Radiosynthesis and quality control of [11C]TASP457 as a clinically useful PET ligand for imaging of histamine H3 receptors in human brain

Abstract Introduction Recently, 6-[(1-cyclobutylpiperidin-4-yl)oxy]-1-(6-[ 11 C]methoxypyridin-3-yl)-3,4-dihydroquinolin-2(1 H )-one ([ 11 C]TASP457, [ 11 C] 2 ) has been developed as a novel PET ligand for histamine H 3 receptors in brain. [ 11 C] 2 is potentially suitable for imaging H 3 receptors in rat and monkey brains, which has motivated us to perform first-in-human study of [ 11 C] 2 for qualifying H 3 receptors in human brain. In this paper, we report an efficient radiosynthesis of [ 11 C] 2 to obtain sufficient radioactivity and high quality for clinical application. Methods In manual synthesis, we optimized the reaction conditions of desmethyl precursor 1 , which contains a 2-hydroxypyridine moiety, with [ 11 C]MeI or [ 11 C]MeOTf. After optimization, we performed automated synthesis and quality control of [ 11 C] 2 . Results Bubbling [ 11 C]MeOTf into a heated mixture of precursor 1 and cesium carbonate in DMF at 100°C for 90s produced [ 11 C] 2 with decay-corrected radiochemical yields of (based on [ 11 C]CO 2 ) 7.9±1.8% ( n =78). The specific activity of [ 11 C] 2 was 156±52GBq/μmol ( n =78) at the end of synthesis. The total synthesis time was approximately 35min from the end of bombardment. All the quality control results of [ 11 C] 2 were in compliance with our in-house quality control/assurance specifications. Conclusion We radiosynthesized [ 11 C]TASP457 ([ 11 C] 2 ) with sufficient amounts of radioactivity and high quality for clinical usefulness. This radioligand is being used for PET assessment of H 3 receptors in human brain in our facility.