Organization
Fukushima Global Medical Science Center Advanced Clinical Research Center Associate Professor
Title
Associate Professor
Contact information
WASHIYAMA Kohshin
Degree
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博士（保健学） ( 2015.3 金沢大学 )
Research Interests
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Radiochemistry, Nuclear medicine, Targeted alpha therapy
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放射性医薬品
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壊変系列核種
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内用放射療法
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アルファ放射体
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アイソトープ治療
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targeted radionuclide therapy
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radiopharmaceuticals
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iv vivoジェネレーター
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in vivo generator
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decay chain
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alpha emitter
Research Areas
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Life Science / Radiological sciences
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Life Science / Radiological sciences
Education
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Kanazawa University Graduate School, Division of Medical Sciences
- 2005.3
Country： Japan
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Kanazawa University
- 2005.3
Country： Japan
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Kanazawa University Graduate School, Division of Science and Technology
- 1999.3
Country： Japan
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Kanazawa University Graduate School of Natural Science and Technology
- 1999.3
Country： Japan
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Kanazawa University Faculty of Science Department of Chemistry
- 1997.3
Country： Japan
Research History
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Kyoto University Visiting Associate Professor
2018.10 - 2019.9
Country：Japan
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デューク大学医療センター放射線科・客員准教授
2018.6 - 2018.12
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Duke University Medical Center, Department of Radio;ogy Visiting Associate Professor
2018.6 - 2018.11
Country：United States
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Fukushima Medical University Advanced Clinical Research Center, Fukushima Global Medical Science Center Associate Professor Ph.D.
2017.10 - Now
Country：Japan
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デューク大学医療センター放射線科・客員助教
2016.11 - 2017.5
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Duke University Medicalcenter Department of Radiology Visitting Assistant Professor
2016.11 - 2017.5
Country：United States
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金沢大学医薬保健研究域保健学系・系内講師
2015.12 - 2017.9
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ヨーテボリ大学サールグレンスカアカデミー放射線物理学科・客員研究員
2012.11 - 2013.3
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University of Gothenburg Sahlgrenska Academy, Deparetment of Radiation Physics Forskare
2012.11 - 2013.3
Country：Sweden
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Kanazawa University Institute of Medical, Pharmaceutical and Health Sciences Faculty of Health Sciences Assistant Professor
2008.4 - 2017.9
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金沢大学医薬保健研究域保健学系・助教
2008.4 - 2015.11
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金沢大学医学系研究科保健学専攻・助教
2007.4 - 2008.3
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Kanazawa University Assistant Professor
2007.4 - 2008.3
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金沢大学医学系研究科保健学専攻・助手
2005.4 - 2007.3
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Kanazawa University Assistant Professor
2005.4 - 2007.3
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金沢大学医学部保健学科・助手
1999.4 - 2005.3
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Kanazawa University Faculty of Medicine, School of Health Sciences Assistant Professor
1999.4 - 2005.3
Country：Japan
Professional Memberships
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日本放射化学会
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日本核医学会
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日本化学会
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Society for Nuclear Medicine
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欧州核医学会
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放射性薬品化学会
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Society for Dose Estimation in Targeted Radioisotope Therapy
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米国核医学会
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日本核医学会
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日本放射線影響学会
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日本放射化学会
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The japanese society of nuclear medicine
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The japan society of nuclear and radiochemical sciences
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The Japan Radiation Research Society
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Society of radiopharmaceuticals sciences
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Society for Nuclear Medicine
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European Association of Nuclear Medicine
Committee Memberships
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内閣府原子力委員会 医療用等ラジオアイソトープ製造・利用専門部会委員
2021.11 - 2022.5
Committee type：Government
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ＩＡＥＡ／ＲＣＡ国内対応委員会 ＩＡＥＡ／ＲＣＡ国内対応委員会委員
2020.8 - Now
Committee type：Government
Qualification acquired
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Chief Person of Radiation Handling （first and second kind）
20010913
Papers
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Development of a phoswich detector composed of ZnS(Ag) and YAP(Ce) for astatine-211 imaging
Yamamoto S., Ukon N., Washiyama K., Hasegawa K., Kamada K., Yoshino M., Yoshikawa A.
Radiation Measurements 153 2022.4（ ISSN:13504487 ）
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Mitsuyoshi Yoshimoto, Yukie Yoshii, Hiroki Matsumoto, Mitsuhiro Shinada, Masashi Takahashi, Chika Igarashi, Fukiko Hihara, Tomoko Tachibana, Ayano Doi, Tatsuya Higashi, Hirofumi Fujii, Kohshin Washiyama
Pharmaceutics 13 ( 10 ) 1706 2021.10（ ISSN:1999-4923 ）
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Adsorption temperature of volatile astatine species formed via dry distillation in a glass tube
Ichiro Nishinaka, Kohshin Washiyama, Kazuyuki Hashimoto
Journal of Radioanalytical and Nuclear Chemistry 329 ( 3 ) 1459 - 1465 2021.9（ ISSN:02365731 ）
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68Ga- and 211At-Labeled RGD Peptides for Radiotheranostics with Multiradionuclides
Ogawa Kazuma,Echigo Hiroaki, Mishiro Kenji , Hirata Saki, Washiyama Kohshin, Kitamura Yoji, Takahashi Kazuhiro, Shiba Kazuhiro, Kinuya Seigo
Molecular Pharmaceutics 18 ( 9 ) 3553 - 3562 2021.8（ ISSN:1543-8384 ）
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Production and supply of alpha particles emitting radionuclides for Targeted Alpha Therapy (TAT)
Radchenko Valery, Morgenstern Alfred, Jalilian Amirreza, Ramogida Caterina, Cutler Cathy S, Duchemin Charlotte, Hoehr Cornelia, Haddad Ferrid, Bruchertseifer Frank, Gausemel Haavar, Yang Hua, Osso Joao Alberto, Washiyama Kohshin, Czerwinski Kenneth, Leufgen Kristen, Pruszynski Marek, Valzdorf Olga, Causey Patrick, Schaffer Paul, Perron Randy, Samsonov Maxim, Wilbur D. Scott, Stora Thierry, Li Yawen
Journal of Nuclear Medicine 62 ( 11 ) 1495 - 1503 2021.7（ ISSN:0161-5505 ）
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Hideaki Shiga, Hiroshi Wakabayashi, Kohshin Washiyama, Tomohiro Noguchi, Tomo Hiromasa, Sadaharu Miyazono, Masami Kumai, Kazuma Ogawa, Junichi Taki, Seigo Kinuya, Takaki Miwa
Molecular neurobiology 57 ( 12 ) 4989 - 4999 2020.12（ ISSN:0893-7648 ）
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Ukon N, Zhao S, Washiyama K, Oriuchi N, Tan C, Shimoyama S, Aoki M, Kubo H, Takahashi K, Ito H
EJNMMI physics 7 ( 1 ) 58 2020.9（ ISSN:2197-7364 ）
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標的α線治療のためのアスタチン-211標識ボンベシン誘導体の予備的評価(Preliminary Evaluation of Astatine-211-Labeled Bombesin Derivatives for Targeted Alpha Therapy)
Aoki Miho, Zhao Songji, Takahashi Kazuhiro, Washiyama Kohshin, Ukon Naoyuki, Tan Chengbo, Shimoyama Saki, Nishijima Ken-ichi, Ogawa Kazuma
Chemical & Pharmaceutical Bulletin 68 ( 6 ) 538 - 545 2020.6（ ISSN:0009-2363 ）
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Noboru Oriuchi, Miho Aoki, Naoyuki Ukon, Kohshin Washiyama, Chengbo Tan, Saki Shimoyama, Ken-Ichi Nishijima, Kazuhiro Takahashi, Hiroshi Ito, Takayuki Ikezoe, Songji Zhao
Scientific reports 10 ( 1 ) 6810 - 6810 2020.4
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【α線治療とDDS】標的アイソトープ治療(TRT)に有用なアルファ放射体の現状
鷲山 幸信
Drug Delivery System 35 ( 2 ) 102 - 113 2020.3（ ISSN:0913-5006 ）
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Eita Maeda, Akihiko Yokoyama, Takumi Taniguch, Kohshin Washiyama, Ichiro Nishinaka
J. Radioanal. Nucl. Chem. 323 ( 2 ) 921 - 926 2020.2（ ISSN:02365731 ）
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Current status of alpha emitters useful for targeted radionuclide therapy
Washiyama K.
