Development of a matter phase controlled Rn/At generator for targeted alpha therapy

• Project/Area Number: 26461848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Fukushima Medical University (2017); Kanazawa University (2014-2016)
• Principal Investigator: Washiyama Kohshin 福島県立医科大学, 公私立大学の部局等, 准教授 (80313675)
• Co-Investigator(Kenkyū-buntansha): 横山 明彦 金沢大学, 物質化学系, 教授 (80230655) ; 西中 一朗 国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所 東海量子ビーム応用研究センター, 主幹研究員(定常) (70354884)
• Project Period (FY): 2014-04-01 – 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 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: α放射体 / ジェネレータ / アスタチン-211 / アイソトープ治療 / 放射線 / がん / 薬学 / ラドン-211 / 癌 / 内用療法 / アスタチン－211

Outline of Final Research Achievements

Although an alpha emitter astatine-211 is the most promising radionuclide for treatment of cancer, its short half-life limited the use of it only at nearby hospitals. Here we produced 211Rn/211At generator using solvent extraction method, which enables to deliver 211At more distant site from production facilities. Moreover, we evaluated the retention of 211Rn in an organic solvent, or hydrocarbon by changing the temperature to change the phase of each hydrocarbon solvent.
211Rn was produced by 209Bi(7Li, 5n)211Rn reaction at the JAEA-Tokai tandem accelerator. 211Rn was extracted by solvent extraction using decane, dodecane, tetradecane, hexadecane as organic solvents. These hydrocarbons were kept at a constant temperature (0 and 20 degrees), and the amount of 211 Rn was periodically measured. As a result, 211Rn was released from all the hydrocarbons at 20 degree, but in the case of hexadecane at 0 degree, 80 to 90% of 211Rn was retained for 10 hours.

Research Products

• [Int'l Joint Research] デューク大学/アルゴンヌ国立研究所(米国)
• [Int'l Joint Research] Duke University(米国)
• [Int'l Joint Research] University of Gothenburg(Sweden)
• [Journal Article] Development of a remotely operable digital rate meter for radiation monitoring (2017)
  • Author(s): Nakayama K, Kita J, Washiyama K.
  • Journal Title: Wellness Health Care. Volume: 41 Pages: 159-166
  • NAID: 120006394953
  • Peer Reviewed / Open Access
• [Journal Article] Production of iodine radionuclides using 7Li ion beams (2017)
  • Author(s): Nishinaka I, Yokoyama A, Washiyama K, Makii H, Hashimoto K.
  • Journal Title: Journal of Radioanalytical and Nuclear Chemistry Volume: 314 Pages: 1947-1965
  • DOI: 10.1007/s10967-017-5525-2
  • Peer Reviewed
• [Journal Article] 標的アイソトープ治療に対するα放射体からのアプローチ (2016)
  • Author(s): 鷲山幸信
  • Journal Title: 放射線 Volume: 41(4) Pages: 211-220
• [Journal Article] Production and separation of astatine isotopes in the 7Li + natPb reaction (2015)
  • Author(s): I. Nisinaka, A. Yokoyama, K. Washiyama, E. Maeda, S. Watanabe, K. Hashimoto, N. S. Ishioka, H. Makii, A. Toyoshima, N. Yamada, R. Amano
  • Journal Title: Journal of Radioanalytical and Nuclear Chemistry Volume: 304(3) Pages: 1077-1083
  • DOI: 10.1007/s10967-015-3975-y
  • Peer Reviewed
• [Journal Article] アイソトープ治療のためのアルファ放射体の製造 (2015)
  • Author(s): 鷲山幸信
  • Journal Title: 放射化学 Volume: 32 Pages: 11-33
  • Peer Reviewed / Open Access
• [Journal Article] Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for alpha radionuclide therapy (2015)
  • Author(s): Ogawa K, Mizuno Y, Washiyama K, Shiba K, Takahashi N, Kozaka T, Watanabe S, Shinohara A, Odani A.
