Development of imaging agents for feeding function as a diagnostic tool and evaluation of drug therapy for obesity

• Project/Area Number: 26293283
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: KAWAMURA KAZUNORI 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 標識薬剤開発部, チームリーダー(定常) (50401766)
• Co-Investigator(Kenkyū-buntansha): 謝 琳 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 標識薬剤開発部, 研究員(任常) (30623558) ; 藤永 雅之 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 標識薬剤開発部, 主任研究員(定常) (70623726) ; 張 明栄 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 標識薬剤開発部, 部長(定常) (80443076) ; 山崎 友照 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 標識薬剤開発部, 研究員(任常) (80627563)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000); Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
• Keywords: 核医学 / PET / 分子イメージング / 摂食 / 肥満 / イミダゾリン受容体 / グレリン受容体 / 分子ｲﾒｰｼﾞﾝｸﾞ / イミダゾリンI2受容体 / 放射線 / 肥満症

Outline of Final Research Achievements

To treat obesity by drug therapy targeted a feeding center, several drugs have been developed. In this study, we developed the positron emission tomography (PET) probe for high affinity and selectivity imidazoline-I2 receptor (I2R), which is named ultrahigh specific activity [11C]BU99008. Also, we demonstrated to image and quantity a small change in a feeding center by obesity, and the relationship between I2R and obesity using [11C]BU99008-PET study in rats. Thus, we concluded that [11C]BU99008-PET study is helpful for the diagnostic tool or evaluation of drug therapy for obesity. Furthermore, we achieved to apply for clinical application using [11C]BU99008-PET study.

