Development of in vivo imaging probes for measurement of cell mass in pancreatic islets.

• Project/Area Number: 21659289
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: SAJI Hideo 京都大学, 大学院・薬学研究科, 教授 (40115853)
• Co-Investigator(Kenkyū-buntansha): TEMMA Takashi 京都大学, 大学院・薬学研究科, 助教 (90378787) ; TOYODA Kentaro 京都大学, 大学院・医学研究科, 助教 (00447971)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Hiroyuki 京都大学, 環境安全保健機構・放射性同位元素総合センター, 助教 (50437240)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2009: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: 糖尿病 / 早期診断 / 分子イメージング / 画像診断

Research Abstract

If a decrease in the amount of pancreatic islets and the amount of pancreatic.-cells can be detected at an early stage, there is a possibility for the prevention and treatment of diabetes. Therefore, a noninvasive technique for imaging of pancreatic islets, particularly a noninvasive technique for imaging of pancreatic islets for determining the amount of the pancreatic islets and the amount of pancreatic.-cells, has been desired for the prevention and diagnosis of diabetes. Among these, a molecular probe that enables the imaging of pancreatic islets, preferably the pancreatic.-cell imaging, has been desired in particular. In designing a molecular probe for imaging of pancreatic.-cells, various targets molecule in pancreatic islet cells, particularly functional proteins specific in the.-cells, are being researched. Among these, GLP-1R and GPR40 are being researched as a target molecule. These data suggest that[111In] K4-Ex4 and[125I] ARKM-405 can be a potential candidate as a SPECT tracer for measuringβ-cell mass in pancreatic islets.