Drug Delivery System 35 ( 2 ) 102 - 113 2020（ ISSN:09135006 ）
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Preliminary evaluation of astatine-211-labeled bombesin derivatives for targeted alpha therapy
Miho Aoki, Songji Zhao, Kazuhiro Takahashi, Kohshin Washiyama, Naoyuki Ukon, Chengbo Tan, Saki Shimoyama, Ken Ichi Nishijima, Kazuma Ogawa
Chemical and Pharmaceutical Bulletin 68 ( 6 ) 538 - 545 2020（ ISSN:0009-2363 ）
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Kobayashi Masato, Kato Toshitaka, Washiyama Kohshin, Ihara Masaaki, Mizutani Asuka, Nishi Kodai, Flores 2nd G Leo, Nishii Ryuichi, Kawai Keiichi
Plos One 14 ( 3 ) e0213397 2019.3（ ISSN:1932-6203 ）
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遠隔利用可能なレートメータの開発
中山 和也, 喜多 譲司, 鷲山 幸信
Journal of Wellness and Health Care 41 ( 2 ) 159 - 166 2018.1（ ISSN:2433-3190 ）
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Reduction of 223Ra retention in the Large Intestine during Targeted Alpha Therapy with 223RaCl2 by Oral BaSO4 Administration in Mice
Hanadate Sayaka, Yoshii Yukie, Washiyama Kohshin, Yoshimoto Mitsuyoshi, Yamamura Tomoo, Watanabe Makoto, Matsumoto Hiroki, Igarashi Mineko, Tsuji B Atsushi, Higashi Tatsuya
International Journal of Sciences: Basic and Applied Research 42 ( 2 ) 95 - 105 2018（ ISSN:2307-4531 ）
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Production of iodine radionuclides using 7Li ion beams
I. Nishinaka, A. Yokoyama, K. Washiyama, H. Makii, K. Hashimoto
J. Radioanal. Nucl. Chem. 314 ( 3 ) 1947 - 1965 2017.12（ ISSN:02365731 ）
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Ogawa Kazuma, Mizuno Yoshiaki, Washiyama Kohshin, Shiba Kazuhiro, Takahashi Naruto, Kozaka Takashi, Watanabe Shigeki, Shinohara Atsushi, Odani Akira
NUCLEAR MEDICINE AND BIOLOGY 42 ( 11 ) 875 - 9 2015.11（ ISSN:0969-8051 ）
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Washiyama K., Amano R., Nozaki T., Ogawa K., Nagatsu K., Sakama M., Ido T., Yamaguchi H.
Nihon Hōshasen Gijutsu Gakkai zasshi 71 ( 10 ) 983 - 993 2015.10（ ISSN:03694305 ）
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低レベル放射能の68Geを用いた68Ge/68Gaジェネレータの作製と放射化学実習への応用
鷲山 幸信, 天野 良平, 野崎 正, 小川 幸次, 永津 弘太郎, 阪間 稔, 井戸 達雄, 山口 博司
日本放射線技術学会雑誌 71 ( 10 ) 983 - 993 2015.10（ ISSN:0369-4305 ）
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Washiyama K, Amano R, Nozaki T, Ogawa K, Nagatsu K, Sakama M, Ido T, Yamaguchi H
Nihon Hoshasen Gijutsu Gakkai zasshi 71 ( 10 ) 983 - 993 2015.10（ ISSN:0369-4305 ）
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鷲山 幸信, 天野 良平, 野崎 正, 小川 幸次, 永津 弘太郎, Sakama Minoru, 井戸 達雄, 山口 博司
Japanese Journal of Radiological Technology Vol.10 ( No.7 ) 1 - 11 2015.10（ ISSN:1881-4883 ）
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[Manufacture and Utilization of a Low-level Radioactive 68Ge/68Ga Generator in a Radiochemistry Laboratory Course].
Washiyama K, Amano R, Nozaki T, Ogawa K, Nagatsu K, Sakama M, Ido T, Yamaguchi H
Nihon Hoshasen Gijutsu Gakkai zasshi 71 ( 10 ) 983 - 93 2015.10（ ISSN:0369-4305 ）
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<sup>68</sup>Ge/<sup>68</sup>Gaジェネレータの作製と放射化学実習への応用
鷲山幸信, 天野良平, 野崎正, 小川幸次, 永津弘太郎, 阪間稔, 井戸達雄, 山口博司
アイソトープ・放射線研究発表会要旨集 52nd 111 2015.6
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Production and separation of astatine isotopes in the 7Li + natPb reaction
I. Nisinaka, A. Yokoyama, K. Washiyama, E. Maeda, S. Watanabe, K. Hashimoto, N. S. Ishioka, H. Makii, A. Toyoshima, N. Yamada, R. Amano
J. Radioanal. Nucl. Chem. 304 ( 3 ) 1077 - 1083 2015.6（ ISSN:02365731 ）
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E.Maeda, A.Yokoyama, T.Taniguchi, K.Washiyama, I.Nishinaka
J. Radioanal. Nucl. Chem. 303 ( 2 ) 1465 - 1468 2015.2（ ISSN:02365731 ）
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Hideaki Shiga, Mikiya Nagaoka, Kohshin Washiyama, Junpei Yamamoto, Kentaro Yamada, Takuya Noda, Masayuki Harita, Ryohei Amano, Takaki Miwa
CHEMICAL SENSES 39 ( 7 ) 595 - 9 2014.9（ ISSN:0379-864X ）
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嗅覚障害原因不明例のタリウム-201嗅神経移行度
志賀 英明, 瀧 淳一, 鷲山 幸信, 山本 純平, 絹谷 清剛, 天野 良平, 古川 仭, 三輪 高喜
日本耳鼻咽喉科学会会報 117 ( 4 ) 485 - 485 2014.4（ ISSN:0030-6622 ）
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【RI内用療法の進歩】 アルファ放射体への展開
鷲山 幸信
PET Journal ( 25 ) 41 - 43 2014.3（ ISSN:2186-022X ）
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Prognostic value of nasal thallium-201 transport to olfactory bulb in patients with olfactory disorders
H. Shiga, J. Taki, K. Washiyama, J. Yamamoto, S. Kinuya, R. Amano, M. Furukawa, T. Miwa
CHEMICAL SENSES 39 ( 1 ) 109 - 110 2014.1（ ISSN:0379-864X ）
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モンテカルロシミュレーションのためのマウスデジタルファントムへの鼻腔および嗅球の定義づけ
鷲山 幸信, 中西 勇介, 木名瀬 栄, 志賀 英明, 越田 吉郎, 天野 良平
核医学 50 ( 3 ) S210 - S210 2013.9（ ISSN:0022-7854 ）
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嗅球除去によるインスリン様成長因子-I脳内輸送の低下
志賀 英明, 長岡 三樹矢, 鷲山 幸信, 山本 純平, 天野 良平, 三輪 高喜
耳鼻咽喉科ニューロサイエンス 27 62 - 64 2013.4
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【基礎と臨床の対話】 放射線治療に資する転移研究 放射線治療に資するがん転移研究 オーバービュー
松本 孔貴, 増永 慎一郎, 皆巳 和賢, 鷲山 幸信, 尾方 俊至, 手島 昭樹, 松浦 成昭, 古澤 佳也
癌の臨床 59 ( 2 ) 141 - 148 2013.4（ ISSN:0021-4949 ）
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【基礎と臨床の対話】 放射線治療に資する転移研究 α放出核種による放射免疫療法の可能性
鷲山 幸信
癌の臨床 59 ( 2 ) 161 - 168 2013.4（ ISSN:0021-4949 ）
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嗅球除去によるインスリン様成長因子-I脳内輸送の低下
志賀 英明, 長岡 三樹矢, 鷲山 幸信, 山本 純平, 天野 良平, 三輪 高喜
耳鼻咽喉科ニューロサイエンス 27 62 - 64 2013.4
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嗅覚障害治療の予後因子としてのタリウム-201嗅神経移行度の有用性
志賀 英明, 瀧 淳一, 鷲山 幸信, 山本 純平, 絹谷 清剛, 天野 良平, 古川 仭, 三輪 高喜
日本耳鼻咽喉科学会会報 116 ( 4 ) 448 - 448 2013.4（ ISSN:0030-6622 ）
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Hideaki SHIGA, Junichi TAKI, Kohshin WASHIYAMA, Junpei YAMAMOTO, Sakae KINASE, Koichi OKUDA, Seigo KINUYA, Naoto WATANABE, Hisao TONAMI, Kichiro KOSHIDA, Ryohei AMANO, Mitsuru FURUKAWA, Takaki MIWA
PLOS ONE 8 ( 2 ) e57671 2013.2（ ISSN:1932-6203 ）
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Internal dosimetry for nasal thallium-201 administration
Kinase S., Washiyama K., Shiga H., Taki J., Nakanishi Y., Koshida K., Miwa T., Kinuya S., Amano R.
