Development of the on-column labelling method for automated preparation of radiopharmaceuticals for PET study

开发用于 PET 研究的放射性药物自动制备的柱上标记方法

基本信息

批准号：
05670760
负责人：
IWATA Ren
金额：
$ 1.02万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670760/
关键词：
PET On-column labelling Automated synthesis Positron-emitter Radiopharmaceutical

项目摘要

A new, convenient on-column method using kieselguhr has been developed for the automated preparations of [<@D111@>D1C] fatty acids and [<@D111@>D1C] amino acids The reaction of [<@D111@>D1C] carbon dioxide with a Grignard reagent and purification by liquid-liquid extraction were carried out in a liquid layr supported by a commercially available kieselauhr, Extrelut<@D1(]SY.encircledR.[)@>D1 (Merck). [<@D111@>D1C] Carbon dioxide was efficiently trapped into a reagent solution kept by an Extrelut column and the free [<@D111@>D1C] fatty acid formed by quenching with dil. HCl was sequentially extracted by flowing an appropriate organic solvent from the reaction column into the solvent and then from the solvent into a short column of Extrelut for [<@D111@>D1C] acetic acid or silica gel for [<@D111@>D1C] palmitic acid. [<@D11@>D1C] Acetic acid was prepared in over 90% radiochemical yield and [<@D111@>D1C] palmitic acid in approx. 50% radiochemical yield, within 15 min, with the same system and procedure.The on-column synthesis of 1-aminocyclopentane-1-[^<11>C] carboxylic acid ( [^<11>C] ACPC) from [^<11>C] HCN was also carried out. The whole synthetic procedure, including the trapping and reaction of [^<11>C] HCN as well as the following extraction and acid hydrolysis, was remarkably simplified, and the preparation has been successfully accommodated to routine production of [^<11>C] ACPC.The established method provides radiochemically pure [^<11>C] ACPC in over 60% radiochemical yield within 40 min after the end of bombardment.Thus, the present study has demonstrated that the on-column labelling based on column extraction can simplify synthetic procedures for the preparation of PET radiopoharmaceuticals and facilitate automation for routine use in PET.

开发了一种使用硅藻土的新型便捷柱上方法，用于自动制备 [<@D111@>D1C] 脂肪酸和 [<@D111@>D1C] 氨基酸 [<@D111@>D1C] 的反应用格氏试剂处理二氧化碳并通过液-液萃取纯化在由市售硅藻土支撑的液层中进行， Extrelut<@D1(]SY.encircledR.[)@>D1（默克）。 [<@D111@>D1C]二氧化碳被有效地捕获到由Extrelut柱保存的试剂溶液中，并且通过用稀释剂淬灭形成游离的[<@D111@>D1C]脂肪酸。通过将合适的有机溶剂从反应柱流入溶剂中，然后从溶剂中流入用于[<@D111@>D1C]乙酸的Extrelut短柱或用于[<@D111@>D1C]乙酸的硅胶，依次萃取HCl ] 棕榈酸。 [<@D11@>D1C] 乙酸的放射化学产率超过 90%，[<@D11@>D1C] 棕榈酸的产率约为 10%。使用相同的系统和程序，15 分钟内放射化学收率达到 50%。从 [^ 柱上合成 1-氨基环戊烷-1-[^ 11 C] 羧酸 ( [^ 11 C] ACPC)还进行了11 C]HCN。整个合成过程，包括[^ 11 C]HCN的捕获和反应以及随后的萃取和酸水解，显着简化，并且该制备已成功适应[^ 11 C]的常规生产。 ] ACPC。所建立的方法在轰击结束后40分钟内以超过60％的放射化学产率提供放射化学纯的[^ 11 C] ACPC。因此，本研究表明，柱上基于柱萃取的标记可以简化制备 PET 放射性药品的合成程序，并促进 PET 常规使用的自动化。