Development of TSPO-PET imaging for noninvasive diagnosis of liver diseases

• Project/Area Number: 24790543
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: XIE Lin 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 研究員 (30623558)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝疾患 / 脂肪肝 / TSPO / PET / [18]FEDAC / 画像診断法 / [18F]FEDAC / 生体分子 / 肝癌

Outline of Final Research Achievements

Due to the limitations of liver biopsy and currently available noninvasive imaging techniques, new noninvasive approaches for diagnosis of liver diseases, especially the most common subgroup fatty liver disease (FLD), have become an urgent requirement. In this study, we focused on the mitochondrial dysfunction that is responsible for disease progression of FLD, and translocator protein (18 kDa)(TSPO)-a mitochondrial transmembrane protein, explored whether TSPO can be used as an imaging biomarker of noninvasive diagnosis and staging of FLD, monitored using PET with a TSPO specific radioligand [18F]FEDAC. Our data demonstrated TSPO is a good imaging biomarker, and [18F]FEDAC-PET can accurate and noninvasive diagnosis and staging of FLD with excellent sensitivity and specificity. Our study may open a novel avenue for noninvasive and reliable clinic screening of FLD focusing on the general population.

Research Products

• [Journal Article] Visualization of acute liver damage induced by cycloheximide in rats using PET with [(18)F]FEDAC, a radiotracer for translocator protein (18 kDa). (2014)
  • Author(s): Hatori A, Yui J, Xie L, Yamasaki T, Kumata K, Fujinaga M, Wakizaka H, Ogawa M, Nengaki N, Kawamura K, Zhang MR.
  • Journal Title: PLoS One. Volume: 9 Issue: 1 Pages: e86625-e86625
  • DOI: 10.1371/journal.pone.0086625
  • Peer Reviewed / Open Access
• [Journal Article] Molecular imaging of ectopic metabotropic glutamate 1 receptor in melanoma with a positron emission tomography radioprobe 18 F-FITM. (2014)
  • Author(s): Xie L, Yui J, Fujinaga M, Hatori A, Yamasaki T, Kumata K, Wakizaka H, Furutsuka K, Takei M, Jin ZH, Furukawa T, Kawamura K, Zhang MR.
  • Journal Title: International Journal of Cancer Volume: in press Issue: 8 Pages: 1852-1859
  • DOI: 10.1002/ijc.28842
  • Peer Reviewed / Open Access
• [Journal Article] Translocator protein (18 kda), a potential molecular imaging biomarker for non-invasively distinguishing non-alcoholic fatty liver disease (2012)
  • Author(s): Xie L, Yui J, Hatori A, Yamasaki T, Kumata K, Wakizaka H, Yoshida Y, Fujinaga M, Kawamura K, Zhang MR
  • Journal Title: Journal of hepatology Volume: 57 Issue: 5 Pages: 1076-1082
  • DOI: 10.1016/j.jhep.2012.07.002
  • Peer Reviewed
• [Presentation] ヒト肝臓検体を用いる脂肪肝に対する 18F-FEDACイメージングの有用性評価 (2014)
  • Author(s): 謝 琳、由井譲二、熊田勝志、羽鳥晶子、山崎友照、季斌、河村和紀、張明栄
  • Organizer: 第54回核医学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-06 – 2014-11-08
• [Presentation] トランスロケータタンパク質（18kDa）、非アルコール性脂肪肝疾患診断の新たな分子イメージングバイオマーカー (2013)
  • Author(s): 謝琳、由井譲二、羽鳥晶子、山崎友照、熊田勝志、脇坂秀克、吉田勇一郎、藤永雅之、河村和紀、張明栄
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 福岡
• [Presentation] Molecular Imaging of Multiple Sclerosis and Non-alcoholic Fatty Liver Disease Using Translocator Protein (18 kDa) Radioligands (2013)
  • Author(s): Lin Xie
  • Organizer: Advance in Probe Discovery for Neuroimaging and Targeted Radiotherapy
  • Place of Presentation: 中国、上海
• [Presentation] Translocator Protein (18 kDa) is a Potential Biomarker for Molecular Imaging of Non-alcoholic Fatty Liver Disease (2012)
  • Author(s): Lin Xie, Joji Yui, Akiko Hatori, Tomoteru Yamasaki, Katsushi Kumata, Hidekatsu Wakizaka, Masayuki Fujinaga, Ming-Rong Zhang
  • Organizer: 世界分子イメージング学会2012年会 (2012WMIC)
  • Place of Presentation: アイルランド、ダブリン
• [Presentation] TSPOを標的とした肝細胞癌の画像診断法の開発に関する研究 (2012)
  • Author(s): 謝 琳、由井 譲二、羽鳥 晶子、山崎 友照、熊田 勝志、脇坂 秀克、張 明栄
  • Organizer: 第52 回日本核医学会学術総会
  • Place of Presentation: 札幌
• [Presentation] [18F]FEDAC-PETによる非アルコール性脂肪肝疾患画像診断法の開発 (2012)
  • Author(s): 謝琳、由井譲二、羽鳥晶子、山崎友照、熊田勝志、脇坂秀克、張明栄
  • Organizer: 第12回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都
• [Remarks] 第53回日本核医学会学術総会において研究奨励賞と優秀ポスター賞を受賞
  • URL: http://www.nirs.go.jp/research/division/mic/newsrelease/131122/index.html
• [Remarks] 脂肪肝の発症及び進行をPETでモニタリングすることに成功
  • URL: http://www.nirs.go.jp/information/press/2012/09_04.shtml
• [Remarks] 2012 WMIC Student Travel Stipend Award 受賞
  • URL: http://www.nirs.go.jp/research/division/mic/newsrelease/120911-2/index.html
• [Remarks] 欧州肝臓学会の雑誌「Journal of Hepatology」の表紙を飾りました
  • URL: http://www.nirs.go.jp/research/division/mic/newsrelease/121206/index.html