Presentation Radiosynthesis and evaluation of [11C]BU99008 with ultra-high specific activity as a PET ligand for imaging I2-imidazoline receptors.

Kawamura, Kazunori  ,  Shimoda, Yoko  ,  Yui, Joji  ,  Fujinaga, Masayuki  ,  Yamasaki, Tomoteru  ,  Hatori, Akiko  ,  Xie, Lin  ,  Zhang, Yiding  ,  Kumata, Katsushi  ,  Ogawa, Masanao  ,  Yusuke, Kurihara  ,  Nengaki, Nobuki  ,  Wakizaka, Hidekatsu  ,  Ming-Rong, Zhang

Objectives: The I2-imidazoline receptor (I2R) is involved in various neuropsychiatric disorders, but the these functionare unknown. In addition, selective I2R ligands promote food intake and may therefore alter eating behavior. Thecarrier dose of PET ligand may modify both binding and pharmacokinetics in small animal imaging studies. Ultra-highspecific activity (SA) is a useful tool to investigate a receptor with low density and small region in the brain [1]. Werecently reported that [11C]FTIMD with ultra-high SA (mean 4470 GBq/μmol) for imaging of I2Rs showed higherspecific-binding than [11C]FTIMD with conventional SA (about 100 GBq/μmol) in the hypothalamus, which is highlyexpressed I2Rs [2]. More recently, Kealey et al. developed [11C]BU99008 as a more potent PET ligand for I2Rimaging [3]. [11C]BU99008 displayed a relatively high brain penetration and specific binding in the porcine and rhesusbrain [3,4]. In this study, to image I2Rs in extremely small region such as hypothalamus, we synthesized andevaluated [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 ultrahighSA, [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 at55∼220 [n = 8] and 5400∼16600 [n = 7] GBq/μmol at the end of synthesis, respectivery, yielding a radioactivitysuitable for injection. In PET studies, the radioactivity after injection of [11C]BU99008 with conventional or ultra-highSA 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 [11C]BU99008 with ultra-high SA would contribute to the detection of I2Rs expression in small regions or with smallchange.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

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