  • Journal Title: Nucl Med Biol, Volume: 42(11) Pages: 875-879
  • DOI: 10.1016/j.nucmedbio.2015.07.001
  • Peer Reviewed
• [Journal Article] Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal antibody MX35 (anti-NaPi2b) and its Humanized Version Rebmab200 (2015)
  • Author(s): Lindegren S, Andrade LN, Bäck T, Machado CM, Horta BB, Buchpiguel C, Moro AM, Okamoto OK, Jacobsson L, Cederkrantz E, Washiyama K, Aneheim E, Palm S, Jensen H, Tuma MC, Chammas R, Hultborn R, Albertsson P
  • Journal Title: PLoS One Volume: 8(2)
  • DOI: 10.1371/journal.pone.0126298
  • Peer Reviewed / Open Access
• [Journal Article] Extraction of astatine isotopes for development of radiopharmaceuticals using a 211Rn-211At generator (2015)
  • Author(s): E. Maeda, A. Yokoyama, T. Taniguchi, K. Washiyama, I. Nishinaka
  • Journal Title: Journal of Radioanalytical and Nuclear Chemistry Volume: 303(2) Pages: 1465-1468
  • DOI: 10.1007/s10967-014-3586-z
  • NAID: 120005516436
  • Peer Reviewed
• [Journal Article] アルファ放射体への展開 (2014)
  • Author(s): 鷲山幸信
  • Journal Title: PETjournal Volume: (25) Pages: 41-43
• [Presentation] Wet chemistry processes utilized in the development of a 211Rn/211At generator for targeted alpha therapy (2017)
  • Author(s): Shin Y, Ooe S, Murakami K, Taniguchi T, Maeda E, Yamada N, Washiyama K, Yokoyama A, Nishinaka I
  • Organizer: 6th Asia-Pacific Symposium on Radiochemistry
  • Int'l Joint Research
• [Presentation] Optimization of 225Ac labeling to DOTA conjugated peptide for targeted alpha therapy (2017)
  • Author(s): Washiyama K, Kato K, Yamamura T, Yoshii Y, Yoshimoto M, Kobayashi M, Kawai K
  • Organizer: ACITINIDES 2017
  • Int'l Joint Research
• [Presentation] Development of method to reduce radiation exposure to the large intestine during 223Ra alpha therapy with barium sulfate (2017)
  • Author(s): Yoshii Y, Hanadate S, Washiyama K, Yoshimoto M, Matsumoto H, Yamamura T, Watanabe M, Tsuji AB, Higashi T.
  • Organizer: ACITINIDES 2017
  • Int'l Joint Research
• [Presentation] Stabillity constants of EDTA, DOTA, EDTMP and DOTMP complex with Th(IV) for nuclear medicine (2017)
  • Author(s): Kitabayashi K, Furuta M, Ohta S, Yamamura T, Washiyama K.
  • Organizer: ACITINIDES 2017
  • Int'l Joint Research
• [Presentation] Administration of barium sulfate reduces radiation exposure in the large intestine during alpha-therapy with radium-223-dichloride (2017)
  • Author(s): Hanadate S, Yoshii Y, Washiyama K, Yoshimoto M, Matsumoto H, Tsuji AB, Higashi T
  • Organizer: SNMMI 2017 Annual Meeting
  • Int'l Joint Research
• [Presentation] Reduction of radiation exposure to the large intestine during 223Ra alpha therapy with oral administration of barium sulfate (2017)
  • Author(s): Hanadate S, Washiyama K, Yoshimoto M, Matsumoto H, Tsuji AB, Higashi T, Yoshii Y
  • Organizer: 10th International Symposium on Targeted Alpha Therapy
  • Int'l Joint Research
• [Presentation] Wet chemistry of radon and astatine for the development of a 211Rn/211At generator (2017)
  • Author(s): Shin Y, Ooe S, Murakami K, Taniguchi T, Maeda E, Yamada N, Washiyama K, Yokoyama A.
