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
Description
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.

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