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 [11C]methyl iodide, corresponding to 1.8 ± 0.5 GBq at EOS. The radiochemical purity was > 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.
Highlights
The synaptic vesicle glycoprotein 2A (SV2A) is localized at synaptic vesicles in neurons and endocrine cells where it is believed to participate in the regulation of neurotransmitter release
The original [11C]UCB-J synthesis was performed as a twostep reaction by 11C-methylation with [11C]methyl iodide under Suzuki-Miyaura coupling conditions (Nabulsi et al 2016). [11C]Methyl iodide was reacted with a palladium (0) catalyst followed by addition and hydrolysis in situ of a trifluoroborate precursor to activate it towards palladium mediated 11C-methylation
The original two-step [11C]UCB-J synthesis method gave in our hands less than 1% radiochemical yield (RCY) based on [11C]methyl iodide, corresponding to 53 ± 15 MBq (n = 3) at end of synthesis (EOS), Table 1
Summary
The synaptic vesicle glycoprotein 2A (SV2A) is localized at synaptic vesicles in neurons and endocrine cells where it is believed to participate in the regulation of neurotransmitter release. The localisation and apparent function of SV2A makes it a promising proxy marker for synaptic density that could be used to study neurodegenerative and psychiatric diseases in the brain (Finnema et al 2016; Chen et al 2018; Koole et al 2019). One of the more promising candidates, [11C]UCB-J, was discovered by UCB Pharma (Braine-l’Alleud, Belgium) among 500+ compounds screened for binding affinity and was identified to have properties suitable for SV2A PET (Mercier et al 2014). Preclinical evaluation at Yale PET centre revealed that [11C]UCB-J was a promising ligand for SV2A imaging (Nabulsi et al 2016) and recent publications have shown that [11C]UCB-J is a suitable PET tracer for human studies (Finnema et al 2016; Chen et al 2018; Koole et al 2019; Holmes et al 2019). The original [11C]UCB-J synthesis was performed as a twostep reaction by 11C-methylation with [11C]methyl iodide under Suzuki-Miyaura coupling conditions (Nabulsi et al 2016). [11C]Methyl iodide was reacted with a palladium (0) catalyst followed by addition and hydrolysis in situ of a trifluoroborate precursor to activate it towards palladium mediated 11C-methylation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