Proceedings of the 19th EGS Users' Meeting in Japan 35 - 40 2012.12
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タリウム-201経鼻投与における頭部被曝線量の推定
志賀 英明, 鷲山 幸信, 木名瀬 栄, 瀧 淳一, 中西 勇介, 越田 吉郎, 絹谷 清剛, 天野 良平, 古川 仭, 三輪 高喜
日本鼻科学会会誌 51 ( 3 ) 429 - 429 2012.9（ ISSN:0910-9153 ）
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鼻腔内に投与した201TlClによる被ばく線量の推定
鷲山 幸信, 木名瀬 栄, 滝 淳一, 中西 勇介, 志賀 英明, 越田 吉郎, 三輪 高喜, 絹谷 清剛, 天野 良平
核医学 49 ( 3 ) S239 - S239 2012.8（ ISSN:0022-7854 ）
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インスリン様成長因子-Iの脳内輸送における嗅神経の重要性
志賀 英明, 鷲山 幸信, 古川 仭, 天野 良平, 三輪 高喜
日本耳鼻咽喉科学会会報 115 ( 4 ) 409 - 409 2012.4（ ISSN:0030-6622 ）
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薬剤性障害モデルにおける漢方製剤の嗅神経保護作用 神経成長因子との関連
山本 純平, 志賀 英明, 鷲山 幸信, 天野 良平, 三輪 高喜
頭頸部自律神経 26 57 - 60 2012.4
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薬剤性障害モデルにおける漢方製剤の嗅神経保護作用 －神経成長因子との関連－
26 57 - 60 2012.4
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Bone Target Radiotracers for Palliative Therapy of Bone Metastases
K. Ogawa, K. Washiyama
CURRENT MEDICINAL CHEMISTRY 19 ( 20 ) 3290 - 300 2012（ ISSN:0929-8673 ）
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Internal Dosimetry for Nasal Thalium-201 Administration
S. Kinase, K. Washiyama, H. Shiga, J. Taki, Y. Nakanishi, K. Koshida, T. Miwa, S. Kinuya, R. Amano
KEK Proceedings 2012-7 35 - 40 2012
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Hideaki Shiga, Junichi Taki, Masato Yamada, Kohshin Washiyama, Ryohei Amano, Yukihiro Matsuura, Osamu Matsui, Osamu Matsui, Shinji Tatsutomi, Sayaka Yagi, Asuka Tsuchida, Tomokazu Yoshizaki, Mitsuru Furukawa, Seigo Kinuya, Seigo Kinuya, Takaki Miwa
Molecular Imaging and Biology 13 ( 6 ) 1262 - 1266 2011.12（ ISSN:15361632 ）
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医療用Gd造影剤投与後のGdおよび体内微量元素のラット体内分布に関する基礎的検討 : MRI法と放射化分析法による検討(平成22年度京都大学原子炉実験所専門研究会,研究紹介)
服部 知里, 鷲山 幸信, 高宮 幸一, 天野 良平
放射化分析 ( 28 ) 19 - 28 2011.11
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タリウム-201経鼻投与の生物学的安全性 嗅覚シンチグラフィーの前臨床試験(Biological Safety of Nasal Thallium-201 Administration: A Preclinical Study for Olfacto-scintigraphy)
Washiyama Kohshin, Shiga Hideaki, Hirota Kyoko, Tsuchida Asuka, Yamamoto Junpei, Yagi Sayaka, Yoshizaki Tomokazu, Furukawa Mitsuru, Amano Ryohei, Miwa Takaki
Journal of Radiation Research 52 ( 4 ) 450 - 455 2011.7（ ISSN:0449-3060 ）
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パクリタキセルによる嗅神経障害に対する加味帰脾湯の予防効果
山本 純平, 志賀 英明, 鷲山 幸信, 天野 良平, 三輪 高喜
日本耳鼻咽喉科学会会報 114 ( 4 ) 464 - 464 2011.4（ ISSN:0030-6622 ）
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Taki Junichi, Shiga Hideaki, Inaki Anri, Wakabayashi Hiroshi, Washiyama Kohshin, Miwa Takaki, Kinuya Seigo
JOURNAL OF NUCLEAR MEDICINE 52 ( 4 ) 450 - 5 2011（ ISSN:0449-3060 ）
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高度嗅覚障害患者におけるTl-201鼻腔内投与による嗅神経シンチグラフィの試み
滝 淳一, 志賀 英明, 三輪 高喜, 鷲山 幸信, 若林 大志, 稲木 杏吏, 絹谷 清剛
核医学 47 ( 3 ) 380 - 381 2010.9（ ISSN:0022-7854 ）
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加味帰脾湯による嗅神経再生効果
志賀 英明, 土田 明日香, 鷲山 幸信, 山本 純平, 八木 清香, 吉崎 智一, 古川 仭, 天野 良平, 三輪 高喜
日本鼻科学会会誌 49 ( 3 ) 431 - 431 2010.7（ ISSN:0910-9153 ）
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Olfactory nerve scintigraphy in normal volunteer by per-nasal Tl-201 administration
Taki Junichi, Yamada Masato, Shiga Hideaki, Miwa Takaki, Washiyama Kohshin, Wakabayashi Hiroshi, Inaki Anri, Kinuya Seigo
JOURNAL OF NUCLEAR MEDICINE 51 2010.5（ ISSN:0161-5505 ）
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【核医学治療】アルファ線を利用した核医学治療
鷲山 幸信
PET Journal ( 9 ) 36 - 38 2010.3（ ISSN:2186-022X ）
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嗅神経画像評価のための201Tlオルファクトシンチグラフィの試み
三輪 高喜, 志賀 英明, 山本 純平, 宮澤 徹, 下出 祐造, 堀口 章子, 山田 奏子, 北村 みわ, 辻 裕之, 鈴鹿 有子, 土田 明日香, 鷲山 幸信, 天野 良平, 瀧 淳一, 絹谷 清剛
頭頸部自律神経 24 40 - 43 2010.3
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嗅神経画像評価のための201Tlオルファクトシンチグラフィの試み
24 40 - 43 2010.3
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Use of thallium transport to visualize functional olfactory nerve regeneration in vivo
Hideaki Shiga, Kohshin Washiyama, Kyoko Hirota, Ryohei Amano, Mitsuru Furukawa, Takaki Miwa
RHINOLOGY 47 ( 4 ) 460 - 4 2009.12（ ISSN:0300-0729 ）
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K. Ogawa, K. Shiba, N. Akhter, M. Yoshimoto, K. Washiyama, S. Kinuya, K. Kawai, H. Mori
Cancer Science 100 ( 11 ) 2188 - 92 2009.11（ ISSN:1347-9032 ）
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腫瘍のσ受容体画像化および放射性核種受容体療法に関する放射性ヨウ素標識vesamicolアナログの評価(Evaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy)
Ogawa Kazuma, Shiba Kazuhiro, Akhter Nasima, Yoshimoto Mitsuyoshi, Washiyama Kohshin, Kinuya Seigo, Kawai Keiichi, Mori Hirofumi
Cancer Science 100 ( 11 ) 2188 - 2192 2009.11（ ISSN:1347-9032 ）
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Tl-201鼻腔内投与による嗅神経シンチグラフィの試み 健常人における検討
滝 淳一, 山田 正人, 志賀 英明, 三輪 高喜, 鷲山 幸信, 若林 大志, 稲木 杏吏, 萱野 大樹, 絹谷 清剛
核医学 46 ( 3 ) 311 - 312 2009.9（ ISSN:0022-7854 ）
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Olfactory Nerve Imaging with SPECT/CT in Rats
志賀英明, 鷲山幸信, 小川数馬, 山口博司, 間賀田泰寛, 天野良平, 古川仭, 三輪高喜
日本鼻科学会会誌 48 ( 2 ) 138 - 141 2009.8（ ISSN:0910-9153 ）
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SPECT/CTによるラット嗅神経の画像評価
志賀 英明, 鷲山 幸信, 小川 数馬, 山口 博司, 間賀田 泰寛, 天野 良平, 古川 仭, 三輪 高喜
日本鼻科学会会誌 48 ( 2 ) 138 - 141 2009.8（ ISSN:0910-9153 ）
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Development of [Y-90]DOTA-conjugated bisphosphonate for treatment of painful bone metastases
Kazuma Ogawa, Hidekazu Kawashima, Kazuhiro Shiba, Kohshin Washiyama, Mitsuyoshi Yoshimoto, Yasushi Kiyono, Masashi Ueda, Hirofumi Mori, Hideo Saji
NUCLEAR MEDICINE AND BIOLOGY 36 ( 2 ) 129 - 35 2009.2（ ISSN:0969-8051 ）
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Safety of thalliumu-201 nasally administration for diagnosis of traumatic olfactory impairment
HIROTA Kyoko, SHIGA Hideki, TSUCHIDA Asuka, WASHIYAMA Koshin, AMANO Ryohei, MIWA Takaki, FURUKAWA Mitusuru
The Japanese journal of taste and smell research 15 ( 3 ) 527 - 528 2008.12（ ISSN:1340-4806 ）
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志賀英明, 鷲山幸信, 広田京子, 土田明日香, 小川数馬, 山口博司, 間賀田泰寛, 天野良平, 三輪高喜, 古川仭
日本味と匂学会誌 15 ( 3 ) 281 - 284 2008.12（ ISSN:1340-4806 ）
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自動血球計数装置pocH-100iVとKX-21NVを用いたマウス血球計測に関する基礎的検討
鷲山 幸信, 大波加 真弘, 天野 良平
Sysmex Journal 31 25 - 37 2008.12（ ISSN:0386-5509 ）
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Olfactory Nerve Scintigram with Nasal Administration of Thallium-201 in vivo
Hideaki Shiga, Kohshin Washiyama, Kyoko Hirota, Kazuma Ogawa, Hiroshi Yamaguchi, Yasuhiro Magata, Ryohei Amano, Takaki Miwa, Mitsuru Furukawa
CHEMICAL SENSES 33 ( 8 ) S98 - S98 2008.10（ ISSN:0379-864X ）
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Hideaki Shiga, Yayoi Kinoshita, Kohshin Washiyama, Daisuke Ogawa, Ryohei Amano, Kyoko Hirota, Toshiaki Tsukatani, Mitsuru Furukawa, Takaki Miwa
CHEMICAL SENSES 33 ( 7 ) 633 - 7 2008.9（ ISSN:0379-864X ）
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Yoshimoto M, Ogawa K, Washiyama K, Shikano N, Mori H, Amano R, Kawai K
