Molecular imaging in tumor proliferation and angiogenesis: Development of a early assessment tool for measuring the tumor response to treatment with molecular targeted drugs

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591742
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Hokkaido University
• Principal Investigator: ZHAO SONGJI 北海道大学, 医学(系)研究科(研究院), 教授 (80374239)
• Co-Investigator(Kenkyū-buntansha): NISHIJIMA Kenichi 北海道大学, 大学院医学研究科, 特任講師 (60364254) ; TAKEI Toshiki 北海道大学, 大学院医学研究科, 助教 (60374493) ; SHIGA Tohru 北海道大学, 大学院医学研究科, 准教授 (80374495)
• Co-Investigator(Renkei-kenkyūsha): KUGE Yuji 北海道大学, アイソトープ総合センター, 教授 (70321958)
• Project Period (FY): 2011 – 2013
• Keywords: がん分子イメージング / がんの分子標的療法 / 細胞増殖 / 血管新生 / PET/CT / SPECT/CT

Research Abstract

An early and accurate identification of the tumor response to therapy with molecular targeted drugs is indispensable for selecting optimal personalized treatment strategies. Thus, in this study we utilized molecular imaging technologies including PET and SPECT for visualizing tumor proliferation and angiogenesis/hypoxia, and demonstrated their usefulness in determining the tumor response to molecular targeted drugs at an earlier time stage using animal models. We also demonstrated the potential of our novel candidate compound for angiogenesis imaging in in vitro and in vivo studies. The present results could provide important evidence that may lead to the development of a novel diagnostic and assessment tool for measuring the tumor response to treatment with molecular targeted drugs, taking advantage of molecular imaging technologies for visualizing changes in tumor pathological states at the molecular and cellular levels.

