Rodnick Melissa E, Brooks Allen F, Hockley Brian G, Henderson Bradford D, Scott Peter J H
Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Appl Radiat Isot. 2013 Aug;78:26-32. doi: 10.1016/j.apradiso.2013.04.017. Epub 2013 Apr 24.
A novel one-pot method for preparing [(18)F]fluoromethylcholine ([(18)F]FCH) via in situ generation of [(18)F]fluoromethyl tosylate ([(18)F]FCH2OTs), and subsequent [(18)F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed.
[(18)F]FCH was prepared using a GE TRACERlab FXFN, although the method should be readily adaptable to any other fluorine-(18) synthesis module. Initially ditosylmethane was fluorinated to generate [(18)F]FCH2OTs. DMAE was then added and the reaction was heated at 120 °C for 10 min to generate [(18)F]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C(18)-Plus and CM-Light Sep-Pak cartridges to provide [(18)F]FCH formulated in USP saline. The formulated product was passed through a 0.22 µm filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25 h from end-of-bombardment.
Typical non-decay-corrected yields of [(18)F]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon ~1.3 Ci [(18)F]fluoride), and doses passed all other quality control (QC) tests.
A one-pot liquid-phase synthesis of [(18)F]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6 µg/10 mL dose or ~3 ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies.
已开发出一种新颖的一锅法，通过原位生成对甲苯磺酸氟甲基酯（[(18)F]FCH2OTs），随后使二甲氨基乙醇（DMAE）进行[(18)F]氟甲基化反应来制备[(18)F]氟甲基胆碱（[(18)F]FCH）。
使用通用电气的TRACERlab FXFN制备[(18)F]FCH，不过该方法应易于适用于任何其他氟-18合成模块。首先将二对甲苯基甲烷进行氟化反应以生成[(18)F]FCH2OTs。然后加入DMAE，并将反应在120℃下加热10分钟以生成[(18)F]FCH。此时间过后，蒸发反应溶剂，并且使用C(18)-Plus和CM-Light Sep-Pak柱通过固相萃取对粗反应混合物进行纯化，以提供用美国药典生理盐水配制的[(18)F]FCH。将配制好的产品通过0.22μm过滤器过滤到无菌剂量瓶中，并提交进行质量控制测试。从轰击结束起总合成时间为1.25小时。
使用该方法制备的[(18)F]FCH的典型非衰变校正产率为91毫居里（基于约1.3居里[(18)F]氟化物，非衰变校正率为7%），并且剂量通过了所有其他质量控制（QC）测试。
已开发出[(18)F]FCH的一锅液相合成法。剂量中含有极低水平的残留DMAE（每10毫升剂量为(31.6)微克或约3 ppm），并通过了所有其他必要的QC测试，证实它们适用于临床成像研究。