Research Products

• [Journal Article] Microwave-assisted Synthesis of Organometallic Complexes of 99mTc(CO) 3and Re(CO) 3 : Its Application to Radiopharmaceuticals (2012)
  • Author(s): Kimura H, Mori D, Harada N, Ono M, Ohmomo Y, Kajimoto T, Kawashima H, Saji H.
  • Journal Title: Chemical & Pharmaceutical Bulletin Volume: 60(1) Pages: 79-85
  • URL: http://dx.doi.org/10.1248/cpb.60.79
  • Peer Reviewed
• [Journal Article] Microwave-assisted Synthesis of Organometallic Complexes of 99mTc(CO)3 and Re(CO)3 : Its Application to Radiopharmaceuticals (2012)
  • Author(s): Hideo Saji, Hiroyuki Kiraura, Daisuke Mori, et al
  • Journal Title: Chemical & Pharmaceutical Bulletin Volume: 60(1) Pages: 79-85
  • NAID: 130001852351
  • Peer Reviewed
• [Journal Article] Effective Synthesis of 99mTc Tricarbonyl Complexes by Microwave Heating (2011)
  • Author(s): Harada N, Kimura H, Ono M, Mori D, Ohmomo Y, Kajimoto T, Kawashima H, Saji H.
  • Journal Title: Journal of Organometallic Chemistry Volume: 696 Pages: 3745-3749
  • URL: http://dx.doi.org/10.1016/j.jorganchem.2011.08.033
  • Peer Reviewed
• [Journal Article] Systems analysis of GLP-1 receptor signaling in pancreatic β-cells (2011)
  • Author(s): Hideo Saji, Yukari Takeda, Akira Amano, et al
  • Journal Title: Am J Physiol Cell Physiol Volume: 301(4)
  • Peer Reviewed
• [Journal Article] GLP-1receptor antagonist as a potential probe for pancreatic beta-cell imaging (2009)
  • Author(s): Mukai E, Toyoda K, Kimura H, KawashimaH, Fujimoto H, Ueda M, Temma T, Hirao K, Nagakawa K, Saji H, Inagaki N.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 389 Pages: 523-6
  • URL: http://dx.doi.org/10.1016/j.bbrc.2009.09.014
  • Peer Reviewed
• [Journal Article] GLP-1 receptor antagonist as a potential probe for pancreatic beta-cell imaging (2009)
  • Author(s): Mukai E, et al.
  • Journal Title: Biochem Biophys Res Commun 389 Pages: 523-6
  • Peer Reviewed
• [Presentation] 膵β細胞GLP-1受容体を標的とするSPECT用イメージングプローブExendin(9-39)誘導体の開発 (2011)
  • Author(s): 小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 第51回日本核医学会学術総会
  • Place of Presentation: つくば国際会議場(茨城)
  • Year and Date: 2011-10-28
• [Presentation] 膵β細胞GLP-1受容体を標的とするSPECT用イメージングプローブExendin(9-39)誘導体の開発 (2011)
  • Author(s): 佐治英郎, 小川祐, 木村寛之, 他
  • Organizer: 第51回日本核医学会学術総会
  • Place of Presentation: つくば国際会議場(エポカルつくば)(茨城県)(招待講演)
  • Year and Date: 2011-10-28
• [Presentation] 膵β細胞GLP-1受容体標的放射性プローブとしてのI-123標識Exendin-4誘導体 (2011)
  • Author(s): 小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 第9回次世代を担う若手のためのフィジカル・ファーマコフォーラム(PPF2011)
  • Place of Presentation: ホテル箱根アカデミー(神奈川県)
  • Year and Date: 2011-09-12
• [Presentation] Radiosynthesis and evaluation of F-18 Exendin-4 derivatives as a PET tracer for the imaging of GLP-1receptors on pancreaticβ-cells (2011)
  • Author(s): Kimura H, Ogawa Y, Kawashima H, Toyoda K, Mukai E, Fujimoto H, Ono M, Hirao K, Inagaki N, Saji H.
  • Organizer: Society of Nuclear Medicine 58th Annual Meeting
  • Place of Presentation: San Antonio, Texas(USA)
  • Year and Date: 2011-06-06
• [Presentation] Development of 123Ilabeled Exendin derivatives for the imaging of GLP-1 receptors on pancreaticβ-cellwith SPECT (2011)
  • Author(s): Ogawa Y, Kimura H, Kawashima H, Toyoda K, Mukai E, Fujimoto H, Hirao K, Ono M, Inagaki N, Saji H.
  • Organizer: Society of Nuclear Medicine 58th Annual Meeting
  • Place of Presentation: San Antonio, Texas(USA)
  • Year and Date: 2011-06-06
• [Presentation] 膵β細胞GLP-1受容体を標的とするSPECT用イメージングプローブの開発 (2011)
  • Author(s): 小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡(静岡県)
  • Year and Date: 2011-03-30
• [Presentation] 膵β細胞GLP-1受容体を標的とするSPECT用イメージングプローブの開発 (2011)
  • Author(s): 小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡市、グランシップ
  • Year and Date: 2011-03-30
• [Presentation] Development of the Imaging Probe Targeting Pancreatic GLP-1Receptors for Noninvasive Detection of Pancreaticυ-cell Mass (2011)
  • Author(s): Ogawa Y, Kimura H, Kawashima H, Toyoda K, Mukai E, Fujimoto H, Hirao K, Ono M, Inagaki N, Saji H.
  • Organizer: The 8th AFMC International Medicinal Chemistry Symposium(AIMECS 11)
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] Synthesis and evaluation of radioiodinated exendin derivatives for the imaging of GLP-1 receptor expression in pancreatic islets. (2010)
  • Author(s): Kimura H, Ogawa Y, Kawashima H, Mukai E, Toyoda K, Fujimoto H, Hirao K, Ono M, Inagaki N, Saji H.
  • Organizer: Society of Nuclear Medicine 57^<th> Annual Meeting
  • Place of Presentation: Salt Lake City, USA
  • Year and Date: 2010-06-08
• [Presentation] Exendin (9-39) をリードとするPET用膵臓B細胞イメージングプローブの開発 (2010)
  • Author(s): 小川祐
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山大学津島キャンパス
  • Year and Date: 2010-03-30
• [Presentation] GLP-1受容体を標的とする放射性ヨウ素標識イメージングプローブの開発 (2010)
  • Author(s): 小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 第50回日本核医学会学術総会
  • Place of Presentation: ソニックシティ(埼玉県)
• [Presentation] GLP-1受容体を標的とする放射性ヨウ素標識イメージングプローブの開発 (2010)
  • Author(s): 小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 第50回日本核医学会学術総会
  • Place of Presentation: さいたま市、大宮ソニックシティ
• [Presentation] DEVELOPMENT OF THE PANCREATIC BETA-CELL IMAGING PROBE FOR PET TARGETING GLP-1 RECEPTOR (2009)
  • Author(s): 小川祐
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州国際会議場
  • Year and Date: 2009-11-05
• [Presentation] GLP-1受容体を標的とする膵β細胞イメージング用放射性プローブの開発 (2009)
  • Author(s): 小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 永川健児, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 第49回日本核医学会学術総会
  • Place of Presentation: 旭川市民文化会館(北海道)
  • Year and Date: 2009-10-02
• [Presentation] GLP-1受容体を標的とする膵B細胞イメージング用放射性プローブの開発 (2009)
  • Author(s): 小川祐
  • Organizer: 第49回日本核医学会学術総会
  • Place of Presentation: 旭川グランドホテル
  • Year and Date: 2009-10-02
• [Presentation] Development of in vivo imaging agents targeting glucagon-like peptide-1receptor(GLP-1R) in pancreatic islets (2009)
  • Author(s): Kimura H, Ogawa Y, Kawashima H, Mukai E, Toyoda K, Fujimoto H, Hirao K, Nagakawa K, Ono M, Inagaki N, Saji H.
  • Organizer: World Molecular Imaging Congress 2009
  • Place of Presentation: Montreal(Canada)
  • Year and Date: 2009-09-25
• [Presentation] Development of in vivo imaging agents targeting glucagon-like peptide-1receptor(GLP-1R) in pancreatic islets (2009)
  • Author(s): Kimura H, Ogawa Y, Kawashima H, Mukai E, Toyoda K, Fujimoto H, Hirao K, Nagakawa K, Ono M, Inagaki N, Saji H.
  • Organizer: Society of Nuclear Medicine 56th Annual Meeting
  • Place of Presentation: Toronto(Canada)
  • Year and Date: 2009-06-13
• [Presentation] Development of in vivo imaging agents targeting glucagon-like peptide-1 receptor (GLP-1R) in pancreatic islets (2009)
  • Author(s): 木村寛之
  • Organizer: SNM's 56th Annual Meeting
  • Place of Presentation: カナダトロント
  • Year and Date: 2009-06-13
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/byotai/
• [Patent(Industrial Property Rights)] 膵島イメージング用分子プローブ及びその使用 (2010)
  • Inventor(s): 稲垣暢也, 佐治英郎, 他
  • Industrial Property Rights Holder: 稲垣暢也, 佐治英郎, 他
  • Filing Date: 2010-12-08
  • Overseas