International Journal of Cancer 123 ( 3 ) 709 - 15 2008.8（ ISSN:0020-7136 ）
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タリウム-201嗅神経シンチグラフィ臨床応用の予備研究
志賀 英明, 鷲山 幸信, 広田 京子, 土田 明日香, 天野 良平, 三輪 高喜, 古川 仭
日本鼻科学会会誌 47 ( 3 ) 276 - 276 2008.8（ ISSN:0910-9153 ）
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外傷性嗅覚障害モデルにおけるタリウム-201嗅神経イメージング
志賀 英明, 鷲山 幸信, 広田 京子, 天野 良平, 三輪 高喜, 古川 仭
日本耳鼻咽喉科学会会報 111 ( 4 ) 290 - 290 2008.4（ ISSN:0030-6622 ）
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Kinoshita Yayoi, Shiga Hideaki, Washiyama Kohshin, Ogawa Daisuke, Amano Ryohei, Ito Makoto, Tsukatani Toshiaki, Furukawa Mitsuru, Miwa Takaki
Chemical Senses 33 ( 1 ) 73 - 8 2008.1（ ISSN:0379-864X ）
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嗅糸切断モデルマウスを用いた201Tlの経鼻的投与法による脳内移行に関する基礎的検討
鷲山 幸信, 小川 大介, 天野 良平, 志賀 英明
核医学 44 ( 3 ) 262 - 262 2007.10（ ISSN:0022-7854 ）
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Comparison of myelotoxicities between Th-227-EDTMP and Ra-223 in rats
K. Washiyama, Y. Imakita, K. Ogawa, M. Yoshimoto, R. Amano, S. Kinuya, T. Mitsugashira, K. Kawai
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 33 S340 - S340 2006.9（ ISSN:1619-7070 ）
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Study of the acute radiation effects in amniocytes using X-ray
K. Washiyama, Y. Imakita, K. Ogawa, M. Yoshimoto, R. Amano, S. Kinuya, T. Mitsugashira, K. Kawai
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 33 S340 - S341 2006.9（ ISSN:1619-7070 ）
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227Th-EDTMP: a potential therapeutic agent for bone metastasis.
Washiyama K, Amano R, Sasaki J, Kinuya S, Tonami N, Shiokawa Y, Mitsugashira T
Nuclear medicine and biology 31 ( 7 ) 901 - 8 2004.10（ ISSN:0969-8051 ）
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Th-227-EDTMP: A potential therapeutic agent for bone metastasis
K Washiyama, R Amano, J Sasaki, S Kinuya, N Tonami, Y Shiokawa, T Mitsugashira
NUCLEAR MEDICINE AND BIOLOGY 31 ( 7 ) 901 - 908 2004.10（ ISSN:0969-8051 ）
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Th-227-EDTMP: A potential therapeutic agent for bone metastasis
K Washiyama, R Amano, J Sasaki, S Kinuya, N Tonami, Y Shiokawa, T Mitsugashira
NUCLEAR MEDICINE AND BIOLOGY 31 ( 7 ) 901 - 908 2004.10（ ISSN:0969-8051 ）
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Matsumura H., Aze T., Oura Y., Kikunaga H., Yokoyama A., Takamiya K., Shibata S., Otsuki T., Yuki H., Sakamoto K., Haba H., Washiyama K., Nagai H., Matsuzaki H.
Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms 223-224 ( SPEC. ISS. ) 807 - 811 2004.8（ ISSN:0168583X ）
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Yield measurements for Be-7 and Be-10 productions from Cu-nat, Ag-nat and Au-197 by bremsstrahlung irradiation at E-0=200 MeV
H Matsumura, T Aze, Y Oura, H Kikunaga, A Yokoyama, K Takamiya, S Shibata, T Otsuki, H Yuki, K Sakamoto, H Haba, K Washiyama, H Nagai, H Matsuzaki
NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS 223 807 - 811 2004.8（ ISSN:0168-583X ）
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Yield measurements for Be-7 and Be-10 productions from Cu-nat, Ag-nat and Au-197 by bremsstrahlung irradiation at E-0=200 MeV
H Matsumura, T Aze, Y Oura, H Kikunaga, A Yokoyama, K Takamiya, S Shibata, T Otsuki, H Yuki, K Sakamoto, H Haba, K Washiyama, H Nagai, H Matsuzaki
NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS 223 807 - 811 2004.8（ ISSN:0168-583X ）
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Amano R., Tarohda T., Washiyama K., Kanayama K., Ono M., Hamajima Y., Yamamoto M.
KURRI Progress Report 2004.4（ ISSN:09191038 ）
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Yield Measurements for ^7Be and ^<10>Be Productions from ^<nat>Cu, ^<nat>Ag and ^<197>Au by Bremsstrahlung Irradiation at E_0=200 MeV(II. Radiochemistry)
Matsumura H, Aze T, Oura Y, Kikunaga H, Yokoyama A, Takamiya K, Shibata S, Otsuki T, Yuki H, Sakamoto K, Haba H, Washiyama K, Nagai H, Matsuzaki H
Rsearch report of Laboratory of Nuclear Science,Tohoku University 36 67 - 72 2003.11（ ISSN:0385-2105 ）
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Tsuji T., Yabushita Y., Tarohda T., Kanayama Y., Washiyama K., Amano R.
Journal of Radioanalytical and Nuclear Chemistry 258 ( 1 ) 49 - 53 2003.10（ ISSN:02365731 ）
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Elemental concentration of manganese and potassium in brain and other organs of fetal, sucking and developmental mice
T Tsuji, Y Yabushita, T Tarohda, Y Kanayama, K Washiyama, R Amano
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY 258 ( 1 ) 49 - 53 2003.9（ ISSN:0236-5731 ）
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Elemental concentration of manganese and potassium in brain and other organs of fetal, sucking and developmental mice
T Tsuji, Y Yabushita, T Tarohda, Y Kanayama, K Washiyama, R Amano
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY 258 ( 1 ) 49 - 53 2003.9（ ISSN:0236-5731 ）
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Yabushita Y., Kanayama Y., Tarohda T., Tuji T., Washiyama K., Amano R.
Journal of Radioanalytical and Nuclear Chemistry 257 ( 2 ) 399 - 403 2003.8（ ISSN:02365731 ）
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Regional distribution of manganese, iron, copper and zinc in the rat brain during development
Amano R., Tarohda T., Washiyama K., Kanayama K., Ono M., Hamajima Y., Yamamoto M.
KURRI Progress Report 2003.4（ ISSN:09191038 ）
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Brain regional distribution of the minor and trace elements, Na, K, Sc, Cr, Mn, Co, Zn and Se, in mice bred under Zn-deficient, -adequate and -excessive diets
Y Yabushita, Y Kanayama, T Tarohda, T Tuji, K Washiyama, R Amano
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY 257 ( 2 ) 399 - 403 2003（ ISSN:0236-5731 ）
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Photorission of Au-197 and Bi-209 at intermediate energies
H Haba, K Sakamoto, M Igarashi, M Kasaoka, K Washiyama, H Matsumura, Y Oura, S Shibata, M Furukawa, Fujiwara, I
CZECHOSLOVAK JOURNAL OF PHYSICS 53 ( supplement ) A265 - A271 2003（ ISSN:0011-4626 ）
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Photorission of Au-197 and Bi-209 at intermediate energies
H Haba, K Sakamoto, M Igarashi, M Kasaoka, K Washiyama, H Matsumura, Y Oura, S Shibata, M Furukawa, Fujiwara, I
CZECHOSLOVAK JOURNAL OF PHYSICS 53 ( supplement ) A265 - A271 2003（ ISSN:0011-4626 ）
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Brain regional distribution of the minor and trace elements, Na, K, Sc, Cr, Mn, Co, Zn and Se, in mice bred under Zn-deficient, -adequate and -excessive diets
Y Yabushita, Y Kanayama, T Tarohda, T Tuji, K Washiyama, R Amano
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY 257 ( 2 ) 399 - 403 2003（ ISSN:0236-5731 ）
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Photofission of <sup>209</sup>Bi at intermediate energies
Haba H., Kasaoka M., Igarashi M., Sakamoto K., Washiyama K., Matsumura H., Oura Y., Shibata S., Furukawa M., Fujiwara I.
