Synthesis of hypoxia imaging agent 1-(5-deoxy-5-fluoro-α-D-arabinofuranosyl)-2-nitroimidazole using microfluidic technology
Synthesis of hypoxia imaging agent 1-(5-deoxy-5-fluoro-α-D-arabinofuranosyl)-2-nitroimidazole using microfluidic technology
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DOI：
10.1016/j.nucmedbio.2010.09.002
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发表时间：
2011-02-01
影响因子：
3.1
通讯作者：
Wuest, Frank
中科院分区：
文献类型：
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作者：
Bouvet, Vincent R.;Wuest, Melinda;Wuest, Frank
前言：微流控技术允许在一个简单的实验装置中进行快速反应，同时使用非常低的体积和数量的起始材料。因此，微流控技术是利用短寿命正电子发射体进行放射性标记反应的理想工具。优化不同反应条件的复杂阵列需要了解与微流控系统相关的不同反应参数及其对放化产额的影响。1-(5-Deoxy-5-fluoro-alpha-D-arabinofuranosyl)-2-nitroimidazole([F-18]Faza)是一种常用的放射性示踪剂，用于肿瘤缺氧的正电子发射计算机断层扫描。本研究描述了利用微流控技术在EMT-6荷瘤小鼠体内放射合成[F-18]Faza以及随后的小动物PET成像。通过对不同反应参数如反应温度、流速、停留时间、标记前体物(1-(2，3-di-O-acetyl-5-O-tosyl-alpha-D-arabinofuranosyl)-2-nitroimidazole)的浓度以及标记前体物与[F-18]氟的体积比的筛选，研究了最佳反应条件。结果：优化的反应条件在低放射性水平(1~50MBq)下，25min内可获得63%(衰变校正后)的[F-18]Faza。较高的放射性水平(0.4-2.1GBq)使高效液相纯化的[F-18]Faza在60min内的放化产率为40%(衰变校正后)，比活度在70-150GBq/mumol的范围内。在EMT-6荷瘤小鼠体内的小动物PET研究显示，放射性在肿瘤内积累(SUV20min 0.74+/-0.08)，导致肿瘤与肌肉的比率随着时间的推移而增加。结论：微流控技术是一种快速、有效的放射合成[F-18]Faza的理想方法，可用于临床前放射药理学研究。详细分析各种反应参数是了解不同反应参数对微流控技术放化产额影响的重要条件。目前正在探索微流控技术，用于在临床相关的放射性水平下合成其他PET放射性示踪剂。(C)2011 Elsevier Inc.保留所有权利。
Introduction: Microfluidic technology allows fast reactions in a simple experimental setup, while using very low volumes and amounts of starting material. Consequently, microfluidic technology is an ideal tool for radiolabeling reactions involving short-lived positron emitters. Optimization of the complex array of different reaction conditions requires knowledge of the different reaction parameters linked to the microfluidic system as well as their influence on the radiochemical yields. 1-(5-Deoxy-5-fluoro-alpha-D-arabinofuranosyl)-2-nitroimidazole ([F-18]FAZA) is a frequently used radiotracer for PET imaging of tumor hypoxia. The present study describes the radiosynthesis of [F-18] FAZA by means of microfluidic technology and subsequent small animal PET imaging in EMT-6 tumor-bearing mice.Methods: Radiosyntheses were performed using the NanoTek Microfluidic Synthesis System (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, residency time, concentration of the labeling precursor (1-(2,3-di-O-acetyl-5-O-tosyl-alpha-D-arabinofuranosyl)-2-nitroimidazole) and the applied volume ratio between the labeling precursor and [F-18]fluoride.Results: Optimized reaction conditions at low radioactivity levels (1 to 50 MBq) afforded 63% (decay-corrected) of HPLC-purified [F-18] FAZA within 25 min. Higher radioactivity levels (0.4 to 2.1 GBq) gave HPLC-purified [F-18]FAZA in radiochemical yields of 40% (decay-corrected) within 60 min at a specific activity in the range of 70 to 150 GBq/mu mol. Small animal PET studies in EMT-6 tumor-bearing mice showed radioactivity accumulation in the tumor (SUV20min 0.74 +/- 0.08) resulting in an increasing tumor-to-muscle ratio over time.Conclusions: Microfluidic technology is an ideal method for the rapid and efficient radiosynthesis of [F-18]FAZA for preclinical radiopharmacological studies. Careful analysis of various reaction parameters is an important requirement for the understanding of the influence of different reaction parameters on the radiochemical yield using microfluidic technology. Exploration of microfluidic technology for the radiosynthesis of other PET radiotracers in clinically relevant radioactivity levels is currently in progress. (C) 2011 Elsevier Inc. All rights reserved.