Development of high accuracy multidrug resistance prediction method using SPECT imaging for individualized anticancer therapy

• Project/Area Number: 15K09949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: KOBAYASHI Masato 金沢大学, 健康増進科学センター, 助教 (30444235)
• Co-Investigator(Kenkyū-buntansha): 川井 恵一 金沢大学, 保健学系, 教授 (30204663)
• 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) ; KUNISHIMA Munetaka 金沢大学, 薬学系, 教授 (10214975) ; NISHII Ryuichi 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, 主任研究員 (60463212) ; SHIKANO Naoto 茨城県立医療大学, 保健医療学部, 准教授 (80295435) ; NISHI Kodai 長崎大学, 原爆後障害医療研究所, 助教 (10719496)
• Research Collaborator: INNIS B Robert National Institute of Mental Health, Molecular Imaging Branch, Chief
• 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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 核医学 / 分子イメージング / 個別化治療 / 多剤耐性 / 薬物トランスポータ / 個別化医療 / SPECT / 小動物イメージング / トランスポータ / 抗がん剤

Outline of Final Research Achievements

We developed high an accuracy multidrug resistance prediction method using SPECT imaging for individualized anticancer therapy. Although [99mTc]sestamibi and [99mTc]tetrofosmin has been reported to be the same method, we clarified that [99mTc]sestamibi had affinity to MDR1 and MRP1, whereas [99mTc]tetrofosmin had affinity to MDR1 and MRP1-3. Thus, these SPECT tracers had different method for multidrug resistance prediction in this study. Additionally, [131I]adsterol was possibility to be higher accuracy multidrug resistance prediction method than [99mTc]sestamibi and [99mTc]tetrofosmin because [131I]adsterol had only affinity to BCRP.

