Prediction of cancer therapeutic effect with molecular targeting agents by molecular imaging of the signal transduction

• Project/Area Number: 18390331
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: YOSHIMOTO Mitsuyoshi Kanazawa University, 保健学系, 助教 (00345638)
• Co-Investigator(Kenkyū-buntansha): KAWAI Keiichi 金沢大学, 保健学系, 教授 (30204663) ; KINUYA Seigo 金沢大学, 医学系, 教授 (20281024) ; OHMOMO Yoshirou 大阪薬科大学, 薬学部, 准教授 (70183241) ; HIRATA Masahiko 大阪薬科大学, 薬学部, 助教 (00268301)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥13,340,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥1,740,000); Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2007: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2006: ¥5,800,000 (Direct Cost: ¥5,800,000)
• Keywords: がん / 分子イメージング / 治療効果予測 / EGFR-TK / シグナル伝達 / 癌 / EGFR / EGFRチロシンキナーゼ / EGFRチロシンキナーゼ阻害剤 / PET / SPECT

Research Abstract

本研究では、キナゾリンを母体化合物とする種々のヨウ素又は臭素誘導体の合成を行った。これらの化合物はEGFR高発現を示すA431細胞に対し増殖阻害効果を示した。さらに、ヨウ素誘導体であるIPHYやIPYKはEGFR-TKに対して高い親和性と選択性を示し、また、体内分布実験においても腫瘍への高集積を確認した。これらのことから、IPHYとIPYKにEGFR-TKイメージング剤としての有用性が確認された。

