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

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\u2009°C for 4\u2009min to produce [11C]UCB-J.ResultsAfter semi-preparative HPLC purification and reformulation in 10% ethanol/phosphate buffered saline, the product was obtained in 39\u2009±\u20095% radiochemical yield based on [11C]methyl iodide, corresponding to 1.8\u2009±\u20090.5\u2009GBq at EOS. The radiochemical purity was >\u200999% and the molar activity was 390\u2009±\u2009180\u2009GBq/μmol at EOS. The product solution contained <\u20092\u2009ppb palladium.ConclusionsA robust and high yielding production method has been developed for [11C]UCB-J, suitable for both preclinical and clinical PET applications.