Fast and reliable method for the preparation of ortho- and para-[¹⁸F]fluorobenzyl halide derivatives: Key intermediates for the preparation of no-carrier-added PET aromatic radiopharmaceuticals

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• 作者：Christian Lemaire^a ; ^{christian.lemaire@ulg.ac.be} ; Lionel Libert^a ; ^{lionel.libert@student.ulg.ac.be} ; Alain Plenevaux^a ; ¹ ; ^{Alain.Plenevaux@ulg.ac.be} ; Joë ; l Aerts^a ; ² ; ^{j.aerts@ulg.ac.be} ; Xavier Franci^b ; ³ ; ^{Xavier.franci@ge.com} ; André ; Luxen^a ; ⁴ ; ^{aluxen@ulg.ac.be}
• 关键词：[18F]fluoride ; SPE ; [18F]fluorobenzyl halide ; [18F]fluorobenzyl azide ; radiofluorination ; Hydrobromic acid ; FDOPA
• 刊名：Journal of Fluorine Chemistry
• 出版年：2012
• 期刊代码：52_00221139
• 类别：ch
• 出版时间：June, 2012
• 卷：138
• 期：Complete
• 页码：48-55
• 文件大小：528 K

摘要

A fast and reliable method suitable for the automated preparation of (substituted) [¹⁸F]fluorobenzyl halides from several [¹⁸F]fluorobenzaldehydes was developed. Aromatic nucleophilic substitution of trimethylammonium benzaldehyde triflate and nitro precursors was realized with no-carrier-added [¹⁸F]fluoride. After labeling, fluorine-18 containing aldehydes were trapped on a Solid Phase Extraction (SPE) cartridge and the subsequent conversion into benzyl halide was directly realized, on-line, on the support. Reduction of the aldehydes (>95%) was near-quantitative with an aqueous solution of NaBH₄. Halogenation was performed on the same support with different aqueous solutions of concentrated acid (HI, HBr, HCl). The conversion of benzyl alcohols into [¹⁸F]fluorobenzyl halides (X = Cl, Br, I) usually proceeded within 2 min at high yields. The halogenation proceeded at room temperature, with the exception of the 2-[¹⁸F]fluoro-3-methoxybenzyl, 2- and 4-[¹⁸F]fluorobenzyl halides, which required the use of HBr/HOAc (33%). With this method, various [¹⁸F]fluorobenzyl chloride, bromide and iodide compounds were obtained with high radiochemical purities (>90%) and with overall radiochemical yields of 15-70%. The radiosynthesis was completed in 30 or 45 min from EOB, starting from the ammonium or nitro precursor, respectively. By using the same solid support, 2- and 4-[¹⁸F]fluorobenzyl bromide and iodide derivatives were near-quantitatively converted (>95%) into the corresponding azido compounds (60 掳C, 5 min). As the reduction and halogenation steps were performed on solid supports, automation of the whole synthesis was straightforward.