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使用单个微流控芯片连续流动合成N-琥珀酰亚胺基4-[¹⁸F]氟苯甲酸酯。

Continuous-Flow Synthesis of N-Succinimidyl 4-[18F]fluorobenzoate Using a Single Microfluidic Chip.

作者信息

Kimura Hiroyuki, Tomatsu Kenji, Saiki Hidekazu, Arimitsu Kenji, Ono Masahiro, Kawashima Hidekazu, Iwata Ren, Nakanishi Hiroaki, Ozeki Eiichi, Kuge Yuji, Saji Hideo

机构信息

Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Kyoto, Japan.

Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Kyoto, Japan.

出版信息

PLoS One. 2016 Jul 13;11(7):e0159303. doi: 10.1371/journal.pone.0159303. eCollection 2016.

Abstract

In the field of positron emission tomography (PET) radiochemistry, compact microreactors provide reliable and reproducible synthesis methods that reduce the use of expensive precursors for radiolabeling and make effective use of the limited space in a hot cell. To develop more compact microreactors for radiosynthesis of 18F-labeled compounds required for the multistep procedure, we attempted radiosynthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) via a three-step procedure using a microreactor. We examined individual steps for [18F]SFB using a batch reactor and microreactor and developed a new continuous-flow synthetic method with a single microfluidic chip to achieve rapid and efficient radiosynthesis of [18F]SFB. In the synthesis of [18F]SFB using this continuous-flow method, the three-step reaction was successfully completed within 6.5 min and the radiochemical yield was 64 ± 2% (n = 5). In addition, it was shown that the quality of [18F]SFB synthesized on this method was equal to that synthesized by conventional methods using a batch reactor in the radiolabeling of bovine serum albumin with [18F]SFB.

摘要

在正电子发射断层扫描(PET)放射化学领域,紧凑型微反应器提供了可靠且可重复的合成方法,减少了用于放射性标记的昂贵前体的使用,并有效利用了热室中的有限空间。为了开发用于多步程序所需的18F标记化合物放射性合成的更紧凑型微反应器,我们尝试使用微反应器通过三步程序进行N-琥珀酰亚胺基4-[18F]氟苯甲酸酯([18F]SFB)的放射性合成。我们使用间歇式反应器和微反应器研究了[18F]SFB的各个步骤,并开发了一种使用单个微流控芯片的新型连续流合成方法,以实现[18F]SFB的快速高效放射性合成。在使用这种连续流方法合成[18F]SFB时,三步反应在6.5分钟内成功完成,放射化学产率为64±2%(n = 5)。此外,结果表明,用这种方法合成的[18F]SFB在牛血清白蛋白用[18F]SFB进行放射性标记方面的质量与使用间歇式反应器的传统方法合成的质量相当。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d18f/4943714/412811233b2e/pone.0159303.g001.jpg

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