设计和实施用于脂肪族支链氨基酸 18F 荧光化的自动 DT-PhotoFluor 放射合成模块

IF 2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Gokce Engudar, Zheliang Yuan, Matthew B. Nodwell, Hua Yang, Chelsey Currie, Stuart McDiarmid, Robert Britton, Paul Schaffer
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引用次数: 0

摘要

在此,我们报告了一种光氟化工艺的自动化和放大,该工艺是生产支链脂肪族放射性标记物(如(S)-5-[18F]氟高亮氨酸((S)-5-[18F]]FHL)的关键。(S)-5-[18F]FHL是一种亮氨酸类似物,主要由L型氨基酸转运体(LAT或L系统)吸收。LAT1 的表达水平与肿瘤增殖、血管生成和治疗效果密切相关,因此成为癌症分子成像的一个有吸引力的靶点。我们之前合成了 (S)-5-[18F]FHL,并在携带 PC3(前列腺)或 U87(胶质瘤)异种移植物的小鼠体内测试了这种示踪剂,以确定其检测和监测多种癌症治疗的可行性。本研究利用自动 DT-PhotoFluor 模块演示了 5-[18F]FHL 的放射合成,放射化学收率为 20.1 ± 4.8%(n = 3),放射化学纯度为 94.5 ± 4.9%(n = 3),合成时间约为 75 分钟。报告中的 DT-PhotoFluor 模块将使摩尔活性更高、可重复性更好,并减少即将进行的首次人体研究的辐射暴露。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Design and implementation of an automated DT-PhotoFluor radiosynthesis module for 18F-fluorination of aliphatic, branched chain amino acids

Design and implementation of an automated DT-PhotoFluor radiosynthesis module for 18F-fluorination of aliphatic, branched chain amino acids

Herein we report the automation and scale-up of a photofluorination process key to the production of branched-chain aliphatic radiotracers such as (S)-5-[18F]fluorohomoleucine ((S)-5-[18F]]FHL). (S)-5-[18F]FHL is a leucine analogue that is primarily taken up by the L-type amino acid transporter (LAT or System L). LAT1 expression levels correlate closely with tumor proliferation, angiogenesis, and treatment outcomes, making it an attractive target for molecular imaging of cancer. We have previously synthesized (S)-5-[18F]FHL and tested this tracer in mice bearing PC3 (prostate) or U87 (glioma) xenografts in order to establish its feasibility for detecting and monitoring treatment for a broad range of cancers. In this study, the radiosynthesis of 5-[18F]FHL is demonstrated on an automated DT-PhotoFluor module with a radiochemical yield of 20.1 ± 4.8% (n = 3), radiochemical purity of 94.5 ± 4.9% (n = 3), and a synthesis time of ~ 75 min. The reported DT-PhotoFluor module will allow for higher molar activity, better reproducibility, and reduced radiation exposure for upcoming first-in-human studies.

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来源期刊
Journal of Flow Chemistry
Journal of Flow Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
6.40
自引率
3.70%
发文量
29
审稿时长
>12 weeks
期刊介绍: The main focus of the journal is flow chemistry in inorganic, organic, analytical and process chemistry in the academic research as well as in applied research and development in the pharmaceutical, agrochemical, fine-chemical, petro- chemical, fragrance industry.
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