  • Organizer: 10th International Symposium on Targeted Alpha Therapy
  • Int'l Joint Research
• [Presentation] 飽和炭化水素溶媒に対するアスタチンの抽出挙動 (2017)
  • Author(s): 鷲山 幸信、新 裕喜、横山 明彦、豊嶋 厚史、 神田 晃充、 篠原 厚、吉村 崇
  • Organizer: 第61回放射化学討論会
• [Presentation] 211Rn－211Atジェネレーター開発のためのアスタチン溶媒抽出の研究 (2017)
  • Author(s): 新 裕喜, 川﨑 康平, 山田 記大, 横山 明彦, 鷲山 幸信, 西中 一朗
  • Organizer: 第61回放射化学討論会
• [Presentation] 225AcのDOTA標識に関する諸条件の検討 (2017)
  • Author(s): 加藤 俊貴、鷲山 幸信、山村 朝雄、吉井 幸恵、吉本 光喜、小林 正和、川井 恵一
  • Organizer: 第57回日本核医学会学術総会
• [Presentation] Melanocortin receptor標的DOTA-ペプチドを利用したメラノーマ特異的放射性薬剤の開発 (2016)
  • Author(s): 加藤俊貴、鷲山幸信、小林正和、石崎淳志、小川数馬、吉本光喜、川井恵一
  • Organizer: 第56回日本核医学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2016-11-03
• [Presentation] Structure and stability of EDTMP and DOTMP complex with Th(IV) for nuclear medicine (2016)
  • Author(s): T. Yamamura, M. Furuya, S. Ohta, K. Washiyama
  • Organizer: Plutonium Futures - The Science 2016
  • Place of Presentation: Baden-Baden, Germany
  • Year and Date: 2016-09-18
  • Int'l Joint Research
• [Presentation] 原子力機構タンデム加速器での7Li イオンビームを用いたアスタチンと ヨウ素放射性同位体の製造と利用 (2016)
  • Author(s): 西中一朗、鷲山幸信、前田英太、谷口拓海、横山明彦、橋本和幸
  • Organizer: 第60回放射化学討論会
  • Place of Presentation: 新潟大学五十嵐キャンパス（新潟県新潟市）
  • Year and Date: 2016-09-10
• [Presentation] 211Rn-211At ジェネレーター開発を目的としたシリンジ密封抽出系のAt/Rn分離係数の研究 (2016)
  • Author(s): 山田記大、新裕喜、大江崇太、村上拳冬、橋本和幸、西中一朗、 鷲山幸信、横山明彦
  • Organizer: 第60回放射化学討論会
  • Place of Presentation: 新潟大学五十嵐キャンパス（新潟県新潟市）
  • Year and Date: 2016-09-10
• [Presentation] Measurement of the 209Bi(7Li, 5n)211Rn, 209Bi(7Li, 6n)210Rn reaction cross sections towards the development of a 211Rn/211At generator (2016)
  • Author(s): K. Washiyama, E. Maeda, I. Nishinaka, K. Hashimoto, H. Makii, A. Yokoyama
  • Organizer: 16th International Workshop on Targetry and Target Chemistry (WTTC16)
  • Place of Presentation: Santa Fe, NM, USA
  • Year and Date: 2016-08-29
  • Int'l Joint Research
• [Presentation] Production and utilization of astatine and iodine radioisotopes using 7Li ion beams at the JAEA tandem accelerator (2016)
  • Author(s): I. Nishinaka, K. Washiyama, E. Maeda, T. Taniguchi, A. Yokoyama, K. Hashimoto
  • Organizer: 16th International Workshop on Targetry and Target Chemistry (WTTC16)
  • Place of Presentation: Santa Fe, NM, USA
  • Year and Date: 2016-08-29
  • Int'l Joint Research
• [Presentation] アイソトープ治療に対するα放射体からのアプローチ (2016)
  • Author(s): 鷲山幸信
  • Organizer: 第63回応用物理学会春季学術講演会
  • Place of Presentation: 東京工業大学（東京都目黒区）
  • Year and Date: 2016-03-20
  • Invited
• [Presentation] Present landscape for Targeted Alpha Therapy (TAT) in the world (2015)
  • Author(s): 鷲山幸信
  • Organizer: 第2回核医学治療国際シンポジウム
  • Place of Presentation: 金沢ニューグランドホテル（石川県金沢市）
  • Year and Date: 2015-12-19
  • Invited
• [Presentation] Production of alpha-emitting radioisotopes using the cyclotron facilities at Osaka University and JAEA Takasaki, and the Tandem accelerator at Tokai, JAEA (2015)
  • Author(s): K. Washiyama, R. Amano, E. Maeda, A. Yokoyama, I. Nishinaka, N. Takahashi, A. Shinohara, S. Watanabe, N. S. Ishioka
  • Organizer: Pacifichem 2015
  • Place of Presentation: Hilton Hawaiian Village, Honolulu, Hawaii, USA.
