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用于评估 I-阿魏酸放射化学纯度的微型色谱系统,I-阿魏酸是核医学应用中的一种新候选药物。

Miniaturized chromatographic systems for radiochemical purity evaluation of I-Ferulic acid as a new candidate in nuclear medicine applications.

机构信息

Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Labeled Compounds Department, Hot Laboratories Center, Egyptian Atomic Energy, P.O. 13759, Cairo, Egypt.

出版信息

Appl Radiat Isot. 2021 Jan;167:109370. doi: 10.1016/j.apradiso.2020.109370. Epub 2020 Oct 8.

Abstract

Recently, the anticancer activity of ferulic acid (FA) which is a caffeic acid derivative has been reported. Therefore, in this study FA was radiocaped with I to explore its potential as a tumor targeting agent. The radiolabeling process was carried out via electrophilic substitution reaction. The factors affecting labeling yield were optimized and the radiochemical purity (RCP) was assessed by various analytical techniques including paper chromatography (PC), thin layer chromatography (TLC), instant thin layer chromatography (ITLC), paper electrophoresis (PE) and high-performance liquid chromatography (HPLC). The RCP assay was extended to the utilization of miniaturized techniques including miniaturized PC (mini-PC), mini-TLC and mini-column chromatography (silica, sephadex-G25). Validation of mini-TLC, as one of I-FA RCP assay methods, was done according to ICH guidelines. Biodistribution studies of I-FA were performed on Ehrlich solid tumor bearing mice at various time points (5, 30, 60, 120 and 240 min), post injection. The radiolabeling yield of I-FA was 96.23 ± 0.45% and the miniaturized chromatographic systems showed high efficacy in RCP evaluation comparable to the conventional ones. Mini-TLC was proved to be specific, accurate, precise and linear. The tumor uptake of I-FA in solid tumor bearing mice was 4.35 ± 0.41 ID/g at 60 min with 2.79 as a tumor/muscle ratio. Consequently, I-FA could be used as a tumor targeting agent for nuclear medicine applications and the fast reaction monitoring could be achieved using miniaturized chromatographic techniques.

摘要

最近,有报道称咖啡酸衍生物阿魏酸(FA)具有抗癌活性。因此,本研究采用亲电取代反应对 FA 进行放射性标记,以探索其作为肿瘤靶向剂的潜力。通过各种分析技术,包括纸层析(PC)、薄层层析(TLC)、即时薄层层析(ITLC)、纸电泳(PE)和高效液相色谱(HPLC),优化了影响标记产率的因素,并评估了放射化学纯度(RCP)。RCP 测定法还扩展到了包括微型 PC(mini-PC)、微型 TLC 和微型柱层析(硅胶、葡聚糖 G25)在内的微型化技术的应用。根据 ICH 指南,对 mini-TLC 作为 I-FA RCP 测定方法之一进行了验证。在注射后不同时间点(5、30、60、120 和 240 分钟),对荷 Ehrlich 实体瘤的小鼠进行 I-FA 的生物分布研究。I-FA 的标记产率为 96.23±0.45%,微型色谱系统在 RCP 评估中显示出与传统方法相当的高效性。Mini-TLC 被证明具有特异性、准确性、精密度和线性。在荷实体瘤的小鼠中,I-FA 在 60 分钟时的肿瘤摄取率为 4.35±0.41 ID/g,肿瘤/肌肉比为 2.79。因此,I-FA 可作为核医学应用的肿瘤靶向剂,使用微型化色谱技术可以实现快速反应监测。

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