Development strategy of tumor diagnostic agent by system upregulated functional biomolecule based on expression analysis of tumor associated transporter

• Project/Area Number: 15K15452
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: KAWAI Keiichi 金沢大学, 保健学系, 教授 (30204663)
• Co-Investigator(Kenkyū-buntansha): 中西 猛夫 金沢大学, 薬学系, 准教授 (30541742) ; 小林 正和 金沢大学, 健康増進科学センター, 助教 (30444235)
• Co-Investigator(Renkei-kenkyūsha): TAMAI Ikumi 金沢大学, 薬学系, 教授 (20155237) ; OKAZAWA Hidehiko 福井大学, 高エネルギー医学研究センター, 教授 (50360813)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ヒト培養細胞 / 遺伝子発現解析 / 機能性分子安定発現系 / 画像診断薬 / ポストFDG 製剤 / アミノ酸トランスポーター / 薬物トランスポーター / 設計戦略 / 癌関連トランスポーター / 機能性分子発現系 / 腫瘍診断薬 / ポストＦＤＧ製剤 / 開発戦略

Outline of Final Research Achievements

In this study, while searching this research for the functional biomolecule used by the database for the gene expression level in the human cultured cells for evaluation of imaging probes, as well as human tumor culturing cells in a stable functional molecule was confirmed with high expression by using the expression system for the screening of imaging agents, the labeled amino acid derivatives are especially taken up also in a post-FDG candidate probe, and the accumulation mechanism of the labeled amino acids which shows high affinity to the amino acid transporters to which high revelation is specifically accepted by a tumor was examined in detail, and the validity of the design strategy was evaluated from correlation with amino acid transporter gene expression and tumor accumulation of the imaging agents.

