Automated GMP production and long-term experience in radiosynthesis of the SV2A tracer [11C]UCB-J.

BACKGROUND: Positron emission tomography (PET) is a non-invasive imaging technique that enables the quantification of specific biological and pharmacological processes in vivo. PET can be used to investigate synaptic density by targeting synaptic vesicle glycoprotein 2A (SV2A), and can measure brain levels of SV2A in patients with epilepsy and other neurologic, neurodegenerative, or psychiatric conditions that involve SV2A. The well-known radiotracer [ 11C]UCB-J ((R)-1-((3-[ 11C]methylpyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) targets SV2A and thereby enables visualization of synaptic density in vivo.

RESULTS: [ 11C]UCB-J synthesis was performed using [ 11C]methyl iodide ([ 11C]CH 3I) produced with a commercial device. Here, we present an in-house-built device for [ 11C]UCB-J production from [ 11C]CH 3I and a suitably treated boronated precursor. The whole radiosynthetic procedure was automated, and has now been in clinical production according to GMP for more than four years. We also address several issues encountered during the production process development and tracer utilisation.

CONCLUSIONS: The developed method enables robust [ 11C]UCB-J production, with a yield of 2.8 ± 0.6 GBq and molar activity of 150 ± 51 GBq/µmol (n = 56) at end of synthesis. The product fulfils all specifications set for a clinical tracer. GMP regulations and guidelines in all aspects of radiopharmaceutical preparation were followed. Although [ 11C]UCB-J production is challenging, good and reliable radiochemical yields can be obtained by using a carefully designed production protocol.