Dosimetry of 211At-labeled compounds using molecular imaging and Monte Carlo simulation

• Project/Area Number: 18K15556
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Ukon Naoyuki 福島県立医科大学, 公私立大学の部局等, 助教 (70792985)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 核医学治療 / α線 / 分子イメージング / モンテカルロシミュレーション / 線量評価 / 医学物理 / α線治療 / 核医学

Outline of Final Research Achievements

In radionuclide therapy, it is important to estimate the tissue absorbed dose according to the injection activity for treatment planning, evaluation of treatment effect, and prediction of side effects. Especially in radionuclide therapy with alpha emitters, it is necessary to accurately measure the distribution reflecting the localization in the tissue due to the short range of alpha particles. Since the alpha particles of 211At cannot be visualized directly, we have established a method to accurately evaluate the disposition of 211At-labeled compounds using a SPECT system with 123I as a surrogate. By predicting the absorbed dose using Monte Carlo simulation based on the accumulation rate of tissues obtained from the images and their disposition, we have developed a method to evaluate the tissue absorbed dose as a basis for estimating the therapeutic effect and side effects before administering 211At-labeled compounds.

Academic Significance and Societal Importance of the Research Achievements

核医学治療における投与量に応じた組織吸収線量の推定技術の発展はこれまで一定の投与量や体重に応じた投与量により実施されていた核医学治療において、より安全かつ効率的な治療が可能となる。特にα線放出核種による核医学治療は近年様々な核種が用いられ、研究されているが確立された線量評価法は存在しない。本研究の成果により組織内の局在性を反映した分布を正確に反映したモンテカルロシミュレーションによる吸収線量予測を行うことで、化合物を投与する前に治療効果や副作用を推定する根拠となる情報を提示できるようになり、これまで判別のつかなかったより多くの治療が可能となることが示唆され、実診療においても資するものである。

