title: Simple preparation and purification of ethanol-free solutions of 3'-deoxy-3'-[18F]fluorothymidine by means of disposable solid-phase extraction cartridges.
abstract: BACKGROUND
  3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) shows great potential as a tracer for proliferative studies with PET. However, its regular application is often limited by low radiochemical yields and the use of a troublesome HPLC separation. Moreover, a high content of ethanol, at least one-fold higher than the European Pharmacopoeia and US Pharmacopoeia's established limit, is always present in the final product. The present study reports an optimization of the reaction conditions and a simple and straightforward purification step which affords a solution of [(18)F]FLT suitable for human use.
  
  
  METHODS
  Several conditions and materials were tested for both the nucleophilic substitution and purification step. The latter was achieved by means of a series of commercial solid-phase extraction cartridges. Very conveniently, the whole one-pot synthesis was carried out on commercial automated modules using basically the same setup employed for the synthesis of [(18)F]FDG.
  
  
  RESULTS
  Under routine conditions, radiochemical yields of 37% [decay-corrected to start of synthesis (SOS)] were achieved in ca. 39 min from SOS, with radiochemical purities >98% (usually >99%). The negligible radiolysis observed could be easily suppressed by adding 0.5% of EtOH. Typical unlabelled chemical impurities detected were thymidine (0.15 ppm), thymine (0.28 ppm) and stavudine (0.05 ppm).
  
  
  CONCLUSIONS
  A reliable, simple and efficient preparation of [(18)F]FLT has been developed, able to afford an ethanol-free solution of the tracer with no need for any HPLC purification. Because of its similarity to the [(18)F]FDG synthesis, the method can be readily implemented on basically all the commercial modules developed for this common radiotracer.
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, V. Venezian, Milan, Italy. claudio.pascali@istitutotumouri.mi.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Pascali
authors.forename: Anna
authors.initials: A
authors.lastname: Bogni
authors.forename: Lorenza
authors.initials: L
authors.lastname: Fugazza
authors.forename: Claudio
authors.initials: C
authors.lastname: Cucchi
authors.forename: Ornella
authors.initials: O
authors.lastname: Crispu
authors.forename: Luca
authors.initials: L
authors.lastname: Laera
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.forename: Greta
authors.initials: G
authors.lastname: Maiocchi
authors.forename: Flavio
authors.initials: F
authors.lastname: Crippa
authors.forename: Emilio
authors.initials: E
authors.lastname: Bombardieri
mesh_terms: D015224:Dideoxynucleosides / Q000009:adverse effects / Q000302:isolation & purification*; D004209:Disposable Equipment; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D012449:Safety; D052616:Solid Phase Extraction / Q000295:instrumentation*; D012996:Solutions
chemical_list: D015224:Dideoxynucleosides; D012996:Solutions; D000431:Ethanol; C002854:alovudine