title: Dose-on-demand of diverse 18F-fluorocholine derivatives through a two-step microfluidic approach.
abstract: BACKGROUND
  The validation and confirmation of clinical usefulness of new and known positron emission tomography (PET) tracers require stable production routes and simple and robust radiochemical procedures. Microfluidic technologies are regarded as an approach that could allow an unprecedented flexibility and productivity in PET radiopharmaceutical research. In this work, we will show how a commercially available microfluidic system can be used for a sequential and repeatable radiosynthesis of three different fluorocholine analogues currently under investigation as tumor tracers.
  
  
  METHODS
  Advion microfluidic system was used for performing the synthesis and purification of [(18)F]fluoromethyl, [(18)F]fluoroethyl or [(18)F]fluoropropyl choline employing a two-step approach, starting from the corresponding alkyl-ditosylate and reacting the [(18)F]fluorotosylate obtained in the first step with neat dimethylethanolamine. The purification was obtained using a recyclable SPE cartridge set.
  
  
  RESULTS
  The three products, fluoromethylcholine, fluoroethylcholine and fluoropropylcholine, were obtained in good to optimum yields (22%-54% decay corrected) with a 15-min procedure. The production could be restarted several times for producing each one of the tracers without decrease in yields and purities, in accordance with a dose-on-demand (DOD) approach. The final products were formulated in isotonic saline solution.
  
  
  CONCLUSIONS
  The described approach gives a proof of principle of the enhanced productivity obtainable using a microfluidic approach; in particular, the possibility to produce the reported tracers in a DOD fashion following a homogeneous synthetic and purification approach will foster further studies on the clinical evaluation of the best fluorocholine analogue for prostate cancer imaging without biasing for differences in radiochemical approach.
authors: Institute of Clinical Physiology of CNR, via Moruzzi 1, 56124 Pisa. pascali@ifc.cnr.it
authors: Giancarlo
authors: G
authors: Pascali
authors: Giovanni
authors: G
authors: Nannavecchia
authors: Sabrina
authors: S
authors: Pitzianti
authors: Piero A
authors: PA
authors: Salvadori
mesh_terms: D002794:Choline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D054879:Halogenation; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D049268:Positron-Emission Tomography; D011854:Radiochemistry / Q000295:instrumentation*; D052616:Solid Phase Extraction
chemical_list: C514960:fluorocholine; D002794:Choline