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

doi:10.7538/tws.2017.30.01.0029

Abstract

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CH₂Br₂与¹⁸F-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

LI Yan-peng;WEN Xin;CHENG Bin;XIE Xin-li;DU Xiao-guang;HAN Xing-min. Automated Radiosynthesis and Bio-distribution of ［¹⁸F］Fluoromethyl Choline[J]. Journal of Isotopes, 2017, 30(1): 29-35.

李彦鹏;温馨;程兵;谢新立;杜晓光;韩星敏. (N-［¹⁸F］氟甲基)-胆碱的自动化合成及其生物分布研究[J]. 同位素, 2017, 30(1): 29-35.

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

(N-［¹⁸F］氟甲基)-胆碱的自动化合成及其生物分布研究

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