title: Automated GMP synthesis of [(18)F]ICMT-11 for in vivo imaging of caspase-3 activity.
abstract: BACKGROUND
  Isatin-5-sulfonamide ([(18)F]ICMT-11) is a sub-nanomolar inhibitor of caspase-3 previously evaluated as an apoptosis imaging agent. Herein, an alternative radiosynthesis of [(18)F]ICMT-11 with increased purity and specific activity is presented. Finally, a GMP-applicable automated radiosynthesis of [(18)F]ICMT-11 is described.
  
  
  METHODS
  The preparation of [(18)F]ICMT-11 was evaluated under a variety of reaction conditions, including reaction solvent, by employing alternative phase transfer catalysts and under different deprotection conditions. Following initial investigations, the process was transferred onto a fully automated GE FASTlab synthesis platform for further development and optimisation.
  
  
  RESULTS
  The synthesis of [(18)F]ICMT-11 was successfully validated under GMP conditions, resulting in a yield of 4.6 ± 0.4 GBq with a radiochemical purity of >98% at EOS and a specific activity of 685 ± 237 GBq/μmol within 90 min. Quality control was carried out in accordance with the European Pharmacopoeia and demonstrated that [(18)F]ICMT-11 can be consistently manufactured on the FASTlab to meet specifications.
  
  
  CONCLUSIONS
  A simplified methodology for the synthesis of the apoptosis imaging agent, [(18)F]ICMT-11, has been achieved by the S(N)2 displacement of a tosylate leaving group with [(18)F]fluoride ion. This results in an increased purity and specific activity over the original copper catalysed "Click" synthetic stratagem reaction involving 2-[(18)F]fluoroethylazide with an alkyne precursor and is now suitable for routine clinical application.
authors.affiliation: Hammersmith Imanet Ltd, (part of GE Healthcare), Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Fortt
authors.forename: Graham
authors.initials: G
authors.lastname: Smith
authors.forename: Ramla O
authors.initials: RO
authors.lastname: Awais
authors.forename: Sajinder K
authors.initials: SK
authors.lastname: Luthra
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D001331:Automation; D001386:Azides / Q000138:chemical synthesis*; D053148:Caspase 3 / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic / Q000379:methods* / Q000592:standards*; D007211:Indoles / Q000138:chemical synthesis*; D057054:Molecular Imaging; D011786:Quality Control; D011854:Radiochemistry
chemical_list: C571272:(18)F-ICMT11; D001386:Azides; D007211:Indoles; D053148:Caspase 3