肺、肌肉对18F-FCH的摄取均较少。荷瘤(胰腺癌)裸鼠的PET/CT显像表明,18F-FCH在裸鼠肾脏、肝脏和脾脏聚集,胰腺癌细胞对18F-FCH未见明显摄取。结果提示,住友CFN多功能模块可自动化、快速合成18F-FCH。18F-FCH在正常小鼠体内分布与文献报道的11C-胆碱相似,具有一定的应用前景,但其对胰腺癌的诊断仍需进一步研究。

关键词: (N-[18F]氟甲基)-胆碱, 自动化合成, 三氟甲基磺酰银, 生物分布