Translation of 11C-labeled tracer synthesis to a CGMP environment as exemplified by [11C]ER176 for PET imaging of human TSPO

Radiotracers labeled with carbon-11 (t(1/2) = 20.4 min) are widely used with positron emission tomography for biomedical research. Radiotracers must be produced for positron emission tomography studies in humans according to prescribed time schedules while also meeting current good manufacturing practice. Translation of an experimental radiosynthesis to a current good manufacturing practice environment is challenging. Here we exemplify such translation with a protocol for the production of an emerging radiotracer for imaging brain translocator protein 18 kDa, namely [C-11]ER176. This radiotracer is produced by rapid conversion of cyclotron-produced [C-11]carbon dioxide into [C-11]iodomethane, which is then used to treat N-desmethyl-ER176 in the presence of base ((BuOK)-Bu-t) at room temperature for 5 min. [C-11]ER176 is separated in high purity by reversed-phase HPLC and formulated for intravenous injection in sterile ethanol-saline. The radiosynthesis is reliable and takes 50 min. Quality control takes another 20 min. All aspects of the protocol, including quality control, are discussed. Radiotracers used in human positron emission tomography studies need to be prepared according to current good manufacturing practice. Here we use the synthesis of [C-11]ER176 as an example to show the translation of an experimental radiosynthesis to a current good manufacturing practice process.

Automated summary

The production of radiotracers for human positron emission tomography studies needs to comply with current good manufacturing practice. This study demonstrates the translation of experimental radiosynthesis into a process that meets current good manufacturing practice guidelines, using the synthesis of [C-11]ER176 as an example.