Neutronic Study on Ac-225 Production for Cancer Therapy by (n,2n) Reaction of Ra-226 or Th-230 Using Fast Reactor Joyo

Abstract

Ac-225 has lately drawn considerable attention as a radioisotope for targeted alpha therapy treatment for certain types of prostate, blood-derived, and disseminated cancers, but its supply is limited. Therefore, we investigated the production method of Ac-225 by nuclear transmutation in a fast neutron reactor. The authors investigated irradiation of Ra-226 or Th-230 as a target nuclide in the experimental fast reactor Joyo, owned and operated by Japan Atomic Energy Agency, which has abundant fast neutrons and a large loading region with high heat removal capacity. Ra-226 is in increasing demand as a target nuclide to produce Ac-225. Therefore, as another option, we selected Th-230, which is 50 times more abundant than Ra-226 in natural uranium, as an alternative nuclide. Irradiation of Ra-226 and Th-230 with high energy neutrons above the threshold causes an (n,2n) reaction, producing Ra-225 and Th-229, respectively, which are the parent nuclides of Ac-225. The analyses showed that 47 GBq of Ac-225 can be generated annually by irradiating 1 g of Ra-226, and 6.5 GBq of Ac-225 can be semi-permanently generated every year by one-time irradiation of 50 g of Th-230 for 10 years (5 EFPY). It can be concluded that 100 MWt Joyo has potential to produce more than 70% of the current global supply of Ac-225 and/or to generate the parent nuclide Th-229, which keeps producing Ac-225 for thousands of years.

225Ac/213Bi radionuclide generators for the separation of 213Bi towards clinical demands

“…50 Approximately 4 TBq (216 Ci) of 225 Ac per year is required to meet the demand for cancer treatment, and the activity for 213 Bi should be increased accordingly. 51 Various approaches have been considered or examined to produce 225 Ac, which can be broadly divided into two categories: direct and in-direct production routes. 50 In the direct route, 225 Ac is the primary product of a nuclear reaction.…”

“…67 It is estimated that no more than 63 GBq (1.7 Ci) per year of 225 Ac can be produced worldwide by the decay of 229 Th. 52,68 Several institutions can generate limited quantities of 225 Ac by this method; for instance, 26.6 GBq (720 mCi) per year produced by Oak Ridge National Lab (ORNL) in Oak Ridge, USA, ∼26.4 (715 mCi) per year produced by Institute of Physics and Power Engineering (IPPE) in Obninsk, Russia, and 13.1 GBq (350 mCi) per year produced by the Institute for Transuranium Elements (ITU) in Karlsruhe, Germany. 30,31,62,67,69,70 In addition, the Belgian Nuclear Research Centre (SCK CEN) in Mol, Belgium, has a limited quantity of high-purity 229 Th became available from legacy thorium sources originating from reactor irradiated 226 Ra.…”

Research and Development for Cyclotron Production of 225Ac from 226Ra—The Challenges in a Country Lacking Natural Resources for Medical Applications

“…If the mass production of radioisotopes in a research test reactor becomes possible in the future, it will be a big step forward for the development of 225 Ac in Japan. The core research on reactor-based 225 Ac production is advocated by Tokyo City University [59]. This research has already been adopted in the "National Issue-Based R&D Promotion Project (Nuclear System R&D Project)" in 2020 in collaboration with the Japan Atomic Energy Agency (JAEA), NucMed Inc., Mitsubishi Heavy Industries, Ltd., and Kanazawa University [60].…”

“…This research has already been adopted in the "National Issue-Based R&D Promotion Project (Nuclear System R&D Project)" in 2020 in collaboration with the Japan Atomic Energy Agency (JAEA), NucMed Inc., Mitsubishi Heavy Industries, Ltd., and Kanazawa University [60]. The primal step in this R and D project is to restart the currently suspended test reactor "Joyo" and, after that, begin irradiating 226 Ra or 230 Th to produce 225 Ac at test and larger scales [59]. From the perspective of securing the important raw material of 226 Ra, the JAEA may be able to contribute by utilizing the former uranium mine at Ningyo-toge Pass.…”

Semi-Permanent Mass Production of Ac-225 for Cancer Therapy by the (3n,x) Reaction in Pressurized Water Reactor

“…Among the various Ac-225 production methods, the accelerator-based method offers Ac-225 production from a small amount of target nuclides with high efficiency, whereas the use of a nuclear reactor offers large amounts of stable neutron irradiation over a long time, large irradiation area, high heat removal capability, and high energy efficiency without the need for external energy supply. We previously reported the use of a fast reactor for Ac-225 production [13]. Using this method, a large amount of Ac-225 can be produced in a short time by generating Ra-225 and its β-decay in a single (n,2n) reaction by fast neutron irradiation of an irradiated target.…”