Department of Chemistry and Biochemistry, University of Hull, Cottingham Road, Hull, HU6 7RX, UK.
Analyst. 2020 Jul 21;145(14):4920-4930. doi: 10.1039/c9an01881f. Epub 2020 Jun 4.
The miniaturisation of positron emission tomography (PET) radiotracer production is facilitating a move towards a dose-on-demand strategy that would enable a stratified approach to patient diagnostics, but while the on-chip synthesis steps have been demonstrated, the subsequent quality control (QC) testing steps have received much less attention. As part of the development of an integrated QC platform for PET tracers, we have developed two microfluidic electrochemical detectors for the pulsed amperometric detection (PAD) of carbohydrate-based radiotracers, with a particular view to the QC testing of the most important tracer, [F]2-fluoro-2-deoxy-d-glucose ([F]FDG). The first device employed a commercial screen-printed electrode (SPE) to enable a single-use format, while the second device incorporated wire electrodes for use as a more permanent fixture in a QC instrument. A flow-injection analysis (FIA)-style setup was used to inject boluses of d-glucose into the chips in a proxy for intended chromatographic separations prior to PAD. In proof-of-concept testing of the devices, the chips featuring the SPE and the wire electrodes yielded limits of detection of 0.1 ppm and 9 ppm, respectively, each below the required limits for [F]FDG, and thus making both methodologies viable for the QC testing of PET radiotracers in a dose-on-demand format.
正电子发射断层扫描(PET)示踪剂生产的小型化正在推动向按需剂量策略的转变,这将使患者诊断能够采用分层方法,但尽管已经证明了芯片上的合成步骤,但随后的质量控制(QC)测试步骤受到的关注要少得多。作为用于 PET 示踪剂的集成 QC 平台开发的一部分,我们已经为基于碳水化合物的放射性示踪剂的脉冲安培检测(PAD)开发了两种微流控电化学检测器,特别关注最重要的示踪剂 [F]2-氟-2-脱氧-d-葡萄糖([F]FDG)的 QC 测试。第一个设备采用商业丝网印刷电极(SPE)以实现一次性使用格式,而第二个设备则采用金属丝电极,以便在 QC 仪器中作为更永久的固定装置使用。采用流动注射分析(FIA)样式设置将 d-葡萄糖的脉冲注入芯片中,以模拟预期的色谱分离,然后进行 PAD。在对设备的概念验证测试中,配备 SPE 和金属丝电极的芯片的检测限分别为 0.1 ppm 和 9 ppm,均低于 [F]FDG 的要求限值,因此这两种方法都可用于按需剂量格式的 PET 放射性示踪剂的 QC 测试。