Investigation of the molecular mechanism of transiently elevated tumor uptake of PET tracers at early time points after X-ray radiation

• Project/Area Number: 15K09976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: TSUJI Atsushi 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 分子イメージング診断治療研究部, チームリーダー(定常) (60303559)
• Co-Investigator(Kenkyū-buntansha): 田畑 祥 慶應義塾大学, 政策・メディア研究科(藤沢), 特任助教 (30708342) ; 加藤 孝一 国立研究開発法人国立精神・神経医療研究センター, 脳病態統合イメージングセンター, 室長 (50382198)
• Research Collaborator: SUDO Hitomi 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分子イメージング診断治療研究部, 研究員 (10415416) ; SUGYO Aya 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分子イメージング診断治療研究部, 技術員 (00415415)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: PET / 放射線 / アミノ酸 / アミノ酸トランスポーター / がん / メタボローム解析

Outline of Final Research Achievements

Contribution of amino acid transporters for PET tracer uptake was markedly different among tumor cells, suggesting the possibility of a new uptake mechanism. Our findings in evaluation for tumor uptake after radiation, there was a need to develop a new PET tracer. Therefore, we developed and evaluated cysteine-based tracers in vitro and in vivo. To explorer pathways associated with the mechanism of transiently elevated uptake, metabolome analysis was conducted. Tumors treated with AIB and X-rays showed increased metabolites on the glycolysis. Our findings warrant further studies to investigate the mechanism of transiently elevated uptake after X-ray radiation.