Radiochimica Acta 90 ( 37438 ) 371 - 382 2002（ ISSN:00338230 ）
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Photofission of Bi-209 at intermediate energies
H Haba, M Kasaoka, M Igarashi, K Washiyama, H Matsumura, Y Oura, S Shibata, K Sakamoto, M Furukawa, Fujiwara, I
RADIOCHIMICA ACTA 90 ( 7 ) 371 - 382 2002（ ISSN:0033-8230 ）
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Photofission of Bi-209 at intermediate energies
H Haba, M Kasaoka, M Igarashi, K Washiyama, H Matsumura, Y Oura, S Shibata, K Sakamoto, M Furukawa, Fujiwara, I
RADIOCHIMICA ACTA 90 ( 7 ) 371 - 382 2002（ ISSN:0033-8230 ）
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Photofission of ^<197>Au at Intermediate Energies
HABA H., IGARASHI M., WASHIYAMA K., MATSUMURA H., YAMASHITA M., SAKAMOTO K., OURA Y., SHIBATA S., FURUKAWA M., FUJIWARA I.
Journal of Nuclear and Radiochemical Sciences 1 ( 2 ) 53 - 61 2000（ ISSN:1345-4749 ）
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Target-dependence of light fragment production in photonuclear reactions at intermediate energies
H Matsumura, K Washiyama, H Haba, Y Miyamoto, Y Oura, K Sakamoto, S Shibata, M Furukawa, Fujiwara, I, H Nagai, T Kobayashi, K Kobayashi
RADIOCHIMICA ACTA 88 ( 6 ) 313 - 328 2000（ ISSN:0033-8230 ）
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Target-dependence of light fragment production in photonuclear reactions at intermediate energies
H Matsumura, K Washiyama, H Haba, Y Miyamoto, Y Oura, K Sakamoto, S Shibata, M Furukawa, Fujiwara, I, H Nagai, T Kobayashi, K Kobayashi
RADIOCHIMICA ACTA 88 ( 6 ) 313 - 328 2000（ ISSN:0033-8230 ）
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Target-dependence of light fragment production in photonuclear reactions at intermediate energies
Matsumura H., Washiyama K., Haba H., Miyamoto Y., Oura Y., Sakamoto K., Shibata S., Furukawa M., Fujiwara I., Nagai H., Kobayashi T., Kobayashi K.
Radiochimica Acta 88 ( 6 ) 313 - 328 2000（ ISSN:00338230 ）
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Photofission onf197Au at Intermediate Energies.
HABA H., IGARASHI M., WASHIYAMA K., MATSUMURA H., YAMASHITA M., SAKAMOTO K., OURA Y., SHIBATA S., FURUKAWA M., FUJIWARA I.
J. NUCL. RADIOCHEM. SCI. 1 ( 2 ) 53 - 61 2000（ ISSN:1345-4749 ）
Books
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秋光信佳, 溝口勝（Column がん治療に対する放射線とアイソトープ（RI）の新しい利用法）
東京大学出版会 2021.5 （ ISBN:978-4-13-052030-0 ）
Presentations
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遠隔操作可能な合成装置を用いた[211At]MABGの合成とその品質評価
日本薬学会第139年会
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有効射程100μmの核弾頭を用いDDS
理研シンポジウム エンジニアネットワーク・ワークショップ 精密武装抗体の合成と機能評価
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動物実験における短寿命アルファ線核種の体内外の分布
日本放射線安全管理学会 第17回学術大会
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短寿命アルファ線核種Ac-225 の合理的規制に向けた飛散率測定
日本放射線安全管理学会 第17回学術大会
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合理的規制のためのラジウム-223およびその子孫核種の飛散率等の測定
日本放射線安全管理学会 第17回学術大会
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短寿命アルファ線放出核種At-211の合理的規制に向けた飛散率測定
日本放射線安全管理学会 第17回学術大会
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短寿命α線核種の飛散率等の基礎データ取得と合理的法規制に向けた安全性検証と放射線管理法の開発
日本放射線安全管理学会 第17回学術大会
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垂直照射法を用いた211Atの製造に関する諸条件の検討
第58回日本核医学会学術総会
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[211At]MABGの⾃動合成装置を⽤いた製造と品質評価
第58回日本核医学会学術総会
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⼩動物⽤飼育ケージ内でのAt-211⽔溶液の⾶散の空間分布の評価
第58回日本核医学会学術総会
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正常マウスにおけるフリー211Atおよびmeta-[211At]astaobenzylguanidine (MABG)の体内動態
第58回日本核医学会学術総会
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225Ac/213Biと211Atの核薬学研究の最先端
第58回日本核医学会学術総会
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Astatine-211の乾式分離法の検討
第58回日本核医学会学術総会
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ラドンガス密封シリンジを利用したRn-At ジェネレーターシステムの開発
第62回放射化学討論会
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短寿命α線核種の合理的規制のためのデータ取得による安全性検証と安全管理・教育方法の開発
第62回放射化学討論会
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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 ―131I との抽出挙動の比較及び酸化剤の効果の調査―
第62回放射化学討論会
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中型サイクロトロンを用いた211At の製造と化学分離
第62回放射化学討論会
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Advanced Clinical Research Center of Fukushima Medical University: two cyclotrons installed facility for basic research and clinical application of medical radioisotopes
17th International Workshop on Targetry and Target Chemistry (WTTC17)
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Initial Experiences on the Production of Astatine‐211 at Fukushima Medical University using “CYPRIS MP-30” Cyclotron
17th International Workshop on Targetry and Target Chemistry (WTTC17)
Research Projects
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がん幹細胞をターゲットとしたα線放出核種を用いた革新的な白血病治療法の開発
Grant number：20H03626 2020.4 - 2023.3
基盤研究(B)
趙 松吉, 池添 隆之, 鷲山 幸信, 西嶋 剣一, 粟生木 美穂, 杉山 暁, 右近 直之, 織内 昇
Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）
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Optimization of pretargeted alpha therapy for multiple types of cancer
Grant number：20H03627 2020.4 - 2023.3
Grant-in-Aid for Scientific Research (B)
Grant amount：\17680000 （ Direct Cost: \13600000 、 Indirect Cost：\4080000 ）
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New application of Ge/Ga generator of nuclear medicine for science education: to students in high schools, undergraduate courses for university students, general public
Grant number：18K02991 2018.4 - 2021.3
Grant-in-Aid for Scientific Research (C)
Grant amount：\2470000 （ Direct Cost: \1900000 、 Indirect Cost：\570000 ）
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アスタチン・ジェネレータシステム構築のための放射性ラドンの化学
Grant number：17K05807 2017.4 - 2020.3
基盤研究(C)
横山 明彦, 鷲山 幸信
Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）
当該年度は主たる利用加速器である日本原子力研究開発機構のタンデムバンデグラフ加速器が回復し、予定していた加速器実験であるLiイオン照射を3回（6月、11月、12月）実施することができたので、ラドン-アスタチン（Rn-At)系の分離精製実験を進めることができた。アスタチン（At)単独の実験については理化学研究所からAｔを3回製造輸送してもらえたのを始め、福島県立医大との共同研究により2回製造輸送ができた。そのためアスタチン抽出実験についての研究も昨年度以上に実施できた。特に薄層クロマトグラフィーを利用したアスタチン化学種同定を始めて、抽出系には複数以上の化学形が関与することが判明し、抽出にかかわるより精密なデータ解析が可能になった。また昨年度から導入したクラウンエーテルを混入させたイオン液体の系は、アスタチン抽出に有効であることが分かったが、水酸化ナトリウム溶液を用いる逆抽出の条件も見出すことができて取り出しのスキーム全体について開発が進んだ。Rn-Atジェネレータの実験では、Rnガスについてシリンジに気相で取り出して保持する方法も開発できたので、Rn扱い方法の選択肢を増やすことができ、ジェネレータのプロトタイプ設計に一歩進んだと考える。また、副生成物であるポロニウム（Po）の除去について新たに取り組んで、有用な陽イオン交換樹脂系を見出した。このPo除去の過程もジェネレータにシステムとして取り込む目途がついた。天然のラドンガスを用いた溶解実験では、水のクラスターとの相互作用の理論計算と比較して溶解状態についての知見を得られたので、これについては国際学会（第18回国際放射化学会議）での発表とともに投稿論文としての発行も果たした。その他の成果は2018年度日本放射化学会・放射化学討論会において発表した。
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Grant number：16H02668 2016.4 - 2019.3
Grant-in-Aid for Scientific Research (A)
Kinuya Seigo
Grant amount：\42380000 （ Direct Cost: \32600000 、 Indirect Cost：\9780000 ）
Preclinical study regarding development of highly effective alpha targeted radiotherapy was performed with 211At. Sufficient amount of 211At could be obtained for clinical application after the optimization of irradiation parameters and conditions of cyclotron. Cyclic RGD peptide against αVβ3 integrin was effectively labeled with 211At as [211At]c[RGDf(4-At)K] at high yield. This radio-compound specifically attached the target molecules and accumulated into tumor xenografts.For imaging, drug design using DOTA as a chelating agent was conducted. Information of radiation protection,regulatory science for the future clinical application was obtained. In addition, platform to obtain clinical POC has been established. The progress in 211At medical usage was reported at several domestic and international conferences.