Research Products

• [Journal Article] Differential expression of Fos and Zif268 in the nigrostriatal system after methamphetamine administration in a rat model of Parkinson's disease (2008)
  • Author(s): Ishida Y, Kawai K, Magata Y, Yoshimoto M, (他7人)
  • Journal Title: Synapse 62(12) Pages: 920-6
  • Peer Reviewed
• [Journal Article] αvβ3 Integrin-targeting radionuclide therapy and imaging with monomeric RGD peptide (2008)
  • Author(s): Yoshimoto M, Kawai K, (他5人)
  • Journal Title: Int.J.Cancer 123(3) Pages: 709-15
  • Peer Reviewed
• [Journal Article] Influences of haemodialysis on the binding sites of human serum albumin : possibility of an efficacious administration plan using binding inhibition (2008)
  • Author(s): Nishio T, Yoshimoto M, Kawai K, (他3人)
  • Journal Title: Nephrol.Dial.Transplant 23(7) Pages: 2304-10
  • Peer Reviewed
• [Journal Article] Usefulness of Competitive Inhibitors of Protein Binding for Improving the Pharmacokinetics of ^<186>Re-MAG^<3>-conjugated Bisphosphonate (^<186>Re-MAG^<3>-HBP), an Agent for Treatment of Painful Bone Metastases (2008)
  • Author(s): Ogawa K, Kawai K, Saji H, (他6人)
  • Journal Title: Eur.J.Nucl.Med.Mol.Imaging in press
  • NAID: 120001130407
  • Peer Reviewed
• [Journal Article] Regional wall thickening in gated myocardial perfusion SPECT in a Japanese population : effect of sex, radiotracer, rotation angles and frame rates (2008)
  • Author(s): Akhter N, Kinuya S, (他5人)
  • Journal Title: Eur J Nucl Med Mol Imaging 35(9) Pages: 1608-15
  • NAID: 120001130402
  • Peer Reviewed
• [Journal Article] A change of in vivo characteristics depending on specific activity of radioiodinated(+)-2-[4-(4-iodophenyl)piperidino]cyclo hexanol [(+)-pIV] as a ligand for sigma receptor imaging (2008)
  • Author(s): Akhter N, Kinuya S, (他5人)
  • Journal Title: Nucl.Med.Biol 35(1) Pages: 29-34
  • Peer Reviewed
• [Journal Article] Evaluation of radioiodinated1-[2-(3, 4-Dimethoxyphenyl)ethyl]-4-(2-iodophenylpropyl)piperazine as a tumor diagnostic agent with functional sigma receptor imaging by single photon emission computed tomography (2008)
  • Author(s): Hirata M, Ohmomo Y, (他4人)
  • Journal Title: Biol.Pharm.Bull 31(5) Pages: 879-83
  • Peer Reviewed
• [Journal Article] Differential expression of Fos and Zif268 in the nigrostriatal system after methamphetamine administration in a rat model of Parkinson's disease. (2008)
  • Author(s): Ishida Y, Kawai K, Magata Y, Ebihara K, Takeda R, Abe H, Yoshimoto M, et al
  • Journal Title: Synapse 62 Pages: 920-926
  • Peer Reviewed
• [Journal Article] α_vβ_3 Integrin-targeting radionuclide therapy and imaging with monomeric RGD peptide. (2008)
  • Author(s): Yoshimoto M, Ogawa K, Washiyama K, Shikano N, Mori H, Amano R. Kawai K.
  • Journal Title: Int. J. Cancer 123 Pages: 709-715
  • Peer Reviewed
• [Journal Article] Influences of haemodialysis on the binding sites of human serum albumin : possibility of an efficacious administration clan using binding inhibition. (2008)
  • Author(s): Nishio T, Takamura N, Nishii R. Tokunaga J, Yoshimoto M, Kawai K.
  • Journal Title: Nephrol. Dial. Transplant. 23 Pages: 2304-2310
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of 3-[^<125>I]iodo-alpha-methyl-L-tyrosine, a tumor imaging agent, after probenecid loading in mice implanted with colon cancer DLD-1 cells (2007)
  • Author(s): Nakajima S, Yoshimoto M, Kawai K, (他8人)
  • Journal Title: Nucl.Med.Biol 34(8) Pages: 1003-8
  • Peer Reviewed
• [Journal Article] Transport of D-[1-^<14>C]-amino acids into Chinese hamster ovary (CHO-K1) cells : implications for use of labeled d-amino acids as molecular imaging agents (2007)
  • Author(s): Shikano N, Yoshimoto M, Kawai K, (他7人)
  • Journal Title: Nucl. Med. Biol 34(6) Pages: 659-65
  • Peer Reviewed
• [Journal Article] In vivo characterization of radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol as a potential sigma-1 receptor imaging agent (2007)
  • Author(s): Akhter N, Kinuya S, (他4人)
  • Journal Title: Nucl. Med. Biol 34(6) Pages: 697-702
  • Peer Reviewed
• [Journal Article] Airway complication occurring during radioiodine treatment for Graves'disease (2007)
  • Author(s): Kinuya S, (他2人)
  • Journal Title: Ann Nucl Med 21(6) Pages: 367-9
  • Peer Reviewed
• [Journal Article] Changes in the levels of CD4+ and CD8+T-lymphocytes after strontium-89 chloride therapy for painful bone metastases in patients correlate with treatment efficacy (2007)
  • Author(s): Li Y, Yang H, Kinuya S, (他8人)
  • Journal Title: Cancer Biother Radiopharm 22(3) Pages: 367-73
  • Peer Reviewed
