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

采用kieselguhr色谱柱自动制备[<@D111@>D1C]脂肪酸和[<@D111@>D1C]氨基酸。[<@D111@>D1C]二氧化碳与格氏试剂反应，液-液萃取纯化，在市买kieselauhr， exrelut <@D1(]SY.encircledR.液相层中进行。() @ > D1(默克公司)。[<@D111@>D1C]二氧化碳被有效地捕获到Extrelut色谱柱保存的试剂溶液和dil淬火形成的游离脂肪酸[<@D111@>D1C]中。用合适的有机溶剂从反应塔中依次萃取HCl，然后用Extrelut短柱萃取[<@D111@>D1C]乙酸，用硅胶萃取[<@D111@>D1C]棕榈酸。[<@D111@>D1C]乙酸的放射化学产率超过90%，[<@D111@>D1C]棕榈酸的放射化学产率约为90%。放射化学产率50%，在15分钟内，用相同的系统和程序。以[^<11>C] HCN为原料，在柱上合成了1-氨基环戊烷-1-[^<11>C]羧酸（[^<11>C] ACPC）。整个合成过程，包括[^<11>C] HCN的捕获和反应以及随后的提取和酸水解，都得到了显著的简化，制备成功地适应了[^<11>C] ACPC的常规生产。所建立的方法在轰炸结束后40分钟内提供放射化学纯度[^<11>C]的ACPC，放射化学产率超过60%。因此，本研究表明，基于柱萃取的柱上标记可以简化PET放射药物制备的合成程序，并促进PET常规使用的自动化。

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.