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

IntroductionRecently, 6-[(1-cyclobutylpiperidin-4-yl)oxy]-1-(6-[11C]methoxypyridin-3-yl)-3,4-dihydroquinolin-2(1H)-one ([11C]TASP457, [11C]2) has been developed as a novel PET ligand for histamine H3 receptors in brain. [11C]2 is potentially suitable for imaging H3 receptors in rat and monkey brains, which has motivated us to perform first-in-human study of [11C]2 for qualifying H3 receptors in human brain. In this paper, we report an efficient radiosynthesis of [11C]2 to obtain sufficient radioactivity and high quality for clinical application.MethodsIn manual synthesis, we optimized the reaction conditions of desmethyl precursor 1, which contains a 2-hydroxypyridine moiety, with [11C]MeI or [11C]MeOTf. After optimization, we performed automated synthesis and quality control of [11C]2.ResultsBubbling [11C]MeOTf into a heated mixture of precursor 1 and cesium carbonate in DMF at 100 °C for 90 s produced [11C]2 with decay-corrected radiochemical yields of (based on [11C]CO2) 7.9 ± 1.8% (n = 78). The specific activity of [11C]2 was 156 ± 52 GBq/μmol (n = 78) at the end of synthesis. The total synthesis time was approximately 35 min from the end of bombardment. All the quality control results of [11C]2 were in compliance with our in-house quality control/assurance specifications.ConclusionWe radiosynthesized [11C]TASP457 ([11C]2) with sufficient amounts of radioactivity and high quality for clinical usefulness. This radioligand is being used for PET assessment of H3 receptors in human brain in our facility.