Automated GMP Synthesis of [18F]ICMT-11 for In Vivo Imaging of Caspase-3 Activity

IntroductionIsatin-5-sulfonamide ([18F]ICMT-11) is a sub-nanomolar inhibitor of caspase-3 previously evaluated as an apoptosis imaging agent. Herein, an alternative radiosynthesis of [18F]ICMT-11 with increased purity and specific activity is presented. Finally, a GMP-applicable automated radiosynthesis of [18F]ICMT-11 is described.MethodsThe preparation of [18F]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.ResultsThe synthesis of [18F]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 [18F]ICMT-11 can be consistently manufactured on the FASTlab to meet specifications.ConclusionsA simplified methodology for the synthesis of the apoptosis imaging agent, [18F]ICMT-11, has been achieved by the SN2 displacement of a tosylate leaving group with [18F]fluoride ion. This results in an increased purity and specific activity over the original copper catalysed “Click” synthetic stratagem reaction involving 2-[18F]fluoroethylazide with an alkyne precursor and is now suitable for routine clinical application.