Positron emission tomography (PET) and microfluidic devices: A breakthrough on the microscale?

Positron emission tomography (PET) and microfluidic devices: A breakthrough on the microscale?
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DOI:
10.1002/anie.200603509
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发表时间:
2007-01-01
影响因子:
16.6
通讯作者:
Audrain, Helen
Audrain, Helen
中科院分区:
化学1区
文献类型:
--
作者:
Audrain, Helen

文献摘要

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正电子发射断层扫描(PET)是一种强大的非侵入性技术,用于研究注射放射性药物后人体和动物体内的生理参数(血流研究、葡萄糖代谢、受体特性、药物分布和机制)。[1]这些成像探针用短寿命放射性同位素标记(例如,18 F,t1/2= 109.7 min; 11 C,t1/2= 20.4 min; 13 N,t1/2= 9.96 min; 15 O,t1/2= 2.07 min),这需要反应过程(反应+纯化+配制+质量控制)尽可能快。由于化学反应是在微米到纳米尺度上进行的,因此需要特殊的设备和方法,如微型反应器和“环内”技术。[2]此外,与放射性有关的工作需要采取谨慎的安全预防措施,以避免对操作人员造成不必要的辐射,并使用安装在铅屏蔽柜(或热室)中的计算机化系统。由于PET放射化学代表了化学中相对较新的领域,因此不断发展以改进制备这些放射性标记化合物的技术。参与这项任务的人面临着巨大的挑战,因为他们寻求将联合收割机自动化与计算机科学相结合,并满足化学过程、辐射屏蔽、用户友好性、微型技术和芯片实验室(Lab-on-a-chip,简称LAB)是一个不断扩展并可能对PET领域有重大帮助的领域。技术;采用该技术的组件和设备的小型化可以提供专用于PET化学的专用设备。几年前出现的用于化学和生物反应的微流体系统[3],其包含不大于几微米(10至500 μm)的通道网络,提供了令人兴奋的优点,例如样品和试剂消耗低,反应加速,分析速度更快,重现性高和自动化。这些特征代表了放射化学家在合成放射性示踪剂时努力实现的目标。然而,目前可用的常规设备并不总是适合所需材料的尺寸或数量,这使得任务比实际应该的复杂。因此,通过在该特定PET领域中使用微芯片或微反应器来缩小化学可能是有益的,特别是考虑到时间尺度,这代表了这些合成中的限制因素。在这一亮点中,将介绍结合这两种现代技术(微芯片和PET)的两个小组的成果。本文介绍了两种不同的方法,即通过控制和转移微量液体,利用同位素标记技术对2-脱氧-2-[18 F]氟代-d-葡萄糖(2-[18 F] FDG)进行放射性标记。的发展
Positron emission tomography (PET) is a powerful noninvasive technique for investigating physiological parameters in the living human and animal body (blood-flow studies, glucose metabolism, receptor properties, drug distribution, and mechanism) after injection of a radiopharmaceutical.[1] These imaging probes are labeled with short-lived radioisotopes (eg, 18F, t1/2= 109.7 min; 11C, t1/2= 20.4 min; 13N, t1/2= 9.96 min; 15O, t1/2= 2.07 min), which necessitates that the reaction process (reaction+ purification+ formulation+ quality control) be as fast as possible. As the chemical reactions are performed on the micro-to nanoscale, special equipment and methods such as miniature reactors and “in-loop” techniques are required.[2] Furthermore, working with radioactivity necessitates careful safety precautions to avoid unnecessary radiation for the operator and the use of computerized systems installed in lead-shielded cabinets (or hot-cells). Because PET radiochemistry represents a relatively new field in chemistry, it is constantly being evolved to improve the techniques for preparing these radiolabeled compounds. Those involved in this task are confronted with enormous challenges as they seek to combine automation with computer science, and fulfill the requirements of the chemical process, radiation shielding, user friendliness, and compactness of the final system to deliver an effective PET chemical production system.One domain that is constantly expanding and could potentially be a significant help to the PET field is microtechnology and lab-on-a-chip (LOC) technology; the miniaturization of components and equipment with this technology could provide special equipment dedicated to PET chemistry. The appearance some years ago of microfluidic systems [3] for chemical and biological reactions, which contain networks of channels no larger than a few micrometers (10 to 500 μm), offer exciting advantages such as low sample and reagent consumption, acceleration of the reactions, faster analysis, high reproducibility, and automation. These characteristics represent the goals that radiochemists strive to fulfill when synthesizing radiotracers. However, the conventional equipment available today is not always suited to the size or the quantity of material required, which renders the task more complicated than it really should be. Scaling down the chemistry by using microchips or microreactors in this particular PET field could therefore be beneficial, especially considering the timescale, which represents the limiting factor in these syntheses. In this Highlight, the results of two groups who combined these two modern technologies, microchips and PET, will be presented. Two different approaches are described on the use of LOC technology for radiolabeling of 2-deoxy-2-[18F] fluoro-d-glucose (2-[18F] FDG) by controlling and transferring minute volumes of liquids. The development of the