• [Journal Article] Therapeutic effects of a 186Re-complex conjugated bisphosphonate for the palliation of metastatic bone pain in an animal model (2007)
  • Author(s): Ogawa K, Kinuya S, (他7人)
  • Journal Title: J.Nucl.Med 48(1) Pages: 122-7
  • NAID: 120007191066
  • Peer Reviewed
• [Journal Article] Intraperitoneal radioimmunotherapy to treat the early phase of peritoneal dissemination of human colon cancer cells in a murine model (2007)
  • Author(s): Kinuya S, ( 他9人)
  • Journal Title: Nucl.Med.Commun 28(2) Pages: 129-33
  • Peer Reviewed
• [Journal Article] Radio-iodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model (2006)
  • Author(s): Yoshimoto M, Kinuya S, Kawai K, (他3人)
  • Journal Title: Nucl. Med. Biol 33(8) Pages: 963-9
  • Peer Reviewed
• [Journal Article] Detection of maleateinduced Fanconi syndrome by decreasing accumulation of 125I-3-iodo-alpha-methyl- L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice : a trial of separate evaluation of reabsorption (2006)
  • Author(s): Shikano N, Yoshimoto M, Kawai K, (他7人)
  • Journal Title: Ann.Nucl.Med 20(3) Pages: 175-81
  • Peer Reviewed
• [Journal Article] RGDペプチドを利用した腫瘍イメージング (2006)
  • Author(s): 吉本光喜
  • Journal Title: 北陸地域アイソトープ研究会誌 8 Pages: 27-30
  • Peer Reviewed
• [Journal Article] Post-FDGを目指した新規腫瘍診断用PET製剤の開発動向 (2006)
  • Author(s): 川井恵一, 吉本光喜, (1, 2番目)
  • Journal Title: 日本放射線技術学会雑誌 62(6) Pages: 764-70
  • NAID: 110004740299
  • Peer Reviewed
• [Journal Article] Respiratory distress caused by radioiodine therapy in patients with differentiated thyroid cancer (2006)
  • Author(s): Kinuya S, (他3 人)
  • Journal Title: Ann.Nucl.Med 20(7) Pages: 99-502
  • NAID: 10018775308
  • Peer Reviewed
• [Journal Article] ^<99m>Tcsestamibi to monitor treatment with antisense oligodeoxynucleotide complementary to MRP mRNA in human breast cancer cells (2006)
  • Author(s): Kinuya S, (他9人)
  • Journal Title: Ann.Nucl.Med 20(1) Pages: 29-34
  • NAID: 10018776834
  • Peer Reviewed
• [Presentation] 放射性ヨウ素標識VMOを用いた癌の血管新生能把握による癌特性診断の可能性 (2008)
  • Author(s): 平田 雅彦
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-28
• [Presentation] EGFR-TKイメージング剤(IPHY)によるゲフィチニブ感受性の評価 (2008)
  • Author(s): 木内智美, 吉本光喜, 平田雅彦, 大桃善朗, 川井恵一
  • Organizer: 第48回日本核医学会総会
  • Place of Presentation: 幕張
• [Presentation] Estimation of Radioiodinated IPHY as an Imaging Agent for Assessment of EGFR-TK Activity (2008)
  • Author(s): Yoshimoto M, Hirata M, Kawai K, OhmomoY
  • Organizer: 2008World Molecular Imaging Congress
  • Place of Presentation: Nice (France)
• [Presentation] ^<[125>I]IPHYによるゲフィチニブの感受性予測 (2008)
  • Author(s): 吉本光喜, 木内智美, 平田雅彦, 大桃善朗, 西井龍一, 川井恵一
  • Organizer: 第3回日本分子イメージング学会
  • Place of Presentation: 大宮
• [Presentation] EGFR-TK阻害剤の治療効果予測を目的としたI-mIPQA-PET診断薬の基礎的検討 (2008)
  • Author(s): 加川信也, 西井龍一, 清野泰, 小川数馬, 東達也, 岸部喜彦, 岩崎甚衛, 吉本光喜, 川井恵一, Juri Gelovani
  • Organizer: 第3回日本分子イメージング学会
  • Place of Presentation: 大宮
• [Presentation] Estimation of Radioiodinated IPHY as an Imaging Agent for Assessment of EGFR-TK Activity. (2008)
  • Author(s): Yoshimoto M, Hirata M, Kawai K, Ohmomo Y.
  • Organizer: 2008 World Molecular Imaging Congress
  • Place of Presentation: ニース(フランス)
• [Presentation] [^<125>I]IPHYによるゲフイチニブの感受性予測 (2008)
  • Author(s): 吉本光喜, 木内智美, 平田雅彦, 大桃善朗, 西井龍一, 川井恵一
  • Organizer: 第3回日本分子イメージング学会
  • Place of Presentation: 大宮
• [Presentation] EGFR-TKイメージング剤(IPHY)によるゲフィチニブ感受性の評価 (2008)
  • Author(s): 木内智美, 吉本光喜, 平田雅彦, 大桃善朗, 川井恵一
  • Organizer: 第48回日本核医学会総会
  • Place of Presentation: 大宮
• [Presentation] 放射性ヨウ素標識ベサミコール誘導体の腫瘍イメージング剤としての評価 (2007)
  • Author(s): 小川数馬, 柴和弘, 吉本光喜, 鷲山幸信, 絹谷清剛, 川井恵一, 森厚文
  • Organizer: 第47回日本核医学会総会
  • Place of Presentation: 仙台
• [Presentation] Evaluation of a radiolabeled sigma ligand for receptor radionuclide therapy (2007)
  • Author(s): Ogawa K, Shiba K, Yoshimoto M, Washiyama K, Akhter N, Kinuya S, Kawai K, Mori H
  • Organizer: The 54^<th> Annual Meeting of the Society of Nuclear Medicine
  • Place of Presentation: Washington DC(USA)
• [Presentation] Evaluation of a vesamicol analog as a sigma receptor ligand for tumor imaging (2006)
  • Author(s): Ogawa K, Shiba K, Yoshimoto M, Akhter N, Washiyama K, Kawai K, Mori H
  • Organizer: 9^<th>World Congress of Nuclear Medicine and Biology
  • Place of Presentation: Seoul (Korea)
• [Presentation] The integrin αvβ3 targeting imaging and radiotherapy with radiolabeled monomeric RGD peptide (2006)
  • Author(s): Yoshimoto M, Ogawa K, Washiyama K, Mori H, Amano R, Kawai K
  • Organizer: The 53rd Annual Meeting of the Society of Nuclear Medicine
  • Place of Presentation: San Diego(USA)