Research Products

• [Journal Article] Differences in accumulation and the transport mechanism of l- and d-methionine in high- and low-grade human glioma cells. (2017)
  • Author(s): Masato Kobayashi , Asuka Mizutani , Kodai Nishi , Syuichi Nakajima , Naoto Shikano , Ryuichi Nishii , Kazuki Fukuchi , Keiichi Kawai
  • Journal Title: Nucl Med Biol. Volume: 44 Pages: 78-82
  • DOI: 10.1016/j.nucmedbio.2016.09.003
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between [14C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [3H]methionine uptake. (2017)
  • Author(s): Kagawa S, Nishii R, Higashi T, Yamauchi H, Ogawa E, Okudaira H, Kobayashi M, Yoshimoto M, Shikano N, Kawai K.
  • Journal Title: Nucl Med Biol. Volume: 44 Pages: 8-15
  • DOI: 10.1016/j.nucmedbio.2017.01.008
  • Peer Reviewed / Open Access
• [Journal Article] A Novel Injection Strategy of Flurbiprofen-axetil by Inhibiting Protein Binding with 6-Methoxy-2-naphthylacetic Acid. (2016)
  • Author(s): Ogata K., Takamura N., Tokunaga J., Ikeda T., Setoguchi N., Tanda K,., Yamasaki T., Nishio T., Kawai K.
  • Journal Title: Eur. J. Drug Metab. Pharmacok. Volume: 41 Issue: 2 Pages: 179-186
  • DOI: 10.1007/s13318-014-0248-z
  • Peer Reviewed
• [Journal Article] Simultaneous acquisition of (99m)Tc- and (123)I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors. (2016)
  • Author(s): Kobayashi M, Matsunari I, Nishi K, Mizutani A, Miyazaki Y, Ogai K, Sugama J, Shiba K, Kawai K, Kinuya S.
  • Journal Title: Ann Nucl Med. Volume: 30 Issue: 4 Pages: 263-271
  • DOI: 10.1007/s12149-015-1055-6
  • Peer Reviewed
• [Journal Article] Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro. (2016)
  • Author(s): Ono M, Baden A, Okudaira H, Kobayashi M, Kawai K, Oka S, Yoshimura H.
  • Journal Title: Int J Mol Sci. Volume: 14
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous Acquisition of 99mTc- and 123I-labeled Radiotracers using a Preclinical SPECT Scanner with CZT Detectors. (2016)
  • Author(s): Kobayashi M., Matsunari I., Nishi K., Mizutani A., Miyazaki Y., Ogai K., Sugama J., Shiba K., Kawai K., Kinuya S.
  • Journal Title: Ann. Nucl. Med. Volume: 30
  • Peer Reviewed
• [Journal Article] In vivo radioactive metabolite analysis for individualized medicine: a basic study of a new method of CYP activity assay using (123)I-IMP. (2015)
  • Author(s): Nishi K, Mizutani A, Shikano N, Fujita K, Kobayashi M, Ono M, Nishii R, Sasaki Y, Kinuya S, Kawai K.
  • Journal Title: Nucl Med Biol Volume: 2 Issue: 2 Pages: 171-176
  • DOI: 10.1016/j.nucmedbio.2014.08.015
  • NAID: 120006986250
  • Peer Reviewed / Open Access
• [Journal Article] Cross-linked human serum albumin dimer has the potential for use as a plasma retaining-agent for the fatty acid-conjugated antidiabetic drugs. (2015)
  • Author(s): Taguchi K, Chuang VTG, Yamasaki K, Urata Y, Tanaka R, Anraku M, Seo H, Kawai K, Maruyama T, Komatsu T, Otagiri M
  • Journal Title: J Pharm Pharmacol. Volume: 67 Issue: 2 Pages: 255-263
  • DOI: 10.1111/jphp.12338
  • Peer Reviewed
• [Journal Article] A strategy for improving FDG accumulation for early detection of metastasis from primary pancreatic cancer: Stimulation of the Warburg effect in AsPC-1 cells. (2015)
  • Author(s): Ogura M, Shikano N, Nakajima S, Sagara J, Yamaguchi N, Kusanagi K, Okui Y, Mizutani A, Kobayashi M, Kawai K.
  • Journal Title: Nuclear Medicine and Biology Volume: 42 Issue: 5 Pages: 475-481
  • DOI: 10.1016/j.nucmedbio.2014.12.017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impact of injection dose, post-reconstruction filtering, and collimator choice on image quality of myocardial perfusion SPECT using cadmium-zinc telluride detectors in the rat. (2015)
  • Author(s): Mizutani A, Matsunari I, Kobayashi M, Nishi K, Fujita W, Miyazaki Y, Nekolla SG, Kawai K.
  • Journal Title: EJNMMI Physics Volume: 2 Issue: 1 Pages: 1-17
  • DOI: 10.1186/s40658-015-0111-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of radioiodine-labeled 4-hydroxyphenylcysteamine for specific diagnosis of malignant melanoma. (2015)
  • Author(s): Kobayashi M, Nishii R, Shikano N, Flores LG 2nd, Mizutani A, Ogai K, Sugama J, Nagamachi S, Kawai K.
  • Journal Title: Nucl Med Biol Volume: 6 Issue: 6 Pages: 536-540
  • DOI: 10.1016/j.nucmedbio.2015.02.004
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of Image Quality with 62Cu and 64Cu-labeled Radiotracers in Positron Emission Tomography Whole-body Phantom Imaging. (2015)
  • Author(s): Kobayashi M., Mori T., Tsujikawa T., Ogai K., Sugama J., Kiyono Y., Kawai K., Okazawa H.
  • Journal Title: Hell. J. Nucl. Med. Volume: 18 Pages: 103-107
  • Peer Reviewed / Open Access
• [Journal Article] [14C]Fluciclovine (alias anti-[14C]FACBC) uptake and ASCT2 expression in castration-resistant prostate cancer cells. (2015)
