DOE User’s meeting July 28, 2020 Somewhere in the world

Current availability of 211At in Japan

Kohshin Washiyama, Ph.D Advanced Clinical Research Center, Fukushima Medical University 211At is available in Japan

Manufacturing facilities Production route and Production The main contributor of Separation metod 211At manufacturing

209Bi(α,2n)211At Research Center for Nuclear More than Dr. Atsushi Toyoshima , Osaka University Two decades Prof. Atsushi Shinohara Physics(RCNP) Dry distillation

Takasaki Ion Accelerators for Advanced Radiation Application(TIARA), Takasaki 209Bi(α,2n)211At Dr. Shigeki Watanabe Advanced Radiation Research Institute, Since 2012 Dr. Noriko S. Ishioka National Institutes for Quantum and Dry distillation Radiological Science and Technology(QST) Quantum Medical Science Directorate, National Institute of Radiological 209Bi(α,2n)211At Dr. Katsuyuki Minegishi Sciences(NIRS), National Institutes for Sine 2013 Dr. Kotaro Nagatsu Quantum and Radiological Science and Dry distillation Technology(QST)

Nishina Center for Accelerator-Based 209Bi(α,2n)211At Science, Institute of Physical and Chemical Since 2015 Dr. Hiromitsu Haba Research(Riken) Dry distillation

Advanced Clinical Research 209Bi(α,2n)211At Dr. Kohshin Washiyama Center(ACRC), Fukushima Medical Since 2016 Prof. Kazuhiro Takahashi University(FMU) Dry distillation

The tandem accelerator facility, Nuclear 209Bi(7Li,5n)211Rn/211At Dr. Ichiro Nishinaka Science Research Institute, Japan Atomic Since 2011 Dry & Wet chemistry Dr. Kazuyuki Hashimoto Energy Agency(JAEA)

2 Production facilities of α-emitters in Japan

211At production facilities (5 places) Dr. Haba 211Rn production facility (1 place) Riken

Dr. Watanabe User facilities including production (more than 13 places)

QST@Takasaki Fukushima Med. Univ.

JAEA@ Tokai Dr. Nishinaka Riken NIRS, QST Osaka Univ.

Dr. Toyoshima Dr. Nagatsu Production facilities of α-emitters in Japan

211At production facilities (5 places) 211Rn production facility (1 place)

User facilities including production (more than 13 places)

QST@Takasaki Fukushima Med. Univ.

JAEA@Tokai

Riken NIRS, QST Osaka Univ. Short-lived RI supply platform program (since 2016)

This program will provide stable supply of research radioisotopes throughout the year and technical support for safe handling. 1. Supply of short life isotopes that cannot be purchased from the commercial base. 2. A prompt and stable supply by the world's highest level of accelerator facility association. 3. Support for the promotion of basic research in a wide range of fields: ex. Development of probes for next generation PET, development of next generation therapeutic drugs, metabolic research of biological trace elements, etc. https://www.rcnp.osaka-u.ac.jp/~ripf/index.html

• Research Center for Nuclear Physics[RCNP], Osaka 7Be, 11C, 18F, 15O, 24Na, 28Mg, 38,39Cl, University (Osaka) 38,42,43 43,46,47 44 48 55 • Nishina Center for Accelerator-Based Science, Riken (Tokyo) K, Sc, Ti, V, Fe, • Cyclotron and Radioisotope Center [CYRIC], Tohoku 56,57,58Co, 57Ni, 61,64,67Cu, 74As, University (Sendai) 83,84,86 86,87,90 • Research Center for ELectron PHoton Science (ELPH), Rb, Y, Tohoku University (Sendai) 88,89,89m,95Zr,….207Bi, 207,210,211At, • TIARA, Takasaki QST (Takasaki) 213 238 255 • Quantum Medical Science Directorate,NIRS, QST (Chiba) Fr, Np, Md Middle sized cyclotron; MP-30 at Fukushima Medical University

MP-30 Cyclotron Beam transport

Target station

PIG ion source 6 Multi-cusp ion source

MP-30 Estimated production yield of 211At Energy 15-30 MeV (Valuable) Proton at TTY = 30.7 MBq/μAh Current 100 µA 2500 Energy 8-15 MeV (Valuable) 10uA Deuteron Current 50 µA 2000 Energy 32 MeV 15uA 1500 Alpha Current 30 µA 20uA ] Ion Source External(PIG:α+Multi-cups:P,D) 1000

Extraction Port 1 MBq [ 500 Max. Targets Depend on Requirement 0 Power 150 kW Room W6.0xD5.5xH3.6 RadioactivityProduced 0 60 120 180 240 Non Shield Weight 60 ton Irradiation time[min] Monthly production of 211At at FMU At at EOB [mCi] EOB at At 211 Produced JUL JUL JUL SEP SEP FEB FEB FEB JAN JAN JAN JUN JUN JUN DEC DEC DEC APR APR APR OCT OCT OCT AUG AUG MAY MAY MAY NOV NOV NOV MAR MAR MAR 2017 2018 2019 2020

Advanced Clinical 7 Research Center Summary

 Before 2010, Japan has only 1 facility that produced 211At.  Owing to the advent of 223Ra with its efficacy to prolong the overall survival of metastatic HRPC patients, Japanese physician change their opinion and they are interested in using α emitters.  Due to the availability of target materials and the usability of cyclotron that can produce α emitters, 211At would be the most appropriate candidate to manufacture.  There exist 5 facilities to produce 211At by direct reaction  There also exist one facility to produce 211Rn that will be a generator to produce 211At.  Due to the short half-life of 211At, At-related chemistry and preclinical studies have been restricted to the 211At production site or its vicinity. However, since the platform has been launched, the availability and sustainable supply of 211At have improved than ever, and as a result, many researchers have had more opportunities to come into contact with 211At.

8 Thank you for your kind attention!

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