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

开发了一种有效、快速的方法，用于将[^ 18 F]氟苄基碘作为多功能标记前体。

基本信息

批准号：
11670861
负责人：
IWATA Ren
金额：
$ 2.11万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

[^<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.

[^ 18 F]氟苄基碘和溴化物([^ 18 F]氟苄基卤)预计与^ 11 C-标记的碘甲烷一样多用途的^ 18 F-氟苄基化前体。 ^ 11 C-甲基化。在本研究中，我们的目标是开发一种方便、快速的方法，用于从[^ 18 F]氟化物自动制备目标化合物。已尝试将构成合成程序的以下三个步骤适应柱上处理。1)从[^ 18 F]氟化物合成[^ 18 F]氟苯甲醛：将起始底物固定在固体上-相支持物并检查[^ 18 F]氟化物的芳族亲核取代。然而，通过该方法获得的[^ 18 F]氟苯甲醛的放射化学产率对于连续反应而言不够高。因此，放弃了柱上方法。2)将[^ 18 F]氟苯甲醛还原成[^ 18 F]氟苯甲醇：在许多还原剂中选择硼氢化钠，因为它在水溶液中使用。虽然氧化铝上的NaBH_4产生相当低的收率，但仅使NaBH_4溶液流过保留[^ 18 F]氟苯甲醛的C18柱的简单柱上方法几乎定量地产生[^ 18 F]氟苯甲醇。因此，在还原后，用CH_2Cl_洗脱[^ 18 F]氟苯甲醇。 2.3)由[^ 18 F]氟苯甲醇合成[^ 18 F]氟苯甲基卤化物：固定到树脂或吸附的卤化试剂对硅胶上的反应进行了研究。据观察，[ 18 F]氟苄基卤化物的放射化学收率非常依赖于从C18柱洗脱的溶剂的干燥度。基于上述结果构建了半自动系统，并通过从[^ 18 F]氟苄基卤制备新的^ 18 F-标记的放射性配体来进行评估。