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

• 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

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.

本文提出了一种新的、简便的硅藻土柱上自动化制备[<@D111 @> D1C]脂肪酸和[<@D111 @> D1C]氨基酸的方法。D1（Merck）。[<@D111@>D1C]二氧化碳被有效地捕获到由Extremut柱保持的试剂溶液中，并且游离的[<@D111@>D1C]脂肪酸通过用dil猝灭而形成。通过使合适的有机溶剂从反应柱流入溶剂中，然后从溶剂流入用于[<@D111 @>D1C]乙酸的Extremut或用于[<@D111 @>D1C]棕榈酸的硅胶的短柱中，依次萃取HCl。[<@D11@>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%。用同样的系统和步骤，在15 min内，放化产率可达50%，并由[^ C] HCN在柱上合成了1-氨基环戊烷-1-[^<11>C]羧酸（[^<11>C] ACPC）<11>。整个合成过程，包括[^ C] HCN的捕集、反应<11>、萃取和酸水解，都得到了显著的简化，并成功地适应于[^ C] ACPC的常规生产<11>。建立的方法在轰击结束后40 min内得到了放化纯的[^<11>C] ACPC，放化产率超过60%。目前的研究表明，基于柱萃取的柱标记可以简化制备PET放射性药物的合成程序，并有利于PET中常规使用的自动化。

项目成果

Masao Tada: "An efficient synthesis of N^ω-[^<18>F]fluoroacetylserotonin (N^ω-[^<18>F]fluoroacetyl-5-hydroxytryptamine)." J.Labeld.Compd.Radiopharm.34. 741-746 (1994)

Masao Tada：“N^ω-[^18F]氟乙酰血清素（N^ω-[^18F]氟乙酰基-5-羟基色胺）的有效合成。J.Labeld.Compd.Radiopharm.34。” 741-746 (1994)

Ren Iwata: "On-column preparation of 1-aminocyclopentane-1-[^<11>C]carboxylic acid." Appl.Radiat.Isot.46(in press). (1995)

Ren Iwata：“1-氨基环戊烷-1-[^ 11 C]羧酸的柱上制备。”

Masao tada et al.: "A rapid synthesis of [fluoroacetyl-^<18>F] fluoromelatonin (N^w- [^<18>F] fluoroacetyl-5-methoxytryptamine), a potential diagonostic imaging agent." J.Labeld.Compd.Radiopharm. 33. 601-606 (1993)

Masao tada等人：“快速合成[氟乙酰基-^ 18 F]氟褪黑素（N^w-[^ 18 F]氟乙酰基-5-甲氧基色胺），一种潜在的诊断成像剂。”

Ren Iwata et al: "Column extraction method for rapid preparation of [^<11>C] acetic and [^<11>C] palmitic acids." Appl.Radiat.Isot.46 (in press). (1995)

Ren Iwata等人：“快速制备[^ 11 C]乙酸和[^ 11 C]棕榈酸的柱萃取方法。”

Ken-ichiro Mizuno et al.: "Improved preparation of L- [methyl-^<11>C] methionine by online [^<11>C] methylation." Applied Radiat.Isot.44. 788-790 (1993)

Ken-ichiro Mizuno 等人：“通过在线[^ 11 C]甲基化改进了L-[甲基-^ 11 C]甲硫氨酸的制备。”