Research Products

• [Journal Article] Antitumor effects of radionuclide treatment using α-emitting meta-211At-astato-benzylguanidine in a PC12 pheochromocytoma model (2018)
  • Author(s): Ohshima Yasuhiro、Sudo Hitomi、Watanabe Shigeki、Nagatsu Kotaro、Tsuji Atsushi B.、Sakashita Tetsuya、Ito Yoichi M.、Yoshinaga Keiichiro、Higashi Tatsuya、Ishioka Noriko S.
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging Volume: 45 Issue: 6 Pages: 999-1010
  • DOI: 10.1007/s00259-017-3919-6
  • Peer Reviewed
• [Journal Article] Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/mTOR inhibitor (2017)
  • Author(s): 3.Aung W, Tsuji AB, Sudo H, Sugyo A, Ukai Y, Kouda K, Kurosawa Y, Furukawa T, Saga T, Higashi T
  • Journal Title: World J Gastroenterol Volume: 23 Pages: 7551-62
  • Peer Reviewed / Open Access
• [Journal Article] Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model (2017)
  • Author(s): 5.Takashima H, Tsuji AB, Saga T, Yasunaga M, Koga Y, Kuroda JI, Yano S, Kuratsu JI, Matsumura Y
  • Journal Title: Sci Rep Volume: 7 Pages: 12341-12341
  • Peer Reviewed / Open Access
• [Journal Article] ynthesis and evaluation of 11C-labeled coumarin analog as an imaging probe for detecting monocarboxylate transporters expression (2017)
  • Author(s): 6.Tateishi H, Tsuji AB, Kato K, Sudo H, Sugyo A, Hanakawa T, Zhang MR, Saga T, Arano Y, Higashi T
  • Journal Title: Bioorg Med Chem Lett Volume: 27 Pages: 4893-7
  • Peer Reviewed
• [Journal Article] Development of antibody-drug conjugates using DDS and molecular imaging (2017)
  • Author(s): 7.Yasunaga M, Manabe S, Tsuji A, Furuta M, Ogata K, Koga Y, Saga T, Matsumura Y
  • Journal Title: Bioengineering Volume: 4
  • NAID: 120006497386
  • Peer Reviewed
• [Journal Article] αVβ3 Integrin-Targeted Radionuclide Therapy with 64Cu-cyclam-RAFT-c(-RGDfK-)4. (2016)
  • Author(s): Jin ZH, Furukawa T, Degardin M, Sugyo A, Tsuji AB, Yamasaki T, Kawamura K, Fujibayashi Y, Zhang MR, Boturyn D, Dumy P, Saga T.
  • Journal Title: Mol Cancer Ther Volume: 15 Issue: 9 Pages: 2076-85
  • DOI: 10.1158/1535-7163.mct-16-0040
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen. (2016)
  • Author(s): Hatayama N, Inubushi M, Naito M, Hirai S, Jin YN, Tsuji AB, Seki K, Itoh M, Saga T, Li XK.．
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 32120-32120
  • DOI: 10.1038/srep32120
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Radioimmunotherapy of pancreatic cancer xenografts in nude mice using 90Y-labeled anti-α6β4 integrin antibody (2016)
  • Author(s): Aung W, Tsuji AB, Sudo H, Sugyo A, Ukai Y, Kouda K, Kurosawa Y, Furukawa T, Saga T
  • Journal Title: Oncotarget Volume: 7 Issue: 25 Pages: 38835-38844
  • DOI: 10.18632/oncotarget.9631
  • Peer Reviewed / Open Access
• [Journal Article] In Vivo Simultaneous Imaging of Vascular Pool and Hypoxia with a HT-29 Tumor Model: the Application of Dual-Isotope SPECT/PET/CT. (2016)
  • Author(s): Adachi N, Yoshii Y, Furukawa T, Yoshimoto M, Takeuchi Y, Inubushi M, Wakizaka H, Zhang MR, Tsuji AB, Takahashi M, Fujibayashi Y, Saga T.
  • Journal Title: International Journal of Sciences Volume: 25 Pages: 26-39
  • Peer Reviewed
• [Journal Article] Immunotargeting of integrin α6β4 for single-photon emission computed tomography and near-infrared fluorescence imaging in a pancreatic cancer model (2016)
  • Author(s): 2.Winn Aung, Atsushi B.Tsuji, Hitomi Sudo, Aya Sugyo, Takako Furukawa, Yoshinori Ukai, Yoshikazu kurozawa, Tsuneo Saga
  • Journal Title: Molecular Imaging Volume: 15
  • DOI: 10.1177/1536012115624917
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Establishment and evaluation of a new highly metastatic tumor cell line 5a-D-Luc-ZsGreen expressing both luciferase and green fluorescent protein (2016)
  • Author(s): Sudo H, Tsuji A B, Sugyo A, Takuwa H, Masamoto K, Tomita Y, Suzuki N, Imamura T, Koizumi M, Saga T
  • Journal Title: Int. J. Oncol. Volume: 48 Issue: 2 Pages: 525-532
  • DOI: 10.3892/ijo.2015.3300
  • Peer Reviewed / Open Access
• [Journal Article] In-vivo imaging of blood-brain barrier permeability using positron emission tomography with 2-amino-[3-11C]isobutyric acid. (2015)
  • Author(s): Okada M, Kikuchi T, Okamura T, Ikoma Y, Tsuji AB, Wakizaka H, Kamakura T, Aoki I, Zhang MR, Kato K.
  • Journal Title: Nucl Med Commun Volume: 36 Issue: 12 Pages: 239-48
  • DOI: 10.1097/mnm.0000000000000385
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preclinical evaluation of 2-amino-2-[11C]methyl-butanoic acid as a potential tumor-imaging agent in a mouse model. (2015)
  • Author(s): Suzuki C, Tsuji AB, Kato K, Sudo H, Zhang MR, Saga T.
  • Journal Title: Nucl Med Commun Volume: 36 Issue: 11 Pages: 1107-1112
  • DOI: 10.1097/mnm.0000000000000364
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preclinical assessment of early tumor response after irradiation by positron emission tomography with 2-amino-[3-11C]isobutyric acid (2015)
  • Author(s): Tsuji AB, Sugyo A, Sudo H, Suzuki C, Wakizaka H, Zhang MR, Kato K, Saga T
  • Journal Title: Oncol Rep Volume: 33 Issue: 5 Pages: 2361-7
  • DOI: 10.3892/or.2015.3868
  • Peer Reviewed / Acknowledgement Compliant
• [Remarks] 分子イメージング診断治療研究部
  • URL: http://www.nirs.go.jp/rd/mit/index.html