Research Products

• [Journal Article] Human dosimetry of free 211At and meta-[211At]astatobenzylguanidine (211At-MABG) estimated using preclinical biodistribution from normal mice (2020)
  • Author(s): Ukon Naoyuki、Zhao Songji、Washiyama Kohshin、Oriuchi Noboru、Tan Chengbo、Shimoyama Saki、Aoki Miho、Kubo Hitoshi、Takahashi Kazuhiro、Ito Hiroshi
  • Journal Title: EJNMMI Physics Volume: 7 Issue: 1 Pages: 58-58
  • DOI: 10.1186/s40658-020-00326-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Biodistribution and dosimetry studies for the optimization of pre-targeted radionuclide therapy using 211At-labeled modified biotin (2020)
  • Author(s): Naoyuki Ukon, Kohshin Washiyama, Akira Sugiyama, Songji Zhao, Toshifumi Tatsumi, Miho Aoki, Kenzo Yamatsugu, Ken-ichi Nishijima, Saki Shimoyama, Taiki Joho, Noboru Oriuchi, Motomu Kanai, Kazuhiro Takahashi, Tatsuhiko Kodama
  • Organizer: The 33rd Annual Congress of the European Association of Nuclear Medicine
  • Int'l Joint Research
• [Presentation] 211At標識イミノビオチンを用いたプリターゲティング法の最適化投与間隔による薬物動態評価 (2020)
  • Author(s): 右近直之、鷲山幸信、杉山暁、巽俊文、山次健三、下山彩希、織内昇、金井求、児玉龍彦、高橋和弘、趙松吉
  • Organizer: 第60回日本核医学会学術総会
• [Presentation] コンパニオン診断薬としての123I-MIBGから推定した211At-MABGの線量評価検討 (2020)
  • Author(s): 右近直之、趙松吉、鷲野弘明、吉永恵一郎、粟生木美穂、西嶋剣一、鷲山幸信、織内昇、高橋和弘、東達也、伊藤浩
  • Organizer: 第60回日本核医学会学術総会
• [Presentation] Possibility of 123I-meta-iodobenzylguanidine (123I-MIBG) as a companion diagnostic drug for therapeutic alpha-emitting meta-211At-astato-benzylguanidine (211At-MABG) in normal mice (2019)
  • Author(s): Keiichiro Yoshinaga, Songji Zhao, Komei Washino, Miho Aoki, Ken-ichi Nishijima, Saki Shimoyama, Naoyuki Ukon, Chengbo Tan, Kohshin Washiyama, Kazuhiro Takahashi, Hiroshi Ito,Tatsuya Higashi
  • Organizer: Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2019 Annual Meeting
  • Int'l Joint Research
• [Presentation] Similarities and differences of dosimetry between meta-[211At]astatobenzylguanidine (211At-MABG) and meta-[123I]iodobenzylguanidine (123I-MIBG) as companion diagnostic drug (2019)
  • Author(s): Naoyuki Ukon, Songji Zhao, Keiichiro Yoshinaga, Komei Washino, Miho Aoki, Ken-ichi Nishijima, Saki Shimoyama, Chengbo Tan, Kohshin Washiyama, Noboru Oriuchi, Kazuhiro Takahashi, Tatsuya Higashi, Hiroshi Ito
  • Organizer: 32nd Annual Congress of the European Association of Nuclear Medicine (EANM)
  • Int'l Joint Research
• [Presentation] An effort to diagnostic and therapeutic nuclear medicine at Fukushima Medical University using two medical cyclotrons (2019)
  • Author(s): Kohshin Washiyama, Miho Aoki, Taiki Joho, Naoyuki Ukon, Ken-ichi Nishijima, Kazuhiro Takahashi, Songji Zhao, Noboru Oriuchi
  • Organizer: International Symposium on Trends in Radiopharmaceuticals (ISTR-2019)
  • Int'l Joint Research
• [Presentation] 小動物用SPECT装置を用いた211Atによる画像化の基礎検討 (2019)
  • Author(s): 右近 直之、趙 松吉、鷲山 幸信、織内 昇、粟生木 美穂、西嶋 剣一、譚 成博、下山 彩希、久保 均、高橋 和弘、伊藤 浩
  • Organizer: 日本分子イメージング学会第14回学会総会・学術集会
• [Presentation] Search for TLC procedure of meta-[211At]astatobenzylguanidine ([211At]MABG) (2019)
  • Author(s): 粟生木 美穂、西嶋 剣一、鷲山 幸信、城寳 大輝、下山 彩希、右近 直之、趙 松吉、鷲野 弘明、高橋 和弘、東 達也、伊藤 浩
  • Organizer: 第59回日本核医学会学術総会
• [Presentation] Evaluation of similarities between 123I-MIBG and 211At-MABG distribution in normal mice (2019)
  • Author(s): 趙 松吉、吉永 恵一郎、粟生木 美穂、右近 直之、下山 彩希、西嶋 剣一、鷲山 幸信、鷲野 弘明、高橋 和弘、東 達也、伊藤 浩
  • Organizer: 第59回日本核医学会学術総会
• [Presentation] Biodistribution and dosimetry of free 211At and meta-[211At]astatobenzylguanidine (MABG) in normal mice (2019)
  • Author(s): Naoyuki Ukon, Songji Zhao, Kohshin Washiyama, Noboru Oriuchi, Miho Aoki, Chengbo Tan, Saki Shimoyama, Hitoshi Kubo, Ken-ichi Nishijima, Kazuhiro Takahashi, Hiroshi Itoh
  • Organizer: The 11th International Symposium on Targeted-Alpha-Therapy (TAT11)
  • Int'l Joint Research
• [Presentation] 211Atの画像化への挑戦 (2019)
  • Author(s): 右近 直之、趙 松吉、鷲山 幸信、織内 昇、粟生木 美穂、西嶋 剣一、譚 成博、下山 彩希、久保 均、高橋 和弘、伊藤 浩
  • Organizer: 第15回小動物インビボイメージング研究会
• [Presentation] 正常マウスにおけるフリー211Atおよびmeta-[211At t]astatobenzylguanidine (MABG)の体内分布 (2018)
  • Author(s): 趙松吉, 粟生木美穂, 鷲山幸信, 右近直之, 譚成博, 下山彩希, 久保均、織内昇、高橋和弘、伊藤浩、竹之下誠一
  • Organizer: 第58回日本核医学会学術総会
• [Presentation] 正常マウスにおけるフリー211Atおよびmeta-[211At]astatobenzylguanidine (MABG)の組織吸収線量評価 (2018)
  • Author(s): 右近直之, 鷲山幸信, 趙松吉, 織内昇, 粟生木美穂, 譚成博, 下山彩希, 久保均, 高橋和弘, 伊藤浩
  • Organizer: 第58回日本核医学会学術総会
• [Presentation] 核種ごとのCross Calibration Factor (CCF) 測定は必要か？～小動物用PET/CT装置における検討～ (2018)
  • Author(s): 右近直之, 趙松吉, 下山彩希, 久保均, 伊藤浩
  • Organizer: 第14回小動物インビボイメージング研究会
• [Presentation] 正常マウスにおけるフリー211Atおよび211At-MABGの体内分布と組織吸収線量評価 (2018)
  • Author(s): 右近直之, 鷲山幸信, 趙松吉, 織内昇, 粟生木美穂, 譚成博, 下山彩希, 久保均, 高橋和弘, 伊藤浩
  • Organizer: 第8回核医学画像解析研究会
• [Presentation] Human internal radiation dose estimation using pharmacokinetics of free 211At and meta-[211At]astatobenzylguanidine (MABG) in normal mice (2018)
  • Author(s): Naoyuki Ukon, Kohshin Washiyama, Zhao Songji, Noboru Oriuchi, Miho Aoki, Chengbo Tan, Saki Shimoyama, Hitoshi Kubo, Kazuhiro Takahashi, Hiroshi Ito
  • Organizer: The 3rd Int. Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science
  • Int'l Joint Research