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

• Published in: Nuclear medicine and biology 2016-11, Vol.43 (11), p.679-684
• Main Authors: Hanyu, Masayuki, Kawamura, Kazunori, Takei, Makoto, Furutsuka, Kenji, Shiomi, Satoshi, Fujishiro, Tomoya, Ogawa, Masanao, Nengaki, Nobuki, Hashimoto, Hiroki, Fukumura, Toshimitsu, Zhang, Ming-Rong
• Format: Article
• Language: English
• Subjects: 2-Hydroxypyridine; [11C]TASP457; Histamine H3 receptor; PET; Quality control; Radiology
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2016.08.004

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 H3 receptors in brain. [11 C] 2 is potentially suitable for imaging H3 receptors in rat and monkey brains, which has motivated us to perform first-in-human study of [11 C] 2 for qualifying H3 receptors in human brain. In this paper, we report 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 2 , 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 90 sec produced [11 C] 2 with 7.9 ± 1.8 % ( n = 78) of the radiochemical yields (decay-corrected, based on [11 C]CO2 ). The specific activity of [11 C] 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 [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 H3 receptors in human brain in our facility.