@misc{oai:repo.qst.go.jp:00071725,
 author = {Kawamura, Kazunori and Shimoda, Yoko and Yui, Joji and Fujinaga, Masayuki and Yamasaki, Tomoteru and Hatori, Akiko and Xie, Lin and Zhang, Yiding and Kumata, Katsushi and Ogawa, Masanao and Yusuke, Kurihara and Nengaki, Nobuki and Wakizaka, Hidekatsu and Zhang, Ming-Rong and 河村 和紀 and 下田 陽子 and 由井 譲二 and 藤永 雅之 and 山崎 友照 and 羽鳥 晶子 and 謝 琳 and 張 一鼎 and 熊田 勝志 and 小川 政直 and 栗原 雄祐 and 念垣 信樹 and 脇坂 秀克 and 張 明栄},
 month = {May},
 note = {Objectives: The I2-imidazoline receptor (I2R) is involved in various neuropsychiatric disorders, but the these function
are unknown. In addition, selective I2R ligands promote food intake and may therefore alter eating behavior. The
carrier dose of PET ligand may modify both binding and pharmacokinetics in small animal imaging studies. Ultra-high
specific activity (SA) is a useful tool to investigate a receptor with low density and small region in the brain [1]. We
recently reported that [11C]FTIMD with ultra-high SA (mean 4470 GBq/μmol) for imaging of I2Rs showed higher
specific-binding than [11C]FTIMD with conventional SA (about 100 GBq/μmol) in the hypothalamus, which is highly
expressed I2Rs [2]. More recently, Kealey et al. developed [11C]BU99008 as a more potent PET ligand for I2R
imaging [3]. [11C]BU99008 displayed a relatively high brain penetration and specific binding in the porcine and rhesus
brain [3,4]. In this study, to image I2Rs in extremely small region such as hypothalamus, we synthesized and
evaluated [11C]BU99008 with ultra-high SA as a PET ligand.
Methods: [11C]BU99008 was prepared by methylation of the BU-precursor and [11C]methyl iodide. In case of ultrahigh
SA, [11C]methyl iodide was produced by iodination of [11C]methane using the single-pass method [1,2].
Biodistribution and brain PET studies were conducted in rats.
Results: [11C]BU99008 with conventional and ultra-high SA were successfully synthesized in the range of SA at
55∼220 [n = 8] and 5400∼16600 [n = 7] GBq/μmol at the end of synthesis, respectivery, yielding a radioactivity
suitable for injection. In PET studies, the radioactivity after injection of [11C]BU99008 with conventional or ultra-high
SA was highly accumulated in the hypothalamus. Pretreatment with BU224 (an high affinity I2R ligand; 1 mg/kg)
significantly decreased the radioactivity (AUC30-60 min) of conventional or ultra-high SA in the hypothalamus to 76%
or 86% of the correspoding control radioactivity (AUC30-60 min), respectively.
Conclusions: [11C]BU99008 with ultra-high SA showed high specific binding in rat brain. PET study using [11
C]BU99008 with ultra-high SA would contribute to the detection of I2Rs expression in small regions or with small
change.
References: [1] Noguchi J, et al (2003), Nucl Med Biol, 30, 335-43. [2] Kawamura K, et al (2012), Nucl Med Biol, 39,
199-206. [3] Kealey S, et al (2013), J Nucl Med, 54, 139-44. [4] Parker CA, et al (2014), J Nucl Med, 55, 838-44.
(No Image Selected), 21st International Symposium on Radiopharmaceutical Sciences},
 title = {Radiosynthesis and evaluation of [11C]BU99008 with ultra-high specific activity as a PET ligand for imaging I2-imidazoline receptors.},
 year = {2015}
}