Improved synthesis of SV2A targeting radiotracer [ 11 C]UCB-J

摘要

Abstract Introduction[11C]UCB-J is a tracer developed for PET (positron emission tomography) that has high affinity towards synaptic vesicle glycoprotein 2A (SV2A), a protein believed to participate in the regulation of neurotransmitter release in neurons and endocrine cells. The localisation of SV2A in the synaptic terminals makes it a viable target for in vivo imaging of synaptic density in the brain. Several SV2A targeting compounds have been evaluated as PET tracers, including [11C]UCB-J, with the aim to facilitate studies of synaptic density in neurological diseases.The original two-step synthesis method failed in our hands to produce sufficient amounts of [11C]UCB-J, but served as an excellent starting point for further optimizations towards a high yielding and simplified one-step method. [11C]Methyl iodide was trapped in a clear THF-water solution containing the trifluoroborate substituted precursor, potassium carbonate and palladium complex. The resulting reaction mixture was heated at 70?°C for 4?min to produce [11C]UCB-J.ResultsAfter semi-preparative HPLC purification and reformulation in 10% ethanol/phosphate buffered saline, the product was obtained in 39?±?5% radiochemical yield based on [11?99% and the molar activity was 390?±?180?GBq/μmol at EOS. The product solution contained ?2?ppb palladium.ConclusionsA robust and high yielding production method has been developed for [11C]UCB-J, suitable for both preclinical and clinical PET applications.