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Grant number：16K14533 2016.4 - 2018.3
Grant-in-Aid for Challenging Exploratory Research
Yamamura Tomoo
Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）
UPc2 complexes were successfully prepared by using the newly-developed heating-block method. Phthalocyanine complexes were successfully purified and its single crystals were obtained by sublimation process. Also, single crystals of [UPc]+ were prepared by electrolysis and the purified complex of superphthalocyanine UO2SPc were prepared. These sublimation transferring method process were developed for samples for AFM. All the processes were designed to be dealt in the glove-box for alpha-emitters.
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物質の三態を制御したRn/Atジェネレータの開発とα線内用療法への展開（国際共同研究強化）
Grant number：15KK0301 2016 - 2019
国際共同研究加速基金(国際共同研究強化)
鷲山 幸信
Grant amount：\14170000 （ Direct Cost: \10900000 、 Indirect Cost：\3270000 ）
2018年度は、予定していた二度目の海外滞在を行い、1）アルゴンヌ国立研究所での滞在中に211Rnの製造実験を行った。また2）デューク大学に滞在し無極性の有機溶媒に対する硝酸溶液下での211Atの溶媒抽出挙動に関する検討を引き続き行った。さらに3）北米でα線を用いた核医学利用の研究を実施している大学ならびに研究所に訪問し、ネットワークの構築を行った。具体的には以下の通りである。
1）アルゴンヌ国立研究所では、受入担当であるJerry A. Nolen氏らとともにタンデム型加速器ATLASを用いて211Rnの製造を行った。アルゴンヌでの211Rn製造は、現地にとっても初めての試みであったため、手始めとして酸化ビスマスを密閉されたチャンバーに封入し、その中の核反応で生成した211Rnを活性炭に吸着させて外部からγ線の計測を行って、その生成量を評価した。211Rnの製造中はターゲット周囲の中性子による線量率が高くなるため、安全管理のスタッフと共に実験環境を構築しながらの実験を行った。次回以降の実験はOff-lineで行う予定である。
2）デューク大学で実施した無極性の有機溶媒に対する硝酸溶液下での211Atの溶媒抽出挙動に関する検討では、抽出後のAtの酸化状態を薄層クロマトグラフィーで評価し、少なくとも3種の化学状態の存在を認めた。帰国後も引き続き福島県立医科大学にて研究を継続している。福島県立医科大学は2018年度に211At製造条件の最適化を行い、現在1GBqの製造を定常的に達成しているため、高放射能による有機溶媒の放射線分解に関する影響を調べることが可能となった。
3）半年間の滞在中に、ワシントン大学とフレッドハッチンソンがん研究センター（シアトル）、ブルックヘブン国立研究所（アップトン）、スローンケタリングがんセンター（ニューヨーク）に訪問し互いの情報交換や意見交換を行った。 -
Sophistication of a Rn-211/At-211 generator system for medical use
Grant number：15K04741 2015.4 - 2019.3
Grant-in-Aid for Scientific Research (C)
NISHINAKA Ichiro, YOKOYAMA Akihiko, WASHIYAMA Kohshin
Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）
Sophistication of a Rn-211/At-211 generator system has been studied to supply an alpha radioactive radioisotope At-211 which is a promissing candidate for targeted alpha therapy of cancers.
Sophistication of an apparatus for the separation and the prification of Rn-211, which was produced by irradiating Bi-209 targets with 60 MeV Li-7 beams at the JAEA tandem accelarator, made it possible to recover Rn-211 from the targets with high yields more than 99.9% and high purity by a simple operation within 30 min. Sophistication of an apparatus for the preparation of an At-211 tracer solution with liquid extraction, in which At-211 was produced through EC-decay of Rn-211, provided approximately 45% recovery yields by a simple operation within 30 min.
Astatine was separated and identified as anions of At-, AO3- and AtO4- by TLC and HPLC. -
Development of radiolabeled compound for diagnosis and therapy of primary tumor and bone metastases
Grant number：15K09948 2015.4 - 2018.3
Grant-in-Aid for Scientific Research (C)
Ogawa Kazuma, WASHIYAMA Kohshin, NAKAYAMA Morio, Ishizaki Atusshi
Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）
A probe containing an aspartic acid peptide linker (D11) as a carrier to bone metastases, an RGD peptide [c(RGDfK) peptide] as a carrier to the primary cancer, and Ga-DOTA as a stable radiometal complex for imaging in one molecule, 67Ga-DOTA-D11-c(RGDfK), was prepared and evaluated to detect both the primary cancer and bone metastases simultaneously. Biodistribution experiments and single photon emission tomography (SPECT) imaging using tumor-bearing mice were performed. 67Ga-DOTA-D11-c(RGDfK) exhibited high uptake in bone and tumor. The accumulation of 67Ga-DOTA-D11-c(RGDfK) in tumor decreased when it was co-injected with c(RGDfK) peptide. Since 90Y-DOTA-D11-c(RGDfK) showed similar characteristics, they have great potential as theranostics system for diagnosis and therapy of both the primary cancer and bone metastases simultaneously.
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Development of a matter phase controlled Rn/At generator for targeted alpha therapy
Grant number：26461848 2014.4 - 2018.3
Grant-in-Aid for Scientific Research (C)
Washiyama Kohshin
Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）
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. -
Development of At-211 labeled peptides for the targeted alpha therapy
Grant number：26461872 2014.4 - 2017.3
Grant-in-Aid for Scientific Research (C)
Watanabe Shigeki, Ohshima Yasuhiro, Sasaki Ichiro
Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）
The use of alpha emitting radionuclides has been promising for development of targeted radionuclide therapy (TRT) because alpha particles give heavier damage to the cell by smaller dose than beta particles which has been employed for the TRT. In this study, we have successfully developed a novel isolation method of alpha emitting astatine-211 from an irradiated Bi target, and At-211 labeled peptides which have high affinity to HER2 overexpressing in some cancer cells such as breast cancer.
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Olfactory training in daily diet and imaging analysis for the olfactory nerve regeneration.
Grant number：25462670 2013.4 - 2017.3
Grant-in-Aid for Scientific Research (C)
SHIGA Hideaki, TAKI Junichi, KINUYA Seigo, WASHIYAMA Kohshin, AMANO Ryohei, YAMAMOTO Junpei
Grant amount：\5200000 （ Direct Cost: \4000000 、 Indirect Cost：\1200000 ）
The subjects with olfactory disorders were randomly selected from among patients who received follow-up visits at the smell clinic at the Kanazawa Medical University Hospital and who gave written informed consent. The subjects were randomized to the nasal stimulation group or the oral stimulation group in the clinical trials with three months olfactory rehabilitation. The achievement ratio of self-training was not significantly different between the two groups. Olfactory thresholds were not improved after three months olfactory rehabilitation in both groups. The olfactory transport of nasally administered thallium-201 was reduced in the patients with olfactory disorders in clinical trials with olfacto-scintigraphy. Furthermore, the nasal transport of insulin-like growth factor-1 to the brain was inhibited in mice with the resected olfactory bulbs.
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Grant number：23550072 2011.4 - 2015.3
Grant-in-Aid for Scientific Research (C)
AMANO Ryohei, WASHIYAMA Kohshin, MIYATI Toshiaki, SHIGA Hideaki
Grant amount：\5330000 （ Direct Cost: \4100000 、 Indirect Cost：\1230000 ）
To assess a radiation energy trannsfer to olfactory bulb from 201Tl localized in nasal cavity, a new site informatic index of nasal cavity and right/left olfactory bulb was given on a digital phantom, Digimouse, to use Monte Carlo simulation for MIRD internal dose computation. And to compare the energy transfers to tumor tissue by alpha-rays emitted among various heavy nuclides and their chemicals localized at the same place, 227Th and 223Ra in the actinium series, and 225Ac in the neptunium series were focused in terms of labeling procedure of their compounds, and observation of localizing in tumor tissue, were discussed by compareing the isotopes(equal Z nuclides) in uranium series and thorium series.
