【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CH2Br2与¹⁸F-气相反应生成18FCH2Br,18FCH2Br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、120min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10min后观察荷瘤裸鼠的PET/CT显像情况。结果显示,¹⁸F-FCH合成时间32min,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5min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,¹⁸FFCH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11 C-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。更多还原

【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 ¹⁸FCH2 Br was produced by the gaseous reaction with ¹⁸F-.Then,the ¹⁸FCH2 OTf,more reactive ¹⁸F fluotomethylating agent than the ¹⁸FCH2 Br,was converted on-line by passing ¹⁸FCH2 Br 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 at10 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 5minutes and then decreasing or in a relatively stable state.The bio-distribution of ¹⁸F-FCH was similar with the reported data of 11 Ccholine.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.更多还原