RT Journal Article SR Electronic T1 Radiosynthesis, Photoisomerization, Biodistribution, and Metabolite Analysis of 11C-PBB3 as a Clinically Useful PET Probe for Imaging of Tau Pathology JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1532 OP 1538 DO 10.2967/jnumed.114.139550 VO 55 IS 9 A1 Hashimoto, Hiroki A1 Kawamura, Kazunori A1 Igarashi, Nobuyuki A1 Takei, Makoto A1 Fujishiro, Tomoya A1 Aihara, Yoshiharu A1 Shiomi, Satoshi A1 Muto, Masatoshi A1 Ito, Takehito A1 Furutsuka, Kenji A1 Yamasaki, Tomoteru A1 Yui, Joji A1 Xie, Lin A1 Ono, Maiko A1 Hatori, Akiko A1 Nemoto, Kazuyoshi A1 Suhara, Tetsuya A1 Higuchi, Makoto A1 Zhang, Ming-Rong YR 2014 UL http://jnm.snmjournals.org/content/55/9/1532.abstract AB 2-((1E,3E)-4-(6-(11C-methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol (11C-PBB3) is a clinically useful PET probe that we developed for in vivo imaging of tau pathology in the human brain. To ensure the availability of this probe among multiple PET facilities, in the present study we established protocols for the radiosynthesis and quality control of 11C-PBB3 and for the characterization of its photoisomerization, biodistribution, and metabolism. Methods: 11C-PBB3 was synthesized by reaction of the tert-butyldimethylsilyl desmethyl precursor (1) with 11C-methyl iodide using potassium hydroxide as a base, followed by deprotection. Photoisomerization of 11C-PBB3 under fluorescent light was determined. The biodistribution and metabolite analysis of 11C-PBB3 was determined in mice using the dissection method. Results: 11C-PBB3 was synthesized with 15.4% ± 2.8% radiochemical yield (decay-corrected, n = 50) based on the cyclotron-produced 11C-CO2 and showed an averaged synthesis time of 35 min from the end of bombardment. The radiochemical purity and specific activity of 11C-PBB3 were 98.0% ± 2.3% and 180.2 ± 44.3 GBq/μmol, respectively, at the end of synthesis (n = 50). 11C-PBB3 showed rapid photoisomerization, and its radiochemical purity decreased to approximately 50% at 10 min after exposure to fluorescent light. After the fluorescent light was switched off, 11C-PBB3 retained more than 95% radiochemical purity over 60 min. A suitable brain uptake (1.92% injected dose/g tissue) of radioactivity was observed at 1 min after the probe injection, which was followed by rapid washout from the brain tissue. More than 70% of total radioactivity in the mouse brain homogenate at 5 min after injection represented the unchanged 11C-PBB3, despite its rapid metabolism in the plasma. Conclusion: 11C-PBB3 was produced with sufficient radioactivity and high quality, demonstrating its clinical utility. The present results of radiosynthesis, photoisomerization, biodistribution, and metabolite analysis could be helpful for the reliable production and application of 11C-PBB3 in diverse PET facilities.