  • Author(s): Ono M, Oka S, Okudaira H, Nakanishi T, Mizotani A, Kobayashi M, Schuster DM, Goodman MM, Shirakami Y, Kawai K.
  • Journal Title: Nuclear Medicine and Biology Volume: 42 Issue: 11 Pages: 887-892
  • DOI: 10.1016/j.nucmedbio.2015.07.005
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Accumulation Difference and transport mechanism of 11C-labeled L- and D-Methionine in Low and High Grade Tumor Cells. (2016)
  • Author(s): Kobayashi M, Ohe K, Nadamura T, Nishi K, Higashi T, Okudaira H, Shikano N, Nishii R, Kawai K.
  • Organizer: The Society of Nuclear Medicine 63th Annual Meeting
  • Place of Presentation: San Diego Convention Center, San Diego, California, U.S.A.
  • Year and Date: 2016-06-11
  • Int'l Joint Research
• [Presentation] Metabolic Aspects of [14C]Acetete in Rabbit Atherosclerotic Arteries at Different Feeding Conditions: In Vitro Evaluation for Atherosclerosis Imaging with [11C]Acetate. (2016)
  • Author(s): Yamasaki K, Yamashita A, Zhao Y, Shimizu Y, Kawai K, Tamaki N, Zhao S, Asada Y, Kuge Y.
  • Organizer: The Society of Nuclear Medicine 63th Annual Meeting
  • Place of Presentation: San Diego Convention Center, San Diego, California, U.S.A.
  • Year and Date: 2016-06-11
  • Int'l Joint Research
• [Presentation] Phase Analysis using ECG-gated Myocardial FDG PET in the Rat in Comparison with Speckle Tracking Echocardiography. (2015)
  • Author(s): Mizutani A., Matsunari I., Kobayashi M., Nishi K., Fujita W., Nekolla S.G., Kawai K., Fukuchi K.
  • Organizer: 28th Annual Congress of the European Association of Nuclear Medicine
  • Place of Presentation: Congress Center Hamburg, Hamburg, Germany
  • Year and Date: 2015-10-10
  • Int'l Joint Research
• [Presentation] Comparison of Image Quality with 62Cu and 64Cu-Radiotracers in Whole Body Tumor Imaging. (2015)
  • Author(s): Kobayashi M., Mori T., Tsujikawa T., Mizutani A., Kiyono Y., Okazawa H., Kawai K.
  • Organizer: World Molecular Imaging Congress 2015
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii, U.S.A.
  • Year and Date: 2015-09-05
  • Int'l Joint Research
• [Presentation] Quantitative Simultaneous Acquisition of Dual Tracer using 99mTc and 123I-labeled Radiotracers in Preclinical SPECT Scanner with CZT Detector. (2015)
  • Author(s): Mizutani A., Kobayashi M., Matsunari I., Nishi K., Miyazaki Y., Kawai K.
  • Organizer: World Molecular Imaging Congress 2015
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii, U.S.A.
  • Year and Date: 2015-09-05
  • Int'l Joint Research
• [Presentation] Development of Benzyl [18F]Fluoroacetate Radiosynthesis for PET Imaging of Ischemic Brain Injury. (2015)
  • Author(s): Kagawa S., Mizuma H., Nishii R., Higashi T., Yamauchi H., Ono M., Tateishi H., Takahashi K., Onoe H., Kawai K.
  • Organizer: World Molecular Imaging Congress 2015
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii, U.S.A.
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] Transport Mechanism and Androgen-stimulated Uptake of Amino Acid PET Tracer [18F]Fluciclovine (anti-[18F]FACBC) in Primary and Castration-resistant Prostate Cancer Cells. (2015)
  • Author(s): Ono M., Okudaira H., Oka S., Nakanishi T, Mizokami A, Kobayashi M., Schuster D.M., Goodman M.M., Yoshimura H., Kawai K.
  • Organizer: 9th International BioMedical Transporters Conference
  • Place of Presentation: Palazzo dei Congressi, Lugano, Switzerland
  • Year and Date: 2015-08-10
  • Int'l Joint Research
• [Presentation] [18F]PTV-F1 PET for OATP Transporter Imaging of the Liver. -Preclinical and Phase I Clinical Study. (2015)
  • Author(s): Nishii R., Kagawa S., Higashi T., Yamauchi H., Kimura H., Kawai K., Nagamachi S., Ono M., Sugiyama Y., Saji H.
  • Organizer: The Society of Nuclear Medicine 62th Annual Meeting
  • Place of Presentation: Baltimore Convention Center, Baltimore, Maryland, U.S.A.
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] Radiosynthesis of [18F]PTV-F1, Pitavastatin (HMG-CoA Reductase Inhibitor) Derivative for Organic Anion Transporter Imaging of Liver. (2015)
  • Author(s): Kagawa S., Nishii R., Higashi T., Yamauchi H., Kawai K., Kimura H., Ono M., Sugiyama Y., Saji H.
  • Organizer: The Society of Nuclear Medicine 62th Annual Meeting
  • Place of Presentation: Baltimore Convention Center, Baltimore, Maryland, U.S.A.
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Remarks] 金沢大学 研究者情報
  • URL: http://ridb.kanazawa-u.ac.jp/public/detail.php?id=2789&page=3&org2_cd=360600
• [Remarks] 金沢大学医薬保健研究域保健学系 量子医療技術学講座 川井研究室
  • URL: http://kawai.w3.kanazawa-u.ac.jp/index.html
• [Remarks] 金沢大学 研究者情報
  • URL: http://ridb.kanazawa-u.ac.jp/public/detail.php?id=2789&page=1&search=1&keyword=%E5%B7%9D%E4%BA%95&andor=AND&tgt1=1&tgt2=&tgt3=&tgt4=