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Grant number：23689056 2011.4 - 2014.3
Grant-in-Aid for Young Scientists (A)
WASHIYAMA Kohshin
Grant amount：\10400000 （ Direct Cost: \8000000 、 Indirect Cost：\2400000 ）
Although an alpha emitter astatine-211 is the most promising raddionuclide 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 product facilities.
211Rn was prodcued by 209Bi(7Li, 5n)211Rn reaction at the JAEA-Tokai tandem accelerator. The irradiated target was dissolved in dilute nitric acid and 211Rn was extracted by solvent extraction using dodecane as a organic solvent. The dodecane was stand for 12 hours to generate 211At, then 211At was back extracted using methanol. It was found that exraction rate of 211Rn into dodecane was 82% while target material and other by-product radionuclides were hardly extracted. The recovery yield of 211At form dodecane to methanol was 98%.
These results showed that 211Rn/211At generator using solvent extraction system is easy to handle and will be feasible product. -
Grant number：23659581 2011 - 2012
Grant-in-Aid for Challenging Exploratory Research
WASHIYAMA Kohshin
Grant amount：\3510000 （ Direct Cost: \2700000 、 Indirect Cost：\810000 ）
Alpha-particle emitting radionuclides are gaining attention inthe field of nuclear medicine. Because of their high linear energy transfer and the short range of alpha particles in tissues, alpha-emitters (211At, 223Ra, and 225Ac) show promise in treating tumors such as leukemia, melanoma, and bone metastases. In this study, labeling of alpha emitter to a peptide DOTA-Re(Arg11)CCMSH, which bound specifically to a receptor expressed on melanoma cells, were evaluated. Preliminary results using gamma-ray emitter 111In showed a high uptake of DOTA-Re(Arg11)CCMSH in melanoma tumors. Therapeutic studies using 225Ac and 227Th are currently underway.
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An application of accelerator produced alpha-emitting radionuclide for radionuclide therapy
Grant number：20790886 2008 - 2010
Grant-in-Aid for Young Scientists (B)
WASHIYAMA Kohshin
Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）
Targeted alpha therapy (TAT) has been applied for cancer therapy and many clinical studies have been performed. Uranium-230 is a promising cyclotron produced alpha-emitting radionuclide for TAT. According to the reaction ^<232>Th(p, 3n)^<230>Pa and following the β- decay of ^<230>Pa, ^<230>U can be produced within the irradiated target. The daughter of ^<230>U, ^<226>Th (T_<1/2>=31m) provides a rapid cascade of 4 alpha particles with a 27.7MeV of total energy. In this study, we investigated the availability of production and radiochemical separation of ^<230>U and its daughters. Protactinium-230 was produced by irradiation of ^<232>ThO_2 target. After irradiation, the target was separated and ^<230>U/^<226>Th generator was constructed. Eluted ^<226>Th from generator was radiolabeled with bone seeking chelate, EDTMP and injected into mice for biodistribution evaluation. Most of all radioactivity were retained on bone.
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Grant number：20550059 2008 - 2010
Grant-in-Aid for Scientific Research (C)
AMANO Ryohei, WASHIYAMA Koushin, MIYATI Toshiaki, YOKOYAMA Akihiko
Grant amount：\5070000 （ Direct Cost: \3900000 、 Indirect Cost：\1170000 ）
In this study, several information and data on the in-vivo-localization of transition metal in brain were obtained by the use of four different nuclear probe detection methods. Especially, using RI technique, we found that trace heavy Tl ion transfers directly from nose to brain bypassing BBB. Intranasal administration of other metal ions was also examined by multi-tracer method. On the bases of results, the usefulness of ^<201>TlCl in rhinological fields was proposed to our other related projects. In correlation of metal imaging and MRI technique, we examined the detection of Mn in brain and behavior of Gd-DTPA in kidney.
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Grant number：19390317 2007 - 2009
Grant-in-Aid for Scientific Research (B)
KINUYA Seigo, KAWAI Keiichi, YOSHIMOTO Mitsuyoshi, WASHIYAMA Koshin, OGAWA Kazuma
Grant amount：\11570000 （ Direct Cost: \8900000 、 Indirect Cost：\2670000 ）
This study aimed to enhance therapeutic efficacy of targeted radionuclide therapy with ^<131>I-MIRG for malignant refractory neuroendcrine tumors. Locoregi onal administration of ^<131>I-MTRG was found to better prolong survival of mice with disseminated tumors than systemic administration. Feasibility of high-dose therapy based on dosimetric analysis was determined firstly in Japan. Fusion images of single photon emission computed tomography (SPFCT) and x-ray CT enabled precise detection of lesions and provided information for accurate dosimetry.
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非平衡型複数α線放出インビボジェネレーターを利用した転移性骨腫瘍治療法の開発
Grant number：18790881 2006 - 2007
若手研究(B)
鷲山 幸信
Grant amount：\2600000 （ Direct Cost: \2600000 ）
これまでに転移性骨腫瘍治療の際に副作用(特に骨髄毒性)を起こさない投与量(最大耐用線量)を決定(^<227>Th-EDTMP:250kBq/kg)した。今年度はさらにα線放出薬剤^<227>Th-EDTMPによる転移性骨腫瘍の治療効果を検証するために、1)骨転移モデルラットを作製し、擬似的に作成した骨転移がどのようにして形成されるかを経時的に観察し、2)α線による疼痛緩和および抗腫瘍効果について検討した。雌性Sprague-Dawley(SD)ラットの左足膝関節から足方1cm遠方の部位に同系乳癌細胞MRMT-1(3×10^3個/3μL)を移植した骨転移モデルラット作製し、骨転移形成の形態画像及び機能画像による経時的評価の検討をした。作製2週間後には全てのラットにおいて単純X線写真上の溶骨化および骨診断用放射性医薬品の集積による骨転移形成が確認された。次にモデルラット作製2週間後に^<227>Th-EDTMPを尾静脈投与し、von Frey filament test及び腫瘍体積測定による治療効果、体重測定及び血球数測定による骨髄毒性を検討した。比較対象にはRI非投与群を作製した。結果として^<227>Th-EDTMPによる骨髄毒性は表れなかったが、治療効果があったと判定するのは困難であった。von Frey filament testによりα線による疼痛緩和を確認できたが、腫瘍体積は^<227>Th-EDTMP投与群および非投与群共に増加した。骨腫瘍が骨髄内から骨外へ浸潤した場合、α線で治療を行うことは、α線の飛程と腫瘍サイズの問題から困難であると考えられる。骨転移が形成に於いて、より早期の段階での治療がα線を用いる場合には有用であることが考えられる。今後さらに骨転移の状態や転移癌の種類を変化させながらの詳細な検討をする必要性がある。
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Development of specific, universal targeted radiotherapy through induction of avidin on cancer cell membrane and internalization of scavenger receptor
Grant number：16591194 2004 - 2006
Grant-in-Aid for Scientific Research (C)
KINUYA Seigo, KAWAI Keiichi, WASHIYAMA Koshin, YOSHIMOTO Mitsuyoshi
Grant amount：\3600000 （ Direct Cost: \3600000 ）
1. We aimed to develop effective non-toxic targeted radiotherapy for malignant tumors. A complex of avidin that has intense binding affinity to biotin and scavenger receptors that would internalize radiolabeled biotin into cells via endocytosis processs. In order to attain this complex named Scavidin, genes determining each molecules were cloned. That is hSR-A-II for human scavenger receptor. Total RNA fraction was extracted from human monocytic leukemia cells, THP-1, after loading 12-o-tetradecanoyl phorbol-13-acetate. hSR-A-II cDNA was amplified by PCR. Avidin cDNA was similarly cloned from materials of fallopian tubes of chicken. A complex coding Scavidin was then obtained by inserting avidin cDNA so that endocytotic functions of hSR-A-II would not be destroyed.
2. Characteristics of radionuclides labeled to targeting molecules extremely affect both effectiveness and toxicity of targeted radiotherapy. Superiority of targeted radiotherapy with ^<186>Re to that with ^<131>I was determined in animal models bearing colon cancer metastases.