Research Products

• [Int'l Joint Research] MD Anderson Cancer Center/National Institutes of Health(米国)
• [Int'l Joint Research] National Institutes of Health/MD Anderson Cancer Center(米国)
• [Int'l Joint Research] National Institutes of Health(米国)
• [Journal Article] Development of radioiodine labeled acetaminophen for specific, high-contrast imaging of malignant melanoma (2018)
  • Author(s): Wen Jing Zhu , Masato Kobayashi , Kohei Yamada , Kodai Nishi , Kotaro Takahashi , Asuka Mizutani , Ryuichi Nishii , Leo G. Flores II , Naoto Shikano , Munetaka Kunishima , Keiichi Kawai
  • Journal Title: Nuclear Medicine and Biology Volume: 59 Pages: 16-21
  • DOI: 10.1016/j.nucmedbio.2017.12.008
  • Peer Reviewed / Int'l Joint Research
• [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] 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] Comparison of four 11C-labeled PET ligands to quantify translocator protein 18?kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176?based on recent publications that measured specific-to-non-displaceable ratios (2017)
  • Author(s): Fujita M, Kobayashi M, Ikawa M, Gunn RN,, Rabiner EA, Owen DR, Zoghbi SS, Haskali MB, Telu S, Pike VW, Innis RB
  • Journal Title: EJNMMI Research Volume: 7 Issue: 1 Pages: 84-84
  • DOI: 10.1186/s13550-017-0334-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 11C-DPA-713 has much greater specific binding to translocator protein 18kDa (TSPO) in human brain than 11C-( R)-PK11195 (2017)
  • Author(s): Kobayashi M, Jiang T, Telu S, Zoghbi SS, Gunn RN, Rabiner EA, Owen DR, Guo Q, Pike VW, Innis RB, Fujita M.
  • Journal Title: Journal of Cerebal Blood Flow and Metabolism Volume: 38 Pages: 393-403
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 11C-DPA-713 has much greater specific binding to translocator protein 18kDa (TSPO) in human brain than 11C-(R)-PK11195. (2017)
  • Author(s): Kobayashi M, Jiang T, Telu S, Zoghhi SS, Gunn R, Rabiner EA, Owen DR, Guo Qi, Pike VW, Innis RB, Fujita M.
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism Volume: 印刷中 Issue: 3 Pages: 393-403
  • DOI: 10.1177/0271678x17699223
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro. (2017)
  • Author(s): Ono M, Oka S, Okudaira H, Kobayashi M, Kawai K, Yoshimura H.
  • Journal Title: International Journal of Molecular Sciences Volume: 17
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Stimultaneous 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: Annals of Nuclear Medicine Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [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] 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] Comprison 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, Mizutani A, Ogai K, Sugama J, Kiyono Y, Kawai K, Okazawa H.
  • Journal Title: Hellenic Society of Nuclear medicine Volume: 18 Pages: 103-107
  • Peer Reviewed / Acknowledgement Compliant
• [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] Impact of image acquisition time on textural features in 18F-FDG PET/MR (2017)
  • Author(s): Tsujikawa T, Kobayashi M, Tsuyoshi H, Yamada S, Oikawa H, Ono Y, Yoshida Y, Okazawa H
  • Organizer: The Society of Nuclear Medicine and Molecular Imaging 2017 Annual Meeting
  • Int'l Joint Research
• [Presentation] 経口標識アミノ酸薬剤を用いた消化管吸収機能の選択的測定法の検討 (2017)
  • Author(s): 井原正明, 高須啓彰，小林正和，水谷明日香，川井恵一
  • Organizer: 第57回日本核医学会学術総会
• [Presentation] Compasion in healthy subjects of four PET radioligands to image translocator protein 18kDa (TSPO). (2016)
  • Author(s): Innis RB, Fujita M, Kobayashi M, Ikawa M, Jiang TH, Haskali MB, Telu S, Castellano S, Taliani S, Zoghbi SS, Pike VW.
  • Organizer: The 11th International Symposium on Functional Neuro Receptor Mapping of the Living Brain
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-07-13
  • Int'l Joint Research
• [Presentation] Different of accumulation and transport mechanism of 11C-labeled L- and D-methionine in high and low-grade tumor cells. (2016)
  • Author(s): Kobayashi M, Mizutani A, Nishi K, Nakajima S, Shikano N, Nishii R, Kawai K.
  • Organizer: SNMMI 2016 Annual Meeting
  • Place of Presentation: Sandiego, USA
  • Year and Date: 2016-06-11
  • Int'l Joint Research
• [Presentation] 99mTc放射性医薬品における腫瘍細胞外排泄機序の違い. (2016)
  • Author(s): 小林正和, 水谷明日香, 辻内孝文, 西弘大, 福地一樹, 川井恵一.
  • Organizer: 第11回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 神戸国際会議場 (兵庫県神戸市)
  • Year and Date: 2016-05-28
• [Presentation] 123I-IMP代謝物分析による臨床薬剤負荷時のCYP活性定量法 (2015)
  • Author(s): 髙橋浩太郎, 水谷明日香，佐野達哉，外間つづみ，西弘大，小林正和，川井恵一．
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京(東京都千代田区)
  • Year and Date: 2015-11-05
• [Presentation] イメージングによる肝臓の薬物代謝酵素CYP活性測定を可能にするヨウ素標識診断薬の開発 (2015)
  • Author(s): 水谷明日香，髙橋浩太郎，外間つづみ，小林正和，北村正典，国嶋宗隆，川井恵一，福地一樹．
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京(東京都千代田区)
  • Year and Date: 2015-11-05
• [Presentation] 62/64Cuを用いた腫瘍診断イメージングの画質比較 (2015)
  • Author(s): 小林正和，水谷明日香，髙橋浩太郎，森哲也，辻川哲也，清野泰，須釜淳子，川井恵一，岡沢秀彦．
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京(東京都千代田区)
  • Year and Date: 2015-11-05
• [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: Honolulu, USA
  • Year and Date: 2015-09-02
  • 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: Honolulu, USA
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] Blockade of translocator protein (TSPO) by XBD173 to measure specific binding of 11C-(R)-PK 11195 in human brain: an ongoing study. (2015)
  • Author(s): Kobayashi M, Jenko K, Zoghbi SS, Morse C, Rallis-Frutos D, Page E, Lohith TG, Ikawa M, Jiang T, Hong J, Pike VW, Innis RB, Fujita M.
  • Organizer: XXVIIth International Symposium on Cerebral Blood Flow, Metabolism and Function and the XIIth International Conference on Quantification of Brain Function with PET
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-06-27
  • Int'l Joint Research
• [Presentation] Blockade of translocator protein (TSPO) to measure specific binding of 11C-(R)-PK 11195 in human brain. (2015)
  • Author(s): Kobayashi M, Jenko K, Zoghbi SS, Lohith T, Rallis-Frutos D, Page E, Ikawa M, Pike V, Innis R, Fujita M.
  • Organizer: The 62th Annual Meeting of the Society of Nuclear Medicine
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2015-06-10
  • Int'l Joint Research
• [Presentation] CZT半導体検出器を搭載したSPECTイメージングにおける投与放射能、コリメータと平滑化フィルター処理の影響. (2015)
  • Author(s): 小林正和，水谷明日香，松成一朗，西弘大，宮崎吉春，柴和弘，川井恵一．
  • Organizer: 第10回分子イメージング学会
  • Place of Presentation: タワーホール船堀(東京都江戸川区)
  • Year and Date: 2015-05-20
• [Patent(Industrial Property Rights)] 細菌感染症の放射性診断薬 (2018)
  • Inventor(s): 小林正和、川井恵一、岡本成史、松榮美紀、
  • Industrial Property Rights Holder: 小林正和、川井恵一、岡本成史、松榮美紀、
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 心臓疾患診断剤，心臓疾患診断用組合せ医薬及び心臓疾患診断用キット (2016)
  • Inventor(s): 小林正和、川井恵一、加奈川優
  • Industrial Property Rights Holder: 小林正和、川井恵一、加奈川優
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-01-19