Research Products

• [Journal Article] Change in the Binding of [11C]BU99008 to Imidazoline I2 Receptor Using Brain PET in Zucker Rats (2018)
  • Author(s): Kawamura Kazunori、Yamasaki Tomoteru、Zhang Yiding、Wakizaka Hidekatsu、Hatori Akiko、Xie Lin、Fujinaga Masayuki、Zhang Ming-Rong
  • Journal Title: Molecular Imaging and Biology Volume: 印刷中 Issue: 1 Pages: 105-112
  • DOI: 10.1007/s11307-018-1206-y
  • Peer Reviewed
• [Journal Article] Developing new PET tracers to image the growth hormone secretagogue receptor 1a (GHS-R1a) (2017)
  • Author(s): Kawamura Kazunori、Fujinaga Masayuki、Shimoda Yoko、Yamasaki Tomoteru、Zhang Yiding、Hatori Akiko、Xie Lin、Wakizaka Hidekatsu、Kumata Katsushi、Ohkubo Takayuki、Kurihara Yusuke、Ogawa Masanao、Nengaki Nobuki、Zhang Ming-Rong
  • Journal Title: Nuclear Medicine and Biology Volume: 52 Pages: 49-56
  • DOI: 10.1016/j.nucmedbio.2017.06.002
  • Peer Reviewed
• [Journal Article] A useful PET probe [11C]BU99008 with ultra-high specific radioactivity for small animal PET imaging of I2-imidazoline receptors in the hypothalamus. (2017)
  • Author(s): Kawamura K, Shimoda Y, Yui J, Zhang Y, Yamasaki T, Wakizaka H, Hatori A, Xie L, Kumata K, Fujinaga M, Ogawa M, Kurihara Y, Nengaki N, Zhang MR.
  • Journal Title: Nuclear Medicine and Biology Volume: 45 Pages: 1-7
  • DOI: 10.1016/j.nucmedbio.2016.10.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In vivo evaluation of a new 18F-labeled PET ligand, [18F]FEBU, for the imaging of I2-imidazoline receptors. (2015)
  • Author(s): Kawamura K, Shimoda Y, Kumata K, Fujinaga M, Yui J, Yamasaki T, Xie L, Hatori A, Wakizaka H, Kurihara Y, Ogawa M, Nengaki N, Zhang MR.
  • Journal Title: Nuclear Medicine and Biology Volume: 42 Issue: 4 Pages: 406-412
  • DOI: 10.1016/j.nucmedbio.2014.12.014
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] In vivo characterizations of [11C]BMS193885 and [11C]Desmethyl-BMS193885 as a PET tracer for neuropeptide Y Y1 receptors (2018)
  • Author(s): Kazunori Kawamura , Wakana Mori , Tomoteru Yamasaki , Yiding Zhang , Masayuki Fujinaga , Akiko Hatori , Lin Xie , Katsushi Kumata , Takayuki Ohkubo , Yusuke Kurihara , Masanao Ogawa , Nobuki Nengaki , Ming-Rong Zhang
  • Organizer: 12th World Congress of the World Federation of Nuclear medicine and Biology
  • Int'l Joint Research
• [Presentation] 新規GHS-R1a選択的PET用プローブの開発と評価 (2017)
  • Author(s): 河村 和紀 , 藤永 雅之 , 下田 陽子 , 山崎 友照 , 張 一鼎 , 羽鳥 晶子 , 謝 琳 , 脇坂 秀克 , 栗原 雄祐 , 大久保 崇之 , 小川 政直 , 念垣 信樹 , 張 明栄
  • Organizer: 第57回日本核医学会学術総会
• [Presentation] Brain PET study using [11C]BU99008 in Zucker fatty versus lean rats. (2017)
  • Author(s): Kazunori Kawamura , Tomoteru Yamasaki , Yiding Zhang , Hidekatsu Wakizaka , Akiko Hatori , Lin Xie , Masayuki Fujinaga , Ming-Rong Zhang
  • Organizer: 2017 World Molecular Imaging Congress
  • Int'l Joint Research
• [Presentation] Synthesis and evaluation of a new 11C-labeled growth hormone secretagogue receptor 1a probe (2017)
  • Author(s): Kazunori Kawamura , Masayuki Fujinaga , Yoko Shimoda , Tomoteru Yamasaki , Yiding Zhang , Akiko Hatori , Lin Xie , Hidekatsu Wakizaka , Yusuke Kurihara , Takayuki Ohkubo , Masanao Ogawa , Nobuki Nengaki , Ming-Rong Zhang
  • Organizer: 22nd International symposium on radiopharmaceutical science
  • Int'l Joint Research
• [Presentation] 肥満ラットでの脳PET定量測定によるイミダゾリンI2受容体及びセロトニントランポーター結合の増加 (2016)
  • Author(s): 河村 和紀, 下田 陽子, 山崎 友照, 由井 譲二, 張 一鼎, 脇坂 秀克, 羽鳥 晶子, 謝 琳, 武井 誠, 張 明栄
  • Organizer: 第５６回日本核医学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2016-11-05
• [Presentation] イミダゾリンI2受容体選択的PET用リガンド[11C]BU99008の超高比放射能化による有用性検討 (2015)
  • Author(s): 河村 和紀 , 下田 陽子 , 由井 譲二 , 張 一鼎 , 山崎 友照 , 脇坂 秀克 , 藤永 雅之 , 熊田 勝志 , 小川 政直 , 張 明栄
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京、東京都
  • Year and Date: 2015-11-05
• [Presentation] PET imaging of a feeding center using [11C]BU99008 with ultra-high specific activity (2015)
  • Author(s): Kazunori Kawamura, Yoko Shimoda, Joji Yui, Yiding Zhang, Tomoteru Yamasaki, Hidekatsu Wakizaka, Masayuki Fujinaga, Katsushi Kumata, Lin Xie, Akiko Hatori, Masanao Ogawa, Yusuke Kurihara, Nobuki Nengaki, Ming-Rong Zhang.
  • Organizer: Annual Congress of the European Association of Nuclear Medicine 2015
  • Place of Presentation: Congress Center Hamburg, Hamburg, Germany
  • Year and Date: 2015-10-10
  • Int'l Joint Research
• [Presentation] Radiosynthesis and evaluation of [11C]BU99008 with ultra-high specific activity as a PET ligand for imaging I2-imidazoline receptors. (2015)
  • Author(s): Kazunori Kawamura , Yoko Shimoda , Joji Yui , Masayuki Fujinaga , Tomoteru Yamasaki , Akiko Hatori , Lin Xie , Yiding Zhang , Katsushi Kumata , Masanao Ogawa , Kurihara Yusuke , Nobuki Nengaki , Hidekatsu Wakizaka , Ming-Rong Zhang.
  • Organizer: 21st International Symposium on Radiopharmaceutical Sciences
  • Place of Presentation: University of Missouri, Columbia, MO, USA
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] イミダゾリンI2受容体イメージング用18F標識PET用プローブの開発 (2014)
  • Author(s): 河村和紀、下田陽子、山﨑友照、由井譲二、熊田勝志、藤永雅之、謝琳、羽鳥晶子、脇坂秀克、小川政直、張明栄
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪府立国際会議場（大阪）
  • Year and Date: 2014-11-06 – 2014-11-08
• [Presentation] Synthesis and evaluation of 18F-labeled imidazoline I2 receptor ligand as a PET probe (2014)
  • Author(s): Kawamura K, Yamasaki T, Shimoda Y, Kumata K, Fujinaga M, Yui J, Xie L, Hatori A, Wakizaka H, Kurihara Y, Ogawa M, Nengaki N, Zhang MR
  • Organizer: 27th Annual Congress of the European Association of Nuclear Medicine
  • Place of Presentation: Gothenburg, Sweden
  • Year and Date: 2014-10-18 – 2014-10-22