Microfluidic Preparation of [18F]FE@SUPPY and [18F]FE@SUPPY:2--comparison with Conventional Radiosyntheses

Introduction: 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.

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.

Results: 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.

Conclusion: The direct comparison of radiosyntheses data applying a conventional method and a microfluidic approach revealed a significant increase of RCIY using the microfluidic approach.