The development of an efficient, rapid method for [^<18>F] fluorobenzyl iodide as a versatile labeling precursor.

[^<18>F]碘化氟苯和溴化氟苯（[^<18>F]氟卤化物）被认为是用于^<18>F氟苯甲基化的通用前体，正如用于^<11> c甲基化的^<11> c标记碘化甲基一样。在本研究中，我们旨在开发一种方便、快速的方法，从[^<18>F]氟化物中自动制备目标化合物。已尝试使构成合成程序的下列三个步骤适应于柱上处理。1)由[^<18>F]氟化物合成[^<18>F]氟苯甲醛：将起始底物固定在固相载体上，并用[^<18>F]氟化物检测芳香族亲核取代。然而，用这种方法得到的[^<18>F]氟苯甲醛的放射化学产率不够高，不能连续反应。因此，放弃了列上法。2)将[^<18>F]氟苯甲醛还原为[^<18>F]氟苯醇：由于在水溶液中使用，在许多还原剂中选择了硼氢化钠。虽然氧化铝上的NaBH_4产率相当低，但一种简单的柱上方法是将NaBH_4溶液通过保留[^<18>F]氟苯甲醛的C18滤筒，几乎可以定量地产[^<18>F]氟苯醇。在[^<18>F]氟苯醇还原后，用CH_2Cl_2.3洗脱[^<18>F]氟苯醇合成[^<18>F]氟酰卤化物，研究了固定在树脂上或吸附在硅胶上的卤化试剂。观察到[^<18>F]氟酰卤化物的放射化学产率与C18墨盒中溶剂洗脱的干燥程度密切相关。在上述结果的基础上构建了半自动化系统，并通过从[^<18>F]氟酰卤化物制备新的^<18>F标记的放射性配体进行了评价。

[^<18>F] Fluorobenzyl iodide and bromide ([^<18>F] fluorobenzyl halide) have been expected to be as versatile a precursor for ^<18>F-fluorobenzylation as ^<11>C-labled methyl iodide for ^<11>C-methylation. In the present study, we have aimed at developing a convenient, rapid method for automated preparation of the target compound from [^<18>F] fluoride. Attempts have been made to adapt the following three steps, constituting the synthesis procedure, to on-column processing.1) Synthesis of [^<18>F] fluorobenzaldehyde from [^<18>F] fluoride : Starting substrates were immobilized on solid-phase-supports and examined for aromatic nucleophilic substitution by [^<18>F] fluoride. However, radiochemical yields of [^<18>F] fluorobenzaldehyde obtained by this method were not high enough for successive reactions. Consequently the on-column method was abandoned.2) Reduction of [^<18>F] fluorobenzaldehyde into [^<18>F] fluorobenzyl alcohol : Sodium borohydride was chosen among many reductive reagents as it was used in aqueous solutions. While NaBH_4 on alumina gave rather lower yields, a simple on-column method of just flowing a NaBH_4 solution through a C18 cartridge retaining [^<18>F] fluorobenzaldehyde yielded [^<18>F] fluorobenzyl alcohol almost quantitatively. Thus after the reduction [^<18>F] fluorobenzyl alcohol was eluted with CH_2Cl_2.3) Synthesis of [^<18>F] fluorobenzyl halide from [^<18>F] fluorobenzyl alcohol : Halogenation reagents immobilized to a resin or adsorbed on silica gel were investigated for the reaction. It was observed that radiochemical yields of [^<18>F] fluorobenzyl halide were very dependent on the dryness of the solvent eluting from the C18 cartridge. A semi-automated system was constructed on the basis of the above results and evaluated by preparing new ^<18>F-labeled radioligands from [^<18>F] fluorobenzyl halide.