Whole body imaging of 123I-oxLDL distribution in mouse with high resolution SPECT system

• Project/Area Number: 24601021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 医学物理学・放射線技術学
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: NAKANO Atsushi 独立行政法人国立循環器病研究センター, 研究所, 研究員 (90217787)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 小動物イメージング / 酸化LDL / 動脈硬化 / RI標識法 / 褐色脂肪組織 / SPECT / 画像解析 / 画像診断

Outline of Final Research Achievements

The oxidized low-density lipoprotein (oxLDL) is involved in vascular endothelial dysfunction, injury and inflammation, and plays a key role in atherogenesis and also related to various cardiovascular dieses. The clearance of oxLDL were studied in middle of 1970’s using RAT, monkey and human. These studies suggested the applied oxLDL rapidly accumulated to liver and cleared from blood in several minutes.
However, the CVD (such as stroke, hart dieses) were strongly related to the micro dose oxLDL in blood. We think, the clearance mechanism may be were breakdown in CVD. We investigated the oxLDL metabolism/distribution of mouse whole body imaging with high resolution SPECT system and found that not only the liver but also many organs including brown fat were involved in oxLDL metabolism.

Research Products

• [Journal Article] Oxidized LDL (oxLDL) activates the angiotensin II type 1 receptor by binding to the lectin-like oxLDL receptor. (2015)
  • Author(s): Yamamoto K, Kakino A, Takeshita H, Hayashi N, Li L, Nakano A, Hanasaki-Yamamoto H, Fujita Y, Imaizumi Y, Toyama-Yokoyama S, Nakama C, Kawai T, Takeda M, Hongyo K, Oguro R, Maekawa Y, Itoh N, Takami Y, Onishi M, Takeya Y, Sugimoto K, Kamide K, Nakagami H, Ohishi M, Kurtz TW, Sawamura T and Rakugi H.
  • Journal Title: The FASEB Journal Volume: Apr 15 Issue: 8 Pages: 3342-3356
  • DOI: 10.1096/fj.15-271627
  • Peer Reviewed / Open Access
• [Presentation] Whole body imaging of 123I-oxLDL distribution in mouse with high resolution SPECT system (2015)
  • Author(s): 中野厚史、銭谷勉、河嶋秀和、飯田秀博、沢村達也
  • Organizer: 日本分子イメージング学会 第10回学会総会・学術集会 / JSMI 2015
  • Place of Presentation: 東京
  • Year and Date: 2015-05-20 – 2015-05-21
• [Presentation] LOX-1 遺伝子欠損SHRSPの作製とその形質の予備的解析 (2014)
  • Author(s): 垣野明美、李 蕾、池末昌弘、中野厚史、藤田佳子、岡澤 慎、真下知士、沢村達也
  • Organizer: 第50回高血圧関連疾患モデル学会学術総会
  • Place of Presentation: 和歌山市
  • Year and Date: 2014-12-05 – 2014-12-06
• [Presentation] Overexpression Of Del-1, An Oxidized LDL Blocking Protein, Suppressed Atherogenesis In Mice Without Lowering Oxidized LDL Concentration, But with Reducing LOX-1 Ligand Containing ApoB Activity (LAB) (2014)
  • Author(s): A.Kakino, A. Nakano, Y. Fujita, T. Sawamura
  • Organizer: 2014 Annual Meeting & Clinical Lab Expo
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-07-27 – 2014-07-31
• [Presentation] AT1 directly interacting with LOX-1 mediates signal transduction induced by oxidized LDL (2014)
  • Author(s): A. Kakino, K. Yamamoto, A. Nakano, L. Li, Y. Fujita, H. Rakugi, T. Sawamura
  • Organizer: 82nd European Atherosclerosis Society Congress (EAS 2014)
  • Place of Presentation: Madrid, SPAIN
  • Year and Date: 2014-05-31 – 2014-06-03
• [Presentation] 放射性ヨウ素標識酸化 LDL（123I-oxLDL）の開発と動脈硬化病変への集積に関する基礎的検討 (2013)
  • Author(s): 河嶋秀和、中野厚史、銭谷 勉、垣野明美、三宅義 徳、沢村達也、飯田秀博
  • Organizer: 日本分子イメージング学会 第8回学会総会・学術集会/JSMI 2013
  • Place of Presentation: 横浜
• [Presentation] 123I-oxLDLのマウス全身動態に関する研究 (2013)
  • Author(s): 中野厚史、河嶋秀和、三宅義徳、沢村達也、飯田秀博
  • Organizer: 日本機械学会 第25回バイオエンジニアリング講演会
  • Place of Presentation: 筑波
• [Presentation] Synthesis and evaluation of iodine-123 labeled oxidized low-density lipoprotein (123I-oxLDL) as a non-invasive imaging probe for vascular disease (2012)
  • Author(s): Kawashima Hidekazu, Nakano Atsushi, Zeniya Tutomu, Kakino Akemi, Miyake Yoshinori, Sawamura Tatsuya, Iida Hidehiro
  • Organizer: World Molecular Imaging Congress 2012
  • Place of Presentation: London
• [Presentation] アテローム性血管病変のイメージングを目的としたヨウ素-123標識酸化LDLの合成と基礎評価 (2012)
  • Author(s): 河嶋秀和、中野厚史、銭谷 勉、垣野明美、三宅義徳、沢村達也、飯田秀博
  • Organizer: 第52回日本核医学会学術総会
  • Place of Presentation: 札幌
• [Presentation] ヨウ素-123 標識酸化LDL（[123I]oxLDL）の体内動態に関する検討
  • Author(s): 河嶋秀和、中野厚史、銭谷 勉、圓見純一郎、垣野明美、三宅義徳、沢村達也、飯田秀博
  • Organizer: 第12回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都