Synthesis and in vitro/in vivo pharmacological evaluation of [11C]-ThioABP, a novel radiotracer for imaging mGluR5 with PETElectronic supplementary information (ESI) available: NMR data for 5, IC50 binding curves, HPLC traces are provided. See DOI: 10.1039/c2md20332d

• Main Authors: Sephton, Selena Milicevic, Mu, Linjing, Müller, Adrienne, Wanger-Baumann, Cindy A, Schibli, Roger, Krämer, Stefanie D, Ametamey, Simon M
• Format: Article
• Language: English
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c2md20332d

We have designed a novel positron emission tomography (PET) radiotracer, [ 11 C]-ThioABP, a thiazole based derivative for imaging the metabotropic glutamate receptor subtype 5 (mGluR5), and prepared the hydroxy oxime precursor 4 in a 15% overall yield. [ 11 C]-ThioABP was radiosynthesized in the Veenstra module and obtained in a decay corrected radiochemical yield of 40% and specific activity of 80-250 GBq μmol −1 at the end of synthesis. ThioABP exhibited excellent binding affinity ( K i ) in vitro of 1.9 ± 0.9 nM and [ 11 C]-ThioABP showed an optimal log D 7.4 of 2.4. The autoradiographic studies on rat brain slices revealed specific binding to mGluR5. In vivo evaluation of [ 11 C]-ThioABP including a displacement study with MMPEP in a dynamic PET scan showed a specificity of [ 11 C]-ThioABP for mGluR5. Radio-TLC metabolite studies showed a good metabolic stability of [ 11 C]-ThioABP in vivo . The comparison of biological properties of [ 11 C]-ThioABP and [ 11 C]-ABP688 revealed similarity between these two compounds. We have developed a novel PET radiotracer, [ 11 C]-ThioABP, for imaging mGluR5 in vivo based on the [ 11 C]-ABP688 scaffold.