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

EJNMMI Radiopharmacy and Chemistry

Jonas Eriksson¹  Eva Schlein²  Johanna Rokka² 

[1] Department of Medicinal Chemistry, Uppsala Biomedical Center, Uppsala University;Department of Public Health and Caring Sciences/Geriatrics, Uppsala University;

关键词: [11C]UCB-J;    SVA2;    Synaptic density;    PET;    Synaptic vesicle glycoprotein;    Suzuki-Miyaura coupling;   

DOI  :  10.1186/s41181-019-0080-5

来源: DOAJ

【 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. Results After 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. Conclusions A robust and high yielding production method has been developed for [11C]UCB-J, suitable for both preclinical and clinical PET applications.

【 授权许可】

Unknown