3. Pre-therapeutic prediction of therapeutic outcomes is a key for so-called tailor-made management of cancer patients ; therefore, scintigraphic assessment with a cationic compound, "mTc-sestamibi, was investigated. -
壊変系列を伴うα線放出核種の化学的変化に対応できるビオチン誘導キレート薬剤の開発
Grant number：14770448 2002 - 2004
若手研究(B)
鷲山 幸信
Grant amount：\3900000 （ Direct Cost: \3900000 ）
本研究ではα線放出核種を対象として、これらの核種を治療に使用するために必要な二官能性キレート薬剤を開発することを目的としてきた。そのための基礎的な条件としてキレート剤の選定、およびキレートと結合した放射性核種が壊変後においても結合を維持できるかといった項目を検討してきた。この検討の際に、骨へ集積しやすいラジウム(Ra)やトリウム(Th)、特にアクチニウム系列核種^<227>Th(T_<1/2>=18.72d)と骨親和性のキレート剤であるEDTMPとの錯体を合成し、動物実験の結果から^<227>Thの選択的骨集積および娘核種^<223>Ra(T_<1/2>=11.435d)の高い骨内保持を確認した(昨年度の報告)。本実験ではさらに^<223>Ra以降の娘核種^<211>Pb(T_<1/2>=36.1m)の骨内保持に関して検討を行った。Raの持つ高い骨集積性と娘核種の骨内保持に影響を与える因子を確認するために^<223>Raと同じ壊変様式を示すトリウム系列核種^<224>Ra(T_<1/2>=3.66d)を用い、それぞれの娘核種^<211>Pb,^<212>Pbの骨内保持率を比較検討した。
Raは骨に対し特異的に集積し、^<223,224>Ra同位体間の集積の違いは見られなかった。投与後初期から経時的に軟組織からのRaの早いクリアランスが観測されたが、骨での取り込み率は一定であった。^<211>Pbは^<223>Ra投与後の経過時間が長期化(3時間後:68.4%,2日後:77.4%,7日後:85.3%)するほど^<211>Pbの骨内保持率は上昇した。これに対し^<212>Pbは^<224>Ra投与後2日で39.1%であった。Pb元素の持つ骨親和性や、系列中のPo同位体の半減期が非常に短いことなどから、Pbの骨内保持には希ガス元素のRnの半減期が重要であることが確認された。特に^<211>Pbの場合、親核種の^<219>Rnの半減期が短い(T_<1/2>=3.96秒)ことが骨からの遊離を少なくしていると考えられる。さらにPb保持率の時間依存性が見られたことからRaの骨内への内在化が示唆された。この結果は^<227>Th-EDTMPを転移性骨腫瘍治療に用いる際に、^<223>Ra以下の娘核種が高い割合で長期間骨に保持され、その結果高い線量を腫瘍に対して照射できる可能性を支持している。 -
Brain regional distributions of some transient metals and their bioinorganic chemical studies by the use of multielemental analysis.
Grant number：14540512 2002 - 2004
Grant-in-Aid for Scientific Research (C)
AMANO Ryohei, WASHIYAMA Koshin, ENOMOTO Shuichi
Grant amount：\3100000 （ Direct Cost: \3100000 ）
This study was undertaken in order to acquire better understanding of the brain regional biobehavior of some transient metals and their bioinorganic chemical studies by the nuclear probe techniques of the multitracer. The followings were found. 1).Mn, Fe, Cu and Zn concentrations were determined in the brain regions of normal Wistar rats using inductively coupled plasma mass spectrometry (ICP-MS), and their maps were illustrated to compare visually the distribution of the elements at the stage of the growth process. Among new findings about their brain distribution, it is especially worth noting that high concentrations of Mn, Fe and Zn were observed in the substantia nigra compared with those in neighboring regions. 2)Using the above technique, the changes in Mn, Fe, Cu and Zn concentrations were also examined in the brain of a 6-hydroxydopamine (OHDA)-induced rat model of Parkinson's disease. The results indicated that Mn, Fe, Cu and Zn levels were increased in the 6-OHDA-lesioned substantia nigra, amygdala and putamen. A marked increase in Fe level was observed in the substantia nigra of model rats. The increase in manganese level occurred earlier than those in the other elements reaching a plateau in the 6-OHDA brain, especially in the substantia nigra. The patterns in these 4 elements may hold the key to the development of Parkinson's disease. 3)We observed the direct transport of radioactive ^<86>Rb^+ and ^<201>Tl^+ via the olfactory nerve transport following intranasal administration in mice. These results evidently indicated the axonal transport of the via the olfactory nerve pathway, from nasal cavity to the olfactory bulb, and moreover to the olfactory cortex through the synaptic junctions. The olfactory transport of the ^<86>Rb^+ and ^<201>Tl^+ should represent the behavior of K^+ in the olfactory system.
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Development ofradiopharmaceuticals for palliative therapy of painful osseous metastases
Grant number：12670860 2000 - 2001
Grant-in-Aid for Scientific Research (C)
TAKAYAMA Teruhiko, ONOGUCHI Masaharu, TSUJI Shiro, AMANO Ryohei, WASHIYAMA Kohshin
Grant amount：\2300000 （ Direct Cost: \2300000 ）
Lutetiura-177(^<177>Lu) has 176(12.2 %), 384(9.1%) and 497(78.6%)keV beta particle emissions which are suitable for tissue irradiation. Gamma emissions of 113(6.4%) and 208(ll.9%)keV allow gamma imaging. Its physical half-life(6.75 days) is reasonable in terms of shelf life.
The preparation of ^<177>Lu-EDTMP(ethylene diamine tetramethylene phosphonic acid) is very simple and this chelate is very stable. In our animal study, ^<177>Lu-EDTMP showed suitable characteristics of rapid blood clearance and selective uptake on bone, which would be necessary for the treatment of palliative pain of bone metastases. The major adverse side effects after administration of ^<177>Lu-EDTMP were platelet and white blood cell count depression. The present study was undertaken to observe the influence of ^<177>Lu-EDTMP on bone marrow. It was clarified that acute radiation death of mouse did not occur by administration of 5MBq, 10MBq or 15MBq of ^<177>Lu-EDTMP, while these dose are likely to cause some myelosuppresion.
And the calculations of radiation dose were performed by utilizing animal distribution data and die MIRD formulations. Estimated radiation dose of bone, bone marrow and whole body were 36.88mGy/3 7MBq, 39.12mGy/37MBq and 5.54mGy/37MBq, respectively.
^<177>Lu-EDTMP appears to be a useful new compound for the palliation of painful skeletal metastases. -
Bioinorganic chemical studies on metal superoxide dismutases and their behavior in brain by the use of multielemental analysis.
Grant number：10640539 1998 - 2000
Grant-in-Aid for Scientific Research (C)
AMANO Ryohei, ENOMOTO Shuichi, WASHIYAMA Koshin
Grant amount：\3100000 （ Direct Cost: \3100000 ）
This study was undertaken in order to acquire better understanding of the biobehavior metal superoxide dismutases by the techniques of multitracer and instrumental neutron activation analysis. The followings were found.
1) The radioactive multitracer technique was applied to a study on the uptake behavior of trace elements in normal C57BL/6N mice. Comparative uptake behavior of ^<46>Sc, ^<54>Mn, ^<59>Fe, ^<58>Co, ^<65>Zn, ^<75>Se, ^<83>Rb and ^<88>Zr tracers was examined among 11 organs (brain, cardiac muscle, lung, liver, spleen, pancreas, kidneys, bone, muscle, eyeballs and testes) and blood, and evaluated in terms of the "tissue uptake rate (the radioactivity percentage of injected dose per gram of tissue, %dose/g)". The multitracer technique revealed reliable data demonstrating characteristic uptake of the 8 trace elements, Sc, Mn, Fe, Co, Zn, Se, Rb and Zn by the brain and other organs, as well as the distinctive feature of the accumulation and retention of each element in the brain. According to these results, it is evident that the metal ions examined in this work are easily transported into the brain, in addition, the high retention of Se, Rb, Mn and Zn in the brain during a fairly long time suggests active involvement of these elements in the brain function.
2) Brain regional uptakes for ^<46>Sc, ^<54>Mn, ^<58>Co, ^<65>Zn, ^<75>Se, and ^<83>Rb in mice were examined using multitracer under deficient and excessive states of an essential trace elements, manganese, zinc or selenium. Zn-deficient and excessive states, and Se-deficient and excessive states influence the brain regional uptake behaviors of other trace elements except respective elements. On the other hand, in the mouse brain under Mn-deficient and excessive states, few interrelation between Mn and other elements was found from 0.4ppm to 300.4ppm. Multitracer technique was found to be very useful to screen the element-element interrelation in brain.
3) Concentrations and uptake behavior of manganese (Mn), zinc (Zn) and selenium (Se) in mouse brain were studied by means of multitracer technique, neutron activation analysis and autoradiography. Comparative concentrations of Mn, Zn and Se and tracer uptake behavior of ^<54>Mn, ^<65>Zn and ^<75>Se were examined in the brain of 1-, 4-, 8-, 21- and 56-day-old mice, and evaluated in terms of brain concentration (part per million, ppm) and brain uptake rate (the radioactivity percentage of injected dose per gram of brain, %dose/g), respectively. As a result, the brain concentrations of Mn was increasing with growth, although those of Se and Zn were hardly changing. On the other hand, the uptakes of the 3 tracers by the brain of 1-day-old mice were much higher than those of other elder ones. Using radioactive ^<54>Mn as a single tracer, autoradiography was examined to known the Mn uptake regional distribution in the brain of 1-, 8- and 21-day-old mice, and observed higher regional uptake of Mn by the cerebral cortex, hippocampus, thalamus and hypothalamus in the young brain.
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2019.5