Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria.
Nucl Med Biol. 2011 Apr;38(3):427-34. doi: 10.1016/j.nucmedbio.2010.09.009. Epub 2010 Dec 3.
Recently, first applications of microfluidic principles for radiosyntheses of positron emission tomography compounds were presented, but direct comparisons with conventional methods were still missing. Therefore, our aims were (1) the set-up of a microfluidic procedure for the preparation of the recently developed adenosine A(3)-receptor tracers [(18)F]FE@SUPPY [5-(2-[(18)F]fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] and [(18)F]FE@SUPPY:2 [5-ethyl-2,4-diethyl-3-((2-[(18)F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] and (2) the direct comparison of reaction conditions and radiochemical yields of the no-carrier-added nucleophilic substitution with [(18)F]fluoride between microfluidic and conventional methods.
For the determination of optimal reaction conditions within an Advion NanoTek synthesizer, 5-50 μl of precursor and dried [(18)F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (26 °C-180 °C) with defined reactant bolus flow rates (10-50 μl/min). Radiochemical incorporation yields (RCIYs) and overall radiochemical yields for large-scale preparations were compared with data from conventional batch-mode syntheses.
Optimal reaction parameters for the microfluidic set-up were determined as follows: 170 °C, 30-μl/min pump rate per reactant (reaction overall flow rate of 60 μl/min) and 5-mg/ml precursor concentration in the reaction mixture. Applying these optimized conditions, we observed a significant increase in RCIY from 88.2% to 94.1% (P < .0001, n ≥ 11) for [(18)F]FE@SUPPY and that from 42.5% to 95.5% (P<.0001, n ≥ 5) for [(18)F]FE@SUPPY:2 using microfluidic instead of conventional heating. Precursor consumption was decreased from 7.5 and 10 mg to 1 mg per large-scale synthesis for both title compounds, respectively.
The direct comparison of radiosyntheses data applying a conventional method and a microfluidic approach revealed a significant increase of RCIY using the microfluidic approach.
最近，首次将微流控原理应用于正电子发射断层扫描化合物的放射合成，但是仍然缺乏与传统方法的直接比较。因此，我们的目标是（1）建立一种用于制备最近开发的腺苷 A（3）受体示踪剂[18 F]FE@SUPPY [5-（2-[[18 F]氟乙基]）-2,4-二乙基-3-（乙基磺酰基）-6-苯基吡啶-5-羧酸酯]和[18 F]FE@SUPPY：2 [5-乙基-2,4-二乙基-3-（（2-[[18 F]氟乙基]磺酰基）-6-苯基吡啶-5-羧酸酯]的微流控程序，以及（2）直接比较微流控和常规方法之间无载体添加亲核取代与[18 F]氟化物的反应条件和放射化学产率。
为了在 Advion NanoTek 合成仪中确定最佳反应条件，同时以定义的反应物脉冲流速（10-50 μl/min）将 5-50 μl 的前体和干燥的[18 F]氟化物溶液推过温度控制的反应器（26°C-180°C）。大规放射化学收率（RCIY）和总体放射化学产率与常规批量合成的数据进行了比较。
确定了微流控装置的最佳反应参数如下：170°C，每个反应物的 30-μl/min 泵速（反应总体流速为 60 μl/min）和反应混合物中 5-mg/ml 的前体浓度。应用这些优化条件，我们观察到[18 F]FE@SUPPY 的 RCIY 从 88.2%显著增加到 94.1%（P<0.0001，n≥11），而[18 F]FE@SUPPY：2 从 42.5%增加到 95.5%（P<0.0001，n≥5）使用微流控代替常规加热。与传统加热相比，每个大规模合成的标题化合物的前体消耗分别从 7.5 和 10mg 减少到 1mg。
应用常规方法和微流控方法直接比较放射合成数据表明，使用微流控方法可显著提高 RCIY。