Research Products

• [Journal Article] Assessment of early changes in ^3H-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression (2013)
  • Author(s): Zhao S, Kuge Y, Zhao Y, Takeuchi S, Hirata K, Takei T, Shiga T, Dsaka-Akita H and Tamaki N
  • Journal Title: BMC Cancer Volume: 13 Pages: 525
  • DOI: 10.1186/1471-2407-13-525
  • Peer Reviewed
• [Journal Article] Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model (2013)
  • Author(s): Murakami M, Zhao S, Zhao Y, Chowdhury NF, Yu W, Nishijima K, Masahiro Yamasaki, Takiguchi M, Tamaki N, Kuge Y
  • Journal Title: Oncology letters Volume: 6 Pages: 667-672
  • DOI: 10.3892/ol.2013.1459
  • Peer Reviewed
• [Journal Article] Biological characteristics of intratumoral ^<18>F-fluoromisonidazole distribution in a rodent model of glioma (2013)
  • Author(s): Hatano T, Zhao S, Zhao Y, Nishijima K, Kuno N, Hanzawa N, Sakamoto K, Tamaki N, and Kuge Y
  • Journal Title: Int J Oncol Volume: 42 Pages: 823-830
  • DOI: 10.3892/ijo.2013.1781
  • Peer Reviewed
• [Journal Article] Evaluation of changes in tumor microenvironment after sorafenib therapy by sequential histology and ^<18>F-fluoromisonidazole hypoxia imaging in renal cell carcinoma (2012)
  • Author(s): Murakami M, Zhao S, Zhao Y, Chowdhury NF, Yu W, Nishijima K, Takiguchi M, Tamaki N, Kuge Y
  • Journal Title: Int J Oncol Volume: 41 Pages: 1593-1600
  • DOI: 10.3892/ijo.2012.1624
  • Peer Reviewed
• [Journal Article] Radiolabeled uracil derivative as a novel SPECT probe for thymidine phosphorylase : suppressed accumulation into tumor cells by target gene knockdown (2011)
  • Author(s): Li H, Zhao S, Jin Y, Nishijima K, Akizawa H, Ohkura K, Tamaki N, Kuge Y
  • Journal Title: Nucl Med Commun Volume: 32 Pages: 1211-1215
  • DOI: 10.1097/MNM.0b013e32834b7ea7
  • Peer Reviewed
• [Journal Article] ^<18>F-Fluorothymidine PET/CT as an early predictor of tumor response to treatment with cetuximab in human lung cancer xenografts (2011)
  • Author(s): Takeuchi S, Zhao S, Kuge Y, Zhao Y, Nishijima K, Hatano T, Shimizu Y, Kinoshita I, Tamaki N, Dosaka-Akita H
  • Journal Title: Oncol Rep Volume: 26 Pages: 725-730
  • DOI: 10.3892/or.2011.1338
  • Peer Reviewed
• [Journal Article] Dynamic ^<11>C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas : an experimental study using small animal PET (2011)
  • Author(s): Zhao S, Kuge Y, Yi M, Zhao Y, Hatano T, Magota K, Nishijima K, Kohanawa, and Tamaki N
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 38 Pages: 1876-1886
  • DOI: 10.1007/s00259-011-1865-2
  • Peer Reviewed
• [Presentation] 腎細胞癌移植モデルにおける抗血管新生剤(sorafenib)の治療反応のFMISO PETによる評価 (2013)
  • Author(s): 趙松吉、于聞文、村上正紘、趙芫、ファティマチョウドリヌスラット、西嶋剣一、右近直之、久保直樹、玉木長良、久下裕司
  • Organizer: 第53回日本核医学学術総会
  • Place of Presentation: 福岡市
  • Year and Date: 20131108-10
• [Presentation] 抗血管新生剤(sorafenib)の抗腫瘍効果の機序:肺癌細胞移植モデルにおけるFMISOによる腫瘍内酸素状態の評価 (2013)
  • Author(s): 于聞文、趙松吉、村上正紘、趙芫、ファティマチョウドリヌスッラト、西嶋剣一、北川善政、玉木長良、久下裕司
  • Organizer: 第53回日本核医学学術総会
  • Place of Presentation: 福岡市
  • Year and Date: 20131108-10
• [Presentation] FMISO PET reflects antiangiogenic tumor response after sorafenib treatment in human renal cell carcinoma xenograft (2013)
  • Author(s): Murakami M, Zhao S, Zhao Y, Chowdhury NF, Yu W, Nishijima K, Takiguchi M, Tamaki N, Kuge Y
  • Organizer: The 60^<th> Society of Nuclear Medicine and Molecular Imaging Annual Meeting
  • Place of Presentation: Vancouver
  • Year and Date: 20130608-12
• [Presentation] Preparation and evaluation of [^<123>I]IIMU for SPECT imaging of thymidine phosphorylase expression in tumors (2013)
  • Author(s): Nishijima K, Zhao S, Zhao Y, Feng F, Shimizu Y, Abo N, Akizawa H, Ohkura K, Tamaki N, Kuge Y
  • Organizer: The 20^<th> International Symposium on Radiopharmaceutical Sciences
  • Place of Presentation: Jeju, Korea
  • Year and Date: 20130512-17
• [Presentation] 腎細胞癌移植マウスにおけるマルチキナーゼ阻害剤Sorafenib治療後のFLTによる治療反応評価 (2012)
  • Author(s): 村上正紘、趙松吉、趙芫、マチョウドリヌスラットファティ、于聞文、西嶋剣一、久保直樹、滝口満喜、玉木長良、久下裕司
  • Organizer: 第52回日本核医学学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 20121011-13
• [Presentation] FLT can early reflect response of tumor proliferation to multikinase inhibitor (sorafenib) treatment in a human renal cell carcinoma xenograft : comparison with Ki-67 (2012)
  • Author(s): Murakami M, Zhao S, Zhao Y, Chowdhury NF, Yu W, Nishijima K, Takiguchi M, Tamaki N, Kuge Y
  • Organizer: The 2012 World Molecular Imaging Congress
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 20120905-08
• [Presentation] FMISO PET reflects antiangiogenic tumor response to multi-kinase inhibitor (sorafenib) in human renal cell carcinoma xenograft (2012)
  • Author(s): Murakami M, Zhao S, Zhao Y, Chowdhury NF, Yu W, Nishijima K, Takiguchi M, Tamaki N, Kuge Y
  • Organizer: The 59^<th> Society of Nuclear Medicine Annual Meeting
  • Place of Presentation: Miami
  • Year and Date: 20120609-13
• [Presentation] チミジンホスホリラーゼを標的とする新規腫瘍イメージング剤(^<123>I-IIMU)の開発:マウス組織におけるチミジンホスホリラーゼ発現と^<123>I-IIMU集積との関係 (2012)
  • Author(s): 趙松吉、李花、西嶋剣一、秋澤宏行、大倉一枝、玉木長良、久下裕司
  • Organizer: 日本分子イメージング学会第7回総会・学術集会
  • Place of Presentation: 浜松市
  • Year and Date: 20120524-25
• [Presentation] ^<18>F-FMISOを用いた腎細胞癌移植モデルにおける抗血管新生療法(sorafenib)の早期治療反応の評価 (2012)
  • Author(s): 村上正紘、趙松吉、趙芫、チョウドリヌスラットファティマ、于聞文、西嶋剣一、滝口満喜、玉木長良、久下裕司
  • Organizer: 日本分子イメージング学会第7回総会・学術集会
  • Place of Presentation: 浜松市
  • Year and Date: 20120524-25
• [Presentation] チミジンホスホリラーゼイメージング剤[^<123>I]5-iodo-6-[(2-iminoimidazolidiny l)methyl]uracilの開発:タンパク結合測定と画像化の検討 (2012)
  • Author(s): 西嶋剣一、越田早織、趙松吉、秋澤宏行、大倉一枝、松本博樹、志賀哲、玉木長良、久下裕司
  • Organizer: 日本薬学会第132回年会
  • Place of Presentation: 札幌市
  • Year and Date: 20120328-31
• [Presentation] ヒト癌移植マウスにおける抗EGFR抗体(Cetuximab)による分子標的療法:^<18>F-FMISOを用いた早期治療効果評価 (2011)
  • Author(s): 趙松吉、久下裕司、趙芫、竹内啓、村上正紘、李花、チョウドリヌスラットファティマ、西嶋剣一、竹井俊樹、秋田弘俊、玉木長良
  • Organizer: 第51回日本核医学会学術総会
  • Place of Presentation: つくば市
  • Year and Date: 20111027-29
• [Presentation] ^<18>F-Fluorothymidine (18F-FLT) as early predictor of tumor response for anti-epidermal growth factor receptor antibody in human lung cancer xenograft (2011)
  • Author(s): Takeuchi S, Zhao S, Kuge Y, Zhao Y, Nishijima K, Shimizu Y, Kinoshita I, Tamaki N, Dosaka-Akita H
  • Organizer: The 14^<th> World Conference on Lung Cancer
  • Place of Presentation: Amsterdam
  • Year and Date: 20110703-07
• [Presentation] FMISO PET can early evaluate antiangiogenic response to anti-EGFR molecular-targeting therapy (cetuximab) in human lung cancer xenograft (2011)
  • Author(s): Zhao S, Kuge Y, Zhao Y, Takeuchi S, Murakami M, Li H, Nusrat C, Nishijima K, Dosaka-Akita H, Tamaki N
  • Organizer: The 58^<th> Society of Nuclear Medicine Annual Meeting
  • Place of Presentation: San Antonio
  • Year and Date: 20110604-08