Development of peptide-based PET probe targeting integrin alpha5beta1

• Project/Area Number: 24591827
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: JIN Zhao-Hui 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, 主任研究員 (70324150)
• Co-Investigator(Kenkyū-buntansha): ZHANG Ming-Rong 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, プログラムリーダー (80443076)
• Co-Investigator(Renkei-kenkyūsha): FURUKAWA Takako 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, チームリーダー (00221557)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: alpha5beta1 integrin / Fluorine-18 / PET imaging / Fibronectin / Radioprobe / 18F

Outline of Final Research Achievements

This study was aimed to develop a novel PET imaging probe targeting the transmembrane glycoprotein receptor, α5β1integrin, by use of the fibronectin-mimetic peptide sequence KSSPHSRNSGSGSGSGSGRGDSP (called PR_b). PR_b was modified and conjugated with the chelating agent p-SCN-Bn-NOTA, and radiolabeled with 18F based on the chelation of 18F-aluminum fluoride. 18F-PR_b was produced with a radiochemical purity of >95%; it exhibited α5β1-binding activity and specificity in cultured cells and in tumor-bearing mice, and had a rapid blood clearance and a predominant renal excretion pathway. In vivo α5β1-positive tumors could be clearly visualized by 18F-PR_b PET imaging. 18F-PR_b was developed as a promising PET imaging agent targeting the α5β1 integrin.

