title: Microfluidic preparation of [18F]FE@SUPPY and [18F]FE@SUPPY:2--comparison with conventional radiosyntheses.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  The direct comparison of radiosyntheses data applying a conventional method and a microfluidic approach revealed a significant increase of RCIY using the microfluidic approach.
authors.affiliation: Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ungersboeck
authors.forename: Cécile
authors.initials: C
authors.lastname: Philippe
authors.forename: Leonhard-Key
authors.initials: LK
authors.lastname: Mien
authors.forename: Daniela
authors.initials: D
authors.lastname: Haeusler
authors.forename: Karem
authors.initials: K
authors.lastname: Shanab
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
authors.forename: Helmut
authors.initials: H
authors.lastname: Spreitzer
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Robert
authors.initials: R
authors.lastname: Dudczak
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
mesh_terms: D002855:Chromatography, Thin Layer; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D009539:Nicotinic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D011854:Radiochemistry / Q000295:instrumentation*
chemical_list: C528136:5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate; D005462:Fluorine Radioisotopes; D009539:Nicotinic Acids