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

Hanyu, Masayuki  ,  Kawamura, Kazunori  ,  Takei, Makoto  ,  Furutsuka, Kenji  ,  Shiomi, Satoshi  ,  Fujishiro, Tomoya  ,  Ogawa, Masanao  ,  Nengaki, Nobuki  ,  Hashimoto, Hiroki  ,  Fukumura, Toshimitsu  ,  Ming-Rong, Zhang

43 ( 11 )  , pp.679 - 684 , 2016-11 , Elsevier
Introduction: Recently, 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 efficient radiosynthesis of [11C]2 to obtain sufficient radioactivity and high quality for clinical application.Methods: In manual synthesis, we optimized the reaction conditions of desmethyl precursor 2, which contains a 2-hydroxypyridine moiety, with [11C]MeI or [11C]MeOTf. After optimization, we performed automated synthesis and quality control of [11C]2.Results: Bubbling [11C]MeOTf into a heated mixture of precursor 1 and cesium carbonate in DMF at 100 °C for 90 sec produced [11C]2 with 7.9 ± 1.8 % (n = 78) of the radiochemical yields (decay-corrected, based on [11C]CO2). The specific activity of [11C]2 was 156 ± 52 GBq/mol (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. Conclusion: We 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.

Number of accesses :  

Other information