Research Products

• [Journal Article] Comparison of intratumoral FDG and Cu-ATSM distributions in cancer tissue originated spheroid (CTOS xenografts, a tumor model retaining the original tumor properties. (2014)
  • Author(s): Furukawa T, Yuan Q, Jin ZH, Aung W, Yoshii Y, Hasegawa S, Endo H, Inoue M, Zhang MR, Fujibayashi Y, Saga T.
  • Journal Title: Nuclear Medicine and Biology Volume: 41 Issue: 8 Pages: 653-659
  • DOI: 10.1016/j.nucmedbio.2014.05.139
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] PET imaging and biodistribution analysis of the effects of succinylated gelatin combined with l-lysine on renal uptake and retention of 64Cu-cyclam-RAFT-c(-RGDfK-)4 in vivo. (2014)
  • Author(s): Jin ZH, Furukawa T, Sogawa C, Claron M, Aung W, Tsuji AB, Wakizaka H, Zhang MR, Boturyn D, Dumy P, Fujibayashi Y, Saga T.
  • Journal Title: European Journal of Pharmaceutics and Biopharmaceutics Volume: 86(3) Issue: 3 Pages: 478-486
  • DOI: 10.1016/j.ejpb.2013.11.006
  • Peer Reviewed
• [Journal Article] Micro-positron emission tomography/contrast-enhanced computed tomography imaging of orthotopic pancreatic tumor-bearing mice using the αvβ3 integrin tracer 64Cu-labeled cyclam-RAFT-c(-RGDfK-)4 (2013)
  • Author(s): Aung W, Jin ZH, Furukawa T, Claron M, Boturyn D, Sogawa C, Tsuji AB, Wakizaka H, Fukumura T, Fujibayashi Y, Dumy P, Saga T.
  • Journal Title: Molecular Imaging Volume: 12(6) Pages: 376-387
  • Peer Reviewed
• [Journal Article] C-Type Natriuretic Peptide Specifically Acts on the Pylorus and Large Intestine in Mouse Gastrointestinal Tract (2013)
  • Author(s): Sogawa C, Wakizaka H, Aung W, Jin ZH, Tsuji AB, Furukawa T, Kunieda T, Saga T.
  • Journal Title: Am J Pathol. Volume: 182 Issue: 1 Pages: 172-179
  • DOI: 10.1016/j.ajpath.2012.09.015
  • Peer Reviewed
• [Journal Article] Positron emission tomography imaging of tumor angiogenesis and monitoring of antiangiogenic efficacy using the novel tetrameric peptide probe 64Cu-cyclam-RAFT-c(-RGDfK-)4. (2012)
  • Author(s): Jin ZH, Furukawa T, Claron M, Boturyn D, Coll JL, Fukumura T, Fujibayashi Y, Dumy P, Saga T.
  • Journal Title: Angiogenesis Volume: 15 Issue: 4 Pages: 569-580
  • DOI: 10.1007/s10456-012-9281-1
  • Peer Reviewed
• [Journal Article] Basic studies on radioimmunotargeting of CD133-positive HCT116 cancer stem cells. (2012)
  • Author(s): Jin ZH, Sogawa C, Furukawa T, Saito Y, Aung W, Fujibayashi Y, Saga T.
  • Journal Title: Molecular Imaging Volume: 11 Pages: 445-450
  • Peer Reviewed
• [Presentation] Comparison of tumor uptake of the radiotracers targeting cancer metabolism (2015)
  • Author(s): Takako Furukawa, Qinghua Yuan , Zhao-Hui Jin, Winn Aung, Tsuneo Saga
  • Organizer: 2015 World Molecular Imaging Congress
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2015-09-02 – 2015-09-05
• [Presentation] Labeling and stability studies for a tetrameric cyclic RGD peptide based radiopharmaceutical 64/67Cu-cyclam-RAFT-c(-RGDfK-)4 (2015)
  • Author(s): Zhao-Hui Jin, Takako Furukawa, Mélissa Degardin, Didier Boturyn, Ming-Rong Zhang, Yasuhisa Fujibayashi, Pascal Dumy, Tsuneo Saga
  • Organizer: 2015 World Molecular Imaging Congress
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2015-09-02 – 2015-09-05
• [Presentation] Development of 18F-labeled fibronectin-mimetic peptide for positron emission tomography imaging of a5b1 integrin expression (2014)
  • Author(s): Zhao-Hui Jin, Takako Furukawa, Katsushi Kumata, Lin Xie, Joji Yui, Hidekatsu Wakizaka, Yasuhisa Fujibayashi, Ming-Rong Zhang, Tsuneo
  • Organizer: 2014 World Molecular Imaging Congress
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2014-09-17 – 2014-09-20
• [Presentation] Zr-89 immuno-PET imaging targeting HER3 expression in mouse models (2014)
  • Author(s): Qinghua Yuan1, Takako Furukawa, Zhao-Hui Jin, Winn Aung, Yukie Yoshii, Aya Sugyo, Kotaro Nagatsu, Hiroko Endo, Masahiro Inoue, Takashi Masuko, Yasuhisa Fujibayashi. Tsuneo Saga
  • Organizer: 2014 World Molecular Imaging Congress
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2014-09-17 – 2014-09-20
• [Presentation] HER3を標的とするZr-89 標識抗体イメージングの基礎検討Zr-89 immuno-PET imaging targeting HER3 in mice (2014)
  • Author(s): 元清華、古川高子、金朝暉、Winn Aung、吉井幸恵、辻厚至、永津弘太郎、遠藤洋子、井上正宏、益子高、佐賀恒夫、藤林靖久
  • Organizer: 第9回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 大阪府豊中市
  • Year and Date: 2014-05-22 – 2014-05-23
• [Presentation] HER3 を標的とするZr-89 標識抗体イメージングの基礎検討 (2014)
  • Author(s): 元清華、古川高子、金朝暉、Winn Aung、吉井幸恵、須堯綾、永津弘太郎、 遠藤洋子、井上正宏、益子高、佐賀恒夫、藤林靖久
  • Organizer: 第９回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 大阪府豊中市・千里ライフサイエンスセンター
• [Presentation] PET imaging and quantification of the effects of succinylated gelatin and/or L-lysine on renal uptake and retention of the novel radiopharmaceutical 64Cu-cyclam-RAFT-c(-RGDfK-)4 (2013)
  • Author(s): Zhao-Hui Jin, Takako Furukawa, Chizuru Sogawa, Atsushi Tsuji, Winn Aung, Michael Claron, Jean-Luc Coll, Didier Boturyn, Pascal Dumy, Tsuneo Saga
  • Organizer: Annual Meeting of Society of Nuclear Medicine and Molecular Imaging (2013 SNMMI)
  • Place of Presentation: Vancouver Convention Center, Vancouver, Canada
• [Presentation] 新規分子プローブ64Cu-cyclam-RAFT-c(-RGDfK-)4を用いた腫瘍血管新生のPETイメージングおよび血管新生抑制剤の治療効果のモニタリング (2012)
  • Author(s): Zhao-Hui Jin, Takako Furukawa, Michael Claron, Didier Boturyn, Jean-Luc Coll, Toshimitsu Fukumura, Yasuhisa Fujibayashi, Pascal Dumy, and Tsuneo Saga
  • Organizer: 第７回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 浜松市アクトシティ浜松
• [Book] Nuclear Oncology (2014)
  • Author(s): Zhao-Hui Jin, Takako Furukawa, Tsuneo Saga
  • Total Pages: 711
  • Publisher: Lippincott Williams and Wilkins
• [Remarks] 腫瘍血管新生のPETイメージング
  • URL: http://www.nirs.go.jp/information/event/2012/12_11.shtml