Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module
Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module
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DOI：
10.1016/j.nucmedbio.2005.06.003
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发表时间：
2005-11-01
影响因子：
3.1
通讯作者：
Moon, DH
中科院分区：
文献类型：
--
作者：
Oh, SJ;Chi, DY;Moon, DH
我们开发了一种新的全自动化的方法来合成[F-18]氟咪唑（[F-18]FMISO）通过修改商业FDG合成仪和其一次性流体路径。采用三步法制备甲苯磺酸酯前体1-（2 ′-硝基-1 ′-咪唑基）-2-O-四氢呋喃基-3-O-甲苯磺酰基丙二醇。以甘油为起始原料，以21%的产率合成了前驱体。自动合成[F-18]FMISO的最佳标记条件是10 mg前体的乙腈溶液（2 ml），在105 ℃下加热360 s，然后在75 ℃下加热280 s，在105 ℃下用1 N HCl水解300 s。使用3.7 GBq的[F-18]F-作为起始活性，通过高效液相色谱法（HPLC）纯化，在60.0 +/- 5.2 min内以58.5 +/- 3.5%的高合成结束（EOS）放射化学产率获得[F-18]FMISO。当添加固相纯化步骤时，每组的EOS放射化学产率为54.5 +/- 2.8%（337 +/- 25 GBq/μ mol），持续70.0 +/- 3.8 min（n=10），衰变校正）。在37.0 GBq的高起始放射性下，我们获得的放射化学产率分别为54.4 +/- 2.9%和52.8 +/-4.2%（n=3）。在HPLC程序之前，固相纯化除去未反应的[F-18]氟化物和极性杂质。长期测试显示98.2 +/-1.5%的良好稳定性。这种新的自动化合成程序结合了高和可重复的产量与使用一次性盒系统的优势。(c)2005年爱思唯尔公司All rights reserved.
We developed a new fully automated method for the synthesis of [F-18]fluoromisonidazole ([F-18]FMISO) by modifying a commercial FDG synthesizer and its disposable fluid pathway. A three-step procedure was used to prepare the tosylate precursor, 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydrofuranyl-3-O-toluenesulfonylpropanediol. Using glycerol as the starting material, the precursor was synthesized with a yield of 21%. The optimal labeling conditions for the automated synthesis of [F-18]FMISO was 10 mg of precursor in acetonitrile (2 ml heated at 105 degrees C for 360 s, followed by heating at 75 degrees C for 280 s and hydrolysis with 1 N HCl at 105 degrees C for 300 s. Using 3.7 GBq of [F-18]F- as a starting activity, [F-18]FMISO was obtained with high end-of-synthesis (EOS) radiochemical yields of 58.5 +/- 3.5% for 60.0 +/- 5.2 min with high-performance liquid chromatography (HPLC) purification. When solid-phase purification steps were added, the EOS radiochemical yields were 54.5 +/- 2.8% (337 +/- 25 GBq/mu mol) for 70.0 +/- 3.8 min (n=10) for each group, decay-corrected). With a high starting radioactivity of 37.0 GBq, we obtained radiochemical yields of 54.4 +/- 2.9% and 52.8 +/- 4.2%, respectively (n=3). The solid-phase purification removed unreacted [F-18]fluoride and polar impurities before the HPLC procedure. Long-term tests showed a good stability of 98.2 +/- 1.5%. This new automated synthesis procedure combines high and reproducible yields with the advantage of using a disposable cassette system. (c) 2005 Elsevier Inc. All rights reserved.