(N-18F氟甲基)-胆碱的自动化合成及其生物分布研究

摘要

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 18FCH2OTf,more reactive 18F fluotomethylating agent than the 18FCH2Br,was converted on-line by passing 18FCH2Br through a heated AgTriflate 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 [18 F]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.%采用住友CFN-multi-P100多功能模块快速、自动化合成(N-[18 F]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CH2Br2与18F-气相反应生成18 FCH2Br,18 FCH2Br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(18 FCH2OTf),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18 F-FCH.将18 F-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18 F-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,18 F-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18 F-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18 F-FCH.18 F-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.