  • Year and Date: 2015-12-15
  • Int'l Joint Research / Invited
• [Presentation] 209Bi(7Li, 5n)211Rn反応をして生成する211Atの製造条件の最適化 (2015)
  • Author(s): 鷲山幸信、前田英太、西中一朗、横山明彦、橋本和幸、牧井宏之
  • Organizer: 第59回放射化学討論会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県仙台市）
  • Year and Date: 2015-09-25
• [Presentation] 核反応209Bi(7Li,5n)211Rnでのα放射線療法用211Atの製造 (2015)
  • Author(s): 西中一朗、鷲山幸信、横山明彦、前田英太、橋本和幸、牧井宏之
  • Organizer: 第59回放射化学討論会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県仙台市）
  • Year and Date: 2015-09-25
• [Presentation] 211Rn/211Atジェネレータの原型としてのシリンジ密封抽出系の構築 (2015)
  • Author(s): 村上拳冬、大江崇太、谷口拓海、橋本和幸、牧井宏之、西中一朗、鷲山幸信、横山明彦
  • Organizer: 第59回放射化学討論会
  • Place of Presentation: 東北大学川内北キャンパス（宮城県仙台市）
  • Year and Date: 2015-09-25
• [Presentation] Development of a 211Rn/211At generator using a wet chemistry approach for targeted alpha therapy applications (2015)
  • Author(s): K. Washiyama, R. Amano, E. Maeda, N. Yamada, T. Taniguchi, A. Yokoyama, I. Nishinaka, A. Toyoshima, H. Makii, K. Hashimoto
  • Organizer: 9th Symposium on Targeted Alpha Therapy
  • Place of Presentation: Palac Prymasowski, Warsaw Poland
  • Year and Date: 2015-05-20
  • Int'l Joint Research
• [Presentation] α線内用療法のための211Rn/211At ジェネレータの作成 (2014)
  • Author(s): 鷲山幸信、前田英太、横山明彦、西中一朗、谷口拓海、山田記大、牧井宏之、豊嶋厚史、天野良平
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-11-06 – 2014-11-08
• [Presentation] 癌のRI内用療法を目的としたシグマ受容体標的放射性薬剤の開発 (2014)
  • Author(s): 水野覚瑛、小川数馬、鷲山幸信、高橋成人、笠松良崇、渡辺茂樹、柴 和弘、小谷明
  • Organizer: 第14 回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都市勧業館/みやこめっせ（京都府京都市）
  • Year and Date: 2014-09-13
• [Presentation] 7Liイオンビームを用いたアスタチン、ヨウ素RIの製造と利用 (2014)
  • Author(s): 西中一朗、横山明彦、鷲山幸信、天野良平、前田英太、谷口拓海、村上拳冬、渡辺茂樹、鈴木博元、石岡典子、橋本和幸、牧井宏之
  • Organizer: 第58回放射化学討論会
  • Place of Presentation: 名古屋大学工学部IB電子情報館（愛知県名古屋市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 有機溶媒を用いたラドン捕集及び壊変生成物の回収に関する基礎的検討 (2014)
  • Author(s): 前田英太、鷲山幸信、山田記大、谷口拓海、村上拳冬、天野良平、西中一朗、横山明彦
  • Organizer: 第58回放射化学討論会
  • Place of Presentation: 名古屋大学工学部IB電子情報館（愛知県名古屋市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 核医薬品利用に向けたアスタチン-211の溶媒抽出とその抽出プロセスにおける化学形の研究 (2014)
  • Author(s): 谷口拓海、前田英太、村上拳冬、西中一朗、鷲山幸信、横山明彦
  • Organizer: 第58回放射化学討論会
  • Place of Presentation: 名古屋大学工学部IB電子情報館（愛知県名古屋市）
  • Year and Date: 2